Immunology

French children with peanut allergy tend to have reactions to other legumes, including soy, lentil, pea, bean, lupin, and fenugreek, and those other allergies often lead to anaphylactic reactions, a retrospective study from France reports.

“Among children allergic to peanut, at least two-thirds were sensitized to one other legume, and legume allergy was diagnosed in one-quarter of the sensitized patients,” wrote senior study author Amandine Divaret-Chauveau, MD, of Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy, and colleagues. The report is in Pediatric Allergy and Immunology.

People worldwide are eating more legumes these days, the authors noted. High in protein, low in unsaturated fats, with low production costs, legumes are important components of increasingly vegetarian, healthy, sustainable diets.

Food allergens are the most common childhood triggers of allergic reactions. Among children in France, legumes cause 14.6% of food-related anaphylactic reactions, with peanut as the main allergen, they added.

Dr. Divaret-Chauveau and colleagues assessed the prevalence and relevance of sensitization to legumes among all children and adolescents aged 1-17 years who had peanut allergy and had been admitted to one academic pediatric allergy department over roughly 3 years, beginning in early 2017. For the 195 study participants, peanut allergy had been confirmed, and they had been documented to have consumed or to have sensitization to at least one non-peanut legume; 69.7% were boys.

The researchers analyzed data on consumption history, skin prick tests, specific immunoglobulin E status, prior allergic reactions, and oral food challenges for each legume. They found the following:

• Among the 195 children with peanut allergy, 98.4% had at least one other atopic disease.
• Of the 195 children with peanut allergy, 122 (63.9%) were sensitized to at least one other legume. Of these 122 children, 66.3% were sensitized to fenugreek, 42.2% to lentil, 39.9% to soy, and 34.2% to lupin.
• Allergy to one or more legumes was confirmed for 27.9% of the 122 sensitized children, including 4.9% who had multiple legume allergies. Lentil, lupin, and pea were the main allergens.
• Of the 118 children also having a non-legume food allergy, the main food allergens were egg (57.6%), cow’s milk (33.0%), cashew (39.0%), pistachio (23.7%), and hazelnut (30.5%).
• Fifty percent of allergic reactions to non-peanut legumes were severe, often showing as asthma. Atopic comorbidities, including asthma, in most participants may have contributed to the severity of allergic reactions, the authors noted.

Allergy awareness needs to grow with plant-based diets

“The high prevalence of legume sensitization reported in our study highlights the need to explore legume consumption in children with PA [peanut allergy], and the need to investigate sensitization in the absence of consumption,” they added.

Jodi A. Shroba, MSN, APRN, CPNP, coordinator for the Food Allergy Program at Children’s Mercy Kansas City, in Missouri, told this news organization that few data are available in the literature regarding allergies to legumes other than peanut.

“It was interesting that these authors found such a high legume sensitization in their peanut-allergic patients,” Ms. Shroba, who was not involved in the study, said by email. “As more people are starting to eat plant-based diets, it is important that we better understand their allergenicity and cross-reactivity so we can better help guide patient management and education.”

Deborah Albright, MD, assistant professor of pediatrics at the University of Pittsburgh, agreed.

“As plant-based protein consumption broadens worldwide, awareness of the potential for cross-reactivity and co-allergy amongst legumes will become increasingly important,” she said by email.

“However, positive allergy tests do not reliably correlate with true food allergy; therefore, the diagnosis of legume co-allergy should be confirmed by the individual patient’s history, a formal food challenge, or both,” advised Dr. Albright. She was not involved in the study.

“Cross-sensitization to other legumes in patients with a single legume allergy is common; however, true clinical reactivity is often not present,” she added. “Also, legume allergy test sensitization rates and objective reactivity on food challenge can vary by region, depending on diet and pollen aeroallergen exposure.

“Systematic exploration of tolerance versus co-allergy to other legumes should be considered in patients allergic to peanut or other legumes,” Dr. Albright said.

The authors recommend further research and registry data collection of legume anaphylaxis.

Details regarding funding for the study were not provided. The authors, Ms. Shroba, and Dr. Albright report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

French children with peanut allergy tend to have reactions to other legumes, including soy, lentil, pea, bean, lupin, and fenugreek, and those other allergies often lead to anaphylactic reactions, a retrospective study from France reports.

“Among children allergic to peanut, at least two-thirds were sensitized to one other legume, and legume allergy was diagnosed in one-quarter of the sensitized patients,” wrote senior study author Amandine Divaret-Chauveau, MD, of Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy, and colleagues. The report is in Pediatric Allergy and Immunology.

People worldwide are eating more legumes these days, the authors noted. High in protein, low in unsaturated fats, with low production costs, legumes are important components of increasingly vegetarian, healthy, sustainable diets.

Food allergens are the most common childhood triggers of allergic reactions. Among children in France, legumes cause 14.6% of food-related anaphylactic reactions, with peanut as the main allergen, they added.

Dr. Divaret-Chauveau and colleagues assessed the prevalence and relevance of sensitization to legumes among all children and adolescents aged 1-17 years who had peanut allergy and had been admitted to one academic pediatric allergy department over roughly 3 years, beginning in early 2017. For the 195 study participants, peanut allergy had been confirmed, and they had been documented to have consumed or to have sensitization to at least one non-peanut legume; 69.7% were boys.

The researchers analyzed data on consumption history, skin prick tests, specific immunoglobulin E status, prior allergic reactions, and oral food challenges for each legume. They found the following:

• Among the 195 children with peanut allergy, 98.4% had at least one other atopic disease.
• Of the 195 children with peanut allergy, 122 (63.9%) were sensitized to at least one other legume. Of these 122 children, 66.3% were sensitized to fenugreek, 42.2% to lentil, 39.9% to soy, and 34.2% to lupin.
• Allergy to one or more legumes was confirmed for 27.9% of the 122 sensitized children, including 4.9% who had multiple legume allergies. Lentil, lupin, and pea were the main allergens.
• Of the 118 children also having a non-legume food allergy, the main food allergens were egg (57.6%), cow’s milk (33.0%), cashew (39.0%), pistachio (23.7%), and hazelnut (30.5%).
• Fifty percent of allergic reactions to non-peanut legumes were severe, often showing as asthma. Atopic comorbidities, including asthma, in most participants may have contributed to the severity of allergic reactions, the authors noted.

Allergy awareness needs to grow with plant-based diets

“The high prevalence of legume sensitization reported in our study highlights the need to explore legume consumption in children with PA [peanut allergy], and the need to investigate sensitization in the absence of consumption,” they added.

Jodi A. Shroba, MSN, APRN, CPNP, coordinator for the Food Allergy Program at Children’s Mercy Kansas City, in Missouri, told this news organization that few data are available in the literature regarding allergies to legumes other than peanut.

“It was interesting that these authors found such a high legume sensitization in their peanut-allergic patients,” Ms. Shroba, who was not involved in the study, said by email. “As more people are starting to eat plant-based diets, it is important that we better understand their allergenicity and cross-reactivity so we can better help guide patient management and education.”

Deborah Albright, MD, assistant professor of pediatrics at the University of Pittsburgh, agreed.

“As plant-based protein consumption broadens worldwide, awareness of the potential for cross-reactivity and co-allergy amongst legumes will become increasingly important,” she said by email.

“However, positive allergy tests do not reliably correlate with true food allergy; therefore, the diagnosis of legume co-allergy should be confirmed by the individual patient’s history, a formal food challenge, or both,” advised Dr. Albright. She was not involved in the study.

“Cross-sensitization to other legumes in patients with a single legume allergy is common; however, true clinical reactivity is often not present,” she added. “Also, legume allergy test sensitization rates and objective reactivity on food challenge can vary by region, depending on diet and pollen aeroallergen exposure.

“Systematic exploration of tolerance versus co-allergy to other legumes should be considered in patients allergic to peanut or other legumes,” Dr. Albright said.

The authors recommend further research and registry data collection of legume anaphylaxis.

Details regarding funding for the study were not provided. The authors, Ms. Shroba, and Dr. Albright report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

French children with peanut allergy tend to have reactions to other legumes, including soy, lentil, pea, bean, lupin, and fenugreek, and those other allergies often lead to anaphylactic reactions, a retrospective study from France reports.

“Among children allergic to peanut, at least two-thirds were sensitized to one other legume, and legume allergy was diagnosed in one-quarter of the sensitized patients,” wrote senior study author Amandine Divaret-Chauveau, MD, of Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy, and colleagues. The report is in Pediatric Allergy and Immunology.

People worldwide are eating more legumes these days, the authors noted. High in protein, low in unsaturated fats, with low production costs, legumes are important components of increasingly vegetarian, healthy, sustainable diets.

Food allergens are the most common childhood triggers of allergic reactions. Among children in France, legumes cause 14.6% of food-related anaphylactic reactions, with peanut as the main allergen, they added.

Dr. Divaret-Chauveau and colleagues assessed the prevalence and relevance of sensitization to legumes among all children and adolescents aged 1-17 years who had peanut allergy and had been admitted to one academic pediatric allergy department over roughly 3 years, beginning in early 2017. For the 195 study participants, peanut allergy had been confirmed, and they had been documented to have consumed or to have sensitization to at least one non-peanut legume; 69.7% were boys.

The researchers analyzed data on consumption history, skin prick tests, specific immunoglobulin E status, prior allergic reactions, and oral food challenges for each legume. They found the following:

• Among the 195 children with peanut allergy, 98.4% had at least one other atopic disease.
• Of the 195 children with peanut allergy, 122 (63.9%) were sensitized to at least one other legume. Of these 122 children, 66.3% were sensitized to fenugreek, 42.2% to lentil, 39.9% to soy, and 34.2% to lupin.
• Allergy to one or more legumes was confirmed for 27.9% of the 122 sensitized children, including 4.9% who had multiple legume allergies. Lentil, lupin, and pea were the main allergens.
• Of the 118 children also having a non-legume food allergy, the main food allergens were egg (57.6%), cow’s milk (33.0%), cashew (39.0%), pistachio (23.7%), and hazelnut (30.5%).
• Fifty percent of allergic reactions to non-peanut legumes were severe, often showing as asthma. Atopic comorbidities, including asthma, in most participants may have contributed to the severity of allergic reactions, the authors noted.

Allergy awareness needs to grow with plant-based diets

“The high prevalence of legume sensitization reported in our study highlights the need to explore legume consumption in children with PA [peanut allergy], and the need to investigate sensitization in the absence of consumption,” they added.

Jodi A. Shroba, MSN, APRN, CPNP, coordinator for the Food Allergy Program at Children’s Mercy Kansas City, in Missouri, told this news organization that few data are available in the literature regarding allergies to legumes other than peanut.

“It was interesting that these authors found such a high legume sensitization in their peanut-allergic patients,” Ms. Shroba, who was not involved in the study, said by email. “As more people are starting to eat plant-based diets, it is important that we better understand their allergenicity and cross-reactivity so we can better help guide patient management and education.”

Deborah Albright, MD, assistant professor of pediatrics at the University of Pittsburgh, agreed.

“As plant-based protein consumption broadens worldwide, awareness of the potential for cross-reactivity and co-allergy amongst legumes will become increasingly important,” she said by email.

“However, positive allergy tests do not reliably correlate with true food allergy; therefore, the diagnosis of legume co-allergy should be confirmed by the individual patient’s history, a formal food challenge, or both,” advised Dr. Albright. She was not involved in the study.

“Cross-sensitization to other legumes in patients with a single legume allergy is common; however, true clinical reactivity is often not present,” she added. “Also, legume allergy test sensitization rates and objective reactivity on food challenge can vary by region, depending on diet and pollen aeroallergen exposure.

“Systematic exploration of tolerance versus co-allergy to other legumes should be considered in patients allergic to peanut or other legumes,” Dr. Albright said.

The authors recommend further research and registry data collection of legume anaphylaxis.

Details regarding funding for the study were not provided. The authors, Ms. Shroba, and Dr. Albright report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Managing children’s cow’s milk allergy is costly to families and to health care systems, largely owing to costs of prescriptions, according to an industry-sponsored study based on data from the United Kingdom.

“This large cohort study provides novel evidence of a significant health economic burden of cow’s milk allergy in children,” Abbie L. Cawood, PhD, RNutr, MICR, head of scientific affairs at Nutricia Ltd in Trowbridge, England, and colleagues wrote in Clinical and Translational Allergy.

“Management of cow’s milk allergy necessitates the exclusion of cow’s milk protein from the diet. Whilst breastmilk remains the ideal nutrient source in infants with cow’s milk allergy, infants who are not exclusively breastfed require a hypoallergenic formula,” added Dr. Cawood, a visiting research fellow at University of Southampton, and her coauthors.

Cow’s milk allergy, an immune‐mediated response to one or more proteins in cow’s milk, is one of the most common childhood food allergies and affects 2%-5% of infants in Europe. Management involves avoiding cow’s milk protein and treating possible related gastrointestinal, skin, respiratory, and other allergic conditions, the authors explained.

In their retrospective matched cohort study, Dr. Cawood and colleagues turned to The Health Improvement Network (THIN), a Cegedim Rx proprietary database of 2.9 million anonymized active patient records. They extracted data from nearly 7,000 case records covering 5 years (2015-2020).

They examined medication prescriptions and health care professional contacts based on diagnosis read-codes and hypoallergenic formula prescriptions and compared health care costs for children with cow’s milk allergy with the costs for those without.

They matched 3,499 children aged 1 year or younger who had confirmed or suspected cow’s milk allergy with the same number of children without cow’s milk allergy. Around half of the participants were boys, and the mean observation period was 4.2 years.
 

Children with cow’s milk allergy need more, costly health care

The researchers found:

• Medications were prescribed to significantly more children with cow’s milk allergy (CMA), at a higher rate, than to those without CMA. In particular, prescriptions for antireflux medication increased by almost 500%.
• Children with CMA needed significantly more health care contacts and at a higher rate than those without CMA.
• CMA was linked with additional potential health care costs of £1381.53 per person per year. Assuming a 2.5% prevalence from the estimated 2%-5% CMA prevalence range and extrapolating to the UK infant population, CMA may have added more than £25.7 million in annual health care costs nationwide.

“Several conditions in infancy necessitate the elimination of cow milk–based formulas and require extensively hydrolyzed or amino acid formulas or, if preferred or able, exclusive breast milk,” Kara E. Coffey, MD, assistant professor of pediatrics at the University of Pittsburgh, said by email.

“This study shows that, regardless of the reason for cow milk–based avoidance, these infants require more healthcare service utilizations (clinic visits, nutritional assessments, prescriptions) than [do] their peers, which is certainly a commitment of a lot of time and money for their families to ensure their ability to grow and thrive,” added Dr. Coffey, who was not involved in the study.

Jodi A. Shroba, MSN, APRN, CPNP, the coordinator for the Food Allergy Program at Children’s Mercy Kansas City, Mo., did not find these numbers surprising.

“Children with food allergies typically have other atopic comorbidities that require more visits to primary care physicians and specialists and more prescriptions,” Ms. Shroba, who was not involved in the study, said by email.

“An intriguing statement is that the U.K. guidelines recommend the involvement of a dietitian for children with cow’s milk allergy,” she noted. “In the United States, having a dietitian involved would be a wonderful addition to care, as avoidance of cow’s milk can cause nutritional and growth deficiencies. But not all healthcare practices have those resources available.

“The higher rate of antibiotic use and the almost 500% increase of antireflux prescriptions by the children with cow’s milk allergy warrant additional research,” she added.

Nutricia Ltd. funded the study. Dr. Cawood and one coauthor are employed by Nutricia, and all other coauthors have been employees of or have other financial relationships with Nutricia. One coauthor is employed by Cegedim Rx, which was funded for this research by Nutricia. Ms. Shroba and Dr. Coffey report no conflicts of interest with the study.

A version of this article first appeared on Medscape.com.

Managing children’s cow’s milk allergy is costly to families and to health care systems, largely owing to costs of prescriptions, according to an industry-sponsored study based on data from the United Kingdom.

“This large cohort study provides novel evidence of a significant health economic burden of cow’s milk allergy in children,” Abbie L. Cawood, PhD, RNutr, MICR, head of scientific affairs at Nutricia Ltd in Trowbridge, England, and colleagues wrote in Clinical and Translational Allergy.

“Management of cow’s milk allergy necessitates the exclusion of cow’s milk protein from the diet. Whilst breastmilk remains the ideal nutrient source in infants with cow’s milk allergy, infants who are not exclusively breastfed require a hypoallergenic formula,” added Dr. Cawood, a visiting research fellow at University of Southampton, and her coauthors.

Cow’s milk allergy, an immune‐mediated response to one or more proteins in cow’s milk, is one of the most common childhood food allergies and affects 2%-5% of infants in Europe. Management involves avoiding cow’s milk protein and treating possible related gastrointestinal, skin, respiratory, and other allergic conditions, the authors explained.

In their retrospective matched cohort study, Dr. Cawood and colleagues turned to The Health Improvement Network (THIN), a Cegedim Rx proprietary database of 2.9 million anonymized active patient records. They extracted data from nearly 7,000 case records covering 5 years (2015-2020).

They examined medication prescriptions and health care professional contacts based on diagnosis read-codes and hypoallergenic formula prescriptions and compared health care costs for children with cow’s milk allergy with the costs for those without.

They matched 3,499 children aged 1 year or younger who had confirmed or suspected cow’s milk allergy with the same number of children without cow’s milk allergy. Around half of the participants were boys, and the mean observation period was 4.2 years.
 

Children with cow’s milk allergy need more, costly health care

The researchers found:

• Medications were prescribed to significantly more children with cow’s milk allergy (CMA), at a higher rate, than to those without CMA. In particular, prescriptions for antireflux medication increased by almost 500%.
• Children with CMA needed significantly more health care contacts and at a higher rate than those without CMA.
• CMA was linked with additional potential health care costs of £1381.53 per person per year. Assuming a 2.5% prevalence from the estimated 2%-5% CMA prevalence range and extrapolating to the UK infant population, CMA may have added more than £25.7 million in annual health care costs nationwide.

“Several conditions in infancy necessitate the elimination of cow milk–based formulas and require extensively hydrolyzed or amino acid formulas or, if preferred or able, exclusive breast milk,” Kara E. Coffey, MD, assistant professor of pediatrics at the University of Pittsburgh, said by email.

“This study shows that, regardless of the reason for cow milk–based avoidance, these infants require more healthcare service utilizations (clinic visits, nutritional assessments, prescriptions) than [do] their peers, which is certainly a commitment of a lot of time and money for their families to ensure their ability to grow and thrive,” added Dr. Coffey, who was not involved in the study.

Jodi A. Shroba, MSN, APRN, CPNP, the coordinator for the Food Allergy Program at Children’s Mercy Kansas City, Mo., did not find these numbers surprising.

“Children with food allergies typically have other atopic comorbidities that require more visits to primary care physicians and specialists and more prescriptions,” Ms. Shroba, who was not involved in the study, said by email.

“An intriguing statement is that the U.K. guidelines recommend the involvement of a dietitian for children with cow’s milk allergy,” she noted. “In the United States, having a dietitian involved would be a wonderful addition to care, as avoidance of cow’s milk can cause nutritional and growth deficiencies. But not all healthcare practices have those resources available.

“The higher rate of antibiotic use and the almost 500% increase of antireflux prescriptions by the children with cow’s milk allergy warrant additional research,” she added.

Nutricia Ltd. funded the study. Dr. Cawood and one coauthor are employed by Nutricia, and all other coauthors have been employees of or have other financial relationships with Nutricia. One coauthor is employed by Cegedim Rx, which was funded for this research by Nutricia. Ms. Shroba and Dr. Coffey report no conflicts of interest with the study.

A version of this article first appeared on Medscape.com.

Managing children’s cow’s milk allergy is costly to families and to health care systems, largely owing to costs of prescriptions, according to an industry-sponsored study based on data from the United Kingdom.

“This large cohort study provides novel evidence of a significant health economic burden of cow’s milk allergy in children,” Abbie L. Cawood, PhD, RNutr, MICR, head of scientific affairs at Nutricia Ltd in Trowbridge, England, and colleagues wrote in Clinical and Translational Allergy.

“Management of cow’s milk allergy necessitates the exclusion of cow’s milk protein from the diet. Whilst breastmilk remains the ideal nutrient source in infants with cow’s milk allergy, infants who are not exclusively breastfed require a hypoallergenic formula,” added Dr. Cawood, a visiting research fellow at University of Southampton, and her coauthors.

Cow’s milk allergy, an immune‐mediated response to one or more proteins in cow’s milk, is one of the most common childhood food allergies and affects 2%-5% of infants in Europe. Management involves avoiding cow’s milk protein and treating possible related gastrointestinal, skin, respiratory, and other allergic conditions, the authors explained.

In their retrospective matched cohort study, Dr. Cawood and colleagues turned to The Health Improvement Network (THIN), a Cegedim Rx proprietary database of 2.9 million anonymized active patient records. They extracted data from nearly 7,000 case records covering 5 years (2015-2020).

They examined medication prescriptions and health care professional contacts based on diagnosis read-codes and hypoallergenic formula prescriptions and compared health care costs for children with cow’s milk allergy with the costs for those without.

They matched 3,499 children aged 1 year or younger who had confirmed or suspected cow’s milk allergy with the same number of children without cow’s milk allergy. Around half of the participants were boys, and the mean observation period was 4.2 years.
 

Children with cow’s milk allergy need more, costly health care

The researchers found:

• Medications were prescribed to significantly more children with cow’s milk allergy (CMA), at a higher rate, than to those without CMA. In particular, prescriptions for antireflux medication increased by almost 500%.
• Children with CMA needed significantly more health care contacts and at a higher rate than those without CMA.
• CMA was linked with additional potential health care costs of £1381.53 per person per year. Assuming a 2.5% prevalence from the estimated 2%-5% CMA prevalence range and extrapolating to the UK infant population, CMA may have added more than £25.7 million in annual health care costs nationwide.

“Several conditions in infancy necessitate the elimination of cow milk–based formulas and require extensively hydrolyzed or amino acid formulas or, if preferred or able, exclusive breast milk,” Kara E. Coffey, MD, assistant professor of pediatrics at the University of Pittsburgh, said by email.

“This study shows that, regardless of the reason for cow milk–based avoidance, these infants require more healthcare service utilizations (clinic visits, nutritional assessments, prescriptions) than [do] their peers, which is certainly a commitment of a lot of time and money for their families to ensure their ability to grow and thrive,” added Dr. Coffey, who was not involved in the study.

Jodi A. Shroba, MSN, APRN, CPNP, the coordinator for the Food Allergy Program at Children’s Mercy Kansas City, Mo., did not find these numbers surprising.

“Children with food allergies typically have other atopic comorbidities that require more visits to primary care physicians and specialists and more prescriptions,” Ms. Shroba, who was not involved in the study, said by email.

“An intriguing statement is that the U.K. guidelines recommend the involvement of a dietitian for children with cow’s milk allergy,” she noted. “In the United States, having a dietitian involved would be a wonderful addition to care, as avoidance of cow’s milk can cause nutritional and growth deficiencies. But not all healthcare practices have those resources available.

“The higher rate of antibiotic use and the almost 500% increase of antireflux prescriptions by the children with cow’s milk allergy warrant additional research,” she added.

Nutricia Ltd. funded the study. Dr. Cawood and one coauthor are employed by Nutricia, and all other coauthors have been employees of or have other financial relationships with Nutricia. One coauthor is employed by Cegedim Rx, which was funded for this research by Nutricia. Ms. Shroba and Dr. Coffey report no conflicts of interest with the study.

A version of this article first appeared on Medscape.com.

