Not all patients with COVID-19 develop the same symptoms, but the immunological determinants of a poor prognosis are unknown. In this preprint article, Yang, Y et al. followed a cohort of 53 clinically moderate and severe patients; they conducted a multiplex screen for 48 cytokines and correlated these results with lab tests, clinical characteristics and viral loads. They found a marked increase of 14 cytokines in patients with COVID-19 compared with healthy controls. Continuously high levels of three of these cytokines (CXCL10, CCL7 and IL-1 receptor antagonist) were associated with increased viral load, loss of lung function, lung injury and a fatal outcome. These observations offer key insights into the immunopathology of COVID-19 and provide new avenues for prognosis and therapy.