{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T16:58:04Z","timestamp":1773680284391,"version":"3.50.1"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T00:00:00Z","timestamp":1657843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Since 2019, the coronavirus (COVID-19) has outbroken continuously, spreading internationally and threatening the public health. However, it was unknown how the disorder at the single-cell level was associated with the pathogenesis of COVID-19. This study presented the disorders of macrophages, epithelial cells, CD8<jats:sup>+<\/jats:sup> T cells, and natural killer (NK) cells at the single-cell level in the courses of COVID-19 and analyzed the immune response to cytokine storm. Compared with the healthy group, patients with COVID-19 had higher proportions of macrophages and lower proportions of T and NK cells, especially proportions of macrophages and epithelial cells with an increase during patients\u2019 conditions from mild to severe. This study suggested that there were high levels of pro-inflammatory and chemokine expressions in cells of COVID-19 and analyzed cell subsets to explore its changes and pathways. It was worth noting that several subsets of macrophages, epithelial cells, CD8 T cells, and NK cells were involved in inflammation pathways, including interleukin-17 (IL-17) signaling pathway and tumor necrosis factor (TNF) signaling pathway. Moreover, the pathways interacting COVID-19 and cytokine receptor with each other were remarkably enriched. In addition, these cell subsets played important roles in inflammation, and their abnormal functions may cause COVID-19. In conclusion, this study provided an immune outlook for COVID-19 at the single-cell level and revealed different pathways in immune response of COVID-19 single cells.<\/jats:p>","DOI":"10.3389\/fimmu.2022.918383","type":"journal-article","created":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T06:38:27Z","timestamp":1657867107000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["A Landscape Study on COVID-19 Immunity at the Single-Cell Level"],"prefix":"10.3389","volume":"13","author":[{"given":"Rongguo","family":"Wei","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zheng","family":"Qin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lulu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Songdong","family":"Meng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1097\/JCMA.0000000000000270","article-title":"The Outbreak of COVID-19: An Overview","volume":"83","author":"Wu","year":"2020","journal-title":"J\u00a0Chin Med Assoc"},{"key":"B2","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.biochi.2020.09.018","article-title":"The Emergence of COVID-19 as a Global Pandemic: Understanding the Epidemiology, Immune Response and Potential Therapeutic Targets of SARS-CoV-2","volume":"179","author":"Muralidar","year":"2020","journal-title":"Biochimie."},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.25705","article-title":"The Progress of 2019 Novel Coronavirus Event in China","volume":"92","author":"Wang","year":"2020","journal-title":"J Med Virol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"107364","DOI":"10.1016\/j.intimp.2020.107364","article-title":"Immunology, Immunopathogenesis and Immunotherapeutics of COVID-19; an Overview","volume":"93","author":"Mohamed Khosroshahi","year":"2021","journal-title":"Int Immunopharmacol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical Features of Patients Infected With 2019 Novel Coronavirus in Wuhan, China","volume":"395","author":"Huang","year":"2020","journal-title":"Lancet."},{"key":"B6","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1002\/JLB.3COVR0520-272R","article-title":"Cytokine Storm and Leukocyte Changes in Mild Versus Severe SARS-CoV-2 Infection: Review of 3939 COVID-19 Patients in China and Emerging Pathogenesis and Therapy Concepts","volume":"108","author":"Wang","year":"2020","journal-title":"J Leukoc Biol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1002\/art.40071","article-title":"Review: Cytokine Storm Syndrome: Looking Toward the Precision Medicine Era","volume":"69","author":"Behrens","year":"2017","journal-title":"Arthritis Rheumatol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0343-0","article-title":"COVID-19: The Vasculature Unleashed","volume":"20","author":"Teuwen","year":"2020","journal-title":"Nat Rev Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(20)30076-X","article-title":"Pathological Findings of COVID-19 Associated With Acute Respiratory Distress Syndrome","volume":"8","author":"Xu","year":"2020","journal-title":"Lancet Respir Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2002032","article-title":"Clinical Characteristics of Coronavirus Disease 2019 in China","volume":"382","author":"Guan","year":"2020","journal-title":"N Engl J Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0331-4","article-title":"Pathological Inflammation in Patients With COVID-19: A Key Role for Monocytes and Macrophages","volume":"20","author":"Merad","year":"2020","journal-title":"Nat Rev Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050828","article-title":"Multiple Organ Infection and the Pathogenesis of SARS","volume":"202","author":"Gu","year":"2005","journal-title":"J Exp Med"},{"key":"B13","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1038\/s41419-020-2636-4","article-title":"The Inhibition of IL-2\/IL-2R Gives Rise to CD8(+) T Cell and Lymphocyte Decrease Through JAK1-STAT5 in Critical Patients With COVID-19 Pneumonia","volume":"11","author":"Shi","year":"2020","journal-title":"Cell Death Dis"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1684\/ecn.2020.0448","article-title":"Interleukin-6 and Severe COVID-19: A Systematic Review and Meta-Analysis","volume":"31","author":"Mojtabavi","year":"2020","journal-title":"Eur Cytokine Netw"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0944-y","article-title":"A Single-Cell Atlas of the Peripheral Immune Response in Patients With Severe COVID-19","volume":"26","author":"Wilk","year":"2020","journal-title":"Nat Med"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03569-1","article-title":"A Molecular Single-Cell Lung Atlas of Lethal COVID-19","volume":"595","author":"Melms","year":"2021","journal-title":"Nature."