The COVID-19 "Bad Tryp" Syndrome: NAD/NADH+, Tryptophan Phenylalanine Metabolism and Thermogenesis like Hecatomb - The Hypothesis of Pathophysiology Based on a Compared COVID-19 and Yellow Fever Inflammatory Skeleton

Abstract

Introduction:There is a significant imbalance in the generation of NAD/NADH+ (niacin), which affects chemical reactions in the intracellular environment in COVID-19 and yellow fever. From tryptophan and its metabolic pathways and oxidative stress, the process of understanding SARS-CoV-2 infection becomes more concrete, as the infection seems to interfere in these metabolic pathways, in addition to the paradoxical role of kynurenine that causes inflammation by blocking the BH4 pathway. Understanding metabolic changes in the elderly, people with type 2 diabetes (DM2), obese people or other chronic diseases with an inflammatory profile is to understand the severity of COVID-19 to improve clinical management.Hypothesis: SARS-CoV-2 may control the human immune response by acting on Furins and Cathepsins or triggering significant hypoxia; promotes the internalization of ACE-2, resulting in low absorption of some amino acids in the intestine, triggering immune suppression and metabolic syndrome (MS).Results: From overweight people to people with higher Body Mass Index (BMI) or insulin resistance, there is a tendency to hyperthermia by thermogenesis due to the consumption of serotonin (5-HT) and norepinephrine (NOR) in fat cells, triggering an increased inflammatory state and cell damage.It is typical of critically ill patients with COVID-19 who have been treated with antipyretic and antimicrobial drugs at elevated temperatures, but the correct treatment is an insulin pump. It is not fever; it is hyperthermia. The state of inflammation is related to the Kynurenine/BH4 imbalance.Objectives: This article aims to raise doubts to generate more discussions and bring more substrates to improve the patient's COVID-19. The primary pathophysiology of COVID-1 may be tryptophan syndrome due to kynurenine/ BH4 imbalance and the maintenance of the hypoxic environment that causes immunosuppression, tolerance and inflammation due to oxidative stress. A signature of innate immunity, oxidative stress, and tryptophan pathway imbalance.

Treatment of 95 post-Covid patients with SSRIs

“…An overactive KP during a severe infection however, is toxic for neurons, especially for serotonin neurons. Not only does the KP hijack tryptophan away from the serotonin pathway, 28,30,31 the metabolite kynurenine and oxidative stress also lowers the level of tetrahydrobiopterin (BH4), 1,55,56 an important coenzyme of the serotonin pathway.…”

“…Moreover, BH4 is an important coenzyme of the dopamine pathway -and to the norepinephrine pathway 20,55 -thus the overactive KP damages these two neurotransmitter systems too. When there is no longer enough tryptophan, this can lead to serotonin depletion.…”

“…Furthermore, folic acid (vit. B11) 63 can promote the conversion of B2 back into B4 55,63 in favour of the serotonin and dopamine pathway.…”

“…Kynurenine and oxidative stress block the enzyme tetrahydrobiopterin (BH4), 1,56 inhibiting both the serotonin pathway and the dopamine pathway. 1,20,55,56 Kynurenic acid is a nicotine-receptor antagonist and a glutaminergic-receptor antagonist. 28,30,32 Quinolinic acid blocks the glutaminergic receptor.…”