Doctors have reported cardiovascular problems related to COVID-19 during the pandemic, but concern about the problem grew after the results of a VA study were released earlier this year. An analysis by Ziyad Al-Aly, an epidemiologist at Washington University in St. Louis, Missouri, and colleagues is one of the largest attempts to characterize what happens to the heart and circulatory system after the acute phase of COVID-19. Researchers compared more than 150,000 veterans who had recovered from acute illness of COVID-19 with their uninfected peers as well as with a pre-pandemic control group.
People who were admitted to intensive care with acute infections had a drastically higher risk of cardiovascular problems over the next year “Heart Concerns”. For some conditions, such as heart swelling and blood clots in the lungs, the risk increased by at least 20 times compared to uninfected peers. But even people who weren’t hospitalized had an increased risk of many conditions, from an 8% increase in the frequency of heart attacks to a 247% increase in the rate of heart inflammation.
For Al-Aly, the study added to a growing body of evidence that a bout of COVID-19 can permanently change some people’s health. These kinds of changes fall under the category of post-acute sequelae of COVID-19, which covers problems that occur after the initial infection. This disorder includes and overlaps with a persistent condition known as prolonged COVID, a term that has many definitions.
Studies suggest that the coronavirus is associated with a range of lasting problems, such as diabetes2, permanent lung damage3 and even brain damage4. As with these conditions, Al-Aly says cardiovascular problems that occur after SARS-CoV-2 infection can reduce a person’s quality of life in the long term. There are treatments for these problems, “but they are not curable conditions,” he adds.Despite its large size, the VA study comes with caveats, researchers say. The study is observational, meaning it reuses data that was collected for other purposes – a method that can introduce bias. For example, the study only considered veterans, meaning the data is skewed toward white men. “We don’t really have a similar study that’s in a more diverse, younger population,” says Eric Topol, a genomicist at Scripps Research in La Jolla, California. He thinks more research is needed before scientists can truly quantify the frequency of cardiovascular problems.
Daniel Tancredi, a medical statistician at the University of California, Davis, points to another potential source of bias. One of the control groups in the VA study had to go more than a year without contracting SARS-CoV-2 to be included in the study. There could be physiological differences that made the control group less likely to get sick, which could also affect their susceptibility to cardiovascular problems. Still, Tancredi thinks the study was well designed and that any bias is likely to be minimal. “I wouldn’t say these numbers are exactly right, but they’re definitely on track,” he says. He hopes future prospective studies will refine Al-Aly’s estimates.
Some other studies point in the same direction. For example, data from the English health system5 show that people who were hospitalized with COVID-19 were about three times more likely than uninfected people to experience major cardiovascular problems within eight months of hospitalization. A second study6 found that within 4 months of infection, people who had COVID-19 had a roughly 2.5-fold increased risk of congestive heart failure compared to those who were not infected.
Health modeler Sarah Wulf Hanson of the Institute for Health Metrics and Evaluation at the University of Washington in Seattle used Al-Aly’s data to estimate how many heart attacks and strokes are associated with COVID-19. Her unpublished work suggests that complications from COVID-19 caused 12,000 extra strokes and 44,000 extra heart attacks in the United States in 2020, numbers that jump to 18,000 strokes and 66,000 heart attacks in 2021. This means that COVID-19 may have increased heart attack rates by about 8% and strokes by about 2%. “It’s sobering,” says Wulf Hanson.
Indirect effects of the COVID-19 pandemic, such as missed medical appointments, stress and the sedentary nature of isolation at home, are likely to have further contributed to the cardiovascular burden of many people, researchers say.However, these numbers do not match what some researchers have seen in the clinic. In a small study7 of 52 people, Gerry McCann, a cardiac imaging specialist at the University of Leicester in the UK, and his colleagues found that people who recovered from hospitalization with COVID-19 did not have a higher incidence of heart disease than a group of people who had similar baseline conditions but remained uninfected. The trial was an order of magnitude smaller than Al-Aly’s, but McCann and his colleagues are working on a larger study with about 1,200 participants. The results haven’t been released yet, but McCann says “the more data we get, the less we’re going to be impressed by the rate of, say, myocardial damage” or heart problems.
