Thymidine Phosphorylase Is Increased in COVID-19 Patients in an Acuity-Dependent Manner

Abstract

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), is a human respiratory disease. Hitherto, there is no effective treatment has been established. Patients with cardiovascular or diabetes comorbidities are a high-risk cohort. COVID-19 is accompanied by excessive systemic thrombotic events, but the mechanism is not yet known. Recent studies have indicated that thymidine phosphorylase (TYMP) plays an important role in platelet activation, thrombosis, and TYMP expression is increased in diabetic patients. By using data provided by the MGH (Massachusetts General Hospital) Emergency Department COVID-19 Cohort with Olink Proteomics, here we show that plasma TYMP level is correlated with the COVID-19 associated thrombotic event, inflammation, and organ damage, as evidenced by the positive correlations with plasma D-dimer, CRP (C reactive protein), and LDH (lactate dehydrogenase), as well as Interferons (IFN). Plasma TYMP is also positively correlated with COVID-19 patients who had respiratory symptoms. TYMP thus could be an acuity marker for COVID-19 diagnosis. Targeting TYMP with tipiracil, a selective TYMP inhibitor, which has been approved by the Food and Drug Administration for clinical use, could be a novel effective medicine for COVID-19.

Thymidine Phosphorylase is Increased in Patients with Infection and Could be a Prognostic Marker for Sepsis and Disseminated Intravascular Coagulation

“…In this study, we found that serum TYMP is negatively correlated with oxygenation index in patients with infections, suggesting that the more severe respiratory insufficiency the patients have, the higher serum TYMP levels are detected. This finding is in line with our previous findings in the COVID-19 patients, in which we found that TYMP was positively correlated with the presence of pulmonary symptoms [20]. Therefore, TYMP may be a valuable marker in evaluating respiratory failure in infection patients.…”

“…Since TYMP is an intracellular protein, the increase of plasma/serum TYMP could be a marker of sepsis-associated organ damage, especially for organs with high TYMP expression, such as lung, kidney, and circulating nucleated cells or platelets. In our recent study, we found that plasma TYMP is positively correlated with LDH levels in severe COVID-19 patients [20]; however, we did not find a positive correlation between TYMP and LDH in the current cohort of patients. This could be resulted from the nature of our small cohort that is a mixture of patients with different organ infection.…”

“…Several inflammatory cytokines (e.g., TNFα, IL-1, IL-6, IL-8, IL-17, interferon-γ [IFN-γ], and granulocyte-colony stimulating factor [G-CSF]) also induce TYMP expression [8,[25][26][27]. Our recent study also indicated that TYMP could be a severity marker for COVID-19 and its plasma levels is positively correlated with SARS-CoV-2 infection-induced inflammation and thrombotic event [20]. These data suggest that TYMP may be a pro-inflammation factor, which is supported by this study.…”

“…TYMP has been reported to play important roles in platelet signaling activation and thrombosis and plasma levels of TYMP are positively correlated with the thrombotic event in patients with COVID-19 [13,14,20]. We thus analyzed the changes of TYMP based on thrombotic evidence and its correlation with thrombotic marker.…”

“…Several studies have implicated that these inflammatory cytokines can upregulate TYMP expression [18,19], and TYMP may also contribute to the generation of several cytokines [8]. Most intriguingly, by using a big database provided by the Massachusetts General Hospital Emergency Department COVID-19 Cohort with Olink Proteomics, Li and Yue recently found that plasma TYMP levels is correlated with the severity of COVID-19, as well as COVID-19-associated acuity markers, such as C reactive protein (CRP), D-dimer, and lactate dehydrogenase (LDH) [20]. It has been suggested that immune response of COVID-19 mirrors the image of Sepsis [21].…”