Infectious Disease Practitioner

An FDA advisory panel lent their support Feb. 26 to a rapid clearance for Janssen/Johnson & Johnson’s COVID-19 vaccine.

The Food and Drug Administration (FDA) is expected to quickly provide an emergency use authorization (EUA) for the vaccine following the recommendation by the panel. The FDA’s Vaccines and Related Biological Products Advisory Committee voted 22-0 on this question: Based on the totality of scientific evidence available, do the benefits of the Johnson & Johnson COVID-19 Vaccine outweigh its risks for use in individuals 18 years of age and older?

The Johnson & Johnson vaccine is expected to offer more convenient dosing and be easier to distribute than the two rival products already available in the United States. Janssen’s vaccine is intended to be given in a single dose. In December, the FDA granted EUAs for the Pfizer/BioNTech and Moderna COVID-19 vaccines, which are each two-dose regimens.

Johnson & Johnson’s vaccine can be stored for at least 3 months at normal refrigerator temperatures of 2°C to 8°C (36°F to 46°F). Its shipping and storage fits into the existing medical supply infrastructure, the company said in its briefing materials for the FDA advisory committee meeting. In contrast, Pfizer’s vaccine is stored in ultracold freezers at temperatures between -80°C and -60°C (-112°F and -76°F), according to the Centers for Disease Control and Prevention. Moderna’s vaccine may be stored in a freezer between -25°C and -15°C (-13°F and 5°F).

But FDA advisers focused more in their deliberations on concerns about Janssen’s vaccine, including emerging reports of allergic reactions.

The advisers also discussed how patients might respond to the widely reported gap between Johnson & Johnson’s topline efficacy rates compared with rivals. The company’s initial unveiling last month of key results for its vaccine caused an initial wave of disappointment, with its overall efficacy against moderate-to-severe COVID-19 28 days postvaccination first reported at about 66% globally. By contrast, results for the Pfizer and Moderna vaccines suggest they have efficacy rates of 95% and 94%.

But in concluding, the advisers spoke of the Janssen vaccine as a much-needed tool to address the COVID-19 pandemic. The death toll in the United States attributed to the virus has reached 501,414, according to the World Health Organization.

“Despite the concerns that were raised during the discussion. I think what we have to keep in mind is that we’re still in the midst of this deadly pandemic,” said FDA adviser Archana Chatterjee, MD, PhD, from Rosalind Franklin University. “There is a shortage of vaccines that are currently authorized, and I think authorization of this vaccine will help meet the needs at the moment.”

The FDA is not bound to accept the recommendations of its advisers, but it often does so.

Anaphylaxis case

FDA advisers raised only a few questions for Johnson & Johnson and FDA staff ahead of their vote. The committee’s deliberations were less contentious and heated than had been during its December reviews of the Pfizer and Moderna vaccines. In those meetings, the panel voted 17-4, with one abstention, in favor of Pfizer’s vaccine and  20-0, with one abstention, on the Moderna vaccine.

“We are very comfortable now with the procedure, as well as the vaccines,” said Arnold Monto, MD, after the Feb. 26 vote on the Janssen vaccine. Dr. Monto, from the University of Michigan School of Public Health in Ann Arbor, has served as the chairman of the FDA panel through its review of all three COVID-19 vaccines.

Among the issues noted in the deliberations was the emergence of a concern about anaphylaxis with the vaccine.

This serious allergic reaction has been seen in people who have taken the Pfizer and Moderna vaccines. Before the week of the panel meeting, though, there had not been reports of anaphylaxis with the Johnson & Johnson vaccine, said Macaya Douoguih, MD, MPH, head of clinical development and medical affairs for Janssen/ Johnson & Johnson’s vaccines division.

However, on February 24, Johnson & Johnson received preliminary reports about two cases of severe allergic reaction from an open-label study in South Africa, with one of these being anaphylaxis, Dr. Douoguih said. The company will continue to closely monitor for these events as outlined in their pharmacovigilance plan, Dr. Douoguih said.

Federal health officials have sought to make clinicians aware of the rare risk for anaphylaxis with COVID vaccines, while reminding the public that this reaction can be managed.

The FDA had Tom Shimabukuro, MD, MPH, MBA, from the CDC, give an update on postmarketing surveillance for the Pfizer and Moderna vaccines as part of the review of the Johnson & Johnson application. Dr. Shimabukuro and CDC colleagues published a report in JAMA on February 14 that looked at an anaphylaxis case reported connected with COVID vaccines between December 14, 2020, and January 18, 2021.

The CDC identified 66 case reports received that met Brighton Collaboration case definition criteria for anaphylaxis (levels 1, 2, or 3): 47 following Pfizer/BioNTech vaccine, for a reporting rate of 4.7 cases/million doses administered, and 19 following Moderna vaccine, for a reporting rate of 2.5 cases/million doses administered, Dr. Shimabukuro and CDC colleagues wrote.

The CDC has published materials to help clinicians prepare for the possibility of this rare event, Dr. Shimabukuro told the FDA advisers.

“The take-home message here is that these are rare events and anaphylaxis, although clinically serious, is treatable,” Dr. Shimabukuro said.

At the conclusion of the meeting, FDA panelist Patrick Moore, MD, MPH, from the University of Pittsburgh in Pennsylvania, stressed the need to convey to the public that the COVID vaccines appear so far to be safe. Many people earlier had doubts about how the FDA could both safely and quickly review the applications for EUAs for these products.

“As of February 26, things are looking good. That could change tomorrow,” Dr. Moore said. But “this whole EUA process does seem to have worked, despite my own personal concerns about it.”

No second-class vaccines

The Johnson & Johnson vaccine, known as Ad26.COV2.S, is composed of a recombinant, replication-incompetent human adenovirus type 26 (Ad26) vector. It’s intended to encode a stabilized form of SARS-CoV-2 spike (S) protein. The Pfizer and Moderna vaccines use a different mechanism. They rely on mRNA.

The FDA advisers also discussed how patients might respond to the widely reported gap between Janssen’s topline efficacy rates compared with rivals. They urged against people parsing study details too finely and seeking to pick and choose their shots.

“It’s important that people do not think that one vaccine is better than another,” said FDA adviser H. Cody Meissner, MD, from Tufts University School of Medicine in Boston.

Dr. Monto agreed, noting that many people in the United States are still waiting for their turn to get COVID vaccines because of the limited early supply.

Trying to game the system to get one vaccine instead of another would not be wise. “In this environment, whatever you can get, get,” Dr. Monto said.

During an open public hearing, Sarah Christopherson, policy advocacy director of the National Women’s Health Network, said that press reports are fueling a damaging impression in the public that there are “first and second-class” vaccines.

“That has the potential to exacerbate existing mistrust” in vaccines, she said. “Public health authorities must address these perceptions head on.”

She urged against attempts to compare the Janssen vaccine to others, noting the potential effects of emerging variants of the virus.

“It’s difficult to make an apples-to-apples comparison between vaccines,” she said.

Johnson & Johnson’s efficacy results, which are lower than those of the mRNA vaccines, may be a reflection of the ways in which SARS-Co-V-2 is mutating and thus becoming more of a threat, according to the company. A key study of the new vaccine, involving about 44,000 people, coincided with the emergence of new SARS-CoV-2 variants, which were emerging in some of the countries where the pivotal COV3001 study was being conducted, the company said.

At least 14 days after vaccination, the Johnson & Johnson COVID vaccine efficacy (95% confidence interval) was 72.0% (58.2, 81.7) in the United States, 68.1% (48.8, 80.7) in Brazil, and 64.0% (41.2, 78.7) in South Africa.

Weakened standards?

Several researchers called on the FDA to maintain a critical attitude when assessing Johnson & Johnson’s application for the EUA, warning of a potential for a permanent erosion of agency rules due to hasty action on COVID vaccines.

They raised concerns about the FDA demanding too little in terms of follow-up studies on COVID vaccines and with persisting murkiness resulting in attempts to determine how well these treatments work beyond the initial study period.

“I worry about FDA lowering its approval standards,” said Peter Doshi, PhD, from The BMJ and a faculty member at the University of Maryland School of Medicine in Baltimore, during an open public hearing at the meeting.

“There’s a real urgency to stand back right now and look at the forest here, as well as the trees, and I urge the committee to consider the effects FDA decisions may have on the entire regulatory approval process,” Dr. Doshi said.

Dr. Doshi asked why Johnson & Johnson did not seek a standard full approval — a biologics license application (BLA) — instead of aiming for the lower bar of an EUA. The FDA already has allowed wide distribution of the Pfizer/BioNTech and Moderna vaccines through EUAs. That removes the sense of urgency that FDA faced last year in his view.

The FDA’s June 2020 guidance on the development of COVID vaccines had asked drugmakers to plan on following participants in COVID vaccine trials for “ideally at least one to two years.” Yet people who got placebo in Moderna and Pfizer trials already are being vaccinated, Dr. Doshi said. And Johnson & Johnson said in its presentation to the FDA that if the Ad26.COV2.S vaccine were granted an EUA, the COV3001 study design would be amended to “facilitate cross-over of placebo participants in all participating countries to receive one dose of active study vaccine as fast as operationally feasible.”

“I’m nervous about the prospect of there never being a COVID vaccine that meets the FDA’s approval standard” for a BLA instead of the more limited EUA, Dr. Doshi said.

Diana Zuckerman, PhD, president of the nonprofit National Center for Health Research, noted that the FDA’s subsequent guidance tailored for EUAs for COVID vaccines “drastically shortened” the follow-up time to a median of 2 months. Dr. Zuckerman said that a crossover design would be “a reasonable compromise, but only if the placebo group has at least 6 months of data.” Dr. Zuckerman opened her remarks in the open public hearing by saying she had inherited Johnson & Johnson stock, so was speaking at the meeting against her own financial interest.

“As soon as a vaccine is authorized, we start losing the placebo group. If FDA lets that happen, that’s a huge loss for public health and a huge loss of information about how we can all stay safe,” Dr. Zuckerman said.



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

An FDA advisory panel lent their support Feb. 26 to a rapid clearance for Janssen/Johnson & Johnson’s COVID-19 vaccine.

The Food and Drug Administration (FDA) is expected to quickly provide an emergency use authorization (EUA) for the vaccine following the recommendation by the panel. The FDA’s Vaccines and Related Biological Products Advisory Committee voted 22-0 on this question: Based on the totality of scientific evidence available, do the benefits of the Johnson & Johnson COVID-19 Vaccine outweigh its risks for use in individuals 18 years of age and older?

The Johnson & Johnson vaccine is expected to offer more convenient dosing and be easier to distribute than the two rival products already available in the United States. Janssen’s vaccine is intended to be given in a single dose. In December, the FDA granted EUAs for the Pfizer/BioNTech and Moderna COVID-19 vaccines, which are each two-dose regimens.

Johnson & Johnson’s vaccine can be stored for at least 3 months at normal refrigerator temperatures of 2°C to 8°C (36°F to 46°F). Its shipping and storage fits into the existing medical supply infrastructure, the company said in its briefing materials for the FDA advisory committee meeting. In contrast, Pfizer’s vaccine is stored in ultracold freezers at temperatures between -80°C and -60°C (-112°F and -76°F), according to the Centers for Disease Control and Prevention. Moderna’s vaccine may be stored in a freezer between -25°C and -15°C (-13°F and 5°F).

But FDA advisers focused more in their deliberations on concerns about Janssen’s vaccine, including emerging reports of allergic reactions.

The advisers also discussed how patients might respond to the widely reported gap between Johnson & Johnson’s topline efficacy rates compared with rivals. The company’s initial unveiling last month of key results for its vaccine caused an initial wave of disappointment, with its overall efficacy against moderate-to-severe COVID-19 28 days postvaccination first reported at about 66% globally. By contrast, results for the Pfizer and Moderna vaccines suggest they have efficacy rates of 95% and 94%.

But in concluding, the advisers spoke of the Janssen vaccine as a much-needed tool to address the COVID-19 pandemic. The death toll in the United States attributed to the virus has reached 501,414, according to the World Health Organization.

“Despite the concerns that were raised during the discussion. I think what we have to keep in mind is that we’re still in the midst of this deadly pandemic,” said FDA adviser Archana Chatterjee, MD, PhD, from Rosalind Franklin University. “There is a shortage of vaccines that are currently authorized, and I think authorization of this vaccine will help meet the needs at the moment.”

The FDA is not bound to accept the recommendations of its advisers, but it often does so.

Anaphylaxis case

FDA advisers raised only a few questions for Johnson & Johnson and FDA staff ahead of their vote. The committee’s deliberations were less contentious and heated than had been during its December reviews of the Pfizer and Moderna vaccines. In those meetings, the panel voted 17-4, with one abstention, in favor of Pfizer’s vaccine and  20-0, with one abstention, on the Moderna vaccine.

“We are very comfortable now with the procedure, as well as the vaccines,” said Arnold Monto, MD, after the Feb. 26 vote on the Janssen vaccine. Dr. Monto, from the University of Michigan School of Public Health in Ann Arbor, has served as the chairman of the FDA panel through its review of all three COVID-19 vaccines.

Among the issues noted in the deliberations was the emergence of a concern about anaphylaxis with the vaccine.

This serious allergic reaction has been seen in people who have taken the Pfizer and Moderna vaccines. Before the week of the panel meeting, though, there had not been reports of anaphylaxis with the Johnson & Johnson vaccine, said Macaya Douoguih, MD, MPH, head of clinical development and medical affairs for Janssen/ Johnson & Johnson’s vaccines division.

However, on February 24, Johnson & Johnson received preliminary reports about two cases of severe allergic reaction from an open-label study in South Africa, with one of these being anaphylaxis, Dr. Douoguih said. The company will continue to closely monitor for these events as outlined in their pharmacovigilance plan, Dr. Douoguih said.

Federal health officials have sought to make clinicians aware of the rare risk for anaphylaxis with COVID vaccines, while reminding the public that this reaction can be managed.

The FDA had Tom Shimabukuro, MD, MPH, MBA, from the CDC, give an update on postmarketing surveillance for the Pfizer and Moderna vaccines as part of the review of the Johnson & Johnson application. Dr. Shimabukuro and CDC colleagues published a report in JAMA on February 14 that looked at an anaphylaxis case reported connected with COVID vaccines between December 14, 2020, and January 18, 2021.

The CDC identified 66 case reports received that met Brighton Collaboration case definition criteria for anaphylaxis (levels 1, 2, or 3): 47 following Pfizer/BioNTech vaccine, for a reporting rate of 4.7 cases/million doses administered, and 19 following Moderna vaccine, for a reporting rate of 2.5 cases/million doses administered, Dr. Shimabukuro and CDC colleagues wrote.

The CDC has published materials to help clinicians prepare for the possibility of this rare event, Dr. Shimabukuro told the FDA advisers.

“The take-home message here is that these are rare events and anaphylaxis, although clinically serious, is treatable,” Dr. Shimabukuro said.

At the conclusion of the meeting, FDA panelist Patrick Moore, MD, MPH, from the University of Pittsburgh in Pennsylvania, stressed the need to convey to the public that the COVID vaccines appear so far to be safe. Many people earlier had doubts about how the FDA could both safely and quickly review the applications for EUAs for these products.

“As of February 26, things are looking good. That could change tomorrow,” Dr. Moore said. But “this whole EUA process does seem to have worked, despite my own personal concerns about it.”

No second-class vaccines

The Johnson & Johnson vaccine, known as Ad26.COV2.S, is composed of a recombinant, replication-incompetent human adenovirus type 26 (Ad26) vector. It’s intended to encode a stabilized form of SARS-CoV-2 spike (S) protein. The Pfizer and Moderna vaccines use a different mechanism. They rely on mRNA.

The FDA advisers also discussed how patients might respond to the widely reported gap between Janssen’s topline efficacy rates compared with rivals. They urged against people parsing study details too finely and seeking to pick and choose their shots.

“It’s important that people do not think that one vaccine is better than another,” said FDA adviser H. Cody Meissner, MD, from Tufts University School of Medicine in Boston.

Dr. Monto agreed, noting that many people in the United States are still waiting for their turn to get COVID vaccines because of the limited early supply.

Trying to game the system to get one vaccine instead of another would not be wise. “In this environment, whatever you can get, get,” Dr. Monto said.

During an open public hearing, Sarah Christopherson, policy advocacy director of the National Women’s Health Network, said that press reports are fueling a damaging impression in the public that there are “first and second-class” vaccines.

“That has the potential to exacerbate existing mistrust” in vaccines, she said. “Public health authorities must address these perceptions head on.”

She urged against attempts to compare the Janssen vaccine to others, noting the potential effects of emerging variants of the virus.

“It’s difficult to make an apples-to-apples comparison between vaccines,” she said.

Johnson & Johnson’s efficacy results, which are lower than those of the mRNA vaccines, may be a reflection of the ways in which SARS-Co-V-2 is mutating and thus becoming more of a threat, according to the company. A key study of the new vaccine, involving about 44,000 people, coincided with the emergence of new SARS-CoV-2 variants, which were emerging in some of the countries where the pivotal COV3001 study was being conducted, the company said.

