{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:23:15Z","timestamp":1790814195438,"version":"4.1.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,3]],"date-time":"2022-01-03T00:00:00Z","timestamp":1641168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017610","name":"Shenzhen Science and Technology Innovation Program","doi-asserted-by":"publisher","award":["kqtd20180411143323605, JSGG20200225152008136"],"award-info":[{"award-number":["kqtd20180411143323605, JSGG20200225152008136"]}],"id":[{"id":"10.13039\/501100017610","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82041043, 8187631"],"award-info":[{"award-number":["82041043, 8187631"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Despite many studies on the immune characteristics of Coronavirus disease 2019 (COVID-19) patients in the progression stage, a detailed understanding of pertinent immune cells in recovered patients is lacking. We performed single-cell RNA sequencing on samples from recovered COVID-19 patients and healthy controls. We created a comprehensive immune landscape with more than 260,000 peripheral blood mononuclear cells (PBMCs) from 41 samples by integrating our dataset with previously reported datasets, which included samples collected between 27 and 47 days after symptom onset. According to our large-scale single-cell analysis, recovered patients, who had severe symptoms (severe\/critical recovered), still exhibited peripheral immune disorders 1\u20132 months after symptom onset. Specifically, in these severe\/critical recovered patients, human leukocyte antigen (HLA) class II and antigen processing pathways were downregulated in both CD14 monocytes and dendritic cells compared to healthy controls, while the proportion of CD14 monocytes increased. These may lead to the downregulation of T-cell differentiation pathways in memory T cells. However, in the mild\/moderate recovered patients, the proportion of plasmacytoid dendritic cells increased compared to healthy controls, accompanied by the upregulation of <jats:italic>HLA-DRA<\/jats:italic> and <jats:italic>HLA-DRB1<\/jats:italic> in both CD14 monocytes and dendritic cells. In addition, T-cell differentiation regulation and memory T cell\u2013related genes <jats:italic>FOS<\/jats:italic>, <jats:italic>JUN<\/jats:italic>, <jats:italic>CD69<\/jats:italic>, <jats:italic>CXCR4<\/jats:italic>, and <jats:italic>CD83<\/jats:italic> were upregulated in the mild\/moderate recovered patients. Further, the immunoglobulin heavy chain V3-21 (<jats:italic>IGHV3-21<\/jats:italic>) gene segment was preferred in B-cell immune repertoires in severe\/critical recovered patients. Collectively, we provide a large-scale single-cell atlas of the peripheral immune response in recovered COVID-19 patients.<\/jats:p>","DOI":"10.3389\/fimmu.2021.781432","type":"journal-article","created":{"date-parts":[[2022,1,3]],"date-time":"2022-01-03T08:42:22Z","timestamp":1641199342000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["Single-Cell Analysis Reveals the Immune Characteristics of Myeloid Cells and Memory T Cells in Recovered COVID-19 Patients With Different Severities"],"prefix":"10.3389","volume":"12","author":[{"given":"Xu","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manik","family":"Garg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qijun","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifang","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengyu","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihua","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yalan","family":"Bi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"George","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Papatheodorou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvis","family":"Brazma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanle","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shisong","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhichao","family":"Miao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuelong","family":"Shu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.cell.2020.05.025","article-title":"Potent Neutralizing Antibodies Against SARS-CoV-2 Identified by High-Throughput Single-Cell Sequencing of Convalescent Patients\u2019 B Cells","volume":"182","author":"Cao","year":"2020","journal-title":"Cell"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0602-4","article-title":"COVID-19 Severity Correlates With Airway Epithelium-Immune Cell Interactions Identified by Single-Cell Analysis","volume":"38","author":"Chua","year":"2020","journal-title":"Nat Biotechnol"},{"key":"B3","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":"B4","doi-asserted-by":"publisher","first-page":"1479","DOI":"10.1016\/j.cell.2020.10.037","article-title":"Multi-Omics Resolves a Sharp Disease-State Shift Between Mild and Moderate COVID-19","volume":"183","author":"Su","year":"2020","journal-title":"Cell"},{"key":"B5","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1038\/s41421-020-0168-9","article-title":"Immune