MDedge Infectious Disease

It would be overused and trite to say that the pandemic has drastically altered all of our lives and will cause lasting impact on how we function in society and medicine for years to come. While it seems that the current trend of the latest Omicron variant is on the downslope, the path to get to this point has been fraught with challenges that have struck at the very core of our society. As a primary care physician on the front lines seeing COVID patients, I have had to deal with not only the disease but the politics around it. As critical and life saving as the vaccines have been, many physicians have not been able to get access to these vaccines and give them to their patients. I am one of those physicians. I practice in Florida, and I still cannot give COVID vaccines in my office. 

I am a firm believer in the ability for physicians to be able to give all the necessary adult vaccines and provide them for their patients. The COVID vaccine exacerbated a majorly flawed system that further increased the health care disparities in the country. The current vaccine system for the majority of adult vaccines involves the physician’s being able to directly purchase supplies from the vaccine manufacturer, administer them to the patients, and be reimbursed.
 

Third parties can purchase vaccines at lower rates than those for physicians

The Affordable Care Act mandates that all vaccines approved by the Advisory Committee on Immunization Practices (ACIP) at the Centers for Disease Control and Prevention must be covered. This allows for better access to care as physicians will be able to purchase, store, and deliver vaccines to their patients. The fallacy in this system is that third parties get involved and rebates or incentives are given to these groups to purchase vaccines at a rate lower than those for physicians.

In addition, many organizations can get access to vaccines before physicians and at a lower cost. That system was flawed to begin with and created a deterrent for access to care and physician involvement in the vaccination process. This was worsened by different states being given the ability to decide how vaccines would be distributed for COVID.

Many pharmacies were able to give out COVID vaccines while many physician offices still have not received access to any of the vaccines. One of the major safety issues with this is that no physicians were involved in the administration of the vaccine, and it is unclear what training was given to the individuals injecting that vaccine. Finally, different places were interpreting the recommendations from ACIP on their own and not necessarily following the appropriate guidelines. All of these factors have further widened the health care disparity gap and made it difficult to provide the COVID vaccines in doctors’ offices.
 

Recommended next steps, solutions to problem

The question is what to do about this. The most important thing is to get the vaccines in arms so they can save lives. In addition, doctors need to be able to get the vaccines in their offices.

Many patients trust their physicians to advise them on what to do regarding health care. The majority of patients want to know if they should get the vaccine and ask for counseling. Physicians answering patients’ questions about vaccines is an important step in overcoming vaccine hesitancy.

Also, doctors need to be informed and supportive of the vaccine process.

The next step is the governmental aspect with those in power making sure that vaccines are accessible to all. Even if the vaccine cannot be given in the office, doctors should still be recommending that patients receive them. Plus, doctors should take every opportunity to ask about what vaccines their patients have received and encourage their patients to get vaccinated.

The COVID-19 vaccines are safe and effective and have been monitored for safety more than any other vaccine. There are multiple systems in place to look for any signals that could indicate an issue was caused by a COVID-19 vaccine. These vaccines can be administered with other vaccines, and there is a great opportunity for physicians to encourage patients to receive these life-saving vaccines.

While it may seem that the COVID-19 case counts are on the downslope, the importance of continuing to vaccinate is predicated on the very real concern that the disease is still circulating and the unvaccinated are still at risk for severe infection.

Dr. Goldman is immediate past governor of the Florida chapter of the American College of Physicians, a regent for the American College of Physicians, vice-president of the Florida Medical Association, and president of the Florida Medical Association Political Action Committee. You can reach Dr. Goldman at [email protected].

It would be overused and trite to say that the pandemic has drastically altered all of our lives and will cause lasting impact on how we function in society and medicine for years to come. While it seems that the current trend of the latest Omicron variant is on the downslope, the path to get to this point has been fraught with challenges that have struck at the very core of our society. As a primary care physician on the front lines seeing COVID patients, I have had to deal with not only the disease but the politics around it. As critical and life saving as the vaccines have been, many physicians have not been able to get access to these vaccines and give them to their patients. I am one of those physicians. I practice in Florida, and I still cannot give COVID vaccines in my office. 

I am a firm believer in the ability for physicians to be able to give all the necessary adult vaccines and provide them for their patients. The COVID vaccine exacerbated a majorly flawed system that further increased the health care disparities in the country. The current vaccine system for the majority of adult vaccines involves the physician’s being able to directly purchase supplies from the vaccine manufacturer, administer them to the patients, and be reimbursed.
 

Third parties can purchase vaccines at lower rates than those for physicians

The Affordable Care Act mandates that all vaccines approved by the Advisory Committee on Immunization Practices (ACIP) at the Centers for Disease Control and Prevention must be covered. This allows for better access to care as physicians will be able to purchase, store, and deliver vaccines to their patients. The fallacy in this system is that third parties get involved and rebates or incentives are given to these groups to purchase vaccines at a rate lower than those for physicians.

In addition, many organizations can get access to vaccines before physicians and at a lower cost. That system was flawed to begin with and created a deterrent for access to care and physician involvement in the vaccination process. This was worsened by different states being given the ability to decide how vaccines would be distributed for COVID.

Many pharmacies were able to give out COVID vaccines while many physician offices still have not received access to any of the vaccines. One of the major safety issues with this is that no physicians were involved in the administration of the vaccine, and it is unclear what training was given to the individuals injecting that vaccine. Finally, different places were interpreting the recommendations from ACIP on their own and not necessarily following the appropriate guidelines. All of these factors have further widened the health care disparity gap and made it difficult to provide the COVID vaccines in doctors’ offices.
 

Recommended next steps, solutions to problem

The question is what to do about this. The most important thing is to get the vaccines in arms so they can save lives. In addition, doctors need to be able to get the vaccines in their offices.

Many patients trust their physicians to advise them on what to do regarding health care. The majority of patients want to know if they should get the vaccine and ask for counseling. Physicians answering patients’ questions about vaccines is an important step in overcoming vaccine hesitancy.

Also, doctors need to be informed and supportive of the vaccine process.

The next step is the governmental aspect with those in power making sure that vaccines are accessible to all. Even if the vaccine cannot be given in the office, doctors should still be recommending that patients receive them. Plus, doctors should take every opportunity to ask about what vaccines their patients have received and encourage their patients to get vaccinated.

The COVID-19 vaccines are safe and effective and have been monitored for safety more than any other vaccine. There are multiple systems in place to look for any signals that could indicate an issue was caused by a COVID-19 vaccine. These vaccines can be administered with other vaccines, and there is a great opportunity for physicians to encourage patients to receive these life-saving vaccines.

While it may seem that the COVID-19 case counts are on the downslope, the importance of continuing to vaccinate is predicated on the very real concern that the disease is still circulating and the unvaccinated are still at risk for severe infection.

Dr. Goldman is immediate past governor of the Florida chapter of the American College of Physicians, a regent for the American College of Physicians, vice-president of the Florida Medical Association, and president of the Florida Medical Association Political Action Committee. You can reach Dr. Goldman at [email protected].

It would be overused and trite to say that the pandemic has drastically altered all of our lives and will cause lasting impact on how we function in society and medicine for years to come. While it seems that the current trend of the latest Omicron variant is on the downslope, the path to get to this point has been fraught with challenges that have struck at the very core of our society. As a primary care physician on the front lines seeing COVID patients, I have had to deal with not only the disease but the politics around it. As critical and life saving as the vaccines have been, many physicians have not been able to get access to these vaccines and give them to their patients. I am one of those physicians. I practice in Florida, and I still cannot give COVID vaccines in my office. 

I am a firm believer in the ability for physicians to be able to give all the necessary adult vaccines and provide them for their patients. The COVID vaccine exacerbated a majorly flawed system that further increased the health care disparities in the country. The current vaccine system for the majority of adult vaccines involves the physician’s being able to directly purchase supplies from the vaccine manufacturer, administer them to the patients, and be reimbursed.
 

Third parties can purchase vaccines at lower rates than those for physicians

The Affordable Care Act mandates that all vaccines approved by the Advisory Committee on Immunization Practices (ACIP) at the Centers for Disease Control and Prevention must be covered. This allows for better access to care as physicians will be able to purchase, store, and deliver vaccines to their patients. The fallacy in this system is that third parties get involved and rebates or incentives are given to these groups to purchase vaccines at a rate lower than those for physicians.

In addition, many organizations can get access to vaccines before physicians and at a lower cost. That system was flawed to begin with and created a deterrent for access to care and physician involvement in the vaccination process. This was worsened by different states being given the ability to decide how vaccines would be distributed for COVID.

Many pharmacies were able to give out COVID vaccines while many physician offices still have not received access to any of the vaccines. One of the major safety issues with this is that no physicians were involved in the administration of the vaccine, and it is unclear what training was given to the individuals injecting that vaccine. Finally, different places were interpreting the recommendations from ACIP on their own and not necessarily following the appropriate guidelines. All of these factors have further widened the health care disparity gap and made it difficult to provide the COVID vaccines in doctors’ offices.
 

Recommended next steps, solutions to problem

The question is what to do about this. The most important thing is to get the vaccines in arms so they can save lives. In addition, doctors need to be able to get the vaccines in their offices.

Many patients trust their physicians to advise them on what to do regarding health care. The majority of patients want to know if they should get the vaccine and ask for counseling. Physicians answering patients’ questions about vaccines is an important step in overcoming vaccine hesitancy.

Also, doctors need to be informed and supportive of the vaccine process.

The next step is the governmental aspect with those in power making sure that vaccines are accessible to all. Even if the vaccine cannot be given in the office, doctors should still be recommending that patients receive them. Plus, doctors should take every opportunity to ask about what vaccines their patients have received and encourage their patients to get vaccinated.

The COVID-19 vaccines are safe and effective and have been monitored for safety more than any other vaccine. There are multiple systems in place to look for any signals that could indicate an issue was caused by a COVID-19 vaccine. These vaccines can be administered with other vaccines, and there is a great opportunity for physicians to encourage patients to receive these life-saving vaccines.

While it may seem that the COVID-19 case counts are on the downslope, the importance of continuing to vaccinate is predicated on the very real concern that the disease is still circulating and the unvaccinated are still at risk for severe infection.

Dr. Goldman is immediate past governor of the Florida chapter of the American College of Physicians, a regent for the American College of Physicians, vice-president of the Florida Medical Association, and president of the Florida Medical Association Political Action Committee. You can reach Dr. Goldman at [email protected].

While evaluating an adolescent who had endured a several-day history of vomiting and diarrhea, I mentioned the likelihood of a viral causation, including SARS-CoV-2 infection. His well-informed mother responded, “He has no respiratory symptoms. Does COVID cause GI disease?”

Indeed, not only is the gastrointestinal tract a potential portal of entry of the virus but it may well be the site of mediation of both local and remote injury and thus a harbinger of more severe clinical phenotypes.

As we learn more about the clinical spectrum of COVID, it is becoming increasingly clear that certain features of GI tract involvement may allow us to establish a timeline of the clinical course and perhaps predict the outcome.
 

The GI tract’s involvement isn’t surprising

The ways in which the GI tract serves as a target organ of SARS-CoV-2 have been postulated in the literature. In part, this is related to the presence of abundant receptors for SARS-CoV-2 cell binding and internalization. The virus uses angiotensin-converting enzyme 2 receptors to enter various cells. These receptors are highly expressed on not only lung cells but also enterocytes. Binding of SARS-CoV-2 to ACE2 receptors allows GI involvement, leading to microscopic mucosal inflammation, increased permeability, and altered intestinal absorption.

The clinical GI manifestations of this include anorexia, nausea, vomiting, diarrhea, and abdominal pain, which may be the earliest, or sole, symptoms of COVID-19, often noted before the onset of fever or respiratory symptoms. In fact, John Ong, MBBS, and colleagues, in a discussion about patients with primary GI SARS-CoV-2 infection and symptoms, use the term “GI-COVID.”
 

Clinical course of GI manifestations

After SARS-CoV-2 exposure, adults most commonly present with respiratory symptoms, with GI symptoms reported in 10%-15% of cases. However, the overall incidence of GI involvement during SARS-CoV-2 infection varies according to age, with children more likely than adults to manifest intestinal symptoms.

There are also differences in incidence reported when comparing hospitalized with nonhospitalized individuals. In early reports from the onset of the COVID-19 pandemic, 11%-43% of hospitalized adult patients manifested GI symptoms. Of note, the presence of GI symptoms was associated with more severe disease and thus predictive of outcomes in those admitted to hospitals.

In a multicenter study that assessed pediatric inpatients with COVID-19, GI manifestations were present in 57% of patients and were the first manifestation in 14%. Adjusted by confounding factors, those with GI symptoms had a higher risk for pediatric intensive care unit admission. Patients admitted to the PICU also had higher serum C-reactive protein and aspartate aminotransferase values.
 

Emerging data on MIS-C

In previously healthy children and adolescents, the severe, life-threatening complication of multisystem inflammatory syndrome in children (MIS-C) may present 2-6 weeks after acute infection with SARS-CoV-2. MIS-C appears to be an immune activation syndrome and is presumed to be the delayed immunologic sequelae of mild/asymptomatic SARS-CoV-2 infection. This response manifests as hyperinflammation in conjunction with a peak in antibody production a few weeks later.

One report of 186 children with MIS-C in the United States noted that the involved organ system included the GI tract in 92%, followed by cardiovascular in 80%, hematologic in 76%, mucocutaneous in 74%, and respiratory in 70%. Affected children were hospitalized for a median of 7 days, with 80% requiring intensive care, 20% receiving mechanical ventilation, and 48% receiving vasoactive support; 2% died. In a similar study of patients hospitalized in New York, 88% had GI symptoms (abdominal pain, vomiting, and/or diarrhea). A retrospective chart review of patients with MIS-C found that the majority had GI symptoms with any portion of the GI tract potentially involved, but ileal and colonic inflammation predominated.

Elizabeth Whittaker, MD, and colleagues described the clinical characteristics of children in eight hospitals in England who met criteria for MIS-C that were temporally associated with SARS-CoV-2. At presentation, all of the patients manifested fever and nonspecific GI symptoms, including vomiting (45%), abdominal pain (53%), and diarrhea (52%). During hospitalization, 50% developed shock with evidence of myocardial dysfunction.

