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Advances in single\u2010cell RNA sequencing (scRNA\u2010seq) technology and genome\u2010wide association study (GWAS) have accelerated the biological and therapeutic interpretation of trait\u2010relevant cell types or states. Here, we constructed a computational framework to integrate atlas\u2010level organoid scRNA\u2010seq data, GWAS summary statistics, expression quantitative trait loci, and gene\u2013drug interaction data for distinguishing critical cell populations and drug targets relevant to coronavirus disease 2019 (COVID\u201019) severity. We found that 39 cell types across eight kinds of organoids were significantly associated with COVID\u201019 outcomes. Notably, subset of lung mesenchymal stem cells increased proximity with fibroblasts predisposed to repair COVID\u201019\u2010damaged lung tissue. Brain endothelial cell subset exhibited significant associations with severe COVID\u201019, and this cell subset showed a notable increase in cell\u2010to\u2010cell interactions with other brain cell types, including microglia. We repurposed 33 druggable genes, including\n                    <jats:italic>IFNAR2<\/jats:italic>\n                    ,\n                    <jats:italic>TYK2<\/jats:italic>\n                    , and\n                    <jats:italic>VIPR2<\/jats:italic>\n                    , and their interacting drugs for COVID\u201019 in a cell\u2010type\u2010specific manner. Overall, our results showcase that host genetic determinants have cellular\u2010specific contribution to COVID\u201019 severity, and identification of cell type\u2010specific drug targets may facilitate to develop effective therapeutics for treating severe COVID\u201019 and its complications.\n                  <\/jats:p>","DOI":"10.1111\/cpr.13558","type":"journal-article","created":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T19:47:41Z","timestamp":1697053661000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Integration of human organoids single\u2010cell transcriptomic profiles and human genetics repurposes critical cell type\u2010specific drug targets for severe\n                    <scp>COVID<\/scp>\n                    \u201019"],"prefix":"10.1111","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1299-4802","authenticated-orcid":false,"given":"Yunlong","family":"Ma","sequence":"first","affiliation":[{"name":"National Engineering Research Center of Ophthalmology and Optometry Eye Hospital, Wenzhou Medical University  Wenzhou China"},{"name":"Department of Biomedical Informatics Institute of Biomedical Big Data, Wenzhou Medical University  Wenzhou China"},{"name":"Oujiang Laboratory, Zhejiang Lab for Regenerative Medicine, Vision and Brain Health  Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijun","family":"Zhou","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Ophthalmology and Optometry Eye Hospital, Wenzhou Medical University  Wenzhou China"},{"name":"Department of Biomedical Informatics Institute of Biomedical Big Data, Wenzhou Medical University  Wenzhou 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