COVID-19 and QT interval prolongation: more than just drug toxicity?

A 70-year-old Caucasian man with a history of hypercholesterolaemia, no relevant family or other medical history and normal electrocardiogram (ECG) presented at the emergency room with a 6-day history of cough, fever, and dyspnoea. Blood oxygen saturation was 95% and chest X-ray showed patchy interstitial bilateral opacities suggestive of COVID-19 pneumonitis. Blood tests revealed lymphopenia (600/mL) and elevated fibrinogen (639 g/L), lactate dehydrogenase (405 U/L), and C-reactive protein (185 mg/L). The polymerase chain reaction for SARS-CoV2 was positive and he received 400 mg of hydroxychloroquine b.i.d. on hospital admission followed by 200 mg b.i.d. for four additional days. This treatment was complemented with 500 mg of azithromycin during these 5 days. The patient had progressive deterioration and was placed under mechanical ventilation (Day 6 from admission). He remained stable for the following 5 days when he developed sinus bradycardia which was reverted with isoproterenol infusion during 2 days. Two days later, bradycardia (42 b.p.m.) reappeared together with deep negative T waves on ECG monitoring. The following day (Day 14) a 12-lead ECG (Figure 1A) showed diffuse T-wave inversion and severe QT (620 ms) and QTc (532 ms and 560 ms by Bazzet and Fridericia methods, respectively) interval prolongation. Isoproterenol infusion quickly restored normal heart rate (70 b.p.m.) and new ECGs (Days 16 and 22) showed normal QTc interval with flat and inverted T waves in most ECG leads (Figure 1B). Electrolyte balance and renal function indicators were within normal values during the whole hospital stay. High-sensitive troponin I was 12, 447, 221, 109, and 56 ng/L on days 6, 14, 15, 16, and 17, respectively (50 ng/L reference value). A transthoracic echocardiogram (Day 22) showed moderate global left ventricular hypertrophy (15 mm of interventricular septum), normal systolic function, and no ventricular segmental defects. This together with clinical improvement led to commencing the patient on intermittent mechanical ventilation (Day 22).