Overstimulation of the ergoreflex—A possible mechanism to explain symptoms in long COVID

Figures

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  FIGURE 1. An illustration of the ergoreflex. Skeletal muscle exercise causes stimulation of the metabo- and mechano-receptors. The signals are integrated centrally and contribute to the ventilatory and cardiovascular responses to exercise. Exaggerated ergoreflex (e.g., heart failure) leads to excessive response relative to work performed, leading to the sensation of breathlessness and fatigue.

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  FIGURE 2. The ergoreflex in chronic heart failure. Following handgrip dynamometer exercise to exhaustion, a cuff is either inflated around the exercising arm at peak exercise (solid line) or not (dotted line). The cuff is deflated after 3 min (end of circulatory occlusion in gray box). Compared to controls, patients with heart failure have an exaggerated ergoreflex response, resulting in greater ventilatory response to exercise. Their ventilatory response is maintained at the same level as maximum exertion throughout circulatory occlusion. Adapted from Piepoli et al. (11).

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  FIGURE 3. We propose ergoreflex overstimulation as a possible pathophysiological mechanism of long COVID. Acute COVID-19 infection predisposes to insulin resistance and sympathetic and renin-angiotensin-aldosterone system overstimulation, which may lead to chronic inflammation and hypercatabolism. This in turn can cause reduction in skeletal mass and function, which increases ergoreflex sensitivity, and perhaps explains the symptoms of long COVID such as breathlessness and fatigue. Solid and dotted arrows represent known and hypothetical relations, respectively.