COVID-19 Updates

To the Editor:

Peer-reviewed publications are important determinants for promotions, academic leadership, and grants in dermatology.¹ The impact of the COVID-19 pandemic on dermatology research productivity remains an area of investigation. We sought to determine authorship trends for males and females during the pandemic.

A cross-sectional retrospective study of the top 20 dermatology journals—determined by impact factor and Google Scholar H5-index—was conducted to identify manuscripts with submission date specified prepandemic (May 1, 2019–October 31, 2019) and during the pandemic (May 1, 2020–October 31, 2020). Submission date, first/last author name, sex, and affiliated country were extracted. Single authors were designated as first authors. Gender API (https://gender-api.com/en/) classified gender. A χ² test (P<.05) compared differences in proportions of female first/last authors from 2019 to 2020.

Overall, 811 and 1061 articles submitted in 2019 and 2020, respectively, were included. There were 1517 articles submitted to clinical journals and 355 articles submitted to basic science journals (Table). For the 7 clinical journals included, there was a 7.7% decrease in the proportion of female last authors in 2020 vs 2019 (P=.002), with the largest decrease between August and September 2020. Although other comparisons did not yield statistically significant differences (P>.05 all)(Table), several trends were observed. For clinical journals, there was a 1.8% decrease in the proportion of female first authors. For the 4 basic science journals included, there was a 4.9% increase and a 0.3% decrease in percentages of female first and last authors, respectively, for 2020 vs 2019.

Our findings indicate that the COVID-19 pandemic may have impacted female authors’ productivity in clinical dermatology publications. In a survey-based study for 2010 to 2011, female physician-researchers (n=437) spent 8.5 more hours per week on domestic activities and childcare and were more likely to take time off for childcare if their partner worked full time compared with males (n=612)(42.6% vs 12.4%, respectively).² Our observation that female last authors had a significant decrease in publications may suggest that this population had a disproportionate burden of domestic labor and childcare during the pandemic. It is possible that last authors, who generally are more senior researchers, may be more likely to have childcare, eldercare, and other types of domestic responsibilities. Similarly, in a study of surgery submissions (n=1068), there were 6%, 7%, and 4% decreases in percentages of female last, corresponding, and first authors, respectively, from 2019 to 2020.³Our study had limitations. Only 11 journals were analyzed because others did not have specified submission dates. Some journals only provided submission information for a subset of articles (eg, those published in the In Press section), which may have accounted for the large discrepancy in submission numbers for 2019 to 2020. Gender could not be determined for 1% of authors and was limited to female and male. Although our study submission time frame (May–October 2020) aimed at identifying research conducted during the height of the COVID-19 pandemic, some of these studies may have been conducted months or years before the pandemic. Future studies should focus on longer and more comprehensive time frames. Finally, estimated dates of stay-at-home orders fail to consider differences within countries.

The proportion of female US-affiliated first and last authors publishing in dermatology journals increased from 12% to 48% in 1976 and from 6% to 31% in 2006,⁴ which is encouraging. However, a gender gap persists, with one-third of National Institutes of Health grants in dermatology and one-fourth of research project grants in dermatology awarded to women.⁵ Consequences of the pandemic on academic productivity may include fewer women represented in higher academic ranks, lower compensation, and lower career satisfaction compared with men.¹ We urge academic institutions and funding agencies to recognize and take action to mitigate long-term sequelae. Extended grant end dates and submission periods, funding opportunities dedicated to women, and prioritization of female-authored submissions are some strategies that can safeguard equitable career progression in dermatology research.

To the Editor:

Peer-reviewed publications are important determinants for promotions, academic leadership, and grants in dermatology.¹ The impact of the COVID-19 pandemic on dermatology research productivity remains an area of investigation. We sought to determine authorship trends for males and females during the pandemic.

A cross-sectional retrospective study of the top 20 dermatology journals—determined by impact factor and Google Scholar H5-index—was conducted to identify manuscripts with submission date specified prepandemic (May 1, 2019–October 31, 2019) and during the pandemic (May 1, 2020–October 31, 2020). Submission date, first/last author name, sex, and affiliated country were extracted. Single authors were designated as first authors. Gender API (https://gender-api.com/en/) classified gender. A χ² test (P<.05) compared differences in proportions of female first/last authors from 2019 to 2020.

Overall, 811 and 1061 articles submitted in 2019 and 2020, respectively, were included. There were 1517 articles submitted to clinical journals and 355 articles submitted to basic science journals (Table). For the 7 clinical journals included, there was a 7.7% decrease in the proportion of female last authors in 2020 vs 2019 (P=.002), with the largest decrease between August and September 2020. Although other comparisons did not yield statistically significant differences (P>.05 all)(Table), several trends were observed. For clinical journals, there was a 1.8% decrease in the proportion of female first authors. For the 4 basic science journals included, there was a 4.9% increase and a 0.3% decrease in percentages of female first and last authors, respectively, for 2020 vs 2019.

Our findings indicate that the COVID-19 pandemic may have impacted female authors’ productivity in clinical dermatology publications. In a survey-based study for 2010 to 2011, female physician-researchers (n=437) spent 8.5 more hours per week on domestic activities and childcare and were more likely to take time off for childcare if their partner worked full time compared with males (n=612)(42.6% vs 12.4%, respectively).² Our observation that female last authors had a significant decrease in publications may suggest that this population had a disproportionate burden of domestic labor and childcare during the pandemic. It is possible that last authors, who generally are more senior researchers, may be more likely to have childcare, eldercare, and other types of domestic responsibilities. Similarly, in a study of surgery submissions (n=1068), there were 6%, 7%, and 4% decreases in percentages of female last, corresponding, and first authors, respectively, from 2019 to 2020.³Our study had limitations. Only 11 journals were analyzed because others did not have specified submission dates. Some journals only provided submission information for a subset of articles (eg, those published in the In Press section), which may have accounted for the large discrepancy in submission numbers for 2019 to 2020. Gender could not be determined for 1% of authors and was limited to female and male. Although our study submission time frame (May–October 2020) aimed at identifying research conducted during the height of the COVID-19 pandemic, some of these studies may have been conducted months or years before the pandemic. Future studies should focus on longer and more comprehensive time frames. Finally, estimated dates of stay-at-home orders fail to consider differences within countries.

The proportion of female US-affiliated first and last authors publishing in dermatology journals increased from 12% to 48% in 1976 and from 6% to 31% in 2006,⁴ which is encouraging. However, a gender gap persists, with one-third of National Institutes of Health grants in dermatology and one-fourth of research project grants in dermatology awarded to women.⁵ Consequences of the pandemic on academic productivity may include fewer women represented in higher academic ranks, lower compensation, and lower career satisfaction compared with men.¹ We urge academic institutions and funding agencies to recognize and take action to mitigate long-term sequelae. Extended grant end dates and submission periods, funding opportunities dedicated to women, and prioritization of female-authored submissions are some strategies that can safeguard equitable career progression in dermatology research.

To the Editor:

Peer-reviewed publications are important determinants for promotions, academic leadership, and grants in dermatology.¹ The impact of the COVID-19 pandemic on dermatology research productivity remains an area of investigation. We sought to determine authorship trends for males and females during the pandemic.

A cross-sectional retrospective study of the top 20 dermatology journals—determined by impact factor and Google Scholar H5-index—was conducted to identify manuscripts with submission date specified prepandemic (May 1, 2019–October 31, 2019) and during the pandemic (May 1, 2020–October 31, 2020). Submission date, first/last author name, sex, and affiliated country were extracted. Single authors were designated as first authors. Gender API (https://gender-api.com/en/) classified gender. A χ² test (P<.05) compared differences in proportions of female first/last authors from 2019 to 2020.

Overall, 811 and 1061 articles submitted in 2019 and 2020, respectively, were included. There were 1517 articles submitted to clinical journals and 355 articles submitted to basic science journals (Table). For the 7 clinical journals included, there was a 7.7% decrease in the proportion of female last authors in 2020 vs 2019 (P=.002), with the largest decrease between August and September 2020. Although other comparisons did not yield statistically significant differences (P>.05 all)(Table), several trends were observed. For clinical journals, there was a 1.8% decrease in the proportion of female first authors. For the 4 basic science journals included, there was a 4.9% increase and a 0.3% decrease in percentages of female first and last authors, respectively, for 2020 vs 2019.

Our findings indicate that the COVID-19 pandemic may have impacted female authors’ productivity in clinical dermatology publications. In a survey-based study for 2010 to 2011, female physician-researchers (n=437) spent 8.5 more hours per week on domestic activities and childcare and were more likely to take time off for childcare if their partner worked full time compared with males (n=612)(42.6% vs 12.4%, respectively).² Our observation that female last authors had a significant decrease in publications may suggest that this population had a disproportionate burden of domestic labor and childcare during the pandemic. It is possible that last authors, who generally are more senior researchers, may be more likely to have childcare, eldercare, and other types of domestic responsibilities. Similarly, in a study of surgery submissions (n=1068), there were 6%, 7%, and 4% decreases in percentages of female last, corresponding, and first authors, respectively, from 2019 to 2020.³Our study had limitations. Only 11 journals were analyzed because others did not have specified submission dates. Some journals only provided submission information for a subset of articles (eg, those published in the In Press section), which may have accounted for the large discrepancy in submission numbers for 2019 to 2020. Gender could not be determined for 1% of authors and was limited to female and male. Although our study submission time frame (May–October 2020) aimed at identifying research conducted during the height of the COVID-19 pandemic, some of these studies may have been conducted months or years before the pandemic. Future studies should focus on longer and more comprehensive time frames. Finally, estimated dates of stay-at-home orders fail to consider differences within countries.

The proportion of female US-affiliated first and last authors publishing in dermatology journals increased from 12% to 48% in 1976 and from 6% to 31% in 2006,⁴ which is encouraging. However, a gender gap persists, with one-third of National Institutes of Health grants in dermatology and one-fourth of research project grants in dermatology awarded to women.⁵ Consequences of the pandemic on academic productivity may include fewer women represented in higher academic ranks, lower compensation, and lower career satisfaction compared with men.¹ We urge academic institutions and funding agencies to recognize and take action to mitigate long-term sequelae. Extended grant end dates and submission periods, funding opportunities dedicated to women, and prioritization of female-authored submissions are some strategies that can safeguard equitable career progression in dermatology research.

The Department of Health & Human Services has issued an advisory to help medical professionals better recognize the mental health symptoms that may come with long COVID.

The nine mental health symptoms highlighted in the advisory are fatigue; cognitive impairment, including brain fog; anxiety; depression; obsessive-compulsive disorder; sleep disorders; PTSD; psychotic disorder; and start of a substance use disorder.

The advisory noted that social factors can contribute to the mental health problems for racial and ethnic minorities; people with limited access to health care; people who already have behavioral health conditions and physical disabilities; and people who are lesbian, gay, bisexual, transgender, queer, or intersex.

“Long COVID has a range of burdensome physical symptoms and can take a toll on a person’s mental health. It can be very challenging for a person, whether they are impacted themselves, or they are a caregiver for someone who is affected,” Health and Human Services Secretary Xavier Becerra said in a statement. “This advisory helps to raise awareness, especially among primary care practitioners and clinicians who are often the ones treating patients with long COVID.”

The department says about 10% of people infected with COVID have at least one long COVID symptom. Physical symptoms include dizziness, stomach upset, heart palpitations, issues with sexual desire or capacity, loss of smell or taste, thirst, chronic coughing, chest pain, and abnormal movements. 

“We know that people living with long COVID need help today, and providers need help understanding what long COVID is and how to treat it,” Admiral Rachel Levine, MD, assistant secretary for health, said in the statement. “This advisory helps bridge that gap for the behavioral health impacts of long COVID.”

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

The Department of Health & Human Services has issued an advisory to help medical professionals better recognize the mental health symptoms that may come with long COVID.

The nine mental health symptoms highlighted in the advisory are fatigue; cognitive impairment, including brain fog; anxiety; depression; obsessive-compulsive disorder; sleep disorders; PTSD; psychotic disorder; and start of a substance use disorder.

The advisory noted that social factors can contribute to the mental health problems for racial and ethnic minorities; people with limited access to health care; people who already have behavioral health conditions and physical disabilities; and people who are lesbian, gay, bisexual, transgender, queer, or intersex.

“Long COVID has a range of burdensome physical symptoms and can take a toll on a person’s mental health. It can be very challenging for a person, whether they are impacted themselves, or they are a caregiver for someone who is affected,” Health and Human Services Secretary Xavier Becerra said in a statement. “This advisory helps to raise awareness, especially among primary care practitioners and clinicians who are often the ones treating patients with long COVID.”

The department says about 10% of people infected with COVID have at least one long COVID symptom. Physical symptoms include dizziness, stomach upset, heart palpitations, issues with sexual desire or capacity, loss of smell or taste, thirst, chronic coughing, chest pain, and abnormal movements. 

“We know that people living with long COVID need help today, and providers need help understanding what long COVID is and how to treat it,” Admiral Rachel Levine, MD, assistant secretary for health, said in the statement. “This advisory helps bridge that gap for the behavioral health impacts of long COVID.”

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

The Department of Health & Human Services has issued an advisory to help medical professionals better recognize the mental health symptoms that may come with long COVID.

The nine mental health symptoms highlighted in the advisory are fatigue; cognitive impairment, including brain fog; anxiety; depression; obsessive-compulsive disorder; sleep disorders; PTSD; psychotic disorder; and start of a substance use disorder.

The advisory noted that social factors can contribute to the mental health problems for racial and ethnic minorities; people with limited access to health care; people who already have behavioral health conditions and physical disabilities; and people who are lesbian, gay, bisexual, transgender, queer, or intersex.

“Long COVID has a range of burdensome physical symptoms and can take a toll on a person’s mental health. It can be very challenging for a person, whether they are impacted themselves, or they are a caregiver for someone who is affected,” Health and Human Services Secretary Xavier Becerra said in a statement. “This advisory helps to raise awareness, especially among primary care practitioners and clinicians who are often the ones treating patients with long COVID.”

The department says about 10% of people infected with COVID have at least one long COVID symptom. Physical symptoms include dizziness, stomach upset, heart palpitations, issues with sexual desire or capacity, loss of smell or taste, thirst, chronic coughing, chest pain, and abnormal movements. 

“We know that people living with long COVID need help today, and providers need help understanding what long COVID is and how to treat it,” Admiral Rachel Levine, MD, assistant secretary for health, said in the statement. “This advisory helps bridge that gap for the behavioral health impacts of long COVID.”

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

Human Rights Watch, the nonprofit that for decades has called attention to the victims of war, famine, and political repression around the world, is taking aim at U.S. hospitals for pushing millions of American patients into debt.

In a new report, the group calls for stronger government action to protect Americans from aggressive billing and debt collection by nonprofit hospitals, which Human Rights Watch said are systematically undermining patients’ human rights.

“Given the high prevalence of hospital-related medical debt in the U.S., this system is clearly not working,” concludes the report, which draws extensively on an ongoing investigation of medical debt by KFF Health News and NPR.

The report continues: “The U.S. model of subsidizing privately operated hospitals with tax exemptions in the hope that they will increase the accessibility of hospital care for un- and underinsured patients allows for abusive medical billing and debt collection practices and undermines human rights, including the right to health.”

Nationwide, about 100 million people – or 41% of adults – have some form of health care debt, a KFF survey conducted for the KFF Health News–NPR project found. And while patient debt is being driven by a range of medical and dental bills, polls and studies suggest hospitals are a major contributor.

About a third of U.S. adults with health care debt owed money for hospitalization, KFF’s polling found. Close to half of those owed at least $5,000. About a quarter owed $10,000 or more.

The scale of this crisis – which is unparalleled among wealthy nations – compelled Human Rights Watch to release the new report, said researcher Matt McConnell, its author. “Historically, Human Rights Watch has been an organization that has focused on international human rights issues,” he said. “But on medical debt, the U.S. is a real outlier. What you see is a system that privileges a few but creates large barriers to people accessing basic health rights.”

Hospital industry officials defend their work, citing hospitals’ broader work to help the communities they serve. “As a field, hospitals provide more benefit to their communities than any other sector in health care,” Melinda Hatton, general counsel at the American Hospital Association, wrote in a response to the Human Right Watch report.

Federal law requires private, tax-exempt hospitals – which make up more than half the nation’s medical centers – to provide care at no cost or at a discount to low-income patients. But reporting by KFF Health News and others has found that many hospitals make this aid difficult for patients to get.

At the same time, thousands of medical centers – including many tax-exempt ones – engage in aggressive debt collection tactics to pursue patients, including garnishing patients’ wages, placing liens on their homes, or selling their debt to third-party debt collectors.

Overall, KFF Health News found that most of the nation’s approximately 5,100 hospitals serving the general public have policies to use legal action or other aggressive tactics against patients. And one in five will deny nonemergency care to people with outstanding debt.

“Medical debt is drowning many low-income and working families while hospitals continue to benefit from nonprofit tax status as they pursue families for medical debt,” said Marceline White, executive director of Economic Action Maryland. The advocacy group has helped enact tighter rules to ensure Maryland hospitals make financial assistance more easily accessible and to restrict hospitals from some aggressive debt collection tactics, such as placing liens on patients’ homes.

Similar efforts are underway in other states, including Colorado, New Mexico, New York, Oregon, and Washington. But many patient and consumer advocates say stronger federal action is needed to expand patient protections.

The Human Rights Watch report – titled “In Sheep’s Clothing: United States’ Poorly Regulated Nonprofit Hospitals Undermine Health Care Access” – lists more than a dozen recommendations. These include:

• Congress should pass legislation to ensure that hospitals provide at least the same amount of charity care as they receive in public subsidies.
• The IRS should set uniform national standards on patients’ eligibility for financial assistance at nonprofit hospitals. Currently, hospitals are free to set their own standards, resulting in widespread variation, which can confuse patients.
• The Consumer Financial Protection Bureau, a federal watchdog agency, should crack down on debt collectors that do not ensure that patients have been screened for financial assistance before being pursued.
• The federal Centers for Medicare & Medicaid Services, which administers the two mammoth public insurance programs, should penalize hospitals that do not provide adequate financial assistance to patients.

“Nonprofit hospitals are contributing to medical debt and engaging in abusive billing and debt collection practices,” Mr. McConnell said. “The reason this keeps happening is the absence of clear guidelines and the federal government’s inadequate enforcement of existing regulations.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – the independent source for health policy research, polling, and journalism.

Human Rights Watch, the nonprofit that for decades has called attention to the victims of war, famine, and political repression around the world, is taking aim at U.S. hospitals for pushing millions of American patients into debt.

In a new report, the group calls for stronger government action to protect Americans from aggressive billing and debt collection by nonprofit hospitals, which Human Rights Watch said are systematically undermining patients’ human rights.

“Given the high prevalence of hospital-related medical debt in the U.S., this system is clearly not working,” concludes the report, which draws extensively on an ongoing investigation of medical debt by KFF Health News and NPR.

The report continues: “The U.S. model of subsidizing privately operated hospitals with tax exemptions in the hope that they will increase the accessibility of hospital care for un- and underinsured patients allows for abusive medical billing and debt collection practices and undermines human rights, including the right to health.”

Nationwide, about 100 million people – or 41% of adults – have some form of health care debt, a KFF survey conducted for the KFF Health News–NPR project found. And while patient debt is being driven by a range of medical and dental bills, polls and studies suggest hospitals are a major contributor.

About a third of U.S. adults with health care debt owed money for hospitalization, KFF’s polling found. Close to half of those owed at least $5,000. About a quarter owed $10,000 or more.

