Infectious Diseases

Unnecessary or incorrect use of topical antifungal medications is driving the spread of fungal infections like ringworm, which are becoming more difficult to treat, according to a January 11 study published in Morbidity and Mortality Weekly Report. 

If a patient’s condition is not caused by a fungus but is treated as such, treatment will be ineffective.

The authors strongly advise primary care clinicians to confirm ringworm diagnoses through lab testing before prescribing treatments such as clotrimazole or combinations of antifungals and corticosteroids. And because many topical treatments are also available over-the-counter, doctors should advise patients about how to use them correctly.

“In the last few years, there have been many antifungal resistant cases of tinea corporisand onychomycosisreported,” or ringworm and finger or toenail infections, respectively, said Shari Lipner, MD, PhD, a dermatologist at Weill Cornell Medicine in New York, and an author of the study.

Many of these cases originated in South Asia and have also been reported in Europe and Canada. In 2023, the first cases of a new strain of antifungal-resistant ringworm were reported in the United States. This species, Trichophyton indotineae, does not respond to topical medications, requiring oral treatment instead.

“It’s really a serious problem and a huge public health concern,” Dr. Lipner said. 

For the new study, Dr. Lipner and colleagues examined prescription patterns from 2021 Medicare Part D claims of topical antifungals. They report that 6.5 million topical antifungal prescriptions were filled that year, some of which included steroids in the formulation. Primary care clinicians wrote 40% of these prescriptions, the most for any clinician group. The estimate is almost certainly an undercount of topical antifungal use because the database did not include over-the-counter purchases or data from other insurance payers.

The number of prescriptions equate to 1 in every 8 Medicare Part D beneficiary receiving an antifungal, the researchers reported. 

“If I think about the patients that come into my office, I’m certainly not giving an antifungal to 1 in 8 of them, and I see a lot of fungal infections,” Dr. Lipner said. The findings suggest to Dr. Lipner that some clinicians are diagnosing ringworm by eyesight alone rather than confirming the diagnosis with techniques such as microscopy, fungal culture testing, or polymerase chain reaction testing. 

Sometimes what looks like ringworm may actually be eczema, in which case, the topical antifungal would not be appropriate, according to Avrom Caplan, MD, a dermatologist at NYU Langone Health in New York.

“If you’re prescribing something to somebody that they don’t need, you’re basically exposing them to the side effects without the benefit,” Dr. Caplan, who was not part of the study, said. 

Dr. Caplan, who reported the first cases of ringworm that only responded to oral medications in the United States, stressed that topical treatments work fine for many ringworm cases today. But if indiscriminate prescribing spurs the development of more resilient fungi, more situations may arise in which only oral medications work in the future, Dr. Caplan said. In addition, oral medications are inherently more demanding on a patient than something they can rub on their skin, Dr. Caplan added.

“We hope that physicians will really think hard about this study and change their practices if they’re not confirming the diagnosis,” Dr. Lipner said.

Dr. Lipner and Dr. Caplan report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Unnecessary or incorrect use of topical antifungal medications is driving the spread of fungal infections like ringworm, which are becoming more difficult to treat, according to a January 11 study published in Morbidity and Mortality Weekly Report. 

If a patient’s condition is not caused by a fungus but is treated as such, treatment will be ineffective.

The authors strongly advise primary care clinicians to confirm ringworm diagnoses through lab testing before prescribing treatments such as clotrimazole or combinations of antifungals and corticosteroids. And because many topical treatments are also available over-the-counter, doctors should advise patients about how to use them correctly.

“In the last few years, there have been many antifungal resistant cases of tinea corporisand onychomycosisreported,” or ringworm and finger or toenail infections, respectively, said Shari Lipner, MD, PhD, a dermatologist at Weill Cornell Medicine in New York, and an author of the study.

Many of these cases originated in South Asia and have also been reported in Europe and Canada. In 2023, the first cases of a new strain of antifungal-resistant ringworm were reported in the United States. This species, Trichophyton indotineae, does not respond to topical medications, requiring oral treatment instead.

“It’s really a serious problem and a huge public health concern,” Dr. Lipner said. 

For the new study, Dr. Lipner and colleagues examined prescription patterns from 2021 Medicare Part D claims of topical antifungals. They report that 6.5 million topical antifungal prescriptions were filled that year, some of which included steroids in the formulation. Primary care clinicians wrote 40% of these prescriptions, the most for any clinician group. The estimate is almost certainly an undercount of topical antifungal use because the database did not include over-the-counter purchases or data from other insurance payers.

The number of prescriptions equate to 1 in every 8 Medicare Part D beneficiary receiving an antifungal, the researchers reported. 

“If I think about the patients that come into my office, I’m certainly not giving an antifungal to 1 in 8 of them, and I see a lot of fungal infections,” Dr. Lipner said. The findings suggest to Dr. Lipner that some clinicians are diagnosing ringworm by eyesight alone rather than confirming the diagnosis with techniques such as microscopy, fungal culture testing, or polymerase chain reaction testing. 

Sometimes what looks like ringworm may actually be eczema, in which case, the topical antifungal would not be appropriate, according to Avrom Caplan, MD, a dermatologist at NYU Langone Health in New York.

“If you’re prescribing something to somebody that they don’t need, you’re basically exposing them to the side effects without the benefit,” Dr. Caplan, who was not part of the study, said. 

Dr. Caplan, who reported the first cases of ringworm that only responded to oral medications in the United States, stressed that topical treatments work fine for many ringworm cases today. But if indiscriminate prescribing spurs the development of more resilient fungi, more situations may arise in which only oral medications work in the future, Dr. Caplan said. In addition, oral medications are inherently more demanding on a patient than something they can rub on their skin, Dr. Caplan added.

“We hope that physicians will really think hard about this study and change their practices if they’re not confirming the diagnosis,” Dr. Lipner said.

Dr. Lipner and Dr. Caplan report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Unnecessary or incorrect use of topical antifungal medications is driving the spread of fungal infections like ringworm, which are becoming more difficult to treat, according to a January 11 study published in Morbidity and Mortality Weekly Report. 

If a patient’s condition is not caused by a fungus but is treated as such, treatment will be ineffective.

The authors strongly advise primary care clinicians to confirm ringworm diagnoses through lab testing before prescribing treatments such as clotrimazole or combinations of antifungals and corticosteroids. And because many topical treatments are also available over-the-counter, doctors should advise patients about how to use them correctly.

“In the last few years, there have been many antifungal resistant cases of tinea corporisand onychomycosisreported,” or ringworm and finger or toenail infections, respectively, said Shari Lipner, MD, PhD, a dermatologist at Weill Cornell Medicine in New York, and an author of the study.

Many of these cases originated in South Asia and have also been reported in Europe and Canada. In 2023, the first cases of a new strain of antifungal-resistant ringworm were reported in the United States. This species, Trichophyton indotineae, does not respond to topical medications, requiring oral treatment instead.

“It’s really a serious problem and a huge public health concern,” Dr. Lipner said. 

For the new study, Dr. Lipner and colleagues examined prescription patterns from 2021 Medicare Part D claims of topical antifungals. They report that 6.5 million topical antifungal prescriptions were filled that year, some of which included steroids in the formulation. Primary care clinicians wrote 40% of these prescriptions, the most for any clinician group. The estimate is almost certainly an undercount of topical antifungal use because the database did not include over-the-counter purchases or data from other insurance payers.

The number of prescriptions equate to 1 in every 8 Medicare Part D beneficiary receiving an antifungal, the researchers reported. 

“If I think about the patients that come into my office, I’m certainly not giving an antifungal to 1 in 8 of them, and I see a lot of fungal infections,” Dr. Lipner said. The findings suggest to Dr. Lipner that some clinicians are diagnosing ringworm by eyesight alone rather than confirming the diagnosis with techniques such as microscopy, fungal culture testing, or polymerase chain reaction testing. 

Sometimes what looks like ringworm may actually be eczema, in which case, the topical antifungal would not be appropriate, according to Avrom Caplan, MD, a dermatologist at NYU Langone Health in New York.

“If you’re prescribing something to somebody that they don’t need, you’re basically exposing them to the side effects without the benefit,” Dr. Caplan, who was not part of the study, said. 

Dr. Caplan, who reported the first cases of ringworm that only responded to oral medications in the United States, stressed that topical treatments work fine for many ringworm cases today. But if indiscriminate prescribing spurs the development of more resilient fungi, more situations may arise in which only oral medications work in the future, Dr. Caplan said. In addition, oral medications are inherently more demanding on a patient than something they can rub on their skin, Dr. Caplan added.

“We hope that physicians will really think hard about this study and change their practices if they’re not confirming the diagnosis,” Dr. Lipner said.

Dr. Lipner and Dr. Caplan report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Daily toothbrushing is associated with a reduced incidence of hospital-acquired pneumonia (HAP), especially in patients on mechanical ventilation. This practice also is associated with lower intensive care unit (ICU) mortality, shorter ICU admissions, and shorter ventilator dependency. These are the findings of a meta-analysis published in JAMA Internal Medicine. Hospital policies must reassess the importance of oral hygiene even, or perhaps especially, in situations in which attention is focused elsewhere.

Oral Microbiota and Lungs

HAP largely results from the aspiration of microorganisms present in the oral cavity. In fact, the oral microbiota comprises an estimated 700 species of bacteria, fungi, viruses, and protozoa. There is a known link between oral health and the development of pneumonia, and rigorous oral hygiene is part of the recommendations for preventing HAP. But the methods that should be used for ensuring good hygiene haven’t been determined. The use of chlorhexidine-based mouthwash is debated because there is no evidence that it prevents pneumonia and because some studies have suggested a link between chlorhexidine and higher mortality rates.

Toothbrushing is potentially more effective than antiseptic at reducing the oral microbiota because the mechanical action breaks up plaque and other biofilms. Yet, guidelines have focused very little on brushing as a measure for preventing hospital-acquired infections, meaning that every hospital has its own way of doing things.
 

What Data Show

Selina Ehrenzeller, MD, and Michael Klompas, MD, MPH, of the department of population medicine at Harvard Medical School, Boston, conducted a systematic literature analysis to identify randomized clinical studies in which daily toothbrushing was shown to affect the risk for HAP in adult hospital inpatients. Fifteen studies met the inclusion criteria and were used for the meta-analysis. The effective population size was 2786 patients.

Daily toothbrushing was associated with a 33% lower risk for HAP (relative risk [RR], 0.67) and a 29% lower risk for ICU mortality (RR, 0.81). Reduction in pneumonia incidence was significant for patients receiving invasive mechanical ventilation (RR, 0.68) but not for patients who were not receiving invasive mechanical ventilation. Toothbrushing for patients in the ICU was associated with fewer days of mechanical ventilation (mean difference, −1.24 days) and a shorter ICU length of stay (mean difference, −1.78 days). Brushing twice a day vs more frequent intervals was associated with similar effect estimates. No differences were seen in duration of stay in various ICU subdepartments and in the use of antibiotics that were linked to daily toothbrushing.
 

Expert Opinion

“This study represents an exciting contribution to infection prevention and reinforces the notion that routine toothbrushing is an essential component of standard of care in ventilated patients,” Rupak Datta, MD, PhD, assistant professor of infectious diseases at Yale University in New Haven, Connecticut, and specialist in antimicrobial resistance in hospital settings, wrote in a commentary on the study. According to Dr. Datta, there is still uncertainty regarding the importance of this practice in preventing nonventilator-HAP, as the investigators could identify only two studies with nonventilated patients that met inclusion criteria. Other studies will be needed to help standardize toothbrushing in hospital patients admitted in general. “As the literature on HAP evolves,” concluded Dr. Datta, “oral hygiene may take on an indispensable role, similar to hand washing, in preventing and controlling hospital-acquired infections.”

This article was translated from Univadis Italy, which is part of the Medscape Professional Network. A version of this article appeared on Medscape.com.

Daily toothbrushing is associated with a reduced incidence of hospital-acquired pneumonia (HAP), especially in patients on mechanical ventilation. This practice also is associated with lower intensive care unit (ICU) mortality, shorter ICU admissions, and shorter ventilator dependency. These are the findings of a meta-analysis published in JAMA Internal Medicine. Hospital policies must reassess the importance of oral hygiene even, or perhaps especially, in situations in which attention is focused elsewhere.

Oral Microbiota and Lungs

HAP largely results from the aspiration of microorganisms present in the oral cavity. In fact, the oral microbiota comprises an estimated 700 species of bacteria, fungi, viruses, and protozoa. There is a known link between oral health and the development of pneumonia, and rigorous oral hygiene is part of the recommendations for preventing HAP. But the methods that should be used for ensuring good hygiene haven’t been determined. The use of chlorhexidine-based mouthwash is debated because there is no evidence that it prevents pneumonia and because some studies have suggested a link between chlorhexidine and higher mortality rates.

Toothbrushing is potentially more effective than antiseptic at reducing the oral microbiota because the mechanical action breaks up plaque and other biofilms. Yet, guidelines have focused very little on brushing as a measure for preventing hospital-acquired infections, meaning that every hospital has its own way of doing things.
 

What Data Show

Selina Ehrenzeller, MD, and Michael Klompas, MD, MPH, of the department of population medicine at Harvard Medical School, Boston, conducted a systematic literature analysis to identify randomized clinical studies in which daily toothbrushing was shown to affect the risk for HAP in adult hospital inpatients. Fifteen studies met the inclusion criteria and were used for the meta-analysis. The effective population size was 2786 patients.

