Tzu-Han Yang1, Chian-Ying Chou1,2, Yi-Fan Yang3, Chian-Shiu Chien4,5, Aliaksandr A Yarmishyn4,5, Tzu-Ying Yang6, Cheng-Hsuan Liu4,5, Kao-Jung Chang4,5, Yi-Ping Yang4,5, Yuh-Lih Chang1,2,7. 1. Department of Pharmacy, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. 2. Faculty of Pharmacy, School of Pharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan, ROC. 3. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, ROC. 4. Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. 5. School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC. 6. Department of Dietetics and Nutrition, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. 7. Department and Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan, ROC.
Abstract
BACKGROUND: Since COVID-19 outbreak, hydroxychloroquine (HCQ) has been tested for effective therapies and the relevant researches have shown controversial results. METHODS: Systematic review and meta-analysis were conducted after a thorough search of relevant studies from databases. Trials that have evaluated HCQ for COVID-19 treatment were recruited for statistical analysis with fixed- and random-effect models. RESULTS: Nine trials involving 4,112 patients were included in present meta-analysis. It was seen that hydroxychloroquine-azithromycin (HCQ-AZI) combination regimen increased the mortality rate in COVID-19 (OR 2.34, 95% CI 1.63-3.36) patients, however, it also showed benefits associated with the viral clearance in patients (OR 27.18, 95% CI 1.29-574.32). HCQ-alone when used as a therapy in COVID-19 did not reveal significant changes in mortality rate, clinical progression, viral clearance and cardiac QT prolongation. Subsequent subgroup analysis showed that HCQ treatment could decrease mortality rate and progression to severe illness in severely-infected COVID-19 patients (OR 0.27, 95% CI 0.13-0.58). A lower risk of mortality rate was also noted in the stratified group of >14 days follow-up period (OR 0.27, 95% CI 0.13-0.58) compared to ≦14 days follow-up period group that conversely showed an increased mortality rate (OR 2.09, 95% CI 1.41-3.10). CONCLUSION: Our results indicated that HCQ-AZI combination treatment increased mortality rate in COVID-19, but it also showed benefits associated with viral clearance in patients. HCQ-alone used for treatment has revealed benefits in decreasing the mortality rate among severely-infected COVID-19 group and showed potential to be used for COVID-19 treatment in long-term follow-up period group. Accordingly, more rigorous, large-scale and long follow-up period studies in patients with COVID-19 are needed.
BACKGROUND: Since COVID-19 outbreak, hydroxychloroquine (HCQ) has been tested for effective therapies and the relevant researches have shown controversial results. METHODS: Systematic review and meta-analysis were conducted after a thorough search of relevant studies from databases. Trials that have evaluated HCQ for COVID-19 treatment were recruited for statistical analysis with fixed- and random-effect models. RESULTS: Nine trials involving 4,112 patients were included in present meta-analysis. It was seen that hydroxychloroquine-azithromycin (HCQ-AZI) combination regimen increased the mortality rate in COVID-19 (OR 2.34, 95% CI 1.63-3.36) patients, however, it also showed benefits associated with the viral clearance in patients (OR 27.18, 95% CI 1.29-574.32). HCQ-alone when used as a therapy in COVID-19 did not reveal significant changes in mortality rate, clinical progression, viral clearance and cardiac QT prolongation. Subsequent subgroup analysis showed that HCQ treatment could decrease mortality rate and progression to severe illness in severely-infectedCOVID-19patients (OR 0.27, 95% CI 0.13-0.58). A lower risk of mortality rate was also noted in the stratified group of >14 days follow-up period (OR 0.27, 95% CI 0.13-0.58) compared to ≦14 days follow-up period group that conversely showed an increased mortality rate (OR 2.09, 95% CI 1.41-3.10). CONCLUSION: Our results indicated that HCQ-AZI combination treatment increased mortality rate in COVID-19, but it also showed benefits associated with viral clearance in patients. HCQ-alone used for treatment has revealed benefits in decreasing the mortality rate among severely-infectedCOVID-19 group and showed potential to be used for COVID-19 treatment in long-term follow-up period group. Accordingly, more rigorous, large-scale and long follow-up period studies in patients with COVID-19 are needed.
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