Implicating Gene and Cell Networks Responsible for Differential COVID-19 Host Responses via an Interactive Single Cell Web Portal

Numerous studies have provided single-cell transcriptome profiles of host responses to SARS-CoV-2 infection. Critically lacking however is a reusable datamine to allow users to compare and explore these data for insight, inference, and hypothesis generation. To accomplish this, we harmonized datasets from blood, bronchoalveolar lavage and tissue samples from COVID-19 and other control conditions and derived a compendium of gene signature modules per cell type, subtype, clinical condition and compartment. We demonstrate approaches for exploring and evaluating their significance via a new interactive web portal (ToppCell). As examples, we develop three hypotheses: (1) a multicellular signaling cascade among alternatively differentiated monocyte-derived macrophages whose tasks include T cell recruitment and activation; (2) novel platelet subtypes with drastically modulated expression of genes responsible for adhesion, coagulation and thrombosis; (3) a multilineage cell activator network able to drive extrafollicular B maturation via an ensemble of genes extensively associated with risk for developing autoimmunity Funding Information: Funding for this study was provided by LungMap (U24 and HL148865), Digestive Health Center (P30, DK078392) and Harold C. Schott Foundation funding of the Harold C. Schott Endowed Chair, UC College of Medicine. Declaration of Interests: The authors declare no competing interest.