Towards an understanding of physical activity-induced post-exertional malaise: Insights into microvascular alterations and immunometabolic interactions in post-COVID condition and myalgic encephalomyelitis/chronic fatigue syndrome - Infection
link.springer.com
Background A considerable number of patients who contracted SARS-CoV-2 are affected by persistent multi-systemic symptoms, referred to as Post-COVID Condition (PCC). Post-exertional malaise (PEM) has been recognized as one of the most frequent manifestations of PCC and is a diagnostic criterion of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Yet, its underlying pathomechanisms remain poorly elucidated. Purpose and methods In this review, we describe current evidence indicating that key pathophysiological features of PCC and ME/CFS are involved in physical activity-induced PEM. Results Upon physical activity, affected patients exhibit a reduced systemic oxygen extraction and oxidative phosphorylation capacity. Accumulating evidence suggests that these are mediated by dysfunctions in mitochondrial capacities and microcirculation that are maintained by latent immune activation, conjointly impairing peripheral bioenergetics. Aggravating deficits in tissue perfusion and oxygen utilization during activities cause exertional intolerance that are frequently accompanied by tachycardia, dyspnea, early cessation of activity and elicit downstream metabolic effects. The accumulation of molecules such as lactate, reactive oxygen species or prostaglandins might trigger local and systemic immune activation. Subsequent intensification of bioenergetic inflexibilities, muscular ionic disturbances and modulation of central nervous system functions can lead to an exacerbation of existing pathologies and symptoms.
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The original was posted on /r/cfs by /u/Dankmemede on 2024-09-09 09:00:27+00:00.

Original Title: New study: Towards an understanding of physical activity-induced post-exertional malaise: Insights into microvascular alterations and immunometabolic interactions in post-COVID condition and myalgic encephalomyelitis/chronic fatigue syndrome

I haven’t seen this study by Scheibenbogen et al here yet, it explains the mechanisms behind PEM. It’s hard to understand, someone on Twitter made a summary which I expanded using ChatGPT:

Activity leads to:

  1. Lactate, ROS accumulation, and energy depletion: Every time we exert ourselves, lactate and reactive oxygen species (ROS) build up, and cellular energy sources (like ATP) become depleted. In healthy individuals, this is normal, but in PEM, mitochondrial dysfunction limits energy production. As a result, metabolic demand rises, and exercise capacity falls. If exertion continues, ROS levels increase and begin to damage mitochondria, worsening energy production further.
  • Practical impact: Activities that normally require moderate energy will now demand significantly more energy, and subsequent activities will produce excessive lactate and ROS, leading to greater stress on the system.
  1. Delayed effects due to immunometabolic interactions: The mitochondrial damage from the initial activity has far-reaching effects on the body’s immune and metabolic functions. This immune response (immunometabolic dysfunction) causes inflammation and disrupts various systems, leading to worsened symptoms after physical activity.
  2. Ionic imbalance: As a downstream consequence of the immunometabolic dysfunction, the body’s ability to regulate electrolytes (ionic balance) becomes impaired. This contributes to abnormal muscle activation, further mitochondrial damage, and triggers additional immune responses.
  3. Self-propagating loop: By exceeding their already limited energy capacity, affected patients are trapped in a cycle where overexertion leads to worsening mitochondrial dysfunction, immune activation, and prolonged recovery, making each future activity more exhausting and harmful.