Роль окислительного стресса в патогенезе COVID-19
https://doi.org/10.18699/SSMJ20250604
Аннотация
Статья посвящена анализу роли окислительного стресса в патогенезе инфекции, вызванной SARSCoV2. Рассматриваются как традиционные, так и альтернативные механизмы нарушения редоксгомеостаза, включая инактивацию ACE2, митохондриальную дисфункцию, нейроиммунный дисбаланс и микробиотаассоциированные пути. Окислительный стресс при COVID19 способствует активации провоспалительных каскадов, транскрипционного фактора NFκB и подавлению Nrf2зависимого сигнального пути, усиливая продукцию цитокинов и формирование «цитокинового шторма». Нарушение антиоксидантной защиты сопровождается иммунной и эндотелиальной дисфункцией, способствуя тромбозам и микрососудистым поражениям. Представлены противоречивые клинические и экспериментальные данные, касающиеся эффективности антиоксидантной терапии. Подчеркивается необходимость стратифицированного подхода и дальнейшего изучения редоксзвеньев патогенеза. Особое внимание уделено нерешенным вопросам, включая исходный редоксстатус пациента и механизмы устойчивой активации NADPHоксидазы и подавления Nrf2сигналинга.
Об авторе
Ю. В. Быков
Ставропольский государственный медицинский университет Минздрава России
Россия
Россия
Быков Юрий Витальевич - к.м.н.
355017, Ставрополь, ул. Мира, 310
Список литературы
1. Guan W., Ni Z., Hu Y., Liang W., Ou C., He J., Liu L., Shan H., Lei C., Hui D.S., … China Medical Treatment Expert Group for Covid-19. Clinical characteristics of coronavirus disease 2019 in China. N. Engl. J. Med. 2020;382(18):1708–1720. doi: 10.1056/NEJMoa2002032
2. Alam M.S., Czajkowsky D.M. SARS-CoV-2 infection and oxidative stress: Pathophysiological insight into thrombosis and therapeutic opportunities. Cytokine Growth Factor Rev. 2021;63:44–57. doi: 10.1016/j.cytogfr.2021.11.001
3. Щулькин А.В., Филимонова А.А. Роль свободно-радикального окисления, гипоксии и их коррекции в патогенезе COVID-19. Терапия. 2020;6(5):187–194. doi: 10.18565/therapy.2020.5.187-194
4. Marczewska A., Wojciechowska C., Marczewski K., Gospodarczyk N., Dolibog P., Czuba Z., Wróbel K., Zalejska-Fiolka J. Elevated levels of IL–1Ra, IL–1β, and oxidative stress in COVID-19: Implications for inflammatory pathogenesis. J. Clin. Med. 2025;14(7):2489. doi: 10.3390/jcm14072489
5. Carvajal J.J., García-Castillo V., Cuellar S.V., Campillay-Véliz C.P., Salazar-Ardiles C., Avellaneda A.M., Muñoz C.A., Retamal-Díaz A., Bueno S.M., González P.A., Kalergis A.M., Lay M.K. New insights into the pathogenesis of SARS-CoV-2 during and after the COVID-19 pandemic. Front. Immunol. 2024;15:1363572. doi: 10.3389/fimmu.2024.1363572
6. Camargo R.L., Bombassaro B., MonfortPires M., Mansour E., Palma A.C., Ribeiro L.C., Ulaf R.G., Bernardes A.F., Nunes T.A., Agrela M.V., … Sposito A.C. Plasma angiotensin ii is increased in critical coronavirus disease 2019. Front. Cardiovasc. Med. 2022;9:847809. doi: 10.3389/fcvm.2022.847809
7. Georgieva E., Ananiev J., Yovchev Y., Arabadzhiev G., Abrashev H., Abrasheva D., Atanasov V., Kostandieva R., Mitev M., Petkova-Parlapanska K., Nikolova G. COVID-19 complications: oxidative stress, inflammation, and mitochondrial and endothelial dysfunction. Int. J. Mol. Sci. 2023;24(19):14876. doi: 10.3390/ijms241914876
