[HTML][HTML] Longitudinal analyses reveal immunological misfiring in severe COVID-19

C Lucas, P Wong, J Klein, TBR Castro, J Silva… - Nature, 2020 - nature.com
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 …
Abstract
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.
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