Background
Objective
Methods
Results
Conclusion
Keywords
Introduction
Yao X, Ye F, Zhang M, et al. In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [published online ahead of print March 9, 2020]. Clin Infect Dis. https://doi.org/10.1093/cid/ciaa237.
Gautret P, Lagier JC, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial [published online ahead of print March 20, 2020]. Int J Antimicrob Agents. https://doi.org/10.1016/j.ijantimicag.2020.105949.
Chorin E, Dai M, Shulman E, et al. The QT interval in patients with COVID-19 treated with hydroxychloroquine and azithromycin [published online ahead of print April 24, 2020]. Nat Med. https://doi.org/10.1038/s41591-020-0888-2.
Methods
Chorin E, Dai M, Shulman E, et al. The QT interval in patients with COVID-19 treated with hydroxychloroquine and azithromycin [published online ahead of print April 24, 2020]. Nat Med. https://doi.org/10.1038/s41591-020-0888-2.
- Drew B.J.
- Ackerman M.J.
- Funk M.
- et al.
Statistical analysis

Results
Characteristic | Value |
---|---|
Age (y) | 64 ± 13 |
Sex: male | 75 (70–81) |
Weight (kg) | 86.0 ± 17.9 |
Coronary artery disease | 12 (8–16) |
Hypertension | 54 (48–60) |
Chronic kidney disease | 11 (7–15) |
Diabetes mellitus | 27 (21–32) |
Chronic obstructive pulmonary disease | 7 (4–10) |
Congestive heart failure | 3 (1–5) |
Creatinine level at initiation (mg/dL) | 1.2 ± 0.9 |
Creatinine level at the maximum QTc interval (mg/dL) | 1.6 ± 1.5 |
CrCl level at initiation (mL/min) | 84 ± 43 |
CrCl level at the maximum QTc interval (mL/min) | 80 ± 52 |
Abnormal LFTs at initiation | 21 (16–27) |
Abnormal LFTs at the maximum QTc interval | 38 (27–48) |
Potassium level at baseline (mEq/L) | 4.1 ± 0.6 |
Potassium level at the maximum QTc interval (mEq/L) | 4.2 ± 0.5 |
QTc-prolonging medications | |
Psychiatric medications | 12 (8–16) |
Antimicrobials | 10 (7–14) |
Amiodarone | 9 (6–13) |
No. of QTc-prolonging medications | 0.3 ± 0.5 |
0 medications | 71 (65–77) |
1 medication | 27 (22–33) |
2 medications | 2 (0–4) |
Baseline QTc interval (ms) | 439 ± 29 |
Maximum QTc interval (ms) | 473 ± 36 |
Maximum ΔQTc interval (ms) | 34 ± 35 |
Day of the maximum QTc interval | 4.1 ± 2.0 |
Baseline JTc interval (ms) | 342 ± 25 |
Maximum JTc interval (ms) | 375 ± 35 |
Maximum ΔJTc interval (ms) | 33 ± 36 |
Day of the maximum JTc interval | 4.1 ± 1.9 |
Mortality | 20 (14–25) |



Characteristic | Baseline QRS duration < 120 ms (n = 222) | Baseline QRS duration ≥ 120 ms (n = 29) | P |
---|---|---|---|
Age (y) | 63 ± 13 | 73 ± 9 | <.01 |
Sex: male | 75 (70 to 81) | 76 (59 to 92) | >.99 |
Weight (kg) | 85.8 ± 17.5 | 87.7 ± 21.1 | .54 |
Coronary artery disease | 10 (6 to 14) | 21 (5 to 36) | .12 |
Hypertension | 53 (47 to 60) | 59 (40 to 78) | .69 |
Chronic kidney disease | 9 (6 to 13) | 21 (5 to 36) | .10 |
Diabetes mellitus | 24 (18 to 30) | 48 (29 to 68) | .01 |
Chronic obstructive pulmonary disease | 8 (4 to 11) | 3 (−4 to 11) | .70 |
Congestive heart failure | 1 (0 to 3) | 14 (0 to 27) | <.01 |
