Infectious Disease Practitioner

On July 22, the Centers for Disease Control and Prevention released updated sexually transmitted infection treatment guidelines to reflect current screening, testing, and treatment recommendations. The guidelines were last updated in 2015.

The new recommendations come at a pivotal moment in the field’s history, Kimberly Workowski, MD, a medical officer at the CDC’s Division of STD Prevention, told this news organization in an email. “The COVID-19 pandemic has caused decreased clinic capacity and drug and diagnostic test kit shortages,” she says. Many of these shortages have been resolved, she added, and it is important that health care professionals use the most current evidence-based recommendations for screening and management of STIs.

Updates to these guidelines were necessary to reflect “continued advances in research in the prevention of STIs, new interventions in terms of STI prevention, and thirdly, changing epidemiology,” Jeffrey Klausner, MD, MPH, an STI specialist with the Keck School of Medicine at the University of Southern California, Los Angeles, said in an interview. “There’s been increased concern about antimicrobial resistance, and that’s really driven some of the key changes in these new STI treatment guidelines.”

Notable updates to the guidelines include the following:

• Updated treatment recommendations for gonorrhea, chlamydia, , and 
• Two-step testing for diagnosing genital  virus
• Expanded risk factors for  testing in pregnant women
• Information on FDA-cleared rectal and oral tests to diagnose chlamydia and gonorrhea
• A recommendation that universal  screening be conducted at least once in a lifetime for adults aged 18 years and older

Dr. Workowski emphasized updates to gonorrhea treatment that built on the recommendation published in December 2020 in Morbidity and Mortality Weekly Report. The CDC now recommends that gonorrhea be treated with a single 500-mg injection of ceftriaxone, and if chlamydial infection is not ruled out, treating with a regimen of 100 mg of oral doxycycline taken twice daily for 7 days. Other gonorrhea treatment recommendations include retesting patients 3 months after treatment and that a test of cure be conducted for people with pharyngeal gonorrhea 1 to 2 weeks after treatment, using either culture or nucleic-acid amplification tests.

“Effectively treating gonorrhea remains a public health priority,” Dr. Workowski said. “Gonorrhea can rapidly develop antibiotic resistance and is the second most commonly reported bacterial STI in the U.S., increasing 56% from 2015 to 2019.”

The updates to syphilis screening for pregnant women are also important, added Dr. Klausner. “We’ve seen a dramatic and shameful rise in congenital syphilis,” he said. In addition to screening all pregnant women at the first prenatal visit, the CDC recommends retesting for syphilis at 28 weeks’ gestation and at delivery if the mother lives in an area where the prevalence of syphilis is high or if she is at risk of acquiring syphilis during pregnancy. An expectant mother is at higher risk if she has multiple sex partners, has an STI during pregnancy, has a partner with an STI, has a new sex partner, or misuses drugs, the recommendations state.

Dr. Klausner also noted that the updates provide more robust guidelines for treating transgender individuals and incarcerated people.

The treatment guidelines are available online along with a wall chart and a pocket guide that summarizes these updates. The mobile app with the 2015 guidelines will be retired at the end of July 2021, Dr. Workowski said. An app with these updated treatment recommendations is in development and will be available later this year.

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

On July 22, the Centers for Disease Control and Prevention released updated sexually transmitted infection treatment guidelines to reflect current screening, testing, and treatment recommendations. The guidelines were last updated in 2015.

The new recommendations come at a pivotal moment in the field’s history, Kimberly Workowski, MD, a medical officer at the CDC’s Division of STD Prevention, told this news organization in an email. “The COVID-19 pandemic has caused decreased clinic capacity and drug and diagnostic test kit shortages,” she says. Many of these shortages have been resolved, she added, and it is important that health care professionals use the most current evidence-based recommendations for screening and management of STIs.

Updates to these guidelines were necessary to reflect “continued advances in research in the prevention of STIs, new interventions in terms of STI prevention, and thirdly, changing epidemiology,” Jeffrey Klausner, MD, MPH, an STI specialist with the Keck School of Medicine at the University of Southern California, Los Angeles, said in an interview. “There’s been increased concern about antimicrobial resistance, and that’s really driven some of the key changes in these new STI treatment guidelines.”

Notable updates to the guidelines include the following:

• Updated treatment recommendations for gonorrhea, chlamydia, , and 
• Two-step testing for diagnosing genital  virus
• Expanded risk factors for  testing in pregnant women
• Information on FDA-cleared rectal and oral tests to diagnose chlamydia and gonorrhea
• A recommendation that universal  screening be conducted at least once in a lifetime for adults aged 18 years and older

Dr. Workowski emphasized updates to gonorrhea treatment that built on the recommendation published in December 2020 in Morbidity and Mortality Weekly Report. The CDC now recommends that gonorrhea be treated with a single 500-mg injection of ceftriaxone, and if chlamydial infection is not ruled out, treating with a regimen of 100 mg of oral doxycycline taken twice daily for 7 days. Other gonorrhea treatment recommendations include retesting patients 3 months after treatment and that a test of cure be conducted for people with pharyngeal gonorrhea 1 to 2 weeks after treatment, using either culture or nucleic-acid amplification tests.

“Effectively treating gonorrhea remains a public health priority,” Dr. Workowski said. “Gonorrhea can rapidly develop antibiotic resistance and is the second most commonly reported bacterial STI in the U.S., increasing 56% from 2015 to 2019.”

The updates to syphilis screening for pregnant women are also important, added Dr. Klausner. “We’ve seen a dramatic and shameful rise in congenital syphilis,” he said. In addition to screening all pregnant women at the first prenatal visit, the CDC recommends retesting for syphilis at 28 weeks’ gestation and at delivery if the mother lives in an area where the prevalence of syphilis is high or if she is at risk of acquiring syphilis during pregnancy. An expectant mother is at higher risk if she has multiple sex partners, has an STI during pregnancy, has a partner with an STI, has a new sex partner, or misuses drugs, the recommendations state.

Dr. Klausner also noted that the updates provide more robust guidelines for treating transgender individuals and incarcerated people.

The treatment guidelines are available online along with a wall chart and a pocket guide that summarizes these updates. The mobile app with the 2015 guidelines will be retired at the end of July 2021, Dr. Workowski said. An app with these updated treatment recommendations is in development and will be available later this year.

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

On July 22, the Centers for Disease Control and Prevention released updated sexually transmitted infection treatment guidelines to reflect current screening, testing, and treatment recommendations. The guidelines were last updated in 2015.

The new recommendations come at a pivotal moment in the field’s history, Kimberly Workowski, MD, a medical officer at the CDC’s Division of STD Prevention, told this news organization in an email. “The COVID-19 pandemic has caused decreased clinic capacity and drug and diagnostic test kit shortages,” she says. Many of these shortages have been resolved, she added, and it is important that health care professionals use the most current evidence-based recommendations for screening and management of STIs.

Updates to these guidelines were necessary to reflect “continued advances in research in the prevention of STIs, new interventions in terms of STI prevention, and thirdly, changing epidemiology,” Jeffrey Klausner, MD, MPH, an STI specialist with the Keck School of Medicine at the University of Southern California, Los Angeles, said in an interview. “There’s been increased concern about antimicrobial resistance, and that’s really driven some of the key changes in these new STI treatment guidelines.”

Notable updates to the guidelines include the following:

• Updated treatment recommendations for gonorrhea, chlamydia, , and 
• Two-step testing for diagnosing genital  virus
• Expanded risk factors for  testing in pregnant women
• Information on FDA-cleared rectal and oral tests to diagnose chlamydia and gonorrhea
• A recommendation that universal  screening be conducted at least once in a lifetime for adults aged 18 years and older

Dr. Workowski emphasized updates to gonorrhea treatment that built on the recommendation published in December 2020 in Morbidity and Mortality Weekly Report. The CDC now recommends that gonorrhea be treated with a single 500-mg injection of ceftriaxone, and if chlamydial infection is not ruled out, treating with a regimen of 100 mg of oral doxycycline taken twice daily for 7 days. Other gonorrhea treatment recommendations include retesting patients 3 months after treatment and that a test of cure be conducted for people with pharyngeal gonorrhea 1 to 2 weeks after treatment, using either culture or nucleic-acid amplification tests.

“Effectively treating gonorrhea remains a public health priority,” Dr. Workowski said. “Gonorrhea can rapidly develop antibiotic resistance and is the second most commonly reported bacterial STI in the U.S., increasing 56% from 2015 to 2019.”

The updates to syphilis screening for pregnant women are also important, added Dr. Klausner. “We’ve seen a dramatic and shameful rise in congenital syphilis,” he said. In addition to screening all pregnant women at the first prenatal visit, the CDC recommends retesting for syphilis at 28 weeks’ gestation and at delivery if the mother lives in an area where the prevalence of syphilis is high or if she is at risk of acquiring syphilis during pregnancy. An expectant mother is at higher risk if she has multiple sex partners, has an STI during pregnancy, has a partner with an STI, has a new sex partner, or misuses drugs, the recommendations state.

Dr. Klausner also noted that the updates provide more robust guidelines for treating transgender individuals and incarcerated people.

The treatment guidelines are available online along with a wall chart and a pocket guide that summarizes these updates. The mobile app with the 2015 guidelines will be retired at the end of July 2021, Dr. Workowski said. An app with these updated treatment recommendations is in development and will be available later this year.

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

A two-drug fixed-dose tablet therapy of dolutegravir/lamivudine (Dovato, ViiV Healthcare; DTG/3TC) shows noninferiority in viral suppression among people with HIV-1 who switch from any type of three- or four-drug antiretroviral (ART) regimens. But, DTG/3TC also shows feasibility as a first-line regimen in a test-and-treat setting, according to two studies presented at the virtual meeting of the International AIDS Society.

The results on the switch to DTG/3TC are from the phase 3 SALSA trial, which compared patients with HIV-1 who either remained on any current three- or four-drug ART regimen or who switched to the two-drug dolutegravir option.

For the primary endpoint, rates of virologic failure at 48 weeks were noninferior in the DTG/3TC group versus the three- or four-drug regimen (.4% vs. 1.2; adjusted difference: –.8% [95% confidence interval, –2.4%, .8%]).

In addition, rates of virologic suppression at week 48 were noninferior, with 94.3% of patients achieving HIV-1 RNA < 50 c/mL in the DTG/3TC group versus 92.7% in the three- or four-drug regimen (adjusted difference: 1.6% [95% CI, –2.8%, 5.9%).

“These data build upon the previous TANGO study and support DTG/3TC as a robust switch option with high levels of efficacy, good safety and tolerability, and a high barrier of resistance,” first author Josep M. Llibre, MD, PhD, consultant, infectious diseases department, Germans Trias i Pujol University Hospital, Barcelona, said in presenting the findings.

The two-drug dolutegravir-based regimen had previously been shown in the phase 3 GEMINI-1 and GEMINI-2 trials to have virologic noninferiority and safety compared with three- or four-drug DTG plus tenofovir/emtricitabine (TDF/FTC) ART regimens in treatment-naive individuals, and, in the subsequent TANGO trial, the regimen was also noninferior versus tenofovir alafenamide–based regimens among treatment-experienced patients, at 144 weeks in both studies.


 

Trial details

The new SALSA trial, designed to broaden the comparison to treatment with any current three- or four-drug ART regimen, involved 493 patients at 120 study sites in 17 countries.

All patients were initially on a three- or four-drug regimen, with HIV-1 RNA of less than 50 c/mL for more than 6 months, and without prior virologic failure or nucleoside reverse transcriptase inhibitors or dolutegravir resistance-associated mutations.

The participants were randomized 1:1 to remain on their current regimen (n = 247) or to switch to the once-daily, fixed-dose tablet two-drug combination of dolutegravir 50 mg/lamivudine 300 mg (n = 246) for 52 weeks.

In addition to the noninferior virologic outcomes, there were no serious drug-related adverse events, no confirmed virologic withdrawals, and no resistance mutations in either group.

Of note, weight increase was higher in the DTG/3TC group (8%; n = 20) versus the current ART arm (2%; n = 5), as has been observed in previous studies. The adjusted mean change in weight from baseline to week 48 in the DTG arm was 2.1 kg versus 0.6 kg in the current ART arm.

Dr. Llibre pointed out that many of the participants who switched were discontinuing regimens such as TDF and efavirenz that are associated with weight loss, “so discontinuation could be more related to weight gain than the introduction of dolutegravir, but this deserves further study,” he noted.

There were no significant differences in changes in eGFR and fasting lipids, or in changes in inflammatory biomarkers between the groups.

Bone and renal biomarkers were more favorable in the dolutegravir two-drug arm, suggesting that bone and renal function was either maintained or even improved with the drug switch, Dr. Llibre noted.

STAT trial: Feasibility of two-drug DTG/3TC as first-line treatment

In further findings presented at the meeting on the STAT trial, researchers evaluated the feasibility not of switching to, but of initiating patients on, the two-drug DTG treatment as a first-line therapy, within 14 days of HIV-1 diagnosis.

The “test-and-treat” approach counters common belief that the regimen should be started only after the traditional three-drug regimens, because of the potential of transmitted resistance and baseline hepatitis B virus coinfection.

In the study of 131 patients, at week 48, 82% (107/131) of all participants and 97% (107/110) of those with available data achieved HIV-1 RNA levels of < 50 c/mL.

While two participants had confirmed virologic failure in the study, there were no treatment-emergent resistance-associated mutations, and neither patient discontinued the two-drug DTG treatment. There were low rates of drug-related adverse events (8%) and they were not serious.

A two-drug fixed-dose tablet therapy of dolutegravir/lamivudine (Dovato, ViiV Healthcare; DTG/3TC) shows noninferiority in viral suppression among people with HIV-1 who switch from any type of three- or four-drug antiretroviral (ART) regimens. But, DTG/3TC also shows feasibility as a first-line regimen in a test-and-treat setting, according to two studies presented at the virtual meeting of the International AIDS Society.

The results on the switch to DTG/3TC are from the phase 3 SALSA trial, which compared patients with HIV-1 who either remained on any current three- or four-drug ART regimen or who switched to the two-drug dolutegravir option.

For the primary endpoint, rates of virologic failure at 48 weeks were noninferior in the DTG/3TC group versus the three- or four-drug regimen (.4% vs. 1.2; adjusted difference: –.8% [95% confidence interval, –2.4%, .8%]).

In addition, rates of virologic suppression at week 48 were noninferior, with 94.3% of patients achieving HIV-1 RNA < 50 c/mL in the DTG/3TC group versus 92.7% in the three- or four-drug regimen (adjusted difference: 1.6% [95% CI, –2.8%, 5.9%).

“These data build upon the previous TANGO study and support DTG/3TC as a robust switch option with high levels of efficacy, good safety and tolerability, and a high barrier of resistance,” first author Josep M. Llibre, MD, PhD, consultant, infectious diseases department, Germans Trias i Pujol University Hospital, Barcelona, said in presenting the findings.

The two-drug dolutegravir-based regimen had previously been shown in the phase 3 GEMINI-1 and GEMINI-2 trials to have virologic noninferiority and safety compared with three- or four-drug DTG plus tenofovir/emtricitabine (TDF/FTC) ART regimens in treatment-naive individuals, and, in the subsequent TANGO trial, the regimen was also noninferior versus tenofovir alafenamide–based regimens among treatment-experienced patients, at 144 weeks in both studies.


 

Trial details

The new SALSA trial, designed to broaden the comparison to treatment with any current three- or four-drug ART regimen, involved 493 patients at 120 study sites in 17 countries.

All patients were initially on a three- or four-drug regimen, with HIV-1 RNA of less than 50 c/mL for more than 6 months, and without prior virologic failure or nucleoside reverse transcriptase inhibitors or dolutegravir resistance-associated mutations.

The participants were randomized 1:1 to remain on their current regimen (n = 247) or to switch to the once-daily, fixed-dose tablet two-drug combination of dolutegravir 50 mg/lamivudine 300 mg (n = 246) for 52 weeks.

In addition to the noninferior virologic outcomes, there were no serious drug-related adverse events, no confirmed virologic withdrawals, and no resistance mutations in either group.

Of note, weight increase was higher in the DTG/3TC group (8%; n = 20) versus the current ART arm (2%; n = 5), as has been observed in previous studies. The adjusted mean change in weight from baseline to week 48 in the DTG arm was 2.1 kg versus 0.6 kg in the current ART arm.

Dr. Llibre pointed out that many of the participants who switched were discontinuing regimens such as TDF and efavirenz that are associated with weight loss, “so discontinuation could be more related to weight gain than the introduction of dolutegravir, but this deserves further study,” he noted.

There were no significant differences in changes in eGFR and fasting lipids, or in changes in inflammatory biomarkers between the groups.

Bone and renal biomarkers were more favorable in the dolutegravir two-drug arm, suggesting that bone and renal function was either maintained or even improved with the drug switch, Dr. Llibre noted.

STAT trial: Feasibility of two-drug DTG/3TC as first-line treatment

In further findings presented at the meeting on the STAT trial, researchers evaluated the feasibility not of switching to, but of initiating patients on, the two-drug DTG treatment as a first-line therapy, within 14 days of HIV-1 diagnosis.

The “test-and-treat” approach counters common belief that the regimen should be started only after the traditional three-drug regimens, because of the potential of transmitted resistance and baseline hepatitis B virus coinfection.

In the study of 131 patients, at week 48, 82% (107/131) of all participants and 97% (107/110) of those with available data achieved HIV-1 RNA levels of < 50 c/mL.

While two participants had confirmed virologic failure in the study, there were no treatment-emergent resistance-associated mutations, and neither patient discontinued the two-drug DTG treatment. There were low rates of drug-related adverse events (8%) and they were not serious.

A two-drug fixed-dose tablet therapy of dolutegravir/lamivudine (Dovato, ViiV Healthcare; DTG/3TC) shows noninferiority in viral suppression among people with HIV-1 who switch from any type of three- or four-drug antiretroviral (ART) regimens. But, DTG/3TC also shows feasibility as a first-line regimen in a test-and-treat setting, according to two studies presented at the virtual meeting of the International AIDS Society.

The results on the switch to DTG/3TC are from the phase 3 SALSA trial, which compared patients with HIV-1 who either remained on any current three- or four-drug ART regimen or who switched to the two-drug dolutegravir option.

For the primary endpoint, rates of virologic failure at 48 weeks were noninferior in the DTG/3TC group versus the three- or four-drug regimen (.4% vs. 1.2; adjusted difference: –.8% [95% confidence interval, –2.4%, .8%]).

In addition, rates of virologic suppression at week 48 were noninferior, with 94.3% of patients achieving HIV-1 RNA < 50 c/mL in the DTG/3TC group versus 92.7% in the three- or four-drug regimen (adjusted difference: 1.6% [95% CI, –2.8%, 5.9%).

“These data build upon the previous TANGO study and support DTG/3TC as a robust switch option with high levels of efficacy, good safety and tolerability, and a high barrier of resistance,” first author Josep M. Llibre, MD, PhD, consultant, infectious diseases department, Germans Trias i Pujol University Hospital, Barcelona, said in presenting the findings.

The two-drug dolutegravir-based regimen had previously been shown in the phase 3 GEMINI-1 and GEMINI-2 trials to have virologic noninferiority and safety compared with three- or four-drug DTG plus tenofovir/emtricitabine (TDF/FTC) ART regimens in treatment-naive individuals, and, in the subsequent TANGO trial, the regimen was also noninferior versus tenofovir alafenamide–based regimens among treatment-experienced patients, at 144 weeks in both studies.


 

Trial details

The new SALSA trial, designed to broaden the comparison to treatment with any current three- or four-drug ART regimen, involved 493 patients at 120 study sites in 17 countries.

All patients were initially on a three- or four-drug regimen, with HIV-1 RNA of less than 50 c/mL for more than 6 months, and without prior virologic failure or nucleoside reverse transcriptase inhibitors or dolutegravir resistance-associated mutations.

The participants were randomized 1:1 to remain on their current regimen (n = 247) or to switch to the once-daily, fixed-dose tablet two-drug combination of dolutegravir 50 mg/lamivudine 300 mg (n = 246) for 52 weeks.

In addition to the noninferior virologic outcomes, there were no serious drug-related adverse events, no confirmed virologic withdrawals, and no resistance mutations in either group.

Of note, weight increase was higher in the DTG/3TC group (8%; n = 20) versus the current ART arm (2%; n = 5), as has been observed in previous studies. The adjusted mean change in weight from baseline to week 48 in the DTG arm was 2.1 kg versus 0.6 kg in the current ART arm.

Dr. Llibre pointed out that many of the participants who switched were discontinuing regimens such as TDF and efavirenz that are associated with weight loss, “so discontinuation could be more related to weight gain than the introduction of dolutegravir, but this deserves further study,” he noted.

There were no significant differences in changes in eGFR and fasting lipids, or in changes in inflammatory biomarkers between the groups.

Bone and renal biomarkers were more favorable in the dolutegravir two-drug arm, suggesting that bone and renal function was either maintained or even improved with the drug switch, Dr. Llibre noted.