Daily toothbrushing was associated with a 33% lower risk for HAP (relative risk [RR], 0.67) and a 29% lower risk for ICU mortality (RR, 0.81). Reduction in pneumonia incidence was significant for patients receiving invasive mechanical ventilation (RR, 0.68) but not for patients who were not receiving invasive mechanical ventilation. Toothbrushing for patients in the ICU was associated with fewer days of mechanical ventilation (mean difference, −1.24 days) and a shorter ICU length of stay (mean difference, −1.78 days). Brushing twice a day vs more frequent intervals was associated with similar effect estimates. No differences were seen in duration of stay in various ICU subdepartments and in the use of antibiotics that were linked to daily toothbrushing.
 

Expert Opinion

“This study represents an exciting contribution to infection prevention and reinforces the notion that routine toothbrushing is an essential component of standard of care in ventilated patients,” Rupak Datta, MD, PhD, assistant professor of infectious diseases at Yale University in New Haven, Connecticut, and specialist in antimicrobial resistance in hospital settings, wrote in a commentary on the study. According to Dr. Datta, there is still uncertainty regarding the importance of this practice in preventing nonventilator-HAP, as the investigators could identify only two studies with nonventilated patients that met inclusion criteria. Other studies will be needed to help standardize toothbrushing in hospital patients admitted in general. “As the literature on HAP evolves,” concluded Dr. Datta, “oral hygiene may take on an indispensable role, similar to hand washing, in preventing and controlling hospital-acquired infections.”

This article was translated from Univadis Italy, which is part of the Medscape Professional Network. A version of this article appeared on Medscape.com.

Daily toothbrushing is associated with a reduced incidence of hospital-acquired pneumonia (HAP), especially in patients on mechanical ventilation. This practice also is associated with lower intensive care unit (ICU) mortality, shorter ICU admissions, and shorter ventilator dependency. These are the findings of a meta-analysis published in JAMA Internal Medicine. Hospital policies must reassess the importance of oral hygiene even, or perhaps especially, in situations in which attention is focused elsewhere.

Oral Microbiota and Lungs

HAP largely results from the aspiration of microorganisms present in the oral cavity. In fact, the oral microbiota comprises an estimated 700 species of bacteria, fungi, viruses, and protozoa. There is a known link between oral health and the development of pneumonia, and rigorous oral hygiene is part of the recommendations for preventing HAP. But the methods that should be used for ensuring good hygiene haven’t been determined. The use of chlorhexidine-based mouthwash is debated because there is no evidence that it prevents pneumonia and because some studies have suggested a link between chlorhexidine and higher mortality rates.

Toothbrushing is potentially more effective than antiseptic at reducing the oral microbiota because the mechanical action breaks up plaque and other biofilms. Yet, guidelines have focused very little on brushing as a measure for preventing hospital-acquired infections, meaning that every hospital has its own way of doing things.
 

What Data Show

Selina Ehrenzeller, MD, and Michael Klompas, MD, MPH, of the department of population medicine at Harvard Medical School, Boston, conducted a systematic literature analysis to identify randomized clinical studies in which daily toothbrushing was shown to affect the risk for HAP in adult hospital inpatients. Fifteen studies met the inclusion criteria and were used for the meta-analysis. The effective population size was 2786 patients.

Daily toothbrushing was associated with a 33% lower risk for HAP (relative risk [RR], 0.67) and a 29% lower risk for ICU mortality (RR, 0.81). Reduction in pneumonia incidence was significant for patients receiving invasive mechanical ventilation (RR, 0.68) but not for patients who were not receiving invasive mechanical ventilation. Toothbrushing for patients in the ICU was associated with fewer days of mechanical ventilation (mean difference, −1.24 days) and a shorter ICU length of stay (mean difference, −1.78 days). Brushing twice a day vs more frequent intervals was associated with similar effect estimates. No differences were seen in duration of stay in various ICU subdepartments and in the use of antibiotics that were linked to daily toothbrushing.
 

Expert Opinion

“This study represents an exciting contribution to infection prevention and reinforces the notion that routine toothbrushing is an essential component of standard of care in ventilated patients,” Rupak Datta, MD, PhD, assistant professor of infectious diseases at Yale University in New Haven, Connecticut, and specialist in antimicrobial resistance in hospital settings, wrote in a commentary on the study. According to Dr. Datta, there is still uncertainty regarding the importance of this practice in preventing nonventilator-HAP, as the investigators could identify only two studies with nonventilated patients that met inclusion criteria. Other studies will be needed to help standardize toothbrushing in hospital patients admitted in general. “As the literature on HAP evolves,” concluded Dr. Datta, “oral hygiene may take on an indispensable role, similar to hand washing, in preventing and controlling hospital-acquired infections.”

This article was translated from Univadis Italy, which is part of the Medscape Professional Network. A version of this article appeared on Medscape.com.

Two doses of the recombinant zoster vaccine (RZV) are effective against herpes zoster (HZ) for 4 years after vaccination, according to a new study published in Annals of Internal Medicine.

Findings from the prospective cohort study showed that people who received two doses of the vaccine, regardless of when they received their second dose, experienced 79% vaccine effectiveness (VE) during the first year, with effectiveness decreasing to 73% by year 4. By contrast, the rate of effectiveness during the first year was 70% for people who received a single dose, falling to 52% effectiveness by year 4.

The findings also showed that the rate of effectiveness was 65% for those taking corticosteroids.

The study was conducted between 2018 and 2022 using data from the Vaccine Safety Datalink, a collaboration between the US Centers for Disease Control and Prevention (CDC) and nine healthcare systems across the country.

Researchers evaluated the incidence of HZ, as determined by a diagnosis and prescription for antiviral medication within 7 days of diagnosis, and monitored RZV status over time.

The findings may quell fears that waiting too long for the second dose reduces the effectiveness of the herpes vaccine, according to Nicola Klein, MD, PhD, director of the Vaccine Study Center at Kaiser Permanente in Oakland, California, who led the study.

The long-term efficacy of the vaccine is especially important because older adults are now living much longer than in previous years, according to Alexandra Tien, MD, a family physician at Medical Associates of Rhode Island in Providence.

“People live these days into their 80s and even 90s,” Dr. Tien said. “That’s a large number of years to need protection for, so it’s really important to have a long-lasting vaccine.”

The CDC currently recommends two doses of RZV separated by 2-6 months for patients aged 50 years and older. Adults older than 19 years who are immunocompromised should receive two doses of RZV separated by 1-2 months, the agency said.

According to Dr. Klein, research does not show whether VE for RZV wanes after 4 years. But interim findings from another study following people in clinical trials found VE levels remained high after 7 years.

The risk for HZ increases with age, reaching a lifetime risk of 50% among adults aged 85 years. Complications like postherpetic neuralgia (PHN) — characterized by long-term tingling, numbness, and disabling pain at the site of the rash — can interfere with the quality of life and ability to function in older adults. The CDC estimates that up to 18% of people with shingles experience PHN, and the risk increases with age.

Just like with any other vaccine, patients sometimes have concerns about the potential side effects of RZV, said Dr. Tien. But those effects, such as muscle pain, nausea, and fever, are mild compared to shingles.

“I always tell patients, with any vaccine, immunization is one of the biggest bangs for your buck in healthcare because you’re preventing a problem,” Dr. Tien said.

This study was funded by the CDC through contracts with participating sites. Study authors reported no disclosures. Dr. Tien reported no disclosures.

A version of this article appeared on Medscape.com.

Two doses of the recombinant zoster vaccine (RZV) are effective against herpes zoster (HZ) for 4 years after vaccination, according to a new study published in Annals of Internal Medicine.

Findings from the prospective cohort study showed that people who received two doses of the vaccine, regardless of when they received their second dose, experienced 79% vaccine effectiveness (VE) during the first year, with effectiveness decreasing to 73% by year 4. By contrast, the rate of effectiveness during the first year was 70% for people who received a single dose, falling to 52% effectiveness by year 4.

The findings also showed that the rate of effectiveness was 65% for those taking corticosteroids.

The study was conducted between 2018 and 2022 using data from the Vaccine Safety Datalink, a collaboration between the US Centers for Disease Control and Prevention (CDC) and nine healthcare systems across the country.

Researchers evaluated the incidence of HZ, as determined by a diagnosis and prescription for antiviral medication within 7 days of diagnosis, and monitored RZV status over time.

The findings may quell fears that waiting too long for the second dose reduces the effectiveness of the herpes vaccine, according to Nicola Klein, MD, PhD, director of the Vaccine Study Center at Kaiser Permanente in Oakland, California, who led the study.

The long-term efficacy of the vaccine is especially important because older adults are now living much longer than in previous years, according to Alexandra Tien, MD, a family physician at Medical Associates of Rhode Island in Providence.

“People live these days into their 80s and even 90s,” Dr. Tien said. “That’s a large number of years to need protection for, so it’s really important to have a long-lasting vaccine.”

The CDC currently recommends two doses of RZV separated by 2-6 months for patients aged 50 years and older. Adults older than 19 years who are immunocompromised should receive two doses of RZV separated by 1-2 months, the agency said.

According to Dr. Klein, research does not show whether VE for RZV wanes after 4 years. But interim findings from another study following people in clinical trials found VE levels remained high after 7 years.

The risk for HZ increases with age, reaching a lifetime risk of 50% among adults aged 85 years. Complications like postherpetic neuralgia (PHN) — characterized by long-term tingling, numbness, and disabling pain at the site of the rash — can interfere with the quality of life and ability to function in older adults. The CDC estimates that up to 18% of people with shingles experience PHN, and the risk increases with age.

Just like with any other vaccine, patients sometimes have concerns about the potential side effects of RZV, said Dr. Tien. But those effects, such as muscle pain, nausea, and fever, are mild compared to shingles.

“I always tell patients, with any vaccine, immunization is one of the biggest bangs for your buck in healthcare because you’re preventing a problem,” Dr. Tien said.

This study was funded by the CDC through contracts with participating sites. Study authors reported no disclosures. Dr. Tien reported no disclosures.

A version of this article appeared on Medscape.com.

Two doses of the recombinant zoster vaccine (RZV) are effective against herpes zoster (HZ) for 4 years after vaccination, according to a new study published in Annals of Internal Medicine.

Findings from the prospective cohort study showed that people who received two doses of the vaccine, regardless of when they received their second dose, experienced 79% vaccine effectiveness (VE) during the first year, with effectiveness decreasing to 73% by year 4. By contrast, the rate of effectiveness during the first year was 70% for people who received a single dose, falling to 52% effectiveness by year 4.

The findings also showed that the rate of effectiveness was 65% for those taking corticosteroids.

The study was conducted between 2018 and 2022 using data from the Vaccine Safety Datalink, a collaboration between the US Centers for Disease Control and Prevention (CDC) and nine healthcare systems across the country.

Researchers evaluated the incidence of HZ, as determined by a diagnosis and prescription for antiviral medication within 7 days of diagnosis, and monitored RZV status over time.

The findings may quell fears that waiting too long for the second dose reduces the effectiveness of the herpes vaccine, according to Nicola Klein, MD, PhD, director of the Vaccine Study Center at Kaiser Permanente in Oakland, California, who led the study.

The long-term efficacy of the vaccine is especially important because older adults are now living much longer than in previous years, according to Alexandra Tien, MD, a family physician at Medical Associates of Rhode Island in Providence.

“People live these days into their 80s and even 90s,” Dr. Tien said. “That’s a large number of years to need protection for, so it’s really important to have a long-lasting vaccine.”

The CDC currently recommends two doses of RZV separated by 2-6 months for patients aged 50 years and older. Adults older than 19 years who are immunocompromised should receive two doses of RZV separated by 1-2 months, the agency said.

According to Dr. Klein, research does not show whether VE for RZV wanes after 4 years. But interim findings from another study following people in clinical trials found VE levels remained high after 7 years.

The risk for HZ increases with age, reaching a lifetime risk of 50% among adults aged 85 years. Complications like postherpetic neuralgia (PHN) — characterized by long-term tingling, numbness, and disabling pain at the site of the rash — can interfere with the quality of life and ability to function in older adults. The CDC estimates that up to 18% of people with shingles experience PHN, and the risk increases with age.

Just like with any other vaccine, patients sometimes have concerns about the potential side effects of RZV, said Dr. Tien. But those effects, such as muscle pain, nausea, and fever, are mild compared to shingles.

“I always tell patients, with any vaccine, immunization is one of the biggest bangs for your buck in healthcare because you’re preventing a problem,” Dr. Tien said.

This study was funded by the CDC through contracts with participating sites. Study authors reported no disclosures. Dr. Tien reported no disclosures.

A version of this article appeared on Medscape.com.

You may have never heard of it, but you may have had it. More evidence points to “long flu” being a real phenomenon, with a large study showing symptoms persist at least 4 weeks or more after some people are hospitalized for the flu.

Researchers compared long flu to long COVID-19 and found long flu happened less often and was less severe overall. This difference could be because the flu mostly affects the lungs whereas COVID can affect any number of organ systems in the body.

The investigators were surprised that both long flu and long COVID were linked to a greater burden of health loss, compared to either initial infection.

“I think COVID and long COVID made us realize that infections have long-term consequences, and often the toll of those long-term consequences is much larger than the toll of acute disease,” said Ziyad Al-Aly, MD, senior author of the study and chief of research and development at the VA St. Louis Health Care System.

