Clinical

An early and influential paper on long COVID that appeared in The Lancet has been flagged with an expression of concern while the journal investigates “data errors” brought to light by a reader.

An editorial that accompanied the paper when it was published in January of last year described it as “the first large cohort study with 6-months’ follow-up” of people hospitalized with COVID-19. The article has received plenty of attention since then.

Titled “6-month consequences of COVID-19 in patients discharged from hospital: a cohort study,” the paper has been cited nearly 1,600 times, according to Clarivate’s Web of Science. Altmetric finds references to it in multiple documents from the World Health Organization.

According to the expression of concern, dated November 24, a reader found inconsistencies between the data in the article and a later paper describing the same cohort of patients after a year of follow-up. That discovery sparked an investigation that is still ongoing:

• On Jan 8, 2021, The Lancet published an Article, 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study, by Chaolin Huang and colleagues. 1 On Aug 28, 2021, The Lancet published an Article, 1-year outcomes in hospital survivors with COVID-19: a longitudinal cohort study, by Lixue Huang and colleagues. 2 We received an inquiry from a researcher on data inconsistencies between these two Articles, and we sought an explanation from the corresponding author of the two papers. On Nov 7, 2022, Lancet editors were informed that inconsistencies between the 6-month and the 1-year data were due to “some variables in the dataset used for the 6-month paper were mistakenly disrupted in order”. In view of the extent of these data errors, we now issue an Expression of Concern about the 6-month paper 1 while we investigate further, including further statistical and clinical review of the corrected data. We will update this notice as soon as we have further information.

The corresponding author of both papers, Bin Cao of China’s National Center for Respiratory Medicine and the China-Japan Friendship Hospital in Beijing, has not responded to our request for comment.

A profile of Cao published in Lancet Infectious Diseases last March described him as “a leading researcher in pneumonia and influenza” who “has been instrumental in increasing knowledge about COVID-19.” In addition to the follow-up study of hospitalized COVID patients:

• Cao’s seminal papers during the COVID-19 pandemic include the first report of the clinical characteristics of COVID-19 patients in Wuhan, the description of the risk factors for mortality for adult inpatients, and the results of trials testing the use of antiviral drugs, including lopinavir-ritonavir, to treat COVID-19 in China.

We reached out to The Lancet’s press office and Richard Horton, the journal’s editor-in-chief, and received this statement:

• The Lancet Group treats all communications between editors and authors or readers as confidential. Investigations are continuing, and the Expression of Concern will be updated as soon as we have further information to share. More information about our policies is available here: 

This year, The Lancet overtook the New England Journal of Medicine as the medical journal with the highest impact factor, in large part due to the papers it published about COVID-19.

We’ve counted retractions for three of those papers, most notably a paper about the use of the drug hydroxychloroquine that claimed to use medical data from a company called Surgisphere. As Retraction Watch readers may remember, the article was retracted after sleuths questioned if the data were real, and the company would not produce it for review.

This article first appeared on Retraction Watch.

An early and influential paper on long COVID that appeared in The Lancet has been flagged with an expression of concern while the journal investigates “data errors” brought to light by a reader.

An editorial that accompanied the paper when it was published in January of last year described it as “the first large cohort study with 6-months’ follow-up” of people hospitalized with COVID-19. The article has received plenty of attention since then.

Titled “6-month consequences of COVID-19 in patients discharged from hospital: a cohort study,” the paper has been cited nearly 1,600 times, according to Clarivate’s Web of Science. Altmetric finds references to it in multiple documents from the World Health Organization.

According to the expression of concern, dated November 24, a reader found inconsistencies between the data in the article and a later paper describing the same cohort of patients after a year of follow-up. That discovery sparked an investigation that is still ongoing:

• On Jan 8, 2021, The Lancet published an Article, 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study, by Chaolin Huang and colleagues. 1 On Aug 28, 2021, The Lancet published an Article, 1-year outcomes in hospital survivors with COVID-19: a longitudinal cohort study, by Lixue Huang and colleagues. 2 We received an inquiry from a researcher on data inconsistencies between these two Articles, and we sought an explanation from the corresponding author of the two papers. On Nov 7, 2022, Lancet editors were informed that inconsistencies between the 6-month and the 1-year data were due to “some variables in the dataset used for the 6-month paper were mistakenly disrupted in order”. In view of the extent of these data errors, we now issue an Expression of Concern about the 6-month paper 1 while we investigate further, including further statistical and clinical review of the corrected data. We will update this notice as soon as we have further information.

The corresponding author of both papers, Bin Cao of China’s National Center for Respiratory Medicine and the China-Japan Friendship Hospital in Beijing, has not responded to our request for comment.

A profile of Cao published in Lancet Infectious Diseases last March described him as “a leading researcher in pneumonia and influenza” who “has been instrumental in increasing knowledge about COVID-19.” In addition to the follow-up study of hospitalized COVID patients:

• Cao’s seminal papers during the COVID-19 pandemic include the first report of the clinical characteristics of COVID-19 patients in Wuhan, the description of the risk factors for mortality for adult inpatients, and the results of trials testing the use of antiviral drugs, including lopinavir-ritonavir, to treat COVID-19 in China.

We reached out to The Lancet’s press office and Richard Horton, the journal’s editor-in-chief, and received this statement:

• The Lancet Group treats all communications between editors and authors or readers as confidential. Investigations are continuing, and the Expression of Concern will be updated as soon as we have further information to share. More information about our policies is available here: 

This year, The Lancet overtook the New England Journal of Medicine as the medical journal with the highest impact factor, in large part due to the papers it published about COVID-19.

We’ve counted retractions for three of those papers, most notably a paper about the use of the drug hydroxychloroquine that claimed to use medical data from a company called Surgisphere. As Retraction Watch readers may remember, the article was retracted after sleuths questioned if the data were real, and the company would not produce it for review.

This article first appeared on Retraction Watch.

An early and influential paper on long COVID that appeared in The Lancet has been flagged with an expression of concern while the journal investigates “data errors” brought to light by a reader.

An editorial that accompanied the paper when it was published in January of last year described it as “the first large cohort study with 6-months’ follow-up” of people hospitalized with COVID-19. The article has received plenty of attention since then.

Titled “6-month consequences of COVID-19 in patients discharged from hospital: a cohort study,” the paper has been cited nearly 1,600 times, according to Clarivate’s Web of Science. Altmetric finds references to it in multiple documents from the World Health Organization.

According to the expression of concern, dated November 24, a reader found inconsistencies between the data in the article and a later paper describing the same cohort of patients after a year of follow-up. That discovery sparked an investigation that is still ongoing:

• On Jan 8, 2021, The Lancet published an Article, 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study, by Chaolin Huang and colleagues. 1 On Aug 28, 2021, The Lancet published an Article, 1-year outcomes in hospital survivors with COVID-19: a longitudinal cohort study, by Lixue Huang and colleagues. 2 We received an inquiry from a researcher on data inconsistencies between these two Articles, and we sought an explanation from the corresponding author of the two papers. On Nov 7, 2022, Lancet editors were informed that inconsistencies between the 6-month and the 1-year data were due to “some variables in the dataset used for the 6-month paper were mistakenly disrupted in order”. In view of the extent of these data errors, we now issue an Expression of Concern about the 6-month paper 1 while we investigate further, including further statistical and clinical review of the corrected data. We will update this notice as soon as we have further information.

The corresponding author of both papers, Bin Cao of China’s National Center for Respiratory Medicine and the China-Japan Friendship Hospital in Beijing, has not responded to our request for comment.

A profile of Cao published in Lancet Infectious Diseases last March described him as “a leading researcher in pneumonia and influenza” who “has been instrumental in increasing knowledge about COVID-19.” In addition to the follow-up study of hospitalized COVID patients:

• Cao’s seminal papers during the COVID-19 pandemic include the first report of the clinical characteristics of COVID-19 patients in Wuhan, the description of the risk factors for mortality for adult inpatients, and the results of trials testing the use of antiviral drugs, including lopinavir-ritonavir, to treat COVID-19 in China.

We reached out to The Lancet’s press office and Richard Horton, the journal’s editor-in-chief, and received this statement:

• The Lancet Group treats all communications between editors and authors or readers as confidential. Investigations are continuing, and the Expression of Concern will be updated as soon as we have further information to share. More information about our policies is available here: 

This year, The Lancet overtook the New England Journal of Medicine as the medical journal with the highest impact factor, in large part due to the papers it published about COVID-19.

We’ve counted retractions for three of those papers, most notably a paper about the use of the drug hydroxychloroquine that claimed to use medical data from a company called Surgisphere. As Retraction Watch readers may remember, the article was retracted after sleuths questioned if the data were real, and the company would not produce it for review.

This article first appeared on Retraction Watch.

COVID-19 vaccines retained the ability to prevent deaths from COVID-19 in children and adolescents regardless of the dominant circulating variant, in a new study.

The vaccine’s effectiveness against infection in the short term has been established, as has the waning effectiveness of the vaccine over time, wrote Juan Manuel Castelli, MD, of the Ministry of Health of Argentina, Buenos Aires, and colleagues, in the British Medical Journal.

However, data on the impact of vaccine effectiveness on mortality in children and adolescents are limited, especially during periods of omicron variant dominance, the researchers said.

In their new study, the researchers reviewed data from 844,460 children and adolescents aged 3-17 years from the National Surveillance System and the Nominalized Federal Vaccination Registry of Argentina, during a time that included a period of omicron dominance.

Argentina began vaccinating adolescents aged 12-17 years against COVID-19 in August 2021 and added children aged 3-11 years in October 2021. Those aged 12-17 years who were considered fully vaccinated received two doses of either Pfizer-BioNTech and/or Moderna vaccines, and fully-vaccinated 3- to 11-year-olds received two doses of Sinopharm vaccine.

The average time from the second vaccine dose to a COVID-19 test was 66 days for those aged 12-17 years and 54 days for 3- to 11-year-olds. The researchers matched COVID-19 cases with uninfected controls, and a total of 139,321 cases were included in the analysis.

Overall, the estimated vaccine effectiveness against COVID-19 was 64.2% during a period of delta dominance (61.2% in children aged 3-11 years and 66.8% in adolescents aged 12-17 years).

During a period of omicron dominance, estimated vaccine effectiveness was 19.9% across all ages (15.9% and 26.0% for younger and older age groups, respectively).

Effectiveness of the vaccine decreased over time, regardless of the dominant variant, but the decline was greater during the omicron dominant period, the researchers noted. During the omicron period, effectiveness in children aged 3-11 years decreased from 37.6% at 15-30 days postvaccination to 2.0% at 60 days or longer after vaccination. In adolescents aged 12-17 years, vaccine effectiveness during the omicron period decreased from 55.8% at 15-30 days postvaccination to 12.4% at 60 days or longer after vaccination.

Despite the waning protection against infection, the vaccine’s effectiveness against death from COVID-19 was 66.9% in children aged 3-11 years and 97.6% in adolescents aged 12-17 during the period of omicron dominance, the researchers noted.

The results are consistent with similar studies showing a decreased vaccine effectiveness against infection but a persistent effectiveness against deaths over time, the researchers wrote in the discussion section of their paper.

“Our results suggest that the primary vaccination schedule is effective in preventing mortality in children and adolescents with COVID-19 regardless of the circulating SARS-CoV-2 variant,” the researchers said.
 

Study limitations and strengths

The study was limited by several factors including the incomplete data on symptoms and hospital admissions, the possible impact of unmeasured confounding variables, and the observational design that prevents conclusions of causality, the researchers noted. However, the results were strengthened by the large sample size and access to detailed vaccination records, they said.

Both heterologous and homologous mRNA vaccine schedules showed similar effectiveness in preventing short-term infection and mortality from COVID-19 during periods of differing dominant variants, they noted.

The study findings support the vaccination of children against COVID-19 as an important public health measure to prevent mortality in children and adolescents, they concluded.
 

Data support value of vaccination, outside experts say

“COVID vaccines may not be as effective over time as the gene variants in the SARS-CoV-2 virus change,” Adrienne G. Randolph, MD, a pediatrician at Harvard Medical School and Boston Children’s Hospital, said in an interview. “Therefore, it is essential to assess vaccine effectiveness over time to look at effectiveness against variants and duration of effectiveness.” Dr. Randolph, who was not involved in the study, said she was not surprised by the findings, which she described as consistent with data from the United States. “COVID vaccines are very effective against preventing life-threatening disease, but the effectiveness against less severe illness for COVID vaccines is not as effective against Omicron,” she noted. 

The take-home message for clinicians is that it’s important to get children vaccinated against COVID to prevent severe and life-threatening illness, said Dr. Randolph. “Although these cases are uncommon in children, it is not possible to predict which children will be the most severely affected by COVID,” she emphasized.

However, “we need more data on the new COVID booster vaccines in children that are designed to be more effective against Omicron’s newer variants,” Dr. Randolph said in an interview. “We also need more data on COVID vaccine effectiveness in the youngest children, under 5 years of age, and data on vaccinating mothers to prevent COVID in infants,” she said.

Tim Joos, MD, a Seattle-based clinician who practices a combination of internal medicine and pediatrics, agreed that future research should continue to assess how the new COVID boosters are faring against new variants, noting that the current study did not include data from children who received the new bivalent vaccine.

“The methodology of this study uses a test negative case control design which is common for estimating vaccine effectiveness post-release of a vaccine, but is subject to biases,” Dr. Joos explained. “These are not the clean effectiveness numbers of the prospective randomized control trials that we are used to hearing about when a vaccine is first being approved.”

“Nevertheless, the study reinforces the initial manufacturers’ studies that the vaccines are effective at preventing infection in the pediatric population,” Dr. Joos said in an interview. The current study also reinforces the effectiveness of vaccines in preventing “the rare but devastating mortality from COVID-19 in the pediatric population.”

Commenting on other research showing an increasing ratio of COVID deaths among vaccinated individuals compared to total COVID deaths, he noted that this finding is “likely reflecting a denominator effect of rapidly declining COVID deaths overall,” partly from the vaccines and partly from immunity after previous natural infection.

The study received no outside funding. The researchers, Dr. Randolph, and Dr. Joos had no financial conflicts to disclose. Dr. Joos serves on the Editorial Advisory Board of Pediatric News.

COVID-19 vaccines retained the ability to prevent deaths from COVID-19 in children and adolescents regardless of the dominant circulating variant, in a new study.

The vaccine’s effectiveness against infection in the short term has been established, as has the waning effectiveness of the vaccine over time, wrote Juan Manuel Castelli, MD, of the Ministry of Health of Argentina, Buenos Aires, and colleagues, in the British Medical Journal.

However, data on the impact of vaccine effectiveness on mortality in children and adolescents are limited, especially during periods of omicron variant dominance, the researchers said.

In their new study, the researchers reviewed data from 844,460 children and adolescents aged 3-17 years from the National Surveillance System and the Nominalized Federal Vaccination Registry of Argentina, during a time that included a period of omicron dominance.

Argentina began vaccinating adolescents aged 12-17 years against COVID-19 in August 2021 and added children aged 3-11 years in October 2021. Those aged 12-17 years who were considered fully vaccinated received two doses of either Pfizer-BioNTech and/or Moderna vaccines, and fully-vaccinated 3- to 11-year-olds received two doses of Sinopharm vaccine.

The average time from the second vaccine dose to a COVID-19 test was 66 days for those aged 12-17 years and 54 days for 3- to 11-year-olds. The researchers matched COVID-19 cases with uninfected controls, and a total of 139,321 cases were included in the analysis.

Overall, the estimated vaccine effectiveness against COVID-19 was 64.2% during a period of delta dominance (61.2% in children aged 3-11 years and 66.8% in adolescents aged 12-17 years).

During a period of omicron dominance, estimated vaccine effectiveness was 19.9% across all ages (15.9% and 26.0% for younger and older age groups, respectively).

Effectiveness of the vaccine decreased over time, regardless of the dominant variant, but the decline was greater during the omicron dominant period, the researchers noted. During the omicron period, effectiveness in children aged 3-11 years decreased from 37.6% at 15-30 days postvaccination to 2.0% at 60 days or longer after vaccination. In adolescents aged 12-17 years, vaccine effectiveness during the omicron period decreased from 55.8% at 15-30 days postvaccination to 12.4% at 60 days or longer after vaccination.

Despite the waning protection against infection, the vaccine’s effectiveness against death from COVID-19 was 66.9% in children aged 3-11 years and 97.6% in adolescents aged 12-17 during the period of omicron dominance, the researchers noted.

The results are consistent with similar studies showing a decreased vaccine effectiveness against infection but a persistent effectiveness against deaths over time, the researchers wrote in the discussion section of their paper.

“Our results suggest that the primary vaccination schedule is effective in preventing mortality in children and adolescents with COVID-19 regardless of the circulating SARS-CoV-2 variant,” the researchers said.
 

Study limitations and strengths

The study was limited by several factors including the incomplete data on symptoms and hospital admissions, the possible impact of unmeasured confounding variables, and the observational design that prevents conclusions of causality, the researchers noted. However, the results were strengthened by the large sample size and access to detailed vaccination records, they said.

Both heterologous and homologous mRNA vaccine schedules showed similar effectiveness in preventing short-term infection and mortality from COVID-19 during periods of differing dominant variants, they noted.

The study findings support the vaccination of children against COVID-19 as an important public health measure to prevent mortality in children and adolescents, they concluded.
 

Data support value of vaccination, outside experts say

“COVID vaccines may not be as effective over time as the gene variants in the SARS-CoV-2 virus change,” Adrienne G. Randolph, MD, a pediatrician at Harvard Medical School and Boston Children’s Hospital, said in an interview. “Therefore, it is essential to assess vaccine effectiveness over time to look at effectiveness against variants and duration of effectiveness.” Dr. Randolph, who was not involved in the study, said she was not surprised by the findings, which she described as consistent with data from the United States. “COVID vaccines are very effective against preventing life-threatening disease, but the effectiveness against less severe illness for COVID vaccines is not as effective against Omicron,” she noted. 

The take-home message for clinicians is that it’s important to get children vaccinated against COVID to prevent severe and life-threatening illness, said Dr. Randolph. “Although these cases are uncommon in children, it is not possible to predict which children will be the most severely affected by COVID,” she emphasized.

However, “we need more data on the new COVID booster vaccines in children that are designed to be more effective against Omicron’s newer variants,” Dr. Randolph said in an interview. “We also need more data on COVID vaccine effectiveness in the youngest children, under 5 years of age, and data on vaccinating mothers to prevent COVID in infants,” she said.

Tim Joos, MD, a Seattle-based clinician who practices a combination of internal medicine and pediatrics, agreed that future research should continue to assess how the new COVID boosters are faring against new variants, noting that the current study did not include data from children who received the new bivalent vaccine.

“The methodology of this study uses a test negative case control design which is common for estimating vaccine effectiveness post-release of a vaccine, but is subject to biases,” Dr. Joos explained. “These are not the clean effectiveness numbers of the prospective randomized control trials that we are used to hearing about when a vaccine is first being approved.”

“Nevertheless, the study reinforces the initial manufacturers’ studies that the vaccines are effective at preventing infection in the pediatric population,” Dr. Joos said in an interview. The current study also reinforces the effectiveness of vaccines in preventing “the rare but devastating mortality from COVID-19 in the pediatric population.”

