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.
Background The cause of end-organ damage and acute respiratory distress syndrome (ARDS) in coronavirus disease 2019 (COVID-19) patients is postulated to be connected to the uncontrolled increase of pro-inflammatory cytokines. The upregulation of many cytokines is dependent on signaling through the Janus kinase 1 (JAK-1) and JAK-2 pathways. Ruxolitinib, a JAK-1 and JAK-2 inhibitor, is documented to have potent anti-inflammatory activity by targeting several cytokines and growth factors with proposed efficacy in the cytokine storm observed in severe COVID-19 patients; therefore, this study examines the efficacy and tolerability of ruxolitinib for adult COVID-19 patients. Materials and Methods This review was conducted using preferred reporting items for aystematic reviews and meta-analyses (PRISMA) methodology. Six reviewers analyzed 1,120 results. Seven studies were selected and validated. A quantitative meta-analysis was further performed to evaluate clinical improvement at day 28, mortality at day 28, and oxygen requirements comparing treatment and standard of care groups. Results 168 individuals were involved in the studies selected: 122 in cohort studies, 4 in case reports, and 41 in randomized controlled studies. The ruxolitinib group had a higher likelihood of clinical improvement by the 28th day of treatment when assessed with the standard of care (SOC) group (odds ratio [OR]: 1.48; 95% confidence interval [CI]: 0.53 - 4.16; P = 0.45; I 2 = 0%). The SOC group was at a higher risk of experiencing serious adverse events (OR: 0.17; 95% CI: 0.03 - 1.13; P = 0.07). Notably the SOC group had a higher likelihood of death (OR: 0.51; 95% CI: 0.11-2.29; P = 0.07; I 2 = 0%). Conclusion Prior studies on ruxolitinib have demonstrated it is able to decrease inflammatory markers. In recent studies on COVID-19, treatment with ruxolitinib decreased the time on mechanical ventilation, hospitalization time, and the need for vasopressor support. Additionally, ruxolitinib showed decreased mortality and demonstrated improvement in lung congestion as evidenced by computerized tomography imaging. These findings warrant further clinical investigation into Ruxolitinib as a potential treatment approach for severe COVID-19.
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