biostudies-literatureDelorey TMNIDDK NIH HHSHoward Hughes Medical InstituteNIMH NIH HHSNIAAA NIH HHSNHGRI NIH HHSNCI NIH HHSWellcome TrustNIGMS NIH HHS107-113https://www.ebi.ac.uk/biostudies/studies/S-EPMC8919505biostudies-literatureUnknown595(7865)COVID-19, which is caused by SARS-CoV-2, can result in acute respiratory distress syndrome and multiple organ failure^1-4, but little is known about its pathophysiology. Here we generated single-cell atlases of 24 lung, 16 kidney, 16 liver and 19 heart autopsy tissue samples and spatial atlases of 14 lung samples from donors who died of COVID-19. Integrated computational analysis uncovered substantial remodelling in the lung epithelial, immune and stromal compartments, with evidence of multiple paths of failed tissue regeneration, including defective alveolar type 2 differentiation and expansion of fibroblasts and putative TP63⁺ intrapulmonary basal-like progenitor cells. Viral RNAs were enriched in mononuclear phagocytic and endothelial lung cells, which induced speciNatureCOVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets.PMC8919505DP2 CA247831T32 GM007753R37 MH107649P30 CA013696R01 AA020744R01 MH107649U01 AA026933R01 MH101244P30 DK046200K08 CA222663R37 CA258829U01 HG009379U54 CA225088Farhi SLMuus CSud MZhang STsai LTJuric DGrzyb JIngber DEJiang ZGGazal SSlyper MHibshoosh HMiller EMRozenblatt-Rosen ONiezen SVellarikkal SKHeimberg GEllinor PTNovak RRueckert EHPrice ALTran VMRaju SSHacohen NBiermann JWaghray ABrook ORHarvey TKatsyv IPlaisted JCosimi LAbbondanza DRoss MDey KKVlachos ISBloom-Ackermann ZBabadi MPorter CBMLi BBarkas NZiegler CGKNormand RReeves JSegerstolpe AGould JGanna APfiffner-Borges JTickle TLPita-Juarez YHShalek AKHether TAtri DSNaderi PJane-Valbuena JSabeti PCNormandin EAshenberg OWarren STata PRSubramanian ASturm ASiddle KJIzar BZollinger DRVillani ACDorceus PEngreitz JMWang YLeney-Greene MHecht JChen JEssene ANiemi MSiciliano MSen PMelms JCBeechem JYang YDelorey TMGupta RMRajagopal JSzabo GPinto CJDivakar PPopov YVMcCabe CRiedel SJagadeesh KAHide WMcLoughlin DEHung DRogers RFleming SJPhillips DPe'er CAmir-Zilberstein LFitzgerald DMFropf RRudy MTodres ESolomon IHGomez JPadera RPant DRegev AMontoro DTMa HStone JRPan LfalseCOVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets.COVID-19, which is caused by SARS-CoV-2, can result in acute respiratory distress syndrome and multiple organ failure^1-4, but little is known about its pathophysiology. Here we generated single-cell atlases of 24 lung, 16 kidney, 16 liver and 19 heart autopsy tissue samples and spatial atlases of 14 lung samples from donors who died of COVID-19. Integrated computational analysis uncovered substantial remodelling in the lung epithelial, immune and stromal compartments, with evidence of multiple paths of failed tissue regeneration, including defective alveolar type 2 differentiation and expansion of fibroblasts and putative TP63⁺ intrapulmonary basal-like progenitor cells. Viral RNAs were enriched in mononuclear phagocytic and endothelial lung cells, which induced speci2021-01-01T00:00:00Z2021 Jul2025-04-29T11:01:38.104Z2025-04-06T19:47:24.52ZS-EPMC89195053391556910.1038/s41586-021-03570-8