“I know, having studied long COVID for the past 4 years, I should not be surprised. But I am in awe of what these infections can do to the long-term health of affected individuals,” said Dr. Al-Aly, who is also a clinical epidemiologist at Washington University in St. Louis.

Dr. Al-Aly and colleagues Yan Xie, PhD, and Taeyoung Choi, MS, analyzed US Department of Veterans Affairs medical records. They compared 81,280 people hospitalized with COVID to 10,985 people hospitalized with the flu before the COVID pandemic. They checked up to 18 months after initial infections to see who developed long flu or long COVID symptoms.

The study was published online in The Lancet Infectious Diseases.

It’s an interesting study, said Aaron E. Glatt, MD, chairman of the Department of Medicine and a hospital epidemiologist at Mount Sinai South Nassau in Oceanside, NY, who was not part of the research.

“There is a concern with many viruses that you can have long-term consequences,” said Dr. Glatt, who is also a fellow of the Infectious Diseases Society of America. He said the possibility of long-term symptoms with the flu is not new, “but it’s nice to have more data.”

People hospitalized with COVID had a 50% higher risk of death during the study period than people hospitalized with the flu. Put another way, for every 100 people admitted to the hospital with COVID, about eight more died than those hospitalized with the flu over the following 18 months. Hospital admissions and admissions to the intensive care unit were also higher in the long COVID group — 20 more people and nine more people, respectively, for every 100 people admitted to the hospital with COVID.

More research is needed, Dr. Glatt said. “With many of these viruses, we don’t understand what they do to the body.” A prospective study to see if antiviral treatments make a difference, for example, would be useful, he noted.

Dr. Al-Aly and colleagues would like to do more studies.

“We need to more deeply understand how and why acute infections cause long-term illness,” he said, noting that he also wants to investigate ways to prevent and treat the long-term effects.

“Much remains to be done, and we are deeply committed to doing our best to develop those answers.”

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

You may have never heard of it, but you may have had it. More evidence points to “long flu” being a real phenomenon, with a large study showing symptoms persist at least 4 weeks or more after some people are hospitalized for the flu.

Researchers compared long flu to long COVID-19 and found long flu happened less often and was less severe overall. This difference could be because the flu mostly affects the lungs whereas COVID can affect any number of organ systems in the body.

The investigators were surprised that both long flu and long COVID were linked to a greater burden of health loss, compared to either initial infection.

“I think COVID and long COVID made us realize that infections have long-term consequences, and often the toll of those long-term consequences is much larger than the toll of acute disease,” said Ziyad Al-Aly, MD, senior author of the study and chief of research and development at the VA St. Louis Health Care System.

“I know, having studied long COVID for the past 4 years, I should not be surprised. But I am in awe of what these infections can do to the long-term health of affected individuals,” said Dr. Al-Aly, who is also a clinical epidemiologist at Washington University in St. Louis.

Dr. Al-Aly and colleagues Yan Xie, PhD, and Taeyoung Choi, MS, analyzed US Department of Veterans Affairs medical records. They compared 81,280 people hospitalized with COVID to 10,985 people hospitalized with the flu before the COVID pandemic. They checked up to 18 months after initial infections to see who developed long flu or long COVID symptoms.

The study was published online in The Lancet Infectious Diseases.

It’s an interesting study, said Aaron E. Glatt, MD, chairman of the Department of Medicine and a hospital epidemiologist at Mount Sinai South Nassau in Oceanside, NY, who was not part of the research.

“There is a concern with many viruses that you can have long-term consequences,” said Dr. Glatt, who is also a fellow of the Infectious Diseases Society of America. He said the possibility of long-term symptoms with the flu is not new, “but it’s nice to have more data.”

People hospitalized with COVID had a 50% higher risk of death during the study period than people hospitalized with the flu. Put another way, for every 100 people admitted to the hospital with COVID, about eight more died than those hospitalized with the flu over the following 18 months. Hospital admissions and admissions to the intensive care unit were also higher in the long COVID group — 20 more people and nine more people, respectively, for every 100 people admitted to the hospital with COVID.

More research is needed, Dr. Glatt said. “With many of these viruses, we don’t understand what they do to the body.” A prospective study to see if antiviral treatments make a difference, for example, would be useful, he noted.

Dr. Al-Aly and colleagues would like to do more studies.

“We need to more deeply understand how and why acute infections cause long-term illness,” he said, noting that he also wants to investigate ways to prevent and treat the long-term effects.

“Much remains to be done, and we are deeply committed to doing our best to develop those answers.”

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

You may have never heard of it, but you may have had it. More evidence points to “long flu” being a real phenomenon, with a large study showing symptoms persist at least 4 weeks or more after some people are hospitalized for the flu.

Researchers compared long flu to long COVID-19 and found long flu happened less often and was less severe overall. This difference could be because the flu mostly affects the lungs whereas COVID can affect any number of organ systems in the body.

The investigators were surprised that both long flu and long COVID were linked to a greater burden of health loss, compared to either initial infection.

“I think COVID and long COVID made us realize that infections have long-term consequences, and often the toll of those long-term consequences is much larger than the toll of acute disease,” said Ziyad Al-Aly, MD, senior author of the study and chief of research and development at the VA St. Louis Health Care System.

“I know, having studied long COVID for the past 4 years, I should not be surprised. But I am in awe of what these infections can do to the long-term health of affected individuals,” said Dr. Al-Aly, who is also a clinical epidemiologist at Washington University in St. Louis.

Dr. Al-Aly and colleagues Yan Xie, PhD, and Taeyoung Choi, MS, analyzed US Department of Veterans Affairs medical records. They compared 81,280 people hospitalized with COVID to 10,985 people hospitalized with the flu before the COVID pandemic. They checked up to 18 months after initial infections to see who developed long flu or long COVID symptoms.

The study was published online in The Lancet Infectious Diseases.

It’s an interesting study, said Aaron E. Glatt, MD, chairman of the Department of Medicine and a hospital epidemiologist at Mount Sinai South Nassau in Oceanside, NY, who was not part of the research.

“There is a concern with many viruses that you can have long-term consequences,” said Dr. Glatt, who is also a fellow of the Infectious Diseases Society of America. He said the possibility of long-term symptoms with the flu is not new, “but it’s nice to have more data.”

People hospitalized with COVID had a 50% higher risk of death during the study period than people hospitalized with the flu. Put another way, for every 100 people admitted to the hospital with COVID, about eight more died than those hospitalized with the flu over the following 18 months. Hospital admissions and admissions to the intensive care unit were also higher in the long COVID group — 20 more people and nine more people, respectively, for every 100 people admitted to the hospital with COVID.

More research is needed, Dr. Glatt said. “With many of these viruses, we don’t understand what they do to the body.” A prospective study to see if antiviral treatments make a difference, for example, would be useful, he noted.

Dr. Al-Aly and colleagues would like to do more studies.

“We need to more deeply understand how and why acute infections cause long-term illness,” he said, noting that he also wants to investigate ways to prevent and treat the long-term effects.

“Much remains to be done, and we are deeply committed to doing our best to develop those answers.”

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

Non–Lyme disease, tick-borne illnesses — such as spotted fever group rickettsiosis (SFGR), ehrlichiosis, and alpha-gal syndrome (AGS) — are emerging public health threats, but whether prior tick exposures are responsible for long-term complications, such as musculoskeletal symptoms or osteoarthritis, has been unclear.

Many patients attribute their nonspecific long-term symptoms, such as musculoskeletal pain, to previous illnesses from tick bites, note authors of a study published in JAMA Network Open. But the researchers, led by Diana L. Zychowski, MD, MPH, with the Division of Infectious Diseases at the University of North Carolina at Chapel Hill, found that Ehrlichia or Rickettsia seropositivity was not associated with chronic musculoskeletal symptoms, though they write that “further investigation into the pathogenesis of [alpha-gal] syndrome is needed.”
 

Tick-Borne Illness Cases Multiplying

Cases of tick-borne illness (TBD) in the United States have multiplied in recent years. More than 50,000 cases of TBD in the United States were reported in 2019, which doubled the number of cases over the previous 2 decades, the authors note.

Most of the cases are Lyme disease, but others — including SFGR and ehrlichiosis — represent an important public health threat, especially in southeastern states, the authors write. Cases of ehrlichiosis, for example, transmitted by the lone star tick, soared more than 10-fold since 2000.

The goal of this study was to evaluate whether there was an association between prior exposure to TBDs endemic to the southeastern United States and chronic musculoskeletal symptoms and radiographic measures of osteoarthritis.

Researchers analyzed 488 blood samples from the fourth visit (2017-2018) of the Johnston County Osteoarthritis (JoCo OA) project, an ongoing population-based study in Johnston County, North Carolina. JoCo OA participants include noninstitutionalized White and Black Johnston County residents 45 years old or older with osteoarthritis.

They measured seroprevalence of Rickettsia- and Ehrlichia-specific immunoglobulin G (IgG) as well as alpha-gal immunoglobulin E (IgE) in patient samples. Only alpha-gal IgE was linked in the study with knee pain, aching, or stiffness. Antibodies to Rickettsia, Ehrlichia, and alpha-gal were not associated with radiographic, symptomatic knee osteoarthritis.

“To our knowledge,” the authors write, “this study was the first population-based seroprevalence study of SFGR, Ehrlichia, and [alpha]-gal.”

The study also found a high prevalence of TBD exposure in the cohort. More than a third (36.5%) had either an alpha-gal IgE level greater than 0.1 IU/mL, a positive test for SFGR IgG antibodies, or a positive test for Ehrlichia IgG antibodies.

Given that not every tick carries an infectious pathogen, the findings show human-tick interactions are common, they write.

“These findings suggest that substantial investment is required to examine the pathogenesis of these TBDs and interventions to reduce human-tick interactions,” the authors conclude.

This study was funded by a Creativity Hub Award from the University of North Carolina Office of the Vice Chancellor for Research. The JoCo OA project is supported in part by grants from the Association of Schools of Public Health/Centers for Disease Control and Prevention (CDC); and grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Authors reported grants from the National Institutes of Health, the CDC, and several pharmaceutical companies.

Non–Lyme disease, tick-borne illnesses — such as spotted fever group rickettsiosis (SFGR), ehrlichiosis, and alpha-gal syndrome (AGS) — are emerging public health threats, but whether prior tick exposures are responsible for long-term complications, such as musculoskeletal symptoms or osteoarthritis, has been unclear.

Many patients attribute their nonspecific long-term symptoms, such as musculoskeletal pain, to previous illnesses from tick bites, note authors of a study published in JAMA Network Open. But the researchers, led by Diana L. Zychowski, MD, MPH, with the Division of Infectious Diseases at the University of North Carolina at Chapel Hill, found that Ehrlichia or Rickettsia seropositivity was not associated with chronic musculoskeletal symptoms, though they write that “further investigation into the pathogenesis of [alpha-gal] syndrome is needed.”
 

Tick-Borne Illness Cases Multiplying

Cases of tick-borne illness (TBD) in the United States have multiplied in recent years. More than 50,000 cases of TBD in the United States were reported in 2019, which doubled the number of cases over the previous 2 decades, the authors note.

Most of the cases are Lyme disease, but others — including SFGR and ehrlichiosis — represent an important public health threat, especially in southeastern states, the authors write. Cases of ehrlichiosis, for example, transmitted by the lone star tick, soared more than 10-fold since 2000.

The goal of this study was to evaluate whether there was an association between prior exposure to TBDs endemic to the southeastern United States and chronic musculoskeletal symptoms and radiographic measures of osteoarthritis.

Researchers analyzed 488 blood samples from the fourth visit (2017-2018) of the Johnston County Osteoarthritis (JoCo OA) project, an ongoing population-based study in Johnston County, North Carolina. JoCo OA participants include noninstitutionalized White and Black Johnston County residents 45 years old or older with osteoarthritis.

They measured seroprevalence of Rickettsia- and Ehrlichia-specific immunoglobulin G (IgG) as well as alpha-gal immunoglobulin E (IgE) in patient samples. Only alpha-gal IgE was linked in the study with knee pain, aching, or stiffness. Antibodies to Rickettsia, Ehrlichia, and alpha-gal were not associated with radiographic, symptomatic knee osteoarthritis.

“To our knowledge,” the authors write, “this study was the first population-based seroprevalence study of SFGR, Ehrlichia, and [alpha]-gal.”

The study also found a high prevalence of TBD exposure in the cohort. More than a third (36.5%) had either an alpha-gal IgE level greater than 0.1 IU/mL, a positive test for SFGR IgG antibodies, or a positive test for Ehrlichia IgG antibodies.

Given that not every tick carries an infectious pathogen, the findings show human-tick interactions are common, they write.

“These findings suggest that substantial investment is required to examine the pathogenesis of these TBDs and interventions to reduce human-tick interactions,” the authors conclude.

This study was funded by a Creativity Hub Award from the University of North Carolina Office of the Vice Chancellor for Research. The JoCo OA project is supported in part by grants from the Association of Schools of Public Health/Centers for Disease Control and Prevention (CDC); and grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Authors reported grants from the National Institutes of Health, the CDC, and several pharmaceutical companies.

Non–Lyme disease, tick-borne illnesses — such as spotted fever group rickettsiosis (SFGR), ehrlichiosis, and alpha-gal syndrome (AGS) — are emerging public health threats, but whether prior tick exposures are responsible for long-term complications, such as musculoskeletal symptoms or osteoarthritis, has been unclear.

