Infectious Disease Practitioner

If you’re among those people in the United States who never had COVID-19, how should you think about your risk?

According to the Centers for Disease Control and Prevention (CDC), more than half of people in the United States are in the never-got-COVID category.

The CDC estimated that by the end of January, 43.4% in the United States had developed antibodies to SARS-CoV-2 triggered by infection, not by vaccination — suggesting nearly 60% of people have never been infected.

Now mask mandates are lifting, and daily case and death numbers are plunging. According to the New York Times tracker, new cases are down 51% for the past 2 weeks, and deaths have fallen 30% in that period.

So as those who have so far escaped the virus venture further out into reopened environments, should they worry more or less about risk than their previously infected counterparts?

Some experts weigh in with caution against feeling invincible.
 

No “suit of armor”

William Schaffner, MD, an infectious disease expert at Vanderbilt University School of Medicine in Nashville, Tenn., said in an interview that science has not been able to determine why some people have been able to be stay COVID-free when the virus was raging and exposure was ubiquitous.

He said it’s important to remember that though some people think they have never had COVID, they may have been asymptomatic or attributed mild symptoms to something else.

“People may have conceivably — but we can’t define them yet — different capacities to ward off viruses or bacteria,” Dr. Schaffner said.

Could it be that some people have a better immune system or genetic component or environmental reason that they are less susceptible to infectious disease? “We can’t define that in 2022 medicine, but it could be,” he said.

More is known about why people with the same COVID exposure may have different levels of illness severity.

“They’re more likely to get seriously ill if they have a list of predisposing conditions — if they’re older, if they’re frail, if they have underlying illness or are obese. All of those things clearly impair the body’s response to virus,” Dr. Schaffner said.

He warns those who have never been infected, though, not to assume they have “a suit of armor.”

All should continue to follow guidance on getting vaccinated, and those vaccinated should continue to get boosted, Dr. Schaffner said.

“Clearly, the data show that if you are vaccinated and boosted, you’re protected much more securely against severe disease,” he said.

If the never-COVIDs develop a respiratory infection, they should still get tested for COVID, Dr. Schaffner said.

He said while both vaccines and previous natural infection offer protection, the duration of that protection is not yet known.

“We have to stay tuned,” Dr. Schaffner said. “There may be a recommendation in the future to get a booster annually or something like that. We need to be open to those down the road.”

Amesh Adalja, MD, senior scholar at the Johns Hopkins Center for Health Security in Baltimore, says it’s unclear why some people have been able to avoid COVID.

“The explanation is likely multifactorial and involves behaviors as well as possible idiosyncrasies with their immune systems that are genetically based,” he said. “It also may be the case that inapparent infections occurred and went undiagnosed.”

Dr. Adalja agrees, though, that this isn’t the time to get overconfident with risk-taking where COVID is concerned.

“People who have not knowingly been infected with COVID should be vaccinated, and after that, be assured that they are protected against serious disease from this virus,” he said.
 

Genetic protection?

A new study in Nature Genetics explains a potential genetic relationship. Study authors found evidence that levels of expression of angiotensin-converting enzyme 2 (ACE2) – which helps regulate blood pressure, wound healing, and inflammation, but has also been shown to serve as an entry point into cells for some coronaviruses like SARS-CoV-2 — influence COVID-19 risk.

Manuel A. Ferreira, PhD, an executive director for analytic genetics at Regeneron Pharmaceuticals, said in an interview that ACE2 receptors — what he calls the “gateways” for SARS-CoV-2 to enter the body — are different in people who have inherited a particular allele.

The researchers have found that that allele is associated with lower risk of SARS-CoV-2 infection.

“It’s quite substantial -- a 40% risk reduction if you carry the allele that reduces ACE2 expression,” he said. They were not able to discern from this study, however, whether that could predict severity of disease.

The team also looked at a series of six genetic variants elsewhere in the genome and developed a risk score to see if it was possible to predict who might be more susceptible to severe COVID.

Dr. Ferreira said the score only slightly improved predictive abilities beyond factors such as age, sex, weight, and comorbidities. Further information will help hone the ability to predict the likelihood of developing severe disease on the basis of genetics, Ferreira said.

“As we identify more genetic risk factors for COVID — variants like the ACE2 variant that will affect your risk of having COVID — the more informative the risk score will be,” he said.

Several authors of the Nature Genetics article are current and/or former employees of AncestryDNA and may hold equity in AncestryDNA. Several are Regeneron employees and/or hold stock in the company. Dr. Ferreira is an employee of Regeneron and holds stock in the company. Dr. Schaffner and Dr. Adalja report no relevant financial relationships.

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

If you’re among those people in the United States who never had COVID-19, how should you think about your risk?

According to the Centers for Disease Control and Prevention (CDC), more than half of people in the United States are in the never-got-COVID category.

The CDC estimated that by the end of January, 43.4% in the United States had developed antibodies to SARS-CoV-2 triggered by infection, not by vaccination — suggesting nearly 60% of people have never been infected.

Now mask mandates are lifting, and daily case and death numbers are plunging. According to the New York Times tracker, new cases are down 51% for the past 2 weeks, and deaths have fallen 30% in that period.

So as those who have so far escaped the virus venture further out into reopened environments, should they worry more or less about risk than their previously infected counterparts?

Some experts weigh in with caution against feeling invincible.
 

No “suit of armor”

William Schaffner, MD, an infectious disease expert at Vanderbilt University School of Medicine in Nashville, Tenn., said in an interview that science has not been able to determine why some people have been able to be stay COVID-free when the virus was raging and exposure was ubiquitous.

He said it’s important to remember that though some people think they have never had COVID, they may have been asymptomatic or attributed mild symptoms to something else.

“People may have conceivably — but we can’t define them yet — different capacities to ward off viruses or bacteria,” Dr. Schaffner said.

Could it be that some people have a better immune system or genetic component or environmental reason that they are less susceptible to infectious disease? “We can’t define that in 2022 medicine, but it could be,” he said.

More is known about why people with the same COVID exposure may have different levels of illness severity.

“They’re more likely to get seriously ill if they have a list of predisposing conditions — if they’re older, if they’re frail, if they have underlying illness or are obese. All of those things clearly impair the body’s response to virus,” Dr. Schaffner said.

He warns those who have never been infected, though, not to assume they have “a suit of armor.”

All should continue to follow guidance on getting vaccinated, and those vaccinated should continue to get boosted, Dr. Schaffner said.

“Clearly, the data show that if you are vaccinated and boosted, you’re protected much more securely against severe disease,” he said.

If the never-COVIDs develop a respiratory infection, they should still get tested for COVID, Dr. Schaffner said.

He said while both vaccines and previous natural infection offer protection, the duration of that protection is not yet known.

“We have to stay tuned,” Dr. Schaffner said. “There may be a recommendation in the future to get a booster annually or something like that. We need to be open to those down the road.”

Amesh Adalja, MD, senior scholar at the Johns Hopkins Center for Health Security in Baltimore, says it’s unclear why some people have been able to avoid COVID.

“The explanation is likely multifactorial and involves behaviors as well as possible idiosyncrasies with their immune systems that are genetically based,” he said. “It also may be the case that inapparent infections occurred and went undiagnosed.”

Dr. Adalja agrees, though, that this isn’t the time to get overconfident with risk-taking where COVID is concerned.

“People who have not knowingly been infected with COVID should be vaccinated, and after that, be assured that they are protected against serious disease from this virus,” he said.
 

Genetic protection?

A new study in Nature Genetics explains a potential genetic relationship. Study authors found evidence that levels of expression of angiotensin-converting enzyme 2 (ACE2) – which helps regulate blood pressure, wound healing, and inflammation, but has also been shown to serve as an entry point into cells for some coronaviruses like SARS-CoV-2 — influence COVID-19 risk.

Manuel A. Ferreira, PhD, an executive director for analytic genetics at Regeneron Pharmaceuticals, said in an interview that ACE2 receptors — what he calls the “gateways” for SARS-CoV-2 to enter the body — are different in people who have inherited a particular allele.

The researchers have found that that allele is associated with lower risk of SARS-CoV-2 infection.

“It’s quite substantial -- a 40% risk reduction if you carry the allele that reduces ACE2 expression,” he said. They were not able to discern from this study, however, whether that could predict severity of disease.

The team also looked at a series of six genetic variants elsewhere in the genome and developed a risk score to see if it was possible to predict who might be more susceptible to severe COVID.

Dr. Ferreira said the score only slightly improved predictive abilities beyond factors such as age, sex, weight, and comorbidities. Further information will help hone the ability to predict the likelihood of developing severe disease on the basis of genetics, Ferreira said.

“As we identify more genetic risk factors for COVID — variants like the ACE2 variant that will affect your risk of having COVID — the more informative the risk score will be,” he said.

Several authors of the Nature Genetics article are current and/or former employees of AncestryDNA and may hold equity in AncestryDNA. Several are Regeneron employees and/or hold stock in the company. Dr. Ferreira is an employee of Regeneron and holds stock in the company. Dr. Schaffner and Dr. Adalja report no relevant financial relationships.

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

If you’re among those people in the United States who never had COVID-19, how should you think about your risk?

According to the Centers for Disease Control and Prevention (CDC), more than half of people in the United States are in the never-got-COVID category.

The CDC estimated that by the end of January, 43.4% in the United States had developed antibodies to SARS-CoV-2 triggered by infection, not by vaccination — suggesting nearly 60% of people have never been infected.

Now mask mandates are lifting, and daily case and death numbers are plunging. According to the New York Times tracker, new cases are down 51% for the past 2 weeks, and deaths have fallen 30% in that period.

So as those who have so far escaped the virus venture further out into reopened environments, should they worry more or less about risk than their previously infected counterparts?

Some experts weigh in with caution against feeling invincible.
 

No “suit of armor”

William Schaffner, MD, an infectious disease expert at Vanderbilt University School of Medicine in Nashville, Tenn., said in an interview that science has not been able to determine why some people have been able to be stay COVID-free when the virus was raging and exposure was ubiquitous.

He said it’s important to remember that though some people think they have never had COVID, they may have been asymptomatic or attributed mild symptoms to something else.

“People may have conceivably — but we can’t define them yet — different capacities to ward off viruses or bacteria,” Dr. Schaffner said.

Could it be that some people have a better immune system or genetic component or environmental reason that they are less susceptible to infectious disease? “We can’t define that in 2022 medicine, but it could be,” he said.

More is known about why people with the same COVID exposure may have different levels of illness severity.

“They’re more likely to get seriously ill if they have a list of predisposing conditions — if they’re older, if they’re frail, if they have underlying illness or are obese. All of those things clearly impair the body’s response to virus,” Dr. Schaffner said.

He warns those who have never been infected, though, not to assume they have “a suit of armor.”

All should continue to follow guidance on getting vaccinated, and those vaccinated should continue to get boosted, Dr. Schaffner said.

“Clearly, the data show that if you are vaccinated and boosted, you’re protected much more securely against severe disease,” he said.

If the never-COVIDs develop a respiratory infection, they should still get tested for COVID, Dr. Schaffner said.

He said while both vaccines and previous natural infection offer protection, the duration of that protection is not yet known.

“We have to stay tuned,” Dr. Schaffner said. “There may be a recommendation in the future to get a booster annually or something like that. We need to be open to those down the road.”

Amesh Adalja, MD, senior scholar at the Johns Hopkins Center for Health Security in Baltimore, says it’s unclear why some people have been able to avoid COVID.

“The explanation is likely multifactorial and involves behaviors as well as possible idiosyncrasies with their immune systems that are genetically based,” he said. “It also may be the case that inapparent infections occurred and went undiagnosed.”

Dr. Adalja agrees, though, that this isn’t the time to get overconfident with risk-taking where COVID is concerned.

“People who have not knowingly been infected with COVID should be vaccinated, and after that, be assured that they are protected against serious disease from this virus,” he said.
 

Genetic protection?

A new study in Nature Genetics explains a potential genetic relationship. Study authors found evidence that levels of expression of angiotensin-converting enzyme 2 (ACE2) – which helps regulate blood pressure, wound healing, and inflammation, but has also been shown to serve as an entry point into cells for some coronaviruses like SARS-CoV-2 — influence COVID-19 risk.

Manuel A. Ferreira, PhD, an executive director for analytic genetics at Regeneron Pharmaceuticals, said in an interview that ACE2 receptors — what he calls the “gateways” for SARS-CoV-2 to enter the body — are different in people who have inherited a particular allele.

The researchers have found that that allele is associated with lower risk of SARS-CoV-2 infection.

“It’s quite substantial -- a 40% risk reduction if you carry the allele that reduces ACE2 expression,” he said. They were not able to discern from this study, however, whether that could predict severity of disease.

The team also looked at a series of six genetic variants elsewhere in the genome and developed a risk score to see if it was possible to predict who might be more susceptible to severe COVID.

Dr. Ferreira said the score only slightly improved predictive abilities beyond factors such as age, sex, weight, and comorbidities. Further information will help hone the ability to predict the likelihood of developing severe disease on the basis of genetics, Ferreira said.

“As we identify more genetic risk factors for COVID — variants like the ACE2 variant that will affect your risk of having COVID — the more informative the risk score will be,” he said.

Several authors of the Nature Genetics article are current and/or former employees of AncestryDNA and may hold equity in AncestryDNA. Several are Regeneron employees and/or hold stock in the company. Dr. Ferreira is an employee of Regeneron and holds stock in the company. Dr. Schaffner and Dr. Adalja report no relevant financial relationships.

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

Pseudomonas aeruginosa persisted in the airways of patients with chronic obstructive pulmonary disease (COPD), based on data from 23 patients over a 1-year period.

P. aeruginosa is cultured in as many as 20% of bacterial exacerbations and has been linked to increased morbidity and mortality in patients with COPD, wrote Josefin Eklöf, MD, of the University of Copenhagen and colleagues. However, its patterns and characteristics have not been well studied, and researchers proposed that P. aerunginosa persists in COPD patients in part because of genetic adaptations in the genes related to antibiotic resistance.

In a study published in Clinical Microbiology and Infection, the researchers identified 23 consecutive patients enrolled in an ongoing randomized clinical trial at four sites in Denmark between Jan. 2018 and Jan. 2020. Participants were randomized 1:1 to targeted antipseudomonal antibiotic treatment for 14 days (between visit day 1 and visit day 14) or no antipseudomonal treatment. Sputum samples were collected at baseline on day 1 and on days 14, 30, 60, 90, and 365.

The researchers sequenced isolates from 23 adult patients over 365 days of follow-up. The recurrence of P. aeruginosa occurred in 19 patients (83%) during this period. Ultimately, a total of 153 isolates were analyzed. The researchers found that each patient carried their own unique lineage, with the except of one patient in whom two distinct lineages were identified.

“Independent mutation of the same gene across multiple lineages may be the result of positive selection of adaptive mutations,” Dr. Eklöf and colleagues wrote. They found 38 genes for P. aeruginosa that were mutated in at least two lineages, which suggested adaptive mutations. Some of the more frequently mutated genes were those important to antibiotic resistance and chronic infections, the researchers said. Specifically, mutations occurred in 40 of 140 pathoadaptive genes, compared with 265 of 5,572 other genes (P < .001). In addition, the 24 total lineages carried 4-6 antibiotic resistance genes, and no evidence suggested that lineages acquired or lost these genes during carriage.