STAT trial: Feasibility of two-drug DTG/3TC as first-line treatment

In further findings presented at the meeting on the STAT trial, researchers evaluated the feasibility not of switching to, but of initiating patients on, the two-drug DTG treatment as a first-line therapy, within 14 days of HIV-1 diagnosis.

The “test-and-treat” approach counters common belief that the regimen should be started only after the traditional three-drug regimens, because of the potential of transmitted resistance and baseline hepatitis B virus coinfection.

In the study of 131 patients, at week 48, 82% (107/131) of all participants and 97% (107/110) of those with available data achieved HIV-1 RNA levels of < 50 c/mL.

While two participants had confirmed virologic failure in the study, there were no treatment-emergent resistance-associated mutations, and neither patient discontinued the two-drug DTG treatment. There were low rates of drug-related adverse events (8%) and they were not serious.

The drug maker Pfizer recently announced that vaccinated people are likely to need a booster shot to be effectively protected against new variants of COVID-19 and that the company would apply for Food and Drug Administration emergency use authorization for the shot. Top government health officials immediately and emphatically announced that the booster isn’t needed right now – and held firm to that position even after Pfizer’s top scientist made his case and shared preliminary data with them on July 12.

This has led to confusion. Should the nearly 60% of adult Americans who have been fully vaccinated seek out a booster or not? Is the protection that has allowed them to see loved ones and go out to dinner fading?

Ultimately, the question of whether a booster is needed is unlikely to determine the FDA’s decision. If recent history is predictive, booster shots will be here before long. That’s because of the outdated, 60-year-old basic standard the FDA uses to authorize medicines for sale: Is a new drug “safe and effective?”

The FDA, using that standard, will very likely have to authorize Pfizer’s booster for emergency use, as it did the company’s prior COVID shot. The booster is likely to be safe – hundreds of millions have taken the earlier shots – and Pfizer reported that it dramatically increases a vaccinated person’s antibodies against SARS-CoV-2. From that perspective, it may also be considered very effective.

But does that kind of efficacy matter? Is a higher level of antibodies needed to protect vaccinated Americans? Though antibody levels may wane some over time, the current vaccines deliver perfectly good immunity so far.

What if a booster is safe and effective in one sense but simply not needed – at least for now?

Reliance on the simple “safe and effective” standard – which certainly sounds reasonable – is a relic of a time when there were far fewer and simpler medicines available to treat diseases and before pharmaceutical manufacturing became one of the world’s biggest businesses.

The FDA’s 1938 landmark legislation focused primarily on safety after more than 100 Americans died from a raspberry-flavored liquid form of an early antibiotic because one of its ingredients was used as antifreeze. The 1962 Kefauver-Harris Amendments to the Federal Food, Drug, and Cosmetic Act set out more specific requirements for drug approval: Companies must scientifically prove a drug’s effectiveness through “adequate and well-controlled studies.”

In today’s pharmaceutical universe, a simple “safe and effective” determination is not always an adequate bar, and it can be manipulated to sell drugs of questionable value. There’s also big money involved: Pfizer is already projecting $26 billion in COVID revenue in 2021.

The United States’ continued use of this standard to let drugs into the market has led to the approval of expensive, not necessarily very effective drugs. In 2014, for example, the FDA approved a toenail fungus drug that can cost up to $1,500 a month and that studies showed cured fewer than 10% of patients after a year of treatment. That’s more effective than doing nothing but less effective and more costly than a number of other treatments for this bothersome malady.

It has also led to a plethora of high-priced drugs to treat diseases like cancers, multiple sclerosis and type 2 diabetes that are all more effective than a placebo but have often not been tested very much against one another to determine which are most effective.

In today’s complex world, clarification is needed to determine just what kind of effectiveness the FDA should demand. And should that be the job of the FDA alone?

For example, should drugmakers prove a drug is significantly more effective than products already on the market? Or demonstrate cost-effectiveness – the health value of a product relative to its price – a metric used by Britain’s health system? And in which cases is effectiveness against a surrogate marker – like an antibody level – a good enough stand-in for whether a drug will have a significant impact on a patient’s health?

In most industrialized countries, broad access to the national market is a two-step process, said Aaron Kesselheim, a professor of medicine at Harvard Medical School, Boston, who studies drug development, marketing and law and recently served on an FDA advisory committee. The first part certifies that a drug is sufficiently safe and effective. That is immediately followed by an independent health technology assessment to see where it fits in the treatment armamentarium, including, in some countries, whether it is useful enough to be sold at all at the stated price. But there’s no such automatic process in the United States.

When Pfizer applies for authorization, the FDA may well clear a booster for the U.S. market. The Centers for Disease Control and Prevention, likely with advice from National Institutes of Health experts, will then have to decide whether to recommend it and for whom. This judgment call usually determines whether insurers will cover it. Pfizer is likely to profit handsomely from a government authorization, and the company will gain some revenue even if only the worried well, who can pay out of pocket, decide to get the shot.

To make any recommendation on a booster, government experts say they need more data. They could, for example, as Anthony S. Fauci, MD, has suggested, eventually green-light the additional vaccine shot only for a small group of patients at high risk for a deadly infection, such as the very old or transplant recipients who take immunosuppressant drugs, as some other countries have done.

But until the United States refines the FDA’s “safe and effective” standard or adds a second layer of vetting, when new products hit the market and manufacturers promote them, Americans will be left to decipher whose version of effective and necessary matters to them.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

The drug maker Pfizer recently announced that vaccinated people are likely to need a booster shot to be effectively protected against new variants of COVID-19 and that the company would apply for Food and Drug Administration emergency use authorization for the shot. Top government health officials immediately and emphatically announced that the booster isn’t needed right now – and held firm to that position even after Pfizer’s top scientist made his case and shared preliminary data with them on July 12.

This has led to confusion. Should the nearly 60% of adult Americans who have been fully vaccinated seek out a booster or not? Is the protection that has allowed them to see loved ones and go out to dinner fading?

Ultimately, the question of whether a booster is needed is unlikely to determine the FDA’s decision. If recent history is predictive, booster shots will be here before long. That’s because of the outdated, 60-year-old basic standard the FDA uses to authorize medicines for sale: Is a new drug “safe and effective?”

The FDA, using that standard, will very likely have to authorize Pfizer’s booster for emergency use, as it did the company’s prior COVID shot. The booster is likely to be safe – hundreds of millions have taken the earlier shots – and Pfizer reported that it dramatically increases a vaccinated person’s antibodies against SARS-CoV-2. From that perspective, it may also be considered very effective.

But does that kind of efficacy matter? Is a higher level of antibodies needed to protect vaccinated Americans? Though antibody levels may wane some over time, the current vaccines deliver perfectly good immunity so far.

What if a booster is safe and effective in one sense but simply not needed – at least for now?

Reliance on the simple “safe and effective” standard – which certainly sounds reasonable – is a relic of a time when there were far fewer and simpler medicines available to treat diseases and before pharmaceutical manufacturing became one of the world’s biggest businesses.

The FDA’s 1938 landmark legislation focused primarily on safety after more than 100 Americans died from a raspberry-flavored liquid form of an early antibiotic because one of its ingredients was used as antifreeze. The 1962 Kefauver-Harris Amendments to the Federal Food, Drug, and Cosmetic Act set out more specific requirements for drug approval: Companies must scientifically prove a drug’s effectiveness through “adequate and well-controlled studies.”

In today’s pharmaceutical universe, a simple “safe and effective” determination is not always an adequate bar, and it can be manipulated to sell drugs of questionable value. There’s also big money involved: Pfizer is already projecting $26 billion in COVID revenue in 2021.

The United States’ continued use of this standard to let drugs into the market has led to the approval of expensive, not necessarily very effective drugs. In 2014, for example, the FDA approved a toenail fungus drug that can cost up to $1,500 a month and that studies showed cured fewer than 10% of patients after a year of treatment. That’s more effective than doing nothing but less effective and more costly than a number of other treatments for this bothersome malady.

It has also led to a plethora of high-priced drugs to treat diseases like cancers, multiple sclerosis and type 2 diabetes that are all more effective than a placebo but have often not been tested very much against one another to determine which are most effective.

In today’s complex world, clarification is needed to determine just what kind of effectiveness the FDA should demand. And should that be the job of the FDA alone?

For example, should drugmakers prove a drug is significantly more effective than products already on the market? Or demonstrate cost-effectiveness – the health value of a product relative to its price – a metric used by Britain’s health system? And in which cases is effectiveness against a surrogate marker – like an antibody level – a good enough stand-in for whether a drug will have a significant impact on a patient’s health?

In most industrialized countries, broad access to the national market is a two-step process, said Aaron Kesselheim, a professor of medicine at Harvard Medical School, Boston, who studies drug development, marketing and law and recently served on an FDA advisory committee. The first part certifies that a drug is sufficiently safe and effective. That is immediately followed by an independent health technology assessment to see where it fits in the treatment armamentarium, including, in some countries, whether it is useful enough to be sold at all at the stated price. But there’s no such automatic process in the United States.

When Pfizer applies for authorization, the FDA may well clear a booster for the U.S. market. The Centers for Disease Control and Prevention, likely with advice from National Institutes of Health experts, will then have to decide whether to recommend it and for whom. This judgment call usually determines whether insurers will cover it. Pfizer is likely to profit handsomely from a government authorization, and the company will gain some revenue even if only the worried well, who can pay out of pocket, decide to get the shot.

To make any recommendation on a booster, government experts say they need more data. They could, for example, as Anthony S. Fauci, MD, has suggested, eventually green-light the additional vaccine shot only for a small group of patients at high risk for a deadly infection, such as the very old or transplant recipients who take immunosuppressant drugs, as some other countries have done.

But until the United States refines the FDA’s “safe and effective” standard or adds a second layer of vetting, when new products hit the market and manufacturers promote them, Americans will be left to decipher whose version of effective and necessary matters to them.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

The drug maker Pfizer recently announced that vaccinated people are likely to need a booster shot to be effectively protected against new variants of COVID-19 and that the company would apply for Food and Drug Administration emergency use authorization for the shot. Top government health officials immediately and emphatically announced that the booster isn’t needed right now – and held firm to that position even after Pfizer’s top scientist made his case and shared preliminary data with them on July 12.

This has led to confusion. Should the nearly 60% of adult Americans who have been fully vaccinated seek out a booster or not? Is the protection that has allowed them to see loved ones and go out to dinner fading?

Ultimately, the question of whether a booster is needed is unlikely to determine the FDA’s decision. If recent history is predictive, booster shots will be here before long. That’s because of the outdated, 60-year-old basic standard the FDA uses to authorize medicines for sale: Is a new drug “safe and effective?”

The FDA, using that standard, will very likely have to authorize Pfizer’s booster for emergency use, as it did the company’s prior COVID shot. The booster is likely to be safe – hundreds of millions have taken the earlier shots – and Pfizer reported that it dramatically increases a vaccinated person’s antibodies against SARS-CoV-2. From that perspective, it may also be considered very effective.

But does that kind of efficacy matter? Is a higher level of antibodies needed to protect vaccinated Americans? Though antibody levels may wane some over time, the current vaccines deliver perfectly good immunity so far.

What if a booster is safe and effective in one sense but simply not needed – at least for now?

Reliance on the simple “safe and effective” standard – which certainly sounds reasonable – is a relic of a time when there were far fewer and simpler medicines available to treat diseases and before pharmaceutical manufacturing became one of the world’s biggest businesses.

The FDA’s 1938 landmark legislation focused primarily on safety after more than 100 Americans died from a raspberry-flavored liquid form of an early antibiotic because one of its ingredients was used as antifreeze. The 1962 Kefauver-Harris Amendments to the Federal Food, Drug, and Cosmetic Act set out more specific requirements for drug approval: Companies must scientifically prove a drug’s effectiveness through “adequate and well-controlled studies.”

In today’s pharmaceutical universe, a simple “safe and effective” determination is not always an adequate bar, and it can be manipulated to sell drugs of questionable value. There’s also big money involved: Pfizer is already projecting $26 billion in COVID revenue in 2021.

The United States’ continued use of this standard to let drugs into the market has led to the approval of expensive, not necessarily very effective drugs. In 2014, for example, the FDA approved a toenail fungus drug that can cost up to $1,500 a month and that studies showed cured fewer than 10% of patients after a year of treatment. That’s more effective than doing nothing but less effective and more costly than a number of other treatments for this bothersome malady.

It has also led to a plethora of high-priced drugs to treat diseases like cancers, multiple sclerosis and type 2 diabetes that are all more effective than a placebo but have often not been tested very much against one another to determine which are most effective.

In today’s complex world, clarification is needed to determine just what kind of effectiveness the FDA should demand. And should that be the job of the FDA alone?

For example, should drugmakers prove a drug is significantly more effective than products already on the market? Or demonstrate cost-effectiveness – the health value of a product relative to its price – a metric used by Britain’s health system? And in which cases is effectiveness against a surrogate marker – like an antibody level – a good enough stand-in for whether a drug will have a significant impact on a patient’s health?

In most industrialized countries, broad access to the national market is a two-step process, said Aaron Kesselheim, a professor of medicine at Harvard Medical School, Boston, who studies drug development, marketing and law and recently served on an FDA advisory committee. The first part certifies that a drug is sufficiently safe and effective. That is immediately followed by an independent health technology assessment to see where it fits in the treatment armamentarium, including, in some countries, whether it is useful enough to be sold at all at the stated price. But there’s no such automatic process in the United States.

When Pfizer applies for authorization, the FDA may well clear a booster for the U.S. market. The Centers for Disease Control and Prevention, likely with advice from National Institutes of Health experts, will then have to decide whether to recommend it and for whom. This judgment call usually determines whether insurers will cover it. Pfizer is likely to profit handsomely from a government authorization, and the company will gain some revenue even if only the worried well, who can pay out of pocket, decide to get the shot.

To make any recommendation on a booster, government experts say they need more data. They could, for example, as Anthony S. Fauci, MD, has suggested, eventually green-light the additional vaccine shot only for a small group of patients at high risk for a deadly infection, such as the very old or transplant recipients who take immunosuppressant drugs, as some other countries have done.

But until the United States refines the FDA’s “safe and effective” standard or adds a second layer of vetting, when new products hit the market and manufacturers promote them, Americans will be left to decipher whose version of effective and necessary matters to them.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

CDC Director Rochelle Walensky, MD, called the COVID-19 Delta variant “one of the most infectious respiratory viruses we know of” and reported more cases and hospitalizations.

“Today, I want to speak about our need to come together against a common enemy. SARS-CoV-2 and the Delta variant is spreading with incredible efficiency, and now represents more than 83% of the virus circulating in the U.S.,” Dr. Walensky said at a news briefing July 22. “It is one of the most infectious respiratory viruses we know of and that I have seen in my 20-year career.”

Dr. Walensky said there were 46,318 cases of COVID-19 reported July 21, with a 7-day average of 37,700 cases per day -- up 53% from the previous week. Hospital admissions average about 3,500 per day, an increase of 32%. The 7-day average of deaths is 237 -- a 19% increase from the previous week.

Meanwhile, there are now 162 million Americans who are fully vaccinated against COVID-19.

Areas with low vaccination coverage continue to have the highest case numbers, she reported, with unvaccinated people accounting for 97% of hospitalizations and deaths.

But there may be early signs of progress. The four states with the highest case rates -- Arkansas, Florida, Louisiana, and Nevada -- had a higher rate of new vaccinations, compared with the national average over the past week, White House COVID-19 Response Coordinator Jeff Zients said.

He also announced that the administration will send $100 million to nearly 2,000 rural health clinics to support vaccine education and outreach efforts.

Dr. Walensky said despite the rising numbers, the CDC mask guidance remains the same, but she encouraged vaccinated people to wear masks if they choose.

“Whether you are vaccinated or not, please know we together are not out of the woods yet,” she said. “We are yet at another pivotal moment in this pandemic, with cases rising again and hospitals reaching their capacity in some areas.”

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

CDC Director Rochelle Walensky, MD, called the COVID-19 Delta variant “one of the most infectious respiratory viruses we know of” and reported more cases and hospitalizations.

“Today, I want to speak about our need to come together against a common enemy. SARS-CoV-2 and the Delta variant is spreading with incredible efficiency, and now represents more than 83% of the virus circulating in the U.S.,” Dr. Walensky said at a news briefing July 22. “It is one of the most infectious respiratory viruses we know of and that I have seen in my 20-year career.”

Dr. Walensky said there were 46,318 cases of COVID-19 reported July 21, with a 7-day average of 37,700 cases per day -- up 53% from the previous week. Hospital admissions average about 3,500 per day, an increase of 32%. The 7-day average of deaths is 237 -- a 19% increase from the previous week.

Meanwhile, there are now 162 million Americans who are fully vaccinated against COVID-19.

Areas with low vaccination coverage continue to have the highest case numbers, she reported, with unvaccinated people accounting for 97% of hospitalizations and deaths.

But there may be early signs of progress. The four states with the highest case rates -- Arkansas, Florida, Louisiana, and Nevada -- had a higher rate of new vaccinations, compared with the national average over the past week, White House COVID-19 Response Coordinator Jeff Zients said.

He also announced that the administration will send $100 million to nearly 2,000 rural health clinics to support vaccine education and outreach efforts.

Dr. Walensky said despite the rising numbers, the CDC mask guidance remains the same, but she encouraged vaccinated people to wear masks if they choose.

“Whether you are vaccinated or not, please know we together are not out of the woods yet,” she said. “We are yet at another pivotal moment in this pandemic, with cases rising again and hospitals reaching their capacity in some areas.”

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

CDC Director Rochelle Walensky, MD, called the COVID-19 Delta variant “one of the most infectious respiratory viruses we know of” and reported more cases and hospitalizations.

“Today, I want to speak about our need to come together against a common enemy. SARS-CoV-2 and the Delta variant is spreading with incredible efficiency, and now represents more than 83% of the virus circulating in the U.S.,” Dr. Walensky said at a news briefing July 22. “It is one of the most infectious respiratory viruses we know of and that I have seen in my 20-year career.”

Dr. Walensky said there were 46,318 cases of COVID-19 reported July 21, with a 7-day average of 37,700 cases per day -- up 53% from the previous week. Hospital admissions average about 3,500 per day, an increase of 32%. The 7-day average of deaths is 237 -- a 19% increase from the previous week.

Meanwhile, there are now 162 million Americans who are fully vaccinated against COVID-19.

Areas with low vaccination coverage continue to have the highest case numbers, she reported, with unvaccinated people accounting for 97% of hospitalizations and deaths.

But there may be early signs of progress. The four states with the highest case rates -- Arkansas, Florida, Louisiana, and Nevada -- had a higher rate of new vaccinations, compared with the national average over the past week, White House COVID-19 Response Coordinator Jeff Zients said.

He also announced that the administration will send $100 million to nearly 2,000 rural health clinics to support vaccine education and outreach efforts.

Dr. Walensky said despite the rising numbers, the CDC mask guidance remains the same, but she encouraged vaccinated people to wear masks if they choose.

“Whether you are vaccinated or not, please know we together are not out of the woods yet,” she said. “We are yet at another pivotal moment in this pandemic, with cases rising again and hospitals reaching their capacity in some areas.”

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

I dream of alien abductions

There he goes! It’s lunchtime and your colleague Tom is going on and on again about that time he was abducted by aliens. It sounds ridiculous, but he does make some convincing arguments. Tom thinks it was real, but could it have all just been in his head?

Engin Akyurt/Pixabay

Lucid dreaming may help explain alleged alien abductions. During a lucid dream, people know that they’re dreaming, and can also have some control over how the dreams play out. During some dream states, a person can feel intense sensations, such as terror and paralysis, so it’s no wonder these dreams feel so real.

In a recent study, scientists encouraged 152 participants who had self-identified as lucid dreamers to dream about aliens. Many (75%) of the participants were able to dream about alien encounters, and 15% “achieved relatively realistic experiences,” the investigators reported.

So cut Tom some slack. He’s not crazy, he might just have lucid dreaming privileges. Tell him he should dream about something more fun, like a vacation in the Bahamas.
 

Follow your heart: Drink more coffee

It seems like the world is divided into coffee drinkers and non–coffee drinkers. Then there’s decaf and regular drinkers. Whichever camp you fall into, know this: The widespread belief that caffeine consumption has an effect on your heart is all beans.

s-photo/iStockphoto.com

In what is the largest investigation of its kind, researchers from the University of California, San Francisco, looked into whether drinking caffeinated coffee was linked to a risk for heart arrhythmia. They also researched whether patients with genetic variants that affect their metabolism could change that association. Almost 400,000 people with a mean age of 56 years participated in the study. More than half of the participants were women.

The investigators analyzed the participants’ self-reported coffee consumption using a technique called Mendelian randomization to leverage genetic data with the participants’ relationship with caffeine, making it an even field and not relying on the participant consumption self-reporting for outcomes as in previous studies.

