European Heart Journal:

Emerging as a new epidemic, long COVID or post-acute sequelae of coronavirus disease 2019 (COVID-19), a condition characterized by the persistence of COVID-19 symptoms beyond 3 months. The long-term impact of COVID-19 on cardiovascular (CV) health and mortality is also emerging as a major global concern.

Definition of Long Covid

UK National Institute for Health and Care Excellence guidelines defined long COVID as persistence of symptoms beyond 4 weeks of SARS-CoV-2 infection. This term comprises two phases: ongoing symptomatic phase (4–12 weeks) and post-COVID-19 syndrome (>12 weeks) based on the duration of symptoms.

More recently, the World Health Organization provided a case definition for post-COVID-19 condition, a term used to refer to persistence of symptoms beyond 3 months of SARS-CoV-2 infection, lasting for at least 2 months and not explained by any other illness.

Long COVID has been proposed to be a form of chronic fatigue syndrome (CFS)/myalgic encephalitis.

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Signs & Symptoms

Cardiopulmonary symptoms including chest pain, shortness of breath, fatigue, palpitations, cough and autonomic manifestations such as postural orthostatic tachycardia are common and associated with significant disability, heightened anxiety, and public awareness.

Long COVID is a vacillating disease, characterized by a diverse range of symptoms spanning multiple organ systems, and commonly includes fatigue, breathlessness, post-exertional malaise (PEM), brain fog, headaches, nausea, vomiting, anxiety, depression, skin rash, joint pain, and palpitations.

A range of cardiovascular (CV) abnormalities has been reported among patients beyond the acute phase and include myocardial inflammation, myocardial infarction, right ventricular dysfunction, and arrhythmias.

Central illustration depicting (A) Pathophysiological mechanisms underlying acute and chronic severe acute respiratory syndrome coronavirus 2-induced myocardial injury (including effects of vaccine) and its relation with timing of infection and onset of long COVID symptoms, (B) post-COVID-19 cardiovascular sequelae, (C) anticipated long-term cardiovascular complications and outcomes, and (D) the unpredictable trajectory of long COVID and its impact on mental health, ability to work, exercise tolerance, and potential to exacerbate the obesity epidemic. ACE2, angiotensin-converting enzyme 2; CCL, chemokine ligand; COVID, coronavirus disease; IL, interleukin; IFN, interferon; Ig, immunoglobulin; PCR, polymerase chain reaction; POTS, postural orthostatic tachycardia syndrome; RNA, ribonucleic acid; TNF, tumour necrosis factor.

Risk factors for long COVID

Risk factors for long COVID tend to be fairly consistent, with female sex, escalating age, obesity, asthma, poor general health, poor pre-pandemic mental health, and poor socio-demographic factors emerging as important determinants across several studies.

In particular, the impact of nationwide lockdowns, remote working, and limited physical activity on pre-existing trends of an increasingly obese population with poor dietary intake and physical activity patterns is noteworthy.

Post-acute COVID-19 cardiovascular sequelae

In a study of 73 435 (median age 61 years, 88% men) non-hospitalized patients using the US Department of Veterans Affairs health services, demonstrated a high risk of death and incident CV and metabolic diseases associated with COVID-19 beyond 30 days of infection.

A UK-based study of 47 780 hospitalized COVID-19 patients (mean age 65 years, 55% men) demonstrated that a diagnosis of COVID-19 was linked to a three-fold increased risk of major adverse CV events up to 4 months from diagnosis (vs. non-hospitalized controls).

Sinus arrhythmia is frequent in the post-acute phase and manifests as transient or sustained periods of sinus tachycardia or bradycardia.

Cardiac abnormalities commonly reported on follow-up imaging include myopericarditis, right ventricular dysfunction, and ischaemia/infarction.

Postural orthostatic tachycardia syndrome was also the most common diagnosis, followed by neurocardiogenic syncope (15%) and orthostatic hypotension (10%).

CT computed tomography; ECG electrocardiography; POTS Postural Orthostatic Tachycardia Syndrome; SPECT Single Photon Emission Computed Tomography; CCTA coronary computed tomography angiography; CMR cardiac magnetic resonance; ESC The European Society of Cardiology; AHA The American Heart Association; EMB Endomyocardial Biopsy