TY - JOUR
T1 - Longitudinal analyses reveal immunological misfiring in severe COVID-19
AU - Yale IMPACT Team
AU - Lucas, Carolina
AU - Wong, Patrick
AU - Klein, Jon
AU - Castro, Tiago B.R.
AU - Silva, Julio
AU - Sundaram, Maria
AU - Ellingson, Mallory K.
AU - Mao, Tianyang
AU - Oh, Ji Eun
AU - Israelow, Benjamin
AU - Takahashi, Takehiro
AU - Tokuyama, Maria
AU - Lu, Peiwen
AU - Venkataraman, Arvind
AU - Park, Annsea
AU - Mohanty, Subhasis
AU - Wang, Haowei
AU - Wyllie, Anne L.
AU - Vogels, Chantal B.F.
AU - Earnest, Rebecca
AU - Lapidus, Sarah
AU - Ott, Isabel M.
AU - Moore, Adam J.
AU - Muenker, M. Catherine
AU - Fournier, John B.
AU - Campbell, Melissa
AU - Odio, Camila D.
AU - Casanovas-Massana, Arnau
AU - Obaid, Abeer
AU - Lu-Culligan, Alice
AU - Nelson, Allison
AU - Brito, Anderson
AU - Nunez, Angela
AU - Martin, Anjelica
AU - Watkins, Annie
AU - Geng, Bertie
AU - Kalinich, Chaney
AU - Harden, Christina
AU - Todeasa, Codruta
AU - Jensen, Cole
AU - Kim, Daniel
AU - McDonald, David
AU - Shepard, Denise
AU - Courchaine, Edward
AU - White, Elizabeth B.
AU - Song, Eric
AU - Silva, Erin
AU - Kudo, Eriko
AU - DeIuliis, Giuseppe
AU - Fauver, Joseph
N1 - Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2020/8/20
Y1 - 2020/8/20
N2 - 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.
AB - 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.
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U2 - 10.1038/s41586-020-2588-y
DO - 10.1038/s41586-020-2588-y
M3 - Article
C2 - 32717743
AN - SCOPUS:85088583601
SN - 0028-0836
VL - 584
SP - 463
EP - 469
JO - Nature
JF - Nature
IS - 7821
ER -