Creatinine level at initiation (mg/dL) | 1.2 ± 0.9 | 1.6 ± 1.4 | .01 |
Creatinine level at the maximum QTc interval (mg/dL) | 1.6 ± 1.5 | 1.7 ± 0.9 | .02 |
CrCl level at initiation (mL/min) | 87 ± 43 | 65 ± 35 | .01 |
CrCl level at the maximum QTc interval (mL/min) | 82 ± 53 | 59 ± 36 | .03 |
Abnormal LFTs at initiation | 22 (17 to 28) | 15 (0 to 29) | .46 |
Abnormal LFTs at the maximum QTc interval | 40 (28 to 52) | 19 (3 to 34) | .23 |
Potassium level at baseline (mEq/L) | 4.1 ± 0.6 | 4.2 ± 0.4 | .65 |
Potassium level at the maximum QTc interval (mEq/L) | 4.2 ± 0.5 | 4.0 ± 0.4 | .16 |
QTc-prolonging medications | |||
Psychiatric medications | 11 (7 to 15) | 17 (3 to 32) | .35 |
Antimicrobials | 11 (7 to 15) | 7 (−3 to 17) | .75 |
Amiodarone | 8 (4 to 11) | 21 (5 to 36) | .04 |
No. of QTc-prolonging medications | 0.3 ± 0.5 | 0.4 ± 0.6 | .12 |
0 medications | 73 (67 to 78) | 59 (40 to 78) | .13 |
1 medication | 26 (20 to 31) | 38 (19 to 57) | .18 |
2 medications | 2 (0 to 4) | 3 (−4 to 11) | .46 |
Baseline QTc interval (ms) | 434 ± 25 | 475 ± 33 | <.01 |
Maximum QTc interval (ms) | 469 ± 34 | 503 ± 39 | <.01 |
Maximum ΔQTc interval (ms) | 35 ± 35 | 29 ± 40 | .43 |
Day of the maximum QTc interval | 4.0 ± 1.9 | 4.8 ± 2.2 | .05 |
Baseline JTc interval (ms) | 344 ± 24 | 333 ± 26 | .06 |
Maximum JTc interval (ms) | 377 ± 35 | 363 ± 33 | .01 |
Maximum ΔJTc interval (ms) | 33 ± 36 | 30 ± 39 | .52 |
Day of the maximum JTc interval | 4.0 ± 1.9 | 4.7 ± 2.3 | .13 |
No. of follow-up ECGs | 2.9 ± 1.3 | 3.2 ± 1.5 | .33 |
Follow-up time (d) | 5.2 ± 2.0 | 5.8 ± 1.9 | .09 |
Variable | P | OR | 95% CI |
---|---|---|---|
Univariate logistic regression | |||
Age | 0.62 | 1.01 | 0.98–1.03 |
Sex: male | 0.25 | 1.66 | 0.7–3.97 |
Weight | 0.25 | 0.99 | 0.97–1.01 |
Coronary artery disease | 0.21 | 1.82 | 0.72–4.61 |
Hypertension | 0.87 | 1.06 | 0.54–2.09 |
Chronic kidney disease | 0.05 | 2.53 | 1.02–6.26 |
Diabetes mellitus | 0.20 | 1.61 | 0.78–3.3 |
Chronic obstructive pulmonary disease | 0.93 | 1.06 | 0.29–3.84 |
Congestive heart failure | 0.01 | 7.70 | 1.66–35.87 |
Creatinine level at initiation | 0.01 | 1.79 | 1.2–2.69 |
Creatinine level at the maximum QTc interval | <0.01 | 1.35 | 1.12–1.63 |
CrCl level at initiation | 0.04 | 0.91 | 0.84–1.0 |
CrCl level at the maximum QTc interval | <0.01 | 0.88 | 0.8–0.95 |
Abnormal LFTs at initiation | 0.72 | 1.16 | 0.51–2.64 |
Abnormal LFTs at the maximum QTc interval | 0.42 | 0.74 | 0.35–1.55 |
Potassium level at baseline | 0.61 | 0.84 | 0.42–1.65 |
Potassium level at the maximum QTc interval | 0.86 | 0.94 | 0.44–1.99 |
Psychiatric medications | 0.21 | 1.82 | 0.72–4.61 |
Antimicrobials | 0.94 | 0.96 | 0.31–2.94 |
Amiodarone | <0.01 | 5.08 | 2.05–12.61 |
No. of QTc-prolonging medications | 0.01 | 2.40 | 1.31–4.38 |
Baseline QTc interval | <0.01 | 1.32 | 1.16–1.51 |
No. of follow-up ECGs | <0.01 | 2.05 | 1.54–2.73 |
Follow-up time | 0.01 | 1.28 | 1.06–1.55 |
Multivariate logistic regression | |||
