The novel coronavirus, which had initially led to pneumonia of unknown etiology in a series of patients in China’s Hubei province in December 2019, has now precipitated a global health crisis [1]. With the number of infected individuals rising across the globe, identification of effective therapeutic strategies and management of their potential side effects has become of paramount importance. In the absence of solid evidence based on randomized controlled trials supporting a specific treatment, many healthcare professionals have resorted to the off-label use of different medications with a wide range of side effects. Hydroxychloroquine, lopinavir/ritonavir (Kaletra), and azithromycin are among these medications with anecdotal reports supporting their effectiveness in the treatment of this infection. However, all three of these medications are known to cause QT interval prolongation and therefore increase the risk of sudden cardiac death [2], [3], [4]. Furthermore, stress, fever, and electrolyte disturbance can make these individuals prone to arrhythmia. Abnormalities in potassium and magnesium levels are known to affect the QT interval [5]. Therefore, effective countermeasures to manage QTc prolonging effects of the treatments used in patients with COVID-19 infection could play a substantial role in the final outcome of the disease.
Herein, in a retrospective observational study, we report on the effectiveness of implementing the strategy of keeping potassium and magnesium levels above 4 mEq/L and 3 mg/dL respectively in preventing QT prolongation through supplementing these electrolytes in 13 patients diagnosed with COVID-19 infection according to positive SARS-CoV-2 PCR results or typical chest CT findings treated with one or a combination of these medications. On admission, baseline QTc assessment was done and at the same time treatment for COVID-19 was initiated unless QTc ≥ 460 ms. QTc was calculated using Bazett's formula. The mean ± SD pretreatment QTc was 417 ± 22 ms. At the same time baseline values for potassium and magnesium were measured and monitored in addition to providing supplementary doses of these electrolytes throughout the treatment in order to keep their levels above the mentioned thresholds suggested by the national protocol for the treatment of patients with COVID-19 infection. The QTc intervals were assessed every other day in order to monitor for QT prolongation. After a week of treatment, the QTc increased by an average of 14 (95% CI −7 to 35) ms, which was not statistically significant (Fig. 1 ). There was no incidence of arrhythmia or sudden cardiac arrest among the studied individuals.
Fig. 1.
. Box plot of corrected QT interval before and after treatment in patients with COVID-19 infection.
Considering that our study had a minimum power of 80% for detecting a QTc prolongation of ≥ 30 ms, our findings provide supporting evidence for close monitoring and correction of the electrolytes during the treatment of patients with COVID-19 infection, particularly in those treated with medications that prolong the QT interval. We believe that our preliminary data can pave the way for randomized controlled trials investigating the efficacy of this intervention in a broader study population.
Ethics Statement
Compliance with Ethical Standards
This investigation was conducted in accordance with the ethical principles and recommendations outlined in the Declaration of Helsinki.
Funding Sources
None.
Prior Presentation
This manuscript has not been presented earlier.
Ethical approval
Ethics approval was waived for this observational study by the local ethics committee.
Informed consent
Written informed consent was obtained from all study participants.
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
References
- 1.Habibzadeh P., Stoneman E.K. The novel coronavirus: A bird's eye view. Int J Occup Environ Med. 2020;11(2):65–71. doi: 10.15171/ijoem.2020.1921. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Cao B., Wang Y., Wen D., Liu W., Wang J., Fan G. A trial of Lopinavir-Ritonavir in adults hospitalized with severe covid-19. N Engl J Med. 2020 doi: 10.1056/NEJMoa2001282. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Choi Y., Lim H.S., Chung D., Choi J.G., Yoon D. Risk evaluation of azithromycin-induced QT prolongation in real-world practice. Biomed Res Int. 2018;2018:1574806. doi: 10.1155/2018/1574806. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Stas P., Faes D., Noyens P. Conduction disorder and QT prolongation secondary to long-term treatment with chloroquine. Int J Cardiol. 2008;127(2):e80–2. doi: 10.1016/j.ijcard.2007.04.055. [DOI] [PubMed] [Google Scholar]
- 5.Goldberger AL, Goldberger ZD, Shvilkin A. Clinical Electrocardiography: A Simplified Approach,Expert Consult: Online and Print,8: Clinical Electrocardiography: A Simplified Approach: Elsevier/Saunders; 2012.