Overall, the results indicate that the recurrence of P. aeruginosa was caused by persistence of the same clonal lineage in each patient. “This pattern of persistence was associated with genetic adaptation related to phenotypes considered important for P. aeruginosa infections,” the researchers said.

The study findings were limited by the relatively small number of samples and isolates per sample, the follow-up of only 1 year, and the inability to account for mutations in the early stage because few patients were naive to P. aeruginosa at the start of the study, the researchers noted. However, the results were strengthened by the relatively large and well-defined study population and high rate of sampling compliance, they said.

Overall, “the findings warrant research to improve therapy, including trial data on possible clinical benefits of attempting antibiotic eradication of P. aeruginosa in this vulnerable group of patients,” they concluded.

The study was supported by the Independent Research Fund Denmark and the Research committee at Copenhagen University Hospital-Herlev and Gentofte Hospital. The researchers had no financial conflicts to disclose.

Pseudomonas aeruginosa persisted in the airways of patients with chronic obstructive pulmonary disease (COPD), based on data from 23 patients over a 1-year period.

P. aeruginosa is cultured in as many as 20% of bacterial exacerbations and has been linked to increased morbidity and mortality in patients with COPD, wrote Josefin Eklöf, MD, of the University of Copenhagen and colleagues. However, its patterns and characteristics have not been well studied, and researchers proposed that P. aerunginosa persists in COPD patients in part because of genetic adaptations in the genes related to antibiotic resistance.

In a study published in Clinical Microbiology and Infection, the researchers identified 23 consecutive patients enrolled in an ongoing randomized clinical trial at four sites in Denmark between Jan. 2018 and Jan. 2020. Participants were randomized 1:1 to targeted antipseudomonal antibiotic treatment for 14 days (between visit day 1 and visit day 14) or no antipseudomonal treatment. Sputum samples were collected at baseline on day 1 and on days 14, 30, 60, 90, and 365.

The researchers sequenced isolates from 23 adult patients over 365 days of follow-up. The recurrence of P. aeruginosa occurred in 19 patients (83%) during this period. Ultimately, a total of 153 isolates were analyzed. The researchers found that each patient carried their own unique lineage, with the except of one patient in whom two distinct lineages were identified.

“Independent mutation of the same gene across multiple lineages may be the result of positive selection of adaptive mutations,” Dr. Eklöf and colleagues wrote. They found 38 genes for P. aeruginosa that were mutated in at least two lineages, which suggested adaptive mutations. Some of the more frequently mutated genes were those important to antibiotic resistance and chronic infections, the researchers said. Specifically, mutations occurred in 40 of 140 pathoadaptive genes, compared with 265 of 5,572 other genes (P < .001). In addition, the 24 total lineages carried 4-6 antibiotic resistance genes, and no evidence suggested that lineages acquired or lost these genes during carriage.

Overall, the results indicate that the recurrence of P. aeruginosa was caused by persistence of the same clonal lineage in each patient. “This pattern of persistence was associated with genetic adaptation related to phenotypes considered important for P. aeruginosa infections,” the researchers said.

The study findings were limited by the relatively small number of samples and isolates per sample, the follow-up of only 1 year, and the inability to account for mutations in the early stage because few patients were naive to P. aeruginosa at the start of the study, the researchers noted. However, the results were strengthened by the relatively large and well-defined study population and high rate of sampling compliance, they said.

Overall, “the findings warrant research to improve therapy, including trial data on possible clinical benefits of attempting antibiotic eradication of P. aeruginosa in this vulnerable group of patients,” they concluded.

The study was supported by the Independent Research Fund Denmark and the Research committee at Copenhagen University Hospital-Herlev and Gentofte Hospital. The researchers had no financial conflicts to disclose.

Pseudomonas aeruginosa persisted in the airways of patients with chronic obstructive pulmonary disease (COPD), based on data from 23 patients over a 1-year period.

P. aeruginosa is cultured in as many as 20% of bacterial exacerbations and has been linked to increased morbidity and mortality in patients with COPD, wrote Josefin Eklöf, MD, of the University of Copenhagen and colleagues. However, its patterns and characteristics have not been well studied, and researchers proposed that P. aerunginosa persists in COPD patients in part because of genetic adaptations in the genes related to antibiotic resistance.

In a study published in Clinical Microbiology and Infection, the researchers identified 23 consecutive patients enrolled in an ongoing randomized clinical trial at four sites in Denmark between Jan. 2018 and Jan. 2020. Participants were randomized 1:1 to targeted antipseudomonal antibiotic treatment for 14 days (between visit day 1 and visit day 14) or no antipseudomonal treatment. Sputum samples were collected at baseline on day 1 and on days 14, 30, 60, 90, and 365.

The researchers sequenced isolates from 23 adult patients over 365 days of follow-up. The recurrence of P. aeruginosa occurred in 19 patients (83%) during this period. Ultimately, a total of 153 isolates were analyzed. The researchers found that each patient carried their own unique lineage, with the except of one patient in whom two distinct lineages were identified.

“Independent mutation of the same gene across multiple lineages may be the result of positive selection of adaptive mutations,” Dr. Eklöf and colleagues wrote. They found 38 genes for P. aeruginosa that were mutated in at least two lineages, which suggested adaptive mutations. Some of the more frequently mutated genes were those important to antibiotic resistance and chronic infections, the researchers said. Specifically, mutations occurred in 40 of 140 pathoadaptive genes, compared with 265 of 5,572 other genes (P < .001). In addition, the 24 total lineages carried 4-6 antibiotic resistance genes, and no evidence suggested that lineages acquired or lost these genes during carriage.

Overall, the results indicate that the recurrence of P. aeruginosa was caused by persistence of the same clonal lineage in each patient. “This pattern of persistence was associated with genetic adaptation related to phenotypes considered important for P. aeruginosa infections,” the researchers said.

The study findings were limited by the relatively small number of samples and isolates per sample, the follow-up of only 1 year, and the inability to account for mutations in the early stage because few patients were naive to P. aeruginosa at the start of the study, the researchers noted. However, the results were strengthened by the relatively large and well-defined study population and high rate of sampling compliance, they said.

Overall, “the findings warrant research to improve therapy, including trial data on possible clinical benefits of attempting antibiotic eradication of P. aeruginosa in this vulnerable group of patients,” they concluded.

The study was supported by the Independent Research Fund Denmark and the Research committee at Copenhagen University Hospital-Herlev and Gentofte Hospital. The researchers had no financial conflicts to disclose.

Even mild cases of COVID-19 are associated with brain changes, including decreased gray matter, an overall reduction in brain volume, and cognitive decline, a new imaging study shows.

In the first study to use magnetic resonance brain imaging, before and after COVID-19, investigators found “greater reduction in grey matter thickness and tissue-contrast in the orbitofrontal cortex and parahippocampal gyrus, greater changes in markers of tissue damage in regions functionally connected to the primary olfactory cortex and greater reduction in global brain size.” However, the researchers urge caution when interpreting the findings.

Gwenaëlle Douaud, PhD, Wellcome Center for Integrative Neuroimaging, Nuffield Department of Clinical Neurosciences, University of Oxford, England, and colleagues describe these brain changes as “modest.”

“Whether these abnormal changes are the hallmark of the spread of the pathogenic effects in the brain, or of the virus itself, and whether these may prefigure a future vulnerability of the limbic system in particular, including memory, for these participants, remains to be investigated,” the researchers wrote.

The findings were published online March 7 in the journal Nature.
 

Gray matter loss

The investigators analyzed data from the UK Biobank, a large-scale biomedical database with genetic and health information for about 500,000 individuals living in the UK. They identified 785 adults aged 51-81 years who had undergone two brain MRIs about 3 years apart. Of these, 401 tested positive for SARS-CoV-2 before the second scan.

Participants also completed cognitive tests at the time of both scans.

Biobank centers use identical MRI scans and scanning methods, including six types of MRI scans, to image distinct regions of the brain and brain function. Results showed that although some loss of gray matter over time is normal, individuals who were infected with SARS-CoV-2 showed a 0.2% to 2% brain tissue loss in the parahippocampal gyrus, the orbitofrontal cortex, and the insula – all of which are largely involved in the sense of smell.

Participants who had contracted COVID-19 also showed a greater reduction in overall brain volume and a decrease in cognitive function.

Most of those with COVID-19 had only mild or moderate symptoms. However, the findings held even after the researchers excluded patients who had been hospitalized.
 

More research needed

“These findings might help explain why some people experience brain symptoms long after the acute infection,” Max Taquet, PhD, National Institute for Health Research Oxford Health BRC senior research fellow, University of Oxford, said in a press release.

Dr. Taquet, who was not a part of the study, noted the causes of these brain changes remain to be determined. Questions remain as to “whether they can be prevented or even reverted, as well as whether similar changes are observed in hospitalized patients,” children, younger adults, and minority groups.

“It is possible that these brain changes are not caused by COVID-19 but represent the natural progression of a disease that itself increased the risk of COVID-19,” Dr. Taquet said.

Other experts expressed concern over the findings and emphasized the need for more research.

“I am very concerned by the alarming use of language in the report with terms such as ‘neurodegenerative,’ “ Alan Carson, MD, professor of neuropsychiatry at the Center for Clinical Brain Sciences at the University of Edinburgh, Scotland, said in a press release. “The size and magnitude of brain changes found is very modest and such changes can be caused by a simple change in mental experience,” Dr. Carson said.

“What this study almost certainly shows is the impact, in terms of neural changes, of being disconnected from one’s sense of smell,” he added.

The study was funded by the Wellcome Trust Collaborative. Full financial conflict information for the study authors is included in the original article. Dr. Taquet has collaborated previously with some of the investigators.

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

Even mild cases of COVID-19 are associated with brain changes, including decreased gray matter, an overall reduction in brain volume, and cognitive decline, a new imaging study shows.

In the first study to use magnetic resonance brain imaging, before and after COVID-19, investigators found “greater reduction in grey matter thickness and tissue-contrast in the orbitofrontal cortex and parahippocampal gyrus, greater changes in markers of tissue damage in regions functionally connected to the primary olfactory cortex and greater reduction in global brain size.” However, the researchers urge caution when interpreting the findings.

Gwenaëlle Douaud, PhD, Wellcome Center for Integrative Neuroimaging, Nuffield Department of Clinical Neurosciences, University of Oxford, England, and colleagues describe these brain changes as “modest.”

“Whether these abnormal changes are the hallmark of the spread of the pathogenic effects in the brain, or of the virus itself, and whether these may prefigure a future vulnerability of the limbic system in particular, including memory, for these participants, remains to be investigated,” the researchers wrote.

The findings were published online March 7 in the journal Nature.
 

Gray matter loss

The investigators analyzed data from the UK Biobank, a large-scale biomedical database with genetic and health information for about 500,000 individuals living in the UK. They identified 785 adults aged 51-81 years who had undergone two brain MRIs about 3 years apart. Of these, 401 tested positive for SARS-CoV-2 before the second scan.

Participants also completed cognitive tests at the time of both scans.

Biobank centers use identical MRI scans and scanning methods, including six types of MRI scans, to image distinct regions of the brain and brain function. Results showed that although some loss of gray matter over time is normal, individuals who were infected with SARS-CoV-2 showed a 0.2% to 2% brain tissue loss in the parahippocampal gyrus, the orbitofrontal cortex, and the insula – all of which are largely involved in the sense of smell.

Participants who had contracted COVID-19 also showed a greater reduction in overall brain volume and a decrease in cognitive function.

Most of those with COVID-19 had only mild or moderate symptoms. However, the findings held even after the researchers excluded patients who had been hospitalized.
 

More research needed

“These findings might help explain why some people experience brain symptoms long after the acute infection,” Max Taquet, PhD, National Institute for Health Research Oxford Health BRC senior research fellow, University of Oxford, said in a press release.

Dr. Taquet, who was not a part of the study, noted the causes of these brain changes remain to be determined. Questions remain as to “whether they can be prevented or even reverted, as well as whether similar changes are observed in hospitalized patients,” children, younger adults, and minority groups.

“It is possible that these brain changes are not caused by COVID-19 but represent the natural progression of a disease that itself increased the risk of COVID-19,” Dr. Taquet said.

Other experts expressed concern over the findings and emphasized the need for more research.

“I am very concerned by the alarming use of language in the report with terms such as ‘neurodegenerative,’ “ Alan Carson, MD, professor of neuropsychiatry at the Center for Clinical Brain Sciences at the University of Edinburgh, Scotland, said in a press release. “The size and magnitude of brain changes found is very modest and such changes can be caused by a simple change in mental experience,” Dr. Carson said.

“What this study almost certainly shows is the impact, in terms of neural changes, of being disconnected from one’s sense of smell,” he added.

The study was funded by the Wellcome Trust Collaborative. Full financial conflict information for the study authors is included in the original article. Dr. Taquet has collaborated previously with some of the investigators.

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

Even mild cases of COVID-19 are associated with brain changes, including decreased gray matter, an overall reduction in brain volume, and cognitive decline, a new imaging study shows.

In the first study to use magnetic resonance brain imaging, before and after COVID-19, investigators found “greater reduction in grey matter thickness and tissue-contrast in the orbitofrontal cortex and parahippocampal gyrus, greater changes in markers of tissue damage in regions functionally connected to the primary olfactory cortex and greater reduction in global brain size.” However, the researchers urge caution when interpreting the findings.

Gwenaëlle Douaud, PhD, Wellcome Center for Integrative Neuroimaging, Nuffield Department of Clinical Neurosciences, University of Oxford, England, and colleagues describe these brain changes as “modest.”

“Whether these abnormal changes are the hallmark of the spread of the pathogenic effects in the brain, or of the virus itself, and whether these may prefigure a future vulnerability of the limbic system in particular, including memory, for these participants, remains to be investigated,” the researchers wrote.

The findings were published online March 7 in the journal Nature.
 

Gray matter loss

The investigators analyzed data from the UK Biobank, a large-scale biomedical database with genetic and health information for about 500,000 individuals living in the UK. They identified 785 adults aged 51-81 years who had undergone two brain MRIs about 3 years apart. Of these, 401 tested positive for SARS-CoV-2 before the second scan.

Participants also completed cognitive tests at the time of both scans.

Biobank centers use identical MRI scans and scanning methods, including six types of MRI scans, to image distinct regions of the brain and brain function. Results showed that although some loss of gray matter over time is normal, individuals who were infected with SARS-CoV-2 showed a 0.2% to 2% brain tissue loss in the parahippocampal gyrus, the orbitofrontal cortex, and the insula – all of which are largely involved in the sense of smell.

Participants who had contracted COVID-19 also showed a greater reduction in overall brain volume and a decrease in cognitive function.

Most of those with COVID-19 had only mild or moderate symptoms. However, the findings held even after the researchers excluded patients who had been hospitalized.
 

More research needed

“These findings might help explain why some people experience brain symptoms long after the acute infection,” Max Taquet, PhD, National Institute for Health Research Oxford Health BRC senior research fellow, University of Oxford, said in a press release.

Dr. Taquet, who was not a part of the study, noted the causes of these brain changes remain to be determined. Questions remain as to “whether they can be prevented or even reverted, as well as whether similar changes are observed in hospitalized patients,” children, younger adults, and minority groups.

“It is possible that these brain changes are not caused by COVID-19 but represent the natural progression of a disease that itself increased the risk of COVID-19,” Dr. Taquet said.

Other experts expressed concern over the findings and emphasized the need for more research.

