Comprehensive mapping of immune perturbations associated with severe COVID-19

By L. Kuri-Cervantes, M. Pampena, Wenzhao Meng, Aaron M. Rosenfeld, C. Ittner, A. Weisman, R. Agyekum, D. Mathew, A. Baxter, L. Vella and 21 more. Science immunology, 2020

717 citations recorded by the source corpus.

Although critical illness has been associated with SARS-CoV-2-induced hyperinflammation, the immune correlates of severe COVID-19 remain unclear. Here, we comprehensively analyzed peripheral blood immune perturbations in 42 SARS-CoV-2 infected and recovered individuals. We identified extensive induction and activation of multiple immune lineages, including T cell activation, oligoclonal plasmablast expansion, and Fc and trafficking receptor modulation on innate lymphocytes and granulocytes, that distinguished severe COVID-19 cases from healthy donors or SARS-CoV-2-recovered or moderate severity patients. We found the neutrophil to lymphocyte ratio to be a prognostic biomarker of disease severity and organ failure. Our findings demonstrate broad innate and adaptive leukocyte perturbations that distinguish dysregulated host responses in severe SARS-CoV-2 infection and warrant therapeutic investigation. Profound plasmablast expansion, innate cell modulation, and T cell activation are defining features of severe COVID-19.

Subfields: Infectious Diseases, Modeling and Simulation

View Paper: https://www.semanticscholar.org/paper/0da9aea44c9c3660a1fbf1e511b9494343d5f247

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In Infectious Diseases

1. A. Aschenbrenner
2. Joachim L. Schultze
3. Alessandro Sette
4. Shane Crotty
5. E. Wherry

Citations in the corpus

• mRNA Vaccines Induce Durable Immune Memory to SARS-CoV-2 and Variants of Concern (2021, methodology): “Reads from an Illumina MiSeq were filtered, annotated, and grouped into clones as described previously (16, 57).”
• COVID-19 and the human innate immune system (2021, background): “discussed in greater detail elsewhere (Sette and Crotty, 2021), NK cells are affected as well (Giamarellos-Bourboulis et al., 2020a; Hadjadj et al., 2020; Kuri-Cervantes et al., 2020; Zheng et al., 2020a).”
• Adaptive immunity to SARS-CoV-2 and COVID-19 (2021, background): “There is heterogeneity in the innate immune responses to SARS-CoV-2, and heterogeneity has been observed in broad studies of adaptive immunity in acute patients (Mathew et al., 2020).”
• Loss of Bcl-6-Expressing T Follicular Helper Cells and Germinal Centers in COVID-19 (2020, neutral): “Although recent studies have also documented circulating activated B cell populations in COVID-19 patients (Mathew et al., 2020; Kuri-Cervantes et al., 2020; Woodruff et al., 2020), the antigen specificity of these cells was not evaluated.”