Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages

The COVID-19 pandemic caused by infection with SARS-CoV-2 has led to more than 200,000 deaths worldwide. Several studies have now established that the hyperinflammatory response induced by SARS-CoV-2 is a major cause of disease severity and death in infected patients. Macrophages are a population of innate immune cells that sense and respond to microbial threats by producing inflammatory molecules that eliminate pathogens and promote tissue repair. However, a dysregulated macrophage response can be damaging to the host, as is seen in the macrophage activation syndrome induced by severe infections, including in infections with the related virus SARS-CoV. Here we describe the potentially pathological roles of macrophages during SARS-CoV-2 infection and discuss ongoing and prospective therapeutic strategies to modulate macrophage activation in patients with COVID-19. This Progress article from Merad and Martin examines our current understanding of the excessive inflammatory responses seen in patients with severe COVID-19. The authors focus on the emerging pathological roles of monocytes and macrophages and discuss the inflammatory pathways that are currently being targeted in the clinic.