Ekologiya cheloveka (Human Ecology)Ekologiya cheloveka (Human Ecology)Экология человека1728-08692949-1444Eco-Vector40952710.17816/humeco409527ORIGINAL STUDY ARTICLESОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯResearch ArticleIntracellular level of HIF-1α as an indicator of the delayed impact of COVID-19 on peripheral blood lymphocytes metabolismВнутриклеточный уровень HIF-1α — информативный показатель отложенного влияния COVID-19 на метаболизм лимфоцитов периферической кровиhttps://orcid.org/0000-0002-5039-22201581-5178ZubatkinaOlga V.ЗубаткинаОльга Владимировна
Russian Federation

Dr. Sci. (Biol.), professor, senior research associate

д.б.н., профессор, старший научный сотрудник

ozbiochem@gmail.comhttps://orcid.org/0000-0001-5080-65024518-6925DobrodeevaLilia K.ДобродееваЛилия Константиновна
Russian Federation

MD, Dr. Sci. (Med.), professor

д.м.н., профессор

dobrodeevalk@mail.ruhttps://orcid.org/0000-0002-4085-409X2532-9912KruglovSergey D.КругловСергей Дмитриевич
Russian Federation
stees67@yandex.ruLaverov Federal Center for Integrated Arctic ResearchФедеральный исследовательский центр комплексного изучения Арктики имени академика Н.П. Лавёрова28072023150820233043133201105202319062023Copyright ©; 2023, Eco-VectorCopyright ©; 2023, Эко-Вектор2023Eco-VectorЭко-Векторhttps://creativecommons.org/licenses/by-nc-nd/4.0https://hum-ecol.ru/1728-0869/article/view/409527

BACKGROUND: COVID-19 infection triggers metabolic alterations that are crucial for both the replication of SARS-CoV-2 and the regulation of the immune response. HIF-1α, which is one of the effectors in the PI3K/Akt/mTOR signal transmission pathway, promotes the reprogramming of metabolism by enhancing aerobic glycolysis.

AIM: To assess whether the intracellular level of HIF-1α can reflect changes in the metabolism of peripheral blood lymphocytes after a COVID-19 infection.

MATERIAL AND METHODS: The sample consisted of 59 volunteers. Thirty eight of them had no history of COVID-19 while 21 reported having COVID-19 infection 2–8 months prior to the study. Serum concentrations of IgG antibodies to SARS-CoV-2 were assessed in both groups. Absolute content of lymphocytes was measured in whole blood, and the concentration of HIF-1α was determined in the lymphocyte lysate by enzyme immunoassay. All data were analyzed using IBM SPSS software (v. 26). Means and standard deviations were calculated for all numeric variables. Normality of the distributions were assessed using Kolmogorov–Smirnov test. Differences between the groups were studied by unpaired Student's t-tests. The differences at p <0.05 were considered statistically significant. Receiver operative characteristic curve was constructed to assess the prognostic value of HIF-1α.

RESULTS: Volunteers with a history of COVID-19 infection had significantly lower concentrations of HIF-1α in peripheral blood lymphocytes compared to their counterparts with no history of COVID-19. Intracellular concentration of HIF-1α was significantly associated with the likelihood of changes in lymphocyte metabolism. HIF-1α concentration of 1.25 ng/106 cells was the most optimal cut-off value.

CONCLUSION: The intracellular level of HIF-1α can serve as an indicator of the potential delayed impact of COVID-19 on the metabolic activity of peripheral lymphocytes. Our research findings hold significant value in monitoring and assessing metabolic alterations in individuals recovering from COVID-19.

Обоснование. Инфекция COVID-19 вызывает метаболические изменения, которые играют решающую роль как в репликации SARS-CoV-2, так и в регуляции иммунного ответа. HIF-1α — один из эффекторов пути передачи сигнала PI3K/Akt/mTOR — способствует перепрограммированию метаболизма через усиление аэробного гликолиза.

Цель. Установить информативность внутриклеточного уровня HIF-1α как показателя изменений метаболизма лимфоцитов периферической крови после перенесённой инфекции COVID-19.

Материал и методы. Обследовано 59 волонтёров, из них 38 человек не имели в анамнезе COVID-19 и 21 — перенесли заболевание за 2–8 мес до начала обследования. В сыворотке крови устанавливали наличие антител класса IgG к SARS-CoV-2. В цельной крови измеряли абсолютное содержание лимфоцитов, в лизате лимфоцитов определяли концентрацию HIF-1α методом иммуноферментного анализа. Статистическую обработку полученных данных проводили с применением пакета программного обеспечения IBM SPSS v. 26. Вычисляли средние значения (М), стандартное отклонение (SD). Нормальность распределения оценивали по критерию Колмогорова–Смирнова, для сравнения средних использовали t-критерий Стьюдента, уровень статистической значимости принимали равным p <0,05. Проводили ROC-анализ с построением характеристической кривой для классификатора HIF-1α.

Результаты. Установлено, что содержание HIF-1α в лимфоцитах периферической крови у переболевших инфекцией COVID-19 по сравнению с неболевшими статистически значимо ниже и остаётся таковым на протяжении 5 мес после заболевания. Модель с классификатором HIF-1α имеет высокую прогностическую силу в отношении вероятности изменений метаболизма лимфоцитов после перенесённой инфекции COVID-19. Оптимальному порогу отсечения соответствует внутриклеточное содержание HIF-1α, равное 1,25 нг/106 кл.

Заключение. Внутриклеточный уровень HIF-1α можно использовать для оценки вероятности отложенного влияния COVID-19 на метаболизм лимфоцитов периферической крови и мониторинга метаболических изменений.

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