Journal of Clinical Outcomes Management

Antipsychotics may protect against SARS-CoV-2 infection or lead to a milder course of illness, new research suggests.

“Counterintuitively,” the investigators noted, vulnerable people with severe mental illness “on antipsychotic treatment showed a lower risk of SARS-CoV-2 infection and a likely better COVID-19 prognosis.”

“These are very interesting findings that reflect a clinical reality where we see few patients with severe COVID-19, despite the presence of various risk factors,” study investigator Manuel Canal-Rivero, PhD, clinical psychologist, Virgen del Rocio University Hospital, Sevilla, Spain, said in a news release.

“The number of COVID-19 patients is lower than expected among this group of people and in cases where a proven infection does occur, the evolution is benign and does not reach a life-threatening clinical situation. These data as a whole seem to point to the protective effect of the medication,” Dr. Canal-Rivero added.

The study was published online as a letter to the editor February 19, 2021, in Schizophrenia Research.
 

A ‘striking’ finding

The researchers assessed the prevalence and prognosis of COVID-19 in 698 patients with serious mental disorders (SMDs) receiving treatment with long-acting injectable antipsychotic medication. The non-SMD population included the catchment area population of 557,576 individuals.

From February to November 2020, 4.1% of the non-SMD population were infected with SARS-CoV-2 versus just 1.3% of the SMD population (9 of 698 patients). All but one patient with SMD had asymptomatic illness (8 of 9, 89%). Accurate information on asymptomatic illness in the non-SMD population was not available.

There were also fewer hospital admissions in the SMD population (0% vs. 8.5%), ICU admissions (0% vs. 0.9%) and deaths because of COVID-19 (0% vs. 1.1%), although the differences were not statistically significant.

In related research, the same investigators found that many of the genes whose expression is altered by SARS-CoV-2 infection are significantly down-regulated by antipsychotic drugs.

“In a striking way, we have shown how antipsychotics reduce the activation of genes involved in many of the inflammatory and immunological pathways associated with the severity of COVID-19 infection,” Benedicto Crespo-Facorro, MD, PhD, University of Sevilla, who led the study, said in the news release.

“Although this finding requires replication, the discovery could be very significant because the treatment of COVID-19 with drugs originally indicated for unrelated clinical situations, that is to say drug repositioning, has been shown to be an interesting source of effective treatments for COVID-19 patients,” he added.
 

Antiviral properties?

In a comment, Samoon Ahmad, MD, professor, department of psychiatry, New York University, said the findings are “fascinating” and should be explored further.

While the findings on long-acting injectable antipsychotic treatment “seem counterintuitive at first, they are in line with other studies,” said Dr. Ahmad, who heads the inpatient psychiatry unit at Bellevue Hospital Center and is founder of the Integrative Center for Wellness in New York.

“We know that certain antipsychotics can suppress the expression of inflammatory cytokines (thereby theoretically preventing cytokine storm) and antidepressant medications appear to activate key cellular proteins that the SARS-CoV-2 virus uses for replication,” explained Dr. Ahmad, who was not associated with the study.

For example, as reported by this news organization, a preliminary study published in 2020 showed that early treatment with the antidepressant fluvoxamine prevented clinical deterioration in adult outpatients with confirmed COVID-19.

The antipsychotic aripiprazole has also shown potential to treat severe COVID-19 infection.

“Consequently, there appears to be a possible explanation as to why these drugs afford patients with severe mental disorders increased protection against the SARS-CoV-2 virus,” Dr. Ahmad said in an interview.

However, he cautioned, there are several factors at play that could influence the results. Therefore, more research is needed before drawing any firm conclusions.

“Still, the possibility that psychiatric medications may have antiviral properties is a tremendous development and I really hope that additional studies confirm the preliminary findings,” Dr. Ahmad said.

The study had no specific funding. The authors and Dr. Ahmad disclosed no relevant financial relationships.

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

Antipsychotics may protect against SARS-CoV-2 infection or lead to a milder course of illness, new research suggests.

“Counterintuitively,” the investigators noted, vulnerable people with severe mental illness “on antipsychotic treatment showed a lower risk of SARS-CoV-2 infection and a likely better COVID-19 prognosis.”

“These are very interesting findings that reflect a clinical reality where we see few patients with severe COVID-19, despite the presence of various risk factors,” study investigator Manuel Canal-Rivero, PhD, clinical psychologist, Virgen del Rocio University Hospital, Sevilla, Spain, said in a news release.

“The number of COVID-19 patients is lower than expected among this group of people and in cases where a proven infection does occur, the evolution is benign and does not reach a life-threatening clinical situation. These data as a whole seem to point to the protective effect of the medication,” Dr. Canal-Rivero added.

The study was published online as a letter to the editor February 19, 2021, in Schizophrenia Research.
 

A ‘striking’ finding

The researchers assessed the prevalence and prognosis of COVID-19 in 698 patients with serious mental disorders (SMDs) receiving treatment with long-acting injectable antipsychotic medication. The non-SMD population included the catchment area population of 557,576 individuals.

From February to November 2020, 4.1% of the non-SMD population were infected with SARS-CoV-2 versus just 1.3% of the SMD population (9 of 698 patients). All but one patient with SMD had asymptomatic illness (8 of 9, 89%). Accurate information on asymptomatic illness in the non-SMD population was not available.

There were also fewer hospital admissions in the SMD population (0% vs. 8.5%), ICU admissions (0% vs. 0.9%) and deaths because of COVID-19 (0% vs. 1.1%), although the differences were not statistically significant.

In related research, the same investigators found that many of the genes whose expression is altered by SARS-CoV-2 infection are significantly down-regulated by antipsychotic drugs.

“In a striking way, we have shown how antipsychotics reduce the activation of genes involved in many of the inflammatory and immunological pathways associated with the severity of COVID-19 infection,” Benedicto Crespo-Facorro, MD, PhD, University of Sevilla, who led the study, said in the news release.

“Although this finding requires replication, the discovery could be very significant because the treatment of COVID-19 with drugs originally indicated for unrelated clinical situations, that is to say drug repositioning, has been shown to be an interesting source of effective treatments for COVID-19 patients,” he added.
 

Antiviral properties?

In a comment, Samoon Ahmad, MD, professor, department of psychiatry, New York University, said the findings are “fascinating” and should be explored further.

While the findings on long-acting injectable antipsychotic treatment “seem counterintuitive at first, they are in line with other studies,” said Dr. Ahmad, who heads the inpatient psychiatry unit at Bellevue Hospital Center and is founder of the Integrative Center for Wellness in New York.

“We know that certain antipsychotics can suppress the expression of inflammatory cytokines (thereby theoretically preventing cytokine storm) and antidepressant medications appear to activate key cellular proteins that the SARS-CoV-2 virus uses for replication,” explained Dr. Ahmad, who was not associated with the study.

For example, as reported by this news organization, a preliminary study published in 2020 showed that early treatment with the antidepressant fluvoxamine prevented clinical deterioration in adult outpatients with confirmed COVID-19.

The antipsychotic aripiprazole has also shown potential to treat severe COVID-19 infection.

“Consequently, there appears to be a possible explanation as to why these drugs afford patients with severe mental disorders increased protection against the SARS-CoV-2 virus,” Dr. Ahmad said in an interview.

However, he cautioned, there are several factors at play that could influence the results. Therefore, more research is needed before drawing any firm conclusions.

“Still, the possibility that psychiatric medications may have antiviral properties is a tremendous development and I really hope that additional studies confirm the preliminary findings,” Dr. Ahmad said.

The study had no specific funding. The authors and Dr. Ahmad disclosed no relevant financial relationships.

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

Antipsychotics may protect against SARS-CoV-2 infection or lead to a milder course of illness, new research suggests.

“Counterintuitively,” the investigators noted, vulnerable people with severe mental illness “on antipsychotic treatment showed a lower risk of SARS-CoV-2 infection and a likely better COVID-19 prognosis.”

“These are very interesting findings that reflect a clinical reality where we see few patients with severe COVID-19, despite the presence of various risk factors,” study investigator Manuel Canal-Rivero, PhD, clinical psychologist, Virgen del Rocio University Hospital, Sevilla, Spain, said in a news release.

“The number of COVID-19 patients is lower than expected among this group of people and in cases where a proven infection does occur, the evolution is benign and does not reach a life-threatening clinical situation. These data as a whole seem to point to the protective effect of the medication,” Dr. Canal-Rivero added.

The study was published online as a letter to the editor February 19, 2021, in Schizophrenia Research.
 

A ‘striking’ finding

The researchers assessed the prevalence and prognosis of COVID-19 in 698 patients with serious mental disorders (SMDs) receiving treatment with long-acting injectable antipsychotic medication. The non-SMD population included the catchment area population of 557,576 individuals.

From February to November 2020, 4.1% of the non-SMD population were infected with SARS-CoV-2 versus just 1.3% of the SMD population (9 of 698 patients). All but one patient with SMD had asymptomatic illness (8 of 9, 89%). Accurate information on asymptomatic illness in the non-SMD population was not available.

There were also fewer hospital admissions in the SMD population (0% vs. 8.5%), ICU admissions (0% vs. 0.9%) and deaths because of COVID-19 (0% vs. 1.1%), although the differences were not statistically significant.

In related research, the same investigators found that many of the genes whose expression is altered by SARS-CoV-2 infection are significantly down-regulated by antipsychotic drugs.

“In a striking way, we have shown how antipsychotics reduce the activation of genes involved in many of the inflammatory and immunological pathways associated with the severity of COVID-19 infection,” Benedicto Crespo-Facorro, MD, PhD, University of Sevilla, who led the study, said in the news release.

“Although this finding requires replication, the discovery could be very significant because the treatment of COVID-19 with drugs originally indicated for unrelated clinical situations, that is to say drug repositioning, has been shown to be an interesting source of effective treatments for COVID-19 patients,” he added.
 

Antiviral properties?

In a comment, Samoon Ahmad, MD, professor, department of psychiatry, New York University, said the findings are “fascinating” and should be explored further.

While the findings on long-acting injectable antipsychotic treatment “seem counterintuitive at first, they are in line with other studies,” said Dr. Ahmad, who heads the inpatient psychiatry unit at Bellevue Hospital Center and is founder of the Integrative Center for Wellness in New York.

“We know that certain antipsychotics can suppress the expression of inflammatory cytokines (thereby theoretically preventing cytokine storm) and antidepressant medications appear to activate key cellular proteins that the SARS-CoV-2 virus uses for replication,” explained Dr. Ahmad, who was not associated with the study.

For example, as reported by this news organization, a preliminary study published in 2020 showed that early treatment with the antidepressant fluvoxamine prevented clinical deterioration in adult outpatients with confirmed COVID-19.

The antipsychotic aripiprazole has also shown potential to treat severe COVID-19 infection.

“Consequently, there appears to be a possible explanation as to why these drugs afford patients with severe mental disorders increased protection against the SARS-CoV-2 virus,” Dr. Ahmad said in an interview.

However, he cautioned, there are several factors at play that could influence the results. Therefore, more research is needed before drawing any firm conclusions.

“Still, the possibility that psychiatric medications may have antiviral properties is a tremendous development and I really hope that additional studies confirm the preliminary findings,” Dr. Ahmad said.

The study had no specific funding. The authors and Dr. Ahmad disclosed no relevant financial relationships.

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

A Food and Drug Administration advisory panel has endorsed a pancreatic islet cell transplant therapy for the treatment of people with type 1 diabetes that can’t be managed with current therapies.

On April 15, the FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee voted 12 to 4 in favor of approval of donislecel (Lantidra). There was one abstention. The panel regarded the drug as having “an overall favorable benefit-risk profile for some patients with type 1 diabetes.” The product consists of purified allogeneic pancreatic islets of Langerhans derived from cadaveric donors and is infused into the portal vein of the liver.

Benefits of the treatment include the potential for insulin independence and elimination of severe hypoglycemia. Risks are those associated with the surgical procedure and with long-term immunosuppression.

The therapy is manufactured by CellTrans. According to Jose Oberholzer, MD, the founder of CellTrans, the proposed indication is for adults with “brittle” type 1 diabetes who meet the American Diabetes Association’s (ADA) criteria for whole-organ pancreas-alone transplant (i.e., transplant of pancreas but not kidney).

The ADA criteria include the following: frequent, severe hypoglycemia, hyperglycemia, and/or ketoacidosis that requires medical attention; clinical or emotional problems regarding the use of exogenous insulin; and consistent failure of insulin-based management to prevent acute diabetes complications.
 

Success in two-thirds of patients in small studies

Dr. Oberholzer presented data from two single-arm open-label studies: a phase 1/2 trial initiated in 2004 with 10 patients, and a phase 3 study with 20 patients that began in 2007. The inclusion criteria differed somewhat between the two studies, but all 30 patients had hypoglycemic unawareness. Mean follow-up was 7.8 years for the phase 1/2 trial and 4.7 years for the phase 3 trial.

For all of the patients, C-peptide levels were positive after transplant. The composite endpoint for success – an A1c level of ≤ 6.5% and the absence of severe hypoglycemic episodes for 1 year – was met by 19 patients (63.3%). For five patients (16.7%), the target A1c level was not achieved, and seven patients (23.3%) experienced a severe episode of hypoglycemia.

Twenty of the 30 patients achieved insulin independence for at least 1 year.

Improvements were also seen at 1 year in mixed meal test outcomes, fasting blood glucose levels, and overall glycemic control. Graft survival 10 years post transplant was achieved by 60% of patients, Dr. Oberholzer said.
 

Adverse events not unexpected, but still of concern

Two patients died, one as a result of fulminant sepsis at 20 months post transplant, and the other as a result of severe dementia 9 years post transplant. Three patients experienced four serious procedure-related events, including one liver laceration and two hepatic hematomas. Elevations in portal pressure occurred in two patients.

Most adverse events were associated with immunosuppression. These included 178 infections in 26 of the 30 patients. The most common of these were herpes virus infections, Epstein-Barr virus infections, oral candidiasis, and cytomegalovirus infections. Twelve infections were severe. Renal function declined persistently in two patients (20%), and six (20%) experienced new-onset proteinuria at 1 year.

The adverse events related to the procedure and the problems associated with immunosuppression were not unexpected and were consistent with those described for patients receiving whole pancreas transplants, FDA reviewer Patricia Beaston, MD, said in her review of the CellTrans data.
 

Panel members support treatment for a small group of patients

During the discussion, several panel members pointed out that the target patient population for this treatment will likely be smaller today than it was when the two studies were initiated, given advances in diabetes care. Those advances include continuous glucose monitoring devices with alarms and closed-loop insulin delivery systems – the “artificial pancreas” that automatically suspends insulin delivery to prevent hypoglycemia.

Panel chair Lisa Butterfield, PhD, a surgeon and immunologist at the University of California, San Francisco, voted in favor of approval. But, she added, “I do support postapproval gathering of data to learn more about the product. ... I don’t know how many patients will really benefit, but I think it’s to be determined.”

Christopher K. Breuer, MD, a general and pediatric surgeon at the Center for Regenerative Medicine, Nationwide Children’s Hospital, Columbus, Ohio, said he supported approval for “two very small subpopulations where it would provide the only viable therapy”: those who are eligible for pancreas transplant but cannot tolerate a major operation, and those who already use the latest automated insulin delivery systems and still do not achieve acceptable glycemic control.

Temporary voting member David Harlan, MD, director of the University of Massachusetts Diabetes Center of Excellence, Worcester, Mass., voted no.

He noted that only about 100 whole pancreas-only transplants are performed annually in the United States and that such transplants are “very effective, so we’re talking about patients who aren’t pancreas transplant candidates who might get this.”

Moreover, Dr. Harlan said, “I’ve seen the awful things that can happen in posttransplant recipients. It’s really hard to get that informed consent from someone when you’re asking them to consider a future that they don’t know. When it works, it’s great. When it doesn’t work, it can be catastrophic. I just worry about opening Pandora’s box.”

The only other diabetes specialist on the panel, temporary voting member Ellen Leschek, MD, said she “reluctantly voted yes because a few people could benefit, but I think it’s a much smaller number than the company may believe.”

Dr. Leschek, of the National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Md., said she’s concerned that “if it’s approved, too many people will get treated this way, when in fact, for a lot of those people, the risks will outweigh the benefits.”

Sandy Feng, MD, PhD, of the department of surgery at the University of California, San Francisco, pointed out that with regard to immunosuppressive therapy, “We’re concerned about the toxicity of what we currently use, but there are additional therapies being developed that might mitigate those toxicities that would be beneficial to this population.”

Dr. Feng, who voted yes, also said, “I do pancreas transplants. I can tell you that there is nothing that [patients with type 1 diabetes] like more than the freedom from dealing with the entire insulin issue. That has made a large impression on me over the last 20-plus years of clinical practice, so I do think this can help some people and will be incredibly meaningful to those people.”

FDA advisory panel members are vetted for conflicts of interest, and special waivers are granted if necessary. No such waivers were granted for this meeting.

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

A Food and Drug Administration advisory panel has endorsed a pancreatic islet cell transplant therapy for the treatment of people with type 1 diabetes that can’t be managed with current therapies.

On April 15, the FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee voted 12 to 4 in favor of approval of donislecel (Lantidra). There was one abstention. The panel regarded the drug as having “an overall favorable benefit-risk profile for some patients with type 1 diabetes.” The product consists of purified allogeneic pancreatic islets of Langerhans derived from cadaveric donors and is infused into the portal vein of the liver.

Benefits of the treatment include the potential for insulin independence and elimination of severe hypoglycemia. Risks are those associated with the surgical procedure and with long-term immunosuppression.

The therapy is manufactured by CellTrans. According to Jose Oberholzer, MD, the founder of CellTrans, the proposed indication is for adults with “brittle” type 1 diabetes who meet the American Diabetes Association’s (ADA) criteria for whole-organ pancreas-alone transplant (i.e., transplant of pancreas but not kidney).

