Longitudinal analyses reveal immunological misfiring in severe COVID-19

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Lucas, Carolina / Wong, Patrick / Klein, Jon / Castro, Tiago B. R. / Silva, Julio / Sundaram, Maria / Ellingson, Mallory K. / Mao, Tianyang / Oh, Ji Eunresearcher / Israelow, Benjamin / Takahashi, Takehiro / Tokuyama, Maria / Lu, Peiwen / Venkataraman, Arvind / Park, Annsea / Mohanty, Subhasis / Wang, Haowei / Wyllie, Anne L. / Vogels, Chantal B. F. / Earnest, Rebecca / Lapidus, Sarah / Ott, Isabel M. / Moore, Adam J. / Muenker, M. Catherine / Fournier, John B. / Campbell, Melissa / Odio, Camila D. / Casanovas-Massana, Arnau / Herbst, Roy / Shaw, Albert C. / Medzhitov, Ruslan / Schulz, Wade L. / Grubaugh, Nathan D. / Dela Cruz, Charles / Farhadian, Shelli / Ko, Albert I. / Omer, Saad B. / Iwasaki, Akiko / Obaid, Abeer / Lu-Culligan, Alice / Nelson, Allison / Brito, Anderson / Nunez, Angela / Martin, Anjelica / Watkins, Annie / Geng, Bertie / Kalinich, Chaney / Harden, Christina / Todeasa, Codruta / Jensen, Cole / Kim, Daniel / McDonald, David / Shepard, Denise / Courchaine, Edward / White, Elizabeth B. / Song, Eric / Silva, Erin / Kudo, Eriko / DeIuliis, Giuseppe / Rahming, Harold / Park, Hong-Jai / Matos, Irene / Nouws, Jessica / Valdez, Jordan / Fauver, Joseph / Lim, Joseph / Rose, Kadi-Ann / Anastasio, Kelly / Brower, Kristina / Glick, Laura / Sharma, Lokesh / Sewanan, Lorenzo / Knaggs, Lynda / Minasyan, Maksym / Batsu, Maria / Petrone, Mary / Kuang, Maxine / Nakahata, Maura / Campbell, Melissa / Linehan, Melissa / Askenase, Michael H. / Simonov, Michael / Smolgovsky, Mikhail / Sonnert, Nicole / Naushad, Nida / Vijayakumar, Pavithra / Martinello, Rick / Datta, Rupak / Handoko, Ryan / Bermejo, Santos / Prophet, Sarah / Bickerton, Sean / Velazquez, Sofia / Alpert, Tara / Rice, Tyler / Khoury-Hanold, William / Peng, Xiaohua / Yang, Yexin / Cao, Yiyun / Strong, Yvette
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.
Publisher
NATURE RESEARCH
Issue Date
2020-08
Language
English
Article Type
Article
Citation

NATURE, v.584, no.7821, pp.463 - 469

ISSN
0028-0836
DOI
10.1038/s41586-020-2588-y
URI
http://hdl.handle.net/10203/277337
Appears in Collection
MSE-Journal Papers(저널논문)
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