Clinician Reviews

The number of U.S. adults who are at least partially vaccinated rose five percentage points to 72% in August, a slightly faster increase than in previous months, according to the latest monthly COVID-19 Vaccine Monitor report of the Kaiser Family Foundation (KFF).

The largest increases in vaccine uptake between July and September were among Hispanic adults and people aged 18-29 years. Roughly equal shares of adults now report being vaccinated across racial and ethnic groups: 71% of White adults, 70% of Black adults, and 73% of Hispanic adults.

Overall, the big takeaway of the latest Kaiser COVID-19 survey is that the partisan divide on all aspects of the pandemic, from vaccination status to attitudes toward vaccination and mask mandates, remains as wide as ever.

The only thing that Republicans, Democrats, and Independents mostly agree on is that COVID-19 will probably become an endemic disease like influenza. Seventy-nine percent of respondents agreed with that statement; 14% predicted that COVID-19 would probably be largely eliminated in future years, like polio.
 

Delta motivated many

The most important factor that recently led people toward being vaccinated against COVID-19 was the surge in cases, hospitalizations, and deaths due to the Delta variant, KFF reports.

Full approval of the Pfizer vaccine by the Food and Drug Administration and the increasing prevalence of vaccine mandates played secondary roles in the vaccination uptick.

Specifically, 10% of the recently vaccinated said the main reason they got shots was the increase in COVID-19 cases due to the Delta variant. Concern about reports of local hospitals and intensive care units filling up with COVID-19 patients was the main motivator for 12% of those who just got shots. Fourteen percent of the recently vaccinated got inoculated mainly because someone they knew had become seriously ill or had died from COVID-19.

The role of the Delta threat is also evident with regard to where those who were recently vaccinated live. Twenty-four percent of those who received their first dose of vaccine after June 1, 2021, reside in counties with a high COVID-19 case rate; 15% of them live in counties with a relatively low case rate.

Despite the recent surge in vaccinations, however, 7% of adults are still taking a wait-and-see approach; 4% said they’d get a shot only if required; and 12% said they definitely wouldn’t get vaccinated. The latter figure has barely budged since January of this year.

Ninety percent of Democrats said they had received at least one dose of the COVID-19 vaccine, vs. 68% of Independents, and 58% of Republicans.

Wealthier, better educated, urban, and older people were more likely to be vaccinated, with one exception: Sixty-eight percent of those aged 18-29 were vaccinated, vs. 66% of those aged 30-49. The group least likely to be vaccinated were uninsured people younger than 65, suggesting that some of them were unaware that the shot is free.
 

Partisan affiliation

Attitudes toward vaccine booster shots – which are now recommended for people older than 65, the immunocompromised, and certain frontline workers – largely fell along party lines and/or reflected whether respondents had been vaccinated.

Discussion of the boosters, KFF said, “appears to be a net positive for people who are already vaccinated, but a net negative for the unvaccinated. While a larger share of vaccinated adults say the information they have seen about boosters has been helpful (54%) than find it confusing (35%), among the unvaccinated almost twice as many find the information confusing as find it helpful (45% vs. 24%).”

Among fully vaccinated adults, 68% of Democrats say they’d definitely get a booster, and 20% say they probably would. Among Republicans, those percentages are 36% and 33%, respectively. Independents fall in between the other groups.

Although 82% of Democrats say the boosters show that scientists are continuing to make vaccines more effective, 52% of Republicans say that it shows that the vaccines are not working as well as promised.

Similarly, partisan attitudes emerged in questions about breakthrough infections. The fact that COVID-19 cases are fairly mild when they occur among persons who have been vaccinated indicates that the vaccines are working, said 87% of Democrats, but only 55% of Republicans agreed with that assessment.

In contrast, just 10% of Democrats but 39% of Republicans said that breakthrough infections mean the vaccines are not working.
 

Vaccine requirements

The public is more evenly divided on vaccine requirements. About 6 in 10 respondents said that vaccines should be required for health care workers (62%) and schoolteachers (58%). Slim majorities supported mandates for federal government employees (55%), college students (55%), and state and local government employees (54%).

On the question of whether employers in general should require their workers to be vaccinated, 48% of respondents said they should, and 50% said they should not.

Similarly, 52% said that all schools should mandate vaccines for eligible students; 46% didn’t approve of such requirements.

Three in four Democrats supported employer vaccine mandates, compared to 45% of Independents and just 20% of Republicans. Large partisan gaps were also seen for government, school, and health care vaccine mandates.

In contrast, 78% of the public favored requiring large employers to give their workers paid time off to get vaccinated and to recover from any side effects.
 

Twenty percent of workers under mandates

One in five workers said their employers require COVID-19 vaccination. Twenty-eight percent of employed people want their employers to require vaccination, and 50% don’t.

Again, the responses broke down along party lines, with 52% of Democrats, 21% of Independents, and 10% of Republicans favoring a vaccine mandate by their employers.

Most unvaccinated people didn’t support an employer mandate. A third of unvaccinated workers said they’d be likely to get vaccinated if their companies required it, but most of them said they would choose weekly testing if offered the option.

Being unable to use gyms, restaurants, or indoor entertainment venues that require vaccination was cited by 13% of the recently vaccinated as the main reason why they got shots.

The public was evenly divided on whether states or local governments should require such businesses to mandate that staff and customers show proof of vaccination. Although the views of the public were tied on this issue overall, 79% of Democrats, 43% of Independents, and 21% of Republicans supported having these kinds of businesses require proof of vaccination.

On school mask mandates, 56% of the respondents supported requiring all students and staff to wear masks. Favoring this kind of mandate were 83% of Democrats, 53% of Independents, and 29% of Republicans.

Partisanship also defined how Democrats and Republicans viewed the current high number of COVID-19 cases. Most Democrats blamed people who don’t wear masks and those who don’t get vaccinated, whereas Republicans were more likely to blame immigrants and tourists bringing COVID-19 into the United States.

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

The number of U.S. adults who are at least partially vaccinated rose five percentage points to 72% in August, a slightly faster increase than in previous months, according to the latest monthly COVID-19 Vaccine Monitor report of the Kaiser Family Foundation (KFF).

The largest increases in vaccine uptake between July and September were among Hispanic adults and people aged 18-29 years. Roughly equal shares of adults now report being vaccinated across racial and ethnic groups: 71% of White adults, 70% of Black adults, and 73% of Hispanic adults.

Overall, the big takeaway of the latest Kaiser COVID-19 survey is that the partisan divide on all aspects of the pandemic, from vaccination status to attitudes toward vaccination and mask mandates, remains as wide as ever.

The only thing that Republicans, Democrats, and Independents mostly agree on is that COVID-19 will probably become an endemic disease like influenza. Seventy-nine percent of respondents agreed with that statement; 14% predicted that COVID-19 would probably be largely eliminated in future years, like polio.
 

Delta motivated many

The most important factor that recently led people toward being vaccinated against COVID-19 was the surge in cases, hospitalizations, and deaths due to the Delta variant, KFF reports.

Full approval of the Pfizer vaccine by the Food and Drug Administration and the increasing prevalence of vaccine mandates played secondary roles in the vaccination uptick.

Specifically, 10% of the recently vaccinated said the main reason they got shots was the increase in COVID-19 cases due to the Delta variant. Concern about reports of local hospitals and intensive care units filling up with COVID-19 patients was the main motivator for 12% of those who just got shots. Fourteen percent of the recently vaccinated got inoculated mainly because someone they knew had become seriously ill or had died from COVID-19.

The role of the Delta threat is also evident with regard to where those who were recently vaccinated live. Twenty-four percent of those who received their first dose of vaccine after June 1, 2021, reside in counties with a high COVID-19 case rate; 15% of them live in counties with a relatively low case rate.

Despite the recent surge in vaccinations, however, 7% of adults are still taking a wait-and-see approach; 4% said they’d get a shot only if required; and 12% said they definitely wouldn’t get vaccinated. The latter figure has barely budged since January of this year.

Ninety percent of Democrats said they had received at least one dose of the COVID-19 vaccine, vs. 68% of Independents, and 58% of Republicans.

Wealthier, better educated, urban, and older people were more likely to be vaccinated, with one exception: Sixty-eight percent of those aged 18-29 were vaccinated, vs. 66% of those aged 30-49. The group least likely to be vaccinated were uninsured people younger than 65, suggesting that some of them were unaware that the shot is free.
 

Partisan affiliation

Attitudes toward vaccine booster shots – which are now recommended for people older than 65, the immunocompromised, and certain frontline workers – largely fell along party lines and/or reflected whether respondents had been vaccinated.

Discussion of the boosters, KFF said, “appears to be a net positive for people who are already vaccinated, but a net negative for the unvaccinated. While a larger share of vaccinated adults say the information they have seen about boosters has been helpful (54%) than find it confusing (35%), among the unvaccinated almost twice as many find the information confusing as find it helpful (45% vs. 24%).”

Among fully vaccinated adults, 68% of Democrats say they’d definitely get a booster, and 20% say they probably would. Among Republicans, those percentages are 36% and 33%, respectively. Independents fall in between the other groups.

Although 82% of Democrats say the boosters show that scientists are continuing to make vaccines more effective, 52% of Republicans say that it shows that the vaccines are not working as well as promised.

Similarly, partisan attitudes emerged in questions about breakthrough infections. The fact that COVID-19 cases are fairly mild when they occur among persons who have been vaccinated indicates that the vaccines are working, said 87% of Democrats, but only 55% of Republicans agreed with that assessment.

In contrast, just 10% of Democrats but 39% of Republicans said that breakthrough infections mean the vaccines are not working.
 

Vaccine requirements

The public is more evenly divided on vaccine requirements. About 6 in 10 respondents said that vaccines should be required for health care workers (62%) and schoolteachers (58%). Slim majorities supported mandates for federal government employees (55%), college students (55%), and state and local government employees (54%).

On the question of whether employers in general should require their workers to be vaccinated, 48% of respondents said they should, and 50% said they should not.

Similarly, 52% said that all schools should mandate vaccines for eligible students; 46% didn’t approve of such requirements.

Three in four Democrats supported employer vaccine mandates, compared to 45% of Independents and just 20% of Republicans. Large partisan gaps were also seen for government, school, and health care vaccine mandates.

In contrast, 78% of the public favored requiring large employers to give their workers paid time off to get vaccinated and to recover from any side effects.
 

Twenty percent of workers under mandates

One in five workers said their employers require COVID-19 vaccination. Twenty-eight percent of employed people want their employers to require vaccination, and 50% don’t.

Again, the responses broke down along party lines, with 52% of Democrats, 21% of Independents, and 10% of Republicans favoring a vaccine mandate by their employers.

Most unvaccinated people didn’t support an employer mandate. A third of unvaccinated workers said they’d be likely to get vaccinated if their companies required it, but most of them said they would choose weekly testing if offered the option.

Being unable to use gyms, restaurants, or indoor entertainment venues that require vaccination was cited by 13% of the recently vaccinated as the main reason why they got shots.

The public was evenly divided on whether states or local governments should require such businesses to mandate that staff and customers show proof of vaccination. Although the views of the public were tied on this issue overall, 79% of Democrats, 43% of Independents, and 21% of Republicans supported having these kinds of businesses require proof of vaccination.

On school mask mandates, 56% of the respondents supported requiring all students and staff to wear masks. Favoring this kind of mandate were 83% of Democrats, 53% of Independents, and 29% of Republicans.

Partisanship also defined how Democrats and Republicans viewed the current high number of COVID-19 cases. Most Democrats blamed people who don’t wear masks and those who don’t get vaccinated, whereas Republicans were more likely to blame immigrants and tourists bringing COVID-19 into the United States.

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

The number of U.S. adults who are at least partially vaccinated rose five percentage points to 72% in August, a slightly faster increase than in previous months, according to the latest monthly COVID-19 Vaccine Monitor report of the Kaiser Family Foundation (KFF).

The largest increases in vaccine uptake between July and September were among Hispanic adults and people aged 18-29 years. Roughly equal shares of adults now report being vaccinated across racial and ethnic groups: 71% of White adults, 70% of Black adults, and 73% of Hispanic adults.

Overall, the big takeaway of the latest Kaiser COVID-19 survey is that the partisan divide on all aspects of the pandemic, from vaccination status to attitudes toward vaccination and mask mandates, remains as wide as ever.

The only thing that Republicans, Democrats, and Independents mostly agree on is that COVID-19 will probably become an endemic disease like influenza. Seventy-nine percent of respondents agreed with that statement; 14% predicted that COVID-19 would probably be largely eliminated in future years, like polio.
 

Delta motivated many

The most important factor that recently led people toward being vaccinated against COVID-19 was the surge in cases, hospitalizations, and deaths due to the Delta variant, KFF reports.

Full approval of the Pfizer vaccine by the Food and Drug Administration and the increasing prevalence of vaccine mandates played secondary roles in the vaccination uptick.

Specifically, 10% of the recently vaccinated said the main reason they got shots was the increase in COVID-19 cases due to the Delta variant. Concern about reports of local hospitals and intensive care units filling up with COVID-19 patients was the main motivator for 12% of those who just got shots. Fourteen percent of the recently vaccinated got inoculated mainly because someone they knew had become seriously ill or had died from COVID-19.

The role of the Delta threat is also evident with regard to where those who were recently vaccinated live. Twenty-four percent of those who received their first dose of vaccine after June 1, 2021, reside in counties with a high COVID-19 case rate; 15% of them live in counties with a relatively low case rate.

Despite the recent surge in vaccinations, however, 7% of adults are still taking a wait-and-see approach; 4% said they’d get a shot only if required; and 12% said they definitely wouldn’t get vaccinated. The latter figure has barely budged since January of this year.

Ninety percent of Democrats said they had received at least one dose of the COVID-19 vaccine, vs. 68% of Independents, and 58% of Republicans.

Wealthier, better educated, urban, and older people were more likely to be vaccinated, with one exception: Sixty-eight percent of those aged 18-29 were vaccinated, vs. 66% of those aged 30-49. The group least likely to be vaccinated were uninsured people younger than 65, suggesting that some of them were unaware that the shot is free.
 

Partisan affiliation

Attitudes toward vaccine booster shots – which are now recommended for people older than 65, the immunocompromised, and certain frontline workers – largely fell along party lines and/or reflected whether respondents had been vaccinated.

Discussion of the boosters, KFF said, “appears to be a net positive for people who are already vaccinated, but a net negative for the unvaccinated. While a larger share of vaccinated adults say the information they have seen about boosters has been helpful (54%) than find it confusing (35%), among the unvaccinated almost twice as many find the information confusing as find it helpful (45% vs. 24%).”

Among fully vaccinated adults, 68% of Democrats say they’d definitely get a booster, and 20% say they probably would. Among Republicans, those percentages are 36% and 33%, respectively. Independents fall in between the other groups.

Although 82% of Democrats say the boosters show that scientists are continuing to make vaccines more effective, 52% of Republicans say that it shows that the vaccines are not working as well as promised.

Similarly, partisan attitudes emerged in questions about breakthrough infections. The fact that COVID-19 cases are fairly mild when they occur among persons who have been vaccinated indicates that the vaccines are working, said 87% of Democrats, but only 55% of Republicans agreed with that assessment.

In contrast, just 10% of Democrats but 39% of Republicans said that breakthrough infections mean the vaccines are not working.
 

Vaccine requirements

The public is more evenly divided on vaccine requirements. About 6 in 10 respondents said that vaccines should be required for health care workers (62%) and schoolteachers (58%). Slim majorities supported mandates for federal government employees (55%), college students (55%), and state and local government employees (54%).

On the question of whether employers in general should require their workers to be vaccinated, 48% of respondents said they should, and 50% said they should not.

Similarly, 52% said that all schools should mandate vaccines for eligible students; 46% didn’t approve of such requirements.

Three in four Democrats supported employer vaccine mandates, compared to 45% of Independents and just 20% of Republicans. Large partisan gaps were also seen for government, school, and health care vaccine mandates.

In contrast, 78% of the public favored requiring large employers to give their workers paid time off to get vaccinated and to recover from any side effects.
 

Twenty percent of workers under mandates

One in five workers said their employers require COVID-19 vaccination. Twenty-eight percent of employed people want their employers to require vaccination, and 50% don’t.

Again, the responses broke down along party lines, with 52% of Democrats, 21% of Independents, and 10% of Republicans favoring a vaccine mandate by their employers.

Most unvaccinated people didn’t support an employer mandate. A third of unvaccinated workers said they’d be likely to get vaccinated if their companies required it, but most of them said they would choose weekly testing if offered the option.

Being unable to use gyms, restaurants, or indoor entertainment venues that require vaccination was cited by 13% of the recently vaccinated as the main reason why they got shots.

The public was evenly divided on whether states or local governments should require such businesses to mandate that staff and customers show proof of vaccination. Although the views of the public were tied on this issue overall, 79% of Democrats, 43% of Independents, and 21% of Republicans supported having these kinds of businesses require proof of vaccination.

On school mask mandates, 56% of the respondents supported requiring all students and staff to wear masks. Favoring this kind of mandate were 83% of Democrats, 53% of Independents, and 29% of Republicans.

Partisanship also defined how Democrats and Republicans viewed the current high number of COVID-19 cases. Most Democrats blamed people who don’t wear masks and those who don’t get vaccinated, whereas Republicans were more likely to blame immigrants and tourists bringing COVID-19 into the United States.

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

A monoclonal antibody combination of casirivimab and imdevimab (REGEN-COV) significantly reduced the risk of COVID-19–related hospitalizations and death from any cause in the phase 3 portion of an adaptive trial of outpatients.

Researchers, led by David Weinreich, MD, MBA, executive vice president of the drug cocktail’s manufacturer Regeneron, found in the randomized trial that the combination also resolved symptoms and reduced the SARS-CoV-2 viral load more quickly, compared with placebo.

Findings were published in the New England Journal of Medicine. 

