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 four 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.

Functional Limitations and Exercise Intolerance in Patients With Post-COVID Condition

“…Notably, we observed no discrepancies between patients with PCC and control participants in exercise intensity corresponding to VT and onset of blood lactate accumulation at 4 mmol, indicating undisturbed metabolic exercise response at baseline and at the 48-hour follow-up. Previous suggestions that earlier lactate accumulation, possibly due to peripheral mitochondrial dysfunction leading to premature conversion to anaerobic glycolysis, occurs in the context of PCC and other postviral diseases have not been conclusively proven . Two reports found decreased VT and increased lactate levels after COVID-19, whereas other studies found no difference in VT between patients with PCC and control participants .…”

A scoping review of regulatory T cell dynamics in convalescent COVID-19 patients – indications for their potential involvement in the development of Long COVID?

“…Previous research has proposed that several phenotypes and distinct sub-diagnoses might exist under the umbrella of Long COVID, some of which with little immunological contribution ( 19 , 90 , 91 ). Since the post-acute sequelae of COVID-19 can most certainly not be attributed to a single pathophysiological mechanism ( 18 ), it is conceivable that a Treg dysregulation contributes to a Long COVID-associated immunopathology in multiple ways ( Figure 4 ), as it has also been suggested in other viral infections. For instance, the investigation of patients infected with hepatitis C virus (HCV) showed that those with chronic infections and HCV persistence exhibited higher Treg levels than recovered subjects ( 92 , 93 ).…”

“…In this context, it bears noting that the overall prevalence and types of symptoms can vary depending on the COVID-19 disease severity. Specifically, the proportion of patients that experience residual symptoms appears to be higher among previously hospitalized patients (16)(17)(18). In addition, the results of a clustering analysis conducted as a part of the REACT-2 study suggest that patients with severe initial symptoms report post-acute respiratory symptoms more often than those with mild or asymptomatic COVID-19 whose symptomatology is rather fatigue-dominant (19).…”

Strain Echocardiography in Acute COVID-19 and Post-COVID Syndrome: More than Just a Snapshot

“…Studies with cardiovascular magnetic resonance imaging suggest a complex picture with ischaemic and inflammatory signs in noninvasive tissue characterization [ 52 , 53 ]. The cause of such a persistent injury is ultimately unclear, and diverse hypotheses have been proposed, including immunological aberrations, autoimmunity, a change in the patient’s microbiome, metabolic dysregulation and microvascular, endothelial or hormonal dysfunctions [ 35 , 54 , 55 , 56 ]. Post-COVID is a multifactorial disease in which microvascular perfusion disturbances and inflammation may be most important denominators for cardiac dysfunction [ 49 ].…”