Many patients attribute their nonspecific long-term symptoms, such as musculoskeletal pain, to previous illnesses from tick bites, note authors of a study published in JAMA Network Open. But the researchers, led by Diana L. Zychowski, MD, MPH, with the Division of Infectious Diseases at the University of North Carolina at Chapel Hill, found that Ehrlichia or Rickettsia seropositivity was not associated with chronic musculoskeletal symptoms, though they write that “further investigation into the pathogenesis of [alpha-gal] syndrome is needed.”
 

Tick-Borne Illness Cases Multiplying

Cases of tick-borne illness (TBD) in the United States have multiplied in recent years. More than 50,000 cases of TBD in the United States were reported in 2019, which doubled the number of cases over the previous 2 decades, the authors note.

Most of the cases are Lyme disease, but others — including SFGR and ehrlichiosis — represent an important public health threat, especially in southeastern states, the authors write. Cases of ehrlichiosis, for example, transmitted by the lone star tick, soared more than 10-fold since 2000.

The goal of this study was to evaluate whether there was an association between prior exposure to TBDs endemic to the southeastern United States and chronic musculoskeletal symptoms and radiographic measures of osteoarthritis.

Researchers analyzed 488 blood samples from the fourth visit (2017-2018) of the Johnston County Osteoarthritis (JoCo OA) project, an ongoing population-based study in Johnston County, North Carolina. JoCo OA participants include noninstitutionalized White and Black Johnston County residents 45 years old or older with osteoarthritis.

They measured seroprevalence of Rickettsia- and Ehrlichia-specific immunoglobulin G (IgG) as well as alpha-gal immunoglobulin E (IgE) in patient samples. Only alpha-gal IgE was linked in the study with knee pain, aching, or stiffness. Antibodies to Rickettsia, Ehrlichia, and alpha-gal were not associated with radiographic, symptomatic knee osteoarthritis.

“To our knowledge,” the authors write, “this study was the first population-based seroprevalence study of SFGR, Ehrlichia, and [alpha]-gal.”

The study also found a high prevalence of TBD exposure in the cohort. More than a third (36.5%) had either an alpha-gal IgE level greater than 0.1 IU/mL, a positive test for SFGR IgG antibodies, or a positive test for Ehrlichia IgG antibodies.

Given that not every tick carries an infectious pathogen, the findings show human-tick interactions are common, they write.

“These findings suggest that substantial investment is required to examine the pathogenesis of these TBDs and interventions to reduce human-tick interactions,” the authors conclude.

This study was funded by a Creativity Hub Award from the University of North Carolina Office of the Vice Chancellor for Research. The JoCo OA project is supported in part by grants from the Association of Schools of Public Health/Centers for Disease Control and Prevention (CDC); and grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Authors reported grants from the National Institutes of Health, the CDC, and several pharmaceutical companies.

Delivered at 34 weeks’ gestation, Baby “Alex” had an enlarged liver and spleen on his initial newborn exam, poor tone, and a diffuse, peeling rash. Baby “Aaliyah” was born at term and appeared healthy. By 1 month of age, she was gaining weight poorly and developed copious nasal drainage and a salmon-colored rash on the soles of her feet.

The connection? Both babies were ultimately diagnosed with congenital syphilis. Infections in both babies could have been prevented if their mothers had been tested for syphilis and treated during pregnancy. Alex’s mom had no prenatal care. Aaliyah’s mom had tested negative for syphilis during her first trimester but had not been re-tested, despite sharing with her health care provider that she had a new sexual partner.

Alex and Aaliyah are representative of what Centers for Disease Control and Prevention (CDC) Chief Medical Officer Debra Houry, MD, MPH, calls a “family tragedy.” Cases of congenital syphilis are rising rapidly in the United States, reaching a 30-year high in 2021.¹ Cases increased by 755% between 2012 and 2021, from 335 in 2012 to 2,865 in 2021. In 2022, cases rose again: 3,761 cases of congenital syphilis were reported, including 231 stillbirths and 51 infant deaths. Infants with congenital syphilis are at risk for lifelong complications, including deafness, blindness, and intellectual disability.

Most of these cases were preventable. Congenital syphilis is rare when pregnant people complete adequate treatment at least 30 days before delivery. In 2022, lack of testing or timely testing contributed to 36.8% of congenital syphilis cases. Nearly 40% of birth parents of infected babies received inadequate treatment during pregnancy, and 11.2% received no treatment or treatment was not documented.

Cases of congenital syphilis have increased in all demographic groups and all US Census Bureau regions, but racial and geographic disparities exist, suggesting ongoing barriers to care related to social determinants of health. In 2021, the highest rates of congenital syphilis were among babies born to individuals who were non-Hispanic American Indian or Alaska Native (384 cases per 100,000 live births), non-Hispanic Native Hawaiian or other Pacific Islander (192 cases per 100,000 live births), and non-Hispanic Black or African American (169 cases per 100,000 live births). Six states had rates of congenital syphilis that exceeded 160 cases per 100,000 population, including Arizona, New Mexico, Louisiana, Mississippi, Texas, and Oklahoma. That is more than twice the national rate of 77.9 cases/100,000.
 

Reducing the Risk

To reduce rates of congenital syphilis in all people, barriers to testing must be eliminated. The CDC recommends that all pregnant people be tested early in pregnancy, with repeat testing at 28 weeks and at delivery for those at increased risk for infection based on individual risk factors or residence in a high-prevalence community. Rapid syphilis testing and treatment during pregnancy is recommended in settings such as emergency departments, syringe service programs, prisons/jails, and maternal and child health programs to minimize missed opportunities for care.

While pediatric clinicians rarely care for pregnant patients, they also have an essential role to play in reducing the adverse health outcomes associated with congenital syphilis. No infant should be discharged from the newborn nursery without confirming that the birth parent was tested for syphilis at least once and was treated appropriately if positive. Appropriate treatment during pregnancy is a single dose of benzathine penicillin G for primary, secondary, or early latent syphilis. Late-latent syphilis or syphilis of unknown duration is treated with three doses of benzathine penicillin G spaced 7-9 days apart. If the doses are given further than 9 days apart, treatment is considered inadequate, and the series of doses must be restarted. Benzathine penicillin G remains in short supply in the United States, but is the only drug recommended to treat syphilis during pregnancy.

Collaboration between obstetrical and newborn care providers is essential. Those who care for newborns need easy access to birthing parents’ syphilis treatment results. As more health care facilities implement routine syphilis testing at delivery, rapid syphilis testing must be available to avoid prolonging newborn hospital stays.

Pediatricians need to maintain an index of suspicion for congenital syphilis, regardless of maternal history, because symptomatic congenital syphilis can mimic a variety of infectious and noninfectious conditions. Most infected infants look normal at birth. While the majority of cases of congenital syphilis are identified in the newborn period, a 2021 paper published in Pediatrics described 84 infants born between 2014 and 2018 who were diagnosed beyond a month of age.² These represented 2.2% of all infants born with congenital syphilis. Common symptoms included rash, snuffles, and hepatomegaly. Sixty-nine percent of infants who had long bone radiographs obtained had findings consistent with congenital syphilis. Typical imaging findings include periostitis and demineralization of the metaphysis and diaphysis of long bones, although fractures can also occur. Case reports describe infants who presented with fractures and were initially evaluated for nonaccidental trauma.³

Another critical approach is to treat syphilis in people of childbearing age before pregnancy occurs. The CDC recommends syphilis testing for sexually active females 18-44 years of age and living in communities with high rates of syphilis. County-specific specific rates of syphilis rates are available at https://www.cdc.gov/nchhstp/atlas/syphilis/. Point-of-care tests are now available for syphilis and may facilitate timely treatment. 

Additional resources describing syphilis testing and treatment are available from the CDC and the American Academy of Pediatrics.

Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She is a member of the AAP’s Committee on Infectious Diseases and one of the lead authors of the AAP’s Recommendations for Prevention and Control of Influenza in Children, 2022-2023. The opinions expressed in this article are her own. Dr. Bryant discloses that she has served as an investigator on clinical trials funded by Pfizer, Enanta, and Gilead. Email her at [email protected]. (Also [email protected].)

References

1. McDonald R et al. Vital Signs: Missed Opportunities for Preventing Congenital Syphilis — United States, 2022. MMWR Morb Mortal Wkly Rep. 2023 Nov 17;72(46):1269-74. doi: 10.15585/mmwr.mm7246e1. 

2. Kimball A et al. Congenital Syphilis Diagnosed Beyond the Neonatal Period in the United States: 2014-2018. Pediatrics. 2021 Sep;148(3):e2020049080. doi: 10.1542/peds.2020-049080. 

3. Jacobs K et al. Congenital Syphilis Misdiagnosed as Suspected Nonaccidental Trauma. Pediatrics. 2019 Oct;144(4):e20191564. doi: 10.1542/peds.2019-1564. 

Delivered at 34 weeks’ gestation, Baby “Alex” had an enlarged liver and spleen on his initial newborn exam, poor tone, and a diffuse, peeling rash. Baby “Aaliyah” was born at term and appeared healthy. By 1 month of age, she was gaining weight poorly and developed copious nasal drainage and a salmon-colored rash on the soles of her feet.

The connection? Both babies were ultimately diagnosed with congenital syphilis. Infections in both babies could have been prevented if their mothers had been tested for syphilis and treated during pregnancy. Alex’s mom had no prenatal care. Aaliyah’s mom had tested negative for syphilis during her first trimester but had not been re-tested, despite sharing with her health care provider that she had a new sexual partner.

Alex and Aaliyah are representative of what Centers for Disease Control and Prevention (CDC) Chief Medical Officer Debra Houry, MD, MPH, calls a “family tragedy.” Cases of congenital syphilis are rising rapidly in the United States, reaching a 30-year high in 2021.¹ Cases increased by 755% between 2012 and 2021, from 335 in 2012 to 2,865 in 2021. In 2022, cases rose again: 3,761 cases of congenital syphilis were reported, including 231 stillbirths and 51 infant deaths. Infants with congenital syphilis are at risk for lifelong complications, including deafness, blindness, and intellectual disability.

Most of these cases were preventable. Congenital syphilis is rare when pregnant people complete adequate treatment at least 30 days before delivery. In 2022, lack of testing or timely testing contributed to 36.8% of congenital syphilis cases. Nearly 40% of birth parents of infected babies received inadequate treatment during pregnancy, and 11.2% received no treatment or treatment was not documented.

Cases of congenital syphilis have increased in all demographic groups and all US Census Bureau regions, but racial and geographic disparities exist, suggesting ongoing barriers to care related to social determinants of health. In 2021, the highest rates of congenital syphilis were among babies born to individuals who were non-Hispanic American Indian or Alaska Native (384 cases per 100,000 live births), non-Hispanic Native Hawaiian or other Pacific Islander (192 cases per 100,000 live births), and non-Hispanic Black or African American (169 cases per 100,000 live births). Six states had rates of congenital syphilis that exceeded 160 cases per 100,000 population, including Arizona, New Mexico, Louisiana, Mississippi, Texas, and Oklahoma. That is more than twice the national rate of 77.9 cases/100,000.
 

Reducing the Risk

To reduce rates of congenital syphilis in all people, barriers to testing must be eliminated. The CDC recommends that all pregnant people be tested early in pregnancy, with repeat testing at 28 weeks and at delivery for those at increased risk for infection based on individual risk factors or residence in a high-prevalence community. Rapid syphilis testing and treatment during pregnancy is recommended in settings such as emergency departments, syringe service programs, prisons/jails, and maternal and child health programs to minimize missed opportunities for care.

While pediatric clinicians rarely care for pregnant patients, they also have an essential role to play in reducing the adverse health outcomes associated with congenital syphilis. No infant should be discharged from the newborn nursery without confirming that the birth parent was tested for syphilis at least once and was treated appropriately if positive. Appropriate treatment during pregnancy is a single dose of benzathine penicillin G for primary, secondary, or early latent syphilis. Late-latent syphilis or syphilis of unknown duration is treated with three doses of benzathine penicillin G spaced 7-9 days apart. If the doses are given further than 9 days apart, treatment is considered inadequate, and the series of doses must be restarted. Benzathine penicillin G remains in short supply in the United States, but is the only drug recommended to treat syphilis during pregnancy.

Collaboration between obstetrical and newborn care providers is essential. Those who care for newborns need easy access to birthing parents’ syphilis treatment results. As more health care facilities implement routine syphilis testing at delivery, rapid syphilis testing must be available to avoid prolonging newborn hospital stays.

Pediatricians need to maintain an index of suspicion for congenital syphilis, regardless of maternal history, because symptomatic congenital syphilis can mimic a variety of infectious and noninfectious conditions. Most infected infants look normal at birth. While the majority of cases of congenital syphilis are identified in the newborn period, a 2021 paper published in Pediatrics described 84 infants born between 2014 and 2018 who were diagnosed beyond a month of age.² These represented 2.2% of all infants born with congenital syphilis. Common symptoms included rash, snuffles, and hepatomegaly. Sixty-nine percent of infants who had long bone radiographs obtained had findings consistent with congenital syphilis. Typical imaging findings include periostitis and demineralization of the metaphysis and diaphysis of long bones, although fractures can also occur. Case reports describe infants who presented with fractures and were initially evaluated for nonaccidental trauma.³

Another critical approach is to treat syphilis in people of childbearing age before pregnancy occurs. The CDC recommends syphilis testing for sexually active females 18-44 years of age and living in communities with high rates of syphilis. County-specific specific rates of syphilis rates are available at https://www.cdc.gov/nchhstp/atlas/syphilis/. Point-of-care tests are now available for syphilis and may facilitate timely treatment. 

