Single-cell RNA-sequencing (scRNA-seq) of NK cells along the time course of the entire COVID-19 disease spectrum reveals a unique gene expression signature. Transcriptional networks of interferon-driven NK cell activation are superimposed by a dominant TGFβ response signature with reduced expression of genes related to cell-cell adhesion, granule exocytosis and cell-mediated cytotoxicity. In severe COVID-19, serum levels of TGFβ peak during the first 2 weeks of infection, and serum obtained from these patients profoundly inhibits NK cell function in a TGFβ-dependent manner. Our data reveal that untimely production of TGFβ is a hallmark of severe COVID-19 and may inhibit NK cell function and early virus control.

Comorbidities including diabetes mellitus, cardiovascular disease, and active cancer significantly increased mortality risk. KTR with dyspnea (OR 5.68, 95% CI 2.11–15.33) and pneumonia (OR 10.64, 95% CI 3.37–33.55) at presentation were at higher mortality risk, while diarrhea decreased the risk (OR 0.61, 95% CI 0.47–0.78). Acute kidney injury was associated with mortality (OR 3.24, 95% CI 1.36–7.70). Inflammatory markers were significantly higher in the non-survivors, including C-reactive protein, procalcitonin, and interleukine-6.