A new guideline aims to help primary care doctors differentiate pollen food syndrome (PFS) – a cross-reactive allergic reaction to certain raw, but not cooked, plant foods – from other food allergies.

The guideline from the British Society of Allergy and Clinical Immunology (BSACI) focuses on birch tree pollen, the major sensitizing PFS allergen in Northern Europe. Providers may be able to diagnose PFS related to birch pollen from clinical history alone, including the foods involved and the rapidity of symptom onset, write lead author Isabel J. Skypala, PhD, RD, of Imperial College London, and her colleagues.

The new BSACI guideline for diagnosis and management of PFS was published in Clinical & Experimental Allergy.
 

PFS is common and increasingly prevalent

PFS – also called oral allergy syndrome and pollen food allergy syndrome – is common and increasingly prevalent. PFS can begin at any age but usually starts in pollen-sensitized school-age children and adults with seasonal allergic rhinitis.

Symptoms from similar proteins in food

Mild to moderate allergic symptoms develop quickly when people sensitized to birch pollen eat raw plant foods that contain proteins similar to those in the pollen, such as pathogenesis-related protein PR-10. The allergens are broken down by cooking or processing.

Symptoms usually occur immediately or within 15 minutes of eating. Patients may have tingling; itching or soreness in the mouth, throat, or ears; mild lip and oral mucosa angioedema; itchy hands, sneezing, or eye symptoms; tongue or pharynx angioedema; perioral rash; cough; abdominal pain; nausea; and/or worsening of eczema. In children, itch and rash may predominate.
 

Triggers depend on pollen type

PFS triggers vary depending on a person’s pollen sensitization, which is affected by their geographic area and local dietary habits. In the United Kingdom, almost 70% of birch-allergic adults and more than 40% of birch-allergic children have PFS, the authors write.

Typical triggers include eating apples, stone fruits, kiwis, carrots, celery, hazelnuts, almonds, walnuts, soymilk, and peanuts, as well as peeling potatoes or other root vegetables. Freshly prepared vegetable or fruit smoothies or juices, celery, soymilk, raw nuts, large quantities of roasted nuts, and concentrated nut products can cause more severe reactions.
 

Diagnostic clinical history

If a patient answers yes to these questions, they almost certainly have PFS, the authors write:

• Are symptoms caused by raw fruits, nuts, carrots, or celery?
• Are the same trigger foods tolerated when they’re cooked well or roasted?
• Do symptoms come immediately or within a few minutes of eating?
• Do symptoms occur in the oropharynx and include tingling, itching, or swelling?
• Does the patient have seasonal allergic rhinitis or sensitization to pollen?

Testing needed for some cases

Allergy tests may be needed for people who report atypical or severe reactions or who also react to cooked or processed plant foods, such as roasted nuts, nuts in foods, fruits or vegetables in juices and smoothies, and soy products other than milk. Tests may also be needed for people who react to foods that are not linked with PFS, such as cashews, pistachios, macadamias, sesame seeds, beans, lentils, and chickpeas.

Whether PFS reactions also occur to roasted hazelnuts, almonds, walnuts, Brazil nuts, or peanuts, either alone or in composite foods such as chocolates, spreads, desserts, and snacks, is unclear.

An oral food challenge to confirm PFS is needed only if the history and diagnostic tests are inconclusive or if the patient is avoiding multiple foods.
 

Dietary management

PFS is managed by excluding known trigger foods. This becomes challenging for patients with preexisting food allergies and for vegetarians and vegans.

Personalized dietary advice is needed to avoid nutritional imbalance, minimize anxiety and unnecessary food restrictions, and improve quality of life. Reactions after accidental exposure often resolve without medication, and if antihistamines are needed, they rarely require self-injectable devices.
 

Guideline helpful beyond the United Kingdom and birch pollen

Allyson S. Larkin, MD, associate professor of pediatrics at the University of Pittsburgh School of Medicine, told this news organization in an email that the guideline summarizes in great detail the pathophysiology behind PFS and highlights how component testing may help diagnose patients and manage the condition.

“Patients worry very much about the progression and severity of allergic reactions,” said Dr. Larkin, who was not involved in the guideline development.

“As the authors note, recognizing the nutritional consequences of dietary restrictions is important, and nutrition consults and suitable alternative suggestions are very helpful for these patients, especially for those with food allergy or who are vegetarian or vegan.”

Jill A. Poole, MD, professor of medicine and chief of the Division of Allergy and Immunology at the University of Nebraska College of Medicine, Omaha, noted that PFS, although common, is underrecognized by the public and by health care providers.

“People are not allergic to the specific food, but they are allergic to a seasonal allergen, such as birch tree, that cross-reacts with the food protein, which is typically changed with cooking,” she explained in an email.

“This differs from reactions by those who have moderate to severe allergic food-specific reactions that may include systemic reactions like anaphylaxis from eating certain foods,” she said.

“Importantly, the number of cross-reacting foods with seasonal pollens continues to grow, and the extent of testing has expanded in recent years,” advised Dr. Poole, who also was not involved in the guideline development. 

The authors recommend further related research into food immunotherapy and other novel PFS treatments. They also want to raise awareness of factors affecting PFS prevalence, such as increased spread and allergenicity of pollen due to climate change, pollution, the global consumption of previously local traditional foods, and the increase in vegetarian and vegan diets.

The authors, Dr. Larkin, and Dr. Poole report no relevant financial relationships involving this guideline. The guideline was not funded.

A version of this article first appeared on Medscape.com.

A new guideline aims to help primary care doctors differentiate pollen food syndrome (PFS) – a cross-reactive allergic reaction to certain raw, but not cooked, plant foods – from other food allergies.

The guideline from the British Society of Allergy and Clinical Immunology (BSACI) focuses on birch tree pollen, the major sensitizing PFS allergen in Northern Europe. Providers may be able to diagnose PFS related to birch pollen from clinical history alone, including the foods involved and the rapidity of symptom onset, write lead author Isabel J. Skypala, PhD, RD, of Imperial College London, and her colleagues.

The new BSACI guideline for diagnosis and management of PFS was published in Clinical & Experimental Allergy.
 

PFS is common and increasingly prevalent

PFS – also called oral allergy syndrome and pollen food allergy syndrome – is common and increasingly prevalent. PFS can begin at any age but usually starts in pollen-sensitized school-age children and adults with seasonal allergic rhinitis.

Symptoms from similar proteins in food

Mild to moderate allergic symptoms develop quickly when people sensitized to birch pollen eat raw plant foods that contain proteins similar to those in the pollen, such as pathogenesis-related protein PR-10. The allergens are broken down by cooking or processing.

Symptoms usually occur immediately or within 15 minutes of eating. Patients may have tingling; itching or soreness in the mouth, throat, or ears; mild lip and oral mucosa angioedema; itchy hands, sneezing, or eye symptoms; tongue or pharynx angioedema; perioral rash; cough; abdominal pain; nausea; and/or worsening of eczema. In children, itch and rash may predominate.
 

Triggers depend on pollen type

PFS triggers vary depending on a person’s pollen sensitization, which is affected by their geographic area and local dietary habits. In the United Kingdom, almost 70% of birch-allergic adults and more than 40% of birch-allergic children have PFS, the authors write.

Typical triggers include eating apples, stone fruits, kiwis, carrots, celery, hazelnuts, almonds, walnuts, soymilk, and peanuts, as well as peeling potatoes or other root vegetables. Freshly prepared vegetable or fruit smoothies or juices, celery, soymilk, raw nuts, large quantities of roasted nuts, and concentrated nut products can cause more severe reactions.
 

Diagnostic clinical history

If a patient answers yes to these questions, they almost certainly have PFS, the authors write:

• Are symptoms caused by raw fruits, nuts, carrots, or celery?
• Are the same trigger foods tolerated when they’re cooked well or roasted?
• Do symptoms come immediately or within a few minutes of eating?
• Do symptoms occur in the oropharynx and include tingling, itching, or swelling?
• Does the patient have seasonal allergic rhinitis or sensitization to pollen?

Testing needed for some cases

Allergy tests may be needed for people who report atypical or severe reactions or who also react to cooked or processed plant foods, such as roasted nuts, nuts in foods, fruits or vegetables in juices and smoothies, and soy products other than milk. Tests may also be needed for people who react to foods that are not linked with PFS, such as cashews, pistachios, macadamias, sesame seeds, beans, lentils, and chickpeas.

Whether PFS reactions also occur to roasted hazelnuts, almonds, walnuts, Brazil nuts, or peanuts, either alone or in composite foods such as chocolates, spreads, desserts, and snacks, is unclear.

An oral food challenge to confirm PFS is needed only if the history and diagnostic tests are inconclusive or if the patient is avoiding multiple foods.
 

Dietary management

PFS is managed by excluding known trigger foods. This becomes challenging for patients with preexisting food allergies and for vegetarians and vegans.

Personalized dietary advice is needed to avoid nutritional imbalance, minimize anxiety and unnecessary food restrictions, and improve quality of life. Reactions after accidental exposure often resolve without medication, and if antihistamines are needed, they rarely require self-injectable devices.
 

Guideline helpful beyond the United Kingdom and birch pollen

Allyson S. Larkin, MD, associate professor of pediatrics at the University of Pittsburgh School of Medicine, told this news organization in an email that the guideline summarizes in great detail the pathophysiology behind PFS and highlights how component testing may help diagnose patients and manage the condition.

“Patients worry very much about the progression and severity of allergic reactions,” said Dr. Larkin, who was not involved in the guideline development.

“As the authors note, recognizing the nutritional consequences of dietary restrictions is important, and nutrition consults and suitable alternative suggestions are very helpful for these patients, especially for those with food allergy or who are vegetarian or vegan.”

Jill A. Poole, MD, professor of medicine and chief of the Division of Allergy and Immunology at the University of Nebraska College of Medicine, Omaha, noted that PFS, although common, is underrecognized by the public and by health care providers.

“People are not allergic to the specific food, but they are allergic to a seasonal allergen, such as birch tree, that cross-reacts with the food protein, which is typically changed with cooking,” she explained in an email.

“This differs from reactions by those who have moderate to severe allergic food-specific reactions that may include systemic reactions like anaphylaxis from eating certain foods,” she said.

“Importantly, the number of cross-reacting foods with seasonal pollens continues to grow, and the extent of testing has expanded in recent years,” advised Dr. Poole, who also was not involved in the guideline development. 

The authors recommend further related research into food immunotherapy and other novel PFS treatments. They also want to raise awareness of factors affecting PFS prevalence, such as increased spread and allergenicity of pollen due to climate change, pollution, the global consumption of previously local traditional foods, and the increase in vegetarian and vegan diets.

The authors, Dr. Larkin, and Dr. Poole report no relevant financial relationships involving this guideline. The guideline was not funded.

A version of this article first appeared on Medscape.com.

A new guideline aims to help primary care doctors differentiate pollen food syndrome (PFS) – a cross-reactive allergic reaction to certain raw, but not cooked, plant foods – from other food allergies.

The guideline from the British Society of Allergy and Clinical Immunology (BSACI) focuses on birch tree pollen, the major sensitizing PFS allergen in Northern Europe. Providers may be able to diagnose PFS related to birch pollen from clinical history alone, including the foods involved and the rapidity of symptom onset, write lead author Isabel J. Skypala, PhD, RD, of Imperial College London, and her colleagues.

The new BSACI guideline for diagnosis and management of PFS was published in Clinical & Experimental Allergy.
 

PFS is common and increasingly prevalent

PFS – also called oral allergy syndrome and pollen food allergy syndrome – is common and increasingly prevalent. PFS can begin at any age but usually starts in pollen-sensitized school-age children and adults with seasonal allergic rhinitis.

Symptoms from similar proteins in food

Mild to moderate allergic symptoms develop quickly when people sensitized to birch pollen eat raw plant foods that contain proteins similar to those in the pollen, such as pathogenesis-related protein PR-10. The allergens are broken down by cooking or processing.

Symptoms usually occur immediately or within 15 minutes of eating. Patients may have tingling; itching or soreness in the mouth, throat, or ears; mild lip and oral mucosa angioedema; itchy hands, sneezing, or eye symptoms; tongue or pharynx angioedema; perioral rash; cough; abdominal pain; nausea; and/or worsening of eczema. In children, itch and rash may predominate.
 

Triggers depend on pollen type

PFS triggers vary depending on a person’s pollen sensitization, which is affected by their geographic area and local dietary habits. In the United Kingdom, almost 70% of birch-allergic adults and more than 40% of birch-allergic children have PFS, the authors write.

Typical triggers include eating apples, stone fruits, kiwis, carrots, celery, hazelnuts, almonds, walnuts, soymilk, and peanuts, as well as peeling potatoes or other root vegetables. Freshly prepared vegetable or fruit smoothies or juices, celery, soymilk, raw nuts, large quantities of roasted nuts, and concentrated nut products can cause more severe reactions.
 

Diagnostic clinical history

If a patient answers yes to these questions, they almost certainly have PFS, the authors write:

• Are symptoms caused by raw fruits, nuts, carrots, or celery?
• Are the same trigger foods tolerated when they’re cooked well or roasted?
• Do symptoms come immediately or within a few minutes of eating?
• Do symptoms occur in the oropharynx and include tingling, itching, or swelling?
• Does the patient have seasonal allergic rhinitis or sensitization to pollen?

Testing needed for some cases

Allergy tests may be needed for people who report atypical or severe reactions or who also react to cooked or processed plant foods, such as roasted nuts, nuts in foods, fruits or vegetables in juices and smoothies, and soy products other than milk. Tests may also be needed for people who react to foods that are not linked with PFS, such as cashews, pistachios, macadamias, sesame seeds, beans, lentils, and chickpeas.

Whether PFS reactions also occur to roasted hazelnuts, almonds, walnuts, Brazil nuts, or peanuts, either alone or in composite foods such as chocolates, spreads, desserts, and snacks, is unclear.

An oral food challenge to confirm PFS is needed only if the history and diagnostic tests are inconclusive or if the patient is avoiding multiple foods.
 

Dietary management

PFS is managed by excluding known trigger foods. This becomes challenging for patients with preexisting food allergies and for vegetarians and vegans.

Personalized dietary advice is needed to avoid nutritional imbalance, minimize anxiety and unnecessary food restrictions, and improve quality of life. Reactions after accidental exposure often resolve without medication, and if antihistamines are needed, they rarely require self-injectable devices.
 

Guideline helpful beyond the United Kingdom and birch pollen

Allyson S. Larkin, MD, associate professor of pediatrics at the University of Pittsburgh School of Medicine, told this news organization in an email that the guideline summarizes in great detail the pathophysiology behind PFS and highlights how component testing may help diagnose patients and manage the condition.

“Patients worry very much about the progression and severity of allergic reactions,” said Dr. Larkin, who was not involved in the guideline development.

“As the authors note, recognizing the nutritional consequences of dietary restrictions is important, and nutrition consults and suitable alternative suggestions are very helpful for these patients, especially for those with food allergy or who are vegetarian or vegan.”

Jill A. Poole, MD, professor of medicine and chief of the Division of Allergy and Immunology at the University of Nebraska College of Medicine, Omaha, noted that PFS, although common, is underrecognized by the public and by health care providers.

“People are not allergic to the specific food, but they are allergic to a seasonal allergen, such as birch tree, that cross-reacts with the food protein, which is typically changed with cooking,” she explained in an email.

“This differs from reactions by those who have moderate to severe allergic food-specific reactions that may include systemic reactions like anaphylaxis from eating certain foods,” she said.

“Importantly, the number of cross-reacting foods with seasonal pollens continues to grow, and the extent of testing has expanded in recent years,” advised Dr. Poole, who also was not involved in the guideline development. 

The authors recommend further related research into food immunotherapy and other novel PFS treatments. They also want to raise awareness of factors affecting PFS prevalence, such as increased spread and allergenicity of pollen due to climate change, pollution, the global consumption of previously local traditional foods, and the increase in vegetarian and vegan diets.

The authors, Dr. Larkin, and Dr. Poole report no relevant financial relationships involving this guideline. The guideline was not funded.

A version of this article first appeared on Medscape.com.

From the Department of Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC.

Abstract

Objective: Inpatient vaccination initiatives are well described in the literature. During the COVID-19 pandemic, hospitals began administering COVID-19 vaccines to hospitalized patients. Although vaccination rates increased, there remained many unvaccinated patients despite community efforts. This quality improvement project aimed to increase the COVID-19 vaccination rates of hospitalized patients on the medicine service at the George Washington University Hospital (GWUH).

Methods: From November 2021 through February 2022, we conducted a Plan-Do-Study-Act (PDSA) cycle with 3 phases. Initial steps included gathering baseline data from the electronic health record and consulting stakeholders. The first 2 phases focused on educating housestaff on the availability, ordering process, and administration of the Pfizer vaccine. The third phase consisted of developing educational pamphlets for patients to be included in their admission packets.

Results: The baseline mean COVID-19 vaccination rate (August to October 2021) of eligible patients on the medicine service was 10.7%. In the months after we implemented the PDSA cycle (November 2021 to February 2022), the mean vaccination rate increased to 15.4%.

Conclusion: This quality improvement project implemented measures to increase administration of the Pfizer vaccine to eligible patients admitted to the medicine service at GWUH. The mean vaccination rate increased from 10.7% in the 3 months prior to implementation to 15.4% during the 4 months post implementation. Other measures to consider in the future include increasing the availability of other COVID-19 vaccines at our hospital and incorporating the vaccine into the admission order set to help facilitate vaccination early in the hospital course.

Keywords: housestaff, quality improvement, PDSA, COVID-19, BNT162b2 vaccine, patient education

Throughout the COVID-19 pandemic, case rates in the United States have fluctuated considerably, corresponding to epidemic waves. In 2021, US daily cases of COVID-19 peaked at nearly 300,000 in early January and reached a nadir of 8000 cases in mid-June.¹ In September 2021, new cases had increased to 200,000 per day due to the prevalence of the Delta variant.¹ Particularly with the emergence of new variants of SARS-CoV-2, vaccination efforts to limit the spread of infection and severity of illness are critical. Data have shown that 2 doses of the BNT162b2 vaccine (Pfizer-BioNTech) were largely protective against severe infection for approximately 6 months.^2,3 When we began this quality improvement (QI) project in September 2021, only 179 million Americans had been fully vaccinated, according to data from the Centers for Disease Control and Prevention, which is just over half of the US population.⁴ An electronic survey conducted in the United States with more than 5 million responses found that, of those who were hesitant about receiving the vaccine, 49% reported a fear of adverse effects and 48% reported a lack of trust in the vaccine.⁵

This QI project sought to target unvaccinated individuals admitted to the internal medicine inpatient service. Vaccinating hospitalized patients is especially important since they are sicker than the general population and at higher risk of having poor outcomes from COVID-19. Inpatient vaccine initiatives, such as administering influenza vaccine prior to discharge, have been successfully implemented in the past.⁶ One large COVID-19 vaccination program featured an admission order set to increase the rates of vaccination among hospitalized patients.⁷ Our QI project piloted a multidisciplinary approach involving the nursing staff, pharmacy, information technology (IT) department, and internal medicine housestaff to increase COVID-19 vaccination rates among hospitalized patients on the medical service. This project aimed to increase inpatient vaccination rates through interventions targeting both primary providers as well as the patients themselves.

Methods

Setting and Interventions

This project was conducted at the George Washington University Hospital (GWUH) in Washington, DC. The clinicians involved in the study were the internal medicine housestaff, and the patients included were adults admitted to the resident medicine ward teams. The project was exempt by the institutional review board and did not require informed consent.

The quality improvement initiative had 3 phases, each featuring a different intervention (Table 1). The first phase involved sending a weekly announcement (via email and a secure health care messaging app) to current residents rotating on the inpatient medicine service. The announcement contained information regarding COVID-19 vaccine availability at the hospital, instructions on ordering the vaccine, and the process of coordinating with pharmacy to facilitate vaccine administration. Thereafter, residents were educated on the process of giving a COVID-19 vaccine to a patient from start to finish. Due to the nature of the residency schedule, different housestaff members rotated in and out of the medicine wards during the intervention periods. The weekly email was sent to the entire internal medicine housestaff, informing all residents about the QI project, while the weekly secure messages served as reminders and were only sent to residents currently on the medicine wards.

In the second phase, we posted paper flyers throughout the hospital to remind housestaff to give the vaccine and again educate them on the process of ordering the vaccine. For the third intervention, a COVID-19 vaccine educational pamphlet was developed for distribution to inpatients at GWUH. The pamphlet included information on vaccine efficacy, safety, side effects, and eligibility. The pamphlet was incorporated in the admission packet that every patient receives upon admission to the hospital. The patients reviewed the pamphlets with nursing staff, who would answer any questions, with residents available to discuss any outstanding concerns.

Measures and Data Gathering

The primary endpoint of the study was inpatient vaccination rate, defined as the number of COVID-19 vaccines administered divided by the number of patients eligible to receive a vaccine (not fully vaccinated). During initial triage, nursing staff documented vaccination status in the electronic health record (EHR), checking a box in a data entry form if a patient had received 0, 1, or 2 doses of the COVID-19 vaccine. The GWUH IT department generated data from this form to determine the number of patients eligible to receive a COVID-19 vaccine. Data were extracted from the medication administration record in the EHR to determine the number of vaccines that were administered to patients during their hospitalization on the inpatient medical service. Each month, the IT department extracted data for the number of eligible patients and the number of vaccines administered. This yielded the monthly vaccination rates. The monthly vaccination rates in the period prior to starting the QI initiative were compared to the rates in the period after the interventions were implemented.

Of note, during the course of this project, patients became eligible for a third COVID-19 vaccine (booster). We decided to continue with the original aim of vaccinating adults who had only received 0 or 1 dose of the vaccine. Therefore, the eligibility criteria remained the same throughout the study. We obtained retrospective data to ensure that the vaccines being counted toward the vaccination rate were vaccines given to patients not yet fully vaccinated and not vaccines given as boosters.

Results

From August to October 2021, the baseline average monthly vaccination rate of patients on the medicine service who were eligible to receive a COVID-19 vaccine was 10.7%. After the first intervention, the vaccination rate increased to 19.7% in November 2021 (Table 2). The second intervention yielded vaccination rates of 11.4% and 11.8% in December 2021 and January 2022, respectively. During the final phase in February 2022, the vaccination rate was 19.0%. At the conclusion of the study, the mean vaccination rate for the intervention months was 15.4% (Figure 1). Process stability and variation are demonstrated with a statistical process control chart (Figure 2).

For this housestaff-driven QI project, we implemented an inpatient COVID-19 vaccination campaign consisting of 3 phases that targeted both providers and patients. During the intervention period, we observed an increased vaccination rate compared to the period just prior to implementation of the QI project. While our interventions may certainly have boosted vaccination rates, we understand other variables could have contributed to increased rates as well. The emergence of variants in the United States, such as omicron in December 2021,⁸ could have precipitated a demand for vaccinations among patients. Holidays in November and December may also have increased patients’ desire to get vaccinated before travel.

We encountered a number of roadblocks that challenged our project, including difficulty identifying patients who were eligible for the vaccine, logistical vaccine administration challenges, and hesitancy among the inpatient population. Accurately identifying patients who were eligible for a vaccine in the EHR was especially challenging in the setting of rapidly changing guidelines regarding COVID-19 vaccination. In September 2021, the US Food and Drug Administration authorized the Pfizer booster for certain populations and later, in November 2021, for all adults. This meant that some fully vaccinated hospitalized patients (those with 2 doses) then qualified for an additional dose of the vaccine and received a dose during hospitalization. To determine the true vaccination rate, we obtained retrospective data that allowed us to track each vaccine administered. If a patient had already received 2 doses of the COVID-19 vaccine, the vaccine administered was counted as a booster and excluded from the calculation of the vaccination rate. Future PDSA cycles could include updating the EHR to capture the whole range of COVID-19 vaccination status (unvaccinated, partially vaccinated, fully vaccinated, fully vaccinated with 1 booster, fully vaccinated with 2 boosters).

