COVID-19 rebound common following treatment with either VV116 or nirmatrelvir-ritonavir

Among patients with mild-to-moderate COVID-19, viral rebound and symptom rebound occur frequently following a standard 5-day course of treatment with either VV116 or nirmatrelvir-ritonavir, as shown in a study from China.

The study included 345 adult patients (mean age 53.2 years, 50.7 percent male) with mild-to-moderate COVID-19. These patients were randomly allocated to receive treatment with VV116 tablets (600 mg every 12 hours on day 1 then 300 mg every 12 hours on days 2 onward; n=165) or nirmatrelvir-ritonavir tablets (300 mg of nirmatrelvir plus 100 mg of ritonavir every 12 hours; n=180). Treatment was administered orally for 5 days, with the patients followed up every other day until day 28 and every week until day 60.

The primary outcome was viral load rebound (VLR), defined as a half-log increase in viral RNA copies per millilitre, which occurred in 33 patients in the VV116 group and in 39 patients in the nirmatrelvir-ritonavir group, with the difference not reaching statistical significance (20.0 percent vs 21.7 percent; p=0.70).

There were also no significant between-group differences observed for most secondary outcomes. For example, the number of patients who had symptom rebound was 41 patients in the VV116 group and 40 in the nirmatrelvir-ritonavir group (25.6 percent vs 24.5 percent; p=0.82).

Data from viral whole-genome sequencing of 24 rebound cases showed no viral lineage shift between the initial infection and the rebound.

As for safety, adverse events such as nausea, vomiting, diarrhoea, and discomfort in the stomach led to treatment discontinuation in two patients in the VV116 group and in six in the nirmatrelvir-ritonavir group. Four and six patients in the respective groups were hospitalized for serious adverse events, and one patient in the VV116 group died during the study period. None of the serious adverse events was related to the study treatment.

More studies are needed to investigate the role of prolonging treatment duration in reducing COVID-19 rebound.