4.7 Article

Phenylalanine and COVID-19: Tracking disease severity markers

Journal

INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 101, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.intimp.2021.108313

Keywords

COVID-19; SARS-CoV-2; Cytokines; Phenylalanine; Tyrosine

Funding

  1. Fundacao de Amparoa Pesquisa do Estado de Sao Paulo -Brasil (FAPESP) [2014/50867-3, 2019/16135-9, 2020/13939-7]
  2. Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior -Brasil (CAPES) [001]

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The study found that serum phenylalanine levels are positively correlated with disease severity in COVID-19 patients, independent of inflammatory cytokines. Patients with mild disease have lower serum phenylalanine levels in the early stages of the disease.
Background: Although there are several severity predictors for COVID-19, none are specific. Serum levels of phenylalanine were recently associated with increased inflammation, higher SOFA scores, ICU admission, and mortality rates among non-COVID-19 patients. Here, we investigated the relationship between phenylalanine and inflammatory markers in adults with COVID-19. Methods: We assessed adults with COVID-19 at hospital admission for clinical and laboratory data. Nuclear magnetic resonance spectroscopy measured serum levels of phenylalanine and other amino acids of its metabolomic pathway. Flow Cytometry measured serum levels of IL-2, IL-4, IL-6, Il-10, TNF-alpha, and IFN-gamma. Linear regression models adjusted for potential confounders assessed the relationship between serum levels of phenylalanine and inflammatory cytokines. Results: Phenylalanine and tyrosine were significantly lower in mild disease as compared to moderate and severe groups. Linear regression models showed that phenylalanine is independently and positively associated with disease severity regardless of the cytokine analyzed and after adjustment for potential confounders. In addition, mild cases showed consistently lower serum phenylalanine levels within the first ten days from disease onset to hospital admission. Conclusions: Phenylalanine is a marker of disease severity. This association is independent of the time between the onset of symptoms and the magnitude of the inflammatory state.

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