Longitudinal analyses reveal immunological misfiring in severe COVID-19

Carolina Lucas, Patrick Wong, Jon Klein, Tiago B. R. Castro, Julio Silva, Maria Sundaram, Mallory K. Ellingson, Tianyang Mao, Ji Eun Oh, Benjamin Israelow, Takehiro Takahashi, Maria Tokuyama, Peiwen Lu, Arvind Venkataraman, Annsea Park, Subhasis Mohanty, Haowei Wang, Anne L. Wyllie, Chantal B. F. Vogels, Rebecca Earnest, Sarah Lapidus, Isabel M. Ott, Adam J. Moore, M. Catherine Muenker, John B. Fournier, Melissa Campbell, Camila D. Odio, Arnau Casanovas-Massana, Roy Herbst, Albert C. Shaw, Ruslan Medzhitov, Wade L. Schulz, Nathan D. Grubaugh, Charles Cruz, Shelli Farhadian, Albert I. Ko, Saad B. Omer and Akiko Iwasaki ()
Additional contact information
Carolina Lucas: Yale University School of Medicine
Patrick Wong: Yale University School of Medicine
Jon Klein: Yale University School of Medicine
Tiago B. R. Castro: The Rockefeller University
Julio Silva: Yale University School of Medicine
Maria Sundaram: Yale School of Public Health
Mallory K. Ellingson: Yale School of Public Health
Tianyang Mao: Yale University School of Medicine
Ji Eun Oh: Yale University School of Medicine
Benjamin Israelow: Yale University School of Medicine
Takehiro Takahashi: Yale University School of Medicine
Maria Tokuyama: Yale University School of Medicine
Peiwen Lu: Yale University School of Medicine
Arvind Venkataraman: Yale University School of Medicine
Annsea Park: Yale University School of Medicine
Subhasis Mohanty: Yale University School of Medicine
Haowei Wang: Yale University School of Medicine
Anne L. Wyllie: Yale School of Public Health
Chantal B. F. Vogels: Yale School of Public Health
Rebecca Earnest: Yale School of Public Health
Sarah Lapidus: Yale School of Public Health
Isabel M. Ott: Yale School of Public Health
Adam J. Moore: Yale School of Public Health
M. Catherine Muenker: Yale School of Public Health
John B. Fournier: Yale University School of Medicine
Melissa Campbell: Yale University School of Medicine
Camila D. Odio: Yale University School of Medicine
Arnau Casanovas-Massana: Yale School of Public Health
Roy Herbst: Yale Cancer Center, and Smilow Cancer Hospital
Albert C. Shaw: Yale University School of Medicine
Ruslan Medzhitov: Yale University School of Medicine
Wade L. Schulz: Yale University School of Medicine
Nathan D. Grubaugh: Yale School of Public Health
Charles Cruz: Yale University School of Medicine
Shelli Farhadian: Yale University School of Medicine
Albert I. Ko: Yale School of Public Health
Saad B. Omer: Yale School of Public Health
Akiko Iwasaki: Yale University School of Medicine

Nature, 2020, vol. 584, issue 7821, 463-469

Abstract: Abstract Recent studies have provided insights into the pathogenesis of coronavirus disease 2019 (COVID-19)1–4. However, the longitudinal immunological correlates of disease outcome remain unclear. Here we serially analysed immune responses in 113 patients with moderate or severe COVID-19. Immune profiling revealed an overall increase in innate cell lineages, with a concomitant reduction in T cell number. An early elevation in cytokine levels was associated with worse disease outcomes. Following an early increase in cytokines, patients with moderate COVID-19 displayed a progressive reduction in type 1 (antiviral) and type 3 (antifungal) responses. By contrast, patients with severe COVID-19 maintained these elevated responses throughout the course of the disease. Moreover, severe COVID-19 was accompanied by an increase in multiple type 2 (anti-helminths) effectors, including interleukin-5 (IL-5), IL-13, immunoglobulin E and eosinophils. Unsupervised clustering analysis identified four immune signatures, representing growth factors (A), type-2/3 cytokines (B), mixed type-1/2/3 cytokines (C), and chemokines (D) that correlated with three distinct disease trajectories. The immune profiles of patients who recovered from moderate COVID-19 were enriched in tissue reparative growth factor signature A, whereas the profiles of those with who developed severe disease had elevated levels of all four signatures. Thus, we have identified a maladapted immune response profile associated with severe COVID-19 and poor clinical outcome, as well as early immune signatures that correlate with divergent disease trajectories.

Date: 2020
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DOI: 10.1038/s41586-020-2588-y

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