Potential long-term cardiovascular complications in Coronavirus Disease 2019 survivors: lessons from past coronavirus diseases

Coronavirus Disease 2019 (COVID-19) is currently an unprecedented dreadful pandemic. Following the identification of its first case in Wuhan, China, in December 2019, the disease has rapidly spread and was declared as a pandemic by the World Health Organization (WHO) on March 11, 2020 (1). On May 08, 2020, the Center for Disease Control and Prevention (CDC) estimated that 3,807,852 persons were infected (in conformity with the case definitions and diagnostic test used in the various affected countries) by the severe acute respiratory syndrome coronavirus 2 (SARS-COV2) worldwide and COVID-19 was responsible for 269,068 global deaths (2). After affecting the respiratory system, the cardiovascular system is one of the main body systems affected by SARS-COV2. Several cardiovascular complications have been described in COVID-19 patients namely: myocarditis, myocardial infarction, heart failure, arrhythmia, venous and arterial thrombosis (3). The pathogenesis of cardiovascular involvement in COVID-19 results either from a direct or indirect mechanism. The direct mechanism involves the viral infiltration of myocardial tissues, cardiac and vascular endothelial cells, resulting in cellular death. On the other hand, the indirect mechanism is due to a severe acute lung inflammatory injury, electrolyte imbalance and iatrogenic effects caused by the use of QT prolongation drugs (chloroquine or hydroxychloroquine and/or azithromycin) (3,4). Also, in animal models, the expression of the Angiotensin Converting Enzyme 2 (ACE 2) in the heart has an important cardio-modulating function. Mice that developed ACE 2 anomalies had severe left ventricular dysfunction. SARS-COV2 appears to down-regulate ACE 2, which may theoretically contribute to myocardial dysfunction (5). It is now established that patients with cardiovascular risk factors or diseases are more prone to poor outcomes and that these patients often die secondary to cardiovascular events in the Intensive Care Unit (ICU) (3). As the COVID-19 pandemic persists due to no evidence-based treatment at this write-up, the long-term prognosis especially due to cardiovascular complications remains uncertain. However, some hypotheses on the long-term outcomes of cured COVID-19 persons can be made from the appraisal of previous coronavirus-related epidemics.

Before the outbreak of COVID-19, two other major coronaviruses had infected human beings. These were the SARS-COV which caused SARS between the years 2002-2003 and the Middle East Respiratory Syndrome Coronavirus (MERS-COV) which caused MERS between the years 2012–2016. At the end of the epidemic of SARS, China reported more than 8,000 cases of the disease and 774 deaths equivalent to a case-fatality rate of 7%. MERS, the second identified coronavirus accounted for a major global health crisis too. MERS first emerged in the year 2012 in Saudi Arabia. Two years following its outbreak, there was a total of 662 infected patients and its case-fatality was 32.97%. Between 2014 to 2016, the number of infections increased to 1,364 cases in Saudi Arabia. Globally, 27 countries in the Middle East, Asia, Europe and North America regions were affected by MERS during its outbreak (6). Several cardiovascular complications were reported during SARS and MERS outbreaks. Cases of acute coronary syndrome and myocardial infarction, transient change in diastolic function after 30 days of follow-up and thromboembolic events have been repeatedly reported during this on-going COVID-19 pandemic (7). A similar high burden of cardiovascular complications was also observed during MERS epidemic with 30% of MERS patients having underlying cardiovascular diseases before being infected by MERS-COV. A systematic review and meta-analysis on prevalence comorbidities in 637 MERS patients reported prevalence rates of 50% for hypertension, 50% for diabetes, and 16% for obesity (8). Furthermore, cardiovascular complications have been reported in an experimental study on MERS-COV infected mice which showed expression of viral in their cardiac tissues, suggesting the pathogenesis of cardiovascular complications caused by MERS (9). Concerning the long-term prognosis, a 12-year follow-up survey of 25 SARS patients with low cardiovascular risk factors and no established cardiovascular diseases at baseline who recovered from SARS found that 68% had hyperlipidemia, 44% had cardiovascular complications and 60% had glucose metabolism disorders. These abnormalities were significantly higher when compared with individuals without a history of SARS (10). As the members of the betacoronavirus family, the phylogenetic proximity between SARS-COV and SARS COV-2 could predict the same long-term cardiovascular complications. However, this hypothesis requires further investigations (4). Another important finding from a study published more than a decade ago is that a substantial proportion of SARS survivors (62%) from developed pulmonary fibrosis (11), a known high-risk factor for cor pulmonale. Moreover, hospitalization for similar chest infections like pneumonia was associated with an increase in both short-term and long-term risk of cardiovascular diseases (12).

