Lactate, Capnia, and Fat Oxidation as Therapeutic Axes for SARS-CoV-2 Spike Protein-Induced Sequelae

Metabolic alterations characterize a large subset of those with post-acute COVID-19 syndrome, and similar symptoms affect those with post-acute COVID-19 vaccination syndrome. These symptoms are characterized by the triumvirate of post-acute COVID-19 (vaccination) syndrome symptoms: post-exertional malaise, fatigue, and cognitive impairment, commonly referred to as brain fog. These symptoms can be recreated through perturbations that disrupt mitochondria, and spike protein has been observed to disrupt mitochondria in vitro, providing mechanistic support for this relationship. Post-acute COVID-19 (vaccination) syndrome patients suffer from a severely decreased lactate threshold and can experience symptoms of overexertion even at low power output. Furthermore, biopsies have revealed disrupted mitochondria, and energetics and physiological studies have shown that lipid oxidation constitutes a significantly reduced fraction of total energy production/consumption in post-acute COVID-19 (vaccination) syndrome patients. This review explores the therapeutic axes of lactate, carbon dioxide, and fatty acid oxidation for resolving the energy production challenges in post-acute COVID-19 (vaccination) syndrome, suggesting interventions that increase the lactate threshold, increase tissue oxygenation (paradoxically through increasing partial pressure of CO₂), and increase the rates at which lipids are oxidized relative to carbohydrates. Analogies from the world of exercise science are introduced, comparing post-acute COVID-19 (vaccination) syndrome to an overabundance of fast-twitch muscle fibers, with oxygenation similar to that experienced at high altitude, and presenting as an inverse 'fat adaptation' phenomenon, as observed in endurance athletes, especially those adopting low-carbohydrate diets.