12-05-2025
Cardiovascular Implications of Long COVID, Severe COVID
As cases of long COVID — often defined as symptoms that weren't present before persisting for 3 or more months after the infection — became more prevalent and alarming, researchers began to zero in on the commonly reported cardiovascular symptoms of fatigue, shortness of breath, chest pain, and palpitations, among others.
Long-COVID patients, much research has found, have significantly higher odds of developing cardiac complications than those without long COVID.
Now, some researchers recommend that severe COVID, such as cases requiring hospitalization, be viewed as an independent cardiovascular risk factor, regardless of the patient's cardiac health history, and that aggressive measures be initiated.
Others say there's not yet enough evidence to recognize severe COVID as an independent risk factor.
How Many Are Affected?
Statistics about how widespread long COVID is vary, with the Centers for Disease Control and Prevention (CDC) estimating in 2022 that more than 40% of US adults reported having COVID, and 1 in 5 were still reporting symptoms. At any one time, according to the National Institutes of Health, a million people are out of work due to long COVID, and as many as 23 million Americans may have long-COVID symptoms.
Severe COVID-19 as a 'Coronary Artery Disease Risk Equivalent'
'Severe COVID is a coronary artery disease risk equivalent,' Stanley Hazen, MD, PhD, co–section head of Preventive Cardiology and Cardiac Rehabilitation and department chair of Cardiovascular and Metabolic Sciences at Cleveland Clinic, Cleveland, told Medscape Medical News .
Stanley Hazen, MD, PhD
He bases that statement on a study his team did, using data from the UK Biobank to identify 10,005 people who were positive for polymerase chain reaction (PCR)–based tests for COVID-19 or who were hospitalized for COVID-19 between February 1, 2020, and December 31, 2020. The researchers also looked at 217,730 population control individuals and 38,860 propensity-matched control individuals during the same time. They used proportional hazard models to evaluate COVID-19 for its association with long-term risks (> 1000 days) for major adverse cardiac events (MACEs) and as a coronary artery disease risk equivalent.
The risk for MACEs was elevated in those with COVID-19 at all levels of severity (hazard ratio [HR], 2.09; P < .0005) and to a greater extent in those hospitalized for COVID-19 (HR, 3.85; P < .0005). Hospitalization for COVID-19, they found, was a coronary artery disease risk equivalent because the risk for incident MACEs in those with severe COVID without a history of cardiovascular disease was even higher than that found in patients with cardiovascular disease without COVID-19 (HR, 1.21; P < .005).
'We had a 3-year period of follow-up,' Hazen said. 'That risk seems to be persistent. If you look at all comers, all with a positive PCR test, we found about a doubling of the risk for heart attack, stroke, and death.'
'We only looked at people who were 50 and older, but it was over 200,000 subjects,' Hazen said. 'The other thing that was clear is that the more severe the infection, the higher the risk of post-COVID cardiac events.'
Over the 3-year follow-up, he said, the risk for a cardiac event was the same in patients with severe COVID and in those with a history of heart attack.
In clinical practice, he pointed out, 'a coronary artery disease risk equivalent has been used as the threshold for escalating preventive efforts in the community.'
Having diabetes, for example, is a coronary artery disease risk equivalent, he said. Based on the research, 'we are arguing that if you had severe COVID, we should be treating these patients as if they have coronary artery disease and really escalate their preventive care.'
For these patients, he recommended a more aggressive lowering of cholesterol levels, such as aiming for a low-density lipoprotein level of below 70 or even lower and to be more aggressive with antiplatelet therapy, such as low-dose aspirin. 'It looks like the degree of infection somehow 'rewires' a person and makes them more proinflammatory long term,' Hazen said.
'We weren't able to look at the effect of vaccination [on the degree of infection or the MACE risk],' he said, as the study was launched before vaccines were available. 'There is every reason to believe vaccines will attenuate this risk because they reduce the likelihood of serious infection.'
In Hazen's view, the most important take-home is that 'we should be looking at COVID as a risk factor' for heart disease, 'and we don't yet.'