COVID-related hospitalization or death from any cause occurred in 18 of 1,355 patients (1.3%) in the group getting 2,400 mg infusions of the study drug, compared with 62 (4.6%) of 1,341 in the matching placebo group, indicating a relative risk reduction of 71.3%; P < .001.

Sunil Joshi, MD, president of the Duval County Medical Society Foundation and an immunologist in Jacksonville, Fla., said in an interview that these findings confirm benefits of REGEN-COV and are very good news for a patient group that includes those age 65 and older with high blood pressure, diabetes, or obesity; and for people not vaccinated, who are all at high risk of hospitalization or death if they get COVID-19.

“Vaccines are critically important,” he said, “but if you were to be infected and know that there’s a way to keep yourself out of the hospital, this is very good news.”
 

Researchers seek lowest doses

This trial found that the effect was similar when researchers cut the doses in half. These outcomes occurred in 7 of 736 (1%) of patients given 1,200 mg of REGEN-COV and in 24 (3.2%) of 748 in the matching placebo group (relative risk reduction, 70.4%; P = .002).

Symptoms were resolved on average 4 days earlier with each REGEN-COV dose than with placebo (10 days vs. 14 days; P < .001 for both comparisons).

Dr. Weinreich said in an interview that trials will continue to find the lowest effective doses that can stand up to all evolving variants.

“This is one of those settings where you don’t want to underdose. You’ve got one shot at this,” he said. “We’d love to do lower doses. It would be more convenient and we could treat more patients, but if it generates more clinical failures or doesn’t work with certain variants, then you’ve done a huge disservice to the world.”

Also new in this study is that researchers tested not only seronegative patients, but patients at high risk regardless of blood antibody status, he said.

“It’s the first suggestion of data that if you’re breaking through a vaccine and you’re at high risk, the use of the cocktail is something to strongly consider because treatment early is better than treatment later,” Dr. Weinreich said.

In addition to efficacy, the phase 3 trial demonstrated the cocktail had a good safety profile. Serious adverse events occurred more often in the placebo group (4%) than in the 1,200-mg group (1.1%) and the 2,400-mg group (1.3%). Infusion reactions (grade 2 or higher) occurred in less than 0.3% of patients in all groups. 

William Fales, MD, state medical director for the Michigan Department of Health and Human Services, said the results confirm the promise of REGEN-COV for reducing hospitalizations and death in a peer-reviewed publication.
 

COVID-19 a moving target

However, Dr. Fales noted that COVID-19 is a moving target with emerging variants. The criteria for populations at high risk have also broadened since the start of the study, he said.

“A great example is pregnancy is now included as high risk, and that would have likely been a specific contraindication of patients in this clinical trial,” he said.

Dr. Fales said Michigan has been using both REGEN-COV and the Eli Lilly combination of bamlanivimab and etesevimab, which also has an emergency use authorization (EUA) from the Food and Drug Administration, with positive results.

REGEN-COV has an EUA to treat people who are at high risk of serious consequences from COVID-19, including those who are already infected (nonhospitalized) or those in certain postexposure prophylaxis settings.

“We’re seeing very low hospitalization rates and few deaths in a state that is predominately Delta,” Dr. Fales said. “So, this makes us feel that we’re doing the right thing and supports the current efforts around the country to make monoclonal antibody therapy available to high-risk patients.”  

Dr. Joshi noted that trial results have been emerging from other monoclonal antibody cocktails with different COVID-19 patient groups.

However, he said in an interview, “how much more effective they would be than this is something we’d have to look at, as 71% effectiveness in keeping people out of the hospital is pretty good for any treatment.”

“These are great numbers, but vaccination itself keeps you from getting the disease in the first place and not just for a short time period. This treatment is just that – a treatment. It gets you through that episode but it doesn’t mean you won’t get sick again. You don’t develop an immune response as you do with the vaccine,” he said.

Dr. Weinreich agreed: “This is not a substitute for a vaccine except for the small group who get the vaccine and their bodies can’t respond to it because they’re significantly immunocompromised.”

The results from this paper “are one piece of a large, multistudy, phase 3 program that basically spans from prophylaxis all the way to hospitalization and pretty much the gamut – all of them – have worked. All of these studies have shown dramatic improvement in whatever the definitive regulatory endpoint is,” Dr. Weinreich said.

He said discussions are ongoing for full regulatory approval in the United States and for expanding the EUA for other populations, including pre-exposure prophylaxis, “which the [United Kingdom’s] authority has already granted us but the FDA has not.”

The study is funded by Regeneron and the Department of Health & Human Services. Dr. Weinreich is a vice president of Regeneron. Dr. Joshi reported no relevant financial relationships. Dr. Fales holds stock in Eli Lilly.

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

A monoclonal antibody combination of casirivimab and imdevimab (REGEN-COV) significantly reduced the risk of COVID-19–related hospitalizations and death from any cause in the phase 3 portion of an adaptive trial of outpatients.

Researchers, led by David Weinreich, MD, MBA, executive vice president of the drug cocktail’s manufacturer Regeneron, found in the randomized trial that the combination also resolved symptoms and reduced the SARS-CoV-2 viral load more quickly, compared with placebo.

Findings were published in the New England Journal of Medicine. 

COVID-related hospitalization or death from any cause occurred in 18 of 1,355 patients (1.3%) in the group getting 2,400 mg infusions of the study drug, compared with 62 (4.6%) of 1,341 in the matching placebo group, indicating a relative risk reduction of 71.3%; P < .001.

Sunil Joshi, MD, president of the Duval County Medical Society Foundation and an immunologist in Jacksonville, Fla., said in an interview that these findings confirm benefits of REGEN-COV and are very good news for a patient group that includes those age 65 and older with high blood pressure, diabetes, or obesity; and for people not vaccinated, who are all at high risk of hospitalization or death if they get COVID-19.

“Vaccines are critically important,” he said, “but if you were to be infected and know that there’s a way to keep yourself out of the hospital, this is very good news.”
 

Researchers seek lowest doses

This trial found that the effect was similar when researchers cut the doses in half. These outcomes occurred in 7 of 736 (1%) of patients given 1,200 mg of REGEN-COV and in 24 (3.2%) of 748 in the matching placebo group (relative risk reduction, 70.4%; P = .002).

Symptoms were resolved on average 4 days earlier with each REGEN-COV dose than with placebo (10 days vs. 14 days; P < .001 for both comparisons).

Dr. Weinreich said in an interview that trials will continue to find the lowest effective doses that can stand up to all evolving variants.

“This is one of those settings where you don’t want to underdose. You’ve got one shot at this,” he said. “We’d love to do lower doses. It would be more convenient and we could treat more patients, but if it generates more clinical failures or doesn’t work with certain variants, then you’ve done a huge disservice to the world.”

Also new in this study is that researchers tested not only seronegative patients, but patients at high risk regardless of blood antibody status, he said.

“It’s the first suggestion of data that if you’re breaking through a vaccine and you’re at high risk, the use of the cocktail is something to strongly consider because treatment early is better than treatment later,” Dr. Weinreich said.

In addition to efficacy, the phase 3 trial demonstrated the cocktail had a good safety profile. Serious adverse events occurred more often in the placebo group (4%) than in the 1,200-mg group (1.1%) and the 2,400-mg group (1.3%). Infusion reactions (grade 2 or higher) occurred in less than 0.3% of patients in all groups. 

William Fales, MD, state medical director for the Michigan Department of Health and Human Services, said the results confirm the promise of REGEN-COV for reducing hospitalizations and death in a peer-reviewed publication.
 

COVID-19 a moving target

However, Dr. Fales noted that COVID-19 is a moving target with emerging variants. The criteria for populations at high risk have also broadened since the start of the study, he said.

“A great example is pregnancy is now included as high risk, and that would have likely been a specific contraindication of patients in this clinical trial,” he said.

Dr. Fales said Michigan has been using both REGEN-COV and the Eli Lilly combination of bamlanivimab and etesevimab, which also has an emergency use authorization (EUA) from the Food and Drug Administration, with positive results.

REGEN-COV has an EUA to treat people who are at high risk of serious consequences from COVID-19, including those who are already infected (nonhospitalized) or those in certain postexposure prophylaxis settings.

“We’re seeing very low hospitalization rates and few deaths in a state that is predominately Delta,” Dr. Fales said. “So, this makes us feel that we’re doing the right thing and supports the current efforts around the country to make monoclonal antibody therapy available to high-risk patients.”  

Dr. Joshi noted that trial results have been emerging from other monoclonal antibody cocktails with different COVID-19 patient groups.

However, he said in an interview, “how much more effective they would be than this is something we’d have to look at, as 71% effectiveness in keeping people out of the hospital is pretty good for any treatment.”

“These are great numbers, but vaccination itself keeps you from getting the disease in the first place and not just for a short time period. This treatment is just that – a treatment. It gets you through that episode but it doesn’t mean you won’t get sick again. You don’t develop an immune response as you do with the vaccine,” he said.

Dr. Weinreich agreed: “This is not a substitute for a vaccine except for the small group who get the vaccine and their bodies can’t respond to it because they’re significantly immunocompromised.”

The results from this paper “are one piece of a large, multistudy, phase 3 program that basically spans from prophylaxis all the way to hospitalization and pretty much the gamut – all of them – have worked. All of these studies have shown dramatic improvement in whatever the definitive regulatory endpoint is,” Dr. Weinreich said.

He said discussions are ongoing for full regulatory approval in the United States and for expanding the EUA for other populations, including pre-exposure prophylaxis, “which the [United Kingdom’s] authority has already granted us but the FDA has not.”

The study is funded by Regeneron and the Department of Health & Human Services. Dr. Weinreich is a vice president of Regeneron. Dr. Joshi reported no relevant financial relationships. Dr. Fales holds stock in Eli Lilly.

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

A monoclonal antibody combination of casirivimab and imdevimab (REGEN-COV) significantly reduced the risk of COVID-19–related hospitalizations and death from any cause in the phase 3 portion of an adaptive trial of outpatients.

Researchers, led by David Weinreich, MD, MBA, executive vice president of the drug cocktail’s manufacturer Regeneron, found in the randomized trial that the combination also resolved symptoms and reduced the SARS-CoV-2 viral load more quickly, compared with placebo.

Findings were published in the New England Journal of Medicine. 

COVID-related hospitalization or death from any cause occurred in 18 of 1,355 patients (1.3%) in the group getting 2,400 mg infusions of the study drug, compared with 62 (4.6%) of 1,341 in the matching placebo group, indicating a relative risk reduction of 71.3%; P < .001.

Sunil Joshi, MD, president of the Duval County Medical Society Foundation and an immunologist in Jacksonville, Fla., said in an interview that these findings confirm benefits of REGEN-COV and are very good news for a patient group that includes those age 65 and older with high blood pressure, diabetes, or obesity; and for people not vaccinated, who are all at high risk of hospitalization or death if they get COVID-19.

“Vaccines are critically important,” he said, “but if you were to be infected and know that there’s a way to keep yourself out of the hospital, this is very good news.”
 

Researchers seek lowest doses

This trial found that the effect was similar when researchers cut the doses in half. These outcomes occurred in 7 of 736 (1%) of patients given 1,200 mg of REGEN-COV and in 24 (3.2%) of 748 in the matching placebo group (relative risk reduction, 70.4%; P = .002).

Symptoms were resolved on average 4 days earlier with each REGEN-COV dose than with placebo (10 days vs. 14 days; P < .001 for both comparisons).

Dr. Weinreich said in an interview that trials will continue to find the lowest effective doses that can stand up to all evolving variants.

“This is one of those settings where you don’t want to underdose. You’ve got one shot at this,” he said. “We’d love to do lower doses. It would be more convenient and we could treat more patients, but if it generates more clinical failures or doesn’t work with certain variants, then you’ve done a huge disservice to the world.”

Also new in this study is that researchers tested not only seronegative patients, but patients at high risk regardless of blood antibody status, he said.

“It’s the first suggestion of data that if you’re breaking through a vaccine and you’re at high risk, the use of the cocktail is something to strongly consider because treatment early is better than treatment later,” Dr. Weinreich said.

In addition to efficacy, the phase 3 trial demonstrated the cocktail had a good safety profile. Serious adverse events occurred more often in the placebo group (4%) than in the 1,200-mg group (1.1%) and the 2,400-mg group (1.3%). Infusion reactions (grade 2 or higher) occurred in less than 0.3% of patients in all groups. 

William Fales, MD, state medical director for the Michigan Department of Health and Human Services, said the results confirm the promise of REGEN-COV for reducing hospitalizations and death in a peer-reviewed publication.
 

COVID-19 a moving target

However, Dr. Fales noted that COVID-19 is a moving target with emerging variants. The criteria for populations at high risk have also broadened since the start of the study, he said.

“A great example is pregnancy is now included as high risk, and that would have likely been a specific contraindication of patients in this clinical trial,” he said.

Dr. Fales said Michigan has been using both REGEN-COV and the Eli Lilly combination of bamlanivimab and etesevimab, which also has an emergency use authorization (EUA) from the Food and Drug Administration, with positive results.

REGEN-COV has an EUA to treat people who are at high risk of serious consequences from COVID-19, including those who are already infected (nonhospitalized) or those in certain postexposure prophylaxis settings.

“We’re seeing very low hospitalization rates and few deaths in a state that is predominately Delta,” Dr. Fales said. “So, this makes us feel that we’re doing the right thing and supports the current efforts around the country to make monoclonal antibody therapy available to high-risk patients.”  

Dr. Joshi noted that trial results have been emerging from other monoclonal antibody cocktails with different COVID-19 patient groups.

However, he said in an interview, “how much more effective they would be than this is something we’d have to look at, as 71% effectiveness in keeping people out of the hospital is pretty good for any treatment.”

“These are great numbers, but vaccination itself keeps you from getting the disease in the first place and not just for a short time period. This treatment is just that – a treatment. It gets you through that episode but it doesn’t mean you won’t get sick again. You don’t develop an immune response as you do with the vaccine,” he said.

Dr. Weinreich agreed: “This is not a substitute for a vaccine except for the small group who get the vaccine and their bodies can’t respond to it because they’re significantly immunocompromised.”

The results from this paper “are one piece of a large, multistudy, phase 3 program that basically spans from prophylaxis all the way to hospitalization and pretty much the gamut – all of them – have worked. All of these studies have shown dramatic improvement in whatever the definitive regulatory endpoint is,” Dr. Weinreich said.

He said discussions are ongoing for full regulatory approval in the United States and for expanding the EUA for other populations, including pre-exposure prophylaxis, “which the [United Kingdom’s] authority has already granted us but the FDA has not.”

The study is funded by Regeneron and the Department of Health & Human Services. Dr. Weinreich is a vice president of Regeneron. Dr. Joshi reported no relevant financial relationships. Dr. Fales holds stock in Eli Lilly.

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

One week after reporting promising results from the trial of their COVID-19 vaccine in children ages 5-11, Pfizer and BioNTech announced they’d submitted the data to the Food and Drug Administration. But that hasn’t stopped some parents from discreetly getting their children under age 12 vaccinated.

“The FDA, you never want to get ahead of their judgment,” Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, told MSNBC on Sept. 28. “But I would imagine in the next few weeks, they will examine that data and hopefully they’ll give the okay so that we can start vaccinating children, hopefully before the end of October.”
 

Lying to vaccinate now

More than half of all parents with children under 12 say they plan to get their kids vaccinated, according to a Gallup poll. Among those who say they’re “very worried” or “somewhat worried” about their children catching COVID, that number goes up to 90% and 72%, respectively.

And although the FDA and the American Academy of Pediatrics have warned against it, some parents whose children can pass for 12 have lied to get them vaccinated already.

Dawn G. is a mom of two in southwest Missouri, where less than 45% of the population has been fully vaccinated. Her son turns 12 in early October, but in-person school started in mid-August.

“It was scary, thinking of him going to school for even 2 months,” she said. “Some parents thought their kid had a low chance of getting COVID, and their kid died. Nobody expects it to be them.”

In July, she and her husband took their son to a walk-in clinic and lied about his age.

“So many things can happen, from bullying to school shootings, and now this added pandemic risk,” she said. “I’ll do anything I can to protect my child, and a birthdate seems so arbitrary. He’ll be 12 in a matter of weeks. It seems ridiculous that that date would stop me from protecting him.”

In northern California, Carrie S. had a similar thought. When the vaccine was authorized for children ages 12-15 in May, the older of her two children got the shot right away. But her youngest doesn’t turn 12 until November.

“We were tempted to get the younger one vaccinated in May, but it didn’t seem like a rush. We were willing to wait to get the dosage right,” she ssaid. “But as Delta came through, there were no options for online school, the CDC was dropping mask expectations –it seemed like the world was ready to forget the pandemic was happening. It seemed like the least-bad option to get her vaccinated so she could go back to school, and we could find some balance of risk in our lives.”
 

Adult vs. pediatric doses

For now, experts advise against getting younger children vaccinated, even those who are the size of an adult, because of the way the human immune system develops.

“It’s not really about size,” said Anne Liu, MD, an immunologist and pediatrics professor at Stanford (Calif.) University. “The immune system behaves differently at different ages. Younger kids tend to have a more exuberant innate immune system, which is the part of the immune system that senses danger, even before it has developed a memory response.”

The adult Pfizer-BioNTech vaccine contains 30 mcg of mRNA, while the pediatric dose is just 10 mcg. That smaller dose produces an immune response similar to what’s seen in adults who receive 30 mcg, according to Pfizer.

“We were one of the sites that was involved in the phase 1 trial, a lot of times that’s called a dose-finding trial,” said Michael Smith, MD, a coinvestigator for the COVID vaccine trials done at Duke University. “And basically, if younger kids got a higher dose, they had more of a reaction, so it hurt more. They had fever, they had more redness and swelling at the site of the injection, and they just felt lousy, more than at the lower doses.”

At this point, with Pfizer’s data showing that younger children need a smaller dose, it doesn’t make sense to lie about your child’s age, said Dr. Smith.