What they found, after the 4-year follow up, was nothing short of myth busting.

“We found no evidence that caffeine consumption leads to a greater risk of arrhythmias,” said senior and corresponding author Gregory Marcus, MD. “Our population-based study provides reassurance that common prohibitions against caffeine to reduce arrhythmia risk are likely unwarranted.”

There was no evidence of a heightened risk of arrhythmias in participants who were genetically predisposed to metabolize caffeine differently from those who were not. And, there was a 3% reduction of arrhythmias in patients who consumed higher amounts of coffee.

We are not lobbying for Big Caffeine, but this study adds to the reported health benefits linked to coffee, which already include reduced risk for cancer, diabetes, and Parkinson’s disease, with an added bonus of anti-inflammatory benefits. So, the next time you’re hesitant to pour that second cup of Joe, just go for it. Your heart can take it.
 

Bored? Feeling down? Don’t play Candy Crush

Now hang on, aren’t those the perfect times to play video games? If there’s nothing else to do, why not open Candy Crush and mindlessly power through the levels?

pxfuel

Because, according to a study by a group of Canadian researchers, it’s actually the worst thing you can do. Well, maybe not literally, but it’s not helpful. Researchers recruited 60 Candy Crush players who were at various levels in the game. They had the participants play early levels that were far too easy or levels balanced with their gameplay abilities.

Players in the easy-level group got bored and quit far earlier than did those in the advanced-level group. The group playing to their abilities were able to access a “flow” state and focus all their attention on the game. While this is all well and good for their gaming performance, according to the researchers, it confirms the theory that playing to escape boredom or negative emotions is more likely to lead to addiction. As with all addictions, the temporary high can give way to a self-repeating loop, causing patients to ignore real life and deepen depression.

The researchers hope their findings will encourage game developers to “consider implementing responsible video gaming tools directly within their games.” Comedy gold. Perhaps Canadians’ idea of capitalism is a little different from that of those south of the border.
 

Hiccups and vaccine refusal

Tonight, LOTME News dives into the fetid cesspool that is international politics and comes out with … hiccups?

But first, a word from our sponsor, Fearless Boxing Club of South Etobicoke, Ontario.

Are you looking to flout public health restrictions? Do you want to spend time in an enclosed space with other people who haven’t gotten the COVID-19 vaccine? Do you “feel safer waiting until more research is done on the side effects being discovered right now”? (We are not making this up.)

Then join the Fearless Boxing Club, because we “will not be accepting any vaccinated members.” Our founders, Mohammed Abedeen and Krystal Glazier-Roscoe, are working hard to exclude “those who received the experimental COVID vaccine.” (Still not making it up.)

And now, back to the news.

Brazilian president Jair Bolsonaro was hospitalized recently for a severe case of hiccups that may have been related to a stab wound he received in 2018. [Nope, didn’t make that up, either.]

djedj/Pixabay

Mr. Bolsonaro had been hiccuping for 10 days, and was experiencing abdominal pain and difficulty speaking, when he entered the hospital on July 14. Since being stabbed while on the campaign trail, he has undergone several operations, which may have led to the partial intestinal obstruction that caused his latest symptoms.

His medical team advised Mr. Bolsonaro to go on a diet to aid his recovery, but when he was released on July 18 he said, “I hope in 10 days I’ll be eating barbecued ribs.” (Maybe this is all just a lucid dream. Probably shouldn’t have had ribs right before bed.)

I dream of alien abductions

There he goes! It’s lunchtime and your colleague Tom is going on and on again about that time he was abducted by aliens. It sounds ridiculous, but he does make some convincing arguments. Tom thinks it was real, but could it have all just been in his head?

Engin Akyurt/Pixabay

Lucid dreaming may help explain alleged alien abductions. During a lucid dream, people know that they’re dreaming, and can also have some control over how the dreams play out. During some dream states, a person can feel intense sensations, such as terror and paralysis, so it’s no wonder these dreams feel so real.

In a recent study, scientists encouraged 152 participants who had self-identified as lucid dreamers to dream about aliens. Many (75%) of the participants were able to dream about alien encounters, and 15% “achieved relatively realistic experiences,” the investigators reported.

So cut Tom some slack. He’s not crazy, he might just have lucid dreaming privileges. Tell him he should dream about something more fun, like a vacation in the Bahamas.
 

Follow your heart: Drink more coffee

It seems like the world is divided into coffee drinkers and non–coffee drinkers. Then there’s decaf and regular drinkers. Whichever camp you fall into, know this: The widespread belief that caffeine consumption has an effect on your heart is all beans.

s-photo/iStockphoto.com

In what is the largest investigation of its kind, researchers from the University of California, San Francisco, looked into whether drinking caffeinated coffee was linked to a risk for heart arrhythmia. They also researched whether patients with genetic variants that affect their metabolism could change that association. Almost 400,000 people with a mean age of 56 years participated in the study. More than half of the participants were women.

The investigators analyzed the participants’ self-reported coffee consumption using a technique called Mendelian randomization to leverage genetic data with the participants’ relationship with caffeine, making it an even field and not relying on the participant consumption self-reporting for outcomes as in previous studies.

What they found, after the 4-year follow up, was nothing short of myth busting.

“We found no evidence that caffeine consumption leads to a greater risk of arrhythmias,” said senior and corresponding author Gregory Marcus, MD. “Our population-based study provides reassurance that common prohibitions against caffeine to reduce arrhythmia risk are likely unwarranted.”

There was no evidence of a heightened risk of arrhythmias in participants who were genetically predisposed to metabolize caffeine differently from those who were not. And, there was a 3% reduction of arrhythmias in patients who consumed higher amounts of coffee.

We are not lobbying for Big Caffeine, but this study adds to the reported health benefits linked to coffee, which already include reduced risk for cancer, diabetes, and Parkinson’s disease, with an added bonus of anti-inflammatory benefits. So, the next time you’re hesitant to pour that second cup of Joe, just go for it. Your heart can take it.
 

Bored? Feeling down? Don’t play Candy Crush

Now hang on, aren’t those the perfect times to play video games? If there’s nothing else to do, why not open Candy Crush and mindlessly power through the levels?

pxfuel

Because, according to a study by a group of Canadian researchers, it’s actually the worst thing you can do. Well, maybe not literally, but it’s not helpful. Researchers recruited 60 Candy Crush players who were at various levels in the game. They had the participants play early levels that were far too easy or levels balanced with their gameplay abilities.

Players in the easy-level group got bored and quit far earlier than did those in the advanced-level group. The group playing to their abilities were able to access a “flow” state and focus all their attention on the game. While this is all well and good for their gaming performance, according to the researchers, it confirms the theory that playing to escape boredom or negative emotions is more likely to lead to addiction. As with all addictions, the temporary high can give way to a self-repeating loop, causing patients to ignore real life and deepen depression.

The researchers hope their findings will encourage game developers to “consider implementing responsible video gaming tools directly within their games.” Comedy gold. Perhaps Canadians’ idea of capitalism is a little different from that of those south of the border.
 

Hiccups and vaccine refusal

Tonight, LOTME News dives into the fetid cesspool that is international politics and comes out with … hiccups?

But first, a word from our sponsor, Fearless Boxing Club of South Etobicoke, Ontario.

Are you looking to flout public health restrictions? Do you want to spend time in an enclosed space with other people who haven’t gotten the COVID-19 vaccine? Do you “feel safer waiting until more research is done on the side effects being discovered right now”? (We are not making this up.)

Then join the Fearless Boxing Club, because we “will not be accepting any vaccinated members.” Our founders, Mohammed Abedeen and Krystal Glazier-Roscoe, are working hard to exclude “those who received the experimental COVID vaccine.” (Still not making it up.)

And now, back to the news.

Brazilian president Jair Bolsonaro was hospitalized recently for a severe case of hiccups that may have been related to a stab wound he received in 2018. [Nope, didn’t make that up, either.]

djedj/Pixabay

Mr. Bolsonaro had been hiccuping for 10 days, and was experiencing abdominal pain and difficulty speaking, when he entered the hospital on July 14. Since being stabbed while on the campaign trail, he has undergone several operations, which may have led to the partial intestinal obstruction that caused his latest symptoms.

His medical team advised Mr. Bolsonaro to go on a diet to aid his recovery, but when he was released on July 18 he said, “I hope in 10 days I’ll be eating barbecued ribs.” (Maybe this is all just a lucid dream. Probably shouldn’t have had ribs right before bed.)

I dream of alien abductions

There he goes! It’s lunchtime and your colleague Tom is going on and on again about that time he was abducted by aliens. It sounds ridiculous, but he does make some convincing arguments. Tom thinks it was real, but could it have all just been in his head?

Engin Akyurt/Pixabay

Lucid dreaming may help explain alleged alien abductions. During a lucid dream, people know that they’re dreaming, and can also have some control over how the dreams play out. During some dream states, a person can feel intense sensations, such as terror and paralysis, so it’s no wonder these dreams feel so real.

In a recent study, scientists encouraged 152 participants who had self-identified as lucid dreamers to dream about aliens. Many (75%) of the participants were able to dream about alien encounters, and 15% “achieved relatively realistic experiences,” the investigators reported.

So cut Tom some slack. He’s not crazy, he might just have lucid dreaming privileges. Tell him he should dream about something more fun, like a vacation in the Bahamas.
 

Follow your heart: Drink more coffee

It seems like the world is divided into coffee drinkers and non–coffee drinkers. Then there’s decaf and regular drinkers. Whichever camp you fall into, know this: The widespread belief that caffeine consumption has an effect on your heart is all beans.

s-photo/iStockphoto.com

In what is the largest investigation of its kind, researchers from the University of California, San Francisco, looked into whether drinking caffeinated coffee was linked to a risk for heart arrhythmia. They also researched whether patients with genetic variants that affect their metabolism could change that association. Almost 400,000 people with a mean age of 56 years participated in the study. More than half of the participants were women.

The investigators analyzed the participants’ self-reported coffee consumption using a technique called Mendelian randomization to leverage genetic data with the participants’ relationship with caffeine, making it an even field and not relying on the participant consumption self-reporting for outcomes as in previous studies.

What they found, after the 4-year follow up, was nothing short of myth busting.

“We found no evidence that caffeine consumption leads to a greater risk of arrhythmias,” said senior and corresponding author Gregory Marcus, MD. “Our population-based study provides reassurance that common prohibitions against caffeine to reduce arrhythmia risk are likely unwarranted.”

There was no evidence of a heightened risk of arrhythmias in participants who were genetically predisposed to metabolize caffeine differently from those who were not. And, there was a 3% reduction of arrhythmias in patients who consumed higher amounts of coffee.

We are not lobbying for Big Caffeine, but this study adds to the reported health benefits linked to coffee, which already include reduced risk for cancer, diabetes, and Parkinson’s disease, with an added bonus of anti-inflammatory benefits. So, the next time you’re hesitant to pour that second cup of Joe, just go for it. Your heart can take it.
 

Bored? Feeling down? Don’t play Candy Crush

Now hang on, aren’t those the perfect times to play video games? If there’s nothing else to do, why not open Candy Crush and mindlessly power through the levels?

pxfuel

Because, according to a study by a group of Canadian researchers, it’s actually the worst thing you can do. Well, maybe not literally, but it’s not helpful. Researchers recruited 60 Candy Crush players who were at various levels in the game. They had the participants play early levels that were far too easy or levels balanced with their gameplay abilities.

Players in the easy-level group got bored and quit far earlier than did those in the advanced-level group. The group playing to their abilities were able to access a “flow” state and focus all their attention on the game. While this is all well and good for their gaming performance, according to the researchers, it confirms the theory that playing to escape boredom or negative emotions is more likely to lead to addiction. As with all addictions, the temporary high can give way to a self-repeating loop, causing patients to ignore real life and deepen depression.

The researchers hope their findings will encourage game developers to “consider implementing responsible video gaming tools directly within their games.” Comedy gold. Perhaps Canadians’ idea of capitalism is a little different from that of those south of the border.
 

Hiccups and vaccine refusal

Tonight, LOTME News dives into the fetid cesspool that is international politics and comes out with … hiccups?

But first, a word from our sponsor, Fearless Boxing Club of South Etobicoke, Ontario.

Are you looking to flout public health restrictions? Do you want to spend time in an enclosed space with other people who haven’t gotten the COVID-19 vaccine? Do you “feel safer waiting until more research is done on the side effects being discovered right now”? (We are not making this up.)

Then join the Fearless Boxing Club, because we “will not be accepting any vaccinated members.” Our founders, Mohammed Abedeen and Krystal Glazier-Roscoe, are working hard to exclude “those who received the experimental COVID vaccine.” (Still not making it up.)

And now, back to the news.

Brazilian president Jair Bolsonaro was hospitalized recently for a severe case of hiccups that may have been related to a stab wound he received in 2018. [Nope, didn’t make that up, either.]

djedj/Pixabay

Mr. Bolsonaro had been hiccuping for 10 days, and was experiencing abdominal pain and difficulty speaking, when he entered the hospital on July 14. Since being stabbed while on the campaign trail, he has undergone several operations, which may have led to the partial intestinal obstruction that caused his latest symptoms.

His medical team advised Mr. Bolsonaro to go on a diet to aid his recovery, but when he was released on July 18 he said, “I hope in 10 days I’ll be eating barbecued ribs.” (Maybe this is all just a lucid dream. Probably shouldn’t have had ribs right before bed.)

Among patients hospitalized for COVID-19, those who had been taking statins had a substantially lower risk of death in a new large observational study.

Results showed that use of statins prior to admission was linked to a greater than 40% reduction in mortality and a greater than 25% reduction in risk of developing a severe outcome.

The findings come an analysis of data from the American Heart Association’s COVID-19 Cardiovascular Disease Registry on more than 10,000 patients hospitalized with COVID-19 at 104 hospitals across the United States published in PLoS One.

While several other studies have suggested benefits of statins in COVID-19, this is by far the largest study so far on this topic.

“I would say this is the most reliable study on statins in COVID-19 to date, with the results adjusted for many confounders, including socioeconomic factors and insurance type,” lead author Lori B. Daniels, MD, told this news organization. “However, it still an observational study and therefore falls short of a randomized study. But I would think a randomized study of statins in COVID-19 is probably not feasible, so this study provides excellent data at an observational level.”

After propensity matching for cardiovascular disease, results showed that most of the benefit of statins occurred in patients with known cardiovascular disease.

“While most patients taking statins will have cardiovascular disease, there are also many patients who take these drugs who don’t have heart disease but do have cardiovascular risk factors, such as those with raised cholesterol, or a family history of cardiovascular disease. For [such patients], the effect of statins was also in the same direction but it was not significant. This doesn’t exclude an effect,” noted Dr. Daniels, who is professor of medicine and director of cardiovascular intensive care at the University of California, San Diego.

“We are not saying that everyone should rush out and take a statin if they do not have risk factors for cardiovascular in order to lower their risk of dying from COVID. But if individuals do have an indication for a statin and are not taking one of these dugs this is another good reason to start taking them now,” she added.

The investigators embarked on the study because, although previous observational studies have found that statins may reduce the severity of COVID-19 infection, these studies have been limited in size with mostly single-center or regional studies, and some results have been conflicting. They therefore conducted the current, much larger analysis, in the AHA COVID-19 CVD Registry which systematically collected hospitalized patient–level data in a broad and diverse hospital and patient population across the United States.

For the analysis, the researchers analyzed data from 10,541 patients hospitalized with COVID-19 through September 2020 at 104 U.S. hospitals enrolled in the AHA registry to evaluate the associations between statin use and outcomes.

Most patients (71%) had either cardiovascular disease, hypertension, or both. Prior to admission, 42% of subjects used statins, with 7% being on statins alone and 35% on statins plus antihypertensives. Death (or discharge to hospice) occurred in 2,212 subjects (21%).

Results showed that outpatient use of statins, either alone or with antihypertensives, was associated with a 41% reduced risk of death (odds ratio, 0.59; 95% confidence interval, 0.50-0.69), after adjusting for demographic characteristics, underlying conditions, insurance status, hospital site, and concurrent medications. Statin use was also associated with a roughly 25% lower adjusted odds of developing severe disease.

Noting that patients on statins are also likely to be on antihypertensive medication, the researchers found that the statin benefit on mortality was seen in both patients taking a statin alone (OR, 0.54) and in those taking statins with an antihypertensive medication (OR, 0.60).

Use of antihypertensive drugs was associated with a smaller, albeit still substantial, 27% lower odds of death (OR, 0.73; 95% CI, 0.62-0.87).

In propensity-matched analyses, use of statins and/or antihypertensives was tied to a 32% reduced risk of death among those with a history of CVD and/or hypertension (OR, 0.68; 95% CI, 0.58-0.81). An observed 16% reduction in odds of death with statins and/or antihypertensive drugs among those without cardiovascular disease and/or hypertension was not statistically significant (OR, 0.84; 95% CI, 0.58-1.22).
 

Stabilizing the underlying disease

The researchers pointed out that the results of the propensity matching analysis are consistent with the hypothesis that the major benefit of these medications accrues from treating and/or stabilizing underlying disease.

“Although it is well known that statins improve long-term outcomes among patients with or at elevated risk for cardiovascular disease, the association with a large short-term benefit which accrues in the setting of hospitalization for COVID-19 is a new and intriguing finding,” they said.

They cited several “plausible mechanisms whereby statins could directly mitigate outcomes in COVID-19 beyond treating underlying disease conditions,” including anti-inflammatory effects and a direct inhibitory effect on the SARS-CoV-2 virus.

Dr. Daniels elaborated more on the potential mechanism at play in an interview: “I think what is happening is that the statin is stabilizing the coronary disease so patients are less likely to die from MI or stroke, and this gives them more time and strength to recover from COVID-19.”

She added: “Statins may also have some direct anti-COVID effects such as an anti-inflammatory actions, but I would guess that this is probably not the primary effect behind what we’re seeing here.”
 

‘Important clinical implications’

The authors say their findings have “important clinical implications.”

They noted that early in the pandemic there was speculation that certain medications, including statins, and the ACE inhibitor/angiotensin receptor blocker (ARB) classes of antihypertensives may confer an increased susceptibility to COVID-19 positivity and/or severity.

“Our study reinforces the AHA and others’ recommendations that not only is it safe to remain on these medications, but they may substantially reduce risk of severe COVID-19 and especially death from COVID-19, particularly statins, and particularly among those with associated underlying conditions,” the authors stressed.

Dr. Daniels added that, although statins are very safe drugs, there are always some patients who prefer not to take medication even if indicated, and others who may have borderline indications and decide not to take a statin at present.

“This study may persuade these patients that taking a statin is the right thing to do. It may give those patients on the cusp of thinking about taking one of these drugs a reason to go ahead,” she said.
 

‘Provocative but not definitive’

Commenting on the study, Robert Harrington, MD, professor of medicine and chair of the department of medicine at Stanford (Calif.) University, said: “These are interesting observational data but as such have all the limitations of nonrandomized comparisons despite the best attempts to adjust for a variety of potential confounders. For example, is this an effect of statins (perhaps through some anti-inflammatory mechanism) or is it more an effect that can be attributed to the patients who are prescribed and taking a statin, compared with those who are not?”

He added: “The primary clinical benefit of statins, based on many large randomized clinical trials, seems to be derived from their LDL lowering effect. Observational studies have suggested potential benefits from anti-inflammatory effects of statins, but the randomized trials have not confirmed these observations. So, the current data are interesting, even provocative, but ultimately hypothesis generating rather than definitive.”

Also commenting on the study, Steven Nissen, MD, professor of medicine at the Cleveland Clinic, said: “While statins have many established benefits, their role in preventing COVID-19 complications is very speculative. Like all observational studies, the current study must be viewed as hypothesis generating, not definitive evidence of benefit. There are many potential confounders. I’m skeptical.”

The authors of this study received no specific funding for this work and report no competing interests. Dr. Harrington was AHA president when the COVID registry was created and he is still a member of the AHA board, which has oversight over the project.

Among patients hospitalized for COVID-19, those who had been taking statins had a substantially lower risk of death in a new large observational study.

Results showed that use of statins prior to admission was linked to a greater than 40% reduction in mortality and a greater than 25% reduction in risk of developing a severe outcome.

The findings come an analysis of data from the American Heart Association’s COVID-19 Cardiovascular Disease Registry on more than 10,000 patients hospitalized with COVID-19 at 104 hospitals across the United States published in PLoS One.

While several other studies have suggested benefits of statins in COVID-19, this is by far the largest study so far on this topic.

“I would say this is the most reliable study on statins in COVID-19 to date, with the results adjusted for many confounders, including socioeconomic factors and insurance type,” lead author Lori B. Daniels, MD, told this news organization. “However, it still an observational study and therefore falls short of a randomized study. But I would think a randomized study of statins in COVID-19 is probably not feasible, so this study provides excellent data at an observational level.”

After propensity matching for cardiovascular disease, results showed that most of the benefit of statins occurred in patients with known cardiovascular disease.