Commenting on other research showing an increasing ratio of COVID deaths among vaccinated individuals compared to total COVID deaths, he noted that this finding is “likely reflecting a denominator effect of rapidly declining COVID deaths overall,” partly from the vaccines and partly from immunity after previous natural infection.

The study received no outside funding. The researchers, Dr. Randolph, and Dr. Joos had no financial conflicts to disclose. Dr. Joos serves on the Editorial Advisory Board of Pediatric News.

COVID-19 vaccines retained the ability to prevent deaths from COVID-19 in children and adolescents regardless of the dominant circulating variant, in a new study.

The vaccine’s effectiveness against infection in the short term has been established, as has the waning effectiveness of the vaccine over time, wrote Juan Manuel Castelli, MD, of the Ministry of Health of Argentina, Buenos Aires, and colleagues, in the British Medical Journal.

However, data on the impact of vaccine effectiveness on mortality in children and adolescents are limited, especially during periods of omicron variant dominance, the researchers said.

In their new study, the researchers reviewed data from 844,460 children and adolescents aged 3-17 years from the National Surveillance System and the Nominalized Federal Vaccination Registry of Argentina, during a time that included a period of omicron dominance.

Argentina began vaccinating adolescents aged 12-17 years against COVID-19 in August 2021 and added children aged 3-11 years in October 2021. Those aged 12-17 years who were considered fully vaccinated received two doses of either Pfizer-BioNTech and/or Moderna vaccines, and fully-vaccinated 3- to 11-year-olds received two doses of Sinopharm vaccine.

The average time from the second vaccine dose to a COVID-19 test was 66 days for those aged 12-17 years and 54 days for 3- to 11-year-olds. The researchers matched COVID-19 cases with uninfected controls, and a total of 139,321 cases were included in the analysis.

Overall, the estimated vaccine effectiveness against COVID-19 was 64.2% during a period of delta dominance (61.2% in children aged 3-11 years and 66.8% in adolescents aged 12-17 years).

During a period of omicron dominance, estimated vaccine effectiveness was 19.9% across all ages (15.9% and 26.0% for younger and older age groups, respectively).

Effectiveness of the vaccine decreased over time, regardless of the dominant variant, but the decline was greater during the omicron dominant period, the researchers noted. During the omicron period, effectiveness in children aged 3-11 years decreased from 37.6% at 15-30 days postvaccination to 2.0% at 60 days or longer after vaccination. In adolescents aged 12-17 years, vaccine effectiveness during the omicron period decreased from 55.8% at 15-30 days postvaccination to 12.4% at 60 days or longer after vaccination.

Despite the waning protection against infection, the vaccine’s effectiveness against death from COVID-19 was 66.9% in children aged 3-11 years and 97.6% in adolescents aged 12-17 during the period of omicron dominance, the researchers noted.

The results are consistent with similar studies showing a decreased vaccine effectiveness against infection but a persistent effectiveness against deaths over time, the researchers wrote in the discussion section of their paper.

“Our results suggest that the primary vaccination schedule is effective in preventing mortality in children and adolescents with COVID-19 regardless of the circulating SARS-CoV-2 variant,” the researchers said.
 

Study limitations and strengths

The study was limited by several factors including the incomplete data on symptoms and hospital admissions, the possible impact of unmeasured confounding variables, and the observational design that prevents conclusions of causality, the researchers noted. However, the results were strengthened by the large sample size and access to detailed vaccination records, they said.

Both heterologous and homologous mRNA vaccine schedules showed similar effectiveness in preventing short-term infection and mortality from COVID-19 during periods of differing dominant variants, they noted.

The study findings support the vaccination of children against COVID-19 as an important public health measure to prevent mortality in children and adolescents, they concluded.
 

Data support value of vaccination, outside experts say

“COVID vaccines may not be as effective over time as the gene variants in the SARS-CoV-2 virus change,” Adrienne G. Randolph, MD, a pediatrician at Harvard Medical School and Boston Children’s Hospital, said in an interview. “Therefore, it is essential to assess vaccine effectiveness over time to look at effectiveness against variants and duration of effectiveness.” Dr. Randolph, who was not involved in the study, said she was not surprised by the findings, which she described as consistent with data from the United States. “COVID vaccines are very effective against preventing life-threatening disease, but the effectiveness against less severe illness for COVID vaccines is not as effective against Omicron,” she noted. 

The take-home message for clinicians is that it’s important to get children vaccinated against COVID to prevent severe and life-threatening illness, said Dr. Randolph. “Although these cases are uncommon in children, it is not possible to predict which children will be the most severely affected by COVID,” she emphasized.

However, “we need more data on the new COVID booster vaccines in children that are designed to be more effective against Omicron’s newer variants,” Dr. Randolph said in an interview. “We also need more data on COVID vaccine effectiveness in the youngest children, under 5 years of age, and data on vaccinating mothers to prevent COVID in infants,” she said.

Tim Joos, MD, a Seattle-based clinician who practices a combination of internal medicine and pediatrics, agreed that future research should continue to assess how the new COVID boosters are faring against new variants, noting that the current study did not include data from children who received the new bivalent vaccine.

“The methodology of this study uses a test negative case control design which is common for estimating vaccine effectiveness post-release of a vaccine, but is subject to biases,” Dr. Joos explained. “These are not the clean effectiveness numbers of the prospective randomized control trials that we are used to hearing about when a vaccine is first being approved.”

“Nevertheless, the study reinforces the initial manufacturers’ studies that the vaccines are effective at preventing infection in the pediatric population,” Dr. Joos said in an interview. The current study also reinforces the effectiveness of vaccines in preventing “the rare but devastating mortality from COVID-19 in the pediatric population.”

Commenting on other research showing an increasing ratio of COVID deaths among vaccinated individuals compared to total COVID deaths, he noted that this finding is “likely reflecting a denominator effect of rapidly declining COVID deaths overall,” partly from the vaccines and partly from immunity after previous natural infection.

The study received no outside funding. The researchers, Dr. Randolph, and Dr. Joos had no financial conflicts to disclose. Dr. Joos serves on the Editorial Advisory Board of Pediatric News.

Roughly 7% of all adult Americans may currently have had long COVID, with symptoms that have lasted 3 months or longer, according to the latest U.S. government survey done in October. More than a quarter say their condition is severe enough to significantly limit their day-to-day activities – yet the problem is only barely starting to get the attention of employers, the health care system, and policymakers.

With no cure or treatment in sight, long COVID is already burdening not only the health care system, but also the economy – and that burden is set to grow. Many experts worry about the possible long-term ripple effects, from increased spending on medical care costs to lost wages due to not being able to work, as well as the policy implications that come with addressing these issues.

“At this point, anyone who’s looking at this seriously would say this is a huge deal,” says senior Brookings Institution fellow Katie Bach, the author of a study that analyzed long COVID’s impact on the labor market.

“We need a real concerted focus on treating these people, which means both research and the clinical side, and figuring out how to build a labor market that is more inclusive of people with disabilities,” she said.

It’s not only that many people are affected. It’s that they are often affected for months and possibly even years.

The U.S. government figures suggest more than 18 million people could have symptoms of long COVID right now. The latest Household Pulse Survey by the Census Bureau and the National Center for Health Statistics takes data from 41,415 people.

A preprint of a study by researchers from City University of New York, posted on medRxiv in September and based on a similar population survey done between June 30 and July 2, drew comparable results. The study has not been peer reviewed.

More than 7% of all those who answered said they had long COVID at the time of the survey, which the researchers said corresponded to approximately 18.5 million U.S. adults. The same study found that a quarter of those, or an estimated 4.7 million adults, said their daily activities were impacted “a lot.”

This can translate into pain not only for the patients, but for governments and employers, too.

In high-income countries around the world, government surveys and other studies are shedding light on the extent to which post-COVID-19 symptoms – commonly known as long COVID – are affecting populations. While results vary, they generally fall within similar ranges.

The World Health Organization estimates that between 10% and 20% of those with COVID-19 go on to have an array of medium- to long-term post-COVID-19 symptoms that range from mild to debilitating. The U.S. Government Accountability Office puts that estimate at 10% to 30%; one of the latest studies published at the end of October in The Journal of the American Medical Association found that 15% of U.S. adults who had tested positive for COVID-19 reported current long COVID symptoms. Elsewhere, a study from the Netherlands published in The Lancet in August found that one in eight COVID-19 cases, or 12.7%, were likely to become long COVID.

“It’s very clear that the condition is devastating people’s lives and livelihoods,” WHO Director-General Tedros Adhanom Ghebreyesus wrote in an article for The Guardian newspaper in October.

“The world has already lost a significant number of the workforce to illness, death, fatigue, unplanned retirement due to an increase in long-term disability, which not only impacts the health system, but is a hit to the overarching economy … the impact of long COVID for all countries is very serious and needs immediate and sustained action equivalent to its scale.”
 

Global snapshot: Lasting symptoms, impact on activities

Patients describe a spectrum of persistent issues, with extreme fatigue, brain fog or cognitive problems, and shortness of breath among the most common complaints. Many also have manageable symptoms that worsen significantly after even mild physical or mental exertion.

Women appear almost twice as likely as men to get long COVID. Many patients have other medical conditions and disabilities that make them more vulnerable to the condition. Those who face greater obstacles accessing health care due to discrimination or socioeconomic inequity are at higher risk as well. 

While many are older, a large number are also in their prime working age. The Census Bureau data show that people ages 40-49 are more likely than any other group to get long COVID, which has broader implications for labor markets and the global economy. Already, experts have estimated that long COVID is likely to cost the U.S. trillions of dollars and affect multiple industries.

“Whether they’re in the financial world, the medical system, lawyers, they’re telling me they’re sitting at the computer screen and they’re unable to process the data,” said Zachary Schwartz, MD, medical director for Vancouver General Hospital’s Post-COVID-19 Recovery Clinic.

“That is what’s most distressing for people, in that they’re not working, they’re not making money, and they don’t know when, or if, they’re going to get better.”

Nearly a third of respondents in the Census Bureau’s Household Pulse Survey who said they have had COVID-19 reported symptoms that lasted 3 months or longer. People between the ages of 30 and 59 were the most affected, with about 32% reporting symptoms. Across the entire adult U.S. population, the survey found that 1 in 7 adults have had long COVID at some point during the pandemic, with about 1 in 18 saying it limited their activity to some degree, and 1 in 50 saying they have faced “a lot” of limits on their activities. Any way these numbers are dissected, long COVID has impacted a large swath of the population.

Yet research into the causes and possible treatments of long COVID is just getting underway.

“The amount of energy and time devoted to it is way, way less than it should, given how many people are likely affected,” said David Cutler, PhD, professor of economics at Harvard University, Cambridge, Mass., who has written about the economic cost of long COVID. “We’re way, way underdoing it here. And I think that’s really a terrible thing.”

Population surveys and studies from around the world show that long COVID lives up to its name, with people reporting serious symptoms for months on end.

In October, Statistics Canada and the Public Health Agency of Canada published early results from a questionnaire done between spring and summer 2022 that found just under 15% of adults who had a confirmed or suspected case of COVID-19 went on to have new or continuing symptoms 3 or more months later. Nearly half, or 47.3%, dealt with symptoms that lasted a year or more. More than one in five said their symptoms “often or always” limited their day-to-day activities, which included routine tasks such as preparing meals, doing errands and chores, and basic functions such as personal care and moving around in their homes.

Nearly three-quarters of workers or students said they missed an average of 20 days of work or school. 

“We haven’t yet been able to determine exactly when symptoms resolve,” said Rainu Kaushal, MD, the senior associate dean for clinical research at Weill Cornell Medicine in New York. She is co-leading a national study on long COVID in adults and children, funded by the National Institutes of Health RECOVER Initiative.

“But there does seem to be, for many of the milder symptoms, resolution at about 4-6 weeks. There seems to be a second point of resolution around 6 months for certain symptoms, and then some symptoms do seem to be permanent, and those tend to be patients who have underlying conditions,” she said.
 

Reducing the risk

Given all the data so far, experts recommend urgent policy changes to help people with long COVID.

“The population needs to be prepared, that understanding long COVID is going to be a very long and difficult process,” said Alexander Charney, MD, PhD, associate professor and the lead principal investigator of the RECOVER adult cohort at Icahn School of Medicine at Mount Sinai in New York. He said the government can do a great deal to help, including setting up a network of connected clinics treating long COVID, standardizing best practices, and sharing information.

“That would go a long way towards making sure that every person feels like they’re not too far away from a clinic where they can get treated for this particular condition,” he said.

But the only known way to prevent long COVID is to prevent COVID-19 infections in the first place, experts say. That means equitable access to tests, therapeutics, and vaccines.

“I will say that avoiding COVID remains the best treatment in the arsenal right now,” said Dr. Kaushal. This means masking, avoiding crowded places with poor ventilation and high exposure risk, and being up to date on vaccinations, she said.

A number of papers – including a large U.K. study published in May 2022, another one from July, and the JAMA study from October – all suggest that vaccinations can help reduce the risk of long COVID.

“I am absolutely of the belief that vaccination has reduced the incidence and overall amount of long COVID … [and is] still by far the best thing the public can do,” said Dr. Schwartz.

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

Roughly 7% of all adult Americans may currently have had long COVID, with symptoms that have lasted 3 months or longer, according to the latest U.S. government survey done in October. More than a quarter say their condition is severe enough to significantly limit their day-to-day activities – yet the problem is only barely starting to get the attention of employers, the health care system, and policymakers.

With no cure or treatment in sight, long COVID is already burdening not only the health care system, but also the economy – and that burden is set to grow. Many experts worry about the possible long-term ripple effects, from increased spending on medical care costs to lost wages due to not being able to work, as well as the policy implications that come with addressing these issues.

“At this point, anyone who’s looking at this seriously would say this is a huge deal,” says senior Brookings Institution fellow Katie Bach, the author of a study that analyzed long COVID’s impact on the labor market.

“We need a real concerted focus on treating these people, which means both research and the clinical side, and figuring out how to build a labor market that is more inclusive of people with disabilities,” she said.

It’s not only that many people are affected. It’s that they are often affected for months and possibly even years.

The U.S. government figures suggest more than 18 million people could have symptoms of long COVID right now. The latest Household Pulse Survey by the Census Bureau and the National Center for Health Statistics takes data from 41,415 people.

A preprint of a study by researchers from City University of New York, posted on medRxiv in September and based on a similar population survey done between June 30 and July 2, drew comparable results. The study has not been peer reviewed.

More than 7% of all those who answered said they had long COVID at the time of the survey, which the researchers said corresponded to approximately 18.5 million U.S. adults. The same study found that a quarter of those, or an estimated 4.7 million adults, said their daily activities were impacted “a lot.”

This can translate into pain not only for the patients, but for governments and employers, too.

In high-income countries around the world, government surveys and other studies are shedding light on the extent to which post-COVID-19 symptoms – commonly known as long COVID – are affecting populations. While results vary, they generally fall within similar ranges.

The World Health Organization estimates that between 10% and 20% of those with COVID-19 go on to have an array of medium- to long-term post-COVID-19 symptoms that range from mild to debilitating. The U.S. Government Accountability Office puts that estimate at 10% to 30%; one of the latest studies published at the end of October in The Journal of the American Medical Association found that 15% of U.S. adults who had tested positive for COVID-19 reported current long COVID symptoms. Elsewhere, a study from the Netherlands published in The Lancet in August found that one in eight COVID-19 cases, or 12.7%, were likely to become long COVID.

“It’s very clear that the condition is devastating people’s lives and livelihoods,” WHO Director-General Tedros Adhanom Ghebreyesus wrote in an article for The Guardian newspaper in October.

“The world has already lost a significant number of the workforce to illness, death, fatigue, unplanned retirement due to an increase in long-term disability, which not only impacts the health system, but is a hit to the overarching economy … the impact of long COVID for all countries is very serious and needs immediate and sustained action equivalent to its scale.”
 

Global snapshot: Lasting symptoms, impact on activities

Patients describe a spectrum of persistent issues, with extreme fatigue, brain fog or cognitive problems, and shortness of breath among the most common complaints. Many also have manageable symptoms that worsen significantly after even mild physical or mental exertion.

Women appear almost twice as likely as men to get long COVID. Many patients have other medical conditions and disabilities that make them more vulnerable to the condition. Those who face greater obstacles accessing health care due to discrimination or socioeconomic inequity are at higher risk as well. 

While many are older, a large number are also in their prime working age. The Census Bureau data show that people ages 40-49 are more likely than any other group to get long COVID, which has broader implications for labor markets and the global economy. Already, experts have estimated that long COVID is likely to cost the U.S. trillions of dollars and affect multiple industries.

“Whether they’re in the financial world, the medical system, lawyers, they’re telling me they’re sitting at the computer screen and they’re unable to process the data,” said Zachary Schwartz, MD, medical director for Vancouver General Hospital’s Post-COVID-19 Recovery Clinic.

“That is what’s most distressing for people, in that they’re not working, they’re not making money, and they don’t know when, or if, they’re going to get better.”

Nearly a third of respondents in the Census Bureau’s Household Pulse Survey who said they have had COVID-19 reported symptoms that lasted 3 months or longer. People between the ages of 30 and 59 were the most affected, with about 32% reporting symptoms. Across the entire adult U.S. population, the survey found that 1 in 7 adults have had long COVID at some point during the pandemic, with about 1 in 18 saying it limited their activity to some degree, and 1 in 50 saying they have faced “a lot” of limits on their activities. Any way these numbers are dissected, long COVID has impacted a large swath of the population.

Yet research into the causes and possible treatments of long COVID is just getting underway.

“The amount of energy and time devoted to it is way, way less than it should, given how many people are likely affected,” said David Cutler, PhD, professor of economics at Harvard University, Cambridge, Mass., who has written about the economic cost of long COVID. “We’re way, way underdoing it here. And I think that’s really a terrible thing.”

Population surveys and studies from around the world show that long COVID lives up to its name, with people reporting serious symptoms for months on end.

In October, Statistics Canada and the Public Health Agency of Canada published early results from a questionnaire done between spring and summer 2022 that found just under 15% of adults who had a confirmed or suspected case of COVID-19 went on to have new or continuing symptoms 3 or more months later. Nearly half, or 47.3%, dealt with symptoms that lasted a year or more. More than one in five said their symptoms “often or always” limited their day-to-day activities, which included routine tasks such as preparing meals, doing errands and chores, and basic functions such as personal care and moving around in their homes.

Nearly three-quarters of workers or students said they missed an average of 20 days of work or school. 

“We haven’t yet been able to determine exactly when symptoms resolve,” said Rainu Kaushal, MD, the senior associate dean for clinical research at Weill Cornell Medicine in New York. She is co-leading a national study on long COVID in adults and children, funded by the National Institutes of Health RECOVER Initiative.

“But there does seem to be, for many of the milder symptoms, resolution at about 4-6 weeks. There seems to be a second point of resolution around 6 months for certain symptoms, and then some symptoms do seem to be permanent, and those tend to be patients who have underlying conditions,” she said.
 