The scale of this crisis – which is unparalleled among wealthy nations – compelled Human Rights Watch to release the new report, said researcher Matt McConnell, its author. “Historically, Human Rights Watch has been an organization that has focused on international human rights issues,” he said. “But on medical debt, the U.S. is a real outlier. What you see is a system that privileges a few but creates large barriers to people accessing basic health rights.”

Hospital industry officials defend their work, citing hospitals’ broader work to help the communities they serve. “As a field, hospitals provide more benefit to their communities than any other sector in health care,” Melinda Hatton, general counsel at the American Hospital Association, wrote in a response to the Human Right Watch report.

Federal law requires private, tax-exempt hospitals – which make up more than half the nation’s medical centers – to provide care at no cost or at a discount to low-income patients. But reporting by KFF Health News and others has found that many hospitals make this aid difficult for patients to get.

At the same time, thousands of medical centers – including many tax-exempt ones – engage in aggressive debt collection tactics to pursue patients, including garnishing patients’ wages, placing liens on their homes, or selling their debt to third-party debt collectors.

Overall, KFF Health News found that most of the nation’s approximately 5,100 hospitals serving the general public have policies to use legal action or other aggressive tactics against patients. And one in five will deny nonemergency care to people with outstanding debt.

“Medical debt is drowning many low-income and working families while hospitals continue to benefit from nonprofit tax status as they pursue families for medical debt,” said Marceline White, executive director of Economic Action Maryland. The advocacy group has helped enact tighter rules to ensure Maryland hospitals make financial assistance more easily accessible and to restrict hospitals from some aggressive debt collection tactics, such as placing liens on patients’ homes.

Similar efforts are underway in other states, including Colorado, New Mexico, New York, Oregon, and Washington. But many patient and consumer advocates say stronger federal action is needed to expand patient protections.

The Human Rights Watch report – titled “In Sheep’s Clothing: United States’ Poorly Regulated Nonprofit Hospitals Undermine Health Care Access” – lists more than a dozen recommendations. These include:

• Congress should pass legislation to ensure that hospitals provide at least the same amount of charity care as they receive in public subsidies.
• The IRS should set uniform national standards on patients’ eligibility for financial assistance at nonprofit hospitals. Currently, hospitals are free to set their own standards, resulting in widespread variation, which can confuse patients.
• The Consumer Financial Protection Bureau, a federal watchdog agency, should crack down on debt collectors that do not ensure that patients have been screened for financial assistance before being pursued.
• The federal Centers for Medicare & Medicaid Services, which administers the two mammoth public insurance programs, should penalize hospitals that do not provide adequate financial assistance to patients.

“Nonprofit hospitals are contributing to medical debt and engaging in abusive billing and debt collection practices,” Mr. McConnell said. “The reason this keeps happening is the absence of clear guidelines and the federal government’s inadequate enforcement of existing regulations.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – the independent source for health policy research, polling, and journalism.

Human Rights Watch, the nonprofit that for decades has called attention to the victims of war, famine, and political repression around the world, is taking aim at U.S. hospitals for pushing millions of American patients into debt.

In a new report, the group calls for stronger government action to protect Americans from aggressive billing and debt collection by nonprofit hospitals, which Human Rights Watch said are systematically undermining patients’ human rights.

“Given the high prevalence of hospital-related medical debt in the U.S., this system is clearly not working,” concludes the report, which draws extensively on an ongoing investigation of medical debt by KFF Health News and NPR.

The report continues: “The U.S. model of subsidizing privately operated hospitals with tax exemptions in the hope that they will increase the accessibility of hospital care for un- and underinsured patients allows for abusive medical billing and debt collection practices and undermines human rights, including the right to health.”

Nationwide, about 100 million people – or 41% of adults – have some form of health care debt, a KFF survey conducted for the KFF Health News–NPR project found. And while patient debt is being driven by a range of medical and dental bills, polls and studies suggest hospitals are a major contributor.

About a third of U.S. adults with health care debt owed money for hospitalization, KFF’s polling found. Close to half of those owed at least $5,000. About a quarter owed $10,000 or more.

The scale of this crisis – which is unparalleled among wealthy nations – compelled Human Rights Watch to release the new report, said researcher Matt McConnell, its author. “Historically, Human Rights Watch has been an organization that has focused on international human rights issues,” he said. “But on medical debt, the U.S. is a real outlier. What you see is a system that privileges a few but creates large barriers to people accessing basic health rights.”

Hospital industry officials defend their work, citing hospitals’ broader work to help the communities they serve. “As a field, hospitals provide more benefit to their communities than any other sector in health care,” Melinda Hatton, general counsel at the American Hospital Association, wrote in a response to the Human Right Watch report.

Federal law requires private, tax-exempt hospitals – which make up more than half the nation’s medical centers – to provide care at no cost or at a discount to low-income patients. But reporting by KFF Health News and others has found that many hospitals make this aid difficult for patients to get.

At the same time, thousands of medical centers – including many tax-exempt ones – engage in aggressive debt collection tactics to pursue patients, including garnishing patients’ wages, placing liens on their homes, or selling their debt to third-party debt collectors.

Overall, KFF Health News found that most of the nation’s approximately 5,100 hospitals serving the general public have policies to use legal action or other aggressive tactics against patients. And one in five will deny nonemergency care to people with outstanding debt.

“Medical debt is drowning many low-income and working families while hospitals continue to benefit from nonprofit tax status as they pursue families for medical debt,” said Marceline White, executive director of Economic Action Maryland. The advocacy group has helped enact tighter rules to ensure Maryland hospitals make financial assistance more easily accessible and to restrict hospitals from some aggressive debt collection tactics, such as placing liens on patients’ homes.

Similar efforts are underway in other states, including Colorado, New Mexico, New York, Oregon, and Washington. But many patient and consumer advocates say stronger federal action is needed to expand patient protections.

The Human Rights Watch report – titled “In Sheep’s Clothing: United States’ Poorly Regulated Nonprofit Hospitals Undermine Health Care Access” – lists more than a dozen recommendations. These include:

• Congress should pass legislation to ensure that hospitals provide at least the same amount of charity care as they receive in public subsidies.
• The IRS should set uniform national standards on patients’ eligibility for financial assistance at nonprofit hospitals. Currently, hospitals are free to set their own standards, resulting in widespread variation, which can confuse patients.
• The Consumer Financial Protection Bureau, a federal watchdog agency, should crack down on debt collectors that do not ensure that patients have been screened for financial assistance before being pursued.
• The federal Centers for Medicare & Medicaid Services, which administers the two mammoth public insurance programs, should penalize hospitals that do not provide adequate financial assistance to patients.

“Nonprofit hospitals are contributing to medical debt and engaging in abusive billing and debt collection practices,” Mr. McConnell said. “The reason this keeps happening is the absence of clear guidelines and the federal government’s inadequate enforcement of existing regulations.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – the independent source for health policy research, polling, and journalism.

Patients with persistent depressive or cognitive symptoms after mild to moderate COVID-19 (COVID-DC) may have gliosis and inflammation, data suggest.

In a case-control study of 40 patients who were treated at a tertiary care psychiatric hospital in Canada, the level of translocator protein total distribution volume (TSPO VT), a marker of gliosis, was 9.23 mL/cm³ among patients with COVID-DC and 7.72 mL/cm³ among control persons. Differences were particularly notable in the ventral striatum and dorsal putamen.

“Most theories assume there is inflammation in the brain [with] long COVID,” but that assumption had not been studied, author Jeffrey H. Meyer, MD, PhD, Canada Research Chair in Neurochemistry of Major Depressive Disorder at the University of Toronto, said in an interview. “Such information is pivotal to developing treatments.”

The study was published online in JAMA Psychiatry.
 

Quantifiable marker

The investigators sought to determine whether levels of TSPO VT, which are quantifiable with PET, are elevated in the dorsal putamen, ventral striatum, prefrontal cortex, anterior cingulate cortex, and hippocampus of patients with COVID-DC, compared with patients without this syndrome. These brain regions were chosen, according to the authors, “because injury in these regions, which can cause gliosis, also induces symptoms of COVID-DC.”

The study was conducted from April 2021 through June 30, 2022. The investigators compared levels of TSPO VT in the selected brain regions of 20 participants with COVID-DC (mean age, 32.7 years; 60% women) with that of 20 control persons (mean age, 33.3 years; 55% women). TSPO VT was measured with fluorine F18–labeled N-(2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide PET.

The difference in TSPO VT was most noticeable in the ventral striatum (mean difference, 1.97 mL/cm³) and dorsal putamen (mean difference, 1.70 mL/cm³). The study authors suggest that gliosis in these areas may explain some of the persistent symptoms reported in structured clinical interviews and assessed on neuropsychological and psychological testing.

For patients with COVID-DC, motor speed on the finger-tapping test was negatively associated with dorsal putamen TSPO VT (r, −0.53). The 10 participants with COVID-DC whose speed was lowest had higher mean dorsal putamen TSPO VT levels than those of control persons by 2.3 mL/cm³.

The investigators could not assess a possible association between the ventral striatum TSPO VT and anhedonia because all participants had these symptoms. No significant correlations were found between depression and TSPO VT in the prefrontal cortex or anterior cingulate cortex.

The authors acknowledged that the study was cross-sectional, and so the duration of persistently elevated TSPO VT is not yet known. In addition, elevation in TSPO VT is not completely specific to glial cells, and although correlations with finger-tapping test performance reflect associations between brain changes and symptoms, they do not prove cause and effect.

“Presently, clinicians can use treatments for symptoms in other illnesses that are [also] common with long COVID. We need better than this,” said Dr. Meyer. “Clients with long COVID should be able to state their symptoms, and the practitioner should have an evidence-based matching treatment to recommend.”

Research is ongoing. “We are acquiring more information regarding different types of inflammation in the brain, whether there is ongoing injury, and whether treatments that influence inflammation are helpful,” said Dr. Meyer.
 

Jigsaw puzzle

“While this is an important piece in the jigsaw puzzle of neuroinflammation in chronic neurological disease, it is important to keep in mind that we still lack understanding of the complex picture for several reasons,” Alexander Gerhard, MD, honorary senior lecturer in neuroscience at the University of Manchester, England, wrote in an accompanying editorial.

Among these reasons is that the PET technique used in the study is noisy and not restricted to glial cells, he wrote. TSPO expression is only one part of the brain’s neuroinflammatory response, but PET techniques “do not currently allow us to distinguish between different states of microglial activation.” In addition, “a much more detailed understanding of microglial activation at different time points” is needed before neuroinflammatory changes can be targeted therapeutically, Dr. Gerhard wrote.

In a comment, Vilma Gabbay, MD, professor of psychiatry and neuroscience and director of biomarkers and dimensional psychiatry in the Psychiatry Research Institute at Montefiore Einstein, Albert Einstein College of Medicine, New York, said that “this is an important initial step to better understand the neuropsychiatric consequences of COVID even in only a mild and moderate viral illness.” TSPO imaging through PET scanning has been used as an index for neuroinflammation and gliosis. Researchers have used it to study neurodegenerative diseases, but as the authors noted, the ligand is not specific for gliosis.

“Follow-up large cohort studies including other measures of neuroimaging modalities assessing circuitry and neurochemistry are needed,” she said. “Similarly, studying the blood-brain barrier will also allow us to better understand how the immune reaction in the blood transitions to the brain.”

This field of research is evolving, and clinical trials are ongoing, Dr. Gabbay added. Meanwhile, clinicians should monitor for, assess, and treat neuropsychiatric symptoms and “follow the literature for new research and management recommendations.”

The study was primarily funded by a Canadian Institutes of Health Research Project grant to the authors, with some funding from the Canadian Institute for Military and Veteran Health Research. Dr. Meyer received support from their Canada Research Chair awards and received grants and support from several pharmaceutical companies outside of the submitted work. Dr. Gerhard and Dr. Gabbay disclosed no relevant financial relationships.

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

Patients with persistent depressive or cognitive symptoms after mild to moderate COVID-19 (COVID-DC) may have gliosis and inflammation, data suggest.

In a case-control study of 40 patients who were treated at a tertiary care psychiatric hospital in Canada, the level of translocator protein total distribution volume (TSPO VT), a marker of gliosis, was 9.23 mL/cm³ among patients with COVID-DC and 7.72 mL/cm³ among control persons. Differences were particularly notable in the ventral striatum and dorsal putamen.

“Most theories assume there is inflammation in the brain [with] long COVID,” but that assumption had not been studied, author Jeffrey H. Meyer, MD, PhD, Canada Research Chair in Neurochemistry of Major Depressive Disorder at the University of Toronto, said in an interview. “Such information is pivotal to developing treatments.”

The study was published online in JAMA Psychiatry.
 

Quantifiable marker

The investigators sought to determine whether levels of TSPO VT, which are quantifiable with PET, are elevated in the dorsal putamen, ventral striatum, prefrontal cortex, anterior cingulate cortex, and hippocampus of patients with COVID-DC, compared with patients without this syndrome. These brain regions were chosen, according to the authors, “because injury in these regions, which can cause gliosis, also induces symptoms of COVID-DC.”

The study was conducted from April 2021 through June 30, 2022. The investigators compared levels of TSPO VT in the selected brain regions of 20 participants with COVID-DC (mean age, 32.7 years; 60% women) with that of 20 control persons (mean age, 33.3 years; 55% women). TSPO VT was measured with fluorine F18–labeled N-(2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide PET.

The difference in TSPO VT was most noticeable in the ventral striatum (mean difference, 1.97 mL/cm³) and dorsal putamen (mean difference, 1.70 mL/cm³). The study authors suggest that gliosis in these areas may explain some of the persistent symptoms reported in structured clinical interviews and assessed on neuropsychological and psychological testing.

For patients with COVID-DC, motor speed on the finger-tapping test was negatively associated with dorsal putamen TSPO VT (r, −0.53). The 10 participants with COVID-DC whose speed was lowest had higher mean dorsal putamen TSPO VT levels than those of control persons by 2.3 mL/cm³.

The investigators could not assess a possible association between the ventral striatum TSPO VT and anhedonia because all participants had these symptoms. No significant correlations were found between depression and TSPO VT in the prefrontal cortex or anterior cingulate cortex.

The authors acknowledged that the study was cross-sectional, and so the duration of persistently elevated TSPO VT is not yet known. In addition, elevation in TSPO VT is not completely specific to glial cells, and although correlations with finger-tapping test performance reflect associations between brain changes and symptoms, they do not prove cause and effect.

“Presently, clinicians can use treatments for symptoms in other illnesses that are [also] common with long COVID. We need better than this,” said Dr. Meyer. “Clients with long COVID should be able to state their symptoms, and the practitioner should have an evidence-based matching treatment to recommend.”

Research is ongoing. “We are acquiring more information regarding different types of inflammation in the brain, whether there is ongoing injury, and whether treatments that influence inflammation are helpful,” said Dr. Meyer.
 

Jigsaw puzzle

“While this is an important piece in the jigsaw puzzle of neuroinflammation in chronic neurological disease, it is important to keep in mind that we still lack understanding of the complex picture for several reasons,” Alexander Gerhard, MD, honorary senior lecturer in neuroscience at the University of Manchester, England, wrote in an accompanying editorial.

Among these reasons is that the PET technique used in the study is noisy and not restricted to glial cells, he wrote. TSPO expression is only one part of the brain’s neuroinflammatory response, but PET techniques “do not currently allow us to distinguish between different states of microglial activation.” In addition, “a much more detailed understanding of microglial activation at different time points” is needed before neuroinflammatory changes can be targeted therapeutically, Dr. Gerhard wrote.

In a comment, Vilma Gabbay, MD, professor of psychiatry and neuroscience and director of biomarkers and dimensional psychiatry in the Psychiatry Research Institute at Montefiore Einstein, Albert Einstein College of Medicine, New York, said that “this is an important initial step to better understand the neuropsychiatric consequences of COVID even in only a mild and moderate viral illness.” TSPO imaging through PET scanning has been used as an index for neuroinflammation and gliosis. Researchers have used it to study neurodegenerative diseases, but as the authors noted, the ligand is not specific for gliosis.

“Follow-up large cohort studies including other measures of neuroimaging modalities assessing circuitry and neurochemistry are needed,” she said. “Similarly, studying the blood-brain barrier will also allow us to better understand how the immune reaction in the blood transitions to the brain.”

This field of research is evolving, and clinical trials are ongoing, Dr. Gabbay added. Meanwhile, clinicians should monitor for, assess, and treat neuropsychiatric symptoms and “follow the literature for new research and management recommendations.”

The study was primarily funded by a Canadian Institutes of Health Research Project grant to the authors, with some funding from the Canadian Institute for Military and Veteran Health Research. Dr. Meyer received support from their Canada Research Chair awards and received grants and support from several pharmaceutical companies outside of the submitted work. Dr. Gerhard and Dr. Gabbay disclosed no relevant financial relationships.

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

Patients with persistent depressive or cognitive symptoms after mild to moderate COVID-19 (COVID-DC) may have gliosis and inflammation, data suggest.

In a case-control study of 40 patients who were treated at a tertiary care psychiatric hospital in Canada, the level of translocator protein total distribution volume (TSPO VT), a marker of gliosis, was 9.23 mL/cm³ among patients with COVID-DC and 7.72 mL/cm³ among control persons. Differences were particularly notable in the ventral striatum and dorsal putamen.

“Most theories assume there is inflammation in the brain [with] long COVID,” but that assumption had not been studied, author Jeffrey H. Meyer, MD, PhD, Canada Research Chair in Neurochemistry of Major Depressive Disorder at the University of Toronto, said in an interview. “Such information is pivotal to developing treatments.”

The study was published online in JAMA Psychiatry.
 

Quantifiable marker

The investigators sought to determine whether levels of TSPO VT, which are quantifiable with PET, are elevated in the dorsal putamen, ventral striatum, prefrontal cortex, anterior cingulate cortex, and hippocampus of patients with COVID-DC, compared with patients without this syndrome. These brain regions were chosen, according to the authors, “because injury in these regions, which can cause gliosis, also induces symptoms of COVID-DC.”

The study was conducted from April 2021 through June 30, 2022. The investigators compared levels of TSPO VT in the selected brain regions of 20 participants with COVID-DC (mean age, 32.7 years; 60% women) with that of 20 control persons (mean age, 33.3 years; 55% women). TSPO VT was measured with fluorine F18–labeled N-(2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide PET.

The difference in TSPO VT was most noticeable in the ventral striatum (mean difference, 1.97 mL/cm³) and dorsal putamen (mean difference, 1.70 mL/cm³). The study authors suggest that gliosis in these areas may explain some of the persistent symptoms reported in structured clinical interviews and assessed on neuropsychological and psychological testing.

For patients with COVID-DC, motor speed on the finger-tapping test was negatively associated with dorsal putamen TSPO VT (r, −0.53). The 10 participants with COVID-DC whose speed was lowest had higher mean dorsal putamen TSPO VT levels than those of control persons by 2.3 mL/cm³.

The investigators could not assess a possible association between the ventral striatum TSPO VT and anhedonia because all participants had these symptoms. No significant correlations were found between depression and TSPO VT in the prefrontal cortex or anterior cingulate cortex.

The authors acknowledged that the study was cross-sectional, and so the duration of persistently elevated TSPO VT is not yet known. In addition, elevation in TSPO VT is not completely specific to glial cells, and although correlations with finger-tapping test performance reflect associations between brain changes and symptoms, they do not prove cause and effect.