“If my two options were having my child get the infection versus getting the vaccine, I’d get the vaccine. But we’re a few weeks away from getting the lower dose approved in kids,” he said. “It’s certainly safer. I don’t expect major, lifelong side effects from the higher dose, but it’s going to hurt, your kid’s going to have a fever, they’re going to feel lousy for a couple days, and they just don’t need that much antigen.”

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

One week after reporting promising results from the trial of their COVID-19 vaccine in children ages 5-11, Pfizer and BioNTech announced they’d submitted the data to the Food and Drug Administration. But that hasn’t stopped some parents from discreetly getting their children under age 12 vaccinated.

“The FDA, you never want to get ahead of their judgment,” Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, told MSNBC on Sept. 28. “But I would imagine in the next few weeks, they will examine that data and hopefully they’ll give the okay so that we can start vaccinating children, hopefully before the end of October.”
 

Lying to vaccinate now

More than half of all parents with children under 12 say they plan to get their kids vaccinated, according to a Gallup poll. Among those who say they’re “very worried” or “somewhat worried” about their children catching COVID, that number goes up to 90% and 72%, respectively.

And although the FDA and the American Academy of Pediatrics have warned against it, some parents whose children can pass for 12 have lied to get them vaccinated already.

Dawn G. is a mom of two in southwest Missouri, where less than 45% of the population has been fully vaccinated. Her son turns 12 in early October, but in-person school started in mid-August.

“It was scary, thinking of him going to school for even 2 months,” she said. “Some parents thought their kid had a low chance of getting COVID, and their kid died. Nobody expects it to be them.”

In July, she and her husband took their son to a walk-in clinic and lied about his age.

“So many things can happen, from bullying to school shootings, and now this added pandemic risk,” she said. “I’ll do anything I can to protect my child, and a birthdate seems so arbitrary. He’ll be 12 in a matter of weeks. It seems ridiculous that that date would stop me from protecting him.”

In northern California, Carrie S. had a similar thought. When the vaccine was authorized for children ages 12-15 in May, the older of her two children got the shot right away. But her youngest doesn’t turn 12 until November.

“We were tempted to get the younger one vaccinated in May, but it didn’t seem like a rush. We were willing to wait to get the dosage right,” she ssaid. “But as Delta came through, there were no options for online school, the CDC was dropping mask expectations –it seemed like the world was ready to forget the pandemic was happening. It seemed like the least-bad option to get her vaccinated so she could go back to school, and we could find some balance of risk in our lives.”
 

Adult vs. pediatric doses

For now, experts advise against getting younger children vaccinated, even those who are the size of an adult, because of the way the human immune system develops.

“It’s not really about size,” said Anne Liu, MD, an immunologist and pediatrics professor at Stanford (Calif.) University. “The immune system behaves differently at different ages. Younger kids tend to have a more exuberant innate immune system, which is the part of the immune system that senses danger, even before it has developed a memory response.”

The adult Pfizer-BioNTech vaccine contains 30 mcg of mRNA, while the pediatric dose is just 10 mcg. That smaller dose produces an immune response similar to what’s seen in adults who receive 30 mcg, according to Pfizer.

“We were one of the sites that was involved in the phase 1 trial, a lot of times that’s called a dose-finding trial,” said Michael Smith, MD, a coinvestigator for the COVID vaccine trials done at Duke University. “And basically, if younger kids got a higher dose, they had more of a reaction, so it hurt more. They had fever, they had more redness and swelling at the site of the injection, and they just felt lousy, more than at the lower doses.”

At this point, with Pfizer’s data showing that younger children need a smaller dose, it doesn’t make sense to lie about your child’s age, said Dr. Smith.

“If my two options were having my child get the infection versus getting the vaccine, I’d get the vaccine. But we’re a few weeks away from getting the lower dose approved in kids,” he said. “It’s certainly safer. I don’t expect major, lifelong side effects from the higher dose, but it’s going to hurt, your kid’s going to have a fever, they’re going to feel lousy for a couple days, and they just don’t need that much antigen.”

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

One week after reporting promising results from the trial of their COVID-19 vaccine in children ages 5-11, Pfizer and BioNTech announced they’d submitted the data to the Food and Drug Administration. But that hasn’t stopped some parents from discreetly getting their children under age 12 vaccinated.

“The FDA, you never want to get ahead of their judgment,” Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, told MSNBC on Sept. 28. “But I would imagine in the next few weeks, they will examine that data and hopefully they’ll give the okay so that we can start vaccinating children, hopefully before the end of October.”
 

Lying to vaccinate now

More than half of all parents with children under 12 say they plan to get their kids vaccinated, according to a Gallup poll. Among those who say they’re “very worried” or “somewhat worried” about their children catching COVID, that number goes up to 90% and 72%, respectively.

And although the FDA and the American Academy of Pediatrics have warned against it, some parents whose children can pass for 12 have lied to get them vaccinated already.

Dawn G. is a mom of two in southwest Missouri, where less than 45% of the population has been fully vaccinated. Her son turns 12 in early October, but in-person school started in mid-August.

“It was scary, thinking of him going to school for even 2 months,” she said. “Some parents thought their kid had a low chance of getting COVID, and their kid died. Nobody expects it to be them.”

In July, she and her husband took their son to a walk-in clinic and lied about his age.

“So many things can happen, from bullying to school shootings, and now this added pandemic risk,” she said. “I’ll do anything I can to protect my child, and a birthdate seems so arbitrary. He’ll be 12 in a matter of weeks. It seems ridiculous that that date would stop me from protecting him.”

In northern California, Carrie S. had a similar thought. When the vaccine was authorized for children ages 12-15 in May, the older of her two children got the shot right away. But her youngest doesn’t turn 12 until November.

“We were tempted to get the younger one vaccinated in May, but it didn’t seem like a rush. We were willing to wait to get the dosage right,” she ssaid. “But as Delta came through, there were no options for online school, the CDC was dropping mask expectations –it seemed like the world was ready to forget the pandemic was happening. It seemed like the least-bad option to get her vaccinated so she could go back to school, and we could find some balance of risk in our lives.”
 

Adult vs. pediatric doses

For now, experts advise against getting younger children vaccinated, even those who are the size of an adult, because of the way the human immune system develops.

“It’s not really about size,” said Anne Liu, MD, an immunologist and pediatrics professor at Stanford (Calif.) University. “The immune system behaves differently at different ages. Younger kids tend to have a more exuberant innate immune system, which is the part of the immune system that senses danger, even before it has developed a memory response.”

The adult Pfizer-BioNTech vaccine contains 30 mcg of mRNA, while the pediatric dose is just 10 mcg. That smaller dose produces an immune response similar to what’s seen in adults who receive 30 mcg, according to Pfizer.

“We were one of the sites that was involved in the phase 1 trial, a lot of times that’s called a dose-finding trial,” said Michael Smith, MD, a coinvestigator for the COVID vaccine trials done at Duke University. “And basically, if younger kids got a higher dose, they had more of a reaction, so it hurt more. They had fever, they had more redness and swelling at the site of the injection, and they just felt lousy, more than at the lower doses.”

At this point, with Pfizer’s data showing that younger children need a smaller dose, it doesn’t make sense to lie about your child’s age, said Dr. Smith.

“If my two options were having my child get the infection versus getting the vaccine, I’d get the vaccine. But we’re a few weeks away from getting the lower dose approved in kids,” he said. “It’s certainly safer. I don’t expect major, lifelong side effects from the higher dose, but it’s going to hurt, your kid’s going to have a fever, they’re going to feel lousy for a couple days, and they just don’t need that much antigen.”

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

A new series of cases of cerebral venous sinus thrombosis (CVST) linked to the adenoviral vector COVID-19 vaccines has been reported, confirming the severity of the reaction and the associated high mortality rate.

The new series comes from an international registry of consecutive patients who experienced CVST within 28 days of COVID-19 vaccination between March 29 and June 18, 2021, from 81 hospitals in 19 countries.

The cases are described in an article published online on Sept. 28. in JAMA Neurology.

“This is a reliable description on the clinical condition of these patients with CVST associated with COVID-19 vaccination. It is striking that this a much worse condition than CVST not associated with COVID-19 vaccination, with a much higher rate of intracerebral hemorrhage and coma and a much higher mortality rate,” senior author Jonathan M. Coutinho, MD, Amsterdam University Medical Centers, told this news organization.

These data confirm the observations from an earlier U.K. cohort in which cases of cerebral venous thrombosis linked to COVID-19 vaccination occurred.

“This is the biggest series, and as an international series, it gives a broader perspective from a larger range of countries,” Dr. Coutinho said. “All the data together show that, although this side effect is rare, the consequences are very severe,” he added.

In the current study, the researchers regarded CVST as being linked to the vaccine if it was accompanied by thrombosis with thrombocytopenia syndrome (TTS), as evidenced by thrombosis and new-onset thrombocytopenia.

In the cohort of 116 patients with CVST after COVID-19 vaccination, 78 (67.2%) had thrombosis with TTS and were thus classified as having had a vaccine-related adverse event. These patients were frequently comatose at presentation (24%) and often had intracerebral hemorrhage (68%) and concomitant thromboembolism (36%); 47% died during hospitalization.

These patients were compared with the 38 patients in the same cohort who had CVST but in whom there was no indication of concomitant thrombosis and thrombocytopenia. The case patients were also compared with a control group of 207 patients with CVST who were included in a separate international registry before the COVID-19 pandemic.

Mortality rates were much higher among the patients deemed to have had a vaccine-related CVST. The in-hospital mortality rate was 47%, compared with 5% among the patients in the same cohort who did not have TTS and 3.9% among the prepandemic control group.

The mortality rate was even higher (61%) among patients in the TTS group for whom the diagnosis was made before the condition garnered attention in the scientific community. The mortality rate was 42% among patients diagnosed later.

Of the 78 patients in whom CVST and TTS occurred after COVID-19 vaccination in this cohort, 76 had received the AstraZeneca vaccine (in 75 patients, CVST and TTS occurred after the first vaccination; in one patient, they occurred after the second vaccination). One patient had received the Johnson & Johnson vaccine, and one had received the Pfizer vaccine.

“After more analysis, the case after the Pfizer vaccination is not believed to be caused by the vaccine,” Dr. Coutinho said. “In that case, the patient had a platelet count just below the lower limit and was taking an immunomodulator drug that is known to be associated with thrombocytopenia.”

For two patients who received the AstraZeneca vaccine, there was also an alternative explanation for the thrombocytopenia.

Dr. Coutinho also pointed out that the Johnson & Johnson vaccine has been used mainly in the United States, and these data were largely from other countries.

The median time from vaccination to CVST symptom onset was 9 days in the TTS group. The median platelet count at hospital admission among patients with postvaccination CVST-TTS was 45. Three patients presented with a normal platelet count and developed thrombocytopenia during admission; two patients presented with mild thrombocytopenia, 30 presented with moderate thrombocytopenia, and 43 presented with severe thrombocytopenia.

Antibodies against platelet factor 4 (PF4) were measured in 69 patients with TTS, of whom 63 (91%) tested positive (the one patient in whom TTS occurred after the patient received the Pfizer vaccine did not test positive). However, the researchers note that sensitivity varies among different PF4 ELISA tests. Findings of platelet activation assays were positive in all 36 tested patients.

In the TTS group, 52 patients (67%) received immunomodulation therapy, most often intravenous immunoglobulins (IVIG). Among patients treated with IVIG, the mortality rate was lower (28%).
 

Different from CVST linked to natural COVID-19 infection

Dr. Coutinho noted that CVST can occur in natural SARS-CoV-2 infection but that vaccine-associated CVST is very different.

“In natural COVID-19 infection, there is an increased risk of thrombosis, and some patients can get CVST as a part of this, but in these cases, this is not accompanied by thrombocytopenia. While the CVST in natural COVID-19 infection is also associated with a bad prognosis, this is more to do with the underlying disease. It is normally the very sick COVID patients who develop CVST, and these patients usually die from the underlying disease rather than the CVST itself,” he explained.

“Clinicians need to be aware of vaccine-related CVST, as it requires very specific and rapid treatment,” Dr. Coutinho stressed.

“Patients presenting with an extremely severe headache (unlike any headache they’ve had before) or with seizures or a focal deficit (weakness in arm or problems with speaking or vision) within 4 weeks of an adenovirus COVID-19 vaccination should ring alarm bells. It is important to do diagnostics quickly, with a platelet count the most important first step, and a rapid CT/MRI scan,” he said.

Other tests that should be conducted are D-dimer for thrombosis and the PF4 antibody test. But results for the PF4 antibody test can take days to come back, and clinicians shouldn’t wait for that, Dr. Coutinho notes.

“Specific treatment needs to be given immediately – with anticoagulation (preferably nonheparin) and immunomodulation with IVIG to stop the immune reaction. Platelets should not be given – that may seem counterintuitive in patients with a low platelet count, but giving platelets makes it worse,” he said.
 

Is there a geographic difference?

Dr. Coutinho pointed out that fewer cases of this vaccine-related CVST are being reported at the current time.

“We are not sure why this is the case. These adenovirus vaccines are not being used much now in Western countries, but our collaboration covers many less developed countries in South America and Asia, which are relying heavily on these vaccines. We are now shifting focus to these countries, but so far we have only seen a handful of cases from these areas,” he said.

He suggested that this may be because these countries started their vaccination programs later and are vaccinating their elderly (who are not so susceptible to this side effect) first, or it may be because of some environmental or genetic factor that has not yet been discovered.

“This is now an important research question – is the risk of vaccine-induced CVST the same in different countries or ethnicities? This could influence decisions on future vaccine strategies,” Dr. Coutinho said.

“So far, female sex is the strongest risk factor for vaccine-induced CVST. In our cohort, 81% of cases were in women. In addition, 95% were White, but that doesn’t allow us to conclude that this is a risk factor, as the majority of people who have been vaccinated are White. So, we have no clear insight into that yet,” he said.

In a comment for this news organization, the lead author of the previous U.K. report of a series of 70 cases of cerebral venous thrombosis linked to COVID-19 vaccination, Richard Perry, PhD, University College Hospital, London, described this new report as “an excellent study, with many of the same strengths and weaknesses as our study and has very similar results.”

Dr. Perry noted that the two studies used slightly different definitions of vaccine-induced thrombotic thrombocytopenia, but the cases reported appear to be very similar overall. “It is reassuring and gratifying to see that they have made such similar observations,” he said.

“And as they have drawn their cases from a broad range of countries whereas ours were all from the U.K., this provides evidence that the observations from both studies are reasonably generalizable,” he added.

Dr. Perry pointed out that this new report states that TTS occurred in one patient after the patient had received a second dose of the AstraZeneca vaccine. “I would like to know more about this case, because we didn’t see any cases after a second dose in our cohort,” he said.

Dr. Coutinho responded that he didn’t believe this was the first reported case after the second dose.

The study did not receive any specific funding. Dr. Coutinho has received grants paid to his institution from Boehringer Ingelheim and Bayer and payments paid to his institution for data safety monitoring board participation by Bayer.

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

A new series of cases of cerebral venous sinus thrombosis (CVST) linked to the adenoviral vector COVID-19 vaccines has been reported, confirming the severity of the reaction and the associated high mortality rate.

The new series comes from an international registry of consecutive patients who experienced CVST within 28 days of COVID-19 vaccination between March 29 and June 18, 2021, from 81 hospitals in 19 countries.

The cases are described in an article published online on Sept. 28. in JAMA Neurology.

“This is a reliable description on the clinical condition of these patients with CVST associated with COVID-19 vaccination. It is striking that this a much worse condition than CVST not associated with COVID-19 vaccination, with a much higher rate of intracerebral hemorrhage and coma and a much higher mortality rate,” senior author Jonathan M. Coutinho, MD, Amsterdam University Medical Centers, told this news organization.

These data confirm the observations from an earlier U.K. cohort in which cases of cerebral venous thrombosis linked to COVID-19 vaccination occurred.

“This is the biggest series, and as an international series, it gives a broader perspective from a larger range of countries,” Dr. Coutinho said. “All the data together show that, although this side effect is rare, the consequences are very severe,” he added.

In the current study, the researchers regarded CVST as being linked to the vaccine if it was accompanied by thrombosis with thrombocytopenia syndrome (TTS), as evidenced by thrombosis and new-onset thrombocytopenia.

In the cohort of 116 patients with CVST after COVID-19 vaccination, 78 (67.2%) had thrombosis with TTS and were thus classified as having had a vaccine-related adverse event. These patients were frequently comatose at presentation (24%) and often had intracerebral hemorrhage (68%) and concomitant thromboembolism (36%); 47% died during hospitalization.

These patients were compared with the 38 patients in the same cohort who had CVST but in whom there was no indication of concomitant thrombosis and thrombocytopenia. The case patients were also compared with a control group of 207 patients with CVST who were included in a separate international registry before the COVID-19 pandemic.

Mortality rates were much higher among the patients deemed to have had a vaccine-related CVST. The in-hospital mortality rate was 47%, compared with 5% among the patients in the same cohort who did not have TTS and 3.9% among the prepandemic control group.

The mortality rate was even higher (61%) among patients in the TTS group for whom the diagnosis was made before the condition garnered attention in the scientific community. The mortality rate was 42% among patients diagnosed later.

Of the 78 patients in whom CVST and TTS occurred after COVID-19 vaccination in this cohort, 76 had received the AstraZeneca vaccine (in 75 patients, CVST and TTS occurred after the first vaccination; in one patient, they occurred after the second vaccination). One patient had received the Johnson & Johnson vaccine, and one had received the Pfizer vaccine.

“After more analysis, the case after the Pfizer vaccination is not believed to be caused by the vaccine,” Dr. Coutinho said. “In that case, the patient had a platelet count just below the lower limit and was taking an immunomodulator drug that is known to be associated with thrombocytopenia.”

For two patients who received the AstraZeneca vaccine, there was also an alternative explanation for the thrombocytopenia.

