Abstract
The COVID-19 pandemic continues, causing colossal damage to the population and the global economy. As COVID-19 is studied, new data are emerging regarding the risk of severe coronavirus infection in patients with α1-antitrypsin deficiency. α1 -Antitrypsin is the main inhibitor and key endogenous regulator of the serine leukocyte proteinase activitry released from the granules of activated neutrophils to the cell surface and into the extracellular space. It has been established that the number of cases of severe course and death of COVID-19 in the territories of 68 countries of the world correlates with the frequency of the spread of mutations in the proteinase inhibitor gene among the population of these countries, at which the concentration of α1-antitrypsin in the human blood plasma is 10 times lower than normal. All this contributes to the revision of a number of provisions of the pathogenesis and therapy of a new coronavirus infection.The review presents an analysis of the literature on the role of an inhibitor of serine leukocyte proteinases in protecting the body from COVID-19. The participation of α1-antitrypsin in the inhibition of SARS-CoV-2 penetration into the respiratory tract epithelial cells, in the protection of the vascular endothelium, blood plasma proteins and elastin of the lung tissue from the damaging effect of leukocyte elastase released during neutrophil degranulation and the formation of neutrophil extracellular traps (NETs) is considered. The role of a1-antitrypsin in suppressing inflammation by limiting the secretion of proinflammatory cytokines and neutrophil extracellular traps into the blood has been shown. The individual links in the pathogenesis of the new coronavirus infection have been detailed, which will allow revising the strategy for reducing the risks of severe course of COVID-19.
Highlights
Аннотация Пандемия COVID-19 продолжается, нанося колоссальный ущерб населению и мировой экономике
With α1-antitrypsin deficiency. α1-Antitrypsin is the main inhibitor and key endogenous regulator of the serine leukocyte proteinase activitry released from the granules of activated neutrophils to the cell surface and into the extracellular space
It has been established that the number of cases of severe course and death of COVID-19 in the territories of 68 countries of the world correlates with the frequency of the spread of mutations in the proteinase inhibitor gene among the population of these countries, at which the concentration of α1-antitrypsin in the human blood plasma is 10 times lower than normal
Summary
Имеющие эти заболевания, относятся к группе риска по тяжёлому течению COVID-19 [2], а сами эти болезни протекают на фоне врождённого (и/или приобретённого) дефицита ААТ [7], то контролирующий активность ЛЭ плазменный ингибитор СЛП (белок ААТ) играет, вероятно, решающую роль как фактор, ограничивающий формирование ДНК-сетей НВЛ и их накоп ление при COVID-19 в лёгких и периферической крови больных [6]. По данным K.Y. Oguntuyo и соавт., сыворотки крови индивидуумов, не имевших контакта с SARSCoV-2, с высокой эффективностью ингибировали проникновение этого вируса в клетки эпителия и ответственным за это был ААТ, действие которого могло быть связано с нейтрализацией протеолитической активности как TMPRSS-2, так и ЛЭ [14]. Дальнейшие полномасштабные клинико-экспериментальные исследования в этом направлении позволят детализировать механизм патогенеза новой коронавирусной инфекции и будут способствовать разработке эффективных средств и методов борьбы с SARS-CoV-2
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