Efficacy and safety of antiviral plus anti-spike monoclonal antibody combination therapy vs. monotherapy for high-risk immunocompromised patients with mild-to-moderate SARS-CoV2 infection during the Omicron era: A prospective cohort study

Introduction: Antivirals and monoclonal antibodies lower the risk of progression in immunocompromised patients. However, combination therapy with both types of agents has not been studied. Patients and methods: This was a single-centre, prospective, cohort study. All immunocompromised patients who received treatment for mild-to-moderate COVID-19 from 1 January 2022 to 30 October 2022 were enrolled. The primary endpoint was COVID-19 progression at 90 days, defined as hospital admission or death due to COVID-19 and/or seronegative persistent COVID-19. Results: A total of 304 patients were included: 43 patients (14.1%) received sotrovimab plus a directacting antiviral, and 261 (85.9%) received monotherapy. Primary outcome occurred more frequently after monotherapy (4.6% vs. 0%, P = 0.154). Among patients with anti-spike immunoglobulin G (anti-S IgG) titre < 750 BAU/mL, COVID-19 progression was more common after monotherapy (23.9% vs. 0%, P = 0.001), including more frequent COVID-related admission (15.2% vs. 0%, P = 0.014) and seronegative persistent COVID-19 (10.9% vs. 0%, P = 0.044). Combination therapy was associated with lower risk of progression (odds ratio [OR] 0.08, 95% confidence interval [95% CI] 0.01-0.64). Anti-S IgG titre < 750 BAU/mL and previous anti-CD20 were associated with higher risk of progression (OR 13.70, 95% CI 2.77-67.68; and OR 3.05, 95% CI 1.20-10.94, respectively). Conclusions: In immunocompromised patients, combination therapy with sotrovimab plus an antiviral may be more effective than monotherapy for SARS-CoV2. (c) 2024 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )