Hydroxychloroquine is associated with slower viral clearance in clinical COVID-19 patients with mild to moderate disease: A retrospective study

Mallat, Jihad; Hamed, Fadi; Balkis, Maher M.; Mohamed, Mohamed A.; Mooty, Mohamad; Malik, Asim; Nusair, Ahmad; Bonilla, Maria-Fernanda

doi:10.1101/2020.04.27.20082180

Cited by 45 publications

(53 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our meta-analysis did not reveal a clinical bene t of HCQ/CQ on in-hospital outcomes for patients with COVID- 19. The use of HCQ/CQ did not result in rapid viral clearance on RT-PCR.…”

Section: Discussioncontrasting

confidence: 51%

“…Later on, four other observational studies reported con icting results on viral clearance at different time-points during the disease. Mallat J et al [19] reported that viral negativity was signi cantly lower with HCQ compared to control group, whereas studies from Chen X et al [20] and Huang M et al [21] did not observe rapid viral clearance by CQ. A large multi-center cohort containing 373 patients (mainly mild to moderate COVID-19) by Huang MX et al [14] reported a signi cantly higher rate of viral clearance at Day 10 (91.0% vs 57.0%) and Day 14 (96.0% vs 80.0%) in the CQ treatment group.…”

Section: Discussionmentioning

confidence: 97%

See 1 more Smart Citation

Lack of Benefit in COVID-19 Patients Treated with Hydroxychloroquine or Chloroquine: A Systematic Review and Meta-Analysis

Chen

Yao

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Hydroxychloroquine (HCQ) and chloroquine (CQ) have been widely used for the treatment of the coronavirus disease 2019 (COVID-19), despite limited clinical evidence and controversial early reports. The aim of this report was to provide a systematic review of the literature and meta-analysis on the use of HCQ/CQ with respect to safety and clinical efficacy of these medications. Methods: We performed a systematic search of the medical databases and included studies if they focused on patients with COVID-19 who received HCQ or CQ alone, or in combination with other treatments, and were compared with a control group. We analyzed two important clinical objectives; viral clearance rate by reverse transcription-polymerase chain reaction (RT-PCR) negativity and all-cause mortality.Results: A total of 14 studies were included in the quantitative synthesis. The use of HCQ/CQ was associated with higher viral clearance rate compared with control group (OR: 3.12, 95% CI: 2.17-4.49 p<0.0001). In the sensitivity analysis, the effect on viral clearance disappeared (OR 1.44, 95% CI: 0.87-2.37, p=0.155). The use of HCQ/CQ was associated with a higher risk of mortality (OR 1.26, 95% CI: 1.05-1.51, p<0.0001). Due to huge heterogeneity between the studies (I2 = 86%, p < 0.01), we performed a meta regression analysis. Both treatment within 24 hours (p=0.047) and comorbidities [hypertension (p=0.025), diabetes (p=0.049) and chronic lung disease (p=0.0064)] contributed to the heterogeneity. HCQ/CQ daily dose (p=0.61) and age (p=0.62) had no impact on effect size. Higher rate of comorbidities led to a higher risk of mortality by using HCQ/CQ. Overall, the use of HCQ/CQ resulted in longer QTc intervals.Conclusions: Our meta-analysis did not reveal a clinical benefit of HCQ/CQ on in-hospital outcomes for patients with COVID-19. The use of HCQ/CQ did not result in rapid viral clearance on RT-PCR. Moreover, our results showed that higher rate of comorbidities led to a higher risk of mortality by using HCQ/CQ.

show abstract

“…Our meta-analysis did not reveal a clinical bene t of HCQ/CQ on in-hospital outcomes for patients with COVID- 19. The use of HCQ/CQ did not result in rapid viral clearance on RT-PCR.…”

Section: Discussioncontrasting

confidence: 51%

Section: Discussionmentioning

confidence: 97%

Lack of Benefit in COVID-19 Patients Treated with Hydroxychloroquine or Chloroquine: A Systematic Review and Meta-Analysis

Chen

Yao

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…The risk of bias among the included RCTs, assessed by the Cochrane risk of bias tool, is presented in Figures 2 and 3. Among the observational studies, one was considered to be at low risk, [19] eight at moderate risk, [20][21][22][23][24][25][26][27] seven at serious risk [12,[28][29][30][31][32][33] and one at a critical risk of bias [5].…”

