Exercise Pathophysiology in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Postacute Sequelae of SARS-CoV-2: More in Common Than Not?

Abstract

Topic importance: Postacute sequelae of SARS-CoV-2 (PASC) is a long-term consequence of acute infection from COVID-19. Clinical overlap between PASC and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) has been observed, with shared symptoms including intractable fatigue, postexertional malaise, and orthostatic intolerance. The mechanistic underpinnings of such symptoms are poorly understood.

Review findings: Early studies suggest deconditioning as the primary explanation for exertional intolerance in PASC. Cardiopulmonary exercise testing reveals perturbations related to systemic blood flow and ventilatory control associated with acute exercise intolerance in PASC, which are not typical of simple detraining. Hemodynamic and gas exchange derangements in PASC have substantial overlap with those observed with ME/CFS, suggestive of shared mechanisms.

Summary: This review illustrates exercise pathophysiologic commonalities between PASC and ME/CFS that will help guide future diagnostics and treatment.

Keywords: CPET; ME/CFS; PASC; hyperventilation; neurovascular dysregulation.

Figure 1

Invasive cardiopulmonary exercise test.

Figure 2

Evaluation of undifferentiated exertional intolerance. ^aBreathing Reserve Index.^{33 b}Peripheral limitation.^{29 c}Age-defined upper limits of normal.^{30 d}The mPAP/Qc slope is age-dependent whereas the TPG/Qc slope is age-independent.^31ePreload failure. Cao₂ = arterial oxygen content; Cvo₂ = venous oxygen content; Hb = hemoglobin; mPAP = mean pulmonary artery pressure; MVV = maximum voluntary ventilation; PAWP = pulmonary artery wedge pressure; PVR = pulmonary vascular resistance; RAP = right atrial pressure; Q_c = cardiac output; TPG = transpulmonary gradient; ULN = upper limit of normal; V_E = minute ventilation; Vo₂ = oxygen uptake.