Reducing the risk

Given all the data so far, experts recommend urgent policy changes to help people with long COVID.

“The population needs to be prepared, that understanding long COVID is going to be a very long and difficult process,” said Alexander Charney, MD, PhD, associate professor and the lead principal investigator of the RECOVER adult cohort at Icahn School of Medicine at Mount Sinai in New York. He said the government can do a great deal to help, including setting up a network of connected clinics treating long COVID, standardizing best practices, and sharing information.

“That would go a long way towards making sure that every person feels like they’re not too far away from a clinic where they can get treated for this particular condition,” he said.

But the only known way to prevent long COVID is to prevent COVID-19 infections in the first place, experts say. That means equitable access to tests, therapeutics, and vaccines.

“I will say that avoiding COVID remains the best treatment in the arsenal right now,” said Dr. Kaushal. This means masking, avoiding crowded places with poor ventilation and high exposure risk, and being up to date on vaccinations, she said.

A number of papers – including a large U.K. study published in May 2022, another one from July, and the JAMA study from October – all suggest that vaccinations can help reduce the risk of long COVID.

“I am absolutely of the belief that vaccination has reduced the incidence and overall amount of long COVID … [and is] still by far the best thing the public can do,” said Dr. Schwartz.

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

Roughly 7% of all adult Americans may currently have had long COVID, with symptoms that have lasted 3 months or longer, according to the latest U.S. government survey done in October. More than a quarter say their condition is severe enough to significantly limit their day-to-day activities – yet the problem is only barely starting to get the attention of employers, the health care system, and policymakers.

With no cure or treatment in sight, long COVID is already burdening not only the health care system, but also the economy – and that burden is set to grow. Many experts worry about the possible long-term ripple effects, from increased spending on medical care costs to lost wages due to not being able to work, as well as the policy implications that come with addressing these issues.

“At this point, anyone who’s looking at this seriously would say this is a huge deal,” says senior Brookings Institution fellow Katie Bach, the author of a study that analyzed long COVID’s impact on the labor market.

“We need a real concerted focus on treating these people, which means both research and the clinical side, and figuring out how to build a labor market that is more inclusive of people with disabilities,” she said.

It’s not only that many people are affected. It’s that they are often affected for months and possibly even years.

The U.S. government figures suggest more than 18 million people could have symptoms of long COVID right now. The latest Household Pulse Survey by the Census Bureau and the National Center for Health Statistics takes data from 41,415 people.

A preprint of a study by researchers from City University of New York, posted on medRxiv in September and based on a similar population survey done between June 30 and July 2, drew comparable results. The study has not been peer reviewed.

More than 7% of all those who answered said they had long COVID at the time of the survey, which the researchers said corresponded to approximately 18.5 million U.S. adults. The same study found that a quarter of those, or an estimated 4.7 million adults, said their daily activities were impacted “a lot.”

This can translate into pain not only for the patients, but for governments and employers, too.

In high-income countries around the world, government surveys and other studies are shedding light on the extent to which post-COVID-19 symptoms – commonly known as long COVID – are affecting populations. While results vary, they generally fall within similar ranges.

The World Health Organization estimates that between 10% and 20% of those with COVID-19 go on to have an array of medium- to long-term post-COVID-19 symptoms that range from mild to debilitating. The U.S. Government Accountability Office puts that estimate at 10% to 30%; one of the latest studies published at the end of October in The Journal of the American Medical Association found that 15% of U.S. adults who had tested positive for COVID-19 reported current long COVID symptoms. Elsewhere, a study from the Netherlands published in The Lancet in August found that one in eight COVID-19 cases, or 12.7%, were likely to become long COVID.

“It’s very clear that the condition is devastating people’s lives and livelihoods,” WHO Director-General Tedros Adhanom Ghebreyesus wrote in an article for The Guardian newspaper in October.

“The world has already lost a significant number of the workforce to illness, death, fatigue, unplanned retirement due to an increase in long-term disability, which not only impacts the health system, but is a hit to the overarching economy … the impact of long COVID for all countries is very serious and needs immediate and sustained action equivalent to its scale.”
 

Global snapshot: Lasting symptoms, impact on activities

Patients describe a spectrum of persistent issues, with extreme fatigue, brain fog or cognitive problems, and shortness of breath among the most common complaints. Many also have manageable symptoms that worsen significantly after even mild physical or mental exertion.

Women appear almost twice as likely as men to get long COVID. Many patients have other medical conditions and disabilities that make them more vulnerable to the condition. Those who face greater obstacles accessing health care due to discrimination or socioeconomic inequity are at higher risk as well. 

While many are older, a large number are also in their prime working age. The Census Bureau data show that people ages 40-49 are more likely than any other group to get long COVID, which has broader implications for labor markets and the global economy. Already, experts have estimated that long COVID is likely to cost the U.S. trillions of dollars and affect multiple industries.

“Whether they’re in the financial world, the medical system, lawyers, they’re telling me they’re sitting at the computer screen and they’re unable to process the data,” said Zachary Schwartz, MD, medical director for Vancouver General Hospital’s Post-COVID-19 Recovery Clinic.

“That is what’s most distressing for people, in that they’re not working, they’re not making money, and they don’t know when, or if, they’re going to get better.”

Nearly a third of respondents in the Census Bureau’s Household Pulse Survey who said they have had COVID-19 reported symptoms that lasted 3 months or longer. People between the ages of 30 and 59 were the most affected, with about 32% reporting symptoms. Across the entire adult U.S. population, the survey found that 1 in 7 adults have had long COVID at some point during the pandemic, with about 1 in 18 saying it limited their activity to some degree, and 1 in 50 saying they have faced “a lot” of limits on their activities. Any way these numbers are dissected, long COVID has impacted a large swath of the population.

Yet research into the causes and possible treatments of long COVID is just getting underway.

“The amount of energy and time devoted to it is way, way less than it should, given how many people are likely affected,” said David Cutler, PhD, professor of economics at Harvard University, Cambridge, Mass., who has written about the economic cost of long COVID. “We’re way, way underdoing it here. And I think that’s really a terrible thing.”

Population surveys and studies from around the world show that long COVID lives up to its name, with people reporting serious symptoms for months on end.

In October, Statistics Canada and the Public Health Agency of Canada published early results from a questionnaire done between spring and summer 2022 that found just under 15% of adults who had a confirmed or suspected case of COVID-19 went on to have new or continuing symptoms 3 or more months later. Nearly half, or 47.3%, dealt with symptoms that lasted a year or more. More than one in five said their symptoms “often or always” limited their day-to-day activities, which included routine tasks such as preparing meals, doing errands and chores, and basic functions such as personal care and moving around in their homes.

Nearly three-quarters of workers or students said they missed an average of 20 days of work or school. 

“We haven’t yet been able to determine exactly when symptoms resolve,” said Rainu Kaushal, MD, the senior associate dean for clinical research at Weill Cornell Medicine in New York. She is co-leading a national study on long COVID in adults and children, funded by the National Institutes of Health RECOVER Initiative.

“But there does seem to be, for many of the milder symptoms, resolution at about 4-6 weeks. There seems to be a second point of resolution around 6 months for certain symptoms, and then some symptoms do seem to be permanent, and those tend to be patients who have underlying conditions,” she said.
 

Reducing the risk

Given all the data so far, experts recommend urgent policy changes to help people with long COVID.

“The population needs to be prepared, that understanding long COVID is going to be a very long and difficult process,” said Alexander Charney, MD, PhD, associate professor and the lead principal investigator of the RECOVER adult cohort at Icahn School of Medicine at Mount Sinai in New York. He said the government can do a great deal to help, including setting up a network of connected clinics treating long COVID, standardizing best practices, and sharing information.

“That would go a long way towards making sure that every person feels like they’re not too far away from a clinic where they can get treated for this particular condition,” he said.

But the only known way to prevent long COVID is to prevent COVID-19 infections in the first place, experts say. That means equitable access to tests, therapeutics, and vaccines.

“I will say that avoiding COVID remains the best treatment in the arsenal right now,” said Dr. Kaushal. This means masking, avoiding crowded places with poor ventilation and high exposure risk, and being up to date on vaccinations, she said.

A number of papers – including a large U.K. study published in May 2022, another one from July, and the JAMA study from October – all suggest that vaccinations can help reduce the risk of long COVID.

“I am absolutely of the belief that vaccination has reduced the incidence and overall amount of long COVID … [and is] still by far the best thing the public can do,” said Dr. Schwartz.

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

To the Editor:

The Moderna COVID-19 messenger RNA (mRNA) vaccine was authorized for use on December 18, 2020, with the second dose beginning on January 15, 2021.^1-3 Some individuals who received the Moderna vaccine experienced an intense rash known as “COVID arm,” a harmless but bothersome adverse effect that typically appears within a week and is a localized and transient immunogenic response.⁴ COVID arm differs from most vaccine adverse effects. The rash emerges not immediately but 5 to 9 days after the initial dose—on average, 1 week later. Apart from being itchy, the rash does not appear to be harmful and is not a reason to hesitate getting vaccinated.

Dermatologists and allergists have been studying this adverse effect, which has been formally termed delayed cutaneous hypersensitivity. Of potential clinical consequence is that the efficacy of the mRNA COVID-19 vaccine may be harmed if postvaccination dermal reactions necessitate systemic corticosteroid therapy. Because this vaccine stimulates an immune response as viral RNA integrates in cells secondary to production of the spike protein of the virus, the skin may be affected secondarily and manifestations of any underlying disease may be aggravated.⁵ We report a patient who developed a psoriasiform dermatitis after the first dose of the Moderna vaccine.

A 65-year-old woman presented to her primary care physician because of the severity of psoriasiform dermatitis that developed 5 days after she received the first dose of the Moderna COVID-19 mRNA vaccine. The patient had a medical history of Sjögren syndrome. Her medication history was negative, and her family history was negative for autoimmune disease. Physical examination by primary care revealed an erythematous scaly rash with plaques and papules on the neck and back (Figure 1). The patient presented again to primary care 2 days later with swollen, painful, discolored digits (Figure 2) and a stiff, sore neck.

Laboratory results were positive for anti–Sjögren syndrome–related antigens A and B. A complete blood cell count; comprehensive metabolic panel; erythrocyte sedimentation rate; and assays of rheumatoid factor, C-reactive protein, and anti–cyclic citrullinated peptide were within reference range. A biopsy of a lesion on the back showed psoriasiform dermatitis with confluent parakeratosis and scattered necrotic keratinocytes. There was superficial perivascular inflammation with rare eosinophils (Figure 3).

The patient was treated with a course of systemic corticosteroids. The rash resolved in 1 week. She did not receive the second dose due to the rash.

Two mRNA COVID-19 vaccines—Pfizer BioNTech and Moderna—have been granted emergency use authorization by the US Food and Drug Administration.⁶ The safety profile of the mRNA-1273 vaccine for the median 2-month follow-up showed no safety concerns.³ Minor localized adverse effects (eg, pain, redness, swelling) have been observed more frequently with the vaccines than with placebo. Systemic symptoms, such as fever, fatigue, headache, and muscle and joint pain, also were seen somewhat more often with the vaccines than with placebo; most such effects occurred 24 to 48 hours after vaccination.^3,6,7 The frequency of unsolicited adverse events and serious adverse events reported during the 28-day period after vaccination generally was similar among participants in the vaccine and placebo groups.³

There are 2 types of reactions to COVID-19 vaccination: immediate and delayed. Immediate reactions usually are due to anaphylaxis, requiring prompt recognition and treatment with epinephrine to stop rapid progression of life-threatening symptoms. Delayed reactions include localized reactions, such as urticaria and benign exanthema; serum sickness and serum sickness–like reactions; fever; and rare skin, organ, and neurologic sequelae.^1,6-8

Cutaneous manifestations, present in 16% to 50% of patients with Sjögren syndrome, are considered one of the most common extraglandular presentations of the syndrome. They are classified as nonvascular (eg, xerosis, angular cheilitis, eyelid dermatitis, annular erythema) and vascular (eg, Raynaud phenomenon, vasculitis).^9-11 Our patient did not have any of those findings. She had not taken any medications before the rash appeared, thereby ruling out a drug reaction.

The differential for our patient included post–urinary tract infection immune-reactive arthritis and rash, which is not typical with Escherichia coli infection but is described with infection with Chlamydia species and Salmonella species. Moreover, post–urinary tract infection immune-reactive arthritis and rash appear mostly on the palms and soles. Systemic lupus erythematosus–like rashes have a different histology and appear on sun-exposed areas; our patient’s rash was found mainly on unexposed areas.¹²

Because our patient received the Moderna vaccine 5 days before the rash appeared and later developed swelling of the digits with morning stiffness, a delayed serum sickness–like reaction secondary to COVID-19 vaccination was possible.^3,6

COVID-19 mRNA vaccines developed by Pfizer-BioNTech and Moderna incorporate a lipid-based nanoparticle carrier system that prevents rapid enzymatic degradation of mRNA and facilitates in vivo delivery of mRNA. This lipid-based nanoparticle carrier system is further stabilized by a polyethylene glycol 2000 lipid conjugate that provides a hydrophilic layer, thus prolonging half-life. The presence of lipid polyethylene glycol 2000 in mRNA vaccines has led to concern that this component could be implicated in anaphylaxis.⁶

COVID-19 antigens can give rise to varying clinical manifestations that are directly related to viral tissue damage or are indirectly induced by the antiviral immune response.^13,14 Hyperactivation of the immune system to eradicate COVID-19 may trigger autoimmunity; several immune-mediated disorders have been described in individuals infected with SARS-CoV-2. Dermal manifestations include cutaneous rash and vasculitis.^13-16 Crucial immunologic steps occur during SARS-CoV-2 infection that may link autoimmunity to COVID-19.^13,14 In preliminary published data on the efficacy of the Moderna vaccine on 45 trial enrollees, 3 did not receive the second dose of vaccination, including 1 who developed urticaria on both legs 5 days after the first dose.¹

Introduction of viral RNA can induce autoimmunity that can be explained by various phenomena, including epitope spreading, molecular mimicry, cryptic antigen, and bystander activation. Remarkably, more than one-third of immunogenic proteins in SARS-CoV-2 have potentially problematic homology to proteins that are key to the human adaptive immune system.⁵

Moreover, SARS-CoV-2 seems to induce organ injury through alternative mechanisms beyond direct viral infection, including immunologic injury. In some situations, hyperactivation of the immune response to SARS-CoV-2 RNA can result in autoimmune disease. COVID-19 has been associated with immune-mediated systemic or organ-selective manifestations, some of which fulfill the diagnostic or classification criteria of specific autoimmune diseases. It is unclear whether those medical disorders are the result of transitory postinfectious epiphenomena.⁵

A few studies have shown that patients with rheumatic disease have an incidence and prevalence of COVID-19 that is similar to the general population. A similar pattern has been detected in COVID-19 morbidity and mortality rates, even among patients with an autoimmune disease, such as rheumatoid arthritis and Sjögren syndrome.^5,17 Furthermore, exacerbation of preexisting rheumatic symptoms may be due to hyperactivation of antiviral pathways in a person with an autoimmune disease.^17-19 The findings in our patient suggested a direct role for the vaccine in skin manifestations, rather than for reactivation or development of new systemic autoimmune processes, such as systemic lupus erythematosus.

Exacerbation of psoriasis following COVID-19 vaccination has been described²⁰; however, the case patient did not have a history of psoriasis. The mechanism(s) of such exacerbation remain unclear; COVID-19 vaccine–induced helper T cells (T_H17) may play a role.²¹ Other skin manifestations encountered following COVID-19 vaccination include lichen planus, leukocytoclastic vasculitic rash, erythema multiforme–like rash, and pityriasis rosea–like rash.^22-25 The immune mechanisms of these manifestations remain unclear.

The clinical presentation of delayed vaccination reactions can be attributed to the timing of symptoms and, in this case, the immune-mediated background of a psoriasiform reaction. Although adverse reactions to the SARS-CoV-2 mRNA vaccine are rare, more individuals should be studied after vaccination to confirm and better understand this phenomenon.

To the Editor:

The Moderna COVID-19 messenger RNA (mRNA) vaccine was authorized for use on December 18, 2020, with the second dose beginning on January 15, 2021.^1-3 Some individuals who received the Moderna vaccine experienced an intense rash known as “COVID arm,” a harmless but bothersome adverse effect that typically appears within a week and is a localized and transient immunogenic response.⁴ COVID arm differs from most vaccine adverse effects. The rash emerges not immediately but 5 to 9 days after the initial dose—on average, 1 week later. Apart from being itchy, the rash does not appear to be harmful and is not a reason to hesitate getting vaccinated.

Dermatologists and allergists have been studying this adverse effect, which has been formally termed delayed cutaneous hypersensitivity. Of potential clinical consequence is that the efficacy of the mRNA COVID-19 vaccine may be harmed if postvaccination dermal reactions necessitate systemic corticosteroid therapy. Because this vaccine stimulates an immune response as viral RNA integrates in cells secondary to production of the spike protein of the virus, the skin may be affected secondarily and manifestations of any underlying disease may be aggravated.⁵ We report a patient who developed a psoriasiform dermatitis after the first dose of the Moderna vaccine.

A 65-year-old woman presented to her primary care physician because of the severity of psoriasiform dermatitis that developed 5 days after she received the first dose of the Moderna COVID-19 mRNA vaccine. The patient had a medical history of Sjögren syndrome. Her medication history was negative, and her family history was negative for autoimmune disease. Physical examination by primary care revealed an erythematous scaly rash with plaques and papules on the neck and back (Figure 1). The patient presented again to primary care 2 days later with swollen, painful, discolored digits (Figure 2) and a stiff, sore neck.

Laboratory results were positive for anti–Sjögren syndrome–related antigens A and B. A complete blood cell count; comprehensive metabolic panel; erythrocyte sedimentation rate; and assays of rheumatoid factor, C-reactive protein, and anti–cyclic citrullinated peptide were within reference range. A biopsy of a lesion on the back showed psoriasiform dermatitis with confluent parakeratosis and scattered necrotic keratinocytes. There was superficial perivascular inflammation with rare eosinophils (Figure 3).

The patient was treated with a course of systemic corticosteroids. The rash resolved in 1 week. She did not receive the second dose due to the rash.

Two mRNA COVID-19 vaccines—Pfizer BioNTech and Moderna—have been granted emergency use authorization by the US Food and Drug Administration.⁶ The safety profile of the mRNA-1273 vaccine for the median 2-month follow-up showed no safety concerns.³ Minor localized adverse effects (eg, pain, redness, swelling) have been observed more frequently with the vaccines than with placebo. Systemic symptoms, such as fever, fatigue, headache, and muscle and joint pain, also were seen somewhat more often with the vaccines than with placebo; most such effects occurred 24 to 48 hours after vaccination.^3,6,7 The frequency of unsolicited adverse events and serious adverse events reported during the 28-day period after vaccination generally was similar among participants in the vaccine and placebo groups.³

There are 2 types of reactions to COVID-19 vaccination: immediate and delayed. Immediate reactions usually are due to anaphylaxis, requiring prompt recognition and treatment with epinephrine to stop rapid progression of life-threatening symptoms. Delayed reactions include localized reactions, such as urticaria and benign exanthema; serum sickness and serum sickness–like reactions; fever; and rare skin, organ, and neurologic sequelae.^1,6-8

Cutaneous manifestations, present in 16% to 50% of patients with Sjögren syndrome, are considered one of the most common extraglandular presentations of the syndrome. They are classified as nonvascular (eg, xerosis, angular cheilitis, eyelid dermatitis, annular erythema) and vascular (eg, Raynaud phenomenon, vasculitis).^9-11 Our patient did not have any of those findings. She had not taken any medications before the rash appeared, thereby ruling out a drug reaction.

