{"doi":"10.1101/2020.04.17.20069930","title":"A single-cell atlas of the peripheral immune response to severe COVID-19","abstract":"<jats:title>ABSTRACT</jats:title>\n                <jats:p>There is an urgent need to better understand the pathophysiology of Coronavirus disease 2019 (COVID-19), the global pandemic caused by SARS-CoV-2. Here, we apply single-cell RNA sequencing (scRNA-seq) to peripheral blood mononuclear cells (PBMCs) of 7 patients hospitalized with confirmed COVID-19 and 6 healthy controls. We identify substantial reconfiguration of peripheral immune cell phenotype in COVID-19, including a heterogeneous interferon-stimulated gene (ISG) signature, HLA class II downregulation, and a novel B cell-derived granulocyte population appearing in patients with acute respiratory failure requiring mechanical ventilation. Importantly, peripheral monocytes and lymphocytes do not express substantial amounts of pro-inflammatory cytokines, suggesting that circulating leukocytes do not significantly contribute to the potential COVID-19 cytokine storm. Collectively, we provide the most thorough cell atlas to date of the peripheral immune response to severe COVID-19.</jats:p>","journal":null,"year":null,"id":628036,"datarank":0.6414999178524083,"base_score":4.276666119016055,"endowment":4.276666119016055,"self_citation_contribution":0.6414999178524083,"citation_network_contribution":0.0,"self_endowment_contribution":0.6414999178524083,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":71,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":105412,"name":"Arjun Rustagi","orcid":"0000-0002-6921-1012","position":1,"is_corresponding":false},{"id":105413,"name":"Nancy Q. Zhao","orcid":"0000-0001-6217-854X","position":2,"is_corresponding":false},{"id":105414,"name":"Jonasel Roque","orcid":null,"position":3,"is_corresponding":false},{"id":1625854,"name":"Giovanny J. Martinez-Colon","orcid":null,"position":4,"is_corresponding":false},{"id":105416,"name":"Julia L. McKechnie","orcid":null,"position":5,"is_corresponding":false},{"id":105417,"name":"Geoffrey T. Ivison","orcid":"0000-0002-3612-0069","position":6,"is_corresponding":false},{"id":105418,"name":"Thanmayi Ranganath","orcid":"0000-0001-9865-2119","position":7,"is_corresponding":false},{"id":105419,"name":"Rosemary Vergara","orcid":"0000-0001-5406-3785","position":8,"is_corresponding":false},{"id":105420,"name":"Taylor Hollis","orcid":null,"position":9,"is_corresponding":false},{"id":105421,"name":"Laura J. Simpson","orcid":null,"position":10,"is_corresponding":false},{"id":97200,"name":"Philip Grant","orcid":null,"position":11,"is_corresponding":false},{"id":105422,"name":"Aruna Subramanian","orcid":"0000-0002-1373-6768","position":12,"is_corresponding":false},{"id":52015,"name":"Angela J. Rogers","orcid":"0000-0001-6969-6200","position":13,"is_corresponding":false},{"id":52017,"name":"Catherine A. Blish","orcid":"0000-0001-6946-7627","position":14,"is_corresponding":false},{"id":52009,"name":"Aaron J. Wilk","orcid":"0000-0003-1430-5852","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"A single-cell atlas of the peripheral immune response to severe COVID-19","abstract":"<jats:title>ABSTRACT</jats:title>\n                <jats:p>There is an urgent need to better understand the pathophysiology of Coronavirus disease 2019 (COVID-19), the global pandemic caused by SARS-CoV-2. Here, we apply single-cell RNA sequencing (scRNA-seq) to peripheral blood mononuclear cells (PBMCs) of 7 patients hospitalized with confirmed COVID-19 and 6 healthy controls. We identify substantial reconfiguration of peripheral immune cell phenotype in COVID-19, including a heterogeneous interferon-stimulated gene (ISG) signature, HLA class II downregulation, and a novel B cell-derived granulocyte population appearing in patients with acute respiratory failure requiring mechanical ventilation. Importantly, peripheral monocytes and lymphocytes do not express substantial amounts of pro-inflammatory cytokines, suggesting that circulating leukocytes do not significantly contribute to the potential COVID-19 cytokine storm. Collectively, we provide the most thorough cell atlas to date of the peripheral immune response to severe COVID-19.</jats:p>","is_dataset_classified":null,"base_score":4.276666119016055,"endowment":4.276666119016055,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"32511639","pmcid":null,"openalex_id":"https://openalex.org/W3017794848","authors":[],"funders":[{"funder_name":"National Institutes of Health","grant_id":"5T32AI007290-27","title":"Molecular and Cellular Immunobiology"},{"funder_name":"National Institutes of Health","grant_id":"5K23HL125663-04","title":"Metabolic derangements in ARDS"},{"funder_name":"National Institutes of Health","grant_id":"5T32GM007365-23","title":"MEDICAL SCIENTIST TRAINING PROGRAM"},{"funder_name":"National Institutes of Health","grant_id":"5T32AI007502-03","title":"EMERGING INFECTIOUS DISEASES"}],"total_grants":4,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[{"year":2019,"count":1},{"year":2020,"count":47},{"year":2021,"count":12},{"year":2022,"count":5},{"year":2023,"count":4},{"year":2024,"count":2}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://www.medrxiv.org/content/medrxiv/early/2020/04/23/2020.04.17.20069930.full.pdf","host_type":"repository"},{"url":"https://www.medrxiv.org/content/medrxiv/early/2020/04/23/2020.04.17.20069930.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/2020.04.17.20069930","host_type":"publisher"},{"url":"https://doi.org/10.1101/2020.04.17.20069930","host_type":"repository"},{"url":"https://pubmed.ncbi.nlm.nih.gov/32511639","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/7276995","host_type":"repository"},{"url":"https://www.nature.com/articles/s41591-020-0944-y.pdf","host_type":""},{"url":"https://dx.doi.org/10.1101/2020.04.17.20069930","host_type":""},{"url":"http://dx.doi.org/10.1101/2020.04.17.20069930","host_type":""}],"fields_of_study":["Single-cell and spatial transcriptomics","SARS-CoV-2 and COVID-19 Research","COVID-19 Clinical Research Studies","0301 basic medicine","03 medical and health sciences","0302 clinical medicine"],"mesh_terms":[],"keywords":["Cytokine storm","Immune system","Peripheral blood mononuclear cell","Immunology","Population","Cell","Biology","Medicine","Coronavirus disease 2019 (COVID-19)","Virology","Disease","Infectious disease (medical specialty)","Pathology","Genetics","In vitro"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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