The ADA criteria include the following: frequent, severe hypoglycemia, hyperglycemia, and/or ketoacidosis that requires medical attention; clinical or emotional problems regarding the use of exogenous insulin; and consistent failure of insulin-based management to prevent acute diabetes complications.
 

Success in two-thirds of patients in small studies

Dr. Oberholzer presented data from two single-arm open-label studies: a phase 1/2 trial initiated in 2004 with 10 patients, and a phase 3 study with 20 patients that began in 2007. The inclusion criteria differed somewhat between the two studies, but all 30 patients had hypoglycemic unawareness. Mean follow-up was 7.8 years for the phase 1/2 trial and 4.7 years for the phase 3 trial.

For all of the patients, C-peptide levels were positive after transplant. The composite endpoint for success – an A1c level of ≤ 6.5% and the absence of severe hypoglycemic episodes for 1 year – was met by 19 patients (63.3%). For five patients (16.7%), the target A1c level was not achieved, and seven patients (23.3%) experienced a severe episode of hypoglycemia.

Twenty of the 30 patients achieved insulin independence for at least 1 year.

Improvements were also seen at 1 year in mixed meal test outcomes, fasting blood glucose levels, and overall glycemic control. Graft survival 10 years post transplant was achieved by 60% of patients, Dr. Oberholzer said.
 

Adverse events not unexpected, but still of concern

Two patients died, one as a result of fulminant sepsis at 20 months post transplant, and the other as a result of severe dementia 9 years post transplant. Three patients experienced four serious procedure-related events, including one liver laceration and two hepatic hematomas. Elevations in portal pressure occurred in two patients.

Most adverse events were associated with immunosuppression. These included 178 infections in 26 of the 30 patients. The most common of these were herpes virus infections, Epstein-Barr virus infections, oral candidiasis, and cytomegalovirus infections. Twelve infections were severe. Renal function declined persistently in two patients (20%), and six (20%) experienced new-onset proteinuria at 1 year.

The adverse events related to the procedure and the problems associated with immunosuppression were not unexpected and were consistent with those described for patients receiving whole pancreas transplants, FDA reviewer Patricia Beaston, MD, said in her review of the CellTrans data.
 

Panel members support treatment for a small group of patients

During the discussion, several panel members pointed out that the target patient population for this treatment will likely be smaller today than it was when the two studies were initiated, given advances in diabetes care. Those advances include continuous glucose monitoring devices with alarms and closed-loop insulin delivery systems – the “artificial pancreas” that automatically suspends insulin delivery to prevent hypoglycemia.

Panel chair Lisa Butterfield, PhD, a surgeon and immunologist at the University of California, San Francisco, voted in favor of approval. But, she added, “I do support postapproval gathering of data to learn more about the product. ... I don’t know how many patients will really benefit, but I think it’s to be determined.”

Christopher K. Breuer, MD, a general and pediatric surgeon at the Center for Regenerative Medicine, Nationwide Children’s Hospital, Columbus, Ohio, said he supported approval for “two very small subpopulations where it would provide the only viable therapy”: those who are eligible for pancreas transplant but cannot tolerate a major operation, and those who already use the latest automated insulin delivery systems and still do not achieve acceptable glycemic control.

Temporary voting member David Harlan, MD, director of the University of Massachusetts Diabetes Center of Excellence, Worcester, Mass., voted no.

He noted that only about 100 whole pancreas-only transplants are performed annually in the United States and that such transplants are “very effective, so we’re talking about patients who aren’t pancreas transplant candidates who might get this.”

Moreover, Dr. Harlan said, “I’ve seen the awful things that can happen in posttransplant recipients. It’s really hard to get that informed consent from someone when you’re asking them to consider a future that they don’t know. When it works, it’s great. When it doesn’t work, it can be catastrophic. I just worry about opening Pandora’s box.”

The only other diabetes specialist on the panel, temporary voting member Ellen Leschek, MD, said she “reluctantly voted yes because a few people could benefit, but I think it’s a much smaller number than the company may believe.”

Dr. Leschek, of the National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Md., said she’s concerned that “if it’s approved, too many people will get treated this way, when in fact, for a lot of those people, the risks will outweigh the benefits.”

Sandy Feng, MD, PhD, of the department of surgery at the University of California, San Francisco, pointed out that with regard to immunosuppressive therapy, “We’re concerned about the toxicity of what we currently use, but there are additional therapies being developed that might mitigate those toxicities that would be beneficial to this population.”

Dr. Feng, who voted yes, also said, “I do pancreas transplants. I can tell you that there is nothing that [patients with type 1 diabetes] like more than the freedom from dealing with the entire insulin issue. That has made a large impression on me over the last 20-plus years of clinical practice, so I do think this can help some people and will be incredibly meaningful to those people.”

FDA advisory panel members are vetted for conflicts of interest, and special waivers are granted if necessary. No such waivers were granted for this meeting.

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

A Food and Drug Administration advisory panel has endorsed a pancreatic islet cell transplant therapy for the treatment of people with type 1 diabetes that can’t be managed with current therapies.

On April 15, the FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee voted 12 to 4 in favor of approval of donislecel (Lantidra). There was one abstention. The panel regarded the drug as having “an overall favorable benefit-risk profile for some patients with type 1 diabetes.” The product consists of purified allogeneic pancreatic islets of Langerhans derived from cadaveric donors and is infused into the portal vein of the liver.

Benefits of the treatment include the potential for insulin independence and elimination of severe hypoglycemia. Risks are those associated with the surgical procedure and with long-term immunosuppression.

The therapy is manufactured by CellTrans. According to Jose Oberholzer, MD, the founder of CellTrans, the proposed indication is for adults with “brittle” type 1 diabetes who meet the American Diabetes Association’s (ADA) criteria for whole-organ pancreas-alone transplant (i.e., transplant of pancreas but not kidney).

The ADA criteria include the following: frequent, severe hypoglycemia, hyperglycemia, and/or ketoacidosis that requires medical attention; clinical or emotional problems regarding the use of exogenous insulin; and consistent failure of insulin-based management to prevent acute diabetes complications.
 

Success in two-thirds of patients in small studies

Dr. Oberholzer presented data from two single-arm open-label studies: a phase 1/2 trial initiated in 2004 with 10 patients, and a phase 3 study with 20 patients that began in 2007. The inclusion criteria differed somewhat between the two studies, but all 30 patients had hypoglycemic unawareness. Mean follow-up was 7.8 years for the phase 1/2 trial and 4.7 years for the phase 3 trial.

For all of the patients, C-peptide levels were positive after transplant. The composite endpoint for success – an A1c level of ≤ 6.5% and the absence of severe hypoglycemic episodes for 1 year – was met by 19 patients (63.3%). For five patients (16.7%), the target A1c level was not achieved, and seven patients (23.3%) experienced a severe episode of hypoglycemia.

Twenty of the 30 patients achieved insulin independence for at least 1 year.

Improvements were also seen at 1 year in mixed meal test outcomes, fasting blood glucose levels, and overall glycemic control. Graft survival 10 years post transplant was achieved by 60% of patients, Dr. Oberholzer said.
 

Adverse events not unexpected, but still of concern

Two patients died, one as a result of fulminant sepsis at 20 months post transplant, and the other as a result of severe dementia 9 years post transplant. Three patients experienced four serious procedure-related events, including one liver laceration and two hepatic hematomas. Elevations in portal pressure occurred in two patients.

Most adverse events were associated with immunosuppression. These included 178 infections in 26 of the 30 patients. The most common of these were herpes virus infections, Epstein-Barr virus infections, oral candidiasis, and cytomegalovirus infections. Twelve infections were severe. Renal function declined persistently in two patients (20%), and six (20%) experienced new-onset proteinuria at 1 year.

The adverse events related to the procedure and the problems associated with immunosuppression were not unexpected and were consistent with those described for patients receiving whole pancreas transplants, FDA reviewer Patricia Beaston, MD, said in her review of the CellTrans data.
 

Panel members support treatment for a small group of patients

During the discussion, several panel members pointed out that the target patient population for this treatment will likely be smaller today than it was when the two studies were initiated, given advances in diabetes care. Those advances include continuous glucose monitoring devices with alarms and closed-loop insulin delivery systems – the “artificial pancreas” that automatically suspends insulin delivery to prevent hypoglycemia.

Panel chair Lisa Butterfield, PhD, a surgeon and immunologist at the University of California, San Francisco, voted in favor of approval. But, she added, “I do support postapproval gathering of data to learn more about the product. ... I don’t know how many patients will really benefit, but I think it’s to be determined.”

Christopher K. Breuer, MD, a general and pediatric surgeon at the Center for Regenerative Medicine, Nationwide Children’s Hospital, Columbus, Ohio, said he supported approval for “two very small subpopulations where it would provide the only viable therapy”: those who are eligible for pancreas transplant but cannot tolerate a major operation, and those who already use the latest automated insulin delivery systems and still do not achieve acceptable glycemic control.

Temporary voting member David Harlan, MD, director of the University of Massachusetts Diabetes Center of Excellence, Worcester, Mass., voted no.

He noted that only about 100 whole pancreas-only transplants are performed annually in the United States and that such transplants are “very effective, so we’re talking about patients who aren’t pancreas transplant candidates who might get this.”

Moreover, Dr. Harlan said, “I’ve seen the awful things that can happen in posttransplant recipients. It’s really hard to get that informed consent from someone when you’re asking them to consider a future that they don’t know. When it works, it’s great. When it doesn’t work, it can be catastrophic. I just worry about opening Pandora’s box.”

The only other diabetes specialist on the panel, temporary voting member Ellen Leschek, MD, said she “reluctantly voted yes because a few people could benefit, but I think it’s a much smaller number than the company may believe.”

Dr. Leschek, of the National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Md., said she’s concerned that “if it’s approved, too many people will get treated this way, when in fact, for a lot of those people, the risks will outweigh the benefits.”

Sandy Feng, MD, PhD, of the department of surgery at the University of California, San Francisco, pointed out that with regard to immunosuppressive therapy, “We’re concerned about the toxicity of what we currently use, but there are additional therapies being developed that might mitigate those toxicities that would be beneficial to this population.”

Dr. Feng, who voted yes, also said, “I do pancreas transplants. I can tell you that there is nothing that [patients with type 1 diabetes] like more than the freedom from dealing with the entire insulin issue. That has made a large impression on me over the last 20-plus years of clinical practice, so I do think this can help some people and will be incredibly meaningful to those people.”

FDA advisory panel members are vetted for conflicts of interest, and special waivers are granted if necessary. No such waivers were granted for this meeting.

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

Most patients who are receiving maintenance hemodialysis develop a good antibody response after being given two doses of the Pfizer-BioNTech COVID-19 vaccine, but their responses are still significantly lower than those of health care workers who do not have kidney disease, the first study of its kind shows.

“It is well known that patients on dialysis may have a reduced response to vaccination,” Ayelet Grupper, MD, of Tel Aviv Medical Center, and colleagues observe. Their study was published online April 6 in the Clinical Journal of the American Society of Nephrology.

“I believe our findings should encourage patients with kidney failure treated with dialysis to be vaccinated as soon as vaccination becomes available for them, while we as caregivers should explore ways to enhance its efficacy in our patients,” senior author Moshe Shashar, MD, noted in a statement from the American Society of Nephrology.

Asked to comment, Peter Blake, MD, professor of medicine, University of Western Ontario, London, pointed out that COVID-19 is very common among hemodialysis patients and that the likelihood of these patients dying from it is very high. Indeed, 1.5% of approximately 12,500 patients receiving dialysis in the province of Ontario have died of COVID-19 – “a horrifying statistic and one that only long-term care home residents can compare with,” he told this news organization.

In the Israeli study, almost all dialysis patients mounted a serologic response to the Pfizer-BioNTech vaccine, which is “good news” overall, Dr. Blake said.

Also commenting on the study, Anushree Shirali, MD, of Yale University, New Haven, Conn., said she was impressed by the fact that most of the dialysis patients in the study mounted at least some IgG response to vaccination, which she said was good “in and of itself,” because that is not always the case with other vaccines.
 

Study compared dialysis patients with health care workers

The Israeli study included 56 patients who were receiving maintenance hemodialysis and 95 health care workers, who served as control persons.

“All participants had been previously vaccinated with the [Pfizer-BioNTech] vaccine, with the recommended dosing interval of 21 days between the first and second doses,” the investigators note. Immunogenicity was assessed using a dedicated immunoassay to quantify the level of IgG antibodies from participants’ plasma.

A cutoff for a positive antibody response was greater than or equal to 50 arbitrary units per milliliter (AU/mL). “All subjects in the control group developed a positive antibody response (≥50 AU/mL) as compared with 96% (54 of 56) in the dialysis group,” Dr. Shashar and colleagues report.

The median IgG level in the dialysis group was 2,900 AU/mL, which is significantly lower than the median of 7,401 AU/mL in the control group (P < .001), they report.

The investigators also observed a significant inverse correlation between older age and antibody levels in both groups.

The odds of being in the lower quartile were significantly higher for older individuals (odds ratio, 1.11 per year of age; P = .004) and for the dialysis group compared with the control group (OR, 2.7; P = .05).

Among the dialysis patients, older age and lower lymphocyte count were associated with antibody response in the lower quartile (OR, 1.22 per 1 year older; P = .03; and OR, 0.83 per 10-e3/mL-higher lymphocyte count; P = .05).

Among recipients older than 70 years, there was little difference in antibody response between the dialysis patients and the control group. Thus, age is clearly an important contributor to a robust humoral response, the authors observe.

For more than 90% of the patients receiving dialysis, the antibody response was well above 50 AU/mL, which was the cutoff for having a positive response.

Nevertheless, the authors suggest that their findings should prompt clinicians to consider either changing the dose or the schedule of COVID-19 vaccination for dialysis patients, as was done, for example, with the hepatitis B vaccine Engerix-B.

Dialysis patients now receive double doses of the hepatitis B vaccine, which is given in a four-series vaccine schedule rather than a three-series vaccine schedule, as is given to healthy individuals.

The authors also call for studies to assess the longevity of vaccine efficacy for dialysis patients and whether current vaccines are effective against variant strains among patients undergoing dialysis.
 

Some suggestion COVID-19 vaccines also elicit T-cell responses

Dr. Shirali said the news regarding the COVID-19 vaccine for dialysis patients is good, given the fact that such patients exhibit a poor response to the hepatitis B vaccine.

“There isn’t a large percentage of dialysis patients who mount a humoral response to the hepatitis B vaccine, even with the change in dosing that we use that is different than it is for the general population,” she told this news organization.

Dr. Shirali also noted that preliminary evidence suggests that COVID-19 vaccines elicit nonantibody and antibody T-cell responses and that such immunity is going to be just as important for protecting dialysis patients against COVID-19 as it is for protecting patients who are not receiving dialysis.

“Antibody responses are just one arm of vaccination,” she explained. “People can form memory T-cell responses with vaccination, and while this has not been well studied with COVID-19, there are preliminary data to suggest that T-cell responses are likely to be effective in the fight against COVID-19.” There is also the possibility that this type of response “may even be more durable than antibody responses,” she said.

The study received no funding. The authors, Dr. Blake and Dr. Shirali, have disclosed no relevant financial relationships.

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

Most patients who are receiving maintenance hemodialysis develop a good antibody response after being given two doses of the Pfizer-BioNTech COVID-19 vaccine, but their responses are still significantly lower than those of health care workers who do not have kidney disease, the first study of its kind shows.

“It is well known that patients on dialysis may have a reduced response to vaccination,” Ayelet Grupper, MD, of Tel Aviv Medical Center, and colleagues observe. Their study was published online April 6 in the Clinical Journal of the American Society of Nephrology.

“I believe our findings should encourage patients with kidney failure treated with dialysis to be vaccinated as soon as vaccination becomes available for them, while we as caregivers should explore ways to enhance its efficacy in our patients,” senior author Moshe Shashar, MD, noted in a statement from the American Society of Nephrology.

Asked to comment, Peter Blake, MD, professor of medicine, University of Western Ontario, London, pointed out that COVID-19 is very common among hemodialysis patients and that the likelihood of these patients dying from it is very high. Indeed, 1.5% of approximately 12,500 patients receiving dialysis in the province of Ontario have died of COVID-19 – “a horrifying statistic and one that only long-term care home residents can compare with,” he told this news organization.

In the Israeli study, almost all dialysis patients mounted a serologic response to the Pfizer-BioNTech vaccine, which is “good news” overall, Dr. Blake said.

Also commenting on the study, Anushree Shirali, MD, of Yale University, New Haven, Conn., said she was impressed by the fact that most of the dialysis patients in the study mounted at least some IgG response to vaccination, which she said was good “in and of itself,” because that is not always the case with other vaccines.
 

Study compared dialysis patients with health care workers

The Israeli study included 56 patients who were receiving maintenance hemodialysis and 95 health care workers, who served as control persons.

“All participants had been previously vaccinated with the [Pfizer-BioNTech] vaccine, with the recommended dosing interval of 21 days between the first and second doses,” the investigators note. Immunogenicity was assessed using a dedicated immunoassay to quantify the level of IgG antibodies from participants’ plasma.

A cutoff for a positive antibody response was greater than or equal to 50 arbitrary units per milliliter (AU/mL). “All subjects in the control group developed a positive antibody response (≥50 AU/mL) as compared with 96% (54 of 56) in the dialysis group,” Dr. Shashar and colleagues report.

The median IgG level in the dialysis group was 2,900 AU/mL, which is significantly lower than the median of 7,401 AU/mL in the control group (P < .001), they report.

The investigators also observed a significant inverse correlation between older age and antibody levels in both groups.

The odds of being in the lower quartile were significantly higher for older individuals (odds ratio, 1.11 per year of age; P = .004) and for the dialysis group compared with the control group (OR, 2.7; P = .05).

Among the dialysis patients, older age and lower lymphocyte count were associated with antibody response in the lower quartile (OR, 1.22 per 1 year older; P = .03; and OR, 0.83 per 10-e3/mL-higher lymphocyte count; P = .05).