Congestive heart failure | 0.53 | 1.79 | 0.3–10.65 |
Creatinine level at initiation | 0.06 | 1.54 | 0.99–2.4 |
Amiodarone | 0.02 | 3.27 | 1.18–9.11 |
Baseline QTc interval | <0.01 | 1.26 | 1.09–1.45 |
Variable | P | OR | 95% CI |
---|---|---|---|
Univariate logistic regression | |||
Age | 0.18 | 1.02 | 0.99–1.04 |
Sex: male | 0.56 | 1.25 | 0.59–2.61 |
Weight | 0.03 | 0.98 | 0.96–1.0 |
Coronary artery disease | 0.05 | 2.32 | 1.01–5.37 |
Hypertension | 0.15 | 1.59 | 0.84–2.98 |
Chronic kidney disease | 0.08 | 2.17 | 0.91–5.16 |
Diabetes mellitus | 0.23 | 1.50 | 0.77–2.92 |
Chronic obstructive pulmonary disease | 0.69 | 0.77 | 0.21–2.77 |
Congestive heart failure | 0.59 | 1.59 | 0.3–8.45 |
Creatinine level at initiation | 0.04 | 1.38 | 1.02–1.87 |
Creatinine level at the maximum QTc interval | 0.01 | 1.27 | 1.05–1.52 |
CrCl level at initiation | 0.07 | 0.93 | 0.86–1.01 |
CrCl level at the maximum QTc interval | <0.01 | 0.90 | 0.83–0.96 |
Abnormal LFTs at initiation | 0.26 | 0.62 | 0.27–1.42 |
Abnormal LFTs at the maximum QTc interval | 0.39 | 0.76 | 0.4–1.43 |
Potassium level at baseline | 0.22 | 1.49 | 0.79–2.82 |
Potassium level at the maximum QTc interval | 0.24 | 1.52 | 0.76–3.04 |
Psychiatric medications | 0.59 | 1.29 | 0.52–3.21 |
Antimicrobials | 0.71 | 1.20 | 0.46–3.16 |
Amiodarone | 0.01 | 3.51 | 1.44–8.55 |
No. of QTc-prolonging medications | 0.03 | 1.88 | 1.07–3.31 |
Baseline QTc interval | <0.01 | 0.78 | 0.69–0.89 |
No. of follow-up ECGs | <0.01 | 1.82 | 1.41–2.34 |
Follow-up time | <0.01 | 1.44 | 1.2–1.74 |
Multivariate logistic regression | |||
Weight | 0.11 | 0.98 | 0.96–1.0 |
Creatinine level at initiation | 0.02 | 1.73 | 1.1–2.7 |
Amiodarone | <0.01 | 5.47 | 1.87–16.02 |
Discussion
Lane JCE, Weaver J, Kostka K, et al. Safety of hydroxychloroquine, alone and in combination with azithromycin, in light of rapid wide-spread use for COVID-19: a multinational, network cohort and self-controlled case series study [published online ahead of print May 31, 2020]. medRxiv. https://doi.org/10.1101/2020.04.08.20054551.
Borba MGS, Val FdA, Sampaio VS, et al; CloroCovid-19 Team. Chloroquine diphosphate in two different dosages as adjunctive therapy of hospitalized patients with severe respiratory syndrome in the context of coronavirus (SARS-CoV-2) infection: preliminary safety results of a randomized, double-blinded, phase IIb clinical trial (CloroCovid-19 Study) [published online ahead of print April 16, 2020]. medRxiv. https://doi.org/10.1101/2020.04.07.20056424.
- Lakkireddy D.R.
- Chung M.K.
- Gopinathannair R.
- et al.
Limitations
Conclusion
Appendix. Supplementary data
- Supplementary Tables 1-3
References
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Gautret P, Lagier JC, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial [published online ahead of print March 20, 2020]. Int J Antimicrob Agents. https://doi.org/10.1016/j.ijantimicag.2020.105949.
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