Virus World

Covid vaccinations substantially reduce the risk of heart failure and potentially dangerous blood clots linked to the infection for up to a year, according to a large study. Researchers analysed health records from more than 20 million people across the UK, Spain and Estonia and found consistent evidence that the jabs protected against serious cardiovascular complications of the disease. Covid vaccines, including those from Oxford-AstraZeneca, Pfizer and Moderna, proved highly effective at preventing severe disease in the pandemic, but medicines regulators also recorded increases in some rare heart and clotting conditions, similar to those found with other vaccines such as flu shots.

The latest study sought to investigate the overall impact of a Covid vaccination, given that infection with the virus itself is known to significantly raise the risk of heart failure and various other serious cardiovascular problems. “What we show in this very large study is that people who are vaccinated are at a very much reduced risk of these complications post-Covid,” said Daniel Prieto-Alhambra, a professor of pharmaco- and device epidemiology at the University of Oxford and a senior author on the study. Writing in the journal Heart, the researchers describe how the adenovirus-based Covid vaccines produced by Oxford-AstraZeneca and Janssen, and the mRNA-based vaccines from Pfizer and Moderna, were most protective against Covid-related heart failure and blood clots in the first month after contracting the virus. In that period, the risk of heart failure was 55% lower, and the risks of blood clots in the veins and arteries were down 78% and 47% respectively, compared with rates in unvaccinated people.

While the protective effects of the vaccines waned over the longer term, those who received Covid shots remained at lower risk of Covid-related heart failure and blood clots than unvaccinated individuals for up to a year, the researchers found. Three to six months after infection, the risk of heart failure in vaccinated people was 39% lower than in unvaccinated people, with the risk of blood clots in the veins and arteries down 47% and 28% respectively. From six to 12 months post-infection, the risks of the same complications were 48%, 50% and 38% lower, respectively, for vaccinated people. The protective effect arises from the vaccines reducing the severity of the disease when people experience breakthrough infections, when the virus takes hold despite a person being vaccinated. “The message overall is that if you are vaccinated, your risk of having post-Covid cardiovascular and thromboembolic complications is reduced quite dramatically,” Prieto-Alhambra said. “Particularly for people who are at high risk, or are scared of having cardiovascular complications or blood clots, this is very reassuring.”

Cites study published in 2024 in BMJ Heart:

https://doi.org/10.1136/heartjnl-2023-323483 

The relationship between coronavirus disease 2019 (COVID-19) and myocardial injury was established at the onset of the COVID-19 pandemic. An increase in the incidence of out-of-hospital cardiac arrest was also observed. This case report aims to point to the prothrombotic and proinflammatory nature of coronavirus infection, leading to simultaneous coronary vessel thrombosis and subsequently to out-of-hospital cardiac arrest. During the COVID-19 pandemic, a 46-year-old male patient with no comorbidities suffered out-of-hospital cardiac arrest (OHCA) with ventricular fibrillation as the first recorded rhythm. The applied cardiopulmonary resuscitation (CPR) measures initiated by bystanders and continued by emergency medical service (EMS) resulted in the return of spontaneous circulation. The stabilized patient was transferred to the tertiary university center.

Electrocardiogram (ECG) revealed “lambda-like” ST-segment elevation in DI and aVL leads, necessitating an immediate coronary angiography, which demonstrated simultaneous occlusion of the left anterior descending (LAD) and right coronary artery (RCA). Primary percutaneous coronary intervention (PCI) with the implantation of one drug-eluting stent (DES) in LAD and two DES in RCA was done. Due to the presence of cardiogenic shock (SCAI C), an intra-aortic balloon pump (IABP) was implanted during the procedure, and due to the comatose state and shockable cardiac arrest, targeted temperature management was initiated. The baseline chest X-ray revealed bilateral interstitial infiltrates, followed by increased proinflammatory markers and a positive polymerase chain reaction (PCR) test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) demasking underlying COVID-19-related pneumonia.

Within the following 48 h, the patient was hemodynamically stable, which enabled weaning from IABP and vasopressor discontinuation. However, due to the worsening of COVID-19 pneumonia, prolonged mechanical ventilation, together with antibiotics and other supportive measures, was needed. The applied therapy resulted in clinical improvement, and the patient was extubated and finally discharged on Day 26, with no neurological sequelae and with mildly reduced left ventricle ejection fraction.

