Clinician Reviews

A controlled study of sleep-deprived young adults has provided the first causal evidence linking the lack of sleep to abdominal obesity and harmful visceral, or “belly” fat. In what the researchers claim is the first-ever study evaluating the relationship between sleep restriction and body fat distribution, they’ve reported the novel finding that the expansion of abdominal adipose tissue, and especially visceral fat, occurred as a function of shortened sleep.

Naima Covassin, PhD, a researcher in cardiovascular medicine at Mayo Clinic in Rochester, Minn., led the randomized, controlled study of 12 healthy, nonobese people randomized to controlled sleep restriction – 2 weeks of 4 hours of sleep a night – or controlled sleep of 9 hours a night, followed by a 3-day recovery period. The study was conducted in the hospital, monitored participants’ caloric intake, and used accelerometry to monitor energy expense. Participants ranged in age from 19 to 39 years.

“What we found was that at the end of 2 weeks these people put on just about a pound, 0.5 kg, of extra weight, which was significant but still very modest,” senior author Virend K. Somers, MD, PhD, said in an interview. “The average person who sleeps 4 hours a night thinks they’re doing OK if they only put on a pound.” Dr. Somers is the Alice Sheets Marriott Professor in Cardiovascular Medicine at Mayo Clinic.

“The problem is,” he said, “that when you do a more specific analysis you find that actually with the 1 pound the significant increase of the fat is in the belly area, particularly inside the belly.”

The study found that the patients on curtailed sleep ate on average an additional 308 calories a day more than their controlled sleep counterparts (95% confidence interval, 59.2-556.8 kcal/day; P = .015), and while that translated into a 0.5-kg weight gain (95% CI, 0.1-0.8 kg; P = .008), it also led to a 7.8-cm² increase visceral adipose tissue (VAT) (95% CI, 0.3-15.3 cm²; P = .042), representing an increase of around 11%. The study used CT on day 1 and day 18 (1 day after the 3-day recovery period) to evaluate the distribution of abdominal fat.

VAT findings post recovery

After the recovery period, however, the study found that VAT in the sleep-curtailed patients kept rising, yet body weight and subcutaneous fat dropped, and the increase in total abdominal fat flattened. “They slept a lot, they ate fewer calories and their weight came down, but, very importantly, their belly fat went up even further,” Dr. Somers said. On average, it increased another 3.125 cm² by day 21.

The findings raised a number of questions that need further exploration, Dr. Somers said. “There’s some biochemical message in the body that’s continuing to send fat to the visceral compartment,” he said. “What we don’t know is whether repetitive episodes of inadequate sleep actually accumulate over the years to give people a preponderance of belly fat.”

The study also showed that the traditional parameters used for evaluating cardiovascular risk are not enough, Dr. Somers said. “If we just did body weight, body mass index, and overall body fat percentage, we’d completely miss this,” he said.

Future investigations should focus on two points, he said: identifying the mechanisms that cause VAT accumulation with less sleep, and whether extending sleep can reverse the process.

“The big worry is obviously the heart,” Dr. Somers said. “Remember, these are not sick people. These are young healthy people who are doing the wrong thing with their body fat; they’re sending the fat to the completely wrong place.”

In an invited editorial, endocrinologist Harold Bays, MD, wrote that the study confirmed the need for evaluating sleep disorders as a potential cause of accumulated VAT. Dr. Bays of the University of Louisville (Ky.) is medical director and president of the Louisville Metabolic and Atherosclerosis Research Center.

“The biggest misconception of many clinicians, and some cardiologists, is that obesity is not a disease,” Dr. Bays said in an interview. “Even when some clinicians believe obesity is a disease, they believe its pathogenic potential is limited to visceral fat.” He noted that subcutaneous fat can lead to accumulation of VAT and epicardial fat, as well as fatty infiltration of the liver and other vital organs, resulting in increased epicardial adipose tissue and indirect adverse effects on the heart.

“Thus, even if disruption of sleep does not increase body weight, if disruption of sleep results in fat dysfunction – “sick fat” or adiposopathy – then this may result in increased CVD risk factors and unhealthy body composition, including an increase in visceral fat,” Dr. Bays said.

The study received funding from the National Institutes of Health. Dr. Somers disclosed relationships with Baker Tilly, Jazz Pharmaceuticals, Bayer, Sleep Number and Respicardia. Coauthors had no disclosures. Dr. Bays is medical director of Your Body Goal and chief science officer of the Obesity Medical Association.

A controlled study of sleep-deprived young adults has provided the first causal evidence linking the lack of sleep to abdominal obesity and harmful visceral, or “belly” fat. In what the researchers claim is the first-ever study evaluating the relationship between sleep restriction and body fat distribution, they’ve reported the novel finding that the expansion of abdominal adipose tissue, and especially visceral fat, occurred as a function of shortened sleep.

Naima Covassin, PhD, a researcher in cardiovascular medicine at Mayo Clinic in Rochester, Minn., led the randomized, controlled study of 12 healthy, nonobese people randomized to controlled sleep restriction – 2 weeks of 4 hours of sleep a night – or controlled sleep of 9 hours a night, followed by a 3-day recovery period. The study was conducted in the hospital, monitored participants’ caloric intake, and used accelerometry to monitor energy expense. Participants ranged in age from 19 to 39 years.

“What we found was that at the end of 2 weeks these people put on just about a pound, 0.5 kg, of extra weight, which was significant but still very modest,” senior author Virend K. Somers, MD, PhD, said in an interview. “The average person who sleeps 4 hours a night thinks they’re doing OK if they only put on a pound.” Dr. Somers is the Alice Sheets Marriott Professor in Cardiovascular Medicine at Mayo Clinic.

“The problem is,” he said, “that when you do a more specific analysis you find that actually with the 1 pound the significant increase of the fat is in the belly area, particularly inside the belly.”

The study found that the patients on curtailed sleep ate on average an additional 308 calories a day more than their controlled sleep counterparts (95% confidence interval, 59.2-556.8 kcal/day; P = .015), and while that translated into a 0.5-kg weight gain (95% CI, 0.1-0.8 kg; P = .008), it also led to a 7.8-cm² increase visceral adipose tissue (VAT) (95% CI, 0.3-15.3 cm²; P = .042), representing an increase of around 11%. The study used CT on day 1 and day 18 (1 day after the 3-day recovery period) to evaluate the distribution of abdominal fat.

VAT findings post recovery

After the recovery period, however, the study found that VAT in the sleep-curtailed patients kept rising, yet body weight and subcutaneous fat dropped, and the increase in total abdominal fat flattened. “They slept a lot, they ate fewer calories and their weight came down, but, very importantly, their belly fat went up even further,” Dr. Somers said. On average, it increased another 3.125 cm² by day 21.

The findings raised a number of questions that need further exploration, Dr. Somers said. “There’s some biochemical message in the body that’s continuing to send fat to the visceral compartment,” he said. “What we don’t know is whether repetitive episodes of inadequate sleep actually accumulate over the years to give people a preponderance of belly fat.”

The study also showed that the traditional parameters used for evaluating cardiovascular risk are not enough, Dr. Somers said. “If we just did body weight, body mass index, and overall body fat percentage, we’d completely miss this,” he said.

Future investigations should focus on two points, he said: identifying the mechanisms that cause VAT accumulation with less sleep, and whether extending sleep can reverse the process.

“The big worry is obviously the heart,” Dr. Somers said. “Remember, these are not sick people. These are young healthy people who are doing the wrong thing with their body fat; they’re sending the fat to the completely wrong place.”

In an invited editorial, endocrinologist Harold Bays, MD, wrote that the study confirmed the need for evaluating sleep disorders as a potential cause of accumulated VAT. Dr. Bays of the University of Louisville (Ky.) is medical director and president of the Louisville Metabolic and Atherosclerosis Research Center.

“The biggest misconception of many clinicians, and some cardiologists, is that obesity is not a disease,” Dr. Bays said in an interview. “Even when some clinicians believe obesity is a disease, they believe its pathogenic potential is limited to visceral fat.” He noted that subcutaneous fat can lead to accumulation of VAT and epicardial fat, as well as fatty infiltration of the liver and other vital organs, resulting in increased epicardial adipose tissue and indirect adverse effects on the heart.

“Thus, even if disruption of sleep does not increase body weight, if disruption of sleep results in fat dysfunction – “sick fat” or adiposopathy – then this may result in increased CVD risk factors and unhealthy body composition, including an increase in visceral fat,” Dr. Bays said.

The study received funding from the National Institutes of Health. Dr. Somers disclosed relationships with Baker Tilly, Jazz Pharmaceuticals, Bayer, Sleep Number and Respicardia. Coauthors had no disclosures. Dr. Bays is medical director of Your Body Goal and chief science officer of the Obesity Medical Association.

A controlled study of sleep-deprived young adults has provided the first causal evidence linking the lack of sleep to abdominal obesity and harmful visceral, or “belly” fat. In what the researchers claim is the first-ever study evaluating the relationship between sleep restriction and body fat distribution, they’ve reported the novel finding that the expansion of abdominal adipose tissue, and especially visceral fat, occurred as a function of shortened sleep.

Naima Covassin, PhD, a researcher in cardiovascular medicine at Mayo Clinic in Rochester, Minn., led the randomized, controlled study of 12 healthy, nonobese people randomized to controlled sleep restriction – 2 weeks of 4 hours of sleep a night – or controlled sleep of 9 hours a night, followed by a 3-day recovery period. The study was conducted in the hospital, monitored participants’ caloric intake, and used accelerometry to monitor energy expense. Participants ranged in age from 19 to 39 years.

“What we found was that at the end of 2 weeks these people put on just about a pound, 0.5 kg, of extra weight, which was significant but still very modest,” senior author Virend K. Somers, MD, PhD, said in an interview. “The average person who sleeps 4 hours a night thinks they’re doing OK if they only put on a pound.” Dr. Somers is the Alice Sheets Marriott Professor in Cardiovascular Medicine at Mayo Clinic.

“The problem is,” he said, “that when you do a more specific analysis you find that actually with the 1 pound the significant increase of the fat is in the belly area, particularly inside the belly.”

The study found that the patients on curtailed sleep ate on average an additional 308 calories a day more than their controlled sleep counterparts (95% confidence interval, 59.2-556.8 kcal/day; P = .015), and while that translated into a 0.5-kg weight gain (95% CI, 0.1-0.8 kg; P = .008), it also led to a 7.8-cm² increase visceral adipose tissue (VAT) (95% CI, 0.3-15.3 cm²; P = .042), representing an increase of around 11%. The study used CT on day 1 and day 18 (1 day after the 3-day recovery period) to evaluate the distribution of abdominal fat.

VAT findings post recovery

After the recovery period, however, the study found that VAT in the sleep-curtailed patients kept rising, yet body weight and subcutaneous fat dropped, and the increase in total abdominal fat flattened. “They slept a lot, they ate fewer calories and their weight came down, but, very importantly, their belly fat went up even further,” Dr. Somers said. On average, it increased another 3.125 cm² by day 21.

The findings raised a number of questions that need further exploration, Dr. Somers said. “There’s some biochemical message in the body that’s continuing to send fat to the visceral compartment,” he said. “What we don’t know is whether repetitive episodes of inadequate sleep actually accumulate over the years to give people a preponderance of belly fat.”

The study also showed that the traditional parameters used for evaluating cardiovascular risk are not enough, Dr. Somers said. “If we just did body weight, body mass index, and overall body fat percentage, we’d completely miss this,” he said.

Future investigations should focus on two points, he said: identifying the mechanisms that cause VAT accumulation with less sleep, and whether extending sleep can reverse the process.

“The big worry is obviously the heart,” Dr. Somers said. “Remember, these are not sick people. These are young healthy people who are doing the wrong thing with their body fat; they’re sending the fat to the completely wrong place.”

In an invited editorial, endocrinologist Harold Bays, MD, wrote that the study confirmed the need for evaluating sleep disorders as a potential cause of accumulated VAT. Dr. Bays of the University of Louisville (Ky.) is medical director and president of the Louisville Metabolic and Atherosclerosis Research Center.

“The biggest misconception of many clinicians, and some cardiologists, is that obesity is not a disease,” Dr. Bays said in an interview. “Even when some clinicians believe obesity is a disease, they believe its pathogenic potential is limited to visceral fat.” He noted that subcutaneous fat can lead to accumulation of VAT and epicardial fat, as well as fatty infiltration of the liver and other vital organs, resulting in increased epicardial adipose tissue and indirect adverse effects on the heart.

“Thus, even if disruption of sleep does not increase body weight, if disruption of sleep results in fat dysfunction – “sick fat” or adiposopathy – then this may result in increased CVD risk factors and unhealthy body composition, including an increase in visceral fat,” Dr. Bays said.

The study received funding from the National Institutes of Health. Dr. Somers disclosed relationships with Baker Tilly, Jazz Pharmaceuticals, Bayer, Sleep Number and Respicardia. Coauthors had no disclosures. Dr. Bays is medical director of Your Body Goal and chief science officer of the Obesity Medical Association.

 Further support for the benefits of regular exercise in reducing severe COVID-19 outcomes has come from a large study, the first to directly measure physical activity in its participants.

Researchers identified 65,361 members of a South African private health plan who had a COVID-19 diagnosis from March 2020 to June 2021 and matched them with physical activity data during the 2 years prior to the country’s March 2020 lockdown captured by smart devices, and clocked gym attendance and mass event participation in a voluntary healthy lifestyle behavior program linked to the insurer.

UberImages/iStock/Getty Images

In all, 20.4% of participants had engaged in low levels of at least moderate-intensity physical activity per week (0-59 minutes), 34.5% in moderate levels (60-149 minutes), and 45.1% in high levels (150 minutes or more).

Overall, 11.1% were hospitalized as a result of COVID-19, 2.4% were admitted to the ICU, 1.3% required a ventilator, and 1.6% died.

As reported in the British Journal of Sports Medicine, analyses adjusted for demographic and other risk factors showed that, with COVID-19 infection, people with high versus low physical activity had a 34% lower risk for hospitalization (risk ratio, 0.66; 95% confidence interval, 0.63-0.70), a 41% lower risk for ICU admission (RR, 0.59; 95% CI, 0.52-0.66), a 45% lower risk of requiring ventilation (RR, 0.55; 95% CI, 0.47-0.64), and a 42% lower risk for death (RR, 0.58; 95% CI, 0.50-0.68).

Even moderate physical exercise, below the recommended guidelines of at least 150 minutes per week, was associated with several benefits, such as a 13% lower risk for hospitalization (RR, 0.87; 95% CI, 0.82-0.91), a 20% lower risk for ICU admission (RR, 0.80; 95% CI, 0.71-0.89), a 27% lower risk of requiring ventilation (RR, 0.73; 95% CI, 0.62-0.84), and a21% lower risk for death (RR, 0.79; 95% CI, 0.69-0.91).

“Should we come across further waves of this pandemic, our advice from a medical point of view should be to promote and facilitate exercise,” senior author Jon Patricios, MD, Wits Sport and Health, University of the Witwatersrand, Johannesburg, South Africa, said in an interview. “The likelihood is that exercise and vaccination are going to be the two most significant interventions in terms of helping to offload the health care system rather than face the catastrophic events endured a year or so ago.”

The study showed that males are at greater risk than females for severe COVID-19 outcomes, as were patients with essential hypertension, diabetes, and chronic renal disease.

It also suggests that the protective benefit of exercise extends to HIV-positive patients and those with rheumatoid arthritis, two groups previously not evaluated, the authors noted.

The results are comparable with previous reports of self-reported exercise and COVID-19 from the United States and South Korea, although the effect of even moderate exercise was more significant, possibly due to the use of direct measures of exercise rather than self-report, Dr. Patricios suggested.

Previous data suggest that regular physical activity may protect against many viral infections including influenza, rhinovirus, and the reactivation of latent herpes viruses, he noted. However, emerging evidence also points to significant decreases in physical activity during the pandemic.

“Regular physical activity should be a message that is strongly, strongly advocated for, particularly in less well-developed countries where we don’t have access or the resources to afford pharmacological interventions in many of these scenarios,” Dr. Patricios said. “It’s frustrating that the message is not driven strongly enough. It should be part of every government’s agenda.”

The cohort all being members of a medical insurance plan could imply some selection bias based on affordability and limit generalizability of the results, the authors noted. Other limitations include a lack of data on sociodemographic criteria such as education, income, and race, as well as behavioral risk factors such as smoking and diet.

Dr. Patricios and one coauthor are editors of the British Journal of Sports Medicine. Several coauthors are employees of Discovery Health, Johannesburg.

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

 Further support for the benefits of regular exercise in reducing severe COVID-19 outcomes has come from a large study, the first to directly measure physical activity in its participants.

Researchers identified 65,361 members of a South African private health plan who had a COVID-19 diagnosis from March 2020 to June 2021 and matched them with physical activity data during the 2 years prior to the country’s March 2020 lockdown captured by smart devices, and clocked gym attendance and mass event participation in a voluntary healthy lifestyle behavior program linked to the insurer.

UberImages/iStock/Getty Images

In all, 20.4% of participants had engaged in low levels of at least moderate-intensity physical activity per week (0-59 minutes), 34.5% in moderate levels (60-149 minutes), and 45.1% in high levels (150 minutes or more).

Overall, 11.1% were hospitalized as a result of COVID-19, 2.4% were admitted to the ICU, 1.3% required a ventilator, and 1.6% died.

As reported in the British Journal of Sports Medicine, analyses adjusted for demographic and other risk factors showed that, with COVID-19 infection, people with high versus low physical activity had a 34% lower risk for hospitalization (risk ratio, 0.66; 95% confidence interval, 0.63-0.70), a 41% lower risk for ICU admission (RR, 0.59; 95% CI, 0.52-0.66), a 45% lower risk of requiring ventilation (RR, 0.55; 95% CI, 0.47-0.64), and a 42% lower risk for death (RR, 0.58; 95% CI, 0.50-0.68).

Even moderate physical exercise, below the recommended guidelines of at least 150 minutes per week, was associated with several benefits, such as a 13% lower risk for hospitalization (RR, 0.87; 95% CI, 0.82-0.91), a 20% lower risk for ICU admission (RR, 0.80; 95% CI, 0.71-0.89), a 27% lower risk of requiring ventilation (RR, 0.73; 95% CI, 0.62-0.84), and a21% lower risk for death (RR, 0.79; 95% CI, 0.69-0.91).

“Should we come across further waves of this pandemic, our advice from a medical point of view should be to promote and facilitate exercise,” senior author Jon Patricios, MD, Wits Sport and Health, University of the Witwatersrand, Johannesburg, South Africa, said in an interview. “The likelihood is that exercise and vaccination are going to be the two most significant interventions in terms of helping to offload the health care system rather than face the catastrophic events endured a year or so ago.”