At least 14 days after vaccination, the Johnson & Johnson COVID vaccine efficacy (95% confidence interval) was 72.0% (58.2, 81.7) in the United States, 68.1% (48.8, 80.7) in Brazil, and 64.0% (41.2, 78.7) in South Africa.

Weakened standards?

Several researchers called on the FDA to maintain a critical attitude when assessing Johnson & Johnson’s application for the EUA, warning of a potential for a permanent erosion of agency rules due to hasty action on COVID vaccines.

They raised concerns about the FDA demanding too little in terms of follow-up studies on COVID vaccines and with persisting murkiness resulting in attempts to determine how well these treatments work beyond the initial study period.

“I worry about FDA lowering its approval standards,” said Peter Doshi, PhD, from The BMJ and a faculty member at the University of Maryland School of Medicine in Baltimore, during an open public hearing at the meeting.

“There’s a real urgency to stand back right now and look at the forest here, as well as the trees, and I urge the committee to consider the effects FDA decisions may have on the entire regulatory approval process,” Dr. Doshi said.

Dr. Doshi asked why Johnson & Johnson did not seek a standard full approval — a biologics license application (BLA) — instead of aiming for the lower bar of an EUA. The FDA already has allowed wide distribution of the Pfizer/BioNTech and Moderna vaccines through EUAs. That removes the sense of urgency that FDA faced last year in his view.

The FDA’s June 2020 guidance on the development of COVID vaccines had asked drugmakers to plan on following participants in COVID vaccine trials for “ideally at least one to two years.” Yet people who got placebo in Moderna and Pfizer trials already are being vaccinated, Dr. Doshi said. And Johnson & Johnson said in its presentation to the FDA that if the Ad26.COV2.S vaccine were granted an EUA, the COV3001 study design would be amended to “facilitate cross-over of placebo participants in all participating countries to receive one dose of active study vaccine as fast as operationally feasible.”

“I’m nervous about the prospect of there never being a COVID vaccine that meets the FDA’s approval standard” for a BLA instead of the more limited EUA, Dr. Doshi said.

Diana Zuckerman, PhD, president of the nonprofit National Center for Health Research, noted that the FDA’s subsequent guidance tailored for EUAs for COVID vaccines “drastically shortened” the follow-up time to a median of 2 months. Dr. Zuckerman said that a crossover design would be “a reasonable compromise, but only if the placebo group has at least 6 months of data.” Dr. Zuckerman opened her remarks in the open public hearing by saying she had inherited Johnson & Johnson stock, so was speaking at the meeting against her own financial interest.

“As soon as a vaccine is authorized, we start losing the placebo group. If FDA lets that happen, that’s a huge loss for public health and a huge loss of information about how we can all stay safe,” Dr. Zuckerman said.



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

An FDA advisory panel lent their support Feb. 26 to a rapid clearance for Janssen/Johnson & Johnson’s COVID-19 vaccine.

The Food and Drug Administration (FDA) is expected to quickly provide an emergency use authorization (EUA) for the vaccine following the recommendation by the panel. The FDA’s Vaccines and Related Biological Products Advisory Committee voted 22-0 on this question: Based on the totality of scientific evidence available, do the benefits of the Johnson & Johnson COVID-19 Vaccine outweigh its risks for use in individuals 18 years of age and older?

The Johnson & Johnson vaccine is expected to offer more convenient dosing and be easier to distribute than the two rival products already available in the United States. Janssen’s vaccine is intended to be given in a single dose. In December, the FDA granted EUAs for the Pfizer/BioNTech and Moderna COVID-19 vaccines, which are each two-dose regimens.

Johnson & Johnson’s vaccine can be stored for at least 3 months at normal refrigerator temperatures of 2°C to 8°C (36°F to 46°F). Its shipping and storage fits into the existing medical supply infrastructure, the company said in its briefing materials for the FDA advisory committee meeting. In contrast, Pfizer’s vaccine is stored in ultracold freezers at temperatures between -80°C and -60°C (-112°F and -76°F), according to the Centers for Disease Control and Prevention. Moderna’s vaccine may be stored in a freezer between -25°C and -15°C (-13°F and 5°F).

But FDA advisers focused more in their deliberations on concerns about Janssen’s vaccine, including emerging reports of allergic reactions.

The advisers also discussed how patients might respond to the widely reported gap between Johnson & Johnson’s topline efficacy rates compared with rivals. The company’s initial unveiling last month of key results for its vaccine caused an initial wave of disappointment, with its overall efficacy against moderate-to-severe COVID-19 28 days postvaccination first reported at about 66% globally. By contrast, results for the Pfizer and Moderna vaccines suggest they have efficacy rates of 95% and 94%.

But in concluding, the advisers spoke of the Janssen vaccine as a much-needed tool to address the COVID-19 pandemic. The death toll in the United States attributed to the virus has reached 501,414, according to the World Health Organization.

“Despite the concerns that were raised during the discussion. I think what we have to keep in mind is that we’re still in the midst of this deadly pandemic,” said FDA adviser Archana Chatterjee, MD, PhD, from Rosalind Franklin University. “There is a shortage of vaccines that are currently authorized, and I think authorization of this vaccine will help meet the needs at the moment.”

The FDA is not bound to accept the recommendations of its advisers, but it often does so.

Anaphylaxis case

FDA advisers raised only a few questions for Johnson & Johnson and FDA staff ahead of their vote. The committee’s deliberations were less contentious and heated than had been during its December reviews of the Pfizer and Moderna vaccines. In those meetings, the panel voted 17-4, with one abstention, in favor of Pfizer’s vaccine and  20-0, with one abstention, on the Moderna vaccine.

“We are very comfortable now with the procedure, as well as the vaccines,” said Arnold Monto, MD, after the Feb. 26 vote on the Janssen vaccine. Dr. Monto, from the University of Michigan School of Public Health in Ann Arbor, has served as the chairman of the FDA panel through its review of all three COVID-19 vaccines.

Among the issues noted in the deliberations was the emergence of a concern about anaphylaxis with the vaccine.

This serious allergic reaction has been seen in people who have taken the Pfizer and Moderna vaccines. Before the week of the panel meeting, though, there had not been reports of anaphylaxis with the Johnson & Johnson vaccine, said Macaya Douoguih, MD, MPH, head of clinical development and medical affairs for Janssen/ Johnson & Johnson’s vaccines division.

However, on February 24, Johnson & Johnson received preliminary reports about two cases of severe allergic reaction from an open-label study in South Africa, with one of these being anaphylaxis, Dr. Douoguih said. The company will continue to closely monitor for these events as outlined in their pharmacovigilance plan, Dr. Douoguih said.

Federal health officials have sought to make clinicians aware of the rare risk for anaphylaxis with COVID vaccines, while reminding the public that this reaction can be managed.

The FDA had Tom Shimabukuro, MD, MPH, MBA, from the CDC, give an update on postmarketing surveillance for the Pfizer and Moderna vaccines as part of the review of the Johnson & Johnson application. Dr. Shimabukuro and CDC colleagues published a report in JAMA on February 14 that looked at an anaphylaxis case reported connected with COVID vaccines between December 14, 2020, and January 18, 2021.

The CDC identified 66 case reports received that met Brighton Collaboration case definition criteria for anaphylaxis (levels 1, 2, or 3): 47 following Pfizer/BioNTech vaccine, for a reporting rate of 4.7 cases/million doses administered, and 19 following Moderna vaccine, for a reporting rate of 2.5 cases/million doses administered, Dr. Shimabukuro and CDC colleagues wrote.

The CDC has published materials to help clinicians prepare for the possibility of this rare event, Dr. Shimabukuro told the FDA advisers.

“The take-home message here is that these are rare events and anaphylaxis, although clinically serious, is treatable,” Dr. Shimabukuro said.

At the conclusion of the meeting, FDA panelist Patrick Moore, MD, MPH, from the University of Pittsburgh in Pennsylvania, stressed the need to convey to the public that the COVID vaccines appear so far to be safe. Many people earlier had doubts about how the FDA could both safely and quickly review the applications for EUAs for these products.

“As of February 26, things are looking good. That could change tomorrow,” Dr. Moore said. But “this whole EUA process does seem to have worked, despite my own personal concerns about it.”

No second-class vaccines

The Johnson & Johnson vaccine, known as Ad26.COV2.S, is composed of a recombinant, replication-incompetent human adenovirus type 26 (Ad26) vector. It’s intended to encode a stabilized form of SARS-CoV-2 spike (S) protein. The Pfizer and Moderna vaccines use a different mechanism. They rely on mRNA.

The FDA advisers also discussed how patients might respond to the widely reported gap between Janssen’s topline efficacy rates compared with rivals. They urged against people parsing study details too finely and seeking to pick and choose their shots.

“It’s important that people do not think that one vaccine is better than another,” said FDA adviser H. Cody Meissner, MD, from Tufts University School of Medicine in Boston.

Dr. Monto agreed, noting that many people in the United States are still waiting for their turn to get COVID vaccines because of the limited early supply.

Trying to game the system to get one vaccine instead of another would not be wise. “In this environment, whatever you can get, get,” Dr. Monto said.

During an open public hearing, Sarah Christopherson, policy advocacy director of the National Women’s Health Network, said that press reports are fueling a damaging impression in the public that there are “first and second-class” vaccines.

“That has the potential to exacerbate existing mistrust” in vaccines, she said. “Public health authorities must address these perceptions head on.”

She urged against attempts to compare the Janssen vaccine to others, noting the potential effects of emerging variants of the virus.

“It’s difficult to make an apples-to-apples comparison between vaccines,” she said.

Johnson & Johnson’s efficacy results, which are lower than those of the mRNA vaccines, may be a reflection of the ways in which SARS-Co-V-2 is mutating and thus becoming more of a threat, according to the company. A key study of the new vaccine, involving about 44,000 people, coincided with the emergence of new SARS-CoV-2 variants, which were emerging in some of the countries where the pivotal COV3001 study was being conducted, the company said.

At least 14 days after vaccination, the Johnson & Johnson COVID vaccine efficacy (95% confidence interval) was 72.0% (58.2, 81.7) in the United States, 68.1% (48.8, 80.7) in Brazil, and 64.0% (41.2, 78.7) in South Africa.

Weakened standards?

Several researchers called on the FDA to maintain a critical attitude when assessing Johnson & Johnson’s application for the EUA, warning of a potential for a permanent erosion of agency rules due to hasty action on COVID vaccines.

They raised concerns about the FDA demanding too little in terms of follow-up studies on COVID vaccines and with persisting murkiness resulting in attempts to determine how well these treatments work beyond the initial study period.

“I worry about FDA lowering its approval standards,” said Peter Doshi, PhD, from The BMJ and a faculty member at the University of Maryland School of Medicine in Baltimore, during an open public hearing at the meeting.

“There’s a real urgency to stand back right now and look at the forest here, as well as the trees, and I urge the committee to consider the effects FDA decisions may have on the entire regulatory approval process,” Dr. Doshi said.

Dr. Doshi asked why Johnson & Johnson did not seek a standard full approval — a biologics license application (BLA) — instead of aiming for the lower bar of an EUA. The FDA already has allowed wide distribution of the Pfizer/BioNTech and Moderna vaccines through EUAs. That removes the sense of urgency that FDA faced last year in his view.

The FDA’s June 2020 guidance on the development of COVID vaccines had asked drugmakers to plan on following participants in COVID vaccine trials for “ideally at least one to two years.” Yet people who got placebo in Moderna and Pfizer trials already are being vaccinated, Dr. Doshi said. And Johnson & Johnson said in its presentation to the FDA that if the Ad26.COV2.S vaccine were granted an EUA, the COV3001 study design would be amended to “facilitate cross-over of placebo participants in all participating countries to receive one dose of active study vaccine as fast as operationally feasible.”

“I’m nervous about the prospect of there never being a COVID vaccine that meets the FDA’s approval standard” for a BLA instead of the more limited EUA, Dr. Doshi said.

Diana Zuckerman, PhD, president of the nonprofit National Center for Health Research, noted that the FDA’s subsequent guidance tailored for EUAs for COVID vaccines “drastically shortened” the follow-up time to a median of 2 months. Dr. Zuckerman said that a crossover design would be “a reasonable compromise, but only if the placebo group has at least 6 months of data.” Dr. Zuckerman opened her remarks in the open public hearing by saying she had inherited Johnson & Johnson stock, so was speaking at the meeting against her own financial interest.

“As soon as a vaccine is authorized, we start losing the placebo group. If FDA lets that happen, that’s a huge loss for public health and a huge loss of information about how we can all stay safe,” Dr. Zuckerman said.



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

Two research teams have identified a new coronavirus variant in New York City and across the Northeast that could evade natural immune responses and some monoclonal antibody treatments, according to CNN.

Jae Young Ju/iStock/Getty Images Plus

The variant, called B.1.526, has appeared in diverse neighborhoods in New York City and is “scattered in the Northeast,” the researchers said.

“We observed a steady increase in the detection rate from late December to mid-February, with an alarming rise to 12.7% in the past two weeks,” researchers from Columbia University Medical Center wrote in a report, which was published as a preprint Feb. 25. 

On Feb. 22, the team released another preprint about the B.1.1.7 and B.1.351 variants first identified in the United Kingdom and South Africa, respectively, which also mentions the B.1.526 variant in the U.S. Neither report has been peer reviewed.

Viruses mutate often, and several coronavirus variants have been identified and followed during the pandemic. Not all mutations are significant or are necessarily more contagious or dangerous. Researchers have been tracking the B.1.526 variant in the U.S. to find out if there are significant mutations that could be a cause for concern.

In the most recent preprints, the variant appears to have the same mutation found in B.1.351, called E484K, which may allow the virus to evade vaccines and the body’s natural immune response. The E484K mutation has shown up in at least 59 lines of the coronavirus, the research team said. That means the virus is evolving independently across the country and world, which could give the virus an advantage.

“A concern is that it might be beginning to overtake other strains, just like the U.K. and South African variants,” David Ho, MD, the lead study author and director of the Aaron Diamond AIDS Research Center at Columbia, told CNN.

“However, we don’t have enough data to firm up this point now,” he said.

In a separate preprint posted Feb. 23, a research team at the California Institute of Technology developed a software tool that noticed the rise of B.1.526 in the New York region. The preprint hasn’t yet been peer reviewed.

“It appears that the frequency of lineage B.1.526 has increased rapidly in New York,” they wrote.

Both teams also reported on another variant, called B.1.427/B.1.429, which appears to be increasing in California. The variant could be more contagious and cause more severe disease, they said, but the research is still in the early stages.

Researchers at the University of California, San Francisco, have tested virus samples from recent outbreaks in California and also found that the variant is becoming more common. The variant didn’t appear in samples from September but was in half of the samples by late January. It has a different pattern of mutations than other variants, and one called L452R may affect the spike protein on the virus and allow it attach to cells more easily.

“Our data shows that this is likely the key mutation that makes this variant more infectious,” Charles Chiu, MD, associate director of the clinical microbiology lab at UCSF, told CNN.

The team also noticed that patients with a B.1.427/B.1.429 infection had more severe COVID-19 cases and needed more oxygen, CNN reported. The team plans to post a preprint once public health officials in San Francisco review the report.

Right now, the CDC provides public data for three variants: B.1.1.7, B.1.351, and P.1, which was first identified in Brazil. The U.S. has reported 1,881 B.1.1.7 cases across 45 states, 46 B.1.351 cases in 14 states, and five P.1 cases in four states, according to a CDC tally as of Feb. 23.

At the moment, lab officials aren’t able to tell patients or doctors whether someone has been infected by a variant, according to Kaiser Health News. High-level labs conduct genomic sequencing on samples and aren’t able to communicate information back to individual people.

But the Association of Public Health Laboratories and public health officials in several states are pushing for federal authorization of a test that could sequence the full genome and notify doctors. The test could be available in coming weeks, the news outlet reported.

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

Two research teams have identified a new coronavirus variant in New York City and across the Northeast that could evade natural immune responses and some monoclonal antibody treatments, according to CNN.

Jae Young Ju/iStock/Getty Images Plus

The variant, called B.1.526, has appeared in diverse neighborhoods in New York City and is “scattered in the Northeast,” the researchers said.

“We observed a steady increase in the detection rate from late December to mid-February, with an alarming rise to 12.7% in the past two weeks,” researchers from Columbia University Medical Center wrote in a report, which was published as a preprint Feb. 25. 

On Feb. 22, the team released another preprint about the B.1.1.7 and B.1.351 variants first identified in the United Kingdom and South Africa, respectively, which also mentions the B.1.526 variant in the U.S. Neither report has been peer reviewed.

Viruses mutate often, and several coronavirus variants have been identified and followed during the pandemic. Not all mutations are significant or are necessarily more contagious or dangerous. Researchers have been tracking the B.1.526 variant in the U.S. to find out if there are significant mutations that could be a cause for concern.

In the most recent preprints, the variant appears to have the same mutation found in B.1.351, called E484K, which may allow the virus to evade vaccines and the body’s natural immune response. The E484K mutation has shown up in at least 59 lines of the coronavirus, the research team said. That means the virus is evolving independently across the country and world, which could give the virus an advantage.

“A concern is that it might be beginning to overtake other strains, just like the U.K. and South African variants,” David Ho, MD, the lead study author and director of the Aaron Diamond AIDS Research Center at Columbia, told CNN.

