Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans

By P. Arunachalam, F. Wimmers, C. K. Mok, Ranawaka A.P.M Perera, Madeleine K. D. Scott, T. Hagan, Natalia Sigal, Yupeng Feng, Laurel Bristow, Owen Tak-Yin Tsang and 21 more. Science, 2020

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Immune profiling of COVID-19 patients Coronavirus disease 2019 (COVID-19) has affected millions of people globally, yet how the human immune system responds to and influences COVID-19 severity remains unclear. Mathew et al. present a comprehensive 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 that are 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 compendium of immune cell information and roadmaps for potential therapeutic interventions. Science, this issue p. eabc8511, p. 1210 Immune responses of COVID-19 patients are cataloged and compared with those of healthy individuals. Coronavirus disease 2019 (COVID-19) represents a global crisis, yet major knowledge gaps remain about human immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We analyzed immune responses in 76 COVID-19 patients and 69 healthy individuals from Hong Kong and Atlanta, Georgia, United States. In the peripheral blood mononuclear cells (PBMCs) of COVID-19 patients, we observed reduced expression of human leukocyte antigen class DR (HLA-DR) and proinflammatory cytokines by myeloid cells as well as impaired mammalian target of rapamycin (mTOR) signaling and interferon-α (IFN-α) production by plasmacytoid dendritic cells. By contrast, we detected enhanced plasma levels of inflammatory mediators—including EN-RAGE, TNFSF14, and oncostatin M—which correlated with disease severity and increased bacterial products in plasma. Single-cell transcriptomics revealed a lack of type I IFNs, reduced HLA-DR in the myeloid cells of patients with severe COVID-19, and transient expression of IFN-stimulated genes. This was consistent with bulk PBMC transcriptomics and transient, low IFN-α levels in plasma during infection. These results reveal mechanisms and potential therapeutic targets for COVID-19.

Subfields: Immunology, Infectious Diseases

View Paper: https://www.semanticscholar.org/paper/220affe24ea24af1706bc132ee2906b021ff4bad

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Citations in the corpus

Molecular Mechanism of SARS-CoVs Orf6 Targeting the Rae1–Nup98 Complex to Compete With mRNA Nuclear Export (2022, background): “A diminished and delayed type I IFN (IFN-I) response in patients with moderate-to-severe COVID-19 is demonstrated in recent findings (Arunachalam et al., 2020; Yu et al., 2020; Galani et al., 2021).”
Diverse Functional Autoantibodies in Patients with COVID-19 (2020, neutral): “Severe disease status (clinical score 4 or 5) was defined as infection meeting all criteria for clinical score 3 and also requiring admission to the ICU and >6 l/min supplementary oxygen to maintain SpO2 >92% (4); or infection requiring invasive mechanical ventilation or extracorporeal membrane oxyg”
Dictionary learning for integrative, multimodal, and massively scalable single-cell analysis (2022, neutral): “Data acquisition source: Supplementary Table 2 and PBMC scRNA datasets 4,62,63,102–112 .”
COVID-19 and the human innate immune system (2021, background): “…Silvin et al., 2020), however, joining forces to address some of the suggested early predictors and validate them in larger multicenter trials (Arunachalam et al., 2020; Su et al., 2020) utilizing high-content, high-throughput, high-resolution technologies is the next step to study COVID19…”