What we know and what we don’t know

In a recently published study, Nature Cardiovascular Research, Researchers are examining the long-term cardiovascular effects of COVID-19.

study: Impact of post-COVID-19 condition on the cardiovascular system. Image credit: YAKOBCHUK VIACHESLAV / Shutterstock.com

Post-COVID-19

Post-COVID-19, also known as Long COVID or Post-Acute Sequelae of COVID-19 (PASC), is a new condition that affects 10-60% of COVID-19 survivors, amounting to 70-420 million people worldwide. Long COVID is characterized by the persistence of symptoms and in some cases the development of new symptoms after recovery from COVID-19.

The World Health Organization (WHO) and the US Centers for Disease Control and Prevention (CDC) estimate that long-term symptoms of COVID-19 may persist for months or years after recovery from initial infection, resulting in a significant reduction in the quality of life (QoL) of infected individuals.

More than 23,000 publications on Long COVID have been published since 2020. Despite the focus on the prevalence and definition of the disease, several studies have aimed to understand the pathophysiology and underlying mechanisms of the disease, with the common goal of finding a treatment.

Despite significant progress, targeted treatment for long COVID remains challenging. Thus, a synthesis of the rapid scientific advances in post-COVID-19 research highlights recent progress while also highlighting important gaps in the literature.

Diagnosing Long COVID

Despite being primarily a respiratory disease, there is growing evidence reporting systemic effects of COVID-19, a hallmark of long COVID, with over 20 symptoms identified so far across the respiratory, cardiovascular, neurological, gastrointestinal and endocrine systems. Common non-specific symptoms include dizziness, fatigue and memory loss.

Given the novelty of the symptoms, clinical diagnostic tests for post-COVID-19 syndrome are theoretical. As a result, the 12-symptom checklist from the National Institutes of Health’s COVID Research to Accelerate Recovery (RECOVER) initiative is the current gold standard for long COVID diagnosis.

Recent cardiovascular-focused research has led to the development of cardiovascular-focused guidelines, such as the American College of Cardiology’s clinical practice guideline documents.

Although cardiovascular complications following COVID-19 infection have been widely reported, the sequelae of this virus are not particularly unique. Cardiovascular effects, including myocarditis, have previously been reported following other viral illnesses, such as influenza and Epstein-Barr virus. However, the mortality rate and incidence of vascular complications from COVID-19 are much higher.

Long COVID is confirmed through a variety of laboratory tests, including complete blood count, metabolic panel, troponin, C-reactive protein, pro-brain natriuretic peptide levels, electrocardiogram (ECG), echocardiogram, etc. In severe cases, magnetic resonance imaging (MRI) and chest x-ray may be used.

How Long COVID Impacts Cardiovascular Health

Long COVID-associated cardiovascular pathophysiology can be categorized into immune dysregulation and inflammation, endothelial dysfunction, microangiopathy, and neuronal signaling dysfunction. Two main phenotypes of Long COVID have been identified: overt cardiovascular disease after COVID-19 (PASC-CVD) and cardiovascular symptoms in the absence of overt disease markers (PASC-CVS).

PASC-CVD patients are often older and at higher risk for endothelial dysfunction, inflammation, and microvascular injury. In comparison, PASC-CVS patients are typically younger and at higher risk for neural signaling dysfunction and immune dysregulation.

The mechanisms responsible for the cardiovascular effects of long COVID could be immediate through direct cellular injury or delayed due to a cascade of responses mediated by immune hyperstimulation.

Cardiovascular symptoms of long COVID

Postural orthostatic tachycardia syndrome (POTS) is one of the most commonly studied cardiovascular conditions, characterized by a rapid increase in heart rate when repeatedly sitting, lying down, and standing up. POTS was identified early in the COVID-19 pandemic and represented the highest prevalence of the PASC-CVS phenotype.

The most common test for POTS is the head-up tilt table test (HUTT), but several studies have found that many POTS patients are not detected by the HUTT, 4 and as a result, estimates of the prevalence of POTS may be significantly underestimated.

Myocardial injury is another common feature post-COVID-19 and, unlike POTS, there is clear biomarker evidence of its prevalence through troponin testing. Myocardial injury is much better characterized as it arises both from the consequences of common severe illness in acute COVID-19, such as hypoxia and shock, as well as from structural cardiac pathology.

Recent studies have elucidated the role of COVID-19 in causing myocardial injury through hypercoagulation, which subsequently increases the risk of heart failure and myocarditis.

Cardiac arrhythmias, or arrhythmias, have been identified through comorbidities such as release of inflammatory cytokines, myocardial scarring and fibrosis, persistent immune dysfunction, and potential gap junction dysfunction.

Although no curative treatment has been identified for long COVID, cardiovascular manifestations of long COVID can be managed symptomatically. These interventions are often based on routine cardiovascular care, which generally produces beneficial outcomes.

Future outlook

Advances in post-COVID-19 diagnostic testing currently under development must be fine-tuned to better inform policymakers and clinicians. Further progress is also needed to identify cardiovascular risk factors associated with long COVID. Development of novel therapeutic interventions to treat the entire long COVID pathology rather than managing the numerous symptoms of long COVID individually is also important.

Large-scale longitudinal studies are needed to better understand the medium- and long-term implications of the post-COVID-19 situation.”