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Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19.
Unterman, Avraham; Sumida, Tomokazu S; Nouri, Nima; Yan, Xiting; Zhao, Amy Y; Gasque, Victor; Schupp, Jonas C; Asashima, Hiromitsu; Liu, Yunqing; Cosme, Carlos; Deng, Wenxuan; Chen, Ming; Raredon, Micha Sam Brickman; Hoehn, Kenneth B; Wang, Guilin; Wang, Zuoheng; DeIuliis, Giuseppe; Ravindra, Neal G; Li, Ningshan; Castaldi, Christopher; Wong, Patrick; Fournier, John; Bermejo, Santos; Sharma, Lokesh; Casanovas-Massana, Arnau; Vogels, Chantal B F; Wyllie, Anne L; Grubaugh, Nathan D; Melillo, Anthony; Meng, Hailong; Stein, Yan; Minasyan, Maksym; Mohanty, Subhasis; Ruff, William E; Cohen, Inessa; Raddassi, Khadir; Niklason, Laura E; Ko, Albert I; Montgomery, Ruth R; Farhadian, Shelli F; Iwasaki, Akiko; Shaw, Albert C; van Dijk, David; Zhao, Hongyu; Kleinstein, Steven H; Hafler, David A; Kaminski, Naftali; Dela Cruz, Charles S.
  • Unterman A; Section of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, USA. ramiu@tlvmc.gov.il.
  • Sumida TS; Pulmonary Institute, Tel Aviv Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel. ramiu@tlvmc.gov.il.
  • Nouri N; Department of Neurology, School of Medicine, Yale University, New Haven, CT, USA. tomokazu.sumida@yale.edu.
  • Yan X; Department of Immunobiology, School of Medicine, Yale University, New Haven, CT, USA. tomokazu.sumida@yale.edu.
  • Zhao AY; Department of Pathology, Yale School of Medicine, New Haven, CT, USA.
  • Gasque V; Center for Medical Informatics, Yale School of Medicine, New Haven, CT, USA.
  • Schupp JC; The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
  • Asashima H; Section of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, USA.
  • Liu Y; Department of Biostatistics, Yale School of Public Health, Yale University, New Haven, CT, USA.
  • Cosme C; Section of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, USA.
  • Deng W; Department of Genetics, Yale School of Medicine, New Haven, CT, USA.
  • Chen M; Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.
  • Raredon MSB; Department of Computer Science, Yale University, New Haven, CT, USA.
  • Hoehn KB; Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.
  • Wang G; Section of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, USA.
  • Wang Z; Department of Respiratory Medicine, Hannover Medical School and Biomedical Research in End-stage and Obstructive Lung Disease Hannover, German Lung Research Center (DZL), Hannover, Germany.
  • DeIuliis G; Department of Neurology, School of Medicine, Yale University, New Haven, CT, USA.
  • Ravindra NG; Department of Immunobiology, School of Medicine, Yale University, New Haven, CT, USA.
  • Li N; Department of Biostatistics, Yale School of Public Health, Yale University, New Haven, CT, USA.
  • Castaldi C; Section of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, USA.
  • Wong P; Department of Biostatistics, Yale School of Public Health, Yale University, New Haven, CT, USA.
  • Fournier J; Department of Biostatistics, Yale School of Public Health, Yale University, New Haven, CT, USA.
  • Bermejo S; Section of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, USA.
  • Sharma L; Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
  • Casanovas-Massana A; Medical Scientist Training Program, Yale School of Medicine, New Haven, CT, USA.
  • Vogels CBF; Department of Pathology, Yale School of Medicine, New Haven, CT, USA.
  • Wyllie AL; Yale Center for Genome Analysis/Keck Biotechnology Resource Laboratory, Department of Molecular Biophysics and Biochemistry, Yale School of Medicine, New Haven, CT, USA.
  • Grubaugh ND; Department of Biostatistics, Yale School of Public Health, Yale University, New Haven, CT, USA.
  • Melillo A; Section of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, USA.
  • Meng H; Department of Computer Science, Yale University, New Haven, CT, USA.
  • Stein Y; Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.
  • Minasyan M; Department of Biostatistics, Yale School of Public Health, Yale University, New Haven, CT, USA.
  • Mohanty S; SJTU-Yale Joint Center for Biostatistics and Data Science, Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
  • Ruff WE; Yale Center for Genome Analysis, Yale School of Medicine, New Haven, CT, USA.
  • Cohen I; Department of Immunobiology, School of Medicine, Yale University, New Haven, CT, USA.
  • Raddassi K; School of Medicine, Yale University, New Haven, CT, USA.
  • Niklason LE; Section of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, USA.
  • Ko AI; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA.
  • Montgomery RR; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA.
  • Farhadian SF; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA.
  • Iwasaki A; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA.
  • Shaw AC; Department of Pathology, Yale School of Medicine, New Haven, CT, USA.
  • van Dijk D; Department of Pathology, Yale School of Medicine, New Haven, CT, USA.
  • Zhao H; Pulmonary Institute, Tel Aviv Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel.
  • Kleinstein SH; Section of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, USA.
  • Hafler DA; Section of Infectious Diseases, Department of Internal Medicine, Yale School of Medicine, Yale University, New Haven, CT, USA.
  • Kaminski N; Department of Neurology, School of Medicine, Yale University, New Haven, CT, USA.
  • Dela Cruz CS; Department of Immunobiology, School of Medicine, Yale University, New Haven, CT, USA.
Nat Commun ; 13(1): 440, 2022 01 21.
Article in English | MEDLINE | ID: covidwho-1641960
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 S100Ahi/HLA-DRlo classical monocytes and activated LAG-3hi 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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Gene Expression Profiling / Adaptive Immunity / Single-Cell Analysis / SARS-CoV-2 / COVID-19 / Immunity, Innate Type of study: Prognostic study Limits: Aged / Female / Humans / Male Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2022 Document Type: Article Affiliation country: S41467-021-27716-4

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Gene Expression Profiling / Adaptive Immunity / Single-Cell Analysis / SARS-CoV-2 / COVID-19 / Immunity, Innate Type of study: Prognostic study Limits: Aged / Female / Humans / Male Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2022 Document Type: Article Affiliation country: S41467-021-27716-4