Table 1.

Description of the included studies in the drug-induced group.

ID	First author (reference)	Type of study	Country	Study Population	Study Purpose	ECG findings
1	Borba MGS9	Randomized clinical trial	Brazil	81 patients (male = 60, female = 21) mean age = 51.1y	To evaluate the efficacy and safety of chloroquine in patients with severe COVID-19.	-prolongation of the QTcF -QTc interval >500 ms:high-dosage group: 7 of 37 [18.9%], low-dosage group: 4 of 36 [11.1%]
2	van den Broek MPH16	Retrospective cohort study	Netherlands	95 patients (Male = 66%) Age (years): 65 (18–91)	To evaluate Chloroquine-induced QTc prolongation in COVID-19 patients	-QTc prolongation (mean = 35 ms (95%CI 28–43 ms) using computerized interpretation and 34 ms (95% CI 25–43 ms) using manual interpretation) -No TdP∗ -QTc more th-an 500 ms in 22 patients (23%) during chloroquine treatment, with no records of prolonged QTc interval prior to the applying medication (p < 0.05)
3	Mercuro NJ17	Cohort	USA	90 COVID-19 positive patients treated with hydroxychloroquine with or without azithromycin (male = 46 (51.1%), female = 44 (48.9%))	Risk of drug-induced QT interval prolongation	- QTc prolongation: • Median increase in QTc = 21 (1–39) ms: 5.5 (−14 to 31) ms in monotherapy, 23 (10–40) ms in combination therapy, p = 0.03 • QTc increase in: critically ill = 26.5,11, 12, 13, 14, 15 not critically ill = 16 (−8 to 35), p = 0.05 • 10 had≥60 ms increase in QTc after treatment (3 in monotherapy, 7 in combination therapy) • 18 had≥500 ms (prolonged) QTc after treatment (7 in monotherapy, 11 in combination therapy) • QTc ≥ 500 ms after treatment in: loop diuretic = 12 out of 39, no loop diuretic = 6 out of 51, likelihood p = 0.03 • QTc ≥ 500 ms after treatment in: patients with baseline QTc ≥ 450 ms: 15 out of 50, patients with baseline QTc< 450 ms: 3 out of 40, likelihood p = 0.008 • Loop diuretic and baseline QTc ≥ 450 ms remained independent for post-treatment prolonged QTc after controlling for 2 or more Systemic Inflammatory Response Syndrome criteria • Age, sex, simultaneous QTc prolonging drugs and comorbidities were not correlated with post-treatment prolonged QTc • 10/90 stopped hydroxychloroquine before 5 days of treatment due to QTc prolongation -PVC∗ (possibly due to hydroxychloroquine) -RBBB∗ (possibly due to hydroxychloroquine) -TdP (1 case, 3 days after hydroxycholoroquine + azithromycin discontinuation due to 499 ms QTc) which later developed other ventricular arrhythmias and was treated with lidocaine
4	Bessiere F18	Case series	France	40 COVID-19 positive patients (male = 32 (80%), female = 8 (20%))	Assessment of QT interval in COVID-19 treated with hydroxychloroquine and +azithromycin	- QT prolongation: 37 patients after antiviral therapy • 14 prolonged QTc after 2–5 days of antiviral therapy: 10 ΔQTc> 60 ms, 7 QTc ≥ 500 ms (1 in monotherapy, 6 in combination therapy, p = 0.03) • Antiviral therapy stopped in 17 patients: 7 because of ECG changes, 10 because of acute renal failure
5	Saleh M19	Prospective observational study	USA	201 hospitalized patients with COVID-19 (male = 115 (57.2%), female = 86 (42.8%))	Effects of chloroquine, hydroxychloroquine, and azithromycin on QTc of COVID-19 patients	-Baseline ECG: 46 had intraventricular conduction delay, incomplete or complete RBBB, LBBB∗ or a ventricular paced rhythm – mean QTc = 439.5 ± 24.8 ms, 8 patients had > 500 msQTc - QTc prolongation: • Mean maximum QTc during cohort = 463.3 ± 42.6 ms: 453.3 ± 37.0 ms in monotherapy, 470.4 ± 45.0 in combination therapy, p = 0.004) • Mean change from baseline to max QTc: 32.8 ± 28.6 ms in monotherapy, 41.6 ± 42.7 in combination therapy, p = 0.19 • Average post-treatment QTc = 454.8 ± 40.1 ms (p < 0.05): 444.7 ± 34.2 in monotherapy, 462.0 ± 42.4 in combination therapy, p = 0.002 • Average QTc increase after 5 days of treatment = 19.33 ± 42.1 ms: 3.9 ± 32.9 in monotherapy, 27.5 ± 44.3 in combination therapy, p < 0.001 • 18 had peak QTc> 500 ms: 7 in monotherapy, 11 in combination therapy, p = 1.00 • 7 discontinue hydroxy due to QTc prolongation • 2 patients required lidocaine to continue hydroxychloroquine: 1 had QTc increase from 458 to 594 ms => IV lidocaine =>QTc reduced to 479 ms => azithromycin discontinued, hydroxychloroquine continued for full 5 day course =>A-fib∗ and acute hypoxic respiratory failure 2 days prior to peak QTc => IV amiodarone. 2 days after finishing hydroxychloroquineQTc = 601 ms (maybe because of furosemide and pantoprazole => IV lidocaine =>QTc = 551 ms =>QTc< 500 ms – the other patient had increased QTc (456 ms–620 ms) after 1 dose of hydroxychloroquine => IV lidocaine =>QTc improved to 550 ms => no further QTc prolongation -New-onset A-fib: 17 patients -Non-sustained monomorphic V-tach: 7 patients -Sustained monomorphic V-tach: 1 patient
6	Chorin, E.20	Consecutive cohort	USA	84 patients with COVID 19 administered hydroxychloroquine and azithromycin as treatment	Evaluation of hydroxychloroquine and azithromycin effect on QTc prolongation in patients with COVID-19	-Prolongation of the QTc from a baseline average of 435 ± 24 ms to a maximal average value of 463 ± 32 ms (p < 0.001) -In ECG documents of 11% of patients, severe QTc prolongation was observed -QTc increased from a baseline average of 447 ± 30 ms to 527 ± 17 ms (p < 0.01) -No TdP (even in severely prolonged QTc cases) -Four patients died from multi-organ failure (no arrhythmia or severe QTc prolongation was noted)

∗Abbreviations: TdP (Torsades de pointes),RBBB/LBBB (right/left bundle branch block), PVC (premature ventricular contraction), A-fib (atrial fibrillation).