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thumbnail Dr. Ziyad Al-Aly of VA St. Louis led both studies, which shined light on serious cardiovascular conditions and mental health disorders that could arise in the weeks or months after initial COVID-19 infection. (Photo by Mary-Dale Amison)

Dr. Ziyad Al-Aly of VA St. Louis led both studies, which shined light on serious cardiovascular conditions and mental health disorders that could arise in the weeks or months after initial COVID-19 infection. (Photo by Mary-Dale Amison)

VA research spells out COVID's down-the-road risks for cardiovascular and mental health

Two studies catalog severe consequences in "long-haul" COVID

February 16, 2022

By Tamar Nordenberg
For VA Research Communications

“Those who go on to experience serious chronic consequences—effects that commonly last a lifetime—are the ones who will bear the scars of this pandemic.”

The most menacing fallout from COVID-19 often shows itself only after the initial “acute” infection passes. A team of VA researchers has been shining a light on COVID’s dangerous and enduring consequences—most recently, in research spotlighting heart and blood vessel conditions and mental health disorders that arise weeks or months after the initial COVID bout. The researchers, with the VA St. Louis Health Care System, published their findings on COVID’s post-acute effects on the heart and blood vessels in the Feb. 7, 2022, issue of Nature Medicine, and findings on the chronic effects on mental health in the Feb. 16, 2022, issue of the British Medical Journal.

The research team found that, even in people not needing hospitalization while infected with COVID-19, serious health issues could persist, or pop up, in the weeks and months after the first, acute stage.

The researchers identified cardiovascular consequences including blood clots, strokes, and heart failure, and mental health issues such as depression, anxiety, sleep disorders, and substance use disorders. It's important to note that the participants in the studies—all Veterans—were all enrolled before Jan. 15, 2021, and that more than 99% were not vaccinated.

COVID-19: far from benign

For many people, COVID-19 infection comes with only mild or moderate symptoms, such as an irksome cough and shortness of breath that last for a few days. But this first phase can be the “tip of the iceberg,” according to the Nature Medicine and BMJ studies’ principal investigator, Dr. Ziyad Al-Aly. “Those who go on to experience serious chronic consequences—effects that commonly last a lifetime—are the ones who will bear the scars of this pandemic.”

Al-Aly heads up both the Clinical Epidemiology Center and the Research and Development Service at the VA St. Louis Health Care System. He is also a nephrologist—a doctor who specializes in kidney disease—and a clinical epidemiologist with expertise in big data. His group analyzes huge data sets too complex for conventional computer software.

In his research, Al-Aly specializes in COVID’s chronic effects, which are known technically as “post-acute sequelae of SARS-CoV-2” and informally as “long COVID” or “long-haul COVID.” Studies conducted by Al-Aly and others have shown that long COVID can affect nearly every organ system. “People return to their doctor with fatigue, brain fog, amnesia, strokes, new-onset diabetes, kidney disease, heart disease, and more,” the physician-researcher says.

From the wide range of chronic consequences of COVID, Al-Aly and his team decided to zero in on the cardiovascular and mental health aftermath because of these health issues’ “profound and wide-reaching ramifications for individual and public health,” says coauthor Dr. Yan Xie, a clinical epidemiologist with the VA St. Louis Clinical Epidemiology Center.

Looking at a study period of about a year, the group compared the cardiovascular and mental health risks for those who had COVID-19 and survived the first 30 days of infection with the same health outcomes among those who were not infected.

Long COVID’s cardiovascular risks

The research team’s in-depth analysis of cardiovascular complications following COVID-19 infection found increased risks for serious conditions such as heart attack, heart failure, blood clots, and stroke. Overall, those with COVID were 55 percent more likely than the non-COVID group to suffer a major adverse cardiovascular event such as heart attack, stroke, or death.

Broken down, the researchers’ major conclusions include:   

  • Heart disease occurred in 4 percent more patients who had COVID than didn’t. This is more significant than it may seem, Al-Aly points out, as it translates into some 3 million people in the United States with these types of complications because of COVID.
  • Those who had been infected with COVID-19 were 72 percent more likely to get coronary artery disease (which is caused by plaque buildup in the artery walls, and presents risks including heart attack).
  • The COVID-19 group was 63 percent more likely to experience a heart attack.
  • The COVID-19 group was 52 percent more likely to have a stroke.

Heightened risks were seen even in people who had mild to moderate COVID-19 symptoms early on, and in those who did not have a known cardiovascular condition before their infection.