Cell Profiling of COVID-19 Patients in the Recovery Stage by Single-Cell Sequencing","volume":"6","author":"Wen","year":"2020","journal-title":"Cell Discov"},{"key":"B6","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":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-0762-x","article-title":"Single-Cell Landscape of Immunological Responses in Patients With COVID-19","volume":"21","author":"Zhang","year":"2020","journal-title":"Nat Immunol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1038\/s41392-020-00263-y","article-title":"Adaptive Immune Responses to SARS-Cov-2 Infection in Severe Versus Mild Individuals","volume":"5","author":"Zhang","year":"2020","journal-title":"Signal Transduct Target Ther"},{"key":"B9","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":"B10","doi-asserted-by":"publisher","DOI":"10.3390\/cells9112374","article-title":"Single-Cell Transcriptome Analysis Highlights a Role for Neutrophils and Inflammatory Macrophages in the Pathogenesis of Severe COVID-19","volume":"9","author":"Shaath","year":"2020","journal-title":"Cells"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-020-00762-2","article-title":"A Human Circulating Immune Cell Landscape in Aging and COVID-19","volume":"11","author":"Zheng","year":"2020","journal-title":"Protein Cell"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.589380","article-title":"T-Cell Hyperactivation and Paralysis in Severe COVID-19 Infection Revealed by Single-Cell Analysis","volume":"11","author":"Kalfaoglu","year":"2020","journal-title":"Front Immunol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1340","DOI":"10.1016\/j.cell.2020.10.001","article-title":"Imbalance of Regulatory and Cytotoxic SARS-CoV-2-Reactive CD4(+) T Cells in COVID-19","volume":"183","author":"Meckiff","year":"2020","journal-title":"Cell"},{"key":"B14","doi-asserted-by":"publisher","first-page":"3936","DOI":"10.1016\/j.cell.2021.06.005","article-title":"SARS-CoV-2 Mrna Vaccination Induces Functionally Diverse Antibodies to NTD, RBD, and S2","volume":"184","author":"Amanat","year":"2021","journal-title":"Cell"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0897-1","article-title":"Antibody Responses to SARS-Cov-2 in Patients With COVID-19","volume":"26","author":"Long","year":"2020","journal-title":"Nat Med"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.632814","article-title":"The Characterization of Disease Severity Associated Igg Subclasses Response in COVID-19 Patients","volume":"12","author":"Luo","year":"2021","journal-title":"Front Immunol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00238-5","article-title":"Seroprevalence and Humoral Immune Durability of Anti-SARS-CoV-2 Antibodies in Wuhan, China: A Longitudinal, Population-Level, Cross-Sectional Study","volume":"397","author":"He","year":"2021","journal-title":"Lancet"},{"key":"B18","doi-asserted-by":"publisher","first-page":"e0244126","DOI":"10.1371\/journal.pone.0244126","article-title":"Antibody Response to SARS-CoV-2 Infection in Humans: A Systematic Review","volume":"15","author":"Post","year":"2020","journal-title":"PLoS One"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00575-4","article-title":"Assessment of Protection Against Reinfection With SARS-Cov-2 Among 4 Million PCR-Tested Individuals in Denmark in 2020: A Population-Level Observational Study","volume":"397","author":"Hansen","year":"2021","journal-title":"Lancet"},{"key":"B20","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.cels.2018.11.005","article-title":"Scrublet: Computational Identification of Cell Doublets in Single-Cell Transcriptomic Data","volume":"8","author":"Wolock","year":"2019","journal-title":"Cell Syst"},{"key":"B21","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s13059-017-1382-0","article-title":"SCANPY: Large-Scale Single-Cell Gene Expression Data Analysis","volume":"19","author":"Wolf","year":"2018","journal-title":"Genome Biol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0619-0","article-title":"Fast, Sensitive and Accurate Integration of Single-Cell Data With Harmony","volume":"16","author":"Korsunsky","year":"2019","journal-title":"Nat Methods"},{"key":"B23","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":"B24","doi-asserted-by":"publisher","first-page":"036114","DOI":"10.1103\/PhysRevE.77.036114","article-title":"Local Leaders in Random Networks","volume":"77","author":"Blondel","year":"2008","journal-title":"Phys Rev E Stat Nonlin Soft Matter Phys"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-020-0825-9","article-title":"Putative Cell Type Discovery From Single-Cell Gene Expression Data","volume":"17","author":"Miao","year":"2020","journal-title":"Nat Methods"},{"key":"B26","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":"B27","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz369","article-title":"G:Profiler: A Web Server for Functional Enrichment Analysis and Conversions of Gene Lists (2019 Update)","volume":"47","author":"Raudvere","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102","article-title":"Gene