The role of clinical and immunological parameters in predicting the effectiveness of additional immunotropic therapy in oxygen-dependent patients with COVID-19 coronavirus disease

Abstract

Aim. The purpose of the research is to find out the role of clinical and immunological parameters in predicting the effectiveness of additional immunotropic therapy in oxygen-dependent patients with the coronavirus disease COVID-19. Material and methods. 79 oxygen-dependent patients with COVID-19 were examined, who received additional therapy with tocilizumab according to current protocols. The patients were divided into groups: I group – 39 patients who recovered; group II – 40 patients with a fatal outcome of the disease. The content of ferritin (Monobind Inc., USA), interleukin (IL) IL-2 (Elabscience, USA), IL-6 (Invitrogen, Austria), monocyte chemotactic protein-1 (MCP-1) (Elabscience, USA) was determined in the blood serum of patients and persons of the control group by the method of immunoenzymatic analysis. Statistical processing of the obtained data was carried out in the program Statistica 13 for Windows (StatSoft Inc., No. JPZ804I382130ARCN10-J). Results. Threshold levels of immunological parameters at different stages of observation, which have prognostic value regarding the risk of a fatal outcome of COVID-19, have been established. After 5 days of tocilizumab administration, the preservation of the indicator of the absolute number of blood lymphocytes ≤1.2 × 109/l (AUC = 0.631, p = 0.039), CRP level >67.5 mg/l (AUC = 0.670, p = 0.020), IL-2 >309.45 pg/ml (AUC = 0.761, p = 0.013), IL-6 >4.66 pg/ml (AUC = 0.871, p < 0.001) indicated a high probability of developing a fatal outcome of the disease in patients with COVID-19. The analysis of the diagnostic significance of ferritin showed the informativeness of the level of its increase as at the time of the start of observation >548.02 ng/ml (AUC = 0.718, p = 0.004) and after 5 days the application of additional immunotropic therapy >443.55 ng/ml (AUC = 0.736, p = 0.026). It has been proven that, in addition to immunological parameters, when assessing the probability of a fatal outcome of COVID-19, such clinical parameters as the presence of febrile fever at the time of the appearance of oxygen dependence (p < 0.05) and the duration of oxygen dependence at the time of additional immunotropic therapy with tocilizumab are informative (p < 0.05). Under the conditions of additional immunotropic therapy with tocilizumab more than 4 days after the onset of oxygen dependence, the probability of ineffectiveness of the specified additional treatment was significant (AUC = 0.756, p < 0.001). Conclusions. The dynamics of immunological parameters in oxygen-dependent patients with COVID-19 during additional immunotropic therapy with tocilizumab has certain features with different treatment results. When predicting the probable risk of a fatal outcome of the disease, clinical parameters are informative, namely the appearance of febrile fever during the development of oxygen dependence and the duration of oxygen dependence until the moment of tocilizumab administration, and immunological parameters, namely the level of the absolute content of lymphocytes, ferritin, CRP, IL-2, IL-6 in the blood.