01 May 2022: Editorial
Editorial: Cardiovascular Complications at One Year After SARS-CoV-2 Infection are Independent of Underlying Cardiovascular Risk Factors or Severity of COVID-19Dinah V. Parums1CDEF*
Med Sci Monit 2022; 28:e937048
ABSTRACT: The consequences of SARS-CoV-2 infection include short-term, long-term, mild, and severe clinical symptoms. The cardiovascular system, including endothelial cells, vascular smooth muscle cells, and cardiac myocytes, are important targets for SARS-CoV-2. In February 2022, the findings from a large US cohort of individuals diagnosed with COVID-19 and two sets of control cohorts evaluated the risk and 12-month cardiovascular disease burden. Individuals who had COVID-19 had a 72% increased risk of heart failure, a 63% increased risk of myocardial infarction, and a 52% increased risk of ischemic stroke compared with controls. These results were independent of gender, race, age, and other cardiovascular risk factors, including diabetes, obesity, hypertension, hyperlipidemia, and chronic kidney disease. As of 25 April 2022, the World Health Organization (WHO) reported that more than 80 million people in the US, more than 22 million people in the UK, and more than 505 million people worldwide were infected with SARS-CoV-2. This Editorial aims to present what is currently known about the cardiovascular outcomes at one year following SARS-CoV-2 infection and highlights that primary care physicians should be mindful of the COVID-19 infection status of their patients when evaluating cardiovascular health.
Keywords: Editorial, Cardiovascular Diseases, COVID-19, SARS-CoV-2, Long COVID
During the first year of the coronavirus disease 2019 (COVID-19) pandemic, some patients who recovered from SARS-CoV-2 infection reported long-term symptoms of long COVID [1,2]. The consequences of SARS-CoV-2 infection include a spectrum of short-term and long-term, mild and severe clinical symptoms [1,2]. These symptoms can range from temporary loss of taste and smell or chronic fatigue to more severe and long-term conditions such as heart failure, stroke, and cognitive impairment [1,2]. During the relatively short time that COVID-19 cases have been reported, the effects of SARS-CoV-2 infection on the cardiovascular system have been published in case reports, case series, and some small population studies.
Preclinical and clinical studies have identified that the cardiovascular system, including endothelial cells, vascular smooth muscle cells, and cardiac myocytes, are important targets for SARS-CoV-2 [3,4]. Although COVID-19 often presents with lung inflammation due to airborne transmission of the virus, the pathogenesis of COVID-19 pneumonia also includes alveolar endothelialitis [3,4]. SARS-CoV-2 enters host cells by binding the spike (S) protein to the angiotensin-converting enzyme 2 (ACE2) receptor . The binding of the S protein to the ACE2 receptor is followed by membrane fusion . The host cell protease, transmembrane serine protease 2 (TMPRSS2), is the principal host protease that enables cell entry of SARS-CoV-2 . ACE2 is a type I transmembrane metallocarboxypeptidase expressed in vascular endothelial cells, cardiac myocytes, and type 2 alveolar pneumocytes . Pre-existing cardiovascular disease is a recognized risk factor for patient morbidity from COVID-19. An early study from the Penn Human Heart Tissue Biobank investigated ACE2 gene expression in left ventricular tissue from 15 patients with hypertrophic cardiomyopathy, 11 patients with dilated cardiomyopathy, and 16 normal controls . ACE2 gene expression was identified in cardiac microvascular pericytes, vascular smooth muscle cells, fibroblasts, and cardiac myocytes . Also, the TMPRSS2 gene was expressed at low levels by all cell types, including cardiac myocytes . Other studies have supported these early findings.
However, ACE2 is not only a SARS-CoV-2 receptor but also regulates the renin-angiotensin system (RAS), which has significant roles in the cardiovascular and immune systems . ACE2 may link SARS-CoV-2 infection, cardiovascular disease, and the immune response . Acute and long-term cardiovascular disease associated with SARS-CoV-2 infection may be driven by an imbalance between disintegrin and metalloproteinase domain-containing protein 17 (ADAM17) required to cleave ACE2 and TMPRSS2 . However, until recently, the post-acute effects of SARS-CoV-2 infection on the cardiovascular system have not been studied in large populations or in a controlled way [6,7].
Lu and colleagues recently reported the findings from a retrospective study of 10,696 patients hospitalized with COVID-19 between March 2020 to June 2021 . Serum troponin-T levels evaluated acute cardiac injury (ACI) during hospitalization and up to 2.5 months following discharge . On hospital admission, 39.7%, or 4,248 patients with COVID-19, had ACI, which developed in almost all patients (93%) within a day after hospital admission . In-hospital mortality was increased for patients with ACI . Of the 2,880 patients with COVID-19 and ACI who survived, 38.7% (1,114 patients) were re-admitted to hospital within 2.5 months . Only 302 out of 673 patients (44.9%) recovered from ACI . This study had a short-term follow-up but showed that persistent cardiac injury is common in patients who recover from COVID-19 .