Published in MDPI (Dec. 25, 2023):

https://doi.org/10.3390/medicina60010039

New data analysis from the Smidt Heart Institute at Cedars-Sinai found that deaths from heart attacks rose significantly during pandemic surges, including the COVID-19 Omicron surges, overall reversing a heart-healthier pre-pandemic trend. Prior to the COVID-19 pandemic, heart attacks were the leading cause of death worldwide but were steadily on the decline. However, the new study—recently published in the Journal of Medical Virology—shows that heart attack death rates took a sharp turn and increased for all age groups during the pandemic. The spikes in heart attack deaths have tracked with surges of COVID-19 infection—even during the presumed less-severe omicron phase of the pandemic. Furthermore, the data showed the increase was most significant among individuals ages 25-44, who are not usually considered at high risk for heart attack.  "The dramatic rise in heart attacks during the pandemic has reversed what was a prior decadelong steady improvement in cardiac deaths," said Yee Hui Yeo, MD, first author of the study and a Cedars-Sinai physician-scientist. "We are still learning the many ways by which COVID-19 affects the body, regardless of age, gender, ethnicity or race." Using data from the Centers for Disease Control and Prevention's National Vital Statistics System, the Cedars-Sinai researchers identified 1,522,699 deaths from heart attacks—medically called acute myocardial infarctions—between April 1, 2012, and March 31, 2022. Investigators then compared age-related mortality rates between pre-pandemic and pandemic periods, as well as demographic groups and regions.

Key findings from the study include:

• In the year before the pandemic, there were 143,787 heart attack deaths; within the first year of the pandemic, this number had increased by 14% to 164,096.
• The excess in acute myocardial infarction-associated mortality has persisted throughout the pandemic, even during the most recent period marked by a surge of the presumed less-virulent omicron variant.
• Researchers found that although acute myocardial infarction deaths during the pandemic increased across all age groups, the relative rise was most significant for the youngest group, ages 25 to 44.
• By the second year of the pandemic, the "observed" compared to "predicted" rates of heart attack death had increased by 29.9% for adults ages 25-44, by 19.6% for adults ages 45-64, and by 13.7% for adults age 65 and older.

"There are several potential explanations for the rapid rise in cardiac deaths in patients with COVID-19, yet still many unanswered questions," said Yeo. "Importantly, our results highlight disparities in mortality that have emerged from the COVID-19 pandemic and that are persisting even through the omicron era." The possible explanations, Yeo said, include that COVID-19 may trigger or accelerate the presentation of preexisting coronary artery disease, even in younger adults. Reasons for the spike in heart-related conditions could also be related to psychological and social challenges associated with the pandemic, including job loss and other financial pressures that can cause acute or chronic stress leading to cardiac disease. The research team members say they have long known that infections such as the flu can increase risk for heart disease and heart attack, but the sharp rise in heart attack deaths is like nothing seen before. "There is something very different about how this virus affects the cardiac risks," said Susan Cheng, MD, MPH, director of the Institute for Research on Healthy Aging in the Department of Cardiology at the Smidt Heart Institute and senior and co-corresponding author of the study. "The difference is likely due to a combination of stress and inflammation, arising from predisposing factors and the way this virus biologically interacts with the cardiovascular system." Yeo, Cheng and the broader Smidt Heart Institute team hope that greater awareness and more research will expand the medical community's ability to manage and mitigate these risks.

Research cited published in J. Med. Virology (Sept. 29, 2022):

https://doi.org/10.1002/jmv.28187 

The cardiovascular complications of acute coronavirus disease 2019 (COVID-19) are well described, but the post-acute cardiovascular manifestations of COVID-19 have not yet been comprehensively characterized. Here we used national healthcare databases from the US Department of Veterans Affairs to build a cohort of 153,760 individuals with COVID-19, as well as two sets of control cohorts with 5,637,647 (contemporary controls) and 5,859,411 (historical controls) individuals, to estimate risks and 1-year burdens of a set of pre-specified incident cardiovascular outcomes. We show that, beyond the first 30 d after infection, individuals with COVID-19 are at increased risk of incident cardiovascular disease spanning several categories, including cerebrovascular disorders, dysrhythmias, ischemic and non-ischemic heart disease, pericarditis, myocarditis, heart failure and thromboembolic disease.

