Studies look at effectiveness of bivalent booster, fluvoxamine plus inhaled budesonide for COVID-19

Efficacy of the bivalent vaccines against COVID-19 was assessed in an updated report from North Carolina, published as a letter to the New England Journal of Medicine on April 12.

The retrospective study reported on more than six million North Carolina residents 12 years of age or older who were eligible for a booster dose from Sept. 1, 2022, to Feb. 10, 2023. A total of 1,279,802 received a booster, and boosted patients comprised 19,462 of the 154,581 SARS-CoV-2 infections, 253 of the 2,208 COVID-19-related hospitalizations, and 79 of the 867 related deaths occurring during the period. Researchers calculated that the boosters were 67.4% (95% CI, 46.2% to 80.2%) effective against severe infection resulting in hospitalization or death after two weeks. Effectiveness dwindled to 47.5% (95% CI, 32.6% to 59.2%) after four weeks, 44.3% (95% CI, 35.7% to 51.7%) after 10 weeks, and 38.4% (95% CI, 13.4% to 56.1%) after 20 weeks. Separating the results by periods when the BA.4-BA.5, BQ.1-BQ.1.1, or XBB-XBB.1.5 subvariants were predominant did not indicate any significant differences. The Moderna bivalent vaccine had higher effectiveness over the study period than the Pfizer-BioNTech bivalent vaccine, the study also found. Experts discussed the timing of additional boosters in an accompanying audio interview. News outlets, including the New York Times, recently reported that the FDA plans to authorize another COVID-19 booster for older and immunocompromised Americans in the near future.

Combination therapy with fluvoxamine and inhaled budesonide reduced risk of progression to severe COVID-19, according to a Brazilian trial in high-risk outpatients, published by Annals of Internal Medicine on April 18.

The trial, conducted at 12 clinical sites in Brazil in 2022, randomized symptomatic adults with confirmed SARS-CoV-2 infection and a known risk factor for progression to severe disease to 100 mg of fluvoxamine plus inhaled 800 mcg of budesonide, twice daily for 10 days (n=738), or matching placebos (n=738). The primary outcome, a composite of being retained in an emergency setting for more than six hours, hospitalized, or having suspected complications due to clinical progression of COVID-19 within 28 days, was significantly lower in the intervention group, at 1.8% (95% credible interval [CrI], 1.1% to 3.0%) versus 3.7% (95% CrI, 2.5% to 5.3%) with placebo (relative risk, 0.50; 95% CrI, 0.25 to 0.92). The probability of superiority with the intervention on this outcome was 98.7%, but no differences were seen in secondary outcomes, including health care attendance, time to hospitalization, mortality, or patient-reported outcomes. More adverse events occurred in the intervention group than in the placebo group, but the differences were not significant.

The study builds on previous trials that evaluated these drugs separately for COVID-19 and seems to show that the combined effect provides greater benefit, the authors said. One significant difference from prior trials is that approximately 95% of this study's population was vaccinated. “Given the safety, tolerability, ease of use, low cost, and widespread availability of these drugs, our findings may be useful for clinicians worldwide who are considering treating outpatients,” the authors wrote. “Although oral therapeutics for COVID-19 are available in the United States and, to a lesser extent, in other high-income countries, they are predominantly prescribed in elderly populations. These drugs are largely unavailable in low- and middle-income countries.”