Mixed findings on remdesivir for COVID-19, news on SARS-CoV-2 vaccines

Recent news on remdesivir has been mixed. On Oct. 8, the final report of the randomized, NIH trial of the drug (previously released in a press release) was published by the New England Journal of Medicine (NEJM). It showed a significant difference in time to clinical improvement and a reduction, although not statistically significant, in mortality with remdesivir. However, on Oct. 15, the World Health Organization released interim results from its Solidarity Therapeutics Trial in a press release and preprint abstract. The 30-country randomized trial included more than 11,000 patients and concluded that “remdesivir, hydroxychloroquine, lopinavir and interferon regimens appeared to have little or no effect on hospitalized COVID-19, as indicated by overall mortality, initiation of ventilation and duration of hospital stay.” The European Medicines Agency also recently announced its investigation of a safety signal regarding the risk of acute kidney injury with remdesivir. The NIH also recently updated its treatment guidelines for COVID-19.

Additional negative data on hydroxychloroquine were published by NEJM on Oct. 8. The study found that patients randomized to hydroxychloroquine were actually less likely to be discharged from the hospital alive within 28 days than those getting usual care (59.6% vs. 62.9%; rate ratio, 0.90 [95% CI, 0.83 to 0.98]). Convalescent plasma didn't show overall benefit either, according to a single-center U.S. study published by Clinical Infectious Diseases on Oct. 10. The 64 patients with severe COVID-19 who received convalescent plasma a median of seven days after onset had similar inpatient mortality to controls. However, there was a signal of benefit in patients older than age 65 years, which the authors said should be investigated in future research. There was also a higher-than-expected rate of transfusion reactions (2.8%) in the study. In some positive news, ivermectin did show promise, according to a retrospective study published by CHEST on Oct. 12. Chart reviews compared 173 COVID-19 patients treated with ivermectin in four Florida hospitals to 107 who didn't receive the drug and found a reduction in overall mortality (15.0% vs. 25.2%; odds ratio [OR], 0.52 [95% CI 0.29 to 0.96]; P=0.03), which was greater in patients with severe pulmonary involvement (38.8% vs. 80.7%; OR, 0.15 [95% CI, 0.05 to 0.47]; P=0.001). The authors called for a randomized trial to confirm the findings.

SARS-CoV-2 vaccines have been a focus of recent news and research. ACP and Annals of Internal Medicine held an online forum on vaccines on Oct. 16, featuring a panel of experts: Anthony S. Fauci, MD, MACP; H. Clifford Lane, MD, MACP; Beth P. Bell, MD; MPH; David A. Kessler, MD; and Rachel Levine, MD. The forum offered current, evidence-based information related to the science, approval processes, and development of clinical recommendations for vaccines, as well as the political and policy environment. The full recording of “ACP and Annals of Internal Medicine COVID-19 Vaccine Forum: What Physicians Need to Know” is available for replay online and is described in an accompanying article published in Annals of Internal Medicine.

On Oct. 14, NEJM published phase 1 trial results for two lipid nanoparticle-formulated, nucleoside-modified RNA vaccine candidates. The industry-funded randomized trial included 195 participants (some of them ages 65 to 85 years) and concluded that safety and efficacy data supported advancing one of the vaccines, which showed fewer adverse reactions, to phase 2 and 3 research. A Chinese study, published by The Lancet Infectious Diseases on Oct. 15, reported that an inactivated vaccine was safe and well tolerated and induced humoral responses against SARS-CoV-2. On Oct. 12, Johnson & Johnson announced that its vaccine trial was currently paused due to an unexplained illness in a participant.

In other COVID-19 news, the FDA provided guidance on having patients test themselves for SARS-CoV-2. The association of COVID-19 with multisystem inflammatory syndrome in adults was described in a Oct. 9 MMWR case series. A Chinese study, published Oct. 13 by Clinical Infectious Diseases, identified prognostic biomarkers among patients hospitalized with COVID-19, with elevated interleukin 6 levels being one of the most significant predictors of death. A Norwegian study, published by Circulation on Oct. 15, suggested that growth differentiation factor 15 could be a useful prognostic biomarker. Finally, in his latest KevinMD column, ACP's Vice President of Membership and Global Engagement, Philip A. Masters, MD, FACP, shared his personal experience as a clinician in the era of COVID-19. Dr. Masters writes: “… the coronavirus pandemic and its effect on the way we are now practicing medicine has certainly made the process of making accurate clinical diagnoses even more challenging than it always has been.”