Low dose of hydroxychloroquine reduces fatality of critically ill patients with COVID-19

Yu, Bo; Li, Chenze; Chen, Peng; Zhou, Ning; Wang, Luyun; Li, Jia; Jiang, Hualiang; Wang, Dao Wen

doi:10.1007/s11427-020-1732-2

Cited by 149 publications

(177 citation statements)

References 21 publications

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“…Mortality outcomes were addressed in 7 observational studies and 2 RCTs. The studies from Yu B et al from China [23] and Membrillo FJ et al from Spain [24] reported reduced in-hospital mortality with the use of HCQ compared to standard care, but there was non-negligible bias in these studies. The rst study reported clinical e cacy of low dose (400mg/day) of HCQ on critically ill patients, whereas the later study reported that high dose (800mg/day) of HCQ was associated with improved survival, which was statistically signi cant only among patients mild COVID-19.…”

Section: Discussionmentioning

confidence: 94%

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

Chen

Yao

et al. 2020

Preprint

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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.

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Section: Discussionmentioning

confidence: 94%

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

Chen

Yao

et al. 2020

Preprint

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“…HCQ/ CQ could inhibit glycosylation of the cell membrane protein angiotensin converting enzyme-2, to which the SARS-Cov-2 is attaching [23]. HCQ/ CQ could downregulate the toll like receptor (TLR) on activated immune cells and block TLR signal transduction, and prohibit several in ammatory factors secretion, such as IL-6 [9,24].…”

Section: Discussionmentioning

confidence: 99%

“…As a derivate of CQ, HCQ is less toxic to retina and heart and is the background treatment in systemic lupus erythematosus (SLE) [8]. Yu and colleagues reported that HCQ treatment could reduce serum interleukin-6 (IL-6) levels in patients with COVID-19 [9]. Except for the antiin ammatory activity, HCQ/ CQ has potential anti-virus effects [10,11].…”

Section: Introductionmentioning

confidence: 99%

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

Chen

Liu

Cheng

et al. 2020

Preprint

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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.

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“…The meta-analysis of death outcome in comparative randomized and non-randomized studies showed no signi cant differences for mortality rate between HCQ with or without AZT regimen and standard treatment group compared with SOC alone (RR 1.08, 95% CI 0.65 to 1.79; participants = 4012; studies = 9; I 2 = 83%; RD -0.01, 95% CI -0.08 to 0.07) (Figure 3c). Sensitivity analysis for HCQ with or without AZT in addition to SOC on mortality compared with SOC alone To evaluate the impact of inverse RRs as well as studies' weight on the meta-analysis results, we conducted sensitivity analyses as according to the substantial low relative weight excluding four studies <50 participants in treatment groups; Barbosa 2020 [26], Gautret 2020 [29], Lee 2020 [25], and Yu 2020 [24]; with total 702 participants from all 4 studies on the meta-analysis. By excluding those studies, no signi cant changes were observed(RR 1.28, 95% CI 0.75 to 2.17) (Supplementary le 2/ gures 3, 4).…”

Section: Hcq With or Without Azt Regimen And Soc Versus Soc Only; Mormentioning

confidence: 99%

Hydroxychloroquine with or without macrolide and standard of care versus standard of care alone for COVID-19 cases: a systematic review and meta-analysis

Shrestha¹,

Budhathoki

Khadka

et al. 2020

Preprint

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Abstract Background: Coronavirus disease (COVID-19) pandemic has been a global health threat. The specific treatment of this disease has not yet been approved. In this review, we aimed at assessing the role of hydroxychloroquine with/without macrolide in terms of efficacy and adverse effects against the standard of care. Methods: Pubmed, Medline, Google Scholar, Cochrane Library, and Clinicaltrials.gov were searched for the quantitative and qualitative synthesis of 13 studies using PRISMA guidelines for a proper review. Assessment of heterogeneity was done using the I-squared (I2) test and fixed/random effect analysis was done to determine the odds/risk ratio among the selected studies.Results: Meta-analysis of our study demonstrated no significant differences in improvement for the virological cure (RR 0.95, 0.67-1.34), whereas a significant relationship was there in radiological progression (pneumonia resolution) (RR 1.40, 1.03-1.91) between the two arms. There are 1.52 times the odds of intubation during treatment (CI 0.61-3.77), 1.08 times the risk of mortality (CI 0.65-1.79), and about 2.21 times increased risk of development of adverse effect (OR 2.21, 0.95-5.17). Though overall it is of no statistical significance, clinical relevance to thinking while using the treatment for COVID-19 is advised. Among randomized controlled trials, the treatment group has 3.5 times (OR 3.48, 1.64-7.42) higher risk of developing adverse effects. There is 2.5 times the likelihood of severe arrhythmias and QT prolongation (OR 2.49, 1.67-3.70) on the treatment arm compared to control.Conclusion: Hydroxychloroquine with/without macrolide has shown no beneficial effect in viral clearance, survival rates while shows significant relation with the radiological improvement compared to standard of care but may increase the risk of intubation, overall side effects, and cardiac complications like arrhythmias and QT prolongation. Thus utilizing this treatment needs to be judged in clinical relevance and proper monitoring.

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Low dose of hydroxychloroquine reduces fatality of critically ill patients with COVID-19

Cited by 149 publications

References 21 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/ Chloroquine in Patients With COVID-19 in Wuhan, China: A Retrospective Study

Hydroxychloroquine with or without macrolide and standard of care versus standard of care alone for COVID-19 cases: a systematic review and meta-analysis

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