“I am very concerned by the alarming use of language in the report with terms such as ‘neurodegenerative,’ “ Alan Carson, MD, professor of neuropsychiatry at the Center for Clinical Brain Sciences at the University of Edinburgh, Scotland, said in a press release. “The size and magnitude of brain changes found is very modest and such changes can be caused by a simple change in mental experience,” Dr. Carson said.

“What this study almost certainly shows is the impact, in terms of neural changes, of being disconnected from one’s sense of smell,” he added.

The study was funded by the Wellcome Trust Collaborative. Full financial conflict information for the study authors is included in the original article. Dr. Taquet has collaborated previously with some of the investigators.

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

New cases of COVID-19 in children continued their descent toward normalcy, falling below 100,000 in a week for the first time since early August 2021, according to the American Academy of Pediatrics and the Children’s Hospital Association.

The sixth consecutive week of declines saw just under 69,000 U.S. children test positive for COVID-19 from Feb. 25 to March 3, a drop of almost 46% from the previous week and 94% since the Omicron-fueled peak of 1.15 million during the week of Jan. 14-20, the AAP and CHA said in their weekly COVID report. The total number of child cases is 12.7 million since the pandemic began, with children representing 19% of all cases.

New admissions also stayed on a downward path, as the rate dropped to 0.24 per 100,000 children aged 0-17 years on March 5, a decline of nearly 81% since hitting 1.25 per 100,000 on Jan. 15. The latest 7-day average for daily admissions, 178 per day from Feb. 27 to March 5, was 29% lower than the previous week and almost 81% lower than the peak of 914 per day for Jan. 10-16, the Centers for Disease Control and Prevention reported.

The story is the same for emergency department visits with diagnosed COVID-19, which are reported as a percentage of all ED visits. On March 4, the 7-day average for children aged 0-11 years was 0.8%, compared with a high of 13.9% in mid-January, while 12- to 15-year-olds had dropped from 12.4% to 0.5% and 16- to 17-year-olds went from 12.6% down to 0.5%, the CDC said on its COVID Data Tracker.

Florida’s surgeon general says no to the vaccine

Vaccination, in the meantime, is struggling to maintain a foothold against the current of declining cases. Florida Surgeon General Joseph Ladapo said that “the Florida Department of Health is going to be the first state to officially recommend against the COVID-19 vaccines for healthy children,” NBC News reported March 7. With such a move, “Florida would become the first state to break from the CDC on vaccines for children,” CNN said in its report.

Vaccinations among children aged 5-11 years, which hit 1.6 million in 1 week shortly after emergency use was authorized in early November, declined quickly shorty thereafter and only rose slightly during the Omicron surge. Since mid-January, the number of children receiving an initial dose has declined for seven consecutive weeks and is now lower than ever, based on CDC data compiled by the AAP.

Just over one-third of children aged 5-11 have gotten at least one dose of COVID-19 vaccine, while 26.4% are fully vaccinated. Among children aged 12-17, just over two-thirds (67.8%) have received at least one dose, 57.8% have completed the vaccine regimen, and 21.9% have gotten a booster, the CDC reported.

As of March 2, “about 8.4 million children 12-17 have yet to receive their initial COVID-19 vaccine dose,” the AAP said. About 64,000 children aged 12-17 had received their first dose in the previous week, the group noted, which was the second-lowest weekly total since the vaccine was approved for children aged 12-15 in May of 2021.

New cases of COVID-19 in children continued their descent toward normalcy, falling below 100,000 in a week for the first time since early August 2021, according to the American Academy of Pediatrics and the Children’s Hospital Association.

The sixth consecutive week of declines saw just under 69,000 U.S. children test positive for COVID-19 from Feb. 25 to March 3, a drop of almost 46% from the previous week and 94% since the Omicron-fueled peak of 1.15 million during the week of Jan. 14-20, the AAP and CHA said in their weekly COVID report. The total number of child cases is 12.7 million since the pandemic began, with children representing 19% of all cases.

New admissions also stayed on a downward path, as the rate dropped to 0.24 per 100,000 children aged 0-17 years on March 5, a decline of nearly 81% since hitting 1.25 per 100,000 on Jan. 15. The latest 7-day average for daily admissions, 178 per day from Feb. 27 to March 5, was 29% lower than the previous week and almost 81% lower than the peak of 914 per day for Jan. 10-16, the Centers for Disease Control and Prevention reported.

The story is the same for emergency department visits with diagnosed COVID-19, which are reported as a percentage of all ED visits. On March 4, the 7-day average for children aged 0-11 years was 0.8%, compared with a high of 13.9% in mid-January, while 12- to 15-year-olds had dropped from 12.4% to 0.5% and 16- to 17-year-olds went from 12.6% down to 0.5%, the CDC said on its COVID Data Tracker.

Florida’s surgeon general says no to the vaccine

Vaccination, in the meantime, is struggling to maintain a foothold against the current of declining cases. Florida Surgeon General Joseph Ladapo said that “the Florida Department of Health is going to be the first state to officially recommend against the COVID-19 vaccines for healthy children,” NBC News reported March 7. With such a move, “Florida would become the first state to break from the CDC on vaccines for children,” CNN said in its report.

Vaccinations among children aged 5-11 years, which hit 1.6 million in 1 week shortly after emergency use was authorized in early November, declined quickly shorty thereafter and only rose slightly during the Omicron surge. Since mid-January, the number of children receiving an initial dose has declined for seven consecutive weeks and is now lower than ever, based on CDC data compiled by the AAP.

Just over one-third of children aged 5-11 have gotten at least one dose of COVID-19 vaccine, while 26.4% are fully vaccinated. Among children aged 12-17, just over two-thirds (67.8%) have received at least one dose, 57.8% have completed the vaccine regimen, and 21.9% have gotten a booster, the CDC reported.

As of March 2, “about 8.4 million children 12-17 have yet to receive their initial COVID-19 vaccine dose,” the AAP said. About 64,000 children aged 12-17 had received their first dose in the previous week, the group noted, which was the second-lowest weekly total since the vaccine was approved for children aged 12-15 in May of 2021.

New cases of COVID-19 in children continued their descent toward normalcy, falling below 100,000 in a week for the first time since early August 2021, according to the American Academy of Pediatrics and the Children’s Hospital Association.

The sixth consecutive week of declines saw just under 69,000 U.S. children test positive for COVID-19 from Feb. 25 to March 3, a drop of almost 46% from the previous week and 94% since the Omicron-fueled peak of 1.15 million during the week of Jan. 14-20, the AAP and CHA said in their weekly COVID report. The total number of child cases is 12.7 million since the pandemic began, with children representing 19% of all cases.

New admissions also stayed on a downward path, as the rate dropped to 0.24 per 100,000 children aged 0-17 years on March 5, a decline of nearly 81% since hitting 1.25 per 100,000 on Jan. 15. The latest 7-day average for daily admissions, 178 per day from Feb. 27 to March 5, was 29% lower than the previous week and almost 81% lower than the peak of 914 per day for Jan. 10-16, the Centers for Disease Control and Prevention reported.

The story is the same for emergency department visits with diagnosed COVID-19, which are reported as a percentage of all ED visits. On March 4, the 7-day average for children aged 0-11 years was 0.8%, compared with a high of 13.9% in mid-January, while 12- to 15-year-olds had dropped from 12.4% to 0.5% and 16- to 17-year-olds went from 12.6% down to 0.5%, the CDC said on its COVID Data Tracker.

Florida’s surgeon general says no to the vaccine

Vaccination, in the meantime, is struggling to maintain a foothold against the current of declining cases. Florida Surgeon General Joseph Ladapo said that “the Florida Department of Health is going to be the first state to officially recommend against the COVID-19 vaccines for healthy children,” NBC News reported March 7. With such a move, “Florida would become the first state to break from the CDC on vaccines for children,” CNN said in its report.

Vaccinations among children aged 5-11 years, which hit 1.6 million in 1 week shortly after emergency use was authorized in early November, declined quickly shorty thereafter and only rose slightly during the Omicron surge. Since mid-January, the number of children receiving an initial dose has declined for seven consecutive weeks and is now lower than ever, based on CDC data compiled by the AAP.

Just over one-third of children aged 5-11 have gotten at least one dose of COVID-19 vaccine, while 26.4% are fully vaccinated. Among children aged 12-17, just over two-thirds (67.8%) have received at least one dose, 57.8% have completed the vaccine regimen, and 21.9% have gotten a booster, the CDC reported.

As of March 2, “about 8.4 million children 12-17 have yet to receive their initial COVID-19 vaccine dose,” the AAP said. About 64,000 children aged 12-17 had received their first dose in the previous week, the group noted, which was the second-lowest weekly total since the vaccine was approved for children aged 12-15 in May of 2021.

The federal government’s efforts to thwart information blocking are underway. As such, physicians would do well to be standing at the ready when the information-blocking regulations, designed to ensure that patients can access their electronic health information (EHI), shift into full gear.

Recently, the Office of the National Coordinator revealed that the Department of Health & Humans Services has received 299 reports of information blocking since inviting anyone who suspected that health care providers, IT developers, or health information networks/exchanges might have interfered with access, exchange, or use of EHI through the Report Information Blocking Portal on April 5, 2021.

The vast majority of these claims – 211 – were filed against providers, while 46 alleged incidents of information blocking were by health IT developers, and two claims point to health information networks/ exchanges. The other 25 claims did not appear to present a claim of information blocking.

Of the 274 possible claims of information blocking recently released by ONC, 176 were made by patients.

The ONC has sent all possible claims to the HHS’s Office of the Inspector General. The claims have not yet been investigated and substantiated.
 

Do the stats tell the story?

The numbers in the recent ONC report do not shed much light on how much impact the regulations are having on information sharing. Health care providers, including physicians, might not yet be complying with the rules because monetary penalties are not in place.

Indeed, HHS has yet to spell out exactly what the disincentives on providers will be, though the 21st Century Cures Act stipulates that regulators could fine up to $1 million per information-blocking incident.

“Some providers might be saying, ‘I’m not going to be penalized at this point … so I can take a little bit longer to think about how I come into compliance.’ That could be just one factor of a host of many that are affecting compliance. We also are still in the middle of a public health emergency. So it’s hard to say at this point” exactly how the regulations will affect information blocking, Lauren Riplinger, vice president of policy and public affairs at the American Health Information Management Association, Chicago, said in an interview.
 

A long time coming

The government first zeroed in on ensuring that patients have access to their information in 2016 when President Obama signed the Cures Act into law. The legislation directed ONC to implement a standardized process for the public to report claims of possible information blocking.

The initiative appears to be picking up steam. The ONC is expected to release monthly reports on the cumulative number of information-blocking claims. The announcement of associated penalties is expected sometime in the future.

Industry leaders are advising health care providers to brush up on compliance. Physicians can look to professional groups such as the American Medical Association, the Medical Group Management Association, and other specialty associations for guidance. In addition, the ONC is educating providers on the rule.

“The ONC has provided a lot of great content for the past couple months, not only in terms of putting out FAQs to help clarify some of the gray areas in the rule, but they also have produced a series of provider-specific webinars where they walk through a potential scenario and address the extent to the rules apply,” Ms. Riplinger said.
 

With education, more is better

These efforts, however, could be expanded, according to MGMA.

“There is a general awareness of the rules, but we encourage ONC to continue educating the provider community: More FAQs and educational webinars would be helpful,” Claire Ernst, director of government affairs for MGMA, said in an interview. “A June 2021 MGMA poll found that 51% of medical groups said they needed more government guidance on complying with the new information-blocking rules.”

Although ONC already has provided some “scenario-based” education, more of this type of guidance could prove valuable.

“This rule is that it is very circumstance based. … and so it’s those more nuanced cases that I think are more challenging for providers to know whether or not they are engaging in information blocking,” Ms. Riplinger noted.

For example, a physician might choose to not upload lab test results to a patient portal and prefer to wait to discuss the results directly with the patient, which could potentially be construed as information blocking under the regulations.

The MGMA is requesting that ONC take a second look at these situations – and possibly adjust the regulations.

“MGMA has heard concerns about the impact of providing immediate results to patients before medical groups have the time to thoroughly review test results and discuss them compassionately with their patients,” Ms. Ernst said. “To address this, ONC could expand the current definition of harm to account for other unintended consequences, such as emotional distress, or provide more flexibility in terms of the time frame.”

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

The federal government’s efforts to thwart information blocking are underway. As such, physicians would do well to be standing at the ready when the information-blocking regulations, designed to ensure that patients can access their electronic health information (EHI), shift into full gear.

Recently, the Office of the National Coordinator revealed that the Department of Health & Humans Services has received 299 reports of information blocking since inviting anyone who suspected that health care providers, IT developers, or health information networks/exchanges might have interfered with access, exchange, or use of EHI through the Report Information Blocking Portal on April 5, 2021.

The vast majority of these claims – 211 – were filed against providers, while 46 alleged incidents of information blocking were by health IT developers, and two claims point to health information networks/ exchanges. The other 25 claims did not appear to present a claim of information blocking.

Of the 274 possible claims of information blocking recently released by ONC, 176 were made by patients.

The ONC has sent all possible claims to the HHS’s Office of the Inspector General. The claims have not yet been investigated and substantiated.
 

Do the stats tell the story?

The numbers in the recent ONC report do not shed much light on how much impact the regulations are having on information sharing. Health care providers, including physicians, might not yet be complying with the rules because monetary penalties are not in place.

Indeed, HHS has yet to spell out exactly what the disincentives on providers will be, though the 21st Century Cures Act stipulates that regulators could fine up to $1 million per information-blocking incident.

“Some providers might be saying, ‘I’m not going to be penalized at this point … so I can take a little bit longer to think about how I come into compliance.’ That could be just one factor of a host of many that are affecting compliance. We also are still in the middle of a public health emergency. So it’s hard to say at this point” exactly how the regulations will affect information blocking, Lauren Riplinger, vice president of policy and public affairs at the American Health Information Management Association, Chicago, said in an interview.
 

A long time coming

The government first zeroed in on ensuring that patients have access to their information in 2016 when President Obama signed the Cures Act into law. The legislation directed ONC to implement a standardized process for the public to report claims of possible information blocking.

The initiative appears to be picking up steam. The ONC is expected to release monthly reports on the cumulative number of information-blocking claims. The announcement of associated penalties is expected sometime in the future.

Industry leaders are advising health care providers to brush up on compliance. Physicians can look to professional groups such as the American Medical Association, the Medical Group Management Association, and other specialty associations for guidance. In addition, the ONC is educating providers on the rule.

“The ONC has provided a lot of great content for the past couple months, not only in terms of putting out FAQs to help clarify some of the gray areas in the rule, but they also have produced a series of provider-specific webinars where they walk through a potential scenario and address the extent to the rules apply,” Ms. Riplinger said.
 

With education, more is better

These efforts, however, could be expanded, according to MGMA.

“There is a general awareness of the rules, but we encourage ONC to continue educating the provider community: More FAQs and educational webinars would be helpful,” Claire Ernst, director of government affairs for MGMA, said in an interview. “A June 2021 MGMA poll found that 51% of medical groups said they needed more government guidance on complying with the new information-blocking rules.”

Although ONC already has provided some “scenario-based” education, more of this type of guidance could prove valuable.

“This rule is that it is very circumstance based. … and so it’s those more nuanced cases that I think are more challenging for providers to know whether or not they are engaging in information blocking,” Ms. Riplinger noted.

For example, a physician might choose to not upload lab test results to a patient portal and prefer to wait to discuss the results directly with the patient, which could potentially be construed as information blocking under the regulations.

