Clinical and Virological Outcome of Monoclonal Antibody Therapies Across Severe Acute Respiratory Syndrome Coronavirus 2 Variants in 245 Immunocompromised Patients: A Multicenter Prospective Cohort Study.

Publication date: Mar 06, 2024

Immunocompromised patients (ICPs) have an increased risk for a severe and prolonged COVID-19. SARS-CoV-2 monoclonal antibodies (mAbs) were extensively used in these patients, but data from randomized trials that focus on ICPs are lacking. We evaluated the clinical and virological outcome of COVID-19 in ICPs treated with mAbs across SARS-CoV-2 variants. In this multicenter prospective cohort study, we enrolled B-cell- and/or T-cell-deficient patients treated with casirivimab/imdevimab, sotrovimab, or tixagevimab/cilgavimab. SARS-CoV-2 RNA was quantified and sequenced weekly, and time to viral clearance, viral genome mutations, hospitalization, and death rates were registered. Two hundred and forty five patients infected with the Delta (50%) or Omicron BA. 1, 2, or 5 (50%) variant were enrolled. Sixty-seven percent were vaccinated; 78 treated as outpatients, of whom 2 required hospital admission, but both survived. Of the 159 patients hospitalized at time of treatment, 43 (27%) required mechanical ventilation or died. The median time to viral clearance was 14 days (interquartile range, 7-22); however, it took >30 days in 15%. Resistance-associated spike mutations emerged in 9 patients in whom the median time to viral clearance was 63 days (95% confidence interval, 57-69; P < .001). Spike mutations were observed in 1 of 42 (2. 4%) patients after treatment with 2 active mAbs, in 5 of 34 (14. 7%) treated with actual monotherapy (sotrovimab), and 3 of 20 (12%) treated with functional monotherapy (ie, tixagevimab/cilgavimab against tixagevimab-resistant variant). Despite treatment with mAbs, morbidity and mortality of COVID-19 in ICPs remained substantial. Combination antiviral therapy should be further explored and may be preferred in severely ICPs.

Concepts Keywords
Antibodies immunocompromised
Coronavirus monoclonal antibodies
Outpatients SARS-CoV-2
Severe spike mutations
Weekly

Semantics

Type Source Name
disease VO Severe acute respiratory syndrome coronavirus 2
disease MESH Immunocompromised Patients
disease MESH COVID-19
disease IDO cell
disease VO time
disease MESH death
disease VO vaccinated
disease MESH morbidity

Original Article

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