“While most patients taking statins will have cardiovascular disease, there are also many patients who take these drugs who don’t have heart disease but do have cardiovascular risk factors, such as those with raised cholesterol, or a family history of cardiovascular disease. For [such patients], the effect of statins was also in the same direction but it was not significant. This doesn’t exclude an effect,” noted Dr. Daniels, who is professor of medicine and director of cardiovascular intensive care at the University of California, San Diego.

“We are not saying that everyone should rush out and take a statin if they do not have risk factors for cardiovascular in order to lower their risk of dying from COVID. But if individuals do have an indication for a statin and are not taking one of these dugs this is another good reason to start taking them now,” she added.

The investigators embarked on the study because, although previous observational studies have found that statins may reduce the severity of COVID-19 infection, these studies have been limited in size with mostly single-center or regional studies, and some results have been conflicting. They therefore conducted the current, much larger analysis, in the AHA COVID-19 CVD Registry which systematically collected hospitalized patient–level data in a broad and diverse hospital and patient population across the United States.

For the analysis, the researchers analyzed data from 10,541 patients hospitalized with COVID-19 through September 2020 at 104 U.S. hospitals enrolled in the AHA registry to evaluate the associations between statin use and outcomes.

Most patients (71%) had either cardiovascular disease, hypertension, or both. Prior to admission, 42% of subjects used statins, with 7% being on statins alone and 35% on statins plus antihypertensives. Death (or discharge to hospice) occurred in 2,212 subjects (21%).

Results showed that outpatient use of statins, either alone or with antihypertensives, was associated with a 41% reduced risk of death (odds ratio, 0.59; 95% confidence interval, 0.50-0.69), after adjusting for demographic characteristics, underlying conditions, insurance status, hospital site, and concurrent medications. Statin use was also associated with a roughly 25% lower adjusted odds of developing severe disease.

Noting that patients on statins are also likely to be on antihypertensive medication, the researchers found that the statin benefit on mortality was seen in both patients taking a statin alone (OR, 0.54) and in those taking statins with an antihypertensive medication (OR, 0.60).

Use of antihypertensive drugs was associated with a smaller, albeit still substantial, 27% lower odds of death (OR, 0.73; 95% CI, 0.62-0.87).

In propensity-matched analyses, use of statins and/or antihypertensives was tied to a 32% reduced risk of death among those with a history of CVD and/or hypertension (OR, 0.68; 95% CI, 0.58-0.81). An observed 16% reduction in odds of death with statins and/or antihypertensive drugs among those without cardiovascular disease and/or hypertension was not statistically significant (OR, 0.84; 95% CI, 0.58-1.22).
 

Stabilizing the underlying disease

The researchers pointed out that the results of the propensity matching analysis are consistent with the hypothesis that the major benefit of these medications accrues from treating and/or stabilizing underlying disease.

“Although it is well known that statins improve long-term outcomes among patients with or at elevated risk for cardiovascular disease, the association with a large short-term benefit which accrues in the setting of hospitalization for COVID-19 is a new and intriguing finding,” they said.

They cited several “plausible mechanisms whereby statins could directly mitigate outcomes in COVID-19 beyond treating underlying disease conditions,” including anti-inflammatory effects and a direct inhibitory effect on the SARS-CoV-2 virus.

Dr. Daniels elaborated more on the potential mechanism at play in an interview: “I think what is happening is that the statin is stabilizing the coronary disease so patients are less likely to die from MI or stroke, and this gives them more time and strength to recover from COVID-19.”

She added: “Statins may also have some direct anti-COVID effects such as an anti-inflammatory actions, but I would guess that this is probably not the primary effect behind what we’re seeing here.”
 

‘Important clinical implications’

The authors say their findings have “important clinical implications.”

They noted that early in the pandemic there was speculation that certain medications, including statins, and the ACE inhibitor/angiotensin receptor blocker (ARB) classes of antihypertensives may confer an increased susceptibility to COVID-19 positivity and/or severity.

“Our study reinforces the AHA and others’ recommendations that not only is it safe to remain on these medications, but they may substantially reduce risk of severe COVID-19 and especially death from COVID-19, particularly statins, and particularly among those with associated underlying conditions,” the authors stressed.

Dr. Daniels added that, although statins are very safe drugs, there are always some patients who prefer not to take medication even if indicated, and others who may have borderline indications and decide not to take a statin at present.

“This study may persuade these patients that taking a statin is the right thing to do. It may give those patients on the cusp of thinking about taking one of these drugs a reason to go ahead,” she said.
 

‘Provocative but not definitive’

Commenting on the study, Robert Harrington, MD, professor of medicine and chair of the department of medicine at Stanford (Calif.) University, said: “These are interesting observational data but as such have all the limitations of nonrandomized comparisons despite the best attempts to adjust for a variety of potential confounders. For example, is this an effect of statins (perhaps through some anti-inflammatory mechanism) or is it more an effect that can be attributed to the patients who are prescribed and taking a statin, compared with those who are not?”

He added: “The primary clinical benefit of statins, based on many large randomized clinical trials, seems to be derived from their LDL lowering effect. Observational studies have suggested potential benefits from anti-inflammatory effects of statins, but the randomized trials have not confirmed these observations. So, the current data are interesting, even provocative, but ultimately hypothesis generating rather than definitive.”

Also commenting on the study, Steven Nissen, MD, professor of medicine at the Cleveland Clinic, said: “While statins have many established benefits, their role in preventing COVID-19 complications is very speculative. Like all observational studies, the current study must be viewed as hypothesis generating, not definitive evidence of benefit. There are many potential confounders. I’m skeptical.”

The authors of this study received no specific funding for this work and report no competing interests. Dr. Harrington was AHA president when the COVID registry was created and he is still a member of the AHA board, which has oversight over the project.

Among patients hospitalized for COVID-19, those who had been taking statins had a substantially lower risk of death in a new large observational study.

Results showed that use of statins prior to admission was linked to a greater than 40% reduction in mortality and a greater than 25% reduction in risk of developing a severe outcome.

The findings come an analysis of data from the American Heart Association’s COVID-19 Cardiovascular Disease Registry on more than 10,000 patients hospitalized with COVID-19 at 104 hospitals across the United States published in PLoS One.

While several other studies have suggested benefits of statins in COVID-19, this is by far the largest study so far on this topic.

“I would say this is the most reliable study on statins in COVID-19 to date, with the results adjusted for many confounders, including socioeconomic factors and insurance type,” lead author Lori B. Daniels, MD, told this news organization. “However, it still an observational study and therefore falls short of a randomized study. But I would think a randomized study of statins in COVID-19 is probably not feasible, so this study provides excellent data at an observational level.”

After propensity matching for cardiovascular disease, results showed that most of the benefit of statins occurred in patients with known cardiovascular disease.

“While most patients taking statins will have cardiovascular disease, there are also many patients who take these drugs who don’t have heart disease but do have cardiovascular risk factors, such as those with raised cholesterol, or a family history of cardiovascular disease. For [such patients], the effect of statins was also in the same direction but it was not significant. This doesn’t exclude an effect,” noted Dr. Daniels, who is professor of medicine and director of cardiovascular intensive care at the University of California, San Diego.

“We are not saying that everyone should rush out and take a statin if they do not have risk factors for cardiovascular in order to lower their risk of dying from COVID. But if individuals do have an indication for a statin and are not taking one of these dugs this is another good reason to start taking them now,” she added.

The investigators embarked on the study because, although previous observational studies have found that statins may reduce the severity of COVID-19 infection, these studies have been limited in size with mostly single-center or regional studies, and some results have been conflicting. They therefore conducted the current, much larger analysis, in the AHA COVID-19 CVD Registry which systematically collected hospitalized patient–level data in a broad and diverse hospital and patient population across the United States.

For the analysis, the researchers analyzed data from 10,541 patients hospitalized with COVID-19 through September 2020 at 104 U.S. hospitals enrolled in the AHA registry to evaluate the associations between statin use and outcomes.

Most patients (71%) had either cardiovascular disease, hypertension, or both. Prior to admission, 42% of subjects used statins, with 7% being on statins alone and 35% on statins plus antihypertensives. Death (or discharge to hospice) occurred in 2,212 subjects (21%).

Results showed that outpatient use of statins, either alone or with antihypertensives, was associated with a 41% reduced risk of death (odds ratio, 0.59; 95% confidence interval, 0.50-0.69), after adjusting for demographic characteristics, underlying conditions, insurance status, hospital site, and concurrent medications. Statin use was also associated with a roughly 25% lower adjusted odds of developing severe disease.

Noting that patients on statins are also likely to be on antihypertensive medication, the researchers found that the statin benefit on mortality was seen in both patients taking a statin alone (OR, 0.54) and in those taking statins with an antihypertensive medication (OR, 0.60).

Use of antihypertensive drugs was associated with a smaller, albeit still substantial, 27% lower odds of death (OR, 0.73; 95% CI, 0.62-0.87).

In propensity-matched analyses, use of statins and/or antihypertensives was tied to a 32% reduced risk of death among those with a history of CVD and/or hypertension (OR, 0.68; 95% CI, 0.58-0.81). An observed 16% reduction in odds of death with statins and/or antihypertensive drugs among those without cardiovascular disease and/or hypertension was not statistically significant (OR, 0.84; 95% CI, 0.58-1.22).
 

Stabilizing the underlying disease

The researchers pointed out that the results of the propensity matching analysis are consistent with the hypothesis that the major benefit of these medications accrues from treating and/or stabilizing underlying disease.

“Although it is well known that statins improve long-term outcomes among patients with or at elevated risk for cardiovascular disease, the association with a large short-term benefit which accrues in the setting of hospitalization for COVID-19 is a new and intriguing finding,” they said.

They cited several “plausible mechanisms whereby statins could directly mitigate outcomes in COVID-19 beyond treating underlying disease conditions,” including anti-inflammatory effects and a direct inhibitory effect on the SARS-CoV-2 virus.

Dr. Daniels elaborated more on the potential mechanism at play in an interview: “I think what is happening is that the statin is stabilizing the coronary disease so patients are less likely to die from MI or stroke, and this gives them more time and strength to recover from COVID-19.”

She added: “Statins may also have some direct anti-COVID effects such as an anti-inflammatory actions, but I would guess that this is probably not the primary effect behind what we’re seeing here.”
 

‘Important clinical implications’

The authors say their findings have “important clinical implications.”

They noted that early in the pandemic there was speculation that certain medications, including statins, and the ACE inhibitor/angiotensin receptor blocker (ARB) classes of antihypertensives may confer an increased susceptibility to COVID-19 positivity and/or severity.

“Our study reinforces the AHA and others’ recommendations that not only is it safe to remain on these medications, but they may substantially reduce risk of severe COVID-19 and especially death from COVID-19, particularly statins, and particularly among those with associated underlying conditions,” the authors stressed.

Dr. Daniels added that, although statins are very safe drugs, there are always some patients who prefer not to take medication even if indicated, and others who may have borderline indications and decide not to take a statin at present.

“This study may persuade these patients that taking a statin is the right thing to do. It may give those patients on the cusp of thinking about taking one of these drugs a reason to go ahead,” she said.
 

‘Provocative but not definitive’

Commenting on the study, Robert Harrington, MD, professor of medicine and chair of the department of medicine at Stanford (Calif.) University, said: “These are interesting observational data but as such have all the limitations of nonrandomized comparisons despite the best attempts to adjust for a variety of potential confounders. For example, is this an effect of statins (perhaps through some anti-inflammatory mechanism) or is it more an effect that can be attributed to the patients who are prescribed and taking a statin, compared with those who are not?”

He added: “The primary clinical benefit of statins, based on many large randomized clinical trials, seems to be derived from their LDL lowering effect. Observational studies have suggested potential benefits from anti-inflammatory effects of statins, but the randomized trials have not confirmed these observations. So, the current data are interesting, even provocative, but ultimately hypothesis generating rather than definitive.”

Also commenting on the study, Steven Nissen, MD, professor of medicine at the Cleveland Clinic, said: “While statins have many established benefits, their role in preventing COVID-19 complications is very speculative. Like all observational studies, the current study must be viewed as hypothesis generating, not definitive evidence of benefit. There are many potential confounders. I’m skeptical.”

The authors of this study received no specific funding for this work and report no competing interests. Dr. Harrington was AHA president when the COVID registry was created and he is still a member of the AHA board, which has oversight over the project.

Catherine O’Neal, MD, an infectious disease physician, took to the podium of the Louisiana governor’s press conference recently and did not mince words.

“The Delta variant is not last year’s virus, and it’s become incredibly apparent to healthcare workers that we are dealing with a different beast,” she said.

Louisiana is one of the least vaccinated states in the country. In the United States as a whole, 48.6% of the population is fully vaccinated. In Louisiana, it’s just 36%, and Delta is bearing down.

Dr. O’Neal spoke about the pressure that rising COVID cases were already putting on her hospital, Our Lady of the Lake Regional Medical Center in Baton Rouge. She talked about watching her peers, 30- and 40-year-olds, become severely ill with the latest iteration of the new coronavirus — the Delta variant — which is sweeping through the United States with astonishing speed, causing new cases, hospitalizations, and deaths to rise again. 

Dr. O’Neal talked about parents who might not be alive to see their children go off to college in a few weeks. She talked about increasing hospital admissions for infected kids and pregnant women on ventilators.

“I want to be clear after seeing what we’ve seen the last two weeks. We only have two choices: We are either going to get vaccinated and end the pandemic, or we’re going to accept death and a lot of it,” Dr. O’Neal said, her voice choked by emotion.

Where Delta goes, death follows

Delta was first identified in India, where it caused a devastating surge in the spring. In a population that was largely unvaccinated, researchers think it may have caused as many as three million deaths. In just a few months’ time, it has sped across the globe.

Research from the United Kingdom shows that Delta is highly contagious. It’s about 60% more easily passed from person to person than the Alpha version (or B.1.1.7, which was first identified in the United Kingdom). 

Where a single infected person might have spread older versions of the virus to two or three others, mathematician and epidemiologist Adam Kucharski, PhD, an associate professor at the London School of Hygiene and Tropical Medicine, thinks that number — called the basic reproduction number — might be around six for Delta, meaning that, on average, each infected person spreads the virus to six others.

“The Delta variant is the most able and fastest and fittest of those viruses,” said Mike Ryan, executive director of the World Health Organization’s Health Emergencies Programme, in a recent press briefing.

Early evidence suggests it may also cause more severe disease in people who are not vaccinated. 

“There’s clearly increased risk of ICU admission, hospitalization, and death,” said Ashleigh Tuite, PhD, MPH, an infectious disease epidemiologist at the University of Toronto in Ontario.

In a study published ahead of peer review, Dr. Tuite and her coauthor, David Fisman, MD, MPH, reviewed the health outcomes for more than 200,000 people who tested positive for SARS-CoV-2 in Ontario between February and June of 2021. Starting in February, Ontario began screening all positive COVID tests for mutations in the N501Y region for signs of mutation.

Compared with versions of the coronavirus that circulated in 2020, having an Alpha, Beta, or Gamma variant modestly increased the odds that an infected person would become sicker. The Delta variant raised the risk even higher, more than doubling the odds that an infected person would need to be hospitalized or could die from their infection.

Emerging evidence from England and Scotland, analyzed by Public Health England, also shows an increased risk for hospitalization with Delta. The increases are in line with the Canadian data. Experts caution that the picture may change over time as more evidence is gathered.

“What is causing that? We don’t know,” Dr. Tuite said.

Enhanced virus

The Delta variants (there’s actually more than one in the same viral family) have about 15 different mutations compared with the original virus. Two of these, L452R and E484Q, are mutations to the spike protein that were first flagged as problematic in other variants because they appear to help the virus escape the antibodies we make to fight it.

It has another mutation away from its binding site that’s also getting researchers’ attention — P681R.

This mutation appears to enhance the “springiness” of the parts of the virus that dock onto our cells, said Alexander Greninger, MD, PhD, assistant director of the UW Medicine Clinical Virology Laboratory at the University of Washington in Seattle. So it’s more likely to be in the right position to infect our cells if we come into contact with it.

Another theory is that P681R may also enhance the virus’s ability to fuse cells together into clumps that have several different nuclei. These balls of fused cells are called syncytia.

“So it turns into a big factory for making viruses,” said Kamran Kadkhoda, PhD, medical director of immunopathology at the Cleveland Clinic in Ohio.

This capability is not unique to Delta or even to the new coronavirus. Earlier versions and other viruses can do the same thing, but according to a recent paper in Nature, the syncytia that Delta creates are larger than the ones created by previous variants.

Scientists aren’t sure what these supersized syncytia mean, exactly, but they have some theories. They may help the virus copy itself more quickly, so a person’s viral load builds up quickly. That may enhance the ability of the virus to transmit from person to person.

And at least one recent study from China supports this idea. That study, which was posted ahead of peer review on the website Virological.org, tracked 167 people infected with Delta back to a single index case. 

China has used extensive contact tracing to identify people that may have been exposed to the virus and sequester them quickly to tamp down its spread. Once a person is isolated or quarantined, they are tested daily with gold-standard PCR testing to determine whether or not they were infected. 

Researchers compared the characteristics of Delta cases with those of people infected in 2020 with previous versions of the virus.

This study found that people infected by Delta tested positive more quickly than their predecessors did. In 2020, it took an average of 6 days for someone to test positive after an exposure. With Delta, it took an average of about 4 days. 

When people tested positive, they had more than 1,000 times more virus in their bodies, suggesting that the Delta variant has a higher growth rate in the body.

This gives Delta a big advantage. According to Angie Rasmussen, PhD, a virologist at the Vaccine and Infectious Disease Organization at the University of Saskatchewan in Canada, who posted a thread about the study on Twitter, if people are shedding 1,000 times more virus, it is much more likely that close contacts will be exposed to enough of it to become infected themselves.

And if they’re shedding earlier in the course of their infections, the virus has more opportunity to spread.

This may help explain why Delta is so much more contagious.

Beyond transmission, Delta’s ability to form syncytia may have two other important consequences. It may help the virus hide from our immune system, and it may make the virus more damaging to the body.

Commonly, when a virus infects a cell, it will corrupt the cell’s protein-making machinery to crank out more copies of itself. When the cell dies, these new copies are released into the plasma outside the cell where they can float over and infect new cells. It’s in this extracellular space where a virus can also be attacked by the neutralizing antibodies our immune system makes to fight it off.

“Antibodies don’t penetrate inside the cell. If these viruses are going from one cell to another by just fusing to each other, antibodies become less useful,” Dr. Kadkhoda said.

Escape artist

Recent studies show that Delta is also able to escape antibodies made in response to vaccination more effectively than the Alpha, or B.1.1.7 strain. The effect was more pronounced in older adults, who tend to have weaker responses to vaccines in general.

This evasion of the immune system is particularly problematic for people who are only partially vaccinated. Data from the United Kingdom show that a single dose of vaccine is only about 31% effective at preventing illness with Delta, and 75% effective at preventing hospitalization. 

After two doses, the vaccines are still highly effective — even against Delta — reaching 80% protection for illness, and 94% for hospitalization, which is why U.S. officials are begging people to get both doses of their shots, and do it as quickly as possible.

Finally, the virus’s ability to form syncytia may leave greater damage behind in the body’s tissues and organs.

“Especially in the lungs,” Dr. Kadkhoda said. The lungs are very fragile tissues. Their tiny air sacs — the alveoli — are only a single-cell thick. They have to be very thin to exchange oxygen in the blood.

“Any damage like that can severely affect any oxygen exchange and the normal housekeeping activities of that tissue,” he said. “In those vital organs, it may be very problematic.”

The research is still early, but studies in animals and cell lines are backing up what doctors say they are seeing in hospitalized patients.

A recent preprint study from researchers in Japan found that hamsters infected with Delta lost more weight — a proxy for how sick they were — compared with hamsters infected with an older version of the virus. The researchers attribute this to the viruses› ability to fuse cells together to form syncytia.

Another investigation, from researchers in India, infected two groups of hamsters — one with the original “wild type” strain of the virus, the other with the Delta variant of the new coronavirus. 

As in the Japanese study, the hamsters infected with Delta lost more weight. When the researchers performed necropsies on the animals, they found more lung damage and bleeding in hamsters infected with Delta. This study was also posted as a preprint ahead of peer review.

German researchers working with pseudotyped versions of the new coronavirus — viruses that have been genetically changed to make them safer to work with — watched what happened after they used these pseudoviruses to infect lung, colon, and kidney cells in the lab.

They, too, found that cells infected with the Delta variant formed more and larger syncytia compared with cells infected with the wild type strain of the virus. The authors write that their findings suggest Delta could “cause more tissue damage, and thus be more pathogenic, than previous variants.”Researchers say it’s important to remember that, while interesting, this research isn’t conclusive. Hamsters and cells aren’t humans. More studies are needed to prove these theories.

Scientists say that what we already know about Delta makes vaccination more important than ever.

“The net effect is really that, you know, this is worrisome in people who are unvaccinated and then people who have breakthrough infections, but it’s not…a reason to panic or to throw up our hands and say you know, this pandemic is never going to end,” Dr. Tuite said, “[b]ecause what we do see is that the vaccines continue to be highly protective.”

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

Catherine O’Neal, MD, an infectious disease physician, took to the podium of the Louisiana governor’s press conference recently and did not mince words.

“The Delta variant is not last year’s virus, and it’s become incredibly apparent to healthcare workers that we are dealing with a different beast,” she said.

Louisiana is one of the least vaccinated states in the country. In the United States as a whole, 48.6% of the population is fully vaccinated. In Louisiana, it’s just 36%, and Delta is bearing down.

Dr. O’Neal spoke about the pressure that rising COVID cases were already putting on her hospital, Our Lady of the Lake Regional Medical Center in Baton Rouge. She talked about watching her peers, 30- and 40-year-olds, become severely ill with the latest iteration of the new coronavirus — the Delta variant — which is sweeping through the United States with astonishing speed, causing new cases, hospitalizations, and deaths to rise again. 

Dr. O’Neal talked about parents who might not be alive to see their children go off to college in a few weeks. She talked about increasing hospital admissions for infected kids and pregnant women on ventilators.

“I want to be clear after seeing what we’ve seen the last two weeks. We only have two choices: We are either going to get vaccinated and end the pandemic, or we’re going to accept death and a lot of it,” Dr. O’Neal said, her voice choked by emotion.

Where Delta goes, death follows

Delta was first identified in India, where it caused a devastating surge in the spring. In a population that was largely unvaccinated, researchers think it may have caused as many as three million deaths. In just a few months’ time, it has sped across the globe.

Research from the United Kingdom shows that Delta is highly contagious. It’s about 60% more easily passed from person to person than the Alpha version (or B.1.1.7, which was first identified in the United Kingdom). 

Where a single infected person might have spread older versions of the virus to two or three others, mathematician and epidemiologist Adam Kucharski, PhD, an associate professor at the London School of Hygiene and Tropical Medicine, thinks that number — called the basic reproduction number — might be around six for Delta, meaning that, on average, each infected person spreads the virus to six others.

“The Delta variant is the most able and fastest and fittest of those viruses,” said Mike Ryan, executive director of the World Health Organization’s Health Emergencies Programme, in a recent press briefing.

Early evidence suggests it may also cause more severe disease in people who are not vaccinated. 

“There’s clearly increased risk of ICU admission, hospitalization, and death,” said Ashleigh Tuite, PhD, MPH, an infectious disease epidemiologist at the University of Toronto in Ontario.

In a study published ahead of peer review, Dr. Tuite and her coauthor, David Fisman, MD, MPH, reviewed the health outcomes for more than 200,000 people who tested positive for SARS-CoV-2 in Ontario between February and June of 2021. Starting in February, Ontario began screening all positive COVID tests for mutations in the N501Y region for signs of mutation.

Compared with versions of the coronavirus that circulated in 2020, having an Alpha, Beta, or Gamma variant modestly increased the odds that an infected person would become sicker. The Delta variant raised the risk even higher, more than doubling the odds that an infected person would need to be hospitalized or could die from their infection.

Emerging evidence from England and Scotland, analyzed by Public Health England, also shows an increased risk for hospitalization with Delta. The increases are in line with the Canadian data. Experts caution that the picture may change over time as more evidence is gathered.

“What is causing that? We don’t know,” Dr. Tuite said.

Enhanced virus

The Delta variants (there’s actually more than one in the same viral family) have about 15 different mutations compared with the original virus. Two of these, L452R and E484Q, are mutations to the spike protein that were first flagged as problematic in other variants because they appear to help the virus escape the antibodies we make to fight it.

It has another mutation away from its binding site that’s also getting researchers’ attention — P681R.

This mutation appears to enhance the “springiness” of the parts of the virus that dock onto our cells, said Alexander Greninger, MD, PhD, assistant director of the UW Medicine Clinical Virology Laboratory at the University of Washington in Seattle. So it’s more likely to be in the right position to infect our cells if we come into contact with it.

Another theory is that P681R may also enhance the virus’s ability to fuse cells together into clumps that have several different nuclei. These balls of fused cells are called syncytia.

“So it turns into a big factory for making viruses,” said Kamran Kadkhoda, PhD, medical director of immunopathology at the Cleveland Clinic in Ohio.

This capability is not unique to Delta or even to the new coronavirus. Earlier versions and other viruses can do the same thing, but according to a recent paper in Nature, the syncytia that Delta creates are larger than the ones created by previous variants.

Scientists aren’t sure what these supersized syncytia mean, exactly, but they have some theories. They may help the virus copy itself more quickly, so a person’s viral load builds up quickly. That may enhance the ability of the virus to transmit from person to person.

And at least one recent study from China supports this idea. That study, which was posted ahead of peer review on the website Virological.org, tracked 167 people infected with Delta back to a single index case. 

China has used extensive contact tracing to identify people that may have been exposed to the virus and sequester them quickly to tamp down its spread. Once a person is isolated or quarantined, they are tested daily with gold-standard PCR testing to determine whether or not they were infected. 

Researchers compared the characteristics of Delta cases with those of people infected in 2020 with previous versions of the virus.

This study found that people infected by Delta tested positive more quickly than their predecessors did. In 2020, it took an average of 6 days for someone to test positive after an exposure. With Delta, it took an average of about 4 days. 

When people tested positive, they had more than 1,000 times more virus in their bodies, suggesting that the Delta variant has a higher growth rate in the body.

This gives Delta a big advantage. According to Angie Rasmussen, PhD, a virologist at the Vaccine and Infectious Disease Organization at the University of Saskatchewan in Canada, who posted a thread about the study on Twitter, if people are shedding 1,000 times more virus, it is much more likely that close contacts will be exposed to enough of it to become infected themselves.

And if they’re shedding earlier in the course of their infections, the virus has more opportunity to spread.

This may help explain why Delta is so much more contagious.

Beyond transmission, Delta’s ability to form syncytia may have two other important consequences. It may help the virus hide from our immune system, and it may make the virus more damaging to the body.

Commonly, when a virus infects a cell, it will corrupt the cell’s protein-making machinery to crank out more copies of itself. When the cell dies, these new copies are released into the plasma outside the cell where they can float over and infect new cells. It’s in this extracellular space where a virus can also be attacked by the neutralizing antibodies our immune system makes to fight it off.

“Antibodies don’t penetrate inside the cell. If these viruses are going from one cell to another by just fusing to each other, antibodies become less useful,” Dr. Kadkhoda said.

Escape artist

Recent studies show that Delta is also able to escape antibodies made in response to vaccination more effectively than the Alpha, or B.1.1.7 strain. The effect was more pronounced in older adults, who tend to have weaker responses to vaccines in general.

This evasion of the immune system is particularly problematic for people who are only partially vaccinated. Data from the United Kingdom show that a single dose of vaccine is only about 31% effective at preventing illness with Delta, and 75% effective at preventing hospitalization. 

After two doses, the vaccines are still highly effective — even against Delta — reaching 80% protection for illness, and 94% for hospitalization, which is why U.S. officials are begging people to get both doses of their shots, and do it as quickly as possible.

Finally, the virus’s ability to form syncytia may leave greater damage behind in the body’s tissues and organs.

“Especially in the lungs,” Dr. Kadkhoda said. The lungs are very fragile tissues. Their tiny air sacs — the alveoli — are only a single-cell thick. They have to be very thin to exchange oxygen in the blood.

“Any damage like that can severely affect any oxygen exchange and the normal housekeeping activities of that tissue,” he said. “In those vital organs, it may be very problematic.”

The research is still early, but studies in animals and cell lines are backing up what doctors say they are seeing in hospitalized patients.

A recent preprint study from researchers in Japan found that hamsters infected with Delta lost more weight — a proxy for how sick they were — compared with hamsters infected with an older version of the virus. The researchers attribute this to the viruses› ability to fuse cells together to form syncytia.

Another investigation, from researchers in India, infected two groups of hamsters — one with the original “wild type” strain of the virus, the other with the Delta variant of the new coronavirus. 

As in the Japanese study, the hamsters infected with Delta lost more weight. When the researchers performed necropsies on the animals, they found more lung damage and bleeding in hamsters infected with Delta. This study was also posted as a preprint ahead of peer review.

German researchers working with pseudotyped versions of the new coronavirus — viruses that have been genetically changed to make them safer to work with — watched what happened after they used these pseudoviruses to infect lung, colon, and kidney cells in the lab.

They, too, found that cells infected with the Delta variant formed more and larger syncytia compared with cells infected with the wild type strain of the virus. The authors write that their findings suggest Delta could “cause more tissue damage, and thus be more pathogenic, than previous variants.”Researchers say it’s important to remember that, while interesting, this research isn’t conclusive. Hamsters and cells aren’t humans. More studies are needed to prove these theories.

Scientists say that what we already know about Delta makes vaccination more important than ever.

“The net effect is really that, you know, this is worrisome in people who are unvaccinated and then people who have breakthrough infections, but it’s not…a reason to panic or to throw up our hands and say you know, this pandemic is never going to end,” Dr. Tuite said, “[b]ecause what we do see is that the vaccines continue to be highly protective.”

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

Catherine O’Neal, MD, an infectious disease physician, took to the podium of the Louisiana governor’s press conference recently and did not mince words.

“The Delta variant is not last year’s virus, and it’s become incredibly apparent to healthcare workers that we are dealing with a different beast,” she said.

Louisiana is one of the least vaccinated states in the country. In the United States as a whole, 48.6% of the population is fully vaccinated. In Louisiana, it’s just 36%, and Delta is bearing down.

Dr. O’Neal spoke about the pressure that rising COVID cases were already putting on her hospital, Our Lady of the Lake Regional Medical Center in Baton Rouge. She talked about watching her peers, 30- and 40-year-olds, become severely ill with the latest iteration of the new coronavirus — the Delta variant — which is sweeping through the United States with astonishing speed, causing new cases, hospitalizations, and deaths to rise again. 

Dr. O’Neal talked about parents who might not be alive to see their children go off to college in a few weeks. She talked about increasing hospital admissions for infected kids and pregnant women on ventilators.

“I want to be clear after seeing what we’ve seen the last two weeks. We only have two choices: We are either going to get vaccinated and end the pandemic, or we’re going to accept death and a lot of it,” Dr. O’Neal said, her voice choked by emotion.

Where Delta goes, death follows

Delta was first identified in India, where it caused a devastating surge in the spring. In a population that was largely unvaccinated, researchers think it may have caused as many as three million deaths. In just a few months’ time, it has sped across the globe.

Research from the United Kingdom shows that Delta is highly contagious. It’s about 60% more easily passed from person to person than the Alpha version (or B.1.1.7, which was first identified in the United Kingdom). 

Where a single infected person might have spread older versions of the virus to two or three others, mathematician and epidemiologist Adam Kucharski, PhD, an associate professor at the London School of Hygiene and Tropical Medicine, thinks that number — called the basic reproduction number — might be around six for Delta, meaning that, on average, each infected person spreads the virus to six others.

“The Delta variant is the most able and fastest and fittest of those viruses,” said Mike Ryan, executive director of the World Health Organization’s Health Emergencies Programme, in a recent press briefing.

Early evidence suggests it may also cause more severe disease in people who are not vaccinated. 

“There’s clearly increased risk of ICU admission, hospitalization, and death,” said Ashleigh Tuite, PhD, MPH, an infectious disease epidemiologist at the University of Toronto in Ontario.

In a study published ahead of peer review, Dr. Tuite and her coauthor, David Fisman, MD, MPH, reviewed the health outcomes for more than 200,000 people who tested positive for SARS-CoV-2 in Ontario between February and June of 2021. Starting in February, Ontario began screening all positive COVID tests for mutations in the N501Y region for signs of mutation.

Compared with versions of the coronavirus that circulated in 2020, having an Alpha, Beta, or Gamma variant modestly increased the odds that an infected person would become sicker. The Delta variant raised the risk even higher, more than doubling the odds that an infected person would need to be hospitalized or could die from their infection.

Emerging evidence from England and Scotland, analyzed by Public Health England, also shows an increased risk for hospitalization with Delta. The increases are in line with the Canadian data. Experts caution that the picture may change over time as more evidence is gathered.

“What is causing that? We don’t know,” Dr. Tuite said.

Enhanced virus

The Delta variants (there’s actually more than one in the same viral family) have about 15 different mutations compared with the original virus. Two of these, L452R and E484Q, are mutations to the spike protein that were first flagged as problematic in other variants because they appear to help the virus escape the antibodies we make to fight it.

It has another mutation away from its binding site that’s also getting researchers’ attention — P681R.

This mutation appears to enhance the “springiness” of the parts of the virus that dock onto our cells, said Alexander Greninger, MD, PhD, assistant director of the UW Medicine Clinical Virology Laboratory at the University of Washington in Seattle. So it’s more likely to be in the right position to infect our cells if we come into contact with it.

Another theory is that P681R may also enhance the virus’s ability to fuse cells together into clumps that have several different nuclei. These balls of fused cells are called syncytia.

“So it turns into a big factory for making viruses,” said Kamran Kadkhoda, PhD, medical director of immunopathology at the Cleveland Clinic in Ohio.

This capability is not unique to Delta or even to the new coronavirus. Earlier versions and other viruses can do the same thing, but according to a recent paper in Nature, the syncytia that Delta creates are larger than the ones created by previous variants.

Scientists aren’t sure what these supersized syncytia mean, exactly, but they have some theories. They may help the virus copy itself more quickly, so a person’s viral load builds up quickly. That may enhance the ability of the virus to transmit from person to person.

And at least one recent study from China supports this idea. That study, which was posted ahead of peer review on the website Virological.org, tracked 167 people infected with Delta back to a single index case. 

China has used extensive contact tracing to identify people that may have been exposed to the virus and sequester them quickly to tamp down its spread. Once a person is isolated or quarantined, they are tested daily with gold-standard PCR testing to determine whether or not they were infected. 

Researchers compared the characteristics of Delta cases with those of people infected in 2020 with previous versions of the virus.

This study found that people infected by Delta tested positive more quickly than their predecessors did. In 2020, it took an average of 6 days for someone to test positive after an exposure. With Delta, it took an average of about 4 days. 

When people tested positive, they had more than 1,000 times more virus in their bodies, suggesting that the Delta variant has a higher growth rate in the body.

This gives Delta a big advantage. According to Angie Rasmussen, PhD, a virologist at the Vaccine and Infectious Disease Organization at the University of Saskatchewan in Canada, who posted a thread about the study on Twitter, if people are shedding 1,000 times more virus, it is much more likely that close contacts will be exposed to enough of it to become infected themselves.

And if they’re shedding earlier in the course of their infections, the virus has more opportunity to spread.

This may help explain why Delta is so much more contagious.

Beyond transmission, Delta’s ability to form syncytia may have two other important consequences. It may help the virus hide from our immune system, and it may make the virus more damaging to the body.

Commonly, when a virus infects a cell, it will corrupt the cell’s protein-making machinery to crank out more copies of itself. When the cell dies, these new copies are released into the plasma outside the cell where they can float over and infect new cells. It’s in this extracellular space where a virus can also be attacked by the neutralizing antibodies our immune system makes to fight it off.

“Antibodies don’t penetrate inside the cell. If these viruses are going from one cell to another by just fusing to each other, antibodies become less useful,” Dr. Kadkhoda said.

Escape artist

Recent studies show that Delta is also able to escape antibodies made in response to vaccination more effectively than the Alpha, or B.1.1.7 strain. The effect was more pronounced in older adults, who tend to have weaker responses to vaccines in general.

This evasion of the immune system is particularly problematic for people who are only partially vaccinated. Data from the United Kingdom show that a single dose of vaccine is only about 31% effective at preventing illness with Delta, and 75% effective at preventing hospitalization. 

After two doses, the vaccines are still highly effective — even against Delta — reaching 80% protection for illness, and 94% for hospitalization, which is why U.S. officials are begging people to get both doses of their shots, and do it as quickly as possible.

Finally, the virus’s ability to form syncytia may leave greater damage behind in the body’s tissues and organs.

“Especially in the lungs,” Dr. Kadkhoda said. The lungs are very fragile tissues. Their tiny air sacs — the alveoli — are only a single-cell thick. They have to be very thin to exchange oxygen in the blood.

“Any damage like that can severely affect any oxygen exchange and the normal housekeeping activities of that tissue,” he said. “In those vital organs, it may be very problematic.”

The research is still early, but studies in animals and cell lines are backing up what doctors say they are seeing in hospitalized patients.

A recent preprint study from researchers in Japan found that hamsters infected with Delta lost more weight — a proxy for how sick they were — compared with hamsters infected with an older version of the virus. The researchers attribute this to the viruses› ability to fuse cells together to form syncytia.

Another investigation, from researchers in India, infected two groups of hamsters — one with the original “wild type” strain of the virus, the other with the Delta variant of the new coronavirus. 

As in the Japanese study, the hamsters infected with Delta lost more weight. When the researchers performed necropsies on the animals, they found more lung damage and bleeding in hamsters infected with Delta. This study was also posted as a preprint ahead of peer review.

German researchers working with pseudotyped versions of the new coronavirus — viruses that have been genetically changed to make them safer to work with — watched what happened after they used these pseudoviruses to infect lung, colon, and kidney cells in the lab.

They, too, found that cells infected with the Delta variant formed more and larger syncytia compared with cells infected with the wild type strain of the virus. The authors write that their findings suggest Delta could “cause more tissue damage, and thus be more pathogenic, than previous variants.”Researchers say it’s important to remember that, while interesting, this research isn’t conclusive. Hamsters and cells aren’t humans. More studies are needed to prove these theories.

Scientists say that what we already know about Delta makes vaccination more important than ever.

“The net effect is really that, you know, this is worrisome in people who are unvaccinated and then people who have breakthrough infections, but it’s not…a reason to panic or to throw up our hands and say you know, this pandemic is never going to end,” Dr. Tuite said, “[b]ecause what we do see is that the vaccines continue to be highly protective.”

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

A single high dose of the antifungal agent liposomal amphotericin B (L-AmB; AmBisome, Gilead Sciences), with a background regimen of flucytosine and fluconazole, is non-inferior and significantly safer in preventing mortality in HIV-associated cryptococcal meningitis than a conventional seven-day regimen that is the current standard of care, according to a new study.

The much-anticipated results suggest an important alternative amid controversy over the drug’s cost and availability.

“The results of this phase 3 [AMBITION-cm] trial make it clear that this approach is just as good as the current World Health Organization-recommended first-line treatment in preventing death,” first author David S. Lawrence, MD, AMBITION study lead clinician, of the London School of Hygiene and Tropical Medicine, United Kingdom, said in an interview.

“The fact that this was the largest ever trial [on HIV-associated cryptococcal meningitis] conducted to date… gives us a high level of confidence in these results,” he said of the study, which was presented at the virtual annual meeting of the International AIDS Society.

“We believe that this should become the WHO-recommended first-line regimen,” he emphasized.

In commenting on the study, Meg Doherty, MD, PhD, director of global HIV, hepatitis, and STI programs at WHO, agreed that a shorter regimen could be vital, particularly in settings with limited resources.

“The results from the AMBITION trial are important for low- and middle-income countries, where the cost and complexity of implementing the current standard seven-day course of L-ambisome or cryptococcal meningitis treatment can put this out of reach for many,” she told this news organization.

“Simplification that maintains the highest quality of care is an important component of the public health approach for HIV treatment and care,” she added.

Dr. Doherty could not comment on any possible changes to WHO recommendations, which are formulated by an independent guideline development group, but a spokesperson said that “WHO is preparing an updated review of the evidence for treating cryptococcal disease as a first step towards updating guidance.”

Conventional treatment toxicities

Cryptococcal meningitis is a leading cause of death in HIV, and the conventional treatment of amphotericin B deoxycholate, though less expensive than L-AmB, is more toxic, causing anemia, renal impairment, and electrolyte abnormalities, Dr. Lawrence explained

Having previously shown a single 10 mg/kg dose of L-AmB to be as effective as the longer regimen of 14 daily doses in terms of clearing cryptococcus from the cerebrospinal fluid, Dr. Lawrence and his colleagues conducted the phase 3 AMBITION-Cm trial to evaluate the effect on mortality, enrolling 844 patients in Botswana, Malawi, South Africa, Uganda, and Zimbabwe who were HIV-positive and had a first episode of cryptococcal meningitis.

Participants in the study were randomized to treatment either with single, high-dose L-AmB (10 mg/kg), combined with 14 days of flucytosine 100 mg/kg/day and fluconazole 1,200 mg/day or to a control group receiving 7 daily doses of AmB deoxycholate (1 mg/kg) plus 7 days of flucytosine 100 mg/kg/day, followed by 7 days of fluconazole 1,200 mg/day.

All patients were also provided with consolidation therapy of fluconazole 800 mg/day for eight weeks. Of the patients, 60.2% were male, their median age was 37, and their median CD4 count was 27 cells/mm³.

