Complex Cardiovascular Impacts of COVID-19

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Complex Cardiovascular Impacts of COVID-19

Complex Cardiovascular Impacts of COVID-19

Researchers are increasingly discovering that the impact of SARS-CoV-2 infection extends to the cardiovascular system.

As the COVID-19 pandemic began in early 2020, doctors in Wuhan, China started reporting that many hospitalized patients with the disease were experiencing heart damage. Heart attacks were becoming more frequent, especially in patients with underlying risk factors, and there were numerous cases of myocarditis, an inflammation of the heart muscle. About a quarter of severe COVID-19 patients showed elevated levels of cardiac troponin, a protein marker for heart damage.

This evidence has shifted the perception of COVID-19, previously considered primarily a form of pneumonia, to a condition with a cardiovascular dimension. “We began to understand that it is also a cardiovascular disease,” said Peter Libby, Professor of Medicine at Harvard Medical School (HMS) and a cardiac specialist at Brigham and Women’s Hospital.

Subsequently, with the decline in hospitalizations and deaths due to COVID-19, largely due to widespread vaccination and increased immunity to severe illness, the virus responsible, SARS-CoV-2, still poses a risk to heart health, especially in individuals with arterial blockages, hypertension, diabetes, and other susceptibility factors. Millions of COVID-19 survivors continue to experience persistent cardiovascular symptoms, including irregular heartbeats, dizziness, and shortness of breath.

As COVID-19 cases surge once again due to the evolution of the virus, particularly with the latest Omicron variant BA.2.86, which carries over 30 mutations that can evade immune system defenses, research into the cardiovascular effects of COVID-19 remains crucial, says Anne-Marie Anagnostopoulos, a cardiac specialist at Beth Israel Deaconess Medical Center and a medical lecturer at HMS. A deeper understanding of the pathophysiology is needed to develop better treatment methods.

Cardiovascular

COVID-19-Induced Cardiovascular Disease

In most individuals, especially those who have been vaccinated, COVID-19 produces flu-like symptoms that typically subside within a few days or weeks. However, some progress to a more dangerous phase characterized by the proliferation of inflammatory proteins called cytokines in the bloodstream. In this so-called cytokine storm, the immune system becomes overactive, resulting in “a range of different problems,” explained Dr. Dara Lee Lewis, a medical lecturer at HMS, the Director of Non-invasive Testing for the Boston Lown Cardiovascular Group, and Co-Director of the Women’s Heart Program. Patients may experience myocardial weakness, low oxygen levels, blood clots, and fluid in the lungs, which may require hospitalization.

Pre-existing cardiovascular risk factors, such as coronary artery disease and obesity, can make individuals more susceptible to metabolic inflammation, increasing the likelihood of adverse outcomes. Lewis explained that people with vulnerable hearts are more likely to die from COVID-19 complications, and in the worst cases, patients might experience a type 1 myocardial infarction, a heart attack caused by a blood clot blocking an artery’s flow.

However, COVID-19 patients are also exceptionally prone to different types of heart attacks, known as type 2 myocardial infarctions. In these cases, the issue is not arterial blockage but rather an imbalance between oxygen supply and oxygen demand. Fever and inflammation can accelerate the heart rate, increasing the metabolic demands of various organs, including the heart. If the infected lungs are unable to efficiently exchange oxygen and carbon dioxide, the strained heart may suffer from oxygen deprivation.

Lee Lewis noted that during the early days of the pandemic, myocarditis was also a major concern, particularly for student athletes. “These kids didn’t need to get back to work and life,” she said, “they needed to get back to competitive sports.” Some of the students she cared for who had COVID-19 exhibited chest pain, rapid heartbeat, shortness of breath, and evidence of myocarditis on MRI scans.

Research reports from around the world indicate that as many as one-third of COVID-19-recovered patients show evidence of asymptomatic myocarditis on imaging. This is concerning because viral myocarditis is a known cause of sudden cardiac death in athletes. “We worry that many of our student athletes won’t be able to return to the field,” Lee Lewis said. Fortunately, asymptomatic cases have generally resolved with affected students making a full recovery.

Driving Understanding of SARS-CoV-2

The close association between COVID-19 and heart health is not entirely surprising. Scientists have known that other types of infections, such as the flu and bacterial sepsis, can exacerbate cardiovascular risk factors. Inactive coronary artery plaques in the elderly are not uncommon. Plaques can become unstable due to local inflammatory reactions triggered by distant infections. COVID-19 has drawn attention to these connections and raised awareness of the interplay between infections and heart disease.

However, as a novel virus, SARS-CoV-2 has presented many new questions. One example was whether the virus infects myocytes, the cells responsible for the heart’s contractions, which was initially a major concern. Subsequent research has shown that myocytes can largely evade infection. Instead, SARS-CoV-2 indirectly damages the heart by releasing inflammatory responses that affect cardiovascular function. After entering the body, SARS-CoV-2 locks onto cells with receptors sensitive to the virus’s spike protein. This spike protein is a key factor in the virus’s infectivity. Once the spike protein interacts with cell-based receptors, it activates and allows SARS-CoV-2 to enter the cell.

Respiratory epithelial cells are believed to be the primary target for infection, and endothelial cells lining blood vessels are also affected. When these cells become infected, they release cytokines that affect other cell types, collectively constituting the inner lining of all blood vessels in the body, known as the vascular endothelium. Lee Lewis described the vascular endothelium as an “organ in its own right” and highlighted the crucial role endothelial cells play in preventing inappropriate blood clots and enabling blood vessels to contract and expand normally.

Under normal circumstances, endothelial cells keep blood flowing in a liquid state. However, when cytokines activate these cells, they switch into a defensive mode, mobilizing macrophages and other immune cells and releasing molecules that promote blood clotting.

“Cytokines communicate with cells throughout the body,” explained Dr. Jeremy Luban, a professor at the University of Massachusetts Medical School and a member of the Massachusetts Pathogen Readiness Alliance’s executive committee, a consortium led by HMS that seeks to mitigate the spread of COVID-19 and prepare for future pandemics. Endothelial cells, which are likely monitored, have to constantly assess blood coagulation and tissue damage status and induce actions such as clotting to prevent harm to the tissues.

Blood clots can be deadly, such as when they block arteries supplying the brain. In the early months of the pandemic, arterial blockages were associated with strokes in many patients, even in young individuals without predisposing risk factors. Autopsies of patients who died from COVID-19 showed evidence of clots throughout the body and multiple organ failure. Up to one-third of hospitalized COVID-19 patients were found to have myocardial damage, which Libby attributed to conditions like microvascular clots and endothelial dysfunction.

POTS and Viral Infections

Microvascular damage is also associated with long-term symptoms in a significant portion of COVID-19 survivors. Since the early days of the pandemic, these “long-haul” patients have reported experiencing symptoms such as chest pain, rapid heartbeat, fatigue, and cognitive issues. The most common post-viral condition reported is postural orthostatic tachycardia syndrome (POTS), which typically occurs following infection. POTS is a disorder of the autonomic nervous system, which controls involuntary bodily functions such as heart rate and blood pressure. Symptoms include lightheadedness and rapid heart rate when a person moves to a standing position.

However, the causes of POTS, which is believed to be associated with autoimmune reactions triggered by infections, remain unclear. In patients with POTS, blood pools in the legs upon standing, which can lead to dizziness and fainting. Without antecedent causes, “we just don’t know why people with POTS develop this autonomic problem after infection,” Lee Lewis explained.

While COVID-19 has deepened our understanding of the interconnectedness of cardiovascular issues and infections, particularly with the virus’s latest Omicron variant BA.2.86, further research is needed to better understand the long-term consequences of viral infections. Much work remains to unravel the precise links between COVID-19 and myocarditis, vascular inflammation, POTS, and other cardiac issues.

The medical community is closely monitoring and researching the long-term cardiovascular effects of COVID-19, especially as new variants of the virus continue to emerge. While vaccines have played a crucial role in reducing the severity of illness and hospitalizations, understanding these effects is essential for better treating and supporting patients who experience cardiac complications associated with COVID-19.