Opportunities for correction of immunosuppression in patients with COVID-19

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Here, we review thematic publications in available literature sources of the databases PubMed, Scopus, Web of Science, eLibrary, 49 of which were dated of the years 1997–2022. Analysis of such reports is aimed at assessing features of cytokine storm-induced hyperinflammatory reaction with signs of immunosuppression accompanied by pronounced lymphopenia and lowered count of CD4+T helpers during severe COVID-19. The prognostic factor for unfavorable prognosis was based on the marker of systemic inflammatory reaction correlating with the disease severity — the soluble IL-2 receptor as well as the neutrophil-to-lymphocyte ratio and the lymphocyte subset imbalance. An immunosuppressive therapy of severe forms of COVID-19, aimed at weakening the inflammatory response, exacerbates immune dysfunction by suppressing the T cell function, mainly due to Th1 lymphocytes involved in recognizing and eliminating intracellular pathogens particularly viruses. Upon that, cell-mediated immunity becomes compromised that relies on cytotoxic T-lymphocytes, natural killer cells and macrophages. Timely and targeted immunocorrection is required to prevent or reduce the immunosuppression that accompanies a severe disease course and leads to serious and prolonged complications, as well as to association of secondary infections. In fight against the cytokine storm, it is important not to miss a time point of developing immunosuppressive condition that transitions into immunoparalysis as follows from recent publications covering the tactics of treating immune-mediated complications of coronavirus infection. The review discusses opportunities for immunosuppressive therapy along with glucocorticosteroids and monoclonal antibodies blocking IL-6 or cognate receptors. Studies using mesenchymal stem cells (MSCs) to reduce systemic inflammatory response at COVID-19 are outlined in the review. The use of antigen-specific Treg and their combinations with antagonists of tumor necrosis factor-α (TNFα), interferon-γ (IFNγ) as well as low-dose IL-2 in patients with SARS-CoV-2 infection were analyzed. The prognostic perspectives for CAR-T cells and CAR-NK cells technology have been considered as novel therapeutic approaches aimed at “training” effector cells to recognize the surface SARS-CoV-2 virus spike-like (S) protein. The feasibility of a therapeutic approach is also emphasized by comparatively analyzed of efficacy of using IL-7 or IL-15 during lymphopenia in patients with COVID-19. Here, side effects complicating immunocorrection come to the fore. Critical evaluation of corrected immunosuppressive conditions in patients with COVID-19 in the post-COVID-19 period by using low-dose IL-2 therapy revealed its ability to repair cellular immune response. As a result, a low-dose IL-2 therapy is recommended as a cytokine replacement therapy in such patients with COVID-19 during hyper-to-hypo-inflammatory phase transition in immune response.

作者简介

Mikhail Kiselevskiy

N.N. Blokhin National Medical Research Center of Oncology; National University of Science and Technology “MISIS”

编辑信件的主要联系方式.
Email: kisele@inbox.ru
ORCID iD: 0000-0002-0132-167X

PhD, MD (Medicine), Professor, Head of the Laboratory of Cell Immunity, Professor, Biomedical Engineering Research and Education Center

俄罗斯联邦, Moscow; Moscow

H. Treshalina

N.N. Blokhin National Medical Research Center of Oncology

Email: treshalina@yandex.ru
ORCID iD: 0000-0002-3878-3958

PhD, MD (Medicine), Professor, Leading Researcher, Laboratory of Cell Immunity, Research Institute of Experimental Diagnostics and Therapy of Tumors

俄罗斯联邦, Moscow

I. Mikhailova

N.N. Blokhin National Medical Research Center of Oncology

Email: irmikhaylova@gmail.com
ORCID iD: 0000-0002-7659-6045

PhD, MD (Medicine), Leading Researcher, Department of Biotherapy, N.N. Trapeznikov Research Institute of Clinical Oncology

俄罗斯联邦, Moscow

D. Martirosyan

Pirogov Russian National Research Medical University

Email: 16710@list.ru

Medical Student

俄罗斯联邦, Moscow

I. Manina

Institute of Allergology and Clinical Immunology

Email: irina.v.manina@gmail.com
ORCID iD: 0000-0002-4674-5484

PhD (Medicine), Chief Physician

俄罗斯联邦, Moscow

V. Reshetnikova

N.N. Blokhin National Medical Research Center of Oncology

Email: veravr@gmail.ru
ORCID iD: 0000-0002-2821-3425

PhD (Engineering Science), Researcher, Laboratory of Cell Immunity, Research Institute of Experimental Diagnostics and Therapy of Tumors

俄罗斯联邦, Moscow

I. Kozlov

Sechenov First Moscow State Medical University; Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology

Email: immunopharmacology@yandex.ru
ORCID iD: 0000-0002-9694-5687

PhD, MD (Medicine), Professor of Department of Organization and Management in the Sphere of Medicines Circulation, Chief of the Laboratory of Experimental and Clinical Pharmacology

俄罗斯联邦, Moscow; Moscow

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