For the primary endpoint in the intention-to-treat analysis of 814 patients, the 10-week mortality rate in the single-dose L-AmB group was 24.82% (101 of 407) and 28.75% (117 of 407) in the control arm, for a difference (-3.93%) that was well within the pre-specified non-inferiority margin of 10%.

As expected, the safety measures were significantly improved with the single-dose of L-AmB: Rates of grade 3 or 4 adverse events within the initial 21 days of treatment in the single-dose L-AmB group were 50% versus 62.3% in the control group, and severe anemia occurred in just 13% of single-dose L-AmB participants, compared with 41% in the AmB deoxycholate control arm (both P < .001), Dr. Lawrence reported.

Furthermore, the average decline in hemoglobin over the first week was 0.3 g/dL in the single-dose L-AmB arm and 1.9 g/dL in the control arm, resulting in the need for more blood transfusions in the control arm (P < .001).

The impact on kidney function was also worse in the higher dose arm, with an average increase in creatinine over the first week of 20.2% in the L-AmB group versus 49.7% in the control group, while hypokalemia and thrombophlebitis were also more common with the higher dose group, Dr. Lawrence noted.

In the adjusted analysis, the single-dose L-AmB measures were in fact superior after adjusting for factors including research site, age, sex, baseline Glasgow Coma Scale, CD4 count, CSF cryptococcal colony-forming units/mL, antiretroviral therapy status, hemoglobin, and CSF opening pressure.

Mortality rate still high – but significantly reduced

The mortality rate of about 25% in the study after the treatment is still significantly higher than typically seen in high-income countries such as the United States, where HIV-associated cryptococcal meningitis is less common and associated with a mortality of roughly 10-15%, Dr. Lawrence noted.

The rate is nevertheless among the lowest mortality rates ever reported within a clinical trial conducted in resource-limited settings, he explained.

“These results are a step in the right direction and a significant improvement on the rates of 40% to 45% reported with two-week L-AmB-based regimens in African settings,” Dr. Lawrence underscored.

Higher cost — but potentially more cost-effective

With a higher cost than AmB deoxycholate, L-AmB’s utilization in resource-limited settings has been a challenge: A single vial of L-AmB ranges from $80 to $200, according to some reports, and while 14-day dosing requires as many as 42 vials of L-AmB, even a 7-day regimen still requires 21 vials.

In comparison, the single-dose L-AmB regimen only requires an average of 10 to 11 vials per patient, but the regimen’s higher safety could translate to far greater cost savings, Dr. Lawrence explained.

“While the AmBisome regimen is technically more expensive in terms of drugs, we expect it to be cost-effective or possibly cost-saving when taking into account that there is less toxicity, fewer blood tests, less transfusions, etc., and possibly shorter duration of hospital admission,” he said.

Cost, supply controversy: ‘Black fungus’-related demand

The drug’s cost — as well as supply issues — have meanwhile become even more of a problem as L-AmB has unexpectedly also become urgently needed in the treatment of mucormycosis in India and Nepal, where the otherwise rare fungal disease, commonly known as “black fungus,” has been increasingly affecting COVID-19 patients and survivors.

Gilead had previously announced in 2018 its intention to make L-AmB more widely available at a price of $16.25 per vial, but “implementation of this has been slow,” Dr. Lawrence said.

As a result, Gilead is facing heightened pressure to implement the lower prices – and also improve substantial supply issues, with Médecins Sans Frontières (Doctors Without Borders) and dozens of other global organizations issuing an open letter to Gilead and partner Viatris in June calling for immediate action to implement the lower price and improve supply of L-AmB.

In a company statement, Gilead responded, detailing its “commit[ment] to the non-profit pricing for the treatment of cryptococcal meningitis” and to efforts to improve the public health crisis in India.

For their part, Dr. Lawrence and his colleagues are working on producing more research on the issue.

“We hope that the conclusive results of the AMBITION trial will give a much needed push to implement this program,” he said.

“We are also currently completing the cost-effectiveness analysis of the study, which we hope will provide additional evidence to support widespread implementation of this regimen and highlight further the urgent need to broaden access to AmBisome and flucytosine,” he said.

The trial was supported by a grant through the European Developing Countries Clinical Trials Partnership (EDCTP), the Swedish International Development Cooperation Agency (SIDA) (TRIA2015-1092), and the Wellcome Trust / Medical Research Council (UK)/UKAID Joint Global Health Trials (MR/P006922/1. The AmBisome was donated by Gilead Sciences. Dr. Lawrence had no disclosures to report.

A single high dose of the antifungal agent liposomal amphotericin B (L-AmB; AmBisome, Gilead Sciences), with a background regimen of flucytosine and fluconazole, is non-inferior and significantly safer in preventing mortality in HIV-associated cryptococcal meningitis than a conventional seven-day regimen that is the current standard of care, according to a new study.

The much-anticipated results suggest an important alternative amid controversy over the drug’s cost and availability.

“The results of this phase 3 [AMBITION-cm] trial make it clear that this approach is just as good as the current World Health Organization-recommended first-line treatment in preventing death,” first author David S. Lawrence, MD, AMBITION study lead clinician, of the London School of Hygiene and Tropical Medicine, United Kingdom, said in an interview.

“The fact that this was the largest ever trial [on HIV-associated cryptococcal meningitis] conducted to date… gives us a high level of confidence in these results,” he said of the study, which was presented at the virtual annual meeting of the International AIDS Society.

“We believe that this should become the WHO-recommended first-line regimen,” he emphasized.

In commenting on the study, Meg Doherty, MD, PhD, director of global HIV, hepatitis, and STI programs at WHO, agreed that a shorter regimen could be vital, particularly in settings with limited resources.

“The results from the AMBITION trial are important for low- and middle-income countries, where the cost and complexity of implementing the current standard seven-day course of L-ambisome or cryptococcal meningitis treatment can put this out of reach for many,” she told this news organization.

“Simplification that maintains the highest quality of care is an important component of the public health approach for HIV treatment and care,” she added.

Dr. Doherty could not comment on any possible changes to WHO recommendations, which are formulated by an independent guideline development group, but a spokesperson said that “WHO is preparing an updated review of the evidence for treating cryptococcal disease as a first step towards updating guidance.”

Conventional treatment toxicities

Cryptococcal meningitis is a leading cause of death in HIV, and the conventional treatment of amphotericin B deoxycholate, though less expensive than L-AmB, is more toxic, causing anemia, renal impairment, and electrolyte abnormalities, Dr. Lawrence explained

Having previously shown a single 10 mg/kg dose of L-AmB to be as effective as the longer regimen of 14 daily doses in terms of clearing cryptococcus from the cerebrospinal fluid, Dr. Lawrence and his colleagues conducted the phase 3 AMBITION-Cm trial to evaluate the effect on mortality, enrolling 844 patients in Botswana, Malawi, South Africa, Uganda, and Zimbabwe who were HIV-positive and had a first episode of cryptococcal meningitis.

Participants in the study were randomized to treatment either with single, high-dose L-AmB (10 mg/kg), combined with 14 days of flucytosine 100 mg/kg/day and fluconazole 1,200 mg/day or to a control group receiving 7 daily doses of AmB deoxycholate (1 mg/kg) plus 7 days of flucytosine 100 mg/kg/day, followed by 7 days of fluconazole 1,200 mg/day.

All patients were also provided with consolidation therapy of fluconazole 800 mg/day for eight weeks. Of the patients, 60.2% were male, their median age was 37, and their median CD4 count was 27 cells/mm³.

For the primary endpoint in the intention-to-treat analysis of 814 patients, the 10-week mortality rate in the single-dose L-AmB group was 24.82% (101 of 407) and 28.75% (117 of 407) in the control arm, for a difference (-3.93%) that was well within the pre-specified non-inferiority margin of 10%.

As expected, the safety measures were significantly improved with the single-dose of L-AmB: Rates of grade 3 or 4 adverse events within the initial 21 days of treatment in the single-dose L-AmB group were 50% versus 62.3% in the control group, and severe anemia occurred in just 13% of single-dose L-AmB participants, compared with 41% in the AmB deoxycholate control arm (both P < .001), Dr. Lawrence reported.

Furthermore, the average decline in hemoglobin over the first week was 0.3 g/dL in the single-dose L-AmB arm and 1.9 g/dL in the control arm, resulting in the need for more blood transfusions in the control arm (P < .001).

The impact on kidney function was also worse in the higher dose arm, with an average increase in creatinine over the first week of 20.2% in the L-AmB group versus 49.7% in the control group, while hypokalemia and thrombophlebitis were also more common with the higher dose group, Dr. Lawrence noted.

In the adjusted analysis, the single-dose L-AmB measures were in fact superior after adjusting for factors including research site, age, sex, baseline Glasgow Coma Scale, CD4 count, CSF cryptococcal colony-forming units/mL, antiretroviral therapy status, hemoglobin, and CSF opening pressure.

Mortality rate still high – but significantly reduced

The mortality rate of about 25% in the study after the treatment is still significantly higher than typically seen in high-income countries such as the United States, where HIV-associated cryptococcal meningitis is less common and associated with a mortality of roughly 10-15%, Dr. Lawrence noted.

The rate is nevertheless among the lowest mortality rates ever reported within a clinical trial conducted in resource-limited settings, he explained.

“These results are a step in the right direction and a significant improvement on the rates of 40% to 45% reported with two-week L-AmB-based regimens in African settings,” Dr. Lawrence underscored.

Higher cost — but potentially more cost-effective

With a higher cost than AmB deoxycholate, L-AmB’s utilization in resource-limited settings has been a challenge: A single vial of L-AmB ranges from $80 to $200, according to some reports, and while 14-day dosing requires as many as 42 vials of L-AmB, even a 7-day regimen still requires 21 vials.

In comparison, the single-dose L-AmB regimen only requires an average of 10 to 11 vials per patient, but the regimen’s higher safety could translate to far greater cost savings, Dr. Lawrence explained.

“While the AmBisome regimen is technically more expensive in terms of drugs, we expect it to be cost-effective or possibly cost-saving when taking into account that there is less toxicity, fewer blood tests, less transfusions, etc., and possibly shorter duration of hospital admission,” he said.

Cost, supply controversy: ‘Black fungus’-related demand

The drug’s cost — as well as supply issues — have meanwhile become even more of a problem as L-AmB has unexpectedly also become urgently needed in the treatment of mucormycosis in India and Nepal, where the otherwise rare fungal disease, commonly known as “black fungus,” has been increasingly affecting COVID-19 patients and survivors.

Gilead had previously announced in 2018 its intention to make L-AmB more widely available at a price of $16.25 per vial, but “implementation of this has been slow,” Dr. Lawrence said.

As a result, Gilead is facing heightened pressure to implement the lower prices – and also improve substantial supply issues, with Médecins Sans Frontières (Doctors Without Borders) and dozens of other global organizations issuing an open letter to Gilead and partner Viatris in June calling for immediate action to implement the lower price and improve supply of L-AmB.

In a company statement, Gilead responded, detailing its “commit[ment] to the non-profit pricing for the treatment of cryptococcal meningitis” and to efforts to improve the public health crisis in India.

For their part, Dr. Lawrence and his colleagues are working on producing more research on the issue.

“We hope that the conclusive results of the AMBITION trial will give a much needed push to implement this program,” he said.

“We are also currently completing the cost-effectiveness analysis of the study, which we hope will provide additional evidence to support widespread implementation of this regimen and highlight further the urgent need to broaden access to AmBisome and flucytosine,” he said.

The trial was supported by a grant through the European Developing Countries Clinical Trials Partnership (EDCTP), the Swedish International Development Cooperation Agency (SIDA) (TRIA2015-1092), and the Wellcome Trust / Medical Research Council (UK)/UKAID Joint Global Health Trials (MR/P006922/1. The AmBisome was donated by Gilead Sciences. Dr. Lawrence had no disclosures to report.

A single high dose of the antifungal agent liposomal amphotericin B (L-AmB; AmBisome, Gilead Sciences), with a background regimen of flucytosine and fluconazole, is non-inferior and significantly safer in preventing mortality in HIV-associated cryptococcal meningitis than a conventional seven-day regimen that is the current standard of care, according to a new study.

The much-anticipated results suggest an important alternative amid controversy over the drug’s cost and availability.

“The results of this phase 3 [AMBITION-cm] trial make it clear that this approach is just as good as the current World Health Organization-recommended first-line treatment in preventing death,” first author David S. Lawrence, MD, AMBITION study lead clinician, of the London School of Hygiene and Tropical Medicine, United Kingdom, said in an interview.

“The fact that this was the largest ever trial [on HIV-associated cryptococcal meningitis] conducted to date… gives us a high level of confidence in these results,” he said of the study, which was presented at the virtual annual meeting of the International AIDS Society.

“We believe that this should become the WHO-recommended first-line regimen,” he emphasized.

In commenting on the study, Meg Doherty, MD, PhD, director of global HIV, hepatitis, and STI programs at WHO, agreed that a shorter regimen could be vital, particularly in settings with limited resources.

“The results from the AMBITION trial are important for low- and middle-income countries, where the cost and complexity of implementing the current standard seven-day course of L-ambisome or cryptococcal meningitis treatment can put this out of reach for many,” she told this news organization.

“Simplification that maintains the highest quality of care is an important component of the public health approach for HIV treatment and care,” she added.

Dr. Doherty could not comment on any possible changes to WHO recommendations, which are formulated by an independent guideline development group, but a spokesperson said that “WHO is preparing an updated review of the evidence for treating cryptococcal disease as a first step towards updating guidance.”

Conventional treatment toxicities

Cryptococcal meningitis is a leading cause of death in HIV, and the conventional treatment of amphotericin B deoxycholate, though less expensive than L-AmB, is more toxic, causing anemia, renal impairment, and electrolyte abnormalities, Dr. Lawrence explained

Having previously shown a single 10 mg/kg dose of L-AmB to be as effective as the longer regimen of 14 daily doses in terms of clearing cryptococcus from the cerebrospinal fluid, Dr. Lawrence and his colleagues conducted the phase 3 AMBITION-Cm trial to evaluate the effect on mortality, enrolling 844 patients in Botswana, Malawi, South Africa, Uganda, and Zimbabwe who were HIV-positive and had a first episode of cryptococcal meningitis.

Participants in the study were randomized to treatment either with single, high-dose L-AmB (10 mg/kg), combined with 14 days of flucytosine 100 mg/kg/day and fluconazole 1,200 mg/day or to a control group receiving 7 daily doses of AmB deoxycholate (1 mg/kg) plus 7 days of flucytosine 100 mg/kg/day, followed by 7 days of fluconazole 1,200 mg/day.

All patients were also provided with consolidation therapy of fluconazole 800 mg/day for eight weeks. Of the patients, 60.2% were male, their median age was 37, and their median CD4 count was 27 cells/mm³.

For the primary endpoint in the intention-to-treat analysis of 814 patients, the 10-week mortality rate in the single-dose L-AmB group was 24.82% (101 of 407) and 28.75% (117 of 407) in the control arm, for a difference (-3.93%) that was well within the pre-specified non-inferiority margin of 10%.

As expected, the safety measures were significantly improved with the single-dose of L-AmB: Rates of grade 3 or 4 adverse events within the initial 21 days of treatment in the single-dose L-AmB group were 50% versus 62.3% in the control group, and severe anemia occurred in just 13% of single-dose L-AmB participants, compared with 41% in the AmB deoxycholate control arm (both P < .001), Dr. Lawrence reported.

Furthermore, the average decline in hemoglobin over the first week was 0.3 g/dL in the single-dose L-AmB arm and 1.9 g/dL in the control arm, resulting in the need for more blood transfusions in the control arm (P < .001).

The impact on kidney function was also worse in the higher dose arm, with an average increase in creatinine over the first week of 20.2% in the L-AmB group versus 49.7% in the control group, while hypokalemia and thrombophlebitis were also more common with the higher dose group, Dr. Lawrence noted.

In the adjusted analysis, the single-dose L-AmB measures were in fact superior after adjusting for factors including research site, age, sex, baseline Glasgow Coma Scale, CD4 count, CSF cryptococcal colony-forming units/mL, antiretroviral therapy status, hemoglobin, and CSF opening pressure.

Mortality rate still high – but significantly reduced

The mortality rate of about 25% in the study after the treatment is still significantly higher than typically seen in high-income countries such as the United States, where HIV-associated cryptococcal meningitis is less common and associated with a mortality of roughly 10-15%, Dr. Lawrence noted.

The rate is nevertheless among the lowest mortality rates ever reported within a clinical trial conducted in resource-limited settings, he explained.

“These results are a step in the right direction and a significant improvement on the rates of 40% to 45% reported with two-week L-AmB-based regimens in African settings,” Dr. Lawrence underscored.

Higher cost — but potentially more cost-effective

With a higher cost than AmB deoxycholate, L-AmB’s utilization in resource-limited settings has been a challenge: A single vial of L-AmB ranges from $80 to $200, according to some reports, and while 14-day dosing requires as many as 42 vials of L-AmB, even a 7-day regimen still requires 21 vials.

In comparison, the single-dose L-AmB regimen only requires an average of 10 to 11 vials per patient, but the regimen’s higher safety could translate to far greater cost savings, Dr. Lawrence explained.

“While the AmBisome regimen is technically more expensive in terms of drugs, we expect it to be cost-effective or possibly cost-saving when taking into account that there is less toxicity, fewer blood tests, less transfusions, etc., and possibly shorter duration of hospital admission,” he said.

Cost, supply controversy: ‘Black fungus’-related demand

The drug’s cost — as well as supply issues — have meanwhile become even more of a problem as L-AmB has unexpectedly also become urgently needed in the treatment of mucormycosis in India and Nepal, where the otherwise rare fungal disease, commonly known as “black fungus,” has been increasingly affecting COVID-19 patients and survivors.

Gilead had previously announced in 2018 its intention to make L-AmB more widely available at a price of $16.25 per vial, but “implementation of this has been slow,” Dr. Lawrence said.

As a result, Gilead is facing heightened pressure to implement the lower prices – and also improve substantial supply issues, with Médecins Sans Frontières (Doctors Without Borders) and dozens of other global organizations issuing an open letter to Gilead and partner Viatris in June calling for immediate action to implement the lower price and improve supply of L-AmB.

In a company statement, Gilead responded, detailing its “commit[ment] to the non-profit pricing for the treatment of cryptococcal meningitis” and to efforts to improve the public health crisis in India.

For their part, Dr. Lawrence and his colleagues are working on producing more research on the issue.

“We hope that the conclusive results of the AMBITION trial will give a much needed push to implement this program,” he said.

“We are also currently completing the cost-effectiveness analysis of the study, which we hope will provide additional evidence to support widespread implementation of this regimen and highlight further the urgent need to broaden access to AmBisome and flucytosine,” he said.

The trial was supported by a grant through the European Developing Countries Clinical Trials Partnership (EDCTP), the Swedish International Development Cooperation Agency (SIDA) (TRIA2015-1092), and the Wellcome Trust / Medical Research Council (UK)/UKAID Joint Global Health Trials (MR/P006922/1. The AmBisome was donated by Gilead Sciences. Dr. Lawrence had no disclosures to report.

With 49% of the U.S. population fully vaccinated against SARS-CoV-2, a new study highlights the degree of vaccine hesitancy among patients with rheumatic disease to get the vaccine.

Halfpoint Images/Moment/Getty Images

The international study, published in May 2021 in Rheumatology, suggests that, of 1,258 patients surveyed worldwide, approximately 40% of patients said they would decline the vaccine.

“Sometimes it’s helpful to talk through their concerns,” said Jeffrey Curtis, MD, MPH, a University of Alabama at Birmingham rheumatologist who leads the American College of Rheumatology COVID-19 vaccine task force. Dr. Curtis recently reviewed the current literature on COVID-19 vaccination in patients with rheumatic and musculoskeletal diseases (RMDs) at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

COVID-19 vaccinations for patients with autoimmune inflammatory rheumatic disease (AIIRD) is not straightforward. The immune response can be blunted by existing treatments and disease flares can occur.

Courtesy UAB Photo

The latest version of COVID-19 vaccination guidance for patients with RMDs from the ACR addresses vaccine use and implementation strategies. The guidance was issued as conditional or provisional because of the lack of evidence. Its principals are largely based on accepted practice for other vaccines. The guidance is routinely updated as new evidence becomes available. In his presentation at GRAPPA, Dr. Curtis reviewed the latest version of the guidance, which he emphasized is a guidance only and not meant to replace clinical judgment or shared decision-making with patients.

“This is a platform for you to start from as you are thinking about and discussing with your patient what might be best for him or her,” he said.
 

Concerns about impact of disease activity, treatments on effectiveness

Dr. Curtis highlighted some controversial aspects of COVID-19 vaccines, including heterogeneity of rheumatic diseases and treatment. Patients with AIIRD, including psoriatic arthritis, spondyloarthritis, RA, and lupus, are at higher risk for hospitalized COVID-19 and worse outcomes, and as such, they are prioritized for vaccination by the Centers for Disease Control and Prevention.

