Dear Editor, Since its first reported case in November 2021 in South Africa 1, the novel SARS-CoV-2 variant Omicron infection has swept across the world. The Omicron variant has over 30 mutations in the spike (S) protein which increase its affinity for ACE2 but decrease the cleavage efficiency of S protein by TMPRSS2, leading to suppressed virulence and reduced replication 2. Furthermore, a population-scale meta-analysis showed that Omicron led to a significantly lower proportion of clinically severe cases 3 despite higher transmissibility compared to other variants 4. However, the underlying nature of host responses to Omicron is not well characterized. Mass spectrometry (MS)-based proteomics enables the systematic investigation of circulating and tissue proteins which sheds light on host responses to SARS-CoV-2 infection 5–8. Here, we report the characteristic proteome profile of blood samples from patients with Omicron infection.

We enrolled 17 individuals infected with Omicron SARS-CoV-2, six infected with the prototype strain, and one infected with Delta. We also included 29 individuals infected by non-COVID-19 respiratory virus and 14 healthy controls (Supplementary Tables S1, S2). These subjects were matched for age, gender, and symptoms. In the Omicron group, 15 of 17 patients had received up to four doses of inactivated COVID-19 vaccines. No patients