biostudies-literatureStephenson ECancer Research UKAction Medical ResearchVersus ArthritisMedical Research CouncilNational Institute for Health Research (NIHR)RosetreesWellcome TrustAcademy of Medical SciencesBiotechnology and Biological Sciences Research Council904-916https://www.ebi.ac.uk/biostudies/studies/S-EPMC8121667biostudies-literatureUnknown27(5)Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16⁺C1QA/B/C⁺) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34⁺ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by exNature medicineSingle-cell multi-omics analysis of the immune response in COVID-19.PMC8121667S_3517MR/W014556/1NIHR201394MC_PC_17230MR/S036113/1ACF-2020-01-007WT107931/Z/15/ZBB/P002293/1DRCPGM\100015214539/Z/18/Z107630/Z/15/ZWT211276/Z/18/Z211153/Z/18/ZACF-2018-01-004MR/P008801/1ACF-2018-01-001211276/Z/18/ZCL-2013-01-003SGL015\1021204721/Z/16/ZBB/V006738/1MR/R015635/121777M94427792911CL-2015-01-002CL-2017-01-004CL-2016-01-001207556/Z/17/Z212516/Z/18/ZMR/K017047/1MR/S005579/1NF-SI-0514-10109213555/Z/18/Z206328/Z/17/ZAMS-SGCL11-DuncanMR/S035842/1Allison JFurlong AHaniffa MStark HStephenson EPointon LDunmore BJTuong ZKSpegarova JSBach KO'Brien CPhelan IPatterson CRossi SWilson NKBarnes JLSmith CMPolwarth GKennet JMartin JStefano GDHorsfall DPublico CCalero-Nieto FJDomingo JHuhn OHunter KCoupland PBradley JROmarjee OJosipovic MPerera MWalker NCalder JIvers TSanchez-Gonzalez AEpping MFawke SHambleton SDougan GKourampa JPolanski KDe Bie EMDDMescia FClatworthy MRRichoz NMarioni JCLaurenti EAnsaripour AGraf SPrigmore ESutcliffe RClapham-Riley DSummers CMeyer KBCambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID-19 BioResource CollaborationDe Sa AMatara CMcGrath Jvan Dongen SJones Ede Wilton ABarr ASCoxhead JMMeadows ALyons PAWebb SKiselev VYRostron AJBunclark KSimpson AJTurner LSelvan MMorgan MDYoshida MMuldoon FPrice JLinger RSchim van der Loeff ICDNikolic MZEngelbert JLehner PJTong ZKingston NBacardit JSungnak WOlabi BGray JJose SWood JWilson CNice FBergamaschi LBaker SMarsden JMackay MBotting RAPolgarova PBullman BHess CHuang CRastall RLindeboom RGHRuffolo VHuang NWeekes MPPapadia SHanrath ATSaleh AHodgson JMichael ASaunders CSmith KGCCaputo DGoh IDann EReynolds GGothe FTreacy CElmer AMather MWWylot MJarvis IButcher HJardine LWorlock KBTordesillas HTilly TSharma RWebster JGopee NRibeiro CGupta RKTownsend PJanes SMSpencer SOwehand WHBower GKania KKing HWGardner LCSCanna LDewhurst EGresley ELScott JOkecha GPond NLegchenko EBetancourt AHewitt SRowlands JSaigal ADuncan CJAStirrups KEKumasaka NToshner MJackson SBaker KFGottgens BThaventhiran JEDGoodfellow IGBucke AKasanicki MKilich EPayne RPMeloy SOvington NO'Donnell CMende NShih JMwaura LFuller SMatheson NJHarris JYong CTeichmann SAGraves BfalseSingle-cell multi-omics analysis of the immune response in COVID-19.Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16⁺C1QA/B/C⁺) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34⁺ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by ex2021-01-01T00:00:00Z2021 May2026-04-30T00:19:45.175Z2025-02-19T03:43:17.998ZS-EPMC81216673387989010.1038/s41591-021-01329-2