Additional resources describing syphilis testing and treatment are available from the CDC and the American Academy of Pediatrics.

Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She is a member of the AAP’s Committee on Infectious Diseases and one of the lead authors of the AAP’s Recommendations for Prevention and Control of Influenza in Children, 2022-2023. The opinions expressed in this article are her own. Dr. Bryant discloses that she has served as an investigator on clinical trials funded by Pfizer, Enanta, and Gilead. Email her at [email protected]. (Also [email protected].)

References

1. McDonald R et al. Vital Signs: Missed Opportunities for Preventing Congenital Syphilis — United States, 2022. MMWR Morb Mortal Wkly Rep. 2023 Nov 17;72(46):1269-74. doi: 10.15585/mmwr.mm7246e1. 

2. Kimball A et al. Congenital Syphilis Diagnosed Beyond the Neonatal Period in the United States: 2014-2018. Pediatrics. 2021 Sep;148(3):e2020049080. doi: 10.1542/peds.2020-049080. 

3. Jacobs K et al. Congenital Syphilis Misdiagnosed as Suspected Nonaccidental Trauma. Pediatrics. 2019 Oct;144(4):e20191564. doi: 10.1542/peds.2019-1564. 

Delivered at 34 weeks’ gestation, Baby “Alex” had an enlarged liver and spleen on his initial newborn exam, poor tone, and a diffuse, peeling rash. Baby “Aaliyah” was born at term and appeared healthy. By 1 month of age, she was gaining weight poorly and developed copious nasal drainage and a salmon-colored rash on the soles of her feet.

The connection? Both babies were ultimately diagnosed with congenital syphilis. Infections in both babies could have been prevented if their mothers had been tested for syphilis and treated during pregnancy. Alex’s mom had no prenatal care. Aaliyah’s mom had tested negative for syphilis during her first trimester but had not been re-tested, despite sharing with her health care provider that she had a new sexual partner.

Alex and Aaliyah are representative of what Centers for Disease Control and Prevention (CDC) Chief Medical Officer Debra Houry, MD, MPH, calls a “family tragedy.” Cases of congenital syphilis are rising rapidly in the United States, reaching a 30-year high in 2021.¹ Cases increased by 755% between 2012 and 2021, from 335 in 2012 to 2,865 in 2021. In 2022, cases rose again: 3,761 cases of congenital syphilis were reported, including 231 stillbirths and 51 infant deaths. Infants with congenital syphilis are at risk for lifelong complications, including deafness, blindness, and intellectual disability.

Most of these cases were preventable. Congenital syphilis is rare when pregnant people complete adequate treatment at least 30 days before delivery. In 2022, lack of testing or timely testing contributed to 36.8% of congenital syphilis cases. Nearly 40% of birth parents of infected babies received inadequate treatment during pregnancy, and 11.2% received no treatment or treatment was not documented.

Cases of congenital syphilis have increased in all demographic groups and all US Census Bureau regions, but racial and geographic disparities exist, suggesting ongoing barriers to care related to social determinants of health. In 2021, the highest rates of congenital syphilis were among babies born to individuals who were non-Hispanic American Indian or Alaska Native (384 cases per 100,000 live births), non-Hispanic Native Hawaiian or other Pacific Islander (192 cases per 100,000 live births), and non-Hispanic Black or African American (169 cases per 100,000 live births). Six states had rates of congenital syphilis that exceeded 160 cases per 100,000 population, including Arizona, New Mexico, Louisiana, Mississippi, Texas, and Oklahoma. That is more than twice the national rate of 77.9 cases/100,000.
 

Reducing the Risk

To reduce rates of congenital syphilis in all people, barriers to testing must be eliminated. The CDC recommends that all pregnant people be tested early in pregnancy, with repeat testing at 28 weeks and at delivery for those at increased risk for infection based on individual risk factors or residence in a high-prevalence community. Rapid syphilis testing and treatment during pregnancy is recommended in settings such as emergency departments, syringe service programs, prisons/jails, and maternal and child health programs to minimize missed opportunities for care.

While pediatric clinicians rarely care for pregnant patients, they also have an essential role to play in reducing the adverse health outcomes associated with congenital syphilis. No infant should be discharged from the newborn nursery without confirming that the birth parent was tested for syphilis at least once and was treated appropriately if positive. Appropriate treatment during pregnancy is a single dose of benzathine penicillin G for primary, secondary, or early latent syphilis. Late-latent syphilis or syphilis of unknown duration is treated with three doses of benzathine penicillin G spaced 7-9 days apart. If the doses are given further than 9 days apart, treatment is considered inadequate, and the series of doses must be restarted. Benzathine penicillin G remains in short supply in the United States, but is the only drug recommended to treat syphilis during pregnancy.

Collaboration between obstetrical and newborn care providers is essential. Those who care for newborns need easy access to birthing parents’ syphilis treatment results. As more health care facilities implement routine syphilis testing at delivery, rapid syphilis testing must be available to avoid prolonging newborn hospital stays.

Pediatricians need to maintain an index of suspicion for congenital syphilis, regardless of maternal history, because symptomatic congenital syphilis can mimic a variety of infectious and noninfectious conditions. Most infected infants look normal at birth. While the majority of cases of congenital syphilis are identified in the newborn period, a 2021 paper published in Pediatrics described 84 infants born between 2014 and 2018 who were diagnosed beyond a month of age.² These represented 2.2% of all infants born with congenital syphilis. Common symptoms included rash, snuffles, and hepatomegaly. Sixty-nine percent of infants who had long bone radiographs obtained had findings consistent with congenital syphilis. Typical imaging findings include periostitis and demineralization of the metaphysis and diaphysis of long bones, although fractures can also occur. Case reports describe infants who presented with fractures and were initially evaluated for nonaccidental trauma.³

Another critical approach is to treat syphilis in people of childbearing age before pregnancy occurs. The CDC recommends syphilis testing for sexually active females 18-44 years of age and living in communities with high rates of syphilis. County-specific specific rates of syphilis rates are available at https://www.cdc.gov/nchhstp/atlas/syphilis/. Point-of-care tests are now available for syphilis and may facilitate timely treatment. 

Additional resources describing syphilis testing and treatment are available from the CDC and the American Academy of Pediatrics.

Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She is a member of the AAP’s Committee on Infectious Diseases and one of the lead authors of the AAP’s Recommendations for Prevention and Control of Influenza in Children, 2022-2023. The opinions expressed in this article are her own. Dr. Bryant discloses that she has served as an investigator on clinical trials funded by Pfizer, Enanta, and Gilead. Email her at [email protected]. (Also [email protected].)

References

1. McDonald R et al. Vital Signs: Missed Opportunities for Preventing Congenital Syphilis — United States, 2022. MMWR Morb Mortal Wkly Rep. 2023 Nov 17;72(46):1269-74. doi: 10.15585/mmwr.mm7246e1. 

2. Kimball A et al. Congenital Syphilis Diagnosed Beyond the Neonatal Period in the United States: 2014-2018. Pediatrics. 2021 Sep;148(3):e2020049080. doi: 10.1542/peds.2020-049080. 

3. Jacobs K et al. Congenital Syphilis Misdiagnosed as Suspected Nonaccidental Trauma. Pediatrics. 2019 Oct;144(4):e20191564. doi: 10.1542/peds.2019-1564. 

On January 5, the Food and Drug Administration (FDA) approved berdazimer gel 10.3% for the treatment of molluscum contagiosum (MC) in adults and children aged 1 year or older.

Approval of berdazimer, a topical nitric oxide–releasing agent, was based largely on a 12-week pivotal phase 3 trial known as B-SIMPLE4, in which 891 patients with a mean age of 6.6 years (range, 0.9-47.5 years) were randomly assigned to treatment with berdazimer gel 10.3% or a vehicle gel applied in a thin layer to all lesions once daily. At 12 weeks, 32.4% of patients in the berdazimer group achieved complete clearance of MC lesions compared with 19.7% of those in the vehicle group (P < .001).

Only 4.1% of patients on berdazimer and 0.7% of those on the vehicle experienced adverse events that led to discontinuation of treatment. The most common adverse events in both groups were application-site pain and erythema, and most of these were mild or moderate.

According to a press release announcing the approval from Ligand Pharmaceuticals, which acquired berdazimer topical gel from Novan in September 2023, the development makes berdazimer topical gel 10.3% the first and only topical prescription medication that can be applied by patients, parents, or caregivers at home; outside of a physician›s office; or outside of other medical settings to treat MC. Nitric oxide has been shown to have antiviral effects, although the mechanism of action of berdazimer for treating molluscum “is unknown,” the company said in the release. 

The drug will be marketed under the name Zelsuvmi and is expected to be available in the second half of 2024.

On July 21, 2023, topical cantharidin became the first approved treatment of MC for adults and pediatric patients aged 2 years or older, with the FDA approval of a drug-device combination (Ycanth) that contains a formulation of cantharidin solution 0.7% and is administered by healthcare professionals. 

A version of this article appeared on Medscape.com.

On January 5, the Food and Drug Administration (FDA) approved berdazimer gel 10.3% for the treatment of molluscum contagiosum (MC) in adults and children aged 1 year or older.

Approval of berdazimer, a topical nitric oxide–releasing agent, was based largely on a 12-week pivotal phase 3 trial known as B-SIMPLE4, in which 891 patients with a mean age of 6.6 years (range, 0.9-47.5 years) were randomly assigned to treatment with berdazimer gel 10.3% or a vehicle gel applied in a thin layer to all lesions once daily. At 12 weeks, 32.4% of patients in the berdazimer group achieved complete clearance of MC lesions compared with 19.7% of those in the vehicle group (P < .001).

Only 4.1% of patients on berdazimer and 0.7% of those on the vehicle experienced adverse events that led to discontinuation of treatment. The most common adverse events in both groups were application-site pain and erythema, and most of these were mild or moderate.

According to a press release announcing the approval from Ligand Pharmaceuticals, which acquired berdazimer topical gel from Novan in September 2023, the development makes berdazimer topical gel 10.3% the first and only topical prescription medication that can be applied by patients, parents, or caregivers at home; outside of a physician›s office; or outside of other medical settings to treat MC. Nitric oxide has been shown to have antiviral effects, although the mechanism of action of berdazimer for treating molluscum “is unknown,” the company said in the release. 

The drug will be marketed under the name Zelsuvmi and is expected to be available in the second half of 2024.

On July 21, 2023, topical cantharidin became the first approved treatment of MC for adults and pediatric patients aged 2 years or older, with the FDA approval of a drug-device combination (Ycanth) that contains a formulation of cantharidin solution 0.7% and is administered by healthcare professionals. 

A version of this article appeared on Medscape.com.

On January 5, the Food and Drug Administration (FDA) approved berdazimer gel 10.3% for the treatment of molluscum contagiosum (MC) in adults and children aged 1 year or older.

Approval of berdazimer, a topical nitric oxide–releasing agent, was based largely on a 12-week pivotal phase 3 trial known as B-SIMPLE4, in which 891 patients with a mean age of 6.6 years (range, 0.9-47.5 years) were randomly assigned to treatment with berdazimer gel 10.3% or a vehicle gel applied in a thin layer to all lesions once daily. At 12 weeks, 32.4% of patients in the berdazimer group achieved complete clearance of MC lesions compared with 19.7% of those in the vehicle group (P < .001).

Only 4.1% of patients on berdazimer and 0.7% of those on the vehicle experienced adverse events that led to discontinuation of treatment. The most common adverse events in both groups were application-site pain and erythema, and most of these were mild or moderate.

According to a press release announcing the approval from Ligand Pharmaceuticals, which acquired berdazimer topical gel from Novan in September 2023, the development makes berdazimer topical gel 10.3% the first and only topical prescription medication that can be applied by patients, parents, or caregivers at home; outside of a physician›s office; or outside of other medical settings to treat MC. Nitric oxide has been shown to have antiviral effects, although the mechanism of action of berdazimer for treating molluscum “is unknown,” the company said in the release. 

The drug will be marketed under the name Zelsuvmi and is expected to be available in the second half of 2024.

On July 21, 2023, topical cantharidin became the first approved treatment of MC for adults and pediatric patients aged 2 years or older, with the FDA approval of a drug-device combination (Ycanth) that contains a formulation of cantharidin solution 0.7% and is administered by healthcare professionals. 

A version of this article appeared on Medscape.com.

A new analysis supports using the smallpox antiviral tecovirimat (TPOXX/ST-246) in HIV patients showing the first symptoms of the human smallpox disease mpox (monkeypox), caused by the variola virus.

In a small prospective matched cohort analysis, people with HIV (PWH) and mpox disease who received tecovirimat within 7 days of symptom onset were 13 times less likely to experience progression, compared with PWH not prescribed tecovirimat within that window. In a matched cohort of 112 PWH, mpox disease progression occurred in 5.4% in an early tecovirimat group and in 26.8% in a late- or no-tecovirimat group, for a paired odds ratio of 13.00 (95% CI, 1.71-99.40; P = .002).

“Results of the present study suggest that tecovirimat treatment should be started early at the time of suspected mpox diagnosis in all PWH, especially in those with nonsuppressed HIV viremia or mucosal site involvement,” wrote a team led by Bruce Aldred, MD, of the Division of Infectious Diseases in the Department of Medicine at Emory University School of Medicine in Atlanta, in JAMA Internal Medicine. Early symptoms of mpox include skin rash and mucosal lesions, along with viral symptoms such as fever, headache, muscle aches, back pain, low energy, and swollen lymph nodes.

