Influence of Hydroxychloroquine Dosage on the Occurrence of Arrhythmia in COVID-19 Infected Ventricle

Abstract

The interaction mechanisms of Hydroxychloroquine (HCQ) in a COVID-19 infected ventricle and its vulnerability to arrhythmogenesis for different dosage levels is not clearly understood. To address this, a 2D transmural anisotropic ventricular tissue model consisting of endocardial, midmyocardial and epicardial myocytes are config-uredfor mild and severe COVID-19 conditions as well as for three dosage levels of HCQ $1 \mu M, 10 \mu M$ and 100 $\mu M)$. Results show that under control and mild COVID conditions, increasing the dosage of HCQ prolongs the QT interval as well as QRS duration, although under severe COVID-19 conditions, inverted T-waves are observed. In addition, on pacing with premature beats (PBs), it is observed that under all condition, premature ventricular complexes (PVCs) are created at $1 \mu M$ and $10 \mu M$ HCQ. However, the PVCs are sustained for a longer duration in presence of $10 \mu M$ HCQ. ST elevation is observed under mild COVID-19 conditions and $1 \mu M$ HCQ and reentrant arrhythmic activity is generated in severe COVID-19 conditions and $10 \mu M$ HCQ dosage. Under all conditions, $100 \mu M$ HCQ doesn't generate arrhythmia or PVCs in presence of PBs. This in-silico ventricular model indicates that the dosage of HCQ as well as pacing sequence influences the appearance of arrhythmic activity and could help in guiding HCQ therapy.