Dynamics of clinical and immunological parameters in patients underwent a moderate COVID-19 and received therapy with janus kinase inhibitor

Abstract

Introduction. The study of the pathogenesis of COVID-19 remains one of the main tasks of modern science. Having studied the mechanisms of the development of the disease, it is possible to reduce the risks of developing a severe course of the disease much more effectively. Respiratory failure, «cytokine storm», thrombotic complications – all this is associated with an unfavorable prognosis of a new coronavirus infection. The targeted therapy used to combat the development of these complications has been successful in treating patients with COVID-19. One of the proactive mechanisms in the pathogenesis of the «cytokine storm» is the blockage of the JAK-STAT signaling pathway with the janus kinase inhibitors.

It is very important to represent the effectiveness of the drugs used, as well as its safety, not only in the acute period of the disease, but also in the post-COVID period. The area of interest are changes of clinical and laboratory parameters and indicators of innate and adaptive immunity after the disease in patients receiving therapy with janus kinase inhibitor.

The aim was to study the clinical and immunological parameters of patients underwent moderate COVID-19 and received therapy with janus kinase inhibitor in the acute period of the disease and 6 months after discharge/recovery.

Material and methods. 30 patients hospitalized with a diagnosis of «coronavirus infection, virus identified, COVID-19, moderate form; complication: interstitial pneumonia» were examined. A janus kinase inhibitor (baricitinib) was included in the complex treatment of patients in this group. The comparison group consisted of 20 patients hospitalized with an identical diagnosis, in the treatment of which the janus kinase inhibitor was not used. The dynamics of laboratory parameters (general clinical, biochemical and immunological) were evaluated at the background of therapy with janus kinase inhibitors upon admission to the hospital, upon discharge as well as 6 months later.

Results. The effectiveness of the use of the janus kinase inhibitor baricitinib is manifested in a decrease of the level of markers for the prognosis of severe infection, as well as reduction of the hospitalization time of patients. By the time of discharge /recovery, there is a decrease in the levels of C-reactive protein, lactate, fibrinogen. The level of lactate dehydrogenase by the time of discharge / recovery is reduced to reference values in the group with the use of baricitinib. 6 months after discharge from the hospital, the normalization of the level of C-reactive protein to reference values is noted. By the time of discharge, a decrease in the levels of IL-10, IL-6 and IFN-γ was recorded. Regardless of the use of the janus kinase inhibitor, changes of the innate and adaptive immunity parameters persist as the increased content of circulating immune complexes and NK cells (CD16+). In case of the use of dexamethasone in preventive therapy without the use of baricitinib in patients 6 months after discharge from the hospital, the level of CD3+CD4+ lymphocytes was significantly higher, and the level of serum IgG was lower.

Conclusion. The use of baricitinib in complex treatment, including GCS therapy, antiviral therapy, anticoagulants, leads to a significant decrease of parameters indicating the development of a «cytokine storm», as well as to decrease in the cytopathic effect of the virus. Dysregulatory processes in the immune system, that occur during the disease, persist even 6 months after the recovery of patients underwent moderate COVID-19.

Keywords:baricitinib; COVID-19; targeted therapy; janus kinase inhibitors; «cytokine storm»; postcovid syndrome

For citation: Sizyakina L.P., Skripkina N.A., Antonova E.A., Sizyakin D.V. Dynamics of clinical and immunological parameters in patients underwent a moderate COVID-19 and received therapy with janus kinase inhibitor. Immunologiya. 2023; 44 (2): 191–201. DOI: https://doi.org/10.33029/0206-4952-2023-44-2-191-201

Funding. The study had no sponsor support.

Conflict of interests. The authors declare no conflict of interests.

Authors contribution. Research concept and design – Sizyakina L.P.; collection and processing of material – Skripkina N.A., Antonova E.A., Sizyakin D.V.; text writing, editing – Skripkina N.A.; the final version and the integrity of the text – Sizyakina L.P.

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