Among recipients older than 70 years, there was little difference in antibody response between the dialysis patients and the control group. Thus, age is clearly an important contributor to a robust humoral response, the authors observe.

For more than 90% of the patients receiving dialysis, the antibody response was well above 50 AU/mL, which was the cutoff for having a positive response.

Nevertheless, the authors suggest that their findings should prompt clinicians to consider either changing the dose or the schedule of COVID-19 vaccination for dialysis patients, as was done, for example, with the hepatitis B vaccine Engerix-B.

Dialysis patients now receive double doses of the hepatitis B vaccine, which is given in a four-series vaccine schedule rather than a three-series vaccine schedule, as is given to healthy individuals.

The authors also call for studies to assess the longevity of vaccine efficacy for dialysis patients and whether current vaccines are effective against variant strains among patients undergoing dialysis.
 

Some suggestion COVID-19 vaccines also elicit T-cell responses

Dr. Shirali said the news regarding the COVID-19 vaccine for dialysis patients is good, given the fact that such patients exhibit a poor response to the hepatitis B vaccine.

“There isn’t a large percentage of dialysis patients who mount a humoral response to the hepatitis B vaccine, even with the change in dosing that we use that is different than it is for the general population,” she told this news organization.

Dr. Shirali also noted that preliminary evidence suggests that COVID-19 vaccines elicit nonantibody and antibody T-cell responses and that such immunity is going to be just as important for protecting dialysis patients against COVID-19 as it is for protecting patients who are not receiving dialysis.

“Antibody responses are just one arm of vaccination,” she explained. “People can form memory T-cell responses with vaccination, and while this has not been well studied with COVID-19, there are preliminary data to suggest that T-cell responses are likely to be effective in the fight against COVID-19.” There is also the possibility that this type of response “may even be more durable than antibody responses,” she said.

The study received no funding. The authors, Dr. Blake and Dr. Shirali, have disclosed no relevant financial relationships.

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

Most patients who are receiving maintenance hemodialysis develop a good antibody response after being given two doses of the Pfizer-BioNTech COVID-19 vaccine, but their responses are still significantly lower than those of health care workers who do not have kidney disease, the first study of its kind shows.

“It is well known that patients on dialysis may have a reduced response to vaccination,” Ayelet Grupper, MD, of Tel Aviv Medical Center, and colleagues observe. Their study was published online April 6 in the Clinical Journal of the American Society of Nephrology.

“I believe our findings should encourage patients with kidney failure treated with dialysis to be vaccinated as soon as vaccination becomes available for them, while we as caregivers should explore ways to enhance its efficacy in our patients,” senior author Moshe Shashar, MD, noted in a statement from the American Society of Nephrology.

Asked to comment, Peter Blake, MD, professor of medicine, University of Western Ontario, London, pointed out that COVID-19 is very common among hemodialysis patients and that the likelihood of these patients dying from it is very high. Indeed, 1.5% of approximately 12,500 patients receiving dialysis in the province of Ontario have died of COVID-19 – “a horrifying statistic and one that only long-term care home residents can compare with,” he told this news organization.

In the Israeli study, almost all dialysis patients mounted a serologic response to the Pfizer-BioNTech vaccine, which is “good news” overall, Dr. Blake said.

Also commenting on the study, Anushree Shirali, MD, of Yale University, New Haven, Conn., said she was impressed by the fact that most of the dialysis patients in the study mounted at least some IgG response to vaccination, which she said was good “in and of itself,” because that is not always the case with other vaccines.
 

Study compared dialysis patients with health care workers

The Israeli study included 56 patients who were receiving maintenance hemodialysis and 95 health care workers, who served as control persons.

“All participants had been previously vaccinated with the [Pfizer-BioNTech] vaccine, with the recommended dosing interval of 21 days between the first and second doses,” the investigators note. Immunogenicity was assessed using a dedicated immunoassay to quantify the level of IgG antibodies from participants’ plasma.

A cutoff for a positive antibody response was greater than or equal to 50 arbitrary units per milliliter (AU/mL). “All subjects in the control group developed a positive antibody response (≥50 AU/mL) as compared with 96% (54 of 56) in the dialysis group,” Dr. Shashar and colleagues report.

The median IgG level in the dialysis group was 2,900 AU/mL, which is significantly lower than the median of 7,401 AU/mL in the control group (P < .001), they report.

The investigators also observed a significant inverse correlation between older age and antibody levels in both groups.

The odds of being in the lower quartile were significantly higher for older individuals (odds ratio, 1.11 per year of age; P = .004) and for the dialysis group compared with the control group (OR, 2.7; P = .05).

Among the dialysis patients, older age and lower lymphocyte count were associated with antibody response in the lower quartile (OR, 1.22 per 1 year older; P = .03; and OR, 0.83 per 10-e3/mL-higher lymphocyte count; P = .05).

Among recipients older than 70 years, there was little difference in antibody response between the dialysis patients and the control group. Thus, age is clearly an important contributor to a robust humoral response, the authors observe.

For more than 90% of the patients receiving dialysis, the antibody response was well above 50 AU/mL, which was the cutoff for having a positive response.

Nevertheless, the authors suggest that their findings should prompt clinicians to consider either changing the dose or the schedule of COVID-19 vaccination for dialysis patients, as was done, for example, with the hepatitis B vaccine Engerix-B.

Dialysis patients now receive double doses of the hepatitis B vaccine, which is given in a four-series vaccine schedule rather than a three-series vaccine schedule, as is given to healthy individuals.

The authors also call for studies to assess the longevity of vaccine efficacy for dialysis patients and whether current vaccines are effective against variant strains among patients undergoing dialysis.
 

Some suggestion COVID-19 vaccines also elicit T-cell responses

Dr. Shirali said the news regarding the COVID-19 vaccine for dialysis patients is good, given the fact that such patients exhibit a poor response to the hepatitis B vaccine.

“There isn’t a large percentage of dialysis patients who mount a humoral response to the hepatitis B vaccine, even with the change in dosing that we use that is different than it is for the general population,” she told this news organization.

Dr. Shirali also noted that preliminary evidence suggests that COVID-19 vaccines elicit nonantibody and antibody T-cell responses and that such immunity is going to be just as important for protecting dialysis patients against COVID-19 as it is for protecting patients who are not receiving dialysis.

“Antibody responses are just one arm of vaccination,” she explained. “People can form memory T-cell responses with vaccination, and while this has not been well studied with COVID-19, there are preliminary data to suggest that T-cell responses are likely to be effective in the fight against COVID-19.” There is also the possibility that this type of response “may even be more durable than antibody responses,” she said.

The study received no funding. The authors, Dr. Blake and Dr. Shirali, have disclosed no relevant financial relationships.

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

The development of unusual movements after COVID-19 vaccination may be a result of functional neurologic disorder rather than being a direct adverse effect of the vaccine, it has been suggested.

Writing in an article published online in JAMA Neurology on April 9, 2021, two neurologists and a psychiatrist report the recent circulation of videos on social media about major neurologic adverse events, including continuous movements of the trunk and limbs or walking difficulties after administration of the COVID-19 vaccine. Some of these videos have been viewed millions of times by the public, they noted.

While these videos may be unsubstantiated, and it is not definitively known if the COVID-19 vaccine was administered in these cases, it was reported in the news that at least one patient was told by their physician that the diagnosis was conversion disorder, also known as functional neurological disorder (FND), the authors noted.

In addition, the Functional Neurological Disorder Society released a statement in January 2021 pointing out that the conditions described in these videos are seemingly consistent with FND, they added.

“We thought it would be useful to explain more about what functional neurological disorder is, as many people are not familiar with it,” lead author David Kim, MD, said in an interview. “We wanted to provide some contextual information about the condition, as these reports may not necessarily mean the vaccine is unsafe.”

Dr. Kim, who is part of the division of cognitive behavioral neurology at Massachusetts General Hospital, Boston, explained that, in FND, physical symptoms can be brought about after events such as head injury, surgery, vaccination, other medical procedures, or life events such as loss of employment.

“Many different factors can bring these symptoms on, and while there are definitely cases associated with stressful events, it is not necessarily stress induced,” he said. “However, the event itself does not cause the condition, rather it is the reaction of the patient to the event.”

FND is now viewed as a true brain-based disorder, Dr. Kim noted. “While in the past it has been described as psychosomatic, we are now moving away from that terminology, toward the idea of a neurological disorder that affects function. It is a neuropsychiatric disorder on the borderline between neurology and psychiatry.”

The authors believed that some of these cases of unusual movements reported after COVID vaccination are likely to be FND.

“In these cases, it is not the substance in the vaccine that is causing the condition, but the common side effects that can occur after vaccination such as aches and chills bring the attention of the patient to their bodily functions and this reaction can become maladaptive, triggering FND,” Dr. Kim said.

“We believe that health care professionals should be more aware of FND at the current time. They need to know that the general public are aware that some people are experiencing movement disorders after COVID vaccination, and that this conversation is happening on social media,” he commented. “If they see patients with these symptoms, they could consider FND to be one possibility.”

The authors emphasized that, because they have not seen the individual patients, they cannot comment on any specific cases.

“But as some of these videos circulating can be consistent with the condition being FND, and especially with news reports indicating that at least one patient was given that diagnosis, we wanted to raise awareness of this condition among health professionals,” Dr. Kim added.  

He explained that, in the past, FND has been a diagnosis of exclusion but now it is diagnosed with a clinical history and physical examination, looking for appropriate rule-in signs. Ancillary testing such as neuroimaging, electrophysiological studies, and blood tests are often used to rule out other conditions.

“Neurologists have a lot of training in this condition, as it is the second most common reason for a patient to visit a neurologist after headache,” Dr. Kim noted.

It is managed with education, counseling, physical rehabilitation and cognitive behavioral therapy. “A key part of the therapeutic process is working with the patient to explain the diagnosis. If they understand the condition, they do better. Patients can learn distraction techniques to allow more fluid movements,” he reported.

“As neurologists, and health care professionals more broadly, we must explain transparently and nonjudgmentally the nature of FND, including that these symptoms are real but not the direct result of toxic vaccine effects,” the authors wrote.

“Transparency and effective communication are needed in our society more than ever, and a condition as prevalent and potentially debilitating as FND can no longer remain marginalized and in the shadows. Effective communication will help educate the public and reduce fears so that patients can make informed decisions for themselves on receiving the vaccine to reduce the risk of COVID-19,” they concluded.

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

The development of unusual movements after COVID-19 vaccination may be a result of functional neurologic disorder rather than being a direct adverse effect of the vaccine, it has been suggested.

Writing in an article published online in JAMA Neurology on April 9, 2021, two neurologists and a psychiatrist report the recent circulation of videos on social media about major neurologic adverse events, including continuous movements of the trunk and limbs or walking difficulties after administration of the COVID-19 vaccine. Some of these videos have been viewed millions of times by the public, they noted.

While these videos may be unsubstantiated, and it is not definitively known if the COVID-19 vaccine was administered in these cases, it was reported in the news that at least one patient was told by their physician that the diagnosis was conversion disorder, also known as functional neurological disorder (FND), the authors noted.

In addition, the Functional Neurological Disorder Society released a statement in January 2021 pointing out that the conditions described in these videos are seemingly consistent with FND, they added.

“We thought it would be useful to explain more about what functional neurological disorder is, as many people are not familiar with it,” lead author David Kim, MD, said in an interview. “We wanted to provide some contextual information about the condition, as these reports may not necessarily mean the vaccine is unsafe.”

Dr. Kim, who is part of the division of cognitive behavioral neurology at Massachusetts General Hospital, Boston, explained that, in FND, physical symptoms can be brought about after events such as head injury, surgery, vaccination, other medical procedures, or life events such as loss of employment.

“Many different factors can bring these symptoms on, and while there are definitely cases associated with stressful events, it is not necessarily stress induced,” he said. “However, the event itself does not cause the condition, rather it is the reaction of the patient to the event.”

FND is now viewed as a true brain-based disorder, Dr. Kim noted. “While in the past it has been described as psychosomatic, we are now moving away from that terminology, toward the idea of a neurological disorder that affects function. It is a neuropsychiatric disorder on the borderline between neurology and psychiatry.”

The authors believed that some of these cases of unusual movements reported after COVID vaccination are likely to be FND.

“In these cases, it is not the substance in the vaccine that is causing the condition, but the common side effects that can occur after vaccination such as aches and chills bring the attention of the patient to their bodily functions and this reaction can become maladaptive, triggering FND,” Dr. Kim said.

“We believe that health care professionals should be more aware of FND at the current time. They need to know that the general public are aware that some people are experiencing movement disorders after COVID vaccination, and that this conversation is happening on social media,” he commented. “If they see patients with these symptoms, they could consider FND to be one possibility.”

The authors emphasized that, because they have not seen the individual patients, they cannot comment on any specific cases.

“But as some of these videos circulating can be consistent with the condition being FND, and especially with news reports indicating that at least one patient was given that diagnosis, we wanted to raise awareness of this condition among health professionals,” Dr. Kim added.  

He explained that, in the past, FND has been a diagnosis of exclusion but now it is diagnosed with a clinical history and physical examination, looking for appropriate rule-in signs. Ancillary testing such as neuroimaging, electrophysiological studies, and blood tests are often used to rule out other conditions.

“Neurologists have a lot of training in this condition, as it is the second most common reason for a patient to visit a neurologist after headache,” Dr. Kim noted.

It is managed with education, counseling, physical rehabilitation and cognitive behavioral therapy. “A key part of the therapeutic process is working with the patient to explain the diagnosis. If they understand the condition, they do better. Patients can learn distraction techniques to allow more fluid movements,” he reported.

“As neurologists, and health care professionals more broadly, we must explain transparently and nonjudgmentally the nature of FND, including that these symptoms are real but not the direct result of toxic vaccine effects,” the authors wrote.

“Transparency and effective communication are needed in our society more than ever, and a condition as prevalent and potentially debilitating as FND can no longer remain marginalized and in the shadows. Effective communication will help educate the public and reduce fears so that patients can make informed decisions for themselves on receiving the vaccine to reduce the risk of COVID-19,” they concluded.

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

The development of unusual movements after COVID-19 vaccination may be a result of functional neurologic disorder rather than being a direct adverse effect of the vaccine, it has been suggested.

Writing in an article published online in JAMA Neurology on April 9, 2021, two neurologists and a psychiatrist report the recent circulation of videos on social media about major neurologic adverse events, including continuous movements of the trunk and limbs or walking difficulties after administration of the COVID-19 vaccine. Some of these videos have been viewed millions of times by the public, they noted.

While these videos may be unsubstantiated, and it is not definitively known if the COVID-19 vaccine was administered in these cases, it was reported in the news that at least one patient was told by their physician that the diagnosis was conversion disorder, also known as functional neurological disorder (FND), the authors noted.

In addition, the Functional Neurological Disorder Society released a statement in January 2021 pointing out that the conditions described in these videos are seemingly consistent with FND, they added.

“We thought it would be useful to explain more about what functional neurological disorder is, as many people are not familiar with it,” lead author David Kim, MD, said in an interview. “We wanted to provide some contextual information about the condition, as these reports may not necessarily mean the vaccine is unsafe.”

Dr. Kim, who is part of the division of cognitive behavioral neurology at Massachusetts General Hospital, Boston, explained that, in FND, physical symptoms can be brought about after events such as head injury, surgery, vaccination, other medical procedures, or life events such as loss of employment.

“Many different factors can bring these symptoms on, and while there are definitely cases associated with stressful events, it is not necessarily stress induced,” he said. “However, the event itself does not cause the condition, rather it is the reaction of the patient to the event.”

FND is now viewed as a true brain-based disorder, Dr. Kim noted. “While in the past it has been described as psychosomatic, we are now moving away from that terminology, toward the idea of a neurological disorder that affects function. It is a neuropsychiatric disorder on the borderline between neurology and psychiatry.”

The authors believed that some of these cases of unusual movements reported after COVID vaccination are likely to be FND.

“In these cases, it is not the substance in the vaccine that is causing the condition, but the common side effects that can occur after vaccination such as aches and chills bring the attention of the patient to their bodily functions and this reaction can become maladaptive, triggering FND,” Dr. Kim said.

“We believe that health care professionals should be more aware of FND at the current time. They need to know that the general public are aware that some people are experiencing movement disorders after COVID vaccination, and that this conversation is happening on social media,” he commented. “If they see patients with these symptoms, they could consider FND to be one possibility.”

The authors emphasized that, because they have not seen the individual patients, they cannot comment on any specific cases.

“But as some of these videos circulating can be consistent with the condition being FND, and especially with news reports indicating that at least one patient was given that diagnosis, we wanted to raise awareness of this condition among health professionals,” Dr. Kim added.  

He explained that, in the past, FND has been a diagnosis of exclusion but now it is diagnosed with a clinical history and physical examination, looking for appropriate rule-in signs. Ancillary testing such as neuroimaging, electrophysiological studies, and blood tests are often used to rule out other conditions.

“Neurologists have a lot of training in this condition, as it is the second most common reason for a patient to visit a neurologist after headache,” Dr. Kim noted.

It is managed with education, counseling, physical rehabilitation and cognitive behavioral therapy. “A key part of the therapeutic process is working with the patient to explain the diagnosis. If they understand the condition, they do better. Patients can learn distraction techniques to allow more fluid movements,” he reported.

“As neurologists, and health care professionals more broadly, we must explain transparently and nonjudgmentally the nature of FND, including that these symptoms are real but not the direct result of toxic vaccine effects,” the authors wrote.

“Transparency and effective communication are needed in our society more than ever, and a condition as prevalent and potentially debilitating as FND can no longer remain marginalized and in the shadows. Effective communication will help educate the public and reduce fears so that patients can make informed decisions for themselves on receiving the vaccine to reduce the risk of COVID-19,” they concluded.

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

Patients with mild to moderate systemic lupus erythematosus (SLE) disease activity without any past history of organ damage may still progress to develop damage, particularly renal and cardiovascular disease, or death, in a relatively short amount of follow-up time, new research suggests.

