Long COVID: a narrative review of the clinical aftermaths of COVID-19 with a focus on the putative pathophysiology and aspects of physical activity

Abstract

The pandemic coronavirus disease 2019 (COVID-19) can cause multi-systemic symptoms that can persist beyond the acute symptomatic phase. The post-acute sequelae of COVID-19 (PASC), also referred to as long COVID, describe the persistence of symptoms and/or long-term complications beyond 4 weeks from the onset of the acute symptoms and are estimated to affect at least 20% of the individuals infected with SARS-CoV-2 regardless of their acute disease severity. The multi-faceted clinical picture of long COVID encompasses a plethora of undulating clinical manifestations impacting various body systems such as fatigue, headache, attention disorder, hair loss and exercise intolerance. The physiological response to exercise testing is characterized by a reduced aerobic capacity, cardiocirculatory limitations, dysfunctional breathing patterns and an impaired ability to extract and use oxygen. Still, to this day, the causative pathophysiological mechanisms of long COVID remain to be elucidated, with long-term organ damage, immune system dysregulation and endotheliopathy being among the hypotheses discussed. Likewise, there is still a paucity of treatment options and evidence-based strategies for the management of the symptoms. In sum, this review explores different aspects of long COVID and maps the literature on what is known about its clinical manifestations, potential pathophysiological mechanisms, and treatment options.

Keywords: COVID-19; exercise; long COVID; long-term symptoms; pathophysiology; post-acute sequelae.

Figure 1.

Time course of long COVID, dominant symptoms over time and proposed clinical phenotypes (Created with BioRender.com).

Figure 2.

Putative pathophysiological mechanisms underlying long COVID and associated clinical findings (Created with BioRender.com).