This double-blind, placebo-controlled RCT evaluated whether a 5-day course of nirmatrelvir-ritonavir (300 mg/100 mg twice daily) vs. placebo in non-hospitalised adults aged 18–65 with acute SARS-CoV-2 infection (symptoms ≤5 days) reduced the risk of long COVID at 3 months.
Long COVID at 3 months occurred in 26% (17/66) of the nirmatrelvir-ritonavir group vs. 43% (33/77) of the placebo group — a relative risk of 0.60 (95% CI 0.37–0.98; p=0.039). The trial was stopped early after enrolling only 144 of a planned 2,000 participants.
- Trial stopped prematurely due to insufficient recruitment (144 of 2,000 planned participants), leaving the study severely underpowered for firm conclusions. - No stratification or block randomisation used, increasing risk of imbalance between groups. - Long COVID was defined by self-reported symptoms only, with no objective functional or biomarker measures.
These results hint that nirmatrelvir-ritonavir during acute COVID-19 may cut the risk of long COVID by roughly 40%, but the very small sample size means findings should be viewed as hypothesis-generating only. Clinicians should await larger confirmatory trials before changing prescribing practice based on long COVID prevention.