8. Orea-Tejada A., Sánchez-Moreno C., AztatziAguilar O.G., Sierra-Vargas M.P., González-Islas D., Debray-García Y., Ortega-Romero M.S., Keirns-Davis C., Cornejo-Cornejo L., Aguilar-Meza J. Plasma endothelial and oxidative stress biomarkers associated with late mortality in hospitalized COVID-19 Patients. J. Clin. Med. 2022;11(14):3950. doi: 10.3390/jcm11143950
9. Wieczfinska J., Kleniewska P., Pawliczak R. Oxidative stress-related mechanisms in SARS-CoV-2 infections. Oxid. Med. Cell Longev. 2022;2022:5589089. doi: 10.1155/2022/5589089
10. Ciacci P., Paraninfi A., Orlando F., Rella S., Maggio E., Oliva A., Cangemi R., Carnevale R., Bartimoccia S., Cammisotto V., … Loffredo L. Endothelial dysfunction, oxidative stress and low-grade endotoxemia in COVID-19 patients hospitalised in medical wards. Microvasc. Res. 2023;149:104557. doi: 10.1016/j.mvr.2023.104557
11. Wu Z., McGoogan J.M. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020;323(13):1239–1242. doi: 10.1001/jama.2020.2648
12. Zhou Y., Zhang Z., Tian J., Xiong S. Risk factors associated with disease progression in a cohort of patients infected with the 2019 novel coronavirus. Ann. Palliat. Med. 2020;9(2):428–436. doi: 10.21037/apm.2020.03.26
13. Laforge M., Elbim C., Frère C., Hémadi M., Massaad C., Nuss P., Benoliel J.J., Becker C. Tissue damage from neutrophil-induced oxidative stress in COVID-19. Nat. Rev. Immunol. 2020;20(9):515–516. doi: 10.1038/s41577-020-0407-1
14. Baqi H.R., Farag H.A.M., El Bilbeisi A.H.H., Askandar R.H., El Afifi A.M. Oxidative stress and its association with covid-19: a narrative review. KJAR. 2020;5(3):97–105. doi: 10.24017/covid.11
15. Delgado-Roche L., Mesta F. Oxidative stress as key player in severe acute respiratory syndrome coronavirus (SARS-CoV) infection. Arch. Med. Res. 2020;51(5):384–387. doi: 10.1016/j.arcmed.2020.04.019
16. Samsonov A., Urlache S.S. Oxidative stress in children and adolescents: insights into human biology. Am. J. Hum. Biol. 2025;37(1):e24200. doi: 10.1002/ajhb.24200
17. Кукес В.Г., Парфенова О.К., Сидоров Н.Г., Олефир Ю.В., Газданова А.А. Окислительный стресс и воспаление в патогенезе COVID-19. Рос. мед. ж. 2020;26(4):244–247. doi: 10.17816/08692106-2020-26-4-244-247
18. Jankauskas S.S., Kansakar U., Sardu C., Varzideh F., Avvisato R., Wang X., Matarese A., Marfella R., Ziosi M., Gambardella J., Santulli G. COVID-19 causes ferroptosis and oxidative stress in human endothelial cells. Antioxidants (Basel). 2023;12(2):326. doi: 10.3390/antiox12020326
19. Орлов Ю.П., Афанасьев В.В., Хиленко И.А. Перспектива сукцинатов в условиях гипоксии при СOVID-19. Антибиотики и химиотерапия. 2021;66(1–2):65–74. doi: 10.37489/0235-2990-2021-66-1-2-65-74
20. Черняк Б.В., Попова Е.Н., Приходько А.С., Гребенчиков О.А., Зиновкина Л.А., Зиновкин Р.А. COVID-19 и окислительный стресс. Биохимия. 2020;85(12):1816–1828. doi: 10.31857/s0320972520120064
21. Pizzino G., Irrera N., Cucinotta M., Pallio G., Mannino F., Arcoraci V., Squadrito F., Altavilla D., Bitto A. Oxidative stress: harms and benefits for human health. Oxid. Med. Cell. Longev. 2017:2017:8416763. doi: 10.1155/2017/8416763
22. Kayesh M.E., Kohara M., Tsukiyama-Kohara K. Effects of oxidative stress on viral infections: an overview. Npj Viruses. 2025;3(1):27. doi: 10.1038/s44298025-00110-3
23. Checa J., Aran J.M. Reactive oxygen species: drivers of physiological and pathological processes. J. Inflamm. Res. 2020:13:1057–1073. doi: 10.2147/JIR. S275595
24. Быков Ю.В. Роль оксидативного стресса в развитии осложнений при сахарном диабете. Мед. вестн. Сев. Кавказа. 2022;17(3):322–327. doi: 10.14300/mnnc.2022.17080
25. Liguori I., Russo G., Curcio F., Bulli G., Aran L., Della-Morte D., Gargiulo G., Testa G., Cacciatore F., Bonaduce D., Abete P. Oxidative stress, aging, and diseases. Clin. Interv. Aging. 2018;13:757–777. doi: 10.2147/CIA.S158513
26. Juan C.A., Perez de la Lastra J.M., Plou F.J., Perez-Lebena E. The chemistry of reactive oxygen species (ROS) revisited: outlining their role in biological macromolecules (DNA, Lipids and Proteins) and induced pathologies. Int. J. Mol. Sci. 2021;22(9):4642. doi: 10.3390/ijms22094642
27. Даренская М.А., Колесникова Л.И., Колесников С.И. COVID-19: окислительный стресс и актуальность антиоксидантной терапии. Вестн. РАМН. 2020;75:318–325. doi: 10.15690/vramn1360
28. Быков Ю.В. Диабетический кетоацидоз и окислительный стресс: патофизиологические механизмы. Сиб. науч. мед. ж. 2023;43(6):6–13. doi: 10.18699/SSMJ20230601
29. Nandi A., Yan L.J., Jana C.K., Das N. Role of catalase in oxidative stress-and age-associated degenerative diseases. Oxid. Med. Cell. Longev. 2019;2019:9613090. doi: 10.1155/2019/9613090
30. Semenova N., Vyrupaeva E., Kolesnikov S., Darenskaya M., Nikitina O., Rychkova L., Kolesnikova L. Persistent post COVID-19 endothelial dysfunction and oxidative stress in women. Pathophysiology. 2024;31(3):436–457. doi: 10.3390/pathophysiology31030033
31. Fukai T., Ushio-Fukai M. Cross-talk between NADPH oxidase and mitochondria: role in ROS signaling and angiogenesis. Cells. 2020;9(8):1849. doi: 10.3390/cells9081849
32. Tan B.L., Norhaizan M.E., Liew W.P.P., Rahman S.H. Antioxidant and oxidative stress: a mutual interplay in age-related diseases. Front. Pharmacol. 2018;9:1162. doi: 10.3389/fphar.2018.01162
33. Mehta P., McAuley D.F., Brown M., Sanchez E., Tattersall R.S., Manson J.J.; HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033–1034. doi: 10.1016/S0140-6736(20)30628-0
34. Mohiuddin M., Kasahara K. The emerging role of oxidative stress in complications of COVID-19 and potential therapeutic approach to diminish oxidative stress. Respir. Med. 2021;187:106605. doi: 10.1016/j.rmed.2021.106605
35. Khomich O.A., Kochetkov S.N., Bartosch B., Ivanov A.V. Redox biology of respiratory viral infections. Viruses. 2018;10(8):392. doi: 10.3390/v10080392
36. Lingappan K. NF-kappaB in Oxidative Stress. Curr. Opin. Toxicol. 2018:7:81–86. doi: 10.1016/j.cotox.2017.11.002
37. Wang Y., Ma J., Jiang Y. Transcription factor Nrf2 as a potential therapeutic target for COVID-19. Cell Stress Chaperones. 2022;28(1):11–20. doi: 10.1007/s12192-022-01296-8