We also encountered logistical challenges with the administration of the COVID-19 vaccine to hospitalized patients. During the intervention period, our pharmacy department required 5 COVID-19 vaccination orders before opening a vial and administering the vaccine doses in order to reduce waste. This policy may have limited our ability to vaccinate eligible inpatients because we were not always able to identify 5 patients simultaneously on the service who were eligible and consented to the vaccine.

The majority of patients who were interested in receiving COVID-19 vaccination had already been vaccinated in the outpatient setting. This fact made the inpatient internal medicine subset of patients a particularly challenging population to target, given their possible hesitancy regarding vaccination. By utilizing a multidisciplinary team and increasing communication of providers and nursing staff, we helped to increase the COVID-19 vaccination rates at our hospital from 10.7% to 15.4%.

Future Directions

Future interventions to consider include increasing the availability of other approved COVID-19 vaccines at our hospital besides the Pfizer-BioNTech vaccine. Furthermore, incorporating the vaccine into the admission order set would help initiate the vaccination process early in the hospital course. We encourage other institutions to utilize similar approaches to not only remind providers about inpatient vaccination, but also educate and encourage patients to receive the vaccine. These measures will help institutions increase inpatient COVID-19 vaccination rates in a high-risk population.

Corresponding author: Anna Rubin, MD, Department of Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC; [email protected]

Disclosures: None reported.

From the Department of Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC.

Abstract

Objective: Inpatient vaccination initiatives are well described in the literature. During the COVID-19 pandemic, hospitals began administering COVID-19 vaccines to hospitalized patients. Although vaccination rates increased, there remained many unvaccinated patients despite community efforts. This quality improvement project aimed to increase the COVID-19 vaccination rates of hospitalized patients on the medicine service at the George Washington University Hospital (GWUH).

Methods: From November 2021 through February 2022, we conducted a Plan-Do-Study-Act (PDSA) cycle with 3 phases. Initial steps included gathering baseline data from the electronic health record and consulting stakeholders. The first 2 phases focused on educating housestaff on the availability, ordering process, and administration of the Pfizer vaccine. The third phase consisted of developing educational pamphlets for patients to be included in their admission packets.

Results: The baseline mean COVID-19 vaccination rate (August to October 2021) of eligible patients on the medicine service was 10.7%. In the months after we implemented the PDSA cycle (November 2021 to February 2022), the mean vaccination rate increased to 15.4%.

Conclusion: This quality improvement project implemented measures to increase administration of the Pfizer vaccine to eligible patients admitted to the medicine service at GWUH. The mean vaccination rate increased from 10.7% in the 3 months prior to implementation to 15.4% during the 4 months post implementation. Other measures to consider in the future include increasing the availability of other COVID-19 vaccines at our hospital and incorporating the vaccine into the admission order set to help facilitate vaccination early in the hospital course.

Keywords: housestaff, quality improvement, PDSA, COVID-19, BNT162b2 vaccine, patient education

Throughout the COVID-19 pandemic, case rates in the United States have fluctuated considerably, corresponding to epidemic waves. In 2021, US daily cases of COVID-19 peaked at nearly 300,000 in early January and reached a nadir of 8000 cases in mid-June.¹ In September 2021, new cases had increased to 200,000 per day due to the prevalence of the Delta variant.¹ Particularly with the emergence of new variants of SARS-CoV-2, vaccination efforts to limit the spread of infection and severity of illness are critical. Data have shown that 2 doses of the BNT162b2 vaccine (Pfizer-BioNTech) were largely protective against severe infection for approximately 6 months.^2,3 When we began this quality improvement (QI) project in September 2021, only 179 million Americans had been fully vaccinated, according to data from the Centers for Disease Control and Prevention, which is just over half of the US population.⁴ An electronic survey conducted in the United States with more than 5 million responses found that, of those who were hesitant about receiving the vaccine, 49% reported a fear of adverse effects and 48% reported a lack of trust in the vaccine.⁵

This QI project sought to target unvaccinated individuals admitted to the internal medicine inpatient service. Vaccinating hospitalized patients is especially important since they are sicker than the general population and at higher risk of having poor outcomes from COVID-19. Inpatient vaccine initiatives, such as administering influenza vaccine prior to discharge, have been successfully implemented in the past.⁶ One large COVID-19 vaccination program featured an admission order set to increase the rates of vaccination among hospitalized patients.⁷ Our QI project piloted a multidisciplinary approach involving the nursing staff, pharmacy, information technology (IT) department, and internal medicine housestaff to increase COVID-19 vaccination rates among hospitalized patients on the medical service. This project aimed to increase inpatient vaccination rates through interventions targeting both primary providers as well as the patients themselves.

Methods

Setting and Interventions

This project was conducted at the George Washington University Hospital (GWUH) in Washington, DC. The clinicians involved in the study were the internal medicine housestaff, and the patients included were adults admitted to the resident medicine ward teams. The project was exempt by the institutional review board and did not require informed consent.

The quality improvement initiative had 3 phases, each featuring a different intervention (Table 1). The first phase involved sending a weekly announcement (via email and a secure health care messaging app) to current residents rotating on the inpatient medicine service. The announcement contained information regarding COVID-19 vaccine availability at the hospital, instructions on ordering the vaccine, and the process of coordinating with pharmacy to facilitate vaccine administration. Thereafter, residents were educated on the process of giving a COVID-19 vaccine to a patient from start to finish. Due to the nature of the residency schedule, different housestaff members rotated in and out of the medicine wards during the intervention periods. The weekly email was sent to the entire internal medicine housestaff, informing all residents about the QI project, while the weekly secure messages served as reminders and were only sent to residents currently on the medicine wards.

In the second phase, we posted paper flyers throughout the hospital to remind housestaff to give the vaccine and again educate them on the process of ordering the vaccine. For the third intervention, a COVID-19 vaccine educational pamphlet was developed for distribution to inpatients at GWUH. The pamphlet included information on vaccine efficacy, safety, side effects, and eligibility. The pamphlet was incorporated in the admission packet that every patient receives upon admission to the hospital. The patients reviewed the pamphlets with nursing staff, who would answer any questions, with residents available to discuss any outstanding concerns.

Measures and Data Gathering

The primary endpoint of the study was inpatient vaccination rate, defined as the number of COVID-19 vaccines administered divided by the number of patients eligible to receive a vaccine (not fully vaccinated). During initial triage, nursing staff documented vaccination status in the electronic health record (EHR), checking a box in a data entry form if a patient had received 0, 1, or 2 doses of the COVID-19 vaccine. The GWUH IT department generated data from this form to determine the number of patients eligible to receive a COVID-19 vaccine. Data were extracted from the medication administration record in the EHR to determine the number of vaccines that were administered to patients during their hospitalization on the inpatient medical service. Each month, the IT department extracted data for the number of eligible patients and the number of vaccines administered. This yielded the monthly vaccination rates. The monthly vaccination rates in the period prior to starting the QI initiative were compared to the rates in the period after the interventions were implemented.

Of note, during the course of this project, patients became eligible for a third COVID-19 vaccine (booster). We decided to continue with the original aim of vaccinating adults who had only received 0 or 1 dose of the vaccine. Therefore, the eligibility criteria remained the same throughout the study. We obtained retrospective data to ensure that the vaccines being counted toward the vaccination rate were vaccines given to patients not yet fully vaccinated and not vaccines given as boosters.

Results

From August to October 2021, the baseline average monthly vaccination rate of patients on the medicine service who were eligible to receive a COVID-19 vaccine was 10.7%. After the first intervention, the vaccination rate increased to 19.7% in November 2021 (Table 2). The second intervention yielded vaccination rates of 11.4% and 11.8% in December 2021 and January 2022, respectively. During the final phase in February 2022, the vaccination rate was 19.0%. At the conclusion of the study, the mean vaccination rate for the intervention months was 15.4% (Figure 1). Process stability and variation are demonstrated with a statistical process control chart (Figure 2).

For this housestaff-driven QI project, we implemented an inpatient COVID-19 vaccination campaign consisting of 3 phases that targeted both providers and patients. During the intervention period, we observed an increased vaccination rate compared to the period just prior to implementation of the QI project. While our interventions may certainly have boosted vaccination rates, we understand other variables could have contributed to increased rates as well. The emergence of variants in the United States, such as omicron in December 2021,⁸ could have precipitated a demand for vaccinations among patients. Holidays in November and December may also have increased patients’ desire to get vaccinated before travel.

We encountered a number of roadblocks that challenged our project, including difficulty identifying patients who were eligible for the vaccine, logistical vaccine administration challenges, and hesitancy among the inpatient population. Accurately identifying patients who were eligible for a vaccine in the EHR was especially challenging in the setting of rapidly changing guidelines regarding COVID-19 vaccination. In September 2021, the US Food and Drug Administration authorized the Pfizer booster for certain populations and later, in November 2021, for all adults. This meant that some fully vaccinated hospitalized patients (those with 2 doses) then qualified for an additional dose of the vaccine and received a dose during hospitalization. To determine the true vaccination rate, we obtained retrospective data that allowed us to track each vaccine administered. If a patient had already received 2 doses of the COVID-19 vaccine, the vaccine administered was counted as a booster and excluded from the calculation of the vaccination rate. Future PDSA cycles could include updating the EHR to capture the whole range of COVID-19 vaccination status (unvaccinated, partially vaccinated, fully vaccinated, fully vaccinated with 1 booster, fully vaccinated with 2 boosters).

We also encountered logistical challenges with the administration of the COVID-19 vaccine to hospitalized patients. During the intervention period, our pharmacy department required 5 COVID-19 vaccination orders before opening a vial and administering the vaccine doses in order to reduce waste. This policy may have limited our ability to vaccinate eligible inpatients because we were not always able to identify 5 patients simultaneously on the service who were eligible and consented to the vaccine.

The majority of patients who were interested in receiving COVID-19 vaccination had already been vaccinated in the outpatient setting. This fact made the inpatient internal medicine subset of patients a particularly challenging population to target, given their possible hesitancy regarding vaccination. By utilizing a multidisciplinary team and increasing communication of providers and nursing staff, we helped to increase the COVID-19 vaccination rates at our hospital from 10.7% to 15.4%.

Future Directions

Future interventions to consider include increasing the availability of other approved COVID-19 vaccines at our hospital besides the Pfizer-BioNTech vaccine. Furthermore, incorporating the vaccine into the admission order set would help initiate the vaccination process early in the hospital course. We encourage other institutions to utilize similar approaches to not only remind providers about inpatient vaccination, but also educate and encourage patients to receive the vaccine. These measures will help institutions increase inpatient COVID-19 vaccination rates in a high-risk population.

Corresponding author: Anna Rubin, MD, Department of Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC; [email protected]

Disclosures: None reported.

From the Department of Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC.

Abstract

Objective: Inpatient vaccination initiatives are well described in the literature. During the COVID-19 pandemic, hospitals began administering COVID-19 vaccines to hospitalized patients. Although vaccination rates increased, there remained many unvaccinated patients despite community efforts. This quality improvement project aimed to increase the COVID-19 vaccination rates of hospitalized patients on the medicine service at the George Washington University Hospital (GWUH).

Methods: From November 2021 through February 2022, we conducted a Plan-Do-Study-Act (PDSA) cycle with 3 phases. Initial steps included gathering baseline data from the electronic health record and consulting stakeholders. The first 2 phases focused on educating housestaff on the availability, ordering process, and administration of the Pfizer vaccine. The third phase consisted of developing educational pamphlets for patients to be included in their admission packets.

Results: The baseline mean COVID-19 vaccination rate (August to October 2021) of eligible patients on the medicine service was 10.7%. In the months after we implemented the PDSA cycle (November 2021 to February 2022), the mean vaccination rate increased to 15.4%.

Conclusion: This quality improvement project implemented measures to increase administration of the Pfizer vaccine to eligible patients admitted to the medicine service at GWUH. The mean vaccination rate increased from 10.7% in the 3 months prior to implementation to 15.4% during the 4 months post implementation. Other measures to consider in the future include increasing the availability of other COVID-19 vaccines at our hospital and incorporating the vaccine into the admission order set to help facilitate vaccination early in the hospital course.

Keywords: housestaff, quality improvement, PDSA, COVID-19, BNT162b2 vaccine, patient education

Throughout the COVID-19 pandemic, case rates in the United States have fluctuated considerably, corresponding to epidemic waves. In 2021, US daily cases of COVID-19 peaked at nearly 300,000 in early January and reached a nadir of 8000 cases in mid-June.¹ In September 2021, new cases had increased to 200,000 per day due to the prevalence of the Delta variant.¹ Particularly with the emergence of new variants of SARS-CoV-2, vaccination efforts to limit the spread of infection and severity of illness are critical. Data have shown that 2 doses of the BNT162b2 vaccine (Pfizer-BioNTech) were largely protective against severe infection for approximately 6 months.^2,3 When we began this quality improvement (QI) project in September 2021, only 179 million Americans had been fully vaccinated, according to data from the Centers for Disease Control and Prevention, which is just over half of the US population.⁴ An electronic survey conducted in the United States with more than 5 million responses found that, of those who were hesitant about receiving the vaccine, 49% reported a fear of adverse effects and 48% reported a lack of trust in the vaccine.⁵

This QI project sought to target unvaccinated individuals admitted to the internal medicine inpatient service. Vaccinating hospitalized patients is especially important since they are sicker than the general population and at higher risk of having poor outcomes from COVID-19. Inpatient vaccine initiatives, such as administering influenza vaccine prior to discharge, have been successfully implemented in the past.⁶ One large COVID-19 vaccination program featured an admission order set to increase the rates of vaccination among hospitalized patients.⁷ Our QI project piloted a multidisciplinary approach involving the nursing staff, pharmacy, information technology (IT) department, and internal medicine housestaff to increase COVID-19 vaccination rates among hospitalized patients on the medical service. This project aimed to increase inpatient vaccination rates through interventions targeting both primary providers as well as the patients themselves.

Methods

Setting and Interventions

This project was conducted at the George Washington University Hospital (GWUH) in Washington, DC. The clinicians involved in the study were the internal medicine housestaff, and the patients included were adults admitted to the resident medicine ward teams. The project was exempt by the institutional review board and did not require informed consent.

The quality improvement initiative had 3 phases, each featuring a different intervention (Table 1). The first phase involved sending a weekly announcement (via email and a secure health care messaging app) to current residents rotating on the inpatient medicine service. The announcement contained information regarding COVID-19 vaccine availability at the hospital, instructions on ordering the vaccine, and the process of coordinating with pharmacy to facilitate vaccine administration. Thereafter, residents were educated on the process of giving a COVID-19 vaccine to a patient from start to finish. Due to the nature of the residency schedule, different housestaff members rotated in and out of the medicine wards during the intervention periods. The weekly email was sent to the entire internal medicine housestaff, informing all residents about the QI project, while the weekly secure messages served as reminders and were only sent to residents currently on the medicine wards.

In the second phase, we posted paper flyers throughout the hospital to remind housestaff to give the vaccine and again educate them on the process of ordering the vaccine. For the third intervention, a COVID-19 vaccine educational pamphlet was developed for distribution to inpatients at GWUH. The pamphlet included information on vaccine efficacy, safety, side effects, and eligibility. The pamphlet was incorporated in the admission packet that every patient receives upon admission to the hospital. The patients reviewed the pamphlets with nursing staff, who would answer any questions, with residents available to discuss any outstanding concerns.

Measures and Data Gathering

The primary endpoint of the study was inpatient vaccination rate, defined as the number of COVID-19 vaccines administered divided by the number of patients eligible to receive a vaccine (not fully vaccinated). During initial triage, nursing staff documented vaccination status in the electronic health record (EHR), checking a box in a data entry form if a patient had received 0, 1, or 2 doses of the COVID-19 vaccine. The GWUH IT department generated data from this form to determine the number of patients eligible to receive a COVID-19 vaccine. Data were extracted from the medication administration record in the EHR to determine the number of vaccines that were administered to patients during their hospitalization on the inpatient medical service. Each month, the IT department extracted data for the number of eligible patients and the number of vaccines administered. This yielded the monthly vaccination rates. The monthly vaccination rates in the period prior to starting the QI initiative were compared to the rates in the period after the interventions were implemented.

Of note, during the course of this project, patients became eligible for a third COVID-19 vaccine (booster). We decided to continue with the original aim of vaccinating adults who had only received 0 or 1 dose of the vaccine. Therefore, the eligibility criteria remained the same throughout the study. We obtained retrospective data to ensure that the vaccines being counted toward the vaccination rate were vaccines given to patients not yet fully vaccinated and not vaccines given as boosters.

Results

From August to October 2021, the baseline average monthly vaccination rate of patients on the medicine service who were eligible to receive a COVID-19 vaccine was 10.7%. After the first intervention, the vaccination rate increased to 19.7% in November 2021 (Table 2). The second intervention yielded vaccination rates of 11.4% and 11.8% in December 2021 and January 2022, respectively. During the final phase in February 2022, the vaccination rate was 19.0%. At the conclusion of the study, the mean vaccination rate for the intervention months was 15.4% (Figure 1). Process stability and variation are demonstrated with a statistical process control chart (Figure 2).

For this housestaff-driven QI project, we implemented an inpatient COVID-19 vaccination campaign consisting of 3 phases that targeted both providers and patients. During the intervention period, we observed an increased vaccination rate compared to the period just prior to implementation of the QI project. While our interventions may certainly have boosted vaccination rates, we understand other variables could have contributed to increased rates as well. The emergence of variants in the United States, such as omicron in December 2021,⁸ could have precipitated a demand for vaccinations among patients. Holidays in November and December may also have increased patients’ desire to get vaccinated before travel.

We encountered a number of roadblocks that challenged our project, including difficulty identifying patients who were eligible for the vaccine, logistical vaccine administration challenges, and hesitancy among the inpatient population. Accurately identifying patients who were eligible for a vaccine in the EHR was especially challenging in the setting of rapidly changing guidelines regarding COVID-19 vaccination. In September 2021, the US Food and Drug Administration authorized the Pfizer booster for certain populations and later, in November 2021, for all adults. This meant that some fully vaccinated hospitalized patients (those with 2 doses) then qualified for an additional dose of the vaccine and received a dose during hospitalization. To determine the true vaccination rate, we obtained retrospective data that allowed us to track each vaccine administered. If a patient had already received 2 doses of the COVID-19 vaccine, the vaccine administered was counted as a booster and excluded from the calculation of the vaccination rate. Future PDSA cycles could include updating the EHR to capture the whole range of COVID-19 vaccination status (unvaccinated, partially vaccinated, fully vaccinated, fully vaccinated with 1 booster, fully vaccinated with 2 boosters).

We also encountered logistical challenges with the administration of the COVID-19 vaccine to hospitalized patients. During the intervention period, our pharmacy department required 5 COVID-19 vaccination orders before opening a vial and administering the vaccine doses in order to reduce waste. This policy may have limited our ability to vaccinate eligible inpatients because we were not always able to identify 5 patients simultaneously on the service who were eligible and consented to the vaccine.

The majority of patients who were interested in receiving COVID-19 vaccination had already been vaccinated in the outpatient setting. This fact made the inpatient internal medicine subset of patients a particularly challenging population to target, given their possible hesitancy regarding vaccination. By utilizing a multidisciplinary team and increasing communication of providers and nursing staff, we helped to increase the COVID-19 vaccination rates at our hospital from 10.7% to 15.4%.

Future Directions

Future interventions to consider include increasing the availability of other approved COVID-19 vaccines at our hospital besides the Pfizer-BioNTech vaccine. Furthermore, incorporating the vaccine into the admission order set would help initiate the vaccination process early in the hospital course. We encourage other institutions to utilize similar approaches to not only remind providers about inpatient vaccination, but also educate and encourage patients to receive the vaccine. These measures will help institutions increase inpatient COVID-19 vaccination rates in a high-risk population.

Corresponding author: Anna Rubin, MD, Department of Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC; [email protected]

Disclosures: None reported.

BY WILL PASS

Don’t count on a runny nose. Young kids with COVID-19 often have no symptoms at all, even when they have a high viral load, according to a study supported by the Centers for Disease Control and Prevention.

Just 14% of adults who tested positive for SARS-CoV-2 were asymptomatic, versus 37% of children aged 0-4 years, in the paper. This raises concern that parents, childcare providers, and preschools may be underestimating infection in seemingly healthy young kids who have been exposed to COVID, wrote lead author Ruth A. Karron, MD, and colleagues in JAMA Network Open.

Methods

The new research involved 690 individuals from 175 households in Maryland who were monitored closely between November 2020 and October 2021. Every week for 8 months, participants completed online symptom checks and underwent PCR testing using nasal swabs, with symptomatic individuals submitting additional swabs for analysis.

“What was different about our study [compared with previous studies] was the intensity of our collection, and the fact that we collected specimens from asymptomatic people,” said Dr. Karron, a pediatrician and professor in the department of international health, Johns Hopkins University, Baltimore, in an interview. “You shed more virus earlier in the infection than later, and the fact that we were sampling every single week meant that we could pick up those early infections.”

The study also stands out for its focus on young children, Dr. Karron said. Enrollment required all households to have at least one child aged 0-4 years, so 256 out of 690 participants (37.1%) were in this youngest age group. The remainder of the population consisted of 100 older children aged 5-17 years (14.5%) and 334 adults aged 18-74 years (48.4%).

Children 4 and under more than twice as likely to be asymptomatic

By the end of the study, 51 participants had tested positive for SARS-CoV-2, among whom 14 had no symptoms. A closer look showed that children 0-4 years of age who contracted COVID were more than twice as likely to be asymptomatic as infected adults (36.8% vs. 14.3%).

The relationship between symptoms and viral load also differed between adults and young children.

While adults with high viral loads – suggesting greater contagiousness – typically had more severe COVID symptoms, no correlation was found in young kids, meaning children with mild or no symptoms could still be highly contagious.

Dr. Karron said these findings should help parents and other stakeholders make better-informed decisions based on known risks. She recommended testing young, asymptomatic children for COVID if they have been exposed to infected individuals, then acting accordingly based on the results.

“If a family is infected with the virus, and the 2-year-old is asymptomatic, and people are thinking about a visit to elderly grandparents who may be frail, one shouldn’t assume that the 2-year-old is uninfected,” Dr. Karron said. “That child should be tested along with other family members.”

Testing should also be considered for young children exposed to COVID at childcare facilities, she added.

But not every expert consulted for this piece shared these opinions of Dr. Karron.

“I question whether that effort is worth it,” said Dean Blumberg, MD, professor and chief of the division of pediatric infectious diseases at UC Davis Health, Sacramento, Calif.

He noted that recent Food and Drug Administration guidance for COVID testing calls for three negative at-home antigen tests to confirm lack of infection.

“That would take 4 days to get those tests done,” he said. “So, it’s a lot of testing. It’s a lot of record keeping, it’s inconvenient, it’s uncomfortable to be tested, and I just question whether it’s worth that effort.”

Applicability of findings to today questioned

Dr. Blumberg also questioned whether the study, which was completed almost a year ago, reflects the current pandemic landscape.

“At the time this study was done, it was predominantly Delta [variant instead of Omicron],” Dr. Blumberg said. “The other issue [with the study] is that … most of the children didn’t have preexisting immunity, so you have to take that into account.”

Preexisting immunity – whether from exposure or vaccination – could lower viral loads, so asymptomatic children today really could be less contagious than they were when the study was done, according to Dr. Blumberg. Kids without symptoms are also less likely to spread the virus, because they aren’t coughing or sneezing, he added.

