Molecular Determinants, Clinical Manifestations and Effects of Immunization on Cardiovascular Health During COVID-19 Pandemic Era - A Review

Abstract

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has enveloped the world into an unprecedented pandemic since 2019. Significant damage to multiple organs, such as the lungs and heart, has been extensively reported. Cardiovascular injury by ACE2 downregulation, hypoxia-induced myocardial injury, and systemic inflammatory responses complicate the disease. This virus causes multisystem inflammatory syndrome in children with similar symptoms to adult SARS-CoV-2-induced myocarditis. While several treatment strategies and immunization programs have been implemented to control the menace of this disease, the risk of long-term cardiovascular damage associated with the disease has not been adequately assessed. In this review, we surveyed and summarized all the available information on the effects of COVID-19 on cardiovascular health as well as comorbidities. We also examined several case reports on post-immunization cardiovascular complications.

FIG 1

Cardiovascular pathology due to SARS-CoV-2 infection (Color version of figure is available online.)

FIG 2

Structural features of SARS-CoV-2 virus (Color version of figure is available online.)

FIG. 3

The life cycle of SARS-CoV-2. (1A) virus entry through endosomes, (1B) virus entry through plasma membrane fusion, (2) virions are endocytosed into endosomes, (3) virus releases RNA, (4) Genomic RNAs are then prepared to initiate translation, (5) polyproteins are translated to form polyproteins pp1a and ppab, (6) Proteolysis of polyproteins 1a and 1ab to form 16 non-structural proteins (7) formation of helicase and RdRp complex, (8) RdRp complex helps development of negative-sense RNAs, (9) Transcription of mRNAs and Ribosomes translate S-spike, M-membrane, N-nucleocapsid, and E-envelope encoding proteins, (10) The nucleocapsids are assembled along with genomic RNA, (11) The precursor of virions is then transferred by vesicles from the RER via the Golgi apparatus to the cell surface, (12) Virions are released by exocytosis, (13) Virus is released in the extracellular environment.^,

FIG 4

The probable mechanism of COVID-19 induced cardiac manifestations: SARS-CoV-2 enters the cells through binding with ACE2 receptors and directly attacking the epithelial cells in the lungs and heart, leading to acute respiratory distress syndrome (ARDS) pneumonia. Along with that, these patients experience hypoxia, which also worsens myocardial damage, causing myocardial infarction, myocarditis, and ischemia (Color version of figure is available online.)

FIG 5

Mechanisms implicated in the pathogenesis of myocardial injuries related to COVID-19 infection. (1) SARS-CoV-2 enter through the ACE2 receptors; (2) Viruses attack alveolar epithelial cells in lungs; (3) Viruses are then recognized by dendritic cells and macrophages followed by the release of large amounts of cytokines; (4) Increased level of proinflammatory cytokines like IL-1, IL-6, IL-8, TNF-α, NF-κB induce cytokine storm; (5) Cytokine storm stimulates the production of ROS in the cells; (6) ROS lead to lung injury, pulmonary edema and acute respiratory distress syndrome (ARDS); (7) Lung injury causes an imbalance between oxygen demand and supply resulting in arterial hypotension causing cardiovascular damage; (8) Cytokine storm-induced ROS causes systemic inflammation leading to cardiac microvascular damage and acute coronary syndrome.

FIG 6

Detailed overview of the bidirectional correlation between COVID-19 and cardiovascular manifestations. Cardiovascular comorbidities in patients with COVID-19, like coronary artery disease and hypertension are associated with heart failure. COVID-19 is most commonly associated with viral pneumonia, but it can also cause cardiac damages like myocarditis, arrhythmias, acute coronary syndrome, and thromboembolism in the cardiovascular system. Finally, several of the drugs that have been recommended as COVID-19 therapies have pro-arrhythmic properties.^, (Color version of figure is available online.)