38. Cuadrado A., Pajares M., Benito C., JiménezVillegas J., Escoll M., Fernández-Ginés R., Garcia Yagüe A.J., Lastra D., Manda G., Rojo A.I., DinkovaKostova A.T. Can activation of Nrf2 be a strategy against COVID-19? Trends Pharmacol. Sci. 2020;41(9):598– 610. doi: 10.1016/j.tips.2020.07.003
39. Zhang Z., Zhang X., Bi K., He Y., Yan W., Yang C.S. Potential protective mechanisms of green tea polyphenol EGCG against COVID-19. Trends Food Sci. Technol. 2021;114:11–24. doi: 10.1016/j.tifs.2021.05.023
40. Olagnier D., Brandtoft A.M., Gunderstofte C., Villadsen N.L., Krapp C., Thielke A.L., Laustsen A., Peri S., Hansen A.L., Bonefeld L., Thyrsted J., … Holm C.K. Nrf2 negatively regulates STING indicating a link between antiviral sensing and metabolic reprogramming. Nat. Commun. 2018;9(1):3506. doi: 10.1038/s41467-018-05861-7
41. Zhang S., Wang J., Wang L., Aliyari S., Cheng G. SARS-CoV-2 virus NSP14 Impairs Nrf2/ HMOX1 activation by targeting Sirtuin 1. Cell. Mol. Immunol. 2022;19(8):872–882. doi: 10.1038/s41423022-00887-w
42. de Angelis M., Anichini G., Palamara A.T., Nencioni L., Gori Savellini G. Dysregulation of intracellular redox homeostasis by the SARS-CoV-2 ORF6 protein. Virol. J. 2023;20(1):239. doi: 10.1186/s12985023-02208-7
43. Yu H., Yang L, Han Z., Zhou X., Zhang Z., Sun T., Zheng F., Yang J., Guan F., Xie J., Liu C. SARS-CoV-2 nucleocapsid protein enhances the level of mitochondrial reactive oxygen species. J. Med. Virol. 2023;95(12):e29270. doi: 10.1002/jmv.29270
44. Agrawal R., Pal V.K., K S.S., Menon G.J., Singh I.R., Malhotra N., Ganesh K., Rajmani R.S., Narain Seshasayee A.S., Chandra N., Joshi M.B., Singh A. Hydrogen sulfide (H2S) coordinates redox balance, carbon metabolism, and mitochondrial bioenergetics to suppress SARS-CoV-2 infection. PLoS Pathog. 2025;21(5):e1013164. doi: 10.1371/journal.ppat.1013164
45. Vlaming-van Eijk L.E., Bulthuis M.L., van der Gun B.T., Wold K.I., Veloo A.C., Vincenti González M.F., de Borst M.H., den Dunnen W.F., JanLuuk Hillebrands, van Goor H., Tami A., Bourgonje A.R. Systemic oxidative stress associates with the development of post-COVID-19 syndrome in non-hospitalized individuals. Redox Biol. 2024:76:103310. doi: 10.1016/j.redox.2024.103310
46. Alam M.S., Czajkowsky D.M. SARS-CoV-2 infection and oxidative stress: Pathophysiological insight into thrombosis and therapeutic opportunities. Cytokine Growth Factor Rev. 2022;63:44–57. doi: 10.1016/j.cytogfr.2021.11.001
47. Fogleman C., Cohen D., Mercier A., Farrell D., Rutz J., Bresz K., Vernon T. J. A Pilot of a randomized control trial of melatonin and vitamin C for mild-to-moderate COVID-19. Am Board Fam. Med. 2022;35(4):695–707. doi: 10.3122/jabfm.2022.04.210529
48. Falahieh F.M., Zarabadipour M., Mirani M., Abdiyan M., Dinparvar M., Alizadeh H., Paktinat S., Hosseinirad H. Effects of moderate COVID-19 infection on semen oxidative status and parameters 14 and 120 days after diagnosis. Reprod. Fertil. Dev. 2021;33(12):683– 690. doi: 10.1071/RD21153
49. Tepebaşı M.Y., İlhan İ., Temel E.N., Sancer O., Öztürk Ö. Investigation of inflammation, oxidative stress, and DNA damage in COVID-19 patients. Cell Stress Chaperones. 2023;28(2):191–199. doi: 10.1007/s12192-023-01330-3