Sara R. Kim, MD, and Janet A. Englund, MD, of the Seattle Children’s Research Institute, University of Washington, said it’s challenging to know how applicable the findings are, although they sided more with the investigators than Dr. Blumberg.

“Given the higher rate of transmissibility and infectivity of the Omicron variant, it is difficult to make direct associations between findings reported during this study period and those present in the current era during which the Omicron variant is circulating,” they wrote in an accompanying editorial. “However, the higher rates of asymptomatic infection observed among children in this study are likely to be consistent with those observed for current and future viral variants.”

Although the experts offered different interpretations of the findings, they shared similar perspectives on vaccination.

“The most important thing that parents can do is get their kids vaccinated, be vaccinated themselves, and have everybody in the household vaccinated and up to date for all doses that are indicated,” Dr. Blumberg said.

Dr. Karron noted that vaccination will be increasingly important in the coming months.

“Summer is ending; school is starting,” she said. “We’re going to be in large groups indoors again very soon. To keep young children safe, I think it’s really important for them to get vaccinated.”

The study was funded by the CDC. The investigators disclosed no other relationships. Dr. Englund disclosed relationships with AstraZeneca, GlaxoSmithKline, Merck, and others. Dr. Kim and Dr. Blumberg disclosed no relevant conflicts of interest.

BY WILL PASS

Don’t count on a runny nose. Young kids with COVID-19 often have no symptoms at all, even when they have a high viral load, according to a study supported by the Centers for Disease Control and Prevention.

Just 14% of adults who tested positive for SARS-CoV-2 were asymptomatic, versus 37% of children aged 0-4 years, in the paper. This raises concern that parents, childcare providers, and preschools may be underestimating infection in seemingly healthy young kids who have been exposed to COVID, wrote lead author Ruth A. Karron, MD, and colleagues in JAMA Network Open.

Methods

The new research involved 690 individuals from 175 households in Maryland who were monitored closely between November 2020 and October 2021. Every week for 8 months, participants completed online symptom checks and underwent PCR testing using nasal swabs, with symptomatic individuals submitting additional swabs for analysis.

“What was different about our study [compared with previous studies] was the intensity of our collection, and the fact that we collected specimens from asymptomatic people,” said Dr. Karron, a pediatrician and professor in the department of international health, Johns Hopkins University, Baltimore, in an interview. “You shed more virus earlier in the infection than later, and the fact that we were sampling every single week meant that we could pick up those early infections.”

The study also stands out for its focus on young children, Dr. Karron said. Enrollment required all households to have at least one child aged 0-4 years, so 256 out of 690 participants (37.1%) were in this youngest age group. The remainder of the population consisted of 100 older children aged 5-17 years (14.5%) and 334 adults aged 18-74 years (48.4%).

Children 4 and under more than twice as likely to be asymptomatic

By the end of the study, 51 participants had tested positive for SARS-CoV-2, among whom 14 had no symptoms. A closer look showed that children 0-4 years of age who contracted COVID were more than twice as likely to be asymptomatic as infected adults (36.8% vs. 14.3%).

The relationship between symptoms and viral load also differed between adults and young children.

While adults with high viral loads – suggesting greater contagiousness – typically had more severe COVID symptoms, no correlation was found in young kids, meaning children with mild or no symptoms could still be highly contagious.

Dr. Karron said these findings should help parents and other stakeholders make better-informed decisions based on known risks. She recommended testing young, asymptomatic children for COVID if they have been exposed to infected individuals, then acting accordingly based on the results.

“If a family is infected with the virus, and the 2-year-old is asymptomatic, and people are thinking about a visit to elderly grandparents who may be frail, one shouldn’t assume that the 2-year-old is uninfected,” Dr. Karron said. “That child should be tested along with other family members.”

Testing should also be considered for young children exposed to COVID at childcare facilities, she added.

But not every expert consulted for this piece shared these opinions of Dr. Karron.

“I question whether that effort is worth it,” said Dean Blumberg, MD, professor and chief of the division of pediatric infectious diseases at UC Davis Health, Sacramento, Calif.

He noted that recent Food and Drug Administration guidance for COVID testing calls for three negative at-home antigen tests to confirm lack of infection.

“That would take 4 days to get those tests done,” he said. “So, it’s a lot of testing. It’s a lot of record keeping, it’s inconvenient, it’s uncomfortable to be tested, and I just question whether it’s worth that effort.”

Applicability of findings to today questioned

Dr. Blumberg also questioned whether the study, which was completed almost a year ago, reflects the current pandemic landscape.

“At the time this study was done, it was predominantly Delta [variant instead of Omicron],” Dr. Blumberg said. “The other issue [with the study] is that … most of the children didn’t have preexisting immunity, so you have to take that into account.”

Preexisting immunity – whether from exposure or vaccination – could lower viral loads, so asymptomatic children today really could be less contagious than they were when the study was done, according to Dr. Blumberg. Kids without symptoms are also less likely to spread the virus, because they aren’t coughing or sneezing, he added.

Sara R. Kim, MD, and Janet A. Englund, MD, of the Seattle Children’s Research Institute, University of Washington, said it’s challenging to know how applicable the findings are, although they sided more with the investigators than Dr. Blumberg.

“Given the higher rate of transmissibility and infectivity of the Omicron variant, it is difficult to make direct associations between findings reported during this study period and those present in the current era during which the Omicron variant is circulating,” they wrote in an accompanying editorial. “However, the higher rates of asymptomatic infection observed among children in this study are likely to be consistent with those observed for current and future viral variants.”

Although the experts offered different interpretations of the findings, they shared similar perspectives on vaccination.

“The most important thing that parents can do is get their kids vaccinated, be vaccinated themselves, and have everybody in the household vaccinated and up to date for all doses that are indicated,” Dr. Blumberg said.

Dr. Karron noted that vaccination will be increasingly important in the coming months.

“Summer is ending; school is starting,” she said. “We’re going to be in large groups indoors again very soon. To keep young children safe, I think it’s really important for them to get vaccinated.”

The study was funded by the CDC. The investigators disclosed no other relationships. Dr. Englund disclosed relationships with AstraZeneca, GlaxoSmithKline, Merck, and others. Dr. Kim and Dr. Blumberg disclosed no relevant conflicts of interest.

BY WILL PASS

Don’t count on a runny nose. Young kids with COVID-19 often have no symptoms at all, even when they have a high viral load, according to a study supported by the Centers for Disease Control and Prevention.

Just 14% of adults who tested positive for SARS-CoV-2 were asymptomatic, versus 37% of children aged 0-4 years, in the paper. This raises concern that parents, childcare providers, and preschools may be underestimating infection in seemingly healthy young kids who have been exposed to COVID, wrote lead author Ruth A. Karron, MD, and colleagues in JAMA Network Open.

Methods

The new research involved 690 individuals from 175 households in Maryland who were monitored closely between November 2020 and October 2021. Every week for 8 months, participants completed online symptom checks and underwent PCR testing using nasal swabs, with symptomatic individuals submitting additional swabs for analysis.

“What was different about our study [compared with previous studies] was the intensity of our collection, and the fact that we collected specimens from asymptomatic people,” said Dr. Karron, a pediatrician and professor in the department of international health, Johns Hopkins University, Baltimore, in an interview. “You shed more virus earlier in the infection than later, and the fact that we were sampling every single week meant that we could pick up those early infections.”

The study also stands out for its focus on young children, Dr. Karron said. Enrollment required all households to have at least one child aged 0-4 years, so 256 out of 690 participants (37.1%) were in this youngest age group. The remainder of the population consisted of 100 older children aged 5-17 years (14.5%) and 334 adults aged 18-74 years (48.4%).

Children 4 and under more than twice as likely to be asymptomatic

By the end of the study, 51 participants had tested positive for SARS-CoV-2, among whom 14 had no symptoms. A closer look showed that children 0-4 years of age who contracted COVID were more than twice as likely to be asymptomatic as infected adults (36.8% vs. 14.3%).

The relationship between symptoms and viral load also differed between adults and young children.

While adults with high viral loads – suggesting greater contagiousness – typically had more severe COVID symptoms, no correlation was found in young kids, meaning children with mild or no symptoms could still be highly contagious.

Dr. Karron said these findings should help parents and other stakeholders make better-informed decisions based on known risks. She recommended testing young, asymptomatic children for COVID if they have been exposed to infected individuals, then acting accordingly based on the results.

“If a family is infected with the virus, and the 2-year-old is asymptomatic, and people are thinking about a visit to elderly grandparents who may be frail, one shouldn’t assume that the 2-year-old is uninfected,” Dr. Karron said. “That child should be tested along with other family members.”

Testing should also be considered for young children exposed to COVID at childcare facilities, she added.

But not every expert consulted for this piece shared these opinions of Dr. Karron.

“I question whether that effort is worth it,” said Dean Blumberg, MD, professor and chief of the division of pediatric infectious diseases at UC Davis Health, Sacramento, Calif.

He noted that recent Food and Drug Administration guidance for COVID testing calls for three negative at-home antigen tests to confirm lack of infection.

“That would take 4 days to get those tests done,” he said. “So, it’s a lot of testing. It’s a lot of record keeping, it’s inconvenient, it’s uncomfortable to be tested, and I just question whether it’s worth that effort.”

Applicability of findings to today questioned

Dr. Blumberg also questioned whether the study, which was completed almost a year ago, reflects the current pandemic landscape.

“At the time this study was done, it was predominantly Delta [variant instead of Omicron],” Dr. Blumberg said. “The other issue [with the study] is that … most of the children didn’t have preexisting immunity, so you have to take that into account.”

Preexisting immunity – whether from exposure or vaccination – could lower viral loads, so asymptomatic children today really could be less contagious than they were when the study was done, according to Dr. Blumberg. Kids without symptoms are also less likely to spread the virus, because they aren’t coughing or sneezing, he added.

Sara R. Kim, MD, and Janet A. Englund, MD, of the Seattle Children’s Research Institute, University of Washington, said it’s challenging to know how applicable the findings are, although they sided more with the investigators than Dr. Blumberg.

“Given the higher rate of transmissibility and infectivity of the Omicron variant, it is difficult to make direct associations between findings reported during this study period and those present in the current era during which the Omicron variant is circulating,” they wrote in an accompanying editorial. “However, the higher rates of asymptomatic infection observed among children in this study are likely to be consistent with those observed for current and future viral variants.”

Although the experts offered different interpretations of the findings, they shared similar perspectives on vaccination.

“The most important thing that parents can do is get their kids vaccinated, be vaccinated themselves, and have everybody in the household vaccinated and up to date for all doses that are indicated,” Dr. Blumberg said.

Dr. Karron noted that vaccination will be increasingly important in the coming months.

“Summer is ending; school is starting,” she said. “We’re going to be in large groups indoors again very soon. To keep young children safe, I think it’s really important for them to get vaccinated.”

The study was funded by the CDC. The investigators disclosed no other relationships. Dr. Englund disclosed relationships with AstraZeneca, GlaxoSmithKline, Merck, and others. Dr. Kim and Dr. Blumberg disclosed no relevant conflicts of interest.

Dr. George Sakoulas is an infectious diseases clinician at Sharp Memorial Hospital in San Diego and professor of pediatrics at the University of California, San Diego School of Medicine. He was the lead investigator in a study published in the May/June 2022 issue of JCOM that found that, when allocated to the appropriate patient type, intravenous immunoglobulin can reduce hospital costs for COVID-19 care. ¹ He joined JCOM’s Editor-in-Chief, Dr. Ebrahim Barkoudah, to discuss the study’s background and highlight its main findings.

The following has been edited for length and clarity.

Dr. Barkoudah Dr. Sakoulas is an investigator and a clinician, bridging both worlds to bring the best evidence to our patients. We’re discussing his new article regarding intravenous immunoglobulin in treating nonventilated COVID-19 patients with moderate-to-severe hypoxia. Dr. Sakoulas, could you please share with our readers the clinical question your study addressed and what your work around COVID-19 management means for clinical practice?

Dr. Sakoulas Thank you. I’m an infectious disease physician. I’ve been treating patients with viral acute respiratory distress syndrome for almost 20 years as an ID doctor. Most of these cases are due to influenza or other viruses. And from time to time, anecdotally and supported by some literature, we’ve been using IVIG, or intravenous immunoglobulin, in some of these cases. And again, I can report anecdotal success with that over the years.

So when COVID emerged in March of 2020, we deployed IVIG in a couple of patients early who were heading downhill. Remember, in March of 2020, we didn’t have the knowledge of steroids helping, patients being ventilated very promptly, and we saw some patients who made a turnaround after treatment with IVIG. We were able to get some support from an industry sponsor and perform and publish a pilot study, enrolling patients early in the pandemic. That study actually showed benefits, which then led the sponsor to fund a phase 3 multicenter clinical trial. Unfortunately, a couple of things happened. First, the trial was designed with the knowledge we had in April of 2020, and again, this is before steroids, before we incorporated proning patients in the ICU, or started ventilating people early. So there were some management changes and evolutions and improvements that happened. And second, the trial was enrolling a very broad repertoire of patients. There were no age limitations, and the trial, ultimately a phase 3 multicenter trial, failed to meet its endpoint.

There were some trends for benefit in younger patients, and as the trial was ongoing, we continued to evolve our knowledge, and we really honed it down to seeing a benefit of using IVIG in patients with COVID with specific criteria in mind. They had to be relatively younger patients, under 65, and not have any major comorbidities. In other words, they weren’t dialysis patients or end-stage disease patients, heart failure patients, cancer or malignancy patients. So, you know, we’re looking at the patients under 65 with obesity, diabetes, and hypertension, who are rapidly declining, going from room air to BiPAP or high-flow oxygen in a short amount of time. And we learned that when using IVIG early, we actually saw patients improve and turn around.

What this article in JCOM highlighted was, number one, incorporating that outcome or that patient type and then looking at the cost of hospitalization of patients who received IVIG versus those that did not. There were 2 groups that were studied. One was the group of patients in that original pilot trial that I discussed who were randomized to receive 1 or the other prospectively; it was an unblinded randomized study. And the second group was a matched case-control study where we had patients treated with IVIG matched by age and comorbidity status and level of hypoxia to patients that did not receive IVIG. We saw a financial benefit in shortening or reducing hospitalizations, really coming down to getting rid of that 20% tail of patients that wound up going to the ICU, getting intubated, and using a high amount of hospital resources that would ramp up the cost of hospitalization. We saw great mitigation of that with IVIG, and even with a small subset of patients, we were able to show a benefit.

Dr. Barkoudah Any thoughts on where we can implement the new findings from your article in our practice at the moment, knowing we now have practice guidelines and protocols to treat COVID-19? There was a tangible benefit in treating the patients the way you approached it in your important work. Could you share with us what would be implementable at the moment?

Dr. Sakoulas I think, fortunately, with the increasing host immunity in the population and decreased virulence of the virus, perhaps we won’t see as many patients of the type that were in these trials going forward, but I suspect we will perhaps in the unvaccinated patients that remain. I believe one-third of the United States is not vaccinated. So there is certainly a vulnerable group of people out there. Potentially, an unvaccinated patient who winds up getting very sick, the patient who is relatively young—what I’m looking at is the 30- to 65-year-old obese, hypertensive, or diabetic patient who comes in and, despite the steroids and the antivirals, rapidly deteriorates into requiring high-flow oxygen. I think implementing IVIG in that patient type would be helpful. I don’t think it’s going to be as helpful in patients who are very elderly, because I think the mechanism of the disease is different in an 80-year-old versus a 50-year-old patient. So again, hopefully, it will not amount to a lot of patients, but I still suspect hospitals are going to see, perhaps in the fall, when they’re expecting a greater number of cases, a trickling of patients that do meet the criteria that I described.

Dr. Barkoudah JCOM’s audience are the QI implementers and hospital leadership. And what caught my eye in your article is your perspective on the pharmacoeconomics of treating COVID-19, and I really appreciate your looking at the cost aspect. Would you talk about the economics of inpatient care, the total care that we provide now that we’re in the age of tocilizumab, and the current state of multiple layers of therapy?

Dr. Sakoulas The reason to look at the economics of it is because IVIG—which is actually not a drug, it’s a blood product—is very expensive. So, we received a considerable amount of administrative pushback implementing this treatment at the beginning outside of the clinical trial setting because it hadn’t been studied on a large scale and because the cost was so high, even though, as a clinician at the bedside, I was seeing a benefit in patients. This study came out of my trying to demonstrate to the folks that are keeping the economics of medicine in mind that, in fact, investing several thousand dollars of treatment in IVIG will save you cost of care, the cost of an ICU bed, the cost of a ventilator, and the cost even of ECMO, which is hugely expensive.

If you look at the numbers in the study, for two-thirds or three-quarters of the patients, your cost of care is actually greater than the controls because you’re giving them IVIG, and it’s increasing the cost of their care, even though three-quarters of the patients are going to do just as well without it. It’s that 20% to 25% of patients that really are going to benefit from it, where you’re reducing your cost of care so much, and you’re getting rid of that very, very expensive 20%, that there’s a cost savings across the board per patient. So, it’s hard to understand when you say you’re losing money on three-quarters of the patients, you’re only saving money on a quarter of the patients, but that cost of saving on that small subset is so substantial it’s really impacting all numbers.

Also, abandoning the outlier principle is sort of an underlying theme in how we think of things. We tend to ignore outliers, not consider them, but I think we really have to pay attention to the more extreme cases because those patients are the ones that drive not just the financial cost of care. Remember, if you’re down to 1 ventilator and you can cut down the use of scarce ICU resources, the cost is sort of even beyond the cost of money. It’s the cost of resources that may become scarce in some settings. So, I think it speaks to that as well.

A lot of the drugs that we use, for example, tocilizumab, were able to be studied in thousands of patients. If you look at the absolute numbers, the benefit of tocilizumab from a magnitude standpoint—low to mid twenties to high twenties—you know, reducing mortality from 29% to 24%. I mean, just take a step back and think about that. Even though it’s statistically significant, try telling a patient, “Well, I’m going to give you this treatment that’s going to reduce mortality from 29% to 24%.” You know, that doesn’t really change anything from a clinical significance standpoint. But they have a P value less than .05, which is our standard, and they were able to do a study with thousands of patients. We didn’t have that luxury with IVIG. No one studied thousands of patients, only retrospectively, and those retrospective studies don’t get the attention because they’re considered biased with all their limitations. But I think one of the difficulties we have here is the balance between statistical and clinical significance. For example, in our pilot study, our ventilation rate was 58% with the non-IVIG patients versus 14% for IVIG patients. So you might say, magnitude-wise, that’s a big number, but the statistical significance of it is borderline because of small numbers.

Anyway, that’s a challenge that we have as clinicians trying to incorporate what’s published—the balancing of statistics, absolute numbers, and practicalities of delivering care. And I think this study highlights some of the nuances that go into that incorporation and those clinical decisions.

Dr. Barkoudah Would you mind sharing with our audience how we can make the connection between the medical outcomes and pharmacoeconomics findings from your article and link it to the bedside and treatment of our patients?

Dr. Sakoulas One of the points this article brings out is the importance of bringing together not just level 1A data, but also small studies with data such as this, where the magnitude of the effect is pretty big but you lose the statistics because of the small numbers. And then also the patients’ aspects of things. I think, as a bedside clinician, you appreciate things, the nuances, much sooner than what percolates out from a level 1A study. Case in point, in the sponsored phase 3 study that we did, and in some other studies that were prospectively done as well, these studies of IVIG simply had an enrollment of patients that was very broad, and not every patient benefits from the same therapy. A great example of this is the sepsis trials with Xigris and those types of agents that failed. You know, there are clinicians to this day who believe that there is a subset of patients that benefit from agents like this. The IVIG story falls a little bit into that category. It comes down to trying to identify the subset of patients that might benefit. And I think we’ve outlined this subset pretty well in our study: the younger, obese diabetic or hypertensive patient who’s rapidly declining.

It really brings together the need to not necessarily toss out these smaller studies, but kind of summarize everything together, and clinicians who are bedside, who are more in tune with the nuances of individual decisions at the individual patient level, might better appreciate these kinds of data. But I think we all have to put it together. IVIG does not make treatment guidelines at national levels and so forth. It’s not even listed in many of them. But there are patients out there who, if you ask them specifically how they felt, including a friend of mine who received the medication, there’s no question from their end, how they felt about this treatment option. Now, some people will get it and will not benefit. We just have to be really tuned into the fact that the same drug does not have the same result for every patient. And just to consider this in the high-risk patients that we talked about in our study.

Dr. Barkoudah While we were prepping for this interview, you made an analogy regarding clinical evidence along the lines of, “Do we need randomized clinical trials to do a parachute-type of experiment,” and we chatted about clinical wisdom. Would you mind sharing with our readers your thoughts on that?

Dr. Sakoulas Sometimes, we try a treatment and it’s very obvious for that particular patient that it helped them. Then you study the treatment in a large trial setting and it doesn’t work. For us bedside clinicians, there are some interventions sometimes that do appear as beneficial as a parachute would be, but yet, there has never been a randomized clinical trial proving that parachutes work. Again, a part of the challenge we have is patients are so different, their immunology is different, the pathogen infecting them is different, the time they present is different. Some present early, some present late. There are just so many moving parts to treating an infection that only a subset of people are going to benefit. And sometimes as clinicians, we’re so nuanced, that we identify a specific subset of patients where we know we can help them. And it’s so obvious for us, like a parachute would be, but to people who are looking at the world from 30,000 feet, they don’t necessarily grasp that because, when you look at all comers, it doesn’t show a benefit.

So the problem is that now those treatments that might help a subset of patients are being denied, and the subset of patients that are going to benefit never get the treatment. Now we have to balance that with a lot of stuff that went on during the pandemic with, you know, ivermectin, hydroxychloroquine, and people pushing those things. Someone asked me once what I thought about hydroxychloroquine, and I said, “Well, somebody in the lab probably showed that it was beneficial, analogous to lighting tissue paper on fire on a plate and taking a cup of water and putting the fire out. Well, now, if you take that cup of water to the Caldor fire that’s burning in California on thousands of acres, you’re not going to be able to put the fire out with that cup of water.” So while it might work in the lab, it’s truly not going to work in a clinical setting. We have to balance individualizing care for patients with some information people are pushing out there that may not be necessarily translatable to the clinical setting.

I think there’s nothing better than being at the bedside, though, and being able to implement something and seeing what works. And really, experience goes a long way in being able to individually treat a patient optimally.

Dr. Barkoudah Thank you for everything you do at the bedside and your work on improving the treatment we have and how we can leverage knowledge to treat our patients. Thank you very much for your time and your scholarly contribution. We appreciate it and I hope the work will continue. We will keep working on treating COVID-19 patients with the best knowledge we have.

Q&A participants: George Sakoulas, MD, Sharp Rees-Stealy Medical Group, La Jolla, CA, and University of California San Diego School of Medicine, San Diego, CA; and Ebrahim Barkoudah, MD, MPH, Department of Medicine, Brigham and Women’s Hospital, Boston, MA.

Disclosures: None reported.

Dr. George Sakoulas is an infectious diseases clinician at Sharp Memorial Hospital in San Diego and professor of pediatrics at the University of California, San Diego School of Medicine. He was the lead investigator in a study published in the May/June 2022 issue of JCOM that found that, when allocated to the appropriate patient type, intravenous immunoglobulin can reduce hospital costs for COVID-19 care. ¹ He joined JCOM’s Editor-in-Chief, Dr. Ebrahim Barkoudah, to discuss the study’s background and highlight its main findings.

The following has been edited for length and clarity.

