Transient symptomatic or viral rebound was observed in up to one-third of subjects with untreated mild to moderate COVID-19.

Rebound of symptoms and reversion to positive testing after viral clearance can occur after treatment with nirmatrelvir-ritonavir (https://emergency.cdc.gov/han/2022/pdf/CDC_HAN_467.pdf) – however, rebound in untreated patients has not been well studied. Investigators analysed data from 563 placebo recipients in the ACTIV-2/A5401 trial with mild-to- moderate COVID-19 to assess the natural course of symptomatic and viral rebound. Participants recorded symptoms daily for 28 days, with collection of anterior nasal swabs daily for 14 days and on days 21 and 28.

Symptom rebound occurred in 26% of participants a median 11 days after symptom onset, with 5% determined to have rebound based on hospitalisation. Risk factors for symptomatic rebound included higher risk for severe disease, female sex and higher initial symptom score and higher viral load at enrolment. In 89% of subjects, rebound lasted one day. Viral rebound occurred in 31% of subjects and was defined as high-level (5 log₁₀ RNA copies/mL or more) in 13%, with 95% of rebounders demonstrating a reduction in viral load at next measurement. Risk factors for viral rebound included lower risk for severe disease and higher median viral load at first measurement. The combination of viral and symptomatic rebound was rare, occurring in 2.7% with high-level rebound and 3.1% with low-level rebound. 

Comment: Rebound of symptoms, viral load or both are common in untreated patients with COVID-19 and are generally brief and clinically insignificant. The extent to which treatment with oral antivirals alters this phenomenon remains unclear. For patients at high risk for progression to severe disease, fears about rebound should not prevent clinicians from prescribing these treatments.

Daniel Kaul, MD, Professor of Medicine, Division of Infectious Diseases, Director, Transplant Infectious Disease Service, University of Michigan Medical School, Ann Arbor, USA.

Deo R, et al. Symptom and viral rebound in untreated SARS-CoV-2 infection. Ann Intern Med 2023; 176: 348-354.

This summary is taken from the following Journal Watch titles: Infectious Diseases, General Medicine, Hospital Medicine.