“However, we don’t have enough data to firm up this point now,” he said.

In a separate preprint posted Feb. 23, a research team at the California Institute of Technology developed a software tool that noticed the rise of B.1.526 in the New York region. The preprint hasn’t yet been peer reviewed.

“It appears that the frequency of lineage B.1.526 has increased rapidly in New York,” they wrote.

Both teams also reported on another variant, called B.1.427/B.1.429, which appears to be increasing in California. The variant could be more contagious and cause more severe disease, they said, but the research is still in the early stages.

Researchers at the University of California, San Francisco, have tested virus samples from recent outbreaks in California and also found that the variant is becoming more common. The variant didn’t appear in samples from September but was in half of the samples by late January. It has a different pattern of mutations than other variants, and one called L452R may affect the spike protein on the virus and allow it attach to cells more easily.

“Our data shows that this is likely the key mutation that makes this variant more infectious,” Charles Chiu, MD, associate director of the clinical microbiology lab at UCSF, told CNN.

The team also noticed that patients with a B.1.427/B.1.429 infection had more severe COVID-19 cases and needed more oxygen, CNN reported. The team plans to post a preprint once public health officials in San Francisco review the report.

Right now, the CDC provides public data for three variants: B.1.1.7, B.1.351, and P.1, which was first identified in Brazil. The U.S. has reported 1,881 B.1.1.7 cases across 45 states, 46 B.1.351 cases in 14 states, and five P.1 cases in four states, according to a CDC tally as of Feb. 23.

At the moment, lab officials aren’t able to tell patients or doctors whether someone has been infected by a variant, according to Kaiser Health News. High-level labs conduct genomic sequencing on samples and aren’t able to communicate information back to individual people.

But the Association of Public Health Laboratories and public health officials in several states are pushing for federal authorization of a test that could sequence the full genome and notify doctors. The test could be available in coming weeks, the news outlet reported.

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

Two research teams have identified a new coronavirus variant in New York City and across the Northeast that could evade natural immune responses and some monoclonal antibody treatments, according to CNN.

Jae Young Ju/iStock/Getty Images Plus

The variant, called B.1.526, has appeared in diverse neighborhoods in New York City and is “scattered in the Northeast,” the researchers said.

“We observed a steady increase in the detection rate from late December to mid-February, with an alarming rise to 12.7% in the past two weeks,” researchers from Columbia University Medical Center wrote in a report, which was published as a preprint Feb. 25. 

On Feb. 22, the team released another preprint about the B.1.1.7 and B.1.351 variants first identified in the United Kingdom and South Africa, respectively, which also mentions the B.1.526 variant in the U.S. Neither report has been peer reviewed.

Viruses mutate often, and several coronavirus variants have been identified and followed during the pandemic. Not all mutations are significant or are necessarily more contagious or dangerous. Researchers have been tracking the B.1.526 variant in the U.S. to find out if there are significant mutations that could be a cause for concern.

In the most recent preprints, the variant appears to have the same mutation found in B.1.351, called E484K, which may allow the virus to evade vaccines and the body’s natural immune response. The E484K mutation has shown up in at least 59 lines of the coronavirus, the research team said. That means the virus is evolving independently across the country and world, which could give the virus an advantage.

“A concern is that it might be beginning to overtake other strains, just like the U.K. and South African variants,” David Ho, MD, the lead study author and director of the Aaron Diamond AIDS Research Center at Columbia, told CNN.

“However, we don’t have enough data to firm up this point now,” he said.

In a separate preprint posted Feb. 23, a research team at the California Institute of Technology developed a software tool that noticed the rise of B.1.526 in the New York region. The preprint hasn’t yet been peer reviewed.

“It appears that the frequency of lineage B.1.526 has increased rapidly in New York,” they wrote.

Both teams also reported on another variant, called B.1.427/B.1.429, which appears to be increasing in California. The variant could be more contagious and cause more severe disease, they said, but the research is still in the early stages.

Researchers at the University of California, San Francisco, have tested virus samples from recent outbreaks in California and also found that the variant is becoming more common. The variant didn’t appear in samples from September but was in half of the samples by late January. It has a different pattern of mutations than other variants, and one called L452R may affect the spike protein on the virus and allow it attach to cells more easily.

“Our data shows that this is likely the key mutation that makes this variant more infectious,” Charles Chiu, MD, associate director of the clinical microbiology lab at UCSF, told CNN.

The team also noticed that patients with a B.1.427/B.1.429 infection had more severe COVID-19 cases and needed more oxygen, CNN reported. The team plans to post a preprint once public health officials in San Francisco review the report.

Right now, the CDC provides public data for three variants: B.1.1.7, B.1.351, and P.1, which was first identified in Brazil. The U.S. has reported 1,881 B.1.1.7 cases across 45 states, 46 B.1.351 cases in 14 states, and five P.1 cases in four states, according to a CDC tally as of Feb. 23.

At the moment, lab officials aren’t able to tell patients or doctors whether someone has been infected by a variant, according to Kaiser Health News. High-level labs conduct genomic sequencing on samples and aren’t able to communicate information back to individual people.

But the Association of Public Health Laboratories and public health officials in several states are pushing for federal authorization of a test that could sequence the full genome and notify doctors. The test could be available in coming weeks, the news outlet reported.

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

About half of 148 patients hospitalized with COVID-19 infection and elevated troponin levels had at least some evidence of myocardial injury on cardiac magnetic resonance (CMR) imaging 2 months later, a new study shows.

“Our results demonstrate that in this subset of patients surviving severe COVID-19 and with troponin elevation, ongoing localized myocardial inflammation, whilst less frequent than previously reported, remains present in a proportion of patients and may represent an emerging issue of clinical relevance,” wrote Marianna Fontana, MD, PhD, of University College London, and colleagues.

The cardiac abnormalities identified were classified as nonischemic (including “myocarditis-like” late gadolinium enhancement [LGE]) in 26% of the cohort; as related to ischemic heart disease (infarction or inducible ischemia) in 22%; and as dual pathology in 6%.

Left ventricular (LV) function was normal in 89% of the 148 patients. In the 17 patients (11%) with LV dysfunction, only four had an ejection fraction below 35%. Of the nine patients whose LV dysfunction was related to myocardial infarction, six had a known history of ischemic heart disease.

European Heart Journal

Glass half full

Taking a “glass half full” approach, co–senior author Graham D. Cole, MD, PhD, noted on Twitter that nearly half the patients had no major cardiac abnormalities on CMR just 2 months after a bout with troponin-positive COVID-19.

“We think this is important: Even in a group who had been very sick with raised troponin, it was common to find no evidence of heart damage,” said Dr. Cole, of the Royal Free London NHS Foundation Trust.

“We believe our data challenge the hypothesis that chronic inflammation, diffuse fibrosis, or long-term LV dysfunction is a dominant feature in those surviving COVID-19,” the investigators concluded in their report.

In an interview, Dr. Fontana explained further: “It has been reported in an early ‘pathfinder’ study that two-thirds of patients recovered from COVID-19 had CMR evidence of abnormal findings with a high incidence of elevated T1 and T2 in keeping with diffuse fibrosis and edema. Our findings with a larger, multicenter study and better controls show low rates of heart impairment and much less ongoing inflammation, which is reassuring.”

She also noted that the different patterns of injury suggest that different mechanisms are at play, including the possibility that “at least some of the found damage might have been preexisting, because people with heart damage are more likely to get severe disease.”

The investigators, including first author Tushar Kotecha, MBChB, PhD, of the Royal Free London NHS Foundation Trust, also noted that myocarditis-like injury was limited to three or fewer myocardial segments in 88% of cases with no associated ventricular dysfunction, and that biventricular function was no different than in those without myocarditis.

“We use the word ‘myocarditis-like’ but we don’t have histology,” Dr. Fontana said. “Our group actually suspects a lot of this will be microvascular clotting (microangiopathic thrombosis). This is exciting, as newer anticoagulation strategies – for example, those being tried in RECOVERY – may have benefit.”

Aloke V. Finn, MD, of the CVPath Institute in Gaithersburg, Md., wishes researchers would stop using the term myocarditis altogether to describe clinical or imaging findings in COVID-19.

“MRI can’t diagnose myocarditis. It is a specific diagnosis that requires, ideally, histology, as the investigators acknowledged,” Dr. Finn said in an interview.

His group at CVPath recently published data showing pathologic evidence of myocarditis after SARS-CoV-2 infection, as reported by theheart.org | Medscape Cardiology.

“As a clinician, when I think of myocarditis, I look at the echo and an LV gram, and I see if there is a wall motion abnormality and troponin elevation, but with normal coronary arteries. And if all that is there, then I think about myocarditis in my differential diagnosis,” he said. “But in most of these cases, as the authors rightly point out, most patients did not have what is necessary to really entertain a diagnosis of myocarditis.”

He agreed with Dr. Fontana’s suggestion that what the CMR might be picking up in these survivors is microthrombi, as his group saw in their recent autopsy study.

“It’s very possible these findings are concordant with the recent autopsy studies done by my group and others in terms of detecting the presence of microthrombi, but we don’t know this for certain because no one has ever studied this entity before in the clinic and we don’t really know how microthrombi might appear on CMR.”
 

Largest study to date

The 148 participants (mean age, 64 years; 70% male) in the largest study to date to investigate convalescing COVID-19 patients who had elevated troponins – something identified early in the pandemic as a risk factor for worse outcomes in COVID-19 – were treated at one of six hospitals in London.

Patients who had abnormal troponin levels were offered an MRI scan of the heart after discharge and were compared with those from a control group of patients who had not had COVID-19 and with 40 healthy volunteers.

Median length of stay was 9 days, and 32% of patients required ventilatory support in the intensive care unit.

Just over half the patients (57%) had hypertension, 7% had had a previous myocardial infarction, 34% had diabetes, 46% had hypercholesterolemia, and 24% were smokers. Mean body mass index was 28.5 kg/m².

CMR follow-up was conducted a median of 68 days after confirmation of a COVID-19 diagnosis.

On Twitter, Dr. Cole noted that the findings are subject to both survivor bias and referral bias. “We didn’t scan frail patients where the clinician felt [CMR] was unlikely to inform management.”

The findings, said Dr. Fontana, “say nothing about what happens to people who are not hospitalized with COVID, or those who are hospitalized but without elevated troponin.”

What they do offer, particularly if replicated, is a way forward in identifying patients at higher or lower risk for long-term sequelae and inform strategies that could improve outcomes, she added.

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

About half of 148 patients hospitalized with COVID-19 infection and elevated troponin levels had at least some evidence of myocardial injury on cardiac magnetic resonance (CMR) imaging 2 months later, a new study shows.

“Our results demonstrate that in this subset of patients surviving severe COVID-19 and with troponin elevation, ongoing localized myocardial inflammation, whilst less frequent than previously reported, remains present in a proportion of patients and may represent an emerging issue of clinical relevance,” wrote Marianna Fontana, MD, PhD, of University College London, and colleagues.

The cardiac abnormalities identified were classified as nonischemic (including “myocarditis-like” late gadolinium enhancement [LGE]) in 26% of the cohort; as related to ischemic heart disease (infarction or inducible ischemia) in 22%; and as dual pathology in 6%.

Left ventricular (LV) function was normal in 89% of the 148 patients. In the 17 patients (11%) with LV dysfunction, only four had an ejection fraction below 35%. Of the nine patients whose LV dysfunction was related to myocardial infarction, six had a known history of ischemic heart disease.

European Heart Journal

Glass half full

Taking a “glass half full” approach, co–senior author Graham D. Cole, MD, PhD, noted on Twitter that nearly half the patients had no major cardiac abnormalities on CMR just 2 months after a bout with troponin-positive COVID-19.

“We think this is important: Even in a group who had been very sick with raised troponin, it was common to find no evidence of heart damage,” said Dr. Cole, of the Royal Free London NHS Foundation Trust.

“We believe our data challenge the hypothesis that chronic inflammation, diffuse fibrosis, or long-term LV dysfunction is a dominant feature in those surviving COVID-19,” the investigators concluded in their report.

In an interview, Dr. Fontana explained further: “It has been reported in an early ‘pathfinder’ study that two-thirds of patients recovered from COVID-19 had CMR evidence of abnormal findings with a high incidence of elevated T1 and T2 in keeping with diffuse fibrosis and edema. Our findings with a larger, multicenter study and better controls show low rates of heart impairment and much less ongoing inflammation, which is reassuring.”

She also noted that the different patterns of injury suggest that different mechanisms are at play, including the possibility that “at least some of the found damage might have been preexisting, because people with heart damage are more likely to get severe disease.”

The investigators, including first author Tushar Kotecha, MBChB, PhD, of the Royal Free London NHS Foundation Trust, also noted that myocarditis-like injury was limited to three or fewer myocardial segments in 88% of cases with no associated ventricular dysfunction, and that biventricular function was no different than in those without myocarditis.

“We use the word ‘myocarditis-like’ but we don’t have histology,” Dr. Fontana said. “Our group actually suspects a lot of this will be microvascular clotting (microangiopathic thrombosis). This is exciting, as newer anticoagulation strategies – for example, those being tried in RECOVERY – may have benefit.”

Aloke V. Finn, MD, of the CVPath Institute in Gaithersburg, Md., wishes researchers would stop using the term myocarditis altogether to describe clinical or imaging findings in COVID-19.

“MRI can’t diagnose myocarditis. It is a specific diagnosis that requires, ideally, histology, as the investigators acknowledged,” Dr. Finn said in an interview.

His group at CVPath recently published data showing pathologic evidence of myocarditis after SARS-CoV-2 infection, as reported by theheart.org | Medscape Cardiology.

“As a clinician, when I think of myocarditis, I look at the echo and an LV gram, and I see if there is a wall motion abnormality and troponin elevation, but with normal coronary arteries. And if all that is there, then I think about myocarditis in my differential diagnosis,” he said. “But in most of these cases, as the authors rightly point out, most patients did not have what is necessary to really entertain a diagnosis of myocarditis.”

He agreed with Dr. Fontana’s suggestion that what the CMR might be picking up in these survivors is microthrombi, as his group saw in their recent autopsy study.

“It’s very possible these findings are concordant with the recent autopsy studies done by my group and others in terms of detecting the presence of microthrombi, but we don’t know this for certain because no one has ever studied this entity before in the clinic and we don’t really know how microthrombi might appear on CMR.”
 

Largest study to date

The 148 participants (mean age, 64 years; 70% male) in the largest study to date to investigate convalescing COVID-19 patients who had elevated troponins – something identified early in the pandemic as a risk factor for worse outcomes in COVID-19 – were treated at one of six hospitals in London.

Patients who had abnormal troponin levels were offered an MRI scan of the heart after discharge and were compared with those from a control group of patients who had not had COVID-19 and with 40 healthy volunteers.

Median length of stay was 9 days, and 32% of patients required ventilatory support in the intensive care unit.

Just over half the patients (57%) had hypertension, 7% had had a previous myocardial infarction, 34% had diabetes, 46% had hypercholesterolemia, and 24% were smokers. Mean body mass index was 28.5 kg/m².

CMR follow-up was conducted a median of 68 days after confirmation of a COVID-19 diagnosis.

On Twitter, Dr. Cole noted that the findings are subject to both survivor bias and referral bias. “We didn’t scan frail patients where the clinician felt [CMR] was unlikely to inform management.”

The findings, said Dr. Fontana, “say nothing about what happens to people who are not hospitalized with COVID, or those who are hospitalized but without elevated troponin.”

What they do offer, particularly if replicated, is a way forward in identifying patients at higher or lower risk for long-term sequelae and inform strategies that could improve outcomes, she added.

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

About half of 148 patients hospitalized with COVID-19 infection and elevated troponin levels had at least some evidence of myocardial injury on cardiac magnetic resonance (CMR) imaging 2 months later, a new study shows.

“Our results demonstrate that in this subset of patients surviving severe COVID-19 and with troponin elevation, ongoing localized myocardial inflammation, whilst less frequent than previously reported, remains present in a proportion of patients and may represent an emerging issue of clinical relevance,” wrote Marianna Fontana, MD, PhD, of University College London, and colleagues.

The cardiac abnormalities identified were classified as nonischemic (including “myocarditis-like” late gadolinium enhancement [LGE]) in 26% of the cohort; as related to ischemic heart disease (infarction or inducible ischemia) in 22%; and as dual pathology in 6%.

Left ventricular (LV) function was normal in 89% of the 148 patients. In the 17 patients (11%) with LV dysfunction, only four had an ejection fraction below 35%. Of the nine patients whose LV dysfunction was related to myocardial infarction, six had a known history of ischemic heart disease.

European Heart Journal

Glass half full

Taking a “glass half full” approach, co–senior author Graham D. Cole, MD, PhD, noted on Twitter that nearly half the patients had no major cardiac abnormalities on CMR just 2 months after a bout with troponin-positive COVID-19.

“We think this is important: Even in a group who had been very sick with raised troponin, it was common to find no evidence of heart damage,” said Dr. Cole, of the Royal Free London NHS Foundation Trust.

