Prognosis of immune state following basic therapy and thymalin treatment in patients with severe COVID-19 infection

Significant changes in cellular and humoral immunity are observed in new coronavirus infection (COVID-19). The cytokine storm develops in cases of severe clinical course, being accompanied by significantly increased levels of pro-inflammatory cytokines, often associated with suppression of immune response. At the same time, the prediction of the immune status is an urgent task, thus allowing timely correction of current therapy. The aim of our research was to evaluate predictive capability for the immune system changes on the 6th day of COVID-19 disease when using standard therapy, or with addition of immunocorrector thymalin to the treatment regimen. A retrospective study was conducted in 87 patients with severe COVID-19. All patients were divided into 2 groups, i.e., (1) controls who received basic treatment; (2) basic treatment supplied with thymalin (10 mg, intramuscular injections daily for 5 days). Assessment of severity and clinical course of COVID-19, and basic treatment regimen for the patients corresponded to current version of the interim Guidelines from the Ministry of Health of the Russian Federation Prevention, diagnosis and treatment of a new coronavirus infection COVID-19. Laboratory studies included complete blood counts, immunogram parameters with the calculation of the ratio of certain types of leukocytes were performed on the 1st and 6th days of observation. Statistical evaluation was made using scripts of the specialized statistical analysis language R (http://cran.r-project.org) version 4.1.3. The blood parameters were evaluated using the binary classification method. The changes in parameters of cellular immunity were classified by means of ROC-analysis. 
We have found that the basic therapy of severely ill COVID-19 patients was not followed by recovery of immune status on the 6th day from the start of treatment. At marginal level, one can only suggest a probable prediction of increase in WBC and MON counts, a decrease in CD4+, NK and CD8+perNK, as well as the CD4+/CD8+ ratio. Addition of thymalin to the basic therapy is largely accompanied by the normalization of immunogram parameters. At the same time, it is possible to predict, with excellent rating, an increased number of T-LIM, including CD4+ and B-LIM, and, with good rating, an increase in the total numbers of LIM, as well as CD8+, HLA-CD3+DR+ and NK cells. The data obtained in severe cases of COVID-19 make it possible to predict changes in immune status, and, hence, the course of the disease, at a high degree of probability.