Long-COVID Syndrome and the Cardiovascular System: A Review of Neurocardiologic Effects on Multiple Systems

Abstract

Purpose of Review Long-COVID syndrome is a multi-organ disorder that persists beyond 12 weeks post-acute SARS-CoV-2 infection (COVID-19). Here, we provide a definition for this syndrome and discuss neuro-cardiology involvement due to the effects of (1) angiotensin-converting enzyme 2 receptors (the entry points for the virus), (2) inflammation, and (3) oxidative stress (the resultant effects of the virus). Recent Findings These effects may produce a spectrum of cardio-neuro effects (e.g., myocardial injury, primary arrhythmia, and cardiac symptoms due to autonomic dysfunction) which may affect all systems of the body. We discuss the symptoms and suggest therapies that target the underlying autonomic dysfunction to relieve the symptoms rather than merely treating symptoms. In addition to treating the autonomic dysfunction, the therapy also treats chronic inflammation and oxidative stress. Together with a full noninvasive cardiac workup, a full assessment of the autonomic nervous system, specifying parasympathetic and sympathetic (P&S) activity, both at rest and in response to challenges, is recommended. Cardiac symptoms must be treated directly. Cardiac treatment is often facilitated by treating the P&S dysfunction. Cardiac symptoms of dyspnea, chest pain, and palpitations, for example, need to be assessed objectively to differentiate cardiac from neural (autonomic) etiology. Summary Long-term myocardial injury commonly involves P&S dysfunction. P&S assessment usually connects symptoms of Long-COVID to the documented autonomic dysfunction(s).

Hyperbaric Oxygen Therapy Counters Oxidative Stress/Inflammation-Driven Symptoms in Long COVID-19 Patients: Preliminary Outcomes

“…The findings of this study show that ROS and oxidative damage to lipids and DNA are significant factors in long COVID-19 patients. Also, our data confirm that the evolution of long COVID-19 is driven by cytokines produced in the body due to inflammation [62], which are often generated in response to viral infections and lead to oxidative stress, with immune status and altered lung function measures.…”

From Cell to Symptoms: The Role of SARS-CoV-2 Cytopathic Effects in the Pathogenesis of COVID-19 and Long COVID

“…The proinflammatory cytokines IL-1, IL-6, IFN-γ and TNF-α depress myocardial function through activation of the neural sphingomyelinase pathway through reduction of nitric oxide-mediated beta-adrenergic signaling [166]. In accordance with these cytopathic effects at the level of the circulatory system, it has been reported that, among the symptoms that persist in long COVID, some cardiovascular events may be frequent, such as arrhythmias, cardiac lesions, chest pain, palpitations, hypotension, increased heart rate, venous and arterial thromboembolic diseases, myocarditis and acute heart failure [24,167,168], which may contribute to increased patient morbidity and mortality. In addition, increased cardiometabolic demand may be a persistent sequela in some recovered patients, which may be related to dysregulation of the RAAS system [24].…”

A Post-Pandemic Enigma: The Cardiovascular Impact of Post-Acute Sequelae of SARS-CoV-2

“…Individuals may also be misdiagnosed due to significant overlap with other disorders characterized by autonomic dysfunction, which include POTS, orthostatic dysfunction, and ME/CFS. 92 Several studies also suggest that autonomic disorders may materialize after viral triggers, such as SARS-CoV-2. 93,94 Use of the Composite Autonomic Symptom Score-31 questionnaire in individuals with PASC has shown significant utility in identifying autonomic symptoms and providing a basis for therapeutic management and longitudinal assessment.…”