Ermias D. Belay, MD, and colleagues described the clinical characteristics of a large cohort of patients with MIS-C that were reported to the U.S. Centers for Disease Control and Prevention. Of 1,733 patients identified, GI symptoms were reported in 53%-67%. Over half developed hypotension or shock and were admitted for intensive care. Younger children more frequently presented with abdominal pain in contrast with adolescents, who more frequently manifest respiratory symptoms.

In a multicenter retrospective study of Italian children with COVID-19 that was conducted from the onset of the pandemic to early 2021, GI symptoms were noted in 38%. These manifestations were mild and self-limiting, comparable to other viral intestinal infections. However, a subset of children (9.5%) had severe GI manifestations of MIS-C, defined as a medical and/or radiologic diagnosis of acute abdomen, appendicitis, intussusception, pancreatitis, abdominal fluid collection, or diffuse adenomesenteritis requiring surgical consultation. Overall, 42% of this group underwent surgery. The authors noted that the clinical presentation of abdominal pain, lymphopenia, and increased C-reactive protein and ferritin levels were associated with a 9- to 30-fold increased probability of these severe sequelae. In addition, the severity of the GI manifestations was correlated with age (5-10 years: overall response, 8.33; >10 years: OR, 6.37). Again, the presence of GI symptoms was a harbinger of hospitalization and PICU admission.

Given that GI symptoms are a common presentation of MIS-C, its diagnosis may be delayed as clinicians first consider other GI/viral infections, inflammatory bowel disease, or Kawasaki disease. Prompt identification of GI involvement and awareness of the potential outcomes may guide the management and improve the outcome.

These studies provide a clear picture of the differential presenting features of COVID-19 and MIS-C. Although there may be other environmental/genetic factors that govern the incidence, impact, and manifestations, COVID’s status as an ongoing pandemic gives these observations worldwide relevance. This is evident in a recent report documenting pronounced GI symptoms in African children with COVID-19.

It should be noted, however, that the published data cited here reflect the impact of the initial variants of SARS-CoV-2. The GI binding, effects, and aftermath of infection with the Delta and Omicron variants is not yet known.
 

Cause and effect, or simply coincidental?

Some insight into MIS-C pathogenesis was provided by Lael M. Yonker, MD, and colleagues in their analysis of biospecimens from 100 children: 19 with MIS-C, 26 with acute COVID-19, and 55 controls. They demonstrated that in children with MIS-C the prolonged presence of SARS-CoV-2 in the GI tract led to the release of zonulin, a biomarker of intestinal permeability, with subsequent trafficking of SARS-CoV-2 antigens into the bloodstream, leading to hyperinflammation. They were then able to decrease plasma SARS-CoV-2 spike antigen levels and inflammatory markers, with resulting clinical improvement after administration of larazotide, a zonulin antagonist.

These observations regarding the potential mechanism and triggers of MIS-C may offer biomarkers for early detection and/or strategies for prevention and treatment of MIS-C.
 

Bottom line

The GI tract is the target of an immune-mediated inflammatory response that is triggered by SARS-CoV-2, with MIS-C being the major manifestation of the resultant high degree of inflammation. These observations will allow an increased awareness of nonrespiratory symptoms of SARS-CoV-2 infection by clinicians working in emergency departments and primary care settings.

Clues that may enhance the ability of pediatric clinicians to recognize the potential for severe GI involvement include the occurrence of abdominal pain, leukopenia, and elevated inflammatory markers. Their presence should raise suspicion of MIS-C and lead to early evaluation.

Of note, COVID-19 mRNA vaccination is associated with a lower incidence of MIS-C in adolescents. This underscores the importance of COVID vaccination for all eligible children. Yet, we clearly have our work cut out for us. Of 107 children with MIS-C who were hospitalized in France, 31% were adolescents eligible for vaccination; however, none had been fully vaccinated. At the end of 2021, CDC data noted that less than 1% of vaccine-eligible children (12-17 years) were fully vaccinated.

The Pfizer-BioNTech vaccine is now authorized for receipt by children aged 5-11 years, the age group that is at highest risk for MIS-C. However, despite the approval of vaccines for these younger children, there is limited access in some parts of the United States at a time of rising incidence.

We look forward to broad availability of pediatric vaccination strategies. In addition, with the intense focus on safe and effective therapeutics for SARS-CoV-2 infection, we hope to soon have strategies to prevent and/or treat the life-threatening manifestations and long-term consequences of MIS-C. For example, the recently reported central role of the gut microbiota in immunity against SARS-CoV-2 infection offer the possibility that “microbiota modulation” may both reduce GI injury and enhance vaccine efficacy.

Dr. Balistreri has disclosed no relevant financial relationships.

William F. Balistreri, MD, is the Dorothy M.M. Kersten Professor of Pediatrics; director emeritus, Pediatric Liver Care Center; medical director emeritus, liver transplantation; and professor, University of Cincinnati College of Medicine, department of pediatrics, Cincinnati Children’s Hospital Medical Center. He has served as director of the division of gastroenterology, hepatology, and nutrition at Cincinnati Children’s for 25 years and frequently covers gastroenterology, liver, and nutrition-related topics for this news organization. Dr Balistreri is currently editor-in-chief of the Journal of Pediatrics, having previously served as editor-in-chief of several journals and textbooks. He also became the first pediatrician to act as president of the American Association for the Study of Liver Diseases. In his spare time, he coaches youth lacrosse.

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

While evaluating an adolescent who had endured a several-day history of vomiting and diarrhea, I mentioned the likelihood of a viral causation, including SARS-CoV-2 infection. His well-informed mother responded, “He has no respiratory symptoms. Does COVID cause GI disease?”

Indeed, not only is the gastrointestinal tract a potential portal of entry of the virus but it may well be the site of mediation of both local and remote injury and thus a harbinger of more severe clinical phenotypes.

As we learn more about the clinical spectrum of COVID, it is becoming increasingly clear that certain features of GI tract involvement may allow us to establish a timeline of the clinical course and perhaps predict the outcome.
 

The GI tract’s involvement isn’t surprising

The ways in which the GI tract serves as a target organ of SARS-CoV-2 have been postulated in the literature. In part, this is related to the presence of abundant receptors for SARS-CoV-2 cell binding and internalization. The virus uses angiotensin-converting enzyme 2 receptors to enter various cells. These receptors are highly expressed on not only lung cells but also enterocytes. Binding of SARS-CoV-2 to ACE2 receptors allows GI involvement, leading to microscopic mucosal inflammation, increased permeability, and altered intestinal absorption.

The clinical GI manifestations of this include anorexia, nausea, vomiting, diarrhea, and abdominal pain, which may be the earliest, or sole, symptoms of COVID-19, often noted before the onset of fever or respiratory symptoms. In fact, John Ong, MBBS, and colleagues, in a discussion about patients with primary GI SARS-CoV-2 infection and symptoms, use the term “GI-COVID.”
 

Clinical course of GI manifestations

After SARS-CoV-2 exposure, adults most commonly present with respiratory symptoms, with GI symptoms reported in 10%-15% of cases. However, the overall incidence of GI involvement during SARS-CoV-2 infection varies according to age, with children more likely than adults to manifest intestinal symptoms.

There are also differences in incidence reported when comparing hospitalized with nonhospitalized individuals. In early reports from the onset of the COVID-19 pandemic, 11%-43% of hospitalized adult patients manifested GI symptoms. Of note, the presence of GI symptoms was associated with more severe disease and thus predictive of outcomes in those admitted to hospitals.

In a multicenter study that assessed pediatric inpatients with COVID-19, GI manifestations were present in 57% of patients and were the first manifestation in 14%. Adjusted by confounding factors, those with GI symptoms had a higher risk for pediatric intensive care unit admission. Patients admitted to the PICU also had higher serum C-reactive protein and aspartate aminotransferase values.
 

Emerging data on MIS-C

In previously healthy children and adolescents, the severe, life-threatening complication of multisystem inflammatory syndrome in children (MIS-C) may present 2-6 weeks after acute infection with SARS-CoV-2. MIS-C appears to be an immune activation syndrome and is presumed to be the delayed immunologic sequelae of mild/asymptomatic SARS-CoV-2 infection. This response manifests as hyperinflammation in conjunction with a peak in antibody production a few weeks later.

One report of 186 children with MIS-C in the United States noted that the involved organ system included the GI tract in 92%, followed by cardiovascular in 80%, hematologic in 76%, mucocutaneous in 74%, and respiratory in 70%. Affected children were hospitalized for a median of 7 days, with 80% requiring intensive care, 20% receiving mechanical ventilation, and 48% receiving vasoactive support; 2% died. In a similar study of patients hospitalized in New York, 88% had GI symptoms (abdominal pain, vomiting, and/or diarrhea). A retrospective chart review of patients with MIS-C found that the majority had GI symptoms with any portion of the GI tract potentially involved, but ileal and colonic inflammation predominated.

Elizabeth Whittaker, MD, and colleagues described the clinical characteristics of children in eight hospitals in England who met criteria for MIS-C that were temporally associated with SARS-CoV-2. At presentation, all of the patients manifested fever and nonspecific GI symptoms, including vomiting (45%), abdominal pain (53%), and diarrhea (52%). During hospitalization, 50% developed shock with evidence of myocardial dysfunction.

Ermias D. Belay, MD, and colleagues described the clinical characteristics of a large cohort of patients with MIS-C that were reported to the U.S. Centers for Disease Control and Prevention. Of 1,733 patients identified, GI symptoms were reported in 53%-67%. Over half developed hypotension or shock and were admitted for intensive care. Younger children more frequently presented with abdominal pain in contrast with adolescents, who more frequently manifest respiratory symptoms.

In a multicenter retrospective study of Italian children with COVID-19 that was conducted from the onset of the pandemic to early 2021, GI symptoms were noted in 38%. These manifestations were mild and self-limiting, comparable to other viral intestinal infections. However, a subset of children (9.5%) had severe GI manifestations of MIS-C, defined as a medical and/or radiologic diagnosis of acute abdomen, appendicitis, intussusception, pancreatitis, abdominal fluid collection, or diffuse adenomesenteritis requiring surgical consultation. Overall, 42% of this group underwent surgery. The authors noted that the clinical presentation of abdominal pain, lymphopenia, and increased C-reactive protein and ferritin levels were associated with a 9- to 30-fold increased probability of these severe sequelae. In addition, the severity of the GI manifestations was correlated with age (5-10 years: overall response, 8.33; >10 years: OR, 6.37). Again, the presence of GI symptoms was a harbinger of hospitalization and PICU admission.

Given that GI symptoms are a common presentation of MIS-C, its diagnosis may be delayed as clinicians first consider other GI/viral infections, inflammatory bowel disease, or Kawasaki disease. Prompt identification of GI involvement and awareness of the potential outcomes may guide the management and improve the outcome.

These studies provide a clear picture of the differential presenting features of COVID-19 and MIS-C. Although there may be other environmental/genetic factors that govern the incidence, impact, and manifestations, COVID’s status as an ongoing pandemic gives these observations worldwide relevance. This is evident in a recent report documenting pronounced GI symptoms in African children with COVID-19.

It should be noted, however, that the published data cited here reflect the impact of the initial variants of SARS-CoV-2. The GI binding, effects, and aftermath of infection with the Delta and Omicron variants is not yet known.
 

Cause and effect, or simply coincidental?

Some insight into MIS-C pathogenesis was provided by Lael M. Yonker, MD, and colleagues in their analysis of biospecimens from 100 children: 19 with MIS-C, 26 with acute COVID-19, and 55 controls. They demonstrated that in children with MIS-C the prolonged presence of SARS-CoV-2 in the GI tract led to the release of zonulin, a biomarker of intestinal permeability, with subsequent trafficking of SARS-CoV-2 antigens into the bloodstream, leading to hyperinflammation. They were then able to decrease plasma SARS-CoV-2 spike antigen levels and inflammatory markers, with resulting clinical improvement after administration of larazotide, a zonulin antagonist.

These observations regarding the potential mechanism and triggers of MIS-C may offer biomarkers for early detection and/or strategies for prevention and treatment of MIS-C.
 

Bottom line

The GI tract is the target of an immune-mediated inflammatory response that is triggered by SARS-CoV-2, with MIS-C being the major manifestation of the resultant high degree of inflammation. These observations will allow an increased awareness of nonrespiratory symptoms of SARS-CoV-2 infection by clinicians working in emergency departments and primary care settings.

Clues that may enhance the ability of pediatric clinicians to recognize the potential for severe GI involvement include the occurrence of abdominal pain, leukopenia, and elevated inflammatory markers. Their presence should raise suspicion of MIS-C and lead to early evaluation.

Of note, COVID-19 mRNA vaccination is associated with a lower incidence of MIS-C in adolescents. This underscores the importance of COVID vaccination for all eligible children. Yet, we clearly have our work cut out for us. Of 107 children with MIS-C who were hospitalized in France, 31% were adolescents eligible for vaccination; however, none had been fully vaccinated. At the end of 2021, CDC data noted that less than 1% of vaccine-eligible children (12-17 years) were fully vaccinated.

The Pfizer-BioNTech vaccine is now authorized for receipt by children aged 5-11 years, the age group that is at highest risk for MIS-C. However, despite the approval of vaccines for these younger children, there is limited access in some parts of the United States at a time of rising incidence.

We look forward to broad availability of pediatric vaccination strategies. In addition, with the intense focus on safe and effective therapeutics for SARS-CoV-2 infection, we hope to soon have strategies to prevent and/or treat the life-threatening manifestations and long-term consequences of MIS-C. For example, the recently reported central role of the gut microbiota in immunity against SARS-CoV-2 infection offer the possibility that “microbiota modulation” may both reduce GI injury and enhance vaccine efficacy.

Dr. Balistreri has disclosed no relevant financial relationships.

William F. Balistreri, MD, is the Dorothy M.M. Kersten Professor of Pediatrics; director emeritus, Pediatric Liver Care Center; medical director emeritus, liver transplantation; and professor, University of Cincinnati College of Medicine, department of pediatrics, Cincinnati Children’s Hospital Medical Center. He has served as director of the division of gastroenterology, hepatology, and nutrition at Cincinnati Children’s for 25 years and frequently covers gastroenterology, liver, and nutrition-related topics for this news organization. Dr Balistreri is currently editor-in-chief of the Journal of Pediatrics, having previously served as editor-in-chief of several journals and textbooks. He also became the first pediatrician to act as president of the American Association for the Study of Liver Diseases. In his spare time, he coaches youth lacrosse.

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

While evaluating an adolescent who had endured a several-day history of vomiting and diarrhea, I mentioned the likelihood of a viral causation, including SARS-CoV-2 infection. His well-informed mother responded, “He has no respiratory symptoms. Does COVID cause GI disease?”

Indeed, not only is the gastrointestinal tract a potential portal of entry of the virus but it may well be the site of mediation of both local and remote injury and thus a harbinger of more severe clinical phenotypes.

As we learn more about the clinical spectrum of COVID, it is becoming increasingly clear that certain features of GI tract involvement may allow us to establish a timeline of the clinical course and perhaps predict the outcome.
 

The GI tract’s involvement isn’t surprising

The ways in which the GI tract serves as a target organ of SARS-CoV-2 have been postulated in the literature. In part, this is related to the presence of abundant receptors for SARS-CoV-2 cell binding and internalization. The virus uses angiotensin-converting enzyme 2 receptors to enter various cells. These receptors are highly expressed on not only lung cells but also enterocytes. Binding of SARS-CoV-2 to ACE2 receptors allows GI involvement, leading to microscopic mucosal inflammation, increased permeability, and altered intestinal absorption.

The clinical GI manifestations of this include anorexia, nausea, vomiting, diarrhea, and abdominal pain, which may be the earliest, or sole, symptoms of COVID-19, often noted before the onset of fever or respiratory symptoms. In fact, John Ong, MBBS, and colleagues, in a discussion about patients with primary GI SARS-CoV-2 infection and symptoms, use the term “GI-COVID.”
 

Clinical course of GI manifestations

After SARS-CoV-2 exposure, adults most commonly present with respiratory symptoms, with GI symptoms reported in 10%-15% of cases. However, the overall incidence of GI involvement during SARS-CoV-2 infection varies according to age, with children more likely than adults to manifest intestinal symptoms.

There are also differences in incidence reported when comparing hospitalized with nonhospitalized individuals. In early reports from the onset of the COVID-19 pandemic, 11%-43% of hospitalized adult patients manifested GI symptoms. Of note, the presence of GI symptoms was associated with more severe disease and thus predictive of outcomes in those admitted to hospitals.

In a multicenter study that assessed pediatric inpatients with COVID-19, GI manifestations were present in 57% of patients and were the first manifestation in 14%. Adjusted by confounding factors, those with GI symptoms had a higher risk for pediatric intensive care unit admission. Patients admitted to the PICU also had higher serum C-reactive protein and aspartate aminotransferase values.
 

Emerging data on MIS-C

In previously healthy children and adolescents, the severe, life-threatening complication of multisystem inflammatory syndrome in children (MIS-C) may present 2-6 weeks after acute infection with SARS-CoV-2. MIS-C appears to be an immune activation syndrome and is presumed to be the delayed immunologic sequelae of mild/asymptomatic SARS-CoV-2 infection. This response manifests as hyperinflammation in conjunction with a peak in antibody production a few weeks later.

One report of 186 children with MIS-C in the United States noted that the involved organ system included the GI tract in 92%, followed by cardiovascular in 80%, hematologic in 76%, mucocutaneous in 74%, and respiratory in 70%. Affected children were hospitalized for a median of 7 days, with 80% requiring intensive care, 20% receiving mechanical ventilation, and 48% receiving vasoactive support; 2% died. In a similar study of patients hospitalized in New York, 88% had GI symptoms (abdominal pain, vomiting, and/or diarrhea). A retrospective chart review of patients with MIS-C found that the majority had GI symptoms with any portion of the GI tract potentially involved, but ileal and colonic inflammation predominated.

Elizabeth Whittaker, MD, and colleagues described the clinical characteristics of children in eight hospitals in England who met criteria for MIS-C that were temporally associated with SARS-CoV-2. At presentation, all of the patients manifested fever and nonspecific GI symptoms, including vomiting (45%), abdominal pain (53%), and diarrhea (52%). During hospitalization, 50% developed shock with evidence of myocardial dysfunction.

Ermias D. Belay, MD, and colleagues described the clinical characteristics of a large cohort of patients with MIS-C that were reported to the U.S. Centers for Disease Control and Prevention. Of 1,733 patients identified, GI symptoms were reported in 53%-67%. Over half developed hypotension or shock and were admitted for intensive care. Younger children more frequently presented with abdominal pain in contrast with adolescents, who more frequently manifest respiratory symptoms.

In a multicenter retrospective study of Italian children with COVID-19 that was conducted from the onset of the pandemic to early 2021, GI symptoms were noted in 38%. These manifestations were mild and self-limiting, comparable to other viral intestinal infections. However, a subset of children (9.5%) had severe GI manifestations of MIS-C, defined as a medical and/or radiologic diagnosis of acute abdomen, appendicitis, intussusception, pancreatitis, abdominal fluid collection, or diffuse adenomesenteritis requiring surgical consultation. Overall, 42% of this group underwent surgery. The authors noted that the clinical presentation of abdominal pain, lymphopenia, and increased C-reactive protein and ferritin levels were associated with a 9- to 30-fold increased probability of these severe sequelae. In addition, the severity of the GI manifestations was correlated with age (5-10 years: overall response, 8.33; >10 years: OR, 6.37). Again, the presence of GI symptoms was a harbinger of hospitalization and PICU admission.

Given that GI symptoms are a common presentation of MIS-C, its diagnosis may be delayed as clinicians first consider other GI/viral infections, inflammatory bowel disease, or Kawasaki disease. Prompt identification of GI involvement and awareness of the potential outcomes may guide the management and improve the outcome.

These studies provide a clear picture of the differential presenting features of COVID-19 and MIS-C. Although there may be other environmental/genetic factors that govern the incidence, impact, and manifestations, COVID’s status as an ongoing pandemic gives these observations worldwide relevance. This is evident in a recent report documenting pronounced GI symptoms in African children with COVID-19.

It should be noted, however, that the published data cited here reflect the impact of the initial variants of SARS-CoV-2. The GI binding, effects, and aftermath of infection with the Delta and Omicron variants is not yet known.
 

Cause and effect, or simply coincidental?

Some insight into MIS-C pathogenesis was provided by Lael M. Yonker, MD, and colleagues in their analysis of biospecimens from 100 children: 19 with MIS-C, 26 with acute COVID-19, and 55 controls. They demonstrated that in children with MIS-C the prolonged presence of SARS-CoV-2 in the GI tract led to the release of zonulin, a biomarker of intestinal permeability, with subsequent trafficking of SARS-CoV-2 antigens into the bloodstream, leading to hyperinflammation. They were then able to decrease plasma SARS-CoV-2 spike antigen levels and inflammatory markers, with resulting clinical improvement after administration of larazotide, a zonulin antagonist.

These observations regarding the potential mechanism and triggers of MIS-C may offer biomarkers for early detection and/or strategies for prevention and treatment of MIS-C.
 

Bottom line

The GI tract is the target of an immune-mediated inflammatory response that is triggered by SARS-CoV-2, with MIS-C being the major manifestation of the resultant high degree of inflammation. These observations will allow an increased awareness of nonrespiratory symptoms of SARS-CoV-2 infection by clinicians working in emergency departments and primary care settings.

Clues that may enhance the ability of pediatric clinicians to recognize the potential for severe GI involvement include the occurrence of abdominal pain, leukopenia, and elevated inflammatory markers. Their presence should raise suspicion of MIS-C and lead to early evaluation.

Of note, COVID-19 mRNA vaccination is associated with a lower incidence of MIS-C in adolescents. This underscores the importance of COVID vaccination for all eligible children. Yet, we clearly have our work cut out for us. Of 107 children with MIS-C who were hospitalized in France, 31% were adolescents eligible for vaccination; however, none had been fully vaccinated. At the end of 2021, CDC data noted that less than 1% of vaccine-eligible children (12-17 years) were fully vaccinated.

The Pfizer-BioNTech vaccine is now authorized for receipt by children aged 5-11 years, the age group that is at highest risk for MIS-C. However, despite the approval of vaccines for these younger children, there is limited access in some parts of the United States at a time of rising incidence.

We look forward to broad availability of pediatric vaccination strategies. In addition, with the intense focus on safe and effective therapeutics for SARS-CoV-2 infection, we hope to soon have strategies to prevent and/or treat the life-threatening manifestations and long-term consequences of MIS-C. For example, the recently reported central role of the gut microbiota in immunity against SARS-CoV-2 infection offer the possibility that “microbiota modulation” may both reduce GI injury and enhance vaccine efficacy.

Dr. Balistreri has disclosed no relevant financial relationships.

William F. Balistreri, MD, is the Dorothy M.M. Kersten Professor of Pediatrics; director emeritus, Pediatric Liver Care Center; medical director emeritus, liver transplantation; and professor, University of Cincinnati College of Medicine, department of pediatrics, Cincinnati Children’s Hospital Medical Center. He has served as director of the division of gastroenterology, hepatology, and nutrition at Cincinnati Children’s for 25 years and frequently covers gastroenterology, liver, and nutrition-related topics for this news organization. Dr Balistreri is currently editor-in-chief of the Journal of Pediatrics, having previously served as editor-in-chief of several journals and textbooks. He also became the first pediatrician to act as president of the American Association for the Study of Liver Diseases. In his spare time, he coaches youth lacrosse.

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

New cases of COVID-19 in U.S. children dropped for the fifth consecutive week, but the rate of decline slowed considerably, according to the American Academy of Pediatrics and the Children’s Hospital Association.

Compared with the 2 previous weeks, when new cases fell by 52.7% and 41.9%, the number of child COVID cases for the week of Feb. 18-24 declined by 27%, with almost 127,000 reported. The national count of new cases has now fallen for five straight weeks since peaking Jan. 14-20, and this week’s figure is the lowest since the pre-Omicron days of mid-November, based on data collected by the AAP and CHA from 49 states (excluding New York), the District of Columbia, New York City, Puerto Rico, and Guam.

Over 12.6 million pediatric cases have been reported by those jurisdictions since the start of the pandemic, representing 19.0% of all cases in the United States, the AAP and CHA said in their weekly COVID report.

The highest cumulative rate among the states, 27.5%, can be found in Vermont, followed by New Hampshire (26.7%) and Alaska (26.6%). Alabama’s 12.1% is lower than any other jurisdiction, but the state stopped reporting during the summer of 2021, just as the Delta surge was beginning. The next two lowest states, Florida (12.8%) and Utah (13.9%), both define children as those aged 0-14 years, so the state with the lowest rate and no qualifiers is Idaho at 14.3%, the AAP/CHA data show.

The downward trend in new cases is reflected in other national measures. The daily rate of new hospital admissions for children aged 0-17 years was 0.32 per 100,000 population on Feb. 26, which is a drop of 75% since admissions peaked at 1.25 per 100,000 on Jan. 15, according to the Centers for Disease Control and Prevention.

The most recent 7-day average (Feb. 20-26) for child admissions with confirmed COVID-19 was 237 per day, compared with 914 per day during the peak week of Jan. 10-16. Emergency department visits with diagnosed COVID, measured as a percentage of all ED visits by age group, are down even more. The 7-day average was 1.2% on Feb. 25 for children aged 0-11 years, compared with a peak of 13.9% in mid-January, the CDC said on its COVID Data Tracker. The current rates for older children are even lower.

The decline of the Omicron surge over the last few weeks is allowing states to end mask mandates in schools around the country. The governors of California, Oregon, and Washington just announced that their states will be lifting their mask requirements on March 11, and New York State will end its mandate on March 2, while New York City is scheduled to go mask-free as of March 7, according to District Administration.

Those types of government moves, however, do not seem to be entirely supported by the public. In a survey conducted Feb. 9-21 by the Kaiser Family Foundation, 43% of the 1,502 respondents said that all students and staff should be required to wear masks in schools, while 40% said that there should be no mask requirements at all.

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New cases of COVID-19 in U.S. children dropped for the fifth consecutive week, but the rate of decline slowed considerably, according to the American Academy of Pediatrics and the Children’s Hospital Association.

Compared with the 2 previous weeks, when new cases fell by 52.7% and 41.9%, the number of child COVID cases for the week of Feb. 18-24 declined by 27%, with almost 127,000 reported. The national count of new cases has now fallen for five straight weeks since peaking Jan. 14-20, and this week’s figure is the lowest since the pre-Omicron days of mid-November, based on data collected by the AAP and CHA from 49 states (excluding New York), the District of Columbia, New York City, Puerto Rico, and Guam.

Over 12.6 million pediatric cases have been reported by those jurisdictions since the start of the pandemic, representing 19.0% of all cases in the United States, the AAP and CHA said in their weekly COVID report.

The highest cumulative rate among the states, 27.5%, can be found in Vermont, followed by New Hampshire (26.7%) and Alaska (26.6%). Alabama’s 12.1% is lower than any other jurisdiction, but the state stopped reporting during the summer of 2021, just as the Delta surge was beginning. The next two lowest states, Florida (12.8%) and Utah (13.9%), both define children as those aged 0-14 years, so the state with the lowest rate and no qualifiers is Idaho at 14.3%, the AAP/CHA data show.

The downward trend in new cases is reflected in other national measures. The daily rate of new hospital admissions for children aged 0-17 years was 0.32 per 100,000 population on Feb. 26, which is a drop of 75% since admissions peaked at 1.25 per 100,000 on Jan. 15, according to the Centers for Disease Control and Prevention.

The most recent 7-day average (Feb. 20-26) for child admissions with confirmed COVID-19 was 237 per day, compared with 914 per day during the peak week of Jan. 10-16. Emergency department visits with diagnosed COVID, measured as a percentage of all ED visits by age group, are down even more. The 7-day average was 1.2% on Feb. 25 for children aged 0-11 years, compared with a peak of 13.9% in mid-January, the CDC said on its COVID Data Tracker. The current rates for older children are even lower.

The decline of the Omicron surge over the last few weeks is allowing states to end mask mandates in schools around the country. The governors of California, Oregon, and Washington just announced that their states will be lifting their mask requirements on March 11, and New York State will end its mandate on March 2, while New York City is scheduled to go mask-free as of March 7, according to District Administration.

Those types of government moves, however, do not seem to be entirely supported by the public. In a survey conducted Feb. 9-21 by the Kaiser Family Foundation, 43% of the 1,502 respondents said that all students and staff should be required to wear masks in schools, while 40% said that there should be no mask requirements at all.

[email protected]

New cases of COVID-19 in U.S. children dropped for the fifth consecutive week, but the rate of decline slowed considerably, according to the American Academy of Pediatrics and the Children’s Hospital Association.

Compared with the 2 previous weeks, when new cases fell by 52.7% and 41.9%, the number of child COVID cases for the week of Feb. 18-24 declined by 27%, with almost 127,000 reported. The national count of new cases has now fallen for five straight weeks since peaking Jan. 14-20, and this week’s figure is the lowest since the pre-Omicron days of mid-November, based on data collected by the AAP and CHA from 49 states (excluding New York), the District of Columbia, New York City, Puerto Rico, and Guam.

Over 12.6 million pediatric cases have been reported by those jurisdictions since the start of the pandemic, representing 19.0% of all cases in the United States, the AAP and CHA said in their weekly COVID report.

The highest cumulative rate among the states, 27.5%, can be found in Vermont, followed by New Hampshire (26.7%) and Alaska (26.6%). Alabama’s 12.1% is lower than any other jurisdiction, but the state stopped reporting during the summer of 2021, just as the Delta surge was beginning. The next two lowest states, Florida (12.8%) and Utah (13.9%), both define children as those aged 0-14 years, so the state with the lowest rate and no qualifiers is Idaho at 14.3%, the AAP/CHA data show.

The downward trend in new cases is reflected in other national measures. The daily rate of new hospital admissions for children aged 0-17 years was 0.32 per 100,000 population on Feb. 26, which is a drop of 75% since admissions peaked at 1.25 per 100,000 on Jan. 15, according to the Centers for Disease Control and Prevention.

The most recent 7-day average (Feb. 20-26) for child admissions with confirmed COVID-19 was 237 per day, compared with 914 per day during the peak week of Jan. 10-16. Emergency department visits with diagnosed COVID, measured as a percentage of all ED visits by age group, are down even more. The 7-day average was 1.2% on Feb. 25 for children aged 0-11 years, compared with a peak of 13.9% in mid-January, the CDC said on its COVID Data Tracker. The current rates for older children are even lower.

The decline of the Omicron surge over the last few weeks is allowing states to end mask mandates in schools around the country. The governors of California, Oregon, and Washington just announced that their states will be lifting their mask requirements on March 11, and New York State will end its mandate on March 2, while New York City is scheduled to go mask-free as of March 7, according to District Administration.

Those types of government moves, however, do not seem to be entirely supported by the public. In a survey conducted Feb. 9-21 by the Kaiser Family Foundation, 43% of the 1,502 respondents said that all students and staff should be required to wear masks in schools, while 40% said that there should be no mask requirements at all.

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Elective surgical procedures should be delayed at least 7 weeks after COVID-19 infection in unvaccinated patients, according to a new joint statement issued by the American Society of Anesthesiologists and the Anesthesia Patient Safety Foundation (APSF).

For patients fully vaccinated against COVID-19 with breakthrough infections, there is no consensus on how vaccination affects the time between COVID-19 infection and elective surgery. Clinicians should use their clinical judgment to schedule procedures, said Randall M. Clark, MD, president of the American Society of Anesthesiologists (ASA). “We need all physicians, anesthesiologists, surgeons, and others to base their decision to go ahead with elective surgery on the patient’s symptoms, their need for the procedure, and whether delays could cause other problems with their health,” he said in an interview.

Prior to these updated recommendations, which were published Feb. 22, the ASA and the APSF recommended a 4-week gap between COVID-19 diagnosis and elective surgery for asymptomatic or mild cases, regardless of a patient’s vaccination status.

Extending the wait time from 4 to 7 weeks was based on a multination study conducted in October 2020 following more than 140,000 surgical patients. Patients with previous COVID-19 infection had an increased risk for complications and death in elective surgery for up to 6 weeks following their diagnosis, compared with patients without COVID-19. Additional research in the United States found that patients with a preoperative COVID diagnosis were at higher risk for postoperative complications of respiratory failure for up to 4 weeks after diagnosis and postoperative pneumonia complications for up to 8 weeks after diagnosis.

Because these studies were conducted in unvaccinated populations or those with low vaccination rates, and preliminary data suggest vaccinated patients with breakthrough infections may have a lower risk for complications and death postinfection, “we felt that it was prudent to just make recommendations specific to unvaccinated patients,” Dr. Clark added.

Although this guidance is “very helpful” in that it summarizes the currently available research to give evidence-based recommendations, the 7-week wait time is a “very conservative estimate,” Brent Matthews, MD, surgeon-in-chief of the surgery care division of Atrium Health, Charlotte, N.C., told this news organization. At Atrium Health, surgery is scheduled at least 21 days after a patient’s COVID-19 diagnosis, regardless of their vaccination status, Dr. Matthews said.

The studies currently available were conducted earlier in the pandemic, when a different variant was prevalent, Dr. Matthews explained. The Omicron variant is currently the most prevalent COVID-19 variant and is less virulent than earlier strains of the virus. The joint statement does note that there is currently “no robust data” on patients infected with the Delta or Omicron variants of COVID-19, and that “the Omicron variant causes less severe disease and is more likely to reside in the oro- and nasopharynx without infiltration and damage to the lungs.”

Still, the new recommendations are a reminder to re-evaluate the potential complications from surgery for previously infected patients and to consider what comorbidities might make them more vulnerable, Dr. Matthews said. “The real power of the joint statement is to get people to ensure that they make an assessment of every patient that comes in front of them who has had a recent positive COVID test.”

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

Elective surgical procedures should be delayed at least 7 weeks after COVID-19 infection in unvaccinated patients, according to a new joint statement issued by the American Society of Anesthesiologists and the Anesthesia Patient Safety Foundation (APSF).

For patients fully vaccinated against COVID-19 with breakthrough infections, there is no consensus on how vaccination affects the time between COVID-19 infection and elective surgery. Clinicians should use their clinical judgment to schedule procedures, said Randall M. Clark, MD, president of the American Society of Anesthesiologists (ASA). “We need all physicians, anesthesiologists, surgeons, and others to base their decision to go ahead with elective surgery on the patient’s symptoms, their need for the procedure, and whether delays could cause other problems with their health,” he said in an interview.

Prior to these updated recommendations, which were published Feb. 22, the ASA and the APSF recommended a 4-week gap between COVID-19 diagnosis and elective surgery for asymptomatic or mild cases, regardless of a patient’s vaccination status.

Extending the wait time from 4 to 7 weeks was based on a multination study conducted in October 2020 following more than 140,000 surgical patients. Patients with previous COVID-19 infection had an increased risk for complications and death in elective surgery for up to 6 weeks following their diagnosis, compared with patients without COVID-19. Additional research in the United States found that patients with a preoperative COVID diagnosis were at higher risk for postoperative complications of respiratory failure for up to 4 weeks after diagnosis and postoperative pneumonia complications for up to 8 weeks after diagnosis.

Because these studies were conducted in unvaccinated populations or those with low vaccination rates, and preliminary data suggest vaccinated patients with breakthrough infections may have a lower risk for complications and death postinfection, “we felt that it was prudent to just make recommendations specific to unvaccinated patients,” Dr. Clark added.

Although this guidance is “very helpful” in that it summarizes the currently available research to give evidence-based recommendations, the 7-week wait time is a “very conservative estimate,” Brent Matthews, MD, surgeon-in-chief of the surgery care division of Atrium Health, Charlotte, N.C., told this news organization. At Atrium Health, surgery is scheduled at least 21 days after a patient’s COVID-19 diagnosis, regardless of their vaccination status, Dr. Matthews said.

The studies currently available were conducted earlier in the pandemic, when a different variant was prevalent, Dr. Matthews explained. The Omicron variant is currently the most prevalent COVID-19 variant and is less virulent than earlier strains of the virus. The joint statement does note that there is currently “no robust data” on patients infected with the Delta or Omicron variants of COVID-19, and that “the Omicron variant causes less severe disease and is more likely to reside in the oro- and nasopharynx without infiltration and damage to the lungs.”

Still, the new recommendations are a reminder to re-evaluate the potential complications from surgery for previously infected patients and to consider what comorbidities might make them more vulnerable, Dr. Matthews said. “The real power of the joint statement is to get people to ensure that they make an assessment of every patient that comes in front of them who has had a recent positive COVID test.”

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

Elective surgical procedures should be delayed at least 7 weeks after COVID-19 infection in unvaccinated patients, according to a new joint statement issued by the American Society of Anesthesiologists and the Anesthesia Patient Safety Foundation (APSF).

For patients fully vaccinated against COVID-19 with breakthrough infections, there is no consensus on how vaccination affects the time between COVID-19 infection and elective surgery. Clinicians should use their clinical judgment to schedule procedures, said Randall M. Clark, MD, president of the American Society of Anesthesiologists (ASA). “We need all physicians, anesthesiologists, surgeons, and others to base their decision to go ahead with elective surgery on the patient’s symptoms, their need for the procedure, and whether delays could cause other problems with their health,” he said in an interview.

Prior to these updated recommendations, which were published Feb. 22, the ASA and the APSF recommended a 4-week gap between COVID-19 diagnosis and elective surgery for asymptomatic or mild cases, regardless of a patient’s vaccination status.

Extending the wait time from 4 to 7 weeks was based on a multination study conducted in October 2020 following more than 140,000 surgical patients. Patients with previous COVID-19 infection had an increased risk for complications and death in elective surgery for up to 6 weeks following their diagnosis, compared with patients without COVID-19. Additional research in the United States found that patients with a preoperative COVID diagnosis were at higher risk for postoperative complications of respiratory failure for up to 4 weeks after diagnosis and postoperative pneumonia complications for up to 8 weeks after diagnosis.

Because these studies were conducted in unvaccinated populations or those with low vaccination rates, and preliminary data suggest vaccinated patients with breakthrough infections may have a lower risk for complications and death postinfection, “we felt that it was prudent to just make recommendations specific to unvaccinated patients,” Dr. Clark added.

Although this guidance is “very helpful” in that it summarizes the currently available research to give evidence-based recommendations, the 7-week wait time is a “very conservative estimate,” Brent Matthews, MD, surgeon-in-chief of the surgery care division of Atrium Health, Charlotte, N.C., told this news organization. At Atrium Health, surgery is scheduled at least 21 days after a patient’s COVID-19 diagnosis, regardless of their vaccination status, Dr. Matthews said.

The studies currently available were conducted earlier in the pandemic, when a different variant was prevalent, Dr. Matthews explained. The Omicron variant is currently the most prevalent COVID-19 variant and is less virulent than earlier strains of the virus. The joint statement does note that there is currently “no robust data” on patients infected with the Delta or Omicron variants of COVID-19, and that “the Omicron variant causes less severe disease and is more likely to reside in the oro- and nasopharynx without infiltration and damage to the lungs.”

Still, the new recommendations are a reminder to re-evaluate the potential complications from surgery for previously infected patients and to consider what comorbidities might make them more vulnerable, Dr. Matthews said. “The real power of the joint statement is to get people to ensure that they make an assessment of every patient that comes in front of them who has had a recent positive COVID test.”

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

Two preprint studies released on Feb. 26 offer additional evidence that the coronavirus pandemic started at a market in Wuhan, China.

By analyzing data from several sources, scientists concluded that the virus came from animals and spread to humans in late 2019 at the Huanan Seafood Market. They added that no evidence supported a theory that the virus came from a laboratory in Wuhan.

“When you look at all the evidence together, it’s an extraordinarily clear picture that the pandemic started at the Huanan market,” Michael Worobey, D.Phil., a co-author on both studies and an evolutionary biologist at the University of Arizona, told the New York Times.

The two reports haven’t yet been peer-reviewed or published in a scientific journal. They were posted on Zenodo, an open-access research repository operated by CERN.

In one study, researchers used spatial analysis to show that the earliest COVID-19 cases, which were diagnosed in December 2019, were linked to the market. Researchers also found that environmental samples that tested positive for the SARS-CoV-2 virus were associated with animal vendors.

In another study, researchers found that two major viral lineages of the coronavirus resulted from at least two events when the virus spread from animals into humans. The first transmission most likely happened in late November or early December 2019, they wrote, and the other likely happened a few weeks later.

Several of the researchers behind the new studies also published a review last summer that said the pandemic originated in an animal, likely at a wildlife market. At that time, they said the first known case was a vendor at the Huanan market.

The new findings provide the strongest evidence yet that the pandemic had animal-related origins, Dr. Worobey told CNN. He called the results a “game, set and match” for the theory that the pandemic began in a lab.

“It’s no longer something that makes sense to imagine that this started any other way,” he said.

In a separate line of research, scientists at the Chinese CDC conducted a new analysis of samples collected at the market in January. They found that the samples included the two main lineages of the coronavirus. They posted the results in a report on the Research Square preprint server Feb. 26.

“The beauty of it is how simply it all adds up now,” Jeremy Kamil, a virologist at Louisiana State University Health Sciences, who wasn’t involved with the new studies, told the New York Times.

The initial spread of the coronavirus was like a firework, Dr. Worobey told CNN, starting at the market and exploding outward. The “overwhelming majority” of cases were specifically linked to the western section of the market, where most of the live-mammal vendors were located, the study authors wrote. Then COVID-19 cases spread into the community from there, and the pattern of transmission changed by January or February 2020.

When researchers tested surfaces at the market for coronavirus genetic material, one stall had the most positives, including a cage where raccoon dogs had been kept.

The study authors said the findings highlight the urgent need to pay attention to situations where wild animals and humans interact closely on a daily basis.

“We need to do a better job of farming and regulating these wild animals,” Robert Garry, one of the co-authors and a professor of microbiology and immunology at the Tulane University School of Medicine, told CNN.

That could include better infrastructure in places like markets where viruses spill over from animals to humans, he said. Surveillance is also key in preventing future pandemics by detecting new respiratory diseases in humans, isolating patients, and sequencing new virus strains.

“This is not the last time this happens,” he said.

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

Two preprint studies released on Feb. 26 offer additional evidence that the coronavirus pandemic started at a market in Wuhan, China.

By analyzing data from several sources, scientists concluded that the virus came from animals and spread to humans in late 2019 at the Huanan Seafood Market. They added that no evidence supported a theory that the virus came from a laboratory in Wuhan.

“When you look at all the evidence together, it’s an extraordinarily clear picture that the pandemic started at the Huanan market,” Michael Worobey, D.Phil., a co-author on both studies and an evolutionary biologist at the University of Arizona, told the New York Times.