Dr. Barkoudah Dr. Sakoulas is an investigator and a clinician, bridging both worlds to bring the best evidence to our patients. We’re discussing his new article regarding intravenous immunoglobulin in treating nonventilated COVID-19 patients with moderate-to-severe hypoxia. Dr. Sakoulas, could you please share with our readers the clinical question your study addressed and what your work around COVID-19 management means for clinical practice?

Dr. Sakoulas Thank you. I’m an infectious disease physician. I’ve been treating patients with viral acute respiratory distress syndrome for almost 20 years as an ID doctor. Most of these cases are due to influenza or other viruses. And from time to time, anecdotally and supported by some literature, we’ve been using IVIG, or intravenous immunoglobulin, in some of these cases. And again, I can report anecdotal success with that over the years.

So when COVID emerged in March of 2020, we deployed IVIG in a couple of patients early who were heading downhill. Remember, in March of 2020, we didn’t have the knowledge of steroids helping, patients being ventilated very promptly, and we saw some patients who made a turnaround after treatment with IVIG. We were able to get some support from an industry sponsor and perform and publish a pilot study, enrolling patients early in the pandemic. That study actually showed benefits, which then led the sponsor to fund a phase 3 multicenter clinical trial. Unfortunately, a couple of things happened. First, the trial was designed with the knowledge we had in April of 2020, and again, this is before steroids, before we incorporated proning patients in the ICU, or started ventilating people early. So there were some management changes and evolutions and improvements that happened. And second, the trial was enrolling a very broad repertoire of patients. There were no age limitations, and the trial, ultimately a phase 3 multicenter trial, failed to meet its endpoint.

There were some trends for benefit in younger patients, and as the trial was ongoing, we continued to evolve our knowledge, and we really honed it down to seeing a benefit of using IVIG in patients with COVID with specific criteria in mind. They had to be relatively younger patients, under 65, and not have any major comorbidities. In other words, they weren’t dialysis patients or end-stage disease patients, heart failure patients, cancer or malignancy patients. So, you know, we’re looking at the patients under 65 with obesity, diabetes, and hypertension, who are rapidly declining, going from room air to BiPAP or high-flow oxygen in a short amount of time. And we learned that when using IVIG early, we actually saw patients improve and turn around.

What this article in JCOM highlighted was, number one, incorporating that outcome or that patient type and then looking at the cost of hospitalization of patients who received IVIG versus those that did not. There were 2 groups that were studied. One was the group of patients in that original pilot trial that I discussed who were randomized to receive 1 or the other prospectively; it was an unblinded randomized study. And the second group was a matched case-control study where we had patients treated with IVIG matched by age and comorbidity status and level of hypoxia to patients that did not receive IVIG. We saw a financial benefit in shortening or reducing hospitalizations, really coming down to getting rid of that 20% tail of patients that wound up going to the ICU, getting intubated, and using a high amount of hospital resources that would ramp up the cost of hospitalization. We saw great mitigation of that with IVIG, and even with a small subset of patients, we were able to show a benefit.

Dr. Barkoudah Any thoughts on where we can implement the new findings from your article in our practice at the moment, knowing we now have practice guidelines and protocols to treat COVID-19? There was a tangible benefit in treating the patients the way you approached it in your important work. Could you share with us what would be implementable at the moment?

Dr. Sakoulas I think, fortunately, with the increasing host immunity in the population and decreased virulence of the virus, perhaps we won’t see as many patients of the type that were in these trials going forward, but I suspect we will perhaps in the unvaccinated patients that remain. I believe one-third of the United States is not vaccinated. So there is certainly a vulnerable group of people out there. Potentially, an unvaccinated patient who winds up getting very sick, the patient who is relatively young—what I’m looking at is the 30- to 65-year-old obese, hypertensive, or diabetic patient who comes in and, despite the steroids and the antivirals, rapidly deteriorates into requiring high-flow oxygen. I think implementing IVIG in that patient type would be helpful. I don’t think it’s going to be as helpful in patients who are very elderly, because I think the mechanism of the disease is different in an 80-year-old versus a 50-year-old patient. So again, hopefully, it will not amount to a lot of patients, but I still suspect hospitals are going to see, perhaps in the fall, when they’re expecting a greater number of cases, a trickling of patients that do meet the criteria that I described.

Dr. Barkoudah JCOM’s audience are the QI implementers and hospital leadership. And what caught my eye in your article is your perspective on the pharmacoeconomics of treating COVID-19, and I really appreciate your looking at the cost aspect. Would you talk about the economics of inpatient care, the total care that we provide now that we’re in the age of tocilizumab, and the current state of multiple layers of therapy?

Dr. Sakoulas The reason to look at the economics of it is because IVIG—which is actually not a drug, it’s a blood product—is very expensive. So, we received a considerable amount of administrative pushback implementing this treatment at the beginning outside of the clinical trial setting because it hadn’t been studied on a large scale and because the cost was so high, even though, as a clinician at the bedside, I was seeing a benefit in patients. This study came out of my trying to demonstrate to the folks that are keeping the economics of medicine in mind that, in fact, investing several thousand dollars of treatment in IVIG will save you cost of care, the cost of an ICU bed, the cost of a ventilator, and the cost even of ECMO, which is hugely expensive.

If you look at the numbers in the study, for two-thirds or three-quarters of the patients, your cost of care is actually greater than the controls because you’re giving them IVIG, and it’s increasing the cost of their care, even though three-quarters of the patients are going to do just as well without it. It’s that 20% to 25% of patients that really are going to benefit from it, where you’re reducing your cost of care so much, and you’re getting rid of that very, very expensive 20%, that there’s a cost savings across the board per patient. So, it’s hard to understand when you say you’re losing money on three-quarters of the patients, you’re only saving money on a quarter of the patients, but that cost of saving on that small subset is so substantial it’s really impacting all numbers.

Also, abandoning the outlier principle is sort of an underlying theme in how we think of things. We tend to ignore outliers, not consider them, but I think we really have to pay attention to the more extreme cases because those patients are the ones that drive not just the financial cost of care. Remember, if you’re down to 1 ventilator and you can cut down the use of scarce ICU resources, the cost is sort of even beyond the cost of money. It’s the cost of resources that may become scarce in some settings. So, I think it speaks to that as well.

A lot of the drugs that we use, for example, tocilizumab, were able to be studied in thousands of patients. If you look at the absolute numbers, the benefit of tocilizumab from a magnitude standpoint—low to mid twenties to high twenties—you know, reducing mortality from 29% to 24%. I mean, just take a step back and think about that. Even though it’s statistically significant, try telling a patient, “Well, I’m going to give you this treatment that’s going to reduce mortality from 29% to 24%.” You know, that doesn’t really change anything from a clinical significance standpoint. But they have a P value less than .05, which is our standard, and they were able to do a study with thousands of patients. We didn’t have that luxury with IVIG. No one studied thousands of patients, only retrospectively, and those retrospective studies don’t get the attention because they’re considered biased with all their limitations. But I think one of the difficulties we have here is the balance between statistical and clinical significance. For example, in our pilot study, our ventilation rate was 58% with the non-IVIG patients versus 14% for IVIG patients. So you might say, magnitude-wise, that’s a big number, but the statistical significance of it is borderline because of small numbers.

Anyway, that’s a challenge that we have as clinicians trying to incorporate what’s published—the balancing of statistics, absolute numbers, and practicalities of delivering care. And I think this study highlights some of the nuances that go into that incorporation and those clinical decisions.

Dr. Barkoudah Would you mind sharing with our audience how we can make the connection between the medical outcomes and pharmacoeconomics findings from your article and link it to the bedside and treatment of our patients?

Dr. Sakoulas One of the points this article brings out is the importance of bringing together not just level 1A data, but also small studies with data such as this, where the magnitude of the effect is pretty big but you lose the statistics because of the small numbers. And then also the patients’ aspects of things. I think, as a bedside clinician, you appreciate things, the nuances, much sooner than what percolates out from a level 1A study. Case in point, in the sponsored phase 3 study that we did, and in some other studies that were prospectively done as well, these studies of IVIG simply had an enrollment of patients that was very broad, and not every patient benefits from the same therapy. A great example of this is the sepsis trials with Xigris and those types of agents that failed. You know, there are clinicians to this day who believe that there is a subset of patients that benefit from agents like this. The IVIG story falls a little bit into that category. It comes down to trying to identify the subset of patients that might benefit. And I think we’ve outlined this subset pretty well in our study: the younger, obese diabetic or hypertensive patient who’s rapidly declining.

It really brings together the need to not necessarily toss out these smaller studies, but kind of summarize everything together, and clinicians who are bedside, who are more in tune with the nuances of individual decisions at the individual patient level, might better appreciate these kinds of data. But I think we all have to put it together. IVIG does not make treatment guidelines at national levels and so forth. It’s not even listed in many of them. But there are patients out there who, if you ask them specifically how they felt, including a friend of mine who received the medication, there’s no question from their end, how they felt about this treatment option. Now, some people will get it and will not benefit. We just have to be really tuned into the fact that the same drug does not have the same result for every patient. And just to consider this in the high-risk patients that we talked about in our study.

Dr. Barkoudah While we were prepping for this interview, you made an analogy regarding clinical evidence along the lines of, “Do we need randomized clinical trials to do a parachute-type of experiment,” and we chatted about clinical wisdom. Would you mind sharing with our readers your thoughts on that?

Dr. Sakoulas Sometimes, we try a treatment and it’s very obvious for that particular patient that it helped them. Then you study the treatment in a large trial setting and it doesn’t work. For us bedside clinicians, there are some interventions sometimes that do appear as beneficial as a parachute would be, but yet, there has never been a randomized clinical trial proving that parachutes work. Again, a part of the challenge we have is patients are so different, their immunology is different, the pathogen infecting them is different, the time they present is different. Some present early, some present late. There are just so many moving parts to treating an infection that only a subset of people are going to benefit. And sometimes as clinicians, we’re so nuanced, that we identify a specific subset of patients where we know we can help them. And it’s so obvious for us, like a parachute would be, but to people who are looking at the world from 30,000 feet, they don’t necessarily grasp that because, when you look at all comers, it doesn’t show a benefit.

So the problem is that now those treatments that might help a subset of patients are being denied, and the subset of patients that are going to benefit never get the treatment. Now we have to balance that with a lot of stuff that went on during the pandemic with, you know, ivermectin, hydroxychloroquine, and people pushing those things. Someone asked me once what I thought about hydroxychloroquine, and I said, “Well, somebody in the lab probably showed that it was beneficial, analogous to lighting tissue paper on fire on a plate and taking a cup of water and putting the fire out. Well, now, if you take that cup of water to the Caldor fire that’s burning in California on thousands of acres, you’re not going to be able to put the fire out with that cup of water.” So while it might work in the lab, it’s truly not going to work in a clinical setting. We have to balance individualizing care for patients with some information people are pushing out there that may not be necessarily translatable to the clinical setting.

I think there’s nothing better than being at the bedside, though, and being able to implement something and seeing what works. And really, experience goes a long way in being able to individually treat a patient optimally.

Dr. Barkoudah Thank you for everything you do at the bedside and your work on improving the treatment we have and how we can leverage knowledge to treat our patients. Thank you very much for your time and your scholarly contribution. We appreciate it and I hope the work will continue. We will keep working on treating COVID-19 patients with the best knowledge we have.

Q&A participants: George Sakoulas, MD, Sharp Rees-Stealy Medical Group, La Jolla, CA, and University of California San Diego School of Medicine, San Diego, CA; and Ebrahim Barkoudah, MD, MPH, Department of Medicine, Brigham and Women’s Hospital, Boston, MA.

Disclosures: None reported.

Dr. George Sakoulas is an infectious diseases clinician at Sharp Memorial Hospital in San Diego and professor of pediatrics at the University of California, San Diego School of Medicine. He was the lead investigator in a study published in the May/June 2022 issue of JCOM that found that, when allocated to the appropriate patient type, intravenous immunoglobulin can reduce hospital costs for COVID-19 care. ¹ He joined JCOM’s Editor-in-Chief, Dr. Ebrahim Barkoudah, to discuss the study’s background and highlight its main findings.

The following has been edited for length and clarity.

Dr. Barkoudah Dr. Sakoulas is an investigator and a clinician, bridging both worlds to bring the best evidence to our patients. We’re discussing his new article regarding intravenous immunoglobulin in treating nonventilated COVID-19 patients with moderate-to-severe hypoxia. Dr. Sakoulas, could you please share with our readers the clinical question your study addressed and what your work around COVID-19 management means for clinical practice?

Dr. Sakoulas Thank you. I’m an infectious disease physician. I’ve been treating patients with viral acute respiratory distress syndrome for almost 20 years as an ID doctor. Most of these cases are due to influenza or other viruses. And from time to time, anecdotally and supported by some literature, we’ve been using IVIG, or intravenous immunoglobulin, in some of these cases. And again, I can report anecdotal success with that over the years.

So when COVID emerged in March of 2020, we deployed IVIG in a couple of patients early who were heading downhill. Remember, in March of 2020, we didn’t have the knowledge of steroids helping, patients being ventilated very promptly, and we saw some patients who made a turnaround after treatment with IVIG. We were able to get some support from an industry sponsor and perform and publish a pilot study, enrolling patients early in the pandemic. That study actually showed benefits, which then led the sponsor to fund a phase 3 multicenter clinical trial. Unfortunately, a couple of things happened. First, the trial was designed with the knowledge we had in April of 2020, and again, this is before steroids, before we incorporated proning patients in the ICU, or started ventilating people early. So there were some management changes and evolutions and improvements that happened. And second, the trial was enrolling a very broad repertoire of patients. There were no age limitations, and the trial, ultimately a phase 3 multicenter trial, failed to meet its endpoint.

There were some trends for benefit in younger patients, and as the trial was ongoing, we continued to evolve our knowledge, and we really honed it down to seeing a benefit of using IVIG in patients with COVID with specific criteria in mind. They had to be relatively younger patients, under 65, and not have any major comorbidities. In other words, they weren’t dialysis patients or end-stage disease patients, heart failure patients, cancer or malignancy patients. So, you know, we’re looking at the patients under 65 with obesity, diabetes, and hypertension, who are rapidly declining, going from room air to BiPAP or high-flow oxygen in a short amount of time. And we learned that when using IVIG early, we actually saw patients improve and turn around.

What this article in JCOM highlighted was, number one, incorporating that outcome or that patient type and then looking at the cost of hospitalization of patients who received IVIG versus those that did not. There were 2 groups that were studied. One was the group of patients in that original pilot trial that I discussed who were randomized to receive 1 or the other prospectively; it was an unblinded randomized study. And the second group was a matched case-control study where we had patients treated with IVIG matched by age and comorbidity status and level of hypoxia to patients that did not receive IVIG. We saw a financial benefit in shortening or reducing hospitalizations, really coming down to getting rid of that 20% tail of patients that wound up going to the ICU, getting intubated, and using a high amount of hospital resources that would ramp up the cost of hospitalization. We saw great mitigation of that with IVIG, and even with a small subset of patients, we were able to show a benefit.

Dr. Barkoudah Any thoughts on where we can implement the new findings from your article in our practice at the moment, knowing we now have practice guidelines and protocols to treat COVID-19? There was a tangible benefit in treating the patients the way you approached it in your important work. Could you share with us what would be implementable at the moment?

Dr. Sakoulas I think, fortunately, with the increasing host immunity in the population and decreased virulence of the virus, perhaps we won’t see as many patients of the type that were in these trials going forward, but I suspect we will perhaps in the unvaccinated patients that remain. I believe one-third of the United States is not vaccinated. So there is certainly a vulnerable group of people out there. Potentially, an unvaccinated patient who winds up getting very sick, the patient who is relatively young—what I’m looking at is the 30- to 65-year-old obese, hypertensive, or diabetic patient who comes in and, despite the steroids and the antivirals, rapidly deteriorates into requiring high-flow oxygen. I think implementing IVIG in that patient type would be helpful. I don’t think it’s going to be as helpful in patients who are very elderly, because I think the mechanism of the disease is different in an 80-year-old versus a 50-year-old patient. So again, hopefully, it will not amount to a lot of patients, but I still suspect hospitals are going to see, perhaps in the fall, when they’re expecting a greater number of cases, a trickling of patients that do meet the criteria that I described.

Dr. Barkoudah JCOM’s audience are the QI implementers and hospital leadership. And what caught my eye in your article is your perspective on the pharmacoeconomics of treating COVID-19, and I really appreciate your looking at the cost aspect. Would you talk about the economics of inpatient care, the total care that we provide now that we’re in the age of tocilizumab, and the current state of multiple layers of therapy?

Dr. Sakoulas The reason to look at the economics of it is because IVIG—which is actually not a drug, it’s a blood product—is very expensive. So, we received a considerable amount of administrative pushback implementing this treatment at the beginning outside of the clinical trial setting because it hadn’t been studied on a large scale and because the cost was so high, even though, as a clinician at the bedside, I was seeing a benefit in patients. This study came out of my trying to demonstrate to the folks that are keeping the economics of medicine in mind that, in fact, investing several thousand dollars of treatment in IVIG will save you cost of care, the cost of an ICU bed, the cost of a ventilator, and the cost even of ECMO, which is hugely expensive.

If you look at the numbers in the study, for two-thirds or three-quarters of the patients, your cost of care is actually greater than the controls because you’re giving them IVIG, and it’s increasing the cost of their care, even though three-quarters of the patients are going to do just as well without it. It’s that 20% to 25% of patients that really are going to benefit from it, where you’re reducing your cost of care so much, and you’re getting rid of that very, very expensive 20%, that there’s a cost savings across the board per patient. So, it’s hard to understand when you say you’re losing money on three-quarters of the patients, you’re only saving money on a quarter of the patients, but that cost of saving on that small subset is so substantial it’s really impacting all numbers.

Also, abandoning the outlier principle is sort of an underlying theme in how we think of things. We tend to ignore outliers, not consider them, but I think we really have to pay attention to the more extreme cases because those patients are the ones that drive not just the financial cost of care. Remember, if you’re down to 1 ventilator and you can cut down the use of scarce ICU resources, the cost is sort of even beyond the cost of money. It’s the cost of resources that may become scarce in some settings. So, I think it speaks to that as well.

A lot of the drugs that we use, for example, tocilizumab, were able to be studied in thousands of patients. If you look at the absolute numbers, the benefit of tocilizumab from a magnitude standpoint—low to mid twenties to high twenties—you know, reducing mortality from 29% to 24%. I mean, just take a step back and think about that. Even though it’s statistically significant, try telling a patient, “Well, I’m going to give you this treatment that’s going to reduce mortality from 29% to 24%.” You know, that doesn’t really change anything from a clinical significance standpoint. But they have a P value less than .05, which is our standard, and they were able to do a study with thousands of patients. We didn’t have that luxury with IVIG. No one studied thousands of patients, only retrospectively, and those retrospective studies don’t get the attention because they’re considered biased with all their limitations. But I think one of the difficulties we have here is the balance between statistical and clinical significance. For example, in our pilot study, our ventilation rate was 58% with the non-IVIG patients versus 14% for IVIG patients. So you might say, magnitude-wise, that’s a big number, but the statistical significance of it is borderline because of small numbers.

Anyway, that’s a challenge that we have as clinicians trying to incorporate what’s published—the balancing of statistics, absolute numbers, and practicalities of delivering care. And I think this study highlights some of the nuances that go into that incorporation and those clinical decisions.

Dr. Barkoudah Would you mind sharing with our audience how we can make the connection between the medical outcomes and pharmacoeconomics findings from your article and link it to the bedside and treatment of our patients?

Dr. Sakoulas One of the points this article brings out is the importance of bringing together not just level 1A data, but also small studies with data such as this, where the magnitude of the effect is pretty big but you lose the statistics because of the small numbers. And then also the patients’ aspects of things. I think, as a bedside clinician, you appreciate things, the nuances, much sooner than what percolates out from a level 1A study. Case in point, in the sponsored phase 3 study that we did, and in some other studies that were prospectively done as well, these studies of IVIG simply had an enrollment of patients that was very broad, and not every patient benefits from the same therapy. A great example of this is the sepsis trials with Xigris and those types of agents that failed. You know, there are clinicians to this day who believe that there is a subset of patients that benefit from agents like this. The IVIG story falls a little bit into that category. It comes down to trying to identify the subset of patients that might benefit. And I think we’ve outlined this subset pretty well in our study: the younger, obese diabetic or hypertensive patient who’s rapidly declining.

It really brings together the need to not necessarily toss out these smaller studies, but kind of summarize everything together, and clinicians who are bedside, who are more in tune with the nuances of individual decisions at the individual patient level, might better appreciate these kinds of data. But I think we all have to put it together. IVIG does not make treatment guidelines at national levels and so forth. It’s not even listed in many of them. But there are patients out there who, if you ask them specifically how they felt, including a friend of mine who received the medication, there’s no question from their end, how they felt about this treatment option. Now, some people will get it and will not benefit. We just have to be really tuned into the fact that the same drug does not have the same result for every patient. And just to consider this in the high-risk patients that we talked about in our study.

Dr. Barkoudah While we were prepping for this interview, you made an analogy regarding clinical evidence along the lines of, “Do we need randomized clinical trials to do a parachute-type of experiment,” and we chatted about clinical wisdom. Would you mind sharing with our readers your thoughts on that?

Dr. Sakoulas Sometimes, we try a treatment and it’s very obvious for that particular patient that it helped them. Then you study the treatment in a large trial setting and it doesn’t work. For us bedside clinicians, there are some interventions sometimes that do appear as beneficial as a parachute would be, but yet, there has never been a randomized clinical trial proving that parachutes work. Again, a part of the challenge we have is patients are so different, their immunology is different, the pathogen infecting them is different, the time they present is different. Some present early, some present late. There are just so many moving parts to treating an infection that only a subset of people are going to benefit. And sometimes as clinicians, we’re so nuanced, that we identify a specific subset of patients where we know we can help them. And it’s so obvious for us, like a parachute would be, but to people who are looking at the world from 30,000 feet, they don’t necessarily grasp that because, when you look at all comers, it doesn’t show a benefit.

So the problem is that now those treatments that might help a subset of patients are being denied, and the subset of patients that are going to benefit never get the treatment. Now we have to balance that with a lot of stuff that went on during the pandemic with, you know, ivermectin, hydroxychloroquine, and people pushing those things. Someone asked me once what I thought about hydroxychloroquine, and I said, “Well, somebody in the lab probably showed that it was beneficial, analogous to lighting tissue paper on fire on a plate and taking a cup of water and putting the fire out. Well, now, if you take that cup of water to the Caldor fire that’s burning in California on thousands of acres, you’re not going to be able to put the fire out with that cup of water.” So while it might work in the lab, it’s truly not going to work in a clinical setting. We have to balance individualizing care for patients with some information people are pushing out there that may not be necessarily translatable to the clinical setting.

I think there’s nothing better than being at the bedside, though, and being able to implement something and seeing what works. And really, experience goes a long way in being able to individually treat a patient optimally.

Dr. Barkoudah Thank you for everything you do at the bedside and your work on improving the treatment we have and how we can leverage knowledge to treat our patients. Thank you very much for your time and your scholarly contribution. We appreciate it and I hope the work will continue. We will keep working on treating COVID-19 patients with the best knowledge we have.

Q&A participants: George Sakoulas, MD, Sharp Rees-Stealy Medical Group, La Jolla, CA, and University of California San Diego School of Medicine, San Diego, CA; and Ebrahim Barkoudah, MD, MPH, Department of Medicine, Brigham and Women’s Hospital, Boston, MA.

Disclosures: None reported.

Evusheld (AstraZeneca), a medication used to prevent SARS-CoV-2 infection in patients at high risk, has problems: Namely, that supplies of the potentially lifesaving drug outweigh demand.

