US Severe Acute Respiratory Syndrome Coronavirus 2 Epsilon Variant: Highly Transmissible but with an Adjusted Muted Host T-Cell Response

Abstract

Background: The multiple mutations comprising the epsilon variant demonstrate the independent convergent evolution of severe acute respiratory syndrome coronavirus (SARS-CoV-2), with its spike protein mutation L452R present in the delta (L452R), kappa (L452R), and lambda (L452Q) variants. Methods: Coronavirus disease 2019 (COVID-19) variants were detected in 1017 patients using whole-genome sequencing and were assessed for outcome and severity. The mechanistic effects of the epsilon versus non-epsilon variants were investigated using a multiomic approach including cellular response assays and paired cell and host transcriptomic and proteomic profiling. Results: We found that patients carrying the epsilon variant had increased mortality risk but not increased hospitalizations (P