The study showed that males are at greater risk than females for severe COVID-19 outcomes, as were patients with essential hypertension, diabetes, and chronic renal disease.

It also suggests that the protective benefit of exercise extends to HIV-positive patients and those with rheumatoid arthritis, two groups previously not evaluated, the authors noted.

The results are comparable with previous reports of self-reported exercise and COVID-19 from the United States and South Korea, although the effect of even moderate exercise was more significant, possibly due to the use of direct measures of exercise rather than self-report, Dr. Patricios suggested.

Previous data suggest that regular physical activity may protect against many viral infections including influenza, rhinovirus, and the reactivation of latent herpes viruses, he noted. However, emerging evidence also points to significant decreases in physical activity during the pandemic.

“Regular physical activity should be a message that is strongly, strongly advocated for, particularly in less well-developed countries where we don’t have access or the resources to afford pharmacological interventions in many of these scenarios,” Dr. Patricios said. “It’s frustrating that the message is not driven strongly enough. It should be part of every government’s agenda.”

The cohort all being members of a medical insurance plan could imply some selection bias based on affordability and limit generalizability of the results, the authors noted. Other limitations include a lack of data on sociodemographic criteria such as education, income, and race, as well as behavioral risk factors such as smoking and diet.

Dr. Patricios and one coauthor are editors of the British Journal of Sports Medicine. Several coauthors are employees of Discovery Health, Johannesburg.

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

 Further support for the benefits of regular exercise in reducing severe COVID-19 outcomes has come from a large study, the first to directly measure physical activity in its participants.

Researchers identified 65,361 members of a South African private health plan who had a COVID-19 diagnosis from March 2020 to June 2021 and matched them with physical activity data during the 2 years prior to the country’s March 2020 lockdown captured by smart devices, and clocked gym attendance and mass event participation in a voluntary healthy lifestyle behavior program linked to the insurer.

UberImages/iStock/Getty Images

In all, 20.4% of participants had engaged in low levels of at least moderate-intensity physical activity per week (0-59 minutes), 34.5% in moderate levels (60-149 minutes), and 45.1% in high levels (150 minutes or more).

Overall, 11.1% were hospitalized as a result of COVID-19, 2.4% were admitted to the ICU, 1.3% required a ventilator, and 1.6% died.

As reported in the British Journal of Sports Medicine, analyses adjusted for demographic and other risk factors showed that, with COVID-19 infection, people with high versus low physical activity had a 34% lower risk for hospitalization (risk ratio, 0.66; 95% confidence interval, 0.63-0.70), a 41% lower risk for ICU admission (RR, 0.59; 95% CI, 0.52-0.66), a 45% lower risk of requiring ventilation (RR, 0.55; 95% CI, 0.47-0.64), and a 42% lower risk for death (RR, 0.58; 95% CI, 0.50-0.68).

Even moderate physical exercise, below the recommended guidelines of at least 150 minutes per week, was associated with several benefits, such as a 13% lower risk for hospitalization (RR, 0.87; 95% CI, 0.82-0.91), a 20% lower risk for ICU admission (RR, 0.80; 95% CI, 0.71-0.89), a 27% lower risk of requiring ventilation (RR, 0.73; 95% CI, 0.62-0.84), and a21% lower risk for death (RR, 0.79; 95% CI, 0.69-0.91).

“Should we come across further waves of this pandemic, our advice from a medical point of view should be to promote and facilitate exercise,” senior author Jon Patricios, MD, Wits Sport and Health, University of the Witwatersrand, Johannesburg, South Africa, said in an interview. “The likelihood is that exercise and vaccination are going to be the two most significant interventions in terms of helping to offload the health care system rather than face the catastrophic events endured a year or so ago.”

The study showed that males are at greater risk than females for severe COVID-19 outcomes, as were patients with essential hypertension, diabetes, and chronic renal disease.

It also suggests that the protective benefit of exercise extends to HIV-positive patients and those with rheumatoid arthritis, two groups previously not evaluated, the authors noted.

The results are comparable with previous reports of self-reported exercise and COVID-19 from the United States and South Korea, although the effect of even moderate exercise was more significant, possibly due to the use of direct measures of exercise rather than self-report, Dr. Patricios suggested.

Previous data suggest that regular physical activity may protect against many viral infections including influenza, rhinovirus, and the reactivation of latent herpes viruses, he noted. However, emerging evidence also points to significant decreases in physical activity during the pandemic.

“Regular physical activity should be a message that is strongly, strongly advocated for, particularly in less well-developed countries where we don’t have access or the resources to afford pharmacological interventions in many of these scenarios,” Dr. Patricios said. “It’s frustrating that the message is not driven strongly enough. It should be part of every government’s agenda.”

The cohort all being members of a medical insurance plan could imply some selection bias based on affordability and limit generalizability of the results, the authors noted. Other limitations include a lack of data on sociodemographic criteria such as education, income, and race, as well as behavioral risk factors such as smoking and diet.

Dr. Patricios and one coauthor are editors of the British Journal of Sports Medicine. Several coauthors are employees of Discovery Health, Johannesburg.

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

BOSTON – Nearly 40% of adults with alopecia areata taking baricitinib, an oral Janus kinase 1 and 2 inhibitor, see significant hair regrowth over 52 weeks, according to updated results from two phase 3 trials presented at the annual meeting of the American Academy of Dermatology.

The results indicate improved response rates and hair growth among trial participants, said Brett King, MD, PhD, an associate professor of dermatology at Yale University, New Haven, Conn. He is the lead author of the analyses and presented the research.

Dr. King presented 36-week results from the clinical trials at the 2021 annual meeting of the European Academy of Dermatology and Venereology. The same results were also published March 26, 2022, in the New England Journal of Medicine.

“Every bit of data we’ve had is hugely important,” Dr. King said in an interview. “Every time we add 16 weeks of data across hundreds of patients, we are making a huge step forward toward the goal of [Food and Drug Administration approval for a medication for alopecia areata.”

All patients enrolled in the two trials, called BRAVE-AA1 and BRAVE-AA2, had severe alopecia areata, defined as a Severity of Alopecia Tool (SALT) score of at least 50, meaning 50% or less scalp coverage. The score ranges from 0 (no hair loss) to 100 (complete hair loss). The primary endpoint was a SALT score of 20 or less (80% scalp hair coverage).

The researchers pooled data from both clinical trials, with a combined enrollment of 1,200, for the 52-week results presented at the meeting. The placebo group stopped at 36 weeks, and these patients were randomly reassigned to either the 4-mg or 2-mg once-daily baricitinib treatment groups.

At baseline, patients enrolled in the trial had a mean SALT score of 85.5. After 52 weeks, 39.0% of patients who received 4 mg of baricitinib had at least 80% scalp coverage. Of this group, nearly three out of four (74.1%) had at least 90% scalp coverage, or a SALT score of 10 or less.

In patients who received 2 mg of baricitinib, 22.6% had a SALT score of 20 or less 20 (at least 80% scalp hair coverage) at 52 weeks, and two-thirds of that group (67.5%) had at least 90% scalp hair coverage at 52 weeks.

Comparatively, at 36 weeks, 35.2% of participants in BRAVE-AA1 and 32.5% of participants in BRAVE-AA2 receiving 4 mg of baricitinib had at least 80% scalp coverage. In the group taking the lower dose, 21.7% and 17.3% of patients in the BRAVE-AA1 and BRAVE-AA2 trials, respectively, had achieved at least 80% scalp coverage at 36 weeks. (These percentages differ slightly from the NEJM article because of a different analysis of missing data, Dr. King said. For comparison of both 36- and 52-week results, the percentages from the EADV are used above.)

The results indicate that 5% more patients reached the primary endpoint in the additional 16 weeks of the trial, Dr. King said.

Alopecia areata is an autoimmune condition where immune cells attack hair follicles, causing the hair to fall out, and is associated with emotional and psychological distress. Any hair follicle can be attacked, but they are rarely destroyed, so hair can regrow.

"Many underestimate the impact of this autoimmune hair loss condition," Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, told this news organization. He was not involved with the trial. "The burden of the disease, which certainly is an emotional but also a physical one, definitely needs to be addressed with indicated FDA-approved drugs," he noted, which is the goal of these trials. 

The BRAVE-AA1 and BRAVE-AA2 trials focused on scalp hair regrowth.

Eyebrow and eyelash growth, secondary outcomes, also improved between 36 and 52 weeks in both groups, calculated using the proportion of participants who had achieved full regrowth or regrowth with minimal gaps. At 36 weeks, about 31%-35% of patients who received 4 mg of baricitinib regrew eyebrow and eyelash hair. By 52 weeks, more than two out of five patients regrew eyebrow (44.1%) and eyelash (45.3%) hair.

“It’s a fantastic achievement and a major step forward in alopecia areata, especially for patients with the most severe and refractory cases,” said Arash Mostaghimi, MD, MPH, the director of inpatient dermatology at Brigham and Women’s Hospital in Boston, Massachusetts. Dr. Mostaghimi is on the advisory board for Eli Lilly, which manufactures baricitinib, and Brigham and Women’s was one of the clinical sites of the trial.

While dermatologists have been aware of how JAK inhibitors can affect hair regrowth in alopecia patients, they have been using these drugs off label, Dr. Friedman said. Therefore, these drugs are expensive and more difficult to access. These trials provide "data that proves the efficacy and safety of [baricitinib] under the umbrella of the FDA portal," he added, which will hopefully lead to an approved indication for alopecia areata, so it can be more accessible to patients.

Adverse events at 52 weeks were consistent with data from 36 weeks, which found that none of these adverse events occurred in more than 10% of participants. The most common adverse events were headache, acne, and increases in muscle-related blood markers. The most common infections reported were pneumonia, herpes zoster, and urinary tract infection. 

In February 2022, the FDA granted priority review for baricitinib for the treatment of severe alopecia areata. Lilly expects a regulatory decision by the end of 2022, they said in a press release. 

Lilly provided funding for the BRAVE-AA1 and BRAVE-AA2 trials. Dr. King reported financial relationships with Aclaris, Arena Pharmaceuticals, Bristol-Myers Squibb, Concert Pharmaceutics, Dermavant, Lilly, Pfizer, Regeneron, Sanofi Genzyme, and Viela Bio. Dr. Mostaghimi has reported serving on an advisory board for Lilly. Dr. Friedman reported no relevant financial relationships.  

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

*This article was updated on 3/28/2022 to include Dr. Friedman's comments, and on 3/31/2022 to correct the statement regarding adverse events reported in the study 

BOSTON – Nearly 40% of adults with alopecia areata taking baricitinib, an oral Janus kinase 1 and 2 inhibitor, see significant hair regrowth over 52 weeks, according to updated results from two phase 3 trials presented at the annual meeting of the American Academy of Dermatology.

The results indicate improved response rates and hair growth among trial participants, said Brett King, MD, PhD, an associate professor of dermatology at Yale University, New Haven, Conn. He is the lead author of the analyses and presented the research.

Dr. King presented 36-week results from the clinical trials at the 2021 annual meeting of the European Academy of Dermatology and Venereology. The same results were also published March 26, 2022, in the New England Journal of Medicine.

“Every bit of data we’ve had is hugely important,” Dr. King said in an interview. “Every time we add 16 weeks of data across hundreds of patients, we are making a huge step forward toward the goal of [Food and Drug Administration approval for a medication for alopecia areata.”

All patients enrolled in the two trials, called BRAVE-AA1 and BRAVE-AA2, had severe alopecia areata, defined as a Severity of Alopecia Tool (SALT) score of at least 50, meaning 50% or less scalp coverage. The score ranges from 0 (no hair loss) to 100 (complete hair loss). The primary endpoint was a SALT score of 20 or less (80% scalp hair coverage).

The researchers pooled data from both clinical trials, with a combined enrollment of 1,200, for the 52-week results presented at the meeting. The placebo group stopped at 36 weeks, and these patients were randomly reassigned to either the 4-mg or 2-mg once-daily baricitinib treatment groups.

At baseline, patients enrolled in the trial had a mean SALT score of 85.5. After 52 weeks, 39.0% of patients who received 4 mg of baricitinib had at least 80% scalp coverage. Of this group, nearly three out of four (74.1%) had at least 90% scalp coverage, or a SALT score of 10 or less.

In patients who received 2 mg of baricitinib, 22.6% had a SALT score of 20 or less 20 (at least 80% scalp hair coverage) at 52 weeks, and two-thirds of that group (67.5%) had at least 90% scalp hair coverage at 52 weeks.

Comparatively, at 36 weeks, 35.2% of participants in BRAVE-AA1 and 32.5% of participants in BRAVE-AA2 receiving 4 mg of baricitinib had at least 80% scalp coverage. In the group taking the lower dose, 21.7% and 17.3% of patients in the BRAVE-AA1 and BRAVE-AA2 trials, respectively, had achieved at least 80% scalp coverage at 36 weeks. (These percentages differ slightly from the NEJM article because of a different analysis of missing data, Dr. King said. For comparison of both 36- and 52-week results, the percentages from the EADV are used above.)

The results indicate that 5% more patients reached the primary endpoint in the additional 16 weeks of the trial, Dr. King said.

Alopecia areata is an autoimmune condition where immune cells attack hair follicles, causing the hair to fall out, and is associated with emotional and psychological distress. Any hair follicle can be attacked, but they are rarely destroyed, so hair can regrow.

"Many underestimate the impact of this autoimmune hair loss condition," Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, told this news organization. He was not involved with the trial. "The burden of the disease, which certainly is an emotional but also a physical one, definitely needs to be addressed with indicated FDA-approved drugs," he noted, which is the goal of these trials. 

The BRAVE-AA1 and BRAVE-AA2 trials focused on scalp hair regrowth.

Eyebrow and eyelash growth, secondary outcomes, also improved between 36 and 52 weeks in both groups, calculated using the proportion of participants who had achieved full regrowth or regrowth with minimal gaps. At 36 weeks, about 31%-35% of patients who received 4 mg of baricitinib regrew eyebrow and eyelash hair. By 52 weeks, more than two out of five patients regrew eyebrow (44.1%) and eyelash (45.3%) hair.

“It’s a fantastic achievement and a major step forward in alopecia areata, especially for patients with the most severe and refractory cases,” said Arash Mostaghimi, MD, MPH, the director of inpatient dermatology at Brigham and Women’s Hospital in Boston, Massachusetts. Dr. Mostaghimi is on the advisory board for Eli Lilly, which manufactures baricitinib, and Brigham and Women’s was one of the clinical sites of the trial.

While dermatologists have been aware of how JAK inhibitors can affect hair regrowth in alopecia patients, they have been using these drugs off label, Dr. Friedman said. Therefore, these drugs are expensive and more difficult to access. These trials provide "data that proves the efficacy and safety of [baricitinib] under the umbrella of the FDA portal," he added, which will hopefully lead to an approved indication for alopecia areata, so it can be more accessible to patients.

Adverse events at 52 weeks were consistent with data from 36 weeks, which found that none of these adverse events occurred in more than 10% of participants. The most common adverse events were headache, acne, and increases in muscle-related blood markers. The most common infections reported were pneumonia, herpes zoster, and urinary tract infection. 

In February 2022, the FDA granted priority review for baricitinib for the treatment of severe alopecia areata. Lilly expects a regulatory decision by the end of 2022, they said in a press release. 

Lilly provided funding for the BRAVE-AA1 and BRAVE-AA2 trials. Dr. King reported financial relationships with Aclaris, Arena Pharmaceuticals, Bristol-Myers Squibb, Concert Pharmaceutics, Dermavant, Lilly, Pfizer, Regeneron, Sanofi Genzyme, and Viela Bio. Dr. Mostaghimi has reported serving on an advisory board for Lilly. Dr. Friedman reported no relevant financial relationships.  

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

*This article was updated on 3/28/2022 to include Dr. Friedman's comments, and on 3/31/2022 to correct the statement regarding adverse events reported in the study 

BOSTON – Nearly 40% of adults with alopecia areata taking baricitinib, an oral Janus kinase 1 and 2 inhibitor, see significant hair regrowth over 52 weeks, according to updated results from two phase 3 trials presented at the annual meeting of the American Academy of Dermatology.

The results indicate improved response rates and hair growth among trial participants, said Brett King, MD, PhD, an associate professor of dermatology at Yale University, New Haven, Conn. He is the lead author of the analyses and presented the research.

Dr. King presented 36-week results from the clinical trials at the 2021 annual meeting of the European Academy of Dermatology and Venereology. The same results were also published March 26, 2022, in the New England Journal of Medicine.

“Every bit of data we’ve had is hugely important,” Dr. King said in an interview. “Every time we add 16 weeks of data across hundreds of patients, we are making a huge step forward toward the goal of [Food and Drug Administration approval for a medication for alopecia areata.”

All patients enrolled in the two trials, called BRAVE-AA1 and BRAVE-AA2, had severe alopecia areata, defined as a Severity of Alopecia Tool (SALT) score of at least 50, meaning 50% or less scalp coverage. The score ranges from 0 (no hair loss) to 100 (complete hair loss). The primary endpoint was a SALT score of 20 or less (80% scalp hair coverage).

The researchers pooled data from both clinical trials, with a combined enrollment of 1,200, for the 52-week results presented at the meeting. The placebo group stopped at 36 weeks, and these patients were randomly reassigned to either the 4-mg or 2-mg once-daily baricitinib treatment groups.

At baseline, patients enrolled in the trial had a mean SALT score of 85.5. After 52 weeks, 39.0% of patients who received 4 mg of baricitinib had at least 80% scalp coverage. Of this group, nearly three out of four (74.1%) had at least 90% scalp coverage, or a SALT score of 10 or less.

In patients who received 2 mg of baricitinib, 22.6% had a SALT score of 20 or less 20 (at least 80% scalp hair coverage) at 52 weeks, and two-thirds of that group (67.5%) had at least 90% scalp hair coverage at 52 weeks.

Comparatively, at 36 weeks, 35.2% of participants in BRAVE-AA1 and 32.5% of participants in BRAVE-AA2 receiving 4 mg of baricitinib had at least 80% scalp coverage. In the group taking the lower dose, 21.7% and 17.3% of patients in the BRAVE-AA1 and BRAVE-AA2 trials, respectively, had achieved at least 80% scalp coverage at 36 weeks. (These percentages differ slightly from the NEJM article because of a different analysis of missing data, Dr. King said. For comparison of both 36- and 52-week results, the percentages from the EADV are used above.)

The results indicate that 5% more patients reached the primary endpoint in the additional 16 weeks of the trial, Dr. King said.