The study, published in Lupus Science & Medicine, also showed that use of hydroxychloroquine lowered the risk of death and renal damage, whereas use of NSAIDs or any antihypertensives increased risk for cardiovascular damage.

“The impact of irreversible organ system damage in the prognosis of SLE remains a major concern because patients who develop damage are more likely to accrue additional damage and die,” wrote Deanna Hill, PhD, of GlaxoSmithKline, Collegeville, Pa., and coauthors, including Michelle Petri, MD, of Johns Hopkins University, Baltimore.

The researchers followed 1,168 adult patients with SLE from the Johns Hopkins Lupus Cohort, most of whom were women, 55% of whom were White and 39% of whom were Black. They divided the follow-up period into three parts: first year after enrollment into the cohort as background, second year as observation period, and the remainder of follow-up time until damage occurred, death, or end of available data.

At baseline, 55% of patients had mild to moderate disease, defined as an adjusted mean SELENA-SLEDAI (Safety of Estrogens in Lupus Erythematosus National Assessment SLE Disease Activity Index) score of less than 3. Patients had a median adjusted mean SELENA-SLEDAI score of 3 in the first year, which dropped to 2 in the observation period and remained there during the rest of follow-up.

Eight percent of patients died during the follow-up period. Each one-unit mean increase in SELENA-SLEDAI score during the 1-year observation period was associated with a significant 22% increase in the subsequent risk of death during the subsequent follow-up period (95% confidence interval, 1.13-1.32; P < .001).

Three-quarters of patients (n = 888) had no history of damage at the start of the follow-up period, but 39% of these patients had developed damage by the end of follow-up. Among patients without prior damage, a single-unit increase in disease activity score was also associated with a 9% increase in the risk of accruing organ damage (95% CI, 1.04-1.15; P < .001) after adjustment for confounding factors.

While only 3% of patients – most of whom were women – developed renal damage during the follow-up period, a one-unit increase in disease activity score was associated with a 24% increase in the risk of renal damage (95% CI, 1.08-1.42, P = .003).

The researchers found that 7% of patients developed cardiovascular damage during the follow-up period, and each one-unit increase in disease activity score was associated with a 17% increase in the risk of cardiovascular damage (95% CI, 1.07-1.29; P < .001).

“The findings in this analysis corroborate the influence of disease activity for renal and cardiovascular damage accrual and death and also extend the findings to patients with SLE and mild to moderate disease activity,” the authors wrote.

Impact of treatment

Researchers also examined the effect of treatments, and found that patients treated with hydroxychloroquine during the 1-year observation period had a 54% lower risk of subsequent death (95% CI, 0.29-0.72; P < .05) and a 70% lower risk of renal damage (95% CI, 0.13-0.68, P < .05). However, patients prescribed NSAIDs had a 66% higher risk of cardiovascular damage, while those who used any antihypertensive had an 81% higher risk of cardiovascular damage.

“This may suggest that the known cardiovascular risk of NSAIDs in the general population is also applicable to patients with SLE and highlights the importance of assessing cardiovascular risk in this patient population,” the authors wrote.

Smoking affected the risk of death: Smokers were 74% more likely to die during the follow-up period than were nonsmokers.

There were no significant differences between different ethnicities in the study. While White patients generally had lower disease activity overall, there was no significant differences in the risk of death or organ damage with ethnicity.

The Hopkins Lupus Cohort is supported by the National Institutes of Health, and the study was funded by GlaxoSmithKline. Three authors were paid employees of GlaxoSmithKline and two were paid consultants or contractors.

Patients with mild to moderate systemic lupus erythematosus (SLE) disease activity without any past history of organ damage may still progress to develop damage, particularly renal and cardiovascular disease, or death, in a relatively short amount of follow-up time, new research suggests.

The study, published in Lupus Science & Medicine, also showed that use of hydroxychloroquine lowered the risk of death and renal damage, whereas use of NSAIDs or any antihypertensives increased risk for cardiovascular damage.

“The impact of irreversible organ system damage in the prognosis of SLE remains a major concern because patients who develop damage are more likely to accrue additional damage and die,” wrote Deanna Hill, PhD, of GlaxoSmithKline, Collegeville, Pa., and coauthors, including Michelle Petri, MD, of Johns Hopkins University, Baltimore.

The researchers followed 1,168 adult patients with SLE from the Johns Hopkins Lupus Cohort, most of whom were women, 55% of whom were White and 39% of whom were Black. They divided the follow-up period into three parts: first year after enrollment into the cohort as background, second year as observation period, and the remainder of follow-up time until damage occurred, death, or end of available data.

At baseline, 55% of patients had mild to moderate disease, defined as an adjusted mean SELENA-SLEDAI (Safety of Estrogens in Lupus Erythematosus National Assessment SLE Disease Activity Index) score of less than 3. Patients had a median adjusted mean SELENA-SLEDAI score of 3 in the first year, which dropped to 2 in the observation period and remained there during the rest of follow-up.

Eight percent of patients died during the follow-up period. Each one-unit mean increase in SELENA-SLEDAI score during the 1-year observation period was associated with a significant 22% increase in the subsequent risk of death during the subsequent follow-up period (95% confidence interval, 1.13-1.32; P < .001).

Three-quarters of patients (n = 888) had no history of damage at the start of the follow-up period, but 39% of these patients had developed damage by the end of follow-up. Among patients without prior damage, a single-unit increase in disease activity score was also associated with a 9% increase in the risk of accruing organ damage (95% CI, 1.04-1.15; P < .001) after adjustment for confounding factors.

While only 3% of patients – most of whom were women – developed renal damage during the follow-up period, a one-unit increase in disease activity score was associated with a 24% increase in the risk of renal damage (95% CI, 1.08-1.42, P = .003).

The researchers found that 7% of patients developed cardiovascular damage during the follow-up period, and each one-unit increase in disease activity score was associated with a 17% increase in the risk of cardiovascular damage (95% CI, 1.07-1.29; P < .001).

“The findings in this analysis corroborate the influence of disease activity for renal and cardiovascular damage accrual and death and also extend the findings to patients with SLE and mild to moderate disease activity,” the authors wrote.

Impact of treatment

Researchers also examined the effect of treatments, and found that patients treated with hydroxychloroquine during the 1-year observation period had a 54% lower risk of subsequent death (95% CI, 0.29-0.72; P < .05) and a 70% lower risk of renal damage (95% CI, 0.13-0.68, P < .05). However, patients prescribed NSAIDs had a 66% higher risk of cardiovascular damage, while those who used any antihypertensive had an 81% higher risk of cardiovascular damage.

“This may suggest that the known cardiovascular risk of NSAIDs in the general population is also applicable to patients with SLE and highlights the importance of assessing cardiovascular risk in this patient population,” the authors wrote.

Smoking affected the risk of death: Smokers were 74% more likely to die during the follow-up period than were nonsmokers.

There were no significant differences between different ethnicities in the study. While White patients generally had lower disease activity overall, there was no significant differences in the risk of death or organ damage with ethnicity.

The Hopkins Lupus Cohort is supported by the National Institutes of Health, and the study was funded by GlaxoSmithKline. Three authors were paid employees of GlaxoSmithKline and two were paid consultants or contractors.

Patients with mild to moderate systemic lupus erythematosus (SLE) disease activity without any past history of organ damage may still progress to develop damage, particularly renal and cardiovascular disease, or death, in a relatively short amount of follow-up time, new research suggests.

The study, published in Lupus Science & Medicine, also showed that use of hydroxychloroquine lowered the risk of death and renal damage, whereas use of NSAIDs or any antihypertensives increased risk for cardiovascular damage.

“The impact of irreversible organ system damage in the prognosis of SLE remains a major concern because patients who develop damage are more likely to accrue additional damage and die,” wrote Deanna Hill, PhD, of GlaxoSmithKline, Collegeville, Pa., and coauthors, including Michelle Petri, MD, of Johns Hopkins University, Baltimore.

The researchers followed 1,168 adult patients with SLE from the Johns Hopkins Lupus Cohort, most of whom were women, 55% of whom were White and 39% of whom were Black. They divided the follow-up period into three parts: first year after enrollment into the cohort as background, second year as observation period, and the remainder of follow-up time until damage occurred, death, or end of available data.

At baseline, 55% of patients had mild to moderate disease, defined as an adjusted mean SELENA-SLEDAI (Safety of Estrogens in Lupus Erythematosus National Assessment SLE Disease Activity Index) score of less than 3. Patients had a median adjusted mean SELENA-SLEDAI score of 3 in the first year, which dropped to 2 in the observation period and remained there during the rest of follow-up.

Eight percent of patients died during the follow-up period. Each one-unit mean increase in SELENA-SLEDAI score during the 1-year observation period was associated with a significant 22% increase in the subsequent risk of death during the subsequent follow-up period (95% confidence interval, 1.13-1.32; P < .001).

Three-quarters of patients (n = 888) had no history of damage at the start of the follow-up period, but 39% of these patients had developed damage by the end of follow-up. Among patients without prior damage, a single-unit increase in disease activity score was also associated with a 9% increase in the risk of accruing organ damage (95% CI, 1.04-1.15; P < .001) after adjustment for confounding factors.

While only 3% of patients – most of whom were women – developed renal damage during the follow-up period, a one-unit increase in disease activity score was associated with a 24% increase in the risk of renal damage (95% CI, 1.08-1.42, P = .003).

The researchers found that 7% of patients developed cardiovascular damage during the follow-up period, and each one-unit increase in disease activity score was associated with a 17% increase in the risk of cardiovascular damage (95% CI, 1.07-1.29; P < .001).

“The findings in this analysis corroborate the influence of disease activity for renal and cardiovascular damage accrual and death and also extend the findings to patients with SLE and mild to moderate disease activity,” the authors wrote.

Impact of treatment

Researchers also examined the effect of treatments, and found that patients treated with hydroxychloroquine during the 1-year observation period had a 54% lower risk of subsequent death (95% CI, 0.29-0.72; P < .05) and a 70% lower risk of renal damage (95% CI, 0.13-0.68, P < .05). However, patients prescribed NSAIDs had a 66% higher risk of cardiovascular damage, while those who used any antihypertensive had an 81% higher risk of cardiovascular damage.

“This may suggest that the known cardiovascular risk of NSAIDs in the general population is also applicable to patients with SLE and highlights the importance of assessing cardiovascular risk in this patient population,” the authors wrote.

Smoking affected the risk of death: Smokers were 74% more likely to die during the follow-up period than were nonsmokers.

There were no significant differences between different ethnicities in the study. While White patients generally had lower disease activity overall, there was no significant differences in the risk of death or organ damage with ethnicity.

The Hopkins Lupus Cohort is supported by the National Institutes of Health, and the study was funded by GlaxoSmithKline. Three authors were paid employees of GlaxoSmithKline and two were paid consultants or contractors.

The recommended pause in use of the Johnson & Johnson COVID-19 vaccine will last at least another week after a Centers for Disease Control and Prevention advisory committee on April 14 decided not to take action.

Johnson &amp; Johnson

The Advisory Committee on Immunization Practices decided there was not adequate information to change again recommend use of the Johnson & Johnson vaccine.

The committee’s decision comes the day after the CDC and Food and Drug Administration recommended that J&J injections be paused after reports of rare, but serious types of blood clots in six patients among the 6.8 million people who had received the J&J vaccine in the United States.

A member of the committee, Beth Bell, MD, said: “I do not want to be sending a message that there is some huge concern here on a different order of magnitude than any other vaccine safety signals that we evaluate. And I don’t want to send a message that there is something fundamentally wrong with the vaccine because that also I don’t agree with.”

At the end of the 4-hour meeting, ACIP members decided to call a meeting in 1 or 2 weeks and evaluate more safety data, specifically reports of people who have received the J&J vaccine in the past 2 weeks.

Some, however, pointed out that delaying a decision could have substantial consequences as well in terms of unused vaccine doses and public confidence.

Committee member Camiile Kotton, MD, described the pause as “devastating.”

“Putting this vaccine on pause for those of us that are frontline health care workers has really been devastating,” she said. “I agree in general that we don’t have enough data to make a decision at this time but we were planning on using this vaccine in the state of Massachusetts for people who were homebound and otherwise not able to get a vaccine. We were planning on using it for our vulnerable inpatient population often with many comorbidities and at high risk for disease but haven’t been able to get vaccinated otherwise.”

Pausing the one-and-done vaccine that doesn’t have the significant refrigeration requirements of the others “is a significant loss,” she said.
 

What is known, not known

Sara Oliver, MD, who leads the COVID-19 Vaccines ACIP Work Group, summarized what is known and unknown about the blood clots.

Among the six cases of cerebral venous sinus thrombosis reported to the Vaccine Adverse Event Reporting System after the J&J shot, all were women aged 18-48 years and all developed the clots 6-13 days after receiving the vaccine.

No cases of these clots have been reported from either the Pfizer or Moderna shots, she noted.

In the United States, the two mRNA vaccine alternatives – the Moderna and Pfizer vaccines – are available “and based on current projections supply of both vaccines are expected to be relatively stable in the near future,” she said.

She said 14 million doses of Pfizer and Moderna are expected each week in the United States and J&J vaccines makes up less than 5% of vaccines administered in the country.

Approximately 13 million J&J doses are available to order or are already at administration sites, she said.

But much more is unknown, she said.

“There may be more cases identified in the coming days to weeks,” Dr. Oliver said, referring back to the average time from vaccination to symptom onset.

Scott Ratzan, MD, editor-in-chief of the Journal of Health Communication: International Perspectives and executive director of Business Partners to CONVINCE (BP2C), a global network of employers that promotes COVID-19 vaccination among employees, suppliers, and customers, applauded ACIP’s delay on making a decision.

Dr. Ratzan, who watched the deliberations online, said in an interview the decision “shows an admirable abundance of caution in the distribution of COVID-19 vaccines.”

“Unfortunately,” he said, “the pause also worsens the existing and pervasive vaccine hesitancy issue.

“We need a rational strategy regarding who should or should not get the J&J/Janssen vaccine since these rare adverse events appear to affect a particular group of people, females aged 18-48. It is essential that we build vaccine confidence and retain the option of using this vaccine for people who are not in this risk group.”

He pointed out there are safety red flags with the Pfizer and Moderna COVID-19 vaccines.

“We should feel reassured about the process of ensuring vaccine safety as the FDA and CDC have quickly addressed risk and shared the data transparently of the J&J vaccine and taken appropriate action,” he said.

ACIP’s executive secretary, Amanda Cohn, MD, said the date for the next meeting would be set by April 16.

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

The recommended pause in use of the Johnson & Johnson COVID-19 vaccine will last at least another week after a Centers for Disease Control and Prevention advisory committee on April 14 decided not to take action.

Johnson &amp; Johnson

The Advisory Committee on Immunization Practices decided there was not adequate information to change again recommend use of the Johnson & Johnson vaccine.

The committee’s decision comes the day after the CDC and Food and Drug Administration recommended that J&J injections be paused after reports of rare, but serious types of blood clots in six patients among the 6.8 million people who had received the J&J vaccine in the United States.

A member of the committee, Beth Bell, MD, said: “I do not want to be sending a message that there is some huge concern here on a different order of magnitude than any other vaccine safety signals that we evaluate. And I don’t want to send a message that there is something fundamentally wrong with the vaccine because that also I don’t agree with.”

At the end of the 4-hour meeting, ACIP members decided to call a meeting in 1 or 2 weeks and evaluate more safety data, specifically reports of people who have received the J&J vaccine in the past 2 weeks.

Some, however, pointed out that delaying a decision could have substantial consequences as well in terms of unused vaccine doses and public confidence.

Committee member Camiile Kotton, MD, described the pause as “devastating.”

“Putting this vaccine on pause for those of us that are frontline health care workers has really been devastating,” she said. “I agree in general that we don’t have enough data to make a decision at this time but we were planning on using this vaccine in the state of Massachusetts for people who were homebound and otherwise not able to get a vaccine. We were planning on using it for our vulnerable inpatient population often with many comorbidities and at high risk for disease but haven’t been able to get vaccinated otherwise.”

Pausing the one-and-done vaccine that doesn’t have the significant refrigeration requirements of the others “is a significant loss,” she said.
 

What is known, not known

Sara Oliver, MD, who leads the COVID-19 Vaccines ACIP Work Group, summarized what is known and unknown about the blood clots.

Among the six cases of cerebral venous sinus thrombosis reported to the Vaccine Adverse Event Reporting System after the J&J shot, all were women aged 18-48 years and all developed the clots 6-13 days after receiving the vaccine.

No cases of these clots have been reported from either the Pfizer or Moderna shots, she noted.

In the United States, the two mRNA vaccine alternatives – the Moderna and Pfizer vaccines – are available “and based on current projections supply of both vaccines are expected to be relatively stable in the near future,” she said.

She said 14 million doses of Pfizer and Moderna are expected each week in the United States and J&J vaccines makes up less than 5% of vaccines administered in the country.

Approximately 13 million J&J doses are available to order or are already at administration sites, she said.

But much more is unknown, she said.

“There may be more cases identified in the coming days to weeks,” Dr. Oliver said, referring back to the average time from vaccination to symptom onset.

Scott Ratzan, MD, editor-in-chief of the Journal of Health Communication: International Perspectives and executive director of Business Partners to CONVINCE (BP2C), a global network of employers that promotes COVID-19 vaccination among employees, suppliers, and customers, applauded ACIP’s delay on making a decision.

Dr. Ratzan, who watched the deliberations online, said in an interview the decision “shows an admirable abundance of caution in the distribution of COVID-19 vaccines.”

“Unfortunately,” he said, “the pause also worsens the existing and pervasive vaccine hesitancy issue.

“We need a rational strategy regarding who should or should not get the J&J/Janssen vaccine since these rare adverse events appear to affect a particular group of people, females aged 18-48. It is essential that we build vaccine confidence and retain the option of using this vaccine for people who are not in this risk group.”

He pointed out there are safety red flags with the Pfizer and Moderna COVID-19 vaccines.

