Evaluation of the Current Therapeutic Approaches for COVID-19: A Systematic Review and a Meta-analysis

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.

Hydroxychloroquine induces oxidative DNA damage and mutation in mammalian cells

“…The recommended dosage of HCQ in COVID-19 patients is generally higher than that in autoimmune disease but in shorter duration, e.g., an initial loading dose (for up to a few days), followed by several days of maintenance dosing [60][61][62]. The administered doses of HCQ in our study are comparable to the therapeutic doses used in patient populations [25,57,[63][64][65], as described above.…”

“…Notably, the observed genotoxic effects of HCQ are manifest at clinically achievable doses. Given the substantial number of the world's population receiving HCQ for the treatment of various chronic diseases [19] or in the context of clinical trials for COVID-19 [3][4][5][6][63][64][65], our findings warrant further investigations into the biological consequences of therapeutic/preventive use of this drug.…”

Role of miR-2392 in driving SARS-CoV-2 infection

“…Therefore, strategies for therapeutic options against COVID-19 are particularly relevant and important to explore to treat severe illnesses and overcome this global pandemic. Currently, most antivirals are repurposed drugs used for other diseases and have shown limited clinical efficacy, such as remdesivir (Abdelrahman et al, 2021). This brings a needed urgency to develop antivirals specifically designed against SARS-CoV-2.…”

Glycophosphopeptical AM3 Food Supplement: A Potential Adjuvant in the Treatment and Vaccination of SARS-CoV-2

“…Another option is the use of several antivirals in combination (Lopinavir, Ritonavir, Ribavirin) associated with Interferon 1b which has been shown to reduce symptoms and reduce the temporality of the infective phases of COVID-19. However, the therapeutic regimen is complex and its availability in hospitals is limited (12).…”