A combination of symptoms and viral rebound after untreated COVID-19 infection is rare, occurring in only three per cent of study participants, an analysis of a COVID-19 trial has found.

Widespread use of nirmatrelvir -- a recommended treatment for outpatients with mild to moderate COVID-19 -- has been accompanied by reports of worsening symptoms and virologic rebound after treatment completion, the researchers said.

Virologic rebound has also been reported in persons who did not receive nirmatrelvir therapy, they said. However, studies that can define the frequencies of symptoms and viral rebound during the natural course of COVID-19 are lacking.

Researchers from Brigham and Women's Hospital in the US conducted an analysis of 563 participants receiving a placebo in a trial.

The study, published in the journal Annals of Internal Medicine, found that a combination of symptoms and high-level viral rebound occurred in only three per cent of participants.

Symptom rebound alone occurred in 26 per cent of participants 11 days after initial symptom onset and viral rebound alone occurred in 31 per cent of participants, the researchers said.

The high-level viral rebound was observed in 13 per cent of participants, they said. The researchers noted that both symptoms and viral rebound were short, lasting only one day in most participants.

These results highlight the importance of accounting for underlying rates of symptom relapse in the absence of antiviral therapy when evaluating the effects of antiviral treatments, they added.