Alopecia areata is an autoimmune condition where immune cells attack hair follicles, causing the hair to fall out, and is associated with emotional and psychological distress. Any hair follicle can be attacked, but they are rarely destroyed, so hair can regrow.

"Many underestimate the impact of this autoimmune hair loss condition," Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, told this news organization. He was not involved with the trial. "The burden of the disease, which certainly is an emotional but also a physical one, definitely needs to be addressed with indicated FDA-approved drugs," he noted, which is the goal of these trials. 

The BRAVE-AA1 and BRAVE-AA2 trials focused on scalp hair regrowth.

Eyebrow and eyelash growth, secondary outcomes, also improved between 36 and 52 weeks in both groups, calculated using the proportion of participants who had achieved full regrowth or regrowth with minimal gaps. At 36 weeks, about 31%-35% of patients who received 4 mg of baricitinib regrew eyebrow and eyelash hair. By 52 weeks, more than two out of five patients regrew eyebrow (44.1%) and eyelash (45.3%) hair.

“It’s a fantastic achievement and a major step forward in alopecia areata, especially for patients with the most severe and refractory cases,” said Arash Mostaghimi, MD, MPH, the director of inpatient dermatology at Brigham and Women’s Hospital in Boston, Massachusetts. Dr. Mostaghimi is on the advisory board for Eli Lilly, which manufactures baricitinib, and Brigham and Women’s was one of the clinical sites of the trial.

While dermatologists have been aware of how JAK inhibitors can affect hair regrowth in alopecia patients, they have been using these drugs off label, Dr. Friedman said. Therefore, these drugs are expensive and more difficult to access. These trials provide "data that proves the efficacy and safety of [baricitinib] under the umbrella of the FDA portal," he added, which will hopefully lead to an approved indication for alopecia areata, so it can be more accessible to patients.

Adverse events at 52 weeks were consistent with data from 36 weeks, which found that none of these adverse events occurred in more than 10% of participants. The most common adverse events were headache, acne, and increases in muscle-related blood markers. The most common infections reported were pneumonia, herpes zoster, and urinary tract infection. 

In February 2022, the FDA granted priority review for baricitinib for the treatment of severe alopecia areata. Lilly expects a regulatory decision by the end of 2022, they said in a press release. 

Lilly provided funding for the BRAVE-AA1 and BRAVE-AA2 trials. Dr. King reported financial relationships with Aclaris, Arena Pharmaceuticals, Bristol-Myers Squibb, Concert Pharmaceutics, Dermavant, Lilly, Pfizer, Regeneron, Sanofi Genzyme, and Viela Bio. Dr. Mostaghimi has reported serving on an advisory board for Lilly. Dr. Friedman reported no relevant financial relationships.  

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

*This article was updated on 3/28/2022 to include Dr. Friedman's comments, and on 3/31/2022 to correct the statement regarding adverse events reported in the study 

BOSTON – Following infection with SARS-CoV-2 infection, patients between the ages of 18 and 65 were at a significantly increased for developing certain cutaneous autoimmune and vascular diseases. This predominately favored systemic disease states with cutaneous involvement, rather than skin-limited processes.

The findings come from a large multicenter analysis that Zachary Holcomb, MD, presented during a late-breaking abstract session at the annual meeting of the American Academy of Dermatology.

Doug Brunk, MDedge News

“Viral triggers have been implicated in the pathogenesis of rheumatologic disease, but information regarding development of autoimmune disease following SARS-CoV-2 infection is limited,” said Dr. Holcomb, chief resident in the Harvard Combined Internal Medicine–Dermatology Residency, Boston. “Given its proposed thromboinflammatory pathobiology, we hypothesized that SARS-CoV-2 infection increases the risk of development of autoimmune disease with cutaneous manifestations and sought to define incidence rates of newly-diagnosed autoimmune diseases following SARS-CoV-2 infection.”

The researchers drew from the TriNetX Dataworks platform, an online cloud-based system that contains aggregated and deidentified patient information from about 75 million patients across 48 health care organizations. The infected cohort was defined as having a positive lab test for severe SARS-CoV-2 within the study window using Logical Observation Identifiers Names and Codes (LOINCs). Healthy controls consisted of a documented health care contact (inpatient or outpatient visit) during the study window without a positive SARS-CoV-2 lab test. Each cohort included patients aged 18-65 at the time of the study, and patients with previously diagnosed cutaneous autoimmune or vascular diseases were excluded from the analysis.

After propensity matching, the COVID-19 infected cohort and the healthy cohort included 1,904,864 patients each, with no baseline differences in age at index event, ethnicity, race, or sex. The study window was between April 1, 2020, and Oct. 1, 2020. The index event was a COVID-19 infection for the infected group and first documented health care contact in the healthy control group. The researchers looked at a window of 60 days following this index event for new incidence of cutaneous or vascular disease.

In the realm of connective tissue and related diseases, they found the incidence was increased among the COVID-19 infected group compared with controls for dermatomyositis (risk ratio, 2.273; P = .0196), scleroderma (RR, 1.959; P = .0001), and systemic lupus erythematosus (RR, 1.401; P < .0001). They also noted a significant decrease in the new incidence of alopecia areata in the COVID-19 infected group compared with controls (RR, 0.527; P < .0001).

No significant differences in the incidence of bullous and papulosquamous diseases were observed between the two groups. However, sarcoidosis was significantly more common in the COVID-19–infected group compared with controls (RR, 2.086; P < .001). “When taking all of these autoinflammatory diseases as a whole, there was an increased incidence in the COVID-19 infected group overall with a RR of 1.168 (P < .0001),” Dr. Holcomb said.

In the realm of vascular skin diseases, there was an increased incidence in the COVID-19 infected group in acrocyanosis (RR, 2.825; P < .001), Raynaud’s phenomenon (RR, 1.462; P < .0001), cutaneous small vessel vasculitis (RR, 1.714; P < .0001), granulomatosis with polyangiitis (RR, 2.667; P = .0002), and temporal arteritis (RR, 1.900; P = .0038).

“Interestingly, despite the academic and lay press reports of COVID toes, we did not see that in our data related to the COVID-infected group,” he said.

Dr. Holcomb acknowledged certain limitations of the study, including a narrow study window with a relatively short follow-up. “We were able to propensity match based on baseline demographics but not necessarily so based on health status and prior autoimmune disease,” he said. In addition, since the study was limited to those aged 18-65, the results may not be generalizable to pediatric and elderly patients, he said.

He described the study findings as “somewhat hypothesis-generating.” For instance, “why would we have more of a systemic process [at play?]. Our theory is that the severe inflammatory nature of COVID-19 leads to a lot of internal organ damage and exposure of autoantigens in that process, with relative skin sparing.”

One of the session moderators, Robert Paul Dellavalle, MD, PhD, professor of dermatology at the University of Colorado, Aurora, characterized the findings as “intriguing” but preliminary. “It would be interesting to look at more recent cohorts and see how vaccination for COVID-19 would impact the incidence rates of some of these diseases,” he said.

When asked for comment, Jeffrey A. Sparks, MD, MMSc, a rheumatologist at Brigham and Women's Hospital and assistant professor of medicine at Harvard Medical School, both in Boston, said, "This is an interesting study that should be followed up. Viral triggers have been known to precede autoimmune diseases so it will be very important to understand whether COVID-19 also impacts systemic autoimmune rheumatic diseases. I would be interested in differences in surveillance between the infection and control groups early in the pandemic. Many patients were avoiding interaction with the health care system at that point." 

Dr. Holcomb reported having no financial disclosures. Dr. Dellavalle disclosed that he is a consultant for Altus Labs and ParaPRO LLC. He has received grants and research funding from Pfizer.

* This story was updated on 3/29/22.

BOSTON – Following infection with SARS-CoV-2 infection, patients between the ages of 18 and 65 were at a significantly increased for developing certain cutaneous autoimmune and vascular diseases. This predominately favored systemic disease states with cutaneous involvement, rather than skin-limited processes.

The findings come from a large multicenter analysis that Zachary Holcomb, MD, presented during a late-breaking abstract session at the annual meeting of the American Academy of Dermatology.

Doug Brunk, MDedge News

“Viral triggers have been implicated in the pathogenesis of rheumatologic disease, but information regarding development of autoimmune disease following SARS-CoV-2 infection is limited,” said Dr. Holcomb, chief resident in the Harvard Combined Internal Medicine–Dermatology Residency, Boston. “Given its proposed thromboinflammatory pathobiology, we hypothesized that SARS-CoV-2 infection increases the risk of development of autoimmune disease with cutaneous manifestations and sought to define incidence rates of newly-diagnosed autoimmune diseases following SARS-CoV-2 infection.”

The researchers drew from the TriNetX Dataworks platform, an online cloud-based system that contains aggregated and deidentified patient information from about 75 million patients across 48 health care organizations. The infected cohort was defined as having a positive lab test for severe SARS-CoV-2 within the study window using Logical Observation Identifiers Names and Codes (LOINCs). Healthy controls consisted of a documented health care contact (inpatient or outpatient visit) during the study window without a positive SARS-CoV-2 lab test. Each cohort included patients aged 18-65 at the time of the study, and patients with previously diagnosed cutaneous autoimmune or vascular diseases were excluded from the analysis.

After propensity matching, the COVID-19 infected cohort and the healthy cohort included 1,904,864 patients each, with no baseline differences in age at index event, ethnicity, race, or sex. The study window was between April 1, 2020, and Oct. 1, 2020. The index event was a COVID-19 infection for the infected group and first documented health care contact in the healthy control group. The researchers looked at a window of 60 days following this index event for new incidence of cutaneous or vascular disease.

In the realm of connective tissue and related diseases, they found the incidence was increased among the COVID-19 infected group compared with controls for dermatomyositis (risk ratio, 2.273; P = .0196), scleroderma (RR, 1.959; P = .0001), and systemic lupus erythematosus (RR, 1.401; P < .0001). They also noted a significant decrease in the new incidence of alopecia areata in the COVID-19 infected group compared with controls (RR, 0.527; P < .0001).

No significant differences in the incidence of bullous and papulosquamous diseases were observed between the two groups. However, sarcoidosis was significantly more common in the COVID-19–infected group compared with controls (RR, 2.086; P < .001). “When taking all of these autoinflammatory diseases as a whole, there was an increased incidence in the COVID-19 infected group overall with a RR of 1.168 (P < .0001),” Dr. Holcomb said.

In the realm of vascular skin diseases, there was an increased incidence in the COVID-19 infected group in acrocyanosis (RR, 2.825; P < .001), Raynaud’s phenomenon (RR, 1.462; P < .0001), cutaneous small vessel vasculitis (RR, 1.714; P < .0001), granulomatosis with polyangiitis (RR, 2.667; P = .0002), and temporal arteritis (RR, 1.900; P = .0038).

“Interestingly, despite the academic and lay press reports of COVID toes, we did not see that in our data related to the COVID-infected group,” he said.

Dr. Holcomb acknowledged certain limitations of the study, including a narrow study window with a relatively short follow-up. “We were able to propensity match based on baseline demographics but not necessarily so based on health status and prior autoimmune disease,” he said. In addition, since the study was limited to those aged 18-65, the results may not be generalizable to pediatric and elderly patients, he said.

He described the study findings as “somewhat hypothesis-generating.” For instance, “why would we have more of a systemic process [at play?]. Our theory is that the severe inflammatory nature of COVID-19 leads to a lot of internal organ damage and exposure of autoantigens in that process, with relative skin sparing.”

One of the session moderators, Robert Paul Dellavalle, MD, PhD, professor of dermatology at the University of Colorado, Aurora, characterized the findings as “intriguing” but preliminary. “It would be interesting to look at more recent cohorts and see how vaccination for COVID-19 would impact the incidence rates of some of these diseases,” he said.

When asked for comment, Jeffrey A. Sparks, MD, MMSc, a rheumatologist at Brigham and Women's Hospital and assistant professor of medicine at Harvard Medical School, both in Boston, said, "This is an interesting study that should be followed up. Viral triggers have been known to precede autoimmune diseases so it will be very important to understand whether COVID-19 also impacts systemic autoimmune rheumatic diseases. I would be interested in differences in surveillance between the infection and control groups early in the pandemic. Many patients were avoiding interaction with the health care system at that point." 

Dr. Holcomb reported having no financial disclosures. Dr. Dellavalle disclosed that he is a consultant for Altus Labs and ParaPRO LLC. He has received grants and research funding from Pfizer.

* This story was updated on 3/29/22.

BOSTON – Following infection with SARS-CoV-2 infection, patients between the ages of 18 and 65 were at a significantly increased for developing certain cutaneous autoimmune and vascular diseases. This predominately favored systemic disease states with cutaneous involvement, rather than skin-limited processes.

The findings come from a large multicenter analysis that Zachary Holcomb, MD, presented during a late-breaking abstract session at the annual meeting of the American Academy of Dermatology.

Doug Brunk, MDedge News

“Viral triggers have been implicated in the pathogenesis of rheumatologic disease, but information regarding development of autoimmune disease following SARS-CoV-2 infection is limited,” said Dr. Holcomb, chief resident in the Harvard Combined Internal Medicine–Dermatology Residency, Boston. “Given its proposed thromboinflammatory pathobiology, we hypothesized that SARS-CoV-2 infection increases the risk of development of autoimmune disease with cutaneous manifestations and sought to define incidence rates of newly-diagnosed autoimmune diseases following SARS-CoV-2 infection.”

The researchers drew from the TriNetX Dataworks platform, an online cloud-based system that contains aggregated and deidentified patient information from about 75 million patients across 48 health care organizations. The infected cohort was defined as having a positive lab test for severe SARS-CoV-2 within the study window using Logical Observation Identifiers Names and Codes (LOINCs). Healthy controls consisted of a documented health care contact (inpatient or outpatient visit) during the study window without a positive SARS-CoV-2 lab test. Each cohort included patients aged 18-65 at the time of the study, and patients with previously diagnosed cutaneous autoimmune or vascular diseases were excluded from the analysis.

After propensity matching, the COVID-19 infected cohort and the healthy cohort included 1,904,864 patients each, with no baseline differences in age at index event, ethnicity, race, or sex. The study window was between April 1, 2020, and Oct. 1, 2020. The index event was a COVID-19 infection for the infected group and first documented health care contact in the healthy control group. The researchers looked at a window of 60 days following this index event for new incidence of cutaneous or vascular disease.

In the realm of connective tissue and related diseases, they found the incidence was increased among the COVID-19 infected group compared with controls for dermatomyositis (risk ratio, 2.273; P = .0196), scleroderma (RR, 1.959; P = .0001), and systemic lupus erythematosus (RR, 1.401; P < .0001). They also noted a significant decrease in the new incidence of alopecia areata in the COVID-19 infected group compared with controls (RR, 0.527; P < .0001).

No significant differences in the incidence of bullous and papulosquamous diseases were observed between the two groups. However, sarcoidosis was significantly more common in the COVID-19–infected group compared with controls (RR, 2.086; P < .001). “When taking all of these autoinflammatory diseases as a whole, there was an increased incidence in the COVID-19 infected group overall with a RR of 1.168 (P < .0001),” Dr. Holcomb said.

In the realm of vascular skin diseases, there was an increased incidence in the COVID-19 infected group in acrocyanosis (RR, 2.825; P < .001), Raynaud’s phenomenon (RR, 1.462; P < .0001), cutaneous small vessel vasculitis (RR, 1.714; P < .0001), granulomatosis with polyangiitis (RR, 2.667; P = .0002), and temporal arteritis (RR, 1.900; P = .0038).

“Interestingly, despite the academic and lay press reports of COVID toes, we did not see that in our data related to the COVID-infected group,” he said.

Dr. Holcomb acknowledged certain limitations of the study, including a narrow study window with a relatively short follow-up. “We were able to propensity match based on baseline demographics but not necessarily so based on health status and prior autoimmune disease,” he said. In addition, since the study was limited to those aged 18-65, the results may not be generalizable to pediatric and elderly patients, he said.

He described the study findings as “somewhat hypothesis-generating.” For instance, “why would we have more of a systemic process [at play?]. Our theory is that the severe inflammatory nature of COVID-19 leads to a lot of internal organ damage and exposure of autoantigens in that process, with relative skin sparing.”

One of the session moderators, Robert Paul Dellavalle, MD, PhD, professor of dermatology at the University of Colorado, Aurora, characterized the findings as “intriguing” but preliminary. “It would be interesting to look at more recent cohorts and see how vaccination for COVID-19 would impact the incidence rates of some of these diseases,” he said.

When asked for comment, Jeffrey A. Sparks, MD, MMSc, a rheumatologist at Brigham and Women's Hospital and assistant professor of medicine at Harvard Medical School, both in Boston, said, "This is an interesting study that should be followed up. Viral triggers have been known to precede autoimmune diseases so it will be very important to understand whether COVID-19 also impacts systemic autoimmune rheumatic diseases. I would be interested in differences in surveillance between the infection and control groups early in the pandemic. Many patients were avoiding interaction with the health care system at that point." 

Dr. Holcomb reported having no financial disclosures. Dr. Dellavalle disclosed that he is a consultant for Altus Labs and ParaPRO LLC. He has received grants and research funding from Pfizer.

* This story was updated on 3/29/22.

Hospitalized COVID-19 survivors showed greater cognitive impairment 6 months later, compared with patients hospitalized for other causes, but the overall disease burden was similar, based on data from 85 adults with COVID-19.

Previous studies have shown that cognitive and neuropsychiatric symptoms can occur from 2-6 months after COVID-19 recovery, and such symptoms are known to be associated with hospitalization for other severe medical conditions, Vardan Nersesjan, MD, of Copenhagen University Hospital, and colleagues wrote.

However, it remains unknown if COVID-19 is associated with a unique pattern of cognitive and mental impairment compared with other similarly severe medical conditions, they said.

In a study published in JAMA Psychiatry (2022 Mar 23. doi: 10.1001/jamapsychiatry.2022.0284), the researchers identified 85 adult COVID-19 survivors and 61 controls with non-COVID medical conditions who were treated and released between July 2020 and July 2021. The COVID-19 patients and controls were matched for age, sex, and ICU status. Cognitive impairment was assessed using the Mini-International Neuropsychiatric Interview, the Montreal Cognitive Assessment (MoCA), neurologic examination, and a semistructured interview to determine subjective symptoms.

The primary outcomes were the total scores on the MoCA and any new-onset psychiatric diagnoses. Secondary outcomes included specific psychiatric diagnoses such as depression, neurologic examination findings, and self-reported neuropsychiatric and cognitive symptoms. The mean age of the COVID-19 patients was 56.8 years, and 42% were women.