“Presently, clinicians can use treatments for symptoms in other illnesses that are [also] common with long COVID. We need better than this,” said Dr. Meyer. “Clients with long COVID should be able to state their symptoms, and the practitioner should have an evidence-based matching treatment to recommend.”

Research is ongoing. “We are acquiring more information regarding different types of inflammation in the brain, whether there is ongoing injury, and whether treatments that influence inflammation are helpful,” said Dr. Meyer.
 

Jigsaw puzzle

“While this is an important piece in the jigsaw puzzle of neuroinflammation in chronic neurological disease, it is important to keep in mind that we still lack understanding of the complex picture for several reasons,” Alexander Gerhard, MD, honorary senior lecturer in neuroscience at the University of Manchester, England, wrote in an accompanying editorial.

Among these reasons is that the PET technique used in the study is noisy and not restricted to glial cells, he wrote. TSPO expression is only one part of the brain’s neuroinflammatory response, but PET techniques “do not currently allow us to distinguish between different states of microglial activation.” In addition, “a much more detailed understanding of microglial activation at different time points” is needed before neuroinflammatory changes can be targeted therapeutically, Dr. Gerhard wrote.

In a comment, Vilma Gabbay, MD, professor of psychiatry and neuroscience and director of biomarkers and dimensional psychiatry in the Psychiatry Research Institute at Montefiore Einstein, Albert Einstein College of Medicine, New York, said that “this is an important initial step to better understand the neuropsychiatric consequences of COVID even in only a mild and moderate viral illness.” TSPO imaging through PET scanning has been used as an index for neuroinflammation and gliosis. Researchers have used it to study neurodegenerative diseases, but as the authors noted, the ligand is not specific for gliosis.

“Follow-up large cohort studies including other measures of neuroimaging modalities assessing circuitry and neurochemistry are needed,” she said. “Similarly, studying the blood-brain barrier will also allow us to better understand how the immune reaction in the blood transitions to the brain.”

This field of research is evolving, and clinical trials are ongoing, Dr. Gabbay added. Meanwhile, clinicians should monitor for, assess, and treat neuropsychiatric symptoms and “follow the literature for new research and management recommendations.”

The study was primarily funded by a Canadian Institutes of Health Research Project grant to the authors, with some funding from the Canadian Institute for Military and Veteran Health Research. Dr. Meyer received support from their Canada Research Chair awards and received grants and support from several pharmaceutical companies outside of the submitted work. Dr. Gerhard and Dr. Gabbay disclosed no relevant financial relationships.

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

A panel of advisers to the Food and Drug Administration unanimously has agreed that the next COVID-19 vaccines should target the XBB variants of the SARS-CoV-2 virus now in circulation in the United States, but questioned whether the population as a whole needs booster shots and how often they should be given.

The Vaccines and Related Biological Products Advisory Committee of the FDA voted 21-0 in favor of the recommendation about the strain to be used in the next crop of vaccines.

In the briefing document for the meeting, FDA staff said the available evidence suggests that a monovalent (single-strain) XBB-lineage vaccine “is warranted” for the 2023-2024 vaccination campaign and would replace the current bivalent vaccine, which targets the original version of the virus and two strains from the Omicron variant.

FDA staff also noted how such a shift would be in line with the World Health Organization toward targeting the XBB family of subvariants. European regulators have done this as well. 

The FDA is not obligated to act on the panel’s recommendations. But the agency often does and is highly likely to do so in this case. Vaccine companies will need the recommendation from the FDA to begin making vaccines for the fall.
 

New shot every year?

The FDA asked its expert panel to vote only on the question about the makeup of future vaccines in terms of which strain to include. 

But panelists also raised other questions during the meeting, including concerns about moves toward tying COVID vaccinations into the model of annual flu shots. 

Paul Offit, MD, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia, argued for greater focus on the response of T cells after vaccination, even in light of the already recognized waning of antibody protection. 

In a recent Substack article, Dr. Offit called T cells the “unsung hero” of the pandemic. They take longer to develop after infection or vaccination than the antibodies that first attack the virus, but immune memory cells called B and T cells “are long-lived,” and their “protection against severe disease often lasts for years and sometimes decades.”

Dr. Offit said he was concerned about using a blanket approach for future recommendations for COVID vaccinations, following the one now in place for influenza vaccines.

The Centers for Disease Control and Prevention recommends flu shots for everyone 6 months and older, with rare exceptions. 

“We need to continue to define who those high-risk groups are and not make this a recommendation for everybody every season,” he said.

Dr. Offit offered his own experience as an example. While he had been vaccinated against the virus’s early Wuhan strain, he still was infected, most likely with a variant that emerged later. 

“That was a drifted virus. That’s why I had a mild infection but I didn’t have a severe infection, because presumably I had T cells which prevented that severe infection, which may last for years,” Dr. Offit said.

Pfizer and Moderna, the two companies that make mRNA-based COVID vaccines, are working on experimental products meant to protect against both flu and SARS-COv-2 in one shot. Novavax, maker of a more traditional protein-based COVID shot, is doing the same. 

The idea of these combination products is to make it more convenient for people to protect against both viruses, while also offering companies some marketing advantages.

But without referring to these drugmakers’ plans for future combo flu-COVID shots, members of the FDA panel raised objections to an assumption of routine annual vaccines against variants of SARS-CoV-2. 

Among the panelists who expressed concerns was Henry H. Bernstein, DO, a former member of the CDC’s Advisory Committee on Immunization Practices. 

Bernstein questioned the approach of dubbing these the “2023-2024 formulas,” as this approach conveyed a sense of an expectation for a need for annual vaccines, as happens with flu. 

“It’s not clear to me that this is a seasonal virus yet,” said Dr. Bernstein, who is also a professor of pediatrics at Hofstra University, Hempstead, N.Y..

In response to Dr. Bernstein’s point, Arnold Monto, MD, the acting chair of the FDA panel, suggested such a pattern could emerge, while also agreeing that it’s too soon to say for sure.

A professor emeritus at the University of Michigan, Ann Arbor, Dr. Monto’s career included pandemic planning and emergency response to virus outbreaks, including the 1968 Hong Kong influenza pandemic, avian influenza, and the original SARS.

“I think it’s premature to say that this virus will not become seasonal,” Dr. Monto said about SARS-CoV-2. “I agree. We’re not there yet, but we may be.”

At the end of the meeting, Dr. Monto recapped the meeting’s key points, noting that there was a general consensus that the XBB.1.5 subvariant would be the best to use in future COVID shots. 

He also noted that Novavax, which makes the more traditional protein-based vaccine, along with Pfizer and Moderna, already have honed in on this subvariant, which would allow for rapid development of updated COVID vaccines.

“The fact that most of the manufacturers are ready to work on an XBB 1.5 [vaccine] is an added reason to select this strain or this variant, given the immunologic data,” Dr. Monto said. 

Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said the demands involved in manufacturing vaccines tilts toward annual changes.

“Practically, we’re going to have one update per year, barring a heroic effort to deal with a strain that pops up that is essentially so different that it requires us to mobilize tremendous resources to address that strain change,” he said.

Dr. Marks questioned the panelists’ concerns about likening flu and COVID vaccination practices. The FDA staff’s intent was to try to help the public understand the need for follow-on vaccination.

“I’m really having trouble understanding that committee’s need to bristle against something that’s similar to influenza. People understand a yearly influenza vaccine,” Dr. Marks said. 

And it’s not certain when another major change in the COVID virus will follow the XBB subvariant, but it’s likely one will – and soon, Dr. Marks said. 

“It looks like, probably by next fall, there’ll be further drift from this,” he said.
 

Informing the public 

Dr. Marks also stressed the need to better convey the benefits of vaccination to people in the United States. 

CDC data estimate that 70% of the U.S. population completed an initial series of the original monovalent vaccines, with only 17% then getting bivalent shots. There’s even a decline among people ages 65 and older. CDC estimates 94% of this group completed their primary series, but only 43% got the bivalent booster dose.

“We have to do better because we have not done a good job today communicating to the American public what’s going on here,” Marks said.

Researchers also are still trying to determine the best timing for people to get additional COVID shots. Finding the “sweet spot” where people can maximize additional protection is tricky, with people most protected if they happen to get shot near the beginning of an uptick in viral spread, the CDC’s Ruth Link-Gelles, PhD, MPH, told the panel during a presentation. 

“You’re going to get the best incremental benefit if it’s been longer since your last vaccine,” she said. “But of course, if you wait too long since your last vaccine, you’re left with very little protection, and so you’re at higher risk of severe illness.”

Like Dr. Marks, Dr. Link-Gelles stressed the need for persuading more people to get follow-on vaccines. 

“Most Americans, at this point, haven’t even received the bivalent and so are a year or more out from their monovalent dose and so have relatively little protection left,” she said.

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

A panel of advisers to the Food and Drug Administration unanimously has agreed that the next COVID-19 vaccines should target the XBB variants of the SARS-CoV-2 virus now in circulation in the United States, but questioned whether the population as a whole needs booster shots and how often they should be given.

The Vaccines and Related Biological Products Advisory Committee of the FDA voted 21-0 in favor of the recommendation about the strain to be used in the next crop of vaccines.

In the briefing document for the meeting, FDA staff said the available evidence suggests that a monovalent (single-strain) XBB-lineage vaccine “is warranted” for the 2023-2024 vaccination campaign and would replace the current bivalent vaccine, which targets the original version of the virus and two strains from the Omicron variant.

FDA staff also noted how such a shift would be in line with the World Health Organization toward targeting the XBB family of subvariants. European regulators have done this as well. 

The FDA is not obligated to act on the panel’s recommendations. But the agency often does and is highly likely to do so in this case. Vaccine companies will need the recommendation from the FDA to begin making vaccines for the fall.
 

New shot every year?

The FDA asked its expert panel to vote only on the question about the makeup of future vaccines in terms of which strain to include. 

But panelists also raised other questions during the meeting, including concerns about moves toward tying COVID vaccinations into the model of annual flu shots. 

Paul Offit, MD, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia, argued for greater focus on the response of T cells after vaccination, even in light of the already recognized waning of antibody protection. 

In a recent Substack article, Dr. Offit called T cells the “unsung hero” of the pandemic. They take longer to develop after infection or vaccination than the antibodies that first attack the virus, but immune memory cells called B and T cells “are long-lived,” and their “protection against severe disease often lasts for years and sometimes decades.”

Dr. Offit said he was concerned about using a blanket approach for future recommendations for COVID vaccinations, following the one now in place for influenza vaccines.

The Centers for Disease Control and Prevention recommends flu shots for everyone 6 months and older, with rare exceptions. 

“We need to continue to define who those high-risk groups are and not make this a recommendation for everybody every season,” he said.

Dr. Offit offered his own experience as an example. While he had been vaccinated against the virus’s early Wuhan strain, he still was infected, most likely with a variant that emerged later. 

“That was a drifted virus. That’s why I had a mild infection but I didn’t have a severe infection, because presumably I had T cells which prevented that severe infection, which may last for years,” Dr. Offit said.

Pfizer and Moderna, the two companies that make mRNA-based COVID vaccines, are working on experimental products meant to protect against both flu and SARS-COv-2 in one shot. Novavax, maker of a more traditional protein-based COVID shot, is doing the same. 

The idea of these combination products is to make it more convenient for people to protect against both viruses, while also offering companies some marketing advantages.

But without referring to these drugmakers’ plans for future combo flu-COVID shots, members of the FDA panel raised objections to an assumption of routine annual vaccines against variants of SARS-CoV-2. 

Among the panelists who expressed concerns was Henry H. Bernstein, DO, a former member of the CDC’s Advisory Committee on Immunization Practices. 

Bernstein questioned the approach of dubbing these the “2023-2024 formulas,” as this approach conveyed a sense of an expectation for a need for annual vaccines, as happens with flu. 

“It’s not clear to me that this is a seasonal virus yet,” said Dr. Bernstein, who is also a professor of pediatrics at Hofstra University, Hempstead, N.Y..

In response to Dr. Bernstein’s point, Arnold Monto, MD, the acting chair of the FDA panel, suggested such a pattern could emerge, while also agreeing that it’s too soon to say for sure.

A professor emeritus at the University of Michigan, Ann Arbor, Dr. Monto’s career included pandemic planning and emergency response to virus outbreaks, including the 1968 Hong Kong influenza pandemic, avian influenza, and the original SARS.

“I think it’s premature to say that this virus will not become seasonal,” Dr. Monto said about SARS-CoV-2. “I agree. We’re not there yet, but we may be.”

At the end of the meeting, Dr. Monto recapped the meeting’s key points, noting that there was a general consensus that the XBB.1.5 subvariant would be the best to use in future COVID shots. 

He also noted that Novavax, which makes the more traditional protein-based vaccine, along with Pfizer and Moderna, already have honed in on this subvariant, which would allow for rapid development of updated COVID vaccines.

“The fact that most of the manufacturers are ready to work on an XBB 1.5 [vaccine] is an added reason to select this strain or this variant, given the immunologic data,” Dr. Monto said. 

Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said the demands involved in manufacturing vaccines tilts toward annual changes.

“Practically, we’re going to have one update per year, barring a heroic effort to deal with a strain that pops up that is essentially so different that it requires us to mobilize tremendous resources to address that strain change,” he said.

Dr. Marks questioned the panelists’ concerns about likening flu and COVID vaccination practices. The FDA staff’s intent was to try to help the public understand the need for follow-on vaccination.

“I’m really having trouble understanding that committee’s need to bristle against something that’s similar to influenza. People understand a yearly influenza vaccine,” Dr. Marks said. 

And it’s not certain when another major change in the COVID virus will follow the XBB subvariant, but it’s likely one will – and soon, Dr. Marks said. 

“It looks like, probably by next fall, there’ll be further drift from this,” he said.
 

Informing the public 

Dr. Marks also stressed the need to better convey the benefits of vaccination to people in the United States. 

CDC data estimate that 70% of the U.S. population completed an initial series of the original monovalent vaccines, with only 17% then getting bivalent shots. There’s even a decline among people ages 65 and older. CDC estimates 94% of this group completed their primary series, but only 43% got the bivalent booster dose.

“We have to do better because we have not done a good job today communicating to the American public what’s going on here,” Marks said.

Researchers also are still trying to determine the best timing for people to get additional COVID shots. Finding the “sweet spot” where people can maximize additional protection is tricky, with people most protected if they happen to get shot near the beginning of an uptick in viral spread, the CDC’s Ruth Link-Gelles, PhD, MPH, told the panel during a presentation. 

“You’re going to get the best incremental benefit if it’s been longer since your last vaccine,” she said. “But of course, if you wait too long since your last vaccine, you’re left with very little protection, and so you’re at higher risk of severe illness.”

Like Dr. Marks, Dr. Link-Gelles stressed the need for persuading more people to get follow-on vaccines. 

“Most Americans, at this point, haven’t even received the bivalent and so are a year or more out from their monovalent dose and so have relatively little protection left,” she said.

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

A panel of advisers to the Food and Drug Administration unanimously has agreed that the next COVID-19 vaccines should target the XBB variants of the SARS-CoV-2 virus now in circulation in the United States, but questioned whether the population as a whole needs booster shots and how often they should be given.

The Vaccines and Related Biological Products Advisory Committee of the FDA voted 21-0 in favor of the recommendation about the strain to be used in the next crop of vaccines.

In the briefing document for the meeting, FDA staff said the available evidence suggests that a monovalent (single-strain) XBB-lineage vaccine “is warranted” for the 2023-2024 vaccination campaign and would replace the current bivalent vaccine, which targets the original version of the virus and two strains from the Omicron variant.

FDA staff also noted how such a shift would be in line with the World Health Organization toward targeting the XBB family of subvariants. European regulators have done this as well. 

The FDA is not obligated to act on the panel’s recommendations. But the agency often does and is highly likely to do so in this case. Vaccine companies will need the recommendation from the FDA to begin making vaccines for the fall.
 

New shot every year?

The FDA asked its expert panel to vote only on the question about the makeup of future vaccines in terms of which strain to include. 

But panelists also raised other questions during the meeting, including concerns about moves toward tying COVID vaccinations into the model of annual flu shots. 

Paul Offit, MD, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia, argued for greater focus on the response of T cells after vaccination, even in light of the already recognized waning of antibody protection. 

In a recent Substack article, Dr. Offit called T cells the “unsung hero” of the pandemic. They take longer to develop after infection or vaccination than the antibodies that first attack the virus, but immune memory cells called B and T cells “are long-lived,” and their “protection against severe disease often lasts for years and sometimes decades.”

Dr. Offit said he was concerned about using a blanket approach for future recommendations for COVID vaccinations, following the one now in place for influenza vaccines.

The Centers for Disease Control and Prevention recommends flu shots for everyone 6 months and older, with rare exceptions. 

“We need to continue to define who those high-risk groups are and not make this a recommendation for everybody every season,” he said.

Dr. Offit offered his own experience as an example. While he had been vaccinated against the virus’s early Wuhan strain, he still was infected, most likely with a variant that emerged later. 

“That was a drifted virus. That’s why I had a mild infection but I didn’t have a severe infection, because presumably I had T cells which prevented that severe infection, which may last for years,” Dr. Offit said.

Pfizer and Moderna, the two companies that make mRNA-based COVID vaccines, are working on experimental products meant to protect against both flu and SARS-COv-2 in one shot. Novavax, maker of a more traditional protein-based COVID shot, is doing the same. 

The idea of these combination products is to make it more convenient for people to protect against both viruses, while also offering companies some marketing advantages.

But without referring to these drugmakers’ plans for future combo flu-COVID shots, members of the FDA panel raised objections to an assumption of routine annual vaccines against variants of SARS-CoV-2. 

Among the panelists who expressed concerns was Henry H. Bernstein, DO, a former member of the CDC’s Advisory Committee on Immunization Practices. 

Bernstein questioned the approach of dubbing these the “2023-2024 formulas,” as this approach conveyed a sense of an expectation for a need for annual vaccines, as happens with flu. 

“It’s not clear to me that this is a seasonal virus yet,” said Dr. Bernstein, who is also a professor of pediatrics at Hofstra University, Hempstead, N.Y..

In response to Dr. Bernstein’s point, Arnold Monto, MD, the acting chair of the FDA panel, suggested such a pattern could emerge, while also agreeing that it’s too soon to say for sure.

A professor emeritus at the University of Michigan, Ann Arbor, Dr. Monto’s career included pandemic planning and emergency response to virus outbreaks, including the 1968 Hong Kong influenza pandemic, avian influenza, and the original SARS.

“I think it’s premature to say that this virus will not become seasonal,” Dr. Monto said about SARS-CoV-2. “I agree. We’re not there yet, but we may be.”

At the end of the meeting, Dr. Monto recapped the meeting’s key points, noting that there was a general consensus that the XBB.1.5 subvariant would be the best to use in future COVID shots. 

He also noted that Novavax, which makes the more traditional protein-based vaccine, along with Pfizer and Moderna, already have honed in on this subvariant, which would allow for rapid development of updated COVID vaccines.

“The fact that most of the manufacturers are ready to work on an XBB 1.5 [vaccine] is an added reason to select this strain or this variant, given the immunologic data,” Dr. Monto said. 

Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said the demands involved in manufacturing vaccines tilts toward annual changes.

“Practically, we’re going to have one update per year, barring a heroic effort to deal with a strain that pops up that is essentially so different that it requires us to mobilize tremendous resources to address that strain change,” he said.

Dr. Marks questioned the panelists’ concerns about likening flu and COVID vaccination practices. The FDA staff’s intent was to try to help the public understand the need for follow-on vaccination.

“I’m really having trouble understanding that committee’s need to bristle against something that’s similar to influenza. People understand a yearly influenza vaccine,” Dr. Marks said. 

