Results
A total of 336 hospitalized patients with suspicious or confirmed COVID-19 were included in the study. Among them, HCQ was administered to 297 patients and 94 of them met the inclusion criteria. Twenty-eight cases were excluded because of concomitant drug use that might affect QTc and 66 cases were included in final analysis (Figure 1). The mean age of the study population was 57.3 (sd=21.7) years and 54.6% was older than 60 years old and 33% was female. Twenty patients (30.3%) had diabetes mellitus (DM) and 25 (37.9%) patients had hypertension (%37,9). In total, 67% of the cases were confirmed while 23% were probable. The HCQ and AZT combination treatment were given 38% of the study group. Twenty-four percent of the patients had ICU admission and 6.25% died. The ICU admission rate among patients who had HCQ mono-theraphy and HCQ plus AZT were similar (25.0% and 23.1%, respectively. p=0.86). The rate of mortality was also similar among mono and combined theraphy group (5.1% and 8.0%, respectively. p=0.64)
The mean baseline QTc was 444.5 (sd=39.5) ms and was similar in both males and females (442.7 and 448.1 respectively p=0.6). Forty-two percent of the cases had baseline QTc more than 450 ms. Among patients who has DM, the mean baseline QTc was 450.9 ms (sd=48.8) while it was 441.8 ms (sd=35) in non-diabetics (p=0.4). The mean interval of baseline QTc was 455.6 (sd=35.8) ms in hypertensive patients, and 437.8 (sd=40.5) ms in patients without hypertension (p=0.076)
In total, 63% of the patients’ QTc levels increased under HCQ treatment and critical QTc prolongation occurred in 8 cases (12%) all of whom were male (Table 1). In the critical QTc prolongation group the mean level of baseline QTc was 457.4 (sd=55.4) ms, while it was 442.75 (sd=37.1) ms in cases without critical QTc prolongation (p=0.3). AZT was given to 25 patients (38%). The patients who had combination therapy with AZT had a mean baseline QTc level of 448.5 (sd=45.7) ms, while the group without AZT had a mean baseline interval of 442.1 (35.6) ms (p=0.53). The control QTc levels were 460.3 (sd=48.6) ms in AZT combination group and were 451.2 (sd=51.8) ms in patients without AZT (p=0.48). Twenty-one cases used oseltamivir in combination with HCQ (32%). Among these patients, the mean baseline QTc level was 439.7 (sd=35.2) ms while it was 446.8 (sd=41.5) ms in non-oseltamivir group (p=0.5). The mean control QTc levels were 465 (sd=52) ms and 449.8 (sd=49.5) ms in patients with and without oseltamivir treatment, respectively (p=0.26).
The comparison of critically QT prolonged patients with others is shown in Table 1. The mean age and frequency of hypertension were similar among each group while male gender and DM were significantly higher among patients with critical QTc prolongation. AZT use was higher in critical QTc prolongation group but it was not significant (p=0.126) while oseltamivir use was significantly higher in critical QTc prolongation group (p=0.047). In the multivariate analysis, DM was found to be higher among patient who had critical QTc prolongation (OR:5.8, %95 Cl:1.11-30.32, p:0.037). Concomitant use of oseltamivir was also higher in the same group (OR:5.3, %95 Cl:1,02-28, p:0.047. Table 2).
Although a significant proportion of critical QTc prolongation was detected in our study population, none of our patients suffered from cardiovascular end points.