As of March 1 of last year, the United States reported more than 30,000 cases, while cases numbered more than 86,000 worldwide.

Despite a lack of effectiveness data in humans, tecovirimat was widely prescribed to PWH with mpox during the 2022 epidemic, which disproportionately affected PWH, particularly those with low CD4+ T-cell counts or severe mpox clinical manifestations who needed urgent therapy. Developed to treat smallpox, tecovirimat has antiviral activity against other orthopoxviruses, and has reduced mpox-related morbidity and mortality in animals.

Based on the animal data, approval was granted by the US Food and Drug Administration (FDA) for human mpox treatment. Dr. Aldred and colleagues undertook this cohort analysis in the absence of human data and with the postoutbreak decline in cases impeding recruitment to a full-scale clinical trial.

Study design

The preponderantly Black cohort included 112 PWH diagnosed with mpox at four Atlanta hospitals from June 1 to October 7, 2022. Patients were grouped in an early cohort receiving tecovirimat within 7 days of symptom onset or a no or late cohort (no tecovirimat or treatment more than 7 days after symptom onset. Multivariate logistic regression models identified factors associated with progression, defined as development of at least one severe CDC mpox criterion after symptom day 7.

The cohorts were then matched 1:1 using propensity scores based on the identified factors, and mpox disease progression was compared.

Of 112 PWH, 56 receive early tecovirimat and 56 received no or late treatment. In the early group, the median (interquartile range [IQR]) age was 35 (30-42) years; 54 individuals (96.4%) were cisgender men, 46 (82.1%) were Black, and 10 (17.9%) were, variously, White, American Indian, Alaska Native, Asian, Native Hawaiian or Other Pacific Islander, or of unknown race.

In the late- or no-tecovirimat group, the median (IQR) age was 36 (32-43) years; 54 (96.4%) were cisgender men, 49 (87.5%) were Black, and 7 (12.5%) were individuals of other or unknown race. Mpox disease progression occurred in 3 PWH in the early-tecovirimat group and 15 PWH (26.8%) in the late- or no-tecovirimat group.

Dr. Aldred and colleagues acknowledged that more research is needed to confirm the findings and cited several study limitations. These included the small sample size, the preponderance of Black participants, and the possibility that unmatched confounding variables could have led to the observation of fewer cases of severe disease in the early-tecovirimat cohort.

This study was supported by a grant from the Emory Center for AIDS Research. Coauthors reported grants from various institutes at the National Institutes of Health as well as from multiple pharmaceutical companies.

A new analysis supports using the smallpox antiviral tecovirimat (TPOXX/ST-246) in HIV patients showing the first symptoms of the human smallpox disease mpox (monkeypox), caused by the variola virus.

In a small prospective matched cohort analysis, people with HIV (PWH) and mpox disease who received tecovirimat within 7 days of symptom onset were 13 times less likely to experience progression, compared with PWH not prescribed tecovirimat within that window. In a matched cohort of 112 PWH, mpox disease progression occurred in 5.4% in an early tecovirimat group and in 26.8% in a late- or no-tecovirimat group, for a paired odds ratio of 13.00 (95% CI, 1.71-99.40; P = .002).

“Results of the present study suggest that tecovirimat treatment should be started early at the time of suspected mpox diagnosis in all PWH, especially in those with nonsuppressed HIV viremia or mucosal site involvement,” wrote a team led by Bruce Aldred, MD, of the Division of Infectious Diseases in the Department of Medicine at Emory University School of Medicine in Atlanta, in JAMA Internal Medicine. Early symptoms of mpox include skin rash and mucosal lesions, along with viral symptoms such as fever, headache, muscle aches, back pain, low energy, and swollen lymph nodes.

As of March 1 of last year, the United States reported more than 30,000 cases, while cases numbered more than 86,000 worldwide.

Despite a lack of effectiveness data in humans, tecovirimat was widely prescribed to PWH with mpox during the 2022 epidemic, which disproportionately affected PWH, particularly those with low CD4+ T-cell counts or severe mpox clinical manifestations who needed urgent therapy. Developed to treat smallpox, tecovirimat has antiviral activity against other orthopoxviruses, and has reduced mpox-related morbidity and mortality in animals.

Based on the animal data, approval was granted by the US Food and Drug Administration (FDA) for human mpox treatment. Dr. Aldred and colleagues undertook this cohort analysis in the absence of human data and with the postoutbreak decline in cases impeding recruitment to a full-scale clinical trial.

Study design

The preponderantly Black cohort included 112 PWH diagnosed with mpox at four Atlanta hospitals from June 1 to October 7, 2022. Patients were grouped in an early cohort receiving tecovirimat within 7 days of symptom onset or a no or late cohort (no tecovirimat or treatment more than 7 days after symptom onset. Multivariate logistic regression models identified factors associated with progression, defined as development of at least one severe CDC mpox criterion after symptom day 7.

The cohorts were then matched 1:1 using propensity scores based on the identified factors, and mpox disease progression was compared.

Of 112 PWH, 56 receive early tecovirimat and 56 received no or late treatment. In the early group, the median (interquartile range [IQR]) age was 35 (30-42) years; 54 individuals (96.4%) were cisgender men, 46 (82.1%) were Black, and 10 (17.9%) were, variously, White, American Indian, Alaska Native, Asian, Native Hawaiian or Other Pacific Islander, or of unknown race.

In the late- or no-tecovirimat group, the median (IQR) age was 36 (32-43) years; 54 (96.4%) were cisgender men, 49 (87.5%) were Black, and 7 (12.5%) were individuals of other or unknown race. Mpox disease progression occurred in 3 PWH in the early-tecovirimat group and 15 PWH (26.8%) in the late- or no-tecovirimat group.

Dr. Aldred and colleagues acknowledged that more research is needed to confirm the findings and cited several study limitations. These included the small sample size, the preponderance of Black participants, and the possibility that unmatched confounding variables could have led to the observation of fewer cases of severe disease in the early-tecovirimat cohort.

This study was supported by a grant from the Emory Center for AIDS Research. Coauthors reported grants from various institutes at the National Institutes of Health as well as from multiple pharmaceutical companies.

A new analysis supports using the smallpox antiviral tecovirimat (TPOXX/ST-246) in HIV patients showing the first symptoms of the human smallpox disease mpox (monkeypox), caused by the variola virus.

In a small prospective matched cohort analysis, people with HIV (PWH) and mpox disease who received tecovirimat within 7 days of symptom onset were 13 times less likely to experience progression, compared with PWH not prescribed tecovirimat within that window. In a matched cohort of 112 PWH, mpox disease progression occurred in 5.4% in an early tecovirimat group and in 26.8% in a late- or no-tecovirimat group, for a paired odds ratio of 13.00 (95% CI, 1.71-99.40; P = .002).

“Results of the present study suggest that tecovirimat treatment should be started early at the time of suspected mpox diagnosis in all PWH, especially in those with nonsuppressed HIV viremia or mucosal site involvement,” wrote a team led by Bruce Aldred, MD, of the Division of Infectious Diseases in the Department of Medicine at Emory University School of Medicine in Atlanta, in JAMA Internal Medicine. Early symptoms of mpox include skin rash and mucosal lesions, along with viral symptoms such as fever, headache, muscle aches, back pain, low energy, and swollen lymph nodes.

As of March 1 of last year, the United States reported more than 30,000 cases, while cases numbered more than 86,000 worldwide.

Despite a lack of effectiveness data in humans, tecovirimat was widely prescribed to PWH with mpox during the 2022 epidemic, which disproportionately affected PWH, particularly those with low CD4+ T-cell counts or severe mpox clinical manifestations who needed urgent therapy. Developed to treat smallpox, tecovirimat has antiviral activity against other orthopoxviruses, and has reduced mpox-related morbidity and mortality in animals.

Based on the animal data, approval was granted by the US Food and Drug Administration (FDA) for human mpox treatment. Dr. Aldred and colleagues undertook this cohort analysis in the absence of human data and with the postoutbreak decline in cases impeding recruitment to a full-scale clinical trial.

Study design

The preponderantly Black cohort included 112 PWH diagnosed with mpox at four Atlanta hospitals from June 1 to October 7, 2022. Patients were grouped in an early cohort receiving tecovirimat within 7 days of symptom onset or a no or late cohort (no tecovirimat or treatment more than 7 days after symptom onset. Multivariate logistic regression models identified factors associated with progression, defined as development of at least one severe CDC mpox criterion after symptom day 7.

The cohorts were then matched 1:1 using propensity scores based on the identified factors, and mpox disease progression was compared.

Of 112 PWH, 56 receive early tecovirimat and 56 received no or late treatment. In the early group, the median (interquartile range [IQR]) age was 35 (30-42) years; 54 individuals (96.4%) were cisgender men, 46 (82.1%) were Black, and 10 (17.9%) were, variously, White, American Indian, Alaska Native, Asian, Native Hawaiian or Other Pacific Islander, or of unknown race.

In the late- or no-tecovirimat group, the median (IQR) age was 36 (32-43) years; 54 (96.4%) were cisgender men, 49 (87.5%) were Black, and 7 (12.5%) were individuals of other or unknown race. Mpox disease progression occurred in 3 PWH in the early-tecovirimat group and 15 PWH (26.8%) in the late- or no-tecovirimat group.

Dr. Aldred and colleagues acknowledged that more research is needed to confirm the findings and cited several study limitations. These included the small sample size, the preponderance of Black participants, and the possibility that unmatched confounding variables could have led to the observation of fewer cases of severe disease in the early-tecovirimat cohort.

This study was supported by a grant from the Emory Center for AIDS Research. Coauthors reported grants from various institutes at the National Institutes of Health as well as from multiple pharmaceutical companies.

The Diagnosis: Cutaneous Sarcoidosis

A biopsy of a plaque on the back confirmed cutaneous sarcoidosis (CS). A chest radiograph demonstrated hilar nodes, and a referral was placed for comanagement with a pulmonologist. Histopathology was critical in making the diagnosis, with well-circumscribed noncaseating granulomas present in the dermis. The granulomas in CS often are described as naked, as there are minimal lymphocytes present and plasma cells normally are absent.¹ Because the lungs are the most common site of involvement, a chest radiograph is necessary to examine for systemic sarcoidosis. Laboratory workup is used to evaluate for lymphopenia, hypercalcemia, elevated blood sedimentation rate, and elevated angiotensin- converting enzyme levels, which are common in systemic sarcoidosis.¹

Sarcoidosis is a multisystemic granulomatous disorder with an unknown etiology. It is believed to develop in genetically predisposed individuals as a reaction to unidentified antigens in the environment.¹ Helper T cells (T_H1) respond to these environmental antigens in those who are susceptible, which leads to the disease process, but paradoxically, even with the elevation of cellular immune activity at the sites of the granulomatous inflammation, the peripheral immune response in these patients is suppressed as shown by lymphopenia.²

Cutaneous sarcoidosis is found in approximately one-third of patients with systemic sarcoidosis but can occur without systemic involvement.^1,2 Sarcoidosis is reported worldwide and affects patients of all races and ethnicities, ages, and sexes but does have a higher prevalence among Black individuals in the United States, patients younger than 40 years (peak incidence, 20–29 years of age), and females.² In 80% of patients, CS occurs before systemic sarcoidosis develops, or they may develop simultaneously.¹

Cutaneous sarcoidosis has a wide range of clinical presentations that are classified as specific and nonspecific. Specific lesions in CS contain noncaseating granulomas while nonspecific lesions in CS appear as reactive processes.² The most common specific presentation of CS includes papules that are brown in pigmentation in lighter skin tones and red to violaceous in darker skin tones (Figure). The most common nonspecific skin manifestation is erythema nodosum, which represents a hypersensitivity reaction. Cutaneous sarcoidosis can appear as hypopigmented or hyperpigmented patches or plaques.¹

Treatments for CS vary based on the individual.¹ For milder and more localized cases, topical or intralesional steroids may be used. If systemic sarcoidosis is suspected or if there is diffuse involvement of the skin, systemic steroids, antimalarials (eg, hydroxychloroquine), low-dose methotrexate, minocycline, allopurinol, azathioprine, isotretinoin, tumor necrosis factor α inhibitors, or psoralen plus long-wave UVA radiation may be used. If systemic sarcoidosis is present, referral to a pulmonologist is recommended for co-management.¹

Cutaneous sarcoidosis is known as the “great imitator,” and there are multiple diseases to consider in the differential that are distinguished by the physical findings.¹ In our case of a middle-aged Black woman with indurated plaques, a few diagnoses to consider were psoriasis, discoid lupus erythematosus (DLE), mycosis fungoides (MF), and tinea infection.

