Stealth replication of SARS-CoV-2 Omicron in the nasal epithelium at physiological temperature

The COVID-19 pandemic was initially characterized by a rapid succession of viral variants that emerged independently of each other, with each of these variants outcompeting the previous one. A major evolutionary shift occurred in late 2021, with the emergence of the highly divergent Omicron BA.1 variant. Since then, all the dominant SARS-CoV-2 variants have been derived from Omicron, for reasons that remain incompletely understood. Here, we compared the replication of SARS-CoV-2 variants in a human nasal epithelium model grown at 37°C and also at 33°C, a temperature that approximates that found in the nasal cavity. In this primary epithelial model, Omicron showed an early replicative advantage that was more marked at 33°C. However, Omicron triggered only a minimal antiviral interferon response at this temperature. Omicron could thus propagate rapidly while partly escaping the innate response at physiological nasal temperature, which helps account for the efficient dissemination of this variant worldwide.