“Governments and health systems around the world should be prepared to deal with the likely significant contribution of the COVID-19 pandemic to a rise in the burden of cardiovascular diseases,” the researchers write in Nature Medicine. “Because of the chronic nature of these conditions, they will likely have long-lasting consequences for patients and health systems and also have broad implications on economic productivity and life expectancy.”

Long COVID’s mental health risks

In their examination of mental health conditions after COVID-19, the researchers identified elevated risks for issues such as anxiety, depression, stress disorders, opioid use, substance use disorders, and sleep conditions.  “We’ve all suffered some sort of distress from this pandemic—maybe a measure of anxiety or difficulty sleeping,” says lead investigator Al-Aly. “But these challenges are magnified, especially in those who were admitted to the hospital during the acute part of their COVID battle but also in many who experienced only mild or moderate symptoms.”

Compared to those who did not have COVID, those in the COVID group had a 60 percent higher risk of having any mental health disorder or mental health-related prescriptions. Findings by the type of mental health issue were:

  • Anxiety: 35 percent higher risk in the COVID-19 group
  • Depression: 39 percent higher risk
  • Sleep disorder: 41 percent higher risk
  • Opioid use: 76 percent higher risk
  • Opioid use disorders: 34 percent higher risk
  • Non-opioid substance use disorders: 20 percent higher risk.

The reasons for the increased mental health risks after COVID are not completely clear, the researchers say. Biologic changes may occur in the body that affect the brain, and nonbiologic changes such as social isolation and trauma may also be at play.

Given the large number of people who have survived COVID-19, the findings on cardiovascular and mental health could translate into a huge impact in the United States and around the world, the authors point out.

VA’s standout data resources

In both studies, the researchers analyzed medical records in a database within VA, which operates the largest integrated health care system in the United States. The analysis in each case included nearly 154,000 patients who had tested positive for COVID-19 in a defined time frame in 2020 and 2021. (The time frame predated the delta and omicron variants, as well as wide availability of vaccines.) Using sophisticated statistical methods, the researchers compared these patients’ health information related to cardiovascular and mental health to data from more than 11 million people who had not had COVID-19 infection—about half of them from the same time frame and the other half from a pre-pandemic timespan.

“A strength of our research was the large number of patients and the ability to leverage the breadth and depth of the VA’s electronic health records system,” highlights Al-Aly. As a pioneer in the use of electronic health records, VA “can offer answers to questions about areas including the pandemic that would be hard for others to address.”

Al-Aly also credits his multidisciplinary research team representing VA, as well as Washington University and Saint Louis University, for making the rigorous analyses possible. “We brought together public health experts from across disciplines, successfully marrying the medical and research perspectives.” Along with Al-Aly and Xie, coauthors on the Nature Medicine article about cardiovascular risks were Evan Xu, with VA St. Louis and Saint Louis University, and VA St. Louis’s Benjamin Bowe. Xu also contributed to the BMJ mental health study.

Urging steps to protect, prepare

The team hopes their research and that of other groups will encourage individuals, health care systems, and policymakers to remain vigilant concerning the virus. 

The best defense against long COVID, according to the researchers: Avoid getting COVID in the first place. That means taking steps such as getting vaccinated and boosted, wearing high-quality masks, and washing hands regularly, Xie specifies. For those who become infected and develop cardiovascular or mental health conditions, Xie says, “We hope our results will make it easier for them and their health care providers to identify these conditions and initiate treatment.”

From a broader, public-policy perspective, Al-Aly urges a prompt and robust response to support the at-risk population, which he hopes from the mental health perspective will avert a suicide crisis and compounded opioid epidemic in upcoming years. Xie, too, emphasizes the importance of responsive action. “There will be millions of people with new heart disease and mental health issues as a result of COVID who will need attention and care. Governments and health systems should be prepared for this. It is very important to address these issues now, before they become much larger crises down the road.”

Al-Aly says he and his colleagues will continue studying long COVID. “As a physician and a researcher myself, working with a group of full-time researchers, we will continue to leverage our expertise to answer questions that the public, including Veterans and Veterans’ organizations, care about.” Al-Aly’s ongoing research includes an examination of the link between long COVID and diabetes. “By generating more awareness of the spectrum of health complications long-haulers face,” he says, “we can work to nip this long COVID crisis in the bud and keep it from ballooning into a larger public health plight.”

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