Abstract
The treatment of post-acute sequelae of Covid-19 (PASC) has been informed primarily by symptomatic parallels with other chronic inflammatory syndromes. This manuscript takes a more systemic approach by examining how a marginal deficiency of tetrahydrobiopterin (BH4) resulting from mutations of the GCH1 (GTP cyclohydrolase 1) gene may result in the uncoupling of inducible Nitric Oxide Synthase (iNOS) early in the initial response of the innate immune system to SARS-CoV-2. The resulting production of superoxide instead of nitric oxide leads to a self-perpetuating cycle of oxidative stress with the potential to impair numerous metabolic processes and damage multiple organ systems. This marginal deficiency of BH4 may be exhibited by 30% or more of the patient population that have heterozygous or homozygous mutations of GCH1. As the cycle of oxidative stress continues, there is less BH4 available for other metabolic needs such as 1) resisting increased ferroptosis with its damage to organs, and 2) regulating the deactivation of the hyperinflammatory state. Finally, possible steps are proposed for clinical treatment of the hypothesized oxidative stress involved with PASC.
【저자키워드】 Ferroptosis, oxidative stress, Post-acute sequelae of COVID-19 (PASC), Uncoupling iNOS, Marginally deficient BH4, GCH1 mutations, AGMO, 【초록키워드】 Treatment, SARS-CoV-2, Mutation, nitric oxide, tetrahydrobiopterin, innate immune system, symptomatic, PASC, hyperinflammatory state, Inflammatory, Clinical treatment, organ systems, deficiency, organs, manuscript, heterozygous, Oxide, approach, initial, resulting, involved, the patient, exhibited, less, impair, Synthase, GCH1, GTP, homozygous mutation, metabolic processe, 【제목키워드】 deficiencies, Marginal,