Efficacy of antiviral therapies for COVID-19: a systematic review of randomized controlled trials.

BACKGROUND: Coronavirus disease 2019 (COVID-19) continues to pose a significant threat to public health worldwide. The purpose of this study was to review current evidence obtained from randomized clinical trials on the efficacy of antivirals for COVID-19 treatment. METHODS: A systematic literature search was performed using PubMed to identify randomized controlled trials published up to September 4, 2021 that examined the efficacy of antivirals for COVID-19 treatment. Studies that were not randomized controlled trials or that did not include treatment of COVID-19 with approved antivirals were excluded. Risk of bias was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) method. Due to study heterogeneity, inferential statistics were not performed and data were expressed as descriptive statistics. RESULTS: Of the 2,284 articles retrieved, 31 (12,440 patients) articles were included. Overall, antivirals were more effective when administered early in the disease course. No antiviral treatment demonstrated efficacy at reducing COVID-19 mortality. Sofosbuvir/daclatasvir results suggested clinical improvement, although statistical power was low. Remdesivir exhibited efficacy in reducing time to recovery, but results were inconsistent across trials. CONCLUSIONS: Although select antivirals have exhibited efficacy to improve clinical outcomes in COVID-19 patients, none demonstrated efficacy in reducing mortality. Larger RCTs are needed to conclusively establish efficacy.

Corticosteroid therapy for COVID-19: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Corticosteroid treatment is an effective and common therapeutic strategy for various inflammatory lung pathologies and may be an effective treatment for coronavirus disease 2019 (COVID-19). The purpose of this systematic review and meta-analysis of current literature was to investigate the clinical outcomes associated with corticosteroid treatment of COVID-19. METHODS: We systematically searched PubMed, medRxiv, Web of Science, and Scopus databases through March 10, 2021 to identify randomized controlled trials (RCTs) that evaluated the effects of corticosteroid therapies for COVID-19 treatment. Outcomes of interest were mortality, need for mechanical ventilation, serious adverse events (SAEs), and superinfection. RESULTS: A total of 7737 patients from 8 RCTs were included in the quantitative meta-analysis, of which 2795 (36.1%) patients received corticosteroids plus standard of care (SOC) while 4942 (63.9%) patients received placebo and/or SOC alone. The odds of mortality were significantly lower in patients that received corticosteroids as compared to SOC (odds ratio [OR] = 0.85 [95% CI: 0.76; 0.95], P = .003). Corticosteroid treatment reduced the odds of a need for mechanical ventilation as compared to SOC (OR = 0.76 [95% CI: 0.59; 0.97], P = .030). There was no significant difference between the corticosteroid and SOC groups with regards to SAEs and superinfections. CONCLUSION: Corticosteroid treatment can reduce the odds for mortality and the need for mechanical ventilation in severe COVID-19 patients.

Bottom-up analysis of emergent properties of N-acetylcysteine as an adjuvant therapy for COVID-19.

N-acetylcysteine (NAC) is an abundantly available antioxidant with a wide range of antidotal properties currently best studied for its use in treating acetaminophen overdose. It has a robustly established safety profile with easily tolerated side effects and presents the Food and Drug Administration's approval for use in treating acetaminophen overdose patients. It has been proven efficacious in off-label uses, such as in respiratory diseases, heart disease, cancer, human immunodeficiency virus infection, and seasonal influenza. Clinical trials have recently shown that NAC's capacity to replenish glutathione stores may significantly improve coronavirus disease 2019 (COVID-19) outcomes, especially in high risk individuals. Interestingly, individuals with glucose 6-phosphate dehydrogenase deficiency have been shown to experience even greater benefit. The same study has concluded that NAC's ability to mitigate the impact of the cytokine storm and prevent elevation of liver enzymes, C-reactive protein, and ferritin is associated with higher success rates weaning from the ventilator and return to normal function in COVID-19 patients. Considering the background knowledge of biochemistry, current uses of NAC in clinical practice, and newly acquired evidence on its potential efficacy against COVID-19, it is worthwhile to investigate further whether this agent can be used as a treatment or adjuvant for COVID-19.

Efficacy of convalescent plasma therapy for COVID-19: A systematic review and meta-analysis.

The purpose of this systematic review and meta-analysis was to examine clinical outcomes associated with convalescent plasma therapy in COVID-19 patients. We performed a literature search on PubMed, medRxiv, Web of Science, and Scopus to identify studies published up to December 10th, 2020 that examined the efficacy of convalescent plasma treatment for COVID-19. The primary endpoints were mortality, clinical improvement, and hospital length of stay. We screened 859 studies that met the search criteria, performed full-text reviews of 56 articles, and identified 15 articles that fulfilled inclusion criteria for meta-analysis. The odds of mortality were significantly lower in the convalescent plasma group compared to the control group (OR = 0.59 [95% CI = 0.44; 0.78], P < .001), although results from two key randomized controlled trials did not support the mortality benefit. The odds of clinical improvement were significantly higher in the convalescent plasma group compared to the control group (OR = 2.02 [95% CI = 1.54; 2.65], P < .001). There was no difference in hospital length of stay between the convalescent plasma group and the control group (MD = -0.49 days [95% CI = -3.11; 2.12], P = .713). In all, these data indicate that a mortality benefit with convalescent plasma is unclear, although there remain benefits with convalescent plasma therapy for COVID-19.

Efficacy and safety of lopinavir/ritonavir in the treatment of COVID-19: A systematic review.

Objectives: To systematically review the clinical literature reporting the use of Lopinavir/ritonavir (LPV/r) for the treatment of patients with Cornonavirus disease 19 (COVID-19) to assess the efficacy of LPV/r for the treatment of COVID-19.Methods: The authors systematically searched PubMed and MedRxiv databases for studies describing treatment of COVID-19 patients using LPV/r compared to other therapies. Articles were excluded if they were case reports, opinion editorials, preclinical studies, single-armed studies, not written in English, not relevant to the topic, or published before May 2020. The included outcomes were viral clearance as measured by reverse-transcription polymerase chain reaction (RT-PCR) negativity and/or improvement on chest computed tomography (CT), mortality, and adverse events.Results: Among 858 total studies, 16 studies met the inclusion criteria and were included in the qualitative review. These studies consisted of 3 randomized control trials, 3 open-label trials, and 10 observational studies. Most of these studies did not report positive clinical outcomes with LPV/r treatment.Conclusion: The systematic review revealed insufficient evidence of effectiveness and clinical benefit of LPV/r in the treatment of COVID-19 patients. Specifically, LPV/r does not appear to improve clinical outcome, mortality, time to RT-PCR negativity, or chest CT clearance in patients with COVID-19.