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Инфекция и иммунитет. 2020; 10: 446-458

Некоторые возможности иммунотерапии при коронавирусной инфекции

Смирнов В. С., Тотолян Арег А.

https://doi.org/10.15789/2220-7619-SPO-1470

Аннотация

Обзор посвящен анализу средств иммуномодулирующей терапии при коронавирусной инфекции, вызванной SARS-CoV-2 (COVID-19). Как известно, существует очень ограниченный арсенал относительно эффективных средств и методов профилактики и лечения COVID-19. Цель подготовленного обзора литературы — проанализировать некоторые терапевтические подходы к терапии COVID-19 с позиций воздействия на систему врожденного иммунитета. Одним из средств с доказанной терапевтической эффективностью является серотерапия плазмой, полученной из крови выздоравливающих больных. Показано, что переливание плазмы сопровождается сокращением вирусной нагрузки и купированием симптомов заболевания. Недостатком серотерапии является ограниченное количество потенциальных доноров плазмы и значительное варьирование содержания в донорской плазме титров специфических антител. Другим подходом к терапии является применение инженерных моноклональных антител против определенных антигенных детерминант вируса, чаще всего против поверхностного спайк-антигена. Антитела, блокирующие этот антиген, способны предотвратить проникновение вируса в клетку и развитие манифестной инфекции. Кроме того, имеются моноклональные антитела, предотвращающие выработку или связывающие избыточное количество провоспалительных цитокинов, таких как IL-6, TNFα и др. Некоторые из подобных антител (тоцилизумаб) уже испытаны при COVID-19, другие пока проходят исследования и испытания. Определенным прорывом в терапии стали хорошо известные препараты хлорохин и дигидрохлорохин, показавшие себя эффективными средствами противовирусной, противовоспалительной и иммуномодулирующей терапии. Наконец, был предложен новый поликомпонентный иммуномодулирующий препарат Цитовир-3, уже прошедший клинические испытания и рекомендованный к применению при профилактике и терапии гриппа и ОРВИ, который может найти свое место при профилактике COVID-19, поскольку возбудитель SARS-CoV-2 также относится к возбудителям острых респираторных вирусных инфекций. Таким образом, в арсенале средств профилактики и лечения COVID-19 имеются препараты для иммуномодулирующей терапии и профилактики иммунных нарушений, развивающихся в ответ на внедрение патогенного вируса и снижающих риск возможного ущерба. Правильное и научно обоснованное их применение позволит повысить эффективность борьбы с пандемией коронавирусной инфекции.

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Russian Journal of Infection and Immunity. 2020; 10: 446-458

Some opportunities for immunotherapy in coronavirus infection

Smirnov V. S., Totolian Areg A.

https://doi.org/10.15789/2220-7619-SPO-1470

Abstract

Here we review means of immunomodulatory therapy for coronavirus infection caused by SARS-CoV-2 (COVID-19). It has been appreciated that highly limited arsenal of relatively effective means and methods of prevention and treatment of the COVID-19 pandemic is available. The goal of our study was to analyze some therapeutic approaches based on available publications for COVID-19 treatment viewed from acting via innate immunity system. Convalescent plasma serotherapy represents one of the means with verified therapeutic efficacy that was accompanied with decreased viral load and relief of the disease symptoms. The drawback of serotherapy results from limited number of potential plasma donors and profound variety in amount of SARS-CoV-2-specific antibodies found in donor plasma. Another approach to COVID-19 therapy is based on using monoclonal antibodies engineered to target specific virus antigenic determinants, most often surface spike antigen. Antibodies blocking such antigen are able to prevent virus entrance into target cells and development of overt infection. On the other hand, there are monoclonal antibodies abrogating production or binding of excessive amounts of pro-inflammatory cytokines, such as IL-6, TNFα, etc., some of which (tocilizumab) have been already tested in COVID-19 therapy, whereas the remaining preparations are being currently investigated and tested. A certain breakthrough in COVID-19 therapy was provided by the well-known drugs chloroquine and dihydrochloroquine, which have proven to be effective as antiviral, anti-inflammatory and immunomodulatory means. Finally, a new multicomponent immunomodulatory preparation Cytovir-3 has been proposed already passed clinical trials and recommended for use in prevention and treatment of influenza and SARS and might have found its own niche in preventing COVID-19, as SARS-CoV-2 also belongs to the group of acute respiratory viruses. Thus, the arsenal of means for COVID-19 prevention and treatment contains the drugs for immunomodulatory therapy and prevention of immune-related disorders developing in response to invasion pathogenic viruses and lowering a risk of possible damage. Hence, correct and scientifically justified use of such remedies will increase overall effectiveness of fight against the coronavirus pandemic.

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