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.