These risks and burdens were evident even among individuals who were not hospitalized during the acute phase of the infection and increased in a graded fashion according to the care setting during the acute phase (non-hospitalized, hospitalized and admitted to intensive care). Our results provide evidence that the risk and 1-year burden of cardiovascular disease in survivors of acute COVID-19 are substantial. Care pathways of those surviving the acute episode of COVID-19 should include attention to cardiovascular health and disease. Individuals with COVID-19 are at increased long-term risk for a wide range of cardiovascular disorders, even for individuals who were not hospitalized during the acute phase of the infection.

Published Nature Medicine (Feb. 7, 2022):

https://doi.org/10.1038/s41591-022-01689-3 

Three-quarters of people who died of COVID-19 harbored the SARS-CoV-2 virus in their hearts, according to the most detailed study of cardiac tissue to date. Those people were also more likely than patients without cardiac invasion to experience abnormal heart rhythms before they died. The study offers insight into how the disease may damage the heart—and how certain treatments may help. The finding “paints a really nice picture” of the connection between the virus and heart problems, says Joseph Maleszewski, a cardiovascular pathologist at the Mayo Clinic who was not involved with the study.  Scientists have ample evidence of heart damage in COVID-19 patients. Some people, for example, show elevated levels of troponins, molecules released in the blood when the heart is injured. Others have experienced inflammation of the sac surrounding the heart—and inflammation of the heart itself. But it’s been unclear whether these problems were caused by the SARS-CoV-2 virus attacking the heart directly, or the damage is due to an overactive immune response. Part of the problem is that previous studies are mixed about whether SARS-CoV-2 can invade heart tissue. Many that haven’t found the virus use real-time polymerase chain reaction (RT-PCR), says James Stone, a cardiovascular pathologist at Massachusetts General Hospital. RT-PCR works by detecting viral RNA in tissue, then making many DNA copies of it. Once there’s enough DNA, a molecule called a fluorescent tag can stick to it and shine to reveal its presence. But Stone says that heart tissue is often processed and preserved using chemicals like paraffin, which can break down the RNA and prevent detection to begin with. So he and his team used another approach: in situ hybridization and NanoString transcriptomic profiling. Like RT-PCR, these techniques use special molecules to attach to and detect pieces of viral RNA, but they do so without having to make DNA copies first. The approach can identify viral RNA even after it’s broken into smaller pieces. The scientists also analyzed about 1000 pieces of heart tissue—more than 20 samples from each of the 41 patients they looked at. That’s double the number of samples per patient in most studies, Stone says. 

SARS-CoV-2 was present in 30 of the hearts, the team reports today in Modern Pathology. And only those patients experienced new atrial fibrillations, fast and irregular heart rhythms, or early or extra heartbeats, compared with the other patients in the study—a correlation Stone calls “pretty phenomenal.” Still, it’s unclear whether the virus attacked the heart directly in these cases. Most of the infected cardiac cells were immune cells, which SARS-CoV-2 could have invaded elsewhere in the body before they traveled to the heart. It’s also unclear whether the virus—rather than the immune cells themselves—is causing the problems. Regardless, the study may help explain why the steroid dexamethasone is so helpful to some patients. The drug was one of the first found to prevent deaths from severe COVID-19. It reduces inflammation, so it may have curbed the presence of SARS-CoV-2–harboring immune cells in the heart, Stone says. Only 50% of the patients treated with dexamethasone had the virus in their hearts, compared with 90% of patients who were not on the drug. But compared with large clinical trials, the number of patients in this new study is small, making it impossible to say that one drug protects the heart better than another, says Nicholas Hendren, a cardiology fellow at the University of Texas Southwestern Medical Center. Still, Maleszewski says the new findings are a call to action. Scientists need to probe more cardiac tissue, he argues, not just to see how COVID-19 kills patients, but to figure out how it hurts the hearts of those that survive. The disease may, for example, create scar tissue that can cause cardiac problems down the line. We’re starting to understand what COVID-19 does to patients when they have it, he says. “What’s not clear is what happens later on.”

