Nat. Biotechnol. https://doi.org/10.1038/s41587-020-00796-1 (2020)

Patients with hypertension and cardiovascular disease face greater risk of developing more severe disease upon SARS-CoV-2 infection. In Nature Biotechnology, Trump et al. utilize single-cell RNA-seq expression to examine differences in the immune responses of patients with COVID-19 who have underlying hypertension. Their study cohort compares patients who are taking angiotensin-converting enzyme inhibitors (ACEIs) with those taking angiotensin receptor blockers (ARBs) or neither antihypertensive therapy, and they also compare non-hypertensive patients with COVID-19 and non-infected individuals with hypertension. While neither treatment increased the expression of the host receptor ACE2, utilized for cell entry by SARS-CoV-2, a higher proportion of patients on ARB therapy experienced severe disease, and these patients had delayed viral clearance as compared to those on ACEI therapy. ACEI versus ARB therapies elicit multiple differences in innate immune responses in both stromal cells lining the nasopharynx and immune cells recruited upon infection. ACEI promoted high antiviral gene expression, whereas ARB treatment had higher proinflammatory gene expression, including high expression of the chemokines CCL3 and CCL4, which were both associated with more severe COVID-19. These differences begin to unravel why some patients differ in their antiviral responses, but further follow-up studies are needed to validate these findings and for mechanistic understanding.