mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-LAA-2229mimmun-2229Research ArticleОБЗОРЫREVIEWSЛипополисахарид и ОРДС, вызванный новой коронавирусной инфекцией: гипотезы и фактыLipopolysaccharide and ARDS caused by new coronavirus infection: hypotheses and factshttps://orcid.org/0000-0002-5486-7262ЯцковИ. А.YatskovI. A.

Ассистент кафедры внутренней медицины № 2

295491, Республика Крым, г. Симферополь, пгт Аэрофлотский, ул. Мальченко, 7, кв. 28

Тел.: 8 (978) 709-40-15.

Assistant Professor, Department of Internal Medicine No. 2

295491, Republic of Crimea, Simferopol, Aeroflotsky smt, Malchenko str., 7, apt. 28, Phone: 7 (978) 709-40-15

egermd@yandex.ruhttps://orcid.org/0000-0001-9640-754XБелоглазовВ. А.BeloglazovV. A.

Д.м.н., профессор, заведующий кафедрой внутренней медицины № 2

г. Симферополь, Республика Крым

PhD, MD (Medicine), Professor, Head, Department of Internal Medicine No. 2

Simferopol, Republic of Crimea

biloglazov@mail.ruhttps://orcid.org/0000-0003-3187-220XРяповаЭ. И.RyapovaE. I.

Студентка кафедры внутренней медицины № 2

г. Симферополь, Республика Крым

Student, Department of Internal Medicine No. 2

Simferopol, Republic of Crimea

elvina.ryapova@bk.ruМедицинская академия имени С. И. Георгиевского – структурное подразделение ФГАОУ ВО «Крымский федеральный университет имени В. И. Вернадского»РоссияS. Georgievsky Medical Academy, V. Vernadsky Crimean Federal UniversityRussian FederationМедицинская академия имени С.И. Георгиевского – структурное подразделение ФГАОУ ВО «Крымский федеральный университет имени В. И. Вернадского»РоссияS. Georgievsky Medical Academy, V. Vernadsky Crimean Federal UniversityRussian Federation202210032022241718Copyright © Яцков И.А., Белоглазов В.А., Ряпова Э.И., 20222022Яцков И.А., Белоглазов В.А., Ряпова Э.И.Yatskov I.A., Beloglazov V.A., Ryapova E.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/2229

В данном обзоре представлены данные из литературных источников, которые дают представление о роли липополисахарида (LPS) грамнегативной флоры в патогенезе острого респираторного дистресс-синдрома (ОРДС), вызванного новой коронавирусной инфекцией SARS-CoV-2. ОРДС – это синдром тяжелой недостаточности дыхания, остро возникающее диффузное воспалительное поражение легких, развивающееся как неспецифическая реакция на различные прямые (аспирация, ингаляция токсичных газов) и системные (сепсис, политравма) повреждающие факторы и приводящее к формированию острой дыхательной недостаточности (ОДН) вследствие нарушения структуры паренхимы легких, нарушения сосудистой проницаемости, уменьшения площади вентилируемой легочной ткани.

ОРДС при коронавирусной инфекции, по-видимому, имеет худшие результаты, чем ОРДС, вызванный другими причинами. Смертность в отделении интенсивной терапии и больнице от типичного ОРДС составляет 35,3% и 40,0% соответственно, тогда как для вызванного COVID-19 ОРДС смертность варьировалась от 26% до 61,5%, а у пациентов, которым была проведена искусственная вентиляция легких, смертность может колебаться от 65,7% до 94%. Факторы риска неблагоприятных исходов включают пожилой возраст; наличие сопутствующих заболеваний, таких как гипертония, сердечно-сосудистые заболевания и сахарный диабет; снижение количества лимфоцитов; травма почек; и повышенный уровень D-димера. Смерть от ОРДС при COVID-19 наступает в результате дыхательной недостаточности (53%), дыхательной недостаточности в сочетании с сердечной недостаточностью (33%), повреждения миокарда и недостаточности кровообращения (7%) или смерти по неизвестной причине.