Research Cited Published in Modern Pathology (March 17, 2021):

https://doi.org/10.1038/s41379-021-00790-1 

Early reports from hospitals document a spike in large vessel blockages, especially among people in their 30s and 40s who tested positive for the coronavirus. Several hospitals in the US have observed strokes in a number of patients being treating for coronavirus, leading to concern that the infection may be causing devastating blockages in the brain. For at least two facilities, these events account for a spike in stroke cases among middle-aged patients.

“Our report shows a seven-fold increase in incidence of sudden stroke in young patients during the past two weeks,” Thomas Oxley, a neurosurgeon at Mount Sinai Health System in New York who describes five of his patients in an upcoming paper in the New England Journal of Medicine, tells CNN. “Most of these patients have no past medical history and were at home with either mild symptoms (or in two cases, no symptoms) of Covid.” Although the numbers of stroke incidents among coronavirus patients remains low, The Washington Post notes that three medical centers in the US will be publishing reports on dozens of COVID-19 patients who experienced strokes. And these appear to be the most serious kind of stroke, called a large vessel occlusion, which might account for the surge in the number of people who have died at home during the pandemic, but this cannot be confirmed.  

Thomas Jefferson University Hospitals and NYU Langone Health found that 40 percent of the 12 people treated for large vessel blockage who also tested positive for SARS-CoV-2 were under age 50, according to the Post. “We are used to thinking of 60 as a young patient when it comes to large vessel occlusions,” Eytan Raz of NYU Langone tells the newspaper. “We have never seen so many in their 50s, 40s and late 30s.” Oxley tells Medscape Medical News that the virus may be causing inflammation in blood vessels, leading to blood clots. Raz speculates that perhaps because younger people don’t suffer the respiratory issues that take a toll on older COVID-19 patients, they survive long enough for the virus to cause damage elsewhere.

Original Study to be published in New England J. Med.  (April 29, 2020)

Cardiovascular autonomic dysfunction (CVAD) is a malfunction of the cardiovascular system caused by deranged autonomic control of circulatory homeostasis. CVAD is an important component of post-COVID-19 syndrome, also termed long COVID, and might affect one-third of highly symptomatic patients with COVID-19. The effects of CVAD can be seen at both the whole-body level, with impairment of heart rate and blood pressure control, and in specific body regions, typically manifesting as microvascular dysfunction. Many severely affected patients with long COVID meet the diagnostic criteria for two common presentations of CVAD: postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia. CVAD can also manifest as disorders associated with hypotension, such as orthostatic or postprandial hypotension, and recurrent reflex syncope. Advances in research, accelerated by the COVID-19 pandemic, have identified new potential pathophysiological mechanisms, diagnostic methods and therapeutic targets in CVAD.

For clinicians who daily see patients with CVAD, knowledge of its symptomatology, detection and appropriate management is more important than ever. In this Review, we define CVAD and its major forms that are encountered in post-COVID-19 syndrome, describe possible CVAD aetiologies, and discuss how CVAD, as a component of post-COVID-19 syndrome, can be diagnosed and managed. Moreover, we outline directions for future research to discover more efficient ways to cope with this prevalent and long-lasting condition. Cardiovascular autonomic dysfunction (CVAD) is a malfunction of the autonomic control of circulatory homeostasis and is an important component of post-COVID-19 syndrome. In this Review, Fedorowski and colleagues define the major forms of CVAD (including postural orthostatic tachycardia syndrome), and discuss the aetiology, diagnosis and management of post-COVID-19 syndrome-associated CVAD.