The differential for our patient included post–urinary tract infection immune-reactive arthritis and rash, which is not typical with Escherichia coli infection but is described with infection with Chlamydia species and Salmonella species. Moreover, post–urinary tract infection immune-reactive arthritis and rash appear mostly on the palms and soles. Systemic lupus erythematosus–like rashes have a different histology and appear on sun-exposed areas; our patient’s rash was found mainly on unexposed areas.¹²

Because our patient received the Moderna vaccine 5 days before the rash appeared and later developed swelling of the digits with morning stiffness, a delayed serum sickness–like reaction secondary to COVID-19 vaccination was possible.^3,6

COVID-19 mRNA vaccines developed by Pfizer-BioNTech and Moderna incorporate a lipid-based nanoparticle carrier system that prevents rapid enzymatic degradation of mRNA and facilitates in vivo delivery of mRNA. This lipid-based nanoparticle carrier system is further stabilized by a polyethylene glycol 2000 lipid conjugate that provides a hydrophilic layer, thus prolonging half-life. The presence of lipid polyethylene glycol 2000 in mRNA vaccines has led to concern that this component could be implicated in anaphylaxis.⁶

COVID-19 antigens can give rise to varying clinical manifestations that are directly related to viral tissue damage or are indirectly induced by the antiviral immune response.^13,14 Hyperactivation of the immune system to eradicate COVID-19 may trigger autoimmunity; several immune-mediated disorders have been described in individuals infected with SARS-CoV-2. Dermal manifestations include cutaneous rash and vasculitis.^13-16 Crucial immunologic steps occur during SARS-CoV-2 infection that may link autoimmunity to COVID-19.^13,14 In preliminary published data on the efficacy of the Moderna vaccine on 45 trial enrollees, 3 did not receive the second dose of vaccination, including 1 who developed urticaria on both legs 5 days after the first dose.¹

Introduction of viral RNA can induce autoimmunity that can be explained by various phenomena, including epitope spreading, molecular mimicry, cryptic antigen, and bystander activation. Remarkably, more than one-third of immunogenic proteins in SARS-CoV-2 have potentially problematic homology to proteins that are key to the human adaptive immune system.⁵

Moreover, SARS-CoV-2 seems to induce organ injury through alternative mechanisms beyond direct viral infection, including immunologic injury. In some situations, hyperactivation of the immune response to SARS-CoV-2 RNA can result in autoimmune disease. COVID-19 has been associated with immune-mediated systemic or organ-selective manifestations, some of which fulfill the diagnostic or classification criteria of specific autoimmune diseases. It is unclear whether those medical disorders are the result of transitory postinfectious epiphenomena.⁵

A few studies have shown that patients with rheumatic disease have an incidence and prevalence of COVID-19 that is similar to the general population. A similar pattern has been detected in COVID-19 morbidity and mortality rates, even among patients with an autoimmune disease, such as rheumatoid arthritis and Sjögren syndrome.^5,17 Furthermore, exacerbation of preexisting rheumatic symptoms may be due to hyperactivation of antiviral pathways in a person with an autoimmune disease.^17-19 The findings in our patient suggested a direct role for the vaccine in skin manifestations, rather than for reactivation or development of new systemic autoimmune processes, such as systemic lupus erythematosus.

Exacerbation of psoriasis following COVID-19 vaccination has been described²⁰; however, the case patient did not have a history of psoriasis. The mechanism(s) of such exacerbation remain unclear; COVID-19 vaccine–induced helper T cells (T_H17) may play a role.²¹ Other skin manifestations encountered following COVID-19 vaccination include lichen planus, leukocytoclastic vasculitic rash, erythema multiforme–like rash, and pityriasis rosea–like rash.^22-25 The immune mechanisms of these manifestations remain unclear.

The clinical presentation of delayed vaccination reactions can be attributed to the timing of symptoms and, in this case, the immune-mediated background of a psoriasiform reaction. Although adverse reactions to the SARS-CoV-2 mRNA vaccine are rare, more individuals should be studied after vaccination to confirm and better understand this phenomenon.

To the Editor:

The Moderna COVID-19 messenger RNA (mRNA) vaccine was authorized for use on December 18, 2020, with the second dose beginning on January 15, 2021.^1-3 Some individuals who received the Moderna vaccine experienced an intense rash known as “COVID arm,” a harmless but bothersome adverse effect that typically appears within a week and is a localized and transient immunogenic response.⁴ COVID arm differs from most vaccine adverse effects. The rash emerges not immediately but 5 to 9 days after the initial dose—on average, 1 week later. Apart from being itchy, the rash does not appear to be harmful and is not a reason to hesitate getting vaccinated.

Dermatologists and allergists have been studying this adverse effect, which has been formally termed delayed cutaneous hypersensitivity. Of potential clinical consequence is that the efficacy of the mRNA COVID-19 vaccine may be harmed if postvaccination dermal reactions necessitate systemic corticosteroid therapy. Because this vaccine stimulates an immune response as viral RNA integrates in cells secondary to production of the spike protein of the virus, the skin may be affected secondarily and manifestations of any underlying disease may be aggravated.⁵ We report a patient who developed a psoriasiform dermatitis after the first dose of the Moderna vaccine.

A 65-year-old woman presented to her primary care physician because of the severity of psoriasiform dermatitis that developed 5 days after she received the first dose of the Moderna COVID-19 mRNA vaccine. The patient had a medical history of Sjögren syndrome. Her medication history was negative, and her family history was negative for autoimmune disease. Physical examination by primary care revealed an erythematous scaly rash with plaques and papules on the neck and back (Figure 1). The patient presented again to primary care 2 days later with swollen, painful, discolored digits (Figure 2) and a stiff, sore neck.

Laboratory results were positive for anti–Sjögren syndrome–related antigens A and B. A complete blood cell count; comprehensive metabolic panel; erythrocyte sedimentation rate; and assays of rheumatoid factor, C-reactive protein, and anti–cyclic citrullinated peptide were within reference range. A biopsy of a lesion on the back showed psoriasiform dermatitis with confluent parakeratosis and scattered necrotic keratinocytes. There was superficial perivascular inflammation with rare eosinophils (Figure 3).

The patient was treated with a course of systemic corticosteroids. The rash resolved in 1 week. She did not receive the second dose due to the rash.

Two mRNA COVID-19 vaccines—Pfizer BioNTech and Moderna—have been granted emergency use authorization by the US Food and Drug Administration.⁶ The safety profile of the mRNA-1273 vaccine for the median 2-month follow-up showed no safety concerns.³ Minor localized adverse effects (eg, pain, redness, swelling) have been observed more frequently with the vaccines than with placebo. Systemic symptoms, such as fever, fatigue, headache, and muscle and joint pain, also were seen somewhat more often with the vaccines than with placebo; most such effects occurred 24 to 48 hours after vaccination.^3,6,7 The frequency of unsolicited adverse events and serious adverse events reported during the 28-day period after vaccination generally was similar among participants in the vaccine and placebo groups.³

There are 2 types of reactions to COVID-19 vaccination: immediate and delayed. Immediate reactions usually are due to anaphylaxis, requiring prompt recognition and treatment with epinephrine to stop rapid progression of life-threatening symptoms. Delayed reactions include localized reactions, such as urticaria and benign exanthema; serum sickness and serum sickness–like reactions; fever; and rare skin, organ, and neurologic sequelae.^1,6-8

Cutaneous manifestations, present in 16% to 50% of patients with Sjögren syndrome, are considered one of the most common extraglandular presentations of the syndrome. They are classified as nonvascular (eg, xerosis, angular cheilitis, eyelid dermatitis, annular erythema) and vascular (eg, Raynaud phenomenon, vasculitis).^9-11 Our patient did not have any of those findings. She had not taken any medications before the rash appeared, thereby ruling out a drug reaction.

The differential for our patient included post–urinary tract infection immune-reactive arthritis and rash, which is not typical with Escherichia coli infection but is described with infection with Chlamydia species and Salmonella species. Moreover, post–urinary tract infection immune-reactive arthritis and rash appear mostly on the palms and soles. Systemic lupus erythematosus–like rashes have a different histology and appear on sun-exposed areas; our patient’s rash was found mainly on unexposed areas.¹²

Because our patient received the Moderna vaccine 5 days before the rash appeared and later developed swelling of the digits with morning stiffness, a delayed serum sickness–like reaction secondary to COVID-19 vaccination was possible.^3,6

COVID-19 mRNA vaccines developed by Pfizer-BioNTech and Moderna incorporate a lipid-based nanoparticle carrier system that prevents rapid enzymatic degradation of mRNA and facilitates in vivo delivery of mRNA. This lipid-based nanoparticle carrier system is further stabilized by a polyethylene glycol 2000 lipid conjugate that provides a hydrophilic layer, thus prolonging half-life. The presence of lipid polyethylene glycol 2000 in mRNA vaccines has led to concern that this component could be implicated in anaphylaxis.⁶

COVID-19 antigens can give rise to varying clinical manifestations that are directly related to viral tissue damage or are indirectly induced by the antiviral immune response.^13,14 Hyperactivation of the immune system to eradicate COVID-19 may trigger autoimmunity; several immune-mediated disorders have been described in individuals infected with SARS-CoV-2. Dermal manifestations include cutaneous rash and vasculitis.^13-16 Crucial immunologic steps occur during SARS-CoV-2 infection that may link autoimmunity to COVID-19.^13,14 In preliminary published data on the efficacy of the Moderna vaccine on 45 trial enrollees, 3 did not receive the second dose of vaccination, including 1 who developed urticaria on both legs 5 days after the first dose.¹

Introduction of viral RNA can induce autoimmunity that can be explained by various phenomena, including epitope spreading, molecular mimicry, cryptic antigen, and bystander activation. Remarkably, more than one-third of immunogenic proteins in SARS-CoV-2 have potentially problematic homology to proteins that are key to the human adaptive immune system.⁵

Moreover, SARS-CoV-2 seems to induce organ injury through alternative mechanisms beyond direct viral infection, including immunologic injury. In some situations, hyperactivation of the immune response to SARS-CoV-2 RNA can result in autoimmune disease. COVID-19 has been associated with immune-mediated systemic or organ-selective manifestations, some of which fulfill the diagnostic or classification criteria of specific autoimmune diseases. It is unclear whether those medical disorders are the result of transitory postinfectious epiphenomena.⁵

A few studies have shown that patients with rheumatic disease have an incidence and prevalence of COVID-19 that is similar to the general population. A similar pattern has been detected in COVID-19 morbidity and mortality rates, even among patients with an autoimmune disease, such as rheumatoid arthritis and Sjögren syndrome.^5,17 Furthermore, exacerbation of preexisting rheumatic symptoms may be due to hyperactivation of antiviral pathways in a person with an autoimmune disease.^17-19 The findings in our patient suggested a direct role for the vaccine in skin manifestations, rather than for reactivation or development of new systemic autoimmune processes, such as systemic lupus erythematosus.

Exacerbation of psoriasis following COVID-19 vaccination has been described²⁰; however, the case patient did not have a history of psoriasis. The mechanism(s) of such exacerbation remain unclear; COVID-19 vaccine–induced helper T cells (T_H17) may play a role.²¹ Other skin manifestations encountered following COVID-19 vaccination include lichen planus, leukocytoclastic vasculitic rash, erythema multiforme–like rash, and pityriasis rosea–like rash.^22-25 The immune mechanisms of these manifestations remain unclear.

The clinical presentation of delayed vaccination reactions can be attributed to the timing of symptoms and, in this case, the immune-mediated background of a psoriasiform reaction. Although adverse reactions to the SARS-CoV-2 mRNA vaccine are rare, more individuals should be studied after vaccination to confirm and better understand this phenomenon.

Getting COVID-19 a second time doubles a person’s chance of dying and triples the likelihood of being hospitalized in the next 6 months, a new study found.

Vaccination and booster status did not improve survival or hospitalization rates among people who were infected more than once.

“Reinfection with COVID-19 increases the risk of both acute outcomes and long COVID,” study author Ziyad Al-Aly, MD, told Reuters. “This was evident in unvaccinated, vaccinated and boosted people.”

The study was published in the journal Nature Medicine.

Researchers analyzed U.S. Department of Veterans Affairs data, including 443,588 people with a first infection of SARS-CoV-2, 40,947 people who were infected two or more times, and 5.3 million people who had not been infected with coronavirus, whose data served as the control group.

“During the past few months, there’s been an air of invincibility among people who have had COVID-19 or their vaccinations and boosters, and especially among people who have had an infection and also received vaccines; some people started to [refer] to these individuals as having a sort of superimmunity to the virus,” Dr. Al-Aly said in a press release from Washington University in St. Louis. “Without ambiguity, our research showed that getting an infection a second, third or fourth time contributes to additional health risks in the acute phase, meaning the first 30 days after infection, and in the months beyond, meaning the long COVID phase.”

Being infected with COVID-19 more than once also dramatically increased the risk of developing lung problems, heart conditions, or brain conditions. The heightened risks persisted for 6 months.

Researchers said a limitation of their study was that data primarily came from White males.

An expert not involved in the study told Reuters that the Veterans Affairs population does not reflect the general population. Patients at VA health facilities are generally older with more than normal health complications, said John Moore, PhD, a professor of microbiology and immunology at Weill Cornell Medicine, New York.

Dr. Al-Aly encouraged people to be vigilant as they plan for the holiday season, Reuters reported.

“We had started seeing a lot of patients coming to the clinic with an air of invincibility,” he told Reuters. “They wondered, ‘Does getting a reinfection really matter?’ The answer is yes, it absolutely does.”

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

Getting COVID-19 a second time doubles a person’s chance of dying and triples the likelihood of being hospitalized in the next 6 months, a new study found.

Vaccination and booster status did not improve survival or hospitalization rates among people who were infected more than once.

“Reinfection with COVID-19 increases the risk of both acute outcomes and long COVID,” study author Ziyad Al-Aly, MD, told Reuters. “This was evident in unvaccinated, vaccinated and boosted people.”

The study was published in the journal Nature Medicine.

Researchers analyzed U.S. Department of Veterans Affairs data, including 443,588 people with a first infection of SARS-CoV-2, 40,947 people who were infected two or more times, and 5.3 million people who had not been infected with coronavirus, whose data served as the control group.

“During the past few months, there’s been an air of invincibility among people who have had COVID-19 or their vaccinations and boosters, and especially among people who have had an infection and also received vaccines; some people started to [refer] to these individuals as having a sort of superimmunity to the virus,” Dr. Al-Aly said in a press release from Washington University in St. Louis. “Without ambiguity, our research showed that getting an infection a second, third or fourth time contributes to additional health risks in the acute phase, meaning the first 30 days after infection, and in the months beyond, meaning the long COVID phase.”

Being infected with COVID-19 more than once also dramatically increased the risk of developing lung problems, heart conditions, or brain conditions. The heightened risks persisted for 6 months.

Researchers said a limitation of their study was that data primarily came from White males.

An expert not involved in the study told Reuters that the Veterans Affairs population does not reflect the general population. Patients at VA health facilities are generally older with more than normal health complications, said John Moore, PhD, a professor of microbiology and immunology at Weill Cornell Medicine, New York.

Dr. Al-Aly encouraged people to be vigilant as they plan for the holiday season, Reuters reported.

“We had started seeing a lot of patients coming to the clinic with an air of invincibility,” he told Reuters. “They wondered, ‘Does getting a reinfection really matter?’ The answer is yes, it absolutely does.”

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

Getting COVID-19 a second time doubles a person’s chance of dying and triples the likelihood of being hospitalized in the next 6 months, a new study found.

Vaccination and booster status did not improve survival or hospitalization rates among people who were infected more than once.

“Reinfection with COVID-19 increases the risk of both acute outcomes and long COVID,” study author Ziyad Al-Aly, MD, told Reuters. “This was evident in unvaccinated, vaccinated and boosted people.”

The study was published in the journal Nature Medicine.

Researchers analyzed U.S. Department of Veterans Affairs data, including 443,588 people with a first infection of SARS-CoV-2, 40,947 people who were infected two or more times, and 5.3 million people who had not been infected with coronavirus, whose data served as the control group.

“During the past few months, there’s been an air of invincibility among people who have had COVID-19 or their vaccinations and boosters, and especially among people who have had an infection and also received vaccines; some people started to [refer] to these individuals as having a sort of superimmunity to the virus,” Dr. Al-Aly said in a press release from Washington University in St. Louis. “Without ambiguity, our research showed that getting an infection a second, third or fourth time contributes to additional health risks in the acute phase, meaning the first 30 days after infection, and in the months beyond, meaning the long COVID phase.”

Being infected with COVID-19 more than once also dramatically increased the risk of developing lung problems, heart conditions, or brain conditions. The heightened risks persisted for 6 months.

Researchers said a limitation of their study was that data primarily came from White males.

An expert not involved in the study told Reuters that the Veterans Affairs population does not reflect the general population. Patients at VA health facilities are generally older with more than normal health complications, said John Moore, PhD, a professor of microbiology and immunology at Weill Cornell Medicine, New York.

Dr. Al-Aly encouraged people to be vigilant as they plan for the holiday season, Reuters reported.

“We had started seeing a lot of patients coming to the clinic with an air of invincibility,” he told Reuters. “They wondered, ‘Does getting a reinfection really matter?’ The answer is yes, it absolutely does.”

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

In an age of changing climate and emerging global pandemics, the ability of residency programs to prepare for and adapt to potential disasters may be paramount in preserving the training of physicians. The current literature regarding residency program disaster preparedness, which focuses predominantly on hurricanes and COVID-19,^1-8 is lacking in recommendations specific to dermatology residency programs. Likewise, the Accreditation Council for Graduate Medical Education (ACGME) guidelines⁹ do not address dermatology-specific concerns in disaster preparedness or response. Herein, we propose recommendations to mitigate the impact of various types of disasters on dermatology residency programs and their trainees with regard to resident safety and wellness, resident education, and patient care (Table).

