key: cord-0705740-2j7lzdnf
authors: Peng, Hor Chee; Hussin, Narwani; Nalliah, Saravanaa; Ooi, Way Ti; Tang, Xing Yi; Zachariah, Sara; Singh, Gurpreet pal Singh Jugindar; Rani, Rosilawati Abdul; Perumal, Kunaraj; Kooi, Cheah Wee
title: Experience of short-term hydroxychloroquine and azithromycin in COVID-19 patients and effect on QTc trend
date: 2020-05-28
journal: J Infect
DOI: 10.1016/j.jinf.2020.05.058
sha: 87b3cfd3ad264a7f0e523500802bfa29d458b1f4
doc_id: 705740
cord_uid: 2j7lzdnf

nan

COVID-19; hydroxychloroquine; azithromycin; QT prolongation; risk assessment Dear Editor,

We have read the paper on concerns in prescribing COVID-19 treatment in this journal with great interest. (1) With the scale of transmission and mortality risk, there is an urgent need to identify an effective antiviral. Combinational hydroxychloroquine and azithromycin emerge as potential therapy but yielded mixed results from clinical studies (2) (3) (4) (5) and raising concerns over cardiovascular safety. (6, 7) We would like to report risk profile, QTc trend and outcomes of 13 COVID-19 confirmed patients admitted to Taiping Hospital, Perak, Malaysia between 21 March 2020 and 13 April 2020, with mild to moderate diseases who were commenced on hydroxychloroquine with without azithromycin.

Diagnosis was confirmed by detection of SARS-CoV-2 from oropharyngeal and/ or nasopharyngeal swabs using reverse transcriptase-polymerase chain reaction (RT-PCR) tests.

We assessed their clinical severity (Stage 1-5) and monitored their disease progression monitor, according to the Malaysian Guideline for COVID-19 Management. (8) Hydroxychloroquine was initiated for all patients with 11 being co-prescribed with azithromycin. Dosage of hydroxychloroquine was initiated at 400mg with a second dose 12 hours apart followed by 200mg twice daily for five days (8) , or adjusted based on risk assessment, at the discretion of treating physician. Azithromycin was initiated at 500mg followed by 250mg daily for five days.

We applied the 10-component Tisdale risk score (9) to assess the patients' risk of developing QT prolongation and monitored their daily 12-lead electrocardiogram up to three days post-treatment.

QT interval was manually calculated from lead II of each electrocardiogram by trained clinicians and corrected for heart rate using Bazett's formula (QTc). QTc interval prolongation was defined as a QTc interval ≥500 ms or an increment of ≥60 ms compared to the baseline value at any time during hospitalization (9) . Drugs that prolong QTc interval were checked using CredibleMeds.org website while drug-drug interactions were examined using Liverpool COVID-19 Drug Interactions.

Among our 13 patients, 53.8% were male with a median age of 52 (27.5, 56.5) years. More than one-third (38.5%) had underlying co-morbidities, with hypertension being the commonest (30.8%), followed by diabetes (15.4%), end-stage renal failure on dialysis (15.4%), coronary artery diseases (7.7%), gout (7.7%) and benign prostatic hypertension (7.7%). None were smokers. Eleven cases had contact exposure to infected patients and two cases were detected through surveillance among patients presented severe acute respiratory tract infections. All other non-critical QT-prolonging medications should be avoided or discontinued prior to hydroxychloroquine initiation. If proton pump inhibitor is indicated, dosing should be spaced by four to six hours. Electrocardiogram and other blood investigations such as electrolytes, renal profile and liver enzymes should be monitored.

We propose a clinical decision support algorithm for treatment initiation to address the cardiovascular safety concerns in COVID-19 patients (Figure 2 ), based on QTc interval 

Prescribing COVID-19 treatments: what we should never forget

No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxychloroquine and azithromycin in patients with severe COVID-19 infection

A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease-19 (COVID-19)

Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial

Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial

Safety considerations with chloroquine, hydroxychloroquine and azithromycin in the management of SARS-CoV-2 infection

Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19

Putrajaya: Ministry of Health

Development and validation of a risk score to predict QT interval prolongation in hospitalized patients. Circulation Cardiovascular quality and outcomes

The authors would like to thank the Director General of Health Malaysia for the permission to publish this paper.

All authors declare no conflict of interest.

The authors received no financial support for the research, authorship, and/or publication of this article.

monitoring. Combinational therapy with azithromycin should be based on clinical risk assessment for QT prolongation.We acknowledge our limitation based on observational study with small study populations. Our experience of risk-based approach in guiding treatment and monitoring might provide insights for future trial or treatment design considerations on similar therapy for COVID-19 patients.(999 words)