“We should feel reassured about the process of ensuring vaccine safety as the FDA and CDC have quickly addressed risk and shared the data transparently of the J&J vaccine and taken appropriate action,” he said.

ACIP’s executive secretary, Amanda Cohn, MD, said the date for the next meeting would be set by April 16.

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

The recommended pause in use of the Johnson & Johnson COVID-19 vaccine will last at least another week after a Centers for Disease Control and Prevention advisory committee on April 14 decided not to take action.

Johnson &amp; Johnson

The Advisory Committee on Immunization Practices decided there was not adequate information to change again recommend use of the Johnson & Johnson vaccine.

The committee’s decision comes the day after the CDC and Food and Drug Administration recommended that J&J injections be paused after reports of rare, but serious types of blood clots in six patients among the 6.8 million people who had received the J&J vaccine in the United States.

A member of the committee, Beth Bell, MD, said: “I do not want to be sending a message that there is some huge concern here on a different order of magnitude than any other vaccine safety signals that we evaluate. And I don’t want to send a message that there is something fundamentally wrong with the vaccine because that also I don’t agree with.”

At the end of the 4-hour meeting, ACIP members decided to call a meeting in 1 or 2 weeks and evaluate more safety data, specifically reports of people who have received the J&J vaccine in the past 2 weeks.

Some, however, pointed out that delaying a decision could have substantial consequences as well in terms of unused vaccine doses and public confidence.

Committee member Camiile Kotton, MD, described the pause as “devastating.”

“Putting this vaccine on pause for those of us that are frontline health care workers has really been devastating,” she said. “I agree in general that we don’t have enough data to make a decision at this time but we were planning on using this vaccine in the state of Massachusetts for people who were homebound and otherwise not able to get a vaccine. We were planning on using it for our vulnerable inpatient population often with many comorbidities and at high risk for disease but haven’t been able to get vaccinated otherwise.”

Pausing the one-and-done vaccine that doesn’t have the significant refrigeration requirements of the others “is a significant loss,” she said.
 

What is known, not known

Sara Oliver, MD, who leads the COVID-19 Vaccines ACIP Work Group, summarized what is known and unknown about the blood clots.

Among the six cases of cerebral venous sinus thrombosis reported to the Vaccine Adverse Event Reporting System after the J&J shot, all were women aged 18-48 years and all developed the clots 6-13 days after receiving the vaccine.

No cases of these clots have been reported from either the Pfizer or Moderna shots, she noted.

In the United States, the two mRNA vaccine alternatives – the Moderna and Pfizer vaccines – are available “and based on current projections supply of both vaccines are expected to be relatively stable in the near future,” she said.

She said 14 million doses of Pfizer and Moderna are expected each week in the United States and J&J vaccines makes up less than 5% of vaccines administered in the country.

Approximately 13 million J&J doses are available to order or are already at administration sites, she said.

But much more is unknown, she said.

“There may be more cases identified in the coming days to weeks,” Dr. Oliver said, referring back to the average time from vaccination to symptom onset.

Scott Ratzan, MD, editor-in-chief of the Journal of Health Communication: International Perspectives and executive director of Business Partners to CONVINCE (BP2C), a global network of employers that promotes COVID-19 vaccination among employees, suppliers, and customers, applauded ACIP’s delay on making a decision.

Dr. Ratzan, who watched the deliberations online, said in an interview the decision “shows an admirable abundance of caution in the distribution of COVID-19 vaccines.”

“Unfortunately,” he said, “the pause also worsens the existing and pervasive vaccine hesitancy issue.

“We need a rational strategy regarding who should or should not get the J&J/Janssen vaccine since these rare adverse events appear to affect a particular group of people, females aged 18-48. It is essential that we build vaccine confidence and retain the option of using this vaccine for people who are not in this risk group.”

He pointed out there are safety red flags with the Pfizer and Moderna COVID-19 vaccines.

“We should feel reassured about the process of ensuring vaccine safety as the FDA and CDC have quickly addressed risk and shared the data transparently of the J&J vaccine and taken appropriate action,” he said.

ACIP’s executive secretary, Amanda Cohn, MD, said the date for the next meeting would be set by April 16.

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

An advisory committee to the Centers for Disease Control and Prevention is addressing the safety of the Johnson & Johnson COVID-19 vaccine on April 14, 2021, after the CDC and Food and Drug Administration recommended that states hold off on using it pending a detailed review of six cases of the same kind of rare but serious event – a blood clot in the vessels that drain blood from the brain combined with a large drop in platelets, which increases the risk for bleeding.

This combination can lead to severe strokes that can lead to brain damage or death. Among the six cases reported, which came to light over the past 3 weeks, one person died, according to the CDC. All six were women and ranged in age from 18 to 48 years.

According to a report from the Vaccine Adverse Event Reporting System (VAERS), which is maintained by the Department of Health & Human Services, the woman who died was 45. She developed a gradually worsening headache about a week after receiving the Johnson & Johnson vaccine.

On March 17, the day she came to the hospital, she was dry heaving. Her headache had suddenly gotten much worse, and the left side of her body was weak, which are signs of a stroke. A CT scan revealed both bleeding in her brain and a clot in her cortical vein. She died the following day.

In addition to VAERS, which accepts reports from anyone, the CDC and FDA are monitoring at least eight other safety systems maintained by hospitals, research centers, long-term care facilities, and insurance companies for signs of trouble with the vaccines. VAERS data is searchable and open to the public. Most of these systems are not publicly available to protect patient privacy. It’s unclear which systems detected the six cases cited by federal regulators.

“These are very serious and potentially fatal problems occurring in a healthy young adult. It’s serious and we need to get to the bottom of it,” said Ed Belongia, MD, director of the Center for Clinical Epidemiology and Population Health at the Marshfield (Wis.) Clinic Research Institute. Dr. Belongia leads a research team that helps the CDC monitor vaccine safety and effectiveness. 

“Safety is always the highest priority, and I think what we’ve seen here in the past 24 hours is our vaccine safety monitoring system is working,” he said.

Others agree. “I think what CDC and FDA have detected is a rare, but likely real adverse event associated with this vaccine,” said Paul Offit, MD, director of vaccine education at Children’s Hospital of Philadelphia.

Although much is still unknown about these events, they follow a similar pattern of blood clots reported with the AstraZeneca vaccine in Europe. That vaccine is now sold under the brand name Vaxzevria. 

This has experts questioning whether all vaccines of this type may cause these rare clots.

“I think it’s likely a class effect,” said Dr. Offit, who was a member of the FDA advisory committee that reviewed clinical trial data on the J&J vaccine before it was authorized for use.
 

Adenovirus vaccines scrutinized

Both the Johnson & Johnson and Vaxzevria vaccines use an adenovirus to ferry genetic instructions for making the coronaviruses spike protein into our cells.

Adenoviruses are common, relatively simple viruses that normally cause mild cold or flu symptoms. The ones used in the vaccine are disabled so they can’t make us sick. They’re more like Trojan horses. 

Once inside our cells, they release the DNA instructions they carry to make the spike protein of the new coronavirus. Those cells then crank out copies of the spike protein, which then get displayed on the outer surface of the cell membrane where they are recognized by the immune system. 

The immune system then makes antibodies and other defenses against the spike so that, when the real coronavirus comes along, our bodies are ready to fight the infection.

There’s no question the vaccine works. In clinical trials, the Johnson & Johnson vaccine was 66% percent effective at preventing against moderate to severe COVID-19 infection, and none of the patients who got COVID-19 after vaccination had to be admitted to the hospital or died.

The idea behind using adenoviruses in vaccines isn’t a new one. In a kind of fight-fire-with-fire approach, the idea is to use a virus, which is good at infecting us, to fight a different kind of virus.

Researchers have been working on the concept for about 10 years, but the COVID-19 vaccines that use this technology are some of the first adenovirus-vector vaccines deployed in humans. 

Only one other adenovirus vaccine, for Ebola, has been approved for use in humans. It was approved in Europe last year. Before the Johnson & Johnson vaccine, no other adenovirus vector has been available for use in humans in the United States.

There are six adenovirus-vector vaccines for COVID-19. In addition to AstraZeneca and Johnson & Johnson, there’s the Russian-developed vaccine Sputnik V, along with CanSino from China, and the Covishield vaccine in India.

Adenovirus vaccines are more stable than the mRNA vaccines. That makes them easier to store and transport. 

But they have a significant downside, too. Because adenoviruses infect humans out in the world, we already make antibodies against them. So there’s always a danger that our immune systems might recognize and react to the vaccine, rendering it ineffective. For that reason, scientists try to carefully select the adenovirus vectors, or carriers, they use.

The two vaccines under investigation for blood clots are slightly different. The Johnson & Johnson vaccine uses the vector AD26, because most of the population lacks preexisting immunity to it. Vaxzevria uses an adenovirus that infects chimpanzees, called ChAdOx1. 

Vaxzevria has been widely used in Europe but has not yet been authorized in the United States.

On April 7, the European Medicines Agency, Europe’s counterpart to the FDA, ruled that unusual blood clots with low blood platelets should be listed as rare side effects on the Vaxzevria vaccine.

The decision came after reviewing 62 cases of cerebral venous sinus thrombosis (CVST) linked to the vaccine and 25 cases of another rare type of clot, called a splanchnic vein thrombosis. Splanchnic veins drain blood from the major organs in the digestive system, including the stomach, liver, and intestines; 18 of those events were fatal.

The reports were culled from reporting in Europe and the United Kingdom, where around 25 million people have received the Vaxzevria vaccine, making these clots exceptionally rare, but serious.

So far, six cases of CVST have been reported in the United States, after more than 7 million doses of the Johnson & Johnson vaccines have been administered.

A key question for U.S. regulators will be the background rate for these types of rare combinations of clots and deplenished platelets. The background rate is the number of events that would be expected to occur naturally in a population of unvaccinated people. On a press call on April 13, Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, was asked about the frequency of this dangerous combination. He said the combination of low platelets and clots was so rare that it was hard to pinpoint, but might be somewhere between 2 and 14 cases per million people over the course of a year.

The first Johnson & Johnson doses were given in early March. That means the six cases came to light within the first few weeks of use of the vaccine in the United States, a very short amount of time.

“These were six cases per million people for 2 weeks, which is the same thing as 25 million per year, so it’s clearly above the background rate,” Dr. Offit said.
 

Studies suggest possible mechanism

On April 9, the New England Journal of Medicine published a detailed evaluation of the 11 patients in Germany and Austria who developed the rare clots after their Vaxzevria vaccines.

The study detected rare antibodies to a signaling protein called platelet factor 4, which helps to coordinate clot formation.

These same type of antibodies form in some people given the blood thinning drug heparin. In those reactions, which are also exceptionally rare, the same type of syndrome develops, leading to large, devastating clots that consume circulating platelets.

It’s not yet clear whether people who develop reactions to the vaccines already have some platelet factor 4 antibodies before they are vaccinated, or whether the vaccines somehow spur the body to make these antibodies, which then launch a kind of autoimmune attack.

The researchers on the paper gave the syndrome a name, vaccine-induced thrombotic thrombocytopenia (VITT).

It’s also not clear why more cases seem to be in women than in men. Andrew Eisenberger, MD, an associate professor of hematology and oncology at Columbia University, New York, said the most common causes of cerebral venous sinus thrombosis have to do with conditions that raise estrogen levels, like pregnancy and hormonal contraception.

“Estrogen naturally leads to changes in several clotting proteins in the blood that may predispose to abnormal blood clotting in a few different sites in the body,” he said. “The clotting changes we are encountering with some of COVID-19 vaccines are likely to be synergistic with the effects of estrogen on the blood.”

No matter the cause, the CDC on April 13 alerted doctors to keep a high index of suspicion for VITT in patients who have received the Johnson & Johnson vaccination within the last 2 weeks. In those patients, the usual course of treatment with blood thinning drugs like heparin may be harmful.

Symptoms to watch for include severe headache or backache, new neurologic symptoms, severe abdominal pain, shortness of breath, leg swelling, tiny red spots on the skin, or easy bruising. 
 

Grappling with evidence

The CDC’s Advisory Committee on Immunization Practices will meet today in an emergency session to review the cases and see if any changes are needed to use of the J&J vaccine in the United States.

Last week, for example, the United Kingdom restricted the use of the AstraZeneca vaccine in people aged younger than 30 years, saying the risks and benefits of vaccination are “more finely balanced” for this age group.

With cases of COVID-19 rising again in the United States, and the Johnson & Johnson vaccine currently the most convenient form of protection against the virus, the committee will have to weigh the risks of that infection against the risk of rare clots caused by vaccination.

They will also likely have to rule out whether any of the cases had COVID. At least one study has reported CVST clots in three patients with confirmed COVID infections. In Europe, COVID infection did not seem to play a role in the formation of the clots with low platelets.

Hilda Bastian, PhD, a clinical trials expert who cofounded the Cochrane Collaboration, said it won’t be an easy task. Much will depend on how certain the committee members feel they know about all the events linked to the vaccine.

“That’s the really, really hard issue from my point of view for them right this moment. Have we missed any? Or how many are we likely to have missed?” asked Dr. Bastian, who lives in Australia.

“In a country that size with that fragmented [of] a health care system, how sure can you be that you know them all? That’s going to be a really difficult situation for them to grapple with, the quality of information that they’ve got,” she said.

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

An advisory committee to the Centers for Disease Control and Prevention is addressing the safety of the Johnson & Johnson COVID-19 vaccine on April 14, 2021, after the CDC and Food and Drug Administration recommended that states hold off on using it pending a detailed review of six cases of the same kind of rare but serious event – a blood clot in the vessels that drain blood from the brain combined with a large drop in platelets, which increases the risk for bleeding.

This combination can lead to severe strokes that can lead to brain damage or death. Among the six cases reported, which came to light over the past 3 weeks, one person died, according to the CDC. All six were women and ranged in age from 18 to 48 years.

According to a report from the Vaccine Adverse Event Reporting System (VAERS), which is maintained by the Department of Health & Human Services, the woman who died was 45. She developed a gradually worsening headache about a week after receiving the Johnson & Johnson vaccine.

On March 17, the day she came to the hospital, she was dry heaving. Her headache had suddenly gotten much worse, and the left side of her body was weak, which are signs of a stroke. A CT scan revealed both bleeding in her brain and a clot in her cortical vein. She died the following day.

In addition to VAERS, which accepts reports from anyone, the CDC and FDA are monitoring at least eight other safety systems maintained by hospitals, research centers, long-term care facilities, and insurance companies for signs of trouble with the vaccines. VAERS data is searchable and open to the public. Most of these systems are not publicly available to protect patient privacy. It’s unclear which systems detected the six cases cited by federal regulators.

“These are very serious and potentially fatal problems occurring in a healthy young adult. It’s serious and we need to get to the bottom of it,” said Ed Belongia, MD, director of the Center for Clinical Epidemiology and Population Health at the Marshfield (Wis.) Clinic Research Institute. Dr. Belongia leads a research team that helps the CDC monitor vaccine safety and effectiveness. 

“Safety is always the highest priority, and I think what we’ve seen here in the past 24 hours is our vaccine safety monitoring system is working,” he said.

Others agree. “I think what CDC and FDA have detected is a rare, but likely real adverse event associated with this vaccine,” said Paul Offit, MD, director of vaccine education at Children’s Hospital of Philadelphia.

Although much is still unknown about these events, they follow a similar pattern of blood clots reported with the AstraZeneca vaccine in Europe. That vaccine is now sold under the brand name Vaxzevria. 

This has experts questioning whether all vaccines of this type may cause these rare clots.

“I think it’s likely a class effect,” said Dr. Offit, who was a member of the FDA advisory committee that reviewed clinical trial data on the J&J vaccine before it was authorized for use.
 

Adenovirus vaccines scrutinized

Both the Johnson & Johnson and Vaxzevria vaccines use an adenovirus to ferry genetic instructions for making the coronaviruses spike protein into our cells.

Adenoviruses are common, relatively simple viruses that normally cause mild cold or flu symptoms. The ones used in the vaccine are disabled so they can’t make us sick. They’re more like Trojan horses. 

Once inside our cells, they release the DNA instructions they carry to make the spike protein of the new coronavirus. Those cells then crank out copies of the spike protein, which then get displayed on the outer surface of the cell membrane where they are recognized by the immune system. 

The immune system then makes antibodies and other defenses against the spike so that, when the real coronavirus comes along, our bodies are ready to fight the infection.

There’s no question the vaccine works. In clinical trials, the Johnson & Johnson vaccine was 66% percent effective at preventing against moderate to severe COVID-19 infection, and none of the patients who got COVID-19 after vaccination had to be admitted to the hospital or died.

The idea behind using adenoviruses in vaccines isn’t a new one. In a kind of fight-fire-with-fire approach, the idea is to use a virus, which is good at infecting us, to fight a different kind of virus.

Researchers have been working on the concept for about 10 years, but the COVID-19 vaccines that use this technology are some of the first adenovirus-vector vaccines deployed in humans. 

Only one other adenovirus vaccine, for Ebola, has been approved for use in humans. It was approved in Europe last year. Before the Johnson & Johnson vaccine, no other adenovirus vector has been available for use in humans in the United States.

There are six adenovirus-vector vaccines for COVID-19. In addition to AstraZeneca and Johnson & Johnson, there’s the Russian-developed vaccine Sputnik V, along with CanSino from China, and the Covishield vaccine in India.

Adenovirus vaccines are more stable than the mRNA vaccines. That makes them easier to store and transport. 

But they have a significant downside, too. Because adenoviruses infect humans out in the world, we already make antibodies against them. So there’s always a danger that our immune systems might recognize and react to the vaccine, rendering it ineffective. For that reason, scientists try to carefully select the adenovirus vectors, or carriers, they use.

The two vaccines under investigation for blood clots are slightly different. The Johnson & Johnson vaccine uses the vector AD26, because most of the population lacks preexisting immunity to it. Vaxzevria uses an adenovirus that infects chimpanzees, called ChAdOx1. 