Resident Safety and Wellness

Role of the Program Director—The role of the program director is critical, serving as a figure of structure and reassurance.^4,7,10 Once concern of disaster arises, the program director should contact the Designated Institutional Official (DIO) to express concerns about possible disruptions to resident training. The DIO should then contact the ACGME within 10 days to report the disaster and submit a request for emergency (eg, pandemic) or extraordinary circumstances (eg, natural disaster) categorization.^4,9 Program directors should promptly prepare plans for program reconfiguration and resident transfers in alignment with ACGME requirements to maintain evaluation and completion of core competencies of training during disasters.⁹ Program directors should prioritize the safety of trainees during the immediate threat with clear guidelines on sheltering, evacuations, or quarantines; a timeline of program recovery based on communication with residents, faculty, and administration should then be established.^10,11

Communication—Establishing a strong line of communication between program directors and residents is paramount. Collection of emergency noninstitutional contact information, establishment of a centralized website for information dissemination, use of noninstitutional email and proxy servers outside of the location of impact, social media updates, on-site use of 2-way radios, and program-wide conference calls when possible should be strongly considered as part of the disaster response.^2-4,12,13

Resident Accommodations and Mental Health—If training is disrupted, residents should be reassured of continued access to salary, housing, food, or other resources as necessary.^3,4,11 There should be clear contingency plans if residents need to leave the program for extended periods of time due to injury, illness, or personal circumstances. Although relevant in all types of disasters, resident mental health and response to trauma also must be addressed. Access to counseling, morale-building opportunities (eg, resident social events), and screening for depression or posttraumatic stress disorder may help promote well-being among residents following traumatic events.¹⁴

Resident Education

Participation in Disaster Relief—Residents may seek to aid in the disaster response, which may prove challenging in the setting of programs with high patient volume.⁴ In coordination with the ACGME and graduate medical education governing bodies, program directors should consider how residents may fulfill dermatology training requirements in conjunction with disaster relief efforts, such as working in an inpatient setting or providing wound care.¹⁰

Continued Didactic Education—The use of online learning and conference calls for continuing the dermatology curriculum is an efficient means to maintaining resident education when meeting in person poses risks to residents.¹⁵ Projections of microscopy images, clinical photographs, or other instructional materials allow for continued instruction on resident examination, histopathology, and diagnostic skills.

Continued Clinical Training—If the home institution cannot support the operation of dermatology clinics, residents should be guaranteed continued training at other institutions. Agreements with other dermatology programs, community hospitals, or private dermatology practices should be established in advance, with consideration given to the number of residents a program can support, funding transfers, and credentialing requirements.^2,4,5

Prolonged Disruptions—Nonessential departments of medical institutions may cease to function during war or mass casualty disasters, and it may be unsafe to send dermatology residents to other institutions or clinical areas. If the threat is prolonged, programs may need to consider allowing current residents a longer duration of training despite potential overlap with incoming dermatology residents.⁷

Patient Care

Disruptions to Clinic Operations—Regarding threats of violence, dangerous exposures, or natural disasters, there should be clear guidelines on sheltering in the clinical setting or stabilizing patients during a procedure.¹¹ Equipment used by residents such as laptops, microscopes, and treatment devices (eg, lasers) should be stored in weather-safe locations that would not be notably impacted by moisture or structural damage to the clinic building. If electricity or internet access are compromised, paper medical records should be available to residents to continue clinical operations. Electronic health records used by residents should regularly be backed up on remote servers or cloud storage to allow continued access to patient health information if on-site servers are not functional.¹² If disruptions are prolonged, residency program administration should coordinate with the institution to ensure there is adequate supply and storage of medications (eg, lidocaine, botulinum toxin) as well as a continued means of delivering biologic medications to patients and an ability to obtain laboratory or dermatopathology services.

In-Person Appointments vs Telemedicine—There are benefits to both residency training and patient care when physicians are able to perform in-person examinations, biopsies, and in-office treatments.¹⁶ Programs should ensure an adequate supply of personal protective equipment to continue in-office appointments, vaccinations, and medical care if a resident or other members of the team are exposed to an infectious disease.⁷ If in-person appointments are limited or impossible, telemedicine capabilities may still allow residents to meet program requirements.^7,10,15 However, reduced patient volume due to decreased elective visits or procedures may complicate the fulfillment of clinical requirements, which may need to be adjusted in the wake of a disaster.⁷

Use of Immunosuppressive Therapies—Residency programs should address the risks of prescribing immunosuppressive therapies (eg, biologics) during an infectious threat with their residents and encourage trainees to counsel patients on the importance of preventative measures to reduce risks for severe infection.¹⁷

Final Thoughts

Disasters often are unpredictable. Dermatology residency programs will not be immune to the future impacts of climate change, violent threats, or emerging pandemics. Lessons from prior natural disasters and the COVID-19 pandemic have made it clear that program directors need to be adaptable. If they plan proactively, comprehensive disaster preparedness can help to maintain high-quality training of dermatology residents in the face of extraordinary and challenging circumstances, promoting the resiliency and sustainability of graduate medical education.

In an age of changing climate and emerging global pandemics, the ability of residency programs to prepare for and adapt to potential disasters may be paramount in preserving the training of physicians. The current literature regarding residency program disaster preparedness, which focuses predominantly on hurricanes and COVID-19,^1-8 is lacking in recommendations specific to dermatology residency programs. Likewise, the Accreditation Council for Graduate Medical Education (ACGME) guidelines⁹ do not address dermatology-specific concerns in disaster preparedness or response. Herein, we propose recommendations to mitigate the impact of various types of disasters on dermatology residency programs and their trainees with regard to resident safety and wellness, resident education, and patient care (Table).

Resident Safety and Wellness

Role of the Program Director—The role of the program director is critical, serving as a figure of structure and reassurance.^4,7,10 Once concern of disaster arises, the program director should contact the Designated Institutional Official (DIO) to express concerns about possible disruptions to resident training. The DIO should then contact the ACGME within 10 days to report the disaster and submit a request for emergency (eg, pandemic) or extraordinary circumstances (eg, natural disaster) categorization.^4,9 Program directors should promptly prepare plans for program reconfiguration and resident transfers in alignment with ACGME requirements to maintain evaluation and completion of core competencies of training during disasters.⁹ Program directors should prioritize the safety of trainees during the immediate threat with clear guidelines on sheltering, evacuations, or quarantines; a timeline of program recovery based on communication with residents, faculty, and administration should then be established.^10,11

Communication—Establishing a strong line of communication between program directors and residents is paramount. Collection of emergency noninstitutional contact information, establishment of a centralized website for information dissemination, use of noninstitutional email and proxy servers outside of the location of impact, social media updates, on-site use of 2-way radios, and program-wide conference calls when possible should be strongly considered as part of the disaster response.^2-4,12,13

Resident Accommodations and Mental Health—If training is disrupted, residents should be reassured of continued access to salary, housing, food, or other resources as necessary.^3,4,11 There should be clear contingency plans if residents need to leave the program for extended periods of time due to injury, illness, or personal circumstances. Although relevant in all types of disasters, resident mental health and response to trauma also must be addressed. Access to counseling, morale-building opportunities (eg, resident social events), and screening for depression or posttraumatic stress disorder may help promote well-being among residents following traumatic events.¹⁴

Resident Education

Participation in Disaster Relief—Residents may seek to aid in the disaster response, which may prove challenging in the setting of programs with high patient volume.⁴ In coordination with the ACGME and graduate medical education governing bodies, program directors should consider how residents may fulfill dermatology training requirements in conjunction with disaster relief efforts, such as working in an inpatient setting or providing wound care.¹⁰

Continued Didactic Education—The use of online learning and conference calls for continuing the dermatology curriculum is an efficient means to maintaining resident education when meeting in person poses risks to residents.¹⁵ Projections of microscopy images, clinical photographs, or other instructional materials allow for continued instruction on resident examination, histopathology, and diagnostic skills.

Continued Clinical Training—If the home institution cannot support the operation of dermatology clinics, residents should be guaranteed continued training at other institutions. Agreements with other dermatology programs, community hospitals, or private dermatology practices should be established in advance, with consideration given to the number of residents a program can support, funding transfers, and credentialing requirements.^2,4,5

Prolonged Disruptions—Nonessential departments of medical institutions may cease to function during war or mass casualty disasters, and it may be unsafe to send dermatology residents to other institutions or clinical areas. If the threat is prolonged, programs may need to consider allowing current residents a longer duration of training despite potential overlap with incoming dermatology residents.⁷

Patient Care

Disruptions to Clinic Operations—Regarding threats of violence, dangerous exposures, or natural disasters, there should be clear guidelines on sheltering in the clinical setting or stabilizing patients during a procedure.¹¹ Equipment used by residents such as laptops, microscopes, and treatment devices (eg, lasers) should be stored in weather-safe locations that would not be notably impacted by moisture or structural damage to the clinic building. If electricity or internet access are compromised, paper medical records should be available to residents to continue clinical operations. Electronic health records used by residents should regularly be backed up on remote servers or cloud storage to allow continued access to patient health information if on-site servers are not functional.¹² If disruptions are prolonged, residency program administration should coordinate with the institution to ensure there is adequate supply and storage of medications (eg, lidocaine, botulinum toxin) as well as a continued means of delivering biologic medications to patients and an ability to obtain laboratory or dermatopathology services.

In-Person Appointments vs Telemedicine—There are benefits to both residency training and patient care when physicians are able to perform in-person examinations, biopsies, and in-office treatments.¹⁶ Programs should ensure an adequate supply of personal protective equipment to continue in-office appointments, vaccinations, and medical care if a resident or other members of the team are exposed to an infectious disease.⁷ If in-person appointments are limited or impossible, telemedicine capabilities may still allow residents to meet program requirements.^7,10,15 However, reduced patient volume due to decreased elective visits or procedures may complicate the fulfillment of clinical requirements, which may need to be adjusted in the wake of a disaster.⁷

Use of Immunosuppressive Therapies—Residency programs should address the risks of prescribing immunosuppressive therapies (eg, biologics) during an infectious threat with their residents and encourage trainees to counsel patients on the importance of preventative measures to reduce risks for severe infection.¹⁷

Final Thoughts

Disasters often are unpredictable. Dermatology residency programs will not be immune to the future impacts of climate change, violent threats, or emerging pandemics. Lessons from prior natural disasters and the COVID-19 pandemic have made it clear that program directors need to be adaptable. If they plan proactively, comprehensive disaster preparedness can help to maintain high-quality training of dermatology residents in the face of extraordinary and challenging circumstances, promoting the resiliency and sustainability of graduate medical education.

In an age of changing climate and emerging global pandemics, the ability of residency programs to prepare for and adapt to potential disasters may be paramount in preserving the training of physicians. The current literature regarding residency program disaster preparedness, which focuses predominantly on hurricanes and COVID-19,^1-8 is lacking in recommendations specific to dermatology residency programs. Likewise, the Accreditation Council for Graduate Medical Education (ACGME) guidelines⁹ do not address dermatology-specific concerns in disaster preparedness or response. Herein, we propose recommendations to mitigate the impact of various types of disasters on dermatology residency programs and their trainees with regard to resident safety and wellness, resident education, and patient care (Table).

Resident Safety and Wellness

Role of the Program Director—The role of the program director is critical, serving as a figure of structure and reassurance.^4,7,10 Once concern of disaster arises, the program director should contact the Designated Institutional Official (DIO) to express concerns about possible disruptions to resident training. The DIO should then contact the ACGME within 10 days to report the disaster and submit a request for emergency (eg, pandemic) or extraordinary circumstances (eg, natural disaster) categorization.^4,9 Program directors should promptly prepare plans for program reconfiguration and resident transfers in alignment with ACGME requirements to maintain evaluation and completion of core competencies of training during disasters.⁹ Program directors should prioritize the safety of trainees during the immediate threat with clear guidelines on sheltering, evacuations, or quarantines; a timeline of program recovery based on communication with residents, faculty, and administration should then be established.^10,11

Communication—Establishing a strong line of communication between program directors and residents is paramount. Collection of emergency noninstitutional contact information, establishment of a centralized website for information dissemination, use of noninstitutional email and proxy servers outside of the location of impact, social media updates, on-site use of 2-way radios, and program-wide conference calls when possible should be strongly considered as part of the disaster response.^2-4,12,13

Resident Accommodations and Mental Health—If training is disrupted, residents should be reassured of continued access to salary, housing, food, or other resources as necessary.^3,4,11 There should be clear contingency plans if residents need to leave the program for extended periods of time due to injury, illness, or personal circumstances. Although relevant in all types of disasters, resident mental health and response to trauma also must be addressed. Access to counseling, morale-building opportunities (eg, resident social events), and screening for depression or posttraumatic stress disorder may help promote well-being among residents following traumatic events.¹⁴

Resident Education

Participation in Disaster Relief—Residents may seek to aid in the disaster response, which may prove challenging in the setting of programs with high patient volume.⁴ In coordination with the ACGME and graduate medical education governing bodies, program directors should consider how residents may fulfill dermatology training requirements in conjunction with disaster relief efforts, such as working in an inpatient setting or providing wound care.¹⁰

Continued Didactic Education—The use of online learning and conference calls for continuing the dermatology curriculum is an efficient means to maintaining resident education when meeting in person poses risks to residents.¹⁵ Projections of microscopy images, clinical photographs, or other instructional materials allow for continued instruction on resident examination, histopathology, and diagnostic skills.

Continued Clinical Training—If the home institution cannot support the operation of dermatology clinics, residents should be guaranteed continued training at other institutions. Agreements with other dermatology programs, community hospitals, or private dermatology practices should be established in advance, with consideration given to the number of residents a program can support, funding transfers, and credentialing requirements.^2,4,5

Prolonged Disruptions—Nonessential departments of medical institutions may cease to function during war or mass casualty disasters, and it may be unsafe to send dermatology residents to other institutions or clinical areas. If the threat is prolonged, programs may need to consider allowing current residents a longer duration of training despite potential overlap with incoming dermatology residents.⁷

Patient Care

Disruptions to Clinic Operations—Regarding threats of violence, dangerous exposures, or natural disasters, there should be clear guidelines on sheltering in the clinical setting or stabilizing patients during a procedure.¹¹ Equipment used by residents such as laptops, microscopes, and treatment devices (eg, lasers) should be stored in weather-safe locations that would not be notably impacted by moisture or structural damage to the clinic building. If electricity or internet access are compromised, paper medical records should be available to residents to continue clinical operations. Electronic health records used by residents should regularly be backed up on remote servers or cloud storage to allow continued access to patient health information if on-site servers are not functional.¹² If disruptions are prolonged, residency program administration should coordinate with the institution to ensure there is adequate supply and storage of medications (eg, lidocaine, botulinum toxin) as well as a continued means of delivering biologic medications to patients and an ability to obtain laboratory or dermatopathology services.

In-Person Appointments vs Telemedicine—There are benefits to both residency training and patient care when physicians are able to perform in-person examinations, biopsies, and in-office treatments.¹⁶ Programs should ensure an adequate supply of personal protective equipment to continue in-office appointments, vaccinations, and medical care if a resident or other members of the team are exposed to an infectious disease.⁷ If in-person appointments are limited or impossible, telemedicine capabilities may still allow residents to meet program requirements.^7,10,15 However, reduced patient volume due to decreased elective visits or procedures may complicate the fulfillment of clinical requirements, which may need to be adjusted in the wake of a disaster.⁷

Use of Immunosuppressive Therapies—Residency programs should address the risks of prescribing immunosuppressive therapies (eg, biologics) during an infectious threat with their residents and encourage trainees to counsel patients on the importance of preventative measures to reduce risks for severe infection.¹⁷

Final Thoughts

Disasters often are unpredictable. Dermatology residency programs will not be immune to the future impacts of climate change, violent threats, or emerging pandemics. Lessons from prior natural disasters and the COVID-19 pandemic have made it clear that program directors need to be adaptable. If they plan proactively, comprehensive disaster preparedness can help to maintain high-quality training of dermatology residents in the face of extraordinary and challenging circumstances, promoting the resiliency and sustainability of graduate medical education.

The nonsteroidal mineralocorticoid receptor antagonist finerenone (Kerendia) unexpectedly showed that it might protect against incident infective pneumonia and COVID-19. The finding was based on secondary analyses run on more than 13,000 people enrolled in the two pivotal trials for finerenone.

Finerenone was approved by the Food and Drug Administration in 2021 for slowing progressive renal dysfunction and preventing cardiovascular events in adults with type 2 diabetes and chronic kidney disease (CKD).
 

‘Striking reduction in the risk of pneumonia’

The “striking reduction in risk of pneumonia” in a new analysis suggests that “the propagation of pulmonary infection into lobar or bronchial consolidation may be reduced by finerenone,” write Bertram Pitt, MD, and coauthors in a report published on October 26 in JAMA Network Open.

They also suggest that if further studies confirm that finerenone treatment reduces complications from pneumonia and COVID-19, it would have “significant medical implications,” especially because of the limited treatment options now available for complications from COVID-19.

The new analyses used the FIDELITY dataset, a prespecified merging of results from the FIDELIO-DKD and FIGARO-DKD trials, which together enrolled 13,026 people with type 2 diabetes and CKD, as determined on the basis of the patients’ having a urine albumin-to-creatinine ratio of at least 30 mg/g.

The primary outcomes of these trials showed that treatment with finerenone led to significant slowing of the progression of CKD and a significant reduction in the incidence of cardiovascular events, compared with placebo during median follow-up of 3 years.

The new, secondary analyses focused on the 6.0% of participants in whom there was evidence of pneumonia and the 1.6% in whom there was evidence of having COVID-19. Pneumonia was the most common serious adverse event in the two trials, a finding consistent with the documented risk for pneumonia faced by people with CKD.
 

Finerenone linked with a 29% relative reduction in pneumonia

When analyzed by treatment, the incidence of pneumonia was 4.7% among those who received finerenone and 6.7% among those who received placebo. This translated into a significant relative risk reduction of 29% associated with finerenone treatment.

Analysis of COVID-19 adverse events showed a 1.3% incidence among those who received finerenone and a 1.8% incidence among those in the placebo group, which translated into a significant 27% relative risk reduction linked with finerenone treatment.

In contrast, the data showed no reduced incidence of several other respiratory infections among the finerenone recipients, including nasopharyngitis, bronchitis, and influenza. The data also showed no signal that pneumonia or COVID-19 was more severe among the people who did not receive finerenone, nor did finerenone treatment appear to affect pneumonia recovery.
 

Analysis based on adverse events reports

These secondary analyses are far from definitive. The authors relied on pneumonia and COVID-19 being reported as adverse events. Each investigator diagnosed pneumonia at their discretion, and the trials did not specify diagnostic criteria. The authors also acknowledge that testing for COVID-19 was “not widespread” and that one of the two pivotal trials largely ran prior to the onset of the COVID-19 pandemic so that only 6 participants developed COVID-19 symptoms out of more than 5,700 enrolled.

The authors hypothesize that several actions of finerenone might potentially help mediate an effect on pneumonia and COVID-19: improvements in pulmonary inflammation and fibrosis, upregulation of expression of angiotensin converting enzyme 2, and amelioration of right heart pressure and pulmonary congestion. Also, antagonizing the mineralocorticoid receptor on monocytes and macrophages may block macrophage infiltration and accumulation of active macrophages, which can mediate the pulmonary tissue damage caused by COVID-19.

The FIDELIO-DKD and FIGARO-DKD trials and the FIDELITY combined database were sponsored by Bayer, the company that markets finerenone (Kerendia). Dr. Pitt has received personal fees from Bayer and personal fees and stock options from numerous other companies. Several coauthors reported having a financial relationship with Bayer, as well as with other companies.

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

The nonsteroidal mineralocorticoid receptor antagonist finerenone (Kerendia) unexpectedly showed that it might protect against incident infective pneumonia and COVID-19. The finding was based on secondary analyses run on more than 13,000 people enrolled in the two pivotal trials for finerenone.