Section: Characteristics Quality and Risk Of Bias Assessment Of Thementioning

confidence: 99%

Hydroxychloroquine in COVID-19: An updated systematic review with meta-analysis

Chacko

Brar²,

Premkumar

2020

Preprint

View full text Add to dashboard Cite

Background Hydroxychloroquine is being administered among patients with COVID19 infection in many healthcare systems across the world considering its in vitro effect against the SARS CoV 2 virus. In spite of several observational studies and a few randomized controlled trials, the effect of hydroxychloroquine on patients with COVID 19 infection remains unclear. We undertook this systematic review with meta-analysis to evaluate the efficacy and safety of hydroxychloroquine among patients with COVID 19 infection. Methods We searched PubMed, Embase, the Cochrane Library, Web of Science, medRxiv, and other relevant resources until May 13, 2020. We included randomized controlled trials and observational studies in which hydroxychloroquine was adminstered and compared to a control group. Data were extracted, and quality assessment of the studies was carried out. We evaluated symptomatic progression, mortality, viral clearance, the evolution of changes on chest CT imaging, and adverse events. A fixed or random-effects model was used depending on outcome heterogeneity. Results We included eleven studies including, three randomized controlled trials and eight observational studies. Among these, 2354 patients received hydroxychloroquine alone or in combination, while 1952 did not. Mortality was reported at different points of time. The overall mortality was not significantly different among patients who received hydroxychloroquine compared to the control group (OR: 1.41, 95% CI: 0.76 to 2.62; p = 0.28). Clinical worsening or lack of symptomatic improvement did not differ between patients who received hydroxychloroquine compared to those who did not (OR 1.1, 95% CI: 0.6 to 2.02; p = 0.76). Viral clearance, assessed by RT-PCR, did not differ significantly between the hydroxychloroquine and the control groups (OR: 1.13, CI: 0.26 to 5.01; p = 0.87). The evolution of changes on chest CT imaging was reported only in two studies; a more pronounced improvement was observed with the use of hydroxychloroquine compared to standard care (OR: 2.68, CI: 1.1 to 6.6; P = 0.03). The incidence of adverse events was significantly higher with hydroxychloroquine (OR: 4.1, CI: 1.42 to 11.88; p = 0.009). Conclusions Our meta-analysis does not suggest improvement in clinical progression, mortality, or viral clearance by RT PCR among patients with COVID 19 infection who are treated with hydroxychloroquine. There was a significantly higher incidence of adverse events with hydroxychloroquine use.

show abstract

“…The median time from con rmed positive to negative nasopharyngeal swab results were 17 days in the HCQ treatment group and 10 days in the control group (P=0.023). It is worth noting that HCQ was administrated at an early stage of the disease course in Mallat's study [29].…”

Section: Discussionmentioning

confidence: 99%

Hydroxychloroquine/ Chloroquine in Patients With COVID-19 in Wuhan, China: A Retrospective Study

Chen

Liu

Cheng

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: We aim to evaluate the treatment value and safety of hydroxychloroquine (HCQ)/ chloroquine (CQ) in COVID-19.Methods: We retrospectively reviewed the medical charts of patients with COVID-19 admitted to an inpatient ward in Wuhan from 2020. 02. 08 to 2020. 03. 05. Patients with HCQ/ CQ and age, gender, disease severity matched ones without HCQ/ CQ were selected at a 1:2 ratio. The clinical, laboratory and imaging findings were compared between these two groups. The multivariate linear regression analysis was performed to identify the factors that might influence patients’ virus shedding periods (VSPs).Results: A total of 14 patients with HCQ/ CQ and 21 matched were analyzed. The HCQ/CQ treatment lasted for an average of 10.36±3.12 days. The VSPs were a little longer in the HCQ/ CQ treatment group (26.57±10.35 days vs. 19.10±7.80 days, P=0.020). There were 3 patients deceased during inpatient period, two patients were with HCQ/ CQ treatment (P=0.551). In the multivariate linear regression analysis, disease durations at admission (t=3.643, P=0.001) and HCQ/CQ treatment (t=2.637, P=0.013) were independent parameters for patients’ VSPs prediction. One patient with CQ had recurrent first-degree atrioventricular block (AVB) and obvious QTc elongation, another one complained about dizziness and blurred vision which disappeared after CQ discontinuation. One patient with HCQ had transient AVB.Conclusions: The HCQ/ CQ administration is not related to neither less mortality cases nor shorter VSPs. HCQ rather than CQ is relative safe and tolerable.

show abstract

Hydroxychloroquine is associated with slower viral clearance in clinical COVID-19 patients with mild to moderate disease: A retrospective study

Cited by 45 publications

References 20 publications

Lack of Benefit in COVID-19 Patients Treated with Hydroxychloroquine or Chloroquine: A Systematic Review and Meta-Analysis

Lack of Benefit in COVID-19 Patients Treated with Hydroxychloroquine or Chloroquine: A Systematic Review and Meta-Analysis

Hydroxychloroquine in COVID-19: An updated systematic review with meta-analysis

Hydroxychloroquine/ Chloroquine in Patients With COVID-19 in Wuhan, China: A Retrospective Study

Contact Info

Product

Resources

About