“We believe our data challenge the hypothesis that chronic inflammation, diffuse fibrosis, or long-term LV dysfunction is a dominant feature in those surviving COVID-19,” the investigators concluded in their report.

In an interview, Dr. Fontana explained further: “It has been reported in an early ‘pathfinder’ study that two-thirds of patients recovered from COVID-19 had CMR evidence of abnormal findings with a high incidence of elevated T1 and T2 in keeping with diffuse fibrosis and edema. Our findings with a larger, multicenter study and better controls show low rates of heart impairment and much less ongoing inflammation, which is reassuring.”

She also noted that the different patterns of injury suggest that different mechanisms are at play, including the possibility that “at least some of the found damage might have been preexisting, because people with heart damage are more likely to get severe disease.”

The investigators, including first author Tushar Kotecha, MBChB, PhD, of the Royal Free London NHS Foundation Trust, also noted that myocarditis-like injury was limited to three or fewer myocardial segments in 88% of cases with no associated ventricular dysfunction, and that biventricular function was no different than in those without myocarditis.

“We use the word ‘myocarditis-like’ but we don’t have histology,” Dr. Fontana said. “Our group actually suspects a lot of this will be microvascular clotting (microangiopathic thrombosis). This is exciting, as newer anticoagulation strategies – for example, those being tried in RECOVERY – may have benefit.”

Aloke V. Finn, MD, of the CVPath Institute in Gaithersburg, Md., wishes researchers would stop using the term myocarditis altogether to describe clinical or imaging findings in COVID-19.

“MRI can’t diagnose myocarditis. It is a specific diagnosis that requires, ideally, histology, as the investigators acknowledged,” Dr. Finn said in an interview.

His group at CVPath recently published data showing pathologic evidence of myocarditis after SARS-CoV-2 infection, as reported by theheart.org | Medscape Cardiology.

“As a clinician, when I think of myocarditis, I look at the echo and an LV gram, and I see if there is a wall motion abnormality and troponin elevation, but with normal coronary arteries. And if all that is there, then I think about myocarditis in my differential diagnosis,” he said. “But in most of these cases, as the authors rightly point out, most patients did not have what is necessary to really entertain a diagnosis of myocarditis.”

He agreed with Dr. Fontana’s suggestion that what the CMR might be picking up in these survivors is microthrombi, as his group saw in their recent autopsy study.

“It’s very possible these findings are concordant with the recent autopsy studies done by my group and others in terms of detecting the presence of microthrombi, but we don’t know this for certain because no one has ever studied this entity before in the clinic and we don’t really know how microthrombi might appear on CMR.”
 

Largest study to date

The 148 participants (mean age, 64 years; 70% male) in the largest study to date to investigate convalescing COVID-19 patients who had elevated troponins – something identified early in the pandemic as a risk factor for worse outcomes in COVID-19 – were treated at one of six hospitals in London.

Patients who had abnormal troponin levels were offered an MRI scan of the heart after discharge and were compared with those from a control group of patients who had not had COVID-19 and with 40 healthy volunteers.

Median length of stay was 9 days, and 32% of patients required ventilatory support in the intensive care unit.

Just over half the patients (57%) had hypertension, 7% had had a previous myocardial infarction, 34% had diabetes, 46% had hypercholesterolemia, and 24% were smokers. Mean body mass index was 28.5 kg/m².

CMR follow-up was conducted a median of 68 days after confirmation of a COVID-19 diagnosis.

On Twitter, Dr. Cole noted that the findings are subject to both survivor bias and referral bias. “We didn’t scan frail patients where the clinician felt [CMR] was unlikely to inform management.”

The findings, said Dr. Fontana, “say nothing about what happens to people who are not hospitalized with COVID, or those who are hospitalized but without elevated troponin.”

What they do offer, particularly if replicated, is a way forward in identifying patients at higher or lower risk for long-term sequelae and inform strategies that could improve outcomes, she added.

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

New findings suggest the Janssen/Johnson & Johnson COVID-19 vaccine can reduce the risk of an immunized person unknowingly passing along the virus to others.

Johnson & Johnson

The single-dose vaccine reduces the risk of asymptomatic transmission by 74% at 71 days, compared with placebo, according to documents released today by the U.S. Food and Drug Administration.

“The decrease in asymptomatic transmission is very welcome news too in curbing the spread of the virus,” Phyllis Tien, MD, told this news organization.

“While the earlier press release reported that the vaccine was effective against preventing severe COVID-19 disease, as well as hospitalizations and death, this new data shows that the vaccine can also decrease transmission, which is very important on a public health level,” said Dr. Tien, professor of medicine in the division of infectious diseases at the University of California, San Francisco.

“It is extremely important in terms of getting to herd immunity,” Paul Goepfert, MD, director of the Alabama Vaccine Research Clinic and infectious disease specialist at the University of Alabama, Birmingham, said in an interview. “It means that this vaccine is likely preventing subsequent transmission after a single dose, which could have huge implications once we get the majority of folks vaccinated.”

The FDA cautioned that the numbers of participants included in the study are relatively small and need to be verified. However, the Johnson & Johnson vaccine might not be the only product offering this advantage. Early data suggest that the Pfizer/BioNTech vaccine also decreases transmission, providing further evidence that the protection offered by immunization goes beyond the individual.

The new analyses were provided by the FDA in advance of its review of the Janssen/Johnson & Johnson vaccine. The agency plans to fully address the Ad26.COV2.S vaccine at its Vaccines and Related Biological Products Advisory Committee Meeting on Friday, including evaluating its safety and efficacy.

The agency’s decision on whether or not to grant emergency use authorization (EUA) to the Johnson & Johnson vaccine could come as early as Friday evening or Saturday.

In addition to the newly released data, officials are likely to discuss phase 3 data, released Jan. 29, that reveal an 85% efficacy for the vaccine against severe COVID-19 illness globally, including data from South America, South Africa, and the United States. When the analysis was restricted to data from U.S. participants, the trial showed a 73% efficacy against moderate to severe COVID-19.

If and when the FDA grants an EUA, it remains unclear how much of the new vaccine will be immediately available. Initially, Johnson & Johnson predicted 18 million doses would be ready by the end of February, but others stated the figure will be closer to 2-4 million. The manufacturer’s contract with the U.S. government stipulates production of 100-million doses by the end of June.

Dr. Tien received support from Johnson & Johnson to conduct the J&J COVID-19 vaccine trial in the SF VA HealthCare System. Dr. Goepfert has disclosed no relevant financial relationships. 

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

New findings suggest the Janssen/Johnson & Johnson COVID-19 vaccine can reduce the risk of an immunized person unknowingly passing along the virus to others.

Johnson & Johnson

The single-dose vaccine reduces the risk of asymptomatic transmission by 74% at 71 days, compared with placebo, according to documents released today by the U.S. Food and Drug Administration.

“The decrease in asymptomatic transmission is very welcome news too in curbing the spread of the virus,” Phyllis Tien, MD, told this news organization.

“While the earlier press release reported that the vaccine was effective against preventing severe COVID-19 disease, as well as hospitalizations and death, this new data shows that the vaccine can also decrease transmission, which is very important on a public health level,” said Dr. Tien, professor of medicine in the division of infectious diseases at the University of California, San Francisco.

“It is extremely important in terms of getting to herd immunity,” Paul Goepfert, MD, director of the Alabama Vaccine Research Clinic and infectious disease specialist at the University of Alabama, Birmingham, said in an interview. “It means that this vaccine is likely preventing subsequent transmission after a single dose, which could have huge implications once we get the majority of folks vaccinated.”

The FDA cautioned that the numbers of participants included in the study are relatively small and need to be verified. However, the Johnson & Johnson vaccine might not be the only product offering this advantage. Early data suggest that the Pfizer/BioNTech vaccine also decreases transmission, providing further evidence that the protection offered by immunization goes beyond the individual.

The new analyses were provided by the FDA in advance of its review of the Janssen/Johnson & Johnson vaccine. The agency plans to fully address the Ad26.COV2.S vaccine at its Vaccines and Related Biological Products Advisory Committee Meeting on Friday, including evaluating its safety and efficacy.

The agency’s decision on whether or not to grant emergency use authorization (EUA) to the Johnson & Johnson vaccine could come as early as Friday evening or Saturday.

In addition to the newly released data, officials are likely to discuss phase 3 data, released Jan. 29, that reveal an 85% efficacy for the vaccine against severe COVID-19 illness globally, including data from South America, South Africa, and the United States. When the analysis was restricted to data from U.S. participants, the trial showed a 73% efficacy against moderate to severe COVID-19.

If and when the FDA grants an EUA, it remains unclear how much of the new vaccine will be immediately available. Initially, Johnson & Johnson predicted 18 million doses would be ready by the end of February, but others stated the figure will be closer to 2-4 million. The manufacturer’s contract with the U.S. government stipulates production of 100-million doses by the end of June.

Dr. Tien received support from Johnson & Johnson to conduct the J&J COVID-19 vaccine trial in the SF VA HealthCare System. Dr. Goepfert has disclosed no relevant financial relationships. 

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

New findings suggest the Janssen/Johnson & Johnson COVID-19 vaccine can reduce the risk of an immunized person unknowingly passing along the virus to others.

Johnson & Johnson

The single-dose vaccine reduces the risk of asymptomatic transmission by 74% at 71 days, compared with placebo, according to documents released today by the U.S. Food and Drug Administration.

“The decrease in asymptomatic transmission is very welcome news too in curbing the spread of the virus,” Phyllis Tien, MD, told this news organization.

“While the earlier press release reported that the vaccine was effective against preventing severe COVID-19 disease, as well as hospitalizations and death, this new data shows that the vaccine can also decrease transmission, which is very important on a public health level,” said Dr. Tien, professor of medicine in the division of infectious diseases at the University of California, San Francisco.

“It is extremely important in terms of getting to herd immunity,” Paul Goepfert, MD, director of the Alabama Vaccine Research Clinic and infectious disease specialist at the University of Alabama, Birmingham, said in an interview. “It means that this vaccine is likely preventing subsequent transmission after a single dose, which could have huge implications once we get the majority of folks vaccinated.”

The FDA cautioned that the numbers of participants included in the study are relatively small and need to be verified. However, the Johnson & Johnson vaccine might not be the only product offering this advantage. Early data suggest that the Pfizer/BioNTech vaccine also decreases transmission, providing further evidence that the protection offered by immunization goes beyond the individual.

The new analyses were provided by the FDA in advance of its review of the Janssen/Johnson & Johnson vaccine. The agency plans to fully address the Ad26.COV2.S vaccine at its Vaccines and Related Biological Products Advisory Committee Meeting on Friday, including evaluating its safety and efficacy.

The agency’s decision on whether or not to grant emergency use authorization (EUA) to the Johnson & Johnson vaccine could come as early as Friday evening or Saturday.

In addition to the newly released data, officials are likely to discuss phase 3 data, released Jan. 29, that reveal an 85% efficacy for the vaccine against severe COVID-19 illness globally, including data from South America, South Africa, and the United States. When the analysis was restricted to data from U.S. participants, the trial showed a 73% efficacy against moderate to severe COVID-19.

If and when the FDA grants an EUA, it remains unclear how much of the new vaccine will be immediately available. Initially, Johnson & Johnson predicted 18 million doses would be ready by the end of February, but others stated the figure will be closer to 2-4 million. The manufacturer’s contract with the U.S. government stipulates production of 100-million doses by the end of June.

Dr. Tien received support from Johnson & Johnson to conduct the J&J COVID-19 vaccine trial in the SF VA HealthCare System. Dr. Goepfert has disclosed no relevant financial relationships. 

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

More than 50% of health care workers infected with SARS-CoV-2 report that their sense of smell has not returned to normal an average of 5 months post infection, new research shows.

Nenad Cavoski/iStock/Getty Images Plus

The findings illustrate that olfactory problems are common not only during the acute COVID-19 phase but also “in the long run” and that these problems should be “taken into consideration” when following up these patients, study investigator Johannes Frasnelli, MD, professor, department of anatomy, Université du Québec à Trois-Rivières, said in an interview.

Loss of the sense of smell can affect quality of life because it affects eating and drinking, and may even be dangerous, said Dr. Frasnelli. “If your sense of smell is impaired, you may unknowingly eat spoiled food, or you may not smell smoke or gas in your home,” he said. In addition, Dr. Frasnelli noted that an impaired sense of smell is associated with higher rates of depression. The findings will be presented at the annual meeting of the American Academy of Neurology in April.

‘Striking’ finding

Research shows that about 60% of patients with COVID-19 lose their sense of smell to some degree during the acute phase of the disease. “But we wanted to go further and look at the longer-term effects of loss of smell and taste,” said Dr. Frasnelli.

The analysis included 813 health care workers in the province of Quebec. For all the patients, SARS-CoV-2 infection was confirmed through testing with a nasopharyngeal viral swab.

Participants completed a 64-item online questionnaire that asked about three senses: olfactory; gustatory, which includes tastes such as sweet, sour, bitter, salty, savory and umami; and trigeminal, which includes sensations such as spiciness of hot peppers and “coolness” of mint.

They were asked to rate these on a scale of 0 (no perception) to 10 (very strong perception) before the infection, during the infection, and currently. They were also asked about other symptoms, including fatigue.

Most respondents had been infected in the first wave of the virus in March and April of 2020 and responded to the questionnaire an average of 5 months later.

The vast majority of respondents (84.1%) were women, which Dr. Frasnelli said was not surprising because women predominate in the health care field.

The analysis showed that average smell ratings were 8.98 before infection, 2.85 during the acute phase, and 7.41 when respondents answered the questionnaire. The sense of taste was less affected and recovered faster than did the sense of smell. Results for taste were 9.20 before infection, 3.59 during the acute phase, and 8.05 after COVID-19.

Among 580 respondents who indicated a compromised sense of smell during the acute phase, the average smell rating when answering the questionnaire was 6.89, compared to 9.03 before the infection. More than half (51.2%) reported not regaining full olfactory function.

The fact that the sense of smell had not returned to normal for half the participants so long after being infected is “novel and quite striking,” said Dr. Frasnelli.

However, he noted, this doesn’t necessarily mean all those with a compromised sense of smell “have huge problems.” In some cases, he said, the problem “is more subtle.”
 

Not a CNS problem?

Respondents also completed a chemosensory dysfunction home test (CD-HT). They were asked to prepare common household food items, such as peanut butter, sugar, salt, and vinegar, in a particular way – for example, to add sugar or salt to water – and provide feedback on how they smell and taste.

For this CD-HT analysis, 18.4% of respondents reported having persistent loss of smell. This, Dr. Frasnelli said, adds to evidence from self-reported responses and suggests that in some cases, the problem is more than senses not returning to normal.

“From the questionnaires, roughly 50% said their sense of smell is still not back to normal, and when we look at the CD home test, we see that almost 20% of subjects indeed have pretty strong impairment of their sense of smell,” he said.

The results showed no sex differences, although Dr. Frasnelli noted that most of the sample were women. “It’s tricky to look at the data with regard to sex because it’s a bit skewed,” he said.

Male respondents were older than female participants, but there was no difference in impairment between age groups. Dr. Frasnelli said this was “quite interesting,” inasmuch as older people usually lose some sense of smell.

The researchers have not yet examined whether the results differ by type of health care worker.

They also have not examined in detail whether infection severity affects the risk for extended olfactory impairment. Although some research suggests that the problem with smell is more common in less severe cases, Dr. Frasnelli noted this could be because loss of smell is not a huge problem for patients battling grave health problems.

As for other symptoms, many respondents reported lingering fatigue; some reported debilitating fatigue, said Dr. Frasnelli. However, he cautioned that this is difficult to interpret, because the participants were health care workers, many of whom returned to work during the pandemic and perhaps had not fully rested.

He also noted that he and his colleagues have not “made the link” between impaired smell and the degree of fatigue.

The COVID-19 virus appears to attack supporting sustentacular cells in the olfactory epithelium, not nerve cells.

“Right now, it seems that the smell problem is not a central nervous system problem but a peripheral problem,” said Dr. Frasnelli. “But we don’t know for sure; it may be that the virus somehow gets into the brain and some symptoms are caused by the effects of the infection on the brain.”

The researchers will extend their research with another questionnaire to assess senses 10-12 months after COVID-19.

Limitations of the study include the subjective nature of the smell and taste ratings and the single time point at which data were collected.
 

Confirmatory findings

Commenting on the research in an interview, Thomas Hummel, MD, professor, smell and taste clinic, department of otorhinolaryngology, Technische Universität Dresden (Germany), said the new results regarding loss of smell after COVID-19 are “very congruent” with what he and his colleagues have observed.

Research shows that up to one in five of those infected with SARS-CoV-2 experience olfactory loss. “While the numbers may vary a bit from study to study or lab to lab, I think 5% to 20% of post–COVID-19 patients exhibit long-term olfactory loss,” Dr. Hummel said.

His group has observed that “many more are not back to normal,” which conforms with what Dr. Frasnelli’s study reveals, said Dr. Hummel.

Also commenting on the research, Kenneth L. Tyler, MD, professor of neurology, University of Colorado at Denver, Aurora, and a fellow of the American Academy of Neurology, said the study was relatively large and the results “interesting.”