Finerenone was approved by the Food and Drug Administration in 2021 for slowing progressive renal dysfunction and preventing cardiovascular events in adults with type 2 diabetes and chronic kidney disease (CKD).
 

‘Striking reduction in the risk of pneumonia’

The “striking reduction in risk of pneumonia” in a new analysis suggests that “the propagation of pulmonary infection into lobar or bronchial consolidation may be reduced by finerenone,” write Bertram Pitt, MD, and coauthors in a report published on October 26 in JAMA Network Open.

They also suggest that if further studies confirm that finerenone treatment reduces complications from pneumonia and COVID-19, it would have “significant medical implications,” especially because of the limited treatment options now available for complications from COVID-19.

The new analyses used the FIDELITY dataset, a prespecified merging of results from the FIDELIO-DKD and FIGARO-DKD trials, which together enrolled 13,026 people with type 2 diabetes and CKD, as determined on the basis of the patients’ having a urine albumin-to-creatinine ratio of at least 30 mg/g.

The primary outcomes of these trials showed that treatment with finerenone led to significant slowing of the progression of CKD and a significant reduction in the incidence of cardiovascular events, compared with placebo during median follow-up of 3 years.

The new, secondary analyses focused on the 6.0% of participants in whom there was evidence of pneumonia and the 1.6% in whom there was evidence of having COVID-19. Pneumonia was the most common serious adverse event in the two trials, a finding consistent with the documented risk for pneumonia faced by people with CKD.
 

Finerenone linked with a 29% relative reduction in pneumonia

When analyzed by treatment, the incidence of pneumonia was 4.7% among those who received finerenone and 6.7% among those who received placebo. This translated into a significant relative risk reduction of 29% associated with finerenone treatment.

Analysis of COVID-19 adverse events showed a 1.3% incidence among those who received finerenone and a 1.8% incidence among those in the placebo group, which translated into a significant 27% relative risk reduction linked with finerenone treatment.

In contrast, the data showed no reduced incidence of several other respiratory infections among the finerenone recipients, including nasopharyngitis, bronchitis, and influenza. The data also showed no signal that pneumonia or COVID-19 was more severe among the people who did not receive finerenone, nor did finerenone treatment appear to affect pneumonia recovery.
 

Analysis based on adverse events reports

These secondary analyses are far from definitive. The authors relied on pneumonia and COVID-19 being reported as adverse events. Each investigator diagnosed pneumonia at their discretion, and the trials did not specify diagnostic criteria. The authors also acknowledge that testing for COVID-19 was “not widespread” and that one of the two pivotal trials largely ran prior to the onset of the COVID-19 pandemic so that only 6 participants developed COVID-19 symptoms out of more than 5,700 enrolled.

The authors hypothesize that several actions of finerenone might potentially help mediate an effect on pneumonia and COVID-19: improvements in pulmonary inflammation and fibrosis, upregulation of expression of angiotensin converting enzyme 2, and amelioration of right heart pressure and pulmonary congestion. Also, antagonizing the mineralocorticoid receptor on monocytes and macrophages may block macrophage infiltration and accumulation of active macrophages, which can mediate the pulmonary tissue damage caused by COVID-19.

The FIDELIO-DKD and FIGARO-DKD trials and the FIDELITY combined database were sponsored by Bayer, the company that markets finerenone (Kerendia). Dr. Pitt has received personal fees from Bayer and personal fees and stock options from numerous other companies. Several coauthors reported having a financial relationship with Bayer, as well as with other companies.

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

The nonsteroidal mineralocorticoid receptor antagonist finerenone (Kerendia) unexpectedly showed that it might protect against incident infective pneumonia and COVID-19. The finding was based on secondary analyses run on more than 13,000 people enrolled in the two pivotal trials for finerenone.

Finerenone was approved by the Food and Drug Administration in 2021 for slowing progressive renal dysfunction and preventing cardiovascular events in adults with type 2 diabetes and chronic kidney disease (CKD).
 

‘Striking reduction in the risk of pneumonia’

The “striking reduction in risk of pneumonia” in a new analysis suggests that “the propagation of pulmonary infection into lobar or bronchial consolidation may be reduced by finerenone,” write Bertram Pitt, MD, and coauthors in a report published on October 26 in JAMA Network Open.

They also suggest that if further studies confirm that finerenone treatment reduces complications from pneumonia and COVID-19, it would have “significant medical implications,” especially because of the limited treatment options now available for complications from COVID-19.

The new analyses used the FIDELITY dataset, a prespecified merging of results from the FIDELIO-DKD and FIGARO-DKD trials, which together enrolled 13,026 people with type 2 diabetes and CKD, as determined on the basis of the patients’ having a urine albumin-to-creatinine ratio of at least 30 mg/g.

The primary outcomes of these trials showed that treatment with finerenone led to significant slowing of the progression of CKD and a significant reduction in the incidence of cardiovascular events, compared with placebo during median follow-up of 3 years.

The new, secondary analyses focused on the 6.0% of participants in whom there was evidence of pneumonia and the 1.6% in whom there was evidence of having COVID-19. Pneumonia was the most common serious adverse event in the two trials, a finding consistent with the documented risk for pneumonia faced by people with CKD.
 

Finerenone linked with a 29% relative reduction in pneumonia

When analyzed by treatment, the incidence of pneumonia was 4.7% among those who received finerenone and 6.7% among those who received placebo. This translated into a significant relative risk reduction of 29% associated with finerenone treatment.

Analysis of COVID-19 adverse events showed a 1.3% incidence among those who received finerenone and a 1.8% incidence among those in the placebo group, which translated into a significant 27% relative risk reduction linked with finerenone treatment.

In contrast, the data showed no reduced incidence of several other respiratory infections among the finerenone recipients, including nasopharyngitis, bronchitis, and influenza. The data also showed no signal that pneumonia or COVID-19 was more severe among the people who did not receive finerenone, nor did finerenone treatment appear to affect pneumonia recovery.
 

Analysis based on adverse events reports

These secondary analyses are far from definitive. The authors relied on pneumonia and COVID-19 being reported as adverse events. Each investigator diagnosed pneumonia at their discretion, and the trials did not specify diagnostic criteria. The authors also acknowledge that testing for COVID-19 was “not widespread” and that one of the two pivotal trials largely ran prior to the onset of the COVID-19 pandemic so that only 6 participants developed COVID-19 symptoms out of more than 5,700 enrolled.

The authors hypothesize that several actions of finerenone might potentially help mediate an effect on pneumonia and COVID-19: improvements in pulmonary inflammation and fibrosis, upregulation of expression of angiotensin converting enzyme 2, and amelioration of right heart pressure and pulmonary congestion. Also, antagonizing the mineralocorticoid receptor on monocytes and macrophages may block macrophage infiltration and accumulation of active macrophages, which can mediate the pulmonary tissue damage caused by COVID-19.

The FIDELIO-DKD and FIGARO-DKD trials and the FIDELITY combined database were sponsored by Bayer, the company that markets finerenone (Kerendia). Dr. Pitt has received personal fees from Bayer and personal fees and stock options from numerous other companies. Several coauthors reported having a financial relationship with Bayer, as well as with other companies.

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

To the Editor:

Nail abnormalities associated with SARS-CoV-2 infection that have been reported in the medical literature include nail psoriasis,¹ Beau lines,² onychomadesis,³ heterogeneous red-white discoloration of the nail bed,⁴ transverse orange nail lesions,³ and the red half‐moon nail sign.^3,5 It has been hypothesized that these nail findings may be an indication of microvascular injury to the distal subungual arcade of the digit or may be indicative of a procoagulant state.^5,6 Currently, there is limited knowledge of the effect of COVID-19 vaccines on nail changes. We report a patient who presented with transverse leukonychia (Mees lines) and Beau lines shortly after each dose of the Pfizer-BioNTech COVID-19 messenger RNA vaccine was administered (with a total of 2 doses administered on presentation).

A 64-year-old woman with a history of rheumatoid arthritis presented with peeling of the fingernails and proximal white discoloration of several fingernails of 2 months’ duration. The patient first noticed whitening of the nails 3 weeks after she recevied the first dose of the COVID-19 vaccine. Five days after receiving the second, she presented to the dermatology clinic and exhibited transverse leukonychia in most fingernails (Figure 1).

Six weeks following the second dose of the COVID-19 vaccine, the patient returned to the dermatology clinic with Beau lines on the second and third fingernails on the right hand (Figure 2A). Subtle erythema of the proximal nail folds and distal fingers was observed in both hands. The patient also exhibited mild onychorrhexis of the left thumbnail and mottled red-brown discoloration of the third finger on the left hand (Figure 2B). Splinter hemorrhages and melanonychia of several fingernails also were observed. Our patient denied any known history of infection with SARS-CoV-2, which was confirmed by a negative COVID-19 polymerase chain reaction test result. She also denied fevers, chills, nausea, and vomiting, she and reported feeling generally well in the context of these postvaccination nail changes.

She reported no trauma or worsening of rheumatoid arthritis before or after COVID-19 vaccination. She was seronegative for rheumatoid arthritis and was being treated with hydroxychloroquine for the last year and methotrexate for the last 2 years. After each dose of the vaccine, methotrexate was withheld for 1 week and then resumed.

Subsequent follow-up examinations revealed the migration and resolution of transverse leukonychia and Beau lines. There also was interval improvement of the splinter hemorrhages. At 17 weeks following the second vaccine dose, all transverse leukonychia and Beau lines had resolved (Figure 3). The patient’s melanonychia remained unchanged.

Laboratory evaluations drawn 1 month following the first dose of the COVID-19 vaccine, including comprehensive metabolic panel; erythrocyte sedimentation rate; C-reactive protein; and vitamin B₁₂, ferritin, and iron levels were within reference range. The complete blood cell count only showed a mildly decreased white blood cell count (3.55×10³/µL [reference range, 4.16–9.95×10³/µL]) and mildly elevated mean corpuscular volume (101.9 fL [reference range, 79.3–98.6 fL), both near the patient’s baseline values prior to vaccination.

Documented cutaneous manifestations of SARS‐CoV‐2 infection have included perniolike lesions (known as COVID toes) and vesicular, urticarial, petechial, livedoid, or retiform purpura eruptions. Less frequently, nail findings in patients infected with COVID-19 have been reported, including Beau lines,² onychomadesis,³ transverse leukonychia,^3,7 and the red half‐moon nail sign.^3,5 Single or multiple nails may be affected. Although the pathogenesis of nail manifestations related to COVID-19 remains unclear, complement-mediated microvascular injury and thrombosis as well as the procoagulant state, which have been associated with COVID-19, may offer possible explanations.^5,6 The presence of microvascular abnormalities was observed in a nail fold video capillaroscopy study of the nails of 82 patients with COVID-19, revealing pericapillary edema, capillary ectasia, sludge flow, meandering capillaries and microvascular derangement, and low capillary density.⁸

Our patient exhibited transverse leukonychia of the fingernails, which is thought to result from abnormal keratinization of the nail plate due to systemic disorders that induce a temporary dysfunction of nail growth.⁹ Fernandez-Nieto et al⁷ reported transverse leukonychia in a patient with COVID-19 that was hypothesized to be due to a transitory nail matrix injury.

Beau lines and onychomadesis, which represent nail matrix arrest, commonly are seen with systemic drug treatments such as chemotherapy and in infectious diseases that precipitate systemic illness, such as hand, foot, and mouth disease. Although histologic examination was not performed in our patient due to cosmetic concerns, we believe that inflammation induced by the vaccine response also can trigger nail abnormalities such as transverse leukonychia and Beau lines. Both SARS-CoV-2 infections and the COVID-19 messenger RNA vaccines can induce systemic inflammation largely due a T_H1-dominant response, and they also can trigger other inflammatory conditions. Reports of lichen planus and psoriasis triggered by vaccination—the hepatitis B vaccine,¹⁰ influenza vaccine,¹¹ and even COVID-19 vaccines^1,12—have been reported. Beau lines have been observed to spontaneously resolve in a self-limiting manner in asymptomatic patients with COVID-19.

Interestingly, our patient only showed 2 nails with Beau lines. We hypothesize that the immune response triggered by vaccination was more subdued than that caused by SARS-CoV-2 infection. Additionally, our patient was already being treated with immunosuppressants, which may have been associated with a reduced immune response despite being withheld right before vaccination. One may debate whether the nail abnormalities observed in our patient constituted an isolated finding from COVID-19 vaccination or were caused by reactivation of rheumatoid arthritis. We favor the former, as the rheumatoid arthritis remained stable before and after COVID-19 vaccination. Laboratory evaluations and physical examination revealed no evidence of flares, and our patient was otherwise healthy. Although the splinter hemorrhages also improved, it is difficult to comment as to whether they were caused by the vaccine or had existed prior to vaccination. However, we believe the melanonychia observed in the nails was unrelated to the vaccine and was likely a chronic manifestation due to long-term hydroxychloroquine and/or methotrexate use.

Given accelerated global vaccination efforts to control the COVID-19 pandemic, more cases of adverse nail manifestations associated with COVID-19 vaccines are expected. Dermatologists should be aware of and use the reported nail findings to educate patients and reassure them that ungual abnormalities are potential adverse effects of COVID-19 vaccines, but they should not discourage vaccination because they usually are temporary and self-resolving.

To the Editor:

Nail abnormalities associated with SARS-CoV-2 infection that have been reported in the medical literature include nail psoriasis,¹ Beau lines,² onychomadesis,³ heterogeneous red-white discoloration of the nail bed,⁴ transverse orange nail lesions,³ and the red half‐moon nail sign.^3,5 It has been hypothesized that these nail findings may be an indication of microvascular injury to the distal subungual arcade of the digit or may be indicative of a procoagulant state.^5,6 Currently, there is limited knowledge of the effect of COVID-19 vaccines on nail changes. We report a patient who presented with transverse leukonychia (Mees lines) and Beau lines shortly after each dose of the Pfizer-BioNTech COVID-19 messenger RNA vaccine was administered (with a total of 2 doses administered on presentation).

A 64-year-old woman with a history of rheumatoid arthritis presented with peeling of the fingernails and proximal white discoloration of several fingernails of 2 months’ duration. The patient first noticed whitening of the nails 3 weeks after she recevied the first dose of the COVID-19 vaccine. Five days after receiving the second, she presented to the dermatology clinic and exhibited transverse leukonychia in most fingernails (Figure 1).

Six weeks following the second dose of the COVID-19 vaccine, the patient returned to the dermatology clinic with Beau lines on the second and third fingernails on the right hand (Figure 2A). Subtle erythema of the proximal nail folds and distal fingers was observed in both hands. The patient also exhibited mild onychorrhexis of the left thumbnail and mottled red-brown discoloration of the third finger on the left hand (Figure 2B). Splinter hemorrhages and melanonychia of several fingernails also were observed. Our patient denied any known history of infection with SARS-CoV-2, which was confirmed by a negative COVID-19 polymerase chain reaction test result. She also denied fevers, chills, nausea, and vomiting, she and reported feeling generally well in the context of these postvaccination nail changes.

She reported no trauma or worsening of rheumatoid arthritis before or after COVID-19 vaccination. She was seronegative for rheumatoid arthritis and was being treated with hydroxychloroquine for the last year and methotrexate for the last 2 years. After each dose of the vaccine, methotrexate was withheld for 1 week and then resumed.

Subsequent follow-up examinations revealed the migration and resolution of transverse leukonychia and Beau lines. There also was interval improvement of the splinter hemorrhages. At 17 weeks following the second vaccine dose, all transverse leukonychia and Beau lines had resolved (Figure 3). The patient’s melanonychia remained unchanged.

Laboratory evaluations drawn 1 month following the first dose of the COVID-19 vaccine, including comprehensive metabolic panel; erythrocyte sedimentation rate; C-reactive protein; and vitamin B₁₂, ferritin, and iron levels were within reference range. The complete blood cell count only showed a mildly decreased white blood cell count (3.55×10³/µL [reference range, 4.16–9.95×10³/µL]) and mildly elevated mean corpuscular volume (101.9 fL [reference range, 79.3–98.6 fL), both near the patient’s baseline values prior to vaccination.

Documented cutaneous manifestations of SARS‐CoV‐2 infection have included perniolike lesions (known as COVID toes) and vesicular, urticarial, petechial, livedoid, or retiform purpura eruptions. Less frequently, nail findings in patients infected with COVID-19 have been reported, including Beau lines,² onychomadesis,³ transverse leukonychia,^3,7 and the red half‐moon nail sign.^3,5 Single or multiple nails may be affected. Although the pathogenesis of nail manifestations related to COVID-19 remains unclear, complement-mediated microvascular injury and thrombosis as well as the procoagulant state, which have been associated with COVID-19, may offer possible explanations.^5,6 The presence of microvascular abnormalities was observed in a nail fold video capillaroscopy study of the nails of 82 patients with COVID-19, revealing pericapillary edema, capillary ectasia, sludge flow, meandering capillaries and microvascular derangement, and low capillary density.⁸

Our patient exhibited transverse leukonychia of the fingernails, which is thought to result from abnormal keratinization of the nail plate due to systemic disorders that induce a temporary dysfunction of nail growth.⁹ Fernandez-Nieto et al⁷ reported transverse leukonychia in a patient with COVID-19 that was hypothesized to be due to a transitory nail matrix injury.

Beau lines and onychomadesis, which represent nail matrix arrest, commonly are seen with systemic drug treatments such as chemotherapy and in infectious diseases that precipitate systemic illness, such as hand, foot, and mouth disease. Although histologic examination was not performed in our patient due to cosmetic concerns, we believe that inflammation induced by the vaccine response also can trigger nail abnormalities such as transverse leukonychia and Beau lines. Both SARS-CoV-2 infections and the COVID-19 messenger RNA vaccines can induce systemic inflammation largely due a T_H1-dominant response, and they also can trigger other inflammatory conditions. Reports of lichen planus and psoriasis triggered by vaccination—the hepatitis B vaccine,¹⁰ influenza vaccine,¹¹ and even COVID-19 vaccines^1,12—have been reported. Beau lines have been observed to spontaneously resolve in a self-limiting manner in asymptomatic patients with COVID-19.

Interestingly, our patient only showed 2 nails with Beau lines. We hypothesize that the immune response triggered by vaccination was more subdued than that caused by SARS-CoV-2 infection. Additionally, our patient was already being treated with immunosuppressants, which may have been associated with a reduced immune response despite being withheld right before vaccination. One may debate whether the nail abnormalities observed in our patient constituted an isolated finding from COVID-19 vaccination or were caused by reactivation of rheumatoid arthritis. We favor the former, as the rheumatoid arthritis remained stable before and after COVID-19 vaccination. Laboratory evaluations and physical examination revealed no evidence of flares, and our patient was otherwise healthy. Although the splinter hemorrhages also improved, it is difficult to comment as to whether they were caused by the vaccine or had existed prior to vaccination. However, we believe the melanonychia observed in the nails was unrelated to the vaccine and was likely a chronic manifestation due to long-term hydroxychloroquine and/or methotrexate use.