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1895","DOI":"10.1016\/j.cell.2021.01.053","article-title":"COVID-19 Immune Features Revealed by a Large-Scale Single-Cell Transcriptome Atlas","volume":"184","author":"Ren","year":"2021","journal-title":"Cell."},{"key":"B18","doi-asserted-by":"publisher","first-page":"eabd1554","DOI":"10.1126\/sciimmunol.abd1554","article-title":"Immunophenotypingof COVID-19 and Influenza Highlights the Role of Type I Interferons in Development of Severe COVID-19","volume":"5","author":"Lee","year":"2020","journal-title":"Sci Immunol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0901-9","article-title":"Single-Cell Landscape of Bronchoalveolar Immune Cells in Patients With COVID-19","volume":"26","author":"Liao","year":"2020","journal-title":"Nat Med"},{"key":"B20","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","article-title":"Comprehensive Integration of Single-Cell Data","volume":"177","author":"Stuart","year":"2019","journal-title":"Cell."},{"key":"B21","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1038\/nbt.4314","article-title":"Dimensionality Reduction for Visualizing Single-Cell Data Using UMAP","volume":"37","author":"Becht","year":"2019","journal-title":"Nat Biotechnol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1186\/s13059-015-0844-5","article-title":"MAST: A Flexible Statistical Framework for Assessing Transcriptional Changes and Characterizing Heterogeneity in Single-Cell RNA Sequencing Data","volume":"16","author":"Finak","year":"2015","journal-title":"Genome Biol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118","article-title":"Clusterprofiler: An R Package for Comparing Biological Themes Among Gene Clusters","volume":"16","author":"Yu","year":"2012","journal-title":"OMICS."},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-018-0020-5","article-title":"ISG15 in Antiviral Immunity and Beyond","volume":"16","author":"Perng","year":"2018","journal-title":"Nat Rev Microbiol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2001017","article-title":"A Novel Coronavirus From Patients With Pneumonia in China, 2019","volume":"382","author":"Zhu","year":"2020","journal-title":"N Engl J Med"},{"key":"B26","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1186\/s13073-021-00881-3","article-title":"IFN-\u03b3 and TNF-\u03b1 Drive a CXCL10+ CCL2+ Macrophage Phenotype Expanded in Severe COVID-19 Lungs and Inflammatory Diseases With Tissue Inflammation","volume":"13","author":"Zhang","year":"2021","journal-title":"Genome Med"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-017-0629-x","article-title":"Pathogenic Human Coronavirus Infections: Causes and Consequences of Cytokine Storm and Immunopathology","volume":"39","author":"Channappanavar","year":"2017","journal-title":"Semin Immunopathol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.23208","article-title":"Inflammatory Responses and Inflammation-Associated Diseases in Organs","volume":"9","author":"Chen","year":"2018","journal-title":"Oncotarget."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1590\/S1679-45082015RB3438","article-title":"Chemokines and Immunity","volume":"13","author":"Palomino","year":"2015","journal-title":"Einstein (Sao Paulo)"},{"key":"B30","article-title":"CXCL10 an Important Chemokine Associated With Cytokine Storm in COVID-19 Infected Patients","volume":"24","author":"Zhang","year":"2020","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"B31","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1093\/intimm\/dxy056","article-title":"Ficolin-1 is a Promising Therapeutic Target for Autoimmune Diseases","volume":"31","author":"Katayama","year":"2019","journal-title":"Int Immunol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"103030","DOI":"10.1016\/j.isci.2021.103030","article-title":"Single-Cell Transcriptome Identifies FCGR3B Upregulated Subtype of Alveolar Macrophages in Patients With Critical COVID-19","volume":"24","author":"Nassir","year":"2021","journal-title":"iScience."},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevImmunol.2014010604","article-title":"NK Cells and Their Ability to Modulate T Cells During Virus Infections","volume":"34","author":"Cook","year":"2014","journal-title":"Crit Rev Immunol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00827","article-title":"Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19)","volume":"11","author":"Diao","year":"2020","journal-title":"Front Immunol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"2728757","DOI":"10.1155\/2021\/2728757","article-title":"Identification of Differentially Expressed Genes in COVID-19 and Integrated Bioinformatics Analysis of Signaling Pathways","volume":"2021","author":"Fang","year":"2021","journal-title":"Genet Res (Camb)"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.918383\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T06:38:31Z","timestamp":1657867111000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.918383\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,15]]},"references-count":35,"alternative-id":["10.3389\/fimmu.2022.918383"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.918383","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,15]]},"article-number":"918383"}}