Set Enrichment Analysis: A Knowledge-Based Approach for Interpreting Genome-Wide Expression Profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc Natl Acad Sci USA"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-03041-6","article-title":"Correlates of Protection Against SARS-CoV-2 in Rhesus Macaques","volume":"590","author":"McMahan","year":"2021","journal-title":"Nature"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.5281\/zenodo.3893991","article-title":"Immunomind\/Immunarch: 0.6.5: Basic Single-Cell Support (0.6.5). Zenodo","author":"Vadim","year":"2021"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1038\/s41467-021-21246-9","article-title":"Inference and Analysis of Cell-Cell Communication Using Cellchat","volume":"12","author":"Jin","year":"2021","journal-title":"Nat Commun"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2015.12.004","article-title":"The Molecular Signatures Database (Msigdb) Hallmark Gene Set Collection","volume":"1","author":"Liberzon","year":"2015","journal-title":"Cell Syst"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw1092","article-title":"KEGG: New Perspectives on Genomes, Pathways, Diseases and Drugs","volume":"45","author":"Kanehisa","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02389","article-title":"Gammadelta T Lymphocytes: An Effector Cell in Autoimmunity and Infection","volume":"9","author":"Shiromizu","year":"2018","journal-title":"Front Immunol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"eaay5516","DOI":"10.1126\/science.aay5516","article-title":"Butyrophilin 2A1 is Essential for Phosphoantigen Reactivity by Gammadelta T Cells","volume":"367","author":"Rigau","year":"2020","journal-title":"Science"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1126\/science.1201730","article-title":"Different B Cell Populations Mediate Early and Late Memory During an Endogenous Immune Response","volume":"331","author":"Pape","year":"2011","journal-title":"Science"},{"key":"B37","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.medj.2021.02.001","article-title":"Persistence of SARS-Cov-2-Specific B and T Cell Responses in Convalescent COVID-19 Patients 6-8 Months After the Infection","volume":"2","author":"Sherina","year":"2021","journal-title":"Med (N Y)"},{"key":"B38","doi-asserted-by":"publisher","first-page":"4043","DOI":"10.1038\/s41467-021-24377-1","article-title":"SARS-CoV-2-Specific T Cell Memory is Sustained in COVID-19 Convalescent Patients for 10 Months With Successful Development of Stem Cell-Like Memory T Cells","volume":"12","author":"Jung","year":"2021","journal-title":"Nat Commun"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1126","DOI":"10.1126\/scitranslmed.abf7517","article-title":"T Cell and Antibody Kinetics Delineate SARS-Cov-2 Peptides Mediating Long-Term Immune Responses in COVID-19 Convalescent Individuals","volume":"10","author":"Bilich","year":"2021","journal-title":"Sci Trans Med"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.26353","article-title":"The Dynamic Changes of Serum Igm and Igg Against SARS-CoV-2 in Patients With COVID-19","volume":"93","author":"Zhou","year":"2021","journal-title":"J Med Virol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1038\/s41392-021-00777-z","article-title":"SARS-CoV-2 Immunity and Functional Recovery of COVID-19 Patients 1-Year After Infection","volume":"6","author":"Zhan","year":"2021","journal-title":"Signal Transduct Target Ther"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0965-6","article-title":"Clinical and Immunological Assessment of Asymptomatic SARS-CoV-2 Infections","volume":"26","author":"Long","year":"2020","journal-title":"Nat Med"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2550-z","article-title":"SARS-CoV-2-Specific T Cell Immunity in Cases of COVID-19 and SARS, and Uninfected Controls","volume":"584","author":"Le Bert","year":"2020","journal-title":"Nature"},{"key":"B44","doi-asserted-by":"publisher","first-page":"eaan5393","DOI":"10.1126\/sciimmunol.aan5393","article-title":"Recovery From the Middle East Respiratory Syndrome is Associated With Antibody and T-Cell Responses","volume":"2","author":"Zhao","year":"2017","journal-title":"Sci Immunol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903490","article-title":"Lack of Peripheral Memory B Cell Responses in Recovered Patients With Severe Acute Respiratory Syndrome: A Six-Year Follow-Up Study","volume":"186","author":"Tang","year":"2011","journal-title":"J Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.781432\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,3]],"date-time":"2022-01-03T08:42:27Z","timestamp":1641199347000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.781432\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,3]]},"references-count":45,"alternative-id":["10.3389\/fimmu.2021.781432"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.781432","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,3]]},"article-number":"781432"}}