Rebound symptoms common with COVID-19 even after placebo treatment

Reference

Smith DM, Li JZ, Moser C, et al. Recurrence of symptoms following a 2-day symptom free period in patients with COVID-19. JAMA Network Open 2022; 5(10):e2238867.

Synopsis

“Paxlovid rebound” has been widely reported by patients and in the media and consists of recurrent symptoms following a 5-day course of Paxlovid (nirmatrelvir/ritonavir) in someone who had initially recovered. But is this causally related to use of the drug? Or is it just part of the natural history of infection with SARS-CoV-2? These authors used data from the placebo group in the ACTIV-2 randomized trial that compared a number of treatments (including Paxlovid with placebo) in outpatients symptomatic with COVID-19 for 10 or fewer days. The current study only reports on recurrences in the placebo group. The 158 participants in the placebo group completed a daily symptom diary for 28 days, tracking 13 symptoms. The participants had a median age of 47 years, 50% were women, 18% self-identified as part of a minority racial group, and 31% were Hispanic. During the 28 days of follow-up, 108 of 158 participants (68%) achieved complete resolution of all symptoms for at least 2 consecutive days. Of these 108, 48 (44%) reported at least one symptom recurring for at least one day during the follow-up period. The most common recurrent symptoms were cough (44%), fatigue (35%), and headache (35%). The recurrent symptoms were largely mild, with no patient reporting severe recurrent symptoms and only 8 of the 48 reporting moderate severity symptoms for at least one day. The interval between resolution of the initial symptoms and recurrence varied from 1 day to more than 2 weeks later, so some of these recurrences may represent a separate viral illness. By my count, approximately half recurred in the first week following resolution. A cool diagram lets you examine these recurrences for individual participants yourself.