The MGMA is requesting that ONC take a second look at these situations – and possibly adjust the regulations.

“MGMA has heard concerns about the impact of providing immediate results to patients before medical groups have the time to thoroughly review test results and discuss them compassionately with their patients,” Ms. Ernst said. “To address this, ONC could expand the current definition of harm to account for other unintended consequences, such as emotional distress, or provide more flexibility in terms of the time frame.”

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

The federal government’s efforts to thwart information blocking are underway. As such, physicians would do well to be standing at the ready when the information-blocking regulations, designed to ensure that patients can access their electronic health information (EHI), shift into full gear.

Recently, the Office of the National Coordinator revealed that the Department of Health & Humans Services has received 299 reports of information blocking since inviting anyone who suspected that health care providers, IT developers, or health information networks/exchanges might have interfered with access, exchange, or use of EHI through the Report Information Blocking Portal on April 5, 2021.

The vast majority of these claims – 211 – were filed against providers, while 46 alleged incidents of information blocking were by health IT developers, and two claims point to health information networks/ exchanges. The other 25 claims did not appear to present a claim of information blocking.

Of the 274 possible claims of information blocking recently released by ONC, 176 were made by patients.

The ONC has sent all possible claims to the HHS’s Office of the Inspector General. The claims have not yet been investigated and substantiated.
 

Do the stats tell the story?

The numbers in the recent ONC report do not shed much light on how much impact the regulations are having on information sharing. Health care providers, including physicians, might not yet be complying with the rules because monetary penalties are not in place.

Indeed, HHS has yet to spell out exactly what the disincentives on providers will be, though the 21st Century Cures Act stipulates that regulators could fine up to $1 million per information-blocking incident.

“Some providers might be saying, ‘I’m not going to be penalized at this point … so I can take a little bit longer to think about how I come into compliance.’ That could be just one factor of a host of many that are affecting compliance. We also are still in the middle of a public health emergency. So it’s hard to say at this point” exactly how the regulations will affect information blocking, Lauren Riplinger, vice president of policy and public affairs at the American Health Information Management Association, Chicago, said in an interview.
 

A long time coming

The government first zeroed in on ensuring that patients have access to their information in 2016 when President Obama signed the Cures Act into law. The legislation directed ONC to implement a standardized process for the public to report claims of possible information blocking.

The initiative appears to be picking up steam. The ONC is expected to release monthly reports on the cumulative number of information-blocking claims. The announcement of associated penalties is expected sometime in the future.

Industry leaders are advising health care providers to brush up on compliance. Physicians can look to professional groups such as the American Medical Association, the Medical Group Management Association, and other specialty associations for guidance. In addition, the ONC is educating providers on the rule.

“The ONC has provided a lot of great content for the past couple months, not only in terms of putting out FAQs to help clarify some of the gray areas in the rule, but they also have produced a series of provider-specific webinars where they walk through a potential scenario and address the extent to the rules apply,” Ms. Riplinger said.
 

With education, more is better

These efforts, however, could be expanded, according to MGMA.

“There is a general awareness of the rules, but we encourage ONC to continue educating the provider community: More FAQs and educational webinars would be helpful,” Claire Ernst, director of government affairs for MGMA, said in an interview. “A June 2021 MGMA poll found that 51% of medical groups said they needed more government guidance on complying with the new information-blocking rules.”

Although ONC already has provided some “scenario-based” education, more of this type of guidance could prove valuable.

“This rule is that it is very circumstance based. … and so it’s those more nuanced cases that I think are more challenging for providers to know whether or not they are engaging in information blocking,” Ms. Riplinger noted.

For example, a physician might choose to not upload lab test results to a patient portal and prefer to wait to discuss the results directly with the patient, which could potentially be construed as information blocking under the regulations.

The MGMA is requesting that ONC take a second look at these situations – and possibly adjust the regulations.

“MGMA has heard concerns about the impact of providing immediate results to patients before medical groups have the time to thoroughly review test results and discuss them compassionately with their patients,” Ms. Ernst said. “To address this, ONC could expand the current definition of harm to account for other unintended consequences, such as emotional distress, or provide more flexibility in terms of the time frame.”

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

The currently available two-dose COVID-19 vaccines were not effective in preventing symptomatic disease caused by the Omicron variant, as determined on the basis of data from more than 800,000 Omicron-infected individuals.

Early laboratory data suggested a substantially lower neutralizing antibody response to the Omicron variant, compared with both the original COVID-19 strain and the Delta variant, write Nick Andrews, PhD, of the United Kingdom Health Security Agency, London, and colleagues.

Vaccines have shown high levels of effectiveness against symptomatic disease and severe disease and death resulting from the original COVID-19 virus and the Alpha variant and modest effectiveness against the Beta and Delta variants, they say.

“Neutralizing antibodies correlate with protection against reinfection and vaccine effectiveness against infection; therefore, reduced vaccine effectiveness against the omicron variant is anticipated on the basis of these early laboratory findings,” they explain.

In a study published in the New England Journal of Medicine, the researchers identified 886,774 adults aged 18 years and older who had been infected with the Omicron variant, 204,154 who had been infected with the Delta variant, and 1,572,621 symptomatic control patients who tested negative for COVID-19 between Nov. 27, 2021, and Jan. 12, 2022. The participants had been vaccinated with two doses of BNT162b2 (Pfizer–BioNTech), ChAdOx1 nCoV-19 (AstraZeneca), or mRNA-1273 (Moderna) vaccine, plus a booster given at least 175 days after a second dose, after Sept. 13, 2021.

Vaccine effectiveness was calculated after primary immunization at weeks 2-4, 5-9, 10-14, 15-19, 20-24, and 25 or longer after the second dose, and at 2-4, 5-9, and 10 or more weeks after boosters.

Omicron infections that occurred starting 14 or more days after a booster occurred a median of 39 days after the booster.

“Vaccine effectiveness was lower for the Omicron variant than for the Delta variant at all intervals after vaccination and for all combinations of primary courses and booster doses investigated,” the researchers write.

Individuals who received two doses of ChAdOx1 nCoV-19 had almost no protection against symptomatic disease caused by Omicron from 20-24 weeks after the second dose. For individuals who received two doses of BNT162b2, effectiveness was 65.5% 2-4 weeks after the second dose, but effectiveness declined to 15.4% after 15-19 weeks and to 8.8% after 25 or more weeks. For individuals who received two doses of mRNA-1273, vaccine effectiveness was 75.1% after 2-4 weeks, but effectiveness declined to 14.9% after 25 or more weeks.

Boosters created a short-term improvement in vaccine effectiveness against the Omicron variant, but this effect also declined over time.

Among individuals who received primary doses of ChAdOx1 nCoV-19, vaccine effectiveness increased to 62.4% 2-4 weeks after a BNT162b2 booster, then declined to 39.6% after 10 or more weeks. After an mRNA-1273 booster, vaccine effectiveness increased to 70.1% at 2-4 weeks and decreased to 60.9% at 5-9 weeks.

Among individuals who received primary doses of BNT162b2, vaccine effectiveness increased to 67.2% 2-4 weeks after a BNT162b2 booster, then declined to 45.7% at 10 or more weeks. After an mRNA-1273 booster, vaccine effectiveness increased to 73.9% at 2-4 weeks, then declined to 64.4% at 5-9 weeks.

Among individuals who received primary doses of mRNA-1273, vaccine effectiveness increased to 64.9% 2-4 weeks after a BNT162b2 booster and 66.3% 2-4 weeks after an mRNA-1273 booster.

The study findings were limited by potential confounding from study participants who had traveled and may have had different levels of vaccine coverage and by the inability to break down estimates on the basis of age and clinical risk that might affect vaccine effectiveness, the researchers note. Other limitations include a lack of data on vaccine effectiveness for a longer period after boosters, they say.

However, the results are consistent with neutralization data for the Omicron variant in studies from the United Kingdom, South Africa, and Germany, they write. “Our findings support maximizing coverage with third doses of vaccine in highly vaccinated populations such as in the United Kingdom. Further follow-up will be needed to assess protection against severe disease and the duration of protection after booster vaccination,” they conclude.
 

Focus on severe disease prevention

Paul Offit, MD, of the University of Pennsylvania, Philadelphia, addressed the topic of vaccine effectiveness in an op-ed published on March 4 in The Philadelphia Inquirer. The following is adapted from the op-ed, with his permission.

“The goal of the COVID vaccine – as is true for all vaccines – is to prevent serious illness,” Dr. Offit wrote.

“For most people with normal immune systems, two doses of mRNA vaccines appear to do exactly that. But not everyone,” wrote Dr. Offit, who serves as director of the Vaccine Education Center at the Children’s Hospital of Philadelphia and also serves on the Food and Drug Administration’s Vaccine Advisory Committee. “Three doses are required to induce high levels of protection against serious illness for people over 65 years of age or for people with other conditions that make them vulnerable, which can be anything from being overweight to having cancer. For people who are immune compromised, four doses might be required,” he noted.

Frequent vaccine boosting, although it may help prevent milder cases of COVID-19, such as those seen with the Omicron variant, is impractical, Dr. Offit emphasized. Instead, a newer, variant-specific vaccine might be needed if a variant emerges that overrides the protection against severe disease currently afforded by the available vaccines, he said. “But we’re not there yet. For now, we are going to have to realize that it is virtually impossible to prevent mild COVID without frequent boosting. So, let’s learn to accept that the goal of COVID vaccines is to prevent severe and not mild illness and stop talking about frequent boosting. Otherwise, we will never be able to live our lives as before,” he wrote.

The study was supported by the U.K. Health Security Agency. The researchers and Dr. Offit have disclosed no relevant financial relationships.

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

The currently available two-dose COVID-19 vaccines were not effective in preventing symptomatic disease caused by the Omicron variant, as determined on the basis of data from more than 800,000 Omicron-infected individuals.

Early laboratory data suggested a substantially lower neutralizing antibody response to the Omicron variant, compared with both the original COVID-19 strain and the Delta variant, write Nick Andrews, PhD, of the United Kingdom Health Security Agency, London, and colleagues.

Vaccines have shown high levels of effectiveness against symptomatic disease and severe disease and death resulting from the original COVID-19 virus and the Alpha variant and modest effectiveness against the Beta and Delta variants, they say.

“Neutralizing antibodies correlate with protection against reinfection and vaccine effectiveness against infection; therefore, reduced vaccine effectiveness against the omicron variant is anticipated on the basis of these early laboratory findings,” they explain.

In a study published in the New England Journal of Medicine, the researchers identified 886,774 adults aged 18 years and older who had been infected with the Omicron variant, 204,154 who had been infected with the Delta variant, and 1,572,621 symptomatic control patients who tested negative for COVID-19 between Nov. 27, 2021, and Jan. 12, 2022. The participants had been vaccinated with two doses of BNT162b2 (Pfizer–BioNTech), ChAdOx1 nCoV-19 (AstraZeneca), or mRNA-1273 (Moderna) vaccine, plus a booster given at least 175 days after a second dose, after Sept. 13, 2021.

Vaccine effectiveness was calculated after primary immunization at weeks 2-4, 5-9, 10-14, 15-19, 20-24, and 25 or longer after the second dose, and at 2-4, 5-9, and 10 or more weeks after boosters.

Omicron infections that occurred starting 14 or more days after a booster occurred a median of 39 days after the booster.

“Vaccine effectiveness was lower for the Omicron variant than for the Delta variant at all intervals after vaccination and for all combinations of primary courses and booster doses investigated,” the researchers write.

Individuals who received two doses of ChAdOx1 nCoV-19 had almost no protection against symptomatic disease caused by Omicron from 20-24 weeks after the second dose. For individuals who received two doses of BNT162b2, effectiveness was 65.5% 2-4 weeks after the second dose, but effectiveness declined to 15.4% after 15-19 weeks and to 8.8% after 25 or more weeks. For individuals who received two doses of mRNA-1273, vaccine effectiveness was 75.1% after 2-4 weeks, but effectiveness declined to 14.9% after 25 or more weeks.

Boosters created a short-term improvement in vaccine effectiveness against the Omicron variant, but this effect also declined over time.

Among individuals who received primary doses of ChAdOx1 nCoV-19, vaccine effectiveness increased to 62.4% 2-4 weeks after a BNT162b2 booster, then declined to 39.6% after 10 or more weeks. After an mRNA-1273 booster, vaccine effectiveness increased to 70.1% at 2-4 weeks and decreased to 60.9% at 5-9 weeks.

Among individuals who received primary doses of BNT162b2, vaccine effectiveness increased to 67.2% 2-4 weeks after a BNT162b2 booster, then declined to 45.7% at 10 or more weeks. After an mRNA-1273 booster, vaccine effectiveness increased to 73.9% at 2-4 weeks, then declined to 64.4% at 5-9 weeks.

Among individuals who received primary doses of mRNA-1273, vaccine effectiveness increased to 64.9% 2-4 weeks after a BNT162b2 booster and 66.3% 2-4 weeks after an mRNA-1273 booster.

The study findings were limited by potential confounding from study participants who had traveled and may have had different levels of vaccine coverage and by the inability to break down estimates on the basis of age and clinical risk that might affect vaccine effectiveness, the researchers note. Other limitations include a lack of data on vaccine effectiveness for a longer period after boosters, they say.

However, the results are consistent with neutralization data for the Omicron variant in studies from the United Kingdom, South Africa, and Germany, they write. “Our findings support maximizing coverage with third doses of vaccine in highly vaccinated populations such as in the United Kingdom. Further follow-up will be needed to assess protection against severe disease and the duration of protection after booster vaccination,” they conclude.
 

Focus on severe disease prevention

Paul Offit, MD, of the University of Pennsylvania, Philadelphia, addressed the topic of vaccine effectiveness in an op-ed published on March 4 in The Philadelphia Inquirer. The following is adapted from the op-ed, with his permission.

“The goal of the COVID vaccine – as is true for all vaccines – is to prevent serious illness,” Dr. Offit wrote.

“For most people with normal immune systems, two doses of mRNA vaccines appear to do exactly that. But not everyone,” wrote Dr. Offit, who serves as director of the Vaccine Education Center at the Children’s Hospital of Philadelphia and also serves on the Food and Drug Administration’s Vaccine Advisory Committee. “Three doses are required to induce high levels of protection against serious illness for people over 65 years of age or for people with other conditions that make them vulnerable, which can be anything from being overweight to having cancer. For people who are immune compromised, four doses might be required,” he noted.

Frequent vaccine boosting, although it may help prevent milder cases of COVID-19, such as those seen with the Omicron variant, is impractical, Dr. Offit emphasized. Instead, a newer, variant-specific vaccine might be needed if a variant emerges that overrides the protection against severe disease currently afforded by the available vaccines, he said. “But we’re not there yet. For now, we are going to have to realize that it is virtually impossible to prevent mild COVID without frequent boosting. So, let’s learn to accept that the goal of COVID vaccines is to prevent severe and not mild illness and stop talking about frequent boosting. Otherwise, we will never be able to live our lives as before,” he wrote.

The study was supported by the U.K. Health Security Agency. The researchers and Dr. Offit have disclosed no relevant financial relationships.

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

The currently available two-dose COVID-19 vaccines were not effective in preventing symptomatic disease caused by the Omicron variant, as determined on the basis of data from more than 800,000 Omicron-infected individuals.

Early laboratory data suggested a substantially lower neutralizing antibody response to the Omicron variant, compared with both the original COVID-19 strain and the Delta variant, write Nick Andrews, PhD, of the United Kingdom Health Security Agency, London, and colleagues.

