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

Area of Science:

• Biochemistry
• Immunology
• Cardiovascular Medicine

Background:

• Coronavirus disease 2019 (COVID-19) presents significant thrombotic risks, particularly in patients with comorbidities.
• The precise mechanisms underlying COVID-19-associated thrombosis remain unclear.
• Thymidine phosphorylase (TYMP) is implicated in platelet activation and thrombosis, with elevated expression in diabetic patients.

Purpose of the Study:

• To investigate the association between plasma TYMP levels and clinical outcomes in COVID-19 patients.
• To explore TYMP as a potential biomarker for COVID-19 severity and thrombosis.
• To evaluate TYMP inhibition as a therapeutic strategy for COVID-19.

Main Methods:

• Utilized data from the Massachusetts General Hospital Emergency Department COVID-19 Cohort.
• Employed Olink Proteomics for plasma protein analysis.
• Correlated plasma TYMP levels with clinical markers of thrombosis, inflammation, and organ damage.

Main Results:

• Plasma TYMP levels positively correlated with D-dimer, C-reactive protein (CRP), and lactate dehydrogenase (LDH).
• Elevated TYMP was associated with increased Interferon (IFN) levels and respiratory symptoms in COVID-19 patients.
• TYMP levels showed a positive correlation with thrombotic events, inflammation, and organ damage.

Conclusions:

• Plasma TYMP serves as a potential acuity marker for COVID-19 diagnosis and severity assessment.
• Targeting TYMP with tipiracil, an FDA-approved inhibitor, represents a promising therapeutic avenue for COVID-19.
• Further research into TYMP's role could lead to novel treatments for COVID-19 complications.