Dr. Coutinho also pointed out that the Johnson & Johnson vaccine has been used mainly in the United States, and these data were largely from other countries.

The median time from vaccination to CVST symptom onset was 9 days in the TTS group. The median platelet count at hospital admission among patients with postvaccination CVST-TTS was 45. Three patients presented with a normal platelet count and developed thrombocytopenia during admission; two patients presented with mild thrombocytopenia, 30 presented with moderate thrombocytopenia, and 43 presented with severe thrombocytopenia.

Antibodies against platelet factor 4 (PF4) were measured in 69 patients with TTS, of whom 63 (91%) tested positive (the one patient in whom TTS occurred after the patient received the Pfizer vaccine did not test positive). However, the researchers note that sensitivity varies among different PF4 ELISA tests. Findings of platelet activation assays were positive in all 36 tested patients.

In the TTS group, 52 patients (67%) received immunomodulation therapy, most often intravenous immunoglobulins (IVIG). Among patients treated with IVIG, the mortality rate was lower (28%).
 

Different from CVST linked to natural COVID-19 infection

Dr. Coutinho noted that CVST can occur in natural SARS-CoV-2 infection but that vaccine-associated CVST is very different.

“In natural COVID-19 infection, there is an increased risk of thrombosis, and some patients can get CVST as a part of this, but in these cases, this is not accompanied by thrombocytopenia. While the CVST in natural COVID-19 infection is also associated with a bad prognosis, this is more to do with the underlying disease. It is normally the very sick COVID patients who develop CVST, and these patients usually die from the underlying disease rather than the CVST itself,” he explained.

“Clinicians need to be aware of vaccine-related CVST, as it requires very specific and rapid treatment,” Dr. Coutinho stressed.

“Patients presenting with an extremely severe headache (unlike any headache they’ve had before) or with seizures or a focal deficit (weakness in arm or problems with speaking or vision) within 4 weeks of an adenovirus COVID-19 vaccination should ring alarm bells. It is important to do diagnostics quickly, with a platelet count the most important first step, and a rapid CT/MRI scan,” he said.

Other tests that should be conducted are D-dimer for thrombosis and the PF4 antibody test. But results for the PF4 antibody test can take days to come back, and clinicians shouldn’t wait for that, Dr. Coutinho notes.

“Specific treatment needs to be given immediately – with anticoagulation (preferably nonheparin) and immunomodulation with IVIG to stop the immune reaction. Platelets should not be given – that may seem counterintuitive in patients with a low platelet count, but giving platelets makes it worse,” he said.
 

Is there a geographic difference?

Dr. Coutinho pointed out that fewer cases of this vaccine-related CVST are being reported at the current time.

“We are not sure why this is the case. These adenovirus vaccines are not being used much now in Western countries, but our collaboration covers many less developed countries in South America and Asia, which are relying heavily on these vaccines. We are now shifting focus to these countries, but so far we have only seen a handful of cases from these areas,” he said.

He suggested that this may be because these countries started their vaccination programs later and are vaccinating their elderly (who are not so susceptible to this side effect) first, or it may be because of some environmental or genetic factor that has not yet been discovered.

“This is now an important research question – is the risk of vaccine-induced CVST the same in different countries or ethnicities? This could influence decisions on future vaccine strategies,” Dr. Coutinho said.

“So far, female sex is the strongest risk factor for vaccine-induced CVST. In our cohort, 81% of cases were in women. In addition, 95% were White, but that doesn’t allow us to conclude that this is a risk factor, as the majority of people who have been vaccinated are White. So, we have no clear insight into that yet,” he said.

In a comment for this news organization, the lead author of the previous U.K. report of a series of 70 cases of cerebral venous thrombosis linked to COVID-19 vaccination, Richard Perry, PhD, University College Hospital, London, described this new report as “an excellent study, with many of the same strengths and weaknesses as our study and has very similar results.”

Dr. Perry noted that the two studies used slightly different definitions of vaccine-induced thrombotic thrombocytopenia, but the cases reported appear to be very similar overall. “It is reassuring and gratifying to see that they have made such similar observations,” he said.

“And as they have drawn their cases from a broad range of countries whereas ours were all from the U.K., this provides evidence that the observations from both studies are reasonably generalizable,” he added.

Dr. Perry pointed out that this new report states that TTS occurred in one patient after the patient had received a second dose of the AstraZeneca vaccine. “I would like to know more about this case, because we didn’t see any cases after a second dose in our cohort,” he said.

Dr. Coutinho responded that he didn’t believe this was the first reported case after the second dose.

The study did not receive any specific funding. Dr. Coutinho has received grants paid to his institution from Boehringer Ingelheim and Bayer and payments paid to his institution for data safety monitoring board participation by Bayer.

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

A new series of cases of cerebral venous sinus thrombosis (CVST) linked to the adenoviral vector COVID-19 vaccines has been reported, confirming the severity of the reaction and the associated high mortality rate.

The new series comes from an international registry of consecutive patients who experienced CVST within 28 days of COVID-19 vaccination between March 29 and June 18, 2021, from 81 hospitals in 19 countries.

The cases are described in an article published online on Sept. 28. in JAMA Neurology.

“This is a reliable description on the clinical condition of these patients with CVST associated with COVID-19 vaccination. It is striking that this a much worse condition than CVST not associated with COVID-19 vaccination, with a much higher rate of intracerebral hemorrhage and coma and a much higher mortality rate,” senior author Jonathan M. Coutinho, MD, Amsterdam University Medical Centers, told this news organization.

These data confirm the observations from an earlier U.K. cohort in which cases of cerebral venous thrombosis linked to COVID-19 vaccination occurred.

“This is the biggest series, and as an international series, it gives a broader perspective from a larger range of countries,” Dr. Coutinho said. “All the data together show that, although this side effect is rare, the consequences are very severe,” he added.

In the current study, the researchers regarded CVST as being linked to the vaccine if it was accompanied by thrombosis with thrombocytopenia syndrome (TTS), as evidenced by thrombosis and new-onset thrombocytopenia.

In the cohort of 116 patients with CVST after COVID-19 vaccination, 78 (67.2%) had thrombosis with TTS and were thus classified as having had a vaccine-related adverse event. These patients were frequently comatose at presentation (24%) and often had intracerebral hemorrhage (68%) and concomitant thromboembolism (36%); 47% died during hospitalization.

These patients were compared with the 38 patients in the same cohort who had CVST but in whom there was no indication of concomitant thrombosis and thrombocytopenia. The case patients were also compared with a control group of 207 patients with CVST who were included in a separate international registry before the COVID-19 pandemic.

Mortality rates were much higher among the patients deemed to have had a vaccine-related CVST. The in-hospital mortality rate was 47%, compared with 5% among the patients in the same cohort who did not have TTS and 3.9% among the prepandemic control group.

The mortality rate was even higher (61%) among patients in the TTS group for whom the diagnosis was made before the condition garnered attention in the scientific community. The mortality rate was 42% among patients diagnosed later.

Of the 78 patients in whom CVST and TTS occurred after COVID-19 vaccination in this cohort, 76 had received the AstraZeneca vaccine (in 75 patients, CVST and TTS occurred after the first vaccination; in one patient, they occurred after the second vaccination). One patient had received the Johnson & Johnson vaccine, and one had received the Pfizer vaccine.

“After more analysis, the case after the Pfizer vaccination is not believed to be caused by the vaccine,” Dr. Coutinho said. “In that case, the patient had a platelet count just below the lower limit and was taking an immunomodulator drug that is known to be associated with thrombocytopenia.”

For two patients who received the AstraZeneca vaccine, there was also an alternative explanation for the thrombocytopenia.

Dr. Coutinho also pointed out that the Johnson & Johnson vaccine has been used mainly in the United States, and these data were largely from other countries.

The median time from vaccination to CVST symptom onset was 9 days in the TTS group. The median platelet count at hospital admission among patients with postvaccination CVST-TTS was 45. Three patients presented with a normal platelet count and developed thrombocytopenia during admission; two patients presented with mild thrombocytopenia, 30 presented with moderate thrombocytopenia, and 43 presented with severe thrombocytopenia.

Antibodies against platelet factor 4 (PF4) were measured in 69 patients with TTS, of whom 63 (91%) tested positive (the one patient in whom TTS occurred after the patient received the Pfizer vaccine did not test positive). However, the researchers note that sensitivity varies among different PF4 ELISA tests. Findings of platelet activation assays were positive in all 36 tested patients.

In the TTS group, 52 patients (67%) received immunomodulation therapy, most often intravenous immunoglobulins (IVIG). Among patients treated with IVIG, the mortality rate was lower (28%).
 

Different from CVST linked to natural COVID-19 infection

Dr. Coutinho noted that CVST can occur in natural SARS-CoV-2 infection but that vaccine-associated CVST is very different.

“In natural COVID-19 infection, there is an increased risk of thrombosis, and some patients can get CVST as a part of this, but in these cases, this is not accompanied by thrombocytopenia. While the CVST in natural COVID-19 infection is also associated with a bad prognosis, this is more to do with the underlying disease. It is normally the very sick COVID patients who develop CVST, and these patients usually die from the underlying disease rather than the CVST itself,” he explained.

“Clinicians need to be aware of vaccine-related CVST, as it requires very specific and rapid treatment,” Dr. Coutinho stressed.

“Patients presenting with an extremely severe headache (unlike any headache they’ve had before) or with seizures or a focal deficit (weakness in arm or problems with speaking or vision) within 4 weeks of an adenovirus COVID-19 vaccination should ring alarm bells. It is important to do diagnostics quickly, with a platelet count the most important first step, and a rapid CT/MRI scan,” he said.

Other tests that should be conducted are D-dimer for thrombosis and the PF4 antibody test. But results for the PF4 antibody test can take days to come back, and clinicians shouldn’t wait for that, Dr. Coutinho notes.

“Specific treatment needs to be given immediately – with anticoagulation (preferably nonheparin) and immunomodulation with IVIG to stop the immune reaction. Platelets should not be given – that may seem counterintuitive in patients with a low platelet count, but giving platelets makes it worse,” he said.
 

Is there a geographic difference?

Dr. Coutinho pointed out that fewer cases of this vaccine-related CVST are being reported at the current time.

“We are not sure why this is the case. These adenovirus vaccines are not being used much now in Western countries, but our collaboration covers many less developed countries in South America and Asia, which are relying heavily on these vaccines. We are now shifting focus to these countries, but so far we have only seen a handful of cases from these areas,” he said.

He suggested that this may be because these countries started their vaccination programs later and are vaccinating their elderly (who are not so susceptible to this side effect) first, or it may be because of some environmental or genetic factor that has not yet been discovered.

“This is now an important research question – is the risk of vaccine-induced CVST the same in different countries or ethnicities? This could influence decisions on future vaccine strategies,” Dr. Coutinho said.

“So far, female sex is the strongest risk factor for vaccine-induced CVST. In our cohort, 81% of cases were in women. In addition, 95% were White, but that doesn’t allow us to conclude that this is a risk factor, as the majority of people who have been vaccinated are White. So, we have no clear insight into that yet,” he said.

In a comment for this news organization, the lead author of the previous U.K. report of a series of 70 cases of cerebral venous thrombosis linked to COVID-19 vaccination, Richard Perry, PhD, University College Hospital, London, described this new report as “an excellent study, with many of the same strengths and weaknesses as our study and has very similar results.”

Dr. Perry noted that the two studies used slightly different definitions of vaccine-induced thrombotic thrombocytopenia, but the cases reported appear to be very similar overall. “It is reassuring and gratifying to see that they have made such similar observations,” he said.

“And as they have drawn their cases from a broad range of countries whereas ours were all from the U.K., this provides evidence that the observations from both studies are reasonably generalizable,” he added.

Dr. Perry pointed out that this new report states that TTS occurred in one patient after the patient had received a second dose of the AstraZeneca vaccine. “I would like to know more about this case, because we didn’t see any cases after a second dose in our cohort,” he said.

Dr. Coutinho responded that he didn’t believe this was the first reported case after the second dose.

The study did not receive any specific funding. Dr. Coutinho has received grants paid to his institution from Boehringer Ingelheim and Bayer and payments paid to his institution for data safety monitoring board participation by Bayer.

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

Many people are confused — patients and healthcare providers alike — in the wake of the U.S. Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC) announcements about who is authorized to get a third or ‘booster’ shot of the Pfizer/BioNTech COVID-19 vaccine.

The official word on boosters from the CDC in the early morning hours of September 24 sparked a jump in people calling about or coming in for a third shot, healthcare providers report. At the same time, the uncertainty from changing federal messages about boosters is causing some chaos, especially in the form of vaccine misinformation.

The confusion started, in part, with the August 13 announcement that immunocompromised Americans were eligible for a booster shot. Next came the initial Biden administration intention to provide most U.S. adults with a third shot starting September 20 — an announcement later rolled back — followed by the Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC) limiting boosters to select groups last week.

“It was only 3% of the population that was going to be getting a third dose, then it was back to everyone being able to get the booster, and then it’s back to a select crew,” Louito Edje, MD, a family physician in private practice in Cincinnati, said in an interview with this news organization.

This kind of mixed messaging is generating more questions than answers.  

“Even though that is following the science, translating the science into policy, it’s really fraught with confusion for patients, especially,” added Dr. Edje, professor educator in the departments of medical education and family and community medicine at UC Health and a fellow of the American Academy of Family Physicians.

When asked if he’s seeing more uncertainty about boosters, community pharmacist Brian Caswell, RPh, said: “I’m going to have to say yes because I’ve been confused myself at times.”

“Yes, there is a lot of confusion,” added Mr. Caswell, owner or co-owner of four pharmacies in Kansas and Missouri and president of the National Community Pharmacists Association. 
 

Boosting misinformation?

“Unfortunately, confusion leads to an acceleration of misinformation,” Mr. Caswell said.

Dr. Edje shared an example. “The folks who have been hesitant to even get the first vaccine appear now a little less likely to want to go ahead and get vaccinated.”

These patients point to breakthrough COVID-19 cases of the Delta variant, which “reinforces that they don’t need to get vaccinated in the first place,” Dr. Edje said.

“That’s unfortunate because it’s a complete fallacy.”

Clearer communication from the federal government could help alleviate confusion, Mr. Caswell said. “I would like to see an official CDC chart that states who is eligible as of a certain date. Something that is accessible through their webpage or a social media source that can be updated. That would help all of us.”

“For myself, I’ve got patients from Kansas, Oklahoma, and Missouri that might be operating under different guidelines. That makes it even more confusing,” he said.

More clarity is needed for individuals seeking boosters as well. “It would help to be very clear with the general public, who are becoming very knowledgeable within this vaccine realm,” Mr. Caswell said.
 

‘Gaming the system’

Although most people seeking a booster shot at one of Caswell’s pharmacies are following official recommendations, there are some who remain ineligible but nonetheless come in for an additional vaccine.

“Even before this announcement last Friday, in the latter part of August when the CDC talked about a booster for immunocompromised, we had interest from people who did not meet the criteria,” Mr. Caswell said.

To the ineligible, he and his staff explain the approval process, why certain decisions are made, and point out that the number of eligible Americans is likely to expand in the future.

“The vast majority of them are understanding,” Mr. Caswell said. “But we’ve had some people who really didn’t want to accept the information, and I don’t know what they’ve done.”

“Some people are gaming the system to get their booster or second shot of J&J,” he said.

For example, Mr. Caswell had a patient who crossed over state lines from Missouri seeking a vaccine booster at Wolkar Drug, a pharmacy in Baxter Springs, Kan. “We found out later he had a J&J shot at a facility or provider in Missouri. He came over to Kansas, signed up for it and got a booster with Moderna.”

“We called and asked him if he was aware of it. He said, ‘yes.’ When we questioned him more about it, he hung up.”

Dr. Edje is likewise seeing interest from some ineligible patients, she said.
 

Crossing a liability line?

Mr. Caswell has asked for advice from lawyers and the State Board of Pharmacy on potential liability if a pharmacist gives a booster to a patient not eligible under the official FDA and CDC guidance.

“We ask patients direct questions about whether they’ve had the COVID vaccine, COVID, and a whole litany of questions they must answer. And we’re assuming they are going to be honest and forthright,” he said. “The pharmacist needs to make sure they make every effort to get that information from the patient.”

Normally, healthcare providers like Mr. Caswell report each COVID-19 vaccination to the state registry after administration. “We have not gone through a police action and checked the registry first,” he said.

But, if people continue to try ‘gaming the system,’ he said, he might have to start checking the state registry before giving someone a booster.

The American Academy of Family Physicians offers advice from the CDC about legal protections for providers.

“As outlined by CDC, any off-label use of the Comirnaty/Pfizer-BioNTech COVID-19 vaccine is not authorized at this time and may not be covered under the PREP Act or the PREP Act declaration. This means that clinicians providing the vaccine outside of the authorized/approved use may not have immunity from claims,” the AAFP website states.

“Per CDC, individuals who receive a third dose may not be eligible for compensation after a possible adverse event. Such use would be in violation of the CDC COVID-19 vaccination program provider agreement and therefore may not be reimbursable and may impact the ability of a provider to remain in the CDC program, in addition to other potential sanctions. Administration fees for off-label doses may not be reimbursed by payers.”
 

Despite confusion, demand is up

Even amid all the uncertainty, there appears to be a jump in enthusiasm for the booster shots.

“The requests have gone up quite a bit. We’ve seen a number of requests from people in person and over the phone looking to get a booster,” Mr. Caswell said. “Since the discussion at the federal level...there has been a lot of interest in the third shot booster, itself, as well as about a booster for J&J.”

“There is quite a bit of excitement out there,” he said.

Dr. Edje agreed: “I take care of a fair number of folks...including the elderly and healthcare professionals. They are already asking for the booster.”

Interestingly, Dr. Edje would like to get a booster herself but is not eligible for the Pfizer third shot. She is a participant in a Moderna vaccine trial and can only receive additional immunization as part of the study.
 