Published in Nature Reviews Cardiology Jan.02, 2024: 

https://doi.org/10.1038/s41569-023-00962-3 

NIH-funded research sheds light on link between COVID-19 infection and increased risk of cardiovascular disease and stroke. SARS-CoV-2, the virus that causes COVID-19, can directly infect the arteries of the heart and cause the fatty plaque inside arteries to become highly inflamed, increasing the risk of heart attack and stroke, according to a study funded by the National Institutes of Health. The findings(link is external), published in the journal Nature Cardiovascular Research, may help explain why certain people who get COVID-19 have a greater chance of developing cardiovascular disease, or if they already have it, develop more heart-related complications. In the study, researchers focused on older people with fatty buildup, known as atherosclerotic plaque, who died from COVID-19. However, because the researchers found the virus infects and replicates in the arteries no matter the levels of plaque, the findings could have broader implications for anybody who gets COVID-19.

“Since the early days of the pandemic, we have known that people who had COVID-19 have an increased risk for cardiovascular disease or stroke up to one year after infection,” said Michelle Olive, Ph.D., acting associate director of the Basic and Early Translational Research Program at the National Heart, Lung, and Blood Institute (NHLBI), part of NIH. “We believe we have uncovered one of the reasons why.” Though previous studies have shown that SARS-CoV-2 can directly infect tissues such as the brain and lungs, less was known about its effect on the coronary arteries. Researchers knew that after the virus reaches the cells, the body’s immune system sends in white blood cells known as macrophages to help clear the virus. In the arteries, macrophages also help remove cholesterol, and when they become overloaded with cholesterol, they morph into a specialized type of cell called foam cells. The researchers thought that if SARS-CoV-2 could directly infect arterial cells, the macrophages that normally are turned loose might increase inflammation in the existing plaque, explained Chiara Giannarelli, M.D., Ph.D., associate professor in the departments of medicine and pathology at New York University’s Grossman School of Medicine and senior author on the study. To test their theory, Giannarelli and her team took tissue from the coronary arteries and plaque of people who had died from COVID-19 and confirmed the virus was in those tissues. Then they took arterial and plaque cells – including macrophages and foam cells – from healthy patients and infected them with SARS-CoV-2 in a lab dish. They found that the virus had also infected those cells and tissues. Additionally, the researchers found that when they compared the infection rates of SARS-CoV-2, they showed that the virus infects macrophages at a higher rate than other arterial cells. Cholesterol-laden foam cells were the most susceptible to infection and unable to readily clear the virus. This suggested that foam cells might act as a reservoir of SARS-CoV-2 in the atherosclerotic plaque. Having more build-up of plaque, and thus a greater number of foam cells, could increase the severity or persistence of COVID-19.

The researchers then turned their attention to the inflammation they predicted might occur in the plaque after infecting it with the virus. They quickly documented the release of molecules, known as cytokines, that are known to increase inflammation and promote the formation of even more plaque. The cytokines were released by infected macrophages and foam cells. The researchers said this may help explain why people who have underlying plaque buildup and then get COVID-19 may have cardiovascular complications long after getting the infection.   “This study is incredibly important as it adds to the larger body of work to better understand COVID-19,” said Olive. “This is just one more study that demonstrates how the virus both infects and causes inflammation in many cells and tissues throughout the body. Ultimately, this is information that will inform future research on both acute and Long COVID.” Though the findings conclusively show that SARS-CoV-2 can infect and replicate in the macrophages of plaques and arterial cells, they are only relevant to the original strains of SARS-CoV-2 that circulated in New York City between May 2020 and May 2021. The study was conducted in a small cohort of older individuals, all of whom had atherosclerosis and other medical conditions; therefore, the results cannot be generalized to younger, healthy individuals.

Published in Nature Cardiovascular Research (Sept. 28, 2023):

https://doi.org/10.1038/s44161-023-00336-5 

Cardiac symptoms are increasingly recognized as late complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in previously well individuals with mild initial illness, but the underlying pathophysiology leading to long-term cardiac symptoms remains unclear. In this study, we conducted serial cardiac assessments in a selected population of individuals with Coronavirus Disease 2019 (COVID-19) with no previous cardiac disease or notable comorbidities by measuring blood biomarkers of heart injury or dysfunction and by performing magnetic resonance imaging. Baseline measurements from 346 individuals with COVID-19 (52% females) were obtained at a median of 109 days (interquartile range (IQR), 77–177 days) after infection, when 73% of participants reported cardiac symptoms, such as exertional dyspnea (62%), palpitations (28%), atypical chest pain (27%) and syncope (3%).