Vaxzevria has been widely used in Europe but has not yet been authorized in the United States.

On April 7, the European Medicines Agency, Europe’s counterpart to the FDA, ruled that unusual blood clots with low blood platelets should be listed as rare side effects on the Vaxzevria vaccine.

The decision came after reviewing 62 cases of cerebral venous sinus thrombosis (CVST) linked to the vaccine and 25 cases of another rare type of clot, called a splanchnic vein thrombosis. Splanchnic veins drain blood from the major organs in the digestive system, including the stomach, liver, and intestines; 18 of those events were fatal.

The reports were culled from reporting in Europe and the United Kingdom, where around 25 million people have received the Vaxzevria vaccine, making these clots exceptionally rare, but serious.

So far, six cases of CVST have been reported in the United States, after more than 7 million doses of the Johnson & Johnson vaccines have been administered.

A key question for U.S. regulators will be the background rate for these types of rare combinations of clots and deplenished platelets. The background rate is the number of events that would be expected to occur naturally in a population of unvaccinated people. On a press call on April 13, Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, was asked about the frequency of this dangerous combination. He said the combination of low platelets and clots was so rare that it was hard to pinpoint, but might be somewhere between 2 and 14 cases per million people over the course of a year.

The first Johnson & Johnson doses were given in early March. That means the six cases came to light within the first few weeks of use of the vaccine in the United States, a very short amount of time.

“These were six cases per million people for 2 weeks, which is the same thing as 25 million per year, so it’s clearly above the background rate,” Dr. Offit said.
 

Studies suggest possible mechanism

On April 9, the New England Journal of Medicine published a detailed evaluation of the 11 patients in Germany and Austria who developed the rare clots after their Vaxzevria vaccines.

The study detected rare antibodies to a signaling protein called platelet factor 4, which helps to coordinate clot formation.

These same type of antibodies form in some people given the blood thinning drug heparin. In those reactions, which are also exceptionally rare, the same type of syndrome develops, leading to large, devastating clots that consume circulating platelets.

It’s not yet clear whether people who develop reactions to the vaccines already have some platelet factor 4 antibodies before they are vaccinated, or whether the vaccines somehow spur the body to make these antibodies, which then launch a kind of autoimmune attack.

The researchers on the paper gave the syndrome a name, vaccine-induced thrombotic thrombocytopenia (VITT).

It’s also not clear why more cases seem to be in women than in men. Andrew Eisenberger, MD, an associate professor of hematology and oncology at Columbia University, New York, said the most common causes of cerebral venous sinus thrombosis have to do with conditions that raise estrogen levels, like pregnancy and hormonal contraception.

“Estrogen naturally leads to changes in several clotting proteins in the blood that may predispose to abnormal blood clotting in a few different sites in the body,” he said. “The clotting changes we are encountering with some of COVID-19 vaccines are likely to be synergistic with the effects of estrogen on the blood.”

No matter the cause, the CDC on April 13 alerted doctors to keep a high index of suspicion for VITT in patients who have received the Johnson & Johnson vaccination within the last 2 weeks. In those patients, the usual course of treatment with blood thinning drugs like heparin may be harmful.

Symptoms to watch for include severe headache or backache, new neurologic symptoms, severe abdominal pain, shortness of breath, leg swelling, tiny red spots on the skin, or easy bruising. 
 

Grappling with evidence

The CDC’s Advisory Committee on Immunization Practices will meet today in an emergency session to review the cases and see if any changes are needed to use of the J&J vaccine in the United States.

Last week, for example, the United Kingdom restricted the use of the AstraZeneca vaccine in people aged younger than 30 years, saying the risks and benefits of vaccination are “more finely balanced” for this age group.

With cases of COVID-19 rising again in the United States, and the Johnson & Johnson vaccine currently the most convenient form of protection against the virus, the committee will have to weigh the risks of that infection against the risk of rare clots caused by vaccination.

They will also likely have to rule out whether any of the cases had COVID. At least one study has reported CVST clots in three patients with confirmed COVID infections. In Europe, COVID infection did not seem to play a role in the formation of the clots with low platelets.

Hilda Bastian, PhD, a clinical trials expert who cofounded the Cochrane Collaboration, said it won’t be an easy task. Much will depend on how certain the committee members feel they know about all the events linked to the vaccine.

“That’s the really, really hard issue from my point of view for them right this moment. Have we missed any? Or how many are we likely to have missed?” asked Dr. Bastian, who lives in Australia.

“In a country that size with that fragmented [of] a health care system, how sure can you be that you know them all? That’s going to be a really difficult situation for them to grapple with, the quality of information that they’ve got,” she said.

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

An advisory committee to the Centers for Disease Control and Prevention is addressing the safety of the Johnson & Johnson COVID-19 vaccine on April 14, 2021, after the CDC and Food and Drug Administration recommended that states hold off on using it pending a detailed review of six cases of the same kind of rare but serious event – a blood clot in the vessels that drain blood from the brain combined with a large drop in platelets, which increases the risk for bleeding.

This combination can lead to severe strokes that can lead to brain damage or death. Among the six cases reported, which came to light over the past 3 weeks, one person died, according to the CDC. All six were women and ranged in age from 18 to 48 years.

According to a report from the Vaccine Adverse Event Reporting System (VAERS), which is maintained by the Department of Health & Human Services, the woman who died was 45. She developed a gradually worsening headache about a week after receiving the Johnson & Johnson vaccine.

On March 17, the day she came to the hospital, she was dry heaving. Her headache had suddenly gotten much worse, and the left side of her body was weak, which are signs of a stroke. A CT scan revealed both bleeding in her brain and a clot in her cortical vein. She died the following day.

In addition to VAERS, which accepts reports from anyone, the CDC and FDA are monitoring at least eight other safety systems maintained by hospitals, research centers, long-term care facilities, and insurance companies for signs of trouble with the vaccines. VAERS data is searchable and open to the public. Most of these systems are not publicly available to protect patient privacy. It’s unclear which systems detected the six cases cited by federal regulators.

“These are very serious and potentially fatal problems occurring in a healthy young adult. It’s serious and we need to get to the bottom of it,” said Ed Belongia, MD, director of the Center for Clinical Epidemiology and Population Health at the Marshfield (Wis.) Clinic Research Institute. Dr. Belongia leads a research team that helps the CDC monitor vaccine safety and effectiveness. 

“Safety is always the highest priority, and I think what we’ve seen here in the past 24 hours is our vaccine safety monitoring system is working,” he said.

Others agree. “I think what CDC and FDA have detected is a rare, but likely real adverse event associated with this vaccine,” said Paul Offit, MD, director of vaccine education at Children’s Hospital of Philadelphia.

Although much is still unknown about these events, they follow a similar pattern of blood clots reported with the AstraZeneca vaccine in Europe. That vaccine is now sold under the brand name Vaxzevria. 

This has experts questioning whether all vaccines of this type may cause these rare clots.

“I think it’s likely a class effect,” said Dr. Offit, who was a member of the FDA advisory committee that reviewed clinical trial data on the J&J vaccine before it was authorized for use.
 

Adenovirus vaccines scrutinized

Both the Johnson & Johnson and Vaxzevria vaccines use an adenovirus to ferry genetic instructions for making the coronaviruses spike protein into our cells.

Adenoviruses are common, relatively simple viruses that normally cause mild cold or flu symptoms. The ones used in the vaccine are disabled so they can’t make us sick. They’re more like Trojan horses. 

Once inside our cells, they release the DNA instructions they carry to make the spike protein of the new coronavirus. Those cells then crank out copies of the spike protein, which then get displayed on the outer surface of the cell membrane where they are recognized by the immune system. 

The immune system then makes antibodies and other defenses against the spike so that, when the real coronavirus comes along, our bodies are ready to fight the infection.

There’s no question the vaccine works. In clinical trials, the Johnson & Johnson vaccine was 66% percent effective at preventing against moderate to severe COVID-19 infection, and none of the patients who got COVID-19 after vaccination had to be admitted to the hospital or died.

The idea behind using adenoviruses in vaccines isn’t a new one. In a kind of fight-fire-with-fire approach, the idea is to use a virus, which is good at infecting us, to fight a different kind of virus.

Researchers have been working on the concept for about 10 years, but the COVID-19 vaccines that use this technology are some of the first adenovirus-vector vaccines deployed in humans. 

Only one other adenovirus vaccine, for Ebola, has been approved for use in humans. It was approved in Europe last year. Before the Johnson & Johnson vaccine, no other adenovirus vector has been available for use in humans in the United States.

There are six adenovirus-vector vaccines for COVID-19. In addition to AstraZeneca and Johnson & Johnson, there’s the Russian-developed vaccine Sputnik V, along with CanSino from China, and the Covishield vaccine in India.

Adenovirus vaccines are more stable than the mRNA vaccines. That makes them easier to store and transport. 

But they have a significant downside, too. Because adenoviruses infect humans out in the world, we already make antibodies against them. So there’s always a danger that our immune systems might recognize and react to the vaccine, rendering it ineffective. For that reason, scientists try to carefully select the adenovirus vectors, or carriers, they use.

The two vaccines under investigation for blood clots are slightly different. The Johnson & Johnson vaccine uses the vector AD26, because most of the population lacks preexisting immunity to it. Vaxzevria uses an adenovirus that infects chimpanzees, called ChAdOx1. 

Vaxzevria has been widely used in Europe but has not yet been authorized in the United States.

On April 7, the European Medicines Agency, Europe’s counterpart to the FDA, ruled that unusual blood clots with low blood platelets should be listed as rare side effects on the Vaxzevria vaccine.

The decision came after reviewing 62 cases of cerebral venous sinus thrombosis (CVST) linked to the vaccine and 25 cases of another rare type of clot, called a splanchnic vein thrombosis. Splanchnic veins drain blood from the major organs in the digestive system, including the stomach, liver, and intestines; 18 of those events were fatal.

The reports were culled from reporting in Europe and the United Kingdom, where around 25 million people have received the Vaxzevria vaccine, making these clots exceptionally rare, but serious.

So far, six cases of CVST have been reported in the United States, after more than 7 million doses of the Johnson & Johnson vaccines have been administered.

A key question for U.S. regulators will be the background rate for these types of rare combinations of clots and deplenished platelets. The background rate is the number of events that would be expected to occur naturally in a population of unvaccinated people. On a press call on April 13, Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, was asked about the frequency of this dangerous combination. He said the combination of low platelets and clots was so rare that it was hard to pinpoint, but might be somewhere between 2 and 14 cases per million people over the course of a year.

The first Johnson & Johnson doses were given in early March. That means the six cases came to light within the first few weeks of use of the vaccine in the United States, a very short amount of time.

“These were six cases per million people for 2 weeks, which is the same thing as 25 million per year, so it’s clearly above the background rate,” Dr. Offit said.
 

Studies suggest possible mechanism

On April 9, the New England Journal of Medicine published a detailed evaluation of the 11 patients in Germany and Austria who developed the rare clots after their Vaxzevria vaccines.

The study detected rare antibodies to a signaling protein called platelet factor 4, which helps to coordinate clot formation.

These same type of antibodies form in some people given the blood thinning drug heparin. In those reactions, which are also exceptionally rare, the same type of syndrome develops, leading to large, devastating clots that consume circulating platelets.

It’s not yet clear whether people who develop reactions to the vaccines already have some platelet factor 4 antibodies before they are vaccinated, or whether the vaccines somehow spur the body to make these antibodies, which then launch a kind of autoimmune attack.

The researchers on the paper gave the syndrome a name, vaccine-induced thrombotic thrombocytopenia (VITT).

It’s also not clear why more cases seem to be in women than in men. Andrew Eisenberger, MD, an associate professor of hematology and oncology at Columbia University, New York, said the most common causes of cerebral venous sinus thrombosis have to do with conditions that raise estrogen levels, like pregnancy and hormonal contraception.

“Estrogen naturally leads to changes in several clotting proteins in the blood that may predispose to abnormal blood clotting in a few different sites in the body,” he said. “The clotting changes we are encountering with some of COVID-19 vaccines are likely to be synergistic with the effects of estrogen on the blood.”

No matter the cause, the CDC on April 13 alerted doctors to keep a high index of suspicion for VITT in patients who have received the Johnson & Johnson vaccination within the last 2 weeks. In those patients, the usual course of treatment with blood thinning drugs like heparin may be harmful.

Symptoms to watch for include severe headache or backache, new neurologic symptoms, severe abdominal pain, shortness of breath, leg swelling, tiny red spots on the skin, or easy bruising. 
 

Grappling with evidence

The CDC’s Advisory Committee on Immunization Practices will meet today in an emergency session to review the cases and see if any changes are needed to use of the J&J vaccine in the United States.

Last week, for example, the United Kingdom restricted the use of the AstraZeneca vaccine in people aged younger than 30 years, saying the risks and benefits of vaccination are “more finely balanced” for this age group.

With cases of COVID-19 rising again in the United States, and the Johnson & Johnson vaccine currently the most convenient form of protection against the virus, the committee will have to weigh the risks of that infection against the risk of rare clots caused by vaccination.

They will also likely have to rule out whether any of the cases had COVID. At least one study has reported CVST clots in three patients with confirmed COVID infections. In Europe, COVID infection did not seem to play a role in the formation of the clots with low platelets.

Hilda Bastian, PhD, a clinical trials expert who cofounded the Cochrane Collaboration, said it won’t be an easy task. Much will depend on how certain the committee members feel they know about all the events linked to the vaccine.

“That’s the really, really hard issue from my point of view for them right this moment. Have we missed any? Or how many are we likely to have missed?” asked Dr. Bastian, who lives in Australia.

“In a country that size with that fragmented [of] a health care system, how sure can you be that you know them all? That’s going to be a really difficult situation for them to grapple with, the quality of information that they’ve got,” she said.

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

On April 13, the Centers for Disease Control and Prevention and the Food and Drug Administration issued a joint statement recommending a pause in Johnson & Johnson vaccine administration, pending review of six reported U.S. cases of a rare and severe type of blood clot occurring after receiving the Johnson & Johnson vaccine. To date, more than 6.8 million doses of that vaccine have been given in the United States, so at this point the rate of detected cases of this problem is less than one in a million.

The six cases occurred in women aged 18-48 years, and symptoms occurred 6-13 days after vaccination. In these cases, cerebral venous sinus thrombosis was seen in addition to thrombocytopenia.

Physicians may receive calls from concerned patients who have received a COVID vaccine. However, more than 95% of the vaccine administrations in the United States to date have been the Pfizer and Moderna messenger RNA vaccines. No association between these vaccines and blood clots has been detected. Also, these six cases occurred within 2 weeks of Johnson & Johnson vaccination, so even among those receiving the Johnson & Johnson vaccine, those who are more than 3 weeks out from their vaccination have no need for concern regarding this rare complication.

Physicians should counsel those who have received the Johnson & Johnson vaccine less than 3 weeks ago to watch for easy bruising, gum bleeding, nose bleeds, leg or arm pain or swelling, severe headache or abdominal pain, shortness of breath, or chest pain. If they notice one or more of those symptoms, they should seek medical attention.

The Centers for Disease Control and Prevention will convene a meeting of the Advisory Committee on Immunization Practices on April 14 to review the six U.S. cases of the Johnson & Johnson vaccine and determine their significance.

Several cases of unusual thromboses and thrombocytopenia have been detected after the Oxford AstraZeneca vaccine, which uses the same adenovirus vector technology as the Johnson & Johnson vaccine, but which is not authorized for use in the United States. The Oxford AstraZeneca vaccine uses a recombinant deficient chimpanzee adenovirus to deliver the message to cells to produce antibody against the SARS-CoV-2 spike protein. The Johnson & Johnson vaccine uses a recombinant deficient human adenovirus to deliver this same message.  

Two recent reports in the New England Journal of Medicine have reported on thrombosis and thrombocytopenia after the Oxford AstraZeneca vaccine in Europe. Both of these reports identified high levels of IgG antibodies to platelet factor 4–polyanion complexes, similar to the mechanism of heparin-induced thrombocytopenia. The term vaccine-induced immune thrombocytopenia was proposed for this phenomenon. Treatment of this condition involves administration of intravenous immunoglobulin and nonheparin anticoagulants. Recent updates from the World Health Organization report that 169 cases of cerebral venous sinus thrombosis and 53 of splanchnic venous thrombosis occurred after 34 million doses of the Oxford AstraZeneca vaccine was administered in the European Union and United Kingdom.

While this pause in Johnson & Johnson vaccination is disappointing news amid increased cases in parts of the country, the Johnson & Johnson vaccines make up less than 5% of the U.S. vaccine doses administered to date. According to the CDC, more than 122 million Americans have received at least one dose and more than 75 million are fully vaccinated.

Dr. Patterson has received an honorarium from Pfizer for an antifungal symposium and is a subinvestigator for the Novavax vaccine. Her spouse served as a consultant for SCYNEXIS, as a speaker for Gilead Sciences and Basilea, and has received a research grant from the National Institutes of Health for the ACTT remdesivir trial.

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

On April 13, the Centers for Disease Control and Prevention and the Food and Drug Administration issued a joint statement recommending a pause in Johnson & Johnson vaccine administration, pending review of six reported U.S. cases of a rare and severe type of blood clot occurring after receiving the Johnson & Johnson vaccine. To date, more than 6.8 million doses of that vaccine have been given in the United States, so at this point the rate of detected cases of this problem is less than one in a million.

The six cases occurred in women aged 18-48 years, and symptoms occurred 6-13 days after vaccination. In these cases, cerebral venous sinus thrombosis was seen in addition to thrombocytopenia.

Physicians may receive calls from concerned patients who have received a COVID vaccine. However, more than 95% of the vaccine administrations in the United States to date have been the Pfizer and Moderna messenger RNA vaccines. No association between these vaccines and blood clots has been detected. Also, these six cases occurred within 2 weeks of Johnson & Johnson vaccination, so even among those receiving the Johnson & Johnson vaccine, those who are more than 3 weeks out from their vaccination have no need for concern regarding this rare complication.

Physicians should counsel those who have received the Johnson & Johnson vaccine less than 3 weeks ago to watch for easy bruising, gum bleeding, nose bleeds, leg or arm pain or swelling, severe headache or abdominal pain, shortness of breath, or chest pain. If they notice one or more of those symptoms, they should seek medical attention.

The Centers for Disease Control and Prevention will convene a meeting of the Advisory Committee on Immunization Practices on April 14 to review the six U.S. cases of the Johnson & Johnson vaccine and determine their significance.

Several cases of unusual thromboses and thrombocytopenia have been detected after the Oxford AstraZeneca vaccine, which uses the same adenovirus vector technology as the Johnson & Johnson vaccine, but which is not authorized for use in the United States. The Oxford AstraZeneca vaccine uses a recombinant deficient chimpanzee adenovirus to deliver the message to cells to produce antibody against the SARS-CoV-2 spike protein. The Johnson & Johnson vaccine uses a recombinant deficient human adenovirus to deliver this same message.  

Two recent reports in the New England Journal of Medicine have reported on thrombosis and thrombocytopenia after the Oxford AstraZeneca vaccine in Europe. Both of these reports identified high levels of IgG antibodies to platelet factor 4–polyanion complexes, similar to the mechanism of heparin-induced thrombocytopenia. The term vaccine-induced immune thrombocytopenia was proposed for this phenomenon. Treatment of this condition involves administration of intravenous immunoglobulin and nonheparin anticoagulants. Recent updates from the World Health Organization report that 169 cases of cerebral venous sinus thrombosis and 53 of splanchnic venous thrombosis occurred after 34 million doses of the Oxford AstraZeneca vaccine was administered in the European Union and United Kingdom.

While this pause in Johnson & Johnson vaccination is disappointing news amid increased cases in parts of the country, the Johnson & Johnson vaccines make up less than 5% of the U.S. vaccine doses administered to date. According to the CDC, more than 122 million Americans have received at least one dose and more than 75 million are fully vaccinated.

Dr. Patterson has received an honorarium from Pfizer for an antifungal symposium and is a subinvestigator for the Novavax vaccine. Her spouse served as a consultant for SCYNEXIS, as a speaker for Gilead Sciences and Basilea, and has received a research grant from the National Institutes of Health for the ACTT remdesivir trial.

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

On April 13, the Centers for Disease Control and Prevention and the Food and Drug Administration issued a joint statement recommending a pause in Johnson & Johnson vaccine administration, pending review of six reported U.S. cases of a rare and severe type of blood clot occurring after receiving the Johnson & Johnson vaccine. To date, more than 6.8 million doses of that vaccine have been given in the United States, so at this point the rate of detected cases of this problem is less than one in a million.

The six cases occurred in women aged 18-48 years, and symptoms occurred 6-13 days after vaccination. In these cases, cerebral venous sinus thrombosis was seen in addition to thrombocytopenia.

Physicians may receive calls from concerned patients who have received a COVID vaccine. However, more than 95% of the vaccine administrations in the United States to date have been the Pfizer and Moderna messenger RNA vaccines. No association between these vaccines and blood clots has been detected. Also, these six cases occurred within 2 weeks of Johnson & Johnson vaccination, so even among those receiving the Johnson & Johnson vaccine, those who are more than 3 weeks out from their vaccination have no need for concern regarding this rare complication.

Physicians should counsel those who have received the Johnson & Johnson vaccine less than 3 weeks ago to watch for easy bruising, gum bleeding, nose bleeds, leg or arm pain or swelling, severe headache or abdominal pain, shortness of breath, or chest pain. If they notice one or more of those symptoms, they should seek medical attention.

The Centers for Disease Control and Prevention will convene a meeting of the Advisory Committee on Immunization Practices on April 14 to review the six U.S. cases of the Johnson & Johnson vaccine and determine their significance.

Several cases of unusual thromboses and thrombocytopenia have been detected after the Oxford AstraZeneca vaccine, which uses the same adenovirus vector technology as the Johnson & Johnson vaccine, but which is not authorized for use in the United States. The Oxford AstraZeneca vaccine uses a recombinant deficient chimpanzee adenovirus to deliver the message to cells to produce antibody against the SARS-CoV-2 spike protein. The Johnson & Johnson vaccine uses a recombinant deficient human adenovirus to deliver this same message.  

Two recent reports in the New England Journal of Medicine have reported on thrombosis and thrombocytopenia after the Oxford AstraZeneca vaccine in Europe. Both of these reports identified high levels of IgG antibodies to platelet factor 4–polyanion complexes, similar to the mechanism of heparin-induced thrombocytopenia. The term vaccine-induced immune thrombocytopenia was proposed for this phenomenon. Treatment of this condition involves administration of intravenous immunoglobulin and nonheparin anticoagulants. Recent updates from the World Health Organization report that 169 cases of cerebral venous sinus thrombosis and 53 of splanchnic venous thrombosis occurred after 34 million doses of the Oxford AstraZeneca vaccine was administered in the European Union and United Kingdom.

While this pause in Johnson & Johnson vaccination is disappointing news amid increased cases in parts of the country, the Johnson & Johnson vaccines make up less than 5% of the U.S. vaccine doses administered to date. According to the CDC, more than 122 million Americans have received at least one dose and more than 75 million are fully vaccinated.

Dr. Patterson has received an honorarium from Pfizer for an antifungal symposium and is a subinvestigator for the Novavax vaccine. Her spouse served as a consultant for SCYNEXIS, as a speaker for Gilead Sciences and Basilea, and has received a research grant from the National Institutes of Health for the ACTT remdesivir trial.

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

COVID vaccines do not work well for patients with hematologic malignancies, new data suggest.

A small study involving 67 such patients shows that nearly half did not produce antibodies and were therefore still at risk of contracting COVID-19, even though they had all received both doses of one of the new mRNA COVID vaccines (Moderna or Pfizer).

“[This] is in stark contrast with the results of phase 1 mRNA vaccine immunogenicity trials, in which robust antibody responses were seen in essentially 100% of participants,” said the authors, led by Mounzer Agha, MD, director of the Mario Lemieux Center for Blood Cancers at the University of Pittsburgh Medical Center’s Hillman Cancer Center.

“Clinicians caring for patients with hematological malignancies and other immunocompromising conditions should be aware of the possibility of COVID-19 vaccine failure,” they emphasized.

“It’s critically important for these patients to be aware of their continued risk [for SARS-CoV-2 infection] and to seek prompt medical attention if they have COVID-19 symptoms, even after vaccination,” Dr. Agha said in a statement.

The study was published online on April 9 as preprint in medRxiv and has not yet undergone peer review.


 

Antibody responses

The authors analyzed responses in a group of 67 patients who had a hematologic malignancy, including chronic lymphocytic leukemia (CLL), lymphoma, and multiple myeloma. Approximately 45% of the patients were receiving therapy for their cancer at the time of vaccination; the rest were under observation.

All patients received two doses of an mRNA COVID vaccine and so were considered to be fully vaccinated.

Antibody responses for these fully vaccinated patients were then analyzed. The median duration between receipt of the second dose of the vaccine and the antibody test was 23 days.

“In total ... 46.3% ... had a negative antibody result after vaccination and were therefore considered to be vaccine nonresponders,” the authors reported.

The worst responses occurred in patients with CLL, of whom only 23% produced measurable antibodies to either vaccine, although approximately 70% of these patients were not receiving any form of cancer therapy at the time of vaccination.

Older patients were more likely not to have a response to either vaccine compared with younger patients, the investigators added.

In contrast, gender, immunoglobulin G levels, the number of days between the second dose and the measurement of antibodies, and status of cancer therapy did not differ among patients who had a response to the vaccines and those who did not.

“Our findings underscore the importance of adherence to nonpharmaceutical interventions to prevent COVID-19 in hematological malignancy patients,” the authors wrote. This is particularly important, given the fact that among patients with hematologic malignancies who become infected with SARS-CoV-2, the mortality rate is in excess of 30%.

Moreover, among such patients, viral shedding may be prolonged, often lasting several months. As such, “these patients should be advised to wear masks and observe social distancing regardless of vaccination status,” the investigators advised.

As of March 2021, guidance from the Centers for Disease Control and Prevention has allowed gatherings of unmasked people who have been vaccinated and of those at low risk for COVID-19 who have not yet been vaccinated. “As we see more national guidance allowing for unmasked gatherings among vaccinated people, clinicians should counsel their immunocompromised patients about the possibility that COVID-19 vaccines may not fully protect them against SARS-CoV-2,” coauthor Ghady Haidar, MD, assistant professor of medicine at the University of Pittsburgh, said in a statement.

“Our results show that the odds of the vaccine producing an antibody response in people with hematologic malignancies are the equivalent of a coin flip,” he said.

The authors have disclosed no relevant financial relationships.
 

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

COVID vaccines do not work well for patients with hematologic malignancies, new data suggest.

A small study involving 67 such patients shows that nearly half did not produce antibodies and were therefore still at risk of contracting COVID-19, even though they had all received both doses of one of the new mRNA COVID vaccines (Moderna or Pfizer).

“[This] is in stark contrast with the results of phase 1 mRNA vaccine immunogenicity trials, in which robust antibody responses were seen in essentially 100% of participants,” said the authors, led by Mounzer Agha, MD, director of the Mario Lemieux Center for Blood Cancers at the University of Pittsburgh Medical Center’s Hillman Cancer Center.

“Clinicians caring for patients with hematological malignancies and other immunocompromising conditions should be aware of the possibility of COVID-19 vaccine failure,” they emphasized.

“It’s critically important for these patients to be aware of their continued risk [for SARS-CoV-2 infection] and to seek prompt medical attention if they have COVID-19 symptoms, even after vaccination,” Dr. Agha said in a statement.

The study was published online on April 9 as preprint in medRxiv and has not yet undergone peer review.


 

Antibody responses

The authors analyzed responses in a group of 67 patients who had a hematologic malignancy, including chronic lymphocytic leukemia (CLL), lymphoma, and multiple myeloma. Approximately 45% of the patients were receiving therapy for their cancer at the time of vaccination; the rest were under observation.

All patients received two doses of an mRNA COVID vaccine and so were considered to be fully vaccinated.

Antibody responses for these fully vaccinated patients were then analyzed. The median duration between receipt of the second dose of the vaccine and the antibody test was 23 days.

“In total ... 46.3% ... had a negative antibody result after vaccination and were therefore considered to be vaccine nonresponders,” the authors reported.

The worst responses occurred in patients with CLL, of whom only 23% produced measurable antibodies to either vaccine, although approximately 70% of these patients were not receiving any form of cancer therapy at the time of vaccination.

Older patients were more likely not to have a response to either vaccine compared with younger patients, the investigators added.

In contrast, gender, immunoglobulin G levels, the number of days between the second dose and the measurement of antibodies, and status of cancer therapy did not differ among patients who had a response to the vaccines and those who did not.

“Our findings underscore the importance of adherence to nonpharmaceutical interventions to prevent COVID-19 in hematological malignancy patients,” the authors wrote. This is particularly important, given the fact that among patients with hematologic malignancies who become infected with SARS-CoV-2, the mortality rate is in excess of 30%.

Moreover, among such patients, viral shedding may be prolonged, often lasting several months. As such, “these patients should be advised to wear masks and observe social distancing regardless of vaccination status,” the investigators advised.

As of March 2021, guidance from the Centers for Disease Control and Prevention has allowed gatherings of unmasked people who have been vaccinated and of those at low risk for COVID-19 who have not yet been vaccinated. “As we see more national guidance allowing for unmasked gatherings among vaccinated people, clinicians should counsel their immunocompromised patients about the possibility that COVID-19 vaccines may not fully protect them against SARS-CoV-2,” coauthor Ghady Haidar, MD, assistant professor of medicine at the University of Pittsburgh, said in a statement.

“Our results show that the odds of the vaccine producing an antibody response in people with hematologic malignancies are the equivalent of a coin flip,” he said.

The authors have disclosed no relevant financial relationships.
 

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

COVID vaccines do not work well for patients with hematologic malignancies, new data suggest.

A small study involving 67 such patients shows that nearly half did not produce antibodies and were therefore still at risk of contracting COVID-19, even though they had all received both doses of one of the new mRNA COVID vaccines (Moderna or Pfizer).

“[This] is in stark contrast with the results of phase 1 mRNA vaccine immunogenicity trials, in which robust antibody responses were seen in essentially 100% of participants,” said the authors, led by Mounzer Agha, MD, director of the Mario Lemieux Center for Blood Cancers at the University of Pittsburgh Medical Center’s Hillman Cancer Center.

“Clinicians caring for patients with hematological malignancies and other immunocompromising conditions should be aware of the possibility of COVID-19 vaccine failure,” they emphasized.

“It’s critically important for these patients to be aware of their continued risk [for SARS-CoV-2 infection] and to seek prompt medical attention if they have COVID-19 symptoms, even after vaccination,” Dr. Agha said in a statement.

The study was published online on April 9 as preprint in medRxiv and has not yet undergone peer review.


 

Antibody responses

The authors analyzed responses in a group of 67 patients who had a hematologic malignancy, including chronic lymphocytic leukemia (CLL), lymphoma, and multiple myeloma. Approximately 45% of the patients were receiving therapy for their cancer at the time of vaccination; the rest were under observation.

All patients received two doses of an mRNA COVID vaccine and so were considered to be fully vaccinated.

Antibody responses for these fully vaccinated patients were then analyzed. The median duration between receipt of the second dose of the vaccine and the antibody test was 23 days.

“In total ... 46.3% ... had a negative antibody result after vaccination and were therefore considered to be vaccine nonresponders,” the authors reported.

The worst responses occurred in patients with CLL, of whom only 23% produced measurable antibodies to either vaccine, although approximately 70% of these patients were not receiving any form of cancer therapy at the time of vaccination.

Older patients were more likely not to have a response to either vaccine compared with younger patients, the investigators added.

In contrast, gender, immunoglobulin G levels, the number of days between the second dose and the measurement of antibodies, and status of cancer therapy did not differ among patients who had a response to the vaccines and those who did not.

“Our findings underscore the importance of adherence to nonpharmaceutical interventions to prevent COVID-19 in hematological malignancy patients,” the authors wrote. This is particularly important, given the fact that among patients with hematologic malignancies who become infected with SARS-CoV-2, the mortality rate is in excess of 30%.

Moreover, among such patients, viral shedding may be prolonged, often lasting several months. As such, “these patients should be advised to wear masks and observe social distancing regardless of vaccination status,” the investigators advised.

As of March 2021, guidance from the Centers for Disease Control and Prevention has allowed gatherings of unmasked people who have been vaccinated and of those at low risk for COVID-19 who have not yet been vaccinated. “As we see more national guidance allowing for unmasked gatherings among vaccinated people, clinicians should counsel their immunocompromised patients about the possibility that COVID-19 vaccines may not fully protect them against SARS-CoV-2,” coauthor Ghady Haidar, MD, assistant professor of medicine at the University of Pittsburgh, said in a statement.

“Our results show that the odds of the vaccine producing an antibody response in people with hematologic malignancies are the equivalent of a coin flip,” he said.

The authors have disclosed no relevant financial relationships.
 

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

Two recent articles in the medical literature provide new information on mucocutaneous manifestations of COVID-19 in children, which may help guide dermatologists in making accurate diagnoses and stratifying children at risk for serious, systemic illness due to the virus.

In a single-center descriptive study carried out over a 9-month period, researchers in Madrid found that of 50 hospitalized children infected with COVID-19, 21 (42%) had mucocutaneous symptoms, most commonly exanthem, followed by conjunctival hyperemia without secretion and red cracked lips or strawberry tongue. In addition, 18 (36%) fulfilled criteria for Multisystem Inflammatory Syndrome in Children (MIS-C).

“Based on findings in adult patients, the skin manifestations of COVID-19 have been classified under five categories: acral pseudo-chilblain, vesicular eruptions, urticarial lesions, maculopapular eruptions, and livedo or necrosis,” David Andina-Martinez, MD, of Hospital Infantil Universitario Niño Jesús, Madrid, and colleagues wrote in the study, which was published online on April 2 in the Journal of the American Academy of Dermatology.

“Chilblain lesions in healthy children and adolescents have received much attention; these lesions resolve without complications after a few weeks,” they added. “Besides, other cutaneous manifestations of COVID-19 in children have been the matter of case reports or small case series. Nevertheless, the mucocutaneous manifestations in hospitalized children infected with SARS-CoV-2 and their implications on the clinical course have not yet been extensively described.”

In an effort to describe the mucocutaneous manifestations in children hospitalized for COVID-19, the researchers evaluated 50 children up to 18 years of age who were admitted between March 1 and Nov. 30, 2020, to Hospital Infantil Universitario Niño Jesús, which was designated as a pediatric reference center during the peak of the pandemic. The main reasons for admission were respiratory illness (40%) and MIS-C (40%).

Of the 50 patients, 44 (88%) had a positive RT-PCR for SARS-CoV-2 and 6 (12%) met clinical suspicion criteria and had a negative RT-PCR with a positive IgG serology. In 34 patients (68%), a close contact with a suspected or confirmed case of COVID-19 was referred, while the source of the infection remained unknown in the remaining 16 patients (32%).

The researchers reported that 21 patients (42%) had mucocutaneous symptoms, most commonly maculopapular exanthem (86%), conjunctival hyperemia (81%), and red cracked lips or strawberry tongue (43%). In addition, 18 of the 21 patients (86%) fulfilled criteria for MIS-C.

“A tricky thing about MIS-C is that it often manifests 4-5 weeks after a child had COVID-19,” said Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn., who was asked to comment on the study. “MIS-C is associated with characteristic bright red lips and a red tongue that might resemble a strawberry. Such oral findings should prompt rapid evaluation for other signs and symptoms. There can be redness of the eyes or other more nonspecific skin findings (large or small areas of redness on the trunk or limbs, sometimes with surface change), but more importantly, fever, a rapid heartbeat, diarrhea, or breathing issues. The risk with MIS-C is a rapid decline in a child’s health, with admission to an intensive care unit.”