Although there is a paucity of contemporary evidence on COVID-19, the high burden of cardiovascular complications associated with its pandemic and lessons from the outcomes of other coronavirus epidemics, there is a high likelihood of long-term cardiovascular sequelae in survivors of COVID-19. Hence, proper clinical surveillance of COVID-19 survivors particularly those with severe form of the disease for cardiovascular complications may be important for prevention, early detection and treatment of these cardiovascular complications which may be potentially fatal. It’s also very important to have well-documented registers of the cardiovascular profile before and after the COVID 19 during this pandemic in order to reinforce prevention strategies.

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was a free submission to the Journal of Xiangya Medicine. The article was sent for external peer review.

Provenance and Peer Review: This article was a standard submission to the journal. The article did not undergo external peer review.

Peer Review File: Available at http://dx.doi.org/10.21037/jxym-20-65

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jxym-20-65). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. WHO. Coronavirus disease (COVID-19) Situation Report. [cited 2020 May 6]. Available online: https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200505covid-19-sitrep-106.pdf?sfvrsn=47090f63_2
2. ECDC. COVID-19 situation update worldwide, as of 14 June 2020. [cited 2020 May 9]. Available online: https://www.ecdc.europa.eu/en/geographical-distribution-2019-ncov-cases
3. Zheng YY, Ma YT, Zhang JY, et al. COVID-19 and the cardiovascular system. Nat Rev Cardiol 2020;17:259-60. [Crossref] [PubMed]
4. Varga Z, Flammer AJ, Steiger P, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet 2020;395:1417-8. [Crossref] [PubMed]
5. Akhmerov A, Marbán E. COVID-19 and the Heart. Circ Res 2020;126:1443-55. [Crossref] [PubMed]
6. Peeri NC, Shrestha N, Rahman MS, et al. The SARS, MERS and novel coronavirus (COVID-19) epidemics, the newest and biggest global health threats: what lessons have we learned? Int J Epidemiol 2020;49:717-26. [Crossref] [PubMed]
7. Madjid M, Safavi-Naeini P, Solomon SD, et al. Potential Effects of Coronaviruses on the Cardiovascular System: A Review. JAMA Cardiol 2020;5:831-40. [Crossref] [PubMed]
8. Badawi A, Ryoo SG. Prevalence of comorbidities in the Middle East respiratory syndrome coronavirus (MERS-CoV): a systematic review and meta-analysis. Int J Infect Dis 2016;49:129-33. [Crossref] [PubMed]
9. Agrawal AS, Garron T, Tao X, et al. Generation of a transgenic mouse model of Middle East respiratory syndrome coronavirus infection and disease. J Virol 2015;89:3659-70. [Crossref] [PubMed]
10. Wu Q, Zhou L, Sun X, et al. Altered Lipid Metabolism in Recovered SARS Patients Twelve Years after Infection. Sci Rep 2017;7:9110. [Crossref] [PubMed]
11. Antonio GE, Wong KT, Hui DS, et al. Thin-section CT in patients with severe acute respiratory syndrome following hospital discharge: preliminary experience. Radiology 2003;228:810-5. [Crossref] [PubMed]
12. Corrales-Medina VF, Alvarez KN, Weissfeld LA, et al. Association between hospitalization for pneumonia and subsequent risk of cardiovascular disease. JAMA 2015;313:264-74. [Crossref] [PubMed]