At least 7 million people who are immunocompromised could benefit from it, as could many others who are undergoing cancer treatment, have received a transplant, or who are allergic to the COVID-19 vaccines. The medication has laboratory-produced antibodies against SARS-CoV-2 and helps the body protect itself. It can slash the chances of becoming infected by 77%, according to the U.S. Food and Drug Administration.

And it’s free to eligible patients (although there may be an out-of-pocket administrative fee in some cases).

Despite all those lifesaving benefits, fewer than 25% of available doses have been used.

To meet demand, the Biden administration secured 1.7 million doses of the medicine, which was granted emergency use authorization by the FDA in December 2021. As of July 25, however, 793,348 doses have been ordered by the administration sites, and only 398,181 doses have been reported as used, a spokesperson for the Department of Health & Human Services tells this news organization.

Each week, a certain amount of doses from the 1.7 million dose stockpile is made available to state and territorial health departments. States have not been asking for their full allotment, the spokesperson said July 28.

Now, HHS and AstraZeneca have taken a number of steps to increase awareness of the medication and access to it.

• On July 27, HHS announced that individual providers and smaller sites of care that don’t currently receive Evusheld through the federal distribution process via the HHS Health Partner Order Portal can now order up to three patient courses of the medicine. These can be 
• Health care providers can use the HHS’s COVID-19 Therapeutics Locator to find Evusheld in their area.
• AstraZeneca has launched a new website with educational materials and says it is working closely with patient and professional groups to inform patients and health care providers.
• A direct-to-consumer ad launched on June 22 and will run in the United States online and on TV (Yahoo, Fox, CBS Sports, MSN, ESPN) and be amplified on social and digital channels through year’s end, an AstraZeneca spokesperson said in an interview.
• AstraZeneca set up a toll-free number for providers: 1-833-EVUSHLD.

Evusheld includes two monoclonal antibodies, tixagevimab and cilgavimab. The medication is given as two consecutive intramuscular injections during a single visit to a doctor’s office, infusion center, or other health care facility. The antibodies bind to the SARS-CoV-2 spike protein and prevent the virus from getting into human cells and infecting them. It’s authorized for use in children and adults aged 12 years and older who weigh at least 88 pounds.

Studies have found that the medication decreases the risk of getting COVID-19 for up to 6 months after it is given. The FDA recommends repeat dosing every 6 months with the doses of 300 mg of each monoclonal antibody. In clinical trials, Evusheld reduced the incidence of COVID-19 symptomatic illness by 77%, compared with placebo.

Physicians monitor patients for an hour after administering Evusheld for allergic reactions. Other possible side effects include cardiac events, but they are not common.
 

Doctors and patients weigh in

Physicians – and patients – from the United States to the United Kingdom and beyond are questioning why the medication is underused while lauding the recent efforts to expand access and increase awareness.

The U.S. federal government may have underestimated the amount of communication needed to increase awareness of the medication and its applications, said infectious disease specialist William Schaffner, MD, professor of preventive medicine at Vanderbilt University School of Medicine, Nashville, Tenn.

“HHS hasn’t made a major educational effort to promote it,” he said in an interview.

Many physicians who need to know about it, such as transplant doctors and rheumatologists, are outside the typical public health communications loop, he said.

Eric Topol, MD, director of the Scripps Research Transational Institute and editor-in-chief of Medscape, has taken to social media to bemoan the lack of awareness.

Another infectious disease expert agrees. “In my experience, the awareness of Evusheld is low amongst many patients as well as many providers,” said Amesh Adalja, MD, a senior scholar at the Johns Hopkins Center for Health Security, Baltimore.

“Initially, there were scarce supplies of the drug, and certain hospital systems tiered eligibility based on degrees of immunosuppression, and only the most immunosuppressed were proactively approached for treatment.”

“Also, many community hospitals never initially ordered Evusheld – they may have been crowded out by academic centers who treat many more immunosuppressed patients and may not currently see it as a priority,” Dr. Adalja said in an interview. “As such, many immunosuppressed patients would have to seek treatment at academic medical centers, where the drug is more likely to be available.”

A version of this article first appeared on Medscape.com.

Evusheld (AstraZeneca), a medication used to prevent SARS-CoV-2 infection in patients at high risk, has problems: Namely, that supplies of the potentially lifesaving drug outweigh demand.

At least 7 million people who are immunocompromised could benefit from it, as could many others who are undergoing cancer treatment, have received a transplant, or who are allergic to the COVID-19 vaccines. The medication has laboratory-produced antibodies against SARS-CoV-2 and helps the body protect itself. It can slash the chances of becoming infected by 77%, according to the U.S. Food and Drug Administration.

And it’s free to eligible patients (although there may be an out-of-pocket administrative fee in some cases).

Despite all those lifesaving benefits, fewer than 25% of available doses have been used.

To meet demand, the Biden administration secured 1.7 million doses of the medicine, which was granted emergency use authorization by the FDA in December 2021. As of July 25, however, 793,348 doses have been ordered by the administration sites, and only 398,181 doses have been reported as used, a spokesperson for the Department of Health & Human Services tells this news organization.

Each week, a certain amount of doses from the 1.7 million dose stockpile is made available to state and territorial health departments. States have not been asking for their full allotment, the spokesperson said July 28.

Now, HHS and AstraZeneca have taken a number of steps to increase awareness of the medication and access to it.

• On July 27, HHS announced that individual providers and smaller sites of care that don’t currently receive Evusheld through the federal distribution process via the HHS Health Partner Order Portal can now order up to three patient courses of the medicine. These can be 
• Health care providers can use the HHS’s COVID-19 Therapeutics Locator to find Evusheld in their area.
• AstraZeneca has launched a new website with educational materials and says it is working closely with patient and professional groups to inform patients and health care providers.
• A direct-to-consumer ad launched on June 22 and will run in the United States online and on TV (Yahoo, Fox, CBS Sports, MSN, ESPN) and be amplified on social and digital channels through year’s end, an AstraZeneca spokesperson said in an interview.
• AstraZeneca set up a toll-free number for providers: 1-833-EVUSHLD.

Evusheld includes two monoclonal antibodies, tixagevimab and cilgavimab. The medication is given as two consecutive intramuscular injections during a single visit to a doctor’s office, infusion center, or other health care facility. The antibodies bind to the SARS-CoV-2 spike protein and prevent the virus from getting into human cells and infecting them. It’s authorized for use in children and adults aged 12 years and older who weigh at least 88 pounds.

Studies have found that the medication decreases the risk of getting COVID-19 for up to 6 months after it is given. The FDA recommends repeat dosing every 6 months with the doses of 300 mg of each monoclonal antibody. In clinical trials, Evusheld reduced the incidence of COVID-19 symptomatic illness by 77%, compared with placebo.

Physicians monitor patients for an hour after administering Evusheld for allergic reactions. Other possible side effects include cardiac events, but they are not common.
 

Doctors and patients weigh in

Physicians – and patients – from the United States to the United Kingdom and beyond are questioning why the medication is underused while lauding the recent efforts to expand access and increase awareness.

The U.S. federal government may have underestimated the amount of communication needed to increase awareness of the medication and its applications, said infectious disease specialist William Schaffner, MD, professor of preventive medicine at Vanderbilt University School of Medicine, Nashville, Tenn.

“HHS hasn’t made a major educational effort to promote it,” he said in an interview.

Many physicians who need to know about it, such as transplant doctors and rheumatologists, are outside the typical public health communications loop, he said.

Eric Topol, MD, director of the Scripps Research Transational Institute and editor-in-chief of Medscape, has taken to social media to bemoan the lack of awareness.

Another infectious disease expert agrees. “In my experience, the awareness of Evusheld is low amongst many patients as well as many providers,” said Amesh Adalja, MD, a senior scholar at the Johns Hopkins Center for Health Security, Baltimore.

“Initially, there were scarce supplies of the drug, and certain hospital systems tiered eligibility based on degrees of immunosuppression, and only the most immunosuppressed were proactively approached for treatment.”

“Also, many community hospitals never initially ordered Evusheld – they may have been crowded out by academic centers who treat many more immunosuppressed patients and may not currently see it as a priority,” Dr. Adalja said in an interview. “As such, many immunosuppressed patients would have to seek treatment at academic medical centers, where the drug is more likely to be available.”

A version of this article first appeared on Medscape.com.

Evusheld (AstraZeneca), a medication used to prevent SARS-CoV-2 infection in patients at high risk, has problems: Namely, that supplies of the potentially lifesaving drug outweigh demand.

At least 7 million people who are immunocompromised could benefit from it, as could many others who are undergoing cancer treatment, have received a transplant, or who are allergic to the COVID-19 vaccines. The medication has laboratory-produced antibodies against SARS-CoV-2 and helps the body protect itself. It can slash the chances of becoming infected by 77%, according to the U.S. Food and Drug Administration.

And it’s free to eligible patients (although there may be an out-of-pocket administrative fee in some cases).

Despite all those lifesaving benefits, fewer than 25% of available doses have been used.

To meet demand, the Biden administration secured 1.7 million doses of the medicine, which was granted emergency use authorization by the FDA in December 2021. As of July 25, however, 793,348 doses have been ordered by the administration sites, and only 398,181 doses have been reported as used, a spokesperson for the Department of Health & Human Services tells this news organization.

Each week, a certain amount of doses from the 1.7 million dose stockpile is made available to state and territorial health departments. States have not been asking for their full allotment, the spokesperson said July 28.

Now, HHS and AstraZeneca have taken a number of steps to increase awareness of the medication and access to it.

• On July 27, HHS announced that individual providers and smaller sites of care that don’t currently receive Evusheld through the federal distribution process via the HHS Health Partner Order Portal can now order up to three patient courses of the medicine. These can be 
• Health care providers can use the HHS’s COVID-19 Therapeutics Locator to find Evusheld in their area.
• AstraZeneca has launched a new website with educational materials and says it is working closely with patient and professional groups to inform patients and health care providers.
• A direct-to-consumer ad launched on June 22 and will run in the United States online and on TV (Yahoo, Fox, CBS Sports, MSN, ESPN) and be amplified on social and digital channels through year’s end, an AstraZeneca spokesperson said in an interview.
• AstraZeneca set up a toll-free number for providers: 1-833-EVUSHLD.

Evusheld includes two monoclonal antibodies, tixagevimab and cilgavimab. The medication is given as two consecutive intramuscular injections during a single visit to a doctor’s office, infusion center, or other health care facility. The antibodies bind to the SARS-CoV-2 spike protein and prevent the virus from getting into human cells and infecting them. It’s authorized for use in children and adults aged 12 years and older who weigh at least 88 pounds.

Studies have found that the medication decreases the risk of getting COVID-19 for up to 6 months after it is given. The FDA recommends repeat dosing every 6 months with the doses of 300 mg of each monoclonal antibody. In clinical trials, Evusheld reduced the incidence of COVID-19 symptomatic illness by 77%, compared with placebo.

Physicians monitor patients for an hour after administering Evusheld for allergic reactions. Other possible side effects include cardiac events, but they are not common.
 

Doctors and patients weigh in

Physicians – and patients – from the United States to the United Kingdom and beyond are questioning why the medication is underused while lauding the recent efforts to expand access and increase awareness.

The U.S. federal government may have underestimated the amount of communication needed to increase awareness of the medication and its applications, said infectious disease specialist William Schaffner, MD, professor of preventive medicine at Vanderbilt University School of Medicine, Nashville, Tenn.

“HHS hasn’t made a major educational effort to promote it,” he said in an interview.

Many physicians who need to know about it, such as transplant doctors and rheumatologists, are outside the typical public health communications loop, he said.

Eric Topol, MD, director of the Scripps Research Transational Institute and editor-in-chief of Medscape, has taken to social media to bemoan the lack of awareness.

Another infectious disease expert agrees. “In my experience, the awareness of Evusheld is low amongst many patients as well as many providers,” said Amesh Adalja, MD, a senior scholar at the Johns Hopkins Center for Health Security, Baltimore.

“Initially, there were scarce supplies of the drug, and certain hospital systems tiered eligibility based on degrees of immunosuppression, and only the most immunosuppressed were proactively approached for treatment.”

“Also, many community hospitals never initially ordered Evusheld – they may have been crowded out by academic centers who treat many more immunosuppressed patients and may not currently see it as a priority,” Dr. Adalja said in an interview. “As such, many immunosuppressed patients would have to seek treatment at academic medical centers, where the drug is more likely to be available.”

A version of this article first appeared on Medscape.com.

MONTREAL – A 66-year-old U.S. man has become the world’s fourth known HIV patient to show complete clearance of the virus after being treated for acute myelogenous leukemia with an allogeneic hematopoietic stem cell transplantation from a naturally HIV-resistant donor, U.S. researchers announced at a meeting of the International AIDS Society.

The man received the transplant nearly 3.5 years ago. Since discontinuation of antiretroviral therapy (ART) more than 17 months ago, he has shown no evidence of HIV-1 RNA rebound and no detectable HIV-1 DNA, reported lead investigator Jana K. Dickter, MD, associate clinical professor in the division of infectious diseases at City of Hope, a Duarte, Calif.–based stem cell transplantation center for patients with blood cancers and patients with HIV/blood cancer.

Known as the City of Hope (COH) patient, he is different from the three previously reported patients in that “he was the oldest person to successfully undergo a stem cell transplant with HIV and leukemia and then achieve remission from both conditions,” Dr. Dickter said during a press briefing for the meeting. “He has been living with HIV the longest of any of the patients to date – more than 31 years prior to transplant – and he had also received the least immunosuppressive preparative regimen prior to transplant,” she added.

She said that, like the three previous patients, known as the Berlin, London, and New York patients, the COH patient received a transplant from a donor with natural resistance to HIV because of a rare CCR5-delta 32 mutation.

Dr. Dickter and her coinvestigators used the term “remission” but went further, suggesting that an “HIV cure is feasible” after transplant, given this and the previous cases.

“It’s a bit early to say the patient is cured, but they are clearly in remission,” said Sharon Lewin, MD, president-elect of the International AIDS Society, which runs the meeting. Nevertheless, Dr. Lewin, professor of medicine at the University of Melbourne and director of the Peter Doherty Institute for Infection and Immunity, in Melbourne, acknowledged that cure is “very likely.”

“Two of the previously reported patients have been off ART for long periods of time – Berlin, 12 years (until Timothy’s death in 2020); London, 4 years – and both had far more extensive investigations to try and find intact virus, including very large blood draws, tissue biopsies, etc. For the New York and now this COH patient, the duration off ART has been much shorter. ... But given the prior cases, it is very likely that the New York and COH patients are indeed cured. But I think it’s too early to make that call, hence my preference to use the word, ‘remission,’ “ she told this news organization.

“Although a transplant is not an option for most people with HIV, these cases are still interesting, still inspiring, and help illuminate the search for a cure,” she added.

Dr. Dickter acknowledged that the complexity of stem cell transplant procedures and their potential for significant side effects make them unsuitable as treatment options for most people with HIV, although she said the COH case is evidence that some HIV patients with blood cancers may not need such intensive pretransplant conditioning regimens.

The COH patient received a reduced-intensity fludarabine and melphalan regimen that had been designed at Dr. Dickter’s center “for older and less fit patients to make transplantation more tolerable,” she said. In addition, the graft-vs.-host disease prophylaxis that the COH patient received included only tacrolimus and sirolimus, whereas the previous patients received additional immunosuppressive therapies, and some also had undergone total body irradiation.

Dr. Dickter has disclosed no relevant financial relationships. Dr. Lewin has relationships with AbbVie, BMS, Esfam, Genentech, Gilead, Immunocore, Merck, Vaxxinity, and Viiv.

A version of this article first appeared on Medscape.com.

MONTREAL – A 66-year-old U.S. man has become the world’s fourth known HIV patient to show complete clearance of the virus after being treated for acute myelogenous leukemia with an allogeneic hematopoietic stem cell transplantation from a naturally HIV-resistant donor, U.S. researchers announced at a meeting of the International AIDS Society.

The man received the transplant nearly 3.5 years ago. Since discontinuation of antiretroviral therapy (ART) more than 17 months ago, he has shown no evidence of HIV-1 RNA rebound and no detectable HIV-1 DNA, reported lead investigator Jana K. Dickter, MD, associate clinical professor in the division of infectious diseases at City of Hope, a Duarte, Calif.–based stem cell transplantation center for patients with blood cancers and patients with HIV/blood cancer.

Known as the City of Hope (COH) patient, he is different from the three previously reported patients in that “he was the oldest person to successfully undergo a stem cell transplant with HIV and leukemia and then achieve remission from both conditions,” Dr. Dickter said during a press briefing for the meeting. “He has been living with HIV the longest of any of the patients to date – more than 31 years prior to transplant – and he had also received the least immunosuppressive preparative regimen prior to transplant,” she added.

She said that, like the three previous patients, known as the Berlin, London, and New York patients, the COH patient received a transplant from a donor with natural resistance to HIV because of a rare CCR5-delta 32 mutation.

Dr. Dickter and her coinvestigators used the term “remission” but went further, suggesting that an “HIV cure is feasible” after transplant, given this and the previous cases.

“It’s a bit early to say the patient is cured, but they are clearly in remission,” said Sharon Lewin, MD, president-elect of the International AIDS Society, which runs the meeting. Nevertheless, Dr. Lewin, professor of medicine at the University of Melbourne and director of the Peter Doherty Institute for Infection and Immunity, in Melbourne, acknowledged that cure is “very likely.”

“Two of the previously reported patients have been off ART for long periods of time – Berlin, 12 years (until Timothy’s death in 2020); London, 4 years – and both had far more extensive investigations to try and find intact virus, including very large blood draws, tissue biopsies, etc. For the New York and now this COH patient, the duration off ART has been much shorter. ... But given the prior cases, it is very likely that the New York and COH patients are indeed cured. But I think it’s too early to make that call, hence my preference to use the word, ‘remission,’ “ she told this news organization.

“Although a transplant is not an option for most people with HIV, these cases are still interesting, still inspiring, and help illuminate the search for a cure,” she added.

Dr. Dickter acknowledged that the complexity of stem cell transplant procedures and their potential for significant side effects make them unsuitable as treatment options for most people with HIV, although she said the COH case is evidence that some HIV patients with blood cancers may not need such intensive pretransplant conditioning regimens.

The COH patient received a reduced-intensity fludarabine and melphalan regimen that had been designed at Dr. Dickter’s center “for older and less fit patients to make transplantation more tolerable,” she said. In addition, the graft-vs.-host disease prophylaxis that the COH patient received included only tacrolimus and sirolimus, whereas the previous patients received additional immunosuppressive therapies, and some also had undergone total body irradiation.

Dr. Dickter has disclosed no relevant financial relationships. Dr. Lewin has relationships with AbbVie, BMS, Esfam, Genentech, Gilead, Immunocore, Merck, Vaxxinity, and Viiv.

A version of this article first appeared on Medscape.com.

MONTREAL – A 66-year-old U.S. man has become the world’s fourth known HIV patient to show complete clearance of the virus after being treated for acute myelogenous leukemia with an allogeneic hematopoietic stem cell transplantation from a naturally HIV-resistant donor, U.S. researchers announced at a meeting of the International AIDS Society.

The man received the transplant nearly 3.5 years ago. Since discontinuation of antiretroviral therapy (ART) more than 17 months ago, he has shown no evidence of HIV-1 RNA rebound and no detectable HIV-1 DNA, reported lead investigator Jana K. Dickter, MD, associate clinical professor in the division of infectious diseases at City of Hope, a Duarte, Calif.–based stem cell transplantation center for patients with blood cancers and patients with HIV/blood cancer.

Known as the City of Hope (COH) patient, he is different from the three previously reported patients in that “he was the oldest person to successfully undergo a stem cell transplant with HIV and leukemia and then achieve remission from both conditions,” Dr. Dickter said during a press briefing for the meeting. “He has been living with HIV the longest of any of the patients to date – more than 31 years prior to transplant – and he had also received the least immunosuppressive preparative regimen prior to transplant,” she added.

She said that, like the three previous patients, known as the Berlin, London, and New York patients, the COH patient received a transplant from a donor with natural resistance to HIV because of a rare CCR5-delta 32 mutation.

Dr. Dickter and her coinvestigators used the term “remission” but went further, suggesting that an “HIV cure is feasible” after transplant, given this and the previous cases.

“It’s a bit early to say the patient is cured, but they are clearly in remission,” said Sharon Lewin, MD, president-elect of the International AIDS Society, which runs the meeting. Nevertheless, Dr. Lewin, professor of medicine at the University of Melbourne and director of the Peter Doherty Institute for Infection and Immunity, in Melbourne, acknowledged that cure is “very likely.”

“Two of the previously reported patients have been off ART for long periods of time – Berlin, 12 years (until Timothy’s death in 2020); London, 4 years – and both had far more extensive investigations to try and find intact virus, including very large blood draws, tissue biopsies, etc. For the New York and now this COH patient, the duration off ART has been much shorter. ... But given the prior cases, it is very likely that the New York and COH patients are indeed cured. But I think it’s too early to make that call, hence my preference to use the word, ‘remission,’ “ she told this news organization.

“Although a transplant is not an option for most people with HIV, these cases are still interesting, still inspiring, and help illuminate the search for a cure,” she added.

Dr. Dickter acknowledged that the complexity of stem cell transplant procedures and their potential for significant side effects make them unsuitable as treatment options for most people with HIV, although she said the COH case is evidence that some HIV patients with blood cancers may not need such intensive pretransplant conditioning regimens.

The COH patient received a reduced-intensity fludarabine and melphalan regimen that had been designed at Dr. Dickter’s center “for older and less fit patients to make transplantation more tolerable,” she said. In addition, the graft-vs.-host disease prophylaxis that the COH patient received included only tacrolimus and sirolimus, whereas the previous patients received additional immunosuppressive therapies, and some also had undergone total body irradiation.

Dr. Dickter has disclosed no relevant financial relationships. Dr. Lewin has relationships with AbbVie, BMS, Esfam, Genentech, Gilead, Immunocore, Merck, Vaxxinity, and Viiv.

A version of this article first appeared on Medscape.com.

The World Health Organization (WHO) named vaccine hesitancy as one of the top 10 threats to public health as of 2019.¹ Although the COVID-19 vaccines manufactured by Pfizer-BioNTech and Moderna, first authorized for use in November 2020 and fully approved in August 2021,² are widely available in most countries, vaccination uptake is insufficient.³

As of June 2022, 78% of the US population had received at least 1 vaccine dose and 66.8% were fully vaccinated against COVID-19.⁴ High confidence in vaccines is associated with greater uptake; thus, engendering confidence in patients is a critical area of intervention for increasing uptake of COVID-19 and other vaccines.⁵ Despite the steady increase in vaccine acceptance observed following the release of the COVID-19 vaccine, acceptance remains suboptimal.^2,6

Demographic characteristics associated with lower vaccine acceptance include younger age, female sex, lower education and/or income, and Black race or Hispanic/Latinx ethnicity (compared to white or Asian non-­Hispanic).^6,7 Moreover, patients who are skeptical of vaccine safety and efficacy are associated with lower intentions to vaccinate. In contrast, patients with a history of receiving influenza vaccinations and those with a greater concern about COVID-19 and their risk of infection have increased vaccine intentions.⁶

Numerous strategies exist to increase vaccine acceptance; however, there does not appear to be a single “best” method to overcome individual or parental vaccine hesitancy for COVID-19 or other vaccines.^8,9 There are no large-scale randomized controlled trials (RCTs) demonstrating one strategy as more effective than another. In this review, we outline a variety of evidenced-based strategies to help patients overcome vaccine hesitancy for COVID-19 and other vaccines, with a focus on practical tips for primary care physicians (PCPs).

