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COVID-19: The Many Ways to Hurt Your Heart

Department of Medical Microbiology and Immunology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2R3, Canada
Li Ka Shing Institute of Virology, University of Alberta, Edmonton, AB T6G 2E1, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, AB T6G 1C9, Canada
Author to whom correspondence should be addressed.
Viruses 2023, 15(2), 416;
Received: 28 January 2023 / Accepted: 30 January 2023 / Published: 1 February 2023
(This article belongs to the Special Issue COVID-19-Associated Myocarditis and Cardiac Pathology)

1. Introduction

Coronavirus disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has become a global pandemic, affecting the lives of billions of individuals. Although the virus primarily affects the lungs and causes mild influenza-like illness to Acute Respiratory Distress Syndrome (ARDS), severe SARS-CoV-2 infection can also cause off-target damage, particularly in the heart and vasculature. People with pre-existing cardiovascular diseases (CVDs) have increased susceptibility and high mortality risk with SARS-CoV-2 infections. Furthermore, patients who have recovered from acute myocardial injury may develop cardiac complications after SARS-CoV-2 infection. The several manuscripts published in this Special Issue on “COVID-19-Associated Myocarditis and Cardiac Pathology” address different forms of COVID-19-mediated cardiac pathology. A general review on the topic by Dmytrenko et al. assessed the epidemiology and pathophysiology of cardiovascular sequelae of COVID-19 and proposed a disease mechanism and directed some possible unanswered questions and future directions regarding cardiac manifestations of COVID-19 [1].

1.1. SARS-CoV-2 and Myocarditis

Most of the COVID-19-related myocarditis cases in clinical samples have been reported based on indirect cardiac tests [2], such as increased troponin level, diffuse ST-segment elevation on the electrocardiogram, diffuse biventricular hypokinesis on cardiac MRI [3], enlarged heart, and LV dysfunction by echocardiography [4]. Histopathological studies after SARS-CoV-2 infection have also revealed diffuse lymphocyte, monocyte, and neutrophil infiltrates, apparent interstitial edema, and limited focal necrosis [5,6,7]. Additionally, endomyocardial biopsy with immunological light microscopy has revealed large, vacuolated CD68+ macrophages with membrane damage and cytoplasmic vacuoles in a patient with COVID-19-related myocarditis [8]. Several animal models and in vitro systems have also been used to improve our understanding of COVID-19 infection and the mechanism of pathogenesis in the heart [9,10,11]. COVID-19 infection of transgenic K18-hACE2 mice is associated with moderate levels of viral RNA in the heart [12,13], with 22% of the heart showing scattered hyper-eosinophilic cardiomyocytes with pyknotic nuclei [13]. Additionally, SARS-CoV-2 infections in a Syrian golden hamster’s model showed focal lymphocytic myocarditis confirmed with CD3+ T lymphocyte staining [14]. In vitro studies using human cell-based heart models, such as cardiac tissue derived from human-induced pluripotent stem cells, have also been developed to understand the direct route of viral entry and pathogenesis and offer an opportunity to study clinically relevant cardiac viral infections [15,16].
In this Issue, Ho et al. reviewed the mechanisms of SARS-CoV-2-induced myocarditis. The authors explain the effects of direct SARS-CoV-2 infections on the heart and how they lead to myocarditis. They also summarize the various mechanisms by which SARS-CoV-2 manipulates host cell biology and outline potential treatment options [17].
Overall, COVID-19-associated myocarditis has proven to be a rare phenomenon, both in humans and in animal models. However, COVID-19 patients who recover from viral myocarditis present more subtle residual myocardial changes, mainly low-grade inflammation and fibrosis [18], which can lead to long-term cardiac complications [19,20,21] and confers a high risk of developing heart failure [22,23,24]. Heart failure is a significant long-term cardiac complication after viral infections [19,21].

1.2. SARS-CoV-2 and Thrombotic Events

COVID-19 is associated with coagulation abnormalities, resulting in venous and arterial thromboembolism [25]. Although the exact incidence is unclear, this includes myocardial infarction, in-stent thrombosis, and sudden left ventricular dysfunction [26]. Thrombotic events are highly variable (17–85%) in COVID-19 patients [27,28,29], and approximately 20% of COVID-19 patients develop venous thromboembolism [30]. In addition, peripheral arterial thromboembolism has been noticed in young COVID-19 patients without prior risk factors, with acute thrombosis involving the aorta presenting as acute limb ischemia [31]. In this Issue, a study by Xue et al. used Syrian hamsters for SARS-CoV-2 infection to advance the knowledge of preclinical studies on an animal model. This study described hematological abnormalities, early cardiopulmonary failure, and early thrombus formation, suggesting a similar level of pathology observed in the acute stages of SARS-CoV-2 infection in human subjects and offers platforms for evaluating the therapeutics of disease pathology [32].

1.3. SARS-CoV-2 and Multisystem Inflammatory Syndrome in Children (MIS-C)

Compared to adults, children are less susceptible to COVID-19 and generally have very mild clinical symptoms. A case series reported by a pediatric intensive care unit in the UK provides evidence of hyperinflammatory syndrome with features of Kawasaki disease in eight children, of which five tested positive for SARS-CoV-2 [33]. Furthermore, Verdoni et al. suggested a possible association between a high incidence of a severe form of Kawasaki disease and SARS-CoV-2, noting a 30-fold increase in the incidence of Kawasaki-like disease among children during the peak of the pandemic [34]. In this Issue, Fabi et al. reported that Multisystem Inflammatory Syndrome in Children (MIS-C) increased during the COVID-19 pandemic, with features that partially overlap with Kawasaki Disease (KD). Their cross-sectional study reported an increased level of IL-8 in MIS-C patients, who responded very rapidly to immunomodulatory treatment [35].

1.4. SARS-CoV-2 Vaccination and Cardiac Complications

Vaccination strategies against SARS-CoV-2 have been found to be effective in reducing infection. However, some vaccines, particularly mRNA-based vaccines, have been associated with multiple side effects, such as myocarditis/pericarditis. Several systematic reviews and meta-analyses have suggested an increased risk of myocarditis/pericarditis after COVID-19 vaccination [36,37,38]. In this Issue, Parra-Lucares et al. reviewed the current literature on vaccination-related cardiac involvement and proposed a pathophysiological mechanism for vaccine-induced myocarditis/pericarditis. They also propose that similarity between viral spike protein and autoantigen generation of autoantibodies may occur [39].

2. Conclusions

SARS-CoV-2 infection not only infects the lungs but also affects the extrapulmonary organs, such as the heart, which may result in long-term health conditions. This Special Issue highlighted the cardiac involvement after SARS-CoV-2 infection as well as vaccination and discussed the mechanism of heart–viral interaction.

Conflicts of Interest

The authors declare no conflict of interest.


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Akter, A.; Clemente-Casares, X. COVID-19: The Many Ways to Hurt Your Heart. Viruses 2023, 15, 416.

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Akter A, Clemente-Casares X. COVID-19: The Many Ways to Hurt Your Heart. Viruses. 2023; 15(2):416.

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Akter, Aklima, and Xavier Clemente-Casares. 2023. "COVID-19: The Many Ways to Hurt Your Heart" Viruses 15, no. 2: 416.

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