MDedge Psychiatry

The Pfizer COVID-19 vaccine was shown to be highly effective in a large trial, but clinicians will be waiting and watching for reactions and adverse events in their vaccinated patients.

A two-dose regimen of the BNT162b2 mRNA COVID-19 vaccine was found to be safe and 95% effective in preventing SARS-CoV-2 infection in persons aged 16 years and older, according to an ongoing phase 2/3 trial. Pfizer and BioNTech published safety and efficacy results from the landmark global phase 1/2/3 trial of their COVID-19 vaccine candidate in the New England Journal of Medicine .

“We previously reported phase 1 safety and immunogenicity results from clinical trials of the vaccine candidate BNT162b2,” lead author Fernando P. Polack, MD, of Vanderbilt University, Nashville, Tenn., and colleagues wrote. “This data set and [present] trial results are the basis for an application for emergency-use authorization,” they explained.
 

The BNT162b2 vaccine trial

Among 43,448 individuals aged 16 years and older, the efficacy, safety, and immunogenicity of the BNT162b2 vaccine candidate was evaluated in a continuous phase 1/2/3 study. Participants were randomly assigned (1:1) to receive two injections of either 30 mcg of BNT162b2 (n = 21,720) or saline placebo (n = 21,728) administered intramuscularly 21 days apart. The safety evaluation, where subjects were monitored 30 minutes post vaccination for acute reactions, was observer blinded.

Eligibility criteria included healthy individuals or those with stable chronic medical conditions, including viral hepatitis B and C, as well as human immunodeficiency virus. Persons with a diagnosis of an immunocompromising condition, those receiving immunosuppressive therapy, and individuals with a medical history of COVID-19 were excluded.

The first primary endpoint was efficacy of BNT162b2 against laboratory-confirmed COVID-19 with onset at least 7 days following the second dose. The primary safety endpoint was local and systemic reactions occurring within 7 days post injection of BNT162b2 or placebo.
 

Safety

“At the data cutoff date of Oct. 9, a total of 37,706 participants had a median of at least 2 months of safety data available after the second dose and contributed to the main safety data set,” the authors wrote.

Among these participants, 83% were White, 28% were Hispanic or Latinx, and 9% were Black or African American; 49% of subjects were female and the median age was 52 years, with 42% over aged 55 years.

Overall, BNT162b2 had a favorable safety profile. Mild to moderate pain at the injection site within 7 days after the injection was the most frequently reported local reaction (<1% across all age groups reported severe pain). Most local reactions resolved within 1-2 days and no grade 4 reactions were reported.

The investigators reported: “Fever (temperature, ≥38° C) was reported after the second dose by 16% of younger vaccine recipients and by 11% of older recipients. Only 0.2% of vaccine recipients and 0.1% of placebo recipients reported fever (temperature, 38.9-40° C) after the first dose, as compared with 0.8% and 0.1%, respectively, after the second dose.”

BNT162b2 recipients had more injection-site pain than those receiving the placebo. After the first and second doses, younger recipients (under 55 years) had more pain at the injection site (83 vs. 14 and 78 vs. 12 events, respectively), redness (5 vs. 1 and 6 vs. 1), and swelling (6 vs. 0 and 6 vs. 0), compared with placebo recipients.

The same trend was observed for patients aged over 55 years, with vaccine recipients reporting more pain at the injection site (71 vs. 9 and 66 vs. 8 events, respectively), redness (5 vs. 1 and 7 vs. 1), and swelling (7 vs. 1 and 7 vs. 1) than placebo recipients.

Pain was less common overall among vaccine recipients aged over 55 years (71% reported pain after the first dose; 66% post second dose) than among younger vaccine recipients (83% post first dose; 78% post second dose).

The most common systemic events following the second dose were fatigue and headache, which occurred in 59% and 52% of younger vaccine recipients and 51% and 39% of older vaccine recipients, respectively. But fatigue and headache were also reported by participants in the placebo group (23% and 24%, respectively, post second dose, among younger vaccine recipients; 17% and 14% among older recipients).

The incidence of serious adverse events was low and similar in the vaccine (0.6%) and placebo (0.5%) arms. Severe systemic events occurred in 2% or less of vaccine recipients following either dose, except for fatigue (3.8%) and headache (2.0%) post second dose. No deaths were considered to be vaccine or placebo related.

“The safety appears comparable to other vaccines, but the relatively short period of observation, 2 months, and the relatively small number of subjects who have received the vaccine (less than 30,000), compared to the hundreds of millions likely to ultimately receive the vaccine, precludes conclusions regarding the potential for rare long term adverse effects,” David L. Bowton, MD, FCCP, a pulmonologist and professor emeritus of critical care anesthesiology at Wake Forest University, Winston-Salem, N.C., said in an interview. “Clinicians should be aware of the risk of anaphylactic reactions and discuss it with their patients [who have] a history of these reactions.”
 

Efficacy

Among 36,523 subjects without evidence of existing or prior COVID-19 infection, 8 cases of COVID-19 with onset at least 7 days after the second dose were seen among vaccine recipients and 162 among placebo recipients, corresponding to 95.0% vaccine efficacy (95% credible interval, 90.3%-97.6%).

“Supplemental analyses indicated that vaccine efficacy among subgroups defined by age, sex, race, ethnicity, obesity, and presence of a coexisting condition was generally consistent with that observed in the overall population,” the authors wrote.

Between the first and second doses, 39 cases of COVID-19 were observed among BNT162b2 recipients and 82 cases among placebo recipients, corresponding to 52% vaccine efficacy during the 21-day interval (95% CI, 29.5%-68.4%) suggesting early protection may begin as soon as 12 days after the first injection.

“This is an incredible achievement given that an effective vaccine has never been developed and approved for use in such a short timeframe,” Dr. Bowton explained. “That the vaccine is highly effective in reducing the incidence of symptomatic COVID-19 seems incontrovertible.”

“This vaccine has shockingly amazing efficacy and is well tolerated, and the results are beyond even optimistic projections,” Douglas S. Paauw, MD, of the University of Washington, Seattle, said in an interview.
 

Questions remain

“It is not yet known if the vaccine prevents asymptomatic infections, with their attendant risk of contagion, as rates of seroconversion of trial participants against betacoronavirus nucleoproteins not included in the vaccine has not been reported,” Dr. Bowton commented.

“Common questions our patients will ask us remain unanswered for now, [including] how long will the protection last, is it safe in pregnant women, and does it prevent asymptomatic infection,” Dr. Paauw explained. “We do not know everything about longer term side effects, but the benefits of this vaccine appear to outweigh the risks of the vaccine.”

The researchers noted these and other limitations in their report, acknowledging that longer follow-up is needed to evaluate long-term safety of the vaccine.

This study was supported by BioNTech and Pfizer. Several authors disclosed financial relationships with Pfizer and other pharmaceutical companies outside the submitted work. Dr. Bowton and Dr. Paauw had no conflicts to disclose.

SOURCE: Polack FP et al. N Engl J Med. 2020 Dec 10. doi: 10.1056/NEJMoa2034577
 

The Pfizer COVID-19 vaccine was shown to be highly effective in a large trial, but clinicians will be waiting and watching for reactions and adverse events in their vaccinated patients.

A two-dose regimen of the BNT162b2 mRNA COVID-19 vaccine was found to be safe and 95% effective in preventing SARS-CoV-2 infection in persons aged 16 years and older, according to an ongoing phase 2/3 trial. Pfizer and BioNTech published safety and efficacy results from the landmark global phase 1/2/3 trial of their COVID-19 vaccine candidate in the New England Journal of Medicine .

“We previously reported phase 1 safety and immunogenicity results from clinical trials of the vaccine candidate BNT162b2,” lead author Fernando P. Polack, MD, of Vanderbilt University, Nashville, Tenn., and colleagues wrote. “This data set and [present] trial results are the basis for an application for emergency-use authorization,” they explained.
 

The BNT162b2 vaccine trial

Among 43,448 individuals aged 16 years and older, the efficacy, safety, and immunogenicity of the BNT162b2 vaccine candidate was evaluated in a continuous phase 1/2/3 study. Participants were randomly assigned (1:1) to receive two injections of either 30 mcg of BNT162b2 (n = 21,720) or saline placebo (n = 21,728) administered intramuscularly 21 days apart. The safety evaluation, where subjects were monitored 30 minutes post vaccination for acute reactions, was observer blinded.

Eligibility criteria included healthy individuals or those with stable chronic medical conditions, including viral hepatitis B and C, as well as human immunodeficiency virus. Persons with a diagnosis of an immunocompromising condition, those receiving immunosuppressive therapy, and individuals with a medical history of COVID-19 were excluded.

The first primary endpoint was efficacy of BNT162b2 against laboratory-confirmed COVID-19 with onset at least 7 days following the second dose. The primary safety endpoint was local and systemic reactions occurring within 7 days post injection of BNT162b2 or placebo.
 

Safety

“At the data cutoff date of Oct. 9, a total of 37,706 participants had a median of at least 2 months of safety data available after the second dose and contributed to the main safety data set,” the authors wrote.

Among these participants, 83% were White, 28% were Hispanic or Latinx, and 9% were Black or African American; 49% of subjects were female and the median age was 52 years, with 42% over aged 55 years.

Overall, BNT162b2 had a favorable safety profile. Mild to moderate pain at the injection site within 7 days after the injection was the most frequently reported local reaction (<1% across all age groups reported severe pain). Most local reactions resolved within 1-2 days and no grade 4 reactions were reported.

The investigators reported: “Fever (temperature, ≥38° C) was reported after the second dose by 16% of younger vaccine recipients and by 11% of older recipients. Only 0.2% of vaccine recipients and 0.1% of placebo recipients reported fever (temperature, 38.9-40° C) after the first dose, as compared with 0.8% and 0.1%, respectively, after the second dose.”

BNT162b2 recipients had more injection-site pain than those receiving the placebo. After the first and second doses, younger recipients (under 55 years) had more pain at the injection site (83 vs. 14 and 78 vs. 12 events, respectively), redness (5 vs. 1 and 6 vs. 1), and swelling (6 vs. 0 and 6 vs. 0), compared with placebo recipients.

The same trend was observed for patients aged over 55 years, with vaccine recipients reporting more pain at the injection site (71 vs. 9 and 66 vs. 8 events, respectively), redness (5 vs. 1 and 7 vs. 1), and swelling (7 vs. 1 and 7 vs. 1) than placebo recipients.

Pain was less common overall among vaccine recipients aged over 55 years (71% reported pain after the first dose; 66% post second dose) than among younger vaccine recipients (83% post first dose; 78% post second dose).

The most common systemic events following the second dose were fatigue and headache, which occurred in 59% and 52% of younger vaccine recipients and 51% and 39% of older vaccine recipients, respectively. But fatigue and headache were also reported by participants in the placebo group (23% and 24%, respectively, post second dose, among younger vaccine recipients; 17% and 14% among older recipients).

The incidence of serious adverse events was low and similar in the vaccine (0.6%) and placebo (0.5%) arms. Severe systemic events occurred in 2% or less of vaccine recipients following either dose, except for fatigue (3.8%) and headache (2.0%) post second dose. No deaths were considered to be vaccine or placebo related.

“The safety appears comparable to other vaccines, but the relatively short period of observation, 2 months, and the relatively small number of subjects who have received the vaccine (less than 30,000), compared to the hundreds of millions likely to ultimately receive the vaccine, precludes conclusions regarding the potential for rare long term adverse effects,” David L. Bowton, MD, FCCP, a pulmonologist and professor emeritus of critical care anesthesiology at Wake Forest University, Winston-Salem, N.C., said in an interview. “Clinicians should be aware of the risk of anaphylactic reactions and discuss it with their patients [who have] a history of these reactions.”
 

Efficacy

Among 36,523 subjects without evidence of existing or prior COVID-19 infection, 8 cases of COVID-19 with onset at least 7 days after the second dose were seen among vaccine recipients and 162 among placebo recipients, corresponding to 95.0% vaccine efficacy (95% credible interval, 90.3%-97.6%).

“Supplemental analyses indicated that vaccine efficacy among subgroups defined by age, sex, race, ethnicity, obesity, and presence of a coexisting condition was generally consistent with that observed in the overall population,” the authors wrote.

Between the first and second doses, 39 cases of COVID-19 were observed among BNT162b2 recipients and 82 cases among placebo recipients, corresponding to 52% vaccine efficacy during the 21-day interval (95% CI, 29.5%-68.4%) suggesting early protection may begin as soon as 12 days after the first injection.

“This is an incredible achievement given that an effective vaccine has never been developed and approved for use in such a short timeframe,” Dr. Bowton explained. “That the vaccine is highly effective in reducing the incidence of symptomatic COVID-19 seems incontrovertible.”

“This vaccine has shockingly amazing efficacy and is well tolerated, and the results are beyond even optimistic projections,” Douglas S. Paauw, MD, of the University of Washington, Seattle, said in an interview.
 

Questions remain

“It is not yet known if the vaccine prevents asymptomatic infections, with their attendant risk of contagion, as rates of seroconversion of trial participants against betacoronavirus nucleoproteins not included in the vaccine has not been reported,” Dr. Bowton commented.

“Common questions our patients will ask us remain unanswered for now, [including] how long will the protection last, is it safe in pregnant women, and does it prevent asymptomatic infection,” Dr. Paauw explained. “We do not know everything about longer term side effects, but the benefits of this vaccine appear to outweigh the risks of the vaccine.”

The researchers noted these and other limitations in their report, acknowledging that longer follow-up is needed to evaluate long-term safety of the vaccine.

This study was supported by BioNTech and Pfizer. Several authors disclosed financial relationships with Pfizer and other pharmaceutical companies outside the submitted work. Dr. Bowton and Dr. Paauw had no conflicts to disclose.

SOURCE: Polack FP et al. N Engl J Med. 2020 Dec 10. doi: 10.1056/NEJMoa2034577
 

The Pfizer COVID-19 vaccine was shown to be highly effective in a large trial, but clinicians will be waiting and watching for reactions and adverse events in their vaccinated patients.

A two-dose regimen of the BNT162b2 mRNA COVID-19 vaccine was found to be safe and 95% effective in preventing SARS-CoV-2 infection in persons aged 16 years and older, according to an ongoing phase 2/3 trial. Pfizer and BioNTech published safety and efficacy results from the landmark global phase 1/2/3 trial of their COVID-19 vaccine candidate in the New England Journal of Medicine .

“We previously reported phase 1 safety and immunogenicity results from clinical trials of the vaccine candidate BNT162b2,” lead author Fernando P. Polack, MD, of Vanderbilt University, Nashville, Tenn., and colleagues wrote. “This data set and [present] trial results are the basis for an application for emergency-use authorization,” they explained.
 

The BNT162b2 vaccine trial

Among 43,448 individuals aged 16 years and older, the efficacy, safety, and immunogenicity of the BNT162b2 vaccine candidate was evaluated in a continuous phase 1/2/3 study. Participants were randomly assigned (1:1) to receive two injections of either 30 mcg of BNT162b2 (n = 21,720) or saline placebo (n = 21,728) administered intramuscularly 21 days apart. The safety evaluation, where subjects were monitored 30 minutes post vaccination for acute reactions, was observer blinded.

Eligibility criteria included healthy individuals or those with stable chronic medical conditions, including viral hepatitis B and C, as well as human immunodeficiency virus. Persons with a diagnosis of an immunocompromising condition, those receiving immunosuppressive therapy, and individuals with a medical history of COVID-19 were excluded.

The first primary endpoint was efficacy of BNT162b2 against laboratory-confirmed COVID-19 with onset at least 7 days following the second dose. The primary safety endpoint was local and systemic reactions occurring within 7 days post injection of BNT162b2 or placebo.
 

Safety

“At the data cutoff date of Oct. 9, a total of 37,706 participants had a median of at least 2 months of safety data available after the second dose and contributed to the main safety data set,” the authors wrote.

Among these participants, 83% were White, 28% were Hispanic or Latinx, and 9% were Black or African American; 49% of subjects were female and the median age was 52 years, with 42% over aged 55 years.

Overall, BNT162b2 had a favorable safety profile. Mild to moderate pain at the injection site within 7 days after the injection was the most frequently reported local reaction (<1% across all age groups reported severe pain). Most local reactions resolved within 1-2 days and no grade 4 reactions were reported.

The investigators reported: “Fever (temperature, ≥38° C) was reported after the second dose by 16% of younger vaccine recipients and by 11% of older recipients. Only 0.2% of vaccine recipients and 0.1% of placebo recipients reported fever (temperature, 38.9-40° C) after the first dose, as compared with 0.8% and 0.1%, respectively, after the second dose.”

BNT162b2 recipients had more injection-site pain than those receiving the placebo. After the first and second doses, younger recipients (under 55 years) had more pain at the injection site (83 vs. 14 and 78 vs. 12 events, respectively), redness (5 vs. 1 and 6 vs. 1), and swelling (6 vs. 0 and 6 vs. 0), compared with placebo recipients.

The same trend was observed for patients aged over 55 years, with vaccine recipients reporting more pain at the injection site (71 vs. 9 and 66 vs. 8 events, respectively), redness (5 vs. 1 and 7 vs. 1), and swelling (7 vs. 1 and 7 vs. 1) than placebo recipients.

Pain was less common overall among vaccine recipients aged over 55 years (71% reported pain after the first dose; 66% post second dose) than among younger vaccine recipients (83% post first dose; 78% post second dose).

The most common systemic events following the second dose were fatigue and headache, which occurred in 59% and 52% of younger vaccine recipients and 51% and 39% of older vaccine recipients, respectively. But fatigue and headache were also reported by participants in the placebo group (23% and 24%, respectively, post second dose, among younger vaccine recipients; 17% and 14% among older recipients).

The incidence of serious adverse events was low and similar in the vaccine (0.6%) and placebo (0.5%) arms. Severe systemic events occurred in 2% or less of vaccine recipients following either dose, except for fatigue (3.8%) and headache (2.0%) post second dose. No deaths were considered to be vaccine or placebo related.

“The safety appears comparable to other vaccines, but the relatively short period of observation, 2 months, and the relatively small number of subjects who have received the vaccine (less than 30,000), compared to the hundreds of millions likely to ultimately receive the vaccine, precludes conclusions regarding the potential for rare long term adverse effects,” David L. Bowton, MD, FCCP, a pulmonologist and professor emeritus of critical care anesthesiology at Wake Forest University, Winston-Salem, N.C., said in an interview. “Clinicians should be aware of the risk of anaphylactic reactions and discuss it with their patients [who have] a history of these reactions.”
 

Efficacy

Among 36,523 subjects without evidence of existing or prior COVID-19 infection, 8 cases of COVID-19 with onset at least 7 days after the second dose were seen among vaccine recipients and 162 among placebo recipients, corresponding to 95.0% vaccine efficacy (95% credible interval, 90.3%-97.6%).

“Supplemental analyses indicated that vaccine efficacy among subgroups defined by age, sex, race, ethnicity, obesity, and presence of a coexisting condition was generally consistent with that observed in the overall population,” the authors wrote.

Between the first and second doses, 39 cases of COVID-19 were observed among BNT162b2 recipients and 82 cases among placebo recipients, corresponding to 52% vaccine efficacy during the 21-day interval (95% CI, 29.5%-68.4%) suggesting early protection may begin as soon as 12 days after the first injection.

“This is an incredible achievement given that an effective vaccine has never been developed and approved for use in such a short timeframe,” Dr. Bowton explained. “That the vaccine is highly effective in reducing the incidence of symptomatic COVID-19 seems incontrovertible.”

“This vaccine has shockingly amazing efficacy and is well tolerated, and the results are beyond even optimistic projections,” Douglas S. Paauw, MD, of the University of Washington, Seattle, said in an interview.
 

Questions remain

“It is not yet known if the vaccine prevents asymptomatic infections, with their attendant risk of contagion, as rates of seroconversion of trial participants against betacoronavirus nucleoproteins not included in the vaccine has not been reported,” Dr. Bowton commented.

“Common questions our patients will ask us remain unanswered for now, [including] how long will the protection last, is it safe in pregnant women, and does it prevent asymptomatic infection,” Dr. Paauw explained. “We do not know everything about longer term side effects, but the benefits of this vaccine appear to outweigh the risks of the vaccine.”

The researchers noted these and other limitations in their report, acknowledging that longer follow-up is needed to evaluate long-term safety of the vaccine.

This study was supported by BioNTech and Pfizer. Several authors disclosed financial relationships with Pfizer and other pharmaceutical companies outside the submitted work. Dr. Bowton and Dr. Paauw had no conflicts to disclose.

SOURCE: Polack FP et al. N Engl J Med. 2020 Dec 10. doi: 10.1056/NEJMoa2034577
 

The 16 million–plus people in the United States, and 72 million worldwide, who have been infected with COVID-19 – and survived – are likely asking themselves the same questions: Am I immune now? Is it over or do I have to brace myself for the possibility of a reinfection? Moreover, could the second time potentially be worse than the first?

I was diagnosed with COVID in March of this year. After spending 10 days in the hospital, and one night in the ICU, it took another 2 months for the air-hunger, headaches, and fatigue to completely resolve. Compared with many other unfortunate victims, I did all right – and I am very grateful for the care I received.

