Janus Kinase-Inhibitor and Type I Interferon Ability to Produce Favorable Clinical Outcomes in COVID-19

Lucas Walz, Avi J. Cohen, Andre P. Rebaza, James Vanchieri, Martin D. Slade, Charles S. Dela Cruz, Lokesh Sharma

doi: https://doi.org/10.1101/2020.08.10.20172189

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2020.08.10.20172189v1.full.pdf

Abstract

Background Novel coronavirus (SARS-CoV-2) has infected over 17 million. Novel therapies are urgently needed. Janus-kinase (JAK) inhibitors and Type I interferons have emerged as potential antiviral candidates for COVID-19 patients for their proven efficacy against diseases with excessive cytokine release and by their ability to promote viral clearance in past coronaviruses, respectively. We conducted a systemic review and meta-analysis to evaluate role of these therapies in COVID-19 patients. Methods MEDLINE and MedRxiv were searched until July 30th, 2020, including studies that compared treatment outcomes of humans treated with JAK-inhibitor or Type I interferon against controls. Inclusion necessitated data with clear risk estimates or those that permitted back-calculation. Results We searched 733 studies, ultimately including four randomized and eleven non-randomized clinical trials. JAK-inhibitor recipients had significantly reduced odds of mortality (OR, 0.12; 95%CI, 0.03-0.39, p=0.0005) and ICU admission (OR, 0.05; 95%CI, 0.01-0.26, p=0.0005), 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=0.03), and increased odds of discharge bordering significance (OR, 1.89; 95%CI, 1.00-3.59, p=0.05). Conclusions JAK-inhibitor treatment is significantly associated with positive clinical outcomes regarding mortality, ICU admission, and discharge. Type I interferon treatment is associated with positive clinical outcomes regarding mortality and discharge. While these data show promise, additional randomized clinical trials are needed to further elucidate the efficacy of JAK-inhibitors and Type I interferons and clinical outcomes in COVID-19.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

Lokesh Sharma is supported by Parker B Francis Fellowship. Charles Dela Cruz is supported by Veterans affairs Merit Grant (BX004661), Department of Defense grant (PR181442), and a U19 supplement for this work (AI089992-09S2).

https://www.medrxiv.org/content/10.1101/2020.08.10.20172189v1