In February 2022, Xie and colleagues reported the findings from a cohort of 153,760 individuals diagnosed with COVID-19 between March 2020 and January 2021 and two control cohorts from the US Department of Veterans Affairs database . This study included 5,637,647 contemporary controls and 5,859,411 historical controls . The study evaluated the risk and 12-month cardiovascular disease burden . Xie and colleagues showed that 30 days after SARS-CoV-2 infection, there was a significantly increased risk of the following: cerebrovascular disease; dysrhythmias; myocarditis; pericarditis; ischemic and non-ischemic heart disease; heart failure; and thromboembolic disease . Individuals who had COVID-19 had a 72% increased risk of heart failure, a 63% increased risk of myocardial infarction, and a 52% increased risk of ischemic stroke compared with controls . These results were independent of gender, race, age, and other cardiovascular risk factors, including diabetes, obesity, hypertension, hyperlipidemia, and chronic kidney disease . Importantly, the risk and disease burden were significantly increased even for non-hospitalized individuals during the acute phase of SARS-CoV-2 infection . However, the risk of post-COVID-19 cardiovascular disease increased from non-hospitalized patients to hospitalized patients and patients admitted for intensive care . This population study shows that the overall risk and 12-month cardiovascular disease burden following acute COVID-19 represents a significant additional chronic health burden [7,8]. A further concern is how these cardiovascular complications of even mild SARS-CoV-2 infection may persist or worsen year on year [7,8]. The collective term, ‘COVID heart,’ has recently been applied to describe the array of cardiac long COVID conditions .
The best way to prevent post-COVID-19 cardiovascular disease is to prevent SARS-CoV-2 infection, and this fact should be a further incentive to increase SARS-CoV-2 vaccine uptake. As of 25 April 2022, the World Health Organization (WHO) reported that more than 80 million people in the US, more than 22 million people in the UK, and more than 505 million people worldwide were infected with SARS-CoV-2, resulting in more than 6 million deaths .
A history of infection with SARS-CoV-2 associated with even mild COVID-19 can result in a long-term increased risk for cardiovascular disease. Primary care physicians should also be mindful of any previous episodes of SARS-CoV-2 infection in their patients when evaluating cardiovascular health. Patient care pathways, medical examinations for occupational health reasons, and medical insurance are also likely to require evaluation and monitoring of cardiovascular health, depending on whether there is a history of COVID-19. Worldwide, government health systems should prepare for the long-term effects on cardiovascular health of the millions of cases of SARS-CoV-2 infection.
1. Halpin S, O’Connor R, Sivan M, Long COVID and chronic COVID syndromes: J Med Virol, 2021; 93(3); 1242-43
2. Parums DV, Editorial: Long COVID, or post-COVID syndrome, and the global impact on health care: Med Sci Monit, 2021; 27; e933446
3. Jackson CB, Farzan M, Chen B, Choe H, Mechanisms of SARS-CoV-2 entry into cells: Nat Rev Mol Cell Biol, 2022; 23(1); 3-20
4. Aleksova A, Gagno G, Sinagra G, Effects of SARS-CoV-2 on cardiovascular system: The dual role of angiotensin-converting enzyme 2 (ACE2) as the virus receptor and homeostasis regulator-review: Int J Mol Sci, 2021; 22(9); 4526
5. Tucker NR, Chaffin M, Bedi KCHuman Cell Atlas Lung Biological Network Consortium Members, Myocyte-specific upregulation of ACE2 in cardiovascular disease: Implications for SARS-CoV-2-mediated myocarditis: Circulation, 2020; 142(7); 708-10
6. Lu JQ, Lu JY, Wang W, Clinical predictors of acute cardiac injury and normalization of troponin after hospital discharge from COVID-19: EBioMedicine, 2022; 76; 103821
7. Xie Y, Xu E, Bowe B, Al-Aly Z, Long-term cardiovascular outcomes of COVID-19: Nat Med, 2022; 28(3); 583-90
8. Sidik SM, Heart-disease risk soars after COVID – even with a mild case: Nature, 2022; 602(7898); 560
9. Abbasi J, The COVID heart-one year After SARS-CoV-2 infection, patients have an array of increased cardiovascular risks: JAMA, 2022; 327(12); 1113-14
10. World Health Organization (WHO): Coronavirus (COVID-19) Dashboard April 25, 2022 Available from: https://covid19.who.int
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