Long Covid May Increase Risk of Heart Disease

By Pia Lindberg, Artur Fedorowski and Axel Carl Carlsson

Most people who get COVID recover within a few weeks. But for some, symptoms persist for months – a condition now known as long COVID. While it’s often associated with fatigue, breathlessness and “brain fog”, growing evidence suggests it may also affect something less visible, but potentially more serious: the heart.

In our recent study, we found that people with long COVID had higher risk of developing cardiovascular disease – including cardiac arrhythmias, heart attack and heart failure. Importantly, the increased risks were seen in people who had never been hospitalised during their initial COVID infection.

Much of the early research on long COVID and heart health focused on patients who were hospitalised, particularly those treated in intensive care. These patients often had multiple risk factors for cardiovascular disease such as being overweight and having hypertension or diabetes. This made it difficult to separate the effects of severe acute illness from the long-term effects of the infection.

However, the majority of people who had COVID were never admitted to a hospital – yet many still developed chronic symptoms of so-called long COVID. To explore the potential risks in this much larger group, we focused specifically on patients who had experienced a mild-to-moderate COVID infection which they managed at home.

We used healthcare data from more than 1.2 million adults living in Stockholm, Sweden. Among them, 9,000 were diagnosed by a doctor with long COVID. We then followed up these patients over time and compared occurrence of new cardiovascular disease – including heart attack, heart failure, arrhythmias, stroke and peripheral arterial disease – with people who did not have long COVID and had no previous cardiovascular disease.

After a follow-up period of up to four years, cardiovascular disease was more common among people with long COVID.

Among women with long COVID, 18% experienced some form of cardiovascular event, compared with 8% of women without long COVID. Among men, the corresponding figures were 21% versus 11%.

These results did not substantially differ even when we adjusted analyses for age, socioeconomic status and underlying health status – including conditions such as high blood pressure, diabetes, high cholesterol, obesity, depression, smoking and alcohol consumption which are known risk factors of cardiovascular disease.

Women with long COVID had more than double the risk of developing cardiovascular disease overall compared with women without long COVID, while men had around a 30% higher risk.

The strongest associations were seen for irregular heart rhythm and coronary heart disease. In women, we also observed an increased risk of heart failure and peripheral arterial disease. However, we did not find an association between long COVID and stroke risk.

Why Long Covid Might Affect the Heart

It’s not fully understood why long COVID is associated with cardiovascular disease, but several biological mechanisms have been proposed.

The virus can affect the lining of blood vessels, leading to what is known as endothelial dysfunction. It may also trigger long-lasting inflammation and changes in the immune system. Together, these processes can affect how blood flows through the body and how the heart functions.

There’s also growing evidence that long COVID can disrupt the autonomic nervous system – the automatic mechanisms that control heart rate and blood pressure. This may potentially explain why irregular heart rhythms and conditions such as postural orthostatic tachycardia syndrome (Pots) are more common in long COVID patients.

Another possibility is that long COVID may not necessarily cause entirely new disease, but rather reveal underlying conditions that had not yet been diagnosed. In some cases, symptoms such as chest pain or palpitations may lead to further medical evaluation, increasing the likelihood that cardiovascular disease is detected.

Our findings suggest that long COVID is not simply a transient condition, even among people who were never severely ill during the acute infection. Instead, it may have longer-term implications for cardiovascular health.

At the same time, it’s important to put the results into context. The overall risk of cardiovascular disease remains relatively low at the population level. But the relative increase in risk is meaningful and comparable to that seen with established cardiovascular risk factors such as hypertension or diabetes.

The increased cardiovascular risk in long COVID has also important implications for healthcare. Patients with long COVID – particularly women and younger patients – may benefit from more structured follow-up, including assessment of cardiovascular symptoms and better management of cardiovascular risk factors

It also suggests that long COVID should be included in future strategies for cardiovascular risk assessment and prevention, not only in specialist care but also in primary care settings where most of these patients are managed.

More research is now needed to understand the long-term trajectory of these risks and whether they persist, decrease or increase over time. Future studies should also explore whether early identification and management of cardiovascular symptoms in long COVID could help reduce the risk of more serious complications later on.

As the number of people living with long COVID continues to grow, understanding its broader health consequences will be essential – not only for each patient, but for healthcare systems as a whole.

Pia Lindberg is a registered nurse at the Karolinska Institutet in Sweden.  

Artur Fedorowski, MD, is Professor of Cardiology at the Karolinska Institutet and Senior Consultant at the Cardiology Clinic of Karolinska University Hospital in Sweden.

Axel Carl Carlsson, PhD, is a Researcher in the Department of Neurobiology at the Karolinska Institutet.

This article originally appeared in The Conversation and is republished with permission.

