Longitudinal analyses reveal immunological misfiring in severe COVID-19

• Published in: Nature (London) Vol. 584; no. 7821; pp. 463 - 469
• Main Authors: 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, 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.08.2020; Nature Publishing Group
• Subjects: 13; 13/106; 13/21; 13/31; 631/250/127; 631/250/255/2514; 631/326/596/4130; 82; Adult; Aged; Aged, 80 and over; Body mass index; Body size; Chemokines; Cluster Analysis; Confidence intervals; Coronavirus Infections - immunology; Coronavirus Infections - physiopathology; Coronaviruses; COVID-19; Cytokines; Cytokines - analysis; Cytokines - immunology; Eosinophils; Eosinophils - immunology; Female; Flow cytometry; Granulocytes; Growth factors; Health care; Humanities and Social Sciences; Humans; Immune response; Immune system; Immunoglobulin E; Immunoglobulin E - analysis; Immunoglobulin E - immunology; Immunology; Interleukin 13; Interleukin 5; Interleukin-13 - analysis; Interleukin-13 - immunology; Interleukin-5 - analysis; Interleukin-5 - immunology; Leukocytes (eosinophilic); Male; Middle Aged; Mortality; multidisciplinary; Neutrophils; Pandemics; Pathogens; Plasma; Pneumonia, Viral - immunology; Pneumonia, Viral - physiopathology; Science; Science (multidisciplinary); Severe acute respiratory syndrome coronavirus 2; Signatures; T-Lymphocytes - cytology; T-Lymphocytes - immunology; Transcription factors; Viral Load; Young Adult
• ISSN: 0028-0836; 1476-4687; 1476-4687
• DOI: 10.1038/s41586-020-2588-y

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. A longitudinal analysis of immune responses in patients with moderate or severe COVID-19 identifies a maladapted immune response profile linked to severe disease.