The two reports haven’t yet been peer-reviewed or published in a scientific journal. They were posted on Zenodo, an open-access research repository operated by CERN.

In one study, researchers used spatial analysis to show that the earliest COVID-19 cases, which were diagnosed in December 2019, were linked to the market. Researchers also found that environmental samples that tested positive for the SARS-CoV-2 virus were associated with animal vendors.

In another study, researchers found that two major viral lineages of the coronavirus resulted from at least two events when the virus spread from animals into humans. The first transmission most likely happened in late November or early December 2019, they wrote, and the other likely happened a few weeks later.

Several of the researchers behind the new studies also published a review last summer that said the pandemic originated in an animal, likely at a wildlife market. At that time, they said the first known case was a vendor at the Huanan market.

The new findings provide the strongest evidence yet that the pandemic had animal-related origins, Dr. Worobey told CNN. He called the results a “game, set and match” for the theory that the pandemic began in a lab.

“It’s no longer something that makes sense to imagine that this started any other way,” he said.

In a separate line of research, scientists at the Chinese CDC conducted a new analysis of samples collected at the market in January. They found that the samples included the two main lineages of the coronavirus. They posted the results in a report on the Research Square preprint server Feb. 26.

“The beauty of it is how simply it all adds up now,” Jeremy Kamil, a virologist at Louisiana State University Health Sciences, who wasn’t involved with the new studies, told the New York Times.

The initial spread of the coronavirus was like a firework, Dr. Worobey told CNN, starting at the market and exploding outward. The “overwhelming majority” of cases were specifically linked to the western section of the market, where most of the live-mammal vendors were located, the study authors wrote. Then COVID-19 cases spread into the community from there, and the pattern of transmission changed by January or February 2020.

When researchers tested surfaces at the market for coronavirus genetic material, one stall had the most positives, including a cage where raccoon dogs had been kept.

The study authors said the findings highlight the urgent need to pay attention to situations where wild animals and humans interact closely on a daily basis.

“We need to do a better job of farming and regulating these wild animals,” Robert Garry, one of the co-authors and a professor of microbiology and immunology at the Tulane University School of Medicine, told CNN.

That could include better infrastructure in places like markets where viruses spill over from animals to humans, he said. Surveillance is also key in preventing future pandemics by detecting new respiratory diseases in humans, isolating patients, and sequencing new virus strains.

“This is not the last time this happens,” he said.

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

Two preprint studies released on Feb. 26 offer additional evidence that the coronavirus pandemic started at a market in Wuhan, China.

By analyzing data from several sources, scientists concluded that the virus came from animals and spread to humans in late 2019 at the Huanan Seafood Market. They added that no evidence supported a theory that the virus came from a laboratory in Wuhan.

“When you look at all the evidence together, it’s an extraordinarily clear picture that the pandemic started at the Huanan market,” Michael Worobey, D.Phil., a co-author on both studies and an evolutionary biologist at the University of Arizona, told the New York Times.

The two reports haven’t yet been peer-reviewed or published in a scientific journal. They were posted on Zenodo, an open-access research repository operated by CERN.

In one study, researchers used spatial analysis to show that the earliest COVID-19 cases, which were diagnosed in December 2019, were linked to the market. Researchers also found that environmental samples that tested positive for the SARS-CoV-2 virus were associated with animal vendors.

In another study, researchers found that two major viral lineages of the coronavirus resulted from at least two events when the virus spread from animals into humans. The first transmission most likely happened in late November or early December 2019, they wrote, and the other likely happened a few weeks later.

Several of the researchers behind the new studies also published a review last summer that said the pandemic originated in an animal, likely at a wildlife market. At that time, they said the first known case was a vendor at the Huanan market.

The new findings provide the strongest evidence yet that the pandemic had animal-related origins, Dr. Worobey told CNN. He called the results a “game, set and match” for the theory that the pandemic began in a lab.

“It’s no longer something that makes sense to imagine that this started any other way,” he said.

In a separate line of research, scientists at the Chinese CDC conducted a new analysis of samples collected at the market in January. They found that the samples included the two main lineages of the coronavirus. They posted the results in a report on the Research Square preprint server Feb. 26.

“The beauty of it is how simply it all adds up now,” Jeremy Kamil, a virologist at Louisiana State University Health Sciences, who wasn’t involved with the new studies, told the New York Times.

The initial spread of the coronavirus was like a firework, Dr. Worobey told CNN, starting at the market and exploding outward. The “overwhelming majority” of cases were specifically linked to the western section of the market, where most of the live-mammal vendors were located, the study authors wrote. Then COVID-19 cases spread into the community from there, and the pattern of transmission changed by January or February 2020.

When researchers tested surfaces at the market for coronavirus genetic material, one stall had the most positives, including a cage where raccoon dogs had been kept.

The study authors said the findings highlight the urgent need to pay attention to situations where wild animals and humans interact closely on a daily basis.

“We need to do a better job of farming and regulating these wild animals,” Robert Garry, one of the co-authors and a professor of microbiology and immunology at the Tulane University School of Medicine, told CNN.

That could include better infrastructure in places like markets where viruses spill over from animals to humans, he said. Surveillance is also key in preventing future pandemics by detecting new respiratory diseases in humans, isolating patients, and sequencing new virus strains.

“This is not the last time this happens,” he said.

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

Antiretroviral therapy (ART) regimens provide long-lasting suppression of HIV replication and have helped people with HIV live healthier lives for decades.  

Today's ART regimens are associated with fewer serious and intolerable adverse effects than those used in the past, but weight gain remains a concern in clinical practice. 

In this ReCAP, Dr David Wohl, from the University of North Carolina at Chapel Hill, reports on the relationship between ART and weight gain, as well as the implications of excessive weight gain in HIV management. 

He shares data from multiple studies, including the ADVANCE trial, which offer insight on how different HIV therapies affect patient weight. 

Dr Wohl also discusses the steps clinicians should take if weight gain does occur in people who are on HIV therapy.  

--

Professor of Medicine; Medical Director, UNC COVID-19 Vaccine Clinic, COVID-19 Monoclonal Antibody Infusion Clinic, University of North Carolina at Chapel Hill 

David Wohl, MD, has disclosed the following relevant financial relationships: 

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Gilead; ViiV; Janssen; Merck 

Serve(d) as a speaker or a member of a speakers bureau for: Gilead 

Received research grant from: Gilead; Merck; ViiV 

Antiretroviral therapy (ART) regimens provide long-lasting suppression of HIV replication and have helped people with HIV live healthier lives for decades.  

Today's ART regimens are associated with fewer serious and intolerable adverse effects than those used in the past, but weight gain remains a concern in clinical practice. 

In this ReCAP, Dr David Wohl, from the University of North Carolina at Chapel Hill, reports on the relationship between ART and weight gain, as well as the implications of excessive weight gain in HIV management. 

He shares data from multiple studies, including the ADVANCE trial, which offer insight on how different HIV therapies affect patient weight. 

Dr Wohl also discusses the steps clinicians should take if weight gain does occur in people who are on HIV therapy.  

--

Professor of Medicine; Medical Director, UNC COVID-19 Vaccine Clinic, COVID-19 Monoclonal Antibody Infusion Clinic, University of North Carolina at Chapel Hill 

David Wohl, MD, has disclosed the following relevant financial relationships: 

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Gilead; ViiV; Janssen; Merck 

Serve(d) as a speaker or a member of a speakers bureau for: Gilead 

Received research grant from: Gilead; Merck; ViiV 

Antiretroviral therapy (ART) regimens provide long-lasting suppression of HIV replication and have helped people with HIV live healthier lives for decades.  

Today's ART regimens are associated with fewer serious and intolerable adverse effects than those used in the past, but weight gain remains a concern in clinical practice. 

In this ReCAP, Dr David Wohl, from the University of North Carolina at Chapel Hill, reports on the relationship between ART and weight gain, as well as the implications of excessive weight gain in HIV management. 

He shares data from multiple studies, including the ADVANCE trial, which offer insight on how different HIV therapies affect patient weight. 

Dr Wohl also discusses the steps clinicians should take if weight gain does occur in people who are on HIV therapy.  

--

Professor of Medicine; Medical Director, UNC COVID-19 Vaccine Clinic, COVID-19 Monoclonal Antibody Infusion Clinic, University of North Carolina at Chapel Hill 

David Wohl, MD, has disclosed the following relevant financial relationships: 

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Gilead; ViiV; Janssen; Merck 

Serve(d) as a speaker or a member of a speakers bureau for: Gilead 

Received research grant from: Gilead; Merck; ViiV 

A study of the nasal microbiome helped researchers predict recurrent polyps in chronic rhinosinusitis patients with more than 90% accuracy, based on data from 85 individuals.

Chronic rhinosinusitis with nasal polyps (CRSwNP) has a significant impact on patient quality of life, but the underlying mechanism of the disease has not been well studied, and treatment options remain limited, wrote Yan Zhao, MD, of Capital Medical University, Beijing, and study coauthors.

Previous research has shown that nasal microbiome composition differs in patients with and without asthma, and some studies suggest that changes in microbiota could contribute to CRSwNP, the authors wrote. The researchers wondered if features of the nasal microbiome can predict the recurrence of nasal polyps after endoscopic sinus surgery and serve as a potential treatment target.

In a study in Allergy, the researchers examined nasal swab samples from 85 adults with CRSwNP who underwent endoscopic sinus surgery between August 2014 and March 2016 at a single center in China. The researchers performed bacterial analysis and gene sequencing on all samples.

The patients ranged in age from 18-73 years, with a mean age of 46 years, and included 64 men and 21 women. The primary outcome was recurrence of polyps. Of the total, 39 individuals had recurrence, and 46 did not.

When the researchers compared microbiota from swab samples of recurrent and nonrecurrent patients, they found differences in composition based on bacterial genus abundance. “Campylobacter, Bdellovibrio, and Aggregatibacter, among others, were more abundant in swabs from CRSwNP recurrence samples, whereas Actinobacillus, Gemella, and Moraxella were more abundant in non-recurrence samples,” they wrote.

The researchers then tested their theory that distinct nasal microbiota could be a predictive marker of risk for future nasal polyp recurrence. They used a training set of 48 samples and constructed models from nasal microbiota alone, clinical features alone, and both together.

The regression model identified Porphyromonas, Bacteroides, Moryella, Aggregatibacter, Butyrivibrio, Shewanella, Pseudoxanthomonas, Friedmanniella, Limnobacter, and Curvibacter as the most important taxa that distinguished recurrence from nonrecurrence in the specimens. When the model was validated, the area under the curve was 0.914, yielding a predictor of nasal polyp recurrence with 91.4% accuracy.

“It is highly likely that proteins, nucleic acids, and other small molecules produced by nasal microbiota are associated with the progression of CRSwNP,” the researchers noted in their discussion of the findings. “Further, the nasal microbiota could maintain a stable community environment through the secretion of various chemical compounds and/or inflammatory factors, thus playing a central role in the development of CRSwNP.”

The study findings were limited by several factors, including the analysis of nasal flora only at the genus level in the screening phase, the use only of bioinformatic analysis for recurrence prediction, and the inclusion only of subjects from a single center, the researchers noted. Future studies should combine predictors to increase accuracy and include deeper sequencing, they said. However, the results support data from previous studies and suggest a strategy to meet the need for predictors of recurrence in CRSwNP, they concluded.

“There is a critical need to understand the role of the upper airway microbiome in different phenotypes of CRS,” said Emily K. Cope, PhD, assistant director at the Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, in an interview. “This was one of the first studies to evaluate the predictive power of the microbiome in recurrence of a common CRS phenotype – CRS with nasal polyps,” she said. “Importantly, the researchers were able to predict recurrence of polyps prior to the disease manifestation,” she noted.  

“Given the nascent state of current upper airway microbiome research, I was surprised that they were able to predict polyp recurrence prior to disease manifestation,” Dr. Cope said. “This is exciting, and I can imagine a future where we use microbiome data to understand risk for disease.”

What is the take-home message for clinicians? Although the immediate clinical implications are limited, Dr. Cope expressed enthusiasm for additional research. “At this point, there’s not a lot we can do without validation studies, but this study is promising. I hope we can understand the mechanism that an altered microbiome might drive (or be a result of) polyposis,” she said.

The study was supported by the National Natural Science Foundation of China, the program for the Changjiang scholars and innovative research team, the Beijing Bai-Qian-Wan talent project, the Public Welfare Development and Reform Pilot Project, the National Science and Technology Major Project, and the CAMS Innovation Fund for Medical Sciences. The researchers and Dr. Cope disclosed no financial conflicts.

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

A study of the nasal microbiome helped researchers predict recurrent polyps in chronic rhinosinusitis patients with more than 90% accuracy, based on data from 85 individuals.

Chronic rhinosinusitis with nasal polyps (CRSwNP) has a significant impact on patient quality of life, but the underlying mechanism of the disease has not been well studied, and treatment options remain limited, wrote Yan Zhao, MD, of Capital Medical University, Beijing, and study coauthors.

Previous research has shown that nasal microbiome composition differs in patients with and without asthma, and some studies suggest that changes in microbiota could contribute to CRSwNP, the authors wrote. The researchers wondered if features of the nasal microbiome can predict the recurrence of nasal polyps after endoscopic sinus surgery and serve as a potential treatment target.

In a study in Allergy, the researchers examined nasal swab samples from 85 adults with CRSwNP who underwent endoscopic sinus surgery between August 2014 and March 2016 at a single center in China. The researchers performed bacterial analysis and gene sequencing on all samples.

The patients ranged in age from 18-73 years, with a mean age of 46 years, and included 64 men and 21 women. The primary outcome was recurrence of polyps. Of the total, 39 individuals had recurrence, and 46 did not.

When the researchers compared microbiota from swab samples of recurrent and nonrecurrent patients, they found differences in composition based on bacterial genus abundance. “Campylobacter, Bdellovibrio, and Aggregatibacter, among others, were more abundant in swabs from CRSwNP recurrence samples, whereas Actinobacillus, Gemella, and Moraxella were more abundant in non-recurrence samples,” they wrote.

The researchers then tested their theory that distinct nasal microbiota could be a predictive marker of risk for future nasal polyp recurrence. They used a training set of 48 samples and constructed models from nasal microbiota alone, clinical features alone, and both together.