Now, as the surge in cases takes new life, I will be on the front lines taking care of patients. Having had an eventful personal encounter with the virus, I now have a unique vantage point and remain fully committed to paying my fortunate circumstances forward. Although I can’t help but have the same question faced by millions of others: Am I safe now?

It is no surprise that studies have shown health care workers comprising 6% of COVID hospital admissions, with one-third of these admissions being nurses. Recently, we heard that over 900 health care workers at Mayo Clinic had acquired the infection in the first 2 weeks of the ongoing second COVID surge. Are these frontline workers protected? Can they return to work with no fear of a rerun? Or, for that matter, anyone who has been afflicted by COVID – are they now forever immune?

There are no clear answers here. But to understand this a little, let’s quickly revisit some basic principles of immunity.
 

Innate and adaptive immunity

Simply put, there are two forms of immunity: innate and adaptive. Innate immunity encompasses our body’s natural protective mechanisms that come into play almost immediately. This enables recognition of the virus and activates an immediate antiviral defense and attempt at removal of the infective agent. This, however, does not always do the job. Accordingly, a couple weeks after the initial exposure to the pathogen, adaptive immunity is invoked. Circulating white blood cells within our body recognize the virus and set off an immune response, involving the activation of T and B cells that actively attack the infective agent. It is this T- and B-cell–mediated immunity that should protect one against a second infection with the same agent.

What about herd immunity?

Herd immunity is defined as essentially yielding to the virus and letting it spread naturally in order to develop community-wide immunity. By consequence of a large proportion of the population becoming immune after exposure to the disease, person-to-person spread can potentially be mitigated. This does not confer immunity to the virus at the individual level; rather, it reduces the risk of vulnerable people coming in contact with the pathogen.

Unfortunately, depending on herd immunity as a way to deal with COVID-19 has not worked well, even in well-contained countries like Sweden, where a disproportionate number of their most vulnerable populations have died. It is self-evident that containment strategies with vaccination may be our best way forward to achieve herd immunity. Not surrendering to the virus.
 

Am I safe from reinfection?

In all honesty, we’re not entirely sure. But it is important to recognize a few points when considering your relative safety.

• The immune system is far from perfect. Not everyone has a robust immune response. And in those who do, the immune response can wane over time, potentially allowing for reinfection. While rare, there have already been some clearly documented reinfections, four that have been confirmed and published; two patients (in Nevada and Ecuador) actually fared worse the second time around.
• The virus can mutate and escape detection by the immune system. One could still be susceptible to reinfection from a different strain. (At least, this remains the case with the influenza virus.) There is some evidence that SARS-CoV-2 does not mutate rapidly, and hence this may not be a problem. But we don’t know for certain, at least as of yet.
• Even a vigorous immune response can be overwhelmed by the virus. It is unclear whether the relative length of time and the amount of virus exposure could undermine a previously primed immune system.

A prior infection and a consequent healthy immunity may help you combat a reinfection but it does not prevent you from harboring or carrying the virus. You may be asymptomatic, but you can still be a carrier and spread the infection. I am a strong advocate for limiting your exposure to others no matter your previous exposure status, in order to limit the spread of the virus.
 

So, what should I do?

I guess the answer is that you can’t be too careful. Not everyone has had their antibody levels tested, and even if positive, it is unclear how well that affords protection. It is best to presume that you are vulnerable for a reinfection and that you can still carry and spread the virus. This may be the safest approach until we actually achieve herd immunity through vaccination.

Even then, for a period of time, there will remain a sense of uncertainty. So, containment strategies inclusive of distancing and masking will and should remain a way of life at least until mid-2021, when we will be in a better position to reassess the landscape.

The surge is back. As I repay my debt and get back to the front line, I will continue to mask up and practice distancing. I am taking no chances of getting reinfected or being an asymptomatic carrier.

I had COVID, I also have antibodies, and I will be taking the vaccine. I implore you all to do the same.

Jag Singh is a physician, scientist, and professor at Harvard. He is passionate about social issues, leadership, digital health, and medical innovations. You can follow him on Twitter @JagSinghMD.

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

The 16 million–plus people in the United States, and 72 million worldwide, who have been infected with COVID-19 – and survived – are likely asking themselves the same questions: Am I immune now? Is it over or do I have to brace myself for the possibility of a reinfection? Moreover, could the second time potentially be worse than the first?

I was diagnosed with COVID in March of this year. After spending 10 days in the hospital, and one night in the ICU, it took another 2 months for the air-hunger, headaches, and fatigue to completely resolve. Compared with many other unfortunate victims, I did all right – and I am very grateful for the care I received.

Now, as the surge in cases takes new life, I will be on the front lines taking care of patients. Having had an eventful personal encounter with the virus, I now have a unique vantage point and remain fully committed to paying my fortunate circumstances forward. Although I can’t help but have the same question faced by millions of others: Am I safe now?

It is no surprise that studies have shown health care workers comprising 6% of COVID hospital admissions, with one-third of these admissions being nurses. Recently, we heard that over 900 health care workers at Mayo Clinic had acquired the infection in the first 2 weeks of the ongoing second COVID surge. Are these frontline workers protected? Can they return to work with no fear of a rerun? Or, for that matter, anyone who has been afflicted by COVID – are they now forever immune?

There are no clear answers here. But to understand this a little, let’s quickly revisit some basic principles of immunity.
 

Innate and adaptive immunity

Simply put, there are two forms of immunity: innate and adaptive. Innate immunity encompasses our body’s natural protective mechanisms that come into play almost immediately. This enables recognition of the virus and activates an immediate antiviral defense and attempt at removal of the infective agent. This, however, does not always do the job. Accordingly, a couple weeks after the initial exposure to the pathogen, adaptive immunity is invoked. Circulating white blood cells within our body recognize the virus and set off an immune response, involving the activation of T and B cells that actively attack the infective agent. It is this T- and B-cell–mediated immunity that should protect one against a second infection with the same agent.

What about herd immunity?

Herd immunity is defined as essentially yielding to the virus and letting it spread naturally in order to develop community-wide immunity. By consequence of a large proportion of the population becoming immune after exposure to the disease, person-to-person spread can potentially be mitigated. This does not confer immunity to the virus at the individual level; rather, it reduces the risk of vulnerable people coming in contact with the pathogen.

Unfortunately, depending on herd immunity as a way to deal with COVID-19 has not worked well, even in well-contained countries like Sweden, where a disproportionate number of their most vulnerable populations have died. It is self-evident that containment strategies with vaccination may be our best way forward to achieve herd immunity. Not surrendering to the virus.
 

Am I safe from reinfection?

In all honesty, we’re not entirely sure. But it is important to recognize a few points when considering your relative safety.

• The immune system is far from perfect. Not everyone has a robust immune response. And in those who do, the immune response can wane over time, potentially allowing for reinfection. While rare, there have already been some clearly documented reinfections, four that have been confirmed and published; two patients (in Nevada and Ecuador) actually fared worse the second time around.
• The virus can mutate and escape detection by the immune system. One could still be susceptible to reinfection from a different strain. (At least, this remains the case with the influenza virus.) There is some evidence that SARS-CoV-2 does not mutate rapidly, and hence this may not be a problem. But we don’t know for certain, at least as of yet.
• Even a vigorous immune response can be overwhelmed by the virus. It is unclear whether the relative length of time and the amount of virus exposure could undermine a previously primed immune system.

A prior infection and a consequent healthy immunity may help you combat a reinfection but it does not prevent you from harboring or carrying the virus. You may be asymptomatic, but you can still be a carrier and spread the infection. I am a strong advocate for limiting your exposure to others no matter your previous exposure status, in order to limit the spread of the virus.
 

So, what should I do?

I guess the answer is that you can’t be too careful. Not everyone has had their antibody levels tested, and even if positive, it is unclear how well that affords protection. It is best to presume that you are vulnerable for a reinfection and that you can still carry and spread the virus. This may be the safest approach until we actually achieve herd immunity through vaccination.

Even then, for a period of time, there will remain a sense of uncertainty. So, containment strategies inclusive of distancing and masking will and should remain a way of life at least until mid-2021, when we will be in a better position to reassess the landscape.

The surge is back. As I repay my debt and get back to the front line, I will continue to mask up and practice distancing. I am taking no chances of getting reinfected or being an asymptomatic carrier.

I had COVID, I also have antibodies, and I will be taking the vaccine. I implore you all to do the same.

Jag Singh is a physician, scientist, and professor at Harvard. He is passionate about social issues, leadership, digital health, and medical innovations. You can follow him on Twitter @JagSinghMD.

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

The 16 million–plus people in the United States, and 72 million worldwide, who have been infected with COVID-19 – and survived – are likely asking themselves the same questions: Am I immune now? Is it over or do I have to brace myself for the possibility of a reinfection? Moreover, could the second time potentially be worse than the first?

I was diagnosed with COVID in March of this year. After spending 10 days in the hospital, and one night in the ICU, it took another 2 months for the air-hunger, headaches, and fatigue to completely resolve. Compared with many other unfortunate victims, I did all right – and I am very grateful for the care I received.

Now, as the surge in cases takes new life, I will be on the front lines taking care of patients. Having had an eventful personal encounter with the virus, I now have a unique vantage point and remain fully committed to paying my fortunate circumstances forward. Although I can’t help but have the same question faced by millions of others: Am I safe now?

It is no surprise that studies have shown health care workers comprising 6% of COVID hospital admissions, with one-third of these admissions being nurses. Recently, we heard that over 900 health care workers at Mayo Clinic had acquired the infection in the first 2 weeks of the ongoing second COVID surge. Are these frontline workers protected? Can they return to work with no fear of a rerun? Or, for that matter, anyone who has been afflicted by COVID – are they now forever immune?

There are no clear answers here. But to understand this a little, let’s quickly revisit some basic principles of immunity.
 

Innate and adaptive immunity

Simply put, there are two forms of immunity: innate and adaptive. Innate immunity encompasses our body’s natural protective mechanisms that come into play almost immediately. This enables recognition of the virus and activates an immediate antiviral defense and attempt at removal of the infective agent. This, however, does not always do the job. Accordingly, a couple weeks after the initial exposure to the pathogen, adaptive immunity is invoked. Circulating white blood cells within our body recognize the virus and set off an immune response, involving the activation of T and B cells that actively attack the infective agent. It is this T- and B-cell–mediated immunity that should protect one against a second infection with the same agent.

What about herd immunity?

Herd immunity is defined as essentially yielding to the virus and letting it spread naturally in order to develop community-wide immunity. By consequence of a large proportion of the population becoming immune after exposure to the disease, person-to-person spread can potentially be mitigated. This does not confer immunity to the virus at the individual level; rather, it reduces the risk of vulnerable people coming in contact with the pathogen.

Unfortunately, depending on herd immunity as a way to deal with COVID-19 has not worked well, even in well-contained countries like Sweden, where a disproportionate number of their most vulnerable populations have died. It is self-evident that containment strategies with vaccination may be our best way forward to achieve herd immunity. Not surrendering to the virus.
 

Am I safe from reinfection?

In all honesty, we’re not entirely sure. But it is important to recognize a few points when considering your relative safety.

• The immune system is far from perfect. Not everyone has a robust immune response. And in those who do, the immune response can wane over time, potentially allowing for reinfection. While rare, there have already been some clearly documented reinfections, four that have been confirmed and published; two patients (in Nevada and Ecuador) actually fared worse the second time around.
• The virus can mutate and escape detection by the immune system. One could still be susceptible to reinfection from a different strain. (At least, this remains the case with the influenza virus.) There is some evidence that SARS-CoV-2 does not mutate rapidly, and hence this may not be a problem. But we don’t know for certain, at least as of yet.
• Even a vigorous immune response can be overwhelmed by the virus. It is unclear whether the relative length of time and the amount of virus exposure could undermine a previously primed immune system.

A prior infection and a consequent healthy immunity may help you combat a reinfection but it does not prevent you from harboring or carrying the virus. You may be asymptomatic, but you can still be a carrier and spread the infection. I am a strong advocate for limiting your exposure to others no matter your previous exposure status, in order to limit the spread of the virus.
 

So, what should I do?

I guess the answer is that you can’t be too careful. Not everyone has had their antibody levels tested, and even if positive, it is unclear how well that affords protection. It is best to presume that you are vulnerable for a reinfection and that you can still carry and spread the virus. This may be the safest approach until we actually achieve herd immunity through vaccination.

Even then, for a period of time, there will remain a sense of uncertainty. So, containment strategies inclusive of distancing and masking will and should remain a way of life at least until mid-2021, when we will be in a better position to reassess the landscape.

The surge is back. As I repay my debt and get back to the front line, I will continue to mask up and practice distancing. I am taking no chances of getting reinfected or being an asymptomatic carrier.

I had COVID, I also have antibodies, and I will be taking the vaccine. I implore you all to do the same.

Jag Singh is a physician, scientist, and professor at Harvard. He is passionate about social issues, leadership, digital health, and medical innovations. You can follow him on Twitter @JagSinghMD.

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

Levels of nicotine and marijuana vaping among adolescents remain elevated but did not increase significantly in the past year, data from the annual Monitoring the Future survey show.

The 2020 survey included responses from 11,821 individuals in 112 schools across the United States from Feb. 11, 2020, to March 14, 2020, at which time data collection ended prematurely because of the COVID-19 pandemic. The results represent approximately 25% of the usual data collection.

A key positive finding in this year’s survey was the relatively stable levels of nicotine vaping from 2019 to 2020, following a trend of notably increased use annually since vaping was added to the survey in 2017.

During the years 2017-2019, the percentage of teens who reported vaping nicotine in the past 12 months increased from 7.5% to 16.5% among 8th graders, from 15.8% to 30.7% among 10th graders, and from 18.8% to 35.3% among 12th graders. However, in 2020, the percentages of teens who reported past-year nicotine vaping were relatively steady at 16.6%, 30.7%, and 34.5%, for 8th-, 10th-, and 12th-grade students, respectively. In addition, reports of daily or near-daily nicotine vaping (defined as 20 occasions in the past 30 days) decreased significantly, from 6.8% to 3.6% among 10th graders and from 11.6% to 5.3% among 12th graders.

“The rapid rise of teen nicotine vaping in recent years has been unprecedented and deeply concerning since we know that nicotine is highly addictive and can be delivered at high doses by vaping devices, which may also contain other toxic chemicals that may be harmful when inhaled,” said Nora D. Volkow, MD, director of the National Institute on Drug Abuse in a press release accompanying the release of the findings. “It is encouraging to see a leveling off of this trend though the rates still remain very high.”

Reports of past-year marijuana vaping remained similar to 2019 levels after a twofold increase in the past 2 years, according to the survey. In early 2020, 8.1%, 19.1%, and 22.1% of 8th, 10th, and 12th graders reported past-year use. However, daily marijuana vaping decreased by more than half from 2019, to 1.1% among 10th graders and 1.5% among 12th graders.

Past-year use of the JUUL devices specifically also declined among older teens, from 28.7% in 2019 to 20% in 2020 among 10th graders and from 28.4% in 2019 to 22.7% in 2020 among 12th graders.

Other trends this year included the increased past-year use of amphetamines, inhalants, and cough medicines among 8th graders, and relatively low reported use among 12th graders of LSD (3.9%), synthetic cannabinoids (2.4%), cocaine (2.9%), ecstasy (1.8%), methamphetamine (1.4%), and heroin (0.3%).

The findings were published in JAMA Pediatrics.

 

Early data show progress

“The MTF survey is the most referenced and reliable longitudinal study reporting current use of tobacco, drugs, and alcohol among young people,” said Mark S. Gold, MD, of Washington University, St. Louis, in an interview.

“The new data, collected before data collection stopped prematurely due to the COVID-19 pandemic, suggests that some progress is being made in slowing the increase in substance use among these, the most vulnerable,” he said.

“The best news was that nicotine vaping decreased significantly after its meteoric increase over the past few years,” Dr. Gold emphasized. “Past-year vaping of marijuana remained steady at alarming levels in 2020, with 8.1% of 8th graders, 19.1% of 10th graders, and 22.1% of 12th graders reporting past-year use, following a two-fold increase over the past 2 years.” The use of all forms of marijuana, including smoking and vaping, did not significantly change in any of the three grades for lifetime use, past 12-month use, past 30-day use, and daily use from 2019 to 2020.

“Teen alcohol use has not significantly changed over the past 5 years,” and cigarette smoking in the last 30 days did not significantly change from 2019 to 2020, said Dr. Gold. However, “as with adults, psychostimulant use is increasing. Past year nonmedical use of amphetamines among 8th graders increased, from 3.5% in 2017 to 5.3% in 2020.”
 

COVID-era limitations

“The data suggest that pre-COVID pandemic vaping, smoking cigarettes, marijuana, and alcohol use had stabilized,” Dr. Gold said. “However, it is very difficult to predict what the COVID era data will show as many young people are at home, on the streets, and unsupervised; while adult substance misuse, substance use disorders, and overdoses are increasing. Drug supplies and access have increased for alcohol, cannabis, vaping, and tobacco as have supply synthetics like methamphetamine and fentanyl.”

In addition, “access to evaluation, intervention, and treatment have been curtailed during the pandemic,” Dr. Gold said. “The loss of peer role models, daily routine, and teacher or other adult supervision and interventions may interact with increasing despair, social isolation, depression, and anxiety in ways that are unknown. “It will not be clear until the next survey if perceived dangerousness has changed in ways that can protect these 8th, 10th, and 12th graders and increase the numbers of never users or current nonusers.”

The Monitoring the Future survey is conducted each year by the University of Michigan’s Institute for Social Research, Ann Arbor, and supported by NIDA, part of the National Institutes of Health. Dr. Gold had no relevant financial conflicts to disclose.

Levels of nicotine and marijuana vaping among adolescents remain elevated but did not increase significantly in the past year, data from the annual Monitoring the Future survey show.

The 2020 survey included responses from 11,821 individuals in 112 schools across the United States from Feb. 11, 2020, to March 14, 2020, at which time data collection ended prematurely because of the COVID-19 pandemic. The results represent approximately 25% of the usual data collection.

A key positive finding in this year’s survey was the relatively stable levels of nicotine vaping from 2019 to 2020, following a trend of notably increased use annually since vaping was added to the survey in 2017.

During the years 2017-2019, the percentage of teens who reported vaping nicotine in the past 12 months increased from 7.5% to 16.5% among 8th graders, from 15.8% to 30.7% among 10th graders, and from 18.8% to 35.3% among 12th graders. However, in 2020, the percentages of teens who reported past-year nicotine vaping were relatively steady at 16.6%, 30.7%, and 34.5%, for 8th-, 10th-, and 12th-grade students, respectively. In addition, reports of daily or near-daily nicotine vaping (defined as 20 occasions in the past 30 days) decreased significantly, from 6.8% to 3.6% among 10th graders and from 11.6% to 5.3% among 12th graders.

“The rapid rise of teen nicotine vaping in recent years has been unprecedented and deeply concerning since we know that nicotine is highly addictive and can be delivered at high doses by vaping devices, which may also contain other toxic chemicals that may be harmful when inhaled,” said Nora D. Volkow, MD, director of the National Institute on Drug Abuse in a press release accompanying the release of the findings. “It is encouraging to see a leveling off of this trend though the rates still remain very high.”

Reports of past-year marijuana vaping remained similar to 2019 levels after a twofold increase in the past 2 years, according to the survey. In early 2020, 8.1%, 19.1%, and 22.1% of 8th, 10th, and 12th graders reported past-year use. However, daily marijuana vaping decreased by more than half from 2019, to 1.1% among 10th graders and 1.5% among 12th graders.

Past-year use of the JUUL devices specifically also declined among older teens, from 28.7% in 2019 to 20% in 2020 among 10th graders and from 28.4% in 2019 to 22.7% in 2020 among 12th graders.

Other trends this year included the increased past-year use of amphetamines, inhalants, and cough medicines among 8th graders, and relatively low reported use among 12th graders of LSD (3.9%), synthetic cannabinoids (2.4%), cocaine (2.9%), ecstasy (1.8%), methamphetamine (1.4%), and heroin (0.3%).

The findings were published in JAMA Pediatrics.

 

Early data show progress

“The MTF survey is the most referenced and reliable longitudinal study reporting current use of tobacco, drugs, and alcohol among young people,” said Mark S. Gold, MD, of Washington University, St. Louis, in an interview.

“The new data, collected before data collection stopped prematurely due to the COVID-19 pandemic, suggests that some progress is being made in slowing the increase in substance use among these, the most vulnerable,” he said.

“The best news was that nicotine vaping decreased significantly after its meteoric increase over the past few years,” Dr. Gold emphasized. “Past-year vaping of marijuana remained steady at alarming levels in 2020, with 8.1% of 8th graders, 19.1% of 10th graders, and 22.1% of 12th graders reporting past-year use, following a two-fold increase over the past 2 years.” The use of all forms of marijuana, including smoking and vaping, did not significantly change in any of the three grades for lifetime use, past 12-month use, past 30-day use, and daily use from 2019 to 2020.

“Teen alcohol use has not significantly changed over the past 5 years,” and cigarette smoking in the last 30 days did not significantly change from 2019 to 2020, said Dr. Gold. However, “as with adults, psychostimulant use is increasing. Past year nonmedical use of amphetamines among 8th graders increased, from 3.5% in 2017 to 5.3% in 2020.”
 

