Systemic laboratory assessment of immunity to mild infection versus severe infection with COVID-19 in humans

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Immune profiling of COVID-19 patients

Coronavirus disease 2019 (COVID-19) has affected millions of people around the world, but how the human immune system responds to and influences the severity of COVID-19 remains unclear. Mathew et al. present a complete atlas of immune modulation associated with COVID-19. They performed high-dimensional flow cytometry of hospitalized COVID-19 patients and found three prominent and distinct immunotypes related to disease severity and clinical parameters. Arunachalam et al. report a systems biology approach to assess the immune system of COVID-19 patients with mild to severe disease. These studies provide a collection of information on immune cells and roadmaps for possible therapeutic interventions.

Science, this issue p. eabc8511, p. 1210

Abstract

Coronavirus disease 2019 (COVID-19) represents a global crisis, but significant knowledge gaps remain on human immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We analyzed the immune responses in 76 COVID-19 patients and 69 healthy individuals from Hong Kong and Atlanta, Georgia, United States. In peripheral blood mononuclear cells (PBMC) from patients with COVID-19, we observed reduced expression of human leukocyte antigen class DR (HLA-DR) and pro-inflammatory cytokines by myeloid cells as well as an alteration of the mammalian target of rapamycin (mTOR) and interferon signaling. -a (IFN-α) production by plasmacytoid dendritic cells. In contrast, we detected increased plasma levels of inflammatory mediators – including EN-RAGE, TNFSF14, and oncostatin M – which were correlated with disease severity and increased bacterial products in plasma. Single-cell transcriptomics revealed a lack of type I IFN, a reduction in HLA-DR in myeloid cells from patients with severe COVID-19, and transient expression of IFN-stimulated genes. This was consistent with the transcriptomics of bulk PBMCs and the low transient IFN-α levels in plasma during infection. These results reveal mechanisms and potential therapeutic targets for COVID-19.



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