And it’s not certain when another major change in the COVID virus will follow the XBB subvariant, but it’s likely one will – and soon, Dr. Marks said. 

“It looks like, probably by next fall, there’ll be further drift from this,” he said.
 

Informing the public 

Dr. Marks also stressed the need to better convey the benefits of vaccination to people in the United States. 

CDC data estimate that 70% of the U.S. population completed an initial series of the original monovalent vaccines, with only 17% then getting bivalent shots. There’s even a decline among people ages 65 and older. CDC estimates 94% of this group completed their primary series, but only 43% got the bivalent booster dose.

“We have to do better because we have not done a good job today communicating to the American public what’s going on here,” Marks said.

Researchers also are still trying to determine the best timing for people to get additional COVID shots. Finding the “sweet spot” where people can maximize additional protection is tricky, with people most protected if they happen to get shot near the beginning of an uptick in viral spread, the CDC’s Ruth Link-Gelles, PhD, MPH, told the panel during a presentation. 

“You’re going to get the best incremental benefit if it’s been longer since your last vaccine,” she said. “But of course, if you wait too long since your last vaccine, you’re left with very little protection, and so you’re at higher risk of severe illness.”

Like Dr. Marks, Dr. Link-Gelles stressed the need for persuading more people to get follow-on vaccines. 

“Most Americans, at this point, haven’t even received the bivalent and so are a year or more out from their monovalent dose and so have relatively little protection left,” she said.

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

MILAN – The impact of the COVID-19 pandemic on patients with rheumatic and nonrheumatic autoimmune diseases is ongoing and not yet fully comprehended. New data presented at the annual European Congress of Rheumatology, primarily derived from the global COVID-19 in Autoimmune Diseases (COVAD) survey but not limited to it, provide reassurance regarding the protection and safety of COVID-19 vaccines for older and younger adults, as well as for pregnant and breastfeeding women. These data also explore the influence of underlying diseases and medications on breakthrough SARS-CoV-2 infections and infection outcomes.

Safety of vaccines in patients with autoimmune or immune-mediated diseases

Following vaccination, even with low levels of antibodies, the risk of severe COVID-19 remains relatively low for patients who receive immunosuppressive therapy for various immune-mediated inflammatory diseases (IMIDs). This encouraging finding comes from the Nor-vaC study, presented by Hilde Ørbo, MD, of the Center for Treatment of Rheumatic and Musculoskeletal Diseases, Diakonhjemmet Hospital, Oslo.

During the presentation, Dr. Ørbo stated: “We did not find any specific diagnosis or medication associated with a significantly higher risk of hospitalization.” Receiving booster doses of the vaccine, having high levels of anti-spike antibodies after vaccination, and achieving hybrid immunity are correlated with further reductions in the risk of breakthrough SARS-CoV-2 infections.

Dr. Hilde Ørbo

Between Feb. 15, 2021, and Feb. 15, 2023, COVID-19 affected a similar proportion among the 729 patients and 350 healthy control persons (67% and 68%, respectively). Among the patients, 22 reported severe COVID-19, whereas none of the healthy control persons did. However, there were no fatalities among the patients. The study cohort consisted of patients with various IMIDs; 70% had an inflammatory joint disease. The use of immunosuppressive medications also varied, with 63% of patients using tumor necrosis factor inhibitors, either as monotherapy or in combination with other treatments, and other patients taking medications such as methotrexate, interleukin inhibitors, Janus kinase inhibitors, vedolizumab (Entyvio), and others.

While being older than 70 years and the presence of comorbidities were identified as risk factors for severe COVID-19, there was a significant reduction in risk with each additional vaccine dose. These results support the protective role of repeated COVID-19 vaccination for patients with IMIDs who are receiving immunosuppressive therapies; they yield a favorable prognosis even with the Omicron variant.

The study further compared the risk of severe COVID-19 between a group with hybrid immunity (having received three vaccine doses and experiencing breakthrough infection with the Omicron variant) and a group that received a fourth vaccine dose within the same time frame. The difference was striking: Hybrid immunity was associated with a 5.8-fold decrease in risk, compared with four-dose vaccination (P < .0001).

The level of antibodies, measured 2-4 weeks after the last vaccination, was predictive of the risk of breakthrough COVID-19. An antibody level above 6000 binding antibody units/mL after vaccination was significantly associated with a reduction in risk. “We can conclude that patients who receive multiple vaccine doses have a lower risk of COVID-19,” Dr. Ørbo said. “In patients who recently experienced breakthrough infections, the administration of a booster vaccine dose might be delayed.”

EULAR

“The virus has undergone changes throughout the pandemic, while the vaccines have remained relatively stable. Are we anticipating more infections over time?” asked Hendrik Schulze-Koops, MD, PhD, of Ludwig Maximilians University of Munich (Germany), the session moderator. In response, Dr. Ørbo stated that 85% of the recorded infections in the study occurred after the emergence of the Omicron variant, and time was considered a covariable in the analysis.

These data shed light on a topic discussed by Pedro Machado, MD, PhD, professor and consultant in rheumatology and neuromuscular diseases at University College London, during his scientific session talk entitled, “Unsolved Issues of COVID Vaccination and Re-vaccination.” Dr. Machado referred to the VROOM study published in 2022, which examined the interruption of methotrexate for 2 weeks following booster administration. Both groups demonstrated a significant antibody response, but the group that stopped taking methotrexate showed double the antibody titers.

However, he emphasized, “what remains unknown is the clinical relevance of these differences in terms of severe infection, hospitalization, or even death. The potential benefit of increased immunogenicity by interrupting conventional synthetic disease-modifying antirheumatic drugs [csDMARDs] such as methotrexate before or after vaccination needs to be balanced against the potential risk of disease flare. Ultimately, decision-making should be individualized based on factors such as comorbidities, disease activity, and other considerations.” The results presented by Dr. Ørbo suggest that, while there may be a clinical difference in terms of severe infection, the overall prognosis for vaccinated patients is reasonably good.

Regarding other DMARDs, such as biologics, the approach may differ. Dr. Machado suggested: “In patients using rituximab or other B cell–depleting therapies, SARS-CoV-2 vaccination should be scheduled in a way that optimizes vaccine immunogenicity. A minimum of 10 B cells/mcL of blood is likely a relevant threshold above which a sufficient cellular and immune response is established.”
 

COVID vaccines are safe for pregnant and breastfeeding women

According to data from the COVAD study, which comprised two global cross-sectional surveys conducted in 2021 and 2022, the COVID-19 vaccine appeared safe for pregnant and breastfeeding women with autoimmune diseases (AID).

Presenter Laura Andreoli, MD, PhD, of the University of Brescia (Italy), said that, although pregnant patients with AID reported more adverse events related to vaccination, these rates were not significantly higher than those among pregnant, healthy control persons who were without AID. No difference in adverse events was observed between breastfeeding women and healthy control persons, and the incidence of disease flares did not significantly differ among all groups.

“In summary, this study provides initial insights into the safety of COVID-19 vaccination during the gestational and postpartum periods in women with autoimmune diseases. These reassuring observations will hopefully improve clinician-patient communication and address hesitancy towards COVID-19 vaccination, as the benefits for the mother and fetus through passive immunization appear to outweigh potential risks,” Dr. Andreoli said in an interview.

“The large number of participants and the global geographical spread of the COVAD survey were very beneficial in gaining access to this important subset of patients,” added Dr. Andreoli. However, she acknowledged that patients with low socioeconomic status and/or high disability were likely underrepresented. While no data on pregnancy outcomes have been collected thus far, Dr. Andreoli expressed the desire to include them in the study’s follow-up.

The COVAD survey data also indicate that, in general, vaccine hesitancy among patients with AID is decreasing; from 2021 to 2022, it declined from 16.5% to 5.1%, as Dr. Machado indicated in his presentation.
 

Multiple factors contribute to breakthrough infections

The risk of breakthrough SARS-CoV-2 infections after vaccination varies among patients with rheumatoid arthritis and rheumatic or nonrheumatic autoimmune diseases, primarily depending on the underlying condition rather than the immunosuppressive medication. Environmental factors also appear to play a role. This complex landscape emerges from a further analysis of the COVAD survey dataset.

Alessia Alunno, MD, PhD, of the University of L’Aquila (Italy), presented a detailed and occasionally counterintuitive picture of similarities and differences among young adult patients (aged 18-35 years), mostly women, with various rheumatic and nonrheumatic diseases in relation to COVID-19. Most notably, the type of disease seemed to have more significance than the immunosuppression resulting from the treatment regimen. This held true for vaccine safety as well as for the risk of breakthrough COVID-19 and symptom profiles.

Patients with rheumatic disease (RMD) and nonrheumatic autoimmune disease (nr-AD) had significantly different therapeutic profiles on average. Before vaccination, 45% of patients with RMD used glucocorticoids (GC), and 91% used immunosuppressants (IS). In contrast, only 9.5% of nr-AD patients used GC, and 21% were taking IS.

Interestingly, the overall prevalence of reported SARS-CoV-2 infections was not influenced by medication and was practically identical (25% to 28%) across all groups. However, there were intriguing differences in the occurrence of infections before and after vaccination between disease groups. Prevaccine infections were less frequent among patients with RMD compared with healthy control persons (adjusted odds ratio, 0.6), while the rates were similar among patients with nr-AD and healthy control persons. On the other hand, breakthrough infections were more frequent in patients with RMD (aOR, 2.7), whereas the rate was similar between healthy control persons and patients with nr-AD.

Despite a much lower rate of GC/IS use, patients with nr-AD experienced repeated infections more frequently. In contrast, patients with RMD were less prone to multiple infections, even compared with healthy control persons (aOR, 0.5).

Regarding the disease profile, fewer than 5% of all infected patients required advanced therapies for SARS-CoV-2 infection. Notably, all SARS-CoV-2 infections in patients with nr-AD were symptomatic, whereas among patients with RMD and healthy control persons, the incidence of asymptomatic infections was 3%. The rate of hospital admissions was 4% for patients with RMD, compared with 2% for patients with nr-AD and 1% for control persons. The RMD group exhibited some differences between prevaccine infections and breakthrough infections, including a significantly lower frequency of loss of smell and taste during breakthrough infections. Overall, patients with RMD and COVID-19 experienced cough, runny nose, throat pain, nausea, and vomiting more frequently. In contrast, patients with nr-AD had a much higher risk of skin rashes during breakthrough infections (aOR, 8.7).

Vaccine adverse events (AEs) were also influenced by the underlying disease. Patients with RMD and those with nr-AD were more likely to experience mild AEs after the first or second dose, compared with healthy control persons (adjusted OR, 2.4 and 2.0, respectively). The most common early, mild AEs across all groups were injection-site pain, headache, and fatigue, but they occurred more frequently in the nr-AD group than in the RMD or healthy control group. Additionally, fever and chills occurred more frequently among the nr-AD group. Late, mild AEs and severe AEs were rare and affected all groups equally.

“The overall incidence of AEs was very low. Our results certainly do not undermine the safety of vaccines,” Dr. Alunno said.

Disease flares were more common after vaccination (10% with RMD and 7% with nr-AD) than after infection (5% with RMD and 1.5% with nr-AD). Furthermore, in many cases, after vaccination, flares required a change of medications, particularly for patients with RMD.

Dr. Naveen Ravichandran

Additional results from the COVAD survey from January to July 2022, presented by Naveen Ravichandran, MD, DM, of Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India, revealed a higher prevalence (OR, 1.2; P = .001) of breakthrough infections among patients with RA. A total of 22.6% of patients with RA experienced breakthrough infections, compared with 20.6% for patients with other autoimmune rheumatic diseases and 18.4% of healthy control persons. Hospitalizations and the need for advanced treatment were also more common among patients with RA (30.9%) than among healthy control persons (13.9%). Patients with RA who had breakthrough infections tended to be older (closer to 50 years of age on average) and female, and they were more likely to have comorbidities and mental disorders. The human development index of the patient’s country of residence also played a role. Further research is necessary to understand how breakthrough infection outcomes are affected by a patient’s socioeconomic situation.

According to Dr. Ravichandran, medication was not a significant factor, except for the use of steroids and rituximab, which were associated with a higher risk of severe COVID-19 and hospitalization. Patients using rituximab, in particular, faced significantly increased odds for hospitalization (OR, 3.4) and severe breakthrough COVID-19 (OR, 3.0).

Session moderator Kim Lauper, MD, of the University of Geneva, cautioned: “The roles of disease and medication are challenging to separate. Some diseases require a more aggressive immunosuppressive regimen. It’s possible that different diseases affect the immune system differently, but it is not easy to demonstrate.”

The complications observed in the data warrant further study, as mentioned by Dr. Schulze-Koops: “We have a problem tied to the time line of the pandemic, where we had different viruses, different population behaviors, different treatments, and different standards of care over time. We also have differences between ethnic communities and regions of the world. But most importantly, we have different viruses: From the original strain to Delta to Omicron, we know they have very different clinical outcomes. I believe we need more scientific research to unravel these factors.”

Dr. Ørbo, Dr. Ravichandran, Dr. Andreoli, and Dr. Alunno reported no relevant financial relationships. Dr. Machado has received grants and/or honoraria from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Janssen, Merck Sharp & Dohme, Novartis, Orphazyme, Pfizer, Roche, and UCB.

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

MILAN – The impact of the COVID-19 pandemic on patients with rheumatic and nonrheumatic autoimmune diseases is ongoing and not yet fully comprehended. New data presented at the annual European Congress of Rheumatology, primarily derived from the global COVID-19 in Autoimmune Diseases (COVAD) survey but not limited to it, provide reassurance regarding the protection and safety of COVID-19 vaccines for older and younger adults, as well as for pregnant and breastfeeding women. These data also explore the influence of underlying diseases and medications on breakthrough SARS-CoV-2 infections and infection outcomes.

Safety of vaccines in patients with autoimmune or immune-mediated diseases

Following vaccination, even with low levels of antibodies, the risk of severe COVID-19 remains relatively low for patients who receive immunosuppressive therapy for various immune-mediated inflammatory diseases (IMIDs). This encouraging finding comes from the Nor-vaC study, presented by Hilde Ørbo, MD, of the Center for Treatment of Rheumatic and Musculoskeletal Diseases, Diakonhjemmet Hospital, Oslo.

During the presentation, Dr. Ørbo stated: “We did not find any specific diagnosis or medication associated with a significantly higher risk of hospitalization.” Receiving booster doses of the vaccine, having high levels of anti-spike antibodies after vaccination, and achieving hybrid immunity are correlated with further reductions in the risk of breakthrough SARS-CoV-2 infections.

Dr. Hilde Ørbo

Between Feb. 15, 2021, and Feb. 15, 2023, COVID-19 affected a similar proportion among the 729 patients and 350 healthy control persons (67% and 68%, respectively). Among the patients, 22 reported severe COVID-19, whereas none of the healthy control persons did. However, there were no fatalities among the patients. The study cohort consisted of patients with various IMIDs; 70% had an inflammatory joint disease. The use of immunosuppressive medications also varied, with 63% of patients using tumor necrosis factor inhibitors, either as monotherapy or in combination with other treatments, and other patients taking medications such as methotrexate, interleukin inhibitors, Janus kinase inhibitors, vedolizumab (Entyvio), and others.

While being older than 70 years and the presence of comorbidities were identified as risk factors for severe COVID-19, there was a significant reduction in risk with each additional vaccine dose. These results support the protective role of repeated COVID-19 vaccination for patients with IMIDs who are receiving immunosuppressive therapies; they yield a favorable prognosis even with the Omicron variant.

The study further compared the risk of severe COVID-19 between a group with hybrid immunity (having received three vaccine doses and experiencing breakthrough infection with the Omicron variant) and a group that received a fourth vaccine dose within the same time frame. The difference was striking: Hybrid immunity was associated with a 5.8-fold decrease in risk, compared with four-dose vaccination (P < .0001).

The level of antibodies, measured 2-4 weeks after the last vaccination, was predictive of the risk of breakthrough COVID-19. An antibody level above 6000 binding antibody units/mL after vaccination was significantly associated with a reduction in risk. “We can conclude that patients who receive multiple vaccine doses have a lower risk of COVID-19,” Dr. Ørbo said. “In patients who recently experienced breakthrough infections, the administration of a booster vaccine dose might be delayed.”

EULAR

“The virus has undergone changes throughout the pandemic, while the vaccines have remained relatively stable. Are we anticipating more infections over time?” asked Hendrik Schulze-Koops, MD, PhD, of Ludwig Maximilians University of Munich (Germany), the session moderator. In response, Dr. Ørbo stated that 85% of the recorded infections in the study occurred after the emergence of the Omicron variant, and time was considered a covariable in the analysis.

These data shed light on a topic discussed by Pedro Machado, MD, PhD, professor and consultant in rheumatology and neuromuscular diseases at University College London, during his scientific session talk entitled, “Unsolved Issues of COVID Vaccination and Re-vaccination.” Dr. Machado referred to the VROOM study published in 2022, which examined the interruption of methotrexate for 2 weeks following booster administration. Both groups demonstrated a significant antibody response, but the group that stopped taking methotrexate showed double the antibody titers.

However, he emphasized, “what remains unknown is the clinical relevance of these differences in terms of severe infection, hospitalization, or even death. The potential benefit of increased immunogenicity by interrupting conventional synthetic disease-modifying antirheumatic drugs [csDMARDs] such as methotrexate before or after vaccination needs to be balanced against the potential risk of disease flare. Ultimately, decision-making should be individualized based on factors such as comorbidities, disease activity, and other considerations.” The results presented by Dr. Ørbo suggest that, while there may be a clinical difference in terms of severe infection, the overall prognosis for vaccinated patients is reasonably good.

Regarding other DMARDs, such as biologics, the approach may differ. Dr. Machado suggested: “In patients using rituximab or other B cell–depleting therapies, SARS-CoV-2 vaccination should be scheduled in a way that optimizes vaccine immunogenicity. A minimum of 10 B cells/mcL of blood is likely a relevant threshold above which a sufficient cellular and immune response is established.”
 

COVID vaccines are safe for pregnant and breastfeeding women

According to data from the COVAD study, which comprised two global cross-sectional surveys conducted in 2021 and 2022, the COVID-19 vaccine appeared safe for pregnant and breastfeeding women with autoimmune diseases (AID).

Presenter Laura Andreoli, MD, PhD, of the University of Brescia (Italy), said that, although pregnant patients with AID reported more adverse events related to vaccination, these rates were not significantly higher than those among pregnant, healthy control persons who were without AID. No difference in adverse events was observed between breastfeeding women and healthy control persons, and the incidence of disease flares did not significantly differ among all groups.

“In summary, this study provides initial insights into the safety of COVID-19 vaccination during the gestational and postpartum periods in women with autoimmune diseases. These reassuring observations will hopefully improve clinician-patient communication and address hesitancy towards COVID-19 vaccination, as the benefits for the mother and fetus through passive immunization appear to outweigh potential risks,” Dr. Andreoli said in an interview.

“The large number of participants and the global geographical spread of the COVAD survey were very beneficial in gaining access to this important subset of patients,” added Dr. Andreoli. However, she acknowledged that patients with low socioeconomic status and/or high disability were likely underrepresented. While no data on pregnancy outcomes have been collected thus far, Dr. Andreoli expressed the desire to include them in the study’s follow-up.

The COVAD survey data also indicate that, in general, vaccine hesitancy among patients with AID is decreasing; from 2021 to 2022, it declined from 16.5% to 5.1%, as Dr. Machado indicated in his presentation.
 

