Cardiac inflammation in COVID-19: Lessons from heart failure

Abstract

Cardiovascular disease (CVD) is the most common co-morbidity associated with COVID-19 and the fatality rate in COVID-19 patients with CVD is higher compared to other comorbidities, such as hypertension and diabetes. Preliminary data suggest that COVID-19 may also cause or worsen cardiac injury in infected patients through multiple mechanisms such as 'cytokine storm', endotheliosis, thrombosis, lymphocytopenia etc. Autopsies of COVID-19 patients reveal an infiltration of inflammatory mononuclear cells in the myocardium, confirming the role of the immune system in mediating cardiovascular damage in response to COVID-19 infection and also suggesting potential causal mechanisms for the development of new cardiac pathologies and/or exacerbation of underlying CVDs in infected patients. In this review, we discuss the potential underlying molecular mechanisms that drive COVID-19-mediated cardiac damage, as well as the short term and expected long-term cardiovascular ramifications of COVID-19 infection in patients.

Keywords: COVID-19; Cytokine storm; Heart failure; Immunopathology; Macrophages; Monocytes; Myocarditis; Myofibroblasts; Neutrophils; SARS-Cov2.

Graphical abstract

Fig. 1

SARS-Cov2 pathogenesis. The life cycle of SARS-CoV-2 in the host cells. The S glycoproteins of the virion bind to the cellular receptors (E.g.: angiotensin-converting enzyme 2 (ACE2) or Neuropilin-1 (NPR-1)) and enters target cells through an endosomal pathway. Following the entry, the virus hijacks the host transcription and translation machinery to synthesize SARS-Cov2 structural proteins. Following the production of structural proteins, nucleocapsids are assembled in the cytoplasm and followed by budding into the lumen of the endoplasmic reticulum (ER)–Golgi intermediate compartment. Virions are then released from the infected cell through exocytosis. The insert highlights S1 and S2 domains of virus spike protein and the polybasic RRAR cleavage site that enhances its association with NPR-1 receptor. (Adapted from “Coronavirus Replication Cycle”, by BioRender.com (2020). Retrieved from https://app.biorender.com/biorender-templates).

Fig. 2

Inflammation and potential remodeling mechanisms in COVID-19 heart. Common mechanisms between ischemic injury and COVID-19 induced cardiac remodeling. A) Myocardial ischemia induces significant cardiomyocyte death followed by recruitment of innate (neutrophils, monocytes, macrophages) and adaptive immune cells (T-lymphocytes) which promote dead cell clearance and wound healing in the short term. In the long run, this immune cell infiltration and associated cytokine release transform fibroblasts to myofibroblasts, resulting in excessive fibrosis and maladaptive cardiac remodeling which may lead to HF. B) Preliminary autopsy reports of COVID-19 patients confirmed infiltration of both innate (monocytes and macrophages) and adaptive immune cells (lymphocytes) in myocardium. In the long run, this immune cell infiltration can potentially trigger maladaptive cardiac remodeling resulting in cardiac fibrosis and decreased cardiac function in patients who recover from severe COVID-19 disease. This figure was created using Servier Medical Art templates, which are licensed under a Creative Commons Attribution 3.0 Unported License; https://smart.servier.com.