QT Prolongation Associated With Chloroquine Based Therapy For Covid-19 Infection

Abstract

COVID -19 has caused unprecedented socio-economic, political and health upheavals not seen since World War II. COVID-19 therapeutics has focused on traditional public health outbreak response tactics-isolation, quarantine, social distancing, and community containment. Specific antiviral agents, anti parasitic agents  are being tried as off label treatments for COVID-19 in the absence of efficacious and safe drugs that have undergone multi centre clinical  trials. Though remdesivir currently has Emergency use authorization (EUA) based on preliminary study, drug regulatory bodies had previously issued EUA to allow hydroxy-chloroquine sulfate and chloroquine phosphate to be used for certain hospitalized patients with COVID-19 pending when a clinical trial is available or feasible. There are cardiovascular related adverse effects particularly QT prolongation and Torsade de Pointes (TdP) which is accentuated when  chloroquine is administered with other QT prolonging drugs or in the presence of metabolic conditions favoring QT prolongation.This review raises the real concern that significant percentage of  COVID-19 patients have risk factors which includes: concomitant use of chloroquine and Azithromycin together, background heart disease in patients with hypertension and diabetes mellitus, factors leading to electrolyte imbalance,  that increase their likelihood of having prolonged QT and TdP. Proper assessment of all patients on chloroquine will be required to reduce the chances of TdP and sudden death. COVID-19 patients who need chloroquine therapy should have a baseline assessment. A risk score has been derived and validated by Tisdale et al, for prediction of drug-associated QT prolongation and can be adapted for COVID-19 patients on chloroquine therapy. If chloroquine-induced TdP has occurred, the patients should be triaged into stable and unstable class. The stable patients are likely to have a spontaneous termination of TdP particularly after withdrawal of chloroquine and other drug-inducing QT prolonging therapy or metabolic derangement. For the stable patients, intravenous magnesium is the first line of choice even in patients with normal magnesium levels.

Keywords : Covid-19, chloroquine based therapy, QT Prolongation, Sudden Death