{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Unterman A"],"funding":["BLRD VA","NCATS NIH HHS","NIA NIH HHS","NIAID NIH HHS","NHLBI NIH HHS","NLM NIH HHS","Department of Defense","NIGMS NIH HHS","Department of Internal Medicine at Yale School of Medicine"],"pagination":["440"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8782894"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["13(1)"],"pubmed_abstract":["Dysregulated immune responses against the SARS-CoV-2 virus are instrumental in severe COVID-19. However, the immune signatures associated with immunopathology are poorly understood. Here we use multi-omics single-cell analysis to probe the dynamic immune responses in hospitalized patients with stable or progressive course of COVID-19, explore V(D)J repertoires, and assess the cellular effects of tocilizumab. Coordinated profiling of gene expression and cell lineage protein markers shows that S100A<sup>hi</sup>/HLA-DR<sup>lo</sup> classical monocytes and activated LAG-3<sup>hi</sup> T cells are hallmarks of progressive disease and highlights the abnormal MHC-II/LAG-3 interaction on myeloid and T cells, respectively. We also find skewed T cell receptor repertories in expanded effector CD8<sup>+</sup> clones, unmutated IGHG<sup>+</sup> B cell clones, and mutated B cell clones with stable somatic hypermutation frequency over time. In conclusion, our in-depth immune profiling reveals dyssynchrony of the innate and adaptive immune interaction in progressive COVID-19."],"journal":["Nature communications"],"pubmed_title":["Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19."],"pmcid":["PMC8782894"],"funding_grant_id":["F30 HL143906","R21 LM012884","U01 HL145567","T32 GM136651","UL1 TR001863","PR181442","R01 HL126094","R01 AI104739","T15 LM007056","K24 AG042489","R35 GM143072","R01 AI121207","I01 BX004661","P01 AI039671","P01 AI073748","U19 AI089992","R01 HL141852"],"pubmed_authors":["Peng X","Mohanty S","Wang G","DeIuliis G","Cosme C","Yale IMPACT Research Team","Vogels CBF","Grubaugh ND","Minasyan M","Ko AI","Ruff WE","Nelson A","Deng W","Wang Z","Kaminski N","Raredon MSB","Farhadian SF","Chen M","Schupp JC","Zhao AY","Li N","Sharma L","Montgomery RR","van Dijk D","Bermejo S","Hoehn KB","Dela Cruz CS","Gasque V","Niklason LE","Fournier J","Hafler DA","Liu Y","Ravindra NG","Iwasaki A","Asashima H","Casanovas-Massana A","Kleinstein SH","Shaw AC","Sumida TS","Zhao H","Wong P","Melillo A","Raddassi K","Unterman A","Yan X","Nouri N","Rainone M","Castaldi C","Stein Y","Cohen I","Shepard D","Meng H","Wyllie AL"],"additional_accession":[]},"is_claimable":false,"name":"Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19.","description":"Dysregulated immune responses against the SARS-CoV-2 virus are instrumental in severe COVID-19. However, the immune signatures associated with immunopathology are poorly understood. Here we use multi-omics single-cell analysis to probe the dynamic immune responses in hospitalized patients with stable or progressive course of COVID-19, explore V(D)J repertoires, and assess the cellular effects of tocilizumab. Coordinated profiling of gene expression and cell lineage protein markers shows that S100A<sup>hi</sup>/HLA-DR<sup>lo</sup> classical monocytes and activated LAG-3<sup>hi</sup> T cells are hallmarks of progressive disease and highlights the abnormal MHC-II/LAG-3 interaction on myeloid and T cells, respectively. We also find skewed T cell receptor repertories in expanded effector CD8<sup>+</sup> clones, unmutated IGHG<sup>+</sup> B cell clones, and mutated B cell clones with stable somatic hypermutation frequency over time. In conclusion, our in-depth immune profiling reveals dyssynchrony of the innate and adaptive immune interaction in progressive COVID-19.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Jan","modification":"2025-04-25T17:13:01.851Z","creation":"2025-04-06T04:03:04.574Z"},"accession":"S-EPMC8782894","cross_references":{"pubmed":["35064122"],"doi":["10.1038/s41467-021-27716-4"]}}