SARS-CoV-2 spike codon mutations and risk of hospitalization after antispike monoclonal antibody therapy in solid...

Neutralizing antispike monoclonal antibody (mAb) therapies were highly efficacious in preventing coronavirus disease 2019 (COVID-19) hospitalization. While severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants may harbor spike protein mutations conferring reduced in vitro susceptibility to these antibodies, the effect of these mutations on clinical outcomes is not well characterized. We conducted a case-control study of solid organ transplant recipients who received an antispike mAb for treatment of mild-to-moderate COVID-19 and had an available sample from initial COVID-19 diagnosis for genotypic sequencing. Patients whose SARS-CoV-2 isolate had at least one spike codon mutation conferring at least fivefold decreased in vitro susceptibility were classified as resistant. Overall, 9 of 41 patients (22%) had at least one spike codon mutation that confers reduced susceptibility to the antispike mAb used for treatment. Specifically, 9 of 12 patients who received sotrovimab had S371L mutation that was predicted to confer a 9.7-fold reduced susceptibility. However, among 22 patients who required hospitalization, 5 had virus with resistance mutation. In contrast, among 19 control patients who did not require hospitalization, 4 also had virus-containing resistance mutations (p > 0.99). In conclusion, spike codon mutations were common, though mutations that conferred a 9.7-fold reduced susceptibility did not predict subsequent hospitalization after treatment with antispike mAb.