However, for AIIRD patients, the immune response to COVID-19 vaccination can be “blunted,” according to one study. This may be because of glucocorticoid use or high disease activity. Immunomodulatory therapies, such as methotrexate, rituximab, and abatacept, are known to diminish vaccine response in general. The evidence is less clear for tumor necrosis factor and Janus kinase inhibitors, but they are thought to have the same impact on vaccine effectiveness, Dr. Curtis said. But in these cases, if the effect of a COVID-19 vaccine drops from 90% to 70%, the benefits of vaccination still far outweighs the risk of contracting COVID-19.

“Although we don’t have strong data with clinical outcomes for autoimmune disease or inflammatory disease patients, I’ll run a hypothetical and say: ‘Look, if this vaccine starts 90%-95% effective, even if it’s only 70% effective in somebody with lupus or vasculitis or someone who is taking a higher dose of steroids, I’ll take 70% over nothing if you chose to be vaccinated,’ ” he said.

The benefit of vaccination also outweighs the potential risk of disease flare, he said. The risk is real, but to date, no studies have pointed to a significant risk of disease flare or worsening. However, there have been reported cases of myocardial infarction.

Autoimmune manifestations after vaccination vs. after infection

Researchers writing in the June 29, 2021, issue of JAMA Cardiology described case reports of acute myocarditis in 23 people who received the BNT162b2-mRNA (Pfizer-BioNTech) or mRNA-1273 (Moderna) messenger RNA (mRNA) COVID-19 vaccines. Plus, there been subsequent reports of myocarditis in other patients, wrote David K. Shay, MD, MPH, in an accompanying editorial. Dr. Shay is a member of the CDC COVID-19 Response Team.

“What do we know about this possible association between myocarditis and immunization with mRNA-based COVID-19 vaccines, and what remains unclear? Acute onset of chest pain 3-5 days after vaccine administration, usually after a second dose, is a typical feature of reported cases and suggests an immune-mediated mechanism,” he said.

The cases of myocarditis are concerning, Dr. Curtis said, but the risk is very low with relatively few cases reported among 161 million fully vaccinated people in the United States.

“Certainly, we’re not seeking to minimize that, but the risk of getting COVID and some of the downstream sequelae (autoimmune manifestations) almost certainly outweigh the risks for some of the autoimmune manifestations or worsening [condition],” he said.

A nationwide cohort study from Denmark of 58,052 patients with inflammatory rheumatic disease published in December 2020 in Rheumatology, found that patients with COVID-19 who had an inflammatory rheumatic disease were more likely to be admitted to the hospital, compared with COVID-19 patients without rheumatic disease. Patients with rheumatic disease had a higher risk of a severe COVID-19 outcome, but it was not a statistically significant difference, said Dr. Curtis, adding that the individual factors such as age and treatment currently received largely determines the risk. The strongest associations between hospitalization for COVID-19 and rheumatic disease were found among patients with RA, vasculitis, and connective tissue disease. Dr. Curtis noted that his own new study results show that risk of death from a COVID-19 infection is higher for patients who have RA or psoriatic arthritis.

There have been published case reports of patients who have developed new-onset lupus, vasculitis, Kawasaki disease, multiple sclerosis, autoimmune cytopenias, and other manifestations after a COVID-19 infection. “These authors suggest that perhaps there is a transient influence on the immune system that leads to a loss of self-tolerance to antigens,” Dr. Curtis said. “Some patients may have an underlying predisposition to autoimmunity in which infections just unmask as we sometimes see with other infections – chronic hepatitis for example.”
 

Antibody tests not recommended

In its COVID-19 guidance, the ACR, like the Food and Drug Administration, recommends health care providers not to routinely order antibody tests for IgM or IgG to assess immunity after a person has been vaccinated or to assess the need for vaccination in an unvaccinated person. More research is needed to determine if antibodies provide protection, and if so, for how long and how much. Plus, the antibody testing process is not clear cut, so ordering the wrong test is possible, Dr. Curtis said. The tests should clearly differentiate between spike proteins or nucleocapsid proteins.

“The bottom line is that you might be ordering the wrong lab test. Even if you’re ordering the right lab test, I would assert that you probably don’t know what to do with the result. I would then ask you, ‘Does it mean they are protected? Does it mean they are not protected? What are you going to do with the results?’ ” he asked.

Kevin Winthrop, MD, MPH, a specialist in infectious diseases at Oregon Health & Science University, Portland, said that, at this point, it’s too early to know what antibody tests mean. “I think it is tempting to test some people, especially patients on B-cell depletion therapy and those on mycophenolate mofetil (MMF). Outside of those two types of [disease-modifying antirheumatic drug] users, I wouldn’t be tempted to test. We don’t know how well protected they are, but we assume they are protected to some extent,” he said. “They’re probably partially protected and as such, they should take the same precautions they were taking a year ago: masking and avoidance. I think that’s just how it’s going to be for those folks for another year until we get this thing sorted out.”
 

Modifications to existing rheumatic disease therapies

In its COVID-19 vaccine guidance, the ACR issued recommendations for some common rheumatic disease therapeutics before and/or after the COVID-19 vaccine is administered. The modifications are limited to MMF, methotrexate, JAK inhibitors, subcutaneous abatacept, acetaminophen, and NSAIDs. The recommendations include: hold mycophenolate for 1 week after vaccination if disease is stable; for patients with well-controlled disease, hold methotrexate for 1 week after each of the two mRNA vaccine doses; for patients with well-controlled disease receiving the Johnson & Johnson vaccine, hold methotrexate for 2 weeks after receiving the vaccine; hold JAK inhibitors for 1 week after each dose; for abatacept subcutaneous, hold treatment for 1 week before and after the first dose; and in patients with stable disease, hold acetaminophen and NSAIDs for 24 hours before vaccination, because taking either before vaccination could blunt the vaccine response, Dr. Curtis said.

Holding medication, such as methotrexate, could risk having a flare-up of disease. One study showed the rate of disease flare-up because of withholding standard treatment may be up to 11%, compared with 5.1% in patients who did not hold treatment, he said.

“The point is, if you hold some of these therapies, whether methotrexate or tofacitinib, arthritis will get a little bit worse,” Dr. Curtis said.

A study published on the preprint server medRxiv found that immunosuppressive therapies blunted the response of SARS-CoV-2 vaccines in patients with chronic inflammatory diseases, most significantly with glucocorticoids and B-cell therapies.

“That’s what’s led to a lot of the guidance statements about holding treatments for a week or 2 for rituximab. If you’re giving it at 6-month intervals, you want to schedule the vaccine dose or series at about month 5, or a month before the next cycle,” he said.

Talking with patients about COVID-19 vaccination

In talking with patients about vaccine safety, Dr. Curtis recommends addressing a few common misperceptions. First, COVID-19 viruses were not created with a live-attenuated virus (which would be contraindicated for immunosuppressed patients). “You can put patients’ mind at ease that none of the vaccine candidates or platforms – even those that say viral vector – put patients at risk for contracting the infection. These are nonreplicating. So, it’s like you extracted the engine that would allow this virus to replicate,” he said.

Of three COVID-19 vaccinations available in the United States, is one better than the other? The ACR COVID-19 vaccine task force did not reach a consensus on safety profiles of the vaccines because, without head-to-head comparisons, it’s impossible to know, he said.

In talking with patients, review the protocol for continuing with prescribed treatment modalities before the patient receives a COVID-19 vaccine. Safety concerns and concerns about the possibility of having a disease flare-up should be addressed, he said.

With 49% of the U.S. population fully vaccinated against SARS-CoV-2, a new study highlights the degree of vaccine hesitancy among patients with rheumatic disease to get the vaccine.

Halfpoint Images/Moment/Getty Images

The international study, published in May 2021 in Rheumatology, suggests that, of 1,258 patients surveyed worldwide, approximately 40% of patients said they would decline the vaccine.

“Sometimes it’s helpful to talk through their concerns,” said Jeffrey Curtis, MD, MPH, a University of Alabama at Birmingham rheumatologist who leads the American College of Rheumatology COVID-19 vaccine task force. Dr. Curtis recently reviewed the current literature on COVID-19 vaccination in patients with rheumatic and musculoskeletal diseases (RMDs) at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

COVID-19 vaccinations for patients with autoimmune inflammatory rheumatic disease (AIIRD) is not straightforward. The immune response can be blunted by existing treatments and disease flares can occur.

Courtesy UAB Photo

The latest version of COVID-19 vaccination guidance for patients with RMDs from the ACR addresses vaccine use and implementation strategies. The guidance was issued as conditional or provisional because of the lack of evidence. Its principals are largely based on accepted practice for other vaccines. The guidance is routinely updated as new evidence becomes available. In his presentation at GRAPPA, Dr. Curtis reviewed the latest version of the guidance, which he emphasized is a guidance only and not meant to replace clinical judgment or shared decision-making with patients.

“This is a platform for you to start from as you are thinking about and discussing with your patient what might be best for him or her,” he said.
 

Concerns about impact of disease activity, treatments on effectiveness

Dr. Curtis highlighted some controversial aspects of COVID-19 vaccines, including heterogeneity of rheumatic diseases and treatment. Patients with AIIRD, including psoriatic arthritis, spondyloarthritis, RA, and lupus, are at higher risk for hospitalized COVID-19 and worse outcomes, and as such, they are prioritized for vaccination by the Centers for Disease Control and Prevention.

However, for AIIRD patients, the immune response to COVID-19 vaccination can be “blunted,” according to one study. This may be because of glucocorticoid use or high disease activity. Immunomodulatory therapies, such as methotrexate, rituximab, and abatacept, are known to diminish vaccine response in general. The evidence is less clear for tumor necrosis factor and Janus kinase inhibitors, but they are thought to have the same impact on vaccine effectiveness, Dr. Curtis said. But in these cases, if the effect of a COVID-19 vaccine drops from 90% to 70%, the benefits of vaccination still far outweighs the risk of contracting COVID-19.

“Although we don’t have strong data with clinical outcomes for autoimmune disease or inflammatory disease patients, I’ll run a hypothetical and say: ‘Look, if this vaccine starts 90%-95% effective, even if it’s only 70% effective in somebody with lupus or vasculitis or someone who is taking a higher dose of steroids, I’ll take 70% over nothing if you chose to be vaccinated,’ ” he said.

The benefit of vaccination also outweighs the potential risk of disease flare, he said. The risk is real, but to date, no studies have pointed to a significant risk of disease flare or worsening. However, there have been reported cases of myocardial infarction.

Autoimmune manifestations after vaccination vs. after infection

Researchers writing in the June 29, 2021, issue of JAMA Cardiology described case reports of acute myocarditis in 23 people who received the BNT162b2-mRNA (Pfizer-BioNTech) or mRNA-1273 (Moderna) messenger RNA (mRNA) COVID-19 vaccines. Plus, there been subsequent reports of myocarditis in other patients, wrote David K. Shay, MD, MPH, in an accompanying editorial. Dr. Shay is a member of the CDC COVID-19 Response Team.

“What do we know about this possible association between myocarditis and immunization with mRNA-based COVID-19 vaccines, and what remains unclear? Acute onset of chest pain 3-5 days after vaccine administration, usually after a second dose, is a typical feature of reported cases and suggests an immune-mediated mechanism,” he said.

The cases of myocarditis are concerning, Dr. Curtis said, but the risk is very low with relatively few cases reported among 161 million fully vaccinated people in the United States.

“Certainly, we’re not seeking to minimize that, but the risk of getting COVID and some of the downstream sequelae (autoimmune manifestations) almost certainly outweigh the risks for some of the autoimmune manifestations or worsening [condition],” he said.

A nationwide cohort study from Denmark of 58,052 patients with inflammatory rheumatic disease published in December 2020 in Rheumatology, found that patients with COVID-19 who had an inflammatory rheumatic disease were more likely to be admitted to the hospital, compared with COVID-19 patients without rheumatic disease. Patients with rheumatic disease had a higher risk of a severe COVID-19 outcome, but it was not a statistically significant difference, said Dr. Curtis, adding that the individual factors such as age and treatment currently received largely determines the risk. The strongest associations between hospitalization for COVID-19 and rheumatic disease were found among patients with RA, vasculitis, and connective tissue disease. Dr. Curtis noted that his own new study results show that risk of death from a COVID-19 infection is higher for patients who have RA or psoriatic arthritis.

There have been published case reports of patients who have developed new-onset lupus, vasculitis, Kawasaki disease, multiple sclerosis, autoimmune cytopenias, and other manifestations after a COVID-19 infection. “These authors suggest that perhaps there is a transient influence on the immune system that leads to a loss of self-tolerance to antigens,” Dr. Curtis said. “Some patients may have an underlying predisposition to autoimmunity in which infections just unmask as we sometimes see with other infections – chronic hepatitis for example.”
 

Antibody tests not recommended

In its COVID-19 guidance, the ACR, like the Food and Drug Administration, recommends health care providers not to routinely order antibody tests for IgM or IgG to assess immunity after a person has been vaccinated or to assess the need for vaccination in an unvaccinated person. More research is needed to determine if antibodies provide protection, and if so, for how long and how much. Plus, the antibody testing process is not clear cut, so ordering the wrong test is possible, Dr. Curtis said. The tests should clearly differentiate between spike proteins or nucleocapsid proteins.

“The bottom line is that you might be ordering the wrong lab test. Even if you’re ordering the right lab test, I would assert that you probably don’t know what to do with the result. I would then ask you, ‘Does it mean they are protected? Does it mean they are not protected? What are you going to do with the results?’ ” he asked.

Kevin Winthrop, MD, MPH, a specialist in infectious diseases at Oregon Health & Science University, Portland, said that, at this point, it’s too early to know what antibody tests mean. “I think it is tempting to test some people, especially patients on B-cell depletion therapy and those on mycophenolate mofetil (MMF). Outside of those two types of [disease-modifying antirheumatic drug] users, I wouldn’t be tempted to test. We don’t know how well protected they are, but we assume they are protected to some extent,” he said. “They’re probably partially protected and as such, they should take the same precautions they were taking a year ago: masking and avoidance. I think that’s just how it’s going to be for those folks for another year until we get this thing sorted out.”
 

Modifications to existing rheumatic disease therapies

In its COVID-19 vaccine guidance, the ACR issued recommendations for some common rheumatic disease therapeutics before and/or after the COVID-19 vaccine is administered. The modifications are limited to MMF, methotrexate, JAK inhibitors, subcutaneous abatacept, acetaminophen, and NSAIDs. The recommendations include: hold mycophenolate for 1 week after vaccination if disease is stable; for patients with well-controlled disease, hold methotrexate for 1 week after each of the two mRNA vaccine doses; for patients with well-controlled disease receiving the Johnson & Johnson vaccine, hold methotrexate for 2 weeks after receiving the vaccine; hold JAK inhibitors for 1 week after each dose; for abatacept subcutaneous, hold treatment for 1 week before and after the first dose; and in patients with stable disease, hold acetaminophen and NSAIDs for 24 hours before vaccination, because taking either before vaccination could blunt the vaccine response, Dr. Curtis said.

Holding medication, such as methotrexate, could risk having a flare-up of disease. One study showed the rate of disease flare-up because of withholding standard treatment may be up to 11%, compared with 5.1% in patients who did not hold treatment, he said.

“The point is, if you hold some of these therapies, whether methotrexate or tofacitinib, arthritis will get a little bit worse,” Dr. Curtis said.

A study published on the preprint server medRxiv found that immunosuppressive therapies blunted the response of SARS-CoV-2 vaccines in patients with chronic inflammatory diseases, most significantly with glucocorticoids and B-cell therapies.

“That’s what’s led to a lot of the guidance statements about holding treatments for a week or 2 for rituximab. If you’re giving it at 6-month intervals, you want to schedule the vaccine dose or series at about month 5, or a month before the next cycle,” he said.

Talking with patients about COVID-19 vaccination

In talking with patients about vaccine safety, Dr. Curtis recommends addressing a few common misperceptions. First, COVID-19 viruses were not created with a live-attenuated virus (which would be contraindicated for immunosuppressed patients). “You can put patients’ mind at ease that none of the vaccine candidates or platforms – even those that say viral vector – put patients at risk for contracting the infection. These are nonreplicating. So, it’s like you extracted the engine that would allow this virus to replicate,” he said.

Of three COVID-19 vaccinations available in the United States, is one better than the other? The ACR COVID-19 vaccine task force did not reach a consensus on safety profiles of the vaccines because, without head-to-head comparisons, it’s impossible to know, he said.

In talking with patients, review the protocol for continuing with prescribed treatment modalities before the patient receives a COVID-19 vaccine. Safety concerns and concerns about the possibility of having a disease flare-up should be addressed, he said.

With 49% of the U.S. population fully vaccinated against SARS-CoV-2, a new study highlights the degree of vaccine hesitancy among patients with rheumatic disease to get the vaccine.

Halfpoint Images/Moment/Getty Images

The international study, published in May 2021 in Rheumatology, suggests that, of 1,258 patients surveyed worldwide, approximately 40% of patients said they would decline the vaccine.

“Sometimes it’s helpful to talk through their concerns,” said Jeffrey Curtis, MD, MPH, a University of Alabama at Birmingham rheumatologist who leads the American College of Rheumatology COVID-19 vaccine task force. Dr. Curtis recently reviewed the current literature on COVID-19 vaccination in patients with rheumatic and musculoskeletal diseases (RMDs) at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

COVID-19 vaccinations for patients with autoimmune inflammatory rheumatic disease (AIIRD) is not straightforward. The immune response can be blunted by existing treatments and disease flares can occur.

Courtesy UAB Photo

The latest version of COVID-19 vaccination guidance for patients with RMDs from the ACR addresses vaccine use and implementation strategies. The guidance was issued as conditional or provisional because of the lack of evidence. Its principals are largely based on accepted practice for other vaccines. The guidance is routinely updated as new evidence becomes available. In his presentation at GRAPPA, Dr. Curtis reviewed the latest version of the guidance, which he emphasized is a guidance only and not meant to replace clinical judgment or shared decision-making with patients.

“This is a platform for you to start from as you are thinking about and discussing with your patient what might be best for him or her,” he said.
 

Concerns about impact of disease activity, treatments on effectiveness

Dr. Curtis highlighted some controversial aspects of COVID-19 vaccines, including heterogeneity of rheumatic diseases and treatment. Patients with AIIRD, including psoriatic arthritis, spondyloarthritis, RA, and lupus, are at higher risk for hospitalized COVID-19 and worse outcomes, and as such, they are prioritized for vaccination by the Centers for Disease Control and Prevention.

However, for AIIRD patients, the immune response to COVID-19 vaccination can be “blunted,” according to one study. This may be because of glucocorticoid use or high disease activity. Immunomodulatory therapies, such as methotrexate, rituximab, and abatacept, are known to diminish vaccine response in general. The evidence is less clear for tumor necrosis factor and Janus kinase inhibitors, but they are thought to have the same impact on vaccine effectiveness, Dr. Curtis said. But in these cases, if the effect of a COVID-19 vaccine drops from 90% to 70%, the benefits of vaccination still far outweighs the risk of contracting COVID-19.

“Although we don’t have strong data with clinical outcomes for autoimmune disease or inflammatory disease patients, I’ll run a hypothetical and say: ‘Look, if this vaccine starts 90%-95% effective, even if it’s only 70% effective in somebody with lupus or vasculitis or someone who is taking a higher dose of steroids, I’ll take 70% over nothing if you chose to be vaccinated,’ ” he said.

The benefit of vaccination also outweighs the potential risk of disease flare, he said. The risk is real, but to date, no studies have pointed to a significant risk of disease flare or worsening. However, there have been reported cases of myocardial infarction.

Autoimmune manifestations after vaccination vs. after infection

Researchers writing in the June 29, 2021, issue of JAMA Cardiology described case reports of acute myocarditis in 23 people who received the BNT162b2-mRNA (Pfizer-BioNTech) or mRNA-1273 (Moderna) messenger RNA (mRNA) COVID-19 vaccines. Plus, there been subsequent reports of myocarditis in other patients, wrote David K. Shay, MD, MPH, in an accompanying editorial. Dr. Shay is a member of the CDC COVID-19 Response Team.

“What do we know about this possible association between myocarditis and immunization with mRNA-based COVID-19 vaccines, and what remains unclear? Acute onset of chest pain 3-5 days after vaccine administration, usually after a second dose, is a typical feature of reported cases and suggests an immune-mediated mechanism,” he said.

The cases of myocarditis are concerning, Dr. Curtis said, but the risk is very low with relatively few cases reported among 161 million fully vaccinated people in the United States.

“Certainly, we’re not seeking to minimize that, but the risk of getting COVID and some of the downstream sequelae (autoimmune manifestations) almost certainly outweigh the risks for some of the autoimmune manifestations or worsening [condition],” he said.

