Regulatory changes for COVID-19 vaccine; data on waning immunity, outpatient therapies

Government agencies made updates to their positions on COVID-19 vaccines last week. On Oct. 29, the FDA authorized a lower-dose series of two shots of the Pfizer-BioNTech vaccine for children ages 5 to 11 years old. The CDC's Advisory Committee on Immunization Practices is expected to consider the topic at its Nov. 2 and 3 meeting. The NIH's COVID-19 treatment guidelines panel advised that an influenza vaccine and a COVID-19 vaccine may be administered concurrently at different injection sites. The panel also said that for patients who have COVID-19, influenza vaccination should be deferred until they are no longer either in isolation or moderately to severely ill. The CDC updated its guidance to allow for a fourth COVID-19 vaccine dose in patients who already received a third vaccine dose due to immune compromise. The agency says that moderately and severely immunocompromised adults who received three doses of an mRNA vaccine may receive a single booster of any of the COVID-19 vaccines at least six months after the third dose.

In vaccine research, a cohort study, published by JAMA Internal Medicine on Nov. 1, looked at the association of the Johnson & Johnson (Janssen) vaccine with cerebral venous sinus thrombosis (CVST), finding that in the 15 days after receipt of the vaccine, the CVST rate among females was 5.1-fold higher compared with before the pandemic. This risk was highest among women ages 40 to 49 years, followed by women ages 30 to 39 years. An Israeli study, published by the New England Journal of Medicine on Oct. 27, described the waning of vaccine-induced immunity over time and with the rise of the delta variant. In July, people who were fully vaccinated in January with the Pfizer-BioNTech vaccine were significantly more likely to become infected than those fully vaccinated in March (rate ratio, 1.6; 95% CI, 1.3 to 2.0), with similar findings for February versus April and March versus May. The rate of severe COVID-19 disease showed a similar pattern. “Our findings are in line with findings from the randomized trial of the BNT162b2 vaccine, which showed a reduction in vaccine efficacy against symptomatic infection from 96% in the first 2 months after vaccination to 84% at 4 to 7 months after vaccination,” said the authors. Meanwhile, the delta variant was not associated with an increase in the severity of illness among hospitalized patients in 14 states, according to a study published by MMWR on Oct. 22.

Potential therapies for outpatients with COVID-19 were the focus of two new studies. Sotrovimab, a monoclonal antibody, showed success in an industry-funded phase 3 trial of 583 high-risk outpatients, published by the New England Journal of Medicine on Oct. 27. Half were given a single 500-mg infusion of the drug, and an interim analysis showed that only three of those patients (1%) had disease progression leading to hospitalization or death compared with 21 patients (7%) who received placebo (relative risk [RR] reduction, 85%; 97.24% CI, 44% to 96%; P=0.002). No intervention patients were admitted to the ICU, while five placebo patients were. There was no increase in adverse events with the drug, and the trial is ongoing, study authors noted. The general state of SARS-CoV-2 antibody research as of June was summarized in a report of a NIH/FDA virtual summit, published by Annals of Internal Medicine on Nov. 2.

The other trial found benefit from fluvoxamine, a selective serotonin reuptake inhibitor, with results published by The Lancet Global Health on Oct. 27. It randomized 741 high-risk symptomatic outpatients in Brazil to fluvoxamine, 100 mg twice daily for 10 days, and 756 to placebo. The proportion of patients requiring extended emergency or tertiary hospital care due to COVID-19 was lower in the fluvoxamine group: 11% (n=79) versus 16% (n=119) (RR, 0.68; 95% credible interval, 0.52 to 0.88). There were 17 deaths in the fluvoxamine group and 25 deaths in the placebo group and no significant difference in treatment-emergent adverse events. The trial was stopped early due to superiority in the treatment arm. “A 10-day course of fluvoxamine costs approximately US$4 even in well-resourced settings. Our study compares favourably with the treatment effects of more expensive treatments including monoclonal antibodies for outpatient treatment,” the authors said. A news article in Nature, published Oct. 29, noted the positive results of the trial but also pointed out some caveats, such as the generalizability of the results outside Brazil and the authors' definition of severe COVID-19.