The COVID-19 pandemic has highlighted the virus's far-reaching effects beyond respiratory issues, impacting cardiovascular, hepatic, renal, gastrointestinal, neurological, and metabolic functions. A substantial number of survivors develop "long-COVID," characterized by persistent health problems extending beyond the typical recovery period. The World Health Organization defines long-COVID as symptoms lasting at least two months, three months after the initial infection, and not attributable to other diagnoses. Common symptoms include fatigue, shortness of breath, and cognitive dysfunction. The epidemiological profile and pathophysiology of long-COVID remain poorly understood, yet its future disease burden necessitates urgent development of effective management strategies. Studies reveal a significant increase in cardiovascular risks (up to 2000%) among COVID-19 survivors, including infarction, arrhythmias, and dysautonomia—often a consequence of chronic inflammation and increased sympathetic nerve activity. This dysautonomia, a key component of "post-COVID Guillain-Barré syndrome" (PCGBS), is linked to neuropsychological sequelae such as anxiety, depression, and cognitive impairment. Given the role of dysautonomia in the pathophysiology of long-COVID, interventions restoring normal sympathovagal function, like CRPs, hold significant therapeutic potential. Cardiovascular rehabilitation programs (CRPs) are multidimensional interventions involving exercises stimulating parasympathetic activity, education on self-care and healthy habits, and patient/caregiver support. Their proven efficacy in various cardiovascular conditions makes them promising candidates for managing long-COVID's cardiovascular complications. This review aims to summarize post-COVID-19 cardiovascular consequences and advocate for the evaluation and implementation of non-invasive management techniques, focusing on CRPs.

The literature review synthesized findings from 54 publications (2009-2022), including epidemiological studies, clinical trials, scientific papers, and reviews. These publications were selected based on their relevance to long-COVID cardiovascular sequelae epidemiology and non-invasive strategies to improve outcomes. Key areas covered included the prevalence of cardiovascular complications in long-COVID, the role of autonomic nervous system dysfunction (specifically PCGBS), existing diagnostic tools for dysautonomia, and the effectiveness and feasibility of CRPs in treating various cardiovascular conditions. The review analyzed studies investigating the efficacy of CRPs in improving cardiorespiratory fitness, reducing cardiovascular risk factors, and improving outcomes in patients with myocardial infarction, stroke, and other cardiovascular diseases. This review also incorporated research on the pathophysiology of long-COVID, including hypotheses related to vascular endothelial dysfunction, persistent viral particles, and immune system dysregulation. Several studies cited provide evidence linking long-COVID to various cardiovascular complications and autonomic dysfunction, highlighting the need for effective interventions.

The authors conducted a literature review focusing on long-COVID, cardiovascular dysfunction, autonomic nervous system involvement, and cardiovascular rehabilitation programs (CRPs). They systematically searched databases for relevant publications from 2020 to 2022 using keywords such as "long-COVID," "cardiovascular," and "autonomic/dysautonomia." Additionally, they included publications from 2009 to 2022 related to "cardiorespiratory fitness," "cardiovascular rehabilitation," and "dysautonomia." The selection process prioritized studies relevant to the epidemiology of long-COVID cardiovascular sequelae, non-invasive strategies for improving cardiovascular and autonomic outcomes, and the clinical feasibility of these strategies. The final review included 54 publications spanning epidemiological studies, clinical trials, scientific papers, and reviews. The review process involved a detailed examination of the selected publications to extract key information related to the pathophysiology of long-COVID, diagnostic tools for dysautonomia, cardiovascular consequences of long-COVID, and the potential benefits of CRPs. This included evaluating the validity and reliability of various methods used in the studies, as well as considering potential biases. The selected studies were analyzed qualitatively to identify common themes, trends, and areas of consensus and disagreement regarding the effectiveness and feasibility of CRPs as a treatment for long-COVID-related cardiovascular issues.

Long-COVID is associated with a significantly increased risk of various cardiovascular diseases, including cerebrovascular diseases, dysrhythmias, cardiac inflammatory disease, ischemic heart disease, heart failure, and thromboembolic disorders. These risks are graded by the severity of the acute COVID-19 infection, and vaccination was shown to reduce the risk of myocarditis and pericarditis. Approximately 13% of acute COVID-19 and long-COVID patients exhibit PCGBS, a form of dysautonomia characterized by microinflammation in autonomic nerve fibers leading to sympathetic nervous system activation and consequent arrhythmogenesis, orthostatic hypotension, and cognitive decline. Several diagnostic tools exist for assessing dysautonomia, including plasma catecholamine measurements, heart rate variability (HRV) analysis, baroreflex sensitivity analysis, and the COMPASS-31 survey. HRV analysis, in particular, emerges as a promising non-invasive tool, particularly when combined with AI processing. Pilot studies suggest that CRPs, encompassing exercise, education, and psychosocial support, show promise in managing long-COVID symptoms. A Japanese pilot study (n=50) demonstrated high adherence, reduced anxiety, improved autonomy, and enhanced quality of life in long-COVID patients following a CRP. Another case study showed a personalized CRP significantly improved dyspnea, fatigue, and functional state in a patient with PCGBS. Existing evidence supports that exercise training improves cardiovascular and autonomic function in various populations. The review emphasizes the need for tailored treatment strategies for long-COVID, considering factors like age and the diverse range of cardiovascular manifestations. The American College of Cardiology recommends testing for abnormal cardiac function in all COVID-19 survivors, especially in immunosuppressed individuals and older adults. There is evidence suggesting that exercise training might offer a complementary therapeutic strategy for long-COVID patients with dysautonomia and cardiovascular dysfunction by improving vascular endothelial function, autonomic function, and myocardial function. However, further research is needed to establish its efficacy comprehensively.

The findings highlight the significant cardiovascular and autonomic consequences of long-COVID, emphasizing the need for effective management strategies. The increased risk of various cardiovascular diseases among COVID-19 survivors necessitates early detection and intervention. The prominence of PCGBS underscores the importance of addressing autonomic dysfunction in long-COVID management. CRPs appear to be a feasible and potentially effective non-invasive therapeutic approach, given their proven efficacy in improving cardiovascular and autonomic function in other clinical populations and the preliminary results from pilot studies in long-COVID patients. HRV analysis, due to its non-invasive nature and potential for AI-assisted interpretation, offers a promising tool for diagnosis and monitoring. The review advocates for further research to establish the efficacy and optimize the implementation of CRPs in long-COVID management, particularly in diverse populations, such as children and adolescents, where data is currently limited.

Long-COVID's lasting cardiovascular sequelae, often mediated by autonomic nervous system dysfunction, underscore the need for new therapeutic approaches. Cardiovascular rehabilitation programs (CRPs) hold potential as a non-invasive management strategy. Further research should focus on larger-scale clinical trials to validate the efficacy of CRPs and investigate their application in diverse populations, including children and adolescents. The development of standardized diagnostic tools, like AI-enhanced HRV analysis, is crucial for early detection and personalized treatment.

The review's reliance on existing literature may limit its ability to capture the full range of current knowledge on long-COVID cardiovascular complications and the efficacy of CRPs. The available data on the pediatric population remains relatively scarce, requiring further research to understand long-COVID's impact and optimal management strategies in this group. The heterogeneity of long-COVID manifestations could also affect the generalizability of findings from individual studies. Future studies should aim to address these limitations by incorporating more robust methodologies, larger and more diverse participant cohorts, and standardized outcome measures.