Vaccines have shown high levels of effectiveness against symptomatic disease and severe disease and death resulting from the original COVID-19 virus and the Alpha variant and modest effectiveness against the Beta and Delta variants, they say.

“Neutralizing antibodies correlate with protection against reinfection and vaccine effectiveness against infection; therefore, reduced vaccine effectiveness against the omicron variant is anticipated on the basis of these early laboratory findings,” they explain.

In a study published in the New England Journal of Medicine, the researchers identified 886,774 adults aged 18 years and older who had been infected with the Omicron variant, 204,154 who had been infected with the Delta variant, and 1,572,621 symptomatic control patients who tested negative for COVID-19 between Nov. 27, 2021, and Jan. 12, 2022. The participants had been vaccinated with two doses of BNT162b2 (Pfizer–BioNTech), ChAdOx1 nCoV-19 (AstraZeneca), or mRNA-1273 (Moderna) vaccine, plus a booster given at least 175 days after a second dose, after Sept. 13, 2021.

Vaccine effectiveness was calculated after primary immunization at weeks 2-4, 5-9, 10-14, 15-19, 20-24, and 25 or longer after the second dose, and at 2-4, 5-9, and 10 or more weeks after boosters.

Omicron infections that occurred starting 14 or more days after a booster occurred a median of 39 days after the booster.

“Vaccine effectiveness was lower for the Omicron variant than for the Delta variant at all intervals after vaccination and for all combinations of primary courses and booster doses investigated,” the researchers write.

Individuals who received two doses of ChAdOx1 nCoV-19 had almost no protection against symptomatic disease caused by Omicron from 20-24 weeks after the second dose. For individuals who received two doses of BNT162b2, effectiveness was 65.5% 2-4 weeks after the second dose, but effectiveness declined to 15.4% after 15-19 weeks and to 8.8% after 25 or more weeks. For individuals who received two doses of mRNA-1273, vaccine effectiveness was 75.1% after 2-4 weeks, but effectiveness declined to 14.9% after 25 or more weeks.

Boosters created a short-term improvement in vaccine effectiveness against the Omicron variant, but this effect also declined over time.

Among individuals who received primary doses of ChAdOx1 nCoV-19, vaccine effectiveness increased to 62.4% 2-4 weeks after a BNT162b2 booster, then declined to 39.6% after 10 or more weeks. After an mRNA-1273 booster, vaccine effectiveness increased to 70.1% at 2-4 weeks and decreased to 60.9% at 5-9 weeks.

Among individuals who received primary doses of BNT162b2, vaccine effectiveness increased to 67.2% 2-4 weeks after a BNT162b2 booster, then declined to 45.7% at 10 or more weeks. After an mRNA-1273 booster, vaccine effectiveness increased to 73.9% at 2-4 weeks, then declined to 64.4% at 5-9 weeks.

Among individuals who received primary doses of mRNA-1273, vaccine effectiveness increased to 64.9% 2-4 weeks after a BNT162b2 booster and 66.3% 2-4 weeks after an mRNA-1273 booster.

The study findings were limited by potential confounding from study participants who had traveled and may have had different levels of vaccine coverage and by the inability to break down estimates on the basis of age and clinical risk that might affect vaccine effectiveness, the researchers note. Other limitations include a lack of data on vaccine effectiveness for a longer period after boosters, they say.

However, the results are consistent with neutralization data for the Omicron variant in studies from the United Kingdom, South Africa, and Germany, they write. “Our findings support maximizing coverage with third doses of vaccine in highly vaccinated populations such as in the United Kingdom. Further follow-up will be needed to assess protection against severe disease and the duration of protection after booster vaccination,” they conclude.
 

Focus on severe disease prevention

Paul Offit, MD, of the University of Pennsylvania, Philadelphia, addressed the topic of vaccine effectiveness in an op-ed published on March 4 in The Philadelphia Inquirer. The following is adapted from the op-ed, with his permission.

“The goal of the COVID vaccine – as is true for all vaccines – is to prevent serious illness,” Dr. Offit wrote.

“For most people with normal immune systems, two doses of mRNA vaccines appear to do exactly that. But not everyone,” wrote Dr. Offit, who serves as director of the Vaccine Education Center at the Children’s Hospital of Philadelphia and also serves on the Food and Drug Administration’s Vaccine Advisory Committee. “Three doses are required to induce high levels of protection against serious illness for people over 65 years of age or for people with other conditions that make them vulnerable, which can be anything from being overweight to having cancer. For people who are immune compromised, four doses might be required,” he noted.

Frequent vaccine boosting, although it may help prevent milder cases of COVID-19, such as those seen with the Omicron variant, is impractical, Dr. Offit emphasized. Instead, a newer, variant-specific vaccine might be needed if a variant emerges that overrides the protection against severe disease currently afforded by the available vaccines, he said. “But we’re not there yet. For now, we are going to have to realize that it is virtually impossible to prevent mild COVID without frequent boosting. So, let’s learn to accept that the goal of COVID vaccines is to prevent severe and not mild illness and stop talking about frequent boosting. Otherwise, we will never be able to live our lives as before,” he wrote.

The study was supported by the U.K. Health Security Agency. The researchers and Dr. Offit have disclosed no relevant financial relationships.

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

The Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee has chosen the influenza vaccine strains for the 2022-2023 season in the northern hemisphere, which begins in the fall of 2022.

On March 3, the committee unanimously voted to endorse the World Health Organization’s recommendations as to which influenza strains to include for coverage by vaccines for the upcoming flu season. Two of the four recommended strains are different from last season.

The committee also heard updates on flu activity this season. So far, data from the U.S. Flu Vaccine Effectiveness (VE) network, which consists of seven study sites, have not shown that the vaccine is protective against influenza A. “We can say that it is not highly effective,” Brendan Flannery, PhD, who leads the U.S. Flu VE network for the Centers for Disease Control and Prevention, said in an interview. He was not involved with the advisory committee meeting. Flu activity this season has been low, he explained, so there are fewer cases his team can use to estimate vaccine efficacy. “If there’s some benefit, it’s hard for us to show that now,” he said.
 

Vaccine strains

The panel voted to include a A/Darwin/9/2021-like strain for the H3N2 component of the vaccine; this is changed from A/Cambodia/e0826360/2020. For the influenza B Victoria lineage component, the committee voted to include a B/Austria/1359417/2021-like virus, a swap from this year’s B/Washington/02/2019-like virus. These changes apply to the egg-based, cell-culture, and recombinant vaccines. Both new strains were included in WHO’s 2022 influenza vaccine strain recommendations for the southern hemisphere.

For the influenza A H1N1 component, the group also agreed to include a A/Victoria/2570/2019 (H1N1) pdm09-like virus for the egg-based vaccine and the A/Wisconsin/588/2019 (H1N1) pdm09-like virus for cell culture or recombinant vaccines. These strains were included for the 2021-2022 season. The panel also voted for the inclusion of a B/Phuket/3073/2013-like virus (B/Yamagata lineage) as the second influenza B strain for the quadrivalent egg-based, cell culture, or recombinant vaccines, which is unchanged from this flu season.
 

‘Sporadic’ flu activity

While there was an uptick in influenza activity this year compared to the 2020-2021 season, hospitalization rates are lower than in the four seasons preceding the pandemic (from 2016-2017 to 2019-2020). As of Feb. 26, the cumulative hospitalization rate for this flu season was 5.2 hospitalizations per 100,000 individuals. There have been eight pediatric deaths due to influenza so far this season, compared to one pediatric death reported to the CDC during the 2020-2021 flu season.

About 4.1% of specimens tested at clinical laboratories were positive for flu. Since Oct. 30, 2.7% of specimens have been positive for influenza this season. Nearly all viruses detected (97.7%) have been influenza A.

Lisa Grohskopf, MD, MPH, a medical officer in the influenza division at the CDC who presented the data at the meeting, described flu activity this season as “sporadic” and noted that activity is increasing in some areas of the country. According to CDC’s weekly influenza surveillance report, most states had minimal influenza-like illness (ILI) activity, although Arkansas, Idaho, Iowa, Kansas, Minnesota, and Utah had slightly higher ILI activity as of Feb. 26. Champaign-Urbana, Illinois; St. Cloud, Minnesota; and Brownwood, Texas, had the highest levels of flu activity in the country.
 

Low vaccine effectiveness

As of Jan. 22, results from the U.S. Flu VE network do not show statistically significant evidence that the flu vaccine is effective. Currently, the vaccine is estimated to be 8% effective against preventing influenza A infection (95% confidence interval, –31% to 36%) and 14% effective against preventing A/H3N2 infection (95% CI, –28% to 43%) for people aged 6 months and older.

The network did not have enough data to provide age-specific VE estimates or estimates of effectiveness against influenza B. This could be due to low flu activity relative to prepandemic years, Dr. Flannery said. Of the 2,758 individuals enrolled in the VE flu network this season, just 147 (5%) tested positive for the flu this season. This is the lowest positivity rate observed in the Flu VE network participants with respiratory illness over the past 10 flu seasons, Dr. Grohskopf noted. In comparison, estimates from the 2019 to 2020 season included 4,112 individuals, and 1,060 tested positive for flu.

“We are really at the bare minimum of what we can use for a flu vaccine effectiveness estimate,” Dr. Flannery said about the more recent data. The network was not able to produce any estimates about flu vaccine effectiveness for the 2020-2021 season because of historically low flu activity.

The Department of Defense also presented vaccine efficacy estimates for the 2021–2022 season. The vaccine has been 36% effective (95% CI, 28%-44%) against all strains of the virus, 33% effective against influenza A (95% CI, 24%-41%), 32% effective against A/H3N2 (95% CI, 3%-53%), and 59% effective against influenza B (95% CI, 42%-71%). These results are from a young, healthy adult population, Lieutenant Commander Courtney Gustin, DrPH, MSN, told the panel, and they may not be reflective of efficacy rates across all age groups.

Though these findings suggest there is low to no measurable benefit against influenza A, Dr. Flannery said the CDC still recommends getting the flu vaccine, as it can be protective against other circulating flu strains. “We have been able to demonstrate protection against other H3 [viruses], B viruses, and H1 viruses in the past,” he said. And as these results only show protection against mild disease, “there is still possibility that there’s benefit against more severe disease,” he added. Studies measuring effectiveness against more severe outcomes are not yet available.

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

The Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee has chosen the influenza vaccine strains for the 2022-2023 season in the northern hemisphere, which begins in the fall of 2022.

On March 3, the committee unanimously voted to endorse the World Health Organization’s recommendations as to which influenza strains to include for coverage by vaccines for the upcoming flu season. Two of the four recommended strains are different from last season.

The committee also heard updates on flu activity this season. So far, data from the U.S. Flu Vaccine Effectiveness (VE) network, which consists of seven study sites, have not shown that the vaccine is protective against influenza A. “We can say that it is not highly effective,” Brendan Flannery, PhD, who leads the U.S. Flu VE network for the Centers for Disease Control and Prevention, said in an interview. He was not involved with the advisory committee meeting. Flu activity this season has been low, he explained, so there are fewer cases his team can use to estimate vaccine efficacy. “If there’s some benefit, it’s hard for us to show that now,” he said.
 

Vaccine strains

The panel voted to include a A/Darwin/9/2021-like strain for the H3N2 component of the vaccine; this is changed from A/Cambodia/e0826360/2020. For the influenza B Victoria lineage component, the committee voted to include a B/Austria/1359417/2021-like virus, a swap from this year’s B/Washington/02/2019-like virus. These changes apply to the egg-based, cell-culture, and recombinant vaccines. Both new strains were included in WHO’s 2022 influenza vaccine strain recommendations for the southern hemisphere.

For the influenza A H1N1 component, the group also agreed to include a A/Victoria/2570/2019 (H1N1) pdm09-like virus for the egg-based vaccine and the A/Wisconsin/588/2019 (H1N1) pdm09-like virus for cell culture or recombinant vaccines. These strains were included for the 2021-2022 season. The panel also voted for the inclusion of a B/Phuket/3073/2013-like virus (B/Yamagata lineage) as the second influenza B strain for the quadrivalent egg-based, cell culture, or recombinant vaccines, which is unchanged from this flu season.
 

‘Sporadic’ flu activity

While there was an uptick in influenza activity this year compared to the 2020-2021 season, hospitalization rates are lower than in the four seasons preceding the pandemic (from 2016-2017 to 2019-2020). As of Feb. 26, the cumulative hospitalization rate for this flu season was 5.2 hospitalizations per 100,000 individuals. There have been eight pediatric deaths due to influenza so far this season, compared to one pediatric death reported to the CDC during the 2020-2021 flu season.

About 4.1% of specimens tested at clinical laboratories were positive for flu. Since Oct. 30, 2.7% of specimens have been positive for influenza this season. Nearly all viruses detected (97.7%) have been influenza A.

Lisa Grohskopf, MD, MPH, a medical officer in the influenza division at the CDC who presented the data at the meeting, described flu activity this season as “sporadic” and noted that activity is increasing in some areas of the country. According to CDC’s weekly influenza surveillance report, most states had minimal influenza-like illness (ILI) activity, although Arkansas, Idaho, Iowa, Kansas, Minnesota, and Utah had slightly higher ILI activity as of Feb. 26. Champaign-Urbana, Illinois; St. Cloud, Minnesota; and Brownwood, Texas, had the highest levels of flu activity in the country.
 

Low vaccine effectiveness

As of Jan. 22, results from the U.S. Flu VE network do not show statistically significant evidence that the flu vaccine is effective. Currently, the vaccine is estimated to be 8% effective against preventing influenza A infection (95% confidence interval, –31% to 36%) and 14% effective against preventing A/H3N2 infection (95% CI, –28% to 43%) for people aged 6 months and older.

The network did not have enough data to provide age-specific VE estimates or estimates of effectiveness against influenza B. This could be due to low flu activity relative to prepandemic years, Dr. Flannery said. Of the 2,758 individuals enrolled in the VE flu network this season, just 147 (5%) tested positive for the flu this season. This is the lowest positivity rate observed in the Flu VE network participants with respiratory illness over the past 10 flu seasons, Dr. Grohskopf noted. In comparison, estimates from the 2019 to 2020 season included 4,112 individuals, and 1,060 tested positive for flu.

“We are really at the bare minimum of what we can use for a flu vaccine effectiveness estimate,” Dr. Flannery said about the more recent data. The network was not able to produce any estimates about flu vaccine effectiveness for the 2020-2021 season because of historically low flu activity.

The Department of Defense also presented vaccine efficacy estimates for the 2021–2022 season. The vaccine has been 36% effective (95% CI, 28%-44%) against all strains of the virus, 33% effective against influenza A (95% CI, 24%-41%), 32% effective against A/H3N2 (95% CI, 3%-53%), and 59% effective against influenza B (95% CI, 42%-71%). These results are from a young, healthy adult population, Lieutenant Commander Courtney Gustin, DrPH, MSN, told the panel, and they may not be reflective of efficacy rates across all age groups.

Though these findings suggest there is low to no measurable benefit against influenza A, Dr. Flannery said the CDC still recommends getting the flu vaccine, as it can be protective against other circulating flu strains. “We have been able to demonstrate protection against other H3 [viruses], B viruses, and H1 viruses in the past,” he said. And as these results only show protection against mild disease, “there is still possibility that there’s benefit against more severe disease,” he added. Studies measuring effectiveness against more severe outcomes are not yet available.

