Long COVID's impact on cardiovascular health: what we do and do not know

In a recent study published in Nature Cardiovascular Research, researchers review the cardiovascular effects of long coronavirus disease 2019 (COVID-19).

Study: Cardiovascular effects of the post-COVID-19 condition. Image Credit: YAKOBCHUK VIACHESLAV / Shutterstock.com

Post-COVID-19

Post-COVID-19, which is also referred to as long COVID and post-acute sequelae of COVID-19 (PASC), is a novel condition affecting 10-60% of COVID-19 survivors, which amounts to 70-420 million individuals throughout the world. Long COVID is characterized by the persistence or, in some cases, development of novel symptoms following recovery from COVID-19.

The World Health Organization (WHO) and United States Centers for Disease Control and Prevention (CDC) estimate that long COVID symptoms can persist for months or even years following initial infection recovery, thereby resulting in significant loss of quality of life (QoL) for affected individuals.  

Since 2020, over 23,000 publications on long COVID have been released. Despite the increased focus on the prevalence and definition of the condition, some studies have aimed to understand the pathophysiology and underlying mechanisms of the disease, with the shared aim of discovering a cure.

Significant progress notwithstanding, a targeted treatment for long COVID remains elusive. Thus, synthesizing the rapid scientific progress in post-COVID-19 research will both highlight recent advances and underscore critical gaps in the literature.

Diagnosing long COVID

Despite being a predominantly respiratory condition, a growing body of evidence reports the systemic effects of COVID-19. This feature is shared by long COVID, with over 20 symptoms identified to date across respiratory, cardiovascular, neurological, gastrointestinal, and endocrine systems. Common nonspecific complaints include dizziness, fatigue, and memory loss.

Due in part to the novelty of the condition, clinical diagnostic tests for post-COVID-19 syndrome remain theoretical. As a result, the National Institutes of Health Researching COVID to Enhance Recovery (RECOVER) Initiative 12-symptom checklist is the current gold standard in long COVID diagnosis.

Recent cardiovascular-focused research has devised cardiovascular-centric guidelines, including the American College of Cardiology practice guideline document.

Although the cardiovascular complications of the post-COVID-19 condition are highly publicized, the sequelae from this virus are not particularly unique. Cardiovascular effects including myocarditis have been long described following other viral illnesses such as influenza and Epstein-Barr virus. However, the mortality rate and incidence of vascular complications is far greater in COVID-19."

Long COVID is confirmed through various clinical tests including complete blood counts, basic metabolic panel, troponin, C-reactive protein, and pro-brain natriuretic peptide levels, electrocardiograms (ECGs), and echocardiograms. In severe cases, magnetic resonance imaging (MRI) and chest X-rays may be used.

The impact of long COVID on cardiovascular health

Long COVID-associated cardiovascular pathophysiology can be classified as immune dysregulation and inflammation, endothelial dysfunction, microvascular injury, and neurological signaling dysfunction. Two main long COVID phenotypes have been identified, of which include overt cardiovascular disease after COVID-19 (PASC-CVD) and those with cardiovascular symptoms despite lacking clear disease markers (PASC-CVS).

PASC-CVD patients are often older and are at an increased risk of endothelial dysfunction, inflammation, and microvascular injury. Comparatively, PASC-CVS patients are typically younger and at a greater risk of neurological signal dysfunction and immune dysregulation.

The mechanisms responsible for the cardiovascular effects of long-COVID can be immediate through direct cytotoxic injury or delayed, which is attributed to a cascade of immune-overstimulation-mediated responses.

Cardiovascular symptoms of long COVID

Postural orthostatic tachycardia syndrome (POTS) is one of the most commonly researched cardiovascular symptoms and is characterized by a sudden increase in one's heart rate when transitioning between sitting, lying down, and standing. POTS was identified at the beginning of the COVID-19 pandemic, with the highest prevalence in the PASC-CVS phenotype.

The most common test for POTS is a head-up tilt-table test (HUTT); however, several studies have found that many POTS patients remain undetected by HUTT. As a result, POTS prevalence estimates may be severe underestimates.

Myocardial injury is another common characteristic of post-COVID-19, which, unlike POTS, has clear biomarker evidence of its prevalence through the troponin test. Myocardial injury is also much better characterized, as it arises both from general critical illness outcomes of acute COVID-19 like hypoxemia and shock, as well as from cardiac structural pathology.

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

Arrhythmias, or irregular heartbeat, have been identified through their comorbidities, including inflammatory cytokine release, myocardial scarring and fibrosis, persistent immune dysfunction, and potential gap junction dysfunction.

While no curative therapies for long COVID have been identified, long COVID cardiovascular symptoms can be managed on a symptom-by-symptom basis. These interventions are often based on routine cardiovascular care with generally beneficial outcomes.

Future outlook

Advances in post-COVID-19 diagnostic tests, which are currently under development, must be fine-tuned to better inform policymakers and clinicians. Additional progress is also needed to identify long COVID-associated cardiovascular risk factors. The development of novel therapeutic interventions to treat the entire condition of long COVID is also crucial, rather than managing each of its numerous symptoms individually.

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

Journal reference:
  • Goerlich, E., Chung, T. H., Hong, G. H., et al. (2024). Cardiovascular effects of the post-COVID-19 condition. Nature Cardiovascular Research; 1-12. doi:10.1038/s44161-023-00414-8
Hugo Francisco de Souza

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Hugo Francisco de Souza

Hugo Francisco de Souza is a scientific writer based in Bangalore, Karnataka, India. His academic passions lie in biogeography, evolutionary biology, and herpetology. He is currently pursuing his Ph.D. from the Centre for Ecological Sciences, Indian Institute of Science, where he studies the origins, dispersal, and speciation of wetland-associated snakes. Hugo has received, amongst others, the DST-INSPIRE fellowship for his doctoral research and the Gold Medal from Pondicherry University for academic excellence during his Masters. His research has been published in high-impact peer-reviewed journals, including PLOS Neglected Tropical Diseases and Systematic Biology. When not working or writing, Hugo can be found consuming copious amounts of anime and manga, composing and making music with his bass guitar, shredding trails on his MTB, playing video games (he prefers the term ‘gaming’), or tinkering with all things tech.

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