Nature 595, 114–119 (2021)

Severe COVID-19 cases are often accompanied by complex host responses that involve diverse cell types. Using a powerful single-nucleus RNA sequencing approach, Izar and colleagues focus on cellular changes in the lungs of 19 patients who died of COVID-19.

The authors identified myeloid cells as the dominant source of dysregulated inflammation in COVID-19 and found evidence of impaired T cell responses. Compromised lung regeneration could be traced back to a failure of alveolar type 2 (AT2) cells to transition into AT1 cells, as observed during normal repair. Instead, AT2 cells persisted in a transient, intermediate progenitor state previously described in fibrotic lung injury.

Further analysis pinpointed the cellular sources of inflammatory cytokines, such as IL-1β, IL-6 and interferons that contributed to the hyperinflammatory environment and probably also the transient state. The authors concluded that myeloid-derived IL-1β might be one of the distinguishing factors in COVID-19 pathology, separating it from other viral or bacterial infections. Increased numbers of pulmonary-fibrosis-promoting fibroblasts were also described.

The atlas describes SARS-CoV-2 lung pathology at a single-cell level and provides an important resource for the evaluation of disease complications and therapeutic options.