Although it “provides more evidence there’s a subset of patients with symptoms even well past the acute phase” of COVID-19, the results are “mostly confirmatory” and include “nothing super surprising,” Dr. Tyler said in an interview.

However, the investigators did attempt to make the study “a little more quantitative” and “to confirm the self-reporting with their validated CD home test,” he said.

Dr. Tyler wondered how representative the sample was and whether the study drew more participants with impaired senses. “If I had a loss of smell or taste, maybe I would be more likely to respond to such a survey,” he said.

He also noted the difficulty of separating loss of smell from loss of taste.

“If you lose your sense of smell, things don’t taste right, so it can be confounding as to how to separate out those two,” he noted.
The study was supported by the Foundation of the Université du Québec à Trois-Rivières and the Province of Quebec. Dr. Frasnelli has received royalties from Styriabooks in Austria for a book on olfaction published in 2019 and has received honoraria for speaking engagements. Dr. Hummel and Dr. Tyler have disclosed no relevant financial relationships.

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

More than 50% of health care workers infected with SARS-CoV-2 report that their sense of smell has not returned to normal an average of 5 months post infection, new research shows.

Nenad Cavoski/iStock/Getty Images Plus

The findings illustrate that olfactory problems are common not only during the acute COVID-19 phase but also “in the long run” and that these problems should be “taken into consideration” when following up these patients, study investigator Johannes Frasnelli, MD, professor, department of anatomy, Université du Québec à Trois-Rivières, said in an interview.

Loss of the sense of smell can affect quality of life because it affects eating and drinking, and may even be dangerous, said Dr. Frasnelli. “If your sense of smell is impaired, you may unknowingly eat spoiled food, or you may not smell smoke or gas in your home,” he said. In addition, Dr. Frasnelli noted that an impaired sense of smell is associated with higher rates of depression. The findings will be presented at the annual meeting of the American Academy of Neurology in April.

‘Striking’ finding

Research shows that about 60% of patients with COVID-19 lose their sense of smell to some degree during the acute phase of the disease. “But we wanted to go further and look at the longer-term effects of loss of smell and taste,” said Dr. Frasnelli.

The analysis included 813 health care workers in the province of Quebec. For all the patients, SARS-CoV-2 infection was confirmed through testing with a nasopharyngeal viral swab.

Participants completed a 64-item online questionnaire that asked about three senses: olfactory; gustatory, which includes tastes such as sweet, sour, bitter, salty, savory and umami; and trigeminal, which includes sensations such as spiciness of hot peppers and “coolness” of mint.

They were asked to rate these on a scale of 0 (no perception) to 10 (very strong perception) before the infection, during the infection, and currently. They were also asked about other symptoms, including fatigue.

Most respondents had been infected in the first wave of the virus in March and April of 2020 and responded to the questionnaire an average of 5 months later.

The vast majority of respondents (84.1%) were women, which Dr. Frasnelli said was not surprising because women predominate in the health care field.

The analysis showed that average smell ratings were 8.98 before infection, 2.85 during the acute phase, and 7.41 when respondents answered the questionnaire. The sense of taste was less affected and recovered faster than did the sense of smell. Results for taste were 9.20 before infection, 3.59 during the acute phase, and 8.05 after COVID-19.

Among 580 respondents who indicated a compromised sense of smell during the acute phase, the average smell rating when answering the questionnaire was 6.89, compared to 9.03 before the infection. More than half (51.2%) reported not regaining full olfactory function.

The fact that the sense of smell had not returned to normal for half the participants so long after being infected is “novel and quite striking,” said Dr. Frasnelli.

However, he noted, this doesn’t necessarily mean all those with a compromised sense of smell “have huge problems.” In some cases, he said, the problem “is more subtle.”
 

Not a CNS problem?

Respondents also completed a chemosensory dysfunction home test (CD-HT). They were asked to prepare common household food items, such as peanut butter, sugar, salt, and vinegar, in a particular way – for example, to add sugar or salt to water – and provide feedback on how they smell and taste.

For this CD-HT analysis, 18.4% of respondents reported having persistent loss of smell. This, Dr. Frasnelli said, adds to evidence from self-reported responses and suggests that in some cases, the problem is more than senses not returning to normal.

“From the questionnaires, roughly 50% said their sense of smell is still not back to normal, and when we look at the CD home test, we see that almost 20% of subjects indeed have pretty strong impairment of their sense of smell,” he said.

The results showed no sex differences, although Dr. Frasnelli noted that most of the sample were women. “It’s tricky to look at the data with regard to sex because it’s a bit skewed,” he said.

Male respondents were older than female participants, but there was no difference in impairment between age groups. Dr. Frasnelli said this was “quite interesting,” inasmuch as older people usually lose some sense of smell.

The researchers have not yet examined whether the results differ by type of health care worker.

They also have not examined in detail whether infection severity affects the risk for extended olfactory impairment. Although some research suggests that the problem with smell is more common in less severe cases, Dr. Frasnelli noted this could be because loss of smell is not a huge problem for patients battling grave health problems.

As for other symptoms, many respondents reported lingering fatigue; some reported debilitating fatigue, said Dr. Frasnelli. However, he cautioned that this is difficult to interpret, because the participants were health care workers, many of whom returned to work during the pandemic and perhaps had not fully rested.

He also noted that he and his colleagues have not “made the link” between impaired smell and the degree of fatigue.

The COVID-19 virus appears to attack supporting sustentacular cells in the olfactory epithelium, not nerve cells.

“Right now, it seems that the smell problem is not a central nervous system problem but a peripheral problem,” said Dr. Frasnelli. “But we don’t know for sure; it may be that the virus somehow gets into the brain and some symptoms are caused by the effects of the infection on the brain.”

The researchers will extend their research with another questionnaire to assess senses 10-12 months after COVID-19.

Limitations of the study include the subjective nature of the smell and taste ratings and the single time point at which data were collected.
 

Confirmatory findings

Commenting on the research in an interview, Thomas Hummel, MD, professor, smell and taste clinic, department of otorhinolaryngology, Technische Universität Dresden (Germany), said the new results regarding loss of smell after COVID-19 are “very congruent” with what he and his colleagues have observed.

Research shows that up to one in five of those infected with SARS-CoV-2 experience olfactory loss. “While the numbers may vary a bit from study to study or lab to lab, I think 5% to 20% of post–COVID-19 patients exhibit long-term olfactory loss,” Dr. Hummel said.

His group has observed that “many more are not back to normal,” which conforms with what Dr. Frasnelli’s study reveals, said Dr. Hummel.

Also commenting on the research, Kenneth L. Tyler, MD, professor of neurology, University of Colorado at Denver, Aurora, and a fellow of the American Academy of Neurology, said the study was relatively large and the results “interesting.”

Although it “provides more evidence there’s a subset of patients with symptoms even well past the acute phase” of COVID-19, the results are “mostly confirmatory” and include “nothing super surprising,” Dr. Tyler said in an interview.

However, the investigators did attempt to make the study “a little more quantitative” and “to confirm the self-reporting with their validated CD home test,” he said.

Dr. Tyler wondered how representative the sample was and whether the study drew more participants with impaired senses. “If I had a loss of smell or taste, maybe I would be more likely to respond to such a survey,” he said.

He also noted the difficulty of separating loss of smell from loss of taste.

“If you lose your sense of smell, things don’t taste right, so it can be confounding as to how to separate out those two,” he noted.
The study was supported by the Foundation of the Université du Québec à Trois-Rivières and the Province of Quebec. Dr. Frasnelli has received royalties from Styriabooks in Austria for a book on olfaction published in 2019 and has received honoraria for speaking engagements. Dr. Hummel and Dr. Tyler have disclosed no relevant financial relationships.

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

More than 50% of health care workers infected with SARS-CoV-2 report that their sense of smell has not returned to normal an average of 5 months post infection, new research shows.

Nenad Cavoski/iStock/Getty Images Plus

The findings illustrate that olfactory problems are common not only during the acute COVID-19 phase but also “in the long run” and that these problems should be “taken into consideration” when following up these patients, study investigator Johannes Frasnelli, MD, professor, department of anatomy, Université du Québec à Trois-Rivières, said in an interview.

Loss of the sense of smell can affect quality of life because it affects eating and drinking, and may even be dangerous, said Dr. Frasnelli. “If your sense of smell is impaired, you may unknowingly eat spoiled food, or you may not smell smoke or gas in your home,” he said. In addition, Dr. Frasnelli noted that an impaired sense of smell is associated with higher rates of depression. The findings will be presented at the annual meeting of the American Academy of Neurology in April.

‘Striking’ finding

Research shows that about 60% of patients with COVID-19 lose their sense of smell to some degree during the acute phase of the disease. “But we wanted to go further and look at the longer-term effects of loss of smell and taste,” said Dr. Frasnelli.

The analysis included 813 health care workers in the province of Quebec. For all the patients, SARS-CoV-2 infection was confirmed through testing with a nasopharyngeal viral swab.

Participants completed a 64-item online questionnaire that asked about three senses: olfactory; gustatory, which includes tastes such as sweet, sour, bitter, salty, savory and umami; and trigeminal, which includes sensations such as spiciness of hot peppers and “coolness” of mint.

They were asked to rate these on a scale of 0 (no perception) to 10 (very strong perception) before the infection, during the infection, and currently. They were also asked about other symptoms, including fatigue.

Most respondents had been infected in the first wave of the virus in March and April of 2020 and responded to the questionnaire an average of 5 months later.

The vast majority of respondents (84.1%) were women, which Dr. Frasnelli said was not surprising because women predominate in the health care field.

The analysis showed that average smell ratings were 8.98 before infection, 2.85 during the acute phase, and 7.41 when respondents answered the questionnaire. The sense of taste was less affected and recovered faster than did the sense of smell. Results for taste were 9.20 before infection, 3.59 during the acute phase, and 8.05 after COVID-19.

Among 580 respondents who indicated a compromised sense of smell during the acute phase, the average smell rating when answering the questionnaire was 6.89, compared to 9.03 before the infection. More than half (51.2%) reported not regaining full olfactory function.

The fact that the sense of smell had not returned to normal for half the participants so long after being infected is “novel and quite striking,” said Dr. Frasnelli.

However, he noted, this doesn’t necessarily mean all those with a compromised sense of smell “have huge problems.” In some cases, he said, the problem “is more subtle.”
 

Not a CNS problem?

Respondents also completed a chemosensory dysfunction home test (CD-HT). They were asked to prepare common household food items, such as peanut butter, sugar, salt, and vinegar, in a particular way – for example, to add sugar or salt to water – and provide feedback on how they smell and taste.

For this CD-HT analysis, 18.4% of respondents reported having persistent loss of smell. This, Dr. Frasnelli said, adds to evidence from self-reported responses and suggests that in some cases, the problem is more than senses not returning to normal.

“From the questionnaires, roughly 50% said their sense of smell is still not back to normal, and when we look at the CD home test, we see that almost 20% of subjects indeed have pretty strong impairment of their sense of smell,” he said.

The results showed no sex differences, although Dr. Frasnelli noted that most of the sample were women. “It’s tricky to look at the data with regard to sex because it’s a bit skewed,” he said.

Male respondents were older than female participants, but there was no difference in impairment between age groups. Dr. Frasnelli said this was “quite interesting,” inasmuch as older people usually lose some sense of smell.

The researchers have not yet examined whether the results differ by type of health care worker.

They also have not examined in detail whether infection severity affects the risk for extended olfactory impairment. Although some research suggests that the problem with smell is more common in less severe cases, Dr. Frasnelli noted this could be because loss of smell is not a huge problem for patients battling grave health problems.

As for other symptoms, many respondents reported lingering fatigue; some reported debilitating fatigue, said Dr. Frasnelli. However, he cautioned that this is difficult to interpret, because the participants were health care workers, many of whom returned to work during the pandemic and perhaps had not fully rested.

He also noted that he and his colleagues have not “made the link” between impaired smell and the degree of fatigue.

The COVID-19 virus appears to attack supporting sustentacular cells in the olfactory epithelium, not nerve cells.

“Right now, it seems that the smell problem is not a central nervous system problem but a peripheral problem,” said Dr. Frasnelli. “But we don’t know for sure; it may be that the virus somehow gets into the brain and some symptoms are caused by the effects of the infection on the brain.”

The researchers will extend their research with another questionnaire to assess senses 10-12 months after COVID-19.

Limitations of the study include the subjective nature of the smell and taste ratings and the single time point at which data were collected.
 

Confirmatory findings

Commenting on the research in an interview, Thomas Hummel, MD, professor, smell and taste clinic, department of otorhinolaryngology, Technische Universität Dresden (Germany), said the new results regarding loss of smell after COVID-19 are “very congruent” with what he and his colleagues have observed.

Research shows that up to one in five of those infected with SARS-CoV-2 experience olfactory loss. “While the numbers may vary a bit from study to study or lab to lab, I think 5% to 20% of post–COVID-19 patients exhibit long-term olfactory loss,” Dr. Hummel said.

His group has observed that “many more are not back to normal,” which conforms with what Dr. Frasnelli’s study reveals, said Dr. Hummel.

Also commenting on the research, Kenneth L. Tyler, MD, professor of neurology, University of Colorado at Denver, Aurora, and a fellow of the American Academy of Neurology, said the study was relatively large and the results “interesting.”

Although it “provides more evidence there’s a subset of patients with symptoms even well past the acute phase” of COVID-19, the results are “mostly confirmatory” and include “nothing super surprising,” Dr. Tyler said in an interview.

However, the investigators did attempt to make the study “a little more quantitative” and “to confirm the self-reporting with their validated CD home test,” he said.

Dr. Tyler wondered how representative the sample was and whether the study drew more participants with impaired senses. “If I had a loss of smell or taste, maybe I would be more likely to respond to such a survey,” he said.

He also noted the difficulty of separating loss of smell from loss of taste.

“If you lose your sense of smell, things don’t taste right, so it can be confounding as to how to separate out those two,” he noted.
The study was supported by the Foundation of the Université du Québec à Trois-Rivières and the Province of Quebec. Dr. Frasnelli has received royalties from Styriabooks in Austria for a book on olfaction published in 2019 and has received honoraria for speaking engagements. Dr. Hummel and Dr. Tyler have disclosed no relevant financial relationships.

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

Exposure to Group A streptococcus (GAS) does not appear to worsen symptoms of Tourette syndrome and other chronic tic disorders (CTDs) in children and adolescents, new research suggests.

Investigators studied over 700 children and teenagers with CTDs, one-third of whom also had attention deficit hyperactivity disorder and one-third who had obsessive-compulsive disorder (OCD).

The youngsters were followed for an average of 16 months and evaluated at 4-month intervals to see if they were infected with GAS. Tic severity was monitored through telephone interviews, in-person visits, and parental reports.

A little less than half the children experienced worsening of tics during the study period, but the researchers found no association between these exacerbations and GAS exposure.

There was also no link between GAS and worsening OCD. However, researchers did find an association between GAS exposure and an increase in hyperactivity and impulsivity in patients with ADHD.

“This study does not support GAS exposures as contributing factors for tic exacerbations in children with CTD,” the authors note.

“Specific work-up or active management of GAS infections is unlikely to help modifying the course of tics in CTD and is therefore not recommended,” they conclude.

The study was published online in Neurology.
 

‘Intense debate’

The association between GAS and CTD stems from the description of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection (PANDAS) – a condition that is now incorporated in the pediatric acute neuropsychiatric syndromes (PANS), the authors note. Tics constitute an “accompanying feature” of this condition.

However, neither population-based nor longitudinal clinical studies “could definitely establish if tic exacerbations in CTD are associated with GAS infections,” they note.  

“The link between streptococcus and tics in children is still a matter of intense debate,” said study author Davide Martino, MD, PhD, director of the Movement Disorders Program at the University of Calgary (Alta.), in a press release.

“We wanted to look at that question, as well as a possible link between strep and behavioral symptoms like obsessive-compulsive disorder and attention deficit hyperactivity disorder,” he said.

The researchers followed 715 children with CTD (mean age 10.7 years, 76.8% male) who were drawn from 16 specialist clinics in nine countries. Almost all (90.8%) had a diagnosis of Tourette syndrome (TS); 31.7% had OCD, and 36.1% had ADHD.

Participants received a throat swab at baseline, and of these, 8.4% tested positive for GAS.

Participants were evaluated over a 16- to 18-month period, consisting of:

• Face-to-face interviews and collection of throat swabs and serum at 4-month intervals.
• Telephone interviews at 4-month intervals, which took place at 2 months between study visit.
• Weekly diaries: Parents were asked to indicate any worsening of tics and focus on detecting the earliest possible tic exacerbation.

Beyond the regularly scheduled visits, parents were instructed to report, by phone or email, any noticeable increase in tic severity and then attend an in-person visit.

Tic exacerbations were defined as an increase of greater than or equal to 6 points on the Yale Global Tic Severity Scale-Total Tic Severity Score (YGTSS-TTS), compared with the previous assessment.

OCD and ADHD symptoms were assessed according to the Yale-Brown Obsessive-Compulsive Scale and the parent-reported Swanson, Nolan, and Pelham-IV (SNAP-IV) questionnaire.

