Long COVID syndrome or post-acute COVID-19 syndrome (PACS) encompasses a wide range of organ dysfunction. It is more common in hospitalized survivors, but, even those who have experienced mild acute COVID-19 have a wide range of frequent, persistent, and disabling symptoms. Cardiovascular complications, including myocardial injury, heart failure, arrhythmias, and coagulation disorders, can manifest not only during the acute phase of COVID-19 but also in long-COVID-19 or PACS syndrome. In this study, German scientists used cardiac magnetic resonance imaging (MRI) to investigate the prevalence and extent of cardiac abnormalities in patients diagnosed with PASC.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped, positive-sense, single-stranded RNA virus. Its genome encodes four structural proteins, namely the spike (S), envelope (E), nucleocapsid (N), and membrane (M) protein. Two host-cell factors are important for SARS-CoV-2 entry into many cell types: angiotensin-converting enzyme 2 (ACE2), which is bound by the S protein, and transmembrane protease, serine 2 (TMPRSS2), which cleaves S-protein, allowing this binding to take place. ACE2 receptors are more highly expressed in the heart than other organs, and in cardiomyocytes from patients with heart failure than in healthy individuals.
A recent in vitro study that utilized a model of human cardiac microtissue demonstrated a high risk of cardiac dysfunction in heart tissues with persistent SARS-CoV-2 infection. Hypoxic conditions mimicking ischemic heart disease further deteriorated cardiac function and disrupted vascular network formation in a heart tissue model infected with SARS-CoV-2. The authors emphasized that an explosive increase in the number of patients infected with SARS-CoV-2 may result in an enormously increased number of patients at potential risk for heart failure. https://discovermednews.com/deterioration-heart-function-cardiac-model-sars-cov-2-infection/
About the Study and Results
This two-center retrospective study investigated the presence and extent of cardiac abnormalities in all patients referred for cardiac MRI due to clinical signs of PASC within two years. The median interval between a positive reverse transcription polymerase chain reaction test for SARS-CoV-2 and cardiac MRI was four months.
The study included 129 patients diagnosed with PASC. 51% were women, and the mean age was 41 years. The most common symptoms of PASC were exertional dyspnea (reported in 23% of patients) and tachycardia/palpitations (reported in 22% of patients). Other symptoms included fatigue, exercise intolerance, and chest pain lasting more than four weeks after the acute infection.
21% of patients diagnosed with PASC had abnormal (<55%) ejection fraction, 19% had left ventricular dilation, 14% had pericardial effusion (>5 mm) and 5% had pleural effusion (>20 mm). There was no case of active myocarditis or an acute myocardial infarction.
Cardiac MRI demonstrated no cardiac abnormalities in 57% of patients diagnosed with PASC. The most common diagnosis was non-ischemic, possibly post-inflammatory fibrosis, which was found in 30% of patients. Post-ischemic fibrosis was found in 4% of patients and structural heart disease in 9% of patients. 8% of patients with normal cardiac results had suspected pulmonary abnormalities (fibrosis/atelectasis).
Conclusion
This study showed that 57% of patients diagnosed with PASC had normal cardiac MRI results. However, a significant portion of the cohort (30%) had signs of non-ischemic myocardial fibrosis, whereas post-ischemic fibrosis was found in 4% of patients.
Cao et al. discovered that the SARS-CoV-2 S protein promotes cardiac fibrosis in obese mice. They suggested that the S protein caused myocardial contractile impairment by inducing long-term aberrances in the cardiac transcriptional signatures of mitochondrial respiratory chain genes. (Mol. Metab. 2023, 74, 101756) https://www.sciencedirect.com/science/article/pii/S221287782300090X?via%3Dihub A recent study that investigated the effects of SARS-CoV-2 S protein on cultured human cardiac fibroblasts (CFs) and the molecular mechanisms underlying cardiac fibrosis induced by SARS-CoV-2 S protein, discovered that SARS-CoV-2 S protein activates CFs and promotes cardiac fibrosis. More specifically, they discovered that the SARS-CoV-2 S1 protein activates human CFs by priming The NOD-, LPR-, and pyrin-domain-containing protein 3 (NLRP3) inflammasomes through nuclear factor kappa-B (NF-κB) signaling in an ACE2-dependent way. https://discovermednews.com/sars-cov-2-spike-protein-activates-human-cardiac-fibroblasts-and-promotes-cardiac-fibrosis/
The authors of the present study noted that they focused only on patients referred for cardiac MRI, and strictly relied on established international guidelines for myocardial inflammation detection. They emphasized that this prevalence of myocardial fibrosis is particularly concerning as it exceeds the prevalence of this disease in the normal adult population. Furthermore, these results suggest that a history of myocarditis might be the reason for the persistent symptoms in patients with PASC.
The article was published in Diagnostics.
Journal Reference
Halfmann MC. et al. Cardiac MRI Findings in Patients Clinically Referred for Evaluation of Post-Acute Sequelae of SARS-CoV-2 Infection. Diagnostics 2023, 13, 2172. (Open Access) https://doi.org/10.3390/diagnostics13132172