Given accelerated global vaccination efforts to control the COVID-19 pandemic, more cases of adverse nail manifestations associated with COVID-19 vaccines are expected. Dermatologists should be aware of and use the reported nail findings to educate patients and reassure them that ungual abnormalities are potential adverse effects of COVID-19 vaccines, but they should not discourage vaccination because they usually are temporary and self-resolving.

To the Editor:

Nail abnormalities associated with SARS-CoV-2 infection that have been reported in the medical literature include nail psoriasis,¹ Beau lines,² onychomadesis,³ heterogeneous red-white discoloration of the nail bed,⁴ transverse orange nail lesions,³ and the red half‐moon nail sign.^3,5 It has been hypothesized that these nail findings may be an indication of microvascular injury to the distal subungual arcade of the digit or may be indicative of a procoagulant state.^5,6 Currently, there is limited knowledge of the effect of COVID-19 vaccines on nail changes. We report a patient who presented with transverse leukonychia (Mees lines) and Beau lines shortly after each dose of the Pfizer-BioNTech COVID-19 messenger RNA vaccine was administered (with a total of 2 doses administered on presentation).

A 64-year-old woman with a history of rheumatoid arthritis presented with peeling of the fingernails and proximal white discoloration of several fingernails of 2 months’ duration. The patient first noticed whitening of the nails 3 weeks after she recevied the first dose of the COVID-19 vaccine. Five days after receiving the second, she presented to the dermatology clinic and exhibited transverse leukonychia in most fingernails (Figure 1).

Six weeks following the second dose of the COVID-19 vaccine, the patient returned to the dermatology clinic with Beau lines on the second and third fingernails on the right hand (Figure 2A). Subtle erythema of the proximal nail folds and distal fingers was observed in both hands. The patient also exhibited mild onychorrhexis of the left thumbnail and mottled red-brown discoloration of the third finger on the left hand (Figure 2B). Splinter hemorrhages and melanonychia of several fingernails also were observed. Our patient denied any known history of infection with SARS-CoV-2, which was confirmed by a negative COVID-19 polymerase chain reaction test result. She also denied fevers, chills, nausea, and vomiting, she and reported feeling generally well in the context of these postvaccination nail changes.

She reported no trauma or worsening of rheumatoid arthritis before or after COVID-19 vaccination. She was seronegative for rheumatoid arthritis and was being treated with hydroxychloroquine for the last year and methotrexate for the last 2 years. After each dose of the vaccine, methotrexate was withheld for 1 week and then resumed.

Subsequent follow-up examinations revealed the migration and resolution of transverse leukonychia and Beau lines. There also was interval improvement of the splinter hemorrhages. At 17 weeks following the second vaccine dose, all transverse leukonychia and Beau lines had resolved (Figure 3). The patient’s melanonychia remained unchanged.

Laboratory evaluations drawn 1 month following the first dose of the COVID-19 vaccine, including comprehensive metabolic panel; erythrocyte sedimentation rate; C-reactive protein; and vitamin B₁₂, ferritin, and iron levels were within reference range. The complete blood cell count only showed a mildly decreased white blood cell count (3.55×10³/µL [reference range, 4.16–9.95×10³/µL]) and mildly elevated mean corpuscular volume (101.9 fL [reference range, 79.3–98.6 fL), both near the patient’s baseline values prior to vaccination.

Documented cutaneous manifestations of SARS‐CoV‐2 infection have included perniolike lesions (known as COVID toes) and vesicular, urticarial, petechial, livedoid, or retiform purpura eruptions. Less frequently, nail findings in patients infected with COVID-19 have been reported, including Beau lines,² onychomadesis,³ transverse leukonychia,^3,7 and the red half‐moon nail sign.^3,5 Single or multiple nails may be affected. Although the pathogenesis of nail manifestations related to COVID-19 remains unclear, complement-mediated microvascular injury and thrombosis as well as the procoagulant state, which have been associated with COVID-19, may offer possible explanations.^5,6 The presence of microvascular abnormalities was observed in a nail fold video capillaroscopy study of the nails of 82 patients with COVID-19, revealing pericapillary edema, capillary ectasia, sludge flow, meandering capillaries and microvascular derangement, and low capillary density.⁸

Our patient exhibited transverse leukonychia of the fingernails, which is thought to result from abnormal keratinization of the nail plate due to systemic disorders that induce a temporary dysfunction of nail growth.⁹ Fernandez-Nieto et al⁷ reported transverse leukonychia in a patient with COVID-19 that was hypothesized to be due to a transitory nail matrix injury.

Beau lines and onychomadesis, which represent nail matrix arrest, commonly are seen with systemic drug treatments such as chemotherapy and in infectious diseases that precipitate systemic illness, such as hand, foot, and mouth disease. Although histologic examination was not performed in our patient due to cosmetic concerns, we believe that inflammation induced by the vaccine response also can trigger nail abnormalities such as transverse leukonychia and Beau lines. Both SARS-CoV-2 infections and the COVID-19 messenger RNA vaccines can induce systemic inflammation largely due a T_H1-dominant response, and they also can trigger other inflammatory conditions. Reports of lichen planus and psoriasis triggered by vaccination—the hepatitis B vaccine,¹⁰ influenza vaccine,¹¹ and even COVID-19 vaccines^1,12—have been reported. Beau lines have been observed to spontaneously resolve in a self-limiting manner in asymptomatic patients with COVID-19.

Interestingly, our patient only showed 2 nails with Beau lines. We hypothesize that the immune response triggered by vaccination was more subdued than that caused by SARS-CoV-2 infection. Additionally, our patient was already being treated with immunosuppressants, which may have been associated with a reduced immune response despite being withheld right before vaccination. One may debate whether the nail abnormalities observed in our patient constituted an isolated finding from COVID-19 vaccination or were caused by reactivation of rheumatoid arthritis. We favor the former, as the rheumatoid arthritis remained stable before and after COVID-19 vaccination. Laboratory evaluations and physical examination revealed no evidence of flares, and our patient was otherwise healthy. Although the splinter hemorrhages also improved, it is difficult to comment as to whether they were caused by the vaccine or had existed prior to vaccination. However, we believe the melanonychia observed in the nails was unrelated to the vaccine and was likely a chronic manifestation due to long-term hydroxychloroquine and/or methotrexate use.

Given accelerated global vaccination efforts to control the COVID-19 pandemic, more cases of adverse nail manifestations associated with COVID-19 vaccines are expected. Dermatologists should be aware of and use the reported nail findings to educate patients and reassure them that ungual abnormalities are potential adverse effects of COVID-19 vaccines, but they should not discourage vaccination because they usually are temporary and self-resolving.

New York City veterinarian Erin Kulick used to be a weekend warrior. Only 2½ years ago, the 38-year-old new mother played ultimate Frisbee and flag football with friends. She went for regular 30-minute runs to burn off stress.

Now, Dr. Kulick is usually so exhausted, she can’t walk nonstop for 15 minutes. She recently tried to take her 4-year-old son, Cooper, to the American Museum of Natural History for his first visit, but ended up on a bench outside the museum, sobbing in the rain, because she couldn’t even get through the first hurdle of standing in line. “I just wanted to be there with my kid,” she said.

Dr. Kulick got sick with COVID-19 at the start of the pandemic in March 2020, 9 months before the first vaccine would be approved. Now she is among the estimated one in five infected Americans, or 19%, whose symptoms developed into long COVID.

Dr. Kulick also is now vaccinated and boosted. Had a vaccine been available sooner, could it have protected her from long COVID?

Evidence is starting to show it’s likely.

“The best way not to have long COVID is not to have COVID at all,” said Leora Horwitz, MD, a professor of population health and medicine at New York University. “To the extent that vaccination can prevent you from getting COVID at all, then it helps to reduce long COVID.”

And just as vaccines reduce the risk of severe disease, hospitalization, and death, they also seem to reduce the risk of long COVID if people do get breakthrough infections. People with more serious initial illness appear more likely to have prolonged symptoms, but those with milder disease can certainly get it, too.

“You’re more likely to have long COVID with more severe disease, and we have ample evidence that vaccination reduces the severity of disease,” Dr. Horwitz said. “We also now have quite a lot of evidence that vaccination does reduce your risk of long COVID – probably because it reduces your risk of severe disease.”

There is little consensus about how much vaccines can lower the risk of long-term COVID symptoms, but several studies suggest that number lies anywhere from 15% to more than 80%.

That might seem like a big variation, but infectious disease experts argue that trying to interpret the gap isn’t as important as noticing what’s consistent across all these studies: “Vaccines do offer some protection, but it’s incomplete,” said Ziyad Al-Aly, MD, chief of research and development at the Veterans Affairs St. Louis Health Care System. Dr. Al-Aly, who has led several large studies on long COVID, said focusing on the fact that vaccines do offer some protection is a much better public health message than looking at the different levels of risk.

“Vaccines do a miraculous job for what they were designed to do,” said Dr. Al-Aly. “Vaccines were designed to reduce the risk of hospitalization ... and for that, vaccines are still holding up, even with all the changes in the virus.”

Still, Elena Azzolini, MD, PhD, head of the Humanitas Research Hospital’s vaccination center in Milan, thinks some studies may have underestimated the level of long COVID protection from vaccines because of limits in the study methods, such as not including enough women, who are more affected by long COVID. Her recent study, which looked at 2,560 health care professionals working in nine Italian centers from March 2020 to April 2022, focused on the risk for healthy women and men in their 20s to their 70s.

In the paper, Dr. Azzolini and associates reported that two or three doses of vaccine reduced the risk of hospitalization from COVID-19 from 42% among those who are unvaccinated to 16%-17%. In other words, they found unvaccinated people in the study were nearly three times as likely to have serious symptoms for longer than 4 weeks.

But Dr. Azzolini and Dr. Al-Aly still say that, even for the vaccinated, as long as COVID is around, masks are necessary. That’s because current vaccines don’t do enough to reduce transmission, said Dr. Al-Aly. “The only way that can really help [stop] transmission is covering our nose and mouth with a mask.”
 

How vaccinations affect people who already have long COVID

Some long COVID patients have said they got better after they get boosted, while some say they’re getting worse, said Dr. Horwitz, who is also a lead investigator at the National Institutes of Health’s flagship RECOVER program, a 4-year research project to study long COVID across the United States. (The NIH is still recruiting volunteers for these studies, which are also open to people who have never had COVID.)

One study published in the British Medical Journal analyzed survey data of more than 28,000 people infected with COVID in the United Kingdom and found a 13% reduction in long-term symptoms after a first dose of the vaccine, although it was unclear from the data if the improvement was sustained.

A second dose was associated with another 8% improvement over a 2-month period. “It’s reassuring that we see an average modest improvement in symptoms, not an average worsening in symptoms,” said Daniel Ayoubkhani, principal statistician at the U.K. Office for National Statistics and lead author of the study. Of course, the experience will differ among different people.

“It doesn’t appear that vaccination is the silver bullet that’s going to eradicate long COVID,” he said, but evidence from multiple studies suggests vaccines may help people with long-term symptoms.

Akiko Iwasaki, PhD, an immunobiologist at Yale University, New Haven, Conn., told a White House summit in July that one of the best ways to prevent long COVID is to develop the next generation of vaccines that also prevent milder cases by blocking transmission in the first place.

Back in New York, Dr. Kulick is now triple vaccinated. She’s due for a fourth dose soon but admits she’s “terrified every time” that she’s going to get sicker.

In her Facebook support group for long COVID, she reads that most people with prolonged symptoms handle it well. She has also noticed some of her symptoms eased after her first two doses of vaccine.

Since being diagnosed, Dr. Kulick learned she has a genetic condition, Ehlers-Danlos syndrome, which affects connective tissues that support skin, joints, organs, and blood vessels, and which her doctors say may have made her more prone to long COVID. She’s also being screened for autoimmune diseases, but for now, the only relief she has found has come from long COVID physical therapy, changes to her diet, and integrative medicine.

Dr. Kulick is still trying to figure out how she can get better while keeping her long hours at her veterinary job – and her health benefits. She is thankful her husband is a devoted caregiver to their son and a professional jazz musician with a schedule that allows for some flexibility.

“But it’s really hard when every week feels like I’ve run a marathon,” she said. “I can barely make it through.”

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

New York City veterinarian Erin Kulick used to be a weekend warrior. Only 2½ years ago, the 38-year-old new mother played ultimate Frisbee and flag football with friends. She went for regular 30-minute runs to burn off stress.

Now, Dr. Kulick is usually so exhausted, she can’t walk nonstop for 15 minutes. She recently tried to take her 4-year-old son, Cooper, to the American Museum of Natural History for his first visit, but ended up on a bench outside the museum, sobbing in the rain, because she couldn’t even get through the first hurdle of standing in line. “I just wanted to be there with my kid,” she said.

Dr. Kulick got sick with COVID-19 at the start of the pandemic in March 2020, 9 months before the first vaccine would be approved. Now she is among the estimated one in five infected Americans, or 19%, whose symptoms developed into long COVID.

Dr. Kulick also is now vaccinated and boosted. Had a vaccine been available sooner, could it have protected her from long COVID?

Evidence is starting to show it’s likely.

“The best way not to have long COVID is not to have COVID at all,” said Leora Horwitz, MD, a professor of population health and medicine at New York University. “To the extent that vaccination can prevent you from getting COVID at all, then it helps to reduce long COVID.”

And just as vaccines reduce the risk of severe disease, hospitalization, and death, they also seem to reduce the risk of long COVID if people do get breakthrough infections. People with more serious initial illness appear more likely to have prolonged symptoms, but those with milder disease can certainly get it, too.

“You’re more likely to have long COVID with more severe disease, and we have ample evidence that vaccination reduces the severity of disease,” Dr. Horwitz said. “We also now have quite a lot of evidence that vaccination does reduce your risk of long COVID – probably because it reduces your risk of severe disease.”

There is little consensus about how much vaccines can lower the risk of long-term COVID symptoms, but several studies suggest that number lies anywhere from 15% to more than 80%.

That might seem like a big variation, but infectious disease experts argue that trying to interpret the gap isn’t as important as noticing what’s consistent across all these studies: “Vaccines do offer some protection, but it’s incomplete,” said Ziyad Al-Aly, MD, chief of research and development at the Veterans Affairs St. Louis Health Care System. Dr. Al-Aly, who has led several large studies on long COVID, said focusing on the fact that vaccines do offer some protection is a much better public health message than looking at the different levels of risk.

“Vaccines do a miraculous job for what they were designed to do,” said Dr. Al-Aly. “Vaccines were designed to reduce the risk of hospitalization ... and for that, vaccines are still holding up, even with all the changes in the virus.”

Still, Elena Azzolini, MD, PhD, head of the Humanitas Research Hospital’s vaccination center in Milan, thinks some studies may have underestimated the level of long COVID protection from vaccines because of limits in the study methods, such as not including enough women, who are more affected by long COVID. Her recent study, which looked at 2,560 health care professionals working in nine Italian centers from March 2020 to April 2022, focused on the risk for healthy women and men in their 20s to their 70s.

In the paper, Dr. Azzolini and associates reported that two or three doses of vaccine reduced the risk of hospitalization from COVID-19 from 42% among those who are unvaccinated to 16%-17%. In other words, they found unvaccinated people in the study were nearly three times as likely to have serious symptoms for longer than 4 weeks.

But Dr. Azzolini and Dr. Al-Aly still say that, even for the vaccinated, as long as COVID is around, masks are necessary. That’s because current vaccines don’t do enough to reduce transmission, said Dr. Al-Aly. “The only way that can really help [stop] transmission is covering our nose and mouth with a mask.”
 

How vaccinations affect people who already have long COVID

Some long COVID patients have said they got better after they get boosted, while some say they’re getting worse, said Dr. Horwitz, who is also a lead investigator at the National Institutes of Health’s flagship RECOVER program, a 4-year research project to study long COVID across the United States. (The NIH is still recruiting volunteers for these studies, which are also open to people who have never had COVID.)

One study published in the British Medical Journal analyzed survey data of more than 28,000 people infected with COVID in the United Kingdom and found a 13% reduction in long-term symptoms after a first dose of the vaccine, although it was unclear from the data if the improvement was sustained.

A second dose was associated with another 8% improvement over a 2-month period. “It’s reassuring that we see an average modest improvement in symptoms, not an average worsening in symptoms,” said Daniel Ayoubkhani, principal statistician at the U.K. Office for National Statistics and lead author of the study. Of course, the experience will differ among different people.

“It doesn’t appear that vaccination is the silver bullet that’s going to eradicate long COVID,” he said, but evidence from multiple studies suggests vaccines may help people with long-term symptoms.

Akiko Iwasaki, PhD, an immunobiologist at Yale University, New Haven, Conn., told a White House summit in July that one of the best ways to prevent long COVID is to develop the next generation of vaccines that also prevent milder cases by blocking transmission in the first place.

Back in New York, Dr. Kulick is now triple vaccinated. She’s due for a fourth dose soon but admits she’s “terrified every time” that she’s going to get sicker.

In her Facebook support group for long COVID, she reads that most people with prolonged symptoms handle it well. She has also noticed some of her symptoms eased after her first two doses of vaccine.

Since being diagnosed, Dr. Kulick learned she has a genetic condition, Ehlers-Danlos syndrome, which affects connective tissues that support skin, joints, organs, and blood vessels, and which her doctors say may have made her more prone to long COVID. She’s also being screened for autoimmune diseases, but for now, the only relief she has found has come from long COVID physical therapy, changes to her diet, and integrative medicine.

Dr. Kulick is still trying to figure out how she can get better while keeping her long hours at her veterinary job – and her health benefits. She is thankful her husband is a devoted caregiver to their son and a professional jazz musician with a schedule that allows for some flexibility.

“But it’s really hard when every week feels like I’ve run a marathon,” she said. “I can barely make it through.”

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

New York City veterinarian Erin Kulick used to be a weekend warrior. Only 2½ years ago, the 38-year-old new mother played ultimate Frisbee and flag football with friends. She went for regular 30-minute runs to burn off stress.

Now, Dr. Kulick is usually so exhausted, she can’t walk nonstop for 15 minutes. She recently tried to take her 4-year-old son, Cooper, to the American Museum of Natural History for his first visit, but ended up on a bench outside the museum, sobbing in the rain, because she couldn’t even get through the first hurdle of standing in line. “I just wanted to be there with my kid,” she said.

Dr. Kulick got sick with COVID-19 at the start of the pandemic in March 2020, 9 months before the first vaccine would be approved. Now she is among the estimated one in five infected Americans, or 19%, whose symptoms developed into long COVID.

Dr. Kulick also is now vaccinated and boosted. Had a vaccine been available sooner, could it have protected her from long COVID?

Evidence is starting to show it’s likely.

“The best way not to have long COVID is not to have COVID at all,” said Leora Horwitz, MD, a professor of population health and medicine at New York University. “To the extent that vaccination can prevent you from getting COVID at all, then it helps to reduce long COVID.”

And just as vaccines reduce the risk of severe disease, hospitalization, and death, they also seem to reduce the risk of long COVID if people do get breakthrough infections. People with more serious initial illness appear more likely to have prolonged symptoms, but those with milder disease can certainly get it, too.