The researchers divided GAS exposures into four categories: new definite exposure; new possible exposure; ongoing definite exposure; and ongoing possible exposure.
 

Unlikely trigger

During the follow-up period, 43.1% (n = 308) of participants experienced tic exacerbations. Of these, 218 participants experienced one exacerbation, while 90 participants experienced two, three, or four exacerbations.

The researchers did not find a significant association between GAS exposure status and tic exacerbation.

Participants who did develop a GAS-associated exacerbation (n = 49) were younger at study exit (9.63 vs. 11.4 years, P < .0001) and were more likely to be male (46/49 vs. 210/259, Fisher’s = .035), compared with participants who developed a non-GAS-associated tic exacerbation (n = 259).

Additional analyses were adjusted for sex, age at onset, exposure to psychotropic medications, exposures to antibiotics, geographical regions, and number of visits in the time interval of interest. These analyses continued to yield no significant association between new or ongoing concurrent GAS exposure episodes and tic exacerbation events.

Of the children in the study, 103 had a positive throat swab, indicating a new definite GAS exposure, whereas 46 had a positive throat swab indicating an ongoing definite exposure (n = 149 visits). Of these visits, only 20 corresponded to tic exacerbations.

There was also no association between GAS exposure and OCD symptom severity. However, it was associated with longitudinal changes (between 17% and 21%, depending on GAS exposure definition) in the severity of hyperactivity-impulsivity symptoms in children with ADHD.

“It is known that immune activation may concur with tic severity in youth with CTDs and that psychosocial stress levels may predict short-term future tic severity in these patients,” the authors write.

“Our findings suggest that GAS is unlikely to be the main trigger for immune activation in these patients,” they add.
 

Brick or cornerstone?

Commenting on the study for this news organization, Margo Thienemann, MD, clinical professor of psychiatry, Stanford (Calif.) University, said that in the clinic population they treat, GAS, other pathogens, and other stresses can “each be associated with PANS symptom exacerbations.”

However, these “would not be likely to cause PANS symptoms exacerbations in the vast majority of individuals, only individuals with genetic backgrounds and immunologic dysfunctions creating susceptibility,” said Dr. Thienemann, who also directs the Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) Clinic at Stanford Children’s Health. She was not involved with the study.

In an accompanying editorial, Andrea Cavanna, MD, PhD, honorary reader in neuropsychiatry, Birmingham (England) Medical School and Keith Coffman, MD, director, Tourette Syndrome Center of Excellence, Children’s Mercy Hospital, Kansas City, Mo., suggest that perhaps the “interaction of psychosocial stress and GAS infections contributes more to tic exacerbation than psychosocial stress alone.”

“Time will tell whether this study stands as another brick – a cornerstone? – in the wall that separates streptococcus from tics,” they write.

The study was supported by the European Union’s Seventh Framework Program. Dr. Martino has received honoraria for lecturing from the Movement Disorders Society, Tourette Syndrome Association of America, and Dystonia Medical Research Foundation Canada; research funding support from Dystonia Medical Research Foundation Canada, the University of Calgary (Alta.), the Michael P. Smith Family, the Owerko Foundation, Ipsen Corporate, the Parkinson Association of Alberta, and the Canadian Institutes for Health Research; and royalties from Springer-Verlag. The other authors’ disclosures are listed in the original article. Dr. Cavanna, Dr. Coffman, and Dr. Thienemann have disclosed no relevant financial relationships.

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

Exposure to Group A streptococcus (GAS) does not appear to worsen symptoms of Tourette syndrome and other chronic tic disorders (CTDs) in children and adolescents, new research suggests.

Investigators studied over 700 children and teenagers with CTDs, one-third of whom also had attention deficit hyperactivity disorder and one-third who had obsessive-compulsive disorder (OCD).

The youngsters were followed for an average of 16 months and evaluated at 4-month intervals to see if they were infected with GAS. Tic severity was monitored through telephone interviews, in-person visits, and parental reports.

A little less than half the children experienced worsening of tics during the study period, but the researchers found no association between these exacerbations and GAS exposure.

There was also no link between GAS and worsening OCD. However, researchers did find an association between GAS exposure and an increase in hyperactivity and impulsivity in patients with ADHD.

“This study does not support GAS exposures as contributing factors for tic exacerbations in children with CTD,” the authors note.

“Specific work-up or active management of GAS infections is unlikely to help modifying the course of tics in CTD and is therefore not recommended,” they conclude.

The study was published online in Neurology.
 

‘Intense debate’

The association between GAS and CTD stems from the description of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection (PANDAS) – a condition that is now incorporated in the pediatric acute neuropsychiatric syndromes (PANS), the authors note. Tics constitute an “accompanying feature” of this condition.

However, neither population-based nor longitudinal clinical studies “could definitely establish if tic exacerbations in CTD are associated with GAS infections,” they note.  

“The link between streptococcus and tics in children is still a matter of intense debate,” said study author Davide Martino, MD, PhD, director of the Movement Disorders Program at the University of Calgary (Alta.), in a press release.

“We wanted to look at that question, as well as a possible link between strep and behavioral symptoms like obsessive-compulsive disorder and attention deficit hyperactivity disorder,” he said.

The researchers followed 715 children with CTD (mean age 10.7 years, 76.8% male) who were drawn from 16 specialist clinics in nine countries. Almost all (90.8%) had a diagnosis of Tourette syndrome (TS); 31.7% had OCD, and 36.1% had ADHD.

Participants received a throat swab at baseline, and of these, 8.4% tested positive for GAS.

Participants were evaluated over a 16- to 18-month period, consisting of:

• Face-to-face interviews and collection of throat swabs and serum at 4-month intervals.
• Telephone interviews at 4-month intervals, which took place at 2 months between study visit.
• Weekly diaries: Parents were asked to indicate any worsening of tics and focus on detecting the earliest possible tic exacerbation.

Beyond the regularly scheduled visits, parents were instructed to report, by phone or email, any noticeable increase in tic severity and then attend an in-person visit.

Tic exacerbations were defined as an increase of greater than or equal to 6 points on the Yale Global Tic Severity Scale-Total Tic Severity Score (YGTSS-TTS), compared with the previous assessment.

OCD and ADHD symptoms were assessed according to the Yale-Brown Obsessive-Compulsive Scale and the parent-reported Swanson, Nolan, and Pelham-IV (SNAP-IV) questionnaire.

The researchers divided GAS exposures into four categories: new definite exposure; new possible exposure; ongoing definite exposure; and ongoing possible exposure.
 

Unlikely trigger

During the follow-up period, 43.1% (n = 308) of participants experienced tic exacerbations. Of these, 218 participants experienced one exacerbation, while 90 participants experienced two, three, or four exacerbations.

The researchers did not find a significant association between GAS exposure status and tic exacerbation.

Participants who did develop a GAS-associated exacerbation (n = 49) were younger at study exit (9.63 vs. 11.4 years, P < .0001) and were more likely to be male (46/49 vs. 210/259, Fisher’s = .035), compared with participants who developed a non-GAS-associated tic exacerbation (n = 259).

Additional analyses were adjusted for sex, age at onset, exposure to psychotropic medications, exposures to antibiotics, geographical regions, and number of visits in the time interval of interest. These analyses continued to yield no significant association between new or ongoing concurrent GAS exposure episodes and tic exacerbation events.

Of the children in the study, 103 had a positive throat swab, indicating a new definite GAS exposure, whereas 46 had a positive throat swab indicating an ongoing definite exposure (n = 149 visits). Of these visits, only 20 corresponded to tic exacerbations.

There was also no association between GAS exposure and OCD symptom severity. However, it was associated with longitudinal changes (between 17% and 21%, depending on GAS exposure definition) in the severity of hyperactivity-impulsivity symptoms in children with ADHD.

“It is known that immune activation may concur with tic severity in youth with CTDs and that psychosocial stress levels may predict short-term future tic severity in these patients,” the authors write.

“Our findings suggest that GAS is unlikely to be the main trigger for immune activation in these patients,” they add.
 

Brick or cornerstone?

Commenting on the study for this news organization, Margo Thienemann, MD, clinical professor of psychiatry, Stanford (Calif.) University, said that in the clinic population they treat, GAS, other pathogens, and other stresses can “each be associated with PANS symptom exacerbations.”

However, these “would not be likely to cause PANS symptoms exacerbations in the vast majority of individuals, only individuals with genetic backgrounds and immunologic dysfunctions creating susceptibility,” said Dr. Thienemann, who also directs the Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) Clinic at Stanford Children’s Health. She was not involved with the study.

In an accompanying editorial, Andrea Cavanna, MD, PhD, honorary reader in neuropsychiatry, Birmingham (England) Medical School and Keith Coffman, MD, director, Tourette Syndrome Center of Excellence, Children’s Mercy Hospital, Kansas City, Mo., suggest that perhaps the “interaction of psychosocial stress and GAS infections contributes more to tic exacerbation than psychosocial stress alone.”

“Time will tell whether this study stands as another brick – a cornerstone? – in the wall that separates streptococcus from tics,” they write.

The study was supported by the European Union’s Seventh Framework Program. Dr. Martino has received honoraria for lecturing from the Movement Disorders Society, Tourette Syndrome Association of America, and Dystonia Medical Research Foundation Canada; research funding support from Dystonia Medical Research Foundation Canada, the University of Calgary (Alta.), the Michael P. Smith Family, the Owerko Foundation, Ipsen Corporate, the Parkinson Association of Alberta, and the Canadian Institutes for Health Research; and royalties from Springer-Verlag. The other authors’ disclosures are listed in the original article. Dr. Cavanna, Dr. Coffman, and Dr. Thienemann have disclosed no relevant financial relationships.

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

Exposure to Group A streptococcus (GAS) does not appear to worsen symptoms of Tourette syndrome and other chronic tic disorders (CTDs) in children and adolescents, new research suggests.

Investigators studied over 700 children and teenagers with CTDs, one-third of whom also had attention deficit hyperactivity disorder and one-third who had obsessive-compulsive disorder (OCD).

The youngsters were followed for an average of 16 months and evaluated at 4-month intervals to see if they were infected with GAS. Tic severity was monitored through telephone interviews, in-person visits, and parental reports.

A little less than half the children experienced worsening of tics during the study period, but the researchers found no association between these exacerbations and GAS exposure.

There was also no link between GAS and worsening OCD. However, researchers did find an association between GAS exposure and an increase in hyperactivity and impulsivity in patients with ADHD.

“This study does not support GAS exposures as contributing factors for tic exacerbations in children with CTD,” the authors note.

“Specific work-up or active management of GAS infections is unlikely to help modifying the course of tics in CTD and is therefore not recommended,” they conclude.

The study was published online in Neurology.
 

‘Intense debate’

The association between GAS and CTD stems from the description of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection (PANDAS) – a condition that is now incorporated in the pediatric acute neuropsychiatric syndromes (PANS), the authors note. Tics constitute an “accompanying feature” of this condition.

However, neither population-based nor longitudinal clinical studies “could definitely establish if tic exacerbations in CTD are associated with GAS infections,” they note.  

“The link between streptococcus and tics in children is still a matter of intense debate,” said study author Davide Martino, MD, PhD, director of the Movement Disorders Program at the University of Calgary (Alta.), in a press release.

“We wanted to look at that question, as well as a possible link between strep and behavioral symptoms like obsessive-compulsive disorder and attention deficit hyperactivity disorder,” he said.

The researchers followed 715 children with CTD (mean age 10.7 years, 76.8% male) who were drawn from 16 specialist clinics in nine countries. Almost all (90.8%) had a diagnosis of Tourette syndrome (TS); 31.7% had OCD, and 36.1% had ADHD.

Participants received a throat swab at baseline, and of these, 8.4% tested positive for GAS.

Participants were evaluated over a 16- to 18-month period, consisting of:

• Face-to-face interviews and collection of throat swabs and serum at 4-month intervals.
• Telephone interviews at 4-month intervals, which took place at 2 months between study visit.
• Weekly diaries: Parents were asked to indicate any worsening of tics and focus on detecting the earliest possible tic exacerbation.

Beyond the regularly scheduled visits, parents were instructed to report, by phone or email, any noticeable increase in tic severity and then attend an in-person visit.

Tic exacerbations were defined as an increase of greater than or equal to 6 points on the Yale Global Tic Severity Scale-Total Tic Severity Score (YGTSS-TTS), compared with the previous assessment.

OCD and ADHD symptoms were assessed according to the Yale-Brown Obsessive-Compulsive Scale and the parent-reported Swanson, Nolan, and Pelham-IV (SNAP-IV) questionnaire.

The researchers divided GAS exposures into four categories: new definite exposure; new possible exposure; ongoing definite exposure; and ongoing possible exposure.
 

Unlikely trigger

During the follow-up period, 43.1% (n = 308) of participants experienced tic exacerbations. Of these, 218 participants experienced one exacerbation, while 90 participants experienced two, three, or four exacerbations.

The researchers did not find a significant association between GAS exposure status and tic exacerbation.

Participants who did develop a GAS-associated exacerbation (n = 49) were younger at study exit (9.63 vs. 11.4 years, P < .0001) and were more likely to be male (46/49 vs. 210/259, Fisher’s = .035), compared with participants who developed a non-GAS-associated tic exacerbation (n = 259).

Additional analyses were adjusted for sex, age at onset, exposure to psychotropic medications, exposures to antibiotics, geographical regions, and number of visits in the time interval of interest. These analyses continued to yield no significant association between new or ongoing concurrent GAS exposure episodes and tic exacerbation events.

Of the children in the study, 103 had a positive throat swab, indicating a new definite GAS exposure, whereas 46 had a positive throat swab indicating an ongoing definite exposure (n = 149 visits). Of these visits, only 20 corresponded to tic exacerbations.

There was also no association between GAS exposure and OCD symptom severity. However, it was associated with longitudinal changes (between 17% and 21%, depending on GAS exposure definition) in the severity of hyperactivity-impulsivity symptoms in children with ADHD.

“It is known that immune activation may concur with tic severity in youth with CTDs and that psychosocial stress levels may predict short-term future tic severity in these patients,” the authors write.

“Our findings suggest that GAS is unlikely to be the main trigger for immune activation in these patients,” they add.
 

Brick or cornerstone?

Commenting on the study for this news organization, Margo Thienemann, MD, clinical professor of psychiatry, Stanford (Calif.) University, said that in the clinic population they treat, GAS, other pathogens, and other stresses can “each be associated with PANS symptom exacerbations.”

However, these “would not be likely to cause PANS symptoms exacerbations in the vast majority of individuals, only individuals with genetic backgrounds and immunologic dysfunctions creating susceptibility,” said Dr. Thienemann, who also directs the Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) Clinic at Stanford Children’s Health. She was not involved with the study.

In an accompanying editorial, Andrea Cavanna, MD, PhD, honorary reader in neuropsychiatry, Birmingham (England) Medical School and Keith Coffman, MD, director, Tourette Syndrome Center of Excellence, Children’s Mercy Hospital, Kansas City, Mo., suggest that perhaps the “interaction of psychosocial stress and GAS infections contributes more to tic exacerbation than psychosocial stress alone.”

“Time will tell whether this study stands as another brick – a cornerstone? – in the wall that separates streptococcus from tics,” they write.

The study was supported by the European Union’s Seventh Framework Program. Dr. Martino has received honoraria for lecturing from the Movement Disorders Society, Tourette Syndrome Association of America, and Dystonia Medical Research Foundation Canada; research funding support from Dystonia Medical Research Foundation Canada, the University of Calgary (Alta.), the Michael P. Smith Family, the Owerko Foundation, Ipsen Corporate, the Parkinson Association of Alberta, and the Canadian Institutes for Health Research; and royalties from Springer-Verlag. The other authors’ disclosures are listed in the original article. Dr. Cavanna, Dr. Coffman, and Dr. Thienemann have disclosed no relevant financial relationships.

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

Each February, the Centers for Disease Control and Prevention, along with multiple professional organizations, releases an updated Recommended Child and Adolescent Immunization Schedule.

Recent years have seen fewer changes in the vaccine schedule, mostly with adjustments based on products coming on or off the market, and sometimes with slight changes in recommendations. This year is no different, with mostly minor changes in store. As most practitioners know, having quick access to the tables that accompany the recommendations is always handy. Table 1 contains the typical, recommended immunization schedule. Table 2 contains the catch-up provisions, and Table 3 provides guidance on vaccines for special circumstances and for children with specific medical conditions.
 

2021 childhood and adolescent immunization schedule

One update is a recommendation that patients with egg allergies who had symptoms more extensive than hives should receive the influenza vaccine in a medical setting where severe allergic reactions or anaphylaxis can be recognized and treated, with the exclusion of two specific preparations, Flublok and Flucelvax.

In regard to the live attenuated influenza vaccine (LAIV), there are several points of reinforcement. First, the nomenclature has generally been changed to “LAIV4” throughout the document because only quadrivalent preparations are available. There are specific recommendations that patients should not receive LAIV4 if they recently took antiviral medication for influenza, with “lockout” periods lasting from 2 days to 17 days, depending on the antiviral preparation used. In addition, there is an emphasis on not using LAIV4 for children younger than 2 years.