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

The Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee has chosen the influenza vaccine strains for the 2022-2023 season in the northern hemisphere, which begins in the fall of 2022.

On March 3, the committee unanimously voted to endorse the World Health Organization’s recommendations as to which influenza strains to include for coverage by vaccines for the upcoming flu season. Two of the four recommended strains are different from last season.

The committee also heard updates on flu activity this season. So far, data from the U.S. Flu Vaccine Effectiveness (VE) network, which consists of seven study sites, have not shown that the vaccine is protective against influenza A. “We can say that it is not highly effective,” Brendan Flannery, PhD, who leads the U.S. Flu VE network for the Centers for Disease Control and Prevention, said in an interview. He was not involved with the advisory committee meeting. Flu activity this season has been low, he explained, so there are fewer cases his team can use to estimate vaccine efficacy. “If there’s some benefit, it’s hard for us to show that now,” he said.
 

Vaccine strains

The panel voted to include a A/Darwin/9/2021-like strain for the H3N2 component of the vaccine; this is changed from A/Cambodia/e0826360/2020. For the influenza B Victoria lineage component, the committee voted to include a B/Austria/1359417/2021-like virus, a swap from this year’s B/Washington/02/2019-like virus. These changes apply to the egg-based, cell-culture, and recombinant vaccines. Both new strains were included in WHO’s 2022 influenza vaccine strain recommendations for the southern hemisphere.

For the influenza A H1N1 component, the group also agreed to include a A/Victoria/2570/2019 (H1N1) pdm09-like virus for the egg-based vaccine and the A/Wisconsin/588/2019 (H1N1) pdm09-like virus for cell culture or recombinant vaccines. These strains were included for the 2021-2022 season. The panel also voted for the inclusion of a B/Phuket/3073/2013-like virus (B/Yamagata lineage) as the second influenza B strain for the quadrivalent egg-based, cell culture, or recombinant vaccines, which is unchanged from this flu season.
 

‘Sporadic’ flu activity

While there was an uptick in influenza activity this year compared to the 2020-2021 season, hospitalization rates are lower than in the four seasons preceding the pandemic (from 2016-2017 to 2019-2020). As of Feb. 26, the cumulative hospitalization rate for this flu season was 5.2 hospitalizations per 100,000 individuals. There have been eight pediatric deaths due to influenza so far this season, compared to one pediatric death reported to the CDC during the 2020-2021 flu season.

About 4.1% of specimens tested at clinical laboratories were positive for flu. Since Oct. 30, 2.7% of specimens have been positive for influenza this season. Nearly all viruses detected (97.7%) have been influenza A.

Lisa Grohskopf, MD, MPH, a medical officer in the influenza division at the CDC who presented the data at the meeting, described flu activity this season as “sporadic” and noted that activity is increasing in some areas of the country. According to CDC’s weekly influenza surveillance report, most states had minimal influenza-like illness (ILI) activity, although Arkansas, Idaho, Iowa, Kansas, Minnesota, and Utah had slightly higher ILI activity as of Feb. 26. Champaign-Urbana, Illinois; St. Cloud, Minnesota; and Brownwood, Texas, had the highest levels of flu activity in the country.
 

Low vaccine effectiveness

As of Jan. 22, results from the U.S. Flu VE network do not show statistically significant evidence that the flu vaccine is effective. Currently, the vaccine is estimated to be 8% effective against preventing influenza A infection (95% confidence interval, –31% to 36%) and 14% effective against preventing A/H3N2 infection (95% CI, –28% to 43%) for people aged 6 months and older.

The network did not have enough data to provide age-specific VE estimates or estimates of effectiveness against influenza B. This could be due to low flu activity relative to prepandemic years, Dr. Flannery said. Of the 2,758 individuals enrolled in the VE flu network this season, just 147 (5%) tested positive for the flu this season. This is the lowest positivity rate observed in the Flu VE network participants with respiratory illness over the past 10 flu seasons, Dr. Grohskopf noted. In comparison, estimates from the 2019 to 2020 season included 4,112 individuals, and 1,060 tested positive for flu.

“We are really at the bare minimum of what we can use for a flu vaccine effectiveness estimate,” Dr. Flannery said about the more recent data. The network was not able to produce any estimates about flu vaccine effectiveness for the 2020-2021 season because of historically low flu activity.

The Department of Defense also presented vaccine efficacy estimates for the 2021–2022 season. The vaccine has been 36% effective (95% CI, 28%-44%) against all strains of the virus, 33% effective against influenza A (95% CI, 24%-41%), 32% effective against A/H3N2 (95% CI, 3%-53%), and 59% effective against influenza B (95% CI, 42%-71%). These results are from a young, healthy adult population, Lieutenant Commander Courtney Gustin, DrPH, MSN, told the panel, and they may not be reflective of efficacy rates across all age groups.

Though these findings suggest there is low to no measurable benefit against influenza A, Dr. Flannery said the CDC still recommends getting the flu vaccine, as it can be protective against other circulating flu strains. “We have been able to demonstrate protection against other H3 [viruses], B viruses, and H1 viruses in the past,” he said. And as these results only show protection against mild disease, “there is still possibility that there’s benefit against more severe disease,” he added. Studies measuring effectiveness against more severe outcomes are not yet available.

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

Scientists have found the coronavirus in 29 kinds of animals, including household pets, livestock, and wildlife, according to researchers’ latest tally.

In most cases, humans infect animals, and animals don’t transmit the virus back to humans. But scientists have expressed concerns about recent research that shows some animals – such as mink and deer – appear to be able to spread the virus to humans.

In addition, the virus will likely continue to circulate in wild animals, which could lead to new mutations, some of which may make the virus less susceptible to people’s immunity from current vaccines. Researchers are calling for better surveillance of animals, especially in the wild, to track any new variants.

“It could be evolving in hosts we are not aware of,” Eman Anis, PhD, an assistant professor of microbiology at the University of Pennsylvania, Philadelphia, told the Philadelphia Inquirer.

Scientists have identified the virus in a growing list of animals, according to the Centers for Disease Control and Prevention, including cats, dogs, ferrets, gorillas, hamsters, hippos, hyenas, mice, otters, pigs, rabbits, and tigers. In many cases, humans spread the coronavirus to pets at home or to wildlife in zoos and sanctuaries.

In the study, published in bioRxiv, researchers identified a person who tested positive after close contact with infected white-tailed deer. The coronavirus had evolved dozens of mutations not found in other strains.

Even with the changes, the virus they found doesn’t appear different enough to evade current vaccines, the researchers reported. The vaccines target the spike protein on the outside of coronavirus cells, and the mutations that happened in deer occurred elsewhere in the virus.

At the same time, scientists have noted that this points to the need to step up monitoring in wild animals before mutations become a problem.

“This is no need to panic, but this is not something we can ignore,” Suresh Kuchipudi, PhD, a professor of veterinary and biomedical sciences at Pennsylvania State University in University Park, told the Inquirer.

Dr. Kuchipudi, who wasn’t involved with the Canadian study, has done other studies that found COVID-19 in deer. As the coronavirus continues to circulate in deer, more mutations will arise, he noted.

“It’s hard to predict what evolution’s going to come up with,” Frederic Bushman, a microbiology professor at the University of Pennsylvania, told the Inquirer.

“The virus will probably change different ways in different animals. Some of them probably won’t infect humans as well,” he said. “But the fear is that maybe some new one will come along that does infect humans well.”

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

Scientists have found the coronavirus in 29 kinds of animals, including household pets, livestock, and wildlife, according to researchers’ latest tally.

In most cases, humans infect animals, and animals don’t transmit the virus back to humans. But scientists have expressed concerns about recent research that shows some animals – such as mink and deer – appear to be able to spread the virus to humans.

In addition, the virus will likely continue to circulate in wild animals, which could lead to new mutations, some of which may make the virus less susceptible to people’s immunity from current vaccines. Researchers are calling for better surveillance of animals, especially in the wild, to track any new variants.

“It could be evolving in hosts we are not aware of,” Eman Anis, PhD, an assistant professor of microbiology at the University of Pennsylvania, Philadelphia, told the Philadelphia Inquirer.

Scientists have identified the virus in a growing list of animals, according to the Centers for Disease Control and Prevention, including cats, dogs, ferrets, gorillas, hamsters, hippos, hyenas, mice, otters, pigs, rabbits, and tigers. In many cases, humans spread the coronavirus to pets at home or to wildlife in zoos and sanctuaries.

In the study, published in bioRxiv, researchers identified a person who tested positive after close contact with infected white-tailed deer. The coronavirus had evolved dozens of mutations not found in other strains.

Even with the changes, the virus they found doesn’t appear different enough to evade current vaccines, the researchers reported. The vaccines target the spike protein on the outside of coronavirus cells, and the mutations that happened in deer occurred elsewhere in the virus.

At the same time, scientists have noted that this points to the need to step up monitoring in wild animals before mutations become a problem.

“This is no need to panic, but this is not something we can ignore,” Suresh Kuchipudi, PhD, a professor of veterinary and biomedical sciences at Pennsylvania State University in University Park, told the Inquirer.

Dr. Kuchipudi, who wasn’t involved with the Canadian study, has done other studies that found COVID-19 in deer. As the coronavirus continues to circulate in deer, more mutations will arise, he noted.

“It’s hard to predict what evolution’s going to come up with,” Frederic Bushman, a microbiology professor at the University of Pennsylvania, told the Inquirer.

“The virus will probably change different ways in different animals. Some of them probably won’t infect humans as well,” he said. “But the fear is that maybe some new one will come along that does infect humans well.”

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

Scientists have found the coronavirus in 29 kinds of animals, including household pets, livestock, and wildlife, according to researchers’ latest tally.

In most cases, humans infect animals, and animals don’t transmit the virus back to humans. But scientists have expressed concerns about recent research that shows some animals – such as mink and deer – appear to be able to spread the virus to humans.

In addition, the virus will likely continue to circulate in wild animals, which could lead to new mutations, some of which may make the virus less susceptible to people’s immunity from current vaccines. Researchers are calling for better surveillance of animals, especially in the wild, to track any new variants.

“It could be evolving in hosts we are not aware of,” Eman Anis, PhD, an assistant professor of microbiology at the University of Pennsylvania, Philadelphia, told the Philadelphia Inquirer.

Scientists have identified the virus in a growing list of animals, according to the Centers for Disease Control and Prevention, including cats, dogs, ferrets, gorillas, hamsters, hippos, hyenas, mice, otters, pigs, rabbits, and tigers. In many cases, humans spread the coronavirus to pets at home or to wildlife in zoos and sanctuaries.

In the study, published in bioRxiv, researchers identified a person who tested positive after close contact with infected white-tailed deer. The coronavirus had evolved dozens of mutations not found in other strains.

Even with the changes, the virus they found doesn’t appear different enough to evade current vaccines, the researchers reported. The vaccines target the spike protein on the outside of coronavirus cells, and the mutations that happened in deer occurred elsewhere in the virus.

At the same time, scientists have noted that this points to the need to step up monitoring in wild animals before mutations become a problem.

“This is no need to panic, but this is not something we can ignore,” Suresh Kuchipudi, PhD, a professor of veterinary and biomedical sciences at Pennsylvania State University in University Park, told the Inquirer.

Dr. Kuchipudi, who wasn’t involved with the Canadian study, has done other studies that found COVID-19 in deer. As the coronavirus continues to circulate in deer, more mutations will arise, he noted.

“It’s hard to predict what evolution’s going to come up with,” Frederic Bushman, a microbiology professor at the University of Pennsylvania, told the Inquirer.

“The virus will probably change different ways in different animals. Some of them probably won’t infect humans as well,” he said. “But the fear is that maybe some new one will come along that does infect humans well.”

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

As the COVID-19 pandemic winds down – for the time being at least – efforts are ramping up to develop next-generation vaccines that can protect against future novel coronaviruses and variants. Several projects are presenting clever combinations of viral parts to the immune system that evoke a robust and hopefully lasting response.

The coming generation of “pan” vaccines aims to tamp down SARS-CoV-2, its closest relatives, and whatever may come into tamer respiratory viruses like the common cold. Whatever the eventual components of this new generation of vaccines, experts agree on the goal: preventing severe disease and death. And a broader approach is critical.

“All the vaccines have been amazing. But we’re playing a whack-a-mole game with the variants. We need to take a step back and ask if a pan-variant vaccine is possible. That’s important because Omicron isn’t the last variant,” said Jacob Lemieux, MD, PhD, instructor in medicine and infectious disease specialist at Massachusetts General Hospital, Boston.
 

A broad spectrum vaccine

The drive to create a vaccine that would deter multiple coronaviruses arose early, among many researchers. An article published in Nature in May 2020 by National Institute of Allergy and Infectious Diseases researcher Luca T. Giurgea, MD, and colleagues said it all in the title: “Universal coronavirus vaccines: the time to start is now.”

Their concerns? The diversity of bat coronaviruses poised to jump into humans; the high mutability of the spike gene that the immune response recognizes; and the persistence of mutations in an RNA virus, which can’t repair errors. 

Work on broader vaccines began in several labs as SARS-CoV-2 spawned variant after variant.

On Sept. 28, NIAID announced funding for developing ‘pan-coronavirus’ vaccines – the quotation marks theirs to indicate that a magic bullet against any new coronavirus is unrealistic. “These new awards are designed to look ahead and prepare for the next generation of coronaviruses with pandemic potential,” said NIAID director Anthony S. Fauci, MD. An initial three awards went to groups at the University of Wisconsin, Brigham and Women’s Hospital, and Duke University.

President Biden mentioned the NIAID funding in his State of the Union Address. He also talked about how the Biomedical Advanced Research and Development Authority, founded in 2006 to prepare for public health emergencies, is spearheading development of new vaccine platforms and vaccines that target a broader swath of pathogen parts.

Meanwhile, individual researchers from eclectic fields are finding new ways to prevent future pandemics.

Artem Babaian, PhD, a computational biologist at the University of Cambridge (England), had the idea to probe National Institutes of Health genome databases, going back more than a decade, for overlooked novel coronaviruses. He started the project while he was between jobs as the pandemic was unfurling, using a telltale enzyme unique to the RNA viruses to fish out COVID cousins. The work is published in Nature and the data freely available at serratus.io.

Among the nearly 132,000 novel RNA viruses Dr. Babaian’s team found, 9 were from previously unrecognized coronaviruses. The novel nine came from “ecologically diverse sources”: a seahorse, an axolotl, an eel, and several fishes. Deciphering the topographies of these coronaviruses may provide clues to developing vaccines that stay ahead of future pandemics.

But optics are important in keeping expectations reasonable. “‘Universal vaccine’ is a misnomer. I think about it as ‘broad spectrum vaccines.’ It’s critical to be up front that these vaccines can never guarantee immunity against all coronaviruses. There are no absolutes in biology, but they hopefully will work against the dangers that we do know exist. A vaccine that mimics exposure to many coronaviruses could protect against a currently unknown coronavirus, especially if slower-evolving antigens are included,” Dr. Babaian said in an interview.

Nikolai Petrovsky, MD, PhD, of Flinders University, Adelaide, and the biotechnology company Vaccine Pty, agrees, calling a literal pan-coronavirus vaccine a “pipe dream. What I do think is achievable is a broadly protective, pan–CoV-19 vaccine – I can say that because we have already developed and tested it, combining antigens rather than trying just one that can do everything.”
 

