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JAK-STAT pathway and COVID-19, potential treatment strategy?

In human organism infections often cause abnormal activity of pro-inflammatory cytokines from interleukin and interferon protein families. Infection with SARS- CoV-2 resulting with COVID-19 disease has already caused global pandemic and is a cause of nearly 250 000 deaths (1st week of May 2020).

During the severe infection development elevated levels of IL-6 and IFNγ could be observed (both are currently under investigation as potential disease progress markers) resulting in so called “cytokine storm”. It has already been proven that both IL-6 and IFNγ efficiently activate JAK-STAT pathway. The usual treatment approach in case of infections does not involve blocking inflammatory response of organism. However in case of severe COVID-19 cases where cytokine storm could be observed. This abnormal activation occurring during cytokine storm is a probable cause of many fatal cases. Therefore blocking JAK-STAT pathway during cytokine storm would potentially decrease pathological inflammatory response resulting with less casualties.

Our group has showed that STAT inhibitors may effectively block inflammatory stimuli driven STAT phosphorylation leading to pro-inflammatory gene expression. Therefore we postulate that JAK-STAT pathway inhibitors may be part of potential anti-inflammatory treatment in severe COVID-19 cases.

JAK inhibitors (indirect STAT inhibitors)- Baricitinib, Fedratinib, and Ruxolitinib have been selected as part of potential treatment strategy combining antiviral and anti-inflammatory approach.

URL Description
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185015/ COVID-19: Immunology and treatment options
https://www.thelancet.com/article/S1473-3099(20)30132-8/fulltext COVID-19: combining antiviral and anti-inflammatory treatments
https://www.researchsquare.com/article/rs-25845/v1 Network theoretic analysis of JAK/STAT pathway and extrapolation to drugs and viruses including COVID-19
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169770/ The COVID‐19 epidemic
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7129451/ Interleukin-6 as a potential biomarker of COVID-19 progression
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7151347/ Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)?
https://www.medrxiv.org/content/10.1101/2020.03.30.20048058v1 Interleukin-6 in COVID-19: A Systematic Review and Meta-Analysis
https://www.medrxiv.org/content/10.1101/2020.04.01.20047381v2 Level of IL-6 predicts respiratory failure in hospitalized symptomatic COVID-19 patients
https://www.sciencedirect.com/science/article/pii/S1684118220300657 TH17 responses in cytokine storm of COVID-19: An emerging target of JAK2 inhibitor Fedratinib
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30628-0/fulltext COVID-19: consider cytokine storm syndromes and immunosuppression