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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HE PREVALENCE OF OVERweight in adolescents is increasing worldwide. In the United States, the proportion of adolescents with a body mass index (BMI) at or above the 95th percentile for age, a widely accepted definition of obesity in adolescents, 1,2 has increased 15.5% to 23.4% in certain ethnic minorities. 3 A similar picture is seen in European countries: the prevalence of overweight in adolescents has increased 8% to 21% in northern European countries and 17% to 23% in southern European countries. 4 Excess weight in adolescents is associated with an increased risk of disorders such as hyperlipidemia and type 2 diabetes 5 and can result in decreased emotional and physical quality of life. 6,7 In addition, childhood obesity results in increased risk of morbidity and mortality in adulthood. 8,9 Long-term follow-up studies of children and adolescents indicate that overweight children have a 15-fold greater risk of becoming overweight adults compared with those children and adolescents who were not overweight. 8 Effective weight management in children and adolescents may therefore have important immediate and future societal health benefits. Treatment of obesity in the pediatric age group, and in particular during adolescence, 10 is notoriously difficult. While behavioral therapy has had some success in treating obesity in young children (aged 6-12 years), most stud-For editorial comment see p 2932.

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