Two updates to the meningococcal group B vaccine are worth reviewing. The first is that children aged 10 years or older with complement deficiency, complement inhibitor use, or asplenia should receive a meningitis B booster dose beginning 1 year after completion of the primary series, with boosters thereafter every 2 or 3 years as long as that patient remains at greater risk. Another recommendation for patients 10 years or older is that, even if they have received a primary series of meningitis B vaccines, they should receive a booster dose in the setting of an outbreak if it has been 1 year or more since completion of their primary series.

Recommendations have generally been relaxed for tetanus prophylaxis in older children, indicating that individuals requiring tetanus prophylaxis or their 10-year tetanus booster after receipt of at least one Tdap vaccine can receive either tetanus-diphtheria toxoid or Tdap.
 

COVID-19 vaccines

Although childhood vaccination against COVID-19 is still currently limited to adolescents involved in clinical trials, pediatricians surely are getting peppered with questions from parents about whether they should be vaccinated and what to make of the recent reports about allergic reactions. Fortunately, there are several resources for pediatricians. First, two reports point out that true anaphylactic reactions to COVID-19 vaccines appear quite rare. The reported data on Pfizer-developed mRNA vaccine demonstrated an anaphylaxis rate of approximately 2 cases per 1 million doses administered. Among the 21 recipients who experienced anaphylaxis (out of over 11 million total doses administered), fully one third had a history of anaphylaxis episodes. The report also reviews vaccine reactions that were reported but were not classified as anaphylaxis, pointing out that when reporting vaccine reactions, we should be very careful in the nomenclature we use.

Reporting on the Moderna mRNA vaccine showed anaphylaxis rates of about 2.5 per 1 million doses, with 50% of the recipients who experienced true anaphylaxis having a history of anaphylaxis. Most of those who experienced anaphylaxis (90% in the Moderna group and 86% in the Pfizer group) exhibited symptoms of anaphylaxis within 30 minutes of receiving the vaccine. The take-home point, and the current CDC recommendation, is that many individuals, even those with a history of anaphylaxis, can still receive COVID-19 vaccines. The rates of observed anaphylaxis after COVID vaccination are far below population rates of a history of allergy or severe allergic reactions. When coupled with an estimated mortality rate of 0.5%-1% for SARS-CoV-2 disease, that CDC recommends that we encourage people, even those with severe allergies, to get vaccinated.

One clear caveat is that individuals with a history of severe anaphylaxis, and even those concerned about allergies, should be observed for a longer period after vaccination (at least 30 minutes) than the 15 minutes recommended for the general population. In addition, individuals with a specific anaphylactic reaction or severe allergic reaction to any injectable vaccine should confer with an immunologist before considering vaccination.

Another useful resource is a column published by the American Medical Association that walks through some talking points for providers when discussing whether a patient should receive COVID-19 vaccination. Advice is offered on answering patient questions about which preparation to get, what side effects to watch for, and how to report an adverse reaction. Providers are reminded to urge patients to complete whichever series they begin (get that second dose!), and that they currently should not have to pay for a vaccine. FAQ resource pages are available for patients and health care providers.
 

More vaccine news: HPV and influenza

Meanwhile, published vaccine reports provide evidence from the field to demonstrate the benefits of vaccination. A study published in the New England Journal of Medicine reported on the effectiveness of human papillomavirus (HPV) vaccine in a Swedish cohort. The report evaluated females aged between 10 and 30 years beginning in 2006 and followed them through 2017, comparing rates of invasive cervical cancer among the group who received one or more HPV vaccine doses with the group who receive none. Even without adjustment, the raw rate of invasive cervical cancer in the vaccinated group was half of that in the unvaccinated group. After full adjustment, some populations experienced incident rate ratios that were greater than 80% reduced. The largest reduction, and therefore the biggest benefit, was among those who received the HPV vaccine before age 17.

A report from the United States looking at the 2018-2019 influenza season demonstrated a vaccine effectiveness rate against hospitalization of 41% and 51% against any ED visit related to influenza. The authors note that there was considerable drift in the influenza A type that appeared late in the influenza season, reducing the overall effectiveness, but that the vaccine was still largely effective.

William T. Basco Jr, MD, MS, is a professor of pediatrics at the Medical University of South Carolina, Charleston, and director of the division of general pediatrics. He is an active health services researcher and has published more than 60 manuscripts in the peer-reviewed literature.

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

Each February, the Centers for Disease Control and Prevention, along with multiple professional organizations, releases an updated Recommended Child and Adolescent Immunization Schedule.

Recent years have seen fewer changes in the vaccine schedule, mostly with adjustments based on products coming on or off the market, and sometimes with slight changes in recommendations. This year is no different, with mostly minor changes in store. As most practitioners know, having quick access to the tables that accompany the recommendations is always handy. Table 1 contains the typical, recommended immunization schedule. Table 2 contains the catch-up provisions, and Table 3 provides guidance on vaccines for special circumstances and for children with specific medical conditions.
 

2021 childhood and adolescent immunization schedule

One update is a recommendation that patients with egg allergies who had symptoms more extensive than hives should receive the influenza vaccine in a medical setting where severe allergic reactions or anaphylaxis can be recognized and treated, with the exclusion of two specific preparations, Flublok and Flucelvax.

In regard to the live attenuated influenza vaccine (LAIV), there are several points of reinforcement. First, the nomenclature has generally been changed to “LAIV4” throughout the document because only quadrivalent preparations are available. There are specific recommendations that patients should not receive LAIV4 if they recently took antiviral medication for influenza, with “lockout” periods lasting from 2 days to 17 days, depending on the antiviral preparation used. In addition, there is an emphasis on not using LAIV4 for children younger than 2 years.

Two updates to the meningococcal group B vaccine are worth reviewing. The first is that children aged 10 years or older with complement deficiency, complement inhibitor use, or asplenia should receive a meningitis B booster dose beginning 1 year after completion of the primary series, with boosters thereafter every 2 or 3 years as long as that patient remains at greater risk. Another recommendation for patients 10 years or older is that, even if they have received a primary series of meningitis B vaccines, they should receive a booster dose in the setting of an outbreak if it has been 1 year or more since completion of their primary series.

Recommendations have generally been relaxed for tetanus prophylaxis in older children, indicating that individuals requiring tetanus prophylaxis or their 10-year tetanus booster after receipt of at least one Tdap vaccine can receive either tetanus-diphtheria toxoid or Tdap.
 

COVID-19 vaccines

Although childhood vaccination against COVID-19 is still currently limited to adolescents involved in clinical trials, pediatricians surely are getting peppered with questions from parents about whether they should be vaccinated and what to make of the recent reports about allergic reactions. Fortunately, there are several resources for pediatricians. First, two reports point out that true anaphylactic reactions to COVID-19 vaccines appear quite rare. The reported data on Pfizer-developed mRNA vaccine demonstrated an anaphylaxis rate of approximately 2 cases per 1 million doses administered. Among the 21 recipients who experienced anaphylaxis (out of over 11 million total doses administered), fully one third had a history of anaphylaxis episodes. The report also reviews vaccine reactions that were reported but were not classified as anaphylaxis, pointing out that when reporting vaccine reactions, we should be very careful in the nomenclature we use.

Reporting on the Moderna mRNA vaccine showed anaphylaxis rates of about 2.5 per 1 million doses, with 50% of the recipients who experienced true anaphylaxis having a history of anaphylaxis. Most of those who experienced anaphylaxis (90% in the Moderna group and 86% in the Pfizer group) exhibited symptoms of anaphylaxis within 30 minutes of receiving the vaccine. The take-home point, and the current CDC recommendation, is that many individuals, even those with a history of anaphylaxis, can still receive COVID-19 vaccines. The rates of observed anaphylaxis after COVID vaccination are far below population rates of a history of allergy or severe allergic reactions. When coupled with an estimated mortality rate of 0.5%-1% for SARS-CoV-2 disease, that CDC recommends that we encourage people, even those with severe allergies, to get vaccinated.

One clear caveat is that individuals with a history of severe anaphylaxis, and even those concerned about allergies, should be observed for a longer period after vaccination (at least 30 minutes) than the 15 minutes recommended for the general population. In addition, individuals with a specific anaphylactic reaction or severe allergic reaction to any injectable vaccine should confer with an immunologist before considering vaccination.

Another useful resource is a column published by the American Medical Association that walks through some talking points for providers when discussing whether a patient should receive COVID-19 vaccination. Advice is offered on answering patient questions about which preparation to get, what side effects to watch for, and how to report an adverse reaction. Providers are reminded to urge patients to complete whichever series they begin (get that second dose!), and that they currently should not have to pay for a vaccine. FAQ resource pages are available for patients and health care providers.
 

More vaccine news: HPV and influenza

Meanwhile, published vaccine reports provide evidence from the field to demonstrate the benefits of vaccination. A study published in the New England Journal of Medicine reported on the effectiveness of human papillomavirus (HPV) vaccine in a Swedish cohort. The report evaluated females aged between 10 and 30 years beginning in 2006 and followed them through 2017, comparing rates of invasive cervical cancer among the group who received one or more HPV vaccine doses with the group who receive none. Even without adjustment, the raw rate of invasive cervical cancer in the vaccinated group was half of that in the unvaccinated group. After full adjustment, some populations experienced incident rate ratios that were greater than 80% reduced. The largest reduction, and therefore the biggest benefit, was among those who received the HPV vaccine before age 17.

A report from the United States looking at the 2018-2019 influenza season demonstrated a vaccine effectiveness rate against hospitalization of 41% and 51% against any ED visit related to influenza. The authors note that there was considerable drift in the influenza A type that appeared late in the influenza season, reducing the overall effectiveness, but that the vaccine was still largely effective.

William T. Basco Jr, MD, MS, is a professor of pediatrics at the Medical University of South Carolina, Charleston, and director of the division of general pediatrics. He is an active health services researcher and has published more than 60 manuscripts in the peer-reviewed literature.

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

Each February, the Centers for Disease Control and Prevention, along with multiple professional organizations, releases an updated Recommended Child and Adolescent Immunization Schedule.

Recent years have seen fewer changes in the vaccine schedule, mostly with adjustments based on products coming on or off the market, and sometimes with slight changes in recommendations. This year is no different, with mostly minor changes in store. As most practitioners know, having quick access to the tables that accompany the recommendations is always handy. Table 1 contains the typical, recommended immunization schedule. Table 2 contains the catch-up provisions, and Table 3 provides guidance on vaccines for special circumstances and for children with specific medical conditions.
 

2021 childhood and adolescent immunization schedule

One update is a recommendation that patients with egg allergies who had symptoms more extensive than hives should receive the influenza vaccine in a medical setting where severe allergic reactions or anaphylaxis can be recognized and treated, with the exclusion of two specific preparations, Flublok and Flucelvax.

In regard to the live attenuated influenza vaccine (LAIV), there are several points of reinforcement. First, the nomenclature has generally been changed to “LAIV4” throughout the document because only quadrivalent preparations are available. There are specific recommendations that patients should not receive LAIV4 if they recently took antiviral medication for influenza, with “lockout” periods lasting from 2 days to 17 days, depending on the antiviral preparation used. In addition, there is an emphasis on not using LAIV4 for children younger than 2 years.

Two updates to the meningococcal group B vaccine are worth reviewing. The first is that children aged 10 years or older with complement deficiency, complement inhibitor use, or asplenia should receive a meningitis B booster dose beginning 1 year after completion of the primary series, with boosters thereafter every 2 or 3 years as long as that patient remains at greater risk. Another recommendation for patients 10 years or older is that, even if they have received a primary series of meningitis B vaccines, they should receive a booster dose in the setting of an outbreak if it has been 1 year or more since completion of their primary series.

Recommendations have generally been relaxed for tetanus prophylaxis in older children, indicating that individuals requiring tetanus prophylaxis or their 10-year tetanus booster after receipt of at least one Tdap vaccine can receive either tetanus-diphtheria toxoid or Tdap.
 

COVID-19 vaccines

Although childhood vaccination against COVID-19 is still currently limited to adolescents involved in clinical trials, pediatricians surely are getting peppered with questions from parents about whether they should be vaccinated and what to make of the recent reports about allergic reactions. Fortunately, there are several resources for pediatricians. First, two reports point out that true anaphylactic reactions to COVID-19 vaccines appear quite rare. The reported data on Pfizer-developed mRNA vaccine demonstrated an anaphylaxis rate of approximately 2 cases per 1 million doses administered. Among the 21 recipients who experienced anaphylaxis (out of over 11 million total doses administered), fully one third had a history of anaphylaxis episodes. The report also reviews vaccine reactions that were reported but were not classified as anaphylaxis, pointing out that when reporting vaccine reactions, we should be very careful in the nomenclature we use.

Reporting on the Moderna mRNA vaccine showed anaphylaxis rates of about 2.5 per 1 million doses, with 50% of the recipients who experienced true anaphylaxis having a history of anaphylaxis. Most of those who experienced anaphylaxis (90% in the Moderna group and 86% in the Pfizer group) exhibited symptoms of anaphylaxis within 30 minutes of receiving the vaccine. The take-home point, and the current CDC recommendation, is that many individuals, even those with a history of anaphylaxis, can still receive COVID-19 vaccines. The rates of observed anaphylaxis after COVID vaccination are far below population rates of a history of allergy or severe allergic reactions. When coupled with an estimated mortality rate of 0.5%-1% for SARS-CoV-2 disease, that CDC recommends that we encourage people, even those with severe allergies, to get vaccinated.

One clear caveat is that individuals with a history of severe anaphylaxis, and even those concerned about allergies, should be observed for a longer period after vaccination (at least 30 minutes) than the 15 minutes recommended for the general population. In addition, individuals with a specific anaphylactic reaction or severe allergic reaction to any injectable vaccine should confer with an immunologist before considering vaccination.

Another useful resource is a column published by the American Medical Association that walks through some talking points for providers when discussing whether a patient should receive COVID-19 vaccination. Advice is offered on answering patient questions about which preparation to get, what side effects to watch for, and how to report an adverse reaction. Providers are reminded to urge patients to complete whichever series they begin (get that second dose!), and that they currently should not have to pay for a vaccine. FAQ resource pages are available for patients and health care providers.
 

More vaccine news: HPV and influenza

Meanwhile, published vaccine reports provide evidence from the field to demonstrate the benefits of vaccination. A study published in the New England Journal of Medicine reported on the effectiveness of human papillomavirus (HPV) vaccine in a Swedish cohort. The report evaluated females aged between 10 and 30 years beginning in 2006 and followed them through 2017, comparing rates of invasive cervical cancer among the group who received one or more HPV vaccine doses with the group who receive none. Even without adjustment, the raw rate of invasive cervical cancer in the vaccinated group was half of that in the unvaccinated group. After full adjustment, some populations experienced incident rate ratios that were greater than 80% reduced. The largest reduction, and therefore the biggest benefit, was among those who received the HPV vaccine before age 17.

A report from the United States looking at the 2018-2019 influenza season demonstrated a vaccine effectiveness rate against hospitalization of 41% and 51% against any ED visit related to influenza. The authors note that there was considerable drift in the influenza A type that appeared late in the influenza season, reducing the overall effectiveness, but that the vaccine was still largely effective.

William T. Basco Jr, MD, MS, is a professor of pediatrics at the Medical University of South Carolina, Charleston, and director of the division of general pediatrics. He is an active health services researcher and has published more than 60 manuscripts in the peer-reviewed literature.

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

The fifth consecutive week with a decline has the number of new COVID-19 cases in children at its lowest level since late October, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

New child cases totaled 70,640 for the week of Feb. 12-18, down from 99,000 the previous week, making for the lowest count since the week of Oct. 23-29, when 61,000 cases were reported, the AAP and CHA said in their weekly COVID-19 report.

The cumulative number of COVID-19 cases in children is now just over 3.1 million, which represents 13.1% of cases among all ages in the United States, based on data gathered from the health departments of 49 states (excluding New York), the District of Columbia, New York City, Puerto Rico, and Guam.

More children in California (439,000) have been infected than in any other state, while Illinois (176,000), Florida (145,000), Tennessee (137,000), Arizona (127,000), Ohio (121,000), and Pennsylvania (111,000) are the only other states with more than 100,000 cases, the AAP/CHA report shows.

Proportionally, the children of Wyoming have been hardest hit: Pediatric cases represent 19.4% of all cases in the state. The other four states with proportions of 18% or more are Alaska, Vermont, South Carolina, and Tennessee. Cumulative rates, however, tell a somewhat different story, as North Dakota leads with just over 8,500 cases per 100,000 children, followed by Tennessee (7,700 per 100,000) and Rhode Island (7,000 per 100,000), the AAP and CHA said.

Deaths in children, which had not been following the trend of fewer new cases over the last few weeks, dropped below double digits for the first time in a month. The six deaths that occurred during the week of Feb. 12-18 bring the total to 247 since the start of the pandemic in the 43 states, along with New York City and Guam, that are reporting such data, according to the report.

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The fifth consecutive week with a decline has the number of new COVID-19 cases in children at its lowest level since late October, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

New child cases totaled 70,640 for the week of Feb. 12-18, down from 99,000 the previous week, making for the lowest count since the week of Oct. 23-29, when 61,000 cases were reported, the AAP and CHA said in their weekly COVID-19 report.

