Human organoids recapitulate the cell type diversity and function of their primary organs holding tremendous potentials for basic and translational research. In light of the vital role of human organoids in drug developments, we have collected and unifiedly processed multiple scRNA-seq datasets across 10 kinds of human organoids with approximate 1.2 million cells. We have developed a computational framework to integrate these human organoids scRNA-seq data, GWAS summary statistics, eQTL data, and gene-drug interaction data for distinguishing critical cell types/subpopulations and drug targets relevant to severe COVID-19. We found that 39 cell types across different human organoids were remarkably associated with COVID-19 severities. Notably, subset of lung mesenchymal stem cells (MSCs) increased proximity with fibroblasts predisposed to repair COVID-19-damaged lung tissue. Intestinal tuft cell subpopulation as a primary physiological target of viral infection with significantly up-regulated genes, including COL3A1, IFITM3, and VIM, contributed high risk to severe COVID-19. Brain endothelial cell subset with high NRP1 and CEBPD expression exhibited significant association with severe COVID-19, and this cell subset showed a notable increase in cell-to-cell interactions with other brain cell types, including microglia. We repurposed 33 druggable genes, including IFNAR2, TYK2, and VIPR2, and their interacting drugs for COVID-19 in a cell-type-specific manner. Collectively, our results showcase that host genetic determinants have cellular specific contribution to COVID-19 severity. Identification of cell type-specific drug targets may facilitate to develop effective therapeutics for treating severe COVID-19 and its complications. Here, we have documented all cellular individual cell association results of COVID-19-relevant cell subpopulations across all human organoids in the scHOB portal.