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

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 of COVID-19 may immune Cathepsins of some amino acids the immune suppression 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, an increased inflammatory state and cell damage. It with COVID-19 who been with antipyretic and antimicrobial at elevated temperatures, but the correct 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. cells macrophages. Monocyte distribution, based on CD14+ CD16+ does not have significant change in the number of classic monocytes (CD14 ++ 16-ve), but an increase in intermediate (CD14++ 16+) and non-classic (CD14+ CD16++) subsets in patients compared to healthy controls. Shown classical double expression of positivity for HLA-DR/CCR2 and HLA-DR/CX3CR1 in patients with COVID-19; however, CCR2 expression was reduced in the intermediate subset in patients with COVID-19. Monocytes are heterogeneous and are classified into different subsets defined by the extent of their cell surface expression of CD14 and CD16. The main subset, termed classical monocytes, consists of CD14highCD16negative monocytes (CD14++ CD16−), while monocytes expressing CD16 are generally divided into an intermediate CD14highCD16low (CD14++ CD16+) subset and a CD14lowCD16high (CD14+ CD16+) subset not classic subset. Differential expression of the chemokine receptors CCR2 and CX3CR1 is associated with these human monocyte subsets with the classic CD14 ++ CD16− subset predominantly expressing CCR2 and the nonclassical CD14 + CD16 ++ subset showing lower CCR2 expression and significantly higher expression of CX3CR1. CCR2 and CX3CR1 are two chemokine receptors that regulate the responses of myeloid cells, such as monocytes and microglia, during inflammation. CCR2 and its ligand are crucial for the the the leading to their exit into cells of the M2 repair The of CX3CR1 and nonclassical monocyte subsets a more phagocytic phenotype greater an the of A shows that SARS-CoV-2, which we detected significantly higher expressions of MPO (~4 fold, p < 0.05) at the nasopharynx region, and speculates this neutrophil burst and even more overexpressed MPO may cause the production of excess hypochlorous acid (HOCl) and other reactive oxidants that also damage the nasopharynx MPO be important can become in