Long COVID and the Heart: 11 Studies
Other research has produced similar links between severe COVID and cardiac issues. For instance, long COVID more than doubles the risk for new cardiac symptoms, researchers conducting a systematic literature review and meta-analysis of 11 studies with 5.8 million people found.
As the definition of long COVID varies, these researchers termed it as symptoms lasting for at least 4 weeks and occurring at least 2 months after the initial SARS-CoV-2 infection. Those with a history of long COVID had a 2.3-2.5 times higher rate of cardiac complications than those without ( P = .01).
Another View: Not Enough Evidence
Kieran Quinn, MD, PhD, a clinician-scientist at Sinai Health System and assistant professor of medicine at the University of Toronto, Toronto, Ontario, Canada, does not agree that a history of severe COVID can be termed a coronary artery disease risk equivalent at this point.
Kieran Quinn, MD, PhD
'I don't believe we have sufficient evidence to recognize is as an independent risk factor that is comparable to more conventional risk factors like smoking, diabetes, and hypertension,' he told Medscape Medical News .
He does agree the cardiac implications are associated with severe and long COVID. With his colleagues, Quinn set out to provide guidance to clinicians on the workup and management of adults with suspected long COVID and unexplained cardiac symptoms, retrieving 260 articles from an extensive databases and examining closely the five studies that met their criteria.
The researchers noted that about 15% of adult Canadians with SARS-CoV-2 infection develop post-COVID condition or long COVID. Among the cardiovascular symptoms are fatigue, shortness of breath, chest pain, and palpitations.
Among the recommendations are to conduct routine tests such as baseline ECGs, thyroid-stimulating hormone, and blood glucose levels but against the routine use of other tests, such as cardiac MRIs, reserving it for those with symptoms suggestive of cardiac involvement.
Comparing COVID, Influenza, Sepsis, and Health Impacts
Quinn pointed, too, to what he calls 'a growing body of literature demonstrating that multiple different types of acute infections can lead to the development of acute and chronic cardiovascular conditions.'
He cited his own study, asking if the risk of newly developing medical and mental health conditions are greater within a year of hospitalization for severe COVID vs influenza or sepsis.
The population-based cohort study in Ontario included all adults who were hospitalized for COVID-19 between April 1, 2020, and October 31, 2021, with historical comparator groups hospitalized for influenza or sepsis and a contemporary comparator group hospitalized for sepsis.
The researchers looked for a new occurrence of 13 conditions, including cardiovascular, neurological, and mental health conditions and rheumatoid arthritis within 1 year of hospitalization. Of the 379,366 adults included, 26,499 survived hospitalizations for COVID, 299,989 were historical control individuals hospitalized for influenza or sepsis, and 52,878 were hospitalized for sepsis.
Hospitalization for COVID-19 vs influenza was associated with an increased 1-year risk for venous thromboembolic disease (adjusted HR, 1.77) but with no increased risk for selected ischemic and nonischemic cerebrovascular and cardiovascular disorders, neurological disorders, rheumatoid arthritis, or mental health conditions compared with influenza or sepsis cohorts.
According to Quinn, it showed that 'apart from an elevated risk of venous thromboembolism within 1 year, the burden of post-acute medical and mental health conditions among those who survived hospitalization for COVID-19 was comparable with other acute infectious illnesses, including the development of chronic cardiovascular conditions like heart failure.'
The take-home point, he suggested, is that 'many of the post-acute consequences of COVID-19 may be related to the severity of infectious illness necessitating hospitalization rather than being the direct consequence of infection with SARS-CoV-2.'
Guidance for Helping Long-COVID Patients
Quinn is also a co-chair of the Canadian Guidelines for Post COVID-19 Condition and pointed to 80 evidence-informed recommendations released recently for the care of people with long COVID, with more guidelines expected in the coming months. 'My advice to all physicians caring for people living with long COVID is to use these guidelines to guide shared decision-making around testing and treatments.'
The CDC also offers clinical guidance for managing long COVID.
Hazen and Quinn had no relevant disclosures.
