Integrative proteomics and metabolomics study reveal enhanced immune responses by COVID‐19 vaccine booster shot against Omicron SARS‐CoV‐2 infection

Since its outbreak in late 2021, the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been widely reported to be able to evade neutralizing antibodies, becoming more transmissible while causing milder symptoms than previous SARS-CoV-2 strains. Understanding the underlying molecular changes of Omicron SARS-CoV-2 infection and corresponding host responses are important to the control of Omicron COVID-19 pandemic. In this study, we report an integrative proteomics and metabolomics investigation of serum samples from 80 COVID-19 patients infected with Omicron SARS-CoV-2, as well as 160 control serum samples from 80 healthy individuals and 80 patients who had flu-like symptoms but were negative for SARS-CoV-2 infection. The multiomics results indicated that Omicron SARS-CoV-2 infection caused significant changes to host serum proteome and metabolome comparing to the healthy controls and patients who had flu-like symptoms without COVID-19. Protein and metabolite changes also pointed to liver dysfunctions and potential damage to other host organs by Omicron SARS-CoV-2 infection. The Omicron COVID-19 patients could be roughly divided into two subgroups based on their proteome differences. Interestingly, the subgroup who mostly had received full vaccination with booster shot had fewer coughing symptom, changed sphingomyelin lipid metabolism, and stronger immune responses including higher numbers of lymphocytes, monocytes, neutrophils, and upregulated proteins related to CD4⁺ T cells, CD8⁺ effector memory T cells (Tem), and conventional dendritic cells, revealing beneficial effects of full COVID-19 vaccination against Omicron SARS-CoV-2 infection through molecular changes.