Single cell multiomic analysis identifies key genes differentially expressed in innate lymphoid cells from COVID-19 patients

Innate lymphoid cells (ILCs) are enriched at mucosal surfaces where they
respond rapidly to environmental stimuli and contribute to both tissue
inflammation and healing. To gain insight into the role of ILCs in the
pathology and recovery from COVID-19 infection, we employed a multi-omic
approach consisting of Abseq and targeted mRNA sequencing to respectively
probe the surface marker expression, transcriptional profile and
heterogeneity of ILCs in peripheral blood of patients with COVID-19
compared with healthy controls.  We found that the frequency of
ILC1 and ILC2 cells was significantly increased in COVID-19
patients.  Moreover, all ILC subsets displayed a significantly
higher frequency of CD69-expressing cells, indicating a heightened state
of activation.  ILC2s from COVID-19 patients had the highest
number of significantly differentially expressed (DE) genes. The most
notable genes DE in COVID-19 vs healthy participants included a) genes
associated with responses to virus infections and b) genes that support
ILC self-proliferation, activation and homeostasis. In addition,
differential gene regulatory network analysis revealed ILC-specific
regulons and their interactions driving the differential gene expression
in each ILC. Overall, this study provides mechanistic insights into the
characteristics of ILC subsets activated during COVID-19 infection.