‘Walk, don’t run’

To quell any potential early rush to get a third shot, U.S. health officials are reminding booster-ineligible people that they still have some protection against COVID-19.

“If you’re a person who ultimately might get a booster that will make you optimally protected, you don’t necessarily need to get it tomorrow,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases told CNN.

CDC Director Rochelle Walensky, MD, also weighed in. She told ABC that boosters for people who received a Moderna or Johnson & Johnson vaccine will be addressed with urgency.

“I want to reiterate that this is a very slow wane. There is no urgency here to go and get your booster immediately. You know, walk don’t run to your booster appointment,” she said.

“We will come and look at the data for Moderna and J&J in very short order.”

Dr. Edje and Mr. Caswell have reported no relevant financial relationships.

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

Many people are confused — patients and healthcare providers alike — in the wake of the U.S. Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC) announcements about who is authorized to get a third or ‘booster’ shot of the Pfizer/BioNTech COVID-19 vaccine.

The official word on boosters from the CDC in the early morning hours of September 24 sparked a jump in people calling about or coming in for a third shot, healthcare providers report. At the same time, the uncertainty from changing federal messages about boosters is causing some chaos, especially in the form of vaccine misinformation.

The confusion started, in part, with the August 13 announcement that immunocompromised Americans were eligible for a booster shot. Next came the initial Biden administration intention to provide most U.S. adults with a third shot starting September 20 — an announcement later rolled back — followed by the Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC) limiting boosters to select groups last week.

“It was only 3% of the population that was going to be getting a third dose, then it was back to everyone being able to get the booster, and then it’s back to a select crew,” Louito Edje, MD, a family physician in private practice in Cincinnati, said in an interview with this news organization.

This kind of mixed messaging is generating more questions than answers.  

“Even though that is following the science, translating the science into policy, it’s really fraught with confusion for patients, especially,” added Dr. Edje, professor educator in the departments of medical education and family and community medicine at UC Health and a fellow of the American Academy of Family Physicians.

When asked if he’s seeing more uncertainty about boosters, community pharmacist Brian Caswell, RPh, said: “I’m going to have to say yes because I’ve been confused myself at times.”

“Yes, there is a lot of confusion,” added Mr. Caswell, owner or co-owner of four pharmacies in Kansas and Missouri and president of the National Community Pharmacists Association. 
 

Boosting misinformation?

“Unfortunately, confusion leads to an acceleration of misinformation,” Mr. Caswell said.

Dr. Edje shared an example. “The folks who have been hesitant to even get the first vaccine appear now a little less likely to want to go ahead and get vaccinated.”

These patients point to breakthrough COVID-19 cases of the Delta variant, which “reinforces that they don’t need to get vaccinated in the first place,” Dr. Edje said.

“That’s unfortunate because it’s a complete fallacy.”

Clearer communication from the federal government could help alleviate confusion, Mr. Caswell said. “I would like to see an official CDC chart that states who is eligible as of a certain date. Something that is accessible through their webpage or a social media source that can be updated. That would help all of us.”

“For myself, I’ve got patients from Kansas, Oklahoma, and Missouri that might be operating under different guidelines. That makes it even more confusing,” he said.

More clarity is needed for individuals seeking boosters as well. “It would help to be very clear with the general public, who are becoming very knowledgeable within this vaccine realm,” Mr. Caswell said.
 

‘Gaming the system’

Although most people seeking a booster shot at one of Caswell’s pharmacies are following official recommendations, there are some who remain ineligible but nonetheless come in for an additional vaccine.

“Even before this announcement last Friday, in the latter part of August when the CDC talked about a booster for immunocompromised, we had interest from people who did not meet the criteria,” Mr. Caswell said.

To the ineligible, he and his staff explain the approval process, why certain decisions are made, and point out that the number of eligible Americans is likely to expand in the future.

“The vast majority of them are understanding,” Mr. Caswell said. “But we’ve had some people who really didn’t want to accept the information, and I don’t know what they’ve done.”

“Some people are gaming the system to get their booster or second shot of J&J,” he said.

For example, Mr. Caswell had a patient who crossed over state lines from Missouri seeking a vaccine booster at Wolkar Drug, a pharmacy in Baxter Springs, Kan. “We found out later he had a J&J shot at a facility or provider in Missouri. He came over to Kansas, signed up for it and got a booster with Moderna.”

“We called and asked him if he was aware of it. He said, ‘yes.’ When we questioned him more about it, he hung up.”

Dr. Edje is likewise seeing interest from some ineligible patients, she said.
 

Crossing a liability line?

Mr. Caswell has asked for advice from lawyers and the State Board of Pharmacy on potential liability if a pharmacist gives a booster to a patient not eligible under the official FDA and CDC guidance.

“We ask patients direct questions about whether they’ve had the COVID vaccine, COVID, and a whole litany of questions they must answer. And we’re assuming they are going to be honest and forthright,” he said. “The pharmacist needs to make sure they make every effort to get that information from the patient.”

Normally, healthcare providers like Mr. Caswell report each COVID-19 vaccination to the state registry after administration. “We have not gone through a police action and checked the registry first,” he said.

But, if people continue to try ‘gaming the system,’ he said, he might have to start checking the state registry before giving someone a booster.

The American Academy of Family Physicians offers advice from the CDC about legal protections for providers.

“As outlined by CDC, any off-label use of the Comirnaty/Pfizer-BioNTech COVID-19 vaccine is not authorized at this time and may not be covered under the PREP Act or the PREP Act declaration. This means that clinicians providing the vaccine outside of the authorized/approved use may not have immunity from claims,” the AAFP website states.

“Per CDC, individuals who receive a third dose may not be eligible for compensation after a possible adverse event. Such use would be in violation of the CDC COVID-19 vaccination program provider agreement and therefore may not be reimbursable and may impact the ability of a provider to remain in the CDC program, in addition to other potential sanctions. Administration fees for off-label doses may not be reimbursed by payers.”
 

Despite confusion, demand is up

Even amid all the uncertainty, there appears to be a jump in enthusiasm for the booster shots.

“The requests have gone up quite a bit. We’ve seen a number of requests from people in person and over the phone looking to get a booster,” Mr. Caswell said. “Since the discussion at the federal level...there has been a lot of interest in the third shot booster, itself, as well as about a booster for J&J.”

“There is quite a bit of excitement out there,” he said.

Dr. Edje agreed: “I take care of a fair number of folks...including the elderly and healthcare professionals. They are already asking for the booster.”

Interestingly, Dr. Edje would like to get a booster herself but is not eligible for the Pfizer third shot. She is a participant in a Moderna vaccine trial and can only receive additional immunization as part of the study.
 

‘Walk, don’t run’

To quell any potential early rush to get a third shot, U.S. health officials are reminding booster-ineligible people that they still have some protection against COVID-19.

“If you’re a person who ultimately might get a booster that will make you optimally protected, you don’t necessarily need to get it tomorrow,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases told CNN.

CDC Director Rochelle Walensky, MD, also weighed in. She told ABC that boosters for people who received a Moderna or Johnson & Johnson vaccine will be addressed with urgency.

“I want to reiterate that this is a very slow wane. There is no urgency here to go and get your booster immediately. You know, walk don’t run to your booster appointment,” she said.

“We will come and look at the data for Moderna and J&J in very short order.”

Dr. Edje and Mr. Caswell have reported no relevant financial relationships.

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

Many people are confused — patients and healthcare providers alike — in the wake of the U.S. Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC) announcements about who is authorized to get a third or ‘booster’ shot of the Pfizer/BioNTech COVID-19 vaccine.

The official word on boosters from the CDC in the early morning hours of September 24 sparked a jump in people calling about or coming in for a third shot, healthcare providers report. At the same time, the uncertainty from changing federal messages about boosters is causing some chaos, especially in the form of vaccine misinformation.

The confusion started, in part, with the August 13 announcement that immunocompromised Americans were eligible for a booster shot. Next came the initial Biden administration intention to provide most U.S. adults with a third shot starting September 20 — an announcement later rolled back — followed by the Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC) limiting boosters to select groups last week.

“It was only 3% of the population that was going to be getting a third dose, then it was back to everyone being able to get the booster, and then it’s back to a select crew,” Louito Edje, MD, a family physician in private practice in Cincinnati, said in an interview with this news organization.

This kind of mixed messaging is generating more questions than answers.  

“Even though that is following the science, translating the science into policy, it’s really fraught with confusion for patients, especially,” added Dr. Edje, professor educator in the departments of medical education and family and community medicine at UC Health and a fellow of the American Academy of Family Physicians.

When asked if he’s seeing more uncertainty about boosters, community pharmacist Brian Caswell, RPh, said: “I’m going to have to say yes because I’ve been confused myself at times.”

“Yes, there is a lot of confusion,” added Mr. Caswell, owner or co-owner of four pharmacies in Kansas and Missouri and president of the National Community Pharmacists Association. 
 

Boosting misinformation?

“Unfortunately, confusion leads to an acceleration of misinformation,” Mr. Caswell said.

Dr. Edje shared an example. “The folks who have been hesitant to even get the first vaccine appear now a little less likely to want to go ahead and get vaccinated.”

These patients point to breakthrough COVID-19 cases of the Delta variant, which “reinforces that they don’t need to get vaccinated in the first place,” Dr. Edje said.

“That’s unfortunate because it’s a complete fallacy.”

Clearer communication from the federal government could help alleviate confusion, Mr. Caswell said. “I would like to see an official CDC chart that states who is eligible as of a certain date. Something that is accessible through their webpage or a social media source that can be updated. That would help all of us.”

“For myself, I’ve got patients from Kansas, Oklahoma, and Missouri that might be operating under different guidelines. That makes it even more confusing,” he said.

More clarity is needed for individuals seeking boosters as well. “It would help to be very clear with the general public, who are becoming very knowledgeable within this vaccine realm,” Mr. Caswell said.
 

‘Gaming the system’

Although most people seeking a booster shot at one of Caswell’s pharmacies are following official recommendations, there are some who remain ineligible but nonetheless come in for an additional vaccine.

“Even before this announcement last Friday, in the latter part of August when the CDC talked about a booster for immunocompromised, we had interest from people who did not meet the criteria,” Mr. Caswell said.

To the ineligible, he and his staff explain the approval process, why certain decisions are made, and point out that the number of eligible Americans is likely to expand in the future.

“The vast majority of them are understanding,” Mr. Caswell said. “But we’ve had some people who really didn’t want to accept the information, and I don’t know what they’ve done.”

“Some people are gaming the system to get their booster or second shot of J&J,” he said.

For example, Mr. Caswell had a patient who crossed over state lines from Missouri seeking a vaccine booster at Wolkar Drug, a pharmacy in Baxter Springs, Kan. “We found out later he had a J&J shot at a facility or provider in Missouri. He came over to Kansas, signed up for it and got a booster with Moderna.”

“We called and asked him if he was aware of it. He said, ‘yes.’ When we questioned him more about it, he hung up.”

Dr. Edje is likewise seeing interest from some ineligible patients, she said.
 

Crossing a liability line?

Mr. Caswell has asked for advice from lawyers and the State Board of Pharmacy on potential liability if a pharmacist gives a booster to a patient not eligible under the official FDA and CDC guidance.

“We ask patients direct questions about whether they’ve had the COVID vaccine, COVID, and a whole litany of questions they must answer. And we’re assuming they are going to be honest and forthright,” he said. “The pharmacist needs to make sure they make every effort to get that information from the patient.”

Normally, healthcare providers like Mr. Caswell report each COVID-19 vaccination to the state registry after administration. “We have not gone through a police action and checked the registry first,” he said.

But, if people continue to try ‘gaming the system,’ he said, he might have to start checking the state registry before giving someone a booster.

The American Academy of Family Physicians offers advice from the CDC about legal protections for providers.

“As outlined by CDC, any off-label use of the Comirnaty/Pfizer-BioNTech COVID-19 vaccine is not authorized at this time and may not be covered under the PREP Act or the PREP Act declaration. This means that clinicians providing the vaccine outside of the authorized/approved use may not have immunity from claims,” the AAFP website states.

“Per CDC, individuals who receive a third dose may not be eligible for compensation after a possible adverse event. Such use would be in violation of the CDC COVID-19 vaccination program provider agreement and therefore may not be reimbursable and may impact the ability of a provider to remain in the CDC program, in addition to other potential sanctions. Administration fees for off-label doses may not be reimbursed by payers.”
 

Despite confusion, demand is up

Even amid all the uncertainty, there appears to be a jump in enthusiasm for the booster shots.

“The requests have gone up quite a bit. We’ve seen a number of requests from people in person and over the phone looking to get a booster,” Mr. Caswell said. “Since the discussion at the federal level...there has been a lot of interest in the third shot booster, itself, as well as about a booster for J&J.”

“There is quite a bit of excitement out there,” he said.

Dr. Edje agreed: “I take care of a fair number of folks...including the elderly and healthcare professionals. They are already asking for the booster.”

Interestingly, Dr. Edje would like to get a booster herself but is not eligible for the Pfizer third shot. She is a participant in a Moderna vaccine trial and can only receive additional immunization as part of the study.
 

‘Walk, don’t run’

To quell any potential early rush to get a third shot, U.S. health officials are reminding booster-ineligible people that they still have some protection against COVID-19.

“If you’re a person who ultimately might get a booster that will make you optimally protected, you don’t necessarily need to get it tomorrow,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases told CNN.

CDC Director Rochelle Walensky, MD, also weighed in. She told ABC that boosters for people who received a Moderna or Johnson & Johnson vaccine will be addressed with urgency.

“I want to reiterate that this is a very slow wane. There is no urgency here to go and get your booster immediately. You know, walk don’t run to your booster appointment,” she said.

“We will come and look at the data for Moderna and J&J in very short order.”

Dr. Edje and Mr. Caswell have reported no relevant financial relationships.

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

Decreased motor function, as well as other adverse outcomes, are linked to post–COVID-19 syndrome in patients with Parkinson’s disease, new research suggests.

Results from a small, international retrospective case study show that about half of participants with Parkinson’s disease who developed post–COVID-19 syndrome experienced a worsening of motor symptoms and that their need for anti-Parkinson’s medication increased.

“In our series of 27 patients with Parkinson’s disease, 85% developed post–COVID-19 symptoms,” said lead investigator Valentina Leta, MD, Parkinson’s Foundation Center of Excellence, Kings College Hospital, London.

The most common long-term effects were worsening of motor function and an increase in the need for daily levodopa. Other adverse effects included fatigue; cognitive disturbances, including brain fog, loss of concentration, and memory deficits; and sleep disturbances, such as insomnia, Dr. Leta said.

The findings were presented at the International Congress of Parkinson’s Disease and Movement Disorders.
 

Long-term sequelae

Previous studies have documented worsening of motor and nonmotor symptoms among patients with Parkinson’s disease in the acute phase of COVID-19. Results of these studies suggest that mortality may be higher among patients with more advanced Parkinson’s disease, comorbidities, and frailty.

Dr. Leta noted that long-term sequelae with so-called long COVID have not been adequately explored, prompting the current study.

The case series included 27 patients with Parkinson’s disease in the United Kingdom, Italy, Romania, and Mexico who were also affected by COVID-19. The investigators defined post–COVID-19 syndrome as “signs and symptoms that develop during or after an infection consistent with COVID-19, continue for more than 12 weeks, and are not explained by an alternative diagnosis.”

Because some of the symptoms are also associated with Parkinson’s disease, symptoms were attributed to post–COVID-19 only if they occurred after a confirmed severe acute respiratory infection with SARS-CoV-2 or if patients experienced an acute or subacute worsening of a pre-existing symptom that had previously been stable.

Among the participants, 59.3% were men. The mean age at the time of Parkinson’s disease diagnosis was 59.0 ± 12.7 years, and the mean Parkinson’s disease duration was 9.2 ± 7.8 years. The patients were in Hoehn and Yahr stage 2.0 ± 1.0 at the time of their COVID-19 diagnosis.

Charlson Comorbidity Index score at COVID-19 diagnosis was 2.0 ± 1.5, and the levodopa equivalent daily dose (LEDD) was 1053.5 ± 842.4 mg.
 

Symptom worsening

“Cognitive disturbances” were defined as brain fog, concentration difficulty, or memory problems. “Peripheral neuropathy symptoms” were defined as having feelings of pins and needles or numbness.

By far, the most prevalent sequelae were worsening motor symptoms and increased need for anti-Parkinson’s medications. Each affected about half of the study cohort, the investigators noted.

Dr. Leta added the non-Parkinson’s disease-specific findings are in line with the existing literature on long COVID in the general population. The severity of COVID-19, as indicated by a history of hospitalization, did not seem to correlate with development of post–COVID-19 syndrome in patients with Parkinson’s disease.

In this series, few patients had respiratory, cardiovascular, gastrointestinal, musculoskeletal, or dermatologic symptoms. Interestingly, only four patients reported a loss of taste or smell.

The investigators noted that in addition to viral illness, the stress of prolonged lockdown during the pandemic and reduced access to health care and rehabilitation programs may contribute to the burden of post–COVID-19 syndrome in patients with Parkinson’s disease.

Study limitations cited include the relatively small sample size and the lack of a control group. The researchers noted the need for larger studies to elucidate the natural history of COVID-19 among patients with Parkinson’s disease in order to raise awareness of their needs and to help develop personalized management strategies.
 

Meaningful addition

Commenting on the findings, Kyle Mitchell, MD, movement disorders neurologist, Duke University, Durham, N.C., said he found the study to be a meaningful addition in light of the fact that data on the challenges that patients with Parkinson’s disease may face after having COVID-19 are limited.

“What I liked about this study was there’s data from multiple countries, what looks like a diverse population of study participants, and really just addressing a question that we get asked a lot in clinic and we see a fair amount, but we don’t really know a lot about: how people with Parkinson’s disease will do during and post COVID-19 infection,” said Dr. Mitchell, who was not involved with the research.

He said the worsening of motor symptoms and the need for increased dopaminergic medication brought some questions to mind.