The cumulative number of COVID-19 cases in children is now just over 3.1 million, which represents 13.1% of cases among all ages in the United States, based on data gathered from the health departments of 49 states (excluding New York), the District of Columbia, New York City, Puerto Rico, and Guam.

More children in California (439,000) have been infected than in any other state, while Illinois (176,000), Florida (145,000), Tennessee (137,000), Arizona (127,000), Ohio (121,000), and Pennsylvania (111,000) are the only other states with more than 100,000 cases, the AAP/CHA report shows.

Proportionally, the children of Wyoming have been hardest hit: Pediatric cases represent 19.4% of all cases in the state. The other four states with proportions of 18% or more are Alaska, Vermont, South Carolina, and Tennessee. Cumulative rates, however, tell a somewhat different story, as North Dakota leads with just over 8,500 cases per 100,000 children, followed by Tennessee (7,700 per 100,000) and Rhode Island (7,000 per 100,000), the AAP and CHA said.

Deaths in children, which had not been following the trend of fewer new cases over the last few weeks, dropped below double digits for the first time in a month. The six deaths that occurred during the week of Feb. 12-18 bring the total to 247 since the start of the pandemic in the 43 states, along with New York City and Guam, that are reporting such data, according to the report.

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The fifth consecutive week with a decline has the number of new COVID-19 cases in children at its lowest level since late October, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

New child cases totaled 70,640 for the week of Feb. 12-18, down from 99,000 the previous week, making for the lowest count since the week of Oct. 23-29, when 61,000 cases were reported, the AAP and CHA said in their weekly COVID-19 report.

The cumulative number of COVID-19 cases in children is now just over 3.1 million, which represents 13.1% of cases among all ages in the United States, based on data gathered from the health departments of 49 states (excluding New York), the District of Columbia, New York City, Puerto Rico, and Guam.

More children in California (439,000) have been infected than in any other state, while Illinois (176,000), Florida (145,000), Tennessee (137,000), Arizona (127,000), Ohio (121,000), and Pennsylvania (111,000) are the only other states with more than 100,000 cases, the AAP/CHA report shows.

Proportionally, the children of Wyoming have been hardest hit: Pediatric cases represent 19.4% of all cases in the state. The other four states with proportions of 18% or more are Alaska, Vermont, South Carolina, and Tennessee. Cumulative rates, however, tell a somewhat different story, as North Dakota leads with just over 8,500 cases per 100,000 children, followed by Tennessee (7,700 per 100,000) and Rhode Island (7,000 per 100,000), the AAP and CHA said.

Deaths in children, which had not been following the trend of fewer new cases over the last few weeks, dropped below double digits for the first time in a month. The six deaths that occurred during the week of Feb. 12-18 bring the total to 247 since the start of the pandemic in the 43 states, along with New York City and Guam, that are reporting such data, according to the report.

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The Food and Drug Administration on Feb. 22 updated its October 2020 guidance for manufacturers developing COVID-19 vaccines, diagnostics, and treatments in the wake of circulating SARS-CoV-2 variants.

The United States is currently facing three main variant threats, according to the Centers for Disease Control and Prevention: B.1.1.7, which originated in the United Kingdom; B.1.351 from South Africa; and the P.1 variant, which originated in Brazil.

Acting FDA Commissioner Janet Woodcock, MD, said on a telephone press briefing call Feb. 22 that the FDA has already been communicating with individual manufacturers as they assess the variants’ effect on their products, but these guidelines are issued for the sake of transparency and to welcome scientific input.
 

Tailoring may be necessary

Dr. Woodcock emphasized that, “at this time, available data suggest the FDA-authorized vaccines are effective in protecting circulating strains of SARS-CoV-2.” However, in the event the strains start to show resistance, it may be necessary to tailor the vaccine to the variant.

In that case, effectiveness of a modified vaccine should be determined by data from clinical immunogenicity studies, which would compare a recipient’s immune response with virus variants induced by the modified vaccine against the immune response to the authorized vaccine, the guidance states.

Manufacturers should also study the vaccine in both nonvaccinated people and people fully vaccinated with the authorized vaccine, according to the guidance.

Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said on the call that the clinical immunogenicity data is needed to understand, for instance, whether a new vaccine strain is able to cover the new and old strain or whether it just covers the new strain. Information is also needed to understand whether the modified vaccine, when given to someone fully vaccinated, will still promote a positive response without introducing safety concerns.

Further discussions will be necessary to decide whether future modified vaccines may be authorized without the need for clinical studies.
 

Variants and testing

The FDA’s updated guidance for test developers, Policy for Evaluating Impact of Viral Mutations on COVID-19 Tests, includes information that test performance can be influenced by the sequence of the variant, prevalence of the variant in the population, or design of the test. For example, molecular tests designed to detect multiple SARS-CoV-2 genetic targets are less susceptible to genetic variants than tests designed to detect a single genetic target.

The FDA already issued a safety alert on Jan. 8 to caution that genetic mutations to the virus in a patient sample can potentially change the performance of a diagnostic test. The FDA identified three tests that had been granted emergency-use authorization (EUA) that are known to be affected.

However, Dr. Woodcock said on the call, “at this time the impact does not appear to be significant.”
 

Updated guidance for therapeutics

The FDA has issued new guidance on the effect of variants on monoclonal antibody treatments.

“The FDA is aware that some of the monoclonal antibodies that have been authorized are less active against some of the SARS-CoV-2 variants that have emerged,” the FDA noted in its press release. “This guidance provides recommendations on efficient approaches to the generation of ... manufacturing and controls data that could potentially support an EUA for monoclonal antibody products that may be effective against emerging variants.”

While the FDA is monitoring the effects of variants, manufacturers bear a lot of the responsibility as well.

The FDA added: “With these guidances, the FDA is encouraging developers of drugs or biological products targeting SARS-CoV-2 to continuously monitor genomic databases for emerging SARS-CoV-2 variants and evaluate phenotypically any specific variants in the product target that are becoming prevalent or could potentially impact its activity.”

Dr.Woodcock added that “we urge all Americans to continue to get tested, get their vaccines when available, and follow important heath measures such as handwashing, masking, and social distancing.”

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

The Food and Drug Administration on Feb. 22 updated its October 2020 guidance for manufacturers developing COVID-19 vaccines, diagnostics, and treatments in the wake of circulating SARS-CoV-2 variants.

The United States is currently facing three main variant threats, according to the Centers for Disease Control and Prevention: B.1.1.7, which originated in the United Kingdom; B.1.351 from South Africa; and the P.1 variant, which originated in Brazil.

Acting FDA Commissioner Janet Woodcock, MD, said on a telephone press briefing call Feb. 22 that the FDA has already been communicating with individual manufacturers as they assess the variants’ effect on their products, but these guidelines are issued for the sake of transparency and to welcome scientific input.
 

Tailoring may be necessary

Dr. Woodcock emphasized that, “at this time, available data suggest the FDA-authorized vaccines are effective in protecting circulating strains of SARS-CoV-2.” However, in the event the strains start to show resistance, it may be necessary to tailor the vaccine to the variant.

In that case, effectiveness of a modified vaccine should be determined by data from clinical immunogenicity studies, which would compare a recipient’s immune response with virus variants induced by the modified vaccine against the immune response to the authorized vaccine, the guidance states.

Manufacturers should also study the vaccine in both nonvaccinated people and people fully vaccinated with the authorized vaccine, according to the guidance.

Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said on the call that the clinical immunogenicity data is needed to understand, for instance, whether a new vaccine strain is able to cover the new and old strain or whether it just covers the new strain. Information is also needed to understand whether the modified vaccine, when given to someone fully vaccinated, will still promote a positive response without introducing safety concerns.

Further discussions will be necessary to decide whether future modified vaccines may be authorized without the need for clinical studies.
 

Variants and testing

The FDA’s updated guidance for test developers, Policy for Evaluating Impact of Viral Mutations on COVID-19 Tests, includes information that test performance can be influenced by the sequence of the variant, prevalence of the variant in the population, or design of the test. For example, molecular tests designed to detect multiple SARS-CoV-2 genetic targets are less susceptible to genetic variants than tests designed to detect a single genetic target.

The FDA already issued a safety alert on Jan. 8 to caution that genetic mutations to the virus in a patient sample can potentially change the performance of a diagnostic test. The FDA identified three tests that had been granted emergency-use authorization (EUA) that are known to be affected.

However, Dr. Woodcock said on the call, “at this time the impact does not appear to be significant.”
 

Updated guidance for therapeutics

The FDA has issued new guidance on the effect of variants on monoclonal antibody treatments.

“The FDA is aware that some of the monoclonal antibodies that have been authorized are less active against some of the SARS-CoV-2 variants that have emerged,” the FDA noted in its press release. “This guidance provides recommendations on efficient approaches to the generation of ... manufacturing and controls data that could potentially support an EUA for monoclonal antibody products that may be effective against emerging variants.”

While the FDA is monitoring the effects of variants, manufacturers bear a lot of the responsibility as well.

The FDA added: “With these guidances, the FDA is encouraging developers of drugs or biological products targeting SARS-CoV-2 to continuously monitor genomic databases for emerging SARS-CoV-2 variants and evaluate phenotypically any specific variants in the product target that are becoming prevalent or could potentially impact its activity.”

Dr.Woodcock added that “we urge all Americans to continue to get tested, get their vaccines when available, and follow important heath measures such as handwashing, masking, and social distancing.”

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

The Food and Drug Administration on Feb. 22 updated its October 2020 guidance for manufacturers developing COVID-19 vaccines, diagnostics, and treatments in the wake of circulating SARS-CoV-2 variants.

The United States is currently facing three main variant threats, according to the Centers for Disease Control and Prevention: B.1.1.7, which originated in the United Kingdom; B.1.351 from South Africa; and the P.1 variant, which originated in Brazil.

Acting FDA Commissioner Janet Woodcock, MD, said on a telephone press briefing call Feb. 22 that the FDA has already been communicating with individual manufacturers as they assess the variants’ effect on their products, but these guidelines are issued for the sake of transparency and to welcome scientific input.
 

Tailoring may be necessary

Dr. Woodcock emphasized that, “at this time, available data suggest the FDA-authorized vaccines are effective in protecting circulating strains of SARS-CoV-2.” However, in the event the strains start to show resistance, it may be necessary to tailor the vaccine to the variant.

In that case, effectiveness of a modified vaccine should be determined by data from clinical immunogenicity studies, which would compare a recipient’s immune response with virus variants induced by the modified vaccine against the immune response to the authorized vaccine, the guidance states.

Manufacturers should also study the vaccine in both nonvaccinated people and people fully vaccinated with the authorized vaccine, according to the guidance.

Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said on the call that the clinical immunogenicity data is needed to understand, for instance, whether a new vaccine strain is able to cover the new and old strain or whether it just covers the new strain. Information is also needed to understand whether the modified vaccine, when given to someone fully vaccinated, will still promote a positive response without introducing safety concerns.

Further discussions will be necessary to decide whether future modified vaccines may be authorized without the need for clinical studies.
 

Variants and testing

The FDA’s updated guidance for test developers, Policy for Evaluating Impact of Viral Mutations on COVID-19 Tests, includes information that test performance can be influenced by the sequence of the variant, prevalence of the variant in the population, or design of the test. For example, molecular tests designed to detect multiple SARS-CoV-2 genetic targets are less susceptible to genetic variants than tests designed to detect a single genetic target.

The FDA already issued a safety alert on Jan. 8 to caution that genetic mutations to the virus in a patient sample can potentially change the performance of a diagnostic test. The FDA identified three tests that had been granted emergency-use authorization (EUA) that are known to be affected.

However, Dr. Woodcock said on the call, “at this time the impact does not appear to be significant.”
 

Updated guidance for therapeutics

The FDA has issued new guidance on the effect of variants on monoclonal antibody treatments.

“The FDA is aware that some of the monoclonal antibodies that have been authorized are less active against some of the SARS-CoV-2 variants that have emerged,” the FDA noted in its press release. “This guidance provides recommendations on efficient approaches to the generation of ... manufacturing and controls data that could potentially support an EUA for monoclonal antibody products that may be effective against emerging variants.”

While the FDA is monitoring the effects of variants, manufacturers bear a lot of the responsibility as well.

The FDA added: “With these guidances, the FDA is encouraging developers of drugs or biological products targeting SARS-CoV-2 to continuously monitor genomic databases for emerging SARS-CoV-2 variants and evaluate phenotypically any specific variants in the product target that are becoming prevalent or could potentially impact its activity.”

Dr.Woodcock added that “we urge all Americans to continue to get tested, get their vaccines when available, and follow important heath measures such as handwashing, masking, and social distancing.”

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

Oxford University is starting a COVID-19 vaccine study with children and young adults aged between 6 and 17 years.

At Oxford and three partner sites in London, Southampton, and Bristol, the phase 2 clinical trial will test whether kids and teens have a good immune response to the AstraZeneca vaccine. Previous trials have shown that the shot is safe in children.

“While most children are relatively unaffected by coronavirus and are unlikely to become unwell with the infection, it is important to establish the safety and immune response to the vaccine in children and young people as some children may benefit from vaccination,” Andrew Pollard, PhD, the chief investigator for the trial and a professor of pediatric infection and immunity at Oxford, said in a statement.

The new trial will enroll 300 volunteers, with up to 240 receiving the vaccine. The control group will receive a meningitis vaccine, which is safe in children and produces similar side effects to the COVID-19 vaccine, such as a sore arm.

COVID-19 vaccine trials have included children over age 12, so this marks the youngest group to be tested so far. Pfizer, Moderna, and Janssen have announced plans to start trials in younger children this spring, according to the Washington Post. Widespread vaccination in children likely won’t occur until 2022, the newspaper reported.

The trial launched on Feb. 12, and the first vaccinations are expected by the end of the month. Parents can visit Oxford’s COVID-19 Vaccine Trial website to sign their children up for the study.

“This study will play an important role in helping to protect children in the future,” Grace Li, a pediatric clinical research fellow for the Oxford Vaccine Group, said in the statement.

“We’ve already seen that the vaccine is safe and effective in adults, and our understanding of how children are affected by the coronavirus continues to evolve,” she said.

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

Oxford University is starting a COVID-19 vaccine study with children and young adults aged between 6 and 17 years.

At Oxford and three partner sites in London, Southampton, and Bristol, the phase 2 clinical trial will test whether kids and teens have a good immune response to the AstraZeneca vaccine. Previous trials have shown that the shot is safe in children.

“While most children are relatively unaffected by coronavirus and are unlikely to become unwell with the infection, it is important to establish the safety and immune response to the vaccine in children and young people as some children may benefit from vaccination,” Andrew Pollard, PhD, the chief investigator for the trial and a professor of pediatric infection and immunity at Oxford, said in a statement.

The new trial will enroll 300 volunteers, with up to 240 receiving the vaccine. The control group will receive a meningitis vaccine, which is safe in children and produces similar side effects to the COVID-19 vaccine, such as a sore arm.

COVID-19 vaccine trials have included children over age 12, so this marks the youngest group to be tested so far. Pfizer, Moderna, and Janssen have announced plans to start trials in younger children this spring, according to the Washington Post. Widespread vaccination in children likely won’t occur until 2022, the newspaper reported.

The trial launched on Feb. 12, and the first vaccinations are expected by the end of the month. Parents can visit Oxford’s COVID-19 Vaccine Trial website to sign their children up for the study.

“This study will play an important role in helping to protect children in the future,” Grace Li, a pediatric clinical research fellow for the Oxford Vaccine Group, said in the statement.

“We’ve already seen that the vaccine is safe and effective in adults, and our understanding of how children are affected by the coronavirus continues to evolve,” she said.

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

Oxford University is starting a COVID-19 vaccine study with children and young adults aged between 6 and 17 years.

At Oxford and three partner sites in London, Southampton, and Bristol, the phase 2 clinical trial will test whether kids and teens have a good immune response to the AstraZeneca vaccine. Previous trials have shown that the shot is safe in children.

“While most children are relatively unaffected by coronavirus and are unlikely to become unwell with the infection, it is important to establish the safety and immune response to the vaccine in children and young people as some children may benefit from vaccination,” Andrew Pollard, PhD, the chief investigator for the trial and a professor of pediatric infection and immunity at Oxford, said in a statement.

The new trial will enroll 300 volunteers, with up to 240 receiving the vaccine. The control group will receive a meningitis vaccine, which is safe in children and produces similar side effects to the COVID-19 vaccine, such as a sore arm.

COVID-19 vaccine trials have included children over age 12, so this marks the youngest group to be tested so far. Pfizer, Moderna, and Janssen have announced plans to start trials in younger children this spring, according to the Washington Post. Widespread vaccination in children likely won’t occur until 2022, the newspaper reported.

The trial launched on Feb. 12, and the first vaccinations are expected by the end of the month. Parents can visit Oxford’s COVID-19 Vaccine Trial website to sign their children up for the study.

“This study will play an important role in helping to protect children in the future,” Grace Li, a pediatric clinical research fellow for the Oxford Vaccine Group, said in the statement.

“We’ve already seen that the vaccine is safe and effective in adults, and our understanding of how children are affected by the coronavirus continues to evolve,” she said.

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