Virus-Induced Acute Respiratory Distress Syndrome Causes Cardiomyopathy Through Eliciting Inflammatory Responses in the Heart

Abstract

BACKGROUND: Viral infections can cause acute respiratory distress syndrome (ARDS), systemic inflammation, and secondary cardiovascular complications. Lung macrophage subsets change during ARDS, but the role of heart macrophages in cardiac injury during viral ARDS remains unknown. Here we investigate how immune signals typical for viral ARDS affect cardiac macrophage subsets, cardiovascular health, and systemic inflammation. METHODS: We assessed cardiac macrophage subsets using immunofluorescence histology of autopsy specimens from 21 patients with COVID-19 with SARS-CoV-2–associated ARDS and 33 patients who died from other causes. In mice, we compared cardiac immune cell dynamics after SARS-CoV-2 infection with ARDS induced by intratracheal instillation of Toll-like receptor ligands and an ACE2 (angiotensin-converting enzyme 2) inhibitor. RESULTS: In humans, SARS-CoV-2 increased total cardiac macrophage counts and led to a higher proportion of CCR2 + (C-C chemokine receptor type 2 positive) macrophages. In mice, SARS-CoV-2 and virus-free lung injury triggered profound remodeling of cardiac resident macrophages, recapitulating the clinical expansion of CCR2 + macrophages. Treating mice exposed to virus-like ARDS with a tumor necrosis factor α–neutralizing antibody reduced cardiac monocytes and inflammatory MHCII lo CCR2 + macrophages while also preserving cardiac function. Virus-like ARDS elevated mortality in mice with pre-existing heart failure. CONCLUSIONS: Our data suggest that viral ARDS promotes cardiac inflammation by expanding the CCR2 + macrophage subset, and the associated cardiac phenotypes in mice can be elicited by activating the host immune system even without viral presence in the heart.

Integrating Bioinformatics and Machine Learning to Investigate the Mechanisms by Which Three Major Respiratory Infectious Diseases Exacerbate Heart Failure

“…Studies have shown that children with congenital heart disease and bronchopneumonia exhibit altered levels of CD3+, CD4+, and CD8+ T cells, indicating impaired cellular immunity, which may predispose them to severe infections and subsequent HF [50]. Furthermore, macrophages have been implicated in cardiac injury during viral ARDS, with an increase in CCR2+ macrophages leading to cardiac inflammation and dysfunction [51]. Therefore, understanding the immune status of HF patients in the context of respiratory infections is crucial.…”

“…Studies have shown that children with congenital heart disease and bronchopneumonia exhibit altered levels of CD3+, CD4+, and CD8+ T cells, indicating impaired cellular immunity, which may predispose them to severe infections and subsequent HF[50]. Furthermore, macrophages have been implicated in cardiac injury during viral ARDS, with an increase in CCR2+ macrophages leading to cardiac inflammation and dysfunction[51].Therefore, understanding the immune status of HF patients in the context of respiratory infections is crucial. The significant differences in immune cell infiltration and associated inflammatory responses provide deeper insights into the mechanisms by which respiratory infections exacerbate HF, paving the way for the development of targeted therapies aimed at modulating immune responses to improve clinical outcomes in HF patients.…”