A nationwide cohort study from Denmark of 58,052 patients with inflammatory rheumatic disease published in December 2020 in Rheumatology, found that patients with COVID-19 who had an inflammatory rheumatic disease were more likely to be admitted to the hospital, compared with COVID-19 patients without rheumatic disease. Patients with rheumatic disease had a higher risk of a severe COVID-19 outcome, but it was not a statistically significant difference, said Dr. Curtis, adding that the individual factors such as age and treatment currently received largely determines the risk. The strongest associations between hospitalization for COVID-19 and rheumatic disease were found among patients with RA, vasculitis, and connective tissue disease. Dr. Curtis noted that his own new study results show that risk of death from a COVID-19 infection is higher for patients who have RA or psoriatic arthritis.

There have been published case reports of patients who have developed new-onset lupus, vasculitis, Kawasaki disease, multiple sclerosis, autoimmune cytopenias, and other manifestations after a COVID-19 infection. “These authors suggest that perhaps there is a transient influence on the immune system that leads to a loss of self-tolerance to antigens,” Dr. Curtis said. “Some patients may have an underlying predisposition to autoimmunity in which infections just unmask as we sometimes see with other infections – chronic hepatitis for example.”
 

Antibody tests not recommended

In its COVID-19 guidance, the ACR, like the Food and Drug Administration, recommends health care providers not to routinely order antibody tests for IgM or IgG to assess immunity after a person has been vaccinated or to assess the need for vaccination in an unvaccinated person. More research is needed to determine if antibodies provide protection, and if so, for how long and how much. Plus, the antibody testing process is not clear cut, so ordering the wrong test is possible, Dr. Curtis said. The tests should clearly differentiate between spike proteins or nucleocapsid proteins.

“The bottom line is that you might be ordering the wrong lab test. Even if you’re ordering the right lab test, I would assert that you probably don’t know what to do with the result. I would then ask you, ‘Does it mean they are protected? Does it mean they are not protected? What are you going to do with the results?’ ” he asked.

Kevin Winthrop, MD, MPH, a specialist in infectious diseases at Oregon Health & Science University, Portland, said that, at this point, it’s too early to know what antibody tests mean. “I think it is tempting to test some people, especially patients on B-cell depletion therapy and those on mycophenolate mofetil (MMF). Outside of those two types of [disease-modifying antirheumatic drug] users, I wouldn’t be tempted to test. We don’t know how well protected they are, but we assume they are protected to some extent,” he said. “They’re probably partially protected and as such, they should take the same precautions they were taking a year ago: masking and avoidance. I think that’s just how it’s going to be for those folks for another year until we get this thing sorted out.”
 

Modifications to existing rheumatic disease therapies

In its COVID-19 vaccine guidance, the ACR issued recommendations for some common rheumatic disease therapeutics before and/or after the COVID-19 vaccine is administered. The modifications are limited to MMF, methotrexate, JAK inhibitors, subcutaneous abatacept, acetaminophen, and NSAIDs. The recommendations include: hold mycophenolate for 1 week after vaccination if disease is stable; for patients with well-controlled disease, hold methotrexate for 1 week after each of the two mRNA vaccine doses; for patients with well-controlled disease receiving the Johnson & Johnson vaccine, hold methotrexate for 2 weeks after receiving the vaccine; hold JAK inhibitors for 1 week after each dose; for abatacept subcutaneous, hold treatment for 1 week before and after the first dose; and in patients with stable disease, hold acetaminophen and NSAIDs for 24 hours before vaccination, because taking either before vaccination could blunt the vaccine response, Dr. Curtis said.

Holding medication, such as methotrexate, could risk having a flare-up of disease. One study showed the rate of disease flare-up because of withholding standard treatment may be up to 11%, compared with 5.1% in patients who did not hold treatment, he said.

“The point is, if you hold some of these therapies, whether methotrexate or tofacitinib, arthritis will get a little bit worse,” Dr. Curtis said.

A study published on the preprint server medRxiv found that immunosuppressive therapies blunted the response of SARS-CoV-2 vaccines in patients with chronic inflammatory diseases, most significantly with glucocorticoids and B-cell therapies.

“That’s what’s led to a lot of the guidance statements about holding treatments for a week or 2 for rituximab. If you’re giving it at 6-month intervals, you want to schedule the vaccine dose or series at about month 5, or a month before the next cycle,” he said.

Talking with patients about COVID-19 vaccination

In talking with patients about vaccine safety, Dr. Curtis recommends addressing a few common misperceptions. First, COVID-19 viruses were not created with a live-attenuated virus (which would be contraindicated for immunosuppressed patients). “You can put patients’ mind at ease that none of the vaccine candidates or platforms – even those that say viral vector – put patients at risk for contracting the infection. These are nonreplicating. So, it’s like you extracted the engine that would allow this virus to replicate,” he said.

Of three COVID-19 vaccinations available in the United States, is one better than the other? The ACR COVID-19 vaccine task force did not reach a consensus on safety profiles of the vaccines because, without head-to-head comparisons, it’s impossible to know, he said.

In talking with patients, review the protocol for continuing with prescribed treatment modalities before the patient receives a COVID-19 vaccine. Safety concerns and concerns about the possibility of having a disease flare-up should be addressed, he said.

The long-acting drug lenacapavir, a first-in-class capsid inhibitor, shows sustained viral suppression in a small cohort of heavily treatment-experienced patients with multidrug-resistant HIV at 26 weeks when combined with an optimized antiretroviral therapy. With regulatory approval, lenacapavir could become the only HIV-1 treatment option given every 6 months.
 

“These data support the use of lenacapavir in patients with multidrug-resistant viruses, and according to its long half-life of two subcutaneous injections per year, [it] could help reduce pill burden,” first author Jean-Michel Molina, MD, PhD, professor of infectious diseases and head of the infectious diseases department at the Saint-Louis and Lariboisière Hospitals, Paris, said in an interview.

Presenting the updated findings from the phase 2/3 CAPELLA trial at the virtual annual meeting of the International AIDS Society conference, Dr. Molina underscored the need for longer-term treatments.

“These patients with multidrug resistances are usually those who have not been fully adherent to their regimen,” he said. “Being able to provide the drug, given every 6 months subcutaneously, provides an ideal treatment for overcoming resistance and lack of adherence.”

The study showed that, after 26 weeks, 81% of heavily treatment-experienced people with HIV in a randomized cohort who were treated with a subcutaneous injection of lenacapavir (927 mg) combined with an optimized background antiretroviral regimen achieved sustained virologic suppression, with an undetectable viral load (<50 copies/mL).

In addition, the lenacapavir-treated patients had a clinically meaningful mean increase in CD4 counts of 81 cells/mcL over the 26 weeks.

The drug was well tolerated, with no drug-related serious adverse events or adverse events leading to discontinuation. The most common adverse events were injection-site reactions, which occurred in 56% of participants, with most being mild or moderate.

Importantly, four participants developed emergent resistances to lenacapavir. One was suppressed with a change in the background regimen and two others were suppressed without a change in regimen.

“We know that these mutations affect viral fitness,” Dr. Molina said in an interview. “We need more studies to assess the real impact of these mutations.”

Dr. Molina noted that a phase 2 study is already underway to evaluate how a pairing of lenacapavir with fellow investigational long-acting drug islatravir (Merck) could offset the risk of developing resistances.

Asked by an audience member whether a two-drug regimen with something like islatravir is likely to successfully prevent resistances, Dr. Molina responded that “it’s too early to know what’s going to happen with [combinations], but these first results are really encouraging when you see the very high rate of being fully suppressed after 26 weeks. The efficacy that we’ve seen after [a previous 2-week analysis] is long lasting.”
 

Lenacapavir targets multiple viral stages

Unlike other antiviral drugs that target just a single stage of viral replication, lenacapavir takes aim at multiple steps in the viral life cycle, including capsid-mediated uptake of HIV-1 proviral DNA, virus assembly and release, and capsid core formation, Dr. Molina explained.

The CAPELLA trial included participants at research centers in North America, Europe, and Asia, with a median age of 52 years; 25% were female, 38% were Black, and their mean HIV-1 RNA (viral load) was 4.17 log copies/mL.

Overall, 72 patients were divided into two cohorts of 36 patients each, including a randomized and nonrandomized cohort. Dr. Molina primarily reported results from the randomized group.

In that group, patients received either a lead-in of oral lenacapavir (600 mg on day 1 and 2 and 300 mg on day 8) or placebo, in combination with patients’ current failing drug regimens in both groups.

At day 15, all participants were switched to the investigator-selected, optimized background treatment regimen, tailored according to patients’ drug-resistance profiles, and those in the lenacapavir group received the subcutaneous injection of lenacapavir; those in the placebo group were switched to the oral lead-in, followed by subcutaneous lenacapavir every 6 months.

Combined data that included six patients from the nonrandomized cohort showed that 79% of patients had a viral load of less than 50 copies/mL at week 26. The 81% viral suppression rate represented the randomized group (29 of 36).

International AIDS Society cochair Hendrik Streeck, MD, director of the Institute of Virology and Institute for HIV Research at the University Bonn (Germany), said a twice-a-year drug could possibly have profound benefits with a reduction in daily pill burden.

“What makes this an interesting drug is that it is long acting, so one can imagine it has the potential to treat individuals such as those who are not very adherent to the antiretroviral therapy, or who can’t easily access treatment, for example in resource-limited settings,” he said in an interview. “The option to treat patients for the next months in advance could be a very important next step.”
 

Further data from CALIBRATE

Additional data on lenacapavir from the phase 2 CALIBRATE study, presented in a separate session, further showed the drug, given orally or subcutaneously in combination with oral daily emtricitabine/tenofovir alafenamide, resulted in high rates of viral suppression among 94% of 157 treatment-naive patients after 28 weeks.

Commenting on the research, session moderator Alexandra Calmy, MD, PhD, of the HIV/AIDS unit and LIPO & Metabolism group, infectious diseases division, Geneva University Hospitals, noted the study offered “interesting data indeed” – with some caveats: “Why position a new drug class in naive patients [when] we already have good options, available for a large range of various populations?”

Dr. Calmy noted that, in general, lenacapavir “would certainly be an added value with an adapted 6-monthly companion drug.”

But she raised another key issue: “When will we have data on pregnancy that would allow lenacapavir to really be a game changer worldwide?”

The study was funded by Gilead Sciences. Dr. Molina reported receiving research funding from Gilead and being on advisory boards for Gilead, Merck, ViiV, and Janssen. Dr. Calmy and Dr. Streeck reported no relevant financial relationships.

The long-acting drug lenacapavir, a first-in-class capsid inhibitor, shows sustained viral suppression in a small cohort of heavily treatment-experienced patients with multidrug-resistant HIV at 26 weeks when combined with an optimized antiretroviral therapy. With regulatory approval, lenacapavir could become the only HIV-1 treatment option given every 6 months.
 

“These data support the use of lenacapavir in patients with multidrug-resistant viruses, and according to its long half-life of two subcutaneous injections per year, [it] could help reduce pill burden,” first author Jean-Michel Molina, MD, PhD, professor of infectious diseases and head of the infectious diseases department at the Saint-Louis and Lariboisière Hospitals, Paris, said in an interview.

Presenting the updated findings from the phase 2/3 CAPELLA trial at the virtual annual meeting of the International AIDS Society conference, Dr. Molina underscored the need for longer-term treatments.

“These patients with multidrug resistances are usually those who have not been fully adherent to their regimen,” he said. “Being able to provide the drug, given every 6 months subcutaneously, provides an ideal treatment for overcoming resistance and lack of adherence.”

The study showed that, after 26 weeks, 81% of heavily treatment-experienced people with HIV in a randomized cohort who were treated with a subcutaneous injection of lenacapavir (927 mg) combined with an optimized background antiretroviral regimen achieved sustained virologic suppression, with an undetectable viral load (<50 copies/mL).

In addition, the lenacapavir-treated patients had a clinically meaningful mean increase in CD4 counts of 81 cells/mcL over the 26 weeks.

The drug was well tolerated, with no drug-related serious adverse events or adverse events leading to discontinuation. The most common adverse events were injection-site reactions, which occurred in 56% of participants, with most being mild or moderate.

Importantly, four participants developed emergent resistances to lenacapavir. One was suppressed with a change in the background regimen and two others were suppressed without a change in regimen.

“We know that these mutations affect viral fitness,” Dr. Molina said in an interview. “We need more studies to assess the real impact of these mutations.”

Dr. Molina noted that a phase 2 study is already underway to evaluate how a pairing of lenacapavir with fellow investigational long-acting drug islatravir (Merck) could offset the risk of developing resistances.

Asked by an audience member whether a two-drug regimen with something like islatravir is likely to successfully prevent resistances, Dr. Molina responded that “it’s too early to know what’s going to happen with [combinations], but these first results are really encouraging when you see the very high rate of being fully suppressed after 26 weeks. The efficacy that we’ve seen after [a previous 2-week analysis] is long lasting.”
 

Lenacapavir targets multiple viral stages

Unlike other antiviral drugs that target just a single stage of viral replication, lenacapavir takes aim at multiple steps in the viral life cycle, including capsid-mediated uptake of HIV-1 proviral DNA, virus assembly and release, and capsid core formation, Dr. Molina explained.

The CAPELLA trial included participants at research centers in North America, Europe, and Asia, with a median age of 52 years; 25% were female, 38% were Black, and their mean HIV-1 RNA (viral load) was 4.17 log copies/mL.

Overall, 72 patients were divided into two cohorts of 36 patients each, including a randomized and nonrandomized cohort. Dr. Molina primarily reported results from the randomized group.

In that group, patients received either a lead-in of oral lenacapavir (600 mg on day 1 and 2 and 300 mg on day 8) or placebo, in combination with patients’ current failing drug regimens in both groups.

At day 15, all participants were switched to the investigator-selected, optimized background treatment regimen, tailored according to patients’ drug-resistance profiles, and those in the lenacapavir group received the subcutaneous injection of lenacapavir; those in the placebo group were switched to the oral lead-in, followed by subcutaneous lenacapavir every 6 months.

Combined data that included six patients from the nonrandomized cohort showed that 79% of patients had a viral load of less than 50 copies/mL at week 26. The 81% viral suppression rate represented the randomized group (29 of 36).

International AIDS Society cochair Hendrik Streeck, MD, director of the Institute of Virology and Institute for HIV Research at the University Bonn (Germany), said a twice-a-year drug could possibly have profound benefits with a reduction in daily pill burden.

“What makes this an interesting drug is that it is long acting, so one can imagine it has the potential to treat individuals such as those who are not very adherent to the antiretroviral therapy, or who can’t easily access treatment, for example in resource-limited settings,” he said in an interview. “The option to treat patients for the next months in advance could be a very important next step.”
 

Further data from CALIBRATE

Additional data on lenacapavir from the phase 2 CALIBRATE study, presented in a separate session, further showed the drug, given orally or subcutaneously in combination with oral daily emtricitabine/tenofovir alafenamide, resulted in high rates of viral suppression among 94% of 157 treatment-naive patients after 28 weeks.

Commenting on the research, session moderator Alexandra Calmy, MD, PhD, of the HIV/AIDS unit and LIPO & Metabolism group, infectious diseases division, Geneva University Hospitals, noted the study offered “interesting data indeed” – with some caveats: “Why position a new drug class in naive patients [when] we already have good options, available for a large range of various populations?”

Dr. Calmy noted that, in general, lenacapavir “would certainly be an added value with an adapted 6-monthly companion drug.”

But she raised another key issue: “When will we have data on pregnancy that would allow lenacapavir to really be a game changer worldwide?”

The study was funded by Gilead Sciences. Dr. Molina reported receiving research funding from Gilead and being on advisory boards for Gilead, Merck, ViiV, and Janssen. Dr. Calmy and Dr. Streeck reported no relevant financial relationships.

The long-acting drug lenacapavir, a first-in-class capsid inhibitor, shows sustained viral suppression in a small cohort of heavily treatment-experienced patients with multidrug-resistant HIV at 26 weeks when combined with an optimized antiretroviral therapy. With regulatory approval, lenacapavir could become the only HIV-1 treatment option given every 6 months.
 

“These data support the use of lenacapavir in patients with multidrug-resistant viruses, and according to its long half-life of two subcutaneous injections per year, [it] could help reduce pill burden,” first author Jean-Michel Molina, MD, PhD, professor of infectious diseases and head of the infectious diseases department at the Saint-Louis and Lariboisière Hospitals, Paris, said in an interview.

Presenting the updated findings from the phase 2/3 CAPELLA trial at the virtual annual meeting of the International AIDS Society conference, Dr. Molina underscored the need for longer-term treatments.

“These patients with multidrug resistances are usually those who have not been fully adherent to their regimen,” he said. “Being able to provide the drug, given every 6 months subcutaneously, provides an ideal treatment for overcoming resistance and lack of adherence.”

The study showed that, after 26 weeks, 81% of heavily treatment-experienced people with HIV in a randomized cohort who were treated with a subcutaneous injection of lenacapavir (927 mg) combined with an optimized background antiretroviral regimen achieved sustained virologic suppression, with an undetectable viral load (<50 copies/mL).

In addition, the lenacapavir-treated patients had a clinically meaningful mean increase in CD4 counts of 81 cells/mcL over the 26 weeks.

The drug was well tolerated, with no drug-related serious adverse events or adverse events leading to discontinuation. The most common adverse events were injection-site reactions, which occurred in 56% of participants, with most being mild or moderate.

Importantly, four participants developed emergent resistances to lenacapavir. One was suppressed with a change in the background regimen and two others were suppressed without a change in regimen.

“We know that these mutations affect viral fitness,” Dr. Molina said in an interview. “We need more studies to assess the real impact of these mutations.”

Dr. Molina noted that a phase 2 study is already underway to evaluate how a pairing of lenacapavir with fellow investigational long-acting drug islatravir (Merck) could offset the risk of developing resistances.

Asked by an audience member whether a two-drug regimen with something like islatravir is likely to successfully prevent resistances, Dr. Molina responded that “it’s too early to know what’s going to happen with [combinations], but these first results are really encouraging when you see the very high rate of being fully suppressed after 26 weeks. The efficacy that we’ve seen after [a previous 2-week analysis] is long lasting.”
 

Lenacapavir targets multiple viral stages

Unlike other antiviral drugs that target just a single stage of viral replication, lenacapavir takes aim at multiple steps in the viral life cycle, including capsid-mediated uptake of HIV-1 proviral DNA, virus assembly and release, and capsid core formation, Dr. Molina explained.

The CAPELLA trial included participants at research centers in North America, Europe, and Asia, with a median age of 52 years; 25% were female, 38% were Black, and their mean HIV-1 RNA (viral load) was 4.17 log copies/mL.

Overall, 72 patients were divided into two cohorts of 36 patients each, including a randomized and nonrandomized cohort. Dr. Molina primarily reported results from the randomized group.

In that group, patients received either a lead-in of oral lenacapavir (600 mg on day 1 and 2 and 300 mg on day 8) or placebo, in combination with patients’ current failing drug regimens in both groups.

At day 15, all participants were switched to the investigator-selected, optimized background treatment regimen, tailored according to patients’ drug-resistance profiles, and those in the lenacapavir group received the subcutaneous injection of lenacapavir; those in the placebo group were switched to the oral lead-in, followed by subcutaneous lenacapavir every 6 months.

Combined data that included six patients from the nonrandomized cohort showed that 79% of patients had a viral load of less than 50 copies/mL at week 26. The 81% viral suppression rate represented the randomized group (29 of 36).

International AIDS Society cochair Hendrik Streeck, MD, director of the Institute of Virology and Institute for HIV Research at the University Bonn (Germany), said a twice-a-year drug could possibly have profound benefits with a reduction in daily pill burden.

“What makes this an interesting drug is that it is long acting, so one can imagine it has the potential to treat individuals such as those who are not very adherent to the antiretroviral therapy, or who can’t easily access treatment, for example in resource-limited settings,” he said in an interview. “The option to treat patients for the next months in advance could be a very important next step.”
 

Further data from CALIBRATE

Additional data on lenacapavir from the phase 2 CALIBRATE study, presented in a separate session, further showed the drug, given orally or subcutaneously in combination with oral daily emtricitabine/tenofovir alafenamide, resulted in high rates of viral suppression among 94% of 157 treatment-naive patients after 28 weeks.

Commenting on the research, session moderator Alexandra Calmy, MD, PhD, of the HIV/AIDS unit and LIPO & Metabolism group, infectious diseases division, Geneva University Hospitals, noted the study offered “interesting data indeed” – with some caveats: “Why position a new drug class in naive patients [when] we already have good options, available for a large range of various populations?”

Dr. Calmy noted that, in general, lenacapavir “would certainly be an added value with an adapted 6-monthly companion drug.”

But she raised another key issue: “When will we have data on pregnancy that would allow lenacapavir to really be a game changer worldwide?”

The study was funded by Gilead Sciences. Dr. Molina reported receiving research funding from Gilead and being on advisory boards for Gilead, Merck, ViiV, and Janssen. Dr. Calmy and Dr. Streeck reported no relevant financial relationships.