Abstract
Background: Limited data on the efficacy and safety of currently applied COVID-19 therapeutics and their impact on COVID-19 outcomes have raised additional concern. Objective and Methods: To estimate the efficacy and safety of COVID-19 therapeutics, we performed meta-analyses of the studies reporting clinical features and treatments of COVID-19 published from January 21 to September 6, 2020. Results: We included 136 studies that involved 102,345 COVID-19 patients. The most prevalent treatments were antibiotics (proportion: 0.59, 95% CI: [0.51, 0.67]) and antivirals (proportion: 0.52, 95% CI: [0.44, 0.60]). The combination of lopinavir/ritonavir and Arbidol was the most effective in treating COVID-19 (standardized mean difference (SMD) = 0.68, 95% CI: [0.15, 1.21]). The use of corticosteroids was associated with a small clinical improvement (SMD = −0.40, 95% CI: [−0.85, −0.23]), but with a higher risk of disease progression and death (mortality: RR = 9.26, 95% CI: [4.81, 17.80]; hospitalization length: RR = 1.54, 95% CI: [1.39, 1.72]; severe adverse events: RR = 2.65, 95% CI: [2.09, 3.37]). The use of hydroxychloroquine was associated with a higher risk of death (RR = 1.68, 95% CI: [1.18, 2.38]). The combination of lopinavir/ritonavir, ribavirin, and interferon-β (RR = 0.34, 95% CI: [0.22, 0.54]); hydroxychloroquine (RR = 0.58, 95% CI: [0.39, 0.58]); and lopinavir/ritonavir (RR = 0.72, 95% CI: [0.56, 0.91]) was associated with reduced hospitalization length. Hydrocortisone (RR = 0.05, 95% CI: [0.03, 0.10]) and remdesivir (RR = 0.74, 95% CI: [0.62, 0.90]) were associated with lower incidence of severe adverse events. Dexamethasone was not significant in reducing disease progression (RR = 0.45, 95% CI: [0.16, 1.25]) and mortality (RR = 0.90, 95% CI: [0.70, 1.16]). The estimated combination of corticosteroids with antivirals was associated with a better clinical improvement than antivirals alone (SMD = −1.09, 95% CI: [−1.64, −0.53]). Conclusion: Antivirals are safe and effective in COVID-19 treatment. Remdesivir cannot significantly reduce COVID-19 mortality and hospitalization length, while it is associated with a lower incidence of severe adverse events. Corticosteroids could increase COVID-19 severity, but it could be beneficial when combined with antivirals. Our data are potentially valuable for the clinical treatment and management of COVID-19 patients.
Highlights
Since the outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, more than 30 million cases and 945,000 deaths have been reported as of September 17, 2020, in the world (Johns Hopkins University, 2020)
This study focused on evaluating the frequently used treatment strategies, including antibiotics, antivirals, corticosteroids, chloroquine or hydroxychloroquine, tocilizumab, interferons, immunoglobulins, and RRT
We found that the combination of lopinavir/ritonavir and Arbidol was significantly effective among COVID-19 treatments
Summary
Since the outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, more than 30 million cases and 945,000 deaths have been reported as of September 17, 2020, in the world (Johns Hopkins University, 2020). Previous experiences from SARS and MERS treatments suggested that several interventions, including antivirals, such as lopinavir/ritonavir and umifenovir, corticosteroids, interferons, ribavirin, and newly introduced drugs, including chloroquine or its derivative hydroxychloroquine, dexamethasone, and convalescent plasma, may improve clinical outcomes in COVID-19 patients, whereas the related data are not conclusive. Since the evidence of the efficacy and safety of these treatments remains lacking, we conducted meta-analyses of the therapeutic approaches for COVID-19 patients. Our meta-analyses aimed to identify the positive benefits (such as clinical improvement) and negative risks (such as long duration of hospitalization, severe adverse events, and increased deaths) of treatment strategies for COVID-19 by comparing different treatments using different meta-analysis models. Limited data on the efficacy and safety of currently applied COVID-19 therapeutics and their impact on COVID-19 outcomes have raised additional concern
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