From heart to muscle: pathophysiological mechanisms underlying long-term physical sequelae from SARS-CoV-2 infection

Abstract

The long-term sequelae of the coronavirus disease 2019 (COVID-19) are multifaceted and, besides the lungs, impact other organs and tissues, even in cases of mild infection. Along with commonly reported symptoms such as fatigue and dyspnea, a significant proportion of those with prior COVID-19 infection also exhibit signs of cardiac damage, muscle weakness, and ultimately, poor exercise tolerance. This review provides an overview of evidence indicating cardiac impairments and persistent endothelial dysfunction in the peripheral vasculature of those previously infected with COVID-19, irrespective of the severity of the acute phase of illness. Additionally, VO2peak appears to be lower in convalescent patients, which may stem, in part, from alterations in O2 transport such as impaired diffusional O2conductance. Together, the persistent multi-organ dysfunction induced by COVID-19 may set previously healthy individuals on a trajectory towards frailty and disease. Given the large proportion of individuals recovering from COVID-19, it is critically important to better understand the physical sequelae of COVID-19, the underlying biological mechanisms contributing to these outcomes, and the long-term effects on future disease risk. This review highlights relevant literature on the pathophysiology post-COVID-19 infection, gaps in the literature, and emphasizes the need for the development of evidence-based rehabilitation guidelines.

Oxygen uptake kinetics and chronotropic responses to exercise are impaired in survivors of severe COVID-19

“…Its pathophysiology mainly involves direct virus-mediated cell damage, endothelial and microvascular injury, and hyperinflammatory response ( 1 ). These acute mechanisms can lead to a spectrum of clinical manifestations ranging from gas-exchange abnormalities to cardiovascular and mitochondrial dysfunction ( 2 , 3 ). In its post-acute phase, the long-lasting effects of the disease include symptoms such as fatigue, dyspnea, and muscle weakness ( 3 ).…”

“…These acute mechanisms can lead to a spectrum of clinical manifestations ranging from gas-exchange abnormalities to cardiovascular and mitochondrial dysfunction ( 2 , 3 ). In its post-acute phase, the long-lasting effects of the disease include symptoms such as fatigue, dyspnea, and muscle weakness ( 3 ). At the same time, COVID-19 survivors often develop exertional intolerance, presenting with reduced exercise capacity ( 4 , 5 ), the etiology of which is still not fully understood.…”

Systematic Review of COVID-19-Related Physical Activity-Based Rehabilitations: Benefits to Be Confirmed by More Robust Methodological Approaches

“…The necessity of restoring their functional capacity seems particularly important for patients who have survived hospitalizations, since half of them present severely impaired physical functioning and a drastically reduced ability to perform daily activities after discharge [ 25 ]. Yet, not only for severe but also for mild forms of the disease, PA might help prevent the risk of complication, reduce the risk of long-lasting disability, and reintroduce patients to their own pre-COVID-19 life [ 26 , 27 , 28 , 29 , 30 , 31 ]. Although there is an impressive number of reviews or recommendation papers mentioning the interest in PA as part of COVID-19 rehabilitation, only a limited amount of clinical evidence is available.…”

‘Long COVID’: Symptom persistence in children hospitalised for COVID‐19

“… 9 , 12 Other studies have suggested that symptoms of long‐COVID, specifically the non‐respiratory symptoms, are due to persistent endothelial dysfunction. 13 , 14 Finally, many studies have shown that the current pandemic has had detrimental psychological impacts on all human populations, including those with cured COVID‐19. 15 , 16 , 17 These psychiatric problems have significant associations with some of the subjective symptoms that are reported by patients with long‐COVID (e.g.…”