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Authors: Mallat et al

Link to paper: https://www.medrxiv.org/content/10.1101/2020.04.27.20082180v1

Journal/ Pre-Print: MedRxiv

Tags: Clinical, Drug discovery/Drug repurpose, Therapeutics

Research Highlights 

1. Hydroxychloroquine (HCQ) treatment increased the time to a SARS-CoV-2 negativity test. (17 days [13-21] HCQ treatment versus 10 days [4-13] days no HCQ treatment, P=0.023). Data adjusted for confounding variables using linear regression analysis.

2. HCQ treatment increased the average hospital stay compared to non-HCQ treatment (17 versus 9 days, respectively, P=0.068).

3. On day 14 of hospital admission, patients who did not receive HCQ tested negative at higher rates (47.8% HCQ treatment Vs 90.9% no HCQ treatment. P=0.016).

Summary 

Hydroxychloroquine (HCQ) has been used for the treatment of COVID-19 patients, with variable reports as to its efficacy. This study included 34 mild-moderate COVID-19 patients (19 had symptoms), where 21 patients were administered HCQ. The authors found that the patients not treated with HCQ progressed to a negative SARS-CoV-2 test (nasopharyngeal swab and PCR test) in a shorter period of time (10 days) compared to HCQ-treated patients (17 days). The authors suggest that the increased time to a negativity test of HCQ-treated patients could be a result of its immunomodulatory effects, although they did not observe statistical differences in inflammatory markers.

Impact for SARS-CoV2/COVID19 research efforts

Inhibit of SARS-CoV2/COVID19 transmission:

Ø The authors find that HCQ treatment results in longer time to a negative test, therefore providing an additional time window for viral transmission.

Treat of SARS-CoV2/COVID19 positive individuals:

Ø This study provides evidence to exert caution about COVID-19 patients being treated with HCQ

Ø No commentary about combination treatments. It does not give information about additional treatments of patients. For example, are the observed effects of HCQ due to combination therapy with azithromycin. 

Study Type

· Clinical Cohort study (e.g. drug trials)

· Patient Case study

Strengths and limitations of the paper

Novelty:

The new insight from this study is that HCQ might lead to reduced viral clearance, prolonging duration of SARS-CoV-2 positivity. 

Standing in the field:

This study reports that HCQ results in slower viral clearance, in contrast to studies by Gautret et al, and more in line with studies finding no change in viral clearance. Additional literature can be found below:

o Papers supporting role of HCQ to improve patient outcome:

§ https://doi.org/10.1038/s41421-020-0156-0

§ https://doi.org/10.1101/2020.03.29.008631doi

§ doi: 10.1016/j.ijantimicag.2020.105949

§ doi: 10.1016/j.tmaid.2020.101663

o Papers reputing role of HCQ in improving patient outcome:

§ DOI: 10.3785/j.issn.1008-9292.2020.03.03

§ https://doi.org/10.1101/2020.04.10.20060558 

Appropriate statistics:

Yes. Multiple statistical tests performed using SPSS 20.0 version.

Most noteworthy; multiple linear regression analysis used to identify whether HCQ was independently associated with primary outcome (Time between positive and negative test) after adjusting for pneumonia or O2 therapy, and symptoms. (i.e. Confounders were taken into account.)

Viral model used: SARS-CoV2

Translatability: These findings are translatable, the study acts as a cautionary tale for HCQ use.

Main limitations:

1. It is not clear why some patients were treated with HCQ and others were not in this retrospective study.

2. Patients with severe COVID-19 were not included in the study.

3. The age of patients included is low, even though many COVID-19 patients who are admitted to hospital are older.

4. More patients in the group treated with HCQ developed symptoms, which could confound results for the negativity of the test.

5. Low number, especially for the non-HCQ treated group.