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In the opening months of the COVID pandemic we saw an abrupt increase in out-of-hospital cardiac arrests. In early April 2020, the New York Fire Department reported a 400% increase in sudden cardiac arrest death calls beginning in late March (see NBC affiliate Massive Spike in NYC ‘Cardiac Arrest’ Deaths Seen as Sign of COVID-19 Under counting).
While most of these cases were never tested for COVID-19, this trend became so pronounced that the city ordered new Standards Of Care During A Pandemic: CPR & Cardiac Arrest, limiting the use of CPR in the field.
By mid-summer of that year, it was apparent that COVID was more than just a respiratory virus (see Nature Med. Review: Extrapulmonary manifestations of COVID-19), and can cause blot clots, along with severe cardiovascular damage.
Since then we've seen numerous studies linking SARS-CoV-2 infection with heart attacks, strokes, and other serious extrapulmonary events. A small sampling include:
Nature: Long-term Neurologic Outcomes of COVID-19
BMJ: Elevated Risk Of Blood Clots Up To 6 Months After COVID Infection
Diabetologia: Incidence of Newly Diagnosed Diabetes After Covid-19
Admittedly, the impact of today's Omicron lineage in a highly vaccinated/previously exposed population is likely far different from what the first wave of the virus in an immunologically naïve population produced.
But the virus continues to kill thousands of people around the globe each month, and with reduced testing, surveillance and reporting, we have only a vague idea as to its ongoing impact on public health.
Yesterday the NIH published the following summary of a study, published in Nature Cardiovascular Research, which finds the SARS-COV-2 virus from early 2020 directly infected coronary arteries, increased plague inflammation, and likely lead to increased cardiac events.
SARS-CoV-2 infects coronary arteries, increases plaque inflammation
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.
This work was funded by the NIH/NHLBI grants 1R01HL165258, R01HL153712, R35HL135799 and R01HL084312. NIAID and NIDDK also provided funding.
The link and Abstract to the open access Study:
SARS-CoV-2 infection triggers pro-atherogenic inflammatory responses in human coronary vesselsNatalia Eberhardt, Maria Gabriela Noval, Ravneet Kaur, Letizia Amadori, Michael Gildea, Swathy Sajja, Dayasagar Das,Burak Cilhoroz, O’ Jay Stewart, Dawn M. Fernandez, Roza Shamailova, Andrea Vasquez Guillen, Sonia Jangra, Michael Schotsaert, Jonathan D. Newman, Peter Faries, Thomas Maldonado, Caron Rockman,Amy Rapkiewicz, Kenneth A. Stapleford, Navneet Narula,Kathryn J. Moore & Chiara Giannarelli
Nature Cardiovascular Research (2023)Cite this article
Abstract
Patients with coronavirus disease 2019 (COVID-19) present increased risk for ischemic cardiovascular complications up to 1 year after infection. Although the systemic inflammatory response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection likely contributes to this increased cardiovascular risk, whether SARS-CoV-2 directly infects the coronary vasculature and attendant atherosclerotic plaques remains unknown.
Here we report that SARS-CoV-2 viral RNA is detectable and replicates in coronary lesions taken at autopsy from severe COVID-19 cases. SARS-CoV-2 targeted plaque macrophages and exhibited a stronger tropism for arterial lesions than adjacent perivascular fat, correlating with macrophage infiltration levels. SARS-CoV-2 entry was increased in cholesterol-loaded primary macrophages and dependent, in part, on neuropilin-1. SARS-CoV-2 induced a robust inflammatory response in cultured macrophages and human atherosclerotic vascular explants with secretion of cytokines known to trigger cardiovascular events.
A recent CIDRAP News Report (see Survey: 18 million Americans say they have long COVID) is a reminder that the impacts of COVID infection can linger long after the acute phase of the illness, and some experts have warned we may see huge increases in COVID-19 related heart failure and neurological diseases in the years ahead.Our data establish that SARS-CoV-2 infects coronary vessels, inducing plaque inflammation that could trigger acute cardiovascular complications and increase the long-term cardiovascular risk.
Clyde W. Yancy, MD, MSc1,2; Gregg C. Fonarow, MD3,4JAMA Cardiol. Published online July 27, 2020. doi:10.1001/jamacardio.2020.3575
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Given that we are still learning about the cumulative impacts of repeated COVID infection - until we know more - even `mild' COVID illness would seem worth avoiding if at all possible.
