Longitudinal analyses reveal immunological misfiring in severe COVID-19

Autor: Lucas, Carolina, Wong, Patrick, Klein, Jon, Castro, Tiago B. R., Silva, Julio, Sundaram, Maria, Ellingson, Mallory K., Mao, Tianyang, Oh, Ji Eun, 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, 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, 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, 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
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Nature
ISSN: 1476-4687
0028-0836
DOI: 10.1038/s41586-020-2588-y
Popis: 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.
Databáze: OpenAIRE