Time to negative PCR conversion amongst high-risk patients with mild-to-moderate Omicron BA.1 and BA.2 COVID-19 treated with sotrovimab or nirmatrelvir

Our aim was to compare the clinical and virological outcomes of Omicron BA.1 and BA.2-infected patients who received Sotrovimab or Nirmatrelvir to prevent severe COVID-19.In the multicentric prospective ANRS 0003S CoCoPrev cohort study, patients at high-risk for progression with mild-to-moderate BA.1 or BA.2 COVID-19 who received Sotrovimab or Nirmatrelvir were included. Proportion of patients with progression to severe COVID-19, time between the start of treatment to negative PCR, SARS-CoV-2 viral decay, and characterization of resistance variants were determined. A multivariable Cox proportional hazard model was used for time to negative PCR and a mixed effect model for the dynamics of viral decay.Among the 255 included patients, of whom 199/255 (80%) received ≥3 vaccine doses, 195/255 (76%) received Sotrovimab and 60/255 (24%) received Nirmatrelvir. At day 28, new COVID-19-related hospitalization occurred in 4/193 (2%, 95%CI 1-5%) Sotrovimab-treated patients, and 0/55 Nirmatrelvir-treated patient (p=0.24). One out of 55 Nirmatrelvir-treated patients died (2%, 95%CI 0-10%). The median time to negative PCR was 11.5 days (95%CI 10.5-13) in Sotrovimab-treated patients vs. 4 days (95% CI 4-9) in Nirmatrelvir-treated patients (p0.001). Viral decay was faster in patients who received Nirmatrelvir (p0.001). In multivariable analysis Nirmatrelvir and nasopharyngeal PCR cycle threshold value were independently associated with a faster conversion to negative PCR (HR 2.35, 95%CI 1.56-3.56, p0.0001, and HR 1.05, 95%CI 1.01-1.08, p=0.01, respectively).Early administration of Nirmatrelvir in high-risk patients, compared to Sotrovimab, was associated with a faster viral clearance. This may participate to decrease transmission and prevent viral resistance.