Long COVID Risk Declining, Mostly Due to Vaccinations

By Crystal Lindell

Rates of Long Covid appear to have declined over the course of the pandemic, according to new research from the Washington University School of Medicine. One reason is that people who are vaccinated against COVID-19 and its variants have about half the risk of developing Long Covid than those who are unvaccinated.

Long Covid refers to a wide range of symptoms that some people experience four or more weeks after an initial infection with COVID-19. Symptoms such as fatigue, body pain and shortness of breath may last for weeks, months or years, and can be mild or severe.  

While the new research only looked at COVID cases through 2022 – making it unclear how newer COVID strains and vaccines in 2023 and 2024 may be impacting Long COVID cases  – it does provide a ray of hope.

Specifically, researchers attributed about 70% of the risk reduction to vaccination against COVID-19 and 30% to changes over time, such as the evolving characteristics of SARS-CoV-2 and improved detection and management of COVID-19. The research was published in The New England Journal of Medicine.

“The research on declining rates of long COVID marks the rare occasion when I have good news to report regarding this virus,” said the study’s senior author, Ziyad Al-Aly, MD, a Washington University clinical epidemiologist and global leader in COVID-19 research. “The findings also show the positive effects of getting vaccinated.”

Although the latest findings sound more reassuring than previous studies, Al-Aly tempered the good news. 

“Long COVID is not over,” said the nephrologist, who treats patients at the John J. Cochran Veterans Hospital in St. Louis. “We cannot let our guard down. This includes getting annual COVID vaccinations, because they are the key to suppressing long COVID risk. If we abandon vaccinations, the risk is likely to increase.”

For the research, Al-Aly and his team analyzed millions of de-identified medical records in a database maintained by the Department of Veterans Affairs, the nation’s largest integrated health-care system. 

The study included over 440,000 veterans with SARS-CoV-2 infections and more than 4.7 million uninfected veterans. Patients included those who were infected by the original strain, as well as those infected by the delta and omicron variants. Some were vaccinated, while others were unvaccinated. 

The Long COVID rate was highest among those with the original strain, about one in every ten (10.4%). No vaccines existed while the original strain circulated.

The rate declined to 9.5% among those in the unvaccinated groups during the delta era and 7.7% during omicron. Among the vaccinated, the rate of Long COVID during delta was 5.3% and 3.5% during omicron.

“You can see a clear and significant difference in risk during the delta and omicron eras between the vaccinated and unvaccinated,” said Al-Aly. “So, if people think COVID is no big deal and decide to forgo vaccinations, they’re essentially doubling their risk of developing long COVID.”

Al-Aly also emphasized that even with the overall decline, the lowest rate — 3.5% — remains a substantial risk. 

“That’s three to four vaccinated individuals out of 100 getting long COVID,” he said. “Multiplied by the large numbers of people who continue to get infected and reinfected, it’s a lot of people. This remaining risk is not trivial. It will continue to add to an already staggering health problem facing people across the world.”

The World Health Organization has documented more than 775 million cases of COVID-19.

Disabled at Higher Risk of Long COVID  

The CDC recently found that Long COVID symptoms were more prevalent among people with disabilities (10.8%) than among those without disabilities (6.6%).

The new data was released as part of the CDC’s annual update to its Disability and Health Data System, which provides quick and easy online access to state-level health data on adults with disabilities.

The report found data that over 70 million adults in the U.S. reported having a disability in 2022.

Older adults reported a higher disability rate (43.9% for those aged 65 and older) compared to younger age groups. The race/ethnic groups with the highest rate of disability, regardless of age, identified as American Indian or Alaska Natives.

The CDC has fact sheets that provide an overview of disability in each state, including the percentages and characteristics of adults with and without disabilities. Click on any state listed here to view that state’s profile.

The findings underscore the fact that people with disabilities are a large part of every community and population.

What Are the Long-Term Risks of Prescription Opioids?

By Roger Chriss, PNN Columnist

A standard critique of prescription opioids is the absence of good long-term data on safety and efficacy. Clinical trials are generally short-term and last only a few weeks, so questions about cumulative long-term risks, including addiction and overdose, remain unclear.

Clinical trials that run for a year or more are complex and costly. Attrition may be high and outcomes may be muddied by the inevitable effects of aging, disease progression, and life events. There are also ethical issues involved with subjecting patients to long-term trials where they may receive nothing more than a placebo.

In other words, launching new trials is often impractical. Fortunately, there are a few other ways to answer questions about long-term opioid risk.

Compare Outcomes

First, we can compare outcomes among patients whose key difference is opioid dosage. In a recent Canadian study, researchers looked at over 2 million individuals in Ontario given an opioid prescription between 2013 and 2016 for pain. They identified 1,121 patients who had a fatal or non-fatal overdose – a minuscule overdose rate of 0.0055 percent.