COVID-era limitations

“The data suggest that pre-COVID pandemic vaping, smoking cigarettes, marijuana, and alcohol use had stabilized,” Dr. Gold said. “However, it is very difficult to predict what the COVID era data will show as many young people are at home, on the streets, and unsupervised; while adult substance misuse, substance use disorders, and overdoses are increasing. Drug supplies and access have increased for alcohol, cannabis, vaping, and tobacco as have supply synthetics like methamphetamine and fentanyl.”

In addition, “access to evaluation, intervention, and treatment have been curtailed during the pandemic,” Dr. Gold said. “The loss of peer role models, daily routine, and teacher or other adult supervision and interventions may interact with increasing despair, social isolation, depression, and anxiety in ways that are unknown. “It will not be clear until the next survey if perceived dangerousness has changed in ways that can protect these 8th, 10th, and 12th graders and increase the numbers of never users or current nonusers.”

The Monitoring the Future survey is conducted each year by the University of Michigan’s Institute for Social Research, Ann Arbor, and supported by NIDA, part of the National Institutes of Health. Dr. Gold had no relevant financial conflicts to disclose.

Levels of nicotine and marijuana vaping among adolescents remain elevated but did not increase significantly in the past year, data from the annual Monitoring the Future survey show.

The 2020 survey included responses from 11,821 individuals in 112 schools across the United States from Feb. 11, 2020, to March 14, 2020, at which time data collection ended prematurely because of the COVID-19 pandemic. The results represent approximately 25% of the usual data collection.

A key positive finding in this year’s survey was the relatively stable levels of nicotine vaping from 2019 to 2020, following a trend of notably increased use annually since vaping was added to the survey in 2017.

During the years 2017-2019, the percentage of teens who reported vaping nicotine in the past 12 months increased from 7.5% to 16.5% among 8th graders, from 15.8% to 30.7% among 10th graders, and from 18.8% to 35.3% among 12th graders. However, in 2020, the percentages of teens who reported past-year nicotine vaping were relatively steady at 16.6%, 30.7%, and 34.5%, for 8th-, 10th-, and 12th-grade students, respectively. In addition, reports of daily or near-daily nicotine vaping (defined as 20 occasions in the past 30 days) decreased significantly, from 6.8% to 3.6% among 10th graders and from 11.6% to 5.3% among 12th graders.

“The rapid rise of teen nicotine vaping in recent years has been unprecedented and deeply concerning since we know that nicotine is highly addictive and can be delivered at high doses by vaping devices, which may also contain other toxic chemicals that may be harmful when inhaled,” said Nora D. Volkow, MD, director of the National Institute on Drug Abuse in a press release accompanying the release of the findings. “It is encouraging to see a leveling off of this trend though the rates still remain very high.”

Reports of past-year marijuana vaping remained similar to 2019 levels after a twofold increase in the past 2 years, according to the survey. In early 2020, 8.1%, 19.1%, and 22.1% of 8th, 10th, and 12th graders reported past-year use. However, daily marijuana vaping decreased by more than half from 2019, to 1.1% among 10th graders and 1.5% among 12th graders.

Past-year use of the JUUL devices specifically also declined among older teens, from 28.7% in 2019 to 20% in 2020 among 10th graders and from 28.4% in 2019 to 22.7% in 2020 among 12th graders.

Other trends this year included the increased past-year use of amphetamines, inhalants, and cough medicines among 8th graders, and relatively low reported use among 12th graders of LSD (3.9%), synthetic cannabinoids (2.4%), cocaine (2.9%), ecstasy (1.8%), methamphetamine (1.4%), and heroin (0.3%).

The findings were published in JAMA Pediatrics.

 

Early data show progress

“The MTF survey is the most referenced and reliable longitudinal study reporting current use of tobacco, drugs, and alcohol among young people,” said Mark S. Gold, MD, of Washington University, St. Louis, in an interview.

“The new data, collected before data collection stopped prematurely due to the COVID-19 pandemic, suggests that some progress is being made in slowing the increase in substance use among these, the most vulnerable,” he said.

“The best news was that nicotine vaping decreased significantly after its meteoric increase over the past few years,” Dr. Gold emphasized. “Past-year vaping of marijuana remained steady at alarming levels in 2020, with 8.1% of 8th graders, 19.1% of 10th graders, and 22.1% of 12th graders reporting past-year use, following a two-fold increase over the past 2 years.” The use of all forms of marijuana, including smoking and vaping, did not significantly change in any of the three grades for lifetime use, past 12-month use, past 30-day use, and daily use from 2019 to 2020.

“Teen alcohol use has not significantly changed over the past 5 years,” and cigarette smoking in the last 30 days did not significantly change from 2019 to 2020, said Dr. Gold. However, “as with adults, psychostimulant use is increasing. Past year nonmedical use of amphetamines among 8th graders increased, from 3.5% in 2017 to 5.3% in 2020.”
 

COVID-era limitations

“The data suggest that pre-COVID pandemic vaping, smoking cigarettes, marijuana, and alcohol use had stabilized,” Dr. Gold said. “However, it is very difficult to predict what the COVID era data will show as many young people are at home, on the streets, and unsupervised; while adult substance misuse, substance use disorders, and overdoses are increasing. Drug supplies and access have increased for alcohol, cannabis, vaping, and tobacco as have supply synthetics like methamphetamine and fentanyl.”

In addition, “access to evaluation, intervention, and treatment have been curtailed during the pandemic,” Dr. Gold said. “The loss of peer role models, daily routine, and teacher or other adult supervision and interventions may interact with increasing despair, social isolation, depression, and anxiety in ways that are unknown. “It will not be clear until the next survey if perceived dangerousness has changed in ways that can protect these 8th, 10th, and 12th graders and increase the numbers of never users or current nonusers.”

The Monitoring the Future survey is conducted each year by the University of Michigan’s Institute for Social Research, Ann Arbor, and supported by NIDA, part of the National Institutes of Health. Dr. Gold had no relevant financial conflicts to disclose.

Sleep medications for older patients who report sleep problems may not be the best treatment given growing evidence of the link between these medications and the risk of incident dementia.

Adults aged 65 years and older who used sleep medications 5-7 days a week demonstrated a 30% increased risk of dementia, compared with those who did not use sleep medications, findings from a prospective study of 6,373 individuals show.

Adults aged 65 and older report a higher burden of sleep problems than other age groups, but major medical associations discourage the use of sleep medications by older adults because of growing evidence of a link between sleep medication use and cognitive decline, wrote Rebecca Robbins, MD, of Brigham and Women’s Hospital, Boston, and colleagues. However, data on this association among adults in the United States are limited, they said.

In a study published in Sleep Medicine, the researchers surveyed 6,373 adults aged 65 years and older who were enrolled in the nationally representative National Health and Aging Trends Study (NHATS). The majority of the participants were non-Hispanic White (71%), 59% were women, and 21% ranged in age from 70 to 74 years.

Participants responded to questions about routine sleep medication use. Routine was defined as “most nights” or “every night.” The data were collected for an 8-year period from 2011 to 2018. The study began in 2011, with a core interview administered annually.

Approximately 15% of the study population reported routine use of sleep medications. Overall, routine use of sleep medication was significantly associated with risk of incident dementia (hazard ratio, 1.30; P < .01) after controlling for multiple variables including age, sex, education level, and chronic conditions.

Dementia screening was conducted by participants rating their memory and then performing a memory-related activity (immediate and delayed 10-word recall) and other exercises to assess executive function and orientation. A separate eight-item informant screener was performed for patient proxies. The researcher noted, “Sensitivity of the NHATS probable dementia screening measure has been determined in previous research to be 66%, and specificity is 87%, with respect to a clinical dementia diagnosis.”

The study findings were limited by several factors including the use of self-reports, the lack of data on type or dose of sleep medication, and lack of data on the indication for the prescription, the researchers noted.

“Also, sleep medication use leads to worse performance on cognitive testing, such as the questionnaires used to screen for dementia in this study, and therefore could have resulted in a false diagnosis of dementia,” they added.

However, the results were strengthened by the large, nationally representative study population and support the need for quality geriatric care, the researchers said.

“Our findings provide further support and evidence that sleep medications are all too commonly administered, yet associated with greater risk for incident dementia, and that the U.S. health care system is in need of creative solutions for addressing poor sleep among older individuals,” they concluded.
 

Implications and alternatives

The study is important as the number of aging Americans increases, said Carolyn M. D’Ambrosio, MD, FCCP, of Brigham and Women’s Hospital and Harvard Medical School, Boston, in an interview. “In the elderly, inability to fall asleep or stay asleep are common issues that are brought to a health care provider,” she said. Dr. D’Ambrosio said she was not surprised by the study findings “as elderly patients often have sleep issues and sometimes a well-meaning health care provider gives them sleep medication to help. We have known that some of these sleep medications such as benzodiazepines affect cognitive performance,” she said.

Dr. D’Ambrosio said she avoids prescribing sleep medications for older adults if possible. “A deep dive into sleep habits, environment, and other things that disrupt sleep often gets to the problem rather than just masking it with a sleep medication,” she noted. Alternatives to improve sleep in older adults include exercise, exposure to bright light during the day, and good healthy sleep habits, all of which contribute to improved sleep in the elderly, said Dr. D’Ambrosio. She also recommends screening older adults for other issues that affect sleep, such as chronic pain.

The current study highlighted the association between sleep medication use and dementia, but it does not show causation, Dr. D’Ambrosio said. “So much more needs to be done to determine whether the sleep medications are causing worsening cognitive function long term, or if the dementia is starting but not yet diagnosed and the sleep medication is given but not the cause of the dementia, she noted.
 

Research gaps and treatment strategies

Older adults experiencing sleep difficulties may try various medications including pharmacologics (e.g., benzodiazepines), over-the-counter agents, such as diphenhydramine or doxylamine preparations, and/or herbal and nutritional supplements such as valerian or melatonin, said Mary Jo S. Farmer, MD, FCCP, of the University of Massachusetts Medical School–Baystate, Springfield, in an interview. “However, sleep medications, particularly benzodiazepines, are strongly discouraged by major medical associations including the American Geriatrics Society in part because of the growing evidence that use of sleep medications is associated with cognitive impairment and decline,” she said.

The current study results contribute to previous work demonstrating that both pharmacologic and nonpharmacologic sleep medication, although commonly administered, is associated with subsequent adverse outcomes in older adults, Dr. Farmer said. This association sets the stage for creative and different solutions for addressing poor sleep among older adults, such as behavioral treatments including cognitive-behavioral therapy, she noted.

Dr. Farmer said, “Areas for future research include exploring the causal link between prescription and/or over-the-counter sleep medication use and incident dementia in a randomized controlled trial,” she added.

“Another interesting opportunity for future research is to explore the indications for sleep medications among older adults since it has been shown in the general population that sleep difficulties represent only 12% of the indication for sleep medication prescriptions,” Dr. Farmer noted. “Future research could examine the strength of the underlying motivation to use sleep medication even in light of suggested long-term effects, and the effectiveness of other measures to avoid or minimize sleep difficulties,” she said.

“My experience is that the majority of ambulatory patients recently seen in sleep clinic want to avoid long-term use of sleep medications and will ask what other measures can be tried to consistently achieve a good night’s sleep without medication use,” Dr. Farmer said. “If medications are used, patients would rather try melatonin than a benzodiazepine. Many patients who come to sleep clinic with sleep medications already prescribed and are subsequently found to have sleep apnea and/or restless legs find that they no longer need sleep medication when these other medical conditions are appropriately diagnosed and managed,” she explained. “Finally, many patients tell me they feel less energetic upon awakening, almost feel hung over, and express being less sharp cognitively when taking pharmacologic sleep medication, whether for short or long periods of time, and therefore they want to avoid continuing with sleep medication use,” she said.

Dr. Farmer’s strategy for developing alternatives to sleep medications in older adults includes taking a careful history, including a complete list of medical problems, review of medications, and a thorough sleep history including usual time of sleep onset, awake time, and the frequency of daytime naps. “Tips for improving the quality of nighttime sleep may include adequately treating pain and other medical conditions such as heartburn, sleep apnea, and restless legs, creating a soothing environment to promote sleep by eliminating noise and bright lights, avoiding stimulant medications and substances such as caffeine and nicotine before bedtime, avoiding excessive amounts of alcohol, avoiding diuretics before bedtime, encouraging physical activity during the day, spending time in the sunlight as much as possible to help regulate the sleep cycle, limiting daytime naps, and establishing a regular sleep schedule,” she said.

The study was supported by National Institutes of Health awards K01HL150339, U54MD000538, K07AG052685, R01AG056531, R01AG056031. Lead author Dr. Robbins had no financial conflicts to disclose. Dr. D’Ambrosio disclosed serving as a section editor for sleep medicine for Dynamed and owning a patent on a circadian programming device. Dr. Farmer had no disclosures.

SOURCE: Robbins R et al. Sleep Med. 2020 Nov 11. doi: 10.1016/j.sleep.2020.11.004.

Sleep medications for older patients who report sleep problems may not be the best treatment given growing evidence of the link between these medications and the risk of incident dementia.

Adults aged 65 years and older who used sleep medications 5-7 days a week demonstrated a 30% increased risk of dementia, compared with those who did not use sleep medications, findings from a prospective study of 6,373 individuals show.

Adults aged 65 and older report a higher burden of sleep problems than other age groups, but major medical associations discourage the use of sleep medications by older adults because of growing evidence of a link between sleep medication use and cognitive decline, wrote Rebecca Robbins, MD, of Brigham and Women’s Hospital, Boston, and colleagues. However, data on this association among adults in the United States are limited, they said.

In a study published in Sleep Medicine, the researchers surveyed 6,373 adults aged 65 years and older who were enrolled in the nationally representative National Health and Aging Trends Study (NHATS). The majority of the participants were non-Hispanic White (71%), 59% were women, and 21% ranged in age from 70 to 74 years.

Participants responded to questions about routine sleep medication use. Routine was defined as “most nights” or “every night.” The data were collected for an 8-year period from 2011 to 2018. The study began in 2011, with a core interview administered annually.

Approximately 15% of the study population reported routine use of sleep medications. Overall, routine use of sleep medication was significantly associated with risk of incident dementia (hazard ratio, 1.30; P < .01) after controlling for multiple variables including age, sex, education level, and chronic conditions.

Dementia screening was conducted by participants rating their memory and then performing a memory-related activity (immediate and delayed 10-word recall) and other exercises to assess executive function and orientation. A separate eight-item informant screener was performed for patient proxies. The researcher noted, “Sensitivity of the NHATS probable dementia screening measure has been determined in previous research to be 66%, and specificity is 87%, with respect to a clinical dementia diagnosis.”

The study findings were limited by several factors including the use of self-reports, the lack of data on type or dose of sleep medication, and lack of data on the indication for the prescription, the researchers noted.

“Also, sleep medication use leads to worse performance on cognitive testing, such as the questionnaires used to screen for dementia in this study, and therefore could have resulted in a false diagnosis of dementia,” they added.

However, the results were strengthened by the large, nationally representative study population and support the need for quality geriatric care, the researchers said.

“Our findings provide further support and evidence that sleep medications are all too commonly administered, yet associated with greater risk for incident dementia, and that the U.S. health care system is in need of creative solutions for addressing poor sleep among older individuals,” they concluded.
 

Implications and alternatives

The study is important as the number of aging Americans increases, said Carolyn M. D’Ambrosio, MD, FCCP, of Brigham and Women’s Hospital and Harvard Medical School, Boston, in an interview. “In the elderly, inability to fall asleep or stay asleep are common issues that are brought to a health care provider,” she said. Dr. D’Ambrosio said she was not surprised by the study findings “as elderly patients often have sleep issues and sometimes a well-meaning health care provider gives them sleep medication to help. We have known that some of these sleep medications such as benzodiazepines affect cognitive performance,” she said.

Dr. D’Ambrosio said she avoids prescribing sleep medications for older adults if possible. “A deep dive into sleep habits, environment, and other things that disrupt sleep often gets to the problem rather than just masking it with a sleep medication,” she noted. Alternatives to improve sleep in older adults include exercise, exposure to bright light during the day, and good healthy sleep habits, all of which contribute to improved sleep in the elderly, said Dr. D’Ambrosio. She also recommends screening older adults for other issues that affect sleep, such as chronic pain.

The current study highlighted the association between sleep medication use and dementia, but it does not show causation, Dr. D’Ambrosio said. “So much more needs to be done to determine whether the sleep medications are causing worsening cognitive function long term, or if the dementia is starting but not yet diagnosed and the sleep medication is given but not the cause of the dementia, she noted.
 

Research gaps and treatment strategies

Older adults experiencing sleep difficulties may try various medications including pharmacologics (e.g., benzodiazepines), over-the-counter agents, such as diphenhydramine or doxylamine preparations, and/or herbal and nutritional supplements such as valerian or melatonin, said Mary Jo S. Farmer, MD, FCCP, of the University of Massachusetts Medical School–Baystate, Springfield, in an interview. “However, sleep medications, particularly benzodiazepines, are strongly discouraged by major medical associations including the American Geriatrics Society in part because of the growing evidence that use of sleep medications is associated with cognitive impairment and decline,” she said.

The current study results contribute to previous work demonstrating that both pharmacologic and nonpharmacologic sleep medication, although commonly administered, is associated with subsequent adverse outcomes in older adults, Dr. Farmer said. This association sets the stage for creative and different solutions for addressing poor sleep among older adults, such as behavioral treatments including cognitive-behavioral therapy, she noted.

Dr. Farmer said, “Areas for future research include exploring the causal link between prescription and/or over-the-counter sleep medication use and incident dementia in a randomized controlled trial,” she added.

“Another interesting opportunity for future research is to explore the indications for sleep medications among older adults since it has been shown in the general population that sleep difficulties represent only 12% of the indication for sleep medication prescriptions,” Dr. Farmer noted. “Future research could examine the strength of the underlying motivation to use sleep medication even in light of suggested long-term effects, and the effectiveness of other measures to avoid or minimize sleep difficulties,” she said.

“My experience is that the majority of ambulatory patients recently seen in sleep clinic want to avoid long-term use of sleep medications and will ask what other measures can be tried to consistently achieve a good night’s sleep without medication use,” Dr. Farmer said. “If medications are used, patients would rather try melatonin than a benzodiazepine. Many patients who come to sleep clinic with sleep medications already prescribed and are subsequently found to have sleep apnea and/or restless legs find that they no longer need sleep medication when these other medical conditions are appropriately diagnosed and managed,” she explained. “Finally, many patients tell me they feel less energetic upon awakening, almost feel hung over, and express being less sharp cognitively when taking pharmacologic sleep medication, whether for short or long periods of time, and therefore they want to avoid continuing with sleep medication use,” she said.

Dr. Farmer’s strategy for developing alternatives to sleep medications in older adults includes taking a careful history, including a complete list of medical problems, review of medications, and a thorough sleep history including usual time of sleep onset, awake time, and the frequency of daytime naps. “Tips for improving the quality of nighttime sleep may include adequately treating pain and other medical conditions such as heartburn, sleep apnea, and restless legs, creating a soothing environment to promote sleep by eliminating noise and bright lights, avoiding stimulant medications and substances such as caffeine and nicotine before bedtime, avoiding excessive amounts of alcohol, avoiding diuretics before bedtime, encouraging physical activity during the day, spending time in the sunlight as much as possible to help regulate the sleep cycle, limiting daytime naps, and establishing a regular sleep schedule,” she said.

The study was supported by National Institutes of Health awards K01HL150339, U54MD000538, K07AG052685, R01AG056531, R01AG056031. Lead author Dr. Robbins had no financial conflicts to disclose. Dr. D’Ambrosio disclosed serving as a section editor for sleep medicine for Dynamed and owning a patent on a circadian programming device. Dr. Farmer had no disclosures.

SOURCE: Robbins R et al. Sleep Med. 2020 Nov 11. doi: 10.1016/j.sleep.2020.11.004.

Sleep medications for older patients who report sleep problems may not be the best treatment given growing evidence of the link between these medications and the risk of incident dementia.

Adults aged 65 years and older who used sleep medications 5-7 days a week demonstrated a 30% increased risk of dementia, compared with those who did not use sleep medications, findings from a prospective study of 6,373 individuals show.

Adults aged 65 and older report a higher burden of sleep problems than other age groups, but major medical associations discourage the use of sleep medications by older adults because of growing evidence of a link between sleep medication use and cognitive decline, wrote Rebecca Robbins, MD, of Brigham and Women’s Hospital, Boston, and colleagues. However, data on this association among adults in the United States are limited, they said.

In a study published in Sleep Medicine, the researchers surveyed 6,373 adults aged 65 years and older who were enrolled in the nationally representative National Health and Aging Trends Study (NHATS). The majority of the participants were non-Hispanic White (71%), 59% were women, and 21% ranged in age from 70 to 74 years.

Participants responded to questions about routine sleep medication use. Routine was defined as “most nights” or “every night.” The data were collected for an 8-year period from 2011 to 2018. The study began in 2011, with a core interview administered annually.