50. Iddir M., Brito A., Dingeo G., Fernandez Del Campo S.S., Samouda H., La Frano M.R., Bohn T. Strengthening the immune system and reducing inflammation and oxidative stress through diet and nutrition: Considerations during the COVID-19 Crisis. Nutrients. 2020;12(6):1562. doi: 10.3390/nu12061562
51. Zhou T., Wu J., Zeng Y., Li J., Yan J., Meng W., Han H., Feng F., He J., Zhao S., Zhou P., Wu Y., Yang Y., Han R., Jin W., Li X., Yang Y., Li X. SARS-CoV-2 triggered oxidative stress and abnormal energy metabolism in gut microbiota. MedComm. (2020). 2022;3(1):e112. doi: 10.1002/mco2.112
52. Zendelovska D., Atanasovska E., Spasovska K., Kirijas M., Kapsarov K., Jakimovski D., Petrushevska M. Effect of supplemental antioxidant-based therapy on the oxidative stress level in COVID-19 patients. Pril. (Makedon. Akad. Nauk. Umet. Odd. Med. Nauki). 2023;44(1):7–16. doi: 10.2478/prilozi-2023-0002
53. Simadibrata D.M., Calvin J., Wijaya A.D., Ibrahim N.A.A. Neutrophil-to-lymphocyte ratio on admission to predict the severity and mortality of COVID-19 patients: a meta-analysis. Am. J. Emerg. Med. 2021;42:60–69. doi: 10.1016/j.ajem.2021.01.006
54. Man M.A., Rajnoveanu R.M., Motoc N.S., Bondor C.I., Chis A.F., Lesan A., Puiu R., Lucaciu S.-R., Dantes E., Gergely-Domokos B., Fira-Mladinescu O. Neutrophil-to-lymphocyte ratio, plateletsto-lymphocyte ratio, and eosinophils correlation with high-resolution computer tomography severity score in COVID-19 patients. PLoS One. 2021;16(6):e0252599. doi: 10.1371/journal.pone.0252599
55. Hule G.P., Bargir U.A., Kulkarni M., Kambli P., Taur P., Desai M., Madkaikar M.R. Does pioglitazone lead to neutrophil extracellular traps formation in chronic granulomatous disease patients? Front. Immunol. 2019;10:1739. doi: 10.3389/fimmu.2019.01739
56. Cecchini R., Cecchini A.L. SARS-CoV-2 infection pathogenesis is related to oxidative stress as a response to aggression. Med. Hypotheses. 2020;143:110102. doi: 10.1016/j.mehy.2020.110102
57. Moro-García M.A., Mayo J.C., Sainz R.M., Alonso-Arias R. Influence of inflammation in the process of T lymphocyte differentiation: proliferative, metabolic, and oxidative changes. Front. Immunol. 2018;9:339. doi: 10.3389/fimmu.2018.00339
58. Bakadia B.M., Boni B.O.O., Ahmed A.A.Q., Yang G. The impact of oxidative stress damage induced by the environmental stressors on COVID-19. Life Sci. 2021:264:118653. doi: 10.1016/j.lfs.2020.118653
59. Patel V.B., Zhong J.C., Grant M.B., Oudit G.Y. Role of the ACE2/angiotensin 1–7 axis of the renin–angiotensin system in heart failure. Circ. Res. 2016;118(8):1313–1326. doi: 10.1161/CIRCRESAHA.116.307708
60. Verdecchia P., Cavallini C., Spanevello A., Angeli F. The pivotal link between ACE2 deficiency and SARS-CoV-2 infection. Eur. J. Intern. Med. 2020;76:14–20. doi: 10.1016/j.ejim.2020.04.037
61. Fodor A., Tiperciuc B., Login C., Orasan O.H., Lazar A.L., Buchman C., Hanghicel P., Sitar-Taut A., Suharoschi R., Vulturar R., Cozma A. Endothelial dysfunction, inflammation, and oxidative stress in COVID-19-mechanisms and therapeutic targets. Oxid. Med. Cell. Longev. 2021;2021:8671713. doi: 10.1155/2021/8671713
62. Hati S., Bhattacharyya S. Impact of thioldisulfide balance on the binding of COVID-19 spike protein with angiotensin-converting enzyme 2 receptor. ACS Omega