But when compared to patients getting relatively low daily doses of 20 morphine milligram equivalents (MME), those who received 200 MME or more had a “high hazard of overdose.”  

A dose of 200 MME may be an extreme example, since Canadian guidelines recommend that initial doses be limited to no more than 50 MME. But researchers said their study proves the value of guidelines. 

“Although the absolute risk of an opioid overdose within the first year of prescription opioid use is low, better alignment of opioid initiation practices with guidelines may reduce opioid-related harm,” they concluded. 

Compare Opioids 

Second, we can compare two opioids: oxycodone and hydrocodone. In a retrospective analysis of patients in Oregon between 2015 and 2017, researchers found that after an initial prescription in opioid-naive people, 0.3% experienced a fatal or non-fatal overdose and 2.8% refilled an opioid prescription at least six times, what the researchers considered “chronic opioid use.” 

Patients who received oxycodone were less likely to develop chronic use than those receiving hydrocodone, but the oxycodone patients had a slightly higher risk of overdose.  

Based on that finding, researchers concluded that “hydrocodone may be the favorable agent” when starting people on opioids. 

Compare Odds

We can also use statistical inference to estimate risks. In an analysis of 13,884 U.S. adults living with chronic pain between 1999 and 2004, epidemiologists found that 5% died from all causes within 3 years and 9% died within 5 years.  

Researchers found that chronic pain patients on opioids had a slightly higher risk of death – and calculated an odds ratio of 1.06 for them dying within three years and 1.03 at five years compared to those not taking opioids.  

It’s hard to infer much from a study like that, because researchers didn’t establish a causal relationship between opioids and death. Since chronic pain itself raises the risk of dying, the findings could simply mean that patients on opioids are sicker, in more pain, and closer to death.  

Despite this, researchers came to the sweeping conclusion that “chronic pain increased the risk of all-cause mortality through opioid prescriptions.” 

Compare Health Outcomes 

Last, we can look at health outcomes. An alarming, preliminary study from Taiwan evaluated chronic pain patients on long-term opioid therapy and found they have significantly higher risk for cancer compared to those not taking opioids. 

The overall hazard ratio for the opioid group was 2.66 – which means they have over twice the risk of having many different types of cancer. 

“Long-term opioid use might be a significant risk factor for breast, gastric, colorectal, ovarian, prostate, lung, pancreatic, head and neck, and esophageal cancers and HCC (hepatocellular carcinoma),” researchers concluded in their study, which has not yet been peer-reviewed. 

Risks of Other Drugs 

These findings help shed light on the long-term risks of prescription opioids, at least compared to healthy control subjects who do not take opioids. However, that is not the situation faced by most people with chronic illness, who are often on multiple medications to manage their pain and other symptoms.  

As a result, we need to know the risks of non-opioid pain management options. For instance, the consequences of cannabis addiction are low compared to opioids. But the cancer risk appears to be substantially higher. A major review in BMC Archives of Public Health found that “cannabinoids including THC and cannabidiol are important community carcinogens exceeding the effects of tobacco or alcohol.”

The risks of non-steroidal anti-inflammatory drugs (NSAIDs) are well-known. According to a 2011 review, “chronic NSAID use increases the risk of peptic ulcer disease, acute renal failure, and stroke/myocardial infarction. Moreover, chronic NSAID use can exacerbate a number of chronic diseases including heart failure and hypertension.” 

For other non-opioid medications, we lack long-term studies. For instance, a 2017 Cochrane review on gabapentin for chronic neuropathic pain notes that “study duration was typically four to 12 weeks.” Cochrane also notes that only short-term trials were conducted for serotonin and norepinephrine reuptake inhibitors like duloxetine for fibromyalgia.  

As for non-pharmacological options like spinal cord stimulators, the situation is similarly uncertain. A new Australian study in the Journal of Patient Safety found that for every 10 stimulators that were surgically implanted, four had to me removed for various reasons. That outcome went unnoticed in short-term studies and emphasizes the need for more careful patient selection and monitoring of outcomes.  

There are real risks to prescription opioids but it would be simplistic to dismiss them entirely. As pain physician Antje Barreveld notes in a recent STAT News op-ed: “Opioids do have a place in pain control and can be safely prescribed, even at high doses, by following best practices while monitoring for risks and side effects.” 

Understanding the long-term risks of prescription opioids will be important as the CDC finalizes its revised opioid guideline, and as regulators, insurers and clinicians decide how to act on them. But more generally, we need long-term studies of all pain management modalities so that we can better understand their risks.

Roger Chriss lives with Ehlers Danlos syndrome and is a proud member of the Ehlers-Danlos Society. Roger is a technical consultant in Washington state, where he specializes in mathematics and research.