Approximately 15% of the study population reported routine use of sleep medications. Overall, routine use of sleep medication was significantly associated with risk of incident dementia (hazard ratio, 1.30; P < .01) after controlling for multiple variables including age, sex, education level, and chronic conditions.

Dementia screening was conducted by participants rating their memory and then performing a memory-related activity (immediate and delayed 10-word recall) and other exercises to assess executive function and orientation. A separate eight-item informant screener was performed for patient proxies. The researcher noted, “Sensitivity of the NHATS probable dementia screening measure has been determined in previous research to be 66%, and specificity is 87%, with respect to a clinical dementia diagnosis.”

The study findings were limited by several factors including the use of self-reports, the lack of data on type or dose of sleep medication, and lack of data on the indication for the prescription, the researchers noted.

“Also, sleep medication use leads to worse performance on cognitive testing, such as the questionnaires used to screen for dementia in this study, and therefore could have resulted in a false diagnosis of dementia,” they added.

However, the results were strengthened by the large, nationally representative study population and support the need for quality geriatric care, the researchers said.

“Our findings provide further support and evidence that sleep medications are all too commonly administered, yet associated with greater risk for incident dementia, and that the U.S. health care system is in need of creative solutions for addressing poor sleep among older individuals,” they concluded.
 

Implications and alternatives

The study is important as the number of aging Americans increases, said Carolyn M. D’Ambrosio, MD, FCCP, of Brigham and Women’s Hospital and Harvard Medical School, Boston, in an interview. “In the elderly, inability to fall asleep or stay asleep are common issues that are brought to a health care provider,” she said. Dr. D’Ambrosio said she was not surprised by the study findings “as elderly patients often have sleep issues and sometimes a well-meaning health care provider gives them sleep medication to help. We have known that some of these sleep medications such as benzodiazepines affect cognitive performance,” she said.

Dr. D’Ambrosio said she avoids prescribing sleep medications for older adults if possible. “A deep dive into sleep habits, environment, and other things that disrupt sleep often gets to the problem rather than just masking it with a sleep medication,” she noted. Alternatives to improve sleep in older adults include exercise, exposure to bright light during the day, and good healthy sleep habits, all of which contribute to improved sleep in the elderly, said Dr. D’Ambrosio. She also recommends screening older adults for other issues that affect sleep, such as chronic pain.

The current study highlighted the association between sleep medication use and dementia, but it does not show causation, Dr. D’Ambrosio said. “So much more needs to be done to determine whether the sleep medications are causing worsening cognitive function long term, or if the dementia is starting but not yet diagnosed and the sleep medication is given but not the cause of the dementia, she noted.
 

Research gaps and treatment strategies

Older adults experiencing sleep difficulties may try various medications including pharmacologics (e.g., benzodiazepines), over-the-counter agents, such as diphenhydramine or doxylamine preparations, and/or herbal and nutritional supplements such as valerian or melatonin, said Mary Jo S. Farmer, MD, FCCP, of the University of Massachusetts Medical School–Baystate, Springfield, in an interview. “However, sleep medications, particularly benzodiazepines, are strongly discouraged by major medical associations including the American Geriatrics Society in part because of the growing evidence that use of sleep medications is associated with cognitive impairment and decline,” she said.

The current study results contribute to previous work demonstrating that both pharmacologic and nonpharmacologic sleep medication, although commonly administered, is associated with subsequent adverse outcomes in older adults, Dr. Farmer said. This association sets the stage for creative and different solutions for addressing poor sleep among older adults, such as behavioral treatments including cognitive-behavioral therapy, she noted.

Dr. Farmer said, “Areas for future research include exploring the causal link between prescription and/or over-the-counter sleep medication use and incident dementia in a randomized controlled trial,” she added.

“Another interesting opportunity for future research is to explore the indications for sleep medications among older adults since it has been shown in the general population that sleep difficulties represent only 12% of the indication for sleep medication prescriptions,” Dr. Farmer noted. “Future research could examine the strength of the underlying motivation to use sleep medication even in light of suggested long-term effects, and the effectiveness of other measures to avoid or minimize sleep difficulties,” she said.

“My experience is that the majority of ambulatory patients recently seen in sleep clinic want to avoid long-term use of sleep medications and will ask what other measures can be tried to consistently achieve a good night’s sleep without medication use,” Dr. Farmer said. “If medications are used, patients would rather try melatonin than a benzodiazepine. Many patients who come to sleep clinic with sleep medications already prescribed and are subsequently found to have sleep apnea and/or restless legs find that they no longer need sleep medication when these other medical conditions are appropriately diagnosed and managed,” she explained. “Finally, many patients tell me they feel less energetic upon awakening, almost feel hung over, and express being less sharp cognitively when taking pharmacologic sleep medication, whether for short or long periods of time, and therefore they want to avoid continuing with sleep medication use,” she said.

Dr. Farmer’s strategy for developing alternatives to sleep medications in older adults includes taking a careful history, including a complete list of medical problems, review of medications, and a thorough sleep history including usual time of sleep onset, awake time, and the frequency of daytime naps. “Tips for improving the quality of nighttime sleep may include adequately treating pain and other medical conditions such as heartburn, sleep apnea, and restless legs, creating a soothing environment to promote sleep by eliminating noise and bright lights, avoiding stimulant medications and substances such as caffeine and nicotine before bedtime, avoiding excessive amounts of alcohol, avoiding diuretics before bedtime, encouraging physical activity during the day, spending time in the sunlight as much as possible to help regulate the sleep cycle, limiting daytime naps, and establishing a regular sleep schedule,” she said.

The study was supported by National Institutes of Health awards K01HL150339, U54MD000538, K07AG052685, R01AG056531, R01AG056031. Lead author Dr. Robbins had no financial conflicts to disclose. Dr. D’Ambrosio disclosed serving as a section editor for sleep medicine for Dynamed and owning a patent on a circadian programming device. Dr. Farmer had no disclosures.

SOURCE: Robbins R et al. Sleep Med. 2020 Nov 11. doi: 10.1016/j.sleep.2020.11.004.

Federal advisers on December 17 overwhelmingly recommended an emergency clearance to Moderna Inc’s COVID-19 vaccine, while noting concerns about potential allergic reactions and the challenges of continuing testing of this medicine.

The US Food and Drug Administration (FDA) put Moderna’s application before its Vaccines and Related Biological Products Advisory Committee. The panel voted 20-0 on this question: “Based on the totality of scientific evidence available, do the benefits of the Moderna COVID-19 Vaccine outweigh its risks for use in individuals 18 years of age and older?” There was one abstention.

The FDA is not bound to act on the recommendations of its advisers, but the agency usually takes the panel’s advice. The FDA cleared the similar Pfizer-BioNTech vaccine on December 11 through an emergency use authorization (EUA), following a positive vote for the product at a December 10 advisory committee meeting. In this case, the FDA staff appeared to be pushing for a broad endorsement of the Moderna vaccine, for which the agency appears likely to soon also grant an EUA.

Marion Gruber, PhD, director of the Office of Vaccines Research and Review at FDA’s Center for Biologics Evaluation and Research, earlier rebuffed attempts by some of the panelists to alter the voting question. Some panelists wanted to make tweaks, including a rephrasing to underscore the limited nature of an EUA, compared with a more complete approval through the biologics license application (BLA) process.

FDA panelist Michael Kurilla, MD, PhD, of the National Institutes of Health was the only panelist to abstain from voting. He said he was uncomfortable with the phrasing of the question.

“In the midst of a pandemic and with limited vaccine supply available, a blanket statement for individuals 18 years and older is just too broad,” he said. “I’m not convinced that for all of those age groups the benefits do actually outweigh the risks.”

In general, though, there was strong support for Moderna’s vaccine. FDA panelist James Hildreth Sr, MD, PhD, of Meharry Medical College in Nashville, Tennessee spoke of the “remarkable achievement” seen in having two vaccines ready for clearance by December for a virus that only emerged as a threat this year.

Study data indicate the primary efficacy endpoint demonstrated vaccine efficacy (VE) of 94.1% (95% CI, 89.3% - 96.8%) for the Moderna vaccine, with 11 COVID-19 cases in the vaccine group and 185 COVID-19 cases in the placebo group, the FDA staff noted during the meeting.

The advisers and FDA staff also honed in on several key issues with COVID-19 vaccines, including the challenge of having people in the placebo groups of studies seek to get cleared vaccines. Also of concern to the panel were early reports of allergic reactions seen with the Pfizer product.

Doran L. Fink, MD, PhD, an FDA official who has been closely involved with the COVID-19 vaccines, told the panel that two healthcare workers in Alaska had allergic reactions minutes after receiving the Pfizer vaccine, one of which was a case of anaphylactic reaction that resulted in hospitalization.

In the United Kingdom, there were two cases reported of notable allergic reactions, leading regulators there to issue a warning that people who have a history of significant allergic reactions should not currently receive the Pfizer-BioNTech vaccine.

The people involved in these incidents have recovered or are recovering, Fink said. But the FDA expects there will be additional reports of allergic reactions to COVID-19 vaccines.

“These cases underscores the need to remain vigilant during the early phase of the vaccination campaign,” Fink said. “To this end, FDA is working with Pfizer to further revise factsheets and prescribing information for their vaccine to draw attention to CDC guidelines for post- vaccination monitoring and management of immediate allergic reactions.”

mRNA vaccines in the lead

An FDA emergency clearance for Moderna’s product would be another vote of confidence in a new approach to making vaccines. Both the Pfizer-BioNTech and Moderna vaccines provide the immune system with a kind of blueprint in the form of genetic material, mRNA. The mRNA sets the stage for the synthesis of the signature spike protein that the SARS-CoV-2 virus uses to attach to and infect human cells.

In a December 15 commentary for this news organization Michael E. Pichichero, MD, wrote that the “revolutionary aspect of mRNA vaccines is the speed at which they can be designed and produced.”

“This is why they lead the pack among the SARS-CoV-2 vaccine candidates and why the National Institute of Allergy and Infectious Diseases provided financial, technical, and/or clinical support. Indeed, once the amino acid sequence of a protein can be determined (a relatively easy task these days) it’s straightforward to synthesize mRNA in the lab — and it can be done incredibly fast,” he wrote.

The FDA allowed one waiver for panelist James K. Hildreth in connection with his personal relationship to a trial participant and his university’s participation in vaccine testing.

This article first appeared on Medscape.com.

Federal advisers on December 17 overwhelmingly recommended an emergency clearance to Moderna Inc’s COVID-19 vaccine, while noting concerns about potential allergic reactions and the challenges of continuing testing of this medicine.

The US Food and Drug Administration (FDA) put Moderna’s application before its Vaccines and Related Biological Products Advisory Committee. The panel voted 20-0 on this question: “Based on the totality of scientific evidence available, do the benefits of the Moderna COVID-19 Vaccine outweigh its risks for use in individuals 18 years of age and older?” There was one abstention.

The FDA is not bound to act on the recommendations of its advisers, but the agency usually takes the panel’s advice. The FDA cleared the similar Pfizer-BioNTech vaccine on December 11 through an emergency use authorization (EUA), following a positive vote for the product at a December 10 advisory committee meeting. In this case, the FDA staff appeared to be pushing for a broad endorsement of the Moderna vaccine, for which the agency appears likely to soon also grant an EUA.

Marion Gruber, PhD, director of the Office of Vaccines Research and Review at FDA’s Center for Biologics Evaluation and Research, earlier rebuffed attempts by some of the panelists to alter the voting question. Some panelists wanted to make tweaks, including a rephrasing to underscore the limited nature of an EUA, compared with a more complete approval through the biologics license application (BLA) process.

FDA panelist Michael Kurilla, MD, PhD, of the National Institutes of Health was the only panelist to abstain from voting. He said he was uncomfortable with the phrasing of the question.

“In the midst of a pandemic and with limited vaccine supply available, a blanket statement for individuals 18 years and older is just too broad,” he said. “I’m not convinced that for all of those age groups the benefits do actually outweigh the risks.”

In general, though, there was strong support for Moderna’s vaccine. FDA panelist James Hildreth Sr, MD, PhD, of Meharry Medical College in Nashville, Tennessee spoke of the “remarkable achievement” seen in having two vaccines ready for clearance by December for a virus that only emerged as a threat this year.

Study data indicate the primary efficacy endpoint demonstrated vaccine efficacy (VE) of 94.1% (95% CI, 89.3% - 96.8%) for the Moderna vaccine, with 11 COVID-19 cases in the vaccine group and 185 COVID-19 cases in the placebo group, the FDA staff noted during the meeting.

The advisers and FDA staff also honed in on several key issues with COVID-19 vaccines, including the challenge of having people in the placebo groups of studies seek to get cleared vaccines. Also of concern to the panel were early reports of allergic reactions seen with the Pfizer product.

Doran L. Fink, MD, PhD, an FDA official who has been closely involved with the COVID-19 vaccines, told the panel that two healthcare workers in Alaska had allergic reactions minutes after receiving the Pfizer vaccine, one of which was a case of anaphylactic reaction that resulted in hospitalization.

In the United Kingdom, there were two cases reported of notable allergic reactions, leading regulators there to issue a warning that people who have a history of significant allergic reactions should not currently receive the Pfizer-BioNTech vaccine.

The people involved in these incidents have recovered or are recovering, Fink said. But the FDA expects there will be additional reports of allergic reactions to COVID-19 vaccines.

“These cases underscores the need to remain vigilant during the early phase of the vaccination campaign,” Fink said. “To this end, FDA is working with Pfizer to further revise factsheets and prescribing information for their vaccine to draw attention to CDC guidelines for post- vaccination monitoring and management of immediate allergic reactions.”

mRNA vaccines in the lead

An FDA emergency clearance for Moderna’s product would be another vote of confidence in a new approach to making vaccines. Both the Pfizer-BioNTech and Moderna vaccines provide the immune system with a kind of blueprint in the form of genetic material, mRNA. The mRNA sets the stage for the synthesis of the signature spike protein that the SARS-CoV-2 virus uses to attach to and infect human cells.

In a December 15 commentary for this news organization Michael E. Pichichero, MD, wrote that the “revolutionary aspect of mRNA vaccines is the speed at which they can be designed and produced.”

“This is why they lead the pack among the SARS-CoV-2 vaccine candidates and why the National Institute of Allergy and Infectious Diseases provided financial, technical, and/or clinical support. Indeed, once the amino acid sequence of a protein can be determined (a relatively easy task these days) it’s straightforward to synthesize mRNA in the lab — and it can be done incredibly fast,” he wrote.

The FDA allowed one waiver for panelist James K. Hildreth in connection with his personal relationship to a trial participant and his university’s participation in vaccine testing.

This article first appeared on Medscape.com.

Federal advisers on December 17 overwhelmingly recommended an emergency clearance to Moderna Inc’s COVID-19 vaccine, while noting concerns about potential allergic reactions and the challenges of continuing testing of this medicine.

The US Food and Drug Administration (FDA) put Moderna’s application before its Vaccines and Related Biological Products Advisory Committee. The panel voted 20-0 on this question: “Based on the totality of scientific evidence available, do the benefits of the Moderna COVID-19 Vaccine outweigh its risks for use in individuals 18 years of age and older?” There was one abstention.

The FDA is not bound to act on the recommendations of its advisers, but the agency usually takes the panel’s advice. The FDA cleared the similar Pfizer-BioNTech vaccine on December 11 through an emergency use authorization (EUA), following a positive vote for the product at a December 10 advisory committee meeting. In this case, the FDA staff appeared to be pushing for a broad endorsement of the Moderna vaccine, for which the agency appears likely to soon also grant an EUA.

Marion Gruber, PhD, director of the Office of Vaccines Research and Review at FDA’s Center for Biologics Evaluation and Research, earlier rebuffed attempts by some of the panelists to alter the voting question. Some panelists wanted to make tweaks, including a rephrasing to underscore the limited nature of an EUA, compared with a more complete approval through the biologics license application (BLA) process.

FDA panelist Michael Kurilla, MD, PhD, of the National Institutes of Health was the only panelist to abstain from voting. He said he was uncomfortable with the phrasing of the question.

“In the midst of a pandemic and with limited vaccine supply available, a blanket statement for individuals 18 years and older is just too broad,” he said. “I’m not convinced that for all of those age groups the benefits do actually outweigh the risks.”

In general, though, there was strong support for Moderna’s vaccine. FDA panelist James Hildreth Sr, MD, PhD, of Meharry Medical College in Nashville, Tennessee spoke of the “remarkable achievement” seen in having two vaccines ready for clearance by December for a virus that only emerged as a threat this year.

Study data indicate the primary efficacy endpoint demonstrated vaccine efficacy (VE) of 94.1% (95% CI, 89.3% - 96.8%) for the Moderna vaccine, with 11 COVID-19 cases in the vaccine group and 185 COVID-19 cases in the placebo group, the FDA staff noted during the meeting.

The advisers and FDA staff also honed in on several key issues with COVID-19 vaccines, including the challenge of having people in the placebo groups of studies seek to get cleared vaccines. Also of concern to the panel were early reports of allergic reactions seen with the Pfizer product.

Doran L. Fink, MD, PhD, an FDA official who has been closely involved with the COVID-19 vaccines, told the panel that two healthcare workers in Alaska had allergic reactions minutes after receiving the Pfizer vaccine, one of which was a case of anaphylactic reaction that resulted in hospitalization.

In the United Kingdom, there were two cases reported of notable allergic reactions, leading regulators there to issue a warning that people who have a history of significant allergic reactions should not currently receive the Pfizer-BioNTech vaccine.

The people involved in these incidents have recovered or are recovering, Fink said. But the FDA expects there will be additional reports of allergic reactions to COVID-19 vaccines.

“These cases underscores the need to remain vigilant during the early phase of the vaccination campaign,” Fink said. “To this end, FDA is working with Pfizer to further revise factsheets and prescribing information for their vaccine to draw attention to CDC guidelines for post- vaccination monitoring and management of immediate allergic reactions.”

mRNA vaccines in the lead

An FDA emergency clearance for Moderna’s product would be another vote of confidence in a new approach to making vaccines. Both the Pfizer-BioNTech and Moderna vaccines provide the immune system with a kind of blueprint in the form of genetic material, mRNA. The mRNA sets the stage for the synthesis of the signature spike protein that the SARS-CoV-2 virus uses to attach to and infect human cells.

In a December 15 commentary for this news organization Michael E. Pichichero, MD, wrote that the “revolutionary aspect of mRNA vaccines is the speed at which they can be designed and produced.”

“This is why they lead the pack among the SARS-CoV-2 vaccine candidates and why the National Institute of Allergy and Infectious Diseases provided financial, technical, and/or clinical support. Indeed, once the amino acid sequence of a protein can be determined (a relatively easy task these days) it’s straightforward to synthesize mRNA in the lab — and it can be done incredibly fast,” he wrote.

The FDA allowed one waiver for panelist James K. Hildreth in connection with his personal relationship to a trial participant and his university’s participation in vaccine testing.

This article first appeared on Medscape.com.

Individuals who have hypertension at any age are more likely to experience more rapid cognitive decline compared with their counterparts with normal blood pressure, new research shows. In a retrospective study of more than 15,000 participants, hypertension during middle age was associated with memory decline, and onset at later ages was linked to worsening memory and global cognition.

The investigators found that prehypertension, defined as systolic pressure of 120-139 mm Hg or diastolic pressure of 80-89 mm Hg, was also linked to accelerated cognitive decline.

Although duration of hypertension was not associated with any marker of cognitive decline, blood pressure control “can substantially reduce hypertension’s deleterious effect on the pace of cognitive decline,” said study investigator Sandhi M. Barreto, MD, PhD, professor of medicine at Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

The findings were published online Dec. 14 in Hypertension.
 

Unanswered questions

Hypertension is an established and highly prevalent risk factor for cognitive decline, but the age at which it begins to affect cognition is unclear. Previous research suggests that onset during middle age is associated with more harmful cognitive effects than onset in later life. One reason for this apparent difference may be that the duration of hypertension influences the magnitude of cognitive decline, the researchers noted.

Other studies have shown that prehypertension is associated with damage to certain organs, but its effects on cognition are uncertain. In addition, the effect of good blood pressure control with antihypertensive medications and the impact on cognition are also unclear.

To investigate, the researchers examined data from the ongoing, multicenter ELSA-Brasil study. ELSA-Brasil follows 15,105 civil servants between the ages of 35 and 74 years. Dr. Barreto and team assessed data from visit 1, which was conducted between 2008 and 2010, and visit 2, which was conducted between 2012 and 2014.

At each visit, participants underwent a memory test, a verbal fluency test, and the Trail Making Test Part B. The investigators calculated Z scores for these tests to derive a global cognitive score.

Blood pressure was measured on the right arm, and hypertension status, age at the time of hypertension diagnosis, duration of hypertension diagnosis, hypertension treatment, and control status were recorded. Other covariables included sex, education, race, smoking status, physical activity, body mass index, and total cholesterol level.

The researchers excluded patients who did not undergo cognitive testing at visit 2, those who had a history of stroke at baseline, and those who initiated antihypertensive medications despite having normotension. After exclusions, the analysis included 7,063 participants (approximately 55% were women, 15% were Black).

