**2.14 Janus kinase (JAK) inhibitors**

The kinase inhibitors are being proposed as a novel modality of COVID-19 treatment. The rationale behind this being the prevention of phosphorylation of key proteins that are involved in the signal transduction that in turn leads to immunological activation and inflammation. This includes the cellular responses to the pro-inflammatory cytokines like IL-6 [90]. JAK inhibitors interfere with the phosphorylation of signal transducer and activator of transcription (STAT) proteins [91, 92]. These proteins are in turn involved in cell signaling, growth, and survival. The immunosuppression may reduce the hyperactive immune state induced by COVID-19. Moreover, JAK inhibitors like baricitinib have a theoretical direct antiviral activity via interference with viral endocytosis. This can prevent viral entry in the cells [93]. NIH has recommended that in the rare circumstances where corticosteroids cannot be used, baricitinib in combination with remdesivir may be used for the treatment of hospitalized, non-intubated patients requiring oxygen supplementation. IDSA guidelines also suggest the use of this combination in hospitalized severe COVID-19 patients [47]. Use of baricitinib without remdesivir is not recommended, except in a clinical trial [94]. As for the use of baricitinib in combination with corticosteroids, there is still insufficient data. Both baricitinib and corticosteroids cause immuno-suppression; hence, there is an additive risk of infection.
