Dynamic changes in radiological parameters, immune cells, selected miRNAs, and cytokine levels in peripheral blood of patients with severe COVID‑19

Tetiana Bukreieva; Vitalii Kyryk; Viktoriia Nikulina; Hanna Svitina; Alyona Vega; Oleksii Chybisov; Iuliia Shablii; Oksana Mankovska; Galyna Lobyntseva; Petro Nemtinov; Inessa Skrypkina; Volodymyr Shablii

doi:10.3892/br.2023.1615

Dynamic changes in radiological parameters, immune cells, selected miRNAs, and cytokine levels in peripheral blood of patients with severe COVID‑19

Biomed Rep. 2023 Mar 21;18(5):33. doi: 10.3892/br.2023.1615. eCollection 2023 May.

Authors

Tetiana Bukreieva^{1

2}, Vitalii Kyryk^{3

4}, Viktoriia Nikulina², Hanna Svitina^{1

2}, Alyona Vega⁵, Oleksii Chybisov⁶, Iuliia Shablii¹, Oksana Mankovska⁷, Galyna Lobyntseva², Petro Nemtinov², Inessa Skrypkina¹, Volodymyr Shablii^{1

2}

Affiliations

¹ Laboratory of Biosynthesis of Nucleic Acids, Department of Functional Genomics, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv 03143, Ukraine.
² Placenta Stem Cell Laboratory, Cryobank, Institute of Cell Therapy, Kyiv 03126, Ukraine.
³ Laboratory of Cell and Tissue Cultures, Department of Cell and Tissue Technologies, State Institute of Genetic and Regenerative Medicine, National Academy of Medical Sciences of Ukraine, Kyiv 04114, Ukraine.
⁴ Laboratory of Pathophysiology and Immunology, D.F. Chebotarev State Institute of Gerontology of The National Academy of Medical Sciences of Ukraine, Kyiv 04114, Ukraine.
⁵ Department of Infectious Diseases, Shupyk National Healthcare University of Ukraine, Kyiv 04112, Ukraine.
⁶ Endoscopic Unit, CNE Kyiv City Clinical Hospital No. 4, Kyiv 03110, Ukraine.
⁷ Department of Molecular Oncogenetics, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv 03143, Ukraine.

Abstract

The present study aimed to investigate the dynamic changes in peripheral blood leucocyte subpopulations, cytokine and miRNA levels, and changes in computed tomography (CT) scores in patients with severe coronavirus disease 2019 (COVID-19) (n=14) and age-matched non-COVID-19 volunteers (n=17), which were included as a reference control group. All data were collected on the day of patient admission (day 0) and on the 7th, 14th and 28th days of follow-up while CT of the lungs was performed on weeks 2, 8, 24 and 48. On day 0, lymphopenia and leucopenia were detected in most patients with COVID-19, as well as an increase in the percentage of banded neutrophils, B cells, and CD4⁺ Treg cells, and a decrease in the content of PD-1^low T cells, classical, plasmacytoid, and regulatory dendritic cells. On day 7, the percentage of T and natural killer cells decreased with a concurrent increase in B cells, but returned to the initial level after treatment discharge. The content of different T and dendritic cell subsets among CD45⁺ cells increased during two weeks and remained elevated, suggesting the activation of an adaptive immune response. The increase of PD-1-positive subpopulations of T and non-T cells and regulatory CD4 T cells in patients with COVID-19 during the observation period suggests the development of an inflammation control mechanism. The levels of interferon γ-induced protein 10 (IP-10), tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 decreased on day 7, but increased again on days 14 and 28. C-reactive protein and granulocyte colony-stimulating factor (G-CSF) levels decreased gradually throughout the observation period. The relative expression levels of microRNA (miR)-21-5p, miR-221-3p, miR-27a-3p, miR-146a-5p, miR-133a-3p, and miR-126-3p were significantly higher at the beginning of hospitalization compared to non-COVID-19 volunteers. The plasma levels of all miRs, except for miR-126-3p, normalized within one week of treatment. At week 48, CT scores were most prominently correlated with the content of lymphocytes, senescent memory T cells, CD127⁺ T cells and CD57⁺ T cells, and increased concentrations of G-CSF, IP-10, and macrophage inflammatory protein-1α.

Keywords: CD4 T cells; CD8 T cells; COVID-19; chest CT; cytokine; dynamic changes; immune cell subpopulations; microRNA.

Grants and funding

Funding: The present study was funded by the National Research Foundation of Ukraine, grant no. 2020.01/0246, ‘Study of the state of respiratory, cardiovascular and immune systems in patients with COVID-19 pneumonia after transplantation of cryopreserved allogeneic mesenchymal stem cells’.