biostudies-literatureUnterman ABLRD VANCATS NIH HHSNIA NIH HHSNIAID NIH HHSNHLBI NIH HHSNLM NIH HHSDepartment of DefenseNIGMS NIH HHSDepartment of Internal Medicine at Yale School of Medicine440https://www.ebi.ac.uk/biostudies/studies/S-EPMC8782894biostudies-literatureUnknown13(1)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^hi/HLA-DR^lo classical monocytes and activated LAG-3^hi 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⁺ clones, unmutated IGHG⁺ 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.Nature communicationsSingle-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19.PMC8782894F30 HL143906R21 LM012884U01 HL145567T32 GM136651UL1 TR001863PR181442R01 HL126094R01 AI104739T15 LM007056K24 AG042489R35 GM143072R01 AI121207I01 BX004661P01 AI039671P01 AI073748U19 AI089992R01 HL141852Peng XMohanty SWang GDeIuliis GCosme CYale IMPACT Research TeamVogels CBFGrubaugh NDMinasyan MKo AIRuff WENelson ADeng WWang ZKaminski NRaredon MSBFarhadian SFChen MSchupp JCZhao AYLi NSharma LMontgomery RRvan Dijk DBermejo SHoehn KBDela Cruz CSGasque VNiklason LEFournier JHafler DALiu YRavindra NGIwasaki AAsashima HCasanovas-Massana AKleinstein SHShaw ACSumida TSZhao HWong PMelillo ARaddassi KUnterman AYan XNouri NRainone MCastaldi CStein YCohen IShepard DMeng HWyllie ALfalseSingle-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19.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^hi/HLA-DR^lo classical monocytes and activated LAG-3^hi 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⁺ clones, unmutated IGHG⁺ 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-19.2022-01-01T00:00:00Z2022 Jan2025-04-25T17:13:01.851Z2025-04-06T04:03:04.574ZS-EPMC87828943506412210.1038/s41467-021-27716-4