Inhibition of kinin B1 receptor alleviates SARS-CoV-2-induced long-lasting cardiovascular complications.

Long COVID has been associated with significant cardiovascular complications, including fibrosis, functional impairment, and chronic inflammatory and immune responses. However, the underlying mechanisms driving these cardiac pathologies following COVID-19 infection remain understudied. Previously, we characterized a mouse model of long COVID and observed enhanced expression of kinin B1 receptor (B1R) in the infected animals. Here, we investigated the role of B1R in mediating long-COVID-induced cardiac pathologies. K18-hACE2 transgenic mice were infected intranasally with SARS-CoV-2 and evaluated at 28 days postinfection (dpi) to model long COVID and the effects of pharmacological blockade of B1R were evaluated. Persistent upregulation of B1R expression was accompanied by apoptosis, disrupted cardiomyocyte architecture, fibrosis, impaired gap junction integrity, and sustained inflammation and immune cell infiltration. B1R blockade restored gap junction integrity, reduced fibrosis and apoptosis, and mitigated inflammation and immune activation. Together, these data indicate that B1R plays a critical role in long-COVID-induced cardiac remodeling and damage, highlighting its potential as a target for treating long-lasting cardiovascular complications following SARS-CoV-2 infection. We are the first to report that elevated B1R expression may drive the long-lasting cardiovascular effects associated with recovery from COVID-19 infection. We have also collected novel evidence showing that blockade of B1R can reduce the cardiac complications associated with long COVID and may serve as a novel therapeutic target to mitigate SARS-CoV-2-induced long-term cardiac damage in affected individuals.