Which talking points are likely to resonate with your patients?

Intervention strategies promote vaccine acceptance by communicating personal benefit, collective benefit, or both to vaccine-­hesitant patients. In a study sample of US undergraduate students, Kim and colleagues¹⁰ found that providing information about the benefits and risks of influenza vaccines resulted in significantly less vaccine intent compared to communicating information only on the benefits. Similarly, Shim and colleagues¹¹ investigated how game theory (acting to maximize personal payoff regardless of payoff to others) and altruism affect influenza vaccination decisions. Through a survey-based study of 427 US university employees, researchers found altruistic motivation had a significant impact on the decision to vaccinate against influenza, resulting in a shift from self-interest to that of the good of the community.¹¹

A German trial on COVID-19 vaccine acceptance by Sprengholz and colleagues¹² found that communications about the benefits of vaccination, availability of financial compensation for vaccination, or a combination of both, did not increase a person’s willingness to get vaccinated. This trial, however, did not separate out individual vs collective benefit, and it was conducted prior to widespread COVID-19 vaccine availability. 

When speaking with patients who are strongly hesitant to vaccination, emphasizing concrete personal benefit may prove more effective than stressing protection of others from illness.

In an online RCT conducted in early 2021, Freeman and colleagues¹³ randomized UK adults to 1 of 10 different “information conditions.” Participants read from 1 of 10 vaccine scripts that varied by the talking points they addressed. The topics that researchers drew from for these scripts included the personal or collective benefit from the COVID-19 vaccine, safety and effectiveness of the vaccine, and the seriousness of the pandemic. They found communications emphasizing personal benefit from vaccination and safety concerns were more effective in participants identified as being strongly hesitant (defined as those who said they would avoid getting the COVID-19 vaccine for as long as possible or who said they’d never get it). However, none of the information arms in this study decreased vaccine hesitancy among those who were doubtful of vaccination (defined as those who said they would delay vaccination or who didn’t know if they would get vaccinated).¹³

Continue to: When encountering patients who are strongly...

When encountering patients who are strongly hesitant to vaccination, an approach emphasizing concrete personal benefit may prove more effective than one stressing protection of others from illness. It is important to note, though, that findings from other countries may not be relevant to US patients due to differences in demographic factors, individual beliefs, and political climate. 

It helps to explain herd immunity by providing concrete examples 

Among the collective benefits of vaccination is the decreased risk of transmitting the disease to others (eg, family, friends, neighbors, colleagues), a quicker “return to normalcy,” and herd immunity.¹³ While individual health benefits may more strongly motivate people to get vaccinated than collective benefits, this may be due to a lack of understanding about herd immunity among the general public. The optimal method of communicating information on herd immunity is not known.¹⁴

Betsch and colleagues¹⁵ found that explaining herd immunity using interactive simulations increased vaccine intent, especially in countries that prioritize the self (rather than prioritizing the group over the individual). In addition to educating study participants about herd immunity, telling them how local vaccine coverage compared to the desired level of coverage helped to increase (influenza) vaccine intent among those who were least informed about herd immunity.¹⁶

Providing concrete examples of the collective benefits of vaccination (eg, protecting grandparents, children too young to be vaccinated, and those at increased risk for severe illness) or sharing stories about how other patients suffered from the disease in question may increase the likelihood of vaccination. One recent trial by Pfattheicher and colleagues¹⁷ found that empathy for those most vulnerable to COVID-19 and increased knowledge about herd immunity were 2 factors associated with greater vaccine intentions.

In this study, the authors induced empathy and increased COVID-19 vaccination intention by having participants read a short story about 2 close siblings who worked together in a nursing facility. In the story, participants learned that both siblings were given a diagnosis of COVID-19 at the same time but only 1 survived.¹⁷

Continue to: Try this 3-pronged approach

Try this 3-pronged approach. Consider explaining herd immunity to vaccine-hesitant patients, pairing this concept with information about local vaccine uptake, and appealing to the patient’s sense of empathy. You might share de-identified information on other patients in your practice or personal network who experienced severe illness, had long-term effects, or died from COVID-19 infection. Such concrete examples may help to increase motivation to vaccinate more than a general appeal to altruism.

Initiate the discussion by emphasizing that community immunity protects those who are vulnerable and lack immunity while providing specific empathetic examples (eg, newborns, cancer survivors) and asking patients to consider friends and family who might be at risk. Additionally, it is essential to explain that although community immunity can decrease the spread of infection, it can only be achieved when enough people are vaccinated. 

Proceed with caution: Addressing conspiracy theories can backfire

Accurate information is critical to improving vaccine intentions; belief in conspiracy theories or misinformation related to COVID-19 is associated with reduced vaccine intentions and uptake.⁶ For example, a study by Loomba and colleagues¹⁸ showed that after exposure to misinformation, US and UK adults reported reduced intentions to vaccinate against COVID-19 once a vaccine became available.

Unfortunately, addressing myths about vaccines can sometimes backfire and unintentionally reinforce vaccine misperceptions.^19,20 This is especially true for patients with the highest levels of concern or mistrust in vaccines. Nyhan and colleagues^21,22 observed the backfire effect in 2 US studies looking at influenza and measles, mumps, and rubella vaccine misperceptions. Although corrective information significantly reduced belief in vaccine myths, they found individuals with the most concerns more strongly endorsed misperceptions when their beliefs were challenged.^21,22

Strategies for correcting vaccine misinformation may vary by type of vaccine; however, placing emphasis on facts delivered by trusted sources appears to be beneficial.

An Australian randomized study by Steffens and colleagues²³ found repeating myths about childhood vaccines, followed by corrective text, to parents of children ages 0 to 5 years had no difference on parental intent to vaccinate their children compared to providing vaccine information as a statement or in a question/answer format. Furthermore, an RCT in Brazil by Carey and colleagues²⁴ found that myth-correction messages about Zika virus failed to reduce misperceptions about the virus and actually reduced the belief in factual information about Zika—­regardless of baseline beliefs in conspiracies. However, a similar experiment in the same study showed that myth-correction messages reduced false beliefs about yellow fever.

Continue to: The authors speculated...

The authors speculated that this may be because Zika is a relatively new virus when compared to yellow fever, and participants may have more pre-existing knowledge about yellow fever.²⁴ These findings are important to keep in mind when addressing misinformation regarding COVID-19. When addressing myth perceptions with patients, consider pivoting the conversation from vaccine myths to the disease itself, focusing on the disease risk and severity of symptoms.^19,20 

Other studies have had positive results when addressing misinformation, including a digital RCT of older adults in the Netherlands by Yousuf and colleagues.²⁵ In this study, participants were randomized to view 1 of 2 versions of an information video on vaccination featuring an informative discussion by celebrity scientists, government officials, and a cardiologist. Video 1 did not include debunking strategies, only information about vaccination; Video 2 provided the same information about vaccines but also described the myths surrounding vaccines and reiterated the truth to debunk the myths.

Findings demonstrated that a significantly higher number of participants in the Video 2 group overcame vaccination myths related to influenza and COVID-19.²⁵ Notably, this study took place prior to the widespread availability of COVID-19 vaccines and did not measure intent to vaccinate against COVID-19.

Taken together, strategies for correcting vaccine misinformation may vary by population as well as type of vaccine; however, placing emphasis on facts delivered by trusted sources appears to be beneficial. When addressing misinformation, PCPs should first focus on key details (not all supporting information) and clearly explain why the misinformation is false before pointing out the actual myth and providing an alternative explanation.²⁰ When caring for patients who express strong concerns over the vaccine in question or have avid beliefs in certain myths or conspiracy theories, it’s best to pivot the conversation back to the disease rather than address the misinformation to avoid a potential backfire effect.

Utilize these effective communication techniques

TABLE 1^{10,13,16,17,19,20} summarizes the “do’s and don’ts” of communicating with vaccine-hesitant patients. PCPs should provide strong recommendations for vaccination, approaching it presumptively—ie, framing it as normative behavior.^19,26 This approach is critical to building patient trust so that vaccine-hesitant patients feel the PCP is truly listening to them and addressing their concerns.²⁷ Additionally, implementing motivational interviewing (MI) and self-determination theory (SDT)²⁸ techniques when discussing vaccinations with patients can improve intentions and uptake.^19,29TABLE 2^19,29 outlines specific techniques based on SDT and MI that PCPs may utilize to communicate with vaccine-hesitant individuals or parents. 

Continue to: The takeaway

Strategies for increasing vaccine intentions include educating hesitant patients about the benefits and risks of vaccines, addressing misinformation, and explaining the personal and collective benefits of vaccination. These strategies appear to be more effective when delivered by a trusted source, such as a health care provider (HCP). Care should be taken when implementing vaccine-acceptance strategies to ensure that they are tailored to specific populations and vaccines.

At this stage in the COVID-19 pandemic, when several vaccines have been widely available for more than a year, we expect that the majority of patients desiring vaccination (ie, those with the greatest vaccine intent) have already received them. With the recent approval of COVID-19 vaccines for children younger than 5 years, we must now advocate for our patients to vaccinate not only themselves, but their children. Patients who remain unvaccinated may be hesitant or outright reject vaccination for a number of reasons, including fear or skepticism over the safety and efficacy of the vaccine, belief in conspiracy theories, belief that COVID-19 is not real or not severe, or mistrust of the government.⁶ Vaccine hesitation or rejection is also often political in nature.

Based on the studies included in this review, we have identified several strategies for reducing vaccine hesitancy, which can be used with vaccine-hesitant patients and parents. We suggest emphasizing the personal benefit of vaccination and focusing on specific disease risks. If time allows, you can also explain the collective benefit of vaccination through herd immunity, including the current levels of local vaccine uptake compared to the desired level for community immunity. Communicating the collective benefits of vaccination may be more effective when paired with a strategy intended to increase empathy and altruism, such as sharing actual stories about those who have suffered from a vaccine-preventable disease.

Build trust by asking your patient: What kind of information do you feel you are missing about the vaccine?

Addressing myths and misinformation related to COVID-19 and other vaccines, with emphasis placed on the correct information delivered by trusted sources may be beneficial for those who are uncertain but not strongly against vaccination. For those who remain staunchly hesitant against vaccination, we recommend focusing on the personal benefits of vaccination with a focus on delivering facts about the risk of the disease in question, rather than trying to refute misinformation.

COVID-19 vaccine acceptance in the United States is disturbingly low among health care workers, particularly nurses, technicians, and those in nonclinical roles, compared to physicians.^6,30 Many of the strategies for addressing vaccine hesitancy among the general population can also apply to health care personnel (eg, vaccine education, addressing misinformation, delivering information from a trusted source). Health care personnel may also be subject to vaccine mandates by their employers, which have demonstrated increases in vaccination rates for influenza.³¹ Given that COVID-19 vaccination recommendations made by HCPs are associated with greater vaccine intentions and uptake,⁶ reducing hesitancy among health care workers is a critical first step to achieving optimal implementation.

CORRESPONDENCE
Nicole Mayo, PhD, 236 Pearl Street, Rochester, NY 14607; [email protected]

The World Health Organization (WHO) named vaccine hesitancy as one of the top 10 threats to public health as of 2019.¹ Although the COVID-19 vaccines manufactured by Pfizer-BioNTech and Moderna, first authorized for use in November 2020 and fully approved in August 2021,² are widely available in most countries, vaccination uptake is insufficient.³

As of June 2022, 78% of the US population had received at least 1 vaccine dose and 66.8% were fully vaccinated against COVID-19.⁴ High confidence in vaccines is associated with greater uptake; thus, engendering confidence in patients is a critical area of intervention for increasing uptake of COVID-19 and other vaccines.⁵ Despite the steady increase in vaccine acceptance observed following the release of the COVID-19 vaccine, acceptance remains suboptimal.^2,6

Demographic characteristics associated with lower vaccine acceptance include younger age, female sex, lower education and/or income, and Black race or Hispanic/Latinx ethnicity (compared to white or Asian non-­Hispanic).^6,7 Moreover, patients who are skeptical of vaccine safety and efficacy are associated with lower intentions to vaccinate. In contrast, patients with a history of receiving influenza vaccinations and those with a greater concern about COVID-19 and their risk of infection have increased vaccine intentions.⁶

Numerous strategies exist to increase vaccine acceptance; however, there does not appear to be a single “best” method to overcome individual or parental vaccine hesitancy for COVID-19 or other vaccines.^8,9 There are no large-scale randomized controlled trials (RCTs) demonstrating one strategy as more effective than another. In this review, we outline a variety of evidenced-based strategies to help patients overcome vaccine hesitancy for COVID-19 and other vaccines, with a focus on practical tips for primary care physicians (PCPs).

Which talking points are likely to resonate with your patients?

Intervention strategies promote vaccine acceptance by communicating personal benefit, collective benefit, or both to vaccine-­hesitant patients. In a study sample of US undergraduate students, Kim and colleagues¹⁰ found that providing information about the benefits and risks of influenza vaccines resulted in significantly less vaccine intent compared to communicating information only on the benefits. Similarly, Shim and colleagues¹¹ investigated how game theory (acting to maximize personal payoff regardless of payoff to others) and altruism affect influenza vaccination decisions. Through a survey-based study of 427 US university employees, researchers found altruistic motivation had a significant impact on the decision to vaccinate against influenza, resulting in a shift from self-interest to that of the good of the community.¹¹

A German trial on COVID-19 vaccine acceptance by Sprengholz and colleagues¹² found that communications about the benefits of vaccination, availability of financial compensation for vaccination, or a combination of both, did not increase a person’s willingness to get vaccinated. This trial, however, did not separate out individual vs collective benefit, and it was conducted prior to widespread COVID-19 vaccine availability. 

When speaking with patients who are strongly hesitant to vaccination, emphasizing concrete personal benefit may prove more effective than stressing protection of others from illness.

In an online RCT conducted in early 2021, Freeman and colleagues¹³ randomized UK adults to 1 of 10 different “information conditions.” Participants read from 1 of 10 vaccine scripts that varied by the talking points they addressed. The topics that researchers drew from for these scripts included the personal or collective benefit from the COVID-19 vaccine, safety and effectiveness of the vaccine, and the seriousness of the pandemic. They found communications emphasizing personal benefit from vaccination and safety concerns were more effective in participants identified as being strongly hesitant (defined as those who said they would avoid getting the COVID-19 vaccine for as long as possible or who said they’d never get it). However, none of the information arms in this study decreased vaccine hesitancy among those who were doubtful of vaccination (defined as those who said they would delay vaccination or who didn’t know if they would get vaccinated).¹³

Continue to: When encountering patients who are strongly...

When encountering patients who are strongly hesitant to vaccination, an approach emphasizing concrete personal benefit may prove more effective than one stressing protection of others from illness. It is important to note, though, that findings from other countries may not be relevant to US patients due to differences in demographic factors, individual beliefs, and political climate. 

It helps to explain herd immunity by providing concrete examples 

Among the collective benefits of vaccination is the decreased risk of transmitting the disease to others (eg, family, friends, neighbors, colleagues), a quicker “return to normalcy,” and herd immunity.¹³ While individual health benefits may more strongly motivate people to get vaccinated than collective benefits, this may be due to a lack of understanding about herd immunity among the general public. The optimal method of communicating information on herd immunity is not known.¹⁴

Betsch and colleagues¹⁵ found that explaining herd immunity using interactive simulations increased vaccine intent, especially in countries that prioritize the self (rather than prioritizing the group over the individual). In addition to educating study participants about herd immunity, telling them how local vaccine coverage compared to the desired level of coverage helped to increase (influenza) vaccine intent among those who were least informed about herd immunity.¹⁶

Providing concrete examples of the collective benefits of vaccination (eg, protecting grandparents, children too young to be vaccinated, and those at increased risk for severe illness) or sharing stories about how other patients suffered from the disease in question may increase the likelihood of vaccination. One recent trial by Pfattheicher and colleagues¹⁷ found that empathy for those most vulnerable to COVID-19 and increased knowledge about herd immunity were 2 factors associated with greater vaccine intentions.

In this study, the authors induced empathy and increased COVID-19 vaccination intention by having participants read a short story about 2 close siblings who worked together in a nursing facility. In the story, participants learned that both siblings were given a diagnosis of COVID-19 at the same time but only 1 survived.¹⁷

Continue to: Try this 3-pronged approach

Try this 3-pronged approach. Consider explaining herd immunity to vaccine-hesitant patients, pairing this concept with information about local vaccine uptake, and appealing to the patient’s sense of empathy. You might share de-identified information on other patients in your practice or personal network who experienced severe illness, had long-term effects, or died from COVID-19 infection. Such concrete examples may help to increase motivation to vaccinate more than a general appeal to altruism.

Initiate the discussion by emphasizing that community immunity protects those who are vulnerable and lack immunity while providing specific empathetic examples (eg, newborns, cancer survivors) and asking patients to consider friends and family who might be at risk. Additionally, it is essential to explain that although community immunity can decrease the spread of infection, it can only be achieved when enough people are vaccinated. 

Proceed with caution: Addressing conspiracy theories can backfire

Accurate information is critical to improving vaccine intentions; belief in conspiracy theories or misinformation related to COVID-19 is associated with reduced vaccine intentions and uptake.⁶ For example, a study by Loomba and colleagues¹⁸ showed that after exposure to misinformation, US and UK adults reported reduced intentions to vaccinate against COVID-19 once a vaccine became available.

Unfortunately, addressing myths about vaccines can sometimes backfire and unintentionally reinforce vaccine misperceptions.^19,20 This is especially true for patients with the highest levels of concern or mistrust in vaccines. Nyhan and colleagues^21,22 observed the backfire effect in 2 US studies looking at influenza and measles, mumps, and rubella vaccine misperceptions. Although corrective information significantly reduced belief in vaccine myths, they found individuals with the most concerns more strongly endorsed misperceptions when their beliefs were challenged.^21,22

Strategies for correcting vaccine misinformation may vary by type of vaccine; however, placing emphasis on facts delivered by trusted sources appears to be beneficial.

An Australian randomized study by Steffens and colleagues²³ found repeating myths about childhood vaccines, followed by corrective text, to parents of children ages 0 to 5 years had no difference on parental intent to vaccinate their children compared to providing vaccine information as a statement or in a question/answer format. Furthermore, an RCT in Brazil by Carey and colleagues²⁴ found that myth-correction messages about Zika virus failed to reduce misperceptions about the virus and actually reduced the belief in factual information about Zika—­regardless of baseline beliefs in conspiracies. However, a similar experiment in the same study showed that myth-correction messages reduced false beliefs about yellow fever.

Continue to: The authors speculated...

The authors speculated that this may be because Zika is a relatively new virus when compared to yellow fever, and participants may have more pre-existing knowledge about yellow fever.²⁴ These findings are important to keep in mind when addressing misinformation regarding COVID-19. When addressing myth perceptions with patients, consider pivoting the conversation from vaccine myths to the disease itself, focusing on the disease risk and severity of symptoms.^19,20 

Other studies have had positive results when addressing misinformation, including a digital RCT of older adults in the Netherlands by Yousuf and colleagues.²⁵ In this study, participants were randomized to view 1 of 2 versions of an information video on vaccination featuring an informative discussion by celebrity scientists, government officials, and a cardiologist. Video 1 did not include debunking strategies, only information about vaccination; Video 2 provided the same information about vaccines but also described the myths surrounding vaccines and reiterated the truth to debunk the myths.

Findings demonstrated that a significantly higher number of participants in the Video 2 group overcame vaccination myths related to influenza and COVID-19.²⁵ Notably, this study took place prior to the widespread availability of COVID-19 vaccines and did not measure intent to vaccinate against COVID-19.

Taken together, strategies for correcting vaccine misinformation may vary by population as well as type of vaccine; however, placing emphasis on facts delivered by trusted sources appears to be beneficial. When addressing misinformation, PCPs should first focus on key details (not all supporting information) and clearly explain why the misinformation is false before pointing out the actual myth and providing an alternative explanation.²⁰ When caring for patients who express strong concerns over the vaccine in question or have avid beliefs in certain myths or conspiracy theories, it’s best to pivot the conversation back to the disease rather than address the misinformation to avoid a potential backfire effect.

Utilize these effective communication techniques

TABLE 1^{10,13,16,17,19,20} summarizes the “do’s and don’ts” of communicating with vaccine-hesitant patients. PCPs should provide strong recommendations for vaccination, approaching it presumptively—ie, framing it as normative behavior.^19,26 This approach is critical to building patient trust so that vaccine-hesitant patients feel the PCP is truly listening to them and addressing their concerns.²⁷ Additionally, implementing motivational interviewing (MI) and self-determination theory (SDT)²⁸ techniques when discussing vaccinations with patients can improve intentions and uptake.^19,29TABLE 2^19,29 outlines specific techniques based on SDT and MI that PCPs may utilize to communicate with vaccine-hesitant individuals or parents. 

Continue to: The takeaway

Strategies for increasing vaccine intentions include educating hesitant patients about the benefits and risks of vaccines, addressing misinformation, and explaining the personal and collective benefits of vaccination. These strategies appear to be more effective when delivered by a trusted source, such as a health care provider (HCP). Care should be taken when implementing vaccine-acceptance strategies to ensure that they are tailored to specific populations and vaccines.

At this stage in the COVID-19 pandemic, when several vaccines have been widely available for more than a year, we expect that the majority of patients desiring vaccination (ie, those with the greatest vaccine intent) have already received them. With the recent approval of COVID-19 vaccines for children younger than 5 years, we must now advocate for our patients to vaccinate not only themselves, but their children. Patients who remain unvaccinated may be hesitant or outright reject vaccination for a number of reasons, including fear or skepticism over the safety and efficacy of the vaccine, belief in conspiracy theories, belief that COVID-19 is not real or not severe, or mistrust of the government.⁶ Vaccine hesitation or rejection is also often political in nature.

Based on the studies included in this review, we have identified several strategies for reducing vaccine hesitancy, which can be used with vaccine-hesitant patients and parents. We suggest emphasizing the personal benefit of vaccination and focusing on specific disease risks. If time allows, you can also explain the collective benefit of vaccination through herd immunity, including the current levels of local vaccine uptake compared to the desired level for community immunity. Communicating the collective benefits of vaccination may be more effective when paired with a strategy intended to increase empathy and altruism, such as sharing actual stories about those who have suffered from a vaccine-preventable disease.

Build trust by asking your patient: What kind of information do you feel you are missing about the vaccine?

Addressing myths and misinformation related to COVID-19 and other vaccines, with emphasis placed on the correct information delivered by trusted sources may be beneficial for those who are uncertain but not strongly against vaccination. For those who remain staunchly hesitant against vaccination, we recommend focusing on the personal benefits of vaccination with a focus on delivering facts about the risk of the disease in question, rather than trying to refute misinformation.

COVID-19 vaccine acceptance in the United States is disturbingly low among health care workers, particularly nurses, technicians, and those in nonclinical roles, compared to physicians.^6,30 Many of the strategies for addressing vaccine hesitancy among the general population can also apply to health care personnel (eg, vaccine education, addressing misinformation, delivering information from a trusted source). Health care personnel may also be subject to vaccine mandates by their employers, which have demonstrated increases in vaccination rates for influenza.³¹ Given that COVID-19 vaccination recommendations made by HCPs are associated with greater vaccine intentions and uptake,⁶ reducing hesitancy among health care workers is a critical first step to achieving optimal implementation.