At visit 1, the mean age of the group was 58.9 years, and 53.4% of participants had 14 or more years of education. In addition, 22% had prehypertension, and 46.8% had hypertension. The median duration of hypertension was 7 years; 29.8% of participants with hypertension were diagnosed with the condition during middle age.

Of those who reported having hypertension at visit 1, 7.3% were not taking any antihypertensive medication. Among participants with hypertension who were taking antihypertensives, 31.2% had uncontrolled blood pressure.
 

Independent predictor

Results showed that prehypertension independently predicted a significantly greater decline in verbal fluency (Z score, –0.0095; P < .01) and global cognitive score (Z score, –0.0049; P < .05) compared with normal blood pressure.

At middle age, hypertension was associated with a steeper decline in memory (Z score, –0.0072; P < .05) compared with normal blood pressure. At older ages, hypertension was linked to a steeper decline in both memory (Z score, –0.0151; P < .001) and global cognitive score (Z score, –0.0080; P < .01). Duration of hypertension, however, did not significantly predict changes in cognition (P < .109).

Among those with hypertension who were taking antihypertensive medications, those with uncontrolled blood pressure experienced greater declines in rapid memory (Z score, –0.0126; P < .01) and global cognitive score (Z score, –0.0074; P < .01) than did those with controlled blood pressure.

The investigators noted that the study participants had a comparatively high level of education, which has been shown to “boost cognitive reserve and lessen the speed of age-related cognitive decline,” Dr. Barreto said. However, “our results indicate that the effect of hypertension on cognitive decline affects individuals of all educational levels similarly,” she said.

Dr. Barreto noted that the findings have two major clinical implications. First, “maintaining blood pressure below prehypertension levels is important to preserve cognitive function or delay cognitive decline,” she said. Secondly, “in hypertensive individuals, keeping blood pressure under control is essential to reduce the speed of cognitive decline.”

The researchers plan to conduct further analyses of the data to clarify the observed relationship between memory and verbal fluency. They also plan to examine how hypertension affects long-term executive function.
 

‘Continuum of risk’

Commenting on the study, Philip B. Gorelick, MD, MPH, adjunct professor of neurology (stroke and neurocritical care) at Northwestern University, Chicago, noted that, so far, research suggests that the risk for stroke associated with blood pressure levels should be understood as representing a continuum rather than as being associated with several discrete points.

“The same may hold true for cognitive decline and dementia. There may be a continuum of risk whereby persons even at so-called elevated but relatively lower levels of blood pressure based on a continuous scale are at risk,” said Dr. Gorelick, who was not involved with the current study.

The investigators relied on a large and well-studied population of civil servants. However, the population’s relative youth and high level of education may limit the generalizability of the findings, he noted. In addition, the follow-up time was relatively short.

“The hard endpoint of dementia was not studied but would be of interest to enhance our understanding of the influence of blood pressure elevation on cognitive decline or dementia during a longer follow-up of the cohort,” Dr. Gorelick said.

The findings also suggest the need to better understand mechanisms that link blood pressure elevation with cognitive decline, he added.

They indicate “the need for additional clinical trials to better elucidate blood pressure lowering targets for cognitive preservation in different groups of persons at risk,” such as those with normal cognition, those with mild cognitive impairment, and those with dementia, said Dr. Gorelick. “For example, is it safe and efficacious to lower blood pressure in persons with more advanced cognitive impairment or dementia?” he asked.

The study was funded by the Brazilian Coordination for the Improvement of Higher Education Personnel. Dr. Barreto has received support from the Research Agency of the State of Minas Gerais. Although Dr. Gorelick was not involved in the ELSA-Brasil cohort study, he serves on a data monitoring committee for a trial of a blood pressure–lowering agent in the preservation of cognition.

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

Individuals who have hypertension at any age are more likely to experience more rapid cognitive decline compared with their counterparts with normal blood pressure, new research shows. In a retrospective study of more than 15,000 participants, hypertension during middle age was associated with memory decline, and onset at later ages was linked to worsening memory and global cognition.

The investigators found that prehypertension, defined as systolic pressure of 120-139 mm Hg or diastolic pressure of 80-89 mm Hg, was also linked to accelerated cognitive decline.

Although duration of hypertension was not associated with any marker of cognitive decline, blood pressure control “can substantially reduce hypertension’s deleterious effect on the pace of cognitive decline,” said study investigator Sandhi M. Barreto, MD, PhD, professor of medicine at Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

The findings were published online Dec. 14 in Hypertension.
 

Unanswered questions

Hypertension is an established and highly prevalent risk factor for cognitive decline, but the age at which it begins to affect cognition is unclear. Previous research suggests that onset during middle age is associated with more harmful cognitive effects than onset in later life. One reason for this apparent difference may be that the duration of hypertension influences the magnitude of cognitive decline, the researchers noted.

Other studies have shown that prehypertension is associated with damage to certain organs, but its effects on cognition are uncertain. In addition, the effect of good blood pressure control with antihypertensive medications and the impact on cognition are also unclear.

To investigate, the researchers examined data from the ongoing, multicenter ELSA-Brasil study. ELSA-Brasil follows 15,105 civil servants between the ages of 35 and 74 years. Dr. Barreto and team assessed data from visit 1, which was conducted between 2008 and 2010, and visit 2, which was conducted between 2012 and 2014.

At each visit, participants underwent a memory test, a verbal fluency test, and the Trail Making Test Part B. The investigators calculated Z scores for these tests to derive a global cognitive score.

Blood pressure was measured on the right arm, and hypertension status, age at the time of hypertension diagnosis, duration of hypertension diagnosis, hypertension treatment, and control status were recorded. Other covariables included sex, education, race, smoking status, physical activity, body mass index, and total cholesterol level.

The researchers excluded patients who did not undergo cognitive testing at visit 2, those who had a history of stroke at baseline, and those who initiated antihypertensive medications despite having normotension. After exclusions, the analysis included 7,063 participants (approximately 55% were women, 15% were Black).

At visit 1, the mean age of the group was 58.9 years, and 53.4% of participants had 14 or more years of education. In addition, 22% had prehypertension, and 46.8% had hypertension. The median duration of hypertension was 7 years; 29.8% of participants with hypertension were diagnosed with the condition during middle age.

Of those who reported having hypertension at visit 1, 7.3% were not taking any antihypertensive medication. Among participants with hypertension who were taking antihypertensives, 31.2% had uncontrolled blood pressure.
 

Independent predictor

Results showed that prehypertension independently predicted a significantly greater decline in verbal fluency (Z score, –0.0095; P < .01) and global cognitive score (Z score, –0.0049; P < .05) compared with normal blood pressure.

At middle age, hypertension was associated with a steeper decline in memory (Z score, –0.0072; P < .05) compared with normal blood pressure. At older ages, hypertension was linked to a steeper decline in both memory (Z score, –0.0151; P < .001) and global cognitive score (Z score, –0.0080; P < .01). Duration of hypertension, however, did not significantly predict changes in cognition (P < .109).

Among those with hypertension who were taking antihypertensive medications, those with uncontrolled blood pressure experienced greater declines in rapid memory (Z score, –0.0126; P < .01) and global cognitive score (Z score, –0.0074; P < .01) than did those with controlled blood pressure.

The investigators noted that the study participants had a comparatively high level of education, which has been shown to “boost cognitive reserve and lessen the speed of age-related cognitive decline,” Dr. Barreto said. However, “our results indicate that the effect of hypertension on cognitive decline affects individuals of all educational levels similarly,” she said.

Dr. Barreto noted that the findings have two major clinical implications. First, “maintaining blood pressure below prehypertension levels is important to preserve cognitive function or delay cognitive decline,” she said. Secondly, “in hypertensive individuals, keeping blood pressure under control is essential to reduce the speed of cognitive decline.”

The researchers plan to conduct further analyses of the data to clarify the observed relationship between memory and verbal fluency. They also plan to examine how hypertension affects long-term executive function.
 

‘Continuum of risk’

Commenting on the study, Philip B. Gorelick, MD, MPH, adjunct professor of neurology (stroke and neurocritical care) at Northwestern University, Chicago, noted that, so far, research suggests that the risk for stroke associated with blood pressure levels should be understood as representing a continuum rather than as being associated with several discrete points.

“The same may hold true for cognitive decline and dementia. There may be a continuum of risk whereby persons even at so-called elevated but relatively lower levels of blood pressure based on a continuous scale are at risk,” said Dr. Gorelick, who was not involved with the current study.

The investigators relied on a large and well-studied population of civil servants. However, the population’s relative youth and high level of education may limit the generalizability of the findings, he noted. In addition, the follow-up time was relatively short.

“The hard endpoint of dementia was not studied but would be of interest to enhance our understanding of the influence of blood pressure elevation on cognitive decline or dementia during a longer follow-up of the cohort,” Dr. Gorelick said.

The findings also suggest the need to better understand mechanisms that link blood pressure elevation with cognitive decline, he added.

They indicate “the need for additional clinical trials to better elucidate blood pressure lowering targets for cognitive preservation in different groups of persons at risk,” such as those with normal cognition, those with mild cognitive impairment, and those with dementia, said Dr. Gorelick. “For example, is it safe and efficacious to lower blood pressure in persons with more advanced cognitive impairment or dementia?” he asked.

The study was funded by the Brazilian Coordination for the Improvement of Higher Education Personnel. Dr. Barreto has received support from the Research Agency of the State of Minas Gerais. Although Dr. Gorelick was not involved in the ELSA-Brasil cohort study, he serves on a data monitoring committee for a trial of a blood pressure–lowering agent in the preservation of cognition.

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

Individuals who have hypertension at any age are more likely to experience more rapid cognitive decline compared with their counterparts with normal blood pressure, new research shows. In a retrospective study of more than 15,000 participants, hypertension during middle age was associated with memory decline, and onset at later ages was linked to worsening memory and global cognition.

The investigators found that prehypertension, defined as systolic pressure of 120-139 mm Hg or diastolic pressure of 80-89 mm Hg, was also linked to accelerated cognitive decline.

Although duration of hypertension was not associated with any marker of cognitive decline, blood pressure control “can substantially reduce hypertension’s deleterious effect on the pace of cognitive decline,” said study investigator Sandhi M. Barreto, MD, PhD, professor of medicine at Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

The findings were published online Dec. 14 in Hypertension.
 

Unanswered questions

Hypertension is an established and highly prevalent risk factor for cognitive decline, but the age at which it begins to affect cognition is unclear. Previous research suggests that onset during middle age is associated with more harmful cognitive effects than onset in later life. One reason for this apparent difference may be that the duration of hypertension influences the magnitude of cognitive decline, the researchers noted.

Other studies have shown that prehypertension is associated with damage to certain organs, but its effects on cognition are uncertain. In addition, the effect of good blood pressure control with antihypertensive medications and the impact on cognition are also unclear.

To investigate, the researchers examined data from the ongoing, multicenter ELSA-Brasil study. ELSA-Brasil follows 15,105 civil servants between the ages of 35 and 74 years. Dr. Barreto and team assessed data from visit 1, which was conducted between 2008 and 2010, and visit 2, which was conducted between 2012 and 2014.

At each visit, participants underwent a memory test, a verbal fluency test, and the Trail Making Test Part B. The investigators calculated Z scores for these tests to derive a global cognitive score.

Blood pressure was measured on the right arm, and hypertension status, age at the time of hypertension diagnosis, duration of hypertension diagnosis, hypertension treatment, and control status were recorded. Other covariables included sex, education, race, smoking status, physical activity, body mass index, and total cholesterol level.

The researchers excluded patients who did not undergo cognitive testing at visit 2, those who had a history of stroke at baseline, and those who initiated antihypertensive medications despite having normotension. After exclusions, the analysis included 7,063 participants (approximately 55% were women, 15% were Black).

At visit 1, the mean age of the group was 58.9 years, and 53.4% of participants had 14 or more years of education. In addition, 22% had prehypertension, and 46.8% had hypertension. The median duration of hypertension was 7 years; 29.8% of participants with hypertension were diagnosed with the condition during middle age.

Of those who reported having hypertension at visit 1, 7.3% were not taking any antihypertensive medication. Among participants with hypertension who were taking antihypertensives, 31.2% had uncontrolled blood pressure.
 

Independent predictor

Results showed that prehypertension independently predicted a significantly greater decline in verbal fluency (Z score, –0.0095; P < .01) and global cognitive score (Z score, –0.0049; P < .05) compared with normal blood pressure.

At middle age, hypertension was associated with a steeper decline in memory (Z score, –0.0072; P < .05) compared with normal blood pressure. At older ages, hypertension was linked to a steeper decline in both memory (Z score, –0.0151; P < .001) and global cognitive score (Z score, –0.0080; P < .01). Duration of hypertension, however, did not significantly predict changes in cognition (P < .109).

Among those with hypertension who were taking antihypertensive medications, those with uncontrolled blood pressure experienced greater declines in rapid memory (Z score, –0.0126; P < .01) and global cognitive score (Z score, –0.0074; P < .01) than did those with controlled blood pressure.

The investigators noted that the study participants had a comparatively high level of education, which has been shown to “boost cognitive reserve and lessen the speed of age-related cognitive decline,” Dr. Barreto said. However, “our results indicate that the effect of hypertension on cognitive decline affects individuals of all educational levels similarly,” she said.

Dr. Barreto noted that the findings have two major clinical implications. First, “maintaining blood pressure below prehypertension levels is important to preserve cognitive function or delay cognitive decline,” she said. Secondly, “in hypertensive individuals, keeping blood pressure under control is essential to reduce the speed of cognitive decline.”

The researchers plan to conduct further analyses of the data to clarify the observed relationship between memory and verbal fluency. They also plan to examine how hypertension affects long-term executive function.
 

‘Continuum of risk’

Commenting on the study, Philip B. Gorelick, MD, MPH, adjunct professor of neurology (stroke and neurocritical care) at Northwestern University, Chicago, noted that, so far, research suggests that the risk for stroke associated with blood pressure levels should be understood as representing a continuum rather than as being associated with several discrete points.

“The same may hold true for cognitive decline and dementia. There may be a continuum of risk whereby persons even at so-called elevated but relatively lower levels of blood pressure based on a continuous scale are at risk,” said Dr. Gorelick, who was not involved with the current study.

The investigators relied on a large and well-studied population of civil servants. However, the population’s relative youth and high level of education may limit the generalizability of the findings, he noted. In addition, the follow-up time was relatively short.

“The hard endpoint of dementia was not studied but would be of interest to enhance our understanding of the influence of blood pressure elevation on cognitive decline or dementia during a longer follow-up of the cohort,” Dr. Gorelick said.

The findings also suggest the need to better understand mechanisms that link blood pressure elevation with cognitive decline, he added.

They indicate “the need for additional clinical trials to better elucidate blood pressure lowering targets for cognitive preservation in different groups of persons at risk,” such as those with normal cognition, those with mild cognitive impairment, and those with dementia, said Dr. Gorelick. “For example, is it safe and efficacious to lower blood pressure in persons with more advanced cognitive impairment or dementia?” he asked.

The study was funded by the Brazilian Coordination for the Improvement of Higher Education Personnel. Dr. Barreto has received support from the Research Agency of the State of Minas Gerais. Although Dr. Gorelick was not involved in the ELSA-Brasil cohort study, he serves on a data monitoring committee for a trial of a blood pressure–lowering agent in the preservation of cognition.

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

If the initial success of the Pfizer-BioNTech rollout continues, and emergency use authorization (EAU) is granted to Moderna and Johnson & Johnson vaccines in development, Operation Warp Speed officials expect to have 300 million doses of COVID-19 vaccines to distribute across the United States between now and March 31.

The initial rollout remains on track, said Alex Azar, US Department of Health and Human Services (HHS) secretary, during a media briefing today. “We continue to have good news to report. As of today, shipments of vaccine will have been delivered to every delivery site identified by public health jurisdictions for our first wave of shipments.”

Anomalies in shipments to California and Alabama arose when temperature monitors showed the Pfizer vaccine dropped lower than the recommended -80 ºC (-112 °F). These vaccine trays remained on delivery trucks and were returned to Pfizer for prompt replacement, said Operation Warp Speed Chief Operating Officer Gen. Gustave F. Perna.

Azar estimated another 2 million doses of the Pfizer vaccine will be available next week. “And if the Moderna vaccine is authorized by the FDA in the coming days, we have allocated nearly 5.9 million doses of that product.”

The Moderna vaccine data released this week look promising, said Moncef Slaoui, PhD, Operation Warp Speed chief scientific adviser. “In the short term, I expect the protection to be quite significant.”

The findings in the first 2 weeks after the first dose show up to 65% protection, he said, and predicted the second-dose efficacy data will be coming in the next few weeks.

Enrollment in the phase 3 Johnson & Johnson trial with nearly 44,000 participants is expected to end December 17. Initial efficacy results are anticipated by early January, with more complete efficacy numbers by late January, Slaoui said.

The AstraZeneca COVID-19 vaccine trial also is underway with enrollment continuing. “We expect accruement to end in late December or early next year, with first results expected probably in February,” Slaoui said.
 

Antibody treatments underutilized

The media briefing also addressed COVID-19 therapeutics. Azar reported low uptake of available antibody therapies. “I want to remind Americans that there are two authorized antibody treatments that Operation Warp Speed has supported. They can help prevent hospitalization in those patients with the highest risk for severe disease.”

The higher-risk group includes those who are 65 and older and people with comorbid conditions that put them at increased risk for COVID-19 hospitalization.

The federal government allocated more than 330,000 doses of these treatments and many states have product available, Azar said.

Slaoui agreed, saying there is a “disappointing level of usage of monoclonal antibody therapy in hospitals. We look forward to that improving.”
 

Up to 3 billion vaccine doses possible

“We now have more than 900 million doses of the vaccine we have contracted delivery for,” Azar said. The government has options to increase that to a total of 3 billion doses.

In addition to the 100 million Pfizer vaccine doses and 100 million Moderna doses already ordered, the government just took an option for another 100 million Moderna doses for the second quarter of 2021. Operation Warp Speed officials are negotiating with Pfizer for additional product as well.

Azar added that there are 100 million doses of the Johnson & Johnson vaccine in active production and expects AstraZeneca can provide 300 million doses of their product.

With the possibility of three or more vaccine products and with 330 million Americans, minus the 70 million or so children under age 16, “we believe we will actually have surplus supplies,” Azar said. Plans are to take the US surplus vaccine and surplus manufacturing capacity “and use that for the benefit of the world community.”

This article first appeared on Medscape.com.

If the initial success of the Pfizer-BioNTech rollout continues, and emergency use authorization (EAU) is granted to Moderna and Johnson & Johnson vaccines in development, Operation Warp Speed officials expect to have 300 million doses of COVID-19 vaccines to distribute across the United States between now and March 31.

The initial rollout remains on track, said Alex Azar, US Department of Health and Human Services (HHS) secretary, during a media briefing today. “We continue to have good news to report. As of today, shipments of vaccine will have been delivered to every delivery site identified by public health jurisdictions for our first wave of shipments.”

Anomalies in shipments to California and Alabama arose when temperature monitors showed the Pfizer vaccine dropped lower than the recommended -80 ºC (-112 °F). These vaccine trays remained on delivery trucks and were returned to Pfizer for prompt replacement, said Operation Warp Speed Chief Operating Officer Gen. Gustave F. Perna.

Azar estimated another 2 million doses of the Pfizer vaccine will be available next week. “And if the Moderna vaccine is authorized by the FDA in the coming days, we have allocated nearly 5.9 million doses of that product.”

The Moderna vaccine data released this week look promising, said Moncef Slaoui, PhD, Operation Warp Speed chief scientific adviser. “In the short term, I expect the protection to be quite significant.”

The findings in the first 2 weeks after the first dose show up to 65% protection, he said, and predicted the second-dose efficacy data will be coming in the next few weeks.

Enrollment in the phase 3 Johnson & Johnson trial with nearly 44,000 participants is expected to end December 17. Initial efficacy results are anticipated by early January, with more complete efficacy numbers by late January, Slaoui said.

The AstraZeneca COVID-19 vaccine trial also is underway with enrollment continuing. “We expect accruement to end in late December or early next year, with first results expected probably in February,” Slaoui said.
 

Antibody treatments underutilized

The media briefing also addressed COVID-19 therapeutics. Azar reported low uptake of available antibody therapies. “I want to remind Americans that there are two authorized antibody treatments that Operation Warp Speed has supported. They can help prevent hospitalization in those patients with the highest risk for severe disease.”

The higher-risk group includes those who are 65 and older and people with comorbid conditions that put them at increased risk for COVID-19 hospitalization.

The federal government allocated more than 330,000 doses of these treatments and many states have product available, Azar said.

Slaoui agreed, saying there is a “disappointing level of usage of monoclonal antibody therapy in hospitals. We look forward to that improving.”
 

Up to 3 billion vaccine doses possible

“We now have more than 900 million doses of the vaccine we have contracted delivery for,” Azar said. The government has options to increase that to a total of 3 billion doses.

In addition to the 100 million Pfizer vaccine doses and 100 million Moderna doses already ordered, the government just took an option for another 100 million Moderna doses for the second quarter of 2021. Operation Warp Speed officials are negotiating with Pfizer for additional product as well.

Azar added that there are 100 million doses of the Johnson & Johnson vaccine in active production and expects AstraZeneca can provide 300 million doses of their product.