“Is this increase in medications permanent, or is it temporary until post-COVID resolves? Or is it truly something where they stay on a higher dose?” he asked.

Dr. Mitchell said he does not believe the worsening of symptoms is specific to COVID-19 and that he sees individuals with Parkinson’s disease who experience setbacks “from any number of infections.” These include urinary tract infections and influenza, which are associated with worsening mobility, rigidity, tremor, fatigue, and cognition.

“People with Parkinson’s disease seem to get hit harder by infections in general,” he said.

The study had no outside funding. Dr. Leta and Dr. Mitchell have disclosed no relevant financial relationships.

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

Decreased motor function, as well as other adverse outcomes, are linked to post–COVID-19 syndrome in patients with Parkinson’s disease, new research suggests.

Results from a small, international retrospective case study show that about half of participants with Parkinson’s disease who developed post–COVID-19 syndrome experienced a worsening of motor symptoms and that their need for anti-Parkinson’s medication increased.

“In our series of 27 patients with Parkinson’s disease, 85% developed post–COVID-19 symptoms,” said lead investigator Valentina Leta, MD, Parkinson’s Foundation Center of Excellence, Kings College Hospital, London.

The most common long-term effects were worsening of motor function and an increase in the need for daily levodopa. Other adverse effects included fatigue; cognitive disturbances, including brain fog, loss of concentration, and memory deficits; and sleep disturbances, such as insomnia, Dr. Leta said.

The findings were presented at the International Congress of Parkinson’s Disease and Movement Disorders.
 

Long-term sequelae

Previous studies have documented worsening of motor and nonmotor symptoms among patients with Parkinson’s disease in the acute phase of COVID-19. Results of these studies suggest that mortality may be higher among patients with more advanced Parkinson’s disease, comorbidities, and frailty.

Dr. Leta noted that long-term sequelae with so-called long COVID have not been adequately explored, prompting the current study.

The case series included 27 patients with Parkinson’s disease in the United Kingdom, Italy, Romania, and Mexico who were also affected by COVID-19. The investigators defined post–COVID-19 syndrome as “signs and symptoms that develop during or after an infection consistent with COVID-19, continue for more than 12 weeks, and are not explained by an alternative diagnosis.”

Because some of the symptoms are also associated with Parkinson’s disease, symptoms were attributed to post–COVID-19 only if they occurred after a confirmed severe acute respiratory infection with SARS-CoV-2 or if patients experienced an acute or subacute worsening of a pre-existing symptom that had previously been stable.

Among the participants, 59.3% were men. The mean age at the time of Parkinson’s disease diagnosis was 59.0 ± 12.7 years, and the mean Parkinson’s disease duration was 9.2 ± 7.8 years. The patients were in Hoehn and Yahr stage 2.0 ± 1.0 at the time of their COVID-19 diagnosis.

Charlson Comorbidity Index score at COVID-19 diagnosis was 2.0 ± 1.5, and the levodopa equivalent daily dose (LEDD) was 1053.5 ± 842.4 mg.
 

Symptom worsening

“Cognitive disturbances” were defined as brain fog, concentration difficulty, or memory problems. “Peripheral neuropathy symptoms” were defined as having feelings of pins and needles or numbness.

By far, the most prevalent sequelae were worsening motor symptoms and increased need for anti-Parkinson’s medications. Each affected about half of the study cohort, the investigators noted.

Dr. Leta added the non-Parkinson’s disease-specific findings are in line with the existing literature on long COVID in the general population. The severity of COVID-19, as indicated by a history of hospitalization, did not seem to correlate with development of post–COVID-19 syndrome in patients with Parkinson’s disease.

In this series, few patients had respiratory, cardiovascular, gastrointestinal, musculoskeletal, or dermatologic symptoms. Interestingly, only four patients reported a loss of taste or smell.

The investigators noted that in addition to viral illness, the stress of prolonged lockdown during the pandemic and reduced access to health care and rehabilitation programs may contribute to the burden of post–COVID-19 syndrome in patients with Parkinson’s disease.

Study limitations cited include the relatively small sample size and the lack of a control group. The researchers noted the need for larger studies to elucidate the natural history of COVID-19 among patients with Parkinson’s disease in order to raise awareness of their needs and to help develop personalized management strategies.
 

Meaningful addition

Commenting on the findings, Kyle Mitchell, MD, movement disorders neurologist, Duke University, Durham, N.C., said he found the study to be a meaningful addition in light of the fact that data on the challenges that patients with Parkinson’s disease may face after having COVID-19 are limited.

“What I liked about this study was there’s data from multiple countries, what looks like a diverse population of study participants, and really just addressing a question that we get asked a lot in clinic and we see a fair amount, but we don’t really know a lot about: how people with Parkinson’s disease will do during and post COVID-19 infection,” said Dr. Mitchell, who was not involved with the research.

He said the worsening of motor symptoms and the need for increased dopaminergic medication brought some questions to mind.

“Is this increase in medications permanent, or is it temporary until post-COVID resolves? Or is it truly something where they stay on a higher dose?” he asked.

Dr. Mitchell said he does not believe the worsening of symptoms is specific to COVID-19 and that he sees individuals with Parkinson’s disease who experience setbacks “from any number of infections.” These include urinary tract infections and influenza, which are associated with worsening mobility, rigidity, tremor, fatigue, and cognition.

“People with Parkinson’s disease seem to get hit harder by infections in general,” he said.

The study had no outside funding. Dr. Leta and Dr. Mitchell have disclosed no relevant financial relationships.

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

Decreased motor function, as well as other adverse outcomes, are linked to post–COVID-19 syndrome in patients with Parkinson’s disease, new research suggests.

Results from a small, international retrospective case study show that about half of participants with Parkinson’s disease who developed post–COVID-19 syndrome experienced a worsening of motor symptoms and that their need for anti-Parkinson’s medication increased.

“In our series of 27 patients with Parkinson’s disease, 85% developed post–COVID-19 symptoms,” said lead investigator Valentina Leta, MD, Parkinson’s Foundation Center of Excellence, Kings College Hospital, London.

The most common long-term effects were worsening of motor function and an increase in the need for daily levodopa. Other adverse effects included fatigue; cognitive disturbances, including brain fog, loss of concentration, and memory deficits; and sleep disturbances, such as insomnia, Dr. Leta said.

The findings were presented at the International Congress of Parkinson’s Disease and Movement Disorders.
 

Long-term sequelae

Previous studies have documented worsening of motor and nonmotor symptoms among patients with Parkinson’s disease in the acute phase of COVID-19. Results of these studies suggest that mortality may be higher among patients with more advanced Parkinson’s disease, comorbidities, and frailty.

Dr. Leta noted that long-term sequelae with so-called long COVID have not been adequately explored, prompting the current study.

The case series included 27 patients with Parkinson’s disease in the United Kingdom, Italy, Romania, and Mexico who were also affected by COVID-19. The investigators defined post–COVID-19 syndrome as “signs and symptoms that develop during or after an infection consistent with COVID-19, continue for more than 12 weeks, and are not explained by an alternative diagnosis.”

Because some of the symptoms are also associated with Parkinson’s disease, symptoms were attributed to post–COVID-19 only if they occurred after a confirmed severe acute respiratory infection with SARS-CoV-2 or if patients experienced an acute or subacute worsening of a pre-existing symptom that had previously been stable.

Among the participants, 59.3% were men. The mean age at the time of Parkinson’s disease diagnosis was 59.0 ± 12.7 years, and the mean Parkinson’s disease duration was 9.2 ± 7.8 years. The patients were in Hoehn and Yahr stage 2.0 ± 1.0 at the time of their COVID-19 diagnosis.

Charlson Comorbidity Index score at COVID-19 diagnosis was 2.0 ± 1.5, and the levodopa equivalent daily dose (LEDD) was 1053.5 ± 842.4 mg.
 

Symptom worsening

“Cognitive disturbances” were defined as brain fog, concentration difficulty, or memory problems. “Peripheral neuropathy symptoms” were defined as having feelings of pins and needles or numbness.

By far, the most prevalent sequelae were worsening motor symptoms and increased need for anti-Parkinson’s medications. Each affected about half of the study cohort, the investigators noted.

Dr. Leta added the non-Parkinson’s disease-specific findings are in line with the existing literature on long COVID in the general population. The severity of COVID-19, as indicated by a history of hospitalization, did not seem to correlate with development of post–COVID-19 syndrome in patients with Parkinson’s disease.

In this series, few patients had respiratory, cardiovascular, gastrointestinal, musculoskeletal, or dermatologic symptoms. Interestingly, only four patients reported a loss of taste or smell.

The investigators noted that in addition to viral illness, the stress of prolonged lockdown during the pandemic and reduced access to health care and rehabilitation programs may contribute to the burden of post–COVID-19 syndrome in patients with Parkinson’s disease.

Study limitations cited include the relatively small sample size and the lack of a control group. The researchers noted the need for larger studies to elucidate the natural history of COVID-19 among patients with Parkinson’s disease in order to raise awareness of their needs and to help develop personalized management strategies.
 

Meaningful addition

Commenting on the findings, Kyle Mitchell, MD, movement disorders neurologist, Duke University, Durham, N.C., said he found the study to be a meaningful addition in light of the fact that data on the challenges that patients with Parkinson’s disease may face after having COVID-19 are limited.

“What I liked about this study was there’s data from multiple countries, what looks like a diverse population of study participants, and really just addressing a question that we get asked a lot in clinic and we see a fair amount, but we don’t really know a lot about: how people with Parkinson’s disease will do during and post COVID-19 infection,” said Dr. Mitchell, who was not involved with the research.

He said the worsening of motor symptoms and the need for increased dopaminergic medication brought some questions to mind.

“Is this increase in medications permanent, or is it temporary until post-COVID resolves? Or is it truly something where they stay on a higher dose?” he asked.

Dr. Mitchell said he does not believe the worsening of symptoms is specific to COVID-19 and that he sees individuals with Parkinson’s disease who experience setbacks “from any number of infections.” These include urinary tract infections and influenza, which are associated with worsening mobility, rigidity, tremor, fatigue, and cognition.

“People with Parkinson’s disease seem to get hit harder by infections in general,” he said.

The study had no outside funding. Dr. Leta and Dr. Mitchell have disclosed no relevant financial relationships.

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

Antipsychotics are not responsible for the increased COVID-related death rate among patients with serious mental illness (SMI), new research shows.

The significant increase in COVID-19 mortality that continues to be reported among those with schizophrenia and schizoaffective disorder “underscores the importance of protective interventions for this group, including priority vaccination,” study investigator Katlyn Nemani, MD, research assistant professor, department of psychiatry, New York University, told this news organization.

The study was published online September 22 in JAMA Psychiatry.
 

Threefold increase in death

Previous research has linked a diagnosis of a schizophrenia spectrum disorder, which includes schizophrenia and schizoaffective disorder, to an almost threefold increase in mortality among patients with COVID-19.

Some population-based research has also reported a link between antipsychotic medication use and increased risk for COVID-related mortality, but these studies did not take psychiatric diagnoses into account.

“This raised the question of whether the increased risk observed in this population is related to underlying psychiatric illness or its treatment,” said Dr. Nemani.

The retrospective cohort study included 464 adults (mean age, 53 years) who were diagnosed with COVID-19 between March 3, 2020, and Feb. 17, 2021, and who had previously been diagnosed with schizophrenia spectrum disorder or bipolar disorder. Of these, 42.2% were treated with an antipsychotic medication.

The primary endpoint was death within 60 days of COVID-19 diagnosis. Covariates included sociodemographic characteristics, such as patient-reported race and ethnicity, age, and insurance type, a psychiatric diagnosis, medical comorbidities, and smoking status.

Of the total, 41 patients (8.8%) died. The 60-day fatality rate was 13.7% among patients with a schizophrenia spectrum disorder (n = 182) and 5.7% among patients with bipolar disorder (n = 282).

Antipsychotic treatment was not significantly associated with mortality (odds ratio, 1.00; 95% confidence interval, 0.48-2.08; P = .99).

“This suggests that antipsychotic medication is unlikely to be responsible for the increased risk we’ve observed in this population, although this finding needs to be replicated,” said Dr. Nemani.
 

Surprise finding

A diagnosis of a schizophrenia spectrum disorder was associated with an almost threefold increased risk for mortality compared with bipolar disorder (OR, 2.88; 95% CI, 1.36-6.11; P = .006).

“This was a surprising finding,” said Dr. Nemani. “A possible explanation is differences in immune function associated with schizophrenia spectrum illness.”

She noted that there is evidence suggesting the immune system may play a role in the pathogenesis of schizophrenia, and research has shown that pneumonia and infection are among the leading causes of premature mortality in this population.

As well, several potential risk factors disproportionately affect people with serious mental illness, including an increase in the prevalence of medical comorbidities such as cardiovascular disease and diabetes, socioeconomic disadvantages, and barriers to accessing timely care. Prior studies have also found that people with SMI are less likely to receive preventive care interventions, including vaccination, said Dr. Nemani.

However, these factors are unlikely to fully account for the increased risk found in the study, she said.

“Our study population was limited to people who had received treatment within the NYU Langone Health System. We took a comprehensive list of sociodemographic and medical risk factors into account, and our research was conducted prior to the availability of COVID-19 vaccines,” she said.

Further research is necessary to understand what underlies the increase in susceptibility to severe infection among patients with schizophrenia and to identify interventions that may mitigate risk, said Dr. Nemani.

“This includes evaluating systems-level factors, such as access to preventive interventions and treatment, as well as investigating underlying immune mechanisms that may contribute to severe and fatal infection,” she said.

The researchers could not validate psychiatric diagnoses or capture deaths not documented in the electronic health record. In addition, the limited sample size precluded analysis of the use of individual antipsychotic medications, which may differ in their associated effects.

“It’s possible individual antipsychotic medications may be associated with harmful or protective effects,” said Dr. Nemani.

The authors have disclosed no relevant financial relationships.

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

Antipsychotics are not responsible for the increased COVID-related death rate among patients with serious mental illness (SMI), new research shows.

The significant increase in COVID-19 mortality that continues to be reported among those with schizophrenia and schizoaffective disorder “underscores the importance of protective interventions for this group, including priority vaccination,” study investigator Katlyn Nemani, MD, research assistant professor, department of psychiatry, New York University, told this news organization.

The study was published online September 22 in JAMA Psychiatry.
 

Threefold increase in death

Previous research has linked a diagnosis of a schizophrenia spectrum disorder, which includes schizophrenia and schizoaffective disorder, to an almost threefold increase in mortality among patients with COVID-19.

Some population-based research has also reported a link between antipsychotic medication use and increased risk for COVID-related mortality, but these studies did not take psychiatric diagnoses into account.

“This raised the question of whether the increased risk observed in this population is related to underlying psychiatric illness or its treatment,” said Dr. Nemani.

The retrospective cohort study included 464 adults (mean age, 53 years) who were diagnosed with COVID-19 between March 3, 2020, and Feb. 17, 2021, and who had previously been diagnosed with schizophrenia spectrum disorder or bipolar disorder. Of these, 42.2% were treated with an antipsychotic medication.

The primary endpoint was death within 60 days of COVID-19 diagnosis. Covariates included sociodemographic characteristics, such as patient-reported race and ethnicity, age, and insurance type, a psychiatric diagnosis, medical comorbidities, and smoking status.

Of the total, 41 patients (8.8%) died. The 60-day fatality rate was 13.7% among patients with a schizophrenia spectrum disorder (n = 182) and 5.7% among patients with bipolar disorder (n = 282).

Antipsychotic treatment was not significantly associated with mortality (odds ratio, 1.00; 95% confidence interval, 0.48-2.08; P = .99).

“This suggests that antipsychotic medication is unlikely to be responsible for the increased risk we’ve observed in this population, although this finding needs to be replicated,” said Dr. Nemani.
 

Surprise finding

A diagnosis of a schizophrenia spectrum disorder was associated with an almost threefold increased risk for mortality compared with bipolar disorder (OR, 2.88; 95% CI, 1.36-6.11; P = .006).

“This was a surprising finding,” said Dr. Nemani. “A possible explanation is differences in immune function associated with schizophrenia spectrum illness.”

She noted that there is evidence suggesting the immune system may play a role in the pathogenesis of schizophrenia, and research has shown that pneumonia and infection are among the leading causes of premature mortality in this population.

As well, several potential risk factors disproportionately affect people with serious mental illness, including an increase in the prevalence of medical comorbidities such as cardiovascular disease and diabetes, socioeconomic disadvantages, and barriers to accessing timely care. Prior studies have also found that people with SMI are less likely to receive preventive care interventions, including vaccination, said Dr. Nemani.

However, these factors are unlikely to fully account for the increased risk found in the study, she said.

“Our study population was limited to people who had received treatment within the NYU Langone Health System. We took a comprehensive list of sociodemographic and medical risk factors into account, and our research was conducted prior to the availability of COVID-19 vaccines,” she said.

Further research is necessary to understand what underlies the increase in susceptibility to severe infection among patients with schizophrenia and to identify interventions that may mitigate risk, said Dr. Nemani.

“This includes evaluating systems-level factors, such as access to preventive interventions and treatment, as well as investigating underlying immune mechanisms that may contribute to severe and fatal infection,” she said.

The researchers could not validate psychiatric diagnoses or capture deaths not documented in the electronic health record. In addition, the limited sample size precluded analysis of the use of individual antipsychotic medications, which may differ in their associated effects.

“It’s possible individual antipsychotic medications may be associated with harmful or protective effects,” said Dr. Nemani.

The authors have disclosed no relevant financial relationships.

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

Antipsychotics are not responsible for the increased COVID-related death rate among patients with serious mental illness (SMI), new research shows.

The significant increase in COVID-19 mortality that continues to be reported among those with schizophrenia and schizoaffective disorder “underscores the importance of protective interventions for this group, including priority vaccination,” study investigator Katlyn Nemani, MD, research assistant professor, department of psychiatry, New York University, told this news organization.