Symptomatic individuals had higher heart rates and higher imaging values or contrast agent accumulation, denoting inflammatory cardiac involvement, compared to asymptomatic individuals. Structural heart disease or high levels of biomarkers of cardiac injury or dysfunction were rare in symptomatic individuals. At follow-up (329 days (IQR, 274–383 days) after infection), 57% of participants had persistent cardiac symptoms. Diffuse myocardial edema was more pronounced in participants who remained symptomatic at follow-up as compared to those who improved. Female gender and diffuse myocardial involvement on baseline imaging independently predicted the presence of cardiac symptoms at follow-up. Ongoing inflammatory cardiac involvement may, at least in part, explain the lingering cardiac symptoms in previously well individuals with mild initial COVID-19 illness. In individuals with long-term cardiac symptoms after an initially mild course of COVID-19 illness, magnetic resonance imaging and measurement of cardiac injury biomarkers commonly detected ongoing cardiac inflammation but not structural heart disease.

Published in Nature Medicine (September 5, 2022):

https://doi.org/10.1038/s41591-022-02000-0 

The U.S. Food and Drug Administration said on Wednesday it plans to move quickly to add a warning about rare cases of heart inflammation in adolescents and young adults to fact sheets for the Pfizer/BioNTech (PFE.N), and Moderna (MRNA.O) COVID-19 vaccines. U.S. Centers for Disease Control and Prevention (CDC) advisory groups, meeting to discuss reported cases of the heart condition after vaccination, found the inflammation in adolescents and young adults is likely linked to the vaccines, but that the benefits of the shots appeared to clearly outweigh the risk. Moderna shares closed down 4.2%, while Pfizer fell 1.4%. 

Health regulators in several countries have been investigating whether the Pfizer/BioNTech and Moderna shots using new mRNA technology present a risk and, if so, how serious. The CDC said that patients with heart inflammation following vaccination generally recover from the symptoms and do well. The U.S. Department of Health And Human Services, joined by leading U.S. doctors groups and public health officials, put out a statement underscoring that the vaccines are safe and effective and that the heart side effect is "extremely rare." "We strongly encourage everyone age 12 and older who are eligible to receive the vaccine under Emergency Use Authorization to get vaccinated," it said. Doctors and hospitals have been warned by the CDC to watch for symptoms of myocarditis or pericarditis, and the FDA warning will further raise awareness. Concerns about the more highly transmissible Delta coronavirus variant taking hold in the United States, and its impact on younger people, have added to the urgency to increase vaccinations even as the inoculation effort here has slowed considerably. read more The number of Americans receiving their first dose of COVID-19 vaccine is down about 85% since peaking in mid-April, and will likely fail to meet President Joe Biden's goal to have delivered at least one shot to 70% of adults by July 4. 

"Based on the available data, a warning statement in the factsheets for both healthcare providers and vaccine recipients and caregivers would be warranted," FDA official Doran Fink said at the advisory committee meeting. Fink, deputy director of the agency's vaccines division, said the FDA expects to move quickly to add the warning after the meeting concludes. The cases of heart inflammation appear to be notably higher in the week after the second vaccine dose and in males. The CDC identified 309 hospitalizations from the heart inflammation in persons under the age of 30, of which 295 have been discharged. Dr. Tom Shimabukuro, deputy director of the CDC's Immunization Safety Office, said in a presentation that data from one of the agency's safety monitoring systems - Vaccine Safety Datalink (VSD) – suggests a rate of 12.6 cases per million in the three weeks after the second shot in 12- to 39-year-olds. "We're observing this in the younger age groups, mainly in people in the teens and early 20s, and observing it more in males, compared to females," Shimabukuro said. "This effect largely kind of disappears once you get into these older age groups - individuals 50 and over." The CDC has been investigating heart inflammation cases mainly in young men for several months.