Dr. Andina-Martinez and his colleagues also contrast the skin findings of MIS-C, which are not generally on the hands or feet, with the so-called “COVID toe” or finger phenomenon, which has also been associated with SARS-CoV-2, particularly in children. “Only one of the patients in this series had skin involvement of a finger, and it only appeared after recovery from MIS-C,” Dr. Ko noted. “Distinguishing COVID toes from MIS-C is important, as COVID toes has a very good outcome, while MIS-C can have severe consequences, including protracted heart disease.”

In other findings, patients who presented with mucocutaneous signs tended to be older than those without skin signs and they presented at the emergency department with poor general status and extreme tachycardia. They also had higher C-reactive protein and D-dimer levels and lower lymphocyte counts and faced a more than a 10-fold increased risk of being admitted to the PICU, compared with patients who did not have skin signs (OR, 10.24; P = .003).

In a separate study published online on April 7 in JAMA Dermatology, Zachary E. Holcomb, MD, of the combined dermatology residency program at Massachusetts General Hospital, Boston, and colleagues presented what is believed to be the first case report of reactive infectious mucocutaneous eruption (RIME) triggered by SARS-CoV-2. RIME is the preferred term for pediatric patients who present with mucositis and rash (often a scant or even absent skin eruption) triggered by various infectious agents.

The patient, a 17-year-old male, presented to the emergency department with 3 days of mouth pain and nonpainful penile erosions. “One week prior, he experienced transient anosmia and ageusia that had since spontaneously resolved,” the researchers wrote. “At that time, he was tested for SARS-CoV-2 infection via nasopharyngeal polymerase chain reaction (PCR), the results of which were positive.”

At presentation, the patient had no fever, his vital signs were normal, and the physical exam revealed shallow erosions of the vermilion lips and hard palate, circumferential erythematous erosions of the periurethral glans penis, and five small vesicles on the trunk and upper extremities. Serum analysis revealed a normal white blood cell count with mild absolute lymphopenia, slightly elevated creatinine level, normal liver function, slightly elevated C-reactive protein level, and normal ferritin level.

Dr. Holcomb and colleagues made a diagnosis of SARS-CoV-2–associated RIME based on microbiological results, which revealed positive repeated SARS-CoV-2 nasopharyngeal PCR and negative nasopharyngeal PCR testing for Mycoplasma pneumoniae, adenovirus, Chlamydophila pneumoniae, human metapneumovirus, influenza A/B, parainfluenza 1 to 4, rhinovirus, and respiratory syncytial virus. In addition, titers of Mycoplasma pneumoniae IgM levels were negative, but Mycoplasma pneumoniae IgG levels were elevated.

The lesions resolved with 60 mg of oral prednisone taken daily for 4 days. A recurrence of oral mucositis 3 months later responded to 80 mg oral prednisone taken daily for 6 days.

“It’s not surprising that SARS-CoV-2 is yet another trigger for RIME,” said Anna Yasmine Kirkorian, MD, chief of the division of dermatology at Children’s National Hospital, Washington, who was asked to comment about the case report.

“The take-home message is for clinicians to be aware of this association and distinguish these patients from those with MIS-C, because patients with MIS-C require monitoring and urgent systemic treatment. RIME and MIS-C may potentially be distinguished clinically based on the nature of the mucositis (hemorrhagic and erosive in RIME, dry, cracked lips with ‘strawberry tongue’ in MIS-C) but more importantly patients with RIME lack laboratory evidence of severe systemic inflammation,” such as ESR, CRP, or ferritin, she said.

“A final interesting point in this article was the recurrence of mucositis in this patient, which could mean that recurrent mucositis/recurrent RIME might be yet another manifestation of ‘long-COVID’ (now called post-Acute Sequelae of SARS-CoV-2 infection) in some patients,” Dr. Kirkorian added. She noted that the American Academy of Dermatology–International League of Dermatologic Societies COVID-19 Dermatology Registry and articles like these “provide invaluable ‘hot off the presses’ information for clinicians who are facing the protean manifestations of a novel viral epidemic.”

The researchers reported having no financial disclosures.
 

[email protected]

Two recent articles in the medical literature provide new information on mucocutaneous manifestations of COVID-19 in children, which may help guide dermatologists in making accurate diagnoses and stratifying children at risk for serious, systemic illness due to the virus.

In a single-center descriptive study carried out over a 9-month period, researchers in Madrid found that of 50 hospitalized children infected with COVID-19, 21 (42%) had mucocutaneous symptoms, most commonly exanthem, followed by conjunctival hyperemia without secretion and red cracked lips or strawberry tongue. In addition, 18 (36%) fulfilled criteria for Multisystem Inflammatory Syndrome in Children (MIS-C).

“Based on findings in adult patients, the skin manifestations of COVID-19 have been classified under five categories: acral pseudo-chilblain, vesicular eruptions, urticarial lesions, maculopapular eruptions, and livedo or necrosis,” David Andina-Martinez, MD, of Hospital Infantil Universitario Niño Jesús, Madrid, and colleagues wrote in the study, which was published online on April 2 in the Journal of the American Academy of Dermatology.

“Chilblain lesions in healthy children and adolescents have received much attention; these lesions resolve without complications after a few weeks,” they added. “Besides, other cutaneous manifestations of COVID-19 in children have been the matter of case reports or small case series. Nevertheless, the mucocutaneous manifestations in hospitalized children infected with SARS-CoV-2 and their implications on the clinical course have not yet been extensively described.”

In an effort to describe the mucocutaneous manifestations in children hospitalized for COVID-19, the researchers evaluated 50 children up to 18 years of age who were admitted between March 1 and Nov. 30, 2020, to Hospital Infantil Universitario Niño Jesús, which was designated as a pediatric reference center during the peak of the pandemic. The main reasons for admission were respiratory illness (40%) and MIS-C (40%).

Of the 50 patients, 44 (88%) had a positive RT-PCR for SARS-CoV-2 and 6 (12%) met clinical suspicion criteria and had a negative RT-PCR with a positive IgG serology. In 34 patients (68%), a close contact with a suspected or confirmed case of COVID-19 was referred, while the source of the infection remained unknown in the remaining 16 patients (32%).

The researchers reported that 21 patients (42%) had mucocutaneous symptoms, most commonly maculopapular exanthem (86%), conjunctival hyperemia (81%), and red cracked lips or strawberry tongue (43%). In addition, 18 of the 21 patients (86%) fulfilled criteria for MIS-C.

“A tricky thing about MIS-C is that it often manifests 4-5 weeks after a child had COVID-19,” said Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn., who was asked to comment on the study. “MIS-C is associated with characteristic bright red lips and a red tongue that might resemble a strawberry. Such oral findings should prompt rapid evaluation for other signs and symptoms. There can be redness of the eyes or other more nonspecific skin findings (large or small areas of redness on the trunk or limbs, sometimes with surface change), but more importantly, fever, a rapid heartbeat, diarrhea, or breathing issues. The risk with MIS-C is a rapid decline in a child’s health, with admission to an intensive care unit.”

Dr. Andina-Martinez and his colleagues also contrast the skin findings of MIS-C, which are not generally on the hands or feet, with the so-called “COVID toe” or finger phenomenon, which has also been associated with SARS-CoV-2, particularly in children. “Only one of the patients in this series had skin involvement of a finger, and it only appeared after recovery from MIS-C,” Dr. Ko noted. “Distinguishing COVID toes from MIS-C is important, as COVID toes has a very good outcome, while MIS-C can have severe consequences, including protracted heart disease.”

In other findings, patients who presented with mucocutaneous signs tended to be older than those without skin signs and they presented at the emergency department with poor general status and extreme tachycardia. They also had higher C-reactive protein and D-dimer levels and lower lymphocyte counts and faced a more than a 10-fold increased risk of being admitted to the PICU, compared with patients who did not have skin signs (OR, 10.24; P = .003).

In a separate study published online on April 7 in JAMA Dermatology, Zachary E. Holcomb, MD, of the combined dermatology residency program at Massachusetts General Hospital, Boston, and colleagues presented what is believed to be the first case report of reactive infectious mucocutaneous eruption (RIME) triggered by SARS-CoV-2. RIME is the preferred term for pediatric patients who present with mucositis and rash (often a scant or even absent skin eruption) triggered by various infectious agents.

The patient, a 17-year-old male, presented to the emergency department with 3 days of mouth pain and nonpainful penile erosions. “One week prior, he experienced transient anosmia and ageusia that had since spontaneously resolved,” the researchers wrote. “At that time, he was tested for SARS-CoV-2 infection via nasopharyngeal polymerase chain reaction (PCR), the results of which were positive.”

At presentation, the patient had no fever, his vital signs were normal, and the physical exam revealed shallow erosions of the vermilion lips and hard palate, circumferential erythematous erosions of the periurethral glans penis, and five small vesicles on the trunk and upper extremities. Serum analysis revealed a normal white blood cell count with mild absolute lymphopenia, slightly elevated creatinine level, normal liver function, slightly elevated C-reactive protein level, and normal ferritin level.

Dr. Holcomb and colleagues made a diagnosis of SARS-CoV-2–associated RIME based on microbiological results, which revealed positive repeated SARS-CoV-2 nasopharyngeal PCR and negative nasopharyngeal PCR testing for Mycoplasma pneumoniae, adenovirus, Chlamydophila pneumoniae, human metapneumovirus, influenza A/B, parainfluenza 1 to 4, rhinovirus, and respiratory syncytial virus. In addition, titers of Mycoplasma pneumoniae IgM levels were negative, but Mycoplasma pneumoniae IgG levels were elevated.

The lesions resolved with 60 mg of oral prednisone taken daily for 4 days. A recurrence of oral mucositis 3 months later responded to 80 mg oral prednisone taken daily for 6 days.

“It’s not surprising that SARS-CoV-2 is yet another trigger for RIME,” said Anna Yasmine Kirkorian, MD, chief of the division of dermatology at Children’s National Hospital, Washington, who was asked to comment about the case report.

“The take-home message is for clinicians to be aware of this association and distinguish these patients from those with MIS-C, because patients with MIS-C require monitoring and urgent systemic treatment. RIME and MIS-C may potentially be distinguished clinically based on the nature of the mucositis (hemorrhagic and erosive in RIME, dry, cracked lips with ‘strawberry tongue’ in MIS-C) but more importantly patients with RIME lack laboratory evidence of severe systemic inflammation,” such as ESR, CRP, or ferritin, she said.

“A final interesting point in this article was the recurrence of mucositis in this patient, which could mean that recurrent mucositis/recurrent RIME might be yet another manifestation of ‘long-COVID’ (now called post-Acute Sequelae of SARS-CoV-2 infection) in some patients,” Dr. Kirkorian added. She noted that the American Academy of Dermatology–International League of Dermatologic Societies COVID-19 Dermatology Registry and articles like these “provide invaluable ‘hot off the presses’ information for clinicians who are facing the protean manifestations of a novel viral epidemic.”

The researchers reported having no financial disclosures.
 

[email protected]

Two recent articles in the medical literature provide new information on mucocutaneous manifestations of COVID-19 in children, which may help guide dermatologists in making accurate diagnoses and stratifying children at risk for serious, systemic illness due to the virus.

In a single-center descriptive study carried out over a 9-month period, researchers in Madrid found that of 50 hospitalized children infected with COVID-19, 21 (42%) had mucocutaneous symptoms, most commonly exanthem, followed by conjunctival hyperemia without secretion and red cracked lips or strawberry tongue. In addition, 18 (36%) fulfilled criteria for Multisystem Inflammatory Syndrome in Children (MIS-C).

“Based on findings in adult patients, the skin manifestations of COVID-19 have been classified under five categories: acral pseudo-chilblain, vesicular eruptions, urticarial lesions, maculopapular eruptions, and livedo or necrosis,” David Andina-Martinez, MD, of Hospital Infantil Universitario Niño Jesús, Madrid, and colleagues wrote in the study, which was published online on April 2 in the Journal of the American Academy of Dermatology.

“Chilblain lesions in healthy children and adolescents have received much attention; these lesions resolve without complications after a few weeks,” they added. “Besides, other cutaneous manifestations of COVID-19 in children have been the matter of case reports or small case series. Nevertheless, the mucocutaneous manifestations in hospitalized children infected with SARS-CoV-2 and their implications on the clinical course have not yet been extensively described.”

In an effort to describe the mucocutaneous manifestations in children hospitalized for COVID-19, the researchers evaluated 50 children up to 18 years of age who were admitted between March 1 and Nov. 30, 2020, to Hospital Infantil Universitario Niño Jesús, which was designated as a pediatric reference center during the peak of the pandemic. The main reasons for admission were respiratory illness (40%) and MIS-C (40%).

Of the 50 patients, 44 (88%) had a positive RT-PCR for SARS-CoV-2 and 6 (12%) met clinical suspicion criteria and had a negative RT-PCR with a positive IgG serology. In 34 patients (68%), a close contact with a suspected or confirmed case of COVID-19 was referred, while the source of the infection remained unknown in the remaining 16 patients (32%).

The researchers reported that 21 patients (42%) had mucocutaneous symptoms, most commonly maculopapular exanthem (86%), conjunctival hyperemia (81%), and red cracked lips or strawberry tongue (43%). In addition, 18 of the 21 patients (86%) fulfilled criteria for MIS-C.

“A tricky thing about MIS-C is that it often manifests 4-5 weeks after a child had COVID-19,” said Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn., who was asked to comment on the study. “MIS-C is associated with characteristic bright red lips and a red tongue that might resemble a strawberry. Such oral findings should prompt rapid evaluation for other signs and symptoms. There can be redness of the eyes or other more nonspecific skin findings (large or small areas of redness on the trunk or limbs, sometimes with surface change), but more importantly, fever, a rapid heartbeat, diarrhea, or breathing issues. The risk with MIS-C is a rapid decline in a child’s health, with admission to an intensive care unit.”

Dr. Andina-Martinez and his colleagues also contrast the skin findings of MIS-C, which are not generally on the hands or feet, with the so-called “COVID toe” or finger phenomenon, which has also been associated with SARS-CoV-2, particularly in children. “Only one of the patients in this series had skin involvement of a finger, and it only appeared after recovery from MIS-C,” Dr. Ko noted. “Distinguishing COVID toes from MIS-C is important, as COVID toes has a very good outcome, while MIS-C can have severe consequences, including protracted heart disease.”

In other findings, patients who presented with mucocutaneous signs tended to be older than those without skin signs and they presented at the emergency department with poor general status and extreme tachycardia. They also had higher C-reactive protein and D-dimer levels and lower lymphocyte counts and faced a more than a 10-fold increased risk of being admitted to the PICU, compared with patients who did not have skin signs (OR, 10.24; P = .003).

In a separate study published online on April 7 in JAMA Dermatology, Zachary E. Holcomb, MD, of the combined dermatology residency program at Massachusetts General Hospital, Boston, and colleagues presented what is believed to be the first case report of reactive infectious mucocutaneous eruption (RIME) triggered by SARS-CoV-2. RIME is the preferred term for pediatric patients who present with mucositis and rash (often a scant or even absent skin eruption) triggered by various infectious agents.

The patient, a 17-year-old male, presented to the emergency department with 3 days of mouth pain and nonpainful penile erosions. “One week prior, he experienced transient anosmia and ageusia that had since spontaneously resolved,” the researchers wrote. “At that time, he was tested for SARS-CoV-2 infection via nasopharyngeal polymerase chain reaction (PCR), the results of which were positive.”

At presentation, the patient had no fever, his vital signs were normal, and the physical exam revealed shallow erosions of the vermilion lips and hard palate, circumferential erythematous erosions of the periurethral glans penis, and five small vesicles on the trunk and upper extremities. Serum analysis revealed a normal white blood cell count with mild absolute lymphopenia, slightly elevated creatinine level, normal liver function, slightly elevated C-reactive protein level, and normal ferritin level.

Dr. Holcomb and colleagues made a diagnosis of SARS-CoV-2–associated RIME based on microbiological results, which revealed positive repeated SARS-CoV-2 nasopharyngeal PCR and negative nasopharyngeal PCR testing for Mycoplasma pneumoniae, adenovirus, Chlamydophila pneumoniae, human metapneumovirus, influenza A/B, parainfluenza 1 to 4, rhinovirus, and respiratory syncytial virus. In addition, titers of Mycoplasma pneumoniae IgM levels were negative, but Mycoplasma pneumoniae IgG levels were elevated.

The lesions resolved with 60 mg of oral prednisone taken daily for 4 days. A recurrence of oral mucositis 3 months later responded to 80 mg oral prednisone taken daily for 6 days.

“It’s not surprising that SARS-CoV-2 is yet another trigger for RIME,” said Anna Yasmine Kirkorian, MD, chief of the division of dermatology at Children’s National Hospital, Washington, who was asked to comment about the case report.

“The take-home message is for clinicians to be aware of this association and distinguish these patients from those with MIS-C, because patients with MIS-C require monitoring and urgent systemic treatment. RIME and MIS-C may potentially be distinguished clinically based on the nature of the mucositis (hemorrhagic and erosive in RIME, dry, cracked lips with ‘strawberry tongue’ in MIS-C) but more importantly patients with RIME lack laboratory evidence of severe systemic inflammation,” such as ESR, CRP, or ferritin, she said.

“A final interesting point in this article was the recurrence of mucositis in this patient, which could mean that recurrent mucositis/recurrent RIME might be yet another manifestation of ‘long-COVID’ (now called post-Acute Sequelae of SARS-CoV-2 infection) in some patients,” Dr. Kirkorian added. She noted that the American Academy of Dermatology–International League of Dermatologic Societies COVID-19 Dermatology Registry and articles like these “provide invaluable ‘hot off the presses’ information for clinicians who are facing the protean manifestations of a novel viral epidemic.”

The researchers reported having no financial disclosures.
 

[email protected]