Cytokines in predicting JAK inhibitors clinical efficacy for COVID-19

   Janus kinases inhibitors (JAKi) have an immunosuppressive effect due to the normalization of levels of proinflammatory cytokines, are used in the treatment of cytokine storm in COVID-19. This fact makes it necessary to search a predictor of an efficacy of this small-molecules.

   The aim of the study. To evaluate the possibility of using cytokines in predicting the efficacy of JAKi in COVID-19.

   Materials and methods. We examined 86 patients with COVID-19: 50 men and 36 women. The age was 57,0; (50,0–65,0) years. The SARS-CoV-2 presence was confirmed by PCR. The control group consisted of 30 healthy donors matched by sex and age. The criterion for the efficacy of JAKi was recovery, in efficacy – switching to another drug, or death. The serum concentration of IL-1β, –6, –8, –17, TNF-α and GM–CSF by ELISA was estimates using Invitrogen test-systems (USA), according to the manufacturer’s instructions.

   Results. In COVID-19 patients who received baricitinib (BTC), compared with healthy individuals, basal (before JAKi starting) IL-6, TNF-α serum concentrations were increased; tofacitinib (TFT) – IL-6, ruxilitinib (RLT) – IL-6 and TNF-α. A decrease of IL-1β and GM–CSF serum concentration was noted before the start of TFT and RLT. Basal concentrations of IL-6 and TNF-α are most statistically strongly associated with the diagnosis COVID-19. After 5 days of treatment with BTC, there was an increase in IL-8 level compared to the basal, a decrease in the GM–CSF concentration and a slight increase IL-6 concentration relative to healthy donors (p < 0.05 in all cases). Basal concentration of IL-17 (more than 13.9 pg/ml) indicated the possibility of successful RLT treatment (area under the ROC-curve = 0.99; AP = 99 %; DS = 80 %; OP+ = 5.0; OP– = 0.2; CI: 0.9–1.0).

   Conclusions. Basal serum concentration of cytokines may predict JAKi efficacy in COVID-19 patients.

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