Ruxolitinib and the Mitigation of Severe COVID-19: A Systematic Review and Meta-analysis

Abstract

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.

Potential Pathophysiological Mechanisms Underlying Multiple Organ Dysfunction in Cytokine Release Syndrome

“…Reduced IL-12 and IL-23 levels result in the inactivation of Th-1 and Th-17 cells. This reduces the production of IL-17, IL-22, TNF- α , IFN- γ , and IL-2, ultimately weakening the inflammatory response [ 128 ]. However, this downregulation increases the body's susceptibility to opportunistic pathogens and the risk of activation of latent infections.…”

Spontaneous complete resolution of alopecia totalis post SARS-CoV-2 infection

“…However, it has been suggested that patients should be counseled about the relative reported safety of continuing JAK inhibitors during COVID-19 to limit AA progression. 9 There is no report of full hair regrowth after COVID-19 in patients with pre-existing AA. However, one case report describes some improvement after a SARS-CoV-2 infection in a 27-year-old female known to have alopecia universalis successfully treated with tofacitinib and who maintained her treatment during her disease.…”

Drugs being tested against covid-19 to slow down its spread and find effective treatment: A systematic review.

“…Furthermore, computed tomography imaging revealed ruxolitinib reduced mortality rates and improved pulmonary congestion. These researches call for further clinical research into Ruxolitinib as a viable therapy option for severe COVID-19 28 .…”