Acta NaturaeActa NaturaeActa Naturae2075-8251Acta Naturae Ltd2761010.32607/actanaturae.27610Research ArticlesЭкспериментальные статьиResearch ArticleIdentifying microRNA expression alterations in erythrocytes, lymphocytes, and monocytes during severe COVID-19Изменения экспрессии микроРНК в эритроцитах, лимфоцитах и моноцитах при тяжелом течении COVID-19ArtamonovA. A.АртамоновА. А.
Russian Federation
kondratovk.kirill@yandex.ruNikitinYu. V.НикитинЮ. В.
Russian Federation
kondratovk.kirill@yandex.ruVelmiskinaA. A.ВельмискинаА. А.
Russian Federation
kondratovk.kirill@yandex.ruMosenkoS. V.МосенкоС. В.
Russian Federation
kondratovk.kirill@yandex.ruShimanskyV. S.ШиманскийВ. С.
Russian Federation
kondratovk.kirill@yandex.ruAsinovskayaA. Yu.АсиновскаяА. Ю.
Russian Federation
kondratovk.kirill@yandex.ruApalkoS. V.АпалькоС. В.
Russian Federation
kondratovk.kirill@yandex.ruSushentsevaN. N.СушенцеваН. Н.
Russian Federation
kondratovk.kirill@yandex.ruIvanovA. M.ИвановА. М.
Russian Federation
kondratovk.kirill@yandex.ruScherbakS. G.ЩербакС. Г.
Russian Federation
kondratovk.kirill@yandex.ruKondratovK. A.КондратовК. А.
Russian Federation
kondratovk.kirill@yandex.ruS. M. Kirov Military Medical AcademyВоенно-медицинская академия им. С. М. КироваCity Hospital No. 40, St. PetersburgГородская больница № 40, Санкт-ПетербургSt. Petersburg State UniversityСанкт-Петербургский государственный университет2204202618124350301202502022026Copyright ©; 2026, Artamonov A.A., Nikitin Y.V., Velmiskina A.A., Mosenko S.V., Shimansky V.S., Asinovskaya A.Y., Apalko S.V., Sushentseva N.N., Ivanov A.M., Scherbak S.G., Kondratov K.A.Copyright ©; 2026, Артамонов А.А., Никитин Ю.В., Вельмискина А.А., Мосенко С.В., Шиманский В.С., Асиновская А.Ю., Апалько С.В., Сушенцева Н.Н., Иванов А.М., Щербак С.Г., Кондратов К.А.2026Artamonov A.A., Nikitin Y.V., Velmiskina A.A., Mosenko S.V., Shimansky V.S., Asinovskaya A.Y., Apalko S.V., Sushentseva N.N., Ivanov A.M., Scherbak S.G., Kondratov K.A.Артамонов А.А., Никитин Ю.В., Вельмискина А.А., Мосенко С.В., Шиманский В.С., Асиновская А.Ю., Апалько С.В., Сушенцева Н.Н., Иванов А.М., Щербак С.Г., Кондратов К.А.https://creativecommons.org/licenses/by/4.0https://actanaturae.ru/2075-8251/article/view/27610

A significant portion of the fatal outcomes during COVID-19 have been traced mainly to cytokine storm, the uncontrolled hyperactivation of the immune system. During a SARS-CoV-2 infection, the blood plasma levels of microRNAs (miRNAs), a class of short regulatory RNAs, get significantly changed. However, it still remains unknown how the levels and characteristics of these molecules are altered in various blood cells during severe COVID-19. The aim of this research was to compare the microRNA levels in erythrocytes, monocytes, and lymphocytes in normal blood cells and those in patients with severe COVID-19-induced by cytokine storm. Erythrocytes and monocytes (five healthy donors and five patients with severe COVID-19) and lymphocytes (four healthy donors and four patients with severe COVID-19) were obtained by fluorescence-activated cell sorting. RNA was isolated from the obtained cells, and next-generation short RNA sequencing was performed. Both the known miRNAs and the novel miRNAs whose expression had changed in severe COVID-19 were analyzed and identified. In the erythrocytes, seven miRNAs had changed expressions (five downregulated; two upregulated); all 13 miRNAs were upregulated in lymphocytes; in monocytes, 11 miRNAs were downregulated and three miRNAs were upregulated. An analysis of the novel miRNAs showed that three, previously unknown miRNAs, were downregulated in lymphocytes and one was upregulated. In monocytes and erythrocytes, no novel, differentially expressed miRNAs were detected. Additionally, we analyzed the signaling pathways altered by miRNAs by performing a miRNA enrichment analysis (MIEAA) using the Gene Ontology miRNA target database (miRTarBase). We observed that in lymphocytes, four pathways were significantly (Q-value < 0.05) enriched and 339 were depleted; in monocytes, 118 pathways were enriched and six were depleted. No significantly altered signaling pathways were detected in erythrocytes.

Существенная часть летальных исходов при тяжелом течении COVID-19 обусловлена неконтролируемой гиперактивацией иммунной системы – цитокиновым штормом. При инфекции SARS-CoV-2 в плазме крови изменяются также уровни одного из классов микроРНК – коротких регуляторных РНК. Однако недостаточно хорошо изучено изменение уровней этих молекул в различных клетках крови при тяжелом течении COVID-19. В представленной работе сравнивали уровни микроРНК в эритроцитах, моноцитах и лимфоцитах в норме и у пациентов с тяжелым COVID-19. Эритроциты и моноциты (пять здоровых доноров и пять пациентов с тяжелым COVID-19), а также лимфоциты (четыре здоровых донора и четыре пациента с тяжелым COVID-19) были получены методом FACS (сортировка клеток с активированной флуоресценцией). Из полученных клеток выделяли РНК и проводили высокопроизводительное секвенирование малых РНК. Были проанализированы и идентифицированы как известные, так и новые микроРНК, экспрессия которых достоверно изменялась при тяжелом COVID-19. В эритроцитах обнаружено изменение экспрессии семи микроРНК (снижение пяти и повышение – двух); в лимфоцитах найдено 13 микроРНК, уровни экспрессии которых достоверно изменялись, причем у всех они были повышены, в моноцитах экспрессия 11 микроРНК была подавлена, а трех активирована. Анализ новых (ранее неизвестных) микроРНК показал снижение экспрессии трех ранее неизвестных микроРНК в лимфоцитах и повышение одной. В моноцитах и эритроцитах новые дифференциально экспрессируемые микроРНК не обнаружены. Дополнительно анализировали сигнальные пути, микроРНК с измененной экспрессией, используя с этой целью анализ обогащения микроРНК (miEAA) и базы данных мишеней микроРНК Gene Ontology (miRTarBase). В лимфоцитах выявили четыре достоверно обогащенных пути (Q-value < 0.05) и 339 обедненных, тогда как в моноцитах 118 путей были обогащены, а шесть обеднены. В эритроцитах достоверно измененных сигнальных путей не обнаружено.

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