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Therapeutic effects of dipyridamole on COVID-19 patients with coagulation dysfunction

By Xiaoyan Liu, Zhe Li, Shuai Liu, Zhanghua Chen, Jing Sun, Zhiyao Zhao, Yi-you Huang, Qingling Zhang, Jun Wang, Yinyi Shi, Yanhui Xu, Huifang Xian, Rongli Fang, Fan Bai, Changxing Ou, Bei Xiong, Andrew M Lew, Jun Cui, Hui Huang, Jincun Zhao, Xuechuan Hong, Yuxia Zhang, Fuling Zhou, Hai-Bin Luo

Posted 29 Feb 2020
medRxiv DOI: 10.1101/2020.02.27.20027557

The human coronavirus HCoV-19 infection can cause acute respiratory distress syndrome (ARDS), hypercoagulability, hypertension, extrapulmonary multiorgan dysfunction. Effective antiviral and anti-coagulation agents with safe clinical profiles are urgently needed to improve the overall prognosis. We screened an FDA approved drug library and found that an anticoagulant agent dipyridamole (DIP) suppressed HCoV-19 replication at an EC50 of 100 nM in vitro. It also elicited potent type I interferon responses and ameliorated lung pathology in a viral pneumonia model. In analysis of twelve HCoV-19 infected patients with prophylactic anti-coagulation therapy, we found that DIP supplementation was associated with significantly increased platelet and lymphocyte counts and decreased D-dimer levels in comparison to control patients. Two weeks after initiation of DIP treatment, 3 of the 6 severe cases (60%) and all 4 of the mild cases (100%) were discharged from the hospital. One critically ill patient with extremely high levels of D-dimer and lymphopenia at the time of receiving DIP passed away. All other patients were in clinical remission. In summary, HCoV-19 infected patients could potentially benefit from DIP adjunctive therapy by reducing viral replication, suppressing hypercoagulability and enhancing immune recovery. Larger scale clinical trials of DIP are needed to validate these therapeutic effects.

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