Unmasking Pandemic Echoes: An In-Depth Review of Long COVID's Unabated Cardiovascular Consequences beyond 2020

Abstract

At the beginning of 2020, coronavirus disease 2019 (COVID-19) emerged as a new pandemic, leading to a worldwide health crisis and overwhelming healthcare systems due to high numbers of hospital admissions, insufficient resources, and a lack of standardized therapeutic protocols. Multiple genetic variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been detected since its first public declaration in 2020, some of them being considered variants of concern (VOCs) corresponding to several pandemic waves. Nevertheless, a growing number of COVID-19 patients are continuously discharged from hospitals, remaining symptomatic even months after their first episode of COVID-19 infection. Long COVID-19 or 'post-acute COVID-19 syndrome' emerged as the new pandemic, being characterized by a high variability of clinical manifestations ranging from cardiorespiratory and neurological symptoms such as chest pain, exertional dyspnoea or cognitive disturbance to psychological disturbances, e.g., depression, anxiety or sleep disturbance with a crucial impact on patients' quality of life. Moreover, Long COVID is viewed as a new cardiovascular risk factor capable of modifying the trajectory of current and future cardiovascular diseases, altering the patients' prognosis. Therefore, in this review we address the current definitions of Long COVID and its pathophysiology, with a focus on cardiovascular manifestations. Furthermore, we aim to review the mechanisms of acute and chronic cardiac injury and the variety of cardiovascular sequelae observed in recovered COVID-19 patients, in addition to the potential role of Long COVID clinics in the medical management of this new condition. We will further address the role of future research for a better understanding of the actual impact of Long COVID and future therapeutic directions.

Keywords: Long COVID; Long Haulers; SARS-CoV-2; chronic inflammation; coronavirus; microthrombosis; myocardial injury; residual dyspnoea.

Figure 1

The spectrum of Long COVID symptoms according to the organ involved. The most commonly reported neurological and cognitive symptoms are brain fog, sleep and memory disturbances and cognitive disturbance, followed by respiratory and cardiovascular symptoms such as palpitations, chest pain and dyspnoea, gastrointestinal symptoms (weight loss, vomiting, diarrhea) and musculoskeletal symptoms (muscle pain or weakness), dominated by chronic fatigue [38].

Figure 2

Potential mechanisms associated with acute myocardial injury in COVID-19. A central role in the pathogenesis of COVID-19 cardiovascular involvement is played by endothelial dysfunction due to a variety of pathophysiological mechanisms, from systemic inflammatory response syndrome including cytokine storm to hypoxia-induced injury or microvascular damage due to perfusion defect, translated in a diverse spectrum of clinical scenarios from acute myocarditis to stress cardiomyopathy [47].