The Israeli health ministry earlier this month said it saw a possible link between such cases and Pfizer's COVID-19 vaccine. read more The CDC said it was still assessing the risk from the condition and did not specifically confirm a causal relationship between the vaccines and the heart issue. It did, however, say that a much-higher-than expected number of young men between the ages of 12 and 24 have experienced heart inflammation after their second vaccine dose. According to data from the U.S. Vaccine Adverse Event Reporting System (VAERS), there were 347 observed cases of heart inflammation in the week after the second vaccine dose in males aged 12 to 24. That compares with expectations of 12 or fewer cases for males in that age range based on U.S. population background incidence rates, the CDC said. Pfizer, whose vaccine has been authorized for use in Americans as young as 12, previously said it had not observed a higher rate of heart inflammation than would normally be expected in the general population. read more Moderna said it is aware of reports of heart inflammation cases following administration of mRNA vaccines. It said it is working with public health and regulatory authorities to assess the issue. Over 138 million Americans have so far been fully vaccinated with one of the two mRNA vaccines, according to CDC data as of Monday.

The family of seven known human coronaviruses are known for their impact on the respiratory tract, not the heart. However, the most recent coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has marked tropism for the heart and can lead to myocarditis (inflammation of the heart), necrosis of its cells, mimicking of a heart attack, arrhythmias, and acute or protracted heart failure (muscle dysfunction). These complications, which at times are the only features of coronavirus disease 2019 (COVID-19) clinical presentation, have occurred even in cases with mild symptoms and in people who did not experience any symptoms. Recent findings of heart involvement in young athletes, including sudden death, have raised concerns about the current limits of our knowledge and potentially high risk and occult prevalence of COVID-19 heart manifestations. The four “common cold” human coronaviruses—HCoV-229E, HCoV-NL63, HCoV-OC43, and HCoV-HKU1—have not been associated with heart abnormalities. There were isolated reports of patients with Middle East respiratory syndrome (MERS; caused by MERS-CoV) with myocarditis and a limited number of case series of cardiac disease in patients with SARS (caused by SARS-CoV) (1). Therefore, a distinct feature of SARS-CoV-2 is its more extensive cardiac involvement, which may also be a consequence of the pandemic and the exposure of tens of millions of people to the virus.

What appears to structurally differentiate SARS-CoV-2 from SARS is a furin polybasic site that, when cleaved, broadens the types of cells (tropism) that the virus can infect (2). The virus targets the angiotensin-converting enzyme 2 (ACE2) receptor throughout the body, facilitating cell entry by way of its spike protein, along with the cooperation of the cellular serine protease transmembrane protease serine 2 (TMPRSS2), heparan sulfate, and other proteases (3). The heart is one of the many organs with high expression of ACE2. Moreover, the affinity of SARS-CoV-2 to ACE2 is significantly greater than that of SARS (4). The tropism to other organs beyond the lungs has been studied from autopsy specimens: SARS-CoV-2 genomic RNA was highest in the lungs, but the heart, kidney, and liver also showed substantial amounts, and copies of the virus were detected in the heart from 16 of 22 patients who died (5). In an autopsy series of 39 patients dying from COVID-19, the virus was not detectable in the myocardium in 38% of patients, whereas 31% had a high viral load above 1000 copies in the heart (6).

Accordingly, SARS-CoV-2 infection can damage the heart both directly and indirectly (see the figure). SARS-CoV-2 exhibited a striking ability to infect cardiomyocytes derived from induced pluripotent stem cells (iPSCs) in vitro, leading to a distinctive pattern of heart muscle cell fragmentation, with “complete dissolution of the contractile machinery” (7). Some of these findings were verified from patient autopsy specimens. In another iPSC study, SARS-CoV-2 infection led to apoptosis and cessation of beating within 72 hours of exposure (8). Besides directly infecting heart muscle cells, viral entry has been documented in the endothelial cells that line the blood vessels to the heart and multiple vascular beds. A secondary immune response to the infected heart and endothelial cells (endothelitis) is just one dimension of many potential indirect effects. These include dysregulation of the renin-angiotensin-aldosterone system that modulates blood pressure, and activation of a proinflammatory response involving platelets, neutrophils, macrophages, and lymphocytes, with release of cytokines and a prothrombotic state. A propensity for clotting, both in the microvasculature and large vessels, has been reported in multiple autopsy series and in young COVID-19 patients with strokes...

Published in Science (Sept. 23, 2020):

https://doi.org/10.1126/science.abe2813