The regression model identified Porphyromonas, Bacteroides, Moryella, Aggregatibacter, Butyrivibrio, Shewanella, Pseudoxanthomonas, Friedmanniella, Limnobacter, and Curvibacter as the most important taxa that distinguished recurrence from nonrecurrence in the specimens. When the model was validated, the area under the curve was 0.914, yielding a predictor of nasal polyp recurrence with 91.4% accuracy.

“It is highly likely that proteins, nucleic acids, and other small molecules produced by nasal microbiota are associated with the progression of CRSwNP,” the researchers noted in their discussion of the findings. “Further, the nasal microbiota could maintain a stable community environment through the secretion of various chemical compounds and/or inflammatory factors, thus playing a central role in the development of CRSwNP.”

The study findings were limited by several factors, including the analysis of nasal flora only at the genus level in the screening phase, the use only of bioinformatic analysis for recurrence prediction, and the inclusion only of subjects from a single center, the researchers noted. Future studies should combine predictors to increase accuracy and include deeper sequencing, they said. However, the results support data from previous studies and suggest a strategy to meet the need for predictors of recurrence in CRSwNP, they concluded.

“There is a critical need to understand the role of the upper airway microbiome in different phenotypes of CRS,” said Emily K. Cope, PhD, assistant director at the Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, in an interview. “This was one of the first studies to evaluate the predictive power of the microbiome in recurrence of a common CRS phenotype – CRS with nasal polyps,” she said. “Importantly, the researchers were able to predict recurrence of polyps prior to the disease manifestation,” she noted.  

“Given the nascent state of current upper airway microbiome research, I was surprised that they were able to predict polyp recurrence prior to disease manifestation,” Dr. Cope said. “This is exciting, and I can imagine a future where we use microbiome data to understand risk for disease.”

What is the take-home message for clinicians? Although the immediate clinical implications are limited, Dr. Cope expressed enthusiasm for additional research. “At this point, there’s not a lot we can do without validation studies, but this study is promising. I hope we can understand the mechanism that an altered microbiome might drive (or be a result of) polyposis,” she said.

The study was supported by the National Natural Science Foundation of China, the program for the Changjiang scholars and innovative research team, the Beijing Bai-Qian-Wan talent project, the Public Welfare Development and Reform Pilot Project, the National Science and Technology Major Project, and the CAMS Innovation Fund for Medical Sciences. The researchers and Dr. Cope disclosed no financial conflicts.

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

A study of the nasal microbiome helped researchers predict recurrent polyps in chronic rhinosinusitis patients with more than 90% accuracy, based on data from 85 individuals.

Chronic rhinosinusitis with nasal polyps (CRSwNP) has a significant impact on patient quality of life, but the underlying mechanism of the disease has not been well studied, and treatment options remain limited, wrote Yan Zhao, MD, of Capital Medical University, Beijing, and study coauthors.

Previous research has shown that nasal microbiome composition differs in patients with and without asthma, and some studies suggest that changes in microbiota could contribute to CRSwNP, the authors wrote. The researchers wondered if features of the nasal microbiome can predict the recurrence of nasal polyps after endoscopic sinus surgery and serve as a potential treatment target.

In a study in Allergy, the researchers examined nasal swab samples from 85 adults with CRSwNP who underwent endoscopic sinus surgery between August 2014 and March 2016 at a single center in China. The researchers performed bacterial analysis and gene sequencing on all samples.

The patients ranged in age from 18-73 years, with a mean age of 46 years, and included 64 men and 21 women. The primary outcome was recurrence of polyps. Of the total, 39 individuals had recurrence, and 46 did not.

When the researchers compared microbiota from swab samples of recurrent and nonrecurrent patients, they found differences in composition based on bacterial genus abundance. “Campylobacter, Bdellovibrio, and Aggregatibacter, among others, were more abundant in swabs from CRSwNP recurrence samples, whereas Actinobacillus, Gemella, and Moraxella were more abundant in non-recurrence samples,” they wrote.

The researchers then tested their theory that distinct nasal microbiota could be a predictive marker of risk for future nasal polyp recurrence. They used a training set of 48 samples and constructed models from nasal microbiota alone, clinical features alone, and both together.

The regression model identified Porphyromonas, Bacteroides, Moryella, Aggregatibacter, Butyrivibrio, Shewanella, Pseudoxanthomonas, Friedmanniella, Limnobacter, and Curvibacter as the most important taxa that distinguished recurrence from nonrecurrence in the specimens. When the model was validated, the area under the curve was 0.914, yielding a predictor of nasal polyp recurrence with 91.4% accuracy.

“It is highly likely that proteins, nucleic acids, and other small molecules produced by nasal microbiota are associated with the progression of CRSwNP,” the researchers noted in their discussion of the findings. “Further, the nasal microbiota could maintain a stable community environment through the secretion of various chemical compounds and/or inflammatory factors, thus playing a central role in the development of CRSwNP.”

The study findings were limited by several factors, including the analysis of nasal flora only at the genus level in the screening phase, the use only of bioinformatic analysis for recurrence prediction, and the inclusion only of subjects from a single center, the researchers noted. Future studies should combine predictors to increase accuracy and include deeper sequencing, they said. However, the results support data from previous studies and suggest a strategy to meet the need for predictors of recurrence in CRSwNP, they concluded.

“There is a critical need to understand the role of the upper airway microbiome in different phenotypes of CRS,” said Emily K. Cope, PhD, assistant director at the Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, in an interview. “This was one of the first studies to evaluate the predictive power of the microbiome in recurrence of a common CRS phenotype – CRS with nasal polyps,” she said. “Importantly, the researchers were able to predict recurrence of polyps prior to the disease manifestation,” she noted.  

“Given the nascent state of current upper airway microbiome research, I was surprised that they were able to predict polyp recurrence prior to disease manifestation,” Dr. Cope said. “This is exciting, and I can imagine a future where we use microbiome data to understand risk for disease.”

What is the take-home message for clinicians? Although the immediate clinical implications are limited, Dr. Cope expressed enthusiasm for additional research. “At this point, there’s not a lot we can do without validation studies, but this study is promising. I hope we can understand the mechanism that an altered microbiome might drive (or be a result of) polyposis,” she said.

The study was supported by the National Natural Science Foundation of China, the program for the Changjiang scholars and innovative research team, the Beijing Bai-Qian-Wan talent project, the Public Welfare Development and Reform Pilot Project, the National Science and Technology Major Project, and the CAMS Innovation Fund for Medical Sciences. The researchers and Dr. Cope disclosed no financial conflicts.

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

Legionnaires’ disease (LD) in the United States appears to be on an upswing that started in 2003, according to a study from the Centers for Disease Control and Prevention.

The reasons for this increased incidence are unclear, the researchers write in Emerging Infectious Diseases.

“The findings revealed a rising national trend in cases, widening racial disparities between Black or African American persons and White persons, and an increasing geographic focus in the Middle Atlantic, the East North Central, and New England,” lead author Albert E. Barskey, MPH, an epidemiologist in CDC’s Division of Bacterial Diseases, Atlanta, said in an email.

“Legionnaires’ disease cannot be diagnosed based on clinical features alone, and studies estimate that it is underdiagnosed, perhaps by 50%,” he added. “Our findings may serve to heighten clinicians’ awareness of this severe pneumonia’s etiology, so with an earlier correct diagnosis, appropriate treatment can be rendered sooner.”

Mr. Barskey and his coauthors at CDC – mathematical statistician Gordana Derado, PhD, and epidemiologist Chris Edens, PhD – used surveillance data to investigate the incidence of LD in the U.S. over time. They compared LD incidence in 2018 with average incidence between 1992 and 2002. The incidence data, from over 80,000 LD cases, were age-standardized using the 2005 U.S. standard population as the reference.

The researchers analyzed LD data reported to CDC by the 50 states, New York City, and Washington, D.C., through the National Notifiable Diseases Surveillance System. They performed regression analysis to identify the optimal year when population parameters changed, and for most analyses, they compared 1992-2002 data with 2003-2018 data.
 

Legionnaires’ disease up in various groups

• The overall age-standardized average incidence grew from 0.48 per 100,000 people during 1992-2002 to 2.71 per 100,000 in 2018 (incidence risk ratio, 5.67; 95% confidence interval, 5.52-5.83).
• LD incidence more than quintupled for people over 34 years of age, with the largest relative increase in those over 85 (RR, 6.50; 95% CI, 5.82-7.27).
• Incidence in men increased slightly more (RR, 5.86; 95% CI, 5.67-6.05) than in women (RR, 5.29; 95% CI, 5.06-5.53).
• Over the years, the racial disparity in incidence grew markedly. Incidence in Black persons increased from 0.47 to 5.21 per 100,000 (RR, 11.04; 95% CI, 10.39-11.73), compared with an increase from 0.37 to 1.99 per 100,000 in White persons (RR, 5.30; 95% CI, 5.12-5.49).
• The relative increase in incidence was highest in the Northeast (RR, 7.04; 95% CI, 6.70-7.40), followed by the Midwest (RR, 6.13; 95% CI, 5.85-6.42), the South (RR, 5.97; 95% CI, 5.67-6.29), and the West (RR, 3.39; 95% CI, 3.11-3.68).

Most LD cases occurred in summer or fall, and the seasonal pattern became more pronounced over time. The average of 57.8% of cases between June and November during 1992-2002 grew to 68.9% in 2003-2018.

Although the study “was hindered by incomplete race and ethnicity data,” Mr. Barskey said, “its breadth was a strength.”
 

Consider legionella in your diagnosis

In an interview, Paul G. Auwaerter, MD, a professor of medicine and the clinical director of the Division of Infectious Diseases at Johns Hopkins University School of Medicine, Baltimore, said he was not surprised by the results. “CDC has been reporting increased incidence of Legionnaires’ disease from water source outbreaks over the years. As a clinician, I very much depend on epidemiologic trends to help me understand the patient in front of me.

“The key point is that there’s more of it around, so consider it in your diagnosis,” he advised.

“Physicians are increasingly beginning to consider Legionella. Because LD is difficult to diagnose by traditional methods such as culture, they may use a PCR test,” said Dr. Auwaerter, who was not involved in the study. “Legionella needs antibiotics that differ a bit from traditional antibiotics used to treat bacterial pneumonia, so a correct diagnosis can inform a more directed therapy.”

“Why the incidence is increasing is the big question, and the authors nicely outline a litany of things,” he said.

The authors and Dr. Auwaerter proposed a number of possible contributing factors to the increased incidence:

• an aging population
• aging municipal and residential water sources that may harbor more organisms
• racial disparities and poverty
• underlying conditions, including diabetes, end-stage renal disease, and some cancers
• occupations in transportation, repair, cleaning services, and construction
• weather patterns
• improved surveillance and reporting

“Why Legionella appears in some locations more than others has not been explained,” Dr. Auwaerter added. “For example, Pittsburgh always seemed to have much more Legionella than Baltimore.”

Mr. Barskey and his team are planning further research into racial disparities and links between weather and climate and Legionnaires’ disease.

The authors are employees of CDC. Dr. Auwaerter has disclosed no relevant financial realtionships.

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

Legionnaires’ disease (LD) in the United States appears to be on an upswing that started in 2003, according to a study from the Centers for Disease Control and Prevention.

The reasons for this increased incidence are unclear, the researchers write in Emerging Infectious Diseases.

“The findings revealed a rising national trend in cases, widening racial disparities between Black or African American persons and White persons, and an increasing geographic focus in the Middle Atlantic, the East North Central, and New England,” lead author Albert E. Barskey, MPH, an epidemiologist in CDC’s Division of Bacterial Diseases, Atlanta, said in an email.

“Legionnaires’ disease cannot be diagnosed based on clinical features alone, and studies estimate that it is underdiagnosed, perhaps by 50%,” he added. “Our findings may serve to heighten clinicians’ awareness of this severe pneumonia’s etiology, so with an earlier correct diagnosis, appropriate treatment can be rendered sooner.”

Mr. Barskey and his coauthors at CDC – mathematical statistician Gordana Derado, PhD, and epidemiologist Chris Edens, PhD – used surveillance data to investigate the incidence of LD in the U.S. over time. They compared LD incidence in 2018 with average incidence between 1992 and 2002. The incidence data, from over 80,000 LD cases, were age-standardized using the 2005 U.S. standard population as the reference.

The researchers analyzed LD data reported to CDC by the 50 states, New York City, and Washington, D.C., through the National Notifiable Diseases Surveillance System. They performed regression analysis to identify the optimal year when population parameters changed, and for most analyses, they compared 1992-2002 data with 2003-2018 data.
 

Legionnaires’ disease up in various groups

• The overall age-standardized average incidence grew from 0.48 per 100,000 people during 1992-2002 to 2.71 per 100,000 in 2018 (incidence risk ratio, 5.67; 95% confidence interval, 5.52-5.83).
• LD incidence more than quintupled for people over 34 years of age, with the largest relative increase in those over 85 (RR, 6.50; 95% CI, 5.82-7.27).
• Incidence in men increased slightly more (RR, 5.86; 95% CI, 5.67-6.05) than in women (RR, 5.29; 95% CI, 5.06-5.53).
• Over the years, the racial disparity in incidence grew markedly. Incidence in Black persons increased from 0.47 to 5.21 per 100,000 (RR, 11.04; 95% CI, 10.39-11.73), compared with an increase from 0.37 to 1.99 per 100,000 in White persons (RR, 5.30; 95% CI, 5.12-5.49).
• The relative increase in incidence was highest in the Northeast (RR, 7.04; 95% CI, 6.70-7.40), followed by the Midwest (RR, 6.13; 95% CI, 5.85-6.42), the South (RR, 5.97; 95% CI, 5.67-6.29), and the West (RR, 3.39; 95% CI, 3.11-3.68).

Most LD cases occurred in summer or fall, and the seasonal pattern became more pronounced over time. The average of 57.8% of cases between June and November during 1992-2002 grew to 68.9% in 2003-2018.

Although the study “was hindered by incomplete race and ethnicity data,” Mr. Barskey said, “its breadth was a strength.”
 

Consider legionella in your diagnosis

In an interview, Paul G. Auwaerter, MD, a professor of medicine and the clinical director of the Division of Infectious Diseases at Johns Hopkins University School of Medicine, Baltimore, said he was not surprised by the results. “CDC has been reporting increased incidence of Legionnaires’ disease from water source outbreaks over the years. As a clinician, I very much depend on epidemiologic trends to help me understand the patient in front of me.

