Acute respiratory distress syndrome (ARDS) and robust cytokine storm are the hallmark of severe COVID-19 cases. Using single-cell RNA sequencing of bronchoalveolar lavage fluid, this preprint study from Liao et al. found that the depletion of tissue-resident alveolar macrophages and the accumulation of monocyte-derived inflammatory macrophages associate with disease severity. Inflammatory macrophages adopted interferon-signalling and monocyte-recruiting chemokine programmes that may drive ARDS. Increased clonal expansion of CD8+ T cells was found in mild cases; this may reflect viral clearance due to the induction of virus-specific cytotoxic T cells, as is seen in influenza virus infection. Overall, these data support therapeutic strategies that target the myeloid cell compartment, such as IL-6 inhibitors, to treat COVID-19-associated inflammation.