Opportunities for correction of immunosuppression in patients with COVID-19

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The review was carried out by searching for thematic information among available literature sources in the databases PubMed, Scopus, Web of Science, eLibrary, 49 of which 1997-2022 editions were included in this review. Analysis of these works is aimed at peculiarities of cytokine storm-induced hyperinflammatory reaction with signs of immunosuppression accompanied by pronounced lymphopenia with reduced number of CD4+T helpers in severe COVID-19 course. The prognostic factor of the unfavorable prognosis is a marker of systemic inflammatory reaction correlating with the severity of the disease - the superiority of the soluble IL-2 receptor, as well as the ratio of neutrophils to lymphocytes and the imbalance of lymphocyte subpopulations. 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 the identification and elimination of intracellular pathogens, in particular viruses. At the same time, cell-mediated immunity suffers, which is provided by cytotoxic T-lymphocytes, natural killers and macrophages. Timely and targeted immunocorrection is needed to prevent or reduce the immunosuppression that accompanies a severe course and leads to serious and prolonged complications, as well as to the addition of secondary infections. In the fight against the cytokine storm, it is important not to miss the moment of development of an immunosuppressive condition transitioning into immunoparalic, which follows from recent publications covering the tactics of treating immune-mediated complications of coronavirus infection. The review considers the possibilities of immunosuppressive therapy, in addition to glucocorticosteroids and monoclonal antibodies that block IL-6 or its receptors. Examples of work using mesenchymal stem cells (MSC) to reduce systemic inflammatory response at COVID-19 are given. The use of antigen-specific Treg and their combinations with antagonists of tumor necrosis factor α (TNFα), interferon γ (IFNγ) and low-dose IL-2 in patients with a SARS-CoV-2 were analyzed. The prognostic perspectives of CAR-T cells and CAR-NK cells technology have been considered in terms of novel therapeutic approaches aimed at "training" effector cells to recognize the surface spike-like (S) protein of the SARS-CoV2 virus. The feasibility of a therapeutic approach to the problem is also emphasized by comparative analysis of the efficacy of IL-7 or IL-15 in lymphopenia in patients with COVID-19. Here, side effects complicating immunocorrection come to the fore. Critical evaluation of correction of immunosuppressive conditions in patients with COVID-19 in the post-covid period with low-dose therapy with IL-2 drugs 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 these patients with COVID-19  during the transition from the hyper-inflammatory to the hypo-inflammatory phase of the immune response.

About the authors

M. Kiselevskiy

FGBU “N.N. Blokhin National Medical Research Center of Oncology”, Moscow

Email: kisele@inbox.ru
ORCID iD: 0000-0002-0132-167X
Russian Federation

H. Treshalina

FGBU “N.N. Blokhin National Medical Research Center of Oncology”, Moscow

FSBI G.F. Gause Institute of New Antibiotics, Moscow

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

I. Mikhailova

FGBU “N.N. Blokhin National Medical Research Center of Oncology”, Moscow

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

D. Martirosyan

FGBU “N.N. Blokhin National Medical Research Center of Oncology”, Moscow

Email: 16710@list.ru
Russian Federation

I. Manina

Institute of Allergology and Clinical Immunology, Moscow

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

V. Reshetnikova

FGBU “N.N. Blokhin National Medical Research Center of Oncology”, Moscow

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

I. Kozlov

Sechenov First Moscow State Medical University, Moscow

Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, Moscow

Author for correspondence.
Email: immunopharmacology@yandex.ru
ORCID iD: 0000-0002-9694-5687
Russian Federation


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