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Understanding the underlying molecular changes of Omicron SARS\u2010CoV\u20102 infection and corresponding host responses are important to the control of Omicron COVID\u201019 pandemic. In this study, we report an integrative proteomics and metabolomics investigation of serum samples from 80 COVID\u201019 patients infected with Omicron SARS\u2010CoV\u20102, as well as 160 control serum samples from 80 healthy individuals and 80 patients who had flu\u2010like symptoms but were negative for SARS\u2010CoV\u20102 infection. The multiomics results indicated that Omicron SARS\u2010CoV\u20102 infection caused significant changes to host serum proteome and metabolome comparing to the healthy controls and patients who had flu\u2010like symptoms without COVID\u201019. Protein and metabolite changes also pointed to liver dysfunctions and potential damage to other host organs by Omicron SARS\u2010CoV\u20102 infection. The Omicron COVID\u201019 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<jats:sup>+<\/jats:sup> T cells, CD8<jats:sup>+<\/jats:sup> effector memory T cells (Tem), and conventional dendritic cells,\u00a0revealing beneficial effects of full COVID\u201019 vaccination against Omicron SARS\u2010CoV\u20102 infection through molecular changes.<\/jats:p>","DOI":"10.1002\/jmv.29219","type":"journal-article","created":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T21:41:59Z","timestamp":1700084519000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Integrative proteomics and metabolomics study reveal enhanced immune responses by COVID\u201019 vaccine booster shot against Omicron SARS\u2010CoV\u20102 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