With the possibility of three or more vaccine products and with 330 million Americans, minus the 70 million or so children under age 16, “we believe we will actually have surplus supplies,” Azar said. Plans are to take the US surplus vaccine and surplus manufacturing capacity “and use that for the benefit of the world community.”

This article first appeared on Medscape.com.

If the initial success of the Pfizer-BioNTech rollout continues, and emergency use authorization (EAU) is granted to Moderna and Johnson & Johnson vaccines in development, Operation Warp Speed officials expect to have 300 million doses of COVID-19 vaccines to distribute across the United States between now and March 31.

The initial rollout remains on track, said Alex Azar, US Department of Health and Human Services (HHS) secretary, during a media briefing today. “We continue to have good news to report. As of today, shipments of vaccine will have been delivered to every delivery site identified by public health jurisdictions for our first wave of shipments.”

Anomalies in shipments to California and Alabama arose when temperature monitors showed the Pfizer vaccine dropped lower than the recommended -80 ºC (-112 °F). These vaccine trays remained on delivery trucks and were returned to Pfizer for prompt replacement, said Operation Warp Speed Chief Operating Officer Gen. Gustave F. Perna.

Azar estimated another 2 million doses of the Pfizer vaccine will be available next week. “And if the Moderna vaccine is authorized by the FDA in the coming days, we have allocated nearly 5.9 million doses of that product.”

The Moderna vaccine data released this week look promising, said Moncef Slaoui, PhD, Operation Warp Speed chief scientific adviser. “In the short term, I expect the protection to be quite significant.”

The findings in the first 2 weeks after the first dose show up to 65% protection, he said, and predicted the second-dose efficacy data will be coming in the next few weeks.

Enrollment in the phase 3 Johnson & Johnson trial with nearly 44,000 participants is expected to end December 17. Initial efficacy results are anticipated by early January, with more complete efficacy numbers by late January, Slaoui said.

The AstraZeneca COVID-19 vaccine trial also is underway with enrollment continuing. “We expect accruement to end in late December or early next year, with first results expected probably in February,” Slaoui said.
 

Antibody treatments underutilized

The media briefing also addressed COVID-19 therapeutics. Azar reported low uptake of available antibody therapies. “I want to remind Americans that there are two authorized antibody treatments that Operation Warp Speed has supported. They can help prevent hospitalization in those patients with the highest risk for severe disease.”

The higher-risk group includes those who are 65 and older and people with comorbid conditions that put them at increased risk for COVID-19 hospitalization.

The federal government allocated more than 330,000 doses of these treatments and many states have product available, Azar said.

Slaoui agreed, saying there is a “disappointing level of usage of monoclonal antibody therapy in hospitals. We look forward to that improving.”
 

Up to 3 billion vaccine doses possible

“We now have more than 900 million doses of the vaccine we have contracted delivery for,” Azar said. The government has options to increase that to a total of 3 billion doses.

In addition to the 100 million Pfizer vaccine doses and 100 million Moderna doses already ordered, the government just took an option for another 100 million Moderna doses for the second quarter of 2021. Operation Warp Speed officials are negotiating with Pfizer for additional product as well.

Azar added that there are 100 million doses of the Johnson & Johnson vaccine in active production and expects AstraZeneca can provide 300 million doses of their product.

With the possibility of three or more vaccine products and with 330 million Americans, minus the 70 million or so children under age 16, “we believe we will actually have surplus supplies,” Azar said. Plans are to take the US surplus vaccine and surplus manufacturing capacity “and use that for the benefit of the world community.”

This article first appeared on Medscape.com.

Evidence continues to accumulate linking e-cigarettes to a range of lung diseases.

ArminStautBerlin/Thinkstock

Results from a large national prospective cohort study of adults demonstrated that the use of electronic cigarettes is associated with an increased risk of asthma, chronic obstructive pulmonary disease (COPD), emphysema, and chronic bronchitis – independent of cigarette smoking and other combustible tobacco product use.

“Our longitudinal results are consistent with the findings of prior population studies,” researchers led by Wubin Xie, DrPH, MPH, wrote in a study published online in JAMA Network Open. “With a more refined study design assessing multiple respiratory conditions and extensive sensitivity checks to mitigate bias from reverse causation and residual confounding by cigarette smoking and other tobacco product use, our results strengthen the evidence of the potential role of e-cigarette use in pulmonary disease pathogenesis. The findings may be used to inform counseling of patients on the potential risks of e-cigarette use.”

Dr. Xie of Boston University, and colleagues used data from the Population Assessment of Tobacco and Health (PATH) study waves 1-4 to examine the association of e-cigarette use with incident respiratory conditions, including COPD, emphysema, chronic bronchitis, and asthma. An earlier analysis of PATH data found an association between e-cigarette use with a composite respiratory disease outcome, but it did not consider the timing of respiratory events over follow-up and was underpowered to evaluate specific respiratory conditions.

The current analysis included data from 21,618 U.S. adults who were surveyed in four waves of PATH between 2013 and 2018. Of these, 49% were men, 65% were non-Hispanic White, 12% were non-Hispanic Black, 16% were Hispanic, and the remainder were non-Hispanic other. Their mean pack-years was 6.7 at baseline, 26% had self-reported hypertension, and their mean body mass index was 27.8 kg/m². The analysis was limited to data from the wave 1 cohort of adults and the prospective follow-up at waves 2-4 from public use files. It excluded adults who reported a history of a respiratory condition such as COPD, emphysema, chronic bronchitis, or asthma at wave 1 (baseline).

Two-thirds of respondents (66%) were never e-cigarette users, 12% were former e-cigarette users, and 5% were current e-cigarette users. After the researchers adjusted for cigarette and other combustible tobacco product use, demographic characteristics, and chronic health conditions, they observed an increased risk of respiratory disease among former e-cigarette users (incidence rate ratio, 1.28) and current e-cigarette users (IRR, 1.31). Among respondents with good self-reported health, the IRR for former e-cigarette users was 1.21 and the IRR for current e-cigarette users was 1.43. As for specific respiratory diseases among current e-cigarette users, the IRR was 1.33 for chronic bronchitis, 1.69 for emphysema, 1.57 for COPD, and 1.31 for asthma.

“Our findings on clinical outcome were consistent with studies assessing in vivo biomarkers of e-cigarette exposure in animal subjects, human participants, and population studies,” the authors wrote. “Studies have documented that exclusive e-cigarette use may be associated with higher exposure to harmful and potentially harmful constituents, compared with tobacco nonuse. The potential mechanisms of the association of e-cigarette exposure with pulmonary diseases include pulmonary inflammation, increased oxidative stress, and inhibited immune response. Animal studies have generated substantial evidence on e-cigarette exposure and emphysematous lung destruction, loss of pulmonary capillaries, reduced small airway function, and airway hyperresponsiveness, suggesting the plausibility of e-cigarettes causing chronic lung diseases.”

They acknowledged certain limitations of the study, including its reliance on self-reported measures of e-cigarette and other tobacco product use and its reliance on self-reported diagnoses of respiratory diseases.

The study was supported by grants from the National Heart, Lung, and Blood Institute; the Food and Drug Administration Center for Tobacco Products; and the American Lung Association Public Policy Research Award. Dr. Xie reported having no financial disclosures. His coauthors reported having received research grants and personal fees from a variety of sources.

SOURCE: Xie W et al. JAMA Netw Open. 2020 Nov 12. doi: 10.1001/jamanetworkopen.2020.20816

Evidence continues to accumulate linking e-cigarettes to a range of lung diseases.

ArminStautBerlin/Thinkstock

Results from a large national prospective cohort study of adults demonstrated that the use of electronic cigarettes is associated with an increased risk of asthma, chronic obstructive pulmonary disease (COPD), emphysema, and chronic bronchitis – independent of cigarette smoking and other combustible tobacco product use.

“Our longitudinal results are consistent with the findings of prior population studies,” researchers led by Wubin Xie, DrPH, MPH, wrote in a study published online in JAMA Network Open. “With a more refined study design assessing multiple respiratory conditions and extensive sensitivity checks to mitigate bias from reverse causation and residual confounding by cigarette smoking and other tobacco product use, our results strengthen the evidence of the potential role of e-cigarette use in pulmonary disease pathogenesis. The findings may be used to inform counseling of patients on the potential risks of e-cigarette use.”

Dr. Xie of Boston University, and colleagues used data from the Population Assessment of Tobacco and Health (PATH) study waves 1-4 to examine the association of e-cigarette use with incident respiratory conditions, including COPD, emphysema, chronic bronchitis, and asthma. An earlier analysis of PATH data found an association between e-cigarette use with a composite respiratory disease outcome, but it did not consider the timing of respiratory events over follow-up and was underpowered to evaluate specific respiratory conditions.

The current analysis included data from 21,618 U.S. adults who were surveyed in four waves of PATH between 2013 and 2018. Of these, 49% were men, 65% were non-Hispanic White, 12% were non-Hispanic Black, 16% were Hispanic, and the remainder were non-Hispanic other. Their mean pack-years was 6.7 at baseline, 26% had self-reported hypertension, and their mean body mass index was 27.8 kg/m². The analysis was limited to data from the wave 1 cohort of adults and the prospective follow-up at waves 2-4 from public use files. It excluded adults who reported a history of a respiratory condition such as COPD, emphysema, chronic bronchitis, or asthma at wave 1 (baseline).

Two-thirds of respondents (66%) were never e-cigarette users, 12% were former e-cigarette users, and 5% were current e-cigarette users. After the researchers adjusted for cigarette and other combustible tobacco product use, demographic characteristics, and chronic health conditions, they observed an increased risk of respiratory disease among former e-cigarette users (incidence rate ratio, 1.28) and current e-cigarette users (IRR, 1.31). Among respondents with good self-reported health, the IRR for former e-cigarette users was 1.21 and the IRR for current e-cigarette users was 1.43. As for specific respiratory diseases among current e-cigarette users, the IRR was 1.33 for chronic bronchitis, 1.69 for emphysema, 1.57 for COPD, and 1.31 for asthma.

“Our findings on clinical outcome were consistent with studies assessing in vivo biomarkers of e-cigarette exposure in animal subjects, human participants, and population studies,” the authors wrote. “Studies have documented that exclusive e-cigarette use may be associated with higher exposure to harmful and potentially harmful constituents, compared with tobacco nonuse. The potential mechanisms of the association of e-cigarette exposure with pulmonary diseases include pulmonary inflammation, increased oxidative stress, and inhibited immune response. Animal studies have generated substantial evidence on e-cigarette exposure and emphysematous lung destruction, loss of pulmonary capillaries, reduced small airway function, and airway hyperresponsiveness, suggesting the plausibility of e-cigarettes causing chronic lung diseases.”

They acknowledged certain limitations of the study, including its reliance on self-reported measures of e-cigarette and other tobacco product use and its reliance on self-reported diagnoses of respiratory diseases.

The study was supported by grants from the National Heart, Lung, and Blood Institute; the Food and Drug Administration Center for Tobacco Products; and the American Lung Association Public Policy Research Award. Dr. Xie reported having no financial disclosures. His coauthors reported having received research grants and personal fees from a variety of sources.

SOURCE: Xie W et al. JAMA Netw Open. 2020 Nov 12. doi: 10.1001/jamanetworkopen.2020.20816

Evidence continues to accumulate linking e-cigarettes to a range of lung diseases.

ArminStautBerlin/Thinkstock

Results from a large national prospective cohort study of adults demonstrated that the use of electronic cigarettes is associated with an increased risk of asthma, chronic obstructive pulmonary disease (COPD), emphysema, and chronic bronchitis – independent of cigarette smoking and other combustible tobacco product use.

“Our longitudinal results are consistent with the findings of prior population studies,” researchers led by Wubin Xie, DrPH, MPH, wrote in a study published online in JAMA Network Open. “With a more refined study design assessing multiple respiratory conditions and extensive sensitivity checks to mitigate bias from reverse causation and residual confounding by cigarette smoking and other tobacco product use, our results strengthen the evidence of the potential role of e-cigarette use in pulmonary disease pathogenesis. The findings may be used to inform counseling of patients on the potential risks of e-cigarette use.”

Dr. Xie of Boston University, and colleagues used data from the Population Assessment of Tobacco and Health (PATH) study waves 1-4 to examine the association of e-cigarette use with incident respiratory conditions, including COPD, emphysema, chronic bronchitis, and asthma. An earlier analysis of PATH data found an association between e-cigarette use with a composite respiratory disease outcome, but it did not consider the timing of respiratory events over follow-up and was underpowered to evaluate specific respiratory conditions.

The current analysis included data from 21,618 U.S. adults who were surveyed in four waves of PATH between 2013 and 2018. Of these, 49% were men, 65% were non-Hispanic White, 12% were non-Hispanic Black, 16% were Hispanic, and the remainder were non-Hispanic other. Their mean pack-years was 6.7 at baseline, 26% had self-reported hypertension, and their mean body mass index was 27.8 kg/m². The analysis was limited to data from the wave 1 cohort of adults and the prospective follow-up at waves 2-4 from public use files. It excluded adults who reported a history of a respiratory condition such as COPD, emphysema, chronic bronchitis, or asthma at wave 1 (baseline).

Two-thirds of respondents (66%) were never e-cigarette users, 12% were former e-cigarette users, and 5% were current e-cigarette users. After the researchers adjusted for cigarette and other combustible tobacco product use, demographic characteristics, and chronic health conditions, they observed an increased risk of respiratory disease among former e-cigarette users (incidence rate ratio, 1.28) and current e-cigarette users (IRR, 1.31). Among respondents with good self-reported health, the IRR for former e-cigarette users was 1.21 and the IRR for current e-cigarette users was 1.43. As for specific respiratory diseases among current e-cigarette users, the IRR was 1.33 for chronic bronchitis, 1.69 for emphysema, 1.57 for COPD, and 1.31 for asthma.

“Our findings on clinical outcome were consistent with studies assessing in vivo biomarkers of e-cigarette exposure in animal subjects, human participants, and population studies,” the authors wrote. “Studies have documented that exclusive e-cigarette use may be associated with higher exposure to harmful and potentially harmful constituents, compared with tobacco nonuse. The potential mechanisms of the association of e-cigarette exposure with pulmonary diseases include pulmonary inflammation, increased oxidative stress, and inhibited immune response. Animal studies have generated substantial evidence on e-cigarette exposure and emphysematous lung destruction, loss of pulmonary capillaries, reduced small airway function, and airway hyperresponsiveness, suggesting the plausibility of e-cigarettes causing chronic lung diseases.”

They acknowledged certain limitations of the study, including its reliance on self-reported measures of e-cigarette and other tobacco product use and its reliance on self-reported diagnoses of respiratory diseases.

The study was supported by grants from the National Heart, Lung, and Blood Institute; the Food and Drug Administration Center for Tobacco Products; and the American Lung Association Public Policy Research Award. Dr. Xie reported having no financial disclosures. His coauthors reported having received research grants and personal fees from a variety of sources.

SOURCE: Xie W et al. JAMA Netw Open. 2020 Nov 12. doi: 10.1001/jamanetworkopen.2020.20816

Coronavirus vaccines have become a reality, as they are now being approved and authorized for use in a growing number of countries including the United States. The U.S. Food and Drug Administration has just issued emergency authorization for the use of the COVID-19 vaccine produced by Pfizer and BioNTech. Close behind is the vaccine developed by Moderna, which has also applied to the FDA for emergency authorization.

scyther5/thinkstock

The efficacy of a two-dose administration of the vaccine has been pegged at 95.0%, and the FDA has said that the 95% credible interval for the vaccine efficacy was 90.3%-97.6%. But as with many initial clinical trials, whether for drugs or vaccines, not all populations were represented in the trial cohort, including individuals who are immunocompromised. At the current time, it is largely unknown how safe or effective the vaccine may be in this large population, many of whom are at high risk for serious COVID-19 complications.

At a special session held during the recent annual meeting of the American Society of Hematology, Anthony Fauci, MD, the nation’s leading infectious disease expert, said that individuals with compromised immune systems, whether because of chemotherapy or a bone marrow transplant, should plan to be vaccinated when the opportunity arises.

In response to a question from ASH President Stephanie J. Lee, MD, of the Fred Hutchinson Cancer Center, Seattle, Dr. Fauci emphasized that, despite being excluded from clinical trials, this population should get vaccinated. “I think we should recommend that they get vaccinated,” he said. “I mean, it is clear that, if you are on immunosuppressive agents, history tells us that you’re not going to have as robust a response as if you had an intact immune system that was not being compromised. But some degree of immunity is better than no degree of immunity.”

That does seem to be the consensus among experts who spoke in interviews: that as long as these are not live attenuated vaccines, they hold no specific risk to an immunocompromised patient, other than any factors specific to the individual that could be a contraindication.

“Patients, family members, friends, and work contacts should be encouraged to receive the vaccine,” said William Stohl, MD, PhD, chief of the division of rheumatology at the University of Southern California, Los Angeles. “Clinicians should advise patients to obtain the vaccine sooner rather than later.”
 

Kevin C. Wang, MD, PhD, of the department of dermatology at Stanford (Calif.) University, agreed. “I am 100% with Dr. Fauci. Everyone should get the vaccine, even if it may not be as effective,” he said. “I would treat it exactly like the flu vaccines that we recommend folks get every year.”

Dr. Wang noted that he couldn’t think of any contraindications unless the immunosuppressed patients have a history of severe allergic reactions to prior vaccinations. “But I would even say patients with history of cancer, upon recommendation of their oncologists, are likely to be suitable candidates for the vaccine,” he added. “I would say clinicians should approach counseling the same way they counsel patients for the flu vaccine, and as far as I know, there are no concerns for systemic drugs commonly used in dermatology patients.”

However, guidance has not yet been issued from either the FDA or the Centers for Disease Control and Prevention regarding the use of the vaccine in immunocompromised individuals. Given the lack of data, the FDA has said that “it will be something that providers will need to consider on an individual basis,” and that individuals should consult with physicians to weigh the potential benefits and potential risks.

The CDC’s Advisory Committee on Immunization Practices has said that clinicians need more guidance on whether to use the vaccine in pregnant or breastfeeding women, the immunocompromised, or those who have a history of allergies. The CDC itself has not yet released its formal guidance on vaccine use.


 

COVID-19 vaccines

Vaccines typically require years of research and testing before reaching the clinic, but this year researchers embarked on a global effort to develop safe and effective coronavirus vaccines in record time. Both the Pfizer/BioNTech and Moderna vaccines have only a few months of phase 3 clinical trial data, so much remains unknown about them, including their duration of effect and any long-term safety signals. In addition to excluding immunocompromised individuals, the clinical trials did not include children or pregnant women, so data are lacking for several population subgroups.

But these will not be the only vaccines available, as the pipeline is already becoming crowded. U.S. clinical trial data from a vaccine jointly being developed by Oxford-AstraZeneca, could potentially be ready, along with a request for FDA emergency use authorization, by late January 2021.

In addition, China and Russia have released vaccines, and there are currently 61 vaccines being investigated in clinical trials and at least 85 preclinical products under active investigation.

The vaccine candidates are using both conventional and novel mechanisms of action to elicit an immune response in patients. Conventional methods include attenuated inactivated (killed) virus and recombinant viral protein vaccines to develop immunity. Novel approaches include replication-deficient, adenovirus vector-based vaccines that contain the viral protein, and mRNA-based vaccines, such as the Pfizer and Moderna vaccines, that encode for a SARS-CoV-2 spike protein.

“The special vaccine concern for immunocompromised individuals is introduction of a live virus,” Dr. Stohl said. “Neither the Moderna nor Pfizer vaccines are live viruses, so there should be no special contraindication for such individuals.”

Live vaccine should be avoided in immunocompromised patients, and currently, live SARS-CoV-2 vaccines are only being developed in India and Turkey.

It is not unusual for vaccine trials to begin with cohorts that exclude participants with various health conditions, including those who are immunocompromised. These groups are generally then evaluated in phase 4 trials, or postmarketing surveillance. While the precise number of immunosuppressed adults in the United States is not known, the numbers are believed to be rising because of increased life expectancy among immunosuppressed adults as a result of advances in treatment and new and wider indications for therapies that can affect the immune system.

According to data from the 2013 National Health Interview Survey, an estimated 2.7% of U.S. adults are immunosuppressed. This population covers a broad array of health conditions and medical specialties; people living with inflammatory or autoimmune conditions, such as inflammatory rheumatic diseases (rheumatoid arthritis, axial spondyloarthritis, lupus); inflammatory bowel disease (Crohn’s disease and ulcerative colitis); psoriasis; multiple sclerosis; organ transplant recipients; patients undergoing chemotherapy; and life-long immunosuppression attributable to HIV infection.

As the vaccines begin to roll out and become available, how should clinicians advise their patients, in the absence of any clinical trial data?


 

Risk vs. benefit

Gilaad Kaplan, MD, MPH, a gastroenterologist and professor of medicine at the University of Calgary (Alta.), noted that the inflammatory bowel disease (IBD) community has dealt with tremendous anxiety during the pandemic because many are immunocompromised because of the medications they use to treat their disease.

