Abstract Number: PB0148
Meeting: ISTH 2021 Congress
Background: 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. Our recent studies found that thymidine phosphorylase (TYMP) plays an important role in platelet activation, thrombosis, and TYMP expression is increased in obese and diabetic patients.
Aims: To test the hypothesis that TYMP participates in the host response to SARS-CoV-2.
Methods: By co-transfection of SARS-CoV-2 spike protein (SP) and human ACE2 into Cos-7 cells, we examined how SP regulates ACE2 and TYMP expression. By using data provided by the MGH (Massachusetts General Hospital) Emergency Department COVID-19 Cohort with Olink Proteomics we analyzed the correlation between plasma TYMP and the severity of COVID-19.
Results: Overexpression of S protein or its receptor-binding domain led to ACE2 shedding into a different size. S protein also increased TYMP expression in Cos-7 cells. In comparing to COVID-19 negative patients, plasma TYMP in COVID-19 patients was significantly increased in a severity-dependent manner. The increase of plasma TYMP was earlier than the increase of C creative protein, a predictive factor for inflammation and future risk of cardiovascular events. The increase of TYMP is positively associated with plasma D-dimer and lactate dehydrogenase, the presence of pulmonary symptoms, as well as IFN-γ and IFN-λ, especially IFN-λ. We also found that TYMP is highly expressed in mouse asthmatic lungs and human type II alveolar epithelial cells and bronchial epithelium, which mediate SARS-CoV-2 entry.
Conclusions: TYMP is positively correlated with COVID-19 acuity and COVID-19-associated thrombotic event, inflammation, and organ damages. TYMP could be an acuity marker for COVID-19 diagnosis. Targeting TYMP could be a novel effective medicine for COVID-19.
To cite this abstract in AMA style:Yue H, Denning K, Li W. Targeting Thymidine Phosphorylase May Be a Novel Therapy for COVID-19 [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/targeting-thymidine-phosphorylase-may-be-a-novel-therapy-for-covid-19/. Accessed November 28, 2023.
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