Multiple factors contribute to breakthrough infections

The risk of breakthrough SARS-CoV-2 infections after vaccination varies among patients with rheumatoid arthritis and rheumatic or nonrheumatic autoimmune diseases, primarily depending on the underlying condition rather than the immunosuppressive medication. Environmental factors also appear to play a role. This complex landscape emerges from a further analysis of the COVAD survey dataset.

Alessia Alunno, MD, PhD, of the University of L’Aquila (Italy), presented a detailed and occasionally counterintuitive picture of similarities and differences among young adult patients (aged 18-35 years), mostly women, with various rheumatic and nonrheumatic diseases in relation to COVID-19. Most notably, the type of disease seemed to have more significance than the immunosuppression resulting from the treatment regimen. This held true for vaccine safety as well as for the risk of breakthrough COVID-19 and symptom profiles.

Patients with rheumatic disease (RMD) and nonrheumatic autoimmune disease (nr-AD) had significantly different therapeutic profiles on average. Before vaccination, 45% of patients with RMD used glucocorticoids (GC), and 91% used immunosuppressants (IS). In contrast, only 9.5% of nr-AD patients used GC, and 21% were taking IS.

Interestingly, the overall prevalence of reported SARS-CoV-2 infections was not influenced by medication and was practically identical (25% to 28%) across all groups. However, there were intriguing differences in the occurrence of infections before and after vaccination between disease groups. Prevaccine infections were less frequent among patients with RMD compared with healthy control persons (adjusted odds ratio, 0.6), while the rates were similar among patients with nr-AD and healthy control persons. On the other hand, breakthrough infections were more frequent in patients with RMD (aOR, 2.7), whereas the rate was similar between healthy control persons and patients with nr-AD.

Despite a much lower rate of GC/IS use, patients with nr-AD experienced repeated infections more frequently. In contrast, patients with RMD were less prone to multiple infections, even compared with healthy control persons (aOR, 0.5).

Regarding the disease profile, fewer than 5% of all infected patients required advanced therapies for SARS-CoV-2 infection. Notably, all SARS-CoV-2 infections in patients with nr-AD were symptomatic, whereas among patients with RMD and healthy control persons, the incidence of asymptomatic infections was 3%. The rate of hospital admissions was 4% for patients with RMD, compared with 2% for patients with nr-AD and 1% for control persons. The RMD group exhibited some differences between prevaccine infections and breakthrough infections, including a significantly lower frequency of loss of smell and taste during breakthrough infections. Overall, patients with RMD and COVID-19 experienced cough, runny nose, throat pain, nausea, and vomiting more frequently. In contrast, patients with nr-AD had a much higher risk of skin rashes during breakthrough infections (aOR, 8.7).

Vaccine adverse events (AEs) were also influenced by the underlying disease. Patients with RMD and those with nr-AD were more likely to experience mild AEs after the first or second dose, compared with healthy control persons (adjusted OR, 2.4 and 2.0, respectively). The most common early, mild AEs across all groups were injection-site pain, headache, and fatigue, but they occurred more frequently in the nr-AD group than in the RMD or healthy control group. Additionally, fever and chills occurred more frequently among the nr-AD group. Late, mild AEs and severe AEs were rare and affected all groups equally.

“The overall incidence of AEs was very low. Our results certainly do not undermine the safety of vaccines,” Dr. Alunno said.

Disease flares were more common after vaccination (10% with RMD and 7% with nr-AD) than after infection (5% with RMD and 1.5% with nr-AD). Furthermore, in many cases, after vaccination, flares required a change of medications, particularly for patients with RMD.

Dr. Naveen Ravichandran

Additional results from the COVAD survey from January to July 2022, presented by Naveen Ravichandran, MD, DM, of Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India, revealed a higher prevalence (OR, 1.2; P = .001) of breakthrough infections among patients with RA. A total of 22.6% of patients with RA experienced breakthrough infections, compared with 20.6% for patients with other autoimmune rheumatic diseases and 18.4% of healthy control persons. Hospitalizations and the need for advanced treatment were also more common among patients with RA (30.9%) than among healthy control persons (13.9%). Patients with RA who had breakthrough infections tended to be older (closer to 50 years of age on average) and female, and they were more likely to have comorbidities and mental disorders. The human development index of the patient’s country of residence also played a role. Further research is necessary to understand how breakthrough infection outcomes are affected by a patient’s socioeconomic situation.

According to Dr. Ravichandran, medication was not a significant factor, except for the use of steroids and rituximab, which were associated with a higher risk of severe COVID-19 and hospitalization. Patients using rituximab, in particular, faced significantly increased odds for hospitalization (OR, 3.4) and severe breakthrough COVID-19 (OR, 3.0).

Session moderator Kim Lauper, MD, of the University of Geneva, cautioned: “The roles of disease and medication are challenging to separate. Some diseases require a more aggressive immunosuppressive regimen. It’s possible that different diseases affect the immune system differently, but it is not easy to demonstrate.”

The complications observed in the data warrant further study, as mentioned by Dr. Schulze-Koops: “We have a problem tied to the time line of the pandemic, where we had different viruses, different population behaviors, different treatments, and different standards of care over time. We also have differences between ethnic communities and regions of the world. But most importantly, we have different viruses: From the original strain to Delta to Omicron, we know they have very different clinical outcomes. I believe we need more scientific research to unravel these factors.”

Dr. Ørbo, Dr. Ravichandran, Dr. Andreoli, and Dr. Alunno reported no relevant financial relationships. Dr. Machado has received grants and/or honoraria from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Janssen, Merck Sharp & Dohme, Novartis, Orphazyme, Pfizer, Roche, and UCB.

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

MILAN – The impact of the COVID-19 pandemic on patients with rheumatic and nonrheumatic autoimmune diseases is ongoing and not yet fully comprehended. New data presented at the annual European Congress of Rheumatology, primarily derived from the global COVID-19 in Autoimmune Diseases (COVAD) survey but not limited to it, provide reassurance regarding the protection and safety of COVID-19 vaccines for older and younger adults, as well as for pregnant and breastfeeding women. These data also explore the influence of underlying diseases and medications on breakthrough SARS-CoV-2 infections and infection outcomes.

Safety of vaccines in patients with autoimmune or immune-mediated diseases

Following vaccination, even with low levels of antibodies, the risk of severe COVID-19 remains relatively low for patients who receive immunosuppressive therapy for various immune-mediated inflammatory diseases (IMIDs). This encouraging finding comes from the Nor-vaC study, presented by Hilde Ørbo, MD, of the Center for Treatment of Rheumatic and Musculoskeletal Diseases, Diakonhjemmet Hospital, Oslo.

During the presentation, Dr. Ørbo stated: “We did not find any specific diagnosis or medication associated with a significantly higher risk of hospitalization.” Receiving booster doses of the vaccine, having high levels of anti-spike antibodies after vaccination, and achieving hybrid immunity are correlated with further reductions in the risk of breakthrough SARS-CoV-2 infections.

Dr. Hilde Ørbo

Between Feb. 15, 2021, and Feb. 15, 2023, COVID-19 affected a similar proportion among the 729 patients and 350 healthy control persons (67% and 68%, respectively). Among the patients, 22 reported severe COVID-19, whereas none of the healthy control persons did. However, there were no fatalities among the patients. The study cohort consisted of patients with various IMIDs; 70% had an inflammatory joint disease. The use of immunosuppressive medications also varied, with 63% of patients using tumor necrosis factor inhibitors, either as monotherapy or in combination with other treatments, and other patients taking medications such as methotrexate, interleukin inhibitors, Janus kinase inhibitors, vedolizumab (Entyvio), and others.

While being older than 70 years and the presence of comorbidities were identified as risk factors for severe COVID-19, there was a significant reduction in risk with each additional vaccine dose. These results support the protective role of repeated COVID-19 vaccination for patients with IMIDs who are receiving immunosuppressive therapies; they yield a favorable prognosis even with the Omicron variant.

The study further compared the risk of severe COVID-19 between a group with hybrid immunity (having received three vaccine doses and experiencing breakthrough infection with the Omicron variant) and a group that received a fourth vaccine dose within the same time frame. The difference was striking: Hybrid immunity was associated with a 5.8-fold decrease in risk, compared with four-dose vaccination (P < .0001).

The level of antibodies, measured 2-4 weeks after the last vaccination, was predictive of the risk of breakthrough COVID-19. An antibody level above 6000 binding antibody units/mL after vaccination was significantly associated with a reduction in risk. “We can conclude that patients who receive multiple vaccine doses have a lower risk of COVID-19,” Dr. Ørbo said. “In patients who recently experienced breakthrough infections, the administration of a booster vaccine dose might be delayed.”

EULAR

“The virus has undergone changes throughout the pandemic, while the vaccines have remained relatively stable. Are we anticipating more infections over time?” asked Hendrik Schulze-Koops, MD, PhD, of Ludwig Maximilians University of Munich (Germany), the session moderator. In response, Dr. Ørbo stated that 85% of the recorded infections in the study occurred after the emergence of the Omicron variant, and time was considered a covariable in the analysis.

These data shed light on a topic discussed by Pedro Machado, MD, PhD, professor and consultant in rheumatology and neuromuscular diseases at University College London, during his scientific session talk entitled, “Unsolved Issues of COVID Vaccination and Re-vaccination.” Dr. Machado referred to the VROOM study published in 2022, which examined the interruption of methotrexate for 2 weeks following booster administration. Both groups demonstrated a significant antibody response, but the group that stopped taking methotrexate showed double the antibody titers.

However, he emphasized, “what remains unknown is the clinical relevance of these differences in terms of severe infection, hospitalization, or even death. The potential benefit of increased immunogenicity by interrupting conventional synthetic disease-modifying antirheumatic drugs [csDMARDs] such as methotrexate before or after vaccination needs to be balanced against the potential risk of disease flare. Ultimately, decision-making should be individualized based on factors such as comorbidities, disease activity, and other considerations.” The results presented by Dr. Ørbo suggest that, while there may be a clinical difference in terms of severe infection, the overall prognosis for vaccinated patients is reasonably good.

Regarding other DMARDs, such as biologics, the approach may differ. Dr. Machado suggested: “In patients using rituximab or other B cell–depleting therapies, SARS-CoV-2 vaccination should be scheduled in a way that optimizes vaccine immunogenicity. A minimum of 10 B cells/mcL of blood is likely a relevant threshold above which a sufficient cellular and immune response is established.”
 

COVID vaccines are safe for pregnant and breastfeeding women

According to data from the COVAD study, which comprised two global cross-sectional surveys conducted in 2021 and 2022, the COVID-19 vaccine appeared safe for pregnant and breastfeeding women with autoimmune diseases (AID).

Presenter Laura Andreoli, MD, PhD, of the University of Brescia (Italy), said that, although pregnant patients with AID reported more adverse events related to vaccination, these rates were not significantly higher than those among pregnant, healthy control persons who were without AID. No difference in adverse events was observed between breastfeeding women and healthy control persons, and the incidence of disease flares did not significantly differ among all groups.

“In summary, this study provides initial insights into the safety of COVID-19 vaccination during the gestational and postpartum periods in women with autoimmune diseases. These reassuring observations will hopefully improve clinician-patient communication and address hesitancy towards COVID-19 vaccination, as the benefits for the mother and fetus through passive immunization appear to outweigh potential risks,” Dr. Andreoli said in an interview.

“The large number of participants and the global geographical spread of the COVAD survey were very beneficial in gaining access to this important subset of patients,” added Dr. Andreoli. However, she acknowledged that patients with low socioeconomic status and/or high disability were likely underrepresented. While no data on pregnancy outcomes have been collected thus far, Dr. Andreoli expressed the desire to include them in the study’s follow-up.

The COVAD survey data also indicate that, in general, vaccine hesitancy among patients with AID is decreasing; from 2021 to 2022, it declined from 16.5% to 5.1%, as Dr. Machado indicated in his presentation.
 

Multiple factors contribute to breakthrough infections

The risk of breakthrough SARS-CoV-2 infections after vaccination varies among patients with rheumatoid arthritis and rheumatic or nonrheumatic autoimmune diseases, primarily depending on the underlying condition rather than the immunosuppressive medication. Environmental factors also appear to play a role. This complex landscape emerges from a further analysis of the COVAD survey dataset.

Alessia Alunno, MD, PhD, of the University of L’Aquila (Italy), presented a detailed and occasionally counterintuitive picture of similarities and differences among young adult patients (aged 18-35 years), mostly women, with various rheumatic and nonrheumatic diseases in relation to COVID-19. Most notably, the type of disease seemed to have more significance than the immunosuppression resulting from the treatment regimen. This held true for vaccine safety as well as for the risk of breakthrough COVID-19 and symptom profiles.

Patients with rheumatic disease (RMD) and nonrheumatic autoimmune disease (nr-AD) had significantly different therapeutic profiles on average. Before vaccination, 45% of patients with RMD used glucocorticoids (GC), and 91% used immunosuppressants (IS). In contrast, only 9.5% of nr-AD patients used GC, and 21% were taking IS.

Interestingly, the overall prevalence of reported SARS-CoV-2 infections was not influenced by medication and was practically identical (25% to 28%) across all groups. However, there were intriguing differences in the occurrence of infections before and after vaccination between disease groups. Prevaccine infections were less frequent among patients with RMD compared with healthy control persons (adjusted odds ratio, 0.6), while the rates were similar among patients with nr-AD and healthy control persons. On the other hand, breakthrough infections were more frequent in patients with RMD (aOR, 2.7), whereas the rate was similar between healthy control persons and patients with nr-AD.

Despite a much lower rate of GC/IS use, patients with nr-AD experienced repeated infections more frequently. In contrast, patients with RMD were less prone to multiple infections, even compared with healthy control persons (aOR, 0.5).

Regarding the disease profile, fewer than 5% of all infected patients required advanced therapies for SARS-CoV-2 infection. Notably, all SARS-CoV-2 infections in patients with nr-AD were symptomatic, whereas among patients with RMD and healthy control persons, the incidence of asymptomatic infections was 3%. The rate of hospital admissions was 4% for patients with RMD, compared with 2% for patients with nr-AD and 1% for control persons. The RMD group exhibited some differences between prevaccine infections and breakthrough infections, including a significantly lower frequency of loss of smell and taste during breakthrough infections. Overall, patients with RMD and COVID-19 experienced cough, runny nose, throat pain, nausea, and vomiting more frequently. In contrast, patients with nr-AD had a much higher risk of skin rashes during breakthrough infections (aOR, 8.7).

Vaccine adverse events (AEs) were also influenced by the underlying disease. Patients with RMD and those with nr-AD were more likely to experience mild AEs after the first or second dose, compared with healthy control persons (adjusted OR, 2.4 and 2.0, respectively). The most common early, mild AEs across all groups were injection-site pain, headache, and fatigue, but they occurred more frequently in the nr-AD group than in the RMD or healthy control group. Additionally, fever and chills occurred more frequently among the nr-AD group. Late, mild AEs and severe AEs were rare and affected all groups equally.

“The overall incidence of AEs was very low. Our results certainly do not undermine the safety of vaccines,” Dr. Alunno said.

Disease flares were more common after vaccination (10% with RMD and 7% with nr-AD) than after infection (5% with RMD and 1.5% with nr-AD). Furthermore, in many cases, after vaccination, flares required a change of medications, particularly for patients with RMD.

Dr. Naveen Ravichandran

Additional results from the COVAD survey from January to July 2022, presented by Naveen Ravichandran, MD, DM, of Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India, revealed a higher prevalence (OR, 1.2; P = .001) of breakthrough infections among patients with RA. A total of 22.6% of patients with RA experienced breakthrough infections, compared with 20.6% for patients with other autoimmune rheumatic diseases and 18.4% of healthy control persons. Hospitalizations and the need for advanced treatment were also more common among patients with RA (30.9%) than among healthy control persons (13.9%). Patients with RA who had breakthrough infections tended to be older (closer to 50 years of age on average) and female, and they were more likely to have comorbidities and mental disorders. The human development index of the patient’s country of residence also played a role. Further research is necessary to understand how breakthrough infection outcomes are affected by a patient’s socioeconomic situation.

According to Dr. Ravichandran, medication was not a significant factor, except for the use of steroids and rituximab, which were associated with a higher risk of severe COVID-19 and hospitalization. Patients using rituximab, in particular, faced significantly increased odds for hospitalization (OR, 3.4) and severe breakthrough COVID-19 (OR, 3.0).

Session moderator Kim Lauper, MD, of the University of Geneva, cautioned: “The roles of disease and medication are challenging to separate. Some diseases require a more aggressive immunosuppressive regimen. It’s possible that different diseases affect the immune system differently, but it is not easy to demonstrate.”

The complications observed in the data warrant further study, as mentioned by Dr. Schulze-Koops: “We have a problem tied to the time line of the pandemic, where we had different viruses, different population behaviors, different treatments, and different standards of care over time. We also have differences between ethnic communities and regions of the world. But most importantly, we have different viruses: From the original strain to Delta to Omicron, we know they have very different clinical outcomes. I believe we need more scientific research to unravel these factors.”

Dr. Ørbo, Dr. Ravichandran, Dr. Andreoli, and Dr. Alunno reported no relevant financial relationships. Dr. Machado has received grants and/or honoraria from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Janssen, Merck Sharp & Dohme, Novartis, Orphazyme, Pfizer, Roche, and UCB.

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

Millions of Americans who were infected with COVID-19 still have not fully recovered their sense of taste or smell, a new report says.

Almost 36 million people were diagnosed in 2021, and 60% of them reported accompanying losses in smell or taste, according to the study by Mass Eye and Ear, which is affiliated with Harvard Medical School, Boston. The study was published in The Laryngoscope.

Most people fully regained the senses, but about 24% didn’t get smell back completely, and more than 3% had no recovery, the researchers reported. The numbers were similar among those who lost the sense of taste, they added.

“Many people never fully recovered,” Neil Bhattacharyya, MD, professor of otolaryngology and one of the study’s authors, told Fortune, estimating that up to 6 million people still have lingering symptoms. “If you lost your sense of smell, did you get it back? There’s about a one in four chance you didn’t. That’s terrible.”

Researchers looked at the records of 30,000 adults who had COVID-19 in 2021. They reported that patients who suffered more severe cases were less likely to regain some or all their senses.

Some patients said they lost appetite because they couldn’t smell food. There’s concern, too, about losing the ability to smell gas and smoke, spoiled food, and dirty diapers.

People with symptoms should see their doctors, Dr. Bhattacharyya said. The symptoms might be caused by something other than lingering COVID-19 effects and might be treatable.
 

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

Millions of Americans who were infected with COVID-19 still have not fully recovered their sense of taste or smell, a new report says.

Almost 36 million people were diagnosed in 2021, and 60% of them reported accompanying losses in smell or taste, according to the study by Mass Eye and Ear, which is affiliated with Harvard Medical School, Boston. The study was published in The Laryngoscope.

Most people fully regained the senses, but about 24% didn’t get smell back completely, and more than 3% had no recovery, the researchers reported. The numbers were similar among those who lost the sense of taste, they added.

“Many people never fully recovered,” Neil Bhattacharyya, MD, professor of otolaryngology and one of the study’s authors, told Fortune, estimating that up to 6 million people still have lingering symptoms. “If you lost your sense of smell, did you get it back? There’s about a one in four chance you didn’t. That’s terrible.”

Researchers looked at the records of 30,000 adults who had COVID-19 in 2021. They reported that patients who suffered more severe cases were less likely to regain some or all their senses.

