Latest on COVID-19 and bamlanivimab, vaccines, long-term effects

An industry-funded trial, published by JAMA on Jan. 21, found that bamlanivimab significantly reduced viral load in outpatients with COVID-19 when combined with etesevimab, but not when given alone. The phase 2/3 trial randomized 613 ambulatory patients with mild to moderate symptoms to an infusion of bamlanivimab (at three different doses), combination treatment (2,800 mg of bamlanivimab and 2,800 mg of etesevimab), or placebo. Compared to the placebo group, the change in viral load from baseline to day 11 was only significant in the combination group. Although the differences were not statistically significant, the proportion of patients with COVID-19-related hospitalizations or ED visits was 5.8% (9 events) for placebo, 1.0% (1 event) for 700 mg of bamlanivimab, 1.9% (2 events) for 2,800 mg, 2.0% (2 events) for 7,000 mg, and 0.9% (1 event) for combination treatment. “Additional study is needed to understand whether the greater reduction of viral load shown by combination therapy would eventually translate to clinical benefit compared with monotherapy,” the authors said.

The CDC updated its interim recommendations on use of the SARS-CoV-2 vaccines on Jan. 21. The agency still recommends that the second doses be given 21 days and 28 days after the first dose of the Pfizer-BioNTech and Moderna vaccines, respectively. However, the updated guidance says that if it is not feasible to adhere to the recommended interval, the second dose may be scheduled for administration up to six weeks after the first. The CDC noted that data are limited on administration beyond this window. The update also addressed whether the vaccines are interchangeable. Although they are not, the new guidance made allowances for exceptional situations in which the first-dose vaccine product cannot be determined or is no longer available.

Another vaccine against SARS-CoV-2 produced antibodies in those who received it, in a trial funded by Johnson & Johnson and published by the New England Journal of Medicine on Jan 13. The phase 1/2a placebo-controlled trial reported on administration of a high or low dose of the vaccine to 805 healthy adults between the ages of 18 and 55 years and 65 years or older, with a second dose to some patients. Neutralizing-antibody titers were detected in at least 90% on day 29 after the first dose. The most reported adverse events were fatigue, headache, myalgia, and injection-site pain, which generally occurred on the day of immunization or the next day. “The interim analysis of our phase 1–2a trial showed that the Ad26.COV2.S vaccine had an acceptable safety and reactogenicity profile and was immunogenic after a single vaccination with either the low or high dose” and supported the decision to move to phase 3 trials with the lower dose, given either once or twice, said the authors.

An analysis of the current state of the vaccines was provided in an article by Anthony S. Fauci, MD, MACP, and others, published by Annals of Internal Medicine on Jan. 19. The article reviewed the data on the two vaccines that have already received emergency use authorizations, as well as the others that are in development, and addressed uncertainties including the duration of protection and the effect of the vaccines on transmission. “It is incumbent on frontline professionals to be well informed about these vaccines to provide evidence-based recommendations to their patients on whether to be vaccinated,” they wrote. “Acknowledging that there is still much to learn while strongly encouraging vaccination is arguably one of the most critical challenges facing health care providers today.”

Physicians received additional information on vaccine allocation and distribution from an online forum held on Jan. 22. During “ACP and Annals of Internal Medicine COVID-19 Vaccine Forum III, Allocation and Distribution: What Physicians Need to Know,” a moderator and four guest experts provided a Q&A addressing rollout strategies and other details regarding COVID-19 vaccination in the U.S. The full recording of the forum is available for replay online and is described in an accompanying article published by Annals of Internal Medicine.

Two recent studies looked at long-term effects of COVID-19, with differing findings. A Chinese study, published by The Lancet on Jan. 8, looked at 1,733 patients who had been treated and discharged between January and May. At a median of 186 days after symptom onset, patients were interviewed about symptoms and health-related quality of life and underwent physical exams, a six-minute walk test, and blood tests. Fatigue or muscle weakness (63%) and sleep difficulties (26%) were the most common symptoms, with 23% having anxiety or depression. The patients were stratified by their severity of illness during hospitalization, and more severely impaired pulmonary diffusion capacities and abnormal chest imaging manifestations were found more often in the more severely ill patients, leading the authors to conclude that “those with severe disease need post-discharge care.”

Another study, published by the Annals of the American Thoracic Society on Jan. 8, included 153 patients seen a median of 75 days after diagnosis with COVID-19. More than half (52%) had been treated as outpatients. At follow-up, only 4% had persistently abnormal chest X-rays, but 62% felt that they had not returned to full health, and 47% had fatigue. Frailty and length of inpatient stay were associated with worse performance on a six-minute walk test, but none of the study's measures of persistent respiratory disease were associated with initial disease severity. The authors concluded that the findings were as a whole reassuring about the longer-term effects of COVID-19 but also “demonstrated the significant morbidity that persists following infection,” which “appears to be unrelated to initial infection severity.” They called for “ongoing support and rehabilitation of patients experiencing long-term side-effects of COVID-19, including programmes to optimise patient's self-management of fatigue and perception of exertion post-COVID-19.” The January ACP Internist offered an expert's perspective on the lingering effects of COVID-19.