At 6 months’ follow-up, cognitive status was significantly lower in COVID-19 survivors, compared with controls, based on total geometric mean MoCA scores (26.7 vs. 27.5, P = .01). However, cognitive status improved significantly from 19.2 at hospital discharge to 26.1 at 6 months in 15 of the COVID-19 patients (P = .004), the researchers noted.

New-onset psychiatric diagnoses occurred in 16 COVID-19 patients and 12 of the controls (19% vs. 20%); this difference was not significant.

Secondary outcomes were not significantly different at 6 months between the groups, with the exception of anosmia, which was significantly more common in the COVID-19 patients; however, the significance disappeared in adjusted analysis, the researchers said.

The study findings were limited by several factors including the inability to prove causality because of the case-control feature and by the inability to detect small differences in neuropsychiatric outcomes, the researchers noted.

However, the results were strengthened by the use of a prospectively matched control group with similar disease severity admitted to the same hospital in the same time frame. Although the overall burden of neuropsychiatric and neurologic symptoms and diagnoses appeared similar in COVID-19 patients and those with other medical conditions, more research in larger populations is needed to determine smaller differences in neuropsychiatric profiles, the researchers noted.

Study fills research gap

The study is important at this time because, although prolonged neuropsychiatric and cognitive symptoms have been reported after COVID-19, the field lacked prospective case-control studies with well-matched controls to investigate whether these outcomes differed from those seen in other critical illnesses that had also required hospitalization, corresponding author Michael E. Benros, MD, of the Mental Health Center, Copenhagen, said in an interview.

“I was surprised that there was a significant worse cognitive functioning among COVID-19 patients 6 months after symptom onset also when compared to this well-matched control group that had been hospitalized for non–COVID-19 illness, although the absolute difference between the groups in cognition score were small,” said Dr. Benros. “Another notable finding is the large improvement in cognitive functioning from discharge to follow-up,” he added on behalf of himself and fellow corresponding author Daniel Kondziella, MD.

The study results show that cognitive function affected by COVID-19 and critical illness as observed at discharge showed a substantial improvement at 6 months after symptom onset, said Dr. Benros. “However, the cognitive function was significantly worse among severely ill COVID-19 patients 6 months after symptom onset when compared to a matched control group of individuals hospitalized for non–COVID-19 illness, although this difference in cognitive function was rather small in absolute numbers, and smaller than what had been suggested by other studies that lacked control groups. Strikingly, neuropsychiatric disorders were similar across the two groups, which was also the case when looking at neuropsychiatric symptoms.

“Larger prospective case-control studies of neuropsychiatric and cognitive functioning after COVID-19, compared with matched controls are still needed to detect smaller differences, and more detailed cognitive domains, and with longer follow-up time, which we are currently conducting,” Dr. Benros said.  
 

Controlled studies will help planning

“Lingering neuropsychiatric complications are common after COVID-19, but only controlled studies can tell us whether these complications are specific to COVID-19, rather than a general effect of having been medically ill,” Alasdair G. Rooney, MRCPsych MD PhD, of the University of Edinburgh, said in an interview. “The answer matters ultimately because COVID-19 is a new disease; societies and health care services need to be able to plan for its specific consequences.”

The health status of the control group is important as well. “Most previous studies had compared COVID-19 survivors against healthy controls or patients from a historical database. This new study compared COVID-19 survivors against those hospitalized for other medical causes over the same period,” Dr. Rooney said. “This is a more stringent test of whether COVID-19 has specific neurocognitive and neuropsychiatric consequences.

“The study found that new-onset neuropsychiatric diagnoses and symptoms were no more likely to occur after COVID-19 than after similarly severe medical illnesses,” Dr. Rooney said. “This negative finding runs counter to some earlier studies and may surprise some.” The findings need to be replicated in larger samples, but the current study shows the importance of prospectively recruiting active controls.

“In a subgroup analysis, some patients showed good improvement in cognitive scores between discharge and follow-up. While unsurprising, this is encouraging and suggests that the early postdischarge months are an important time for neurocognitive recovery,” Dr. Rooney noted.

“The findings suggest that COVID-19 may impair attention more selectively than other medical causes of hospitalization. COVID-19 survivors may also be at higher risk of significant overall cognitive impairment than survivors of similarly severe medical illnesses, after a similar duration,” said Dr. Rooney. “If the results are replicated by other prospective studies, they would suggest that there is something about COVID-19 that causes clinically significant neurocognitive difficulties in a minority of survivors.

“Larger well-controlled studies are required, with longer follow-up and more detailed neurocognitive testing,” as the duration of impairment and scope for further recovery are not known, Dr. Rooney added. Also unknown is whether COVID-19 affects attention permanently, or whether recovery is simply slower after COVID-19 compared to other medical illnesses.

“Knowing who is at the greatest risk of severe cognitive impairment after COVID-19 is important and likely to allow tailoring of more effective shielding strategies,” said Dr. Rooney. “This study was conducted before the widespread availability of vaccines for COVID-19. Long-term neuropsychiatric outcomes in vaccinated patients remain largely unknown. Arguably, these are now more important to understand, as future COVID-19 waves will occur mainly among vaccinated individuals.”

The study was supported by the Lundbeck Foundation and the Novo Nordisk Foundation. Lead author Dr. Nersesjan had no financial conflicts to disclose. Dr. Benros reported grants from Lundbeck Foundation and Novo Nordisk Foundation during the conduct of the study. Dr. Rooney had no financial conflicts to disclose.

This article was updated 3/25/22.

Hospitalized COVID-19 survivors showed greater cognitive impairment 6 months later, compared with patients hospitalized for other causes, but the overall disease burden was similar, based on data from 85 adults with COVID-19.

Previous studies have shown that cognitive and neuropsychiatric symptoms can occur from 2-6 months after COVID-19 recovery, and such symptoms are known to be associated with hospitalization for other severe medical conditions, Vardan Nersesjan, MD, of Copenhagen University Hospital, and colleagues wrote.

However, it remains unknown if COVID-19 is associated with a unique pattern of cognitive and mental impairment compared with other similarly severe medical conditions, they said.

In a study published in JAMA Psychiatry (2022 Mar 23. doi: 10.1001/jamapsychiatry.2022.0284), the researchers identified 85 adult COVID-19 survivors and 61 controls with non-COVID medical conditions who were treated and released between July 2020 and July 2021. The COVID-19 patients and controls were matched for age, sex, and ICU status. Cognitive impairment was assessed using the Mini-International Neuropsychiatric Interview, the Montreal Cognitive Assessment (MoCA), neurologic examination, and a semistructured interview to determine subjective symptoms.

The primary outcomes were the total scores on the MoCA and any new-onset psychiatric diagnoses. Secondary outcomes included specific psychiatric diagnoses such as depression, neurologic examination findings, and self-reported neuropsychiatric and cognitive symptoms. The mean age of the COVID-19 patients was 56.8 years, and 42% were women.

At 6 months’ follow-up, cognitive status was significantly lower in COVID-19 survivors, compared with controls, based on total geometric mean MoCA scores (26.7 vs. 27.5, P = .01). However, cognitive status improved significantly from 19.2 at hospital discharge to 26.1 at 6 months in 15 of the COVID-19 patients (P = .004), the researchers noted.

New-onset psychiatric diagnoses occurred in 16 COVID-19 patients and 12 of the controls (19% vs. 20%); this difference was not significant.

Secondary outcomes were not significantly different at 6 months between the groups, with the exception of anosmia, which was significantly more common in the COVID-19 patients; however, the significance disappeared in adjusted analysis, the researchers said.

The study findings were limited by several factors including the inability to prove causality because of the case-control feature and by the inability to detect small differences in neuropsychiatric outcomes, the researchers noted.

However, the results were strengthened by the use of a prospectively matched control group with similar disease severity admitted to the same hospital in the same time frame. Although the overall burden of neuropsychiatric and neurologic symptoms and diagnoses appeared similar in COVID-19 patients and those with other medical conditions, more research in larger populations is needed to determine smaller differences in neuropsychiatric profiles, the researchers noted.

Study fills research gap

The study is important at this time because, although prolonged neuropsychiatric and cognitive symptoms have been reported after COVID-19, the field lacked prospective case-control studies with well-matched controls to investigate whether these outcomes differed from those seen in other critical illnesses that had also required hospitalization, corresponding author Michael E. Benros, MD, of the Mental Health Center, Copenhagen, said in an interview.

“I was surprised that there was a significant worse cognitive functioning among COVID-19 patients 6 months after symptom onset also when compared to this well-matched control group that had been hospitalized for non–COVID-19 illness, although the absolute difference between the groups in cognition score were small,” said Dr. Benros. “Another notable finding is the large improvement in cognitive functioning from discharge to follow-up,” he added on behalf of himself and fellow corresponding author Daniel Kondziella, MD.

The study results show that cognitive function affected by COVID-19 and critical illness as observed at discharge showed a substantial improvement at 6 months after symptom onset, said Dr. Benros. “However, the cognitive function was significantly worse among severely ill COVID-19 patients 6 months after symptom onset when compared to a matched control group of individuals hospitalized for non–COVID-19 illness, although this difference in cognitive function was rather small in absolute numbers, and smaller than what had been suggested by other studies that lacked control groups. Strikingly, neuropsychiatric disorders were similar across the two groups, which was also the case when looking at neuropsychiatric symptoms.

“Larger prospective case-control studies of neuropsychiatric and cognitive functioning after COVID-19, compared with matched controls are still needed to detect smaller differences, and more detailed cognitive domains, and with longer follow-up time, which we are currently conducting,” Dr. Benros said.  
 

Controlled studies will help planning

“Lingering neuropsychiatric complications are common after COVID-19, but only controlled studies can tell us whether these complications are specific to COVID-19, rather than a general effect of having been medically ill,” Alasdair G. Rooney, MRCPsych MD PhD, of the University of Edinburgh, said in an interview. “The answer matters ultimately because COVID-19 is a new disease; societies and health care services need to be able to plan for its specific consequences.”

The health status of the control group is important as well. “Most previous studies had compared COVID-19 survivors against healthy controls or patients from a historical database. This new study compared COVID-19 survivors against those hospitalized for other medical causes over the same period,” Dr. Rooney said. “This is a more stringent test of whether COVID-19 has specific neurocognitive and neuropsychiatric consequences.

“The study found that new-onset neuropsychiatric diagnoses and symptoms were no more likely to occur after COVID-19 than after similarly severe medical illnesses,” Dr. Rooney said. “This negative finding runs counter to some earlier studies and may surprise some.” The findings need to be replicated in larger samples, but the current study shows the importance of prospectively recruiting active controls.

“In a subgroup analysis, some patients showed good improvement in cognitive scores between discharge and follow-up. While unsurprising, this is encouraging and suggests that the early postdischarge months are an important time for neurocognitive recovery,” Dr. Rooney noted.

“The findings suggest that COVID-19 may impair attention more selectively than other medical causes of hospitalization. COVID-19 survivors may also be at higher risk of significant overall cognitive impairment than survivors of similarly severe medical illnesses, after a similar duration,” said Dr. Rooney. “If the results are replicated by other prospective studies, they would suggest that there is something about COVID-19 that causes clinically significant neurocognitive difficulties in a minority of survivors.

“Larger well-controlled studies are required, with longer follow-up and more detailed neurocognitive testing,” as the duration of impairment and scope for further recovery are not known, Dr. Rooney added. Also unknown is whether COVID-19 affects attention permanently, or whether recovery is simply slower after COVID-19 compared to other medical illnesses.

“Knowing who is at the greatest risk of severe cognitive impairment after COVID-19 is important and likely to allow tailoring of more effective shielding strategies,” said Dr. Rooney. “This study was conducted before the widespread availability of vaccines for COVID-19. Long-term neuropsychiatric outcomes in vaccinated patients remain largely unknown. Arguably, these are now more important to understand, as future COVID-19 waves will occur mainly among vaccinated individuals.”

The study was supported by the Lundbeck Foundation and the Novo Nordisk Foundation. Lead author Dr. Nersesjan had no financial conflicts to disclose. Dr. Benros reported grants from Lundbeck Foundation and Novo Nordisk Foundation during the conduct of the study. Dr. Rooney had no financial conflicts to disclose.

This article was updated 3/25/22.

Hospitalized COVID-19 survivors showed greater cognitive impairment 6 months later, compared with patients hospitalized for other causes, but the overall disease burden was similar, based on data from 85 adults with COVID-19.

Previous studies have shown that cognitive and neuropsychiatric symptoms can occur from 2-6 months after COVID-19 recovery, and such symptoms are known to be associated with hospitalization for other severe medical conditions, Vardan Nersesjan, MD, of Copenhagen University Hospital, and colleagues wrote.

However, it remains unknown if COVID-19 is associated with a unique pattern of cognitive and mental impairment compared with other similarly severe medical conditions, they said.

In a study published in JAMA Psychiatry (2022 Mar 23. doi: 10.1001/jamapsychiatry.2022.0284), the researchers identified 85 adult COVID-19 survivors and 61 controls with non-COVID medical conditions who were treated and released between July 2020 and July 2021. The COVID-19 patients and controls were matched for age, sex, and ICU status. Cognitive impairment was assessed using the Mini-International Neuropsychiatric Interview, the Montreal Cognitive Assessment (MoCA), neurologic examination, and a semistructured interview to determine subjective symptoms.

The primary outcomes were the total scores on the MoCA and any new-onset psychiatric diagnoses. Secondary outcomes included specific psychiatric diagnoses such as depression, neurologic examination findings, and self-reported neuropsychiatric and cognitive symptoms. The mean age of the COVID-19 patients was 56.8 years, and 42% were women.

At 6 months’ follow-up, cognitive status was significantly lower in COVID-19 survivors, compared with controls, based on total geometric mean MoCA scores (26.7 vs. 27.5, P = .01). However, cognitive status improved significantly from 19.2 at hospital discharge to 26.1 at 6 months in 15 of the COVID-19 patients (P = .004), the researchers noted.

New-onset psychiatric diagnoses occurred in 16 COVID-19 patients and 12 of the controls (19% vs. 20%); this difference was not significant.

Secondary outcomes were not significantly different at 6 months between the groups, with the exception of anosmia, which was significantly more common in the COVID-19 patients; however, the significance disappeared in adjusted analysis, the researchers said.

The study findings were limited by several factors including the inability to prove causality because of the case-control feature and by the inability to detect small differences in neuropsychiatric outcomes, the researchers noted.

However, the results were strengthened by the use of a prospectively matched control group with similar disease severity admitted to the same hospital in the same time frame. Although the overall burden of neuropsychiatric and neurologic symptoms and diagnoses appeared similar in COVID-19 patients and those with other medical conditions, more research in larger populations is needed to determine smaller differences in neuropsychiatric profiles, the researchers noted.

Study fills research gap

The study is important at this time because, although prolonged neuropsychiatric and cognitive symptoms have been reported after COVID-19, the field lacked prospective case-control studies with well-matched controls to investigate whether these outcomes differed from those seen in other critical illnesses that had also required hospitalization, corresponding author Michael E. Benros, MD, of the Mental Health Center, Copenhagen, said in an interview.

“I was surprised that there was a significant worse cognitive functioning among COVID-19 patients 6 months after symptom onset also when compared to this well-matched control group that had been hospitalized for non–COVID-19 illness, although the absolute difference between the groups in cognition score were small,” said Dr. Benros. “Another notable finding is the large improvement in cognitive functioning from discharge to follow-up,” he added on behalf of himself and fellow corresponding author Daniel Kondziella, MD.

The study results show that cognitive function affected by COVID-19 and critical illness as observed at discharge showed a substantial improvement at 6 months after symptom onset, said Dr. Benros. “However, the cognitive function was significantly worse among severely ill COVID-19 patients 6 months after symptom onset when compared to a matched control group of individuals hospitalized for non–COVID-19 illness, although this difference in cognitive function was rather small in absolute numbers, and smaller than what had been suggested by other studies that lacked control groups. Strikingly, neuropsychiatric disorders were similar across the two groups, which was also the case when looking at neuropsychiatric symptoms.

“Larger prospective case-control studies of neuropsychiatric and cognitive functioning after COVID-19, compared with matched controls are still needed to detect smaller differences, and more detailed cognitive domains, and with longer follow-up time, which we are currently conducting,” Dr. Benros said.  
 

Controlled studies will help planning

“Lingering neuropsychiatric complications are common after COVID-19, but only controlled studies can tell us whether these complications are specific to COVID-19, rather than a general effect of having been medically ill,” Alasdair G. Rooney, MRCPsych MD PhD, of the University of Edinburgh, said in an interview. “The answer matters ultimately because COVID-19 is a new disease; societies and health care services need to be able to plan for its specific consequences.”

The health status of the control group is important as well. “Most previous studies had compared COVID-19 survivors against healthy controls or patients from a historical database. This new study compared COVID-19 survivors against those hospitalized for other medical causes over the same period,” Dr. Rooney said. “This is a more stringent test of whether COVID-19 has specific neurocognitive and neuropsychiatric consequences.

“The study found that new-onset neuropsychiatric diagnoses and symptoms were no more likely to occur after COVID-19 than after similarly severe medical illnesses,” Dr. Rooney said. “This negative finding runs counter to some earlier studies and may surprise some.” The findings need to be replicated in larger samples, but the current study shows the importance of prospectively recruiting active controls.

“In a subgroup analysis, some patients showed good improvement in cognitive scores between discharge and follow-up. While unsurprising, this is encouraging and suggests that the early postdischarge months are an important time for neurocognitive recovery,” Dr. Rooney noted.

“The findings suggest that COVID-19 may impair attention more selectively than other medical causes of hospitalization. COVID-19 survivors may also be at higher risk of significant overall cognitive impairment than survivors of similarly severe medical illnesses, after a similar duration,” said Dr. Rooney. “If the results are replicated by other prospective studies, they would suggest that there is something about COVID-19 that causes clinically significant neurocognitive difficulties in a minority of survivors.

“Larger well-controlled studies are required, with longer follow-up and more detailed neurocognitive testing,” as the duration of impairment and scope for further recovery are not known, Dr. Rooney added. Also unknown is whether COVID-19 affects attention permanently, or whether recovery is simply slower after COVID-19 compared to other medical illnesses.

“Knowing who is at the greatest risk of severe cognitive impairment after COVID-19 is important and likely to allow tailoring of more effective shielding strategies,” said Dr. Rooney. “This study was conducted before the widespread availability of vaccines for COVID-19. Long-term neuropsychiatric outcomes in vaccinated patients remain largely unknown. Arguably, these are now more important to understand, as future COVID-19 waves will occur mainly among vaccinated individuals.”