Some patients said they lost appetite because they couldn’t smell food. There’s concern, too, about losing the ability to smell gas and smoke, spoiled food, and dirty diapers.

People with symptoms should see their doctors, Dr. Bhattacharyya said. The symptoms might be caused by something other than lingering COVID-19 effects and might be treatable.
 

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

Millions of Americans who were infected with COVID-19 still have not fully recovered their sense of taste or smell, a new report says.

Almost 36 million people were diagnosed in 2021, and 60% of them reported accompanying losses in smell or taste, according to the study by Mass Eye and Ear, which is affiliated with Harvard Medical School, Boston. The study was published in The Laryngoscope.

Most people fully regained the senses, but about 24% didn’t get smell back completely, and more than 3% had no recovery, the researchers reported. The numbers were similar among those who lost the sense of taste, they added.

“Many people never fully recovered,” Neil Bhattacharyya, MD, professor of otolaryngology and one of the study’s authors, told Fortune, estimating that up to 6 million people still have lingering symptoms. “If you lost your sense of smell, did you get it back? There’s about a one in four chance you didn’t. That’s terrible.”

Researchers looked at the records of 30,000 adults who had COVID-19 in 2021. They reported that patients who suffered more severe cases were less likely to regain some or all their senses.

Some patients said they lost appetite because they couldn’t smell food. There’s concern, too, about losing the ability to smell gas and smoke, spoiled food, and dirty diapers.

People with symptoms should see their doctors, Dr. Bhattacharyya said. The symptoms might be caused by something other than lingering COVID-19 effects and might be treatable.
 

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

Scientists think that a person in Ohio who has been infected with COVID-19 for 2 years is shedding thousands of times more of the virus than normal, according to wastewater monitoring data. The strain of the virus appears to be unique, the researchers said. 

The mutated version of the virus was discovered by a team of researchers, led by University of Missouri–Columbia virologist Marc Johnson, PhD, that has been studying standalone mutations identified in wastewater. On Twitter, Dr. Johnson said their work could help warn people of a potential risk.

“If you knew of an exposure of a group of people to a deadly disease, there would be an obligation to inform them,” he wrote.

He believes the infected person lives in Columbus, works at a courthouse in a nearby county, and has gut health problems. The county where the person works has a population of just 15,000 people but had record COVID wastewater levels in May, The Columbus Dispatch reported. The unique COVID strain that Dr. Johnson is researching was the only COVID strain found in Fayette County’s wastewater.

“This person was shedding thousands of times more material than a normal person ever would,” Dr. Johnson told the Dispatch. “I think this person isn’t well. ... I’m guessing they have GI issues.”

Monitoring wastewater for COVID-19 is only used to inform public health officials of community levels and spread of the virus. People with COVID are not tracked down using such information.

The Centers for Disease Control and Prevention told the Dispatch that the findings do not mean there’s a public health threat.

“Unusual or ‘cryptic’ sequences identified in wastewater may represent viruses that can replicate in particular individuals, but not in the general population,” the CDC wrote in a statement to the newspaper. “This can be because of a compromised immune system. CDC and other institutions conduct studies in immunocompromised individuals to understand persistent infection and virus evolution.”

Ohio health officials told the newspaper that they don’t consider the situation a public health threat because the cryptic strain hasn’t spread beyond two sewer sheds for those 2  years.

Dr. Johnson and colleagues have been researching other unique COVID strains found in wastewater. They wrote a paper about a case in Wisconsin currently in preprint.

In the paper, the researchers suggest some people are persistently infected, calling them “prolonged shedders.” The researchers wrote that prolonged shedders could be human or “nonhuman,” and that “increased global monitoring of such lineages in wastewater could help anticipate future circulating mutations and/or variants of concern.”

Earlier in 2023, the CDC announced it was ending its community-level reporting of COVID test data and would rely more heavily on hospitalization reports and wastewater monitoring. COVID hospitalizations dipped to 7,212 nationally for the week of June 1-8, which is a 6% decline from the week prior, according to the CDC. That number of hospitalizations equals about two hospitalizations per 100,000 people.

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

Scientists think that a person in Ohio who has been infected with COVID-19 for 2 years is shedding thousands of times more of the virus than normal, according to wastewater monitoring data. The strain of the virus appears to be unique, the researchers said. 

The mutated version of the virus was discovered by a team of researchers, led by University of Missouri–Columbia virologist Marc Johnson, PhD, that has been studying standalone mutations identified in wastewater. On Twitter, Dr. Johnson said their work could help warn people of a potential risk.

“If you knew of an exposure of a group of people to a deadly disease, there would be an obligation to inform them,” he wrote.

He believes the infected person lives in Columbus, works at a courthouse in a nearby county, and has gut health problems. The county where the person works has a population of just 15,000 people but had record COVID wastewater levels in May, The Columbus Dispatch reported. The unique COVID strain that Dr. Johnson is researching was the only COVID strain found in Fayette County’s wastewater.

“This person was shedding thousands of times more material than a normal person ever would,” Dr. Johnson told the Dispatch. “I think this person isn’t well. ... I’m guessing they have GI issues.”

Monitoring wastewater for COVID-19 is only used to inform public health officials of community levels and spread of the virus. People with COVID are not tracked down using such information.

The Centers for Disease Control and Prevention told the Dispatch that the findings do not mean there’s a public health threat.

“Unusual or ‘cryptic’ sequences identified in wastewater may represent viruses that can replicate in particular individuals, but not in the general population,” the CDC wrote in a statement to the newspaper. “This can be because of a compromised immune system. CDC and other institutions conduct studies in immunocompromised individuals to understand persistent infection and virus evolution.”

Ohio health officials told the newspaper that they don’t consider the situation a public health threat because the cryptic strain hasn’t spread beyond two sewer sheds for those 2  years.

Dr. Johnson and colleagues have been researching other unique COVID strains found in wastewater. They wrote a paper about a case in Wisconsin currently in preprint.

In the paper, the researchers suggest some people are persistently infected, calling them “prolonged shedders.” The researchers wrote that prolonged shedders could be human or “nonhuman,” and that “increased global monitoring of such lineages in wastewater could help anticipate future circulating mutations and/or variants of concern.”

Earlier in 2023, the CDC announced it was ending its community-level reporting of COVID test data and would rely more heavily on hospitalization reports and wastewater monitoring. COVID hospitalizations dipped to 7,212 nationally for the week of June 1-8, which is a 6% decline from the week prior, according to the CDC. That number of hospitalizations equals about two hospitalizations per 100,000 people.

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

Scientists think that a person in Ohio who has been infected with COVID-19 for 2 years is shedding thousands of times more of the virus than normal, according to wastewater monitoring data. The strain of the virus appears to be unique, the researchers said. 

The mutated version of the virus was discovered by a team of researchers, led by University of Missouri–Columbia virologist Marc Johnson, PhD, that has been studying standalone mutations identified in wastewater. On Twitter, Dr. Johnson said their work could help warn people of a potential risk.

“If you knew of an exposure of a group of people to a deadly disease, there would be an obligation to inform them,” he wrote.

He believes the infected person lives in Columbus, works at a courthouse in a nearby county, and has gut health problems. The county where the person works has a population of just 15,000 people but had record COVID wastewater levels in May, The Columbus Dispatch reported. The unique COVID strain that Dr. Johnson is researching was the only COVID strain found in Fayette County’s wastewater.

“This person was shedding thousands of times more material than a normal person ever would,” Dr. Johnson told the Dispatch. “I think this person isn’t well. ... I’m guessing they have GI issues.”

Monitoring wastewater for COVID-19 is only used to inform public health officials of community levels and spread of the virus. People with COVID are not tracked down using such information.

The Centers for Disease Control and Prevention told the Dispatch that the findings do not mean there’s a public health threat.

“Unusual or ‘cryptic’ sequences identified in wastewater may represent viruses that can replicate in particular individuals, but not in the general population,” the CDC wrote in a statement to the newspaper. “This can be because of a compromised immune system. CDC and other institutions conduct studies in immunocompromised individuals to understand persistent infection and virus evolution.”

Ohio health officials told the newspaper that they don’t consider the situation a public health threat because the cryptic strain hasn’t spread beyond two sewer sheds for those 2  years.

Dr. Johnson and colleagues have been researching other unique COVID strains found in wastewater. They wrote a paper about a case in Wisconsin currently in preprint.

In the paper, the researchers suggest some people are persistently infected, calling them “prolonged shedders.” The researchers wrote that prolonged shedders could be human or “nonhuman,” and that “increased global monitoring of such lineages in wastewater could help anticipate future circulating mutations and/or variants of concern.”

Earlier in 2023, the CDC announced it was ending its community-level reporting of COVID test data and would rely more heavily on hospitalization reports and wastewater monitoring. COVID hospitalizations dipped to 7,212 nationally for the week of June 1-8, which is a 6% decline from the week prior, according to the CDC. That number of hospitalizations equals about two hospitalizations per 100,000 people.

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

Frailty is an age-associated, nonspecific vulnerability to adverse health outcomes. Frailty can also be described as a complex of symptoms characterized by impaired stress tolerance due to a decline in the functionality of different organs.¹ The prevalence of frailty varies widely depending on the method of measurement and the population studied.^2-4 It is a nonconstant factor that increases with age. A deficit accumulation frailty index (FI) is one method used to measure frailty.⁵ This approach sees frailty as a multidimensional risk state measured by quantity rather than the nature of health concerns. A deficit accumulation FI does not require physical testing but correlates well with other phenotypic FIs.⁶ It is, however, time consuming, as ≥ 30 deficits need to be measured to offer greater stability to the frailty estimate.

Health care is seeing increasing utilization of big data analytics to derive predictive models and help with resource allocation. There are currently 2 existing automated tools to predict health care utilization and mortality at the US Department of Veterans Affairs (VA): the VA Frailty Index (VA-FI-10) and the Care Assessment Need (CAN). VA-FI-10 is an International Statistical Classification of Diseases, Tenth Revision (ICD-10) update of the VA-FI that was created in March 2021. The VA-FI-10 is a claims-based frailty assessment tool using 31 health deficits. Calculating the VA-FI-10 requires defining an index date and lookback period (typically 3 years) relative to which it will be calculated.⁷

CAN is a set of risk-stratifying statistical models run on veterans receiving VA primary care services as part of a patient aligned care team (PACT) using electronic health record data.⁸ Each veteran is stratified based on the individual’s risks of hospitalization, death, and hospitalization or death. These 3 events are predicted for 90-day and 1-year time periods for a total of 6 distinct outcomes. CAN is currently on its third iteration (CAN 2.5) and scores range from 0 (low) to 99 (high). CAN scores are updated weekly. The 1-year hospitalization probabilities for all patients range from 0.8% to 93.1%. For patients with a CAN score of 50, the probability of being hospitalized within a year ranges from 4.5% to 5.2%, which increases to 32.2% to 36% for veterans with a CAN score of 95. The probability range widens significantly (32.2%-93.1%) for patients in the top 5 CAN scores (95-99).

CAN scores are a potential screening tool for frailty among older adults; they are generated automatically and provide acceptable diagnostic accuracy. Hence, the CAN score may be a useful tool for primary care practitioners for the detection of frailty in their patients. The CAN score has shown a moderate positive association with the FRAIL Scale.^9,10 The population-based studies that have used the FI approach (differing FIs, depending on the data available) give robust results: People accumulate an average of 0.03 deficits per year after the age of 70 years.¹¹ Interventions to delay or reverse frailty have not been clearly defined with heterogeneity in the definition of frailty and measurement of frailty outcomes.^12,13 The prevalence of frailty in the veteran population is substantially higher than the prevalence in community populations with a similar age distribution. There is also mounting evidence that veterans accumulate deficits more rapidly than their civilian counterparts.¹⁴

COVID-19 was declared a pandemic in March 2020 and had many impacts on global health that were most marked in the first year. These included reductions in hospital visits for non-COVID-19 health concerns, a reduction in completed screening tests, an initial reduction in other infectious diseases (attributable to quarantines), and an increase or worsening of mental health concerns.^15,16

We aimed to investigate whether frailty increased disproportionately in a subset of older veterans in the first year of the COVID-19 pandemic when compared with the previous year using CAN scores. This single institution, longitudinal cohort study was determined to be exempt from institutional review board review but was approved by the Phoenix VA Health Care System (PVAHCS) Research and Development Committee.

Methods

The Office of Clinical Systems Development and Evaluation (CSDE–10E2A) produces a weekly CAN Score Report to help identify the highest-risk patients in a primary care panel or cohort. CAN scores range from 0 (lowest risk) to 99 (highest risk), indicating how likely a patient is to experience hospitalization or death compared with other VA patients. CAN scores are calculated with statistical prediction models that use data elements from the following Corporate Data Warehouse (CDW) domains: demographics, health care utilization, laboratory tests, medical conditions, medications, and vital signs (eAppendix available online at 10.12788/fp.0385).

The CAN Score Report is generated weekly and stored on a CDW server. A patient will receive all 6 distinct CAN scores if they are: (1) assigned to a primary care PACT on the risk date; (2) a veteran; (3) not hospitalized in a VA facility on the risk date; and (4) alive as of the risk date. New to CAN 2.5 is that patients who meet criteria 1, 2, and 4 but are hospitalized in a VA facility on the risk date will receive CAN scores for the 1-year and 90-day mortality models.

Utilizing VA Informatics and Computing Infrastructure (VA HSR RES 13-457, US Department of Veterans Affairs [2008]), we obtained 2 lists of veterans aged 70 to 75 years on February 8, 2019, with a calculated CAN score of ≥ 75 for 1-year mortality and 1-year hospitalization on that date. A veteran with a CAN score of ≥ 75 is likely to be prefrail or frail.^9,10 Veterans who did not have a corresponding calculated CAN score on February 7, 2020, and February 12, 2021, were excluded. COVID-19 was declared a public health emergency in the United States on January 31, 2020, and the World Health Organization declared COVID-19 a pandemic on March 11, 2020.¹⁷ We picked February 7, 2020, within this time frame and without any other special significance. We picked additional CAN score calculation dates approximately 1 year prior and 1 year after this date. Veterans had to be alive on February 12, 2021, (the last date of the CAN score) to be included in the cohorts.

Statistical Analyses

The difference in CAN score from one year to the next was calculated for each patient. The difference between 2019 and 2020 was compared with the difference between 2020 to 2021 using a paired t test. Yearly CAN score values were analyzed using repeated measures analysis of variance. The number of patients that showed an increase in CAN score (ie, increased risk of either mortality or hospitalization within the year) or a decrease (lower risk) was compared using the χ² test. IBM SPSS v26 and GraphPad Prism v18 were used for statistical analysis. P < .05 was considered statistically significant.

Results

There were 3538 veterans at PVAHCS who met the inclusion criteria and had a 1-year mortality CAN score ≥ 75 on February 8, 2019.

In the hospitalization group, there were 6046 veterans in the analysis; 57 veterans missing a 1-year hospitalization CAN score that were excluded. The mean age was 71.7 (1.3) years and included 5874 male (97.2%) and 172 female (2.8%) veterans. There was a decline in mean 1-year hospitalization CAN scores in our subset of frail older veterans by 2.8 (95% CI, -3.1 to -2.6) in the year preceding the COVID-19 pandemic. This mean decline slowed significantly to 1.5 (95% CI, -1.8 to -1.2; P < .0001) after the first year of the COVID-19 pandemic. Mean CAN scores for 1-year hospitalization were 84.6 (95% CI, 84.4 to 84.8), 81.8 (95% CI, 81.5 to 82.1), and 80.2 (95% CI, 79.9 to 80.6) for 2019, 2020, and 2021, respectively.

We also calculated the number of veterans with increasing, stable, and decreasing CAN scores across each of our defined periods in both the 1-year mortality and hospitalization groups.

Discussion

We studied frailty trends in an older veteran subpopulation enrolled at the PVAHCS 1 year prior and into the COVID-19 pandemic using CAN scores. Frailty is a dynamic state. Previous frailty assessments aimed to identify patients at the highest risk of death. With the advent of advanced therapeutics for several diseases, the number of medical conditions that are now managed as chronic illnesses continues to grow. There is a role for repeated measures of frailty to try to identify frailty trends.¹⁹ These trends may assist us in resource allocation, identifying interventions that work and those that do not.

Some studies have shown an overall declining lethality of frailty. This may reflect improvements in the care and management of chronic conditions, screening tests, and increased awareness of healthy lifestyles.²⁰ Another study of frailty trajectories in a veteran population in the 5 years preceding death showed multiple trajectories (stable, gradually increasing, rapidly increasing, and recovering).¹⁹

The PACT is a primary care model implemented at VA medical centers in April 2010. It is a patient-centered medical home model (PCMH) with several components. The VA treats a population of socioeconomically vulnerable patients with complex chronic illness management needs. Some of the components of a PACT model relevant to our study include facilitated self-management support for veterans in between practitioner visits via care partners, peer-to-peer and transitional care programs, physical activity and diet programs, primary care mental health, integration between primary and specialty care, and telehealth.²¹ A previous study has shown that VA primary care clinics with the most PCMH components in place had greater improvements in several chronic disease quality measures than in clinics with a lower number of PCMH components.²²

Limitations

Our study is limited by our older veteran population demographics. We chose only a subset of older veterans at a single VA center for this study and cannot extrapolate the results to all older frail veterans or community dwelling older adults. Robust individuals may also transition to prefrailty and frailty over longer periods; our study monitored frailty trends over 2 years.

CAN scores are not quality measures to improve upon. Allocation and utilization of additional resources may clinically benefit a patient but increase their CAN scores. Although our results are statistically significant, we are unable to make any conclusions about clinical significance.

Conclusions

Our study results indicate frailty as determined by 1-year mortality CAN scores significantly increased in a subset of older veterans during the first year of the COVID-19 pandemic when compared with the previous year. Whether this change in frailty is temporary or long lasting remains to be seen. Automated CAN scores can be effectively utilized to monitor frailty trends in certain veteran populations over longer periods.

Acknowledgments

This material is the result of work supported with resources and the use of facilities at the Phoenix Veterans Affairs Health Care System.

Frailty is an age-associated, nonspecific vulnerability to adverse health outcomes. Frailty can also be described as a complex of symptoms characterized by impaired stress tolerance due to a decline in the functionality of different organs.¹ The prevalence of frailty varies widely depending on the method of measurement and the population studied.^2-4 It is a nonconstant factor that increases with age. A deficit accumulation frailty index (FI) is one method used to measure frailty.⁵ This approach sees frailty as a multidimensional risk state measured by quantity rather than the nature of health concerns. A deficit accumulation FI does not require physical testing but correlates well with other phenotypic FIs.⁶ It is, however, time consuming, as ≥ 30 deficits need to be measured to offer greater stability to the frailty estimate.

Health care is seeing increasing utilization of big data analytics to derive predictive models and help with resource allocation. There are currently 2 existing automated tools to predict health care utilization and mortality at the US Department of Veterans Affairs (VA): the VA Frailty Index (VA-FI-10) and the Care Assessment Need (CAN). VA-FI-10 is an International Statistical Classification of Diseases, Tenth Revision (ICD-10) update of the VA-FI that was created in March 2021. The VA-FI-10 is a claims-based frailty assessment tool using 31 health deficits. Calculating the VA-FI-10 requires defining an index date and lookback period (typically 3 years) relative to which it will be calculated.⁷

CAN is a set of risk-stratifying statistical models run on veterans receiving VA primary care services as part of a patient aligned care team (PACT) using electronic health record data.⁸ Each veteran is stratified based on the individual’s risks of hospitalization, death, and hospitalization or death. These 3 events are predicted for 90-day and 1-year time periods for a total of 6 distinct outcomes. CAN is currently on its third iteration (CAN 2.5) and scores range from 0 (low) to 99 (high). CAN scores are updated weekly. The 1-year hospitalization probabilities for all patients range from 0.8% to 93.1%. For patients with a CAN score of 50, the probability of being hospitalized within a year ranges from 4.5% to 5.2%, which increases to 32.2% to 36% for veterans with a CAN score of 95. The probability range widens significantly (32.2%-93.1%) for patients in the top 5 CAN scores (95-99).

CAN scores are a potential screening tool for frailty among older adults; they are generated automatically and provide acceptable diagnostic accuracy. Hence, the CAN score may be a useful tool for primary care practitioners for the detection of frailty in their patients. The CAN score has shown a moderate positive association with the FRAIL Scale.^9,10 The population-based studies that have used the FI approach (differing FIs, depending on the data available) give robust results: People accumulate an average of 0.03 deficits per year after the age of 70 years.¹¹ Interventions to delay or reverse frailty have not been clearly defined with heterogeneity in the definition of frailty and measurement of frailty outcomes.^12,13 The prevalence of frailty in the veteran population is substantially higher than the prevalence in community populations with a similar age distribution. There is also mounting evidence that veterans accumulate deficits more rapidly than their civilian counterparts.¹⁴

COVID-19 was declared a pandemic in March 2020 and had many impacts on global health that were most marked in the first year. These included reductions in hospital visits for non-COVID-19 health concerns, a reduction in completed screening tests, an initial reduction in other infectious diseases (attributable to quarantines), and an increase or worsening of mental health concerns.^15,16

We aimed to investigate whether frailty increased disproportionately in a subset of older veterans in the first year of the COVID-19 pandemic when compared with the previous year using CAN scores. This single institution, longitudinal cohort study was determined to be exempt from institutional review board review but was approved by the Phoenix VA Health Care System (PVAHCS) Research and Development Committee.

Methods

The Office of Clinical Systems Development and Evaluation (CSDE–10E2A) produces a weekly CAN Score Report to help identify the highest-risk patients in a primary care panel or cohort. CAN scores range from 0 (lowest risk) to 99 (highest risk), indicating how likely a patient is to experience hospitalization or death compared with other VA patients. CAN scores are calculated with statistical prediction models that use data elements from the following Corporate Data Warehouse (CDW) domains: demographics, health care utilization, laboratory tests, medical conditions, medications, and vital signs (eAppendix available online at 10.12788/fp.0385).

The CAN Score Report is generated weekly and stored on a CDW server. A patient will receive all 6 distinct CAN scores if they are: (1) assigned to a primary care PACT on the risk date; (2) a veteran; (3) not hospitalized in a VA facility on the risk date; and (4) alive as of the risk date. New to CAN 2.5 is that patients who meet criteria 1, 2, and 4 but are hospitalized in a VA facility on the risk date will receive CAN scores for the 1-year and 90-day mortality models.

Utilizing VA Informatics and Computing Infrastructure (VA HSR RES 13-457, US Department of Veterans Affairs [2008]), we obtained 2 lists of veterans aged 70 to 75 years on February 8, 2019, with a calculated CAN score of ≥ 75 for 1-year mortality and 1-year hospitalization on that date. A veteran with a CAN score of ≥ 75 is likely to be prefrail or frail.^9,10 Veterans who did not have a corresponding calculated CAN score on February 7, 2020, and February 12, 2021, were excluded. COVID-19 was declared a public health emergency in the United States on January 31, 2020, and the World Health Organization declared COVID-19 a pandemic on March 11, 2020.¹⁷ We picked February 7, 2020, within this time frame and without any other special significance. We picked additional CAN score calculation dates approximately 1 year prior and 1 year after this date. Veterans had to be alive on February 12, 2021, (the last date of the CAN score) to be included in the cohorts.

Statistical Analyses

The difference in CAN score from one year to the next was calculated for each patient. The difference between 2019 and 2020 was compared with the difference between 2020 to 2021 using a paired t test. Yearly CAN score values were analyzed using repeated measures analysis of variance. The number of patients that showed an increase in CAN score (ie, increased risk of either mortality or hospitalization within the year) or a decrease (lower risk) was compared using the χ² test. IBM SPSS v26 and GraphPad Prism v18 were used for statistical analysis. P < .05 was considered statistically significant.

Results

There were 3538 veterans at PVAHCS who met the inclusion criteria and had a 1-year mortality CAN score ≥ 75 on February 8, 2019.

In the hospitalization group, there were 6046 veterans in the analysis; 57 veterans missing a 1-year hospitalization CAN score that were excluded. The mean age was 71.7 (1.3) years and included 5874 male (97.2%) and 172 female (2.8%) veterans. There was a decline in mean 1-year hospitalization CAN scores in our subset of frail older veterans by 2.8 (95% CI, -3.1 to -2.6) in the year preceding the COVID-19 pandemic. This mean decline slowed significantly to 1.5 (95% CI, -1.8 to -1.2; P < .0001) after the first year of the COVID-19 pandemic. Mean CAN scores for 1-year hospitalization were 84.6 (95% CI, 84.4 to 84.8), 81.8 (95% CI, 81.5 to 82.1), and 80.2 (95% CI, 79.9 to 80.6) for 2019, 2020, and 2021, respectively.

We also calculated the number of veterans with increasing, stable, and decreasing CAN scores across each of our defined periods in both the 1-year mortality and hospitalization groups.

Discussion

We studied frailty trends in an older veteran subpopulation enrolled at the PVAHCS 1 year prior and into the COVID-19 pandemic using CAN scores. Frailty is a dynamic state. Previous frailty assessments aimed to identify patients at the highest risk of death. With the advent of advanced therapeutics for several diseases, the number of medical conditions that are now managed as chronic illnesses continues to grow. There is a role for repeated measures of frailty to try to identify frailty trends.¹⁹ These trends may assist us in resource allocation, identifying interventions that work and those that do not.

Some studies have shown an overall declining lethality of frailty. This may reflect improvements in the care and management of chronic conditions, screening tests, and increased awareness of healthy lifestyles.²⁰ Another study of frailty trajectories in a veteran population in the 5 years preceding death showed multiple trajectories (stable, gradually increasing, rapidly increasing, and recovering).¹⁹

The PACT is a primary care model implemented at VA medical centers in April 2010. It is a patient-centered medical home model (PCMH) with several components. The VA treats a population of socioeconomically vulnerable patients with complex chronic illness management needs. Some of the components of a PACT model relevant to our study include facilitated self-management support for veterans in between practitioner visits via care partners, peer-to-peer and transitional care programs, physical activity and diet programs, primary care mental health, integration between primary and specialty care, and telehealth.²¹ A previous study has shown that VA primary care clinics with the most PCMH components in place had greater improvements in several chronic disease quality measures than in clinics with a lower number of PCMH components.²²

Limitations

Our study is limited by our older veteran population demographics. We chose only a subset of older veterans at a single VA center for this study and cannot extrapolate the results to all older frail veterans or community dwelling older adults. Robust individuals may also transition to prefrailty and frailty over longer periods; our study monitored frailty trends over 2 years.

CAN scores are not quality measures to improve upon. Allocation and utilization of additional resources may clinically benefit a patient but increase their CAN scores. Although our results are statistically significant, we are unable to make any conclusions about clinical significance.

Conclusions

Our study results indicate frailty as determined by 1-year mortality CAN scores significantly increased in a subset of older veterans during the first year of the COVID-19 pandemic when compared with the previous year. Whether this change in frailty is temporary or long lasting remains to be seen. Automated CAN scores can be effectively utilized to monitor frailty trends in certain veteran populations over longer periods.

Acknowledgments

This material is the result of work supported with resources and the use of facilities at the Phoenix Veterans Affairs Health Care System.

Frailty is an age-associated, nonspecific vulnerability to adverse health outcomes. Frailty can also be described as a complex of symptoms characterized by impaired stress tolerance due to a decline in the functionality of different organs.¹ The prevalence of frailty varies widely depending on the method of measurement and the population studied.^2-4 It is a nonconstant factor that increases with age. A deficit accumulation frailty index (FI) is one method used to measure frailty.⁵ This approach sees frailty as a multidimensional risk state measured by quantity rather than the nature of health concerns. A deficit accumulation FI does not require physical testing but correlates well with other phenotypic FIs.⁶ It is, however, time consuming, as ≥ 30 deficits need to be measured to offer greater stability to the frailty estimate.

Health care is seeing increasing utilization of big data analytics to derive predictive models and help with resource allocation. There are currently 2 existing automated tools to predict health care utilization and mortality at the US Department of Veterans Affairs (VA): the VA Frailty Index (VA-FI-10) and the Care Assessment Need (CAN). VA-FI-10 is an International Statistical Classification of Diseases, Tenth Revision (ICD-10) update of the VA-FI that was created in March 2021. The VA-FI-10 is a claims-based frailty assessment tool using 31 health deficits. Calculating the VA-FI-10 requires defining an index date and lookback period (typically 3 years) relative to which it will be calculated.⁷

CAN is a set of risk-stratifying statistical models run on veterans receiving VA primary care services as part of a patient aligned care team (PACT) using electronic health record data.⁸ Each veteran is stratified based on the individual’s risks of hospitalization, death, and hospitalization or death. These 3 events are predicted for 90-day and 1-year time periods for a total of 6 distinct outcomes. CAN is currently on its third iteration (CAN 2.5) and scores range from 0 (low) to 99 (high). CAN scores are updated weekly. The 1-year hospitalization probabilities for all patients range from 0.8% to 93.1%. For patients with a CAN score of 50, the probability of being hospitalized within a year ranges from 4.5% to 5.2%, which increases to 32.2% to 36% for veterans with a CAN score of 95. The probability range widens significantly (32.2%-93.1%) for patients in the top 5 CAN scores (95-99).

CAN scores are a potential screening tool for frailty among older adults; they are generated automatically and provide acceptable diagnostic accuracy. Hence, the CAN score may be a useful tool for primary care practitioners for the detection of frailty in their patients. The CAN score has shown a moderate positive association with the FRAIL Scale.^9,10 The population-based studies that have used the FI approach (differing FIs, depending on the data available) give robust results: People accumulate an average of 0.03 deficits per year after the age of 70 years.¹¹ Interventions to delay or reverse frailty have not been clearly defined with heterogeneity in the definition of frailty and measurement of frailty outcomes.^12,13 The prevalence of frailty in the veteran population is substantially higher than the prevalence in community populations with a similar age distribution. There is also mounting evidence that veterans accumulate deficits more rapidly than their civilian counterparts.¹⁴

COVID-19 was declared a pandemic in March 2020 and had many impacts on global health that were most marked in the first year. These included reductions in hospital visits for non-COVID-19 health concerns, a reduction in completed screening tests, an initial reduction in other infectious diseases (attributable to quarantines), and an increase or worsening of mental health concerns.^15,16

We aimed to investigate whether frailty increased disproportionately in a subset of older veterans in the first year of the COVID-19 pandemic when compared with the previous year using CAN scores. This single institution, longitudinal cohort study was determined to be exempt from institutional review board review but was approved by the Phoenix VA Health Care System (PVAHCS) Research and Development Committee.

Methods

The Office of Clinical Systems Development and Evaluation (CSDE–10E2A) produces a weekly CAN Score Report to help identify the highest-risk patients in a primary care panel or cohort. CAN scores range from 0 (lowest risk) to 99 (highest risk), indicating how likely a patient is to experience hospitalization or death compared with other VA patients. CAN scores are calculated with statistical prediction models that use data elements from the following Corporate Data Warehouse (CDW) domains: demographics, health care utilization, laboratory tests, medical conditions, medications, and vital signs (eAppendix available online at 10.12788/fp.0385).

The CAN Score Report is generated weekly and stored on a CDW server. A patient will receive all 6 distinct CAN scores if they are: (1) assigned to a primary care PACT on the risk date; (2) a veteran; (3) not hospitalized in a VA facility on the risk date; and (4) alive as of the risk date. New to CAN 2.5 is that patients who meet criteria 1, 2, and 4 but are hospitalized in a VA facility on the risk date will receive CAN scores for the 1-year and 90-day mortality models.

Utilizing VA Informatics and Computing Infrastructure (VA HSR RES 13-457, US Department of Veterans Affairs [2008]), we obtained 2 lists of veterans aged 70 to 75 years on February 8, 2019, with a calculated CAN score of ≥ 75 for 1-year mortality and 1-year hospitalization on that date. A veteran with a CAN score of ≥ 75 is likely to be prefrail or frail.^9,10 Veterans who did not have a corresponding calculated CAN score on February 7, 2020, and February 12, 2021, were excluded. COVID-19 was declared a public health emergency in the United States on January 31, 2020, and the World Health Organization declared COVID-19 a pandemic on March 11, 2020.¹⁷ We picked February 7, 2020, within this time frame and without any other special significance. We picked additional CAN score calculation dates approximately 1 year prior and 1 year after this date. Veterans had to be alive on February 12, 2021, (the last date of the CAN score) to be included in the cohorts.

Statistical Analyses

The difference in CAN score from one year to the next was calculated for each patient. The difference between 2019 and 2020 was compared with the difference between 2020 to 2021 using a paired t test. Yearly CAN score values were analyzed using repeated measures analysis of variance. The number of patients that showed an increase in CAN score (ie, increased risk of either mortality or hospitalization within the year) or a decrease (lower risk) was compared using the χ² test. IBM SPSS v26 and GraphPad Prism v18 were used for statistical analysis. P < .05 was considered statistically significant.

Results

There were 3538 veterans at PVAHCS who met the inclusion criteria and had a 1-year mortality CAN score ≥ 75 on February 8, 2019.

In the hospitalization group, there were 6046 veterans in the analysis; 57 veterans missing a 1-year hospitalization CAN score that were excluded. The mean age was 71.7 (1.3) years and included 5874 male (97.2%) and 172 female (2.8%) veterans. There was a decline in mean 1-year hospitalization CAN scores in our subset of frail older veterans by 2.8 (95% CI, -3.1 to -2.6) in the year preceding the COVID-19 pandemic. This mean decline slowed significantly to 1.5 (95% CI, -1.8 to -1.2; P < .0001) after the first year of the COVID-19 pandemic. Mean CAN scores for 1-year hospitalization were 84.6 (95% CI, 84.4 to 84.8), 81.8 (95% CI, 81.5 to 82.1), and 80.2 (95% CI, 79.9 to 80.6) for 2019, 2020, and 2021, respectively.

We also calculated the number of veterans with increasing, stable, and decreasing CAN scores across each of our defined periods in both the 1-year mortality and hospitalization groups.

Discussion

We studied frailty trends in an older veteran subpopulation enrolled at the PVAHCS 1 year prior and into the COVID-19 pandemic using CAN scores. Frailty is a dynamic state. Previous frailty assessments aimed to identify patients at the highest risk of death. With the advent of advanced therapeutics for several diseases, the number of medical conditions that are now managed as chronic illnesses continues to grow. There is a role for repeated measures of frailty to try to identify frailty trends.¹⁹ These trends may assist us in resource allocation, identifying interventions that work and those that do not.

Some studies have shown an overall declining lethality of frailty. This may reflect improvements in the care and management of chronic conditions, screening tests, and increased awareness of healthy lifestyles.²⁰ Another study of frailty trajectories in a veteran population in the 5 years preceding death showed multiple trajectories (stable, gradually increasing, rapidly increasing, and recovering).¹⁹

The PACT is a primary care model implemented at VA medical centers in April 2010. It is a patient-centered medical home model (PCMH) with several components. The VA treats a population of socioeconomically vulnerable patients with complex chronic illness management needs. Some of the components of a PACT model relevant to our study include facilitated self-management support for veterans in between practitioner visits via care partners, peer-to-peer and transitional care programs, physical activity and diet programs, primary care mental health, integration between primary and specialty care, and telehealth.²¹ A previous study has shown that VA primary care clinics with the most PCMH components in place had greater improvements in several chronic disease quality measures than in clinics with a lower number of PCMH components.²²

Limitations

Our study is limited by our older veteran population demographics. We chose only a subset of older veterans at a single VA center for this study and cannot extrapolate the results to all older frail veterans or community dwelling older adults. Robust individuals may also transition to prefrailty and frailty over longer periods; our study monitored frailty trends over 2 years.

CAN scores are not quality measures to improve upon. Allocation and utilization of additional resources may clinically benefit a patient but increase their CAN scores. Although our results are statistically significant, we are unable to make any conclusions about clinical significance.

Conclusions

Our study results indicate frailty as determined by 1-year mortality CAN scores significantly increased in a subset of older veterans during the first year of the COVID-19 pandemic when compared with the previous year. Whether this change in frailty is temporary or long lasting remains to be seen. Automated CAN scores can be effectively utilized to monitor frailty trends in certain veteran populations over longer periods.

Acknowledgments

This material is the result of work supported with resources and the use of facilities at the Phoenix Veterans Affairs Health Care System.

Pyogenic hepatic abscess (PHA) is a collection of pus in the liver caused by bacterial infection of the liver parenchyma. This potentially life-threatening condition has a mortality rate reported to be as high as 47%.¹ The incidence of PHA is reported to be 2.3 per 100,000 individuals and is more common in immunosuppressed individuals and those with diabetes mellitus, cancer, and liver transplant.^2,3 PHA infections are usually polymicrobial and most commonly include enteric organisms like Escherichia coli and Klebsiella pneumoniae.⁴

We present a rare cause of PHA with Fusobacterium nucleatum (F nucleatum) in an immunocompetent patient with poor oral health, history of diverticulitis, and recent COVID-19 infection whose only symptoms were chest pain and a 4-week history of fever and malaise.

Case Presentation

A 52-year-old man initially presented to the C.W. Bill Young Veterans Affairs Medical Center (CWBYVAMC) emergency department in Bay Pines, Florida, for fever, malaise, and right-sided chest pain on inspiration. The fever and malaise began while he was on vacation 4 weeks prior. He originally presented to an outside hospital where he tested positive for COVID-19 and was recommended ibuprofen and rest. His symptoms did not improve, and he returned a second time to the outside hospital 2 weeks later and was diagnosed with pneumonia and placed on outpatient antibiotics. The patient subsequently returned to CWBYVAMC 2 weeks after starting antibiotics when he began to develop right-sided inspiratory chest pain. He reported no other recent travel and no abdominal pain. The patient’s history was significant for diverticulitis 2 years before. A colonoscopy was performed during that time and showed no masses.

On presentation, the patient was febrile with a temperature of 100.8 °F; otherwise, his vital signs were stable. Physical examinations, including abdominal, respiratory, and cardiovascular, were unremarkable. The initial laboratory workup revealed a white blood cell (WBC) count of 18.7 K/μL (reference range, 5-10 K/μL) and microcytic anemia with a hemoglobin level of 8.8 g/dL. The comprehensive metabolic panel revealed normal aspartate transaminase, alanine transaminase, and total bilirubin levels and elevated alkaline phosphatase of 215 U/L (reference range, 44-147 U/L), revealing possible mild intrahepatic cholestasis. Urinalysis showed trace proteinuria and urobilinogen. Coagulation studies showed elevated D-dimer and procalcitonin levels at 1.9 ng/mL (reference range, < 0.1 ng/mL) and 1.21 ng/mL (reference range, < 0.5 ng/mL), respectively, with normal prothrombin and partial thromboplastin times. The patient had a normal troponin, fecal, and blood culture; entamoeba serology was negative.

