Chloroquine, Hydroxychloroquine & Macrolides in COVID-19 -> Beginning of the End

Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis

Design: Multinational registry analysis including 671 hospitals in North America, South America, Europe, Africa, Asia, and Australia.

Subjects: Patients hospitalized between Dec 20, 2019, and April 14, 2020, and tested positive for SARS-CoV-2. Data abstracted from Surgical Outcomes Collaborative (Surgisphere Corporation, Chicago, IL, USA) database.

Treatment group: Patients who received either HCQ or CQ either alone or in combination with a macrolide. There were four groups of patients:

1. HCQ,

2. HCQ+macrolide

3. CQ

4. CQ+macrolide

Excluded: Patients who received treatment after 48 h of diagnosis of COVID-19; patients who received the study drugs while on mechanical ventilation; patients who were treated with remdesivir.

Primary outcome:

In-hospital mortality. Overall mortality was 10698 (11·1%) of 96032.

Odds ratios for in-hospital mortality

Cox regression analysis

Increased risk of in-hospital death: Age, BMI, black race or Hispanic ethnicity (versus white race), coronary artery disease, congestive heart failure, history of arrhythmia, diabetes, hypertension, hyperlipidemia, COPD, being a current smoker

Decreased risk of in-hospital death: Female gender, Asian, ACE inhibitors (but not angiotensin receptor blockers), statins

Secondary outcome

Dysrhythmias: non-sustained (less than 6 seconds) or sustained VT or VF

Patients with coronary artery disease, congestive heart failure, history of cardiac arrhythmia, and COPD had a higher risk of arrhythmias

Odds ratio for arrhythmias

Propensity matching showed that the associations between the drug regimens and mortality, need for mechanical ventilation, length of stay, and the occurrence of de-novo ventricular arrhythmias were consistent with the primary analysis.

Strengths –

1. A large number of patients – biggest data available to date
2. Very useful to understand common patterns emerging in COVID-19. i. Morbidly obese male patients with age >60 years with at least one CVS co-morbidity are at high risk for mortality. ii.COPD and immunocompromised patients are somehow not affected contrary to what was hypothesised initially.

Limitations –

1. Observational study design – lots of confounding factors
2. Cause-effect relationship between drug therapy and survival should not be interfered.
3. Baseline QTc was not measured in any of the patient.
4. Stratification of arrhythmia patterns is not provided.
5. Study does not include those receiving mechanical ventilation prior to commencement of these drugs.

Summary –

Very insightful study

Raises the question of further need of RCT for macrolide and HCQ. However, prophylaxis use of HCQ is still debatable.

HCQ and macrolide should not be prescribed to COVID-19 patients.