The study was published online September 22 in JAMA Psychiatry.
 

Threefold increase in death

Previous research has linked a diagnosis of a schizophrenia spectrum disorder, which includes schizophrenia and schizoaffective disorder, to an almost threefold increase in mortality among patients with COVID-19.

Some population-based research has also reported a link between antipsychotic medication use and increased risk for COVID-related mortality, but these studies did not take psychiatric diagnoses into account.

“This raised the question of whether the increased risk observed in this population is related to underlying psychiatric illness or its treatment,” said Dr. Nemani.

The retrospective cohort study included 464 adults (mean age, 53 years) who were diagnosed with COVID-19 between March 3, 2020, and Feb. 17, 2021, and who had previously been diagnosed with schizophrenia spectrum disorder or bipolar disorder. Of these, 42.2% were treated with an antipsychotic medication.

The primary endpoint was death within 60 days of COVID-19 diagnosis. Covariates included sociodemographic characteristics, such as patient-reported race and ethnicity, age, and insurance type, a psychiatric diagnosis, medical comorbidities, and smoking status.

Of the total, 41 patients (8.8%) died. The 60-day fatality rate was 13.7% among patients with a schizophrenia spectrum disorder (n = 182) and 5.7% among patients with bipolar disorder (n = 282).

Antipsychotic treatment was not significantly associated with mortality (odds ratio, 1.00; 95% confidence interval, 0.48-2.08; P = .99).

“This suggests that antipsychotic medication is unlikely to be responsible for the increased risk we’ve observed in this population, although this finding needs to be replicated,” said Dr. Nemani.
 

Surprise finding

A diagnosis of a schizophrenia spectrum disorder was associated with an almost threefold increased risk for mortality compared with bipolar disorder (OR, 2.88; 95% CI, 1.36-6.11; P = .006).

“This was a surprising finding,” said Dr. Nemani. “A possible explanation is differences in immune function associated with schizophrenia spectrum illness.”

She noted that there is evidence suggesting the immune system may play a role in the pathogenesis of schizophrenia, and research has shown that pneumonia and infection are among the leading causes of premature mortality in this population.

As well, several potential risk factors disproportionately affect people with serious mental illness, including an increase in the prevalence of medical comorbidities such as cardiovascular disease and diabetes, socioeconomic disadvantages, and barriers to accessing timely care. Prior studies have also found that people with SMI are less likely to receive preventive care interventions, including vaccination, said Dr. Nemani.

However, these factors are unlikely to fully account for the increased risk found in the study, she said.

“Our study population was limited to people who had received treatment within the NYU Langone Health System. We took a comprehensive list of sociodemographic and medical risk factors into account, and our research was conducted prior to the availability of COVID-19 vaccines,” she said.

Further research is necessary to understand what underlies the increase in susceptibility to severe infection among patients with schizophrenia and to identify interventions that may mitigate risk, said Dr. Nemani.

“This includes evaluating systems-level factors, such as access to preventive interventions and treatment, as well as investigating underlying immune mechanisms that may contribute to severe and fatal infection,” she said.

The researchers could not validate psychiatric diagnoses or capture deaths not documented in the electronic health record. In addition, the limited sample size precluded analysis of the use of individual antipsychotic medications, which may differ in their associated effects.

“It’s possible individual antipsychotic medications may be associated with harmful or protective effects,” said Dr. Nemani.

The authors have disclosed no relevant financial relationships.

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

COVID vaccination rates among pregnant people remain low, despite data that shows the vaccines can prevent the high risk of severe disease during pregnancy.

About 30% of pregnant people are vaccinated, according to the latest CDC data, with only 18% obtaining a dose during pregnancy. Health officials have been tracking the timing of vaccination before and during pregnancy.

The vaccination rates are even lower among pregnant Black people, CDC data shows. About 15% are fully vaccinated, compared with 25% of pregnant Hispanic and Latino people, 34% of pregnant White people, and 46% of pregnant Asian people.

“This puts them at severe risk of severe disease from COVID-19,” Rochelle Walensky, MD, the CDC director, said during a news briefing with the White House COVID-19 Response Team.

“We know that pregnant women are at increased risk of severe disease, of hospitalization and ventilation,” she said. “They’re also at increased risk for adverse events to their baby.”

Those who give birth while infected with COVID-19 had “significantly higher rates” of intensive care unit admission, intubation, ventilation, and death, according to a recent study published in JAMA Network Open.

Dr. Walensky said on Sept. 28 that studies show COVID-19 vaccines can be taken at any time while pregnant or breastfeeding. She noted that the vaccines are safe for both mothers and their babies.

“We’ve actually seen that some antibody from the vaccine traverses [the placenta] to the baby and, in fact, could potentially protect the baby,” she said.

Public health officials say the low vaccination rates can be attributed to caution around the time of pregnancy, concern for the baby, barriers to health care, and misinformation promoted online.

“Pregnancy is a precious time. It’s also a time that a lot of women have fear,” Pam Oliver, MD, an obstetrics and gynecology doctor and executive vice president of North Carolina’s Novant Health, told USA Today.

“It is natural to have questions,” she said. “So, let’s talk about what we know, let’s put it in perspective.”

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

COVID vaccination rates among pregnant people remain low, despite data that shows the vaccines can prevent the high risk of severe disease during pregnancy.

About 30% of pregnant people are vaccinated, according to the latest CDC data, with only 18% obtaining a dose during pregnancy. Health officials have been tracking the timing of vaccination before and during pregnancy.

The vaccination rates are even lower among pregnant Black people, CDC data shows. About 15% are fully vaccinated, compared with 25% of pregnant Hispanic and Latino people, 34% of pregnant White people, and 46% of pregnant Asian people.

“This puts them at severe risk of severe disease from COVID-19,” Rochelle Walensky, MD, the CDC director, said during a news briefing with the White House COVID-19 Response Team.

“We know that pregnant women are at increased risk of severe disease, of hospitalization and ventilation,” she said. “They’re also at increased risk for adverse events to their baby.”

Those who give birth while infected with COVID-19 had “significantly higher rates” of intensive care unit admission, intubation, ventilation, and death, according to a recent study published in JAMA Network Open.

Dr. Walensky said on Sept. 28 that studies show COVID-19 vaccines can be taken at any time while pregnant or breastfeeding. She noted that the vaccines are safe for both mothers and their babies.

“We’ve actually seen that some antibody from the vaccine traverses [the placenta] to the baby and, in fact, could potentially protect the baby,” she said.

Public health officials say the low vaccination rates can be attributed to caution around the time of pregnancy, concern for the baby, barriers to health care, and misinformation promoted online.

“Pregnancy is a precious time. It’s also a time that a lot of women have fear,” Pam Oliver, MD, an obstetrics and gynecology doctor and executive vice president of North Carolina’s Novant Health, told USA Today.

“It is natural to have questions,” she said. “So, let’s talk about what we know, let’s put it in perspective.”

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

COVID vaccination rates among pregnant people remain low, despite data that shows the vaccines can prevent the high risk of severe disease during pregnancy.

About 30% of pregnant people are vaccinated, according to the latest CDC data, with only 18% obtaining a dose during pregnancy. Health officials have been tracking the timing of vaccination before and during pregnancy.

The vaccination rates are even lower among pregnant Black people, CDC data shows. About 15% are fully vaccinated, compared with 25% of pregnant Hispanic and Latino people, 34% of pregnant White people, and 46% of pregnant Asian people.

“This puts them at severe risk of severe disease from COVID-19,” Rochelle Walensky, MD, the CDC director, said during a news briefing with the White House COVID-19 Response Team.

“We know that pregnant women are at increased risk of severe disease, of hospitalization and ventilation,” she said. “They’re also at increased risk for adverse events to their baby.”

Those who give birth while infected with COVID-19 had “significantly higher rates” of intensive care unit admission, intubation, ventilation, and death, according to a recent study published in JAMA Network Open.

Dr. Walensky said on Sept. 28 that studies show COVID-19 vaccines can be taken at any time while pregnant or breastfeeding. She noted that the vaccines are safe for both mothers and their babies.

“We’ve actually seen that some antibody from the vaccine traverses [the placenta] to the baby and, in fact, could potentially protect the baby,” she said.

Public health officials say the low vaccination rates can be attributed to caution around the time of pregnancy, concern for the baby, barriers to health care, and misinformation promoted online.

“Pregnancy is a precious time. It’s also a time that a lot of women have fear,” Pam Oliver, MD, an obstetrics and gynecology doctor and executive vice president of North Carolina’s Novant Health, told USA Today.

“It is natural to have questions,” she said. “So, let’s talk about what we know, let’s put it in perspective.”

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

Women who have taken hormone replacement therapy for menopausal symptoms will be relieved by findings from a large British case-control study reporting no overall increased risk of dementia as long as exposure is not long term.

Publishing results online Sept. 29 in BMJ, ( Yana Vinogradova, PhD, a senior research fellow at the University of Nottingham (England), and colleagues made this observation after conducting nested case-control studies involving more than 700,000 women in two U.K. primary care databases. The investigators undertook the study to clarify disparate findings over the past 2 decades on dementia risk associated with menopausal hormone replacement,

“The findings show that menopausal hormone therapy, or MHT, is generally safe for women who require it,” Dr. Vinogradova said in an interview. “A small risk association was found for future development of Alzheimer’s disease increasing with the length of menopausal hormone treatment.” This finding applied only to combined treatments of estrogen plus progestin and became measurable only after long-term use of 5 years or more. “These risk associations, only for long-term use of MHT, are in line with findings related to breast cancer risk,” she said.

The findings also align with previous biological speculations that estrogen combined with progestin may have a harmful effect on the aging brain, she added, “but we also cannot completely rule out other possible factors from our study. For example, some women who were in fact suffering from early signs of Alzheimer’s disease similar to menopausal symptoms may have continued with their menopausal therapy for longer than other women.”

Concerns about the risk of dementia with MHT date back to 2003 when data from the Women’s Health Initiative Memory Study showed that incidence of all-cause dementia doubled in women age 65 years and older after treatment with conjugated equine estrogens and medroxyprogesterone acetate for an average of 4 years. More recently, Finnish research has yielded conflicting data about risks.

The study

The investigators used two U.K. primary care databases (QResearch and CPRD) to analyze MHT prescriptions for 118,501 women age 55 and older diagnosed with dementia between 1998 and 2020 and 497,416 female controls matched by age and general practice, but with no record of dementia.

The cohort was older: mean age of cases was 83.5 years and mean duration of treatment was 16 years for an average age of 67.7 at first captured prescription, considerably later than when most women begin MHT. Relevant factors such as family history, smoking, alcohol consumption, preexisting conditions, and other prescribed drugs were taken into account.

Overall, 16,291 (14%) dementia cases and 68,726 (14%) controls had been exposed to MHT in the period up to 3 years before diagnosis.

After adjusting for potentially confounding factors, the researchers found no overall associations between hormone therapy and risk of dementia, regardless of hormone type, application, dose, or duration of treatment. Within the subgroup of women younger than 80 years who had been taking estrogen-only therapy for 10 years or more, a slightly decreased risk of dementia emerged: odds ratio, 0.85; 95% confidence interval, 0.76-0.94.

However, an analysis of dementia cases with a diagnosis specifically of Alzheimer’s disease showed a slight increase in risk associated with estrogen-progestin therapy. Increased risks of developing specifically Alzheimer’s disease emerged in those who had used combination therapy for 5-9 years (OR, 1.11; 95% CI, 1.04-1.20) and also for 10 years or more (OR, 1.19; 95% CI, 1.06-1.33). This risk rose gradually with each year of exposure, reaching an average 11% increased risk for use from 5-9 years and an average 19% for use 10 years or more – equivalent to, respectively, five and seven extra cases per 10,000 woman-years.

According to Jill M. Rabin, MD, a professor at the Feinstein Institutes for Medical Research and an ob.gyn. with Northwell Health in Manhasset, N.Y., the findings make sense for two reasons. “First, there are other health issues noted in women taking long-term combination hormonal therapy such as an increased risk of breast cancer,” she said in an interview. “Second, progesterone is recommended for women who have retained their uterus in order to counteract the potential effects of estrogen on the uterine lining causing possible overgrowth. There are systemic effects however of progesterone, as it counteracts estrogen, potentially decreasing its benefit on the neurological system.”

She added that this analysis is synchronous with other biological studies demonstrating possible neuroprotective effects of estrogen on the brain, especially among younger women. “The vascular system in the newly menopausal female is noted to have less endothelial and intimal thickening, better blood flow and oxygenation, and in general less vascular damage. Estrogen in these relatively younger, newly menopausal women may help to stabilize the vasculature as well as the neurologic system. On the other hand, estrogen therapy over the age of 80 may be delivered to a neurovasculature damaged with age and time, may be somewhat less beneficial.” Older women also have fewer estrogen receptors and, in general, other medical comorbidities.

According to the authors, the findings will be helpful to policy-makers, doctors, and patients when making choices about hormone therapy.

In an accompanying editorial, two U.S. researchers called the findings reassuring. Pauline M. Maki, PhD, of the University of Illinois at Chicago, and JoAnn E. Manson, MD, DrPH, of Brigham and Women’s Hospital, Harvard Medical School, and Harvard T.H. Chan School of Public Health in Boston, however, pointed out that the current study with its older cohort and older age at MHT initiation could not address the important issue of the “timing hypothesis” – namely, that earlier initiation of hormone therapy might confer greater protection against Alzheimer’s disease, compared with later use.

And while the current observations do not change the recommendation that MHT should not be used to prevent dementia, they are helpful for providers to put dementia findings in context for patients. “The primary indication for hormone therapy continues to be the treatment of vasomotor symptoms, and the current study should provide reassurance for women and their providers when treatment is prescribed for that reason,” they wrote.

This study was funded by the U.K. National Institute for Health Research School for Primary Care Research.

Coauthor Dr. Julia Hippisley-Cox is a director of QResearch, EMIS Health, which supplies the QResearch database used for this work, and is a founder and shareholder of ClinRisk., which produces software to implement clinical risk algorithms.

Women who have taken hormone replacement therapy for menopausal symptoms will be relieved by findings from a large British case-control study reporting no overall increased risk of dementia as long as exposure is not long term.

Publishing results online Sept. 29 in BMJ, ( Yana Vinogradova, PhD, a senior research fellow at the University of Nottingham (England), and colleagues made this observation after conducting nested case-control studies involving more than 700,000 women in two U.K. primary care databases. The investigators undertook the study to clarify disparate findings over the past 2 decades on dementia risk associated with menopausal hormone replacement,

“The findings show that menopausal hormone therapy, or MHT, is generally safe for women who require it,” Dr. Vinogradova said in an interview. “A small risk association was found for future development of Alzheimer’s disease increasing with the length of menopausal hormone treatment.” This finding applied only to combined treatments of estrogen plus progestin and became measurable only after long-term use of 5 years or more. “These risk associations, only for long-term use of MHT, are in line with findings related to breast cancer risk,” she said.

The findings also align with previous biological speculations that estrogen combined with progestin may have a harmful effect on the aging brain, she added, “but we also cannot completely rule out other possible factors from our study. For example, some women who were in fact suffering from early signs of Alzheimer’s disease similar to menopausal symptoms may have continued with their menopausal therapy for longer than other women.”

Concerns about the risk of dementia with MHT date back to 2003 when data from the Women’s Health Initiative Memory Study showed that incidence of all-cause dementia doubled in women age 65 years and older after treatment with conjugated equine estrogens and medroxyprogesterone acetate for an average of 4 years. More recently, Finnish research has yielded conflicting data about risks.

The study

The investigators used two U.K. primary care databases (QResearch and CPRD) to analyze MHT prescriptions for 118,501 women age 55 and older diagnosed with dementia between 1998 and 2020 and 497,416 female controls matched by age and general practice, but with no record of dementia.

The cohort was older: mean age of cases was 83.5 years and mean duration of treatment was 16 years for an average age of 67.7 at first captured prescription, considerably later than when most women begin MHT. Relevant factors such as family history, smoking, alcohol consumption, preexisting conditions, and other prescribed drugs were taken into account.

Overall, 16,291 (14%) dementia cases and 68,726 (14%) controls had been exposed to MHT in the period up to 3 years before diagnosis.

After adjusting for potentially confounding factors, the researchers found no overall associations between hormone therapy and risk of dementia, regardless of hormone type, application, dose, or duration of treatment. Within the subgroup of women younger than 80 years who had been taking estrogen-only therapy for 10 years or more, a slightly decreased risk of dementia emerged: odds ratio, 0.85; 95% confidence interval, 0.76-0.94.

However, an analysis of dementia cases with a diagnosis specifically of Alzheimer’s disease showed a slight increase in risk associated with estrogen-progestin therapy. Increased risks of developing specifically Alzheimer’s disease emerged in those who had used combination therapy for 5-9 years (OR, 1.11; 95% CI, 1.04-1.20) and also for 10 years or more (OR, 1.19; 95% CI, 1.06-1.33). This risk rose gradually with each year of exposure, reaching an average 11% increased risk for use from 5-9 years and an average 19% for use 10 years or more – equivalent to, respectively, five and seven extra cases per 10,000 woman-years.

According to Jill M. Rabin, MD, a professor at the Feinstein Institutes for Medical Research and an ob.gyn. with Northwell Health in Manhasset, N.Y., the findings make sense for two reasons. “First, there are other health issues noted in women taking long-term combination hormonal therapy such as an increased risk of breast cancer,” she said in an interview. “Second, progesterone is recommended for women who have retained their uterus in order to counteract the potential effects of estrogen on the uterine lining causing possible overgrowth. There are systemic effects however of progesterone, as it counteracts estrogen, potentially decreasing its benefit on the neurological system.”

