New research on Pfizer pill, mental disorders after COVID-19, vaccine reactions

Data on the effectiveness of nirmatrelvir/ritonavir (Paxlovid) against COVID-19 were published by the New England Journal of Medicine on Feb. 16. The phase 2/3 trial was funded by Pfizer and randomized symptomatic, unvaccinated, high-risk outpatients with COVID-19 to either 300 mg of nirmatrelvir plus 100 mg of ritonavir or placebo every 12 hours for five days. An interim analysis found incidence of hospitalization or death to be 0.77% in the 389 patients given the drug (with zero deaths) versus 7.01% in the 385 placebo patients (with seven deaths). The trial was then terminated for meeting its efficacy end point. A final analysis of all enrolled patients found similar results, with an overall relative risk reduction of 88.9% with the drug. Adverse events were similar between groups. One limitation of the study was that none of the patients were vaccinated; a trial in high-risk vaccinated patients is under way, the study authors noted. They also cautioned about the risk of drug interactions with ritonavir. An accompanying editorial noted that patients at low risk for severe COVID-19 showed very small absolute benefit from the drug; therefore, patients at highest risk should be prioritized for treatment, which should be started within five days.

COVID-19 infection was followed by increased risk of new mental health disorders, according to a study published by The BMJ on Feb. 16. It compared 153,848 veterans who had COVID-19 with 5 million controls who didn't have COVID-19, finding significantly increased risk of incident anxiety, depression, stress and adjustment disorders; increased use of antidepressants, benzodiazepines, and opioids; and higher rates of neurocognitive decline and sleep disorders. Risk of mental health disorders was particularly associated with hospitalization but also increased in outpatients with COVID-19 versus controls. A historical analysis also found higher risk in patients hospitalized with COVID-19 versus flu. A linked opinion by the study authors called for greater attention to mental health after COVID-19. “Some may use our findings to gaslight or dismiss long covid as a psychosomatic condition or explain the myriad manifestations of long covid as the result of mental illness,” they wrote, arguing instead the study should be taken to show SARS-CoV-2 as “a systemic virus that may provoke damage and clinical consequences in nearly every organ system—including mental health disorders and neurocognitive decline.” An accompanying editorial noted that the study was limited by the risk of confounding and the possibility that more mental health care was offered to patients with COVID-19.

Two studies looked at the safety of COVID-19 vaccines. A meta-analysis, published by JAMA Internal Medicine on Feb. 21, reviewed 22 studies of second doses of the mRNA vaccines, which included 1,366 people who had immediate allergic reactions to the first shot. It found that only six individuals developed severe immediate allergic reactions (absolute risk, 0.16%) and 232 (13.65%) developed mild symptoms after their second vaccination. “These findings suggest that revaccination of individuals with an immediate allergic reaction to a first SARS-CoV-2 mRNA vaccine dose in a supervised setting equipped to manage severe allergic reactions can be safe,” the authors concluded. The other study, published by MMWR on Feb. 11, found that boosters were associated with fewer local and systemic reactions than primary vaccine doses.

In other COVID-19 research, a randomized trial in Malaysia found that ivermectin had no effect on COVID-19 patients' risk of progression to severe disease, mechanical ventilation, ICU admission, or 28-day in-hospital mortality, according to results published by JAMA Internal Medicine on Feb. 18. A Canadian study, published by JAMA on Feb. 17, matched 9,087 omicron cases with an equal number of delta cases and found omicron to be associated with reduced risk for hospitalization or death, ICU admission or death, or death (hazard ratios of 0.41, 0.19, and 0.12, respectively). However, residence in a socially vulnerable ZIP code was associated with higher risk of ICU admission, mechanical ventilation, organ dysfunction or failure, and in-hospital death, according to a Michigan analysis of hospitalized patients published by Annals of Internal Medicine on Feb. 22. Finally, MMWR published two studies on Feb. 18 that investigated risk of COVID-19 spread during conventions, looking at a cluster of infections and the effectiveness of preventive measures.