“For example, many patients with IBD are on biologics like anti-TNF [tumor necrosis factor] therapies, which are also used in other immune-mediated inflammatory diseases such as rheumatoid arthritis,” he said. “Understandably, individuals with IBD on immunosuppressive medications are concerned about the risk of severe complications due to COVID-19.”

The entire IBD community, along with the world, celebrated the announcement that multiple vaccines are protective against SARS-CoV-2, he noted. “Vaccines offer the potential to reduce the spread of COVID-19, allowing society to revert back to normalcy,” Dr. Kaplan said. “Moreover, for vulnerable populations, including those who are immunocompromised, vaccines offer the potential to directly protect them from the morbidity and mortality associated with COVID-19.”

That said, even though the news of vaccines are extremely promising, some cautions must be raised regarding their use in immunocompromised populations, such as persons with IBD. “The current trials, to my knowledge, did not include immunocompromised individuals and thus, we can only extrapolate from what we know from other trials of different vaccines,” he explained. “We know from prior vaccines studies that the immune response following vaccination is less robust in those who are immunocompromised as compared to a healthy control population.”

Dr. Kaplan also pointed to recent reports of allergic reactions that have been reported in healthy individuals. “We don’t know whether side effects, like allergic reactions, may be different in unstudied populations,” he said. “Thus, the medical and scientific community should prioritize clinical studies of safety and effectiveness of COVID-19 vaccines in immunocompromised populations.”

So, what does this mean for an individual with an immune-mediated inflammatory disease like Crohn’s disease or ulcerative colitis who is immunocompromised? Dr. Kaplan explained that it is a balance between the potential harm of being infected with COVID-19 and the uncertainty of receiving a vaccine in an understudied population. For those who are highly susceptible to dying from COVID-19, such as an older adult with IBD, or someone who faces high exposure, such as a health care worker, the potential protection of the vaccine greatly outweighs the uncertainty.

“However, for individuals who are at otherwise lower risk – for example, young and able to work from home – then waiting a few extra months for postmarketing surveillance studies in immunocompromised populations may be a reasonable approach, as long as these individuals are taking great care to avoid infection,” he said.
 

No waiting needed

Joel M. Gelfand, MD, MSCE, professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia, feels that the newly approved vaccine should be safe for most of his patients.

“Patients with psoriatic disease should get the mRNA-based COVID-19 vaccine as soon as possible based on eligibility as determined by the CDC and local public health officials,” he said. “It is not a live vaccine, and therefore patients on biologics or other immune-modulating or immune-suppressing treatment can receive it.”

However, the impact of psoriasis treatment on immune response to the mRNA-based vaccines is not known. Dr. Gelfand noted that, extrapolating from the vaccine literature, there is some evidence that methotrexate reduces response to the influenza vaccine. “However, the clinical significance of this finding is not clear,” he said. “Since the mRNA vaccine needs to be taken twice, a few weeks apart, I do not recommend interrupting or delaying treatment for psoriatic disease while undergoing vaccination for COVID-19.”

Given the reports of allergic reactions, he added that it is advisable for patients with a history of life-threatening allergic reactions such as anaphylaxis or who have been advised to carry an epinephrine autoinjector, to talk with their health care provider to determine if COVID-19 vaccination is medically appropriate.

The National Psoriasis Foundation has issued guidance on COVID-19, explained Steven R. Feldman, MD, PhD, professor of dermatology, pathology, and social sciences & health policy at Wake Forest University, Winston-Salem, N.C., who is also a member of the committee that is working on those guidelines and keeping them up to date. “We are in the process of updating the guidelines with information on COVID vaccines,” he said.

He agreed that there are no contraindications for psoriasis patients to receive the vaccine, regardless of whether they are on immunosuppressive treatment, even though definitive data are lacking. “Fortunately, there’s a lot of good data coming out of Italy that patients with psoriasis on biologics do not appear to be at increased risk of getting COVID or of having worse outcomes from COVID,” he said.

Patients are going to ask about the vaccines, and when counseling them, clinicians should discuss the available data, the residual uncertainty, and patients’ concerns should be considered, Dr. Feldman explained. “There may be some concern that steroids and cyclosporine would reduce the effectiveness of vaccines, but there is no concern that any of the drugs would cause increased risk from nonlive vaccines.”

He added that there is evidence that “patients on biologics who receive nonlive vaccines do develop antibody responses and are immunized.”


 

Boosting efficacy

Even prior to making their announcement, the American College of Rheumatology had said that they would endorse the vaccine for all patients, explained rheumatologist Brett Smith, DO, from Blount Memorial Physicians Group and East Tennessee Children’s Hospital, Alcoa. “The vaccine is safe for all patients, but the problem may be that it’s not as effective,” he said. “But we don’t know that because it hasn’t been tested.”

With other vaccines, biologic medicines are held for 2 weeks before and afterwards, to get the best response. “But some patients don’t want to stop the medication,” Dr. Smith said. “They are afraid that their symptoms will return.”

As for counseling patients as to whether they should receive this vaccine, he explained that he typically doesn’t try to sway patients one way or another until they are really high risk. “When I counsel, it really depends on the individual situation. And for this vaccine, we have to be open to the fact that many people have already made up their mind.”

There are a lot of questions regarding the vaccine. One is the short time frame of development. “Vaccines typically take 6-10 years to come on the market, and this one is now available after a 3-month study,” Dr. Smith said. “Some have already decided that it’s too new for them.”

The process is also new, and patients need to understand that it doesn’t contain an active virus and “you can’t catch coronavirus from it.”

Dr. Smith also explained that, because the vaccine may be less effective in a person using biologic therapies, there is currently no information available on repeat vaccination. “These are all unanswered questions,” he said. “If the antibodies wane in a short time, can we be revaccinated and in what time frame? We just don’t know that yet.”

Marcelo Bonomi, MD, a medical oncologist from The Ohio State University Comprehensive Cancer Center, Columbus, explained that one way to ensure a more optimal response to the vaccine would be to wait until the patient has finished chemotherapy.* “The vaccine can be offered at that time, and in the meantime, they can take other steps to avoid infection,” he said. “If they are very immunosuppressed, it isn’t worth trying to give the vaccine.”

Cancer patients should be encouraged to stay as healthy as possible, and to wear masks and social distance. “It’s a comprehensive approach. Eat healthy, avoid alcohol and tobacco, and exercise. [These things] will help boost the immune system,” Dr. Bonomi said. “Family members should be encouraged to get vaccinated, which will help them avoid infection and exposing the patient.”

Jim Boonyaratanakornkit, MD, PhD, an infectious disease specialist who cares for cancer patients at the Fred Hutchinson Cancer Research Center, agreed. “Giving a vaccine right after a transplant is a futile endeavor,” he said. “We need to wait 6 months to have an immune response.”

He pointed out there may be a continuing higher number of cases, with high levels peaking in Washington in February and March. “Close friends and family should be vaccinated if possible,” he said, “which will help interrupt transmission.”

The vaccines are using new platforms that are totally different, and there is no clear data as to how long the antibodies will persist. “We know that they last for at least 4 months,” said Dr. Boonyaratanakornkit. “We don’t know what level of antibody will protect them from COVID-19 infection. Current studies are being conducted, but we don’t have that information for anyone yet.”
 

*Correction, 1/7/21: An earlier version of this article misattributed quotes from Dr. Marcelo Bonomi.

Coronavirus vaccines have become a reality, as they are now being approved and authorized for use in a growing number of countries including the United States. The U.S. Food and Drug Administration has just issued emergency authorization for the use of the COVID-19 vaccine produced by Pfizer and BioNTech. Close behind is the vaccine developed by Moderna, which has also applied to the FDA for emergency authorization.

scyther5/thinkstock

The efficacy of a two-dose administration of the vaccine has been pegged at 95.0%, and the FDA has said that the 95% credible interval for the vaccine efficacy was 90.3%-97.6%. But as with many initial clinical trials, whether for drugs or vaccines, not all populations were represented in the trial cohort, including individuals who are immunocompromised. At the current time, it is largely unknown how safe or effective the vaccine may be in this large population, many of whom are at high risk for serious COVID-19 complications.

At a special session held during the recent annual meeting of the American Society of Hematology, Anthony Fauci, MD, the nation’s leading infectious disease expert, said that individuals with compromised immune systems, whether because of chemotherapy or a bone marrow transplant, should plan to be vaccinated when the opportunity arises.

In response to a question from ASH President Stephanie J. Lee, MD, of the Fred Hutchinson Cancer Center, Seattle, Dr. Fauci emphasized that, despite being excluded from clinical trials, this population should get vaccinated. “I think we should recommend that they get vaccinated,” he said. “I mean, it is clear that, if you are on immunosuppressive agents, history tells us that you’re not going to have as robust a response as if you had an intact immune system that was not being compromised. But some degree of immunity is better than no degree of immunity.”

That does seem to be the consensus among experts who spoke in interviews: that as long as these are not live attenuated vaccines, they hold no specific risk to an immunocompromised patient, other than any factors specific to the individual that could be a contraindication.

“Patients, family members, friends, and work contacts should be encouraged to receive the vaccine,” said William Stohl, MD, PhD, chief of the division of rheumatology at the University of Southern California, Los Angeles. “Clinicians should advise patients to obtain the vaccine sooner rather than later.”
 

Kevin C. Wang, MD, PhD, of the department of dermatology at Stanford (Calif.) University, agreed. “I am 100% with Dr. Fauci. Everyone should get the vaccine, even if it may not be as effective,” he said. “I would treat it exactly like the flu vaccines that we recommend folks get every year.”

Dr. Wang noted that he couldn’t think of any contraindications unless the immunosuppressed patients have a history of severe allergic reactions to prior vaccinations. “But I would even say patients with history of cancer, upon recommendation of their oncologists, are likely to be suitable candidates for the vaccine,” he added. “I would say clinicians should approach counseling the same way they counsel patients for the flu vaccine, and as far as I know, there are no concerns for systemic drugs commonly used in dermatology patients.”

However, guidance has not yet been issued from either the FDA or the Centers for Disease Control and Prevention regarding the use of the vaccine in immunocompromised individuals. Given the lack of data, the FDA has said that “it will be something that providers will need to consider on an individual basis,” and that individuals should consult with physicians to weigh the potential benefits and potential risks.

The CDC’s Advisory Committee on Immunization Practices has said that clinicians need more guidance on whether to use the vaccine in pregnant or breastfeeding women, the immunocompromised, or those who have a history of allergies. The CDC itself has not yet released its formal guidance on vaccine use.


 

COVID-19 vaccines

Vaccines typically require years of research and testing before reaching the clinic, but this year researchers embarked on a global effort to develop safe and effective coronavirus vaccines in record time. Both the Pfizer/BioNTech and Moderna vaccines have only a few months of phase 3 clinical trial data, so much remains unknown about them, including their duration of effect and any long-term safety signals. In addition to excluding immunocompromised individuals, the clinical trials did not include children or pregnant women, so data are lacking for several population subgroups.

But these will not be the only vaccines available, as the pipeline is already becoming crowded. U.S. clinical trial data from a vaccine jointly being developed by Oxford-AstraZeneca, could potentially be ready, along with a request for FDA emergency use authorization, by late January 2021.

In addition, China and Russia have released vaccines, and there are currently 61 vaccines being investigated in clinical trials and at least 85 preclinical products under active investigation.

The vaccine candidates are using both conventional and novel mechanisms of action to elicit an immune response in patients. Conventional methods include attenuated inactivated (killed) virus and recombinant viral protein vaccines to develop immunity. Novel approaches include replication-deficient, adenovirus vector-based vaccines that contain the viral protein, and mRNA-based vaccines, such as the Pfizer and Moderna vaccines, that encode for a SARS-CoV-2 spike protein.

“The special vaccine concern for immunocompromised individuals is introduction of a live virus,” Dr. Stohl said. “Neither the Moderna nor Pfizer vaccines are live viruses, so there should be no special contraindication for such individuals.”

Live vaccine should be avoided in immunocompromised patients, and currently, live SARS-CoV-2 vaccines are only being developed in India and Turkey.

It is not unusual for vaccine trials to begin with cohorts that exclude participants with various health conditions, including those who are immunocompromised. These groups are generally then evaluated in phase 4 trials, or postmarketing surveillance. While the precise number of immunosuppressed adults in the United States is not known, the numbers are believed to be rising because of increased life expectancy among immunosuppressed adults as a result of advances in treatment and new and wider indications for therapies that can affect the immune system.

According to data from the 2013 National Health Interview Survey, an estimated 2.7% of U.S. adults are immunosuppressed. This population covers a broad array of health conditions and medical specialties; people living with inflammatory or autoimmune conditions, such as inflammatory rheumatic diseases (rheumatoid arthritis, axial spondyloarthritis, lupus); inflammatory bowel disease (Crohn’s disease and ulcerative colitis); psoriasis; multiple sclerosis; organ transplant recipients; patients undergoing chemotherapy; and life-long immunosuppression attributable to HIV infection.

As the vaccines begin to roll out and become available, how should clinicians advise their patients, in the absence of any clinical trial data?


 

Risk vs. benefit

Gilaad Kaplan, MD, MPH, a gastroenterologist and professor of medicine at the University of Calgary (Alta.), noted that the inflammatory bowel disease (IBD) community has dealt with tremendous anxiety during the pandemic because many are immunocompromised because of the medications they use to treat their disease.

“For example, many patients with IBD are on biologics like anti-TNF [tumor necrosis factor] therapies, which are also used in other immune-mediated inflammatory diseases such as rheumatoid arthritis,” he said. “Understandably, individuals with IBD on immunosuppressive medications are concerned about the risk of severe complications due to COVID-19.”

The entire IBD community, along with the world, celebrated the announcement that multiple vaccines are protective against SARS-CoV-2, he noted. “Vaccines offer the potential to reduce the spread of COVID-19, allowing society to revert back to normalcy,” Dr. Kaplan said. “Moreover, for vulnerable populations, including those who are immunocompromised, vaccines offer the potential to directly protect them from the morbidity and mortality associated with COVID-19.”

That said, even though the news of vaccines are extremely promising, some cautions must be raised regarding their use in immunocompromised populations, such as persons with IBD. “The current trials, to my knowledge, did not include immunocompromised individuals and thus, we can only extrapolate from what we know from other trials of different vaccines,” he explained. “We know from prior vaccines studies that the immune response following vaccination is less robust in those who are immunocompromised as compared to a healthy control population.”

Dr. Kaplan also pointed to recent reports of allergic reactions that have been reported in healthy individuals. “We don’t know whether side effects, like allergic reactions, may be different in unstudied populations,” he said. “Thus, the medical and scientific community should prioritize clinical studies of safety and effectiveness of COVID-19 vaccines in immunocompromised populations.”

So, what does this mean for an individual with an immune-mediated inflammatory disease like Crohn’s disease or ulcerative colitis who is immunocompromised? Dr. Kaplan explained that it is a balance between the potential harm of being infected with COVID-19 and the uncertainty of receiving a vaccine in an understudied population. For those who are highly susceptible to dying from COVID-19, such as an older adult with IBD, or someone who faces high exposure, such as a health care worker, the potential protection of the vaccine greatly outweighs the uncertainty.

“However, for individuals who are at otherwise lower risk – for example, young and able to work from home – then waiting a few extra months for postmarketing surveillance studies in immunocompromised populations may be a reasonable approach, as long as these individuals are taking great care to avoid infection,” he said.
 

No waiting needed

Joel M. Gelfand, MD, MSCE, professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia, feels that the newly approved vaccine should be safe for most of his patients.

“Patients with psoriatic disease should get the mRNA-based COVID-19 vaccine as soon as possible based on eligibility as determined by the CDC and local public health officials,” he said. “It is not a live vaccine, and therefore patients on biologics or other immune-modulating or immune-suppressing treatment can receive it.”

However, the impact of psoriasis treatment on immune response to the mRNA-based vaccines is not known. Dr. Gelfand noted that, extrapolating from the vaccine literature, there is some evidence that methotrexate reduces response to the influenza vaccine. “However, the clinical significance of this finding is not clear,” he said. “Since the mRNA vaccine needs to be taken twice, a few weeks apart, I do not recommend interrupting or delaying treatment for psoriatic disease while undergoing vaccination for COVID-19.”

Given the reports of allergic reactions, he added that it is advisable for patients with a history of life-threatening allergic reactions such as anaphylaxis or who have been advised to carry an epinephrine autoinjector, to talk with their health care provider to determine if COVID-19 vaccination is medically appropriate.

The National Psoriasis Foundation has issued guidance on COVID-19, explained Steven R. Feldman, MD, PhD, professor of dermatology, pathology, and social sciences & health policy at Wake Forest University, Winston-Salem, N.C., who is also a member of the committee that is working on those guidelines and keeping them up to date. “We are in the process of updating the guidelines with information on COVID vaccines,” he said.

He agreed that there are no contraindications for psoriasis patients to receive the vaccine, regardless of whether they are on immunosuppressive treatment, even though definitive data are lacking. “Fortunately, there’s a lot of good data coming out of Italy that patients with psoriasis on biologics do not appear to be at increased risk of getting COVID or of having worse outcomes from COVID,” he said.

Patients are going to ask about the vaccines, and when counseling them, clinicians should discuss the available data, the residual uncertainty, and patients’ concerns should be considered, Dr. Feldman explained. “There may be some concern that steroids and cyclosporine would reduce the effectiveness of vaccines, but there is no concern that any of the drugs would cause increased risk from nonlive vaccines.”

He added that there is evidence that “patients on biologics who receive nonlive vaccines do develop antibody responses and are immunized.”


 

Boosting efficacy

Even prior to making their announcement, the American College of Rheumatology had said that they would endorse the vaccine for all patients, explained rheumatologist Brett Smith, DO, from Blount Memorial Physicians Group and East Tennessee Children’s Hospital, Alcoa. “The vaccine is safe for all patients, but the problem may be that it’s not as effective,” he said. “But we don’t know that because it hasn’t been tested.”

With other vaccines, biologic medicines are held for 2 weeks before and afterwards, to get the best response. “But some patients don’t want to stop the medication,” Dr. Smith said. “They are afraid that their symptoms will return.”

As for counseling patients as to whether they should receive this vaccine, he explained that he typically doesn’t try to sway patients one way or another until they are really high risk. “When I counsel, it really depends on the individual situation. And for this vaccine, we have to be open to the fact that many people have already made up their mind.”

There are a lot of questions regarding the vaccine. One is the short time frame of development. “Vaccines typically take 6-10 years to come on the market, and this one is now available after a 3-month study,” Dr. Smith said. “Some have already decided that it’s too new for them.”

The process is also new, and patients need to understand that it doesn’t contain an active virus and “you can’t catch coronavirus from it.”

Dr. Smith also explained that, because the vaccine may be less effective in a person using biologic therapies, there is currently no information available on repeat vaccination. “These are all unanswered questions,” he said. “If the antibodies wane in a short time, can we be revaccinated and in what time frame? We just don’t know that yet.”

Marcelo Bonomi, MD, a medical oncologist from The Ohio State University Comprehensive Cancer Center, Columbus, explained that one way to ensure a more optimal response to the vaccine would be to wait until the patient has finished chemotherapy.* “The vaccine can be offered at that time, and in the meantime, they can take other steps to avoid infection,” he said. “If they are very immunosuppressed, it isn’t worth trying to give the vaccine.”

Cancer patients should be encouraged to stay as healthy as possible, and to wear masks and social distance. “It’s a comprehensive approach. Eat healthy, avoid alcohol and tobacco, and exercise. [These things] will help boost the immune system,” Dr. Bonomi said. “Family members should be encouraged to get vaccinated, which will help them avoid infection and exposing the patient.”

Jim Boonyaratanakornkit, MD, PhD, an infectious disease specialist who cares for cancer patients at the Fred Hutchinson Cancer Research Center, agreed. “Giving a vaccine right after a transplant is a futile endeavor,” he said. “We need to wait 6 months to have an immune response.”

He pointed out there may be a continuing higher number of cases, with high levels peaking in Washington in February and March. “Close friends and family should be vaccinated if possible,” he said, “which will help interrupt transmission.”

The vaccines are using new platforms that are totally different, and there is no clear data as to how long the antibodies will persist. “We know that they last for at least 4 months,” said Dr. Boonyaratanakornkit. “We don’t know what level of antibody will protect them from COVID-19 infection. Current studies are being conducted, but we don’t have that information for anyone yet.”
 

*Correction, 1/7/21: An earlier version of this article misattributed quotes from Dr. Marcelo Bonomi.

Coronavirus vaccines have become a reality, as they are now being approved and authorized for use in a growing number of countries including the United States. The U.S. Food and Drug Administration has just issued emergency authorization for the use of the COVID-19 vaccine produced by Pfizer and BioNTech. Close behind is the vaccine developed by Moderna, which has also applied to the FDA for emergency authorization.

scyther5/thinkstock

The efficacy of a two-dose administration of the vaccine has been pegged at 95.0%, and the FDA has said that the 95% credible interval for the vaccine efficacy was 90.3%-97.6%. But as with many initial clinical trials, whether for drugs or vaccines, not all populations were represented in the trial cohort, including individuals who are immunocompromised. At the current time, it is largely unknown how safe or effective the vaccine may be in this large population, many of whom are at high risk for serious COVID-19 complications.

