SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes.

We investigated SARS-CoV-2 potential tropism by surveying expression of viral entry-associated genes in single-cell RNA-sequencing data from multiple tissues from healthy human donors. We co-detected these transcripts in specific respiratory, corneal and intestinal epithelial cells, potentially explaining the high efficiency of SARS-CoV-2 transmission. These genes are co-expressed in nasal epithelial cells with genes involved in innate immunity, highlighting the cells' potential role in initial viral infection, spread and clearance. The study offers a useful resource for further lines of inquiry with valuable clinical samples from COVID-19 patients and we provide our data in a comprehensive, open and user-friendly fashion at www.covid19cellatlas.org.

Keywords

HCA Lung Biological Network

Journal Title

Nat Med

Journal ISSN

1078-8956
1546-170X

Volume Title

26

Publisher

Springer Science and Business Media LLC

Publisher DOI

https://doi.org/10.1038/s41591-020-0868-6

Rights

Sponsorship

Wellcome Trust (211276/D/18/Z)
Medical Research Council (MR/P009581/1)
Medical Research Council (MR/S035907/1)
Wellcome Trust (108082/A/15/Z)
Medical Research Council (MC_PC_12009)
Medical Research Council (G0701448)
National Centre for the Replacement Refinement and Reduction of Animals in Research (NC/N001540/1)
Medical Research Council (MR/R015635/1)
European Research Council (741707)
European Commission Horizon 2020 (H2020) Societal Challenges (874656)
Engineering and Physical Sciences Research Council (TS/H001220/1)
Medical Research Council (MC_PC_17230)

This work was supported by the Wellcome Sanger Institute core funding (WT206194) and the Wellcome Strategic Scientific Support award “Pilot projects for the Human Cell Atlas” (WT211276/Z/18/Z), a Seed Network grant from the Chan Zuckerberg Initiative to P.B., T.D., T.E.D., O.E., P.H., N.H., N.K., M.K., K.B.M., A.M., M.C.N., M.N., D.P., J.R., P.R.T., S.Q., A.R., O.R., M.S., J.S., J.G.S., C.E.S., H.B.S., D.S., A.T., J.W. and K.Z. and by the European Union’s H2020 research and innovation program under grant agreement No 874656 (discovAIR) to P.B., A.B., M.K., S.L., J.L., K.B.M., M.C.N., K.S.P., C.S., H.B.S., J.S., F.J.T. and M.vd.B. W.S. acknowledges funding from the Newton Fund, Medical Research Council (MRC), The Thailand Research Fund (TRF), and Thailand’s National Science and Technology Development Agency (NSTDA). M.C.N acknowledges funding from GSK Ltd, Netherlands Lung Foundation project no. 5.1.14.020 and 4.1.18.226. T.D. acknowledges funding from HubMap consortium and Stanford Child Health Research Institute- Woods Family Faculty Scholarship. T.E.D. acknowledges funding from HubMap. P.H. acknowledges funding from LENDULET-BIOMAG Grant (2018-342) and the European Regional Development Funds (GINOP-2.3.2-15-2016-00006, GINOP-2.3.2-15-2016-00026, GINOP-2.3.2-15-2016-00037). J.L.B. acknowledges funding from Medical Research Council (MRC), and the UK Regenerative Medicine Platform (MR/ 5005579/1). P.B. acknowledges funding from Fondation pour la Recherche Médicale (DEQ20180339158), Agence Nationale de la Recherche (UCAJEDI, ANR-15-IDEX-01; SAHARRA, ANR-19-CE14-0027; France Génomique, ANR-10-INBS-09-03), and Conseil Départemental des Alpes Maritimes (2016-294DGADSH-CV; 2019-390DGADSH-CV). N.E.B. and J.K. acknowledge funding from NIH grant R01HL145372 and DOD grant W81XWH1910416. I.G. acknowledges funding from NIH (5R24HD000836) and the Eunice Kennedy Shriver National Institute of Child Health and Human. N.H., J.G.S. and C.E.S. acknowledge funding by the Leducq foundation. N.H. is recipient of an ERC Advanced Grant. J.K. acknowledges funding from NIH grant K08HL130595 and the Doris Duke Charitable Foundation. N.K. acknowledges funding from NIH grants R01HL127349, U01HL145567 and an unrestricted grant from Three Lakes Foundation. M.K. acknowledges HHMI and Wall Center for Pulmonary Vascular Disease. H.L. acknowledges funding from National Research Foundation of Korea. K.M. acknowledges funding from Wellcome Trust. A.M. acknowledges funding from NIH grants HL135124, AG049665 and AI135964. M.Z.N. acknowledges funding from Rutherford Fund Fellowship allocated by the Medical Research Council and the UK Regenerative Medicine Platform (MR/ 5005579/1 to M.Z.N.). M.Z.N. and M.Y. have been funded by the Rosetrees Grant (Grant number M899). M.N. acknowledges funding from a BHF/DZHK grant and British Heart Foundation (PG/16/47/32156). J.O.-M. acknowledges funding from Richard and Susan Smith Family Foundation. D.P. acknowledges funding from Alan and Sandra Gerry Metastasis and Tumor Ecosystems Center. J.P. acknowledges funding from National Health and Medical Research Council. P.R.T. acknowledges funding from R01HL146557 from NHLBI/NIH. E.L.R. acknowledges funding from MRC MR/P009581/1 and MR/SO35907/1. A.R. and O. R. acknowledge HHMI, the Klarman Cell Observatory, and the Manton Foundation. K.S.-P. acknowledges NIHR Cambridge Biomedical Research Centre. C.S. acknowledges Swedish research Council, Swedish Cancer Society, and CPI. H.B.S. acknowledges German Center for Lung Research and Helmholtz Association. J.S. acknowledges Boehringer Ingelheim, by the German Research Foundation (DFG; EXC2151/1, ImmunoSensation2 - the immune sensory system, project number 390873048), project numbers 329123747, 347286815) and by the HGF grant sparse2big. A.K.S. acknowledges the Beckman Young Investigator Program, a Sloan Fellowship in Chemistry, the NIH (5U24AI118672), and the Bill and Melinda Gates Foundation. F.J.T. acknowledges the German Center for Lung Research. M.vd.B. acknowledges from Ministry of Economic Affairs and Climate Policy by means of the PPP. K.B.W. is funded by the University College London-Birkbeck MRC Doctoral Training Programme. J.W. and Y.Y. acknowledge NIH, U01 HL148856 LungMap Phase II. R.X. acknowledges the NIH (DK043351). H.Z. is supported by the National Key R&D Program (no. 2019YFA0801703) and National Natural Science Foundation of China (no. 31871370)

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