CORRESPONDENCE
Nicole Mayo, PhD, 236 Pearl Street, Rochester, NY 14607; [email protected]

The World Health Organization (WHO) named vaccine hesitancy as one of the top 10 threats to public health as of 2019.¹ Although the COVID-19 vaccines manufactured by Pfizer-BioNTech and Moderna, first authorized for use in November 2020 and fully approved in August 2021,² are widely available in most countries, vaccination uptake is insufficient.³

As of June 2022, 78% of the US population had received at least 1 vaccine dose and 66.8% were fully vaccinated against COVID-19.⁴ High confidence in vaccines is associated with greater uptake; thus, engendering confidence in patients is a critical area of intervention for increasing uptake of COVID-19 and other vaccines.⁵ Despite the steady increase in vaccine acceptance observed following the release of the COVID-19 vaccine, acceptance remains suboptimal.^2,6

Demographic characteristics associated with lower vaccine acceptance include younger age, female sex, lower education and/or income, and Black race or Hispanic/Latinx ethnicity (compared to white or Asian non-­Hispanic).^6,7 Moreover, patients who are skeptical of vaccine safety and efficacy are associated with lower intentions to vaccinate. In contrast, patients with a history of receiving influenza vaccinations and those with a greater concern about COVID-19 and their risk of infection have increased vaccine intentions.⁶

Numerous strategies exist to increase vaccine acceptance; however, there does not appear to be a single “best” method to overcome individual or parental vaccine hesitancy for COVID-19 or other vaccines.^8,9 There are no large-scale randomized controlled trials (RCTs) demonstrating one strategy as more effective than another. In this review, we outline a variety of evidenced-based strategies to help patients overcome vaccine hesitancy for COVID-19 and other vaccines, with a focus on practical tips for primary care physicians (PCPs).

Which talking points are likely to resonate with your patients?

Intervention strategies promote vaccine acceptance by communicating personal benefit, collective benefit, or both to vaccine-­hesitant patients. In a study sample of US undergraduate students, Kim and colleagues¹⁰ found that providing information about the benefits and risks of influenza vaccines resulted in significantly less vaccine intent compared to communicating information only on the benefits. Similarly, Shim and colleagues¹¹ investigated how game theory (acting to maximize personal payoff regardless of payoff to others) and altruism affect influenza vaccination decisions. Through a survey-based study of 427 US university employees, researchers found altruistic motivation had a significant impact on the decision to vaccinate against influenza, resulting in a shift from self-interest to that of the good of the community.¹¹

A German trial on COVID-19 vaccine acceptance by Sprengholz and colleagues¹² found that communications about the benefits of vaccination, availability of financial compensation for vaccination, or a combination of both, did not increase a person’s willingness to get vaccinated. This trial, however, did not separate out individual vs collective benefit, and it was conducted prior to widespread COVID-19 vaccine availability. 

When speaking with patients who are strongly hesitant to vaccination, emphasizing concrete personal benefit may prove more effective than stressing protection of others from illness.

In an online RCT conducted in early 2021, Freeman and colleagues¹³ randomized UK adults to 1 of 10 different “information conditions.” Participants read from 1 of 10 vaccine scripts that varied by the talking points they addressed. The topics that researchers drew from for these scripts included the personal or collective benefit from the COVID-19 vaccine, safety and effectiveness of the vaccine, and the seriousness of the pandemic. They found communications emphasizing personal benefit from vaccination and safety concerns were more effective in participants identified as being strongly hesitant (defined as those who said they would avoid getting the COVID-19 vaccine for as long as possible or who said they’d never get it). However, none of the information arms in this study decreased vaccine hesitancy among those who were doubtful of vaccination (defined as those who said they would delay vaccination or who didn’t know if they would get vaccinated).¹³

Continue to: When encountering patients who are strongly...

When encountering patients who are strongly hesitant to vaccination, an approach emphasizing concrete personal benefit may prove more effective than one stressing protection of others from illness. It is important to note, though, that findings from other countries may not be relevant to US patients due to differences in demographic factors, individual beliefs, and political climate. 

It helps to explain herd immunity by providing concrete examples 

Among the collective benefits of vaccination is the decreased risk of transmitting the disease to others (eg, family, friends, neighbors, colleagues), a quicker “return to normalcy,” and herd immunity.¹³ While individual health benefits may more strongly motivate people to get vaccinated than collective benefits, this may be due to a lack of understanding about herd immunity among the general public. The optimal method of communicating information on herd immunity is not known.¹⁴

Betsch and colleagues¹⁵ found that explaining herd immunity using interactive simulations increased vaccine intent, especially in countries that prioritize the self (rather than prioritizing the group over the individual). In addition to educating study participants about herd immunity, telling them how local vaccine coverage compared to the desired level of coverage helped to increase (influenza) vaccine intent among those who were least informed about herd immunity.¹⁶

Providing concrete examples of the collective benefits of vaccination (eg, protecting grandparents, children too young to be vaccinated, and those at increased risk for severe illness) or sharing stories about how other patients suffered from the disease in question may increase the likelihood of vaccination. One recent trial by Pfattheicher and colleagues¹⁷ found that empathy for those most vulnerable to COVID-19 and increased knowledge about herd immunity were 2 factors associated with greater vaccine intentions.

In this study, the authors induced empathy and increased COVID-19 vaccination intention by having participants read a short story about 2 close siblings who worked together in a nursing facility. In the story, participants learned that both siblings were given a diagnosis of COVID-19 at the same time but only 1 survived.¹⁷

Continue to: Try this 3-pronged approach

Try this 3-pronged approach. Consider explaining herd immunity to vaccine-hesitant patients, pairing this concept with information about local vaccine uptake, and appealing to the patient’s sense of empathy. You might share de-identified information on other patients in your practice or personal network who experienced severe illness, had long-term effects, or died from COVID-19 infection. Such concrete examples may help to increase motivation to vaccinate more than a general appeal to altruism.

Initiate the discussion by emphasizing that community immunity protects those who are vulnerable and lack immunity while providing specific empathetic examples (eg, newborns, cancer survivors) and asking patients to consider friends and family who might be at risk. Additionally, it is essential to explain that although community immunity can decrease the spread of infection, it can only be achieved when enough people are vaccinated. 

Proceed with caution: Addressing conspiracy theories can backfire

Accurate information is critical to improving vaccine intentions; belief in conspiracy theories or misinformation related to COVID-19 is associated with reduced vaccine intentions and uptake.⁶ For example, a study by Loomba and colleagues¹⁸ showed that after exposure to misinformation, US and UK adults reported reduced intentions to vaccinate against COVID-19 once a vaccine became available.

Unfortunately, addressing myths about vaccines can sometimes backfire and unintentionally reinforce vaccine misperceptions.^19,20 This is especially true for patients with the highest levels of concern or mistrust in vaccines. Nyhan and colleagues^21,22 observed the backfire effect in 2 US studies looking at influenza and measles, mumps, and rubella vaccine misperceptions. Although corrective information significantly reduced belief in vaccine myths, they found individuals with the most concerns more strongly endorsed misperceptions when their beliefs were challenged.^21,22

Strategies for correcting vaccine misinformation may vary by type of vaccine; however, placing emphasis on facts delivered by trusted sources appears to be beneficial.

An Australian randomized study by Steffens and colleagues²³ found repeating myths about childhood vaccines, followed by corrective text, to parents of children ages 0 to 5 years had no difference on parental intent to vaccinate their children compared to providing vaccine information as a statement or in a question/answer format. Furthermore, an RCT in Brazil by Carey and colleagues²⁴ found that myth-correction messages about Zika virus failed to reduce misperceptions about the virus and actually reduced the belief in factual information about Zika—­regardless of baseline beliefs in conspiracies. However, a similar experiment in the same study showed that myth-correction messages reduced false beliefs about yellow fever.

Continue to: The authors speculated...

The authors speculated that this may be because Zika is a relatively new virus when compared to yellow fever, and participants may have more pre-existing knowledge about yellow fever.²⁴ These findings are important to keep in mind when addressing misinformation regarding COVID-19. When addressing myth perceptions with patients, consider pivoting the conversation from vaccine myths to the disease itself, focusing on the disease risk and severity of symptoms.^19,20 

Other studies have had positive results when addressing misinformation, including a digital RCT of older adults in the Netherlands by Yousuf and colleagues.²⁵ In this study, participants were randomized to view 1 of 2 versions of an information video on vaccination featuring an informative discussion by celebrity scientists, government officials, and a cardiologist. Video 1 did not include debunking strategies, only information about vaccination; Video 2 provided the same information about vaccines but also described the myths surrounding vaccines and reiterated the truth to debunk the myths.

Findings demonstrated that a significantly higher number of participants in the Video 2 group overcame vaccination myths related to influenza and COVID-19.²⁵ Notably, this study took place prior to the widespread availability of COVID-19 vaccines and did not measure intent to vaccinate against COVID-19.

Taken together, strategies for correcting vaccine misinformation may vary by population as well as type of vaccine; however, placing emphasis on facts delivered by trusted sources appears to be beneficial. When addressing misinformation, PCPs should first focus on key details (not all supporting information) and clearly explain why the misinformation is false before pointing out the actual myth and providing an alternative explanation.²⁰ When caring for patients who express strong concerns over the vaccine in question or have avid beliefs in certain myths or conspiracy theories, it’s best to pivot the conversation back to the disease rather than address the misinformation to avoid a potential backfire effect.

Utilize these effective communication techniques

TABLE 1^{10,13,16,17,19,20} summarizes the “do’s and don’ts” of communicating with vaccine-hesitant patients. PCPs should provide strong recommendations for vaccination, approaching it presumptively—ie, framing it as normative behavior.^19,26 This approach is critical to building patient trust so that vaccine-hesitant patients feel the PCP is truly listening to them and addressing their concerns.²⁷ Additionally, implementing motivational interviewing (MI) and self-determination theory (SDT)²⁸ techniques when discussing vaccinations with patients can improve intentions and uptake.^19,29TABLE 2^19,29 outlines specific techniques based on SDT and MI that PCPs may utilize to communicate with vaccine-hesitant individuals or parents. 

Continue to: The takeaway

Strategies for increasing vaccine intentions include educating hesitant patients about the benefits and risks of vaccines, addressing misinformation, and explaining the personal and collective benefits of vaccination. These strategies appear to be more effective when delivered by a trusted source, such as a health care provider (HCP). Care should be taken when implementing vaccine-acceptance strategies to ensure that they are tailored to specific populations and vaccines.

At this stage in the COVID-19 pandemic, when several vaccines have been widely available for more than a year, we expect that the majority of patients desiring vaccination (ie, those with the greatest vaccine intent) have already received them. With the recent approval of COVID-19 vaccines for children younger than 5 years, we must now advocate for our patients to vaccinate not only themselves, but their children. Patients who remain unvaccinated may be hesitant or outright reject vaccination for a number of reasons, including fear or skepticism over the safety and efficacy of the vaccine, belief in conspiracy theories, belief that COVID-19 is not real or not severe, or mistrust of the government.⁶ Vaccine hesitation or rejection is also often political in nature.

Based on the studies included in this review, we have identified several strategies for reducing vaccine hesitancy, which can be used with vaccine-hesitant patients and parents. We suggest emphasizing the personal benefit of vaccination and focusing on specific disease risks. If time allows, you can also explain the collective benefit of vaccination through herd immunity, including the current levels of local vaccine uptake compared to the desired level for community immunity. Communicating the collective benefits of vaccination may be more effective when paired with a strategy intended to increase empathy and altruism, such as sharing actual stories about those who have suffered from a vaccine-preventable disease.

Build trust by asking your patient: What kind of information do you feel you are missing about the vaccine?

Addressing myths and misinformation related to COVID-19 and other vaccines, with emphasis placed on the correct information delivered by trusted sources may be beneficial for those who are uncertain but not strongly against vaccination. For those who remain staunchly hesitant against vaccination, we recommend focusing on the personal benefits of vaccination with a focus on delivering facts about the risk of the disease in question, rather than trying to refute misinformation.

COVID-19 vaccine acceptance in the United States is disturbingly low among health care workers, particularly nurses, technicians, and those in nonclinical roles, compared to physicians.^6,30 Many of the strategies for addressing vaccine hesitancy among the general population can also apply to health care personnel (eg, vaccine education, addressing misinformation, delivering information from a trusted source). Health care personnel may also be subject to vaccine mandates by their employers, which have demonstrated increases in vaccination rates for influenza.³¹ Given that COVID-19 vaccination recommendations made by HCPs are associated with greater vaccine intentions and uptake,⁶ reducing hesitancy among health care workers is a critical first step to achieving optimal implementation.

CORRESPONDENCE
Nicole Mayo, PhD, 236 Pearl Street, Rochester, NY 14607; [email protected]

It’s rare for a child to die after a tonsillectomy, but children who die are more likely to have a complex chronic condition such as cerebral palsy or Down syndrome, according to a retrospective cohort study published in JAMA.

“Among children undergoing tonsillectomy, the rate of postoperative death was 7 per 100,000 operations overall, [but] among children with complex chronic conditions, the rate of postoperative death was 117 per 100,000 operations, representing 44% of overall deaths,” write researchers at the University of Wisconsin–Madison. “These findings may inform decisionmaking for pediatric tonsillectomy.”

The rate of death in children after tonsillectomy has been uncertain, the authors write. Specific mortality rates for children at increased risk for complications, including those under 3 years old and those with sleep-disordered breathing or complex chronic conditions, have not been available.

To learn how likely children undergoing tonsillectomy are to die after their surgery, as well as which children are most at risk, lead study author M. Bruce Edmonson, MD, MPH, department of pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, and his colleagues drew data from five states, including ambulatory surgery, inpatient, and emergency department discharge data sets provided by the Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality for California, Florida, Maryland, New York, and Wisconsin.

Participants included 504,262 patients under 21 years of age whose discharge records linked their inpatient or outpatient tonsillectomy, with or without adenoidectomy, with at least 90 days of follow-up.

In a longitudinal analysis, the research team investigated postoperative death within 30 days or during a surgical stay lasting over 30 days. They calculated postoperative mortality per 100,000 operations, both overall and classified by age group, sleep-disordered breathing, and complex chronic conditions.

The 504,262 children ranged in age from 0 to 20 years and underwent a total of 505,182 tonsillectomies. Of these, 10.1% were performed in children aged under 3 years, 28.9% in children with sleep-disordered breathing, and 2.8% in those with complex chronic conditions.

The 36 linked postoperative deaths occurred between 2 and 20.5 days after surgical admission, and 19 (53%) of the deaths occurred after surgical discharge.

The unadjusted mortality rate was 7.04 (95% confidence interval, 4.97-9.98) deaths per 100,000 procedures. In multivariable models, children younger than 3 years and children with sleep-disordered breathing were not significantly more likely to die.

But children with complex chronic conditions were significantly more likely to die than were children without those conditions (117.22 vs. 3.87 deaths per 100,000 procedures, respectively).

Children with complex chronic conditions underwent only 2.8% of all tonsillectomies, but they accounted for 44% of postoperative deaths. Most deaths linked with complex chronic conditions occurred among children with neurologic, neuromuscular, congenital, or genetic disorders.
 

Findings can help providers advise patients and their families about tonsillectomy risks

Kavita Dedhia, MD, MSHP, attending otolaryngologist, Division of Otolaryngology, Children’s Hospital of Philadelphia, Pennsylvania, told this news organization that she was not surprised by the findings.

“This study suggests that mortality is an extremely rare complication of tonsillectomy, and that children with complex medical conditions are at highest risk,” Dr. Dedhia, who was not involved in the study, said in an email.

“Due to their underlying comorbidities, medically fragile children are considered to be at higher risk while undergoing anesthesia and surgical procedures,” she added.

Dr. Dedhia noted that nonpatient factors the study did not explore may have affected the mortality rates, including each hospital’s experience with managing children with complex medical conditions, as well as whether the hospitals were tertiary care facilities, and pediatric or adult hospitals.

She would like to know what hospital or practice characteristics may have contributed to the mortality risk and whether increased mortality in these patients is limited to tonsillectomy or is also found with other surgical procedures.

“The strength of this study is that it is large and multi-regional and that it informs providers about patient factors impacting mortality in pediatric tonsillectomy,” Dr. Dedhia said. “This study arms surgeons with data to discuss mortality risk with the families of medically complex children undergoing tonsillectomy.”

The study authors and Dr. Dedhia report no relevant financial relationships. Funding information was not provided.

A version of this article first appeared on Medscape.com.

It’s rare for a child to die after a tonsillectomy, but children who die are more likely to have a complex chronic condition such as cerebral palsy or Down syndrome, according to a retrospective cohort study published in JAMA.

“Among children undergoing tonsillectomy, the rate of postoperative death was 7 per 100,000 operations overall, [but] among children with complex chronic conditions, the rate of postoperative death was 117 per 100,000 operations, representing 44% of overall deaths,” write researchers at the University of Wisconsin–Madison. “These findings may inform decisionmaking for pediatric tonsillectomy.”

The rate of death in children after tonsillectomy has been uncertain, the authors write. Specific mortality rates for children at increased risk for complications, including those under 3 years old and those with sleep-disordered breathing or complex chronic conditions, have not been available.

To learn how likely children undergoing tonsillectomy are to die after their surgery, as well as which children are most at risk, lead study author M. Bruce Edmonson, MD, MPH, department of pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, and his colleagues drew data from five states, including ambulatory surgery, inpatient, and emergency department discharge data sets provided by the Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality for California, Florida, Maryland, New York, and Wisconsin.

Participants included 504,262 patients under 21 years of age whose discharge records linked their inpatient or outpatient tonsillectomy, with or without adenoidectomy, with at least 90 days of follow-up.

In a longitudinal analysis, the research team investigated postoperative death within 30 days or during a surgical stay lasting over 30 days. They calculated postoperative mortality per 100,000 operations, both overall and classified by age group, sleep-disordered breathing, and complex chronic conditions.

The 504,262 children ranged in age from 0 to 20 years and underwent a total of 505,182 tonsillectomies. Of these, 10.1% were performed in children aged under 3 years, 28.9% in children with sleep-disordered breathing, and 2.8% in those with complex chronic conditions.

The 36 linked postoperative deaths occurred between 2 and 20.5 days after surgical admission, and 19 (53%) of the deaths occurred after surgical discharge.

The unadjusted mortality rate was 7.04 (95% confidence interval, 4.97-9.98) deaths per 100,000 procedures. In multivariable models, children younger than 3 years and children with sleep-disordered breathing were not significantly more likely to die.

But children with complex chronic conditions were significantly more likely to die than were children without those conditions (117.22 vs. 3.87 deaths per 100,000 procedures, respectively).

Children with complex chronic conditions underwent only 2.8% of all tonsillectomies, but they accounted for 44% of postoperative deaths. Most deaths linked with complex chronic conditions occurred among children with neurologic, neuromuscular, congenital, or genetic disorders.
 

Findings can help providers advise patients and their families about tonsillectomy risks

Kavita Dedhia, MD, MSHP, attending otolaryngologist, Division of Otolaryngology, Children’s Hospital of Philadelphia, Pennsylvania, told this news organization that she was not surprised by the findings.

“This study suggests that mortality is an extremely rare complication of tonsillectomy, and that children with complex medical conditions are at highest risk,” Dr. Dedhia, who was not involved in the study, said in an email.

“Due to their underlying comorbidities, medically fragile children are considered to be at higher risk while undergoing anesthesia and surgical procedures,” she added.

Dr. Dedhia noted that nonpatient factors the study did not explore may have affected the mortality rates, including each hospital’s experience with managing children with complex medical conditions, as well as whether the hospitals were tertiary care facilities, and pediatric or adult hospitals.

She would like to know what hospital or practice characteristics may have contributed to the mortality risk and whether increased mortality in these patients is limited to tonsillectomy or is also found with other surgical procedures.

“The strength of this study is that it is large and multi-regional and that it informs providers about patient factors impacting mortality in pediatric tonsillectomy,” Dr. Dedhia said. “This study arms surgeons with data to discuss mortality risk with the families of medically complex children undergoing tonsillectomy.”

The study authors and Dr. Dedhia report no relevant financial relationships. Funding information was not provided.

A version of this article first appeared on Medscape.com.

It’s rare for a child to die after a tonsillectomy, but children who die are more likely to have a complex chronic condition such as cerebral palsy or Down syndrome, according to a retrospective cohort study published in JAMA.

“Among children undergoing tonsillectomy, the rate of postoperative death was 7 per 100,000 operations overall, [but] among children with complex chronic conditions, the rate of postoperative death was 117 per 100,000 operations, representing 44% of overall deaths,” write researchers at the University of Wisconsin–Madison. “These findings may inform decisionmaking for pediatric tonsillectomy.”

The rate of death in children after tonsillectomy has been uncertain, the authors write. Specific mortality rates for children at increased risk for complications, including those under 3 years old and those with sleep-disordered breathing or complex chronic conditions, have not been available.

To learn how likely children undergoing tonsillectomy are to die after their surgery, as well as which children are most at risk, lead study author M. Bruce Edmonson, MD, MPH, department of pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, and his colleagues drew data from five states, including ambulatory surgery, inpatient, and emergency department discharge data sets provided by the Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality for California, Florida, Maryland, New York, and Wisconsin.

Participants included 504,262 patients under 21 years of age whose discharge records linked their inpatient or outpatient tonsillectomy, with or without adenoidectomy, with at least 90 days of follow-up.

In a longitudinal analysis, the research team investigated postoperative death within 30 days or during a surgical stay lasting over 30 days. They calculated postoperative mortality per 100,000 operations, both overall and classified by age group, sleep-disordered breathing, and complex chronic conditions.

The 504,262 children ranged in age from 0 to 20 years and underwent a total of 505,182 tonsillectomies. Of these, 10.1% were performed in children aged under 3 years, 28.9% in children with sleep-disordered breathing, and 2.8% in those with complex chronic conditions.

The 36 linked postoperative deaths occurred between 2 and 20.5 days after surgical admission, and 19 (53%) of the deaths occurred after surgical discharge.

The unadjusted mortality rate was 7.04 (95% confidence interval, 4.97-9.98) deaths per 100,000 procedures. In multivariable models, children younger than 3 years and children with sleep-disordered breathing were not significantly more likely to die.

But children with complex chronic conditions were significantly more likely to die than were children without those conditions (117.22 vs. 3.87 deaths per 100,000 procedures, respectively).

Children with complex chronic conditions underwent only 2.8% of all tonsillectomies, but they accounted for 44% of postoperative deaths. Most deaths linked with complex chronic conditions occurred among children with neurologic, neuromuscular, congenital, or genetic disorders.
 

Findings can help providers advise patients and their families about tonsillectomy risks

Kavita Dedhia, MD, MSHP, attending otolaryngologist, Division of Otolaryngology, Children’s Hospital of Philadelphia, Pennsylvania, told this news organization that she was not surprised by the findings.

“This study suggests that mortality is an extremely rare complication of tonsillectomy, and that children with complex medical conditions are at highest risk,” Dr. Dedhia, who was not involved in the study, said in an email.

“Due to their underlying comorbidities, medically fragile children are considered to be at higher risk while undergoing anesthesia and surgical procedures,” she added.

Dr. Dedhia noted that nonpatient factors the study did not explore may have affected the mortality rates, including each hospital’s experience with managing children with complex medical conditions, as well as whether the hospitals were tertiary care facilities, and pediatric or adult hospitals.

She would like to know what hospital or practice characteristics may have contributed to the mortality risk and whether increased mortality in these patients is limited to tonsillectomy or is also found with other surgical procedures.

“The strength of this study is that it is large and multi-regional and that it informs providers about patient factors impacting mortality in pediatric tonsillectomy,” Dr. Dedhia said. “This study arms surgeons with data to discuss mortality risk with the families of medically complex children undergoing tonsillectomy.”

The study authors and Dr. Dedhia report no relevant financial relationships. Funding information was not provided.

A version of this article first appeared on Medscape.com.