Sotrovimab neutralizing SARS-CoV-2: Risk factors for post-infusion clinical events

Abstract Background Sotrovimab has been developed to neutralize SARS-CoV-2 which remained effective at the advent of B.1 lineage of the Omicron variant. To investigate post-infusion clinical events and their risk factors, we performed a retrospective study.Methods Subjects were a consecutive series of inpatients with COVID-19 undergoing an infusion of sotrovimab in our institute. In accordance with previous clinical trials, we included patients at risk but permitted SARS-CoV-2 vaccinees. For statistical analyses, we reviewed background factors of demographics, imaging, and laboratory findings for the outcome of post-infusion events such as temperature over 38 degrees Celsius (Temp38) and pulse oximetry below 94%.Results Of a total of 136 patients, the median follow-up was 47 days. Among 110 fully vaccinated patients (80.9%) for SARS-CoV-2, 2-time vaccinees accounted for 88 while 3-time vaccinees were 22. Three patients (2.2%) showed worsening of COVID-19; one developed hypoxia and two died. For the outcome of Temp38 (N=41), multivariate analysis showed that factors at risk were younger age (<66.5) (Odds Ratio [OR] 4.364, 95% Confidence Interval [CI] 1.562 – 12.194, P=0.005) and pre-infusion temperature more than 36.7 degrees Celsius (OR 7.256, 95% CI 2.695 – 21.455, P<0.001). For post-infusion reduced oximetry (N=17), symptomatic days (>2) (OR 8.657, 95% CI 1.030 – 72.786, P=0.047) and pulse oximetry (<96.5%) (OR 7.160, 95% CI 2.071 – 24.751, P=0.002) were at risk. Oxygen was supplied for a median of 1.5 days (range, 1 - 5). We observed vomiting (N=1) and elevated aminotransferase levels (N=1). Conclusions With fully vaccinated patients predominant, antibody-dependent enhancement may have brought about post-infusion fever in the younger population prone to increase antibody titers. Likewise, patients undergoing delayed infusion after symptom onset may have produced antibody, leading into respiratory distress or lowered oximetry. Limitations for this study included inherent difficulty in distinguishing AE from worsening of COVID-19. Thus for 24 hours after infusion of sotrovimab, COVID-19 patients younger than 66.5 years may have temperature elevation, indicating the need for preparation of post-infusion fever. Those undergoing infusion after 3 symptomatic days or more may develop an oximetry decrease, thus demanding pulse oximetry monitoring.