A computed tomograph (CT) angiography of the chest was performed to rule out pulmonary embolism, revealing liver lesions suspicious for abscess or metastatic disease. Minimal pleural effusion was detected bilaterally. A subsequent CT confirmed the presence of hepatic lesions consistent with an abscess (Figure 1).

Discussion

F nucleatum is a gram-negative, nonmotile, spindle-shaped rod found in dental plaques.⁵ The incidence of F nucleatum bacteremia is 0.34 per 100,000 people and increases with age, with the median age being 53.5 years.⁶ Although our patient did not present with F nucleatum bacteremia, it is possible that bacteremia was present before hospitalization but resolved by the time the sample was drawn for culture. F nucleatum bacteremia can lead to a variety of presentations. The most common primary diagnoses are intra-abdominal infections (eg, PHA, respiratory tract infections, and hematological disorders).^1,6

PHA Presentation

The most common presenting symptoms of PHA are fever (88%), abdominal pain (79%), and vomiting (50%).⁴ The patient’s presentation of inspiratory right-sided chest pain is likely due to irritation of the diaphragmatic pleura of the right lung secondary to the abscess formation. The patient did not experience abdominal pain throughout the course of this disease or on palpation of his right upper quadrant. To our knowledge, this is the only case of PHA in the literature of a patient with inspiratory chest pain without respiratory infection, abdominal pain, and cardiac abnormalities. There was no radiologic evidence or signs of hypoxia on admission to CWBYVAMC, which makes respiratory infection an unlikely cause of the chest pain. Moreover, the patient presented with new-onset chest pain 2 weeks after the diagnosis of pneumonia.

Common laboratory findings of PHA include transaminitis, leukocytosis, and bilirubinemia.⁴ Of note, increased procalcitonin has also been associated with PHA and extreme elevation (> 200 μg/L) may be a useful biomarker to identify F nucleatum infections before the presence of leukocytosis.³ CT of PHA usually reveals right lobe involvement, and F nucleatum infection usually demonstrates multiple abscesses.^4,7

Contributing Factors in F nucleatum PHA

F nucleatum is associated with several oral diseases, such as periodontitis and gingivitis.⁸ It is important to do an oral inspection on patients with F nucleatum infections because it can spread from oral cavities to different body parts.

F nucleatum is also found in the gut.⁹ Any disease that can cause a break in the gastrointestinal mucosa may result in F nucleatum bacteremia and PHA. This may be why F nucleatum has been associated with a variety of different diseases, such as diverticulitis, inflammatory bowel disease, appendicitis, and colorectal cancer.^10,11 Our patient had a history of diverticulosis with diverticulitis. Bawa and colleagues described a patient with recurrent diverticulitis who developed F nucleatum bacteremia and PHA.¹¹ Our patient did not have any signs of diverticulitis.

Our patient’s COVID-19 infection also had a role in delaying the appropriate treatment of PHA. Without any symptoms of PHA, a diagnosis is difficult in a patient with a positive COVID-19 test, and treatment was delayed 1 month. Moreover, COVID-19 has been reported to delay the diagnosis of PHA even in the absence of a positive COVID-19 test. Collins and Diamond presented a patient during the COVID-19 pandemic who developed a periodontal abscess, which resulted in F nucleatum bacteremia and PHA due to delayed hospital presentation after the patient’s practitioners recommended self-isolation, despite a negative COVID-19 test.¹² This highlights the impact that COVID-19 may have on the timely diagnosis and treatment of patients with PHA.

Malignancy has been associated with F nucleatum bacteremia.^1,13 Possibly the association is due to gastrointestinal mucosa malignancy’s ability to cause micro-abrasions, resulting in F nucleatum bacteremia.¹⁰ Additionally, F nucleatum may promote the development of colorectal neoplasms.⁸ Due to this association, screening for colorectal cancer in patients with F nucleatum infection is important. In our patient, a colonoscopy was performed during the patient’s hospitalization for diverticulitis 2 years prior. No signs of colorectal neoplasm were noted

Conclusions

PHA due to F nucleatum is a rare but potentially life-threatening condition that must be diagnosed and treated promptly. It usually presents with fever, abdominal pain, and vomiting but can present with chest pain in the absence of a respiratory infection, cardiac abnormalities, and abdominal pain, as in our patient. A wide spectrum of infections can occur with F nucleatum, including PHA.

Suspicion for infection with this organism should be kept high in middle-aged and older individuals who present with an indolent disease course and have risk factors, such as poor oral health and comorbidities. Suspicion should be kept high even in the event of COVID-19 infection, especially in individuals with prolonged fever without other signs indicating respiratory infection. We believe that the most likely causes of this patient’s infection were his dental caries and periodontal disease. The timing of his symptoms is not consistent with his previous episode of diverticulitis. Due to the mortality of PHA, diagnosis and treatment must be prompt. Initial treatment with drainage and empiric anaerobic coverage is recommended, followed by a tailored antibiotic regiment if indicated by culture, and further drainage if suggested by imaging.

Pyogenic hepatic abscess (PHA) is a collection of pus in the liver caused by bacterial infection of the liver parenchyma. This potentially life-threatening condition has a mortality rate reported to be as high as 47%.¹ The incidence of PHA is reported to be 2.3 per 100,000 individuals and is more common in immunosuppressed individuals and those with diabetes mellitus, cancer, and liver transplant.^2,3 PHA infections are usually polymicrobial and most commonly include enteric organisms like Escherichia coli and Klebsiella pneumoniae.⁴

We present a rare cause of PHA with Fusobacterium nucleatum (F nucleatum) in an immunocompetent patient with poor oral health, history of diverticulitis, and recent COVID-19 infection whose only symptoms were chest pain and a 4-week history of fever and malaise.

Case Presentation

A 52-year-old man initially presented to the C.W. Bill Young Veterans Affairs Medical Center (CWBYVAMC) emergency department in Bay Pines, Florida, for fever, malaise, and right-sided chest pain on inspiration. The fever and malaise began while he was on vacation 4 weeks prior. He originally presented to an outside hospital where he tested positive for COVID-19 and was recommended ibuprofen and rest. His symptoms did not improve, and he returned a second time to the outside hospital 2 weeks later and was diagnosed with pneumonia and placed on outpatient antibiotics. The patient subsequently returned to CWBYVAMC 2 weeks after starting antibiotics when he began to develop right-sided inspiratory chest pain. He reported no other recent travel and no abdominal pain. The patient’s history was significant for diverticulitis 2 years before. A colonoscopy was performed during that time and showed no masses.

On presentation, the patient was febrile with a temperature of 100.8 °F; otherwise, his vital signs were stable. Physical examinations, including abdominal, respiratory, and cardiovascular, were unremarkable. The initial laboratory workup revealed a white blood cell (WBC) count of 18.7 K/μL (reference range, 5-10 K/μL) and microcytic anemia with a hemoglobin level of 8.8 g/dL. The comprehensive metabolic panel revealed normal aspartate transaminase, alanine transaminase, and total bilirubin levels and elevated alkaline phosphatase of 215 U/L (reference range, 44-147 U/L), revealing possible mild intrahepatic cholestasis. Urinalysis showed trace proteinuria and urobilinogen. Coagulation studies showed elevated D-dimer and procalcitonin levels at 1.9 ng/mL (reference range, < 0.1 ng/mL) and 1.21 ng/mL (reference range, < 0.5 ng/mL), respectively, with normal prothrombin and partial thromboplastin times. The patient had a normal troponin, fecal, and blood culture; entamoeba serology was negative.

A computed tomograph (CT) angiography of the chest was performed to rule out pulmonary embolism, revealing liver lesions suspicious for abscess or metastatic disease. Minimal pleural effusion was detected bilaterally. A subsequent CT confirmed the presence of hepatic lesions consistent with an abscess (Figure 1).

Discussion

F nucleatum is a gram-negative, nonmotile, spindle-shaped rod found in dental plaques.⁵ The incidence of F nucleatum bacteremia is 0.34 per 100,000 people and increases with age, with the median age being 53.5 years.⁶ Although our patient did not present with F nucleatum bacteremia, it is possible that bacteremia was present before hospitalization but resolved by the time the sample was drawn for culture. F nucleatum bacteremia can lead to a variety of presentations. The most common primary diagnoses are intra-abdominal infections (eg, PHA, respiratory tract infections, and hematological disorders).^1,6

PHA Presentation

The most common presenting symptoms of PHA are fever (88%), abdominal pain (79%), and vomiting (50%).⁴ The patient’s presentation of inspiratory right-sided chest pain is likely due to irritation of the diaphragmatic pleura of the right lung secondary to the abscess formation. The patient did not experience abdominal pain throughout the course of this disease or on palpation of his right upper quadrant. To our knowledge, this is the only case of PHA in the literature of a patient with inspiratory chest pain without respiratory infection, abdominal pain, and cardiac abnormalities. There was no radiologic evidence or signs of hypoxia on admission to CWBYVAMC, which makes respiratory infection an unlikely cause of the chest pain. Moreover, the patient presented with new-onset chest pain 2 weeks after the diagnosis of pneumonia.

Common laboratory findings of PHA include transaminitis, leukocytosis, and bilirubinemia.⁴ Of note, increased procalcitonin has also been associated with PHA and extreme elevation (> 200 μg/L) may be a useful biomarker to identify F nucleatum infections before the presence of leukocytosis.³ CT of PHA usually reveals right lobe involvement, and F nucleatum infection usually demonstrates multiple abscesses.^4,7

Contributing Factors in F nucleatum PHA

F nucleatum is associated with several oral diseases, such as periodontitis and gingivitis.⁸ It is important to do an oral inspection on patients with F nucleatum infections because it can spread from oral cavities to different body parts.

F nucleatum is also found in the gut.⁹ Any disease that can cause a break in the gastrointestinal mucosa may result in F nucleatum bacteremia and PHA. This may be why F nucleatum has been associated with a variety of different diseases, such as diverticulitis, inflammatory bowel disease, appendicitis, and colorectal cancer.^10,11 Our patient had a history of diverticulosis with diverticulitis. Bawa and colleagues described a patient with recurrent diverticulitis who developed F nucleatum bacteremia and PHA.¹¹ Our patient did not have any signs of diverticulitis.

Our patient’s COVID-19 infection also had a role in delaying the appropriate treatment of PHA. Without any symptoms of PHA, a diagnosis is difficult in a patient with a positive COVID-19 test, and treatment was delayed 1 month. Moreover, COVID-19 has been reported to delay the diagnosis of PHA even in the absence of a positive COVID-19 test. Collins and Diamond presented a patient during the COVID-19 pandemic who developed a periodontal abscess, which resulted in F nucleatum bacteremia and PHA due to delayed hospital presentation after the patient’s practitioners recommended self-isolation, despite a negative COVID-19 test.¹² This highlights the impact that COVID-19 may have on the timely diagnosis and treatment of patients with PHA.

Malignancy has been associated with F nucleatum bacteremia.^1,13 Possibly the association is due to gastrointestinal mucosa malignancy’s ability to cause micro-abrasions, resulting in F nucleatum bacteremia.¹⁰ Additionally, F nucleatum may promote the development of colorectal neoplasms.⁸ Due to this association, screening for colorectal cancer in patients with F nucleatum infection is important. In our patient, a colonoscopy was performed during the patient’s hospitalization for diverticulitis 2 years prior. No signs of colorectal neoplasm were noted

Conclusions

PHA due to F nucleatum is a rare but potentially life-threatening condition that must be diagnosed and treated promptly. It usually presents with fever, abdominal pain, and vomiting but can present with chest pain in the absence of a respiratory infection, cardiac abnormalities, and abdominal pain, as in our patient. A wide spectrum of infections can occur with F nucleatum, including PHA.

Suspicion for infection with this organism should be kept high in middle-aged and older individuals who present with an indolent disease course and have risk factors, such as poor oral health and comorbidities. Suspicion should be kept high even in the event of COVID-19 infection, especially in individuals with prolonged fever without other signs indicating respiratory infection. We believe that the most likely causes of this patient’s infection were his dental caries and periodontal disease. The timing of his symptoms is not consistent with his previous episode of diverticulitis. Due to the mortality of PHA, diagnosis and treatment must be prompt. Initial treatment with drainage and empiric anaerobic coverage is recommended, followed by a tailored antibiotic regiment if indicated by culture, and further drainage if suggested by imaging.

Pyogenic hepatic abscess (PHA) is a collection of pus in the liver caused by bacterial infection of the liver parenchyma. This potentially life-threatening condition has a mortality rate reported to be as high as 47%.¹ The incidence of PHA is reported to be 2.3 per 100,000 individuals and is more common in immunosuppressed individuals and those with diabetes mellitus, cancer, and liver transplant.^2,3 PHA infections are usually polymicrobial and most commonly include enteric organisms like Escherichia coli and Klebsiella pneumoniae.⁴

We present a rare cause of PHA with Fusobacterium nucleatum (F nucleatum) in an immunocompetent patient with poor oral health, history of diverticulitis, and recent COVID-19 infection whose only symptoms were chest pain and a 4-week history of fever and malaise.

Case Presentation

A 52-year-old man initially presented to the C.W. Bill Young Veterans Affairs Medical Center (CWBYVAMC) emergency department in Bay Pines, Florida, for fever, malaise, and right-sided chest pain on inspiration. The fever and malaise began while he was on vacation 4 weeks prior. He originally presented to an outside hospital where he tested positive for COVID-19 and was recommended ibuprofen and rest. His symptoms did not improve, and he returned a second time to the outside hospital 2 weeks later and was diagnosed with pneumonia and placed on outpatient antibiotics. The patient subsequently returned to CWBYVAMC 2 weeks after starting antibiotics when he began to develop right-sided inspiratory chest pain. He reported no other recent travel and no abdominal pain. The patient’s history was significant for diverticulitis 2 years before. A colonoscopy was performed during that time and showed no masses.

On presentation, the patient was febrile with a temperature of 100.8 °F; otherwise, his vital signs were stable. Physical examinations, including abdominal, respiratory, and cardiovascular, were unremarkable. The initial laboratory workup revealed a white blood cell (WBC) count of 18.7 K/μL (reference range, 5-10 K/μL) and microcytic anemia with a hemoglobin level of 8.8 g/dL. The comprehensive metabolic panel revealed normal aspartate transaminase, alanine transaminase, and total bilirubin levels and elevated alkaline phosphatase of 215 U/L (reference range, 44-147 U/L), revealing possible mild intrahepatic cholestasis. Urinalysis showed trace proteinuria and urobilinogen. Coagulation studies showed elevated D-dimer and procalcitonin levels at 1.9 ng/mL (reference range, < 0.1 ng/mL) and 1.21 ng/mL (reference range, < 0.5 ng/mL), respectively, with normal prothrombin and partial thromboplastin times. The patient had a normal troponin, fecal, and blood culture; entamoeba serology was negative.

A computed tomograph (CT) angiography of the chest was performed to rule out pulmonary embolism, revealing liver lesions suspicious for abscess or metastatic disease. Minimal pleural effusion was detected bilaterally. A subsequent CT confirmed the presence of hepatic lesions consistent with an abscess (Figure 1).

Discussion

F nucleatum is a gram-negative, nonmotile, spindle-shaped rod found in dental plaques.⁵ The incidence of F nucleatum bacteremia is 0.34 per 100,000 people and increases with age, with the median age being 53.5 years.⁶ Although our patient did not present with F nucleatum bacteremia, it is possible that bacteremia was present before hospitalization but resolved by the time the sample was drawn for culture. F nucleatum bacteremia can lead to a variety of presentations. The most common primary diagnoses are intra-abdominal infections (eg, PHA, respiratory tract infections, and hematological disorders).^1,6

PHA Presentation

The most common presenting symptoms of PHA are fever (88%), abdominal pain (79%), and vomiting (50%).⁴ The patient’s presentation of inspiratory right-sided chest pain is likely due to irritation of the diaphragmatic pleura of the right lung secondary to the abscess formation. The patient did not experience abdominal pain throughout the course of this disease or on palpation of his right upper quadrant. To our knowledge, this is the only case of PHA in the literature of a patient with inspiratory chest pain without respiratory infection, abdominal pain, and cardiac abnormalities. There was no radiologic evidence or signs of hypoxia on admission to CWBYVAMC, which makes respiratory infection an unlikely cause of the chest pain. Moreover, the patient presented with new-onset chest pain 2 weeks after the diagnosis of pneumonia.

Common laboratory findings of PHA include transaminitis, leukocytosis, and bilirubinemia.⁴ Of note, increased procalcitonin has also been associated with PHA and extreme elevation (> 200 μg/L) may be a useful biomarker to identify F nucleatum infections before the presence of leukocytosis.³ CT of PHA usually reveals right lobe involvement, and F nucleatum infection usually demonstrates multiple abscesses.^4,7

Contributing Factors in F nucleatum PHA

F nucleatum is associated with several oral diseases, such as periodontitis and gingivitis.⁸ It is important to do an oral inspection on patients with F nucleatum infections because it can spread from oral cavities to different body parts.

F nucleatum is also found in the gut.⁹ Any disease that can cause a break in the gastrointestinal mucosa may result in F nucleatum bacteremia and PHA. This may be why F nucleatum has been associated with a variety of different diseases, such as diverticulitis, inflammatory bowel disease, appendicitis, and colorectal cancer.^10,11 Our patient had a history of diverticulosis with diverticulitis. Bawa and colleagues described a patient with recurrent diverticulitis who developed F nucleatum bacteremia and PHA.¹¹ Our patient did not have any signs of diverticulitis.

Our patient’s COVID-19 infection also had a role in delaying the appropriate treatment of PHA. Without any symptoms of PHA, a diagnosis is difficult in a patient with a positive COVID-19 test, and treatment was delayed 1 month. Moreover, COVID-19 has been reported to delay the diagnosis of PHA even in the absence of a positive COVID-19 test. Collins and Diamond presented a patient during the COVID-19 pandemic who developed a periodontal abscess, which resulted in F nucleatum bacteremia and PHA due to delayed hospital presentation after the patient’s practitioners recommended self-isolation, despite a negative COVID-19 test.¹² This highlights the impact that COVID-19 may have on the timely diagnosis and treatment of patients with PHA.

Malignancy has been associated with F nucleatum bacteremia.^1,13 Possibly the association is due to gastrointestinal mucosa malignancy’s ability to cause micro-abrasions, resulting in F nucleatum bacteremia.¹⁰ Additionally, F nucleatum may promote the development of colorectal neoplasms.⁸ Due to this association, screening for colorectal cancer in patients with F nucleatum infection is important. In our patient, a colonoscopy was performed during the patient’s hospitalization for diverticulitis 2 years prior. No signs of colorectal neoplasm were noted

Conclusions

PHA due to F nucleatum is a rare but potentially life-threatening condition that must be diagnosed and treated promptly. It usually presents with fever, abdominal pain, and vomiting but can present with chest pain in the absence of a respiratory infection, cardiac abnormalities, and abdominal pain, as in our patient. A wide spectrum of infections can occur with F nucleatum, including PHA.

Suspicion for infection with this organism should be kept high in middle-aged and older individuals who present with an indolent disease course and have risk factors, such as poor oral health and comorbidities. Suspicion should be kept high even in the event of COVID-19 infection, especially in individuals with prolonged fever without other signs indicating respiratory infection. We believe that the most likely causes of this patient’s infection were his dental caries and periodontal disease. The timing of his symptoms is not consistent with his previous episode of diverticulitis. Due to the mortality of PHA, diagnosis and treatment must be prompt. Initial treatment with drainage and empiric anaerobic coverage is recommended, followed by a tailored antibiotic regiment if indicated by culture, and further drainage if suggested by imaging.