“The key point is that there’s more of it around, so consider it in your diagnosis,” he advised.

“Physicians are increasingly beginning to consider Legionella. Because LD is difficult to diagnose by traditional methods such as culture, they may use a PCR test,” said Dr. Auwaerter, who was not involved in the study. “Legionella needs antibiotics that differ a bit from traditional antibiotics used to treat bacterial pneumonia, so a correct diagnosis can inform a more directed therapy.”

“Why the incidence is increasing is the big question, and the authors nicely outline a litany of things,” he said.

The authors and Dr. Auwaerter proposed a number of possible contributing factors to the increased incidence:

• an aging population
• aging municipal and residential water sources that may harbor more organisms
• racial disparities and poverty
• underlying conditions, including diabetes, end-stage renal disease, and some cancers
• occupations in transportation, repair, cleaning services, and construction
• weather patterns
• improved surveillance and reporting

“Why Legionella appears in some locations more than others has not been explained,” Dr. Auwaerter added. “For example, Pittsburgh always seemed to have much more Legionella than Baltimore.”

Mr. Barskey and his team are planning further research into racial disparities and links between weather and climate and Legionnaires’ disease.

The authors are employees of CDC. Dr. Auwaerter has disclosed no relevant financial realtionships.

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

Legionnaires’ disease (LD) in the United States appears to be on an upswing that started in 2003, according to a study from the Centers for Disease Control and Prevention.

The reasons for this increased incidence are unclear, the researchers write in Emerging Infectious Diseases.

“The findings revealed a rising national trend in cases, widening racial disparities between Black or African American persons and White persons, and an increasing geographic focus in the Middle Atlantic, the East North Central, and New England,” lead author Albert E. Barskey, MPH, an epidemiologist in CDC’s Division of Bacterial Diseases, Atlanta, said in an email.

“Legionnaires’ disease cannot be diagnosed based on clinical features alone, and studies estimate that it is underdiagnosed, perhaps by 50%,” he added. “Our findings may serve to heighten clinicians’ awareness of this severe pneumonia’s etiology, so with an earlier correct diagnosis, appropriate treatment can be rendered sooner.”

Mr. Barskey and his coauthors at CDC – mathematical statistician Gordana Derado, PhD, and epidemiologist Chris Edens, PhD – used surveillance data to investigate the incidence of LD in the U.S. over time. They compared LD incidence in 2018 with average incidence between 1992 and 2002. The incidence data, from over 80,000 LD cases, were age-standardized using the 2005 U.S. standard population as the reference.

The researchers analyzed LD data reported to CDC by the 50 states, New York City, and Washington, D.C., through the National Notifiable Diseases Surveillance System. They performed regression analysis to identify the optimal year when population parameters changed, and for most analyses, they compared 1992-2002 data with 2003-2018 data.
 

Legionnaires’ disease up in various groups

• The overall age-standardized average incidence grew from 0.48 per 100,000 people during 1992-2002 to 2.71 per 100,000 in 2018 (incidence risk ratio, 5.67; 95% confidence interval, 5.52-5.83).
• LD incidence more than quintupled for people over 34 years of age, with the largest relative increase in those over 85 (RR, 6.50; 95% CI, 5.82-7.27).
• Incidence in men increased slightly more (RR, 5.86; 95% CI, 5.67-6.05) than in women (RR, 5.29; 95% CI, 5.06-5.53).
• Over the years, the racial disparity in incidence grew markedly. Incidence in Black persons increased from 0.47 to 5.21 per 100,000 (RR, 11.04; 95% CI, 10.39-11.73), compared with an increase from 0.37 to 1.99 per 100,000 in White persons (RR, 5.30; 95% CI, 5.12-5.49).
• The relative increase in incidence was highest in the Northeast (RR, 7.04; 95% CI, 6.70-7.40), followed by the Midwest (RR, 6.13; 95% CI, 5.85-6.42), the South (RR, 5.97; 95% CI, 5.67-6.29), and the West (RR, 3.39; 95% CI, 3.11-3.68).

Most LD cases occurred in summer or fall, and the seasonal pattern became more pronounced over time. The average of 57.8% of cases between June and November during 1992-2002 grew to 68.9% in 2003-2018.

Although the study “was hindered by incomplete race and ethnicity data,” Mr. Barskey said, “its breadth was a strength.”
 

Consider legionella in your diagnosis

In an interview, Paul G. Auwaerter, MD, a professor of medicine and the clinical director of the Division of Infectious Diseases at Johns Hopkins University School of Medicine, Baltimore, said he was not surprised by the results. “CDC has been reporting increased incidence of Legionnaires’ disease from water source outbreaks over the years. As a clinician, I very much depend on epidemiologic trends to help me understand the patient in front of me.

“The key point is that there’s more of it around, so consider it in your diagnosis,” he advised.

“Physicians are increasingly beginning to consider Legionella. Because LD is difficult to diagnose by traditional methods such as culture, they may use a PCR test,” said Dr. Auwaerter, who was not involved in the study. “Legionella needs antibiotics that differ a bit from traditional antibiotics used to treat bacterial pneumonia, so a correct diagnosis can inform a more directed therapy.”

“Why the incidence is increasing is the big question, and the authors nicely outline a litany of things,” he said.

The authors and Dr. Auwaerter proposed a number of possible contributing factors to the increased incidence:

• an aging population
• aging municipal and residential water sources that may harbor more organisms
• racial disparities and poverty
• underlying conditions, including diabetes, end-stage renal disease, and some cancers
• occupations in transportation, repair, cleaning services, and construction
• weather patterns
• improved surveillance and reporting

“Why Legionella appears in some locations more than others has not been explained,” Dr. Auwaerter added. “For example, Pittsburgh always seemed to have much more Legionella than Baltimore.”

Mr. Barskey and his team are planning further research into racial disparities and links between weather and climate and Legionnaires’ disease.

The authors are employees of CDC. Dr. Auwaerter has disclosed no relevant financial realtionships.

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

Circulating antiphospholipid autoantibodies may contribute to endothelial cell activation and dysfunction in severe COVID-19, researchers report.

In 2020, the same researchers reported results from a preclinical study demonstrating that autoantibodies from patients with active COVID-19 caused clotting in mice.

The new study, published in Arthritis and Rheumatology, found higher-than-expected levels of antiphospholipid autoantibodies in the blood samples of 244 patients hospitalized with COVID-19.

“While endothelial dysfunction has been implicated in the widespread thromboinflammatory complications of COVID-19, the upstream mediators of endotheliopathy remain for the most part cryptic,” write Hui Shi, MD, PhD, and coauthors from the University of Michigan, Ann Arbor, and the National Heart, Lung, and Blood Institute.

When asked for comment on the study, Eline T. Luning Prak, MD, PhD, professor of pathology and laboratory medicine at the Hospital of the University of Pennsylvania in Philadelphia, said, “The autopsy cases for COVID-19 strongly point to thromboembolic complications in many individuals who succumbed to sequelae of the infection.

“Importantly, however, many factors can contribute to this pathology, including the inflammatory milieu, monocyte activation, neutrophil extracellular traps, immune complexes, complement, as well as effects on endothelial cells,” explained Dr. Luning Prak, who was not involved in the study.

“The findings in this paper nicely complement another study by Schmaier et al. that came out recently in JCI Insight that also suggests that endothelial cells can be activated by antibodies, she said.
 

‘Even stronger connection between autoantibody formation and clotting in COVID-19’

Dr. Shi and her team cultured human endothelial cells in serum or plasma from 244 patients hospitalized with COVID-19 and plasma from 100 patients with non-COVID sepsis. Using in-cell enzyme-linked immunosorbent assay, they measured levels of key cell adhesion molecules.

After analysis, the researchers found that serum from COVID-19 patients activated cultured endothelial cells to express surface adhesion molecules essential to inflammation and thrombosis, particularly E-selectin, ICAM-1, and VCAM-1.

“The presence of circulating antiphospholipid antibodies was a strong marker of the ability of COVID-19 serum to activate endothelium,” they explain.

Further analyses revealed that, for a subset of serum samples from patients with severe infection, this activation could be mitigated by depleting total immunoglobulin G.

In addition, supplementation of control serum with patient IgG was adequate to trigger endothelial activation.

On the basis of these results, the researchers hypothesize that antiphospholipid autoantibodies may characterize antibody profiles in severe COVID-19 that activate the endothelium and transition the usually quiescent blood-vessel wall interface toward inflammation and coagulation.

“[These findings] provide an even stronger connection between autoantibody formation and clotting in COVID-19,” Dr. Shi said in an accompanying press release.

Clinical implications

From a clinical perspective, Dr. Shi and her team question whether patients with severe COVID-19 should be tested for antiphospholipid antibodies to assess their risk of thrombosis and progression to respiratory failure.

Moreover, they question whether patients with high antiphospholipid antibody titers might benefit from therapies used in conventional cases of severe antiphospholipid syndrome, such as plasmapheresis, anticoagulation therapy, and complement inhibition, Dr. Shi added.

The researchers hope to answer these and other remaining questions in future studies. “Eventually, we may be able to repurpose treatments used in traditional cases of antiphospholipid syndrome for COVID-19.

“As we await definitive solutions to the pandemic, these findings add important context to the complex interplay between SARS-CoV-2 infection, the human immune system, and vascular immunobiology,” she concluded.

The study was supported by grants from the Rheumatology Research Foundation, the Michigan Medicine Frankel Cardiovascular Center, and the A. Alfred Taubman Medical Research Institute. One author is an inventor on an unrelated pending patent to the University of Michigan. The other authors and Dr. Luning Prak have disclosed no relevant financial relationships.

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

Circulating antiphospholipid autoantibodies may contribute to endothelial cell activation and dysfunction in severe COVID-19, researchers report.

In 2020, the same researchers reported results from a preclinical study demonstrating that autoantibodies from patients with active COVID-19 caused clotting in mice.

The new study, published in Arthritis and Rheumatology, found higher-than-expected levels of antiphospholipid autoantibodies in the blood samples of 244 patients hospitalized with COVID-19.

“While endothelial dysfunction has been implicated in the widespread thromboinflammatory complications of COVID-19, the upstream mediators of endotheliopathy remain for the most part cryptic,” write Hui Shi, MD, PhD, and coauthors from the University of Michigan, Ann Arbor, and the National Heart, Lung, and Blood Institute.

When asked for comment on the study, Eline T. Luning Prak, MD, PhD, professor of pathology and laboratory medicine at the Hospital of the University of Pennsylvania in Philadelphia, said, “The autopsy cases for COVID-19 strongly point to thromboembolic complications in many individuals who succumbed to sequelae of the infection.

“Importantly, however, many factors can contribute to this pathology, including the inflammatory milieu, monocyte activation, neutrophil extracellular traps, immune complexes, complement, as well as effects on endothelial cells,” explained Dr. Luning Prak, who was not involved in the study.

“The findings in this paper nicely complement another study by Schmaier et al. that came out recently in JCI Insight that also suggests that endothelial cells can be activated by antibodies, she said.
 

‘Even stronger connection between autoantibody formation and clotting in COVID-19’

Dr. Shi and her team cultured human endothelial cells in serum or plasma from 244 patients hospitalized with COVID-19 and plasma from 100 patients with non-COVID sepsis. Using in-cell enzyme-linked immunosorbent assay, they measured levels of key cell adhesion molecules.

After analysis, the researchers found that serum from COVID-19 patients activated cultured endothelial cells to express surface adhesion molecules essential to inflammation and thrombosis, particularly E-selectin, ICAM-1, and VCAM-1.

“The presence of circulating antiphospholipid antibodies was a strong marker of the ability of COVID-19 serum to activate endothelium,” they explain.

Further analyses revealed that, for a subset of serum samples from patients with severe infection, this activation could be mitigated by depleting total immunoglobulin G.

In addition, supplementation of control serum with patient IgG was adequate to trigger endothelial activation.

On the basis of these results, the researchers hypothesize that antiphospholipid autoantibodies may characterize antibody profiles in severe COVID-19 that activate the endothelium and transition the usually quiescent blood-vessel wall interface toward inflammation and coagulation.

“[These findings] provide an even stronger connection between autoantibody formation and clotting in COVID-19,” Dr. Shi said in an accompanying press release.

Clinical implications

From a clinical perspective, Dr. Shi and her team question whether patients with severe COVID-19 should be tested for antiphospholipid antibodies to assess their risk of thrombosis and progression to respiratory failure.

Moreover, they question whether patients with high antiphospholipid antibody titers might benefit from therapies used in conventional cases of severe antiphospholipid syndrome, such as plasmapheresis, anticoagulation therapy, and complement inhibition, Dr. Shi added.

The researchers hope to answer these and other remaining questions in future studies. “Eventually, we may be able to repurpose treatments used in traditional cases of antiphospholipid syndrome for COVID-19.

“As we await definitive solutions to the pandemic, these findings add important context to the complex interplay between SARS-CoV-2 infection, the human immune system, and vascular immunobiology,” she concluded.

The study was supported by grants from the Rheumatology Research Foundation, the Michigan Medicine Frankel Cardiovascular Center, and the A. Alfred Taubman Medical Research Institute. One author is an inventor on an unrelated pending patent to the University of Michigan. The other authors and Dr. Luning Prak have disclosed no relevant financial relationships.

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

Circulating antiphospholipid autoantibodies may contribute to endothelial cell activation and dysfunction in severe COVID-19, researchers report.

In 2020, the same researchers reported results from a preclinical study demonstrating that autoantibodies from patients with active COVID-19 caused clotting in mice.

The new study, published in Arthritis and Rheumatology, found higher-than-expected levels of antiphospholipid autoantibodies in the blood samples of 244 patients hospitalized with COVID-19.

“While endothelial dysfunction has been implicated in the widespread thromboinflammatory complications of COVID-19, the upstream mediators of endotheliopathy remain for the most part cryptic,” write Hui Shi, MD, PhD, and coauthors from the University of Michigan, Ann Arbor, and the National Heart, Lung, and Blood Institute.

When asked for comment on the study, Eline T. Luning Prak, MD, PhD, professor of pathology and laboratory medicine at the Hospital of the University of Pennsylvania in Philadelphia, said, “The autopsy cases for COVID-19 strongly point to thromboembolic complications in many individuals who succumbed to sequelae of the infection.