Большое количество исследований показывают, что ЛПС прямо или косвенно участвует во всех патогенетических звеньях ОРДС, вызванного вирусом SARS-CoV-2, а именно: ухудшает течение воспалительных заболеваний легких на фоне снижения уровня ангиотензинпревращающего фермента 2 (ACE2); увеличивает генерацию активных форм кислорода (АФК) посредством НАДФН-оксидазы и последующую дезактивацию эндотелиальной синтазы оксида азота (eNOS) и снижение биодоступности эндотелиального NO, что приводит к эндотелиальной дисфункции; взаимодействует с белками сурфактантов. SP-A и SP-D, способствуя раннему разрушению монослоя и снижению поверхностного натяжения; взаимодействует с растворимой формой CD14-рецептора, что также оказывает провоспалительное воздействие на эпителиальные и эндотелиальные клетки; через рецепторы TLR4 приводит к активации p38MAPK, деградации белка IêBá и последующей транслокации p65 NF-êB в ядро, что приводит к транскрипции IL-6 и молекул адгезии (ICAM-1, VCAM-1 и E-селектин); а также, как показано в исследовании Petruk и соавт. (2020), непосредственно связываясь с S-белком вируса в сочетании с LPS усиливает активацию ядерного факторакаппа B (NF-êB) в моноцитарных клетках THP- 1 и цитокиновые ответы в мононуклеарных клетках крови. Данные патофизиологические механизмы требуют дальнейшего глубокого изучения с целью понимания природы изменений, возникающих на фоне новой коронавирусной инфекции SARS-CoV-2.

This review presents data from the literature that provide insight into the role of the lipopolysaccharide (LPS) of the Gram-negative bacteria in pathogenesis of acute respiratory distress syndrome (ARDS) caused by the novel SARS-CoV-2 coronavirus infection. ARDS is a syndrome of severe respiratory failure, an acutely occurring diffuse inflammatory lesion of lung tissue that develops as a nonspecific reaction to various direct (aspiration, inhalation of toxic gases), and systemic (sepsis, polytrauma) damaging factors and leading to development of acute respiratory failure (ARF), due to impaired structure of the lung parenchyma, disturbances in vascular permeability, decreased area of ventilated lung tissue. ARDS from coronavirus infection appears to have worse outcomes than ARDS from other causes. Mortality from typical ARDS at the intensive care units and hospitals is 35.3% and 40.0%, respectively, while the lethality rates for COVID-19-associated ARDS, ranged from 26% to 61.5%. Among patients who underwent artificial ventilation of the lungs, the mortality rates can range from 65.7% to 94%. Risk factors for poor outcomes include, e.g., older age, presence of concomitant diseases such as hypertension, cardiovascular disease and diabetes mellitus; decreased number of lymphocytes, kidney injury, and increased D-dimer levels. Death with ARDS in COVID-19 occurs as a result of respiratory failure (53%), respiratory failure combined with heart failure (33%), myocardial damage and circulatory failure (7%), or death from an unknown cause. A large number of studies show that bacterial LPS is directly or indirectly involved in all pathogenetic links of ARDS caused by the SARS-CoV-2 virus, i.e., worsening the course of inflammatory lung diseases due to decreased level of angiotensin-converting enzyme 2 (ACE2); increasing generation of reactive oxygen species (ROS) via NADPH oxidase and subsequent inactivation of endothelial nitric oxide synthase (eNOS) and decreasing bioavailability of endothelial NO, thus leading to endothelial dysfunction; interacting with proteins of surfactants. SP-A and SP-D, promoting early destruction of the cellular monolayers and lowering surface tension, interact with soluble CD14 receptor, which also has a pro-inflammatory effect on epithelial and endothelial cells, leading to p38MAPK activation via TLR4 receptors, causing degradation of IêBá protein and subsequent translocation of p65 NF-êB into the nucleus, thus inducing transcription of IL-6 and adhesion molecules (ICAM-1, VCAM-1 and E-selectin), and, as shown by Petruk et al. (2020), causing direct binding to the viral S protein in combination with LPS, thus enhancing activation of nuclear factor-kappa B (NF-êB) in monocytic THP-1 cells and cytokine responses in mononuclear blood cells. These pathophysiological mechanisms require further in-depth study in order to understand the nature of changes that occur in the patients with new SARS-CoV-2 infection.

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