Clinical outcomes of sotrovimab in seronegative patients with severe COVID-19: A multicenter retrospective study

The effectiveness of sotrovimab in severely immunocompromised inpatients with coronavirus disease (COVID-19) remains uncertain, particularly with the emergence of Omicron subvariants. This study aimed to evaluate the clinical outcomes of patients with severe COVID-19 who were seronegative for anti-S antibodies and who received sotrovimab. We conducted a retrospective cohort study at 4 teaching hospitals in the Andalusian Health System. Eligible participants were adults hospitalized with severe COVID-19, with negative anti-S serology, and treated with sotrovimab between December 2021 and March 2023. The primary outcomes were respiratory progression requiring advanced respiratory support and 28-day mortality rate. Secondary outcomes included the length of hospital stay and causes of readmission. Seventy-nine patients (58.2%) were male, with a median age of 72 years. Immunosuppression was mainly caused by hematologic malignancies (51.9%), solid organ transplantation (17.7%), and systemic autoimmune diseases (13.9%). The median time from symptom onset to sotrovimab infusion was 12 days and the median hospital stay was 13 days. The overall mortality rate was 36.7%, with 32.9% being directly attributable to COVID-19. No adverse reactions to sotrovimab were reported. In univariate analysis, older age and higher severity at admission were associated with disease progression. Patients were treated during periods dominated by Omicron subvariants BA.1, BA.2, BA.3, BQ.1, and XBB.1.5. The high mortality in this cohort underscores the extreme vulnerability of severely immunocompromised patients with COVID-19. These findings support further research into early and prolonged antiviral strategies, potentially combining agents, given the limitations of sotrovimab in the advanced disease stages.