The study was supported by the Lundbeck Foundation and the Novo Nordisk Foundation. Lead author Dr. Nersesjan had no financial conflicts to disclose. Dr. Benros reported grants from Lundbeck Foundation and Novo Nordisk Foundation during the conduct of the study. Dr. Rooney had no financial conflicts to disclose.

This article was updated 3/25/22.

People with higher (above the median) consumption of artificial sweeteners – especially aspartame and acesulfame-potassium (acesulfame-K) – had a 13% higher risk of overall cancer over 8 years than those who did not consume these sweeteners.

Higher consumption of aspartame was associated with a 22% increased risk of breast cancer and a 15% increased risk of obesity-related cancer, compared with not consuming any of these sweeteners.*

BigRedCurlyGuy/Thinkstock

These findings from the Nutri-Santé population-based observational study in France were published online March 24, 2022, in PLoS Medicine.

“Our findings do not support the use of artificial sweeteners as safe alternatives for sugar in foods or beverages and provide important and novel information to address the controversies about their potential adverse health effect,” Charlotte Debras, of the French National Institute for Health and Medical Research (Inserm) and Sorbonne Paris Nord University, and colleagues wrote.

“Results from the NutriNet-Santé cohort (n = 102,865) suggest that artificial sweeteners found in many food and beverage brands worldwide may be associated with increased cancer risk, in line with several experimental in vivo/in vitro studies. These findings provide novel information for the re-evaluation of these food additives by health agencies,” they wrote.

Commenting to the U.K. Science Media Center, Duane Mellor, PhD, registered dietitian and senior teaching fellow, Aston (England) University, said: “This study does not prove or even suggest that we should go back to sugar and turn our backs on artificial sweeteners or diet drinks.  

“It does, however, suggest that artificial sweeteners are not a perfect replacement for sugar, they come with their own potential risks, as does sugar. The ideal answer is probably to move away from both, however, that may be unappealing to many who like a little sweetness in their life, so ditching the regular or diet soft drink (soda) for water may not be a well-received health message.”
 

Important analysis, interpret with caution

“I think that this is an important analysis, but the results need to be interpreted with caution,” another expert, John L. Sievenpiper, MD, PhD, associate professor, departments of nutritional sciences and medicine, University of Toronto, said in an interview.

“Large observational studies like this one that assess the exposure to low and no calorie sweeteners with obesity-related chronic diseases are at risk of reverse causality,” he explained. This is “a caveat that is well recognized by investigators in this field ... and guideline and policy makers.”

Reverse causality is a possibility because “it is likely that many high consumers of low- and no-calorie sweeteners (of which aspartame and acesulfame-K are the most common) will be consuming these sweeteners as a weight-loss strategy,” he added, “as opposed to these sweeteners causing obesity and its complications (including cancers).”

His team recently published a Diabetes and Nutrition Study Group–commissioned systematic review and meta-analysis of 17 randomized controlled trials (JAMA Netw Open. 2022;5[3]:e222092). Their findings “suggest that over the moderate term [low- and no-calorie sweetened beverages] are a viable alternative to water as a replacement strategy in adults with overweight or obesity who are at risk for or have diabetes,” states one of two syntheses (the other is in press in Diabetes Care) for the update of the European Association for the Study of Diabetes guidelines coming in the fall of 2022. 

“The bottom line” for the current study, according to Dr. Sievenpiper, “is that it is difficult to disentangle the signals for low- and no-calorie sweeteners from obesity itself and the signals for the sugars and calories that they are replacing/displacing in this analysis. Substitution analyses would be useful to address some of these concerns.”
 

Conflicting results

Recent epidemiologic and animal studies about a possible link between artificial sweeteners and risk of cancer have had conflicting results, and information about specific types of sweeteners and consumption of artificially sweetened foods as well as beverages is lacking, Ms. Debras and colleagues wrote.

They aimed to investigate the associations between intakes of artificial sweeteners (total and the most common ones – aspartame, acesulfame-K, and sucralose) and cancer risk (overall risk and most frequent types – breast, prostate, and obesity-related cancers) in the ongoing NutriNet-Santé study.

“Obesity-related cancers are cancers for which obesity is involved in their etiology as one of the risk (or protective) factors, as recognized by the World Cancer Research Fund (independently of participant BMI [body mass index] status): colorectal, stomach, liver, mouth, pharynx, larynx, esophageal, breast (with opposite associations pre- and post menopause), ovarian, endometrial, and prostate cancers,” the researchers explained.

According to a recent study , “obesity increases the risk of breast cancer in postmenopausal women but, conversely, it appears to be protective in premenopausal women,” Dr. Sievenpiper noted.

The ongoing NutriNet-Santé study was initiated in 2009 to investigate associations between nutrition and health in the French population. Participants aged 18 and older with Internet access enroll voluntarily and self-report medical history and sociodemographic, diet, lifestyle, and health data.

The current cohort included 102,865 adults who enrolled in 2009-2021.

Consumption of artificial sweeteners was determined from repeated 24-hour dietary records that included brand names of processed foods.

At enrollment, participants were an average age of 42 years and 79% were women. They had a mean BMI of 24 kg/m2. On average, they had 5.6 dietary records.

Most participants did not consume artificial sweeteners (63%); those who did were classified as lower consumers (18.5%) or higher consumers (18.5%).

Aspartame was the most common artificial sweetener (58% of intake), followed by acesulfame-K (29%) and sucralose (10%), and these were mostly in soft drinks (53%), table-top sweeteners (29%), and yogurt/cottage cheese (8%). 

During a median 7.7-year follow-up, 3,358 incident cancers – 982 breast, 403 prostate, and 2023 obesity-related cancers – were diagnosed in participants who were a mean age of 60.

Compared with nonconsumers, higher consumers of artificial sweeteners had a higher risk of overall cancer (hazard ratio, 1.13; 95% confidence interval, 1.03-1.25; P-trend = .002), after adjusting for age, sex, education, physical activity, smoking, BMI, height, weight gain during follow-up, diabetes, family history of cancer, number of 24-hour dietary records, baseline caloric intake, and consumption of alcohol, sodium, saturated fatty acids, fiber, sugar, fruit and vegetables, whole-grain foods, and dairy products.

Participants who were higher consumers of aspartame had an increased risk of overall cancer (HR, 1.15; 95% CI, 1.03-1.28; P = .002), as did higher consumers of acesulfame-K (HR, 1.13; 95% CI, 1.01-1.26; P = .007), compared with nonconsumers, after adjusting for the multiple variables. 

Higher consumers of aspartame had a higher risk of breast cancer (HR, 1.22; 95% CI, 1.01-1.48; P = .036) and obesity-related cancers (HR, 1.15; 95% CI, 1.01-1.32; P = .026) than nonconsumers.

Higher consumers of total artificial sweeteners had a higher risk of obesity-related cancers than nonconsumers (HR, 1.13; 95% CI, 1.00-1.28; P = .036).

The researchers acknowledged that study limitations include potential selection bias, residual confounding, and reverse causality, though sensitivity analyses were performed to address these concerns.

The NutriNet-Santé study was supported by several French public institutions. Ms. Debras was supported by a grant from the French National Cancer Institute. This project has received funding from the European Research Council, the French National Cancer Institute, the French Ministry of Health, and the IdEx Université de Paris. Dr. Sievenpiper has reported receiving funding from the Tate and Lyle Nutritional Research Fund at the University of Toronto, the Nutrition Trialists Fund at the University of Toronto, and the International Sweeteners Association.

Correction, 3/31: An earlier version of this article erroneously stated that there was a 22% increased risk of overall cancer, rather than breast cancer. 

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

People with higher (above the median) consumption of artificial sweeteners – especially aspartame and acesulfame-potassium (acesulfame-K) – had a 13% higher risk of overall cancer over 8 years than those who did not consume these sweeteners.

Higher consumption of aspartame was associated with a 22% increased risk of breast cancer and a 15% increased risk of obesity-related cancer, compared with not consuming any of these sweeteners.*

BigRedCurlyGuy/Thinkstock

These findings from the Nutri-Santé population-based observational study in France were published online March 24, 2022, in PLoS Medicine.

“Our findings do not support the use of artificial sweeteners as safe alternatives for sugar in foods or beverages and provide important and novel information to address the controversies about their potential adverse health effect,” Charlotte Debras, of the French National Institute for Health and Medical Research (Inserm) and Sorbonne Paris Nord University, and colleagues wrote.

“Results from the NutriNet-Santé cohort (n = 102,865) suggest that artificial sweeteners found in many food and beverage brands worldwide may be associated with increased cancer risk, in line with several experimental in vivo/in vitro studies. These findings provide novel information for the re-evaluation of these food additives by health agencies,” they wrote.

Commenting to the U.K. Science Media Center, Duane Mellor, PhD, registered dietitian and senior teaching fellow, Aston (England) University, said: “This study does not prove or even suggest that we should go back to sugar and turn our backs on artificial sweeteners or diet drinks.  

“It does, however, suggest that artificial sweeteners are not a perfect replacement for sugar, they come with their own potential risks, as does sugar. The ideal answer is probably to move away from both, however, that may be unappealing to many who like a little sweetness in their life, so ditching the regular or diet soft drink (soda) for water may not be a well-received health message.”
 

Important analysis, interpret with caution

“I think that this is an important analysis, but the results need to be interpreted with caution,” another expert, John L. Sievenpiper, MD, PhD, associate professor, departments of nutritional sciences and medicine, University of Toronto, said in an interview.

“Large observational studies like this one that assess the exposure to low and no calorie sweeteners with obesity-related chronic diseases are at risk of reverse causality,” he explained. This is “a caveat that is well recognized by investigators in this field ... and guideline and policy makers.”

Reverse causality is a possibility because “it is likely that many high consumers of low- and no-calorie sweeteners (of which aspartame and acesulfame-K are the most common) will be consuming these sweeteners as a weight-loss strategy,” he added, “as opposed to these sweeteners causing obesity and its complications (including cancers).”

His team recently published a Diabetes and Nutrition Study Group–commissioned systematic review and meta-analysis of 17 randomized controlled trials (JAMA Netw Open. 2022;5[3]:e222092). Their findings “suggest that over the moderate term [low- and no-calorie sweetened beverages] are a viable alternative to water as a replacement strategy in adults with overweight or obesity who are at risk for or have diabetes,” states one of two syntheses (the other is in press in Diabetes Care) for the update of the European Association for the Study of Diabetes guidelines coming in the fall of 2022. 

“The bottom line” for the current study, according to Dr. Sievenpiper, “is that it is difficult to disentangle the signals for low- and no-calorie sweeteners from obesity itself and the signals for the sugars and calories that they are replacing/displacing in this analysis. Substitution analyses would be useful to address some of these concerns.”
 

Conflicting results

Recent epidemiologic and animal studies about a possible link between artificial sweeteners and risk of cancer have had conflicting results, and information about specific types of sweeteners and consumption of artificially sweetened foods as well as beverages is lacking, Ms. Debras and colleagues wrote.

They aimed to investigate the associations between intakes of artificial sweeteners (total and the most common ones – aspartame, acesulfame-K, and sucralose) and cancer risk (overall risk and most frequent types – breast, prostate, and obesity-related cancers) in the ongoing NutriNet-Santé study.

“Obesity-related cancers are cancers for which obesity is involved in their etiology as one of the risk (or protective) factors, as recognized by the World Cancer Research Fund (independently of participant BMI [body mass index] status): colorectal, stomach, liver, mouth, pharynx, larynx, esophageal, breast (with opposite associations pre- and post menopause), ovarian, endometrial, and prostate cancers,” the researchers explained.

According to a recent study , “obesity increases the risk of breast cancer in postmenopausal women but, conversely, it appears to be protective in premenopausal women,” Dr. Sievenpiper noted.

The ongoing NutriNet-Santé study was initiated in 2009 to investigate associations between nutrition and health in the French population. Participants aged 18 and older with Internet access enroll voluntarily and self-report medical history and sociodemographic, diet, lifestyle, and health data.

The current cohort included 102,865 adults who enrolled in 2009-2021.

Consumption of artificial sweeteners was determined from repeated 24-hour dietary records that included brand names of processed foods.

At enrollment, participants were an average age of 42 years and 79% were women. They had a mean BMI of 24 kg/m2. On average, they had 5.6 dietary records.

Most participants did not consume artificial sweeteners (63%); those who did were classified as lower consumers (18.5%) or higher consumers (18.5%).

Aspartame was the most common artificial sweetener (58% of intake), followed by acesulfame-K (29%) and sucralose (10%), and these were mostly in soft drinks (53%), table-top sweeteners (29%), and yogurt/cottage cheese (8%). 

During a median 7.7-year follow-up, 3,358 incident cancers – 982 breast, 403 prostate, and 2023 obesity-related cancers – were diagnosed in participants who were a mean age of 60.

Compared with nonconsumers, higher consumers of artificial sweeteners had a higher risk of overall cancer (hazard ratio, 1.13; 95% confidence interval, 1.03-1.25; P-trend = .002), after adjusting for age, sex, education, physical activity, smoking, BMI, height, weight gain during follow-up, diabetes, family history of cancer, number of 24-hour dietary records, baseline caloric intake, and consumption of alcohol, sodium, saturated fatty acids, fiber, sugar, fruit and vegetables, whole-grain foods, and dairy products.

Participants who were higher consumers of aspartame had an increased risk of overall cancer (HR, 1.15; 95% CI, 1.03-1.28; P = .002), as did higher consumers of acesulfame-K (HR, 1.13; 95% CI, 1.01-1.26; P = .007), compared with nonconsumers, after adjusting for the multiple variables. 

Higher consumers of aspartame had a higher risk of breast cancer (HR, 1.22; 95% CI, 1.01-1.48; P = .036) and obesity-related cancers (HR, 1.15; 95% CI, 1.01-1.32; P = .026) than nonconsumers.

Higher consumers of total artificial sweeteners had a higher risk of obesity-related cancers than nonconsumers (HR, 1.13; 95% CI, 1.00-1.28; P = .036).

The researchers acknowledged that study limitations include potential selection bias, residual confounding, and reverse causality, though sensitivity analyses were performed to address these concerns.

The NutriNet-Santé study was supported by several French public institutions. Ms. Debras was supported by a grant from the French National Cancer Institute. This project has received funding from the European Research Council, the French National Cancer Institute, the French Ministry of Health, and the IdEx Université de Paris. Dr. Sievenpiper has reported receiving funding from the Tate and Lyle Nutritional Research Fund at the University of Toronto, the Nutrition Trialists Fund at the University of Toronto, and the International Sweeteners Association.

Correction, 3/31: An earlier version of this article erroneously stated that there was a 22% increased risk of overall cancer, rather than breast cancer. 

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

People with higher (above the median) consumption of artificial sweeteners – especially aspartame and acesulfame-potassium (acesulfame-K) – had a 13% higher risk of overall cancer over 8 years than those who did not consume these sweeteners.

Higher consumption of aspartame was associated with a 22% increased risk of breast cancer and a 15% increased risk of obesity-related cancer, compared with not consuming any of these sweeteners.*

BigRedCurlyGuy/Thinkstock

These findings from the Nutri-Santé population-based observational study in France were published online March 24, 2022, in PLoS Medicine.

“Our findings do not support the use of artificial sweeteners as safe alternatives for sugar in foods or beverages and provide important and novel information to address the controversies about their potential adverse health effect,” Charlotte Debras, of the French National Institute for Health and Medical Research (Inserm) and Sorbonne Paris Nord University, and colleagues wrote.

“Results from the NutriNet-Santé cohort (n = 102,865) suggest that artificial sweeteners found in many food and beverage brands worldwide may be associated with increased cancer risk, in line with several experimental in vivo/in vitro studies. These findings provide novel information for the re-evaluation of these food additives by health agencies,” they wrote.

Commenting to the U.K. Science Media Center, Duane Mellor, PhD, registered dietitian and senior teaching fellow, Aston (England) University, said: “This study does not prove or even suggest that we should go back to sugar and turn our backs on artificial sweeteners or diet drinks.  

“It does, however, suggest that artificial sweeteners are not a perfect replacement for sugar, they come with their own potential risks, as does sugar. The ideal answer is probably to move away from both, however, that may be unappealing to many who like a little sweetness in their life, so ditching the regular or diet soft drink (soda) for water may not be a well-received health message.”
 

Important analysis, interpret with caution

“I think that this is an important analysis, but the results need to be interpreted with caution,” another expert, John L. Sievenpiper, MD, PhD, associate professor, departments of nutritional sciences and medicine, University of Toronto, said in an interview.

“Large observational studies like this one that assess the exposure to low and no calorie sweeteners with obesity-related chronic diseases are at risk of reverse causality,” he explained. This is “a caveat that is well recognized by investigators in this field ... and guideline and policy makers.”

Reverse causality is a possibility because “it is likely that many high consumers of low- and no-calorie sweeteners (of which aspartame and acesulfame-K are the most common) will be consuming these sweeteners as a weight-loss strategy,” he added, “as opposed to these sweeteners causing obesity and its complications (including cancers).”

His team recently published a Diabetes and Nutrition Study Group–commissioned systematic review and meta-analysis of 17 randomized controlled trials (JAMA Netw Open. 2022;5[3]:e222092). Their findings “suggest that over the moderate term [low- and no-calorie sweetened beverages] are a viable alternative to water as a replacement strategy in adults with overweight or obesity who are at risk for or have diabetes,” states one of two syntheses (the other is in press in Diabetes Care) for the update of the European Association for the Study of Diabetes guidelines coming in the fall of 2022. 

“The bottom line” for the current study, according to Dr. Sievenpiper, “is that it is difficult to disentangle the signals for low- and no-calorie sweeteners from obesity itself and the signals for the sugars and calories that they are replacing/displacing in this analysis. Substitution analyses would be useful to address some of these concerns.”
 

Conflicting results

Recent epidemiologic and animal studies about a possible link between artificial sweeteners and risk of cancer have had conflicting results, and information about specific types of sweeteners and consumption of artificially sweetened foods as well as beverages is lacking, Ms. Debras and colleagues wrote.

They aimed to investigate the associations between intakes of artificial sweeteners (total and the most common ones – aspartame, acesulfame-K, and sucralose) and cancer risk (overall risk and most frequent types – breast, prostate, and obesity-related cancers) in the ongoing NutriNet-Santé study.

“Obesity-related cancers are cancers for which obesity is involved in their etiology as one of the risk (or protective) factors, as recognized by the World Cancer Research Fund (independently of participant BMI [body mass index] status): colorectal, stomach, liver, mouth, pharynx, larynx, esophageal, breast (with opposite associations pre- and post menopause), ovarian, endometrial, and prostate cancers,” the researchers explained.

According to a recent study , “obesity increases the risk of breast cancer in postmenopausal women but, conversely, it appears to be protective in premenopausal women,” Dr. Sievenpiper noted.

The ongoing NutriNet-Santé study was initiated in 2009 to investigate associations between nutrition and health in the French population. Participants aged 18 and older with Internet access enroll voluntarily and self-report medical history and sociodemographic, diet, lifestyle, and health data.

The current cohort included 102,865 adults who enrolled in 2009-2021.

Consumption of artificial sweeteners was determined from repeated 24-hour dietary records that included brand names of processed foods.

At enrollment, participants were an average age of 42 years and 79% were women. They had a mean BMI of 24 kg/m2. On average, they had 5.6 dietary records.

Most participants did not consume artificial sweeteners (63%); those who did were classified as lower consumers (18.5%) or higher consumers (18.5%).

Aspartame was the most common artificial sweetener (58% of intake), followed by acesulfame-K (29%) and sucralose (10%), and these were mostly in soft drinks (53%), table-top sweeteners (29%), and yogurt/cottage cheese (8%). 

During a median 7.7-year follow-up, 3,358 incident cancers – 982 breast, 403 prostate, and 2023 obesity-related cancers – were diagnosed in participants who were a mean age of 60.

Compared with nonconsumers, higher consumers of artificial sweeteners had a higher risk of overall cancer (hazard ratio, 1.13; 95% confidence interval, 1.03-1.25; P-trend = .002), after adjusting for age, sex, education, physical activity, smoking, BMI, height, weight gain during follow-up, diabetes, family history of cancer, number of 24-hour dietary records, baseline caloric intake, and consumption of alcohol, sodium, saturated fatty acids, fiber, sugar, fruit and vegetables, whole-grain foods, and dairy products.

Participants who were higher consumers of aspartame had an increased risk of overall cancer (HR, 1.15; 95% CI, 1.03-1.28; P = .002), as did higher consumers of acesulfame-K (HR, 1.13; 95% CI, 1.01-1.26; P = .007), compared with nonconsumers, after adjusting for the multiple variables. 

Higher consumers of aspartame had a higher risk of breast cancer (HR, 1.22; 95% CI, 1.01-1.48; P = .036) and obesity-related cancers (HR, 1.15; 95% CI, 1.01-1.32; P = .026) than nonconsumers.

Higher consumers of total artificial sweeteners had a higher risk of obesity-related cancers than nonconsumers (HR, 1.13; 95% CI, 1.00-1.28; P = .036).

The researchers acknowledged that study limitations include potential selection bias, residual confounding, and reverse causality, though sensitivity analyses were performed to address these concerns.

The NutriNet-Santé study was supported by several French public institutions. Ms. Debras was supported by a grant from the French National Cancer Institute. This project has received funding from the European Research Council, the French National Cancer Institute, the French Ministry of Health, and the IdEx Université de Paris. Dr. Sievenpiper has reported receiving funding from the Tate and Lyle Nutritional Research Fund at the University of Toronto, the Nutrition Trialists Fund at the University of Toronto, and the International Sweeteners Association.

Correction, 3/31: An earlier version of this article erroneously stated that there was a 22% increased risk of overall cancer, rather than breast cancer. 

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

One nurse is headed to federal prison and another faces a similar fate for participating in a pair of prison contraband schemes.

Former contract nurse Joseph Nwancha, RN, 41, of Baltimore, Maryland, was sentenced to 30 months in federal prison followed by 3 years of supervised release for his role in a scheme to smuggle narcotics, tobacco, cell phones, and other contraband into a state prison.

In his plea deal, Mr. Nwancha said that he was regularly the on-duty nurse during evenings and nights at Maryland Correctional Institute Jessup, which housed approximately 1,100 male inmates. This made it possible for him to have private contact with inmates without prison employees or other inmates observing the interactions.

According to court documents, beginning in September 2017, Corey Alston, an inmate at the medium-security prison, began bribing Mr. Nwancha to bring contraband into the prison. The inmate’s sister, Ashley Alston, discussed the bribe payments with Mr. Nwancha via text messages and later met with Mr. Nwancha to give him money. In his plea deal, Mr. Nwancha also admitted to having similar arrangements with other inmates.

On Nov. 28, 2017, Mr. Nwancha was stopped at MCIJ and was found to be in possession of approximately 230 g of K2, a synthetic cannabinoid, intended for Mr. Alston and other inmates, according to the court documents. A cell phone recovered from Mr. Nwancha contained text-message conversations discussing bribe payments and other details related to the smuggling operation. The next day, Mr. Nwancha fled to Dublin where he remained until his arrest and extradition, the document says.

According to the Maryland Board of Nursing, Mr. Nwancha earned his license to practice in 2013, and it expired in 2019.

The Washington Post reported that Mr. Nwancha was part of a smuggling ring involving at least 25 people, including corrections officers, in which conspirators would receive “bribes, kickbacks, and sexual favors” in exchange for smuggling contraband into the facility.

Jeane Arnette, RN, of Leavenworth, Kan., pleaded guilty to a scheme in which she used her role as a nurse to smuggle contraband, including cell phones, into the Leavenworth Detention Center.

Ms. Arnette, 61, pleaded guilty on Mach 10 to conspiracy to provide contraband to federal prison inmates. The Kansas City Star says Ms. Arnette worked at the prison from August 2020 through September 2021 and allegedly attempted to smuggle contraband on at least 15 occasions to one inmate. Investigators alleged she was paid through Cash App for the transactions.

She is scheduled to be sentenced June 9 and faces a maximum penalty of 5 years in prison.
 

New York nurse indicted in COVID-19 vaccine card scam

A New York licensed practical nurse faces charges of conspiring to defraud the U.S. Department of Health & Human Services and conspiring to commit forgery in a scheme to distribute and sell false COVID-19 vaccination cards.

According to the indictment, Steven Rodriguez, of Long Beach, N.Y., 27, a nurse at a Hempstead, N.Y.–based clinic, conspired with Jia Liu, 26, of New York, who is a member of the U.S. Marine Corps Reserve, to provide the fake vaccination cards. The cards were sold to unvaccinated Marine Corps reservists who did not want to comply with U.S. Department of Defense vaccination regulations.

In the scheme, Mr. Liu purchased stolen, blank COVID-19 vaccination cards from Mr. Rodriguez, then forged and distributed them for profit. Mr. Liu also directed buyers to meet Mr. Rodriguez in person at the health care clinic where, rather than administer the vaccination, Mr. Rodriguez would destroy the vial of vaccine intended for that patient, then provide a forged vaccination card. Mr. Rodriguez then made false entries in immunization databases indicating that the buyer had been vaccinated. Mr. Liu was also charged with one count of conspiring to defraud the Department of Defense, according to prosecutors.

Using code words such as “gift cards,” “Pokemon cards,” and “Cardi Bs,” the men sent messages on encrypted messaging apps and on social media to inform potential buyers of the opportunity to buy the fake cards, prosecutors said.

Overall, according to the indictment, Mr. Rodriguez and Mr. Liu distributed at least 300 stolen or false COVID-19 vaccination cards, created more than 70 false entries in immunization databases, and destroyed multiple doses of COVID-19 vaccine. “The defendants put military and other communities at risk of contracting a virus that has already claimed nearly one million lives in this country,” Breon Peace, U.S. Attorney for the Eastern District of New York, said when announcing the charges.

Mr. Rodriguez’s lawyer said in an email to The New York Times that the charges are “disturbing” but added, “This young man has no prior record and has a good family, which is why he was released on an unsecured signature bond with the consent of the government.”

Mr. Rodriguez acquired his LPN license in 2018, and it was valid as of press time, according to the New York Office of the Professions database.

Mr. Liu, who also faces charges in connection with the January 6 riot on Capitol Hill, was released on a $250,000 bond to home detention with GPS monitoring, according to the same report.

If convicted, the men could each face up to 10 years in prison.
 

Pennsylvania nurse practitioner faces 22 felony charges

A Bradford County, Pennsylvania, nurse practitioner is facing nearly two dozen felony violations of state law.

Stephanie King, CRNP, 45, of Ulster, Pennsylvania, is accused of prescribing medicines without a collaborating physician, as well as with multiple counts of false billing.

The felony charges include three violations of the state’s Controlled Substance, Drug, Device and Cosmetic Act; two counts of insurance fraud; six counts of Medicaid fraud; six counts of forgery; two counts of tampering with public records; and three counts of theft by deception.

According to local press reports, Ms. King was the owner and operator of the Center for Holistic and Integrative Mental Health in Athens, Pa. The charging documents allege that, beginning in November 2016, Ms. King entered into a sexual relationship with a patient and billed a private insurer for their trysts. Ms. King subsequently entered a relationship with another patient. Although she discontinued medical care for this patient after the affair began, she continued to prescribe controlled substances for him, according to the indictment.

In addition, prosecutors allege that Ms. King renewed previous collaboration agreements without the knowledge of her physician collaborators. Under Pennsylvania law, nurse practitioners are required to enter into collaborative agreements with Pennsylvania-licensed physicians in order to perform medical diagnoses and prescribe controlled substances.

The investigation found that Ms. King falsely billed more than $300,000 to private insurers and $100,000 to the Commonwealth of Pennsylvania for services that did not meet acceptable medical treatment standards. In addition, she is alleged to have written more than 3,750 prescriptions to patients during the time she did not meet the State of Pennsylvania’s requirements to prescribe.

Her license, originally obtained in 2011, was suspended on March 25, 2020.
 

Massachusetts nurse pleads guilty of tampering with patients’ fentanyl

A Massachusetts nurse was charged with and has agreed to plead guilty to one count of tampering with a controlled substance while working in the postsurgery recovery unit at a Massachusetts hospital as well as at an outpatient vascular surgery center.

According to the charging documents, Hugo Vieira, 41, of Berkley, Massachusetts, removed fentanyl from vials meant for patients undergoing or recovering from surgery. He then replaced the fentanyl with saline. Investigators identified 60 vials that had been tampered with at the vascular surgery center and two at the hospital.

Mr. Viera faces up to 10 years in prison followed by 3 years of supervised release and a fine of up to $250,000 for the tampering charge.

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

One nurse is headed to federal prison and another faces a similar fate for participating in a pair of prison contraband schemes.

Former contract nurse Joseph Nwancha, RN, 41, of Baltimore, Maryland, was sentenced to 30 months in federal prison followed by 3 years of supervised release for his role in a scheme to smuggle narcotics, tobacco, cell phones, and other contraband into a state prison.

In his plea deal, Mr. Nwancha said that he was regularly the on-duty nurse during evenings and nights at Maryland Correctional Institute Jessup, which housed approximately 1,100 male inmates. This made it possible for him to have private contact with inmates without prison employees or other inmates observing the interactions.

According to court documents, beginning in September 2017, Corey Alston, an inmate at the medium-security prison, began bribing Mr. Nwancha to bring contraband into the prison. The inmate’s sister, Ashley Alston, discussed the bribe payments with Mr. Nwancha via text messages and later met with Mr. Nwancha to give him money. In his plea deal, Mr. Nwancha also admitted to having similar arrangements with other inmates.

On Nov. 28, 2017, Mr. Nwancha was stopped at MCIJ and was found to be in possession of approximately 230 g of K2, a synthetic cannabinoid, intended for Mr. Alston and other inmates, according to the court documents. A cell phone recovered from Mr. Nwancha contained text-message conversations discussing bribe payments and other details related to the smuggling operation. The next day, Mr. Nwancha fled to Dublin where he remained until his arrest and extradition, the document says.

According to the Maryland Board of Nursing, Mr. Nwancha earned his license to practice in 2013, and it expired in 2019.

The Washington Post reported that Mr. Nwancha was part of a smuggling ring involving at least 25 people, including corrections officers, in which conspirators would receive “bribes, kickbacks, and sexual favors” in exchange for smuggling contraband into the facility.

Jeane Arnette, RN, of Leavenworth, Kan., pleaded guilty to a scheme in which she used her role as a nurse to smuggle contraband, including cell phones, into the Leavenworth Detention Center.

Ms. Arnette, 61, pleaded guilty on Mach 10 to conspiracy to provide contraband to federal prison inmates. The Kansas City Star says Ms. Arnette worked at the prison from August 2020 through September 2021 and allegedly attempted to smuggle contraband on at least 15 occasions to one inmate. Investigators alleged she was paid through Cash App for the transactions.

She is scheduled to be sentenced June 9 and faces a maximum penalty of 5 years in prison.
 

New York nurse indicted in COVID-19 vaccine card scam

A New York licensed practical nurse faces charges of conspiring to defraud the U.S. Department of Health & Human Services and conspiring to commit forgery in a scheme to distribute and sell false COVID-19 vaccination cards.

According to the indictment, Steven Rodriguez, of Long Beach, N.Y., 27, a nurse at a Hempstead, N.Y.–based clinic, conspired with Jia Liu, 26, of New York, who is a member of the U.S. Marine Corps Reserve, to provide the fake vaccination cards. The cards were sold to unvaccinated Marine Corps reservists who did not want to comply with U.S. Department of Defense vaccination regulations.

In the scheme, Mr. Liu purchased stolen, blank COVID-19 vaccination cards from Mr. Rodriguez, then forged and distributed them for profit. Mr. Liu also directed buyers to meet Mr. Rodriguez in person at the health care clinic where, rather than administer the vaccination, Mr. Rodriguez would destroy the vial of vaccine intended for that patient, then provide a forged vaccination card. Mr. Rodriguez then made false entries in immunization databases indicating that the buyer had been vaccinated. Mr. Liu was also charged with one count of conspiring to defraud the Department of Defense, according to prosecutors.

Using code words such as “gift cards,” “Pokemon cards,” and “Cardi Bs,” the men sent messages on encrypted messaging apps and on social media to inform potential buyers of the opportunity to buy the fake cards, prosecutors said.

Overall, according to the indictment, Mr. Rodriguez and Mr. Liu distributed at least 300 stolen or false COVID-19 vaccination cards, created more than 70 false entries in immunization databases, and destroyed multiple doses of COVID-19 vaccine. “The defendants put military and other communities at risk of contracting a virus that has already claimed nearly one million lives in this country,” Breon Peace, U.S. Attorney for the Eastern District of New York, said when announcing the charges.

Mr. Rodriguez’s lawyer said in an email to The New York Times that the charges are “disturbing” but added, “This young man has no prior record and has a good family, which is why he was released on an unsecured signature bond with the consent of the government.”

Mr. Rodriguez acquired his LPN license in 2018, and it was valid as of press time, according to the New York Office of the Professions database.

Mr. Liu, who also faces charges in connection with the January 6 riot on Capitol Hill, was released on a $250,000 bond to home detention with GPS monitoring, according to the same report.

If convicted, the men could each face up to 10 years in prison.
 

Pennsylvania nurse practitioner faces 22 felony charges

A Bradford County, Pennsylvania, nurse practitioner is facing nearly two dozen felony violations of state law.

Stephanie King, CRNP, 45, of Ulster, Pennsylvania, is accused of prescribing medicines without a collaborating physician, as well as with multiple counts of false billing.

The felony charges include three violations of the state’s Controlled Substance, Drug, Device and Cosmetic Act; two counts of insurance fraud; six counts of Medicaid fraud; six counts of forgery; two counts of tampering with public records; and three counts of theft by deception.

According to local press reports, Ms. King was the owner and operator of the Center for Holistic and Integrative Mental Health in Athens, Pa. The charging documents allege that, beginning in November 2016, Ms. King entered into a sexual relationship with a patient and billed a private insurer for their trysts. Ms. King subsequently entered a relationship with another patient. Although she discontinued medical care for this patient after the affair began, she continued to prescribe controlled substances for him, according to the indictment.

In addition, prosecutors allege that Ms. King renewed previous collaboration agreements without the knowledge of her physician collaborators. Under Pennsylvania law, nurse practitioners are required to enter into collaborative agreements with Pennsylvania-licensed physicians in order to perform medical diagnoses and prescribe controlled substances.

The investigation found that Ms. King falsely billed more than $300,000 to private insurers and $100,000 to the Commonwealth of Pennsylvania for services that did not meet acceptable medical treatment standards. In addition, she is alleged to have written more than 3,750 prescriptions to patients during the time she did not meet the State of Pennsylvania’s requirements to prescribe.

Her license, originally obtained in 2011, was suspended on March 25, 2020.
 

Massachusetts nurse pleads guilty of tampering with patients’ fentanyl

A Massachusetts nurse was charged with and has agreed to plead guilty to one count of tampering with a controlled substance while working in the postsurgery recovery unit at a Massachusetts hospital as well as at an outpatient vascular surgery center.

According to the charging documents, Hugo Vieira, 41, of Berkley, Massachusetts, removed fentanyl from vials meant for patients undergoing or recovering from surgery. He then replaced the fentanyl with saline. Investigators identified 60 vials that had been tampered with at the vascular surgery center and two at the hospital.

Mr. Viera faces up to 10 years in prison followed by 3 years of supervised release and a fine of up to $250,000 for the tampering charge.

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

One nurse is headed to federal prison and another faces a similar fate for participating in a pair of prison contraband schemes.

Former contract nurse Joseph Nwancha, RN, 41, of Baltimore, Maryland, was sentenced to 30 months in federal prison followed by 3 years of supervised release for his role in a scheme to smuggle narcotics, tobacco, cell phones, and other contraband into a state prison.

In his plea deal, Mr. Nwancha said that he was regularly the on-duty nurse during evenings and nights at Maryland Correctional Institute Jessup, which housed approximately 1,100 male inmates. This made it possible for him to have private contact with inmates without prison employees or other inmates observing the interactions.

According to court documents, beginning in September 2017, Corey Alston, an inmate at the medium-security prison, began bribing Mr. Nwancha to bring contraband into the prison. The inmate’s sister, Ashley Alston, discussed the bribe payments with Mr. Nwancha via text messages and later met with Mr. Nwancha to give him money. In his plea deal, Mr. Nwancha also admitted to having similar arrangements with other inmates.

On Nov. 28, 2017, Mr. Nwancha was stopped at MCIJ and was found to be in possession of approximately 230 g of K2, a synthetic cannabinoid, intended for Mr. Alston and other inmates, according to the court documents. A cell phone recovered from Mr. Nwancha contained text-message conversations discussing bribe payments and other details related to the smuggling operation. The next day, Mr. Nwancha fled to Dublin where he remained until his arrest and extradition, the document says.

According to the Maryland Board of Nursing, Mr. Nwancha earned his license to practice in 2013, and it expired in 2019.

