Frequency of COVID-19 rebound debated in research, ACP/Annals forum

The phenomenon of SARS-CoV-2 rebound was discussed by two new research reports and an online forum.

The first report, published as letter by the New England Journal of Medicine on Sept. 7, reported rebound cases from the manufacturer-funded EPIC-HR3 trial, which randomized symptomatic, unvaccinated, high-risk outpatients with COVID-19 to either nirmatrelvir-ritonavir (Paxlovid) or placebo within five days of symptom onset. Nasopharyngeal swab samples were taken at enrollment and on trial days 3, 5, 10, and 14. Viral rebound (defined as a half-log increase in viral load on day 10 and/or 14) occurred in 23 of 990 patients (2.3%) taking nirmatrelvir-ritonavir and in 17 of 980 (1.7%) given placebo. “Thus, the incidence of viral load rebound was similar in the nirmatrelvir-ritonavir group and the placebo group,” said the study authors, who work for Pfizer. “Our findings suggest that viral load rebound may be a feature of some SARS-CoV-2 infections and that the natural history of Covid-19 requires continued study.” Limitations of the study include that it was conducted when the delta variant of COVID-19 was predominant, the authors noted.

The other report, also a letter to the New England Journal of Medicine published Sept. 7, described some cases of rebound. The first was a 71-year-old man who started a five-day course of nirmatrelvir-ritonavir the day he began experiencing symptoms and tested positive for COVID-19. He was asymptomatic from day 2 through day 8, but on days 9 through 12 had a return of typical cold symptoms and tested positive. The second patient, a 69-year-old man, had cold symptoms and positive results days 0 through 3 and began nirmatrelvir-ritonavir on day 1. He was asymptomatic and negative on days 4 to 9 but had return of symptoms and positive results on day 10, lasting for three days. The letter reported additional rebound cases among family members of the two patients, leading the authors to suggest “that rebound after nirmatrelvir-ritonavir therapy is not uncommon.” They called for additional research “to determine the cause, frequency, duration, and spectrum of rebound symptoms along with the relation to antiviral treatment.”

Viral rebound was among the topics discussed when ACP and Annals of Internal Medicine presented “COVID-19 Forum X: Current Clinical Challenges in COVID-19 Prevention and Management” on Wednesday, Sept. 7. The 10th edition of the forum series featured expert panelists discussing current strategies for preventing and managing SARS-CoV-2 infection, as well as answering questions submitted by clinicians prior to the webinar. The forum was moderated by George M. Abraham, MD, MPH, MACP, ACP's Immediate Past President and professor of medicine at the University of Massachusetts Medical School in Worcester.

The panelists included:

• Sabrina A. Assoumou, MD, MPH, assistant professor of medicine and inaugural Louis W. Sullivan, MD, Professor of Medicine at Boston University School of Medicine;
• Carlos del Rio, MD, FACP, executive associate dean and distinguished professor in the department of medicine, division of infectious diseases at Emory University School of Medicine in Atlanta; and
• Camille N. Kotton, MD, clinical director of transplant and immunocompromised host infectious diseases at Massachusetts General Hospital and associate professor at Harvard Medical School in Boston.

The full recording of the forum is available for replay and is published in Annals of Internal Medicine along with commentary by Christine Laine, MD, MPH, FACP, Annals Editor-in-Chief and ACP Senior Vice President, and Deborah Cotton, MD, MPH, FACP, Annals Deputy Editor.