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Infection with SARS-CoV-2 causes human COVID-19 (HCoV-19). In severe illness, COVID 19 infection results in lymphopenia, elevated D-dimer levels, hypercoagulation, hypertension, acute respiratory distress syndrome (ARDS), and acute cardiac injury. Dipyridamole (DIP) is an FDA- approved drug which inhibits adenosine uptake that leads to increased extracellular adenosine which in turn stimulates adenosine receptor mediated vasodilatory, anti-platelet and anti-inflammatory effects. These effects are also augmented by DIP's inhibition of phosphodiesterase.
In addition, DIP appears to bind to the HCoV-19 protease enzyme and also suppresses HCoV-19 proliferation in Vero E6 cells with an IC50 less than or equal to 100 nM.
Plasma concentrations in humans from routine dosing regimens (regimen of 50 mg three times per day) exceed this IC50 value for the duration of the dosing interval. In vivo anti-viral effect for DIP, very recently has been demonstrated in vesicular stomatitis virus-induced pneumonia with prolongation of survival (1).
There is limited clinical data on dipyridamole in COVID-19 patients. At this writing, the remdesivir and hydroxychloroquine are now approved for investigations, by the FDA to treat these patients. Although the exact mechanism by which these drugs may work in this infection is not known, DIP exerts its potential salutary effect via different mechanism.
In a preliminary, un-randomized trial with a small number of COVID19 patients treated with prophylactic anticoagulation therapy (Hubei China, January 2020) --the addition of DIP led to increased platelet and lymphocyte counts with reduced D-dimer level, compared to standard of care patients (1).
Additionally, 2 weeks after DIP treatment of 12 patients, 3 of the severe cases and all 4 of the mild-to-moderate cases were discharged from the hospital. One patient died while 3 remaining patients were in remission in the hospital. In the control group, 3 of the 3 mild-to-moderate cases and 1 of 4 severe cases were discharged and only 1 was in remission in the severe group with 1 death. However, the trial was not randomized and was small in size, hence there was no statistical analysis for clinical outcomes.
100 will be enrolled with in an open label, randomized controlled trial with 50 being randomized to receive dipyridamole, 100 mg tid for 7 days being added to Standard Care.
(1). Therapeutic effects of dipyridamole on COVID-19 patients with coagulation dysfunction Xiaoyan Liu, Zhou, Hai-Bin Luo, et. al doi: https://doi.org/10.1101/2020.02.27.20027557
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