The Washington Post reported that Mr. Nwancha was part of a smuggling ring involving at least 25 people, including corrections officers, in which conspirators would receive “bribes, kickbacks, and sexual favors” in exchange for smuggling contraband into the facility.

Jeane Arnette, RN, of Leavenworth, Kan., pleaded guilty to a scheme in which she used her role as a nurse to smuggle contraband, including cell phones, into the Leavenworth Detention Center.

Ms. Arnette, 61, pleaded guilty on Mach 10 to conspiracy to provide contraband to federal prison inmates. The Kansas City Star says Ms. Arnette worked at the prison from August 2020 through September 2021 and allegedly attempted to smuggle contraband on at least 15 occasions to one inmate. Investigators alleged she was paid through Cash App for the transactions.

She is scheduled to be sentenced June 9 and faces a maximum penalty of 5 years in prison.
 

New York nurse indicted in COVID-19 vaccine card scam

A New York licensed practical nurse faces charges of conspiring to defraud the U.S. Department of Health & Human Services and conspiring to commit forgery in a scheme to distribute and sell false COVID-19 vaccination cards.

According to the indictment, Steven Rodriguez, of Long Beach, N.Y., 27, a nurse at a Hempstead, N.Y.–based clinic, conspired with Jia Liu, 26, of New York, who is a member of the U.S. Marine Corps Reserve, to provide the fake vaccination cards. The cards were sold to unvaccinated Marine Corps reservists who did not want to comply with U.S. Department of Defense vaccination regulations.

In the scheme, Mr. Liu purchased stolen, blank COVID-19 vaccination cards from Mr. Rodriguez, then forged and distributed them for profit. Mr. Liu also directed buyers to meet Mr. Rodriguez in person at the health care clinic where, rather than administer the vaccination, Mr. Rodriguez would destroy the vial of vaccine intended for that patient, then provide a forged vaccination card. Mr. Rodriguez then made false entries in immunization databases indicating that the buyer had been vaccinated. Mr. Liu was also charged with one count of conspiring to defraud the Department of Defense, according to prosecutors.

Using code words such as “gift cards,” “Pokemon cards,” and “Cardi Bs,” the men sent messages on encrypted messaging apps and on social media to inform potential buyers of the opportunity to buy the fake cards, prosecutors said.

Overall, according to the indictment, Mr. Rodriguez and Mr. Liu distributed at least 300 stolen or false COVID-19 vaccination cards, created more than 70 false entries in immunization databases, and destroyed multiple doses of COVID-19 vaccine. “The defendants put military and other communities at risk of contracting a virus that has already claimed nearly one million lives in this country,” Breon Peace, U.S. Attorney for the Eastern District of New York, said when announcing the charges.

Mr. Rodriguez’s lawyer said in an email to The New York Times that the charges are “disturbing” but added, “This young man has no prior record and has a good family, which is why he was released on an unsecured signature bond with the consent of the government.”

Mr. Rodriguez acquired his LPN license in 2018, and it was valid as of press time, according to the New York Office of the Professions database.

Mr. Liu, who also faces charges in connection with the January 6 riot on Capitol Hill, was released on a $250,000 bond to home detention with GPS monitoring, according to the same report.

If convicted, the men could each face up to 10 years in prison.
 

Pennsylvania nurse practitioner faces 22 felony charges

A Bradford County, Pennsylvania, nurse practitioner is facing nearly two dozen felony violations of state law.

Stephanie King, CRNP, 45, of Ulster, Pennsylvania, is accused of prescribing medicines without a collaborating physician, as well as with multiple counts of false billing.

The felony charges include three violations of the state’s Controlled Substance, Drug, Device and Cosmetic Act; two counts of insurance fraud; six counts of Medicaid fraud; six counts of forgery; two counts of tampering with public records; and three counts of theft by deception.

According to local press reports, Ms. King was the owner and operator of the Center for Holistic and Integrative Mental Health in Athens, Pa. The charging documents allege that, beginning in November 2016, Ms. King entered into a sexual relationship with a patient and billed a private insurer for their trysts. Ms. King subsequently entered a relationship with another patient. Although she discontinued medical care for this patient after the affair began, she continued to prescribe controlled substances for him, according to the indictment.

In addition, prosecutors allege that Ms. King renewed previous collaboration agreements without the knowledge of her physician collaborators. Under Pennsylvania law, nurse practitioners are required to enter into collaborative agreements with Pennsylvania-licensed physicians in order to perform medical diagnoses and prescribe controlled substances.

The investigation found that Ms. King falsely billed more than $300,000 to private insurers and $100,000 to the Commonwealth of Pennsylvania for services that did not meet acceptable medical treatment standards. In addition, she is alleged to have written more than 3,750 prescriptions to patients during the time she did not meet the State of Pennsylvania’s requirements to prescribe.

Her license, originally obtained in 2011, was suspended on March 25, 2020.
 

Massachusetts nurse pleads guilty of tampering with patients’ fentanyl

A Massachusetts nurse was charged with and has agreed to plead guilty to one count of tampering with a controlled substance while working in the postsurgery recovery unit at a Massachusetts hospital as well as at an outpatient vascular surgery center.

According to the charging documents, Hugo Vieira, 41, of Berkley, Massachusetts, removed fentanyl from vials meant for patients undergoing or recovering from surgery. He then replaced the fentanyl with saline. Investigators identified 60 vials that had been tampered with at the vascular surgery center and two at the hospital.

Mr. Viera faces up to 10 years in prison followed by 3 years of supervised release and a fine of up to $250,000 for the tampering charge.

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

Despite his insistence that he was not scratching his abdomen, the lack of primary lesions and the appearance of horizontally oriented excoriations over the abdomen in multiple stages of healing were consistent with neurotic excoriations.

Neurotic excoriation is frequently associated with psychiatric disease, especially obsessive-compulsive disorder and depression.¹ Stimulant-use, either by prescription or illicit, can lead to increased self-grooming behaviors, motor tics, and scratching. High doses of stimulants can trigger paranoia and tactile hallucinations.

In this case, the preponderance of skin lesions occurring on the left side of the patient’s abdomen fit with a right-handed individual, which the patient was. On his anterior lower legs, there were linear excoriations oriented vertically. Close observation of the patient during history taking revealed unconscious skin-picking behavior, and dead skin and debris could be noted under his fingernails. Two punch biopsies of active lesions were consistent with excoriations and excluded inflammatory causes of itching. (Careful evaluation for scabies, eczema, urticaria, and contact dermatitis was also performed.)

In this case, the patient’s psychiatrist reduced his dosage of lisdexamfetamine to a starting dose of 30 mg daily, which led to decreased skin scratching behavior. While the patient continued to have limited insight into the nature of his skin changes, progress was measured by a reduction in the number of active lesions.

‌

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

Despite his insistence that he was not scratching his abdomen, the lack of primary lesions and the appearance of horizontally oriented excoriations over the abdomen in multiple stages of healing were consistent with neurotic excoriations.

Neurotic excoriation is frequently associated with psychiatric disease, especially obsessive-compulsive disorder and depression.¹ Stimulant-use, either by prescription or illicit, can lead to increased self-grooming behaviors, motor tics, and scratching. High doses of stimulants can trigger paranoia and tactile hallucinations.

In this case, the preponderance of skin lesions occurring on the left side of the patient’s abdomen fit with a right-handed individual, which the patient was. On his anterior lower legs, there were linear excoriations oriented vertically. Close observation of the patient during history taking revealed unconscious skin-picking behavior, and dead skin and debris could be noted under his fingernails. Two punch biopsies of active lesions were consistent with excoriations and excluded inflammatory causes of itching. (Careful evaluation for scabies, eczema, urticaria, and contact dermatitis was also performed.)

In this case, the patient’s psychiatrist reduced his dosage of lisdexamfetamine to a starting dose of 30 mg daily, which led to decreased skin scratching behavior. While the patient continued to have limited insight into the nature of his skin changes, progress was measured by a reduction in the number of active lesions.

‌

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

Despite his insistence that he was not scratching his abdomen, the lack of primary lesions and the appearance of horizontally oriented excoriations over the abdomen in multiple stages of healing were consistent with neurotic excoriations.

Neurotic excoriation is frequently associated with psychiatric disease, especially obsessive-compulsive disorder and depression.¹ Stimulant-use, either by prescription or illicit, can lead to increased self-grooming behaviors, motor tics, and scratching. High doses of stimulants can trigger paranoia and tactile hallucinations.

In this case, the preponderance of skin lesions occurring on the left side of the patient’s abdomen fit with a right-handed individual, which the patient was. On his anterior lower legs, there were linear excoriations oriented vertically. Close observation of the patient during history taking revealed unconscious skin-picking behavior, and dead skin and debris could be noted under his fingernails. Two punch biopsies of active lesions were consistent with excoriations and excluded inflammatory causes of itching. (Careful evaluation for scabies, eczema, urticaria, and contact dermatitis was also performed.)

In this case, the patient’s psychiatrist reduced his dosage of lisdexamfetamine to a starting dose of 30 mg daily, which led to decreased skin scratching behavior. While the patient continued to have limited insight into the nature of his skin changes, progress was measured by a reduction in the number of active lesions.

‌

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

Seroprevalence surveys suggest that, from the beginning of the pandemic to 2022, more than a third of the global population had been infected with SARS-CoV-2. As large numbers of people continue to be infected, the efficacy and duration of natural immunity, in terms of protection against SARS-CoV-2 reinfections and severe disease, are of crucial significance. The virus’s epidemiologic trajectory will be influenced by the trends in vaccine-induced and hybrid immunity.

Omicron’s immune evasion

Cases of SARS-CoV-2 reinfection are increasing around the world. According to data from the U.K. Health Security Agency, 650,000 people in England have been infected twice, and most of them were reinfected in the past 2 months. Before mid-November 2021, reinfections accounted for about 1% of reported cases, but the rate has now increased to around 10%. The reinfection risk was 16 times higher between mid-December 2021 and early January 2022. Experts believe that this spike in reinfections is related to the spread of Omicron, which overtook Delta as the dominant variant. Nonetheless, other aspects should also be considered.

Omicron’s greater propensity to spread is not unrelated to its ability to evade the body’s immune defenses. This aspect was raised in a letter recently published in the New England Journal of Medicine. The authors reported that the effectiveness of previous infection in preventing reinfection against the Alpha, Beta, and Delta variants was around 90%, but it was only 56% against Omicron.
 

Natural immunity

Natural immunity showed roughly similar effectiveness regarding protection against reinfection across different SARS-CoV-2 variants, with the exception of the Omicron variant. The risk of hospitalization and death was also reduced in SARS-CoV-2 reinfections versus primary infections. Observational studies indicate that natural immunity may offer equal or greater protection against SARS-CoV-2 infections, compared with immunization with two doses of an mRNA vaccine, but the data are not fully consistent.

Natural immunity seems to be relatively long-lasting. Data from Denmark and Austria show no evidence that protection against reinfections wanes after 6 months. Some investigations indicate that protection against reinfection is lowest 4-5 months after initial infection and increases thereafter, a finding that might hypothetically be explained by persistent viral shedding; that is, misclassification of prolonged SARS-CoV-2 infections as reinfections. While no comparison was made against information pertaining to unvaccinated, not previously-infected individuals, preliminary data from Israel suggest that protection from reinfection can decrease from 6 to more than 12 months after the first SARS-CoV-2 infection. Taken together, epidemiologic studies indicate that protection against reinfections by natural immunity lasts over 1 year with only moderate, if any, decline over this period. Among older individuals, immunocompromised patients, and those with certain comorbidities or exposure risk (for example, health care workers), rates of reinfection may be higher. It is plausible that reinfection risk may be a function of exposure risk.

There is accumulating evidence that reinfections may be significantly less severe than primary infections with SARS-CoV-2. Reduced clinical severity of SARS-CoV-2 reinfections naturally also makes sense from a biologic point of view, inasmuch as a previously primed immune system should be better prepared for a rechallenge with this virus.
 

Vaccine-induced immunity

The short-term (<4 months) efficacy of mRNA vaccines against SARS-CoV-2 is high and varies from 94.1% (Moderna) to 95% (BioNTech/Pfizer). This has been confirmed by randomized controlled trials and was subsequently confirmed in effectiveness studies in real-world settings. Waning efficacy was observed with respect to protection against SARS-CoV-2 infections (for example, only approximately 20% after about half a year in Qatar), whereas protection against severe disease was either sustained or showed only a moderate decline.

In individuals who received two doses of the BioNTech/Pfizer vaccine at least 5 months earlier, an additional vaccine dose, a so-called booster, significantly lowered mortality and severe illness. These findings suggest that the booster restored and probably exceeded the initial short-term efficacy of the initial vaccination.

Data are still emerging regarding the efficacy of boosters against the Omicron variants. Preliminary data suggest a far lower ability to restore protection from infection and vaccination. However, fatalities and hospitalizations remain low.
 

Natural immunity vs. vaccine-induced immunity

Comparisons of natural immunity with vaccine-induced immunity are complicated by a series of biases and by combinations of biases – for example, the biases of comparisons between infected and uninfected, plus the biases of comparisons between vaccinated and nonvaccinated, with strong potential selection biases and confounding. Of particular note, the proportion of people previously infected and/or vaccinated may influence estimates of effectiveness. Regarding this point, one study compared unvaccinated patients with a prior SARS-CoV-2 infection and vaccinated individuals followed up from a week after the second vaccine dose onward versus a group of unvaccinated, not previously infected individuals. The findings showed that, compared with unvaccinated, not previously infected individuals, the natural immunity group and the vaccinated group had similar protection of 94.8% and 92.8% against infection, of 94.1% and 94.2% against hospitalization, and of 96.4% and 94.4% against severe illness, respectively.

Hybrid immunity

The combination of a previous SARS-CoV-2 infection and a respective vaccination is called hybrid immunity. This combination seems to confer the greatest protection against SARS-CoV-2 infections, but several knowledge gaps remain regarding this issue.

Data from Israel showed that, when the time since the last immunity-conferring event (either primary infection or vaccination) was the same, the rates of SARS-CoV-2 infections were similar in the following groups: individuals who had a previous infection and no vaccination, individuals who had an infection and were then vaccinated with a single dose after at least 3 months, and individuals who were vaccinated (two doses) and then infected. Severe disease was relatively rare overall.

Data on the efficacy of hybrid immunity point in the direction of hybrid immunity being superior, as compared with either vaccine-induced (without a booster) immunity or natural immunity alone. Timing and mode of vaccination of previously infected individuals to achieve optimal hybrid immunity are central questions that remain to be addressed in future studies.

Given that vaccination rates are continuously increasing and that, by the beginning of 2022, perhaps half or more of the global population had already been infected with SARS-CoV-2, with the vast majority of this group not being officially detected, it would appear logical that future infection waves, even with highly transmissible variants of SARS-CoV-2, may be limited with respect to their maximum potential health burden. The advent of Omicron suggests that massive surges can occur even in populations with extremely high rates of previous vaccination and variable rates of prior infections. However, even then, the accompanying burden of hospitalizations and deaths is far less than what was seen in 2020 and 2021. One may argue that the pandemic has already transitioned to the endemic phase and that Omicron is an endemic wave occurring in the setting of already widespread population immunity.

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

Seroprevalence surveys suggest that, from the beginning of the pandemic to 2022, more than a third of the global population had been infected with SARS-CoV-2. As large numbers of people continue to be infected, the efficacy and duration of natural immunity, in terms of protection against SARS-CoV-2 reinfections and severe disease, are of crucial significance. The virus’s epidemiologic trajectory will be influenced by the trends in vaccine-induced and hybrid immunity.

Omicron’s immune evasion

Cases of SARS-CoV-2 reinfection are increasing around the world. According to data from the U.K. Health Security Agency, 650,000 people in England have been infected twice, and most of them were reinfected in the past 2 months. Before mid-November 2021, reinfections accounted for about 1% of reported cases, but the rate has now increased to around 10%. The reinfection risk was 16 times higher between mid-December 2021 and early January 2022. Experts believe that this spike in reinfections is related to the spread of Omicron, which overtook Delta as the dominant variant. Nonetheless, other aspects should also be considered.

Omicron’s greater propensity to spread is not unrelated to its ability to evade the body’s immune defenses. This aspect was raised in a letter recently published in the New England Journal of Medicine. The authors reported that the effectiveness of previous infection in preventing reinfection against the Alpha, Beta, and Delta variants was around 90%, but it was only 56% against Omicron.
 

Natural immunity

Natural immunity showed roughly similar effectiveness regarding protection against reinfection across different SARS-CoV-2 variants, with the exception of the Omicron variant. The risk of hospitalization and death was also reduced in SARS-CoV-2 reinfections versus primary infections. Observational studies indicate that natural immunity may offer equal or greater protection against SARS-CoV-2 infections, compared with immunization with two doses of an mRNA vaccine, but the data are not fully consistent.

Natural immunity seems to be relatively long-lasting. Data from Denmark and Austria show no evidence that protection against reinfections wanes after 6 months. Some investigations indicate that protection against reinfection is lowest 4-5 months after initial infection and increases thereafter, a finding that might hypothetically be explained by persistent viral shedding; that is, misclassification of prolonged SARS-CoV-2 infections as reinfections. While no comparison was made against information pertaining to unvaccinated, not previously-infected individuals, preliminary data from Israel suggest that protection from reinfection can decrease from 6 to more than 12 months after the first SARS-CoV-2 infection. Taken together, epidemiologic studies indicate that protection against reinfections by natural immunity lasts over 1 year with only moderate, if any, decline over this period. Among older individuals, immunocompromised patients, and those with certain comorbidities or exposure risk (for example, health care workers), rates of reinfection may be higher. It is plausible that reinfection risk may be a function of exposure risk.

There is accumulating evidence that reinfections may be significantly less severe than primary infections with SARS-CoV-2. Reduced clinical severity of SARS-CoV-2 reinfections naturally also makes sense from a biologic point of view, inasmuch as a previously primed immune system should be better prepared for a rechallenge with this virus.
 

Vaccine-induced immunity

The short-term (<4 months) efficacy of mRNA vaccines against SARS-CoV-2 is high and varies from 94.1% (Moderna) to 95% (BioNTech/Pfizer). This has been confirmed by randomized controlled trials and was subsequently confirmed in effectiveness studies in real-world settings. Waning efficacy was observed with respect to protection against SARS-CoV-2 infections (for example, only approximately 20% after about half a year in Qatar), whereas protection against severe disease was either sustained or showed only a moderate decline.

In individuals who received two doses of the BioNTech/Pfizer vaccine at least 5 months earlier, an additional vaccine dose, a so-called booster, significantly lowered mortality and severe illness. These findings suggest that the booster restored and probably exceeded the initial short-term efficacy of the initial vaccination.

