The serum amino acid profile in COVID-19
Alptug Atila Amino Acids volume 53, pages1569–1588 (2021)
The pandemic of the coronavirus disease (COVID-19) caused by SARS-CoV-2 affects millions of people worldwide. There are still many unknown aspects to this infection which affects the whole world. In addition, the potential impacts caused by this infection are still unclear. Amino acid metabolism, in particular, contains significant clues in terms of the development and prevention of many diseases. Therefore, this study aimed to compare amino acid profile of COVID-19 and healthy subject. In this study, the amino acid profiles of patients with asymptomatic, mild, moderate, and severe/critical SARS-CoV-2 infection were scanned with LC–MS/MS. The amino acid profile encompassing 30 amino acids in 142 people including 30 control and 112 COVID-19 patients was examined. 20 amino acids showed significant differences when compared to the control group in COVID-19 patient groups with different levels of severity in the statistical analyses conducted. It was detected that the branched-chain amino acids (BCAAs) changed in correlation with one another, and L-2-aminobutyric acid and L-phenylalanine had biomarker potential for COVID-19. Moreover, it was concluded that L-2-aminobutyric acid could provide prognostic information about the course of the disease. We believe that a new viewpoint will develop regarding the diagnosis, treatment, and prognosis as a result of the evaluation of the serum amino acid profiles of COVID-19 patients. Determining L-phenylalanine and L-2-aminobutyric levels can be used in laboratories as a COVID-19-biomarker.
Also, supplementing COVID patients with taurine and BCAAs can be beneficial for treatment protocols.
To sum up the above information, it has been observed that there was an increase in the amino acid metabolism of COVID-19 patients, and a decrease was observed as a result of this catabolic activity, especially in leucine, isoleucine, valine, taurine, Trans 4-hydroxy L-pyroline, L-pyroline, L-threonine, L-glutamine, L-histidine and L-citrulline serum levels. However, although COVID-19 caused a decrease in the general amino acid levels, interestingly, it caused a significant increase in L-phenylalanine levels when compared to healthy patients, and L-phenylalanine was notable as a differential marker for COVID-19 patients, according to ROC analysis. Alanine is an important substrate in the hepatic synthesis of glucose necessary for the ATP synthesis in leucocytes (Newsholme and Newsholme 1989), and therefore, it affects the immune response. There is significant evidence regarding the fact that 2 mM-alanine support to the culture environment in B-lymphocyte hybridoma-cells prevents apoptosis and increases cell growth and antibody production (Duval et al. 1991; Franěk and Šrámková 1996). Also, in a study conducted on septic sheep, the plasma L-phenylalanine levels significantly increased when compared to healthy sheep (Hoskin et al. 2016). The increase in the phenylalanine amount in HIV-infected patients was thought to be due to the distortion of gastrointestinal phenylalanine intirosine metabolism (Innocenti et al. 2020). In the study conducted on test subjects with sepsis, the plasma L-phenylalanine level was found to be high, and these values were reduced to normal in the treated groups (Cui et al. 2020). Huang et al. also specified that the increased phenylalanine levels show a correlation with renal failure and low albumin levels is an independent predictor of death (Huang et al. 2019). In this study, ROC analysis was increased and showed that L-phenylalanine could be valuable as a differential criterion in the diagnosis of the disease.
Consequently, COVID-19 affects the metabolic pathways of patients with a general destructive process and causes a significant decrease in the levels of many amino acids. The determination of these decreasing levels of amino acids may be a factor that would assist in diagnosis, and their replacement will also be valuable in terms of treatment protocols. The increasing parameters that could be used specifically as diagnosis criteria in COVID patients are serum L-phenylalanine and L-2-aminobutyric acid levels, and an increase has also been observed in correlation with the severity of the disease (Fig. . This situation puts forward L-phenylalanine and L-2-aminobutyric acid as a potential target for differential diagnosis. In conclusion future clinical studies determining L-phenylalanine and L-2-aminobutyric levels can be used in laboratories as a COVID-19-biomarker. Also, supplementing COVID patients with taurine and BCAAs can be beneficial for treatment protocols. However, clinical and experimental studies with wider scope are needed to support these findings.