Sotrovimab in Severe COVID-19 anti-S Seronegative Immunocompromised Patients: Multicenter Retrospective Cohort

Abstract Purpose: Sotrovimab’s effectiveness remains uncertain in severely immunocompromised inpatients with COVID-19, particularly amidst the emergence of Omicron subvariants. Our study aimed to evaluate the clinical progress and safety of severe COVID-19 at-risk inpatients treated with sotrovimab. Methods: Retrospective multicentric cohort study (four teaching hospitals from Andalusian Health System) that included adult inpatients with inmunosupression with severe COVID-19 and negative anti-S serology who received sotrovimab from December 2021 to March 2023. Primary outcomes focused on respiratory progression (High-flow oxygen/Invasive and Non-invasive respiratory support and mortality at 28-day) while secondary variables encompassed hospital stay duration and readmission reasons. Results: 79 patients were included, 58.2% were male, with a median age of 72 years (P₂₅-P₇₅ 65-79). Significant immunosuppression factors included hematologic neoplasms in 51.9% of patients, solid organ transplants in 17.7%, and 13.9% with systemic autoimmune diseases. The median interval between symptom onset and sotrovimab infusion was 12 days (P₂₅-P₇₅8-22), with a median hospital stay of 13 days (P₂₅-P₇₅ 13-26). 36.7% of patients deceased, with 32.9% attributed directly to COVID-19. No adverse reactions to sotrovimab were reported. Univariate analysis linked age and severity at admission to COVID-19 clinical progression (p<0.05). Patients included in the study were distributed among dominant subvariants across five periods: BA.1 (15%), BA.2 (25%), BA.3 (31.3%), BQ.1 (16.3%), and XBB.1.5 (11.4%). Conclusions The study underscores the need for further investigations to establish sotrovimab's efficacy in severe COVID-19 cases among immunocompromise. Early treatment initiation may be crucial considering potential limitations in its use for advanced clinical forms.