Immunity lures

The broader vaccines in development display viral antigens, such as spike proteins, to the immune system on diverse frameworks. Here are a few approaches.

Ferritin nanoparticles: A candidate vaccine from the emerging infectious diseases branch of Water Reed National Military Medical Center began phase 1 human trials in April 2021. Called SpFN, the vaccine consists of arrays of ferritin nanoparticles linked to spike proteins from various variants and species. Ferritin is a protein that binds and stores iron in the body.

“The repetitive and ordered display of the coronavirus spike protein on a multifaced nanoparticle may stimulate immunity in such a way as to translate into significantly broader protection,” said Walter Reed’s branch director and vaccine coinventor Kayvon Modjarrad, MD, PhD.

A second vaccine targets only the “bullseye” part of the spike that the virus uses to attach and gain access to human cells, called the receptor-binding domain (RBD), of SARS-CoV-2 variants and of the virus behind the original SARS. The preclinical data appeared in Science Translational Medicine.

Barton Haynes, MD and colleagues at the Duke Human Vaccine Institute are also using ferritin to design and develop a “pan-betacoronavirus vaccine,” referring to the genus to which SARS-CoV-2 belongs. They say their results in macaques, published in Nature, “demonstrate that current mRNA-based vaccines may provide some protection from future outbreaks of zoonotic betacoronaviruses.”

Mosaic nanoparticles: Graduate student Alexander Cohen is leading an effort at CalTech, in the lab of Pamela Bjorkman, PhD, that uses nanoparticles consisting of proteins from a bacterium (Strep pyogenes) to which RBDs from spike proteins of four or eight different betacoronaviruses are attached. The strategy demonstrates that the whole is greater than the sum of the parts.

“Alex’s results show that it is possible to raise diverse neutralizing antibody responses, even against coronavirus strains that were not represented on the injected nanoparticle. We are hopeful that this technology could be used to protect against future animal coronaviruses that cross into humans,” said Dr. Björkman. The work appeared in Science.

Candidate vaccines from Inovio Pharmaceuticals also use a mosaic spike strategy, but with DNA rings (plasmids) rather than nanoparticles. One version works against pre-Omicron variants and is being tested against Omicron, and another with “pan–COVID-19” coverage has tested well in animal models. Inovio’s vaccines are delivered into the skin using a special device that applies an electric pulse that increases the cells’ permeability.

Chimeric spikes: Yet another approach is to fashion vaccines from various parts of the betacoronaviruses that are most closely related to SARS-CoV-2 – the pathogens behind Middle East respiratory syndrome and severe acute respiratory syndrome as well as several bat viruses and a few pangolin ones. The abundance and ubiquity of these viruses provide a toolbox of sorts, with instructions written in the language of RNA, from which to select, dissect, recombine, and customize vaccines.

“SARS-like viruses can recombine and exhibit great genetic diversity in several parts of the genome. We designed chimeric spikes to improve coverage of a multiplexed vaccine,” said David Martinez, PhD.

His team at the University of North Carolina at Chapel Hill has developed mRNA vaccines that deliver “scrambled coronavirus spikes” representing various parts, not just the RBD, as described in Science.

In mice, the chimeric vaccines elicit robust T- and B-cell immune responses, which stimulate antibody production and control other facets of building immunity.
 

Beyond the spike bullseye

The challenge of developing pan-coronavirus vaccines is dual. “The very best vaccines are highly specific to each strain, and the universal vaccines have to sacrifice effectiveness to get broad coverage. Life is a trade-off.” Dr. Petrovsky told this news organization. 

Efforts to broaden vaccine efficacy venture beyond targeting the RBD bullseyes of the spike triplets that festoon the virus. Some projects are focusing on less changeable spike parts that are more alike among less closely related coronaviruses than is the mutation-prone RBD. For example, the peptides that twist into the “stem-helix” portion of the part of the spike that adheres to host cells are the basis of some candidate vaccines now in preclinical studies.

Still other vaccines aren’t spike based at all. French company Osivax, for example, is working on a vaccine that targets the nucleocapsid protein that shields the viral RNA. The hope is that presenting various faces of the pathogen may spark immunity beyond an initial antibody rush and evoke more diverse and lasting T-cell responses.

With the myriad efforts to back up the first generation of COVID-19 vaccines with new ones offering broader protection, it appears that science may have finally learned from history.

“After the SARS outbreak, we lost interest and failed to complete development of a vaccine for use in case of a recurrent outbreak. We must not make the same mistake again,” Dr. Giurgea and colleagues wrote in their Nature article about universal coronavirus vaccines.

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

As the COVID-19 pandemic winds down – for the time being at least – efforts are ramping up to develop next-generation vaccines that can protect against future novel coronaviruses and variants. Several projects are presenting clever combinations of viral parts to the immune system that evoke a robust and hopefully lasting response.

The coming generation of “pan” vaccines aims to tamp down SARS-CoV-2, its closest relatives, and whatever may come into tamer respiratory viruses like the common cold. Whatever the eventual components of this new generation of vaccines, experts agree on the goal: preventing severe disease and death. And a broader approach is critical.

“All the vaccines have been amazing. But we’re playing a whack-a-mole game with the variants. We need to take a step back and ask if a pan-variant vaccine is possible. That’s important because Omicron isn’t the last variant,” said Jacob Lemieux, MD, PhD, instructor in medicine and infectious disease specialist at Massachusetts General Hospital, Boston.
 

A broad spectrum vaccine

The drive to create a vaccine that would deter multiple coronaviruses arose early, among many researchers. An article published in Nature in May 2020 by National Institute of Allergy and Infectious Diseases researcher Luca T. Giurgea, MD, and colleagues said it all in the title: “Universal coronavirus vaccines: the time to start is now.”

Their concerns? The diversity of bat coronaviruses poised to jump into humans; the high mutability of the spike gene that the immune response recognizes; and the persistence of mutations in an RNA virus, which can’t repair errors. 

Work on broader vaccines began in several labs as SARS-CoV-2 spawned variant after variant.

On Sept. 28, NIAID announced funding for developing ‘pan-coronavirus’ vaccines – the quotation marks theirs to indicate that a magic bullet against any new coronavirus is unrealistic. “These new awards are designed to look ahead and prepare for the next generation of coronaviruses with pandemic potential,” said NIAID director Anthony S. Fauci, MD. An initial three awards went to groups at the University of Wisconsin, Brigham and Women’s Hospital, and Duke University.

President Biden mentioned the NIAID funding in his State of the Union Address. He also talked about how the Biomedical Advanced Research and Development Authority, founded in 2006 to prepare for public health emergencies, is spearheading development of new vaccine platforms and vaccines that target a broader swath of pathogen parts.

Meanwhile, individual researchers from eclectic fields are finding new ways to prevent future pandemics.

Artem Babaian, PhD, a computational biologist at the University of Cambridge (England), had the idea to probe National Institutes of Health genome databases, going back more than a decade, for overlooked novel coronaviruses. He started the project while he was between jobs as the pandemic was unfurling, using a telltale enzyme unique to the RNA viruses to fish out COVID cousins. The work is published in Nature and the data freely available at serratus.io.

Among the nearly 132,000 novel RNA viruses Dr. Babaian’s team found, 9 were from previously unrecognized coronaviruses. The novel nine came from “ecologically diverse sources”: a seahorse, an axolotl, an eel, and several fishes. Deciphering the topographies of these coronaviruses may provide clues to developing vaccines that stay ahead of future pandemics.

But optics are important in keeping expectations reasonable. “‘Universal vaccine’ is a misnomer. I think about it as ‘broad spectrum vaccines.’ It’s critical to be up front that these vaccines can never guarantee immunity against all coronaviruses. There are no absolutes in biology, but they hopefully will work against the dangers that we do know exist. A vaccine that mimics exposure to many coronaviruses could protect against a currently unknown coronavirus, especially if slower-evolving antigens are included,” Dr. Babaian said in an interview.

Nikolai Petrovsky, MD, PhD, of Flinders University, Adelaide, and the biotechnology company Vaccine Pty, agrees, calling a literal pan-coronavirus vaccine a “pipe dream. What I do think is achievable is a broadly protective, pan–CoV-19 vaccine – I can say that because we have already developed and tested it, combining antigens rather than trying just one that can do everything.”
 

Immunity lures

The broader vaccines in development display viral antigens, such as spike proteins, to the immune system on diverse frameworks. Here are a few approaches.

Ferritin nanoparticles: A candidate vaccine from the emerging infectious diseases branch of Water Reed National Military Medical Center began phase 1 human trials in April 2021. Called SpFN, the vaccine consists of arrays of ferritin nanoparticles linked to spike proteins from various variants and species. Ferritin is a protein that binds and stores iron in the body.

“The repetitive and ordered display of the coronavirus spike protein on a multifaced nanoparticle may stimulate immunity in such a way as to translate into significantly broader protection,” said Walter Reed’s branch director and vaccine coinventor Kayvon Modjarrad, MD, PhD.

A second vaccine targets only the “bullseye” part of the spike that the virus uses to attach and gain access to human cells, called the receptor-binding domain (RBD), of SARS-CoV-2 variants and of the virus behind the original SARS. The preclinical data appeared in Science Translational Medicine.

Barton Haynes, MD and colleagues at the Duke Human Vaccine Institute are also using ferritin to design and develop a “pan-betacoronavirus vaccine,” referring to the genus to which SARS-CoV-2 belongs. They say their results in macaques, published in Nature, “demonstrate that current mRNA-based vaccines may provide some protection from future outbreaks of zoonotic betacoronaviruses.”

Mosaic nanoparticles: Graduate student Alexander Cohen is leading an effort at CalTech, in the lab of Pamela Bjorkman, PhD, that uses nanoparticles consisting of proteins from a bacterium (Strep pyogenes) to which RBDs from spike proteins of four or eight different betacoronaviruses are attached. The strategy demonstrates that the whole is greater than the sum of the parts.

“Alex’s results show that it is possible to raise diverse neutralizing antibody responses, even against coronavirus strains that were not represented on the injected nanoparticle. We are hopeful that this technology could be used to protect against future animal coronaviruses that cross into humans,” said Dr. Björkman. The work appeared in Science.

Candidate vaccines from Inovio Pharmaceuticals also use a mosaic spike strategy, but with DNA rings (plasmids) rather than nanoparticles. One version works against pre-Omicron variants and is being tested against Omicron, and another with “pan–COVID-19” coverage has tested well in animal models. Inovio’s vaccines are delivered into the skin using a special device that applies an electric pulse that increases the cells’ permeability.

Chimeric spikes: Yet another approach is to fashion vaccines from various parts of the betacoronaviruses that are most closely related to SARS-CoV-2 – the pathogens behind Middle East respiratory syndrome and severe acute respiratory syndrome as well as several bat viruses and a few pangolin ones. The abundance and ubiquity of these viruses provide a toolbox of sorts, with instructions written in the language of RNA, from which to select, dissect, recombine, and customize vaccines.

“SARS-like viruses can recombine and exhibit great genetic diversity in several parts of the genome. We designed chimeric spikes to improve coverage of a multiplexed vaccine,” said David Martinez, PhD.

His team at the University of North Carolina at Chapel Hill has developed mRNA vaccines that deliver “scrambled coronavirus spikes” representing various parts, not just the RBD, as described in Science.

In mice, the chimeric vaccines elicit robust T- and B-cell immune responses, which stimulate antibody production and control other facets of building immunity.
 

Beyond the spike bullseye

The challenge of developing pan-coronavirus vaccines is dual. “The very best vaccines are highly specific to each strain, and the universal vaccines have to sacrifice effectiveness to get broad coverage. Life is a trade-off.” Dr. Petrovsky told this news organization. 

Efforts to broaden vaccine efficacy venture beyond targeting the RBD bullseyes of the spike triplets that festoon the virus. Some projects are focusing on less changeable spike parts that are more alike among less closely related coronaviruses than is the mutation-prone RBD. For example, the peptides that twist into the “stem-helix” portion of the part of the spike that adheres to host cells are the basis of some candidate vaccines now in preclinical studies.

Still other vaccines aren’t spike based at all. French company Osivax, for example, is working on a vaccine that targets the nucleocapsid protein that shields the viral RNA. The hope is that presenting various faces of the pathogen may spark immunity beyond an initial antibody rush and evoke more diverse and lasting T-cell responses.

With the myriad efforts to back up the first generation of COVID-19 vaccines with new ones offering broader protection, it appears that science may have finally learned from history.

“After the SARS outbreak, we lost interest and failed to complete development of a vaccine for use in case of a recurrent outbreak. We must not make the same mistake again,” Dr. Giurgea and colleagues wrote in their Nature article about universal coronavirus vaccines.

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

As the COVID-19 pandemic winds down – for the time being at least – efforts are ramping up to develop next-generation vaccines that can protect against future novel coronaviruses and variants. Several projects are presenting clever combinations of viral parts to the immune system that evoke a robust and hopefully lasting response.

The coming generation of “pan” vaccines aims to tamp down SARS-CoV-2, its closest relatives, and whatever may come into tamer respiratory viruses like the common cold. Whatever the eventual components of this new generation of vaccines, experts agree on the goal: preventing severe disease and death. And a broader approach is critical.

“All the vaccines have been amazing. But we’re playing a whack-a-mole game with the variants. We need to take a step back and ask if a pan-variant vaccine is possible. That’s important because Omicron isn’t the last variant,” said Jacob Lemieux, MD, PhD, instructor in medicine and infectious disease specialist at Massachusetts General Hospital, Boston.
 

A broad spectrum vaccine

The drive to create a vaccine that would deter multiple coronaviruses arose early, among many researchers. An article published in Nature in May 2020 by National Institute of Allergy and Infectious Diseases researcher Luca T. Giurgea, MD, and colleagues said it all in the title: “Universal coronavirus vaccines: the time to start is now.”

Their concerns? The diversity of bat coronaviruses poised to jump into humans; the high mutability of the spike gene that the immune response recognizes; and the persistence of mutations in an RNA virus, which can’t repair errors. 

Work on broader vaccines began in several labs as SARS-CoV-2 spawned variant after variant.

On Sept. 28, NIAID announced funding for developing ‘pan-coronavirus’ vaccines – the quotation marks theirs to indicate that a magic bullet against any new coronavirus is unrealistic. “These new awards are designed to look ahead and prepare for the next generation of coronaviruses with pandemic potential,” said NIAID director Anthony S. Fauci, MD. An initial three awards went to groups at the University of Wisconsin, Brigham and Women’s Hospital, and Duke University.

President Biden mentioned the NIAID funding in his State of the Union Address. He also talked about how the Biomedical Advanced Research and Development Authority, founded in 2006 to prepare for public health emergencies, is spearheading development of new vaccine platforms and vaccines that target a broader swath of pathogen parts.

Meanwhile, individual researchers from eclectic fields are finding new ways to prevent future pandemics.

Artem Babaian, PhD, a computational biologist at the University of Cambridge (England), had the idea to probe National Institutes of Health genome databases, going back more than a decade, for overlooked novel coronaviruses. He started the project while he was between jobs as the pandemic was unfurling, using a telltale enzyme unique to the RNA viruses to fish out COVID cousins. The work is published in Nature and the data freely available at serratus.io.

Among the nearly 132,000 novel RNA viruses Dr. Babaian’s team found, 9 were from previously unrecognized coronaviruses. The novel nine came from “ecologically diverse sources”: a seahorse, an axolotl, an eel, and several fishes. Deciphering the topographies of these coronaviruses may provide clues to developing vaccines that stay ahead of future pandemics.

But optics are important in keeping expectations reasonable. “‘Universal vaccine’ is a misnomer. I think about it as ‘broad spectrum vaccines.’ It’s critical to be up front that these vaccines can never guarantee immunity against all coronaviruses. There are no absolutes in biology, but they hopefully will work against the dangers that we do know exist. A vaccine that mimics exposure to many coronaviruses could protect against a currently unknown coronavirus, especially if slower-evolving antigens are included,” Dr. Babaian said in an interview.

Nikolai Petrovsky, MD, PhD, of Flinders University, Adelaide, and the biotechnology company Vaccine Pty, agrees, calling a literal pan-coronavirus vaccine a “pipe dream. What I do think is achievable is a broadly protective, pan–CoV-19 vaccine – I can say that because we have already developed and tested it, combining antigens rather than trying just one that can do everything.”
 

Immunity lures

The broader vaccines in development display viral antigens, such as spike proteins, to the immune system on diverse frameworks. Here are a few approaches.

Ferritin nanoparticles: A candidate vaccine from the emerging infectious diseases branch of Water Reed National Military Medical Center began phase 1 human trials in April 2021. Called SpFN, the vaccine consists of arrays of ferritin nanoparticles linked to spike proteins from various variants and species. Ferritin is a protein that binds and stores iron in the body.

“The repetitive and ordered display of the coronavirus spike protein on a multifaced nanoparticle may stimulate immunity in such a way as to translate into significantly broader protection,” said Walter Reed’s branch director and vaccine coinventor Kayvon Modjarrad, MD, PhD.

A second vaccine targets only the “bullseye” part of the spike that the virus uses to attach and gain access to human cells, called the receptor-binding domain (RBD), of SARS-CoV-2 variants and of the virus behind the original SARS. The preclinical data appeared in Science Translational Medicine.

Barton Haynes, MD and colleagues at the Duke Human Vaccine Institute are also using ferritin to design and develop a “pan-betacoronavirus vaccine,” referring to the genus to which SARS-CoV-2 belongs. They say their results in macaques, published in Nature, “demonstrate that current mRNA-based vaccines may provide some protection from future outbreaks of zoonotic betacoronaviruses.”

Mosaic nanoparticles: Graduate student Alexander Cohen is leading an effort at CalTech, in the lab of Pamela Bjorkman, PhD, that uses nanoparticles consisting of proteins from a bacterium (Strep pyogenes) to which RBDs from spike proteins of four or eight different betacoronaviruses are attached. The strategy demonstrates that the whole is greater than the sum of the parts.

“Alex’s results show that it is possible to raise diverse neutralizing antibody responses, even against coronavirus strains that were not represented on the injected nanoparticle. We are hopeful that this technology could be used to protect against future animal coronaviruses that cross into humans,” said Dr. Björkman. The work appeared in Science.

Candidate vaccines from Inovio Pharmaceuticals also use a mosaic spike strategy, but with DNA rings (plasmids) rather than nanoparticles. One version works against pre-Omicron variants and is being tested against Omicron, and another with “pan–COVID-19” coverage has tested well in animal models. Inovio’s vaccines are delivered into the skin using a special device that applies an electric pulse that increases the cells’ permeability.

Chimeric spikes: Yet another approach is to fashion vaccines from various parts of the betacoronaviruses that are most closely related to SARS-CoV-2 – the pathogens behind Middle East respiratory syndrome and severe acute respiratory syndrome as well as several bat viruses and a few pangolin ones. The abundance and ubiquity of these viruses provide a toolbox of sorts, with instructions written in the language of RNA, from which to select, dissect, recombine, and customize vaccines.

“SARS-like viruses can recombine and exhibit great genetic diversity in several parts of the genome. We designed chimeric spikes to improve coverage of a multiplexed vaccine,” said David Martinez, PhD.

His team at the University of North Carolina at Chapel Hill has developed mRNA vaccines that deliver “scrambled coronavirus spikes” representing various parts, not just the RBD, as described in Science.

In mice, the chimeric vaccines elicit robust T- and B-cell immune responses, which stimulate antibody production and control other facets of building immunity.
 

Beyond the spike bullseye

The challenge of developing pan-coronavirus vaccines is dual. “The very best vaccines are highly specific to each strain, and the universal vaccines have to sacrifice effectiveness to get broad coverage. Life is a trade-off.” Dr. Petrovsky told this news organization. 

Efforts to broaden vaccine efficacy venture beyond targeting the RBD bullseyes of the spike triplets that festoon the virus. Some projects are focusing on less changeable spike parts that are more alike among less closely related coronaviruses than is the mutation-prone RBD. For example, the peptides that twist into the “stem-helix” portion of the part of the spike that adheres to host cells are the basis of some candidate vaccines now in preclinical studies.

Still other vaccines aren’t spike based at all. French company Osivax, for example, is working on a vaccine that targets the nucleocapsid protein that shields the viral RNA. The hope is that presenting various faces of the pathogen may spark immunity beyond an initial antibody rush and evoke more diverse and lasting T-cell responses.

With the myriad efforts to back up the first generation of COVID-19 vaccines with new ones offering broader protection, it appears that science may have finally learned from history.

“After the SARS outbreak, we lost interest and failed to complete development of a vaccine for use in case of a recurrent outbreak. We must not make the same mistake again,” Dr. Giurgea and colleagues wrote in their Nature article about universal coronavirus vaccines.

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

Data from the first 6 months after the rollout of mRNA COVID-19 vaccines in the United States released today show that adverse effects from shots are typically mild and short-lived.

Findings of the large study, compiled after nearly 300 million doses were administered, were published online March 7 in The Lancet Infectious Diseases.

Researchers, led by Hannah G. Rosenblum, MD, with the Centers for Disease Control and Prevention COVID Response Team, used passive U.S. surveillance data collected through the Vaccine Adverse Event Reporting System (VAERS), and the active system, v-safe, starting in December 2020 through the first 6 months of the U.S. COVID-19 vaccination program. V-safe is a voluntary, smartphone-based system set up in 2020 specifically for monitoring reactions to COVID-19 and health effects after vaccination. The health effects information from v-safe is presented in this study for the first time.

Of the 298.7 million doses of mRNA vaccines administered in the U.S. during the study period, VAERS processed 340,522 reports. Of those, 313,499 (92.1%) were nonserious; 22,527 (6.6%) were serious (nondeath); and 4,496 (1.3%) were deaths.

From v-safe reporting, researchers learned that about 71% of the 7.9 million participants reported local or systemic reactions, more frequently after dose 2 than after dose 1. Of those reporting reactions after dose 1, about two-thirds (68.6%) reported a local reaction and 52.7% reported a systemic reaction.

Among other findings:

• Injection-site pain occurred after dose 1 in 66.2% of participants and 68.6% after dose 2.
• One-third of participants (33.9%) reported fatigue after dose 1 and 55.7% after dose 2.
• Headache was reported among 27% of participants after dose 1 and 46.2% after dose 2.
• When injection site pain, fatigue, or headaches were reported, the reports were usually in the first week after vaccination.
• Reports of being unable to work or do normal daily activities, or instances of seeking medical care, occurred more commonly after dose 2 (32.1%) than after dose 1 (11.9%). Fewer than 1% of participants reported seeking medical care after dose 1 or 2 of the vaccine.
• Reactions and health effects were reported more often in female than in male recipients, and in people younger than 65 years, compared with older people.
• Serious adverse events, including myocarditis, have been identified following mRNA vaccinations, but the events are rare.

The authors wrote that these results are consistent with preauthorization clinical trials and early postauthorization reports.

“On the basis of our findings, mild to moderate transient reactogenicity should be anticipated,” they said, “particularly among younger and female vaccine recipients.”
 

‘Robust and reassuring data’

“The safety monitoring of the mRNA COVID-19 vaccines stands out as the most comprehensive of any vaccine in U.S. history. The use of these complementary monitoring systems has provided robust and reassuring data,” Matthew S. Krantz, MD, with the division of allergy, pulmonary, and critical care medicine at Vanderbilt University, Nashville, Tenn., and Elizabeth J. Phillips, MD, with the department of pathology, microbiology, and immunology at Vanderbilt, wrote in a related commentary in The Lancet Infectious Diseases.

They point out that the v-safe reports of reactions are consistent with those reported from clinical trials and a large population study in the United Kingdom.

Dr. Phillips said in a press release, “[A]lthough approximately one in 1,000 individuals vaccinated may have an adverse effect, most of these are nonserious. No unusual patterns emerged in the cause of death or serious adverse effects among VAERS reports. For adverse events of special interest, it is reassuring that there were no unexpected signals other than myopericarditis and anaphylaxis, already known to be associated with mRNA vaccines.”

The study authors and editorialists have disclosed no relevant financial relationships.

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

Data from the first 6 months after the rollout of mRNA COVID-19 vaccines in the United States released today show that adverse effects from shots are typically mild and short-lived.

Findings of the large study, compiled after nearly 300 million doses were administered, were published online March 7 in The Lancet Infectious Diseases.

Researchers, led by Hannah G. Rosenblum, MD, with the Centers for Disease Control and Prevention COVID Response Team, used passive U.S. surveillance data collected through the Vaccine Adverse Event Reporting System (VAERS), and the active system, v-safe, starting in December 2020 through the first 6 months of the U.S. COVID-19 vaccination program. V-safe is a voluntary, smartphone-based system set up in 2020 specifically for monitoring reactions to COVID-19 and health effects after vaccination. The health effects information from v-safe is presented in this study for the first time.

Of the 298.7 million doses of mRNA vaccines administered in the U.S. during the study period, VAERS processed 340,522 reports. Of those, 313,499 (92.1%) were nonserious; 22,527 (6.6%) were serious (nondeath); and 4,496 (1.3%) were deaths.

From v-safe reporting, researchers learned that about 71% of the 7.9 million participants reported local or systemic reactions, more frequently after dose 2 than after dose 1. Of those reporting reactions after dose 1, about two-thirds (68.6%) reported a local reaction and 52.7% reported a systemic reaction.

Among other findings:

• Injection-site pain occurred after dose 1 in 66.2% of participants and 68.6% after dose 2.
• One-third of participants (33.9%) reported fatigue after dose 1 and 55.7% after dose 2.
• Headache was reported among 27% of participants after dose 1 and 46.2% after dose 2.
• When injection site pain, fatigue, or headaches were reported, the reports were usually in the first week after vaccination.
• Reports of being unable to work or do normal daily activities, or instances of seeking medical care, occurred more commonly after dose 2 (32.1%) than after dose 1 (11.9%). Fewer than 1% of participants reported seeking medical care after dose 1 or 2 of the vaccine.
• Reactions and health effects were reported more often in female than in male recipients, and in people younger than 65 years, compared with older people.
• Serious adverse events, including myocarditis, have been identified following mRNA vaccinations, but the events are rare.

The authors wrote that these results are consistent with preauthorization clinical trials and early postauthorization reports.

“On the basis of our findings, mild to moderate transient reactogenicity should be anticipated,” they said, “particularly among younger and female vaccine recipients.”
 

‘Robust and reassuring data’

“The safety monitoring of the mRNA COVID-19 vaccines stands out as the most comprehensive of any vaccine in U.S. history. The use of these complementary monitoring systems has provided robust and reassuring data,” Matthew S. Krantz, MD, with the division of allergy, pulmonary, and critical care medicine at Vanderbilt University, Nashville, Tenn., and Elizabeth J. Phillips, MD, with the department of pathology, microbiology, and immunology at Vanderbilt, wrote in a related commentary in The Lancet Infectious Diseases.

They point out that the v-safe reports of reactions are consistent with those reported from clinical trials and a large population study in the United Kingdom.

Dr. Phillips said in a press release, “[A]lthough approximately one in 1,000 individuals vaccinated may have an adverse effect, most of these are nonserious. No unusual patterns emerged in the cause of death or serious adverse effects among VAERS reports. For adverse events of special interest, it is reassuring that there were no unexpected signals other than myopericarditis and anaphylaxis, already known to be associated with mRNA vaccines.”

The study authors and editorialists have disclosed no relevant financial relationships.

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

Data from the first 6 months after the rollout of mRNA COVID-19 vaccines in the United States released today show that adverse effects from shots are typically mild and short-lived.

Findings of the large study, compiled after nearly 300 million doses were administered, were published online March 7 in The Lancet Infectious Diseases.

Researchers, led by Hannah G. Rosenblum, MD, with the Centers for Disease Control and Prevention COVID Response Team, used passive U.S. surveillance data collected through the Vaccine Adverse Event Reporting System (VAERS), and the active system, v-safe, starting in December 2020 through the first 6 months of the U.S. COVID-19 vaccination program. V-safe is a voluntary, smartphone-based system set up in 2020 specifically for monitoring reactions to COVID-19 and health effects after vaccination. The health effects information from v-safe is presented in this study for the first time.

Of the 298.7 million doses of mRNA vaccines administered in the U.S. during the study period, VAERS processed 340,522 reports. Of those, 313,499 (92.1%) were nonserious; 22,527 (6.6%) were serious (nondeath); and 4,496 (1.3%) were deaths.

From v-safe reporting, researchers learned that about 71% of the 7.9 million participants reported local or systemic reactions, more frequently after dose 2 than after dose 1. Of those reporting reactions after dose 1, about two-thirds (68.6%) reported a local reaction and 52.7% reported a systemic reaction.

Among other findings:

• Injection-site pain occurred after dose 1 in 66.2% of participants and 68.6% after dose 2.
• One-third of participants (33.9%) reported fatigue after dose 1 and 55.7% after dose 2.
• Headache was reported among 27% of participants after dose 1 and 46.2% after dose 2.
• When injection site pain, fatigue, or headaches were reported, the reports were usually in the first week after vaccination.
• Reports of being unable to work or do normal daily activities, or instances of seeking medical care, occurred more commonly after dose 2 (32.1%) than after dose 1 (11.9%). Fewer than 1% of participants reported seeking medical care after dose 1 or 2 of the vaccine.
• Reactions and health effects were reported more often in female than in male recipients, and in people younger than 65 years, compared with older people.
• Serious adverse events, including myocarditis, have been identified following mRNA vaccinations, but the events are rare.

The authors wrote that these results are consistent with preauthorization clinical trials and early postauthorization reports.

“On the basis of our findings, mild to moderate transient reactogenicity should be anticipated,” they said, “particularly among younger and female vaccine recipients.”
 

‘Robust and reassuring data’

“The safety monitoring of the mRNA COVID-19 vaccines stands out as the most comprehensive of any vaccine in U.S. history. The use of these complementary monitoring systems has provided robust and reassuring data,” Matthew S. Krantz, MD, with the division of allergy, pulmonary, and critical care medicine at Vanderbilt University, Nashville, Tenn., and Elizabeth J. Phillips, MD, with the department of pathology, microbiology, and immunology at Vanderbilt, wrote in a related commentary in The Lancet Infectious Diseases.

They point out that the v-safe reports of reactions are consistent with those reported from clinical trials and a large population study in the United Kingdom.

Dr. Phillips said in a press release, “[A]lthough approximately one in 1,000 individuals vaccinated may have an adverse effect, most of these are nonserious. No unusual patterns emerged in the cause of death or serious adverse effects among VAERS reports. For adverse events of special interest, it is reassuring that there were no unexpected signals other than myopericarditis and anaphylaxis, already known to be associated with mRNA vaccines.”

The study authors and editorialists have disclosed no relevant financial relationships.

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