In December 2019, a cluster of patients with pneumonia were identified in Wuhan, China. Initially the cause of this outbreak was unknown, but by early January 2020, Chinese scientists isolated a novel coronavirus and tentatively linked it to the growing patient cohort.

The new virus was related to the coronavirus that was responsible for the global SARS outbreak in 2002 and was labelled SARS-CoV-2. In February 2020 the WHO designated the condition caused by SARS-CoV-2 as “Coronavirus Disease 2019” or “COVID-19”. By March 2020 COVID-19 had emerged as an international pandemic that threatened to overwhelm healthcare systems world-wide and pushed the global economy to the brink of collapse.

A Not-So Grand Entrance

SARS-CoV-2 enters the body through the respiratory system where it causes much of its damage. The clinical spectrum of the disease is wide, ranging from asymptomatic infection to severe pneumonia, respiratory failure, and death. Treatment for more severe cases is largely aimed at maintaining respiratory function.

The respiratory system is a critical target of the virus, but the cardiovascular system is also intimately involved in COVID-19 from infection, disease development, and treatment. Despite the widely acknowledged role of the heart and circulatory system in COVID-19 there remain many myths and misconceptions about the virus and the cardiovascular system, from the beginning to end of the disease.

To the Heart of the Problem

Up to 40% of people hospitalized with COVID-19 have pre-existing cardiovascular disease. COVID-19 patients with cardiovascular disease are 3-4 times more likely to be admitted to ICU than those without cardiovascular co-morbidities. The overall mortality rate for COVID-19 is generally reported to be around 2%. In patients with cardiovascular disease, mortality jumps to 10.5%, which is even greater than the 6% rate reported for patients with chronic respiratory disease.

Why the complications associated with cardiovascular disease? It turns out infection may damage the heart. For those with heart disease this may be too much to handle.

Troponin is a protein in heart muscle that is released into the blood when the muscle is damaged. Clinically, elevated troponins are used to diagnose heart attacks and other conditions that cause heart muscle to die. A meta-analysis of 4 studies including 341 patients found increased troponin levels in COVID-19 patients, and that the serum levels of troponin corresponded with the severity of illness.

Even those without cardiovascular disease are at risk for heart damage. In 59% of patients with COVID-19 there was clinical evidence of cardiac injury. Some studies found myocarditis in COVID patients, which is an infection of heart muscle by the virus. Cardiac arrhythmias occur in 7% of COVID-19 patients, a rate that rises to an astounding 44% in ICU patients. Infected patients are at a greater risk of developing blood clots and almost a quarter of COVID-19 patients experience some form of heart failure. Beyond myocarditis it’s not clear whether the damage to the heart is directly caused by the virus, or by other problems like reduced kidney function.

The Long Game

The long-term effects of COVID-19 on cardiovascular disease are not yet known, but the impact of infectious diseases and previous coronarvirus outbreaks provide some insight into possible future effects. Viral infections like influenza increase the risk of heart attacks and stroke up to 1 year after infection, threats that are decreased with vaccination. In a study of 25 people who were infected with SARS-CoV circulating lipids remained disrupted 12 years later. Pneumonia increases the risk of cardiovascular disease for up to 10 years following its occurrence. These past experiences suggest that long after the pandemic has subsided the impact of COVID-19 may remain.

ACE2 of Hearts

The protein ACE2 is a key tool some coronaviruses use to infect cells. ACE2 is part of the renin-angiotensin system that regulates blood pressure. Increased activity of the renin-angiotensin system escalates the production of the hormone angiotensin II, which causes high blood pressure. But ACE2 is part of an arm of the system that protects the cardiovascular system by breaking down angiotensin II into a peptide that decreases blood pressure.

The SARS coronavirus uses a spike protein to bind to ACE2 on cells and stimulate them to take up the virus. Research on the SARS-CoV-2 virus shows that it retains the same spike protein and likely uses the same mechanism to infect cells.

After cells of the respiratory system, heart muscle cells are among the cells with the  highest levels of ACE2. The relatively high levels of an entry protein in the heart may explain why cardiac damage is so prevalent in people infected with SARS-CoV-2. It has also been shown that cardiovascular conditions like heart attacks and heart failure increase the expression of ACE2 protein, which may explain the increased risk of infection in patients with pre-existing cardiovascular disease.

Mythical ACE

Early reports from China indicated that high blood pressure was linked to worse outcomes in those with COVID-19. Some studies in rodents showed that ACE inhibitors – a common treatment for high blood pressure – increased the levels of ACE2. The correlation between ACE inhibitor treatment and increased expression of ACE2 led to the rumour that treatment with these drugs worsens infection and mortality. Clinical data in humans, however, found no such changes with treatment and fail to support this hypothesis.

The link between high blood pressure and poor COVID-19 outcomes may come from the cardiovascular disease itself. While nearly half of Chinese adults over 35 years of age have high blood pressure, less than 1/3 are given treatment, and less than 10% have their hypertension controlled by medications. Therefore, the hypothesized link between anti-hypertensive medications like ACE inhibitors is not supported by clinical data. In fact, treatment statistics suggest that the majority of infected patients are not treated by the medications that are purported to increase the risk of infection.

How to Avoid a Broken Heart

Clinical trials for effective COVID-19 treatments have just started and a vaccine is likely a year or more away. Maintaining social distancing is the best way to flatten the curve and reduce the spread of SARS-CoV-2. After all, you don’t want to go breaking someone’s heart.