She added that this analysis is synchronous with other biological studies demonstrating possible neuroprotective effects of estrogen on the brain, especially among younger women. “The vascular system in the newly menopausal female is noted to have less endothelial and intimal thickening, better blood flow and oxygenation, and in general less vascular damage. Estrogen in these relatively younger, newly menopausal women may help to stabilize the vasculature as well as the neurologic system. On the other hand, estrogen therapy over the age of 80 may be delivered to a neurovasculature damaged with age and time, may be somewhat less beneficial.” Older women also have fewer estrogen receptors and, in general, other medical comorbidities.

According to the authors, the findings will be helpful to policy-makers, doctors, and patients when making choices about hormone therapy.

In an accompanying editorial, two U.S. researchers called the findings reassuring. Pauline M. Maki, PhD, of the University of Illinois at Chicago, and JoAnn E. Manson, MD, DrPH, of Brigham and Women’s Hospital, Harvard Medical School, and Harvard T.H. Chan School of Public Health in Boston, however, pointed out that the current study with its older cohort and older age at MHT initiation could not address the important issue of the “timing hypothesis” – namely, that earlier initiation of hormone therapy might confer greater protection against Alzheimer’s disease, compared with later use.

And while the current observations do not change the recommendation that MHT should not be used to prevent dementia, they are helpful for providers to put dementia findings in context for patients. “The primary indication for hormone therapy continues to be the treatment of vasomotor symptoms, and the current study should provide reassurance for women and their providers when treatment is prescribed for that reason,” they wrote.

This study was funded by the U.K. National Institute for Health Research School for Primary Care Research.

Coauthor Dr. Julia Hippisley-Cox is a director of QResearch, EMIS Health, which supplies the QResearch database used for this work, and is a founder and shareholder of ClinRisk., which produces software to implement clinical risk algorithms.

Women who have taken hormone replacement therapy for menopausal symptoms will be relieved by findings from a large British case-control study reporting no overall increased risk of dementia as long as exposure is not long term.

Publishing results online Sept. 29 in BMJ, ( Yana Vinogradova, PhD, a senior research fellow at the University of Nottingham (England), and colleagues made this observation after conducting nested case-control studies involving more than 700,000 women in two U.K. primary care databases. The investigators undertook the study to clarify disparate findings over the past 2 decades on dementia risk associated with menopausal hormone replacement,

“The findings show that menopausal hormone therapy, or MHT, is generally safe for women who require it,” Dr. Vinogradova said in an interview. “A small risk association was found for future development of Alzheimer’s disease increasing with the length of menopausal hormone treatment.” This finding applied only to combined treatments of estrogen plus progestin and became measurable only after long-term use of 5 years or more. “These risk associations, only for long-term use of MHT, are in line with findings related to breast cancer risk,” she said.

The findings also align with previous biological speculations that estrogen combined with progestin may have a harmful effect on the aging brain, she added, “but we also cannot completely rule out other possible factors from our study. For example, some women who were in fact suffering from early signs of Alzheimer’s disease similar to menopausal symptoms may have continued with their menopausal therapy for longer than other women.”

Concerns about the risk of dementia with MHT date back to 2003 when data from the Women’s Health Initiative Memory Study showed that incidence of all-cause dementia doubled in women age 65 years and older after treatment with conjugated equine estrogens and medroxyprogesterone acetate for an average of 4 years. More recently, Finnish research has yielded conflicting data about risks.

The study

The investigators used two U.K. primary care databases (QResearch and CPRD) to analyze MHT prescriptions for 118,501 women age 55 and older diagnosed with dementia between 1998 and 2020 and 497,416 female controls matched by age and general practice, but with no record of dementia.

The cohort was older: mean age of cases was 83.5 years and mean duration of treatment was 16 years for an average age of 67.7 at first captured prescription, considerably later than when most women begin MHT. Relevant factors such as family history, smoking, alcohol consumption, preexisting conditions, and other prescribed drugs were taken into account.

Overall, 16,291 (14%) dementia cases and 68,726 (14%) controls had been exposed to MHT in the period up to 3 years before diagnosis.

After adjusting for potentially confounding factors, the researchers found no overall associations between hormone therapy and risk of dementia, regardless of hormone type, application, dose, or duration of treatment. Within the subgroup of women younger than 80 years who had been taking estrogen-only therapy for 10 years or more, a slightly decreased risk of dementia emerged: odds ratio, 0.85; 95% confidence interval, 0.76-0.94.

However, an analysis of dementia cases with a diagnosis specifically of Alzheimer’s disease showed a slight increase in risk associated with estrogen-progestin therapy. Increased risks of developing specifically Alzheimer’s disease emerged in those who had used combination therapy for 5-9 years (OR, 1.11; 95% CI, 1.04-1.20) and also for 10 years or more (OR, 1.19; 95% CI, 1.06-1.33). This risk rose gradually with each year of exposure, reaching an average 11% increased risk for use from 5-9 years and an average 19% for use 10 years or more – equivalent to, respectively, five and seven extra cases per 10,000 woman-years.

According to Jill M. Rabin, MD, a professor at the Feinstein Institutes for Medical Research and an ob.gyn. with Northwell Health in Manhasset, N.Y., the findings make sense for two reasons. “First, there are other health issues noted in women taking long-term combination hormonal therapy such as an increased risk of breast cancer,” she said in an interview. “Second, progesterone is recommended for women who have retained their uterus in order to counteract the potential effects of estrogen on the uterine lining causing possible overgrowth. There are systemic effects however of progesterone, as it counteracts estrogen, potentially decreasing its benefit on the neurological system.”

She added that this analysis is synchronous with other biological studies demonstrating possible neuroprotective effects of estrogen on the brain, especially among younger women. “The vascular system in the newly menopausal female is noted to have less endothelial and intimal thickening, better blood flow and oxygenation, and in general less vascular damage. Estrogen in these relatively younger, newly menopausal women may help to stabilize the vasculature as well as the neurologic system. On the other hand, estrogen therapy over the age of 80 may be delivered to a neurovasculature damaged with age and time, may be somewhat less beneficial.” Older women also have fewer estrogen receptors and, in general, other medical comorbidities.

According to the authors, the findings will be helpful to policy-makers, doctors, and patients when making choices about hormone therapy.

In an accompanying editorial, two U.S. researchers called the findings reassuring. Pauline M. Maki, PhD, of the University of Illinois at Chicago, and JoAnn E. Manson, MD, DrPH, of Brigham and Women’s Hospital, Harvard Medical School, and Harvard T.H. Chan School of Public Health in Boston, however, pointed out that the current study with its older cohort and older age at MHT initiation could not address the important issue of the “timing hypothesis” – namely, that earlier initiation of hormone therapy might confer greater protection against Alzheimer’s disease, compared with later use.

And while the current observations do not change the recommendation that MHT should not be used to prevent dementia, they are helpful for providers to put dementia findings in context for patients. “The primary indication for hormone therapy continues to be the treatment of vasomotor symptoms, and the current study should provide reassurance for women and their providers when treatment is prescribed for that reason,” they wrote.

This study was funded by the U.K. National Institute for Health Research School for Primary Care Research.

Coauthor Dr. Julia Hippisley-Cox is a director of QResearch, EMIS Health, which supplies the QResearch database used for this work, and is a founder and shareholder of ClinRisk., which produces software to implement clinical risk algorithms.

Both high C-reactive protein (CRP) and older age predict mortality from COVID-19 in patients with diabetes, new research suggests.

The data, from the retrospective ACCREDIT cohort study, were presented at the virtual annual meeting of the European Association for the Study of Diabetes (EASD 2021) by Daniel Kevin Llanera, MD.

The combination of older age and high levels of the inflammatory marker CRP were linked to a tripled risk for death by day 7 after hospitalization for COVID-19 among people with diabetes. But, in contrast to other studies, recent A1c and body mass index did not predict COVID-19 outcomes.

“Both of these variables are easily available upon admission to hospital,” Dr. Llanera, who now works at Imperial College, London, said in an EASD press release.

“This means we can easily identify patients early on in their hospital stay who will likely require more aggressive interventions to try and improve survival.”

“It makes sense that CRP and age are important,” said Simon Heller, MB BChir, DM, of the University of Sheffield, England. “It may be that diabetes alone overwhelmed the additional effects of obesity and A1c.

“Certainly in other studies, age was the overwhelming bad prognostic sign among people with diabetes, and perhaps long-term diabetes has effects on the immune system which we haven’t yet identified.”
 

Kidney disease in younger patients also linked to poorer outcomes

The study, conducted when Dr. Llanera worked for the Countess of Chester NHS Foundation Trust, involved 1,004 patients with diabetes admitted with COVID-19 to seven hospitals in northwest England from Jan. 1 through June 30, 2020. The patients were a mean age of 74.1 years, 60.7% were male, and 45% were in the most deprived quintile based on the U.K. government deprivation index. Overall, 56.2% had macrovascular complications and 49.6% had microvascular complications.

They had a median BMI of 27.6 kg/m², which is lower than that reported in previous studies and might explain the difference, Dr. Llanera noted.

The primary outcome, death within 7 days of admission, occurred in 24%. By day 30, 33% had died. These rates are higher than the rate found in previous studies, possibly because of greater socioeconomic deprivation and older age of the population, Dr. Llanera speculated.

A total of 7.5% of patients received intensive care by day 7 and 9.8% required intravenous insulin infusions.

On univariate analysis, insulin infusion was found to be protective, with those receiving it half as likely to die as those who didn’t need IV insulin (odds ratio [OR], 0.5).

In contrast, chronic kidney disease in people younger than 70 years increased the risk of death more than twofold (OR, 2.74), as did type 2 diabetes compared with other diabetes types (OR, 2.52).

As in previous studies, use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers were not associated with COVID-19 outcomes, nor was the presence of diabetes-related complications.

In multivariate analysis, CRP and age emerged as the most significant predictors of the primary outcome, with those deemed high risk by a logistic regression model having an OR of 3.44 for death by day 7 compared with those at lower risk based on the two factors.

Data for glycemic control during the time of hospitalization weren’t available for this study, Dr. Llanera said in response to a question.

“We didn’t look into glycemic control during admission, just at entry, so I can’t answer whether strict glucose control is of benefit. I think it’s worth exploring further whether the use of IV insulin may be of benefit.”

Dr. Llanera also pointed out that people with diabetic kidney disease are in a chronic proinflammatory state and have immune dysregulation, thus potentially hindering their ability to “fight off” the virus.

“In addition, ACE2 receptors are upregulated in the kidneys of patients with diabetic kidney disease. These are molecules that facilitate entry of SARS-CoV-2 into the cells. This may lead to direct attack of the kidneys by the virus, possibly leading to worse overall outcomes,” he said.

Dr. Llanera has reported no relevant financial relationships. Dr. Heller has reported serving as consultant or speaker for Novo Nordisk, Eli Lilly, Sanofi Aventis, Mannkind, Zealand, MSD, and Boehringer Ingelheim.

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

Both high C-reactive protein (CRP) and older age predict mortality from COVID-19 in patients with diabetes, new research suggests.

The data, from the retrospective ACCREDIT cohort study, were presented at the virtual annual meeting of the European Association for the Study of Diabetes (EASD 2021) by Daniel Kevin Llanera, MD.

The combination of older age and high levels of the inflammatory marker CRP were linked to a tripled risk for death by day 7 after hospitalization for COVID-19 among people with diabetes. But, in contrast to other studies, recent A1c and body mass index did not predict COVID-19 outcomes.

“Both of these variables are easily available upon admission to hospital,” Dr. Llanera, who now works at Imperial College, London, said in an EASD press release.

“This means we can easily identify patients early on in their hospital stay who will likely require more aggressive interventions to try and improve survival.”

“It makes sense that CRP and age are important,” said Simon Heller, MB BChir, DM, of the University of Sheffield, England. “It may be that diabetes alone overwhelmed the additional effects of obesity and A1c.

“Certainly in other studies, age was the overwhelming bad prognostic sign among people with diabetes, and perhaps long-term diabetes has effects on the immune system which we haven’t yet identified.”
 

Kidney disease in younger patients also linked to poorer outcomes

The study, conducted when Dr. Llanera worked for the Countess of Chester NHS Foundation Trust, involved 1,004 patients with diabetes admitted with COVID-19 to seven hospitals in northwest England from Jan. 1 through June 30, 2020. The patients were a mean age of 74.1 years, 60.7% were male, and 45% were in the most deprived quintile based on the U.K. government deprivation index. Overall, 56.2% had macrovascular complications and 49.6% had microvascular complications.

They had a median BMI of 27.6 kg/m², which is lower than that reported in previous studies and might explain the difference, Dr. Llanera noted.

The primary outcome, death within 7 days of admission, occurred in 24%. By day 30, 33% had died. These rates are higher than the rate found in previous studies, possibly because of greater socioeconomic deprivation and older age of the population, Dr. Llanera speculated.

A total of 7.5% of patients received intensive care by day 7 and 9.8% required intravenous insulin infusions.

On univariate analysis, insulin infusion was found to be protective, with those receiving it half as likely to die as those who didn’t need IV insulin (odds ratio [OR], 0.5).

In contrast, chronic kidney disease in people younger than 70 years increased the risk of death more than twofold (OR, 2.74), as did type 2 diabetes compared with other diabetes types (OR, 2.52).

As in previous studies, use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers were not associated with COVID-19 outcomes, nor was the presence of diabetes-related complications.

In multivariate analysis, CRP and age emerged as the most significant predictors of the primary outcome, with those deemed high risk by a logistic regression model having an OR of 3.44 for death by day 7 compared with those at lower risk based on the two factors.

Data for glycemic control during the time of hospitalization weren’t available for this study, Dr. Llanera said in response to a question.

“We didn’t look into glycemic control during admission, just at entry, so I can’t answer whether strict glucose control is of benefit. I think it’s worth exploring further whether the use of IV insulin may be of benefit.”

Dr. Llanera also pointed out that people with diabetic kidney disease are in a chronic proinflammatory state and have immune dysregulation, thus potentially hindering their ability to “fight off” the virus.

“In addition, ACE2 receptors are upregulated in the kidneys of patients with diabetic kidney disease. These are molecules that facilitate entry of SARS-CoV-2 into the cells. This may lead to direct attack of the kidneys by the virus, possibly leading to worse overall outcomes,” he said.

Dr. Llanera has reported no relevant financial relationships. Dr. Heller has reported serving as consultant or speaker for Novo Nordisk, Eli Lilly, Sanofi Aventis, Mannkind, Zealand, MSD, and Boehringer Ingelheim.

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

Both high C-reactive protein (CRP) and older age predict mortality from COVID-19 in patients with diabetes, new research suggests.

The data, from the retrospective ACCREDIT cohort study, were presented at the virtual annual meeting of the European Association for the Study of Diabetes (EASD 2021) by Daniel Kevin Llanera, MD.

The combination of older age and high levels of the inflammatory marker CRP were linked to a tripled risk for death by day 7 after hospitalization for COVID-19 among people with diabetes. But, in contrast to other studies, recent A1c and body mass index did not predict COVID-19 outcomes.

“Both of these variables are easily available upon admission to hospital,” Dr. Llanera, who now works at Imperial College, London, said in an EASD press release.

“This means we can easily identify patients early on in their hospital stay who will likely require more aggressive interventions to try and improve survival.”

“It makes sense that CRP and age are important,” said Simon Heller, MB BChir, DM, of the University of Sheffield, England. “It may be that diabetes alone overwhelmed the additional effects of obesity and A1c.

“Certainly in other studies, age was the overwhelming bad prognostic sign among people with diabetes, and perhaps long-term diabetes has effects on the immune system which we haven’t yet identified.”
 

Kidney disease in younger patients also linked to poorer outcomes

The study, conducted when Dr. Llanera worked for the Countess of Chester NHS Foundation Trust, involved 1,004 patients with diabetes admitted with COVID-19 to seven hospitals in northwest England from Jan. 1 through June 30, 2020. The patients were a mean age of 74.1 years, 60.7% were male, and 45% were in the most deprived quintile based on the U.K. government deprivation index. Overall, 56.2% had macrovascular complications and 49.6% had microvascular complications.

They had a median BMI of 27.6 kg/m², which is lower than that reported in previous studies and might explain the difference, Dr. Llanera noted.

The primary outcome, death within 7 days of admission, occurred in 24%. By day 30, 33% had died. These rates are higher than the rate found in previous studies, possibly because of greater socioeconomic deprivation and older age of the population, Dr. Llanera speculated.

A total of 7.5% of patients received intensive care by day 7 and 9.8% required intravenous insulin infusions.

On univariate analysis, insulin infusion was found to be protective, with those receiving it half as likely to die as those who didn’t need IV insulin (odds ratio [OR], 0.5).

In contrast, chronic kidney disease in people younger than 70 years increased the risk of death more than twofold (OR, 2.74), as did type 2 diabetes compared with other diabetes types (OR, 2.52).

As in previous studies, use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers were not associated with COVID-19 outcomes, nor was the presence of diabetes-related complications.

In multivariate analysis, CRP and age emerged as the most significant predictors of the primary outcome, with those deemed high risk by a logistic regression model having an OR of 3.44 for death by day 7 compared with those at lower risk based on the two factors.

Data for glycemic control during the time of hospitalization weren’t available for this study, Dr. Llanera said in response to a question.

“We didn’t look into glycemic control during admission, just at entry, so I can’t answer whether strict glucose control is of benefit. I think it’s worth exploring further whether the use of IV insulin may be of benefit.”

Dr. Llanera also pointed out that people with diabetic kidney disease are in a chronic proinflammatory state and have immune dysregulation, thus potentially hindering their ability to “fight off” the virus.

“In addition, ACE2 receptors are upregulated in the kidneys of patients with diabetic kidney disease. These are molecules that facilitate entry of SARS-CoV-2 into the cells. This may lead to direct attack of the kidneys by the virus, possibly leading to worse overall outcomes,” he said.

Dr. Llanera has reported no relevant financial relationships. Dr. Heller has reported serving as consultant or speaker for Novo Nordisk, Eli Lilly, Sanofi Aventis, Mannkind, Zealand, MSD, and Boehringer Ingelheim.

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