At a special session held during the recent annual meeting of the American Society of Hematology, Anthony Fauci, MD, the nation’s leading infectious disease expert, said that individuals with compromised immune systems, whether because of chemotherapy or a bone marrow transplant, should plan to be vaccinated when the opportunity arises.

In response to a question from ASH President Stephanie J. Lee, MD, of the Fred Hutchinson Cancer Center, Seattle, Dr. Fauci emphasized that, despite being excluded from clinical trials, this population should get vaccinated. “I think we should recommend that they get vaccinated,” he said. “I mean, it is clear that, if you are on immunosuppressive agents, history tells us that you’re not going to have as robust a response as if you had an intact immune system that was not being compromised. But some degree of immunity is better than no degree of immunity.”

That does seem to be the consensus among experts who spoke in interviews: that as long as these are not live attenuated vaccines, they hold no specific risk to an immunocompromised patient, other than any factors specific to the individual that could be a contraindication.

“Patients, family members, friends, and work contacts should be encouraged to receive the vaccine,” said William Stohl, MD, PhD, chief of the division of rheumatology at the University of Southern California, Los Angeles. “Clinicians should advise patients to obtain the vaccine sooner rather than later.”
 

Kevin C. Wang, MD, PhD, of the department of dermatology at Stanford (Calif.) University, agreed. “I am 100% with Dr. Fauci. Everyone should get the vaccine, even if it may not be as effective,” he said. “I would treat it exactly like the flu vaccines that we recommend folks get every year.”

Dr. Wang noted that he couldn’t think of any contraindications unless the immunosuppressed patients have a history of severe allergic reactions to prior vaccinations. “But I would even say patients with history of cancer, upon recommendation of their oncologists, are likely to be suitable candidates for the vaccine,” he added. “I would say clinicians should approach counseling the same way they counsel patients for the flu vaccine, and as far as I know, there are no concerns for systemic drugs commonly used in dermatology patients.”

However, guidance has not yet been issued from either the FDA or the Centers for Disease Control and Prevention regarding the use of the vaccine in immunocompromised individuals. Given the lack of data, the FDA has said that “it will be something that providers will need to consider on an individual basis,” and that individuals should consult with physicians to weigh the potential benefits and potential risks.

The CDC’s Advisory Committee on Immunization Practices has said that clinicians need more guidance on whether to use the vaccine in pregnant or breastfeeding women, the immunocompromised, or those who have a history of allergies. The CDC itself has not yet released its formal guidance on vaccine use.


 

COVID-19 vaccines

Vaccines typically require years of research and testing before reaching the clinic, but this year researchers embarked on a global effort to develop safe and effective coronavirus vaccines in record time. Both the Pfizer/BioNTech and Moderna vaccines have only a few months of phase 3 clinical trial data, so much remains unknown about them, including their duration of effect and any long-term safety signals. In addition to excluding immunocompromised individuals, the clinical trials did not include children or pregnant women, so data are lacking for several population subgroups.

But these will not be the only vaccines available, as the pipeline is already becoming crowded. U.S. clinical trial data from a vaccine jointly being developed by Oxford-AstraZeneca, could potentially be ready, along with a request for FDA emergency use authorization, by late January 2021.

In addition, China and Russia have released vaccines, and there are currently 61 vaccines being investigated in clinical trials and at least 85 preclinical products under active investigation.

The vaccine candidates are using both conventional and novel mechanisms of action to elicit an immune response in patients. Conventional methods include attenuated inactivated (killed) virus and recombinant viral protein vaccines to develop immunity. Novel approaches include replication-deficient, adenovirus vector-based vaccines that contain the viral protein, and mRNA-based vaccines, such as the Pfizer and Moderna vaccines, that encode for a SARS-CoV-2 spike protein.

“The special vaccine concern for immunocompromised individuals is introduction of a live virus,” Dr. Stohl said. “Neither the Moderna nor Pfizer vaccines are live viruses, so there should be no special contraindication for such individuals.”

Live vaccine should be avoided in immunocompromised patients, and currently, live SARS-CoV-2 vaccines are only being developed in India and Turkey.

It is not unusual for vaccine trials to begin with cohorts that exclude participants with various health conditions, including those who are immunocompromised. These groups are generally then evaluated in phase 4 trials, or postmarketing surveillance. While the precise number of immunosuppressed adults in the United States is not known, the numbers are believed to be rising because of increased life expectancy among immunosuppressed adults as a result of advances in treatment and new and wider indications for therapies that can affect the immune system.

According to data from the 2013 National Health Interview Survey, an estimated 2.7% of U.S. adults are immunosuppressed. This population covers a broad array of health conditions and medical specialties; people living with inflammatory or autoimmune conditions, such as inflammatory rheumatic diseases (rheumatoid arthritis, axial spondyloarthritis, lupus); inflammatory bowel disease (Crohn’s disease and ulcerative colitis); psoriasis; multiple sclerosis; organ transplant recipients; patients undergoing chemotherapy; and life-long immunosuppression attributable to HIV infection.

As the vaccines begin to roll out and become available, how should clinicians advise their patients, in the absence of any clinical trial data?


 

Risk vs. benefit

Gilaad Kaplan, MD, MPH, a gastroenterologist and professor of medicine at the University of Calgary (Alta.), noted that the inflammatory bowel disease (IBD) community has dealt with tremendous anxiety during the pandemic because many are immunocompromised because of the medications they use to treat their disease.

“For example, many patients with IBD are on biologics like anti-TNF [tumor necrosis factor] therapies, which are also used in other immune-mediated inflammatory diseases such as rheumatoid arthritis,” he said. “Understandably, individuals with IBD on immunosuppressive medications are concerned about the risk of severe complications due to COVID-19.”

The entire IBD community, along with the world, celebrated the announcement that multiple vaccines are protective against SARS-CoV-2, he noted. “Vaccines offer the potential to reduce the spread of COVID-19, allowing society to revert back to normalcy,” Dr. Kaplan said. “Moreover, for vulnerable populations, including those who are immunocompromised, vaccines offer the potential to directly protect them from the morbidity and mortality associated with COVID-19.”

That said, even though the news of vaccines are extremely promising, some cautions must be raised regarding their use in immunocompromised populations, such as persons with IBD. “The current trials, to my knowledge, did not include immunocompromised individuals and thus, we can only extrapolate from what we know from other trials of different vaccines,” he explained. “We know from prior vaccines studies that the immune response following vaccination is less robust in those who are immunocompromised as compared to a healthy control population.”

Dr. Kaplan also pointed to recent reports of allergic reactions that have been reported in healthy individuals. “We don’t know whether side effects, like allergic reactions, may be different in unstudied populations,” he said. “Thus, the medical and scientific community should prioritize clinical studies of safety and effectiveness of COVID-19 vaccines in immunocompromised populations.”

So, what does this mean for an individual with an immune-mediated inflammatory disease like Crohn’s disease or ulcerative colitis who is immunocompromised? Dr. Kaplan explained that it is a balance between the potential harm of being infected with COVID-19 and the uncertainty of receiving a vaccine in an understudied population. For those who are highly susceptible to dying from COVID-19, such as an older adult with IBD, or someone who faces high exposure, such as a health care worker, the potential protection of the vaccine greatly outweighs the uncertainty.

“However, for individuals who are at otherwise lower risk – for example, young and able to work from home – then waiting a few extra months for postmarketing surveillance studies in immunocompromised populations may be a reasonable approach, as long as these individuals are taking great care to avoid infection,” he said.
 

No waiting needed

Joel M. Gelfand, MD, MSCE, professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia, feels that the newly approved vaccine should be safe for most of his patients.

“Patients with psoriatic disease should get the mRNA-based COVID-19 vaccine as soon as possible based on eligibility as determined by the CDC and local public health officials,” he said. “It is not a live vaccine, and therefore patients on biologics or other immune-modulating or immune-suppressing treatment can receive it.”

However, the impact of psoriasis treatment on immune response to the mRNA-based vaccines is not known. Dr. Gelfand noted that, extrapolating from the vaccine literature, there is some evidence that methotrexate reduces response to the influenza vaccine. “However, the clinical significance of this finding is not clear,” he said. “Since the mRNA vaccine needs to be taken twice, a few weeks apart, I do not recommend interrupting or delaying treatment for psoriatic disease while undergoing vaccination for COVID-19.”

Given the reports of allergic reactions, he added that it is advisable for patients with a history of life-threatening allergic reactions such as anaphylaxis or who have been advised to carry an epinephrine autoinjector, to talk with their health care provider to determine if COVID-19 vaccination is medically appropriate.

The National Psoriasis Foundation has issued guidance on COVID-19, explained Steven R. Feldman, MD, PhD, professor of dermatology, pathology, and social sciences & health policy at Wake Forest University, Winston-Salem, N.C., who is also a member of the committee that is working on those guidelines and keeping them up to date. “We are in the process of updating the guidelines with information on COVID vaccines,” he said.

He agreed that there are no contraindications for psoriasis patients to receive the vaccine, regardless of whether they are on immunosuppressive treatment, even though definitive data are lacking. “Fortunately, there’s a lot of good data coming out of Italy that patients with psoriasis on biologics do not appear to be at increased risk of getting COVID or of having worse outcomes from COVID,” he said.

Patients are going to ask about the vaccines, and when counseling them, clinicians should discuss the available data, the residual uncertainty, and patients’ concerns should be considered, Dr. Feldman explained. “There may be some concern that steroids and cyclosporine would reduce the effectiveness of vaccines, but there is no concern that any of the drugs would cause increased risk from nonlive vaccines.”

He added that there is evidence that “patients on biologics who receive nonlive vaccines do develop antibody responses and are immunized.”


 

Boosting efficacy

Even prior to making their announcement, the American College of Rheumatology had said that they would endorse the vaccine for all patients, explained rheumatologist Brett Smith, DO, from Blount Memorial Physicians Group and East Tennessee Children’s Hospital, Alcoa. “The vaccine is safe for all patients, but the problem may be that it’s not as effective,” he said. “But we don’t know that because it hasn’t been tested.”

With other vaccines, biologic medicines are held for 2 weeks before and afterwards, to get the best response. “But some patients don’t want to stop the medication,” Dr. Smith said. “They are afraid that their symptoms will return.”

As for counseling patients as to whether they should receive this vaccine, he explained that he typically doesn’t try to sway patients one way or another until they are really high risk. “When I counsel, it really depends on the individual situation. And for this vaccine, we have to be open to the fact that many people have already made up their mind.”

There are a lot of questions regarding the vaccine. One is the short time frame of development. “Vaccines typically take 6-10 years to come on the market, and this one is now available after a 3-month study,” Dr. Smith said. “Some have already decided that it’s too new for them.”

The process is also new, and patients need to understand that it doesn’t contain an active virus and “you can’t catch coronavirus from it.”

Dr. Smith also explained that, because the vaccine may be less effective in a person using biologic therapies, there is currently no information available on repeat vaccination. “These are all unanswered questions,” he said. “If the antibodies wane in a short time, can we be revaccinated and in what time frame? We just don’t know that yet.”

Marcelo Bonomi, MD, a medical oncologist from The Ohio State University Comprehensive Cancer Center, Columbus, explained that one way to ensure a more optimal response to the vaccine would be to wait until the patient has finished chemotherapy.* “The vaccine can be offered at that time, and in the meantime, they can take other steps to avoid infection,” he said. “If they are very immunosuppressed, it isn’t worth trying to give the vaccine.”

Cancer patients should be encouraged to stay as healthy as possible, and to wear masks and social distance. “It’s a comprehensive approach. Eat healthy, avoid alcohol and tobacco, and exercise. [These things] will help boost the immune system,” Dr. Bonomi said. “Family members should be encouraged to get vaccinated, which will help them avoid infection and exposing the patient.”

Jim Boonyaratanakornkit, MD, PhD, an infectious disease specialist who cares for cancer patients at the Fred Hutchinson Cancer Research Center, agreed. “Giving a vaccine right after a transplant is a futile endeavor,” he said. “We need to wait 6 months to have an immune response.”

He pointed out there may be a continuing higher number of cases, with high levels peaking in Washington in February and March. “Close friends and family should be vaccinated if possible,” he said, “which will help interrupt transmission.”

The vaccines are using new platforms that are totally different, and there is no clear data as to how long the antibodies will persist. “We know that they last for at least 4 months,” said Dr. Boonyaratanakornkit. “We don’t know what level of antibody will protect them from COVID-19 infection. Current studies are being conducted, but we don’t have that information for anyone yet.”
 

*Correction, 1/7/21: An earlier version of this article misattributed quotes from Dr. Marcelo Bonomi.

You can now buy vegan eggnog, made from almond milk. The fact that someone created this wasn’t a surprise – plant milks are taking over. That it gave me such pleasure was. It’s rich, and if you love eggnog, like all normal people, it’s amazingly satisfying when mixed in a Nespresso latte swirled creamy white and brown. It seems some things, like Netflix’s The Crown, my Peloton spin classes, long Sunday walks on the beach, and the best mushroom risotto I ever made were still pleasurable this year, despite all. I’d daresay, there was joy even in the time of COVID.

But, before we get to that, it might be useful to distinguish between joy and pleasure.

Pleasure is pretty constant. It pops up even in the worst times. It seems, there’s plenty to be found even now. Unless, perhaps it’s just me. The label my mother pinned on me as a boy has remained into adulthood: “Easy to please.” There’s hardly a movie I’ve seen that I didn’t like. I’m quite comfortable in the middle seat. I thought the EPIC updates this year were nice. I’ve liked the vast majority of pizzas I’ve ever eaten – even those contaminated with Truffle salt. Easy to please is a gift, not something I’ve acquired through hours of meditation or aesthetic fasts. But surely pleasure isn’t the same as joy. No one has tears of pleasure. (Not to mention, pleasure as a verb has obvious NSFW connotations; not true of joy).

No, joy is waaay bigger. Joy is shared. Joy is to the whole world. Joy is what happens when you have a baby. Pleasure is what happens when you remembered to put a burp cloth in the car. Pleasure is when three patients in a row take merely 5 minutes each. Joy is when an itchy patient is cured.

2020 was one of the most miserable years in the last century. We didn’t expect it, but we ought to have. I mean really, how many plagues have we endured? How many times has inequality led to social unrest? Many times. We, by luck and dint of hard work, have always managed to get through. Although suffering would surely have been greater during those times of sickness and loss, I don’t believe joy would have been less. Indeed, maybe it is those difficulties and that suffering that allows us to feel joy in the first place. It is only once you summit that you experience joy. The run-up is just pain.

It is no coincidence that it is now during this cold, dark, difficult part of the year that we wish joy. We’ve made it. We light the darkness with candles to joyously celebrate Mawlid, Diwali, then Hanukkah and Christmas. Had malls been open now, you’d hear amongst the din of ringing bells Rejoice! Rejoice! O Emmanuel! You’d sing along, “Joy to the world, now we sing, let the Angel voices ring.” Joy: A pleasure so great and so deserved, it is shared by all. It is good news, hope, gratitude.

A joy shared amongst us all is also coming. Through the wrenching pain of watching patients suffocate, fogged shields, and bleached masks, through canceled Thanksgivings, through weekends spent in the OR on the backlog of patients, after months spent sitting in empty clinics, though the long, orange-cone-winding lines of testing, at last, at last a vaccine is here to light the darkness.

Let the sea resound, and everything in it,
the world, and all who live in it.
Let the rivers clap their hands,
let the mountains sing together for joy.
Joy to the world.
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

You can now buy vegan eggnog, made from almond milk. The fact that someone created this wasn’t a surprise – plant milks are taking over. That it gave me such pleasure was. It’s rich, and if you love eggnog, like all normal people, it’s amazingly satisfying when mixed in a Nespresso latte swirled creamy white and brown. It seems some things, like Netflix’s The Crown, my Peloton spin classes, long Sunday walks on the beach, and the best mushroom risotto I ever made were still pleasurable this year, despite all. I’d daresay, there was joy even in the time of COVID.

But, before we get to that, it might be useful to distinguish between joy and pleasure.

Pleasure is pretty constant. It pops up even in the worst times. It seems, there’s plenty to be found even now. Unless, perhaps it’s just me. The label my mother pinned on me as a boy has remained into adulthood: “Easy to please.” There’s hardly a movie I’ve seen that I didn’t like. I’m quite comfortable in the middle seat. I thought the EPIC updates this year were nice. I’ve liked the vast majority of pizzas I’ve ever eaten – even those contaminated with Truffle salt. Easy to please is a gift, not something I’ve acquired through hours of meditation or aesthetic fasts. But surely pleasure isn’t the same as joy. No one has tears of pleasure. (Not to mention, pleasure as a verb has obvious NSFW connotations; not true of joy).

No, joy is waaay bigger. Joy is shared. Joy is to the whole world. Joy is what happens when you have a baby. Pleasure is what happens when you remembered to put a burp cloth in the car. Pleasure is when three patients in a row take merely 5 minutes each. Joy is when an itchy patient is cured.

2020 was one of the most miserable years in the last century. We didn’t expect it, but we ought to have. I mean really, how many plagues have we endured? How many times has inequality led to social unrest? Many times. We, by luck and dint of hard work, have always managed to get through. Although suffering would surely have been greater during those times of sickness and loss, I don’t believe joy would have been less. Indeed, maybe it is those difficulties and that suffering that allows us to feel joy in the first place. It is only once you summit that you experience joy. The run-up is just pain.

It is no coincidence that it is now during this cold, dark, difficult part of the year that we wish joy. We’ve made it. We light the darkness with candles to joyously celebrate Mawlid, Diwali, then Hanukkah and Christmas. Had malls been open now, you’d hear amongst the din of ringing bells Rejoice! Rejoice! O Emmanuel! You’d sing along, “Joy to the world, now we sing, let the Angel voices ring.” Joy: A pleasure so great and so deserved, it is shared by all. It is good news, hope, gratitude.

A joy shared amongst us all is also coming. Through the wrenching pain of watching patients suffocate, fogged shields, and bleached masks, through canceled Thanksgivings, through weekends spent in the OR on the backlog of patients, after months spent sitting in empty clinics, though the long, orange-cone-winding lines of testing, at last, at last a vaccine is here to light the darkness.

Let the sea resound, and everything in it,
the world, and all who live in it.
Let the rivers clap their hands,
let the mountains sing together for joy.
Joy to the world.
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

You can now buy vegan eggnog, made from almond milk. The fact that someone created this wasn’t a surprise – plant milks are taking over. That it gave me such pleasure was. It’s rich, and if you love eggnog, like all normal people, it’s amazingly satisfying when mixed in a Nespresso latte swirled creamy white and brown. It seems some things, like Netflix’s The Crown, my Peloton spin classes, long Sunday walks on the beach, and the best mushroom risotto I ever made were still pleasurable this year, despite all. I’d daresay, there was joy even in the time of COVID.

But, before we get to that, it might be useful to distinguish between joy and pleasure.

Pleasure is pretty constant. It pops up even in the worst times. It seems, there’s plenty to be found even now. Unless, perhaps it’s just me. The label my mother pinned on me as a boy has remained into adulthood: “Easy to please.” There’s hardly a movie I’ve seen that I didn’t like. I’m quite comfortable in the middle seat. I thought the EPIC updates this year were nice. I’ve liked the vast majority of pizzas I’ve ever eaten – even those contaminated with Truffle salt. Easy to please is a gift, not something I’ve acquired through hours of meditation or aesthetic fasts. But surely pleasure isn’t the same as joy. No one has tears of pleasure. (Not to mention, pleasure as a verb has obvious NSFW connotations; not true of joy).

No, joy is waaay bigger. Joy is shared. Joy is to the whole world. Joy is what happens when you have a baby. Pleasure is what happens when you remembered to put a burp cloth in the car. Pleasure is when three patients in a row take merely 5 minutes each. Joy is when an itchy patient is cured.

2020 was one of the most miserable years in the last century. We didn’t expect it, but we ought to have. I mean really, how many plagues have we endured? How many times has inequality led to social unrest? Many times. We, by luck and dint of hard work, have always managed to get through. Although suffering would surely have been greater during those times of sickness and loss, I don’t believe joy would have been less. Indeed, maybe it is those difficulties and that suffering that allows us to feel joy in the first place. It is only once you summit that you experience joy. The run-up is just pain.

It is no coincidence that it is now during this cold, dark, difficult part of the year that we wish joy. We’ve made it. We light the darkness with candles to joyously celebrate Mawlid, Diwali, then Hanukkah and Christmas. Had malls been open now, you’d hear amongst the din of ringing bells Rejoice! Rejoice! O Emmanuel! You’d sing along, “Joy to the world, now we sing, let the Angel voices ring.” Joy: A pleasure so great and so deserved, it is shared by all. It is good news, hope, gratitude.

A joy shared amongst us all is also coming. Through the wrenching pain of watching patients suffocate, fogged shields, and bleached masks, through canceled Thanksgivings, through weekends spent in the OR on the backlog of patients, after months spent sitting in empty clinics, though the long, orange-cone-winding lines of testing, at last, at last a vaccine is here to light the darkness.

Let the sea resound, and everything in it,
the world, and all who live in it.
Let the rivers clap their hands,
let the mountains sing together for joy.
Joy to the world.
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].