JAK-inhibitor and type I interferon ability to produce favorable clinical outcomes in COVID-19 patients: a systematic review and meta-analysis

Abstract

Background The spread of a highly pathogenic, novel coronavirus (SARS-CoV-2) has emerged as a once-in-a-century pandemic, having already infected over 63 million people worldwide. Novel therapies are urgently needed. Janus kinase-inhibitors and Type I interferons have emerged as potential antiviral candidates for COVID-19 patients due to their proven efficacy against diseases with excessive cytokine release and their direct antiviral ability against viruses including coronaviruses, respectively. Methods A search of MEDLINE and MedRxiv was conducted by three investigators from inception until July 30th 2020 and included any study type that compared treatment outcomes of humans treated with Janus kinase-inhibitor or Type I interferon against controls. Inclusion necessitated data with clearly indicated risk estimates or those that permitted their back-calculation. Outcomes were synthesized using RevMan. Results Of 733 searched studies, we included four randomized and eleven non-randomized trials. Five of the studies were unpublished. Those who received Janus kinase-inhibitor had significantly reduced odds of mortality (OR, 0.12; 95% CI, 0.03–0.39, p< 0.001) and ICU admission (OR, 0.05; 95% CI, 0.01–0.26, p< 0.001), and had significantly increased odds of hospital discharge (OR, 22.76; 95% CI, 10.68–48.54, p< 0.00001) when compared to standard treatment group. Type I interferon recipients had significantly reduced odds of mortality (OR, 0.19; 95% CI, 0.04–0.85, p< 0.05), and increased odds of discharge bordering significance (OR, 1.89; 95% CI, 1.00–3.59, p=0.05). Conclusions Janus kinase-inhibitor treatment is significantly associated with positive clinical outcomes in terms of mortality, ICU admission, and discharge. Type I interferon treatment is associated with positive clinical outcomes in regard to mortality and discharge. While these data show promise, additional well-conducted RCTs are needed to further elucidate the relationship between clinical outcomes and Janus kinase-inhibitors and Type I interferons in COVID-19 patients.

Circulating Type I Interferon Levels and COVID-19 Severity: A Systematic Review and Meta-Analysis

“…A systematic review and meta-analysis have been previously performed to evaluate the effects of IFN-I and Janus Kinaseinhibitors as treatments for COVID-19 patients and their effectiveness to produce positive outcomes (56). They found that IFN-I treatment is associated with positive clinical outcomes regarding mortality and discharge (56). The time to start IFN-I treatment might be crucial (57).…”

“…In a descriptive review of literature about the role of IFN-I in treating COVID-19, it is highlighted that IFN-α use at the early phase of COVID-19 presents a positive outcome, but IFN-β-1a and -1b are more effective to hinder COVID-19 ( 55 ). A systematic review and meta-analysis have been previously performed to evaluate the effects of IFN-I and Janus Kinase-inhibitors as treatments for COVID-19 patients and their effectiveness to produce positive outcomes ( 56 ). They found that IFN-I treatment is associated with positive clinical outcomes regarding mortality and discharge ( 56 ).…”

Parallel Outbreaks of Deadly Pathogens (SARS-CoV-2, H5N8, EVD, Black fungi) around the World in 2021: Priorities for Achieving Control with Socio-Economic and Public Health Impact

“…For critical condition, tocilizumab, a recombinant monoclonal immunoglobulin G1, also showed satisfactory effect against the infection [85]. Interferon alpha and Janus-kinase inhibitor are also recommended, as they showed a significant decrease in SARS-CoV-2 virus replication [86], mortality rate and ICU admission of COVID-19 patients [87]. Convalescent plasma transfusion might also be a promising treatment against COVID-19 as its use reduces mortality in critically ill patients increasing neutralizing antibody titers and decreasing SARS-CoV-2 viral RNA [88,89].…”

“…Most dramatically, more than 70% of morality rate bearing black fungus have no effective treatment except antifungal, antibiotics, intravenous (IV) medication or through a surgery [87]. Importantly, utilizing its experience of Ebola outbreak, Democratic Republic of Congo has established a multisectoral public health approach for community based screening testing, contact tracing, risk communication, community engagement and case management to fight against COVID-19 and other deadly super contagious pathogens [51].…”

Nasopharyngeal Type-I Interferon for Immediately Available Prophylaxis Against Emerging Respiratory Viral Infections

“…The potential of IFN-1 as a treatment for viral respiratory infections is strongly suggested by the limited IFN-1 responses of SARS-CoV-2-infected patients (3,4). The COVID-19 experience demonstrated that patients with SARS-CoV-2 are both (a) very susceptible to IFN-I and (b) uniquely adept at evading endogenous IFN-I by delaying or suppressing IFN-I expression (3)(4)(5)(6)(7). The ability of SARS-CoV-2 to inhibit endogenous IFN-I expression appears to make interferon pathway dysregulation critical to developing severe disease (5).…”