Data are still emerging regarding the efficacy of boosters against the Omicron variants. Preliminary data suggest a far lower ability to restore protection from infection and vaccination. However, fatalities and hospitalizations remain low.
 

Natural immunity vs. vaccine-induced immunity

Comparisons of natural immunity with vaccine-induced immunity are complicated by a series of biases and by combinations of biases – for example, the biases of comparisons between infected and uninfected, plus the biases of comparisons between vaccinated and nonvaccinated, with strong potential selection biases and confounding. Of particular note, the proportion of people previously infected and/or vaccinated may influence estimates of effectiveness. Regarding this point, one study compared unvaccinated patients with a prior SARS-CoV-2 infection and vaccinated individuals followed up from a week after the second vaccine dose onward versus a group of unvaccinated, not previously infected individuals. The findings showed that, compared with unvaccinated, not previously infected individuals, the natural immunity group and the vaccinated group had similar protection of 94.8% and 92.8% against infection, of 94.1% and 94.2% against hospitalization, and of 96.4% and 94.4% against severe illness, respectively.

Hybrid immunity

The combination of a previous SARS-CoV-2 infection and a respective vaccination is called hybrid immunity. This combination seems to confer the greatest protection against SARS-CoV-2 infections, but several knowledge gaps remain regarding this issue.

Data from Israel showed that, when the time since the last immunity-conferring event (either primary infection or vaccination) was the same, the rates of SARS-CoV-2 infections were similar in the following groups: individuals who had a previous infection and no vaccination, individuals who had an infection and were then vaccinated with a single dose after at least 3 months, and individuals who were vaccinated (two doses) and then infected. Severe disease was relatively rare overall.

Data on the efficacy of hybrid immunity point in the direction of hybrid immunity being superior, as compared with either vaccine-induced (without a booster) immunity or natural immunity alone. Timing and mode of vaccination of previously infected individuals to achieve optimal hybrid immunity are central questions that remain to be addressed in future studies.

Given that vaccination rates are continuously increasing and that, by the beginning of 2022, perhaps half or more of the global population had already been infected with SARS-CoV-2, with the vast majority of this group not being officially detected, it would appear logical that future infection waves, even with highly transmissible variants of SARS-CoV-2, may be limited with respect to their maximum potential health burden. The advent of Omicron suggests that massive surges can occur even in populations with extremely high rates of previous vaccination and variable rates of prior infections. However, even then, the accompanying burden of hospitalizations and deaths is far less than what was seen in 2020 and 2021. One may argue that the pandemic has already transitioned to the endemic phase and that Omicron is an endemic wave occurring in the setting of already widespread population immunity.

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

Seroprevalence surveys suggest that, from the beginning of the pandemic to 2022, more than a third of the global population had been infected with SARS-CoV-2. As large numbers of people continue to be infected, the efficacy and duration of natural immunity, in terms of protection against SARS-CoV-2 reinfections and severe disease, are of crucial significance. The virus’s epidemiologic trajectory will be influenced by the trends in vaccine-induced and hybrid immunity.

Omicron’s immune evasion

Cases of SARS-CoV-2 reinfection are increasing around the world. According to data from the U.K. Health Security Agency, 650,000 people in England have been infected twice, and most of them were reinfected in the past 2 months. Before mid-November 2021, reinfections accounted for about 1% of reported cases, but the rate has now increased to around 10%. The reinfection risk was 16 times higher between mid-December 2021 and early January 2022. Experts believe that this spike in reinfections is related to the spread of Omicron, which overtook Delta as the dominant variant. Nonetheless, other aspects should also be considered.

Omicron’s greater propensity to spread is not unrelated to its ability to evade the body’s immune defenses. This aspect was raised in a letter recently published in the New England Journal of Medicine. The authors reported that the effectiveness of previous infection in preventing reinfection against the Alpha, Beta, and Delta variants was around 90%, but it was only 56% against Omicron.
 

Natural immunity

Natural immunity showed roughly similar effectiveness regarding protection against reinfection across different SARS-CoV-2 variants, with the exception of the Omicron variant. The risk of hospitalization and death was also reduced in SARS-CoV-2 reinfections versus primary infections. Observational studies indicate that natural immunity may offer equal or greater protection against SARS-CoV-2 infections, compared with immunization with two doses of an mRNA vaccine, but the data are not fully consistent.

Natural immunity seems to be relatively long-lasting. Data from Denmark and Austria show no evidence that protection against reinfections wanes after 6 months. Some investigations indicate that protection against reinfection is lowest 4-5 months after initial infection and increases thereafter, a finding that might hypothetically be explained by persistent viral shedding; that is, misclassification of prolonged SARS-CoV-2 infections as reinfections. While no comparison was made against information pertaining to unvaccinated, not previously-infected individuals, preliminary data from Israel suggest that protection from reinfection can decrease from 6 to more than 12 months after the first SARS-CoV-2 infection. Taken together, epidemiologic studies indicate that protection against reinfections by natural immunity lasts over 1 year with only moderate, if any, decline over this period. Among older individuals, immunocompromised patients, and those with certain comorbidities or exposure risk (for example, health care workers), rates of reinfection may be higher. It is plausible that reinfection risk may be a function of exposure risk.

There is accumulating evidence that reinfections may be significantly less severe than primary infections with SARS-CoV-2. Reduced clinical severity of SARS-CoV-2 reinfections naturally also makes sense from a biologic point of view, inasmuch as a previously primed immune system should be better prepared for a rechallenge with this virus.
 

Vaccine-induced immunity

The short-term (<4 months) efficacy of mRNA vaccines against SARS-CoV-2 is high and varies from 94.1% (Moderna) to 95% (BioNTech/Pfizer). This has been confirmed by randomized controlled trials and was subsequently confirmed in effectiveness studies in real-world settings. Waning efficacy was observed with respect to protection against SARS-CoV-2 infections (for example, only approximately 20% after about half a year in Qatar), whereas protection against severe disease was either sustained or showed only a moderate decline.

In individuals who received two doses of the BioNTech/Pfizer vaccine at least 5 months earlier, an additional vaccine dose, a so-called booster, significantly lowered mortality and severe illness. These findings suggest that the booster restored and probably exceeded the initial short-term efficacy of the initial vaccination.

Data are still emerging regarding the efficacy of boosters against the Omicron variants. Preliminary data suggest a far lower ability to restore protection from infection and vaccination. However, fatalities and hospitalizations remain low.
 

Natural immunity vs. vaccine-induced immunity

Comparisons of natural immunity with vaccine-induced immunity are complicated by a series of biases and by combinations of biases – for example, the biases of comparisons between infected and uninfected, plus the biases of comparisons between vaccinated and nonvaccinated, with strong potential selection biases and confounding. Of particular note, the proportion of people previously infected and/or vaccinated may influence estimates of effectiveness. Regarding this point, one study compared unvaccinated patients with a prior SARS-CoV-2 infection and vaccinated individuals followed up from a week after the second vaccine dose onward versus a group of unvaccinated, not previously infected individuals. The findings showed that, compared with unvaccinated, not previously infected individuals, the natural immunity group and the vaccinated group had similar protection of 94.8% and 92.8% against infection, of 94.1% and 94.2% against hospitalization, and of 96.4% and 94.4% against severe illness, respectively.

Hybrid immunity

The combination of a previous SARS-CoV-2 infection and a respective vaccination is called hybrid immunity. This combination seems to confer the greatest protection against SARS-CoV-2 infections, but several knowledge gaps remain regarding this issue.

Data from Israel showed that, when the time since the last immunity-conferring event (either primary infection or vaccination) was the same, the rates of SARS-CoV-2 infections were similar in the following groups: individuals who had a previous infection and no vaccination, individuals who had an infection and were then vaccinated with a single dose after at least 3 months, and individuals who were vaccinated (two doses) and then infected. Severe disease was relatively rare overall.

Data on the efficacy of hybrid immunity point in the direction of hybrid immunity being superior, as compared with either vaccine-induced (without a booster) immunity or natural immunity alone. Timing and mode of vaccination of previously infected individuals to achieve optimal hybrid immunity are central questions that remain to be addressed in future studies.

Given that vaccination rates are continuously increasing and that, by the beginning of 2022, perhaps half or more of the global population had already been infected with SARS-CoV-2, with the vast majority of this group not being officially detected, it would appear logical that future infection waves, even with highly transmissible variants of SARS-CoV-2, may be limited with respect to their maximum potential health burden. The advent of Omicron suggests that massive surges can occur even in populations with extremely high rates of previous vaccination and variable rates of prior infections. However, even then, the accompanying burden of hospitalizations and deaths is far less than what was seen in 2020 and 2021. One may argue that the pandemic has already transitioned to the endemic phase and that Omicron is an endemic wave occurring in the setting of already widespread population immunity.

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

The stress of living through a pandemic may cause brain inflammation even in those uninfected with SARS-CoV-2, a study suggests.

Healthy individuals who tested negative for the virus that causes COVID-19 had elevated levels of inflammatory markers known to be involved in depression, stress, and mental fatigue. The study indicates a possible link between pandemic-associated stressors and neuroimmune responses.

“The most important finding is the evidence of neuroinflammation in noninfected, otherwise healthy participants, which may explain the variety of sickness-behavior-like symptoms experienced by many during the pandemic,” lead author Ludovica Brusaferri, PhD, a postdoctoral research fellow at Massachusetts General Hospital and Harvard Medical School in Boston, told this news organization.

The study was published online Feb. 16 in Brain, Behavior, and Immunity.
 

Impact of pandemic stress?

Reports of psychological distress have increased considerably in the United States during the pandemic, including among those not infected with SARS-CoV-2.

To better understand the effects of the pandemic on brain and mental health, the investigators retrospectively analyzed data collected from 57 people who were enrolled as control subjects for unrelated studies before the pandemic began.

They also enrolled 15 people living in Massachusetts during that state’s 2-month lockdown/stay-at-home order from March to May 2020, all of whom had tested negative for COVID-19 antibodies.

The investigators used PET and MRI imaging and blood sample analyses to investigate whether there were any differences in the brains of healthy people before and during the pandemic following the lockdown.

Compared with the control group, the pandemic cohort had elevated levels of 18 kDa translocator protein (TSPO) and myoinositol, inflammatory markers in the brain. Increased TSPO has been associated with depression and suicidal thoughts and elevated myoinositol has been linked to schizophrenia.

Blood levels of two inflammatory markers, interleukin-16 and monocyte chemoattractant protein-1, were also elevated in the pandemic cohort, although to a lesser extent.

TSPO levels were especially high in participants in the pandemic cohort who reported moodiness and mental and physical fatigue, compared with those reporting few or no symptoms.

“These findings provide support to a role for neuroinflammation in stress, an observation that, if replicated, might help guide the development of novel treatments focused on the reduction of brain inflammation,” study author Marco Loggia, PhD, codirector of the Center for Integrative Pain NeuroImaging at Mass General and Harvard Medical School, told this news organization.

Although the data showing increased neuroinflammation were collected when participants were under a stay-at-home order, the researchers said it’s not clear that this was the cause.

“We’re not saying it is the lockdown that was causing it,” Dr. Loggia said. “It could have been social isolation, changes in diet, or changes in exercise patterns. We don’t know exactly what the cause was so, maybe.”
 

A significant contribution

Commenting on the study for this news organization, Ning Quan, PhD, professor of biomedical science at Florida Atlantic University, Boca Raton, said although questions remain, the findings offer valuable information.

“This study contributes significantly to our understanding of how pandemic stress might impact our brain and behavior,” Dr. Quan said. “The main advance that this paper provides is that fatigue or brain fog could be induced in individuals with COVID infection during the pandemic.”

However, Dr. Quan added, the study has a number of limitations, including a small sample size, which makes it difficult to generalize the results.

“Another issue is the subjects of the study all lived in Massachusetts,” Dr. Quan added. “Subjects from different states or different countries could yield different results.”

The study was funded by the National Institutes of Health and by the Landreth Family Foundation. The study authors and Dr. Quan have disclosed no relevant financial relationships.

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

The stress of living through a pandemic may cause brain inflammation even in those uninfected with SARS-CoV-2, a study suggests.

Healthy individuals who tested negative for the virus that causes COVID-19 had elevated levels of inflammatory markers known to be involved in depression, stress, and mental fatigue. The study indicates a possible link between pandemic-associated stressors and neuroimmune responses.

“The most important finding is the evidence of neuroinflammation in noninfected, otherwise healthy participants, which may explain the variety of sickness-behavior-like symptoms experienced by many during the pandemic,” lead author Ludovica Brusaferri, PhD, a postdoctoral research fellow at Massachusetts General Hospital and Harvard Medical School in Boston, told this news organization.

The study was published online Feb. 16 in Brain, Behavior, and Immunity.
 

Impact of pandemic stress?

Reports of psychological distress have increased considerably in the United States during the pandemic, including among those not infected with SARS-CoV-2.

To better understand the effects of the pandemic on brain and mental health, the investigators retrospectively analyzed data collected from 57 people who were enrolled as control subjects for unrelated studies before the pandemic began.

They also enrolled 15 people living in Massachusetts during that state’s 2-month lockdown/stay-at-home order from March to May 2020, all of whom had tested negative for COVID-19 antibodies.

The investigators used PET and MRI imaging and blood sample analyses to investigate whether there were any differences in the brains of healthy people before and during the pandemic following the lockdown.

Compared with the control group, the pandemic cohort had elevated levels of 18 kDa translocator protein (TSPO) and myoinositol, inflammatory markers in the brain. Increased TSPO has been associated with depression and suicidal thoughts and elevated myoinositol has been linked to schizophrenia.

Blood levels of two inflammatory markers, interleukin-16 and monocyte chemoattractant protein-1, were also elevated in the pandemic cohort, although to a lesser extent.

TSPO levels were especially high in participants in the pandemic cohort who reported moodiness and mental and physical fatigue, compared with those reporting few or no symptoms.

“These findings provide support to a role for neuroinflammation in stress, an observation that, if replicated, might help guide the development of novel treatments focused on the reduction of brain inflammation,” study author Marco Loggia, PhD, codirector of the Center for Integrative Pain NeuroImaging at Mass General and Harvard Medical School, told this news organization.

Although the data showing increased neuroinflammation were collected when participants were under a stay-at-home order, the researchers said it’s not clear that this was the cause.

“We’re not saying it is the lockdown that was causing it,” Dr. Loggia said. “It could have been social isolation, changes in diet, or changes in exercise patterns. We don’t know exactly what the cause was so, maybe.”
 

A significant contribution

Commenting on the study for this news organization, Ning Quan, PhD, professor of biomedical science at Florida Atlantic University, Boca Raton, said although questions remain, the findings offer valuable information.

“This study contributes significantly to our understanding of how pandemic stress might impact our brain and behavior,” Dr. Quan said. “The main advance that this paper provides is that fatigue or brain fog could be induced in individuals with COVID infection during the pandemic.”

However, Dr. Quan added, the study has a number of limitations, including a small sample size, which makes it difficult to generalize the results.

“Another issue is the subjects of the study all lived in Massachusetts,” Dr. Quan added. “Subjects from different states or different countries could yield different results.”

The study was funded by the National Institutes of Health and by the Landreth Family Foundation. The study authors and Dr. Quan have disclosed no relevant financial relationships.

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

The stress of living through a pandemic may cause brain inflammation even in those uninfected with SARS-CoV-2, a study suggests.

Healthy individuals who tested negative for the virus that causes COVID-19 had elevated levels of inflammatory markers known to be involved in depression, stress, and mental fatigue. The study indicates a possible link between pandemic-associated stressors and neuroimmune responses.

“The most important finding is the evidence of neuroinflammation in noninfected, otherwise healthy participants, which may explain the variety of sickness-behavior-like symptoms experienced by many during the pandemic,” lead author Ludovica Brusaferri, PhD, a postdoctoral research fellow at Massachusetts General Hospital and Harvard Medical School in Boston, told this news organization.

The study was published online Feb. 16 in Brain, Behavior, and Immunity.
 

Impact of pandemic stress?

Reports of psychological distress have increased considerably in the United States during the pandemic, including among those not infected with SARS-CoV-2.

To better understand the effects of the pandemic on brain and mental health, the investigators retrospectively analyzed data collected from 57 people who were enrolled as control subjects for unrelated studies before the pandemic began.

They also enrolled 15 people living in Massachusetts during that state’s 2-month lockdown/stay-at-home order from March to May 2020, all of whom had tested negative for COVID-19 antibodies.

The investigators used PET and MRI imaging and blood sample analyses to investigate whether there were any differences in the brains of healthy people before and during the pandemic following the lockdown.

Compared with the control group, the pandemic cohort had elevated levels of 18 kDa translocator protein (TSPO) and myoinositol, inflammatory markers in the brain. Increased TSPO has been associated with depression and suicidal thoughts and elevated myoinositol has been linked to schizophrenia.

Blood levels of two inflammatory markers, interleukin-16 and monocyte chemoattractant protein-1, were also elevated in the pandemic cohort, although to a lesser extent.

TSPO levels were especially high in participants in the pandemic cohort who reported moodiness and mental and physical fatigue, compared with those reporting few or no symptoms.

“These findings provide support to a role for neuroinflammation in stress, an observation that, if replicated, might help guide the development of novel treatments focused on the reduction of brain inflammation,” study author Marco Loggia, PhD, codirector of the Center for Integrative Pain NeuroImaging at Mass General and Harvard Medical School, told this news organization.

Although the data showing increased neuroinflammation were collected when participants were under a stay-at-home order, the researchers said it’s not clear that this was the cause.

“We’re not saying it is the lockdown that was causing it,” Dr. Loggia said. “It could have been social isolation, changes in diet, or changes in exercise patterns. We don’t know exactly what the cause was so, maybe.”
 

A significant contribution

Commenting on the study for this news organization, Ning Quan, PhD, professor of biomedical science at Florida Atlantic University, Boca Raton, said although questions remain, the findings offer valuable information.

“This study contributes significantly to our understanding of how pandemic stress might impact our brain and behavior,” Dr. Quan said. “The main advance that this paper provides is that fatigue or brain fog could be induced in individuals with COVID infection during the pandemic.”

However, Dr. Quan added, the study has a number of limitations, including a small sample size, which makes it difficult to generalize the results.

“Another issue is the subjects of the study all lived in Massachusetts,” Dr. Quan added. “Subjects from different states or different countries could yield different results.”

The study was funded by the National Institutes of Health and by the Landreth Family Foundation. The study authors and Dr. Quan have disclosed no relevant financial relationships.

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