First COVID-19 vaccine receives interim recommendation, new data, guidance on baricitinib plus remdesivir, and more

The FDA issued an emergency use authorization for the first mRNA vaccine against SARS-CoV-2, and the CDC's Advisory Committee on Immunization Practices made an interim recommendation for its use in those ages 16 years and older. New research looked at combination therapy for hospitalized patients and risk factors for in-hospital death.

The FDA Vaccines and Related Biological Products Advisory Committee voted Dec. 10 in favor of the mRNA COVID-19 vaccine developed by Pfizer and BioNTech, leading to an emergency use authorization (EUA) on Dec. 11. On Dec. 12, the CDC's Advisory Committee on Immunization Practices issued an interim recommendation on the vaccine for those ages 16 years and older, with details published Dec. 13 by MMWR. On Dec. 15, ACP issued a statement in support of the ACIP's recommendation, as well as the addition of an amendment to the 2021 Adult Immunization Schedule to include use of COVID-19 vaccines.

Earlier on Dec. 10, results from a phase 3 manufacturer-funded trial of the mRNA vaccine were published by the New England Journal of Medicine (NEJM). Overall, 43,448 people ages 16 years and older received two injections 21 days apart, 21,720 with the vaccine and 21,728 with placebo. Eight cases of COVID-19 occurred at least seven days after the second dose in the vaccine group versus 162 cases in the placebo group, for an overall efficacy of 95%. Ten cases of severe COVID-19 occurred after the first injection, nine in the placebo group and one in the vaccine group. Incidence of serious adverse events was low and was similar between groups.

An accompanying editorial said that while unanswered questions remain regarding safety and distribution, “the remarkable level of safety and efficacy the vaccine has demonstrated thus far make this a problem that we should welcome solving. What appears to be a dramatic success for vaccination holds the promise of saving uncounted lives and giving us a pathway out of what has been a global disaster.”

In other COVID-19 news, a study published Dec. 11 by NEJM looked at the effect of baricitinib plus remdesivir in adults hospitalized with COVID-19. In a double-blind, randomized, placebo-controlled trial, 1,033 patients received remdesivir for up to 10 days and were randomly assigned to receive up to 14 days of baricitinib (n=515) or placebo (n=518). The study's primary outcome was time to recovery, with clinical status at day 15 as the key secondary outcome.

In the combination treatment group, the median time to recovery was seven days versus eight days in the control group (rate ratio for recovery, 1.16 [95% CI, 1.01 to 1.32]; P=0.03). Patients in the combination group were also more likely to have improved clinical status at day 15 (odds ratio, 1.3; 95% CI, 1.0 to 1.6), and patients who received high-flow oxygen or noninvasive ventilation at enrollment had a time to recovery of 10 days with combination treatment versus 18 days with control (rate ratio for recovery, 1.51; 95% CI, 1.10 to 2.08). The control group had a higher mortality rate at 28 days than the combination treatment group (7.8% vs. 5.1%; hazard ratio, 0.65 [95% CI, 0.39 to 1.09]), as well as higher rates of serious adverse events (21.0% vs. 16%) and new infections (11.2% vs. 5.9%). “Baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status among patients with Covid-19, notably among those receiving high-flow oxygen or noninvasive ventilation,” the authors concluded. They also pointed out that combination treatment was associated with fewer serious adverse events.

However, on Dec. 14, the NIH's COVID-19 Treatment Guidelines Panel issued an updated statement on baricitinib, which received an EUA from the FDA on Nov. 19 for use with remdesivir in some COVID-19 patients. In the statement, which was based primarily on the results of the new NEJM study, the NIH panel said that there are insufficient data to recommend for or against baricitinib in combination with remdesivir for the treatment of COVID-19 in hospitalized patients in cases where corticosteroids can be used instead. The panel said it recommends baricitinib in combination with remdesivir in hospitalized, nonintubated patients with COVID-19 who require oxygen supplementation only in the rare circumstances where corticosteroids cannot be used. It recommended against use of baricitinib in the absence of remdesivir, except in a clinical trial. The panel also noted that data are insufficient to recommend for or against the use of baricitinib in combination with corticosteroids for COVID-19 treatment.

“More data are needed to clarify the role of baricitinib in the management of COVID-19, especially data from randomized trials that compare the use of baricitinib with the current standard of care and evaluate which subpopulations benefit the most from baricitinib,” the panel said. “Health care providers are encouraged to discuss participation in baricitinib clinical trials with their patients.”

Finally, a cohort study published Dec. 10 by JAMA Network Open looked at risk factors associated with in-hospital death in patients with COVID-19. Researchers used the Premier Healthcare Database, which includes 592 acute care hospitals in the United States, to evaluate inpatient and hospital-based outpatient visits with a principal or secondary diagnosis of COVID-19 between April 1 and May 30. The primary outcome measures were in-hospital mortality, ICU admission, invasive mechanical ventilation, total hospital length of stay, ICU length of stay, acute complications, and treatment patterns.

Among 64,781 patients with COVID-19, 45.5% outpatients and 54.5% inpatients, the median age was 46 and 65 years, respectively; 49.4% were men, 39.9% were White, and 22.1% were Black. The in-hospital mortality rate for inpatients was 20.3%. Overall, 15.9% of inpatients received invasive mechanical ventilation and 19.4% were admitted to the ICU. Median length of inpatient stay was six days, and median length of ICU stay was five days.

Acute respiratory failure (55.8%), acute kidney failure (33.9%), and sepsis (33.7%) were common among inpatients. Age had the strongest association with death; for example, for patients 80 years of age and older versus those ages 18 to 34 years, the odds ratio (OR) for death was 16.20 (95% CI, 11.58 to 22.67; P<0.001). In contrast, statins (OR, 0.60; 95% CI, 0.56 to 0.65; P<0.001), angiotensin-converting enzyme inhibitors (OR, 0.53; 95% CI, 0.46 to 0.60; P<0.001), and calcium-channel blockers (OR, 0.73; 95% CI, 0.68 to 0.79; P<0.001) were each associated with decreased odds of death. Patients who received both azithromycin and hydroxychloroquine had increased odds of death versus those who did not receive these drugs (OR, 1.21; 95% CI, 1.11 to 1.31; P<0.001).

The authors noted that while 13.4% of the U.S. population identifies as Black and 76.3% identifies as White, Black patients made up 22.1% of the study sample. In addition, while Black patients in this study had 25% lower odds of dying in the hospital versus White patients, it was not possible to adjust for socioeconomic status or structural disparities, the authors said. They concluded that COVID-19 was associated with high rates of ICU admission and in-hospital mortality and that use of statins, angiotensin-converting enzyme inhibitors, and calcium-channel blockers was associated with decreased odds of death. “Understanding the potential benefits of unproven treatments will require future randomized trials,” they wrote.