Details

Autor(en) / Beteiligte

• 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

Titel

Longitudinal analyses reveal immunological misfiring in severe COVID-19

Ist Teil von

• Nature (London), 2020-08, Vol.584 (7821), p.463-469

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2020

Link zum Volltext

Beschreibungen/Notizen

• Recent studies have provided insights into the pathogenesis of coronavirus disease 2019 (COVID-19) . 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.