Despite the incomplete picture of the cardiovascular effects of COVID-19, doctors advise caution. An expert panel convened by the American College of Cardiology advises doctors to test people who have had COVID-19 for cardiovascular problems if they have risk factors such as older age or immunosuppression.
How do researchers gather additional information?
Answers to many questions about the long-term effects of COVID-19 could be provided by an extensive study called Researching COVID to Enhance Recovery, or RECOVER, a project whose goal is to follow 60,000 people for up to 4 years at more than 200 locations in the Czech Republic. United States. The study will include participants with long-term COVID, people who have been infected and recovered, and others who have never been infected. “It’s a lifelong record,” says Katz, who is the trial’s principal investigator. He and his colleagues plan to study children, adults, pregnant people and infants born during the trial.
Most RECOVER participants fill out questionnaires about their health and undergo non-invasive tests. Researchers are trying to gather additional information for about 20% of participants, for example by temporarily inserting small tubes into the adults’ hearts to obtain localized measurements of indicators such as blood pressure and oxygen levels. After several years, researchers hope to have completed the catalog of long-term symptoms of COVID, understand who develops them and begin to understand why they occur.
In the UK, McCann leads a cardiovascular task force for a similar project called the Posthospitalization COVID-19 study, or PHOSP-COVID. This multicenter study focuses on people who have been hospitalized with COVID-19 and aims to reveal the prevalence of persistent symptoms, who is most at risk, and how the virus causes persistent health problems. So far, the group has found that only about one-quarter of people who have been hospitalized feel fully recovered one year after infection. And the team identified immune markers that are associated with the worst cases of long-lasting COVID9.
How does the virus damage the heart?
The effect of COVID-19 on the heart could be related to a key protein that the virus uses to enter cells. It binds to a protein called ACE2, which can be found on the surfaces of dozens of types of human cells. This, Al-Aly says, gives it “access and permission to enter almost any cell in the body.”When the virus enters the endothelial cells that line blood vessels, Topol says, that’s likely where many cardiovascular problems begin. Blood clots naturally form to heal damage caused while the body clears the infection. These clots can clog blood vessels, leading to damage as minor as leg pain or as severe as a heart attack. A study10 based on more than 500,000 cases of COVID-19 found that people who were infected had a 167% higher risk of developing a blood clot within two weeks of infection than people who had the flu. Robert Harrington, a cardiologist at Stanford University in California, says that even after the initial infection, plaque can build up where the immune response has damaged the lining of the blood vessels, causing the vessels to narrow. This can lead to problems such as heart attacks and strokes, even months after the initial wound has healed. “These early complications can definitely translate into later complications,” says Harrington.
SARS-CoV-2 could also leave its fingerprints on the immune system. When Akiko Iwasaki, an immunologist at Yale University in New Haven, Connecticut, and her colleagues characterized antibodies from hospitalized people during the acute phase of COVID-19, they found plenty of antibodies against human tissue11. Iwasaki suspects that when SARS-CoV-2 boosts someone’s immune system, it may inadvertently activate immune cells that attack the body—cells that remain silent when the immune system is not in overdrive. These immune cells could damage many organs, including the heart.
Damage to blood vessels can cause attacks on the immune system. “You can think of this damage as accumulating over time,” says Iwasaki. When the cardiovascular system is attacked on enough fronts, that’s when people can experience serious consequences, such as a stroke or heart attack.
What about reinfection and new variants?
Vaccination, reinfection, and the Omicron variant of SARS-CoV-2 all raise new questions about the cardiovascular effects of the virus. A paper published in May by Al-Alym and colleagues suggests that vaccination reduces but does not eliminate the risk of developing these long-term problems12. Hanson is also eager to model whether reinfections increase risk and whether the relatively mild but widespread variant of Omicron will affect the cardiovascular system as drastically as other variants. “We’re kind of buzzing about the follow-up data between the Omicron cases,” he says.
Source Reference: Saima May Sidik, Heart disease after COVID: what the data say, Nature New Feature (2022), https://www.nature.com/articles/d41586-022-02074-3
