The Risk of Cardiovascular Sequelae in Post-Acute COVID-19

Corresponding Author

T he COVID-19 pandemic, caused by SARS-CoV-2, has had an immense impact on global and individual health.Since the start of the pandemic in late 2019, there have been over 760 million confirmed cases of COVID-19 infection, with nearly 7 million deaths attributable to the disease. 1 In addition to the acute phase, which refers to the period within 3 months of infection, long COVID or post-acute sequelae of SARS-CoV-2 has been reported in individuals of all ages, backgrounds, and severity of initial infection. 2The World Health Organization (WHO) defines post-acute COVID-19 as the continuation or development of new symptoms 3 months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least 2 months without any other explanation.Individuals with post-acute COVID-19 may experience various symptoms, including fatigue, headache, chest pain, depression, and anxiety, among others.Undoubtedly, this has a significant impact on both individual health and the health care systems. 3ong the many reported long COVID-19 symptoms, the cardiovascular sequelae have received considerable attention.Dyspnea, palpitations, chest pain, and thromboembolism 4,5 are recognized symptoms during the post-acute phase (Figure 1), and various pathophysiological mechanisms have been proposed to explain their occurrence or recurrence.
One such proposition is that SARS-CoV-2 infects endothelial cells expressing angiotensin-converting enzyme 2 receptors, leading to cardiovascular endotheliitis. 6This causes damage to the vasculature, which can precipitate myocardial infarction, thrombosis, and other cardiovascular sequelae. 7Of note, cardiovascular autonomic dysfunction, including postural orthostatic tachycardia syndrome, is also posited to occur in the post-acute COVID period. 8,9wever, it remains unclear to what extent these symptoms can be attributed to prior COVID-19 infection.[12] The current study by McAlister et al 13  As a cohort study relying on administrative data, there are several limitations outlined by the authors.
For instance, the number of vaccinated individuals was very small (<3%), and the strain of COVID analyzed in this study may differ from the current dominant COVID variants.
In addition to the limitations discussed in the article, another consideration could be to present the episodes of acute presentations as a ratio of preexisting disease prevalence.For example, despite COVID-19 patients having a higher likelihood of presenting with hypertension in the post-acute phase (0.6% vs 0.4%), the prevalence of pre-existing hypertension is also greater among COVID-19 patients compared to the control group (2.5% vs 1.7%).This trend holds for all statistically significant sequelae studied (heart failure 0.8% vs 0.4%, diabetes mellitus 4.5% vs 2.0%, and renal disease 0.6% vs 0.3%).
Therefore, the question arises as to whether the increased likelihood of post-acute presentations can be partially explained as an acute exacerbation of preexisting conditions.However, the authors demonstrated that when considering only the new diagnosis or incidence of the aforementioned cardiovascular complications, statistically significant results were maintained.

FUNDING SUPPORT AND AUTHOR DISCLOSURES
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.cchahal@wellspan.orgOR chahal.anwar@mayo.edu.

R E F E R E N C E S
in this issue of JACC: Advances evaluates long COVID in the context of hospitalizations or emergency department (ED) visits for cardiovascular complaints (including diabetes mellitus, hypertension, and heart failure) using the strict WHO definition.The authors conducted a retrospective cohort study using data sets from the universal access health care system of Alberta, Canada.They compared all adults in Alberta who had a confirmed COVID-19 infection (by real-time polymerase chain reaction) to matched controls (matched by age, sex, and Charlson comorbidity index score) who tested negative for COVID-19 during the contemporaneous period of March 1, 2020, to June 30, 2021.They assessed the likelihood of ED visits or hospitalization during the post-acute COVID-19 phase (3-9 months postinfection).They found that cases were more likely than controls to have ED visits or hospitalizations for diabetes (1.5% vs 0.7%, P < 0.0001), hypertension (0.6% vs 0.4%, P < 0.0001), heart failure (0.2% vs 0.1%, P ¼ 0.0002), and kidney injury (0.3% vs 0.2%, P < 0.0001).The results were even more pronounced when considering only COVID-19 hospitalization survivors compared to the appropriate control group.However, there was no statistical difference in the likelihood of presentation with acute coronary syndrome, stroke, cardiac arrhythmias, or bleeding.The authors deserve commendation for their comprehensive data collection, which included all cases that tested positive for COVID-19 by real-time polymerase chain reaction (177,892 cases), thereby minimizing selection bias among the Alberta population.Additionally, they addressed a focused question using appropriate statistical tools and adjusted for confounding variables.They also implemented an adequate follow-up period of 6 months (ie, 3-9 months postinfection), fully complying with the WHO definition of post-acute COVID-19 sequelae (ie, long COVID), a feature lacking in many previous publications on post-acute COVID-19 symptoms.Importantly, the article aimed to raise awareness among clinicians regarding the impact of long COVID and the importance of screening COVID survivors for specific cardiovascular complications, such as diabetes mellitus, hypertension, heart failure, and kidney dysfunction.This information could potentially inform public health policymaking, particularly in resource allocation and optimization for the secondary prevention of COVID-19 sequelae.

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Dr C. Anwar A. Chahal, Department of Cardiology, Center for Inherited Cardiovascular Diseases, Genomic and Precision Medicine, WellSpan Health, 30 Monument Road, York, Pennsylvania 17403, USA.E-mail: