Alteration in innate immune cues assessed by analyzing peripheral blood immune system in post-covid patients

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Abstract

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has led to global morbidity and mortality. Some patients fully recover from COVID-19, whereas around 45% subjects suffer from various persistent symptoms (fatigue, cognitive impairment, impaired thermoregulation, skin diseases, etc.) for at least four months after SARS-CoV-2 infection regardless of disease severity. Such persistent post-infection effects are known as long-COVID, post-acute effects of COVID-19, or post-COVID state. SARS-CoV-2 infection is accompanied by damage to the innate immune system. Considering the role of natural killer cells and the activation of the complement system in COVID-19 as well as the regulatory properties related to CD46 and its potential involvement in cell virus entry, we found necessary to study immune system parameters associated with impairment of these innate immune cues on various leukocyte subpopulations in post-COVID patients. We studied 92 immune system parameters, including: pan-leukocyte markers for gated lymphocytes, phenotyping of T cells, T-helper inducers, cytotoxic T-lymphocytes, NK- and TNK-cells, T-regulatory cells/suppressors, B-lymphocytes, including B-memory cells, activated helpers, early activation of lymphocytes, activated T-lymphocytes, and late lymphocyte activation markers. Levels of total IgM, IgG, IgA, specific IgM, IgG to coronavirus COVID-19, C1-inhibitor, C3a, and C5a complement components were measured by enzyme immunoassay using Multiscan FC Thermoscientific enzyme immunoassay analyzer (China) and Vector Best reagent kits (Russia). A complete blood count was conducted to study 25 parameters: leukocyte, erythrocyte, and platelet hematopoietic lineages as well as the quantitative and qualitative composition of hematopoietic lineages. Our study results showed that in some patients, six months after suffering from COVID-19, there was a decrease in the level of NK cells (48%) and CD46+ pan-leukocyte marker cells (64.5%). A decrease in NK cell levels was accompanied by increased level of total T- and B-lymphocytes, and altered platelet and erythroid hematopoietic lineages. In patients with reduced CD46 expression on T-lymphocytes, both their total count and NK cell count were significantly reduced. Our data also suggest that CD46 might be potentially involved in development of SARS-CoV-2 infection and the post-COVID state. Thus, in 50–65% of patients who have experienced SARS-CoV-2 infection, damage to the innate immune system persists after six months being accompanied by impaired erythroid and platelet hematopoietic lineages. The data obtained indicate a need for using immunocorrective therapy in such patients.

About the authors

Maria A. Dobrynina

Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Sciences; State Research Center of the Russian Federation — Federal Medical Biophysical Center named after A.I. Burnazyan of the Federal Medical and Biological Agency of the Russian Federation

Author for correspondence.
Email: mzurochka@mail.ru

PhD (Medicine), Researcher, Laboratory of Immunology of the Inflammation;  Associate Professor, Department of Internal Medicine, Medical and Biological University of Innovation and Continuing Education

Russian Federation, Yekaterinburg; Moscow

Aleksandr V. Zurochka

Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Sciences; South Ural State University (National Research University)

Email: av_zurochka@mail.ru

DSc (Medicine), Professor, Honored Scientist of the Russian Federation, Leading Researcher; Head of the Biotechnology Laboratory, Russian-Chinese Center

Russian Federation, Yekaterinburg; Chelyabinsk

Mariia V. Komelkova

Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Sciences; South Ural State University (National Research University)

Email: mkomelkova@mail.ru

DSc (Biology), Head of the Laboratory of Systemic Pathology and Promising Medicines, Russian-Chinese Center

Russian Federation, Yekaterinburg; Chelyabinsk

Vladimir A. Zurochka

Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Sciences; South Ural State University (National Research University)

Email: v_zurochka@mail.ru

DSc (Medicine), Senior Researcher; Senior Researcher, Biotechnology Laboratory, Russian-Chinese Center

Russian Federation, Yekaterinburg; Chelyabinsk

Evgeny A. Praskurnichiy

State Research Center of the Russian Federation — Federal Medical Biophysical Center named after A.I. Burnazyan of the Federal Medical and Biological Agency of the Russian Federation

Email: praskurnichey@mail.ru

DSc (Medicine), Professor, Head of the Department of Internal Medicine, Medical and Biological University of Innovation and Continuing Education

Russian Federation, Moscow

Liana V. Ryabova

South Ural State Medical University of the Ministry of Health of the Russian Federation

Email: lianarabowa@rambler.ru

DSc (Medicine), Associate Professor, Professor of the Department of Life Safety, Disaster Medicine, Emergency Medicine

Russian Federation, Chelyabinsk

Alexey P. Sarapultsev

Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Sciences; South Ural State University (National Research University)

Email: a.sarapultsev@gmail.com

DSc (Biology), Leading Researcher, Laboratory of Immunopathophysiology; Head of the Russian-Chinese Center

Russian Federation, Yekaterinburg; Chelyabinsk

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Copyright (c) 2023 Dobrynina M.A., Zurochka A.V., Komelkova M.V., Zurochka V.A., Praskurnichiy E.A., Ryabova L.V., Sarapultsev A.P.

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