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, Yale IMPACT Team, Roy Herbst, Albert C Shaw, Ruslan Medzhitov, Wade L Schulz, Nathan D Grubaugh, Charles Dela Cruz, Shelli Farhadian, Albert I Ko, Saad B Omer, Akiko Iwasaki, Abeer Obaid, Alice Lu-Culligan, Allison Nelson, Anderson Brito, Angela Nunez, Anjelica Martin, Annie Watkins, Bertie Geng, Chaney Kalinich, Christina Harden, Codruta Todeasa, Cole Jensen, Daniel Kim, David McDonald, Denise Shepard, Edward Courchaine, Elizabeth B White, Eric Song, Erin Silva, Eriko Kudo, Giuseppe DeIuliis, Harold Rahming, Hong-Jai Park, Irene Matos, Jessica Nouws, Jordan Valdez, Joseph Fauver, Joseph Lim, Kadi-Ann Rose, Kelly Anastasio, Kristina Brower, Laura Glick, Lokesh Sharma, Lorenzo Sewanan, Lynda Knaggs, Maksym Minasyan, Maria Batsu, Mary Petrone, Maxine Kuang, Maura Nakahata, Melissa Campbell, Melissa Linehan, Michael H Askenase, Michael Simonov, Mikhail Smolgovsky, Nicole Sonnert, Nida Naushad, Pavithra Vijayakumar, Rick Martinello, Rupak Datta, Ryan Handoko, Santos Bermejo, Sarah Prophet, Sean Bickerton, Sofia Velazquez, Tara Alpert, Tyler Rice, William Khoury-Hanold, Xiaohua Peng, Yexin Yang, Yiyun Cao, Yvette Strong, 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, Yale IMPACT Team, Roy Herbst, Albert C Shaw, Ruslan Medzhitov, Wade L Schulz, Nathan D Grubaugh, Charles Dela Cruz, Shelli Farhadian, Albert I Ko, Saad B Omer, Akiko Iwasaki, Abeer Obaid, Alice Lu-Culligan, Allison Nelson, Anderson Brito, Angela Nunez, Anjelica Martin, Annie Watkins, Bertie Geng, Chaney Kalinich, Christina Harden, Codruta Todeasa, Cole Jensen, Daniel Kim, David McDonald, Denise Shepard, Edward Courchaine, Elizabeth B White, Eric Song, Erin Silva, Eriko Kudo, Giuseppe DeIuliis, Harold Rahming, Hong-Jai Park, Irene Matos, Jessica Nouws, Jordan Valdez, Joseph Fauver, Joseph Lim, Kadi-Ann Rose, Kelly Anastasio, Kristina Brower, Laura Glick, Lokesh Sharma, Lorenzo Sewanan, Lynda Knaggs, Maksym Minasyan, Maria Batsu, Mary Petrone, Maxine Kuang, Maura Nakahata, Melissa Campbell, Melissa Linehan, Michael H Askenase, Michael Simonov, Mikhail Smolgovsky, Nicole Sonnert, Nida Naushad, Pavithra Vijayakumar, Rick Martinello, Rupak Datta, Ryan Handoko, Santos Bermejo, Sarah Prophet, Sean Bickerton, Sofia Velazquez, Tara Alpert, Tyler Rice, William Khoury-Hanold, Xiaohua Peng, Yexin Yang, Yiyun Cao, Yvette Strong
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.
Conflict of interest statement
Competing interests
The authors declare no competing financial interests.
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Source: PubMed