“Importantly, however, many factors can contribute to this pathology, including the inflammatory milieu, monocyte activation, neutrophil extracellular traps, immune complexes, complement, as well as effects on endothelial cells,” explained Dr. Luning Prak, who was not involved in the study.

“The findings in this paper nicely complement another study by Schmaier et al. that came out recently in JCI Insight that also suggests that endothelial cells can be activated by antibodies, she said.
 

‘Even stronger connection between autoantibody formation and clotting in COVID-19’

Dr. Shi and her team cultured human endothelial cells in serum or plasma from 244 patients hospitalized with COVID-19 and plasma from 100 patients with non-COVID sepsis. Using in-cell enzyme-linked immunosorbent assay, they measured levels of key cell adhesion molecules.

After analysis, the researchers found that serum from COVID-19 patients activated cultured endothelial cells to express surface adhesion molecules essential to inflammation and thrombosis, particularly E-selectin, ICAM-1, and VCAM-1.

“The presence of circulating antiphospholipid antibodies was a strong marker of the ability of COVID-19 serum to activate endothelium,” they explain.

Further analyses revealed that, for a subset of serum samples from patients with severe infection, this activation could be mitigated by depleting total immunoglobulin G.

In addition, supplementation of control serum with patient IgG was adequate to trigger endothelial activation.

On the basis of these results, the researchers hypothesize that antiphospholipid autoantibodies may characterize antibody profiles in severe COVID-19 that activate the endothelium and transition the usually quiescent blood-vessel wall interface toward inflammation and coagulation.

“[These findings] provide an even stronger connection between autoantibody formation and clotting in COVID-19,” Dr. Shi said in an accompanying press release.

Clinical implications

From a clinical perspective, Dr. Shi and her team question whether patients with severe COVID-19 should be tested for antiphospholipid antibodies to assess their risk of thrombosis and progression to respiratory failure.

Moreover, they question whether patients with high antiphospholipid antibody titers might benefit from therapies used in conventional cases of severe antiphospholipid syndrome, such as plasmapheresis, anticoagulation therapy, and complement inhibition, Dr. Shi added.

The researchers hope to answer these and other remaining questions in future studies. “Eventually, we may be able to repurpose treatments used in traditional cases of antiphospholipid syndrome for COVID-19.

“As we await definitive solutions to the pandemic, these findings add important context to the complex interplay between SARS-CoV-2 infection, the human immune system, and vascular immunobiology,” she concluded.

The study was supported by grants from the Rheumatology Research Foundation, the Michigan Medicine Frankel Cardiovascular Center, and the A. Alfred Taubman Medical Research Institute. One author is an inventor on an unrelated pending patent to the University of Michigan. The other authors and Dr. Luning Prak have disclosed no relevant financial relationships.

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

Anecdotal reports have linked the vaccines against COVID-19 to the sudden loss of hearing in some people. But a new study has found no evidence for such a connection with any of the three approved shots. 

The analysis of data from the Centers for Disease Control and Prevention’s Vaccine Adverse Event Reporting System (VAERS) found that the incidence of sudden onset hearing loss was not elevated – and might even be a bit lower than expected – in the first few weeks after the injections.

“We’re not finding a signal,” said Eric J. Formeister, MD, a neurotology fellow at the Johns Hopkins University, Baltimore, and the first author of the U.S. study, which appeared Feb. 24 in JAMA Otolaryngology – Head and Neck Surgery.

Dr. Formeister and colleagues undertook the study in response to reports of hearing problems, including hearing loss and tinnitus, that occurred soon after COVID-19 vaccination.

They analyzed reports of sudden hearing loss, experienced within 21 days of vaccination, logged in VAERS. Anyone can report a potential event to the database, which does not require medical documentation in support of the adverse event. To minimize potential misdiagnoses, Dr. Formeister and colleagues reviewed only those reports that indicated that a doctor had diagnosed sudden hearing loss, leaving 555 cases (305 in women; mean age 54 years) between December 2020 and July 2021.

Dividing these reports by the total doses of vaccines administered in the United States during that period yielded an incidence rate of 0.6 cases of sudden hearing loss for every 100,000 people, Dr. Formeister and colleagues reported.

When the researchers divided all cases of hearing loss in the VAERS database (2,170) by the number of people who had received two doses of vaccine, the incidence rate increased to 28 per 100,000 people. For comparison, the authors reported, the incidence of sudden hearing loss within the United States population is between 11 and 77 per 100,000 people, depending on age.

“There was not an increase in cases of sudden [sensorineural] hearing loss associated with COVID-19 vaccination compared to previously published reports before the COVID-19 vaccination era,” study coauthor Elliott D. Kozin, MD, assistant professor of otolaryngology–head and neck surgery at Harvard Medical School, Boston, said in an interview.

Another reassuring sign: If hearing loss were linked to the vaccines, the researchers said, they would expect to see an increase in the number of complaints in lockstep with an increase in the number of doses administered. However, the opposite was true. “[T]he rate of reports per 100,000 doses decreased across the vaccination period, despite large concomitant increases in the absolute number of vaccine doses administered per week,” the researchers reported.

They also looked at case reports of 21 men and women who had experienced sudden hearing loss after having received COVID-19 vaccines, to see if they could discern any clinically relevant signs of people most likely to experience the adverse event. However, the group had a range of preexisting conditions and varying times after receiving a vaccine when their hearing loss occurred, leading Dr. Formeister’s team to conclude that they could find no clear markers of risk.

“When we examined patients across several institutions, there was no obvious pattern. The patient demographics and clinical findings were variable,” Dr. Kozin said. A provisional interpretation of this data, he added, is that no link exists between COVID-19 vaccination and predictable hearing deficits, although the analysis covered a small number of patients.

“Association does not necessarily imply a causal relationship,” said Michael Brenner, MD, FACS, associate professor of otolaryngology–head and neck surgery at the University of Michigan, Ann Arbor. Dr. Brenner, who was not involved in the study, said any hearing loss attributed to the COVID-19 vaccines could have had other causes besides the injections.

But a second study, also published in JAMA Otolaryngology – Head and Neck Surgery on Feb. 24, leaves open the possibility of a link. Researchers in Israel looked for increases in steroid prescriptions used to treat sudden hearing loss as vaccination with the Pfizer version of the shot became widespread in that country. Their conclusion: The vaccine might be associated with a slightly increased risk of sudden hearing loss, although if so, that risk is likely “very small” and the benefits of vaccination “outweigh its potential association” with the side effect.

Dr. Brenner agreed. “The evidence supports [the] clear public health benefit of COVID-19 vaccination, and the scale of those benefits dwarfs associations with hearing, which are of uncertain significance,” he said.

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

Anecdotal reports have linked the vaccines against COVID-19 to the sudden loss of hearing in some people. But a new study has found no evidence for such a connection with any of the three approved shots. 

The analysis of data from the Centers for Disease Control and Prevention’s Vaccine Adverse Event Reporting System (VAERS) found that the incidence of sudden onset hearing loss was not elevated – and might even be a bit lower than expected – in the first few weeks after the injections.

“We’re not finding a signal,” said Eric J. Formeister, MD, a neurotology fellow at the Johns Hopkins University, Baltimore, and the first author of the U.S. study, which appeared Feb. 24 in JAMA Otolaryngology – Head and Neck Surgery.

Dr. Formeister and colleagues undertook the study in response to reports of hearing problems, including hearing loss and tinnitus, that occurred soon after COVID-19 vaccination.

They analyzed reports of sudden hearing loss, experienced within 21 days of vaccination, logged in VAERS. Anyone can report a potential event to the database, which does not require medical documentation in support of the adverse event. To minimize potential misdiagnoses, Dr. Formeister and colleagues reviewed only those reports that indicated that a doctor had diagnosed sudden hearing loss, leaving 555 cases (305 in women; mean age 54 years) between December 2020 and July 2021.

Dividing these reports by the total doses of vaccines administered in the United States during that period yielded an incidence rate of 0.6 cases of sudden hearing loss for every 100,000 people, Dr. Formeister and colleagues reported.

When the researchers divided all cases of hearing loss in the VAERS database (2,170) by the number of people who had received two doses of vaccine, the incidence rate increased to 28 per 100,000 people. For comparison, the authors reported, the incidence of sudden hearing loss within the United States population is between 11 and 77 per 100,000 people, depending on age.

“There was not an increase in cases of sudden [sensorineural] hearing loss associated with COVID-19 vaccination compared to previously published reports before the COVID-19 vaccination era,” study coauthor Elliott D. Kozin, MD, assistant professor of otolaryngology–head and neck surgery at Harvard Medical School, Boston, said in an interview.

Another reassuring sign: If hearing loss were linked to the vaccines, the researchers said, they would expect to see an increase in the number of complaints in lockstep with an increase in the number of doses administered. However, the opposite was true. “[T]he rate of reports per 100,000 doses decreased across the vaccination period, despite large concomitant increases in the absolute number of vaccine doses administered per week,” the researchers reported.

They also looked at case reports of 21 men and women who had experienced sudden hearing loss after having received COVID-19 vaccines, to see if they could discern any clinically relevant signs of people most likely to experience the adverse event. However, the group had a range of preexisting conditions and varying times after receiving a vaccine when their hearing loss occurred, leading Dr. Formeister’s team to conclude that they could find no clear markers of risk.

“When we examined patients across several institutions, there was no obvious pattern. The patient demographics and clinical findings were variable,” Dr. Kozin said. A provisional interpretation of this data, he added, is that no link exists between COVID-19 vaccination and predictable hearing deficits, although the analysis covered a small number of patients.

“Association does not necessarily imply a causal relationship,” said Michael Brenner, MD, FACS, associate professor of otolaryngology–head and neck surgery at the University of Michigan, Ann Arbor. Dr. Brenner, who was not involved in the study, said any hearing loss attributed to the COVID-19 vaccines could have had other causes besides the injections.

But a second study, also published in JAMA Otolaryngology – Head and Neck Surgery on Feb. 24, leaves open the possibility of a link. Researchers in Israel looked for increases in steroid prescriptions used to treat sudden hearing loss as vaccination with the Pfizer version of the shot became widespread in that country. Their conclusion: The vaccine might be associated with a slightly increased risk of sudden hearing loss, although if so, that risk is likely “very small” and the benefits of vaccination “outweigh its potential association” with the side effect.

Dr. Brenner agreed. “The evidence supports [the] clear public health benefit of COVID-19 vaccination, and the scale of those benefits dwarfs associations with hearing, which are of uncertain significance,” he said.

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

Anecdotal reports have linked the vaccines against COVID-19 to the sudden loss of hearing in some people. But a new study has found no evidence for such a connection with any of the three approved shots. 

The analysis of data from the Centers for Disease Control and Prevention’s Vaccine Adverse Event Reporting System (VAERS) found that the incidence of sudden onset hearing loss was not elevated – and might even be a bit lower than expected – in the first few weeks after the injections.

“We’re not finding a signal,” said Eric J. Formeister, MD, a neurotology fellow at the Johns Hopkins University, Baltimore, and the first author of the U.S. study, which appeared Feb. 24 in JAMA Otolaryngology – Head and Neck Surgery.

Dr. Formeister and colleagues undertook the study in response to reports of hearing problems, including hearing loss and tinnitus, that occurred soon after COVID-19 vaccination.

They analyzed reports of sudden hearing loss, experienced within 21 days of vaccination, logged in VAERS. Anyone can report a potential event to the database, which does not require medical documentation in support of the adverse event. To minimize potential misdiagnoses, Dr. Formeister and colleagues reviewed only those reports that indicated that a doctor had diagnosed sudden hearing loss, leaving 555 cases (305 in women; mean age 54 years) between December 2020 and July 2021.

Dividing these reports by the total doses of vaccines administered in the United States during that period yielded an incidence rate of 0.6 cases of sudden hearing loss for every 100,000 people, Dr. Formeister and colleagues reported.

When the researchers divided all cases of hearing loss in the VAERS database (2,170) by the number of people who had received two doses of vaccine, the incidence rate increased to 28 per 100,000 people. For comparison, the authors reported, the incidence of sudden hearing loss within the United States population is between 11 and 77 per 100,000 people, depending on age.

“There was not an increase in cases of sudden [sensorineural] hearing loss associated with COVID-19 vaccination compared to previously published reports before the COVID-19 vaccination era,” study coauthor Elliott D. Kozin, MD, assistant professor of otolaryngology–head and neck surgery at Harvard Medical School, Boston, said in an interview.

Another reassuring sign: If hearing loss were linked to the vaccines, the researchers said, they would expect to see an increase in the number of complaints in lockstep with an increase in the number of doses administered. However, the opposite was true. “[T]he rate of reports per 100,000 doses decreased across the vaccination period, despite large concomitant increases in the absolute number of vaccine doses administered per week,” the researchers reported.

They also looked at case reports of 21 men and women who had experienced sudden hearing loss after having received COVID-19 vaccines, to see if they could discern any clinically relevant signs of people most likely to experience the adverse event. However, the group had a range of preexisting conditions and varying times after receiving a vaccine when their hearing loss occurred, leading Dr. Formeister’s team to conclude that they could find no clear markers of risk.

“When we examined patients across several institutions, there was no obvious pattern. The patient demographics and clinical findings were variable,” Dr. Kozin said. A provisional interpretation of this data, he added, is that no link exists between COVID-19 vaccination and predictable hearing deficits, although the analysis covered a small number of patients.

“Association does not necessarily imply a causal relationship,” said Michael Brenner, MD, FACS, associate professor of otolaryngology–head and neck surgery at the University of Michigan, Ann Arbor. Dr. Brenner, who was not involved in the study, said any hearing loss attributed to the COVID-19 vaccines could have had other causes besides the injections.

But a second study, also published in JAMA Otolaryngology – Head and Neck Surgery on Feb. 24, leaves open the possibility of a link. Researchers in Israel looked for increases in steroid prescriptions used to treat sudden hearing loss as vaccination with the Pfizer version of the shot became widespread in that country. Their conclusion: The vaccine might be associated with a slightly increased risk of sudden hearing loss, although if so, that risk is likely “very small” and the benefits of vaccination “outweigh its potential association” with the side effect.

Dr. Brenner agreed. “The evidence supports [the] clear public health benefit of COVID-19 vaccination, and the scale of those benefits dwarfs associations with hearing, which are of uncertain significance,” he said.

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