MEE N5195 VI, The Heart Saver 
 
How many people are at risk?
Doctors have reported cardiovascular problems related to COVID-19 throughout the pandemic, but concerns over this issue surged after the results of the VA study came out earlier this year. The analysis by Ziyad Al-Aly, an epidemiologist at Washington University in St. Louis, Missouri, and his colleagues is one of the most extensive efforts to characterize what happens to the heart and circulatory system after the acute phase of COVID-19. The researchers compared more than 150,000 veterans who had recovered from acute COVID-19 with their uninfected peers, as well as with a pre-pandemic control group.
 
People who had been admitted to intensive care with acute infections had a drastically higher risk of cardiovascular problems during the next year. For some conditions, such as swelling of the heart and blood clots in the lungs, the risk shot up at least 20-fold compared with that in uninfected peers. But even people who had not been hospitalized had increased risks of many conditions, ranging from an 8% increase in the rate of heart attacks to a 247% increase in the rate of heart inflammation.
 
How does the virus harm the heart?
COVID-19's effect on the heart could be related to the 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 cell. This, says Al-Aly, 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 probably where many cardiovascular problems start. Blood clots form naturally 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 COVID-19 cases found that people who had been infected had a 167% higher risk of developing a blood clot in the two weeks after infection than people who had had influenza. Robert Harrington, a cardiologist at Stanford University in California, says that even after the initial infection, plaques can accumulate where the immune response has damaged the lining of 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. “Those early complications can definitely translate into later complications,” Harrington says.
 
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 a plethora of antibodies against human tissue11. Iwasaki suspects that when SARS-CoV-2 ramps up someone’s immune system, it might inadvertently activate immune cells that attack the body — cells that stay quiet when the immune system isn’t in overdrive. These immune cells could damage many organs, including the heart.
 
Damage to blood vessels can compound attacks on the immune system. “You can think of this damage as accumulating over time,” says Iwasaki. When the cardiovascular system has been assaulted on enough fronts, that’s when people can experience serious consequences, such as a stroke or heart attack.

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References
1. Al-Aly, Z., Heart disease after COVID: what the data say.nature. (2022).
2. Bazdyrev, E. et al. Pharmaceuticals 14, 807 (2021).
3. Boldrini, M., Canoll, P. D. & Klein, R. S. JAMA Psychiatry 78, 682–683 (2021).
4. Ayoubkhani, D. et al. BMJ 372, n693 (2021).
5. The PHOSP-COVID Collaborative Group. Lancet Respir. Med. 10, 761–775 (2022).