Identification of immune correlates of fatal outcomes in critically ill COVID-19 patients

• DOI: 10.1371/journal.ppat.1009804
• Publication Date: 2021-09-16T17:28:22Z
• Authors: Jonathan Youngs; Nicholas M. Provine; Nicholas Lim; Hannah R. Sharpe; Ali Amini; Yi-Ling Chen; Jian Luo; Matthew D. Edmans; Panagiota Zacharo...; Wentao Chen; Oliver Sampson; Robert Paton; William J. Hurt; David A. Duncan; Anna L. McNaughton; Vincent N. Miao; Susannah Leaver; Duncan L. A. Wyncoll; Jonathan Ball; Philip Hopkins; ; ; Donal T. Skelly; Eleanor Barnes; Susanna Dunachie; Graham Ogg; Teresa Lambe; Ian Pavord; Alex K. Shalek; Craig P. Thompson; Luzheng Xue; Derek C. Macallan; Philip Goulder; Paul Klenerman; Tihana Bicanic
• Keywords: Identification; 2019-20 coronavirus outbreak

Prior studies have demonstrated that immunologic dysfunction underpins severe illness in COVID-19 patients, but lacked an in-depth analysis of the drivers death most critically ill patients. We performed immunophenotyping viral antigen-specific and unconventional T cell responses, neutralizing antibodies, serum proteins patients with SARS-CoV-2 infection, using influenza SARS-CoV-2-convalescent health care workers, healthy adults as controls. identify mucosal-associated invariant (MAIT) activation independent significant predictor (HR = 5.92, 95% CI 2.49–14.1). MAIT correlates several other mortality-associated measures including broad CD8 + cells non-Vδ2 γδT cells, elevated levels cytokines chemokines, GM-CSF, CXCL10, CCL2, IL-6. is also a disease severity (ECMO/death HR 4.43, 1.08–18.2). Single-cell RNA-sequencing reveals shift from focused IFNα-driven signals ICU who survive to pro-inflammatory responses fatal –a feature not observed influenza. conclude infection driven by uncoordinated inflammatory drive hierarchy activation, elements which can serve prognostic indicators potential targets for immune intervention.