Cardiovascular Disease and Outcomes Among Patients With SARS-CoV-2 Infection (COVID-19)

Overview

The coronavirus disease of 2019 (COVID-19) has affected over 2.4 million individuals worldwide and has resulted in \>171,000 deaths. Cardiovascular disease (CVD) is an important contributor to death in these patients. Those who develop cardiac injury during infection have a 4-fold increased risk of death. Furthermore, pre-existing CVD or cardiovascular risk factors (e.g. diabetes, hypertension) are associated with worse outcomes. Given the recent emergence of this disease, there is limited understanding of: (i) the risk factors for cardiovascular events, (ii) blood biomarkers for early recognition, and drug targeting, of patients at risk of adverse outcomes, and (iii) the short term subclinical and clinical cardiovascular manifestations in those who survive to discharge.

COVID-19 and CVD: On March 11, 2020 the coronavirus disease of 2019 (COVID-19), which is caused by infection with SARS-CoV-2 virus, was declared a pandemic by the World Health Organization. Incredibly, \>2,400,000 cases and \>171,000 deaths have been reported globally as of April 21, 2020. While the overall case fatality is \~5%, the mortality rate is dramatically higher in selected populations, particularly in those with preexistent and/or new-onset cardiovascular disease (CVD)2. Early reports suggest that up to 20-28% of hospitalized patients with confirmed COVID-19 (COVID-19+) have evidence of cardiovascular injury, defined as troponin elevation with or without other cardiovascular manifestations such as ischemia, ventricular arrhythmias, and left ventricular dysfunction (LVD). While SARS-CoV-1 virus can directly infect the heart4, it is still not clear whether this is the case for SARS-CoV-2. Nevertheless, cardiovascular injury may result from indirect damage secondary to hypoxemia, sepsis, cytokine release, endothelial injury or from direct myocardial involvement. Regardless of the mechanism, early studies demonstrate that cardiovascular injury is associated with a 4-fold increased risk of death, independent of age, cardiovascular risk factors, preexistent CVD, non-CVD comorbidities, and ARDS (Acute Respiratory Distress Syndrome).The presence of CVD and cardiac injury appear to have a synergistic effect on adverse prognosis.5 However, the long-term consequences of this acute cardiovascular injury are not known, but are likely to be significant. Therefore, understanding early markers of cardiovascular injury, their association with adverse events (cardiovascular and non-cardiovascular) and post-discharge cardiovascular consequences of COVID-19 will allow better care of these patients. Rationale for the study This study will address the above-mentioned knowledge gaps by focusing on patients with a broad spectrum of disease severity. It will include patients admitted to the hospital (sicker group) and those discharged from the emergency department (healthier group). It will focus on endothelial and cardiac blood biomarkers to facilitate early recognition of patients at risk for adverse events and characterize in-hospital and post-discharge cardiovascular sequelae of COVID-19. Ultimately, the intention is to identify patients at risk, reduce in-hospital and post-discharge adverse events, and determine the need for longer-term CVD prevention strategies and follow-up in survivors. Endothelial cells (ECs) line every blood vessel within the human body and play a key role in CVD. During early COVID-19 infection ECs in the alveolar unit in the lung are likely injured due to the antiviral response of the lung cells. Furthermore, ECs also have receptors on their surface that can allow the virus to enter into the circulation and travel to other organs, including the heart. Therefore, damage to the endothelium, both directly or due to the body's antiviral inflammatory response, can contribute to cardiac injury and poor overall outcomes. Cardiac injury can be identified by the release of cardiac markers in the blood such as troponin I and B-type natriuretic peptides, which can often be seen before overt heart dysfunction occurs. Therefore, we propose that measurement of both endothelial activation and cardiac-specific markers from patient's blood early after infection (i.e. at presentation) and during hospital admission, can serve as an indicator of early cardiovascular injury. Correlating these findings with abnormalities in cardiac functional tests as well as cardiovascular and non-cardiovascular adverse outcomes during admission and follow-up, will help us use these biomarkers to institute targeted prevention strategies. Given that the majority of patients (\>95%) who are infected with the virus survive, and cardiac injury during the infection is common, it is likely that there is significant unrecognized cardiac injury in survivors. This is often undetected during admission or in those discharged from the emergency department (ER) due to inability to perform complete cardiovascular assessment. To understand subclinical cardiovascular injury, all patients will be brought back 3-6 months for complete cardiac assessment using echocardiography, cardiac MRI, and bloodwork. This knowledge will enable strategies to prevent subsequent overt CVD events and to determine the need for further investigations and long-term follow-up in COVID-19 survivors.