Psoriasis is a common disease, and 90% of patients have chronic plaquelike disease with well-demarcated erythematous plaques that have a silver-gray scale and a positive Auspitz sign (also known as pinpoint bleeding).³ Plaques often are distributed on the trunk, limb extensors, and scalp, along with nail changes. Some patients also have joint pain, indicating psoriatic arthritis. The etiology of psoriasis is unknown, but it develops due to unrestrained keratinocyte proliferation and defective differentiation, which leads to histopathology showing regular acanthosis and papillary dermal ectasia with rouleaux. Mild cases typically are treated with topical steroids or vitamin D, while more severe cases are treated with methotrexate, cyclosporine, retinoids, or biologics.³

Discoid lupus erythematosus occurs 4 times more often in Black patients than in White patients. Clinically, DLE begins as well-defined, erythematous, scaly patches that expand with hyperpigmentation at the periphery and leave an atrophic, scarred, hypopigmented center.⁴ It typically is localized to the head and neck, but in cases where it disseminates elsewhere on the body, the risk for systemic lupus erythematosus increases from 1.2% to 28%.5 Histopathology of DLE shows vacuolar degeneration of the basal cell layer in the epidermis along with patchy lymphocytic infiltrate in the dermis. Treatments range from topical steroids for mild cases to antimalarial agents, retinoids, anti-inflammatory drugs, and calcineurin inhibitors for more severe cases.⁴

Although there are multiple types of cutaneous T-cell lymphoma, the most common is MF, which traditionally is nonaggressive. The typical patient with MF is older than 60 years and presents with indolent, ongoing, flat to minimally indurated patches or plaques that have cigarette paper scale. As MF progresses, some plaques grow into tumors and can become more aggressive. Histologically, MF changes based on its clinical stage, with the initial phase showing epidermotropic atypical lymphocytes and later phases showing less epitheliotropic, larger, atypical lymphocytes. The treatment algorithm varies depending on cutaneous T-cell lymphoma staging.⁶

Tinea infections are caused by dermatophytes. In prepubertal children, they predominantly appear as tinea corporis (on the body) or tinea capitis (on the scalp), but in adults they appear as tinea cruris (on the groin), tinea pedis (on the feet), or tinea unguium (on the nails).⁷ Tinea infections classically are known to appear as an annular patch with an active erythematous scaling border and central clearing. The patches can be pruritic. Potassium hydroxide preparation of a skin scraping is a quick test to use in the office; if the results are inconclusive, a culture may be required. Treatment depends on the location of the infection but typically involves either topical or oral antifungal agents.⁷

The Diagnosis: Cutaneous Sarcoidosis

A biopsy of a plaque on the back confirmed cutaneous sarcoidosis (CS). A chest radiograph demonstrated hilar nodes, and a referral was placed for comanagement with a pulmonologist. Histopathology was critical in making the diagnosis, with well-circumscribed noncaseating granulomas present in the dermis. The granulomas in CS often are described as naked, as there are minimal lymphocytes present and plasma cells normally are absent.¹ Because the lungs are the most common site of involvement, a chest radiograph is necessary to examine for systemic sarcoidosis. Laboratory workup is used to evaluate for lymphopenia, hypercalcemia, elevated blood sedimentation rate, and elevated angiotensin- converting enzyme levels, which are common in systemic sarcoidosis.¹

Sarcoidosis is a multisystemic granulomatous disorder with an unknown etiology. It is believed to develop in genetically predisposed individuals as a reaction to unidentified antigens in the environment.¹ Helper T cells (T_H1) respond to these environmental antigens in those who are susceptible, which leads to the disease process, but paradoxically, even with the elevation of cellular immune activity at the sites of the granulomatous inflammation, the peripheral immune response in these patients is suppressed as shown by lymphopenia.²

Cutaneous sarcoidosis is found in approximately one-third of patients with systemic sarcoidosis but can occur without systemic involvement.^1,2 Sarcoidosis is reported worldwide and affects patients of all races and ethnicities, ages, and sexes but does have a higher prevalence among Black individuals in the United States, patients younger than 40 years (peak incidence, 20–29 years of age), and females.² In 80% of patients, CS occurs before systemic sarcoidosis develops, or they may develop simultaneously.¹

Cutaneous sarcoidosis has a wide range of clinical presentations that are classified as specific and nonspecific. Specific lesions in CS contain noncaseating granulomas while nonspecific lesions in CS appear as reactive processes.² The most common specific presentation of CS includes papules that are brown in pigmentation in lighter skin tones and red to violaceous in darker skin tones (Figure). The most common nonspecific skin manifestation is erythema nodosum, which represents a hypersensitivity reaction. Cutaneous sarcoidosis can appear as hypopigmented or hyperpigmented patches or plaques.¹

Treatments for CS vary based on the individual.¹ For milder and more localized cases, topical or intralesional steroids may be used. If systemic sarcoidosis is suspected or if there is diffuse involvement of the skin, systemic steroids, antimalarials (eg, hydroxychloroquine), low-dose methotrexate, minocycline, allopurinol, azathioprine, isotretinoin, tumor necrosis factor α inhibitors, or psoralen plus long-wave UVA radiation may be used. If systemic sarcoidosis is present, referral to a pulmonologist is recommended for co-management.¹

Cutaneous sarcoidosis is known as the “great imitator,” and there are multiple diseases to consider in the differential that are distinguished by the physical findings.¹ In our case of a middle-aged Black woman with indurated plaques, a few diagnoses to consider were psoriasis, discoid lupus erythematosus (DLE), mycosis fungoides (MF), and tinea infection.

Psoriasis is a common disease, and 90% of patients have chronic plaquelike disease with well-demarcated erythematous plaques that have a silver-gray scale and a positive Auspitz sign (also known as pinpoint bleeding).³ Plaques often are distributed on the trunk, limb extensors, and scalp, along with nail changes. Some patients also have joint pain, indicating psoriatic arthritis. The etiology of psoriasis is unknown, but it develops due to unrestrained keratinocyte proliferation and defective differentiation, which leads to histopathology showing regular acanthosis and papillary dermal ectasia with rouleaux. Mild cases typically are treated with topical steroids or vitamin D, while more severe cases are treated with methotrexate, cyclosporine, retinoids, or biologics.³

Discoid lupus erythematosus occurs 4 times more often in Black patients than in White patients. Clinically, DLE begins as well-defined, erythematous, scaly patches that expand with hyperpigmentation at the periphery and leave an atrophic, scarred, hypopigmented center.⁴ It typically is localized to the head and neck, but in cases where it disseminates elsewhere on the body, the risk for systemic lupus erythematosus increases from 1.2% to 28%.5 Histopathology of DLE shows vacuolar degeneration of the basal cell layer in the epidermis along with patchy lymphocytic infiltrate in the dermis. Treatments range from topical steroids for mild cases to antimalarial agents, retinoids, anti-inflammatory drugs, and calcineurin inhibitors for more severe cases.⁴

Although there are multiple types of cutaneous T-cell lymphoma, the most common is MF, which traditionally is nonaggressive. The typical patient with MF is older than 60 years and presents with indolent, ongoing, flat to minimally indurated patches or plaques that have cigarette paper scale. As MF progresses, some plaques grow into tumors and can become more aggressive. Histologically, MF changes based on its clinical stage, with the initial phase showing epidermotropic atypical lymphocytes and later phases showing less epitheliotropic, larger, atypical lymphocytes. The treatment algorithm varies depending on cutaneous T-cell lymphoma staging.⁶

Tinea infections are caused by dermatophytes. In prepubertal children, they predominantly appear as tinea corporis (on the body) or tinea capitis (on the scalp), but in adults they appear as tinea cruris (on the groin), tinea pedis (on the feet), or tinea unguium (on the nails).⁷ Tinea infections classically are known to appear as an annular patch with an active erythematous scaling border and central clearing. The patches can be pruritic. Potassium hydroxide preparation of a skin scraping is a quick test to use in the office; if the results are inconclusive, a culture may be required. Treatment depends on the location of the infection but typically involves either topical or oral antifungal agents.⁷

The Diagnosis: Cutaneous Sarcoidosis

A biopsy of a plaque on the back confirmed cutaneous sarcoidosis (CS). A chest radiograph demonstrated hilar nodes, and a referral was placed for comanagement with a pulmonologist. Histopathology was critical in making the diagnosis, with well-circumscribed noncaseating granulomas present in the dermis. The granulomas in CS often are described as naked, as there are minimal lymphocytes present and plasma cells normally are absent.¹ Because the lungs are the most common site of involvement, a chest radiograph is necessary to examine for systemic sarcoidosis. Laboratory workup is used to evaluate for lymphopenia, hypercalcemia, elevated blood sedimentation rate, and elevated angiotensin- converting enzyme levels, which are common in systemic sarcoidosis.¹

Sarcoidosis is a multisystemic granulomatous disorder with an unknown etiology. It is believed to develop in genetically predisposed individuals as a reaction to unidentified antigens in the environment.¹ Helper T cells (T_H1) respond to these environmental antigens in those who are susceptible, which leads to the disease process, but paradoxically, even with the elevation of cellular immune activity at the sites of the granulomatous inflammation, the peripheral immune response in these patients is suppressed as shown by lymphopenia.²

Cutaneous sarcoidosis is found in approximately one-third of patients with systemic sarcoidosis but can occur without systemic involvement.^1,2 Sarcoidosis is reported worldwide and affects patients of all races and ethnicities, ages, and sexes but does have a higher prevalence among Black individuals in the United States, patients younger than 40 years (peak incidence, 20–29 years of age), and females.² In 80% of patients, CS occurs before systemic sarcoidosis develops, or they may develop simultaneously.¹

Cutaneous sarcoidosis has a wide range of clinical presentations that are classified as specific and nonspecific. Specific lesions in CS contain noncaseating granulomas while nonspecific lesions in CS appear as reactive processes.² The most common specific presentation of CS includes papules that are brown in pigmentation in lighter skin tones and red to violaceous in darker skin tones (Figure). The most common nonspecific skin manifestation is erythema nodosum, which represents a hypersensitivity reaction. Cutaneous sarcoidosis can appear as hypopigmented or hyperpigmented patches or plaques.¹

Treatments for CS vary based on the individual.¹ For milder and more localized cases, topical or intralesional steroids may be used. If systemic sarcoidosis is suspected or if there is diffuse involvement of the skin, systemic steroids, antimalarials (eg, hydroxychloroquine), low-dose methotrexate, minocycline, allopurinol, azathioprine, isotretinoin, tumor necrosis factor α inhibitors, or psoralen plus long-wave UVA radiation may be used. If systemic sarcoidosis is present, referral to a pulmonologist is recommended for co-management.¹

Cutaneous sarcoidosis is known as the “great imitator,” and there are multiple diseases to consider in the differential that are distinguished by the physical findings.¹ In our case of a middle-aged Black woman with indurated plaques, a few diagnoses to consider were psoriasis, discoid lupus erythematosus (DLE), mycosis fungoides (MF), and tinea infection.

Psoriasis is a common disease, and 90% of patients have chronic plaquelike disease with well-demarcated erythematous plaques that have a silver-gray scale and a positive Auspitz sign (also known as pinpoint bleeding).³ Plaques often are distributed on the trunk, limb extensors, and scalp, along with nail changes. Some patients also have joint pain, indicating psoriatic arthritis. The etiology of psoriasis is unknown, but it develops due to unrestrained keratinocyte proliferation and defective differentiation, which leads to histopathology showing regular acanthosis and papillary dermal ectasia with rouleaux. Mild cases typically are treated with topical steroids or vitamin D, while more severe cases are treated with methotrexate, cyclosporine, retinoids, or biologics.³

Discoid lupus erythematosus occurs 4 times more often in Black patients than in White patients. Clinically, DLE begins as well-defined, erythematous, scaly patches that expand with hyperpigmentation at the periphery and leave an atrophic, scarred, hypopigmented center.⁴ It typically is localized to the head and neck, but in cases where it disseminates elsewhere on the body, the risk for systemic lupus erythematosus increases from 1.2% to 28%.5 Histopathology of DLE shows vacuolar degeneration of the basal cell layer in the epidermis along with patchy lymphocytic infiltrate in the dermis. Treatments range from topical steroids for mild cases to antimalarial agents, retinoids, anti-inflammatory drugs, and calcineurin inhibitors for more severe cases.⁴

Although there are multiple types of cutaneous T-cell lymphoma, the most common is MF, which traditionally is nonaggressive. The typical patient with MF is older than 60 years and presents with indolent, ongoing, flat to minimally indurated patches or plaques that have cigarette paper scale. As MF progresses, some plaques grow into tumors and can become more aggressive. Histologically, MF changes based on its clinical stage, with the initial phase showing epidermotropic atypical lymphocytes and later phases showing less epitheliotropic, larger, atypical lymphocytes. The treatment algorithm varies depending on cutaneous T-cell lymphoma staging.⁶

Tinea infections are caused by dermatophytes. In prepubertal children, they predominantly appear as tinea corporis (on the body) or tinea capitis (on the scalp), but in adults they appear as tinea cruris (on the groin), tinea pedis (on the feet), or tinea unguium (on the nails).⁷ Tinea infections classically are known to appear as an annular patch with an active erythematous scaling border and central clearing. The patches can be pruritic. Potassium hydroxide preparation of a skin scraping is a quick test to use in the office; if the results are inconclusive, a culture may be required. Treatment depends on the location of the infection but typically involves either topical or oral antifungal agents.⁷

While COVID has now claimed more than 1 million lives in the United States alone, these aren’t the only fatalities caused at least in part by the virus. A small but growing number of Americans are surviving acute infections only to succumb months later to the lingering health problems caused by long COVID.

Much of the attention on long COVID has centered on the sometimes debilitating symptoms that strike people with the condition, with no formal diagnostic tests or standard treatments available, and the effect it has on quality of life. But new figures from the US Centers for Disease Control and Prevention (CDC) show that long COVID can also be deadly.