“You’re more likely to have long COVID with more severe disease, and we have ample evidence that vaccination reduces the severity of disease,” Dr. Horwitz said. “We also now have quite a lot of evidence that vaccination does reduce your risk of long COVID – probably because it reduces your risk of severe disease.”

There is little consensus about how much vaccines can lower the risk of long-term COVID symptoms, but several studies suggest that number lies anywhere from 15% to more than 80%.

That might seem like a big variation, but infectious disease experts argue that trying to interpret the gap isn’t as important as noticing what’s consistent across all these studies: “Vaccines do offer some protection, but it’s incomplete,” said Ziyad Al-Aly, MD, chief of research and development at the Veterans Affairs St. Louis Health Care System. Dr. Al-Aly, who has led several large studies on long COVID, said focusing on the fact that vaccines do offer some protection is a much better public health message than looking at the different levels of risk.

“Vaccines do a miraculous job for what they were designed to do,” said Dr. Al-Aly. “Vaccines were designed to reduce the risk of hospitalization ... and for that, vaccines are still holding up, even with all the changes in the virus.”

Still, Elena Azzolini, MD, PhD, head of the Humanitas Research Hospital’s vaccination center in Milan, thinks some studies may have underestimated the level of long COVID protection from vaccines because of limits in the study methods, such as not including enough women, who are more affected by long COVID. Her recent study, which looked at 2,560 health care professionals working in nine Italian centers from March 2020 to April 2022, focused on the risk for healthy women and men in their 20s to their 70s.

In the paper, Dr. Azzolini and associates reported that two or three doses of vaccine reduced the risk of hospitalization from COVID-19 from 42% among those who are unvaccinated to 16%-17%. In other words, they found unvaccinated people in the study were nearly three times as likely to have serious symptoms for longer than 4 weeks.

But Dr. Azzolini and Dr. Al-Aly still say that, even for the vaccinated, as long as COVID is around, masks are necessary. That’s because current vaccines don’t do enough to reduce transmission, said Dr. Al-Aly. “The only way that can really help [stop] transmission is covering our nose and mouth with a mask.”
 

How vaccinations affect people who already have long COVID

Some long COVID patients have said they got better after they get boosted, while some say they’re getting worse, said Dr. Horwitz, who is also a lead investigator at the National Institutes of Health’s flagship RECOVER program, a 4-year research project to study long COVID across the United States. (The NIH is still recruiting volunteers for these studies, which are also open to people who have never had COVID.)

One study published in the British Medical Journal analyzed survey data of more than 28,000 people infected with COVID in the United Kingdom and found a 13% reduction in long-term symptoms after a first dose of the vaccine, although it was unclear from the data if the improvement was sustained.

A second dose was associated with another 8% improvement over a 2-month period. “It’s reassuring that we see an average modest improvement in symptoms, not an average worsening in symptoms,” said Daniel Ayoubkhani, principal statistician at the U.K. Office for National Statistics and lead author of the study. Of course, the experience will differ among different people.

“It doesn’t appear that vaccination is the silver bullet that’s going to eradicate long COVID,” he said, but evidence from multiple studies suggests vaccines may help people with long-term symptoms.

Akiko Iwasaki, PhD, an immunobiologist at Yale University, New Haven, Conn., told a White House summit in July that one of the best ways to prevent long COVID is to develop the next generation of vaccines that also prevent milder cases by blocking transmission in the first place.

Back in New York, Dr. Kulick is now triple vaccinated. She’s due for a fourth dose soon but admits she’s “terrified every time” that she’s going to get sicker.

In her Facebook support group for long COVID, she reads that most people with prolonged symptoms handle it well. She has also noticed some of her symptoms eased after her first two doses of vaccine.

Since being diagnosed, Dr. Kulick learned she has a genetic condition, Ehlers-Danlos syndrome, which affects connective tissues that support skin, joints, organs, and blood vessels, and which her doctors say may have made her more prone to long COVID. She’s also being screened for autoimmune diseases, but for now, the only relief she has found has come from long COVID physical therapy, changes to her diet, and integrative medicine.

Dr. Kulick is still trying to figure out how she can get better while keeping her long hours at her veterinary job – and her health benefits. She is thankful her husband is a devoted caregiver to their son and a professional jazz musician with a schedule that allows for some flexibility.

“But it’s really hard when every week feels like I’ve run a marathon,” she said. “I can barely make it through.”

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

One in eight adults (12.7%) diagnosed with COVID-19 will likely experience long-term symptoms, a large study published in The Lancet indicates.

The researchers determined that percentage by comparing long-term symptoms in people infected by SARS-CoV-2 with similar symptoms in uninfected people over the same time period.

Among the group of infected study participants in the Netherlands, 21.4% had at least one new or severely increased symptom 3-5 months after infection compared with before infection. When that group of 21.4% was compared with 8.7% of uninfected people in the same study, the researchers were able to calculate a prevalence 12.7% with long COVID.

“This finding shows that post–COVID-19 condition is an urgent problem with a mounting human toll,” the study authors wrote.

The research design was novel, two editorialists said in an accompanying commentary.

Christopher Brightling, PhD, and Rachael Evans, MBChB, PhD, of the Institute for Lung Health, University of Leicester (England), noted: “This is a major advance on prior long COVID prevalence estimates as it includes a matched uninfected group and accounts for symptoms before COVID-19 infection.”
 

Symptoms that persist

The Lancet study found that 3-5 months after COVID (compared with before COVID) and compared with the non-COVID comparison group, the symptoms that persist were chest pain, breathing difficulties, pain when breathing, muscle pain, loss of taste and/or smell, tingling extremities, lump in throat, feeling hot and cold alternately, heavy limbs, and tiredness.

The authors noted that symptoms such as brain fog were found to be relevant to long COVID after the data collection period for this paper and were not included in this research.

Researcher Aranka V. Ballering, MSc, PhD candidate, said in an interview that the researchers found fever is a symptom that is clearly present during the acute phase of the disease and it peaks the day of the COVID-19 diagnosis, but also wears off.

Loss of taste and smell, however, rapidly increases in severity when COVID-19 is diagnosed, but also persists and is still present 3-5 months after COVID.

Ms. Ballering, with the department of psychiatry at the University of Groningen (the Netherlands), said she was surprised by the sex difference made evident in their research: “Women showed more severe persistent symptoms than men.”
 

Closer to a clearer definition

The authors said their findings also pinpoint symptoms that bring us closer to a better definition of long COVID, which has many different definitions globally.

“These symptoms have the highest discriminative ability to distinguish between post–COVID-19 condition and non–COVID-19–related symptoms,” they wrote.

Researchers collected data by asking participants in the northern Netherlands, who were part of the population-based Lifelines COVID-19 study, to regularly complete digital questionnaires on 23 symptoms commonly associated with long COVID. The questionnaire was sent out 24 times to the same people between March 2020 and August 2021. At that time, people had the Alpha or earlier variants.

Participants were considered COVID-19 positive if they had either a positive test or a doctor’s diagnosis of COVID-19.

Of 76,422 study participants, the 5.5% (4,231) who had COVID were matched to 8,462 controls. Researchers accounted for sex, age, and time of completing questionnaires.
 

Effect of hospitalization, vaccination unclear

Ms. Ballering said it’s unclear from this data whether vaccination or whether a person was hospitalized would change the prevalence of persistent symptoms.

Because of the period when the data were collected, “the vast majority of our study population was not fully vaccinated,” she said.

However, she pointed to recent research that shows that immunization against COVID is only partially effective against persistent somatic symptoms after COVID.

Also, only 5% of men and 2.5% of women in the study were hospitalized as a result of COVID-19, so the findings can’t easily be generalized to hospitalized patients.

The Lifelines study was an add-on study to the multidisciplinary, prospective, population-based, observational Dutch Lifelines cohort study examining 167,729 people in the Netherlands. Almost all were White, a limitation of the study, and 58% were female. Average age was 54.

The editorialists also noted additional limitations of the study were that this research “did not fully consider the impact on mental health” and was conducted in one region in the Netherlands.

Janko Nikolich-Žugich, MD, PhD, director of the Aegis Consortium for Pandemic-Free Future and head of the immunobiology department at University of Arizona, Tucson, said in an interview that he agreed with the editorialists that a primary benefit of this study is that it corrected for symptoms people had before COVID, something other studies have not been able to do.

However, he cautioned about generalizing the results for the United States and other countries because of the lack of diversity in the study population with regard to education level, socioeconomic factors, and race. He pointed out that access issues are also different in the Netherlands, which has universal health care.

He said brain fog as a symptom of long COVID is of high interest and will be important to include in future studies that are able to extend the study period.

The work was funded by ZonMw; the Dutch Ministry of Health, Welfare, and Sport; Dutch Ministry of Economic Affairs; University Medical Center Groningen, University of Groningen; and the provinces of Drenthe, Friesland, and Groningen. The study authors and Dr. Nikolich-Žugich have reported no relevant financial relationships. Dr. Brightling has received consultancy and or grants paid to his institution from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Novartis, Chiesi, Genentech, Roche, Sanofi, Regeneron, Mologic, and 4DPharma for asthma and chronic obstructive pulmonary disease research. Dr. Evans has received consultancy fees from AstraZeneca on the topic of long COVID and from GlaxoSmithKline on digital health, and speaker’s fees from Boehringer Ingelheim on long COVID.

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

One in eight adults (12.7%) diagnosed with COVID-19 will likely experience long-term symptoms, a large study published in The Lancet indicates.

The researchers determined that percentage by comparing long-term symptoms in people infected by SARS-CoV-2 with similar symptoms in uninfected people over the same time period.

Among the group of infected study participants in the Netherlands, 21.4% had at least one new or severely increased symptom 3-5 months after infection compared with before infection. When that group of 21.4% was compared with 8.7% of uninfected people in the same study, the researchers were able to calculate a prevalence 12.7% with long COVID.

“This finding shows that post–COVID-19 condition is an urgent problem with a mounting human toll,” the study authors wrote.

The research design was novel, two editorialists said in an accompanying commentary.

Christopher Brightling, PhD, and Rachael Evans, MBChB, PhD, of the Institute for Lung Health, University of Leicester (England), noted: “This is a major advance on prior long COVID prevalence estimates as it includes a matched uninfected group and accounts for symptoms before COVID-19 infection.”
 

Symptoms that persist

The Lancet study found that 3-5 months after COVID (compared with before COVID) and compared with the non-COVID comparison group, the symptoms that persist were chest pain, breathing difficulties, pain when breathing, muscle pain, loss of taste and/or smell, tingling extremities, lump in throat, feeling hot and cold alternately, heavy limbs, and tiredness.

The authors noted that symptoms such as brain fog were found to be relevant to long COVID after the data collection period for this paper and were not included in this research.

Researcher Aranka V. Ballering, MSc, PhD candidate, said in an interview that the researchers found fever is a symptom that is clearly present during the acute phase of the disease and it peaks the day of the COVID-19 diagnosis, but also wears off.

Loss of taste and smell, however, rapidly increases in severity when COVID-19 is diagnosed, but also persists and is still present 3-5 months after COVID.

Ms. Ballering, with the department of psychiatry at the University of Groningen (the Netherlands), said she was surprised by the sex difference made evident in their research: “Women showed more severe persistent symptoms than men.”
 

Closer to a clearer definition

The authors said their findings also pinpoint symptoms that bring us closer to a better definition of long COVID, which has many different definitions globally.

“These symptoms have the highest discriminative ability to distinguish between post–COVID-19 condition and non–COVID-19–related symptoms,” they wrote.

Researchers collected data by asking participants in the northern Netherlands, who were part of the population-based Lifelines COVID-19 study, to regularly complete digital questionnaires on 23 symptoms commonly associated with long COVID. The questionnaire was sent out 24 times to the same people between March 2020 and August 2021. At that time, people had the Alpha or earlier variants.

Participants were considered COVID-19 positive if they had either a positive test or a doctor’s diagnosis of COVID-19.

Of 76,422 study participants, the 5.5% (4,231) who had COVID were matched to 8,462 controls. Researchers accounted for sex, age, and time of completing questionnaires.
 

Effect of hospitalization, vaccination unclear

Ms. Ballering said it’s unclear from this data whether vaccination or whether a person was hospitalized would change the prevalence of persistent symptoms.

Because of the period when the data were collected, “the vast majority of our study population was not fully vaccinated,” she said.

However, she pointed to recent research that shows that immunization against COVID is only partially effective against persistent somatic symptoms after COVID.

Also, only 5% of men and 2.5% of women in the study were hospitalized as a result of COVID-19, so the findings can’t easily be generalized to hospitalized patients.

The Lifelines study was an add-on study to the multidisciplinary, prospective, population-based, observational Dutch Lifelines cohort study examining 167,729 people in the Netherlands. Almost all were White, a limitation of the study, and 58% were female. Average age was 54.

The editorialists also noted additional limitations of the study were that this research “did not fully consider the impact on mental health” and was conducted in one region in the Netherlands.

Janko Nikolich-Žugich, MD, PhD, director of the Aegis Consortium for Pandemic-Free Future and head of the immunobiology department at University of Arizona, Tucson, said in an interview that he agreed with the editorialists that a primary benefit of this study is that it corrected for symptoms people had before COVID, something other studies have not been able to do.

However, he cautioned about generalizing the results for the United States and other countries because of the lack of diversity in the study population with regard to education level, socioeconomic factors, and race. He pointed out that access issues are also different in the Netherlands, which has universal health care.

He said brain fog as a symptom of long COVID is of high interest and will be important to include in future studies that are able to extend the study period.

The work was funded by ZonMw; the Dutch Ministry of Health, Welfare, and Sport; Dutch Ministry of Economic Affairs; University Medical Center Groningen, University of Groningen; and the provinces of Drenthe, Friesland, and Groningen. The study authors and Dr. Nikolich-Žugich have reported no relevant financial relationships. Dr. Brightling has received consultancy and or grants paid to his institution from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Novartis, Chiesi, Genentech, Roche, Sanofi, Regeneron, Mologic, and 4DPharma for asthma and chronic obstructive pulmonary disease research. Dr. Evans has received consultancy fees from AstraZeneca on the topic of long COVID and from GlaxoSmithKline on digital health, and speaker’s fees from Boehringer Ingelheim on long COVID.

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

One in eight adults (12.7%) diagnosed with COVID-19 will likely experience long-term symptoms, a large study published in The Lancet indicates.

The researchers determined that percentage by comparing long-term symptoms in people infected by SARS-CoV-2 with similar symptoms in uninfected people over the same time period.

Among the group of infected study participants in the Netherlands, 21.4% had at least one new or severely increased symptom 3-5 months after infection compared with before infection. When that group of 21.4% was compared with 8.7% of uninfected people in the same study, the researchers were able to calculate a prevalence 12.7% with long COVID.

“This finding shows that post–COVID-19 condition is an urgent problem with a mounting human toll,” the study authors wrote.

The research design was novel, two editorialists said in an accompanying commentary.

Christopher Brightling, PhD, and Rachael Evans, MBChB, PhD, of the Institute for Lung Health, University of Leicester (England), noted: “This is a major advance on prior long COVID prevalence estimates as it includes a matched uninfected group and accounts for symptoms before COVID-19 infection.”
 

Symptoms that persist

The Lancet study found that 3-5 months after COVID (compared with before COVID) and compared with the non-COVID comparison group, the symptoms that persist were chest pain, breathing difficulties, pain when breathing, muscle pain, loss of taste and/or smell, tingling extremities, lump in throat, feeling hot and cold alternately, heavy limbs, and tiredness.

The authors noted that symptoms such as brain fog were found to be relevant to long COVID after the data collection period for this paper and were not included in this research.

Researcher Aranka V. Ballering, MSc, PhD candidate, said in an interview that the researchers found fever is a symptom that is clearly present during the acute phase of the disease and it peaks the day of the COVID-19 diagnosis, but also wears off.

Loss of taste and smell, however, rapidly increases in severity when COVID-19 is diagnosed, but also persists and is still present 3-5 months after COVID.

Ms. Ballering, with the department of psychiatry at the University of Groningen (the Netherlands), said she was surprised by the sex difference made evident in their research: “Women showed more severe persistent symptoms than men.”
 

Closer to a clearer definition

The authors said their findings also pinpoint symptoms that bring us closer to a better definition of long COVID, which has many different definitions globally.

“These symptoms have the highest discriminative ability to distinguish between post–COVID-19 condition and non–COVID-19–related symptoms,” they wrote.

Researchers collected data by asking participants in the northern Netherlands, who were part of the population-based Lifelines COVID-19 study, to regularly complete digital questionnaires on 23 symptoms commonly associated with long COVID. The questionnaire was sent out 24 times to the same people between March 2020 and August 2021. At that time, people had the Alpha or earlier variants.

Participants were considered COVID-19 positive if they had either a positive test or a doctor’s diagnosis of COVID-19.

Of 76,422 study participants, the 5.5% (4,231) who had COVID were matched to 8,462 controls. Researchers accounted for sex, age, and time of completing questionnaires.
 

Effect of hospitalization, vaccination unclear

Ms. Ballering said it’s unclear from this data whether vaccination or whether a person was hospitalized would change the prevalence of persistent symptoms.

Because of the period when the data were collected, “the vast majority of our study population was not fully vaccinated,” she said.

However, she pointed to recent research that shows that immunization against COVID is only partially effective against persistent somatic symptoms after COVID.

Also, only 5% of men and 2.5% of women in the study were hospitalized as a result of COVID-19, so the findings can’t easily be generalized to hospitalized patients.

The Lifelines study was an add-on study to the multidisciplinary, prospective, population-based, observational Dutch Lifelines cohort study examining 167,729 people in the Netherlands. Almost all were White, a limitation of the study, and 58% were female. Average age was 54.

The editorialists also noted additional limitations of the study were that this research “did not fully consider the impact on mental health” and was conducted in one region in the Netherlands.

Janko Nikolich-Žugich, MD, PhD, director of the Aegis Consortium for Pandemic-Free Future and head of the immunobiology department at University of Arizona, Tucson, said in an interview that he agreed with the editorialists that a primary benefit of this study is that it corrected for symptoms people had before COVID, something other studies have not been able to do.

However, he cautioned about generalizing the results for the United States and other countries because of the lack of diversity in the study population with regard to education level, socioeconomic factors, and race. He pointed out that access issues are also different in the Netherlands, which has universal health care.

He said brain fog as a symptom of long COVID is of high interest and will be important to include in future studies that are able to extend the study period.

The work was funded by ZonMw; the Dutch Ministry of Health, Welfare, and Sport; Dutch Ministry of Economic Affairs; University Medical Center Groningen, University of Groningen; and the provinces of Drenthe, Friesland, and Groningen. The study authors and Dr. Nikolich-Žugich have reported no relevant financial relationships. Dr. Brightling has received consultancy and or grants paid to his institution from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Novartis, Chiesi, Genentech, Roche, Sanofi, Regeneron, Mologic, and 4DPharma for asthma and chronic obstructive pulmonary disease research. Dr. Evans has received consultancy fees from AstraZeneca on the topic of long COVID and from GlaxoSmithKline on digital health, and speaker’s fees from Boehringer Ingelheim on long COVID.

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