More than 5000 Americans have died from long COVID since the start of the pandemic, according to new estimates from the CDC.

This total, based on death certificate data collected by the CDC, includes a preliminary tally of 1491 long COVID deaths in 2023 in addition to 3544 fatalities previously reported from January 2020 through June 2022.

Guidance issued in 2023 on how to formally report long COVID as a cause of death on death certificates should help get a more accurate count of these fatalities going forward, said Robert Anderson, PhD, chief mortality statistician for the CDC, Atlanta, Georgia.

“We hope that the guidance will help cause of death certifiers be more aware of the impact of long COVID and more likely to report long COVID as a cause of death when appropriate,” Dr. Anderson said. “That said, we do not expect that this guidance will have a dramatic impact on the trend.”

There’s no standard definition or diagnostic test for long COVID. It’s typically diagnosed when people have symptoms at least 3 months after an acute infection that weren’t present before they got sick. As of the end of last year, about 7% of American adults had experienced long COVID at some point, the CDC estimated in September 2023.

The new death tally indicates long COVID remains a significant public health threat and is likely to grow in the years ahead, even though the pandemic may no longer be considered a global health crisis, experts said.

For example, the death certificate figures indicate:

COVID-19 was the third leading cause of American deaths in 2020 and 2021, and the fourth leading cause of death in the United States in 2023.

Nearly 1% of the more than one million deaths related to COVID-19 since the start of the pandemic have been attributed to long COVID, according to data released by the CDC.

The proportion of COVID-related deaths from long COVID peaked in June 2021 at 1.2% and again in April 2022 at 3.8%, according to the CDC. Both of these peaks coincided with periods of declining fatalities from acute infections.

“I do expect that deaths associated with long COVID will make up an increasingly larger proportion of total deaths associated with COVID-19,” said Mark Czeisler, PhD, a researcher at Harvard Medical School, Boston, Massachusetts, who has studied long COVID fatalities. 

Months and even years after an acute infection, long COVID can contribute to serious and potentially life-threatening conditions that impact nearly every major system in the body, according to the CDC guidelines for identifying the condition on death certificates. 

This means long COVID may often be listed as an underlying cause of death when people with this condition die of issues related to their heart, lungs, brain or kidneys, the CDC guidelines noted.

The risk for long COVID fatalities remains elevated for at least 6 months for people with milder acute infections and for at least 2 years in severe cases that require hospitalization, some previous research suggested.

As happens with other acute infections, certain people are more at risk for fatal case of long COVID. Age, race, and ethnicity have all been cited as risk factors by researchers who have been tracking the condition since the start of the pandemic.

Half of long COVID fatalities from July 2021 to June 2022 occurred in people aged 65 years and older, and another 23% were recorded among people aged 50-64 years old, according a report from CDC.

Long COVID death rates also varied by race and ethnicity, from a high of 14.1 cases per million among America Indian and Alaskan natives to a low of 1.5 cases per million among Asian people, the CDC found. Death rates per million were 6.7 for White individuals, 6.4 for Black people, and 4.7 for Hispanic people.

The disproportionate share of Black and Hispanic people who developed and died from severe acute infections may have left fewer survivors to develop long COVID, limiting long COVID fatalities among these groups, the CDC report concluded.

It’s also possible that long COVID fatalities were undercounted in these populations because they faced challenges accessing healthcare or seeing providers who could recognize the hallmark symptoms of long COVID.

It’s also difficult to distinguish between how many deaths related to the virus ultimately occur as a result of long COVID rather than acute infections. That’s because it may depend on a variety of factors, including how consistently medical examiners follow the CDC guidelines, said Ziyad Al-Aly, MD, chief of research at the Veterans Affairs, St. Louis Health Care System and a senior clinical epidemiologist at Washington University in St. Louis.

“Long COVID remains massively underdiagnosed, and death in people with long COVID is misattributed to other things,” Dr. Al-Aly said.

An accurate test for long COVID could help lead to a more accurate count of these fatalities, Dr. Czeisler said. Some preliminary research suggests that it might one day be possible to diagnose long COVID with a blood test.

“The timeline for such a test and the extent to which it would be widely applied is uncertain,” Dr. Czeisler noted, “though that would certainly be a gamechanger.”

A version of this article appeared on Medscape.com.

While COVID has now claimed more than 1 million lives in the United States alone, these aren’t the only fatalities caused at least in part by the virus. A small but growing number of Americans are surviving acute infections only to succumb months later to the lingering health problems caused by long COVID.

Much of the attention on long COVID has centered on the sometimes debilitating symptoms that strike people with the condition, with no formal diagnostic tests or standard treatments available, and the effect it has on quality of life. But new figures from the US Centers for Disease Control and Prevention (CDC) show that long COVID can also be deadly.

More than 5000 Americans have died from long COVID since the start of the pandemic, according to new estimates from the CDC.

This total, based on death certificate data collected by the CDC, includes a preliminary tally of 1491 long COVID deaths in 2023 in addition to 3544 fatalities previously reported from January 2020 through June 2022.

Guidance issued in 2023 on how to formally report long COVID as a cause of death on death certificates should help get a more accurate count of these fatalities going forward, said Robert Anderson, PhD, chief mortality statistician for the CDC, Atlanta, Georgia.

“We hope that the guidance will help cause of death certifiers be more aware of the impact of long COVID and more likely to report long COVID as a cause of death when appropriate,” Dr. Anderson said. “That said, we do not expect that this guidance will have a dramatic impact on the trend.”

There’s no standard definition or diagnostic test for long COVID. It’s typically diagnosed when people have symptoms at least 3 months after an acute infection that weren’t present before they got sick. As of the end of last year, about 7% of American adults had experienced long COVID at some point, the CDC estimated in September 2023.

The new death tally indicates long COVID remains a significant public health threat and is likely to grow in the years ahead, even though the pandemic may no longer be considered a global health crisis, experts said.

For example, the death certificate figures indicate:

COVID-19 was the third leading cause of American deaths in 2020 and 2021, and the fourth leading cause of death in the United States in 2023.

Nearly 1% of the more than one million deaths related to COVID-19 since the start of the pandemic have been attributed to long COVID, according to data released by the CDC.

The proportion of COVID-related deaths from long COVID peaked in June 2021 at 1.2% and again in April 2022 at 3.8%, according to the CDC. Both of these peaks coincided with periods of declining fatalities from acute infections.

“I do expect that deaths associated with long COVID will make up an increasingly larger proportion of total deaths associated with COVID-19,” said Mark Czeisler, PhD, a researcher at Harvard Medical School, Boston, Massachusetts, who has studied long COVID fatalities. 

Months and even years after an acute infection, long COVID can contribute to serious and potentially life-threatening conditions that impact nearly every major system in the body, according to the CDC guidelines for identifying the condition on death certificates. 

This means long COVID may often be listed as an underlying cause of death when people with this condition die of issues related to their heart, lungs, brain or kidneys, the CDC guidelines noted.

The risk for long COVID fatalities remains elevated for at least 6 months for people with milder acute infections and for at least 2 years in severe cases that require hospitalization, some previous research suggested.

As happens with other acute infections, certain people are more at risk for fatal case of long COVID. Age, race, and ethnicity have all been cited as risk factors by researchers who have been tracking the condition since the start of the pandemic.

Half of long COVID fatalities from July 2021 to June 2022 occurred in people aged 65 years and older, and another 23% were recorded among people aged 50-64 years old, according a report from CDC.

Long COVID death rates also varied by race and ethnicity, from a high of 14.1 cases per million among America Indian and Alaskan natives to a low of 1.5 cases per million among Asian people, the CDC found. Death rates per million were 6.7 for White individuals, 6.4 for Black people, and 4.7 for Hispanic people.

The disproportionate share of Black and Hispanic people who developed and died from severe acute infections may have left fewer survivors to develop long COVID, limiting long COVID fatalities among these groups, the CDC report concluded.

It’s also possible that long COVID fatalities were undercounted in these populations because they faced challenges accessing healthcare or seeing providers who could recognize the hallmark symptoms of long COVID.

It’s also difficult to distinguish between how many deaths related to the virus ultimately occur as a result of long COVID rather than acute infections. That’s because it may depend on a variety of factors, including how consistently medical examiners follow the CDC guidelines, said Ziyad Al-Aly, MD, chief of research at the Veterans Affairs, St. Louis Health Care System and a senior clinical epidemiologist at Washington University in St. Louis.

“Long COVID remains massively underdiagnosed, and death in people with long COVID is misattributed to other things,” Dr. Al-Aly said.

An accurate test for long COVID could help lead to a more accurate count of these fatalities, Dr. Czeisler said. Some preliminary research suggests that it might one day be possible to diagnose long COVID with a blood test.

“The timeline for such a test and the extent to which it would be widely applied is uncertain,” Dr. Czeisler noted, “though that would certainly be a gamechanger.”

A version of this article appeared on Medscape.com.

While COVID has now claimed more than 1 million lives in the United States alone, these aren’t the only fatalities caused at least in part by the virus. A small but growing number of Americans are surviving acute infections only to succumb months later to the lingering health problems caused by long COVID.

Much of the attention on long COVID has centered on the sometimes debilitating symptoms that strike people with the condition, with no formal diagnostic tests or standard treatments available, and the effect it has on quality of life. But new figures from the US Centers for Disease Control and Prevention (CDC) show that long COVID can also be deadly.

More than 5000 Americans have died from long COVID since the start of the pandemic, according to new estimates from the CDC.

This total, based on death certificate data collected by the CDC, includes a preliminary tally of 1491 long COVID deaths in 2023 in addition to 3544 fatalities previously reported from January 2020 through June 2022.

Guidance issued in 2023 on how to formally report long COVID as a cause of death on death certificates should help get a more accurate count of these fatalities going forward, said Robert Anderson, PhD, chief mortality statistician for the CDC, Atlanta, Georgia.

“We hope that the guidance will help cause of death certifiers be more aware of the impact of long COVID and more likely to report long COVID as a cause of death when appropriate,” Dr. Anderson said. “That said, we do not expect that this guidance will have a dramatic impact on the trend.”

There’s no standard definition or diagnostic test for long COVID. It’s typically diagnosed when people have symptoms at least 3 months after an acute infection that weren’t present before they got sick. As of the end of last year, about 7% of American adults had experienced long COVID at some point, the CDC estimated in September 2023.

The new death tally indicates long COVID remains a significant public health threat and is likely to grow in the years ahead, even though the pandemic may no longer be considered a global health crisis, experts said.

For example, the death certificate figures indicate:

COVID-19 was the third leading cause of American deaths in 2020 and 2021, and the fourth leading cause of death in the United States in 2023.

Nearly 1% of the more than one million deaths related to COVID-19 since the start of the pandemic have been attributed to long COVID, according to data released by the CDC.

The proportion of COVID-related deaths from long COVID peaked in June 2021 at 1.2% and again in April 2022 at 3.8%, according to the CDC. Both of these peaks coincided with periods of declining fatalities from acute infections.

“I do expect that deaths associated with long COVID will make up an increasingly larger proportion of total deaths associated with COVID-19,” said Mark Czeisler, PhD, a researcher at Harvard Medical School, Boston, Massachusetts, who has studied long COVID fatalities. 

Months and even years after an acute infection, long COVID can contribute to serious and potentially life-threatening conditions that impact nearly every major system in the body, according to the CDC guidelines for identifying the condition on death certificates. 

This means long COVID may often be listed as an underlying cause of death when people with this condition die of issues related to their heart, lungs, brain or kidneys, the CDC guidelines noted.

The risk for long COVID fatalities remains elevated for at least 6 months for people with milder acute infections and for at least 2 years in severe cases that require hospitalization, some previous research suggested.

As happens with other acute infections, certain people are more at risk for fatal case of long COVID. Age, race, and ethnicity have all been cited as risk factors by researchers who have been tracking the condition since the start of the pandemic.

Half of long COVID fatalities from July 2021 to June 2022 occurred in people aged 65 years and older, and another 23% were recorded among people aged 50-64 years old, according a report from CDC.

Long COVID death rates also varied by race and ethnicity, from a high of 14.1 cases per million among America Indian and Alaskan natives to a low of 1.5 cases per million among Asian people, the CDC found. Death rates per million were 6.7 for White individuals, 6.4 for Black people, and 4.7 for Hispanic people.

The disproportionate share of Black and Hispanic people who developed and died from severe acute infections may have left fewer survivors to develop long COVID, limiting long COVID fatalities among these groups, the CDC report concluded.

It’s also possible that long COVID fatalities were undercounted in these populations because they faced challenges accessing healthcare or seeing providers who could recognize the hallmark symptoms of long COVID.

It’s also difficult to distinguish between how many deaths related to the virus ultimately occur as a result of long COVID rather than acute infections. That’s because it may depend on a variety of factors, including how consistently medical examiners follow the CDC guidelines, said Ziyad Al-Aly, MD, chief of research at the Veterans Affairs, St. Louis Health Care System and a senior clinical epidemiologist at Washington University in St. Louis.

“Long COVID remains massively underdiagnosed, and death in people with long COVID is misattributed to other things,” Dr. Al-Aly said.

An accurate test for long COVID could help lead to a more accurate count of these fatalities, Dr. Czeisler said. Some preliminary research suggests that it might one day be possible to diagnose long COVID with a blood test.

“The timeline for such a test and the extent to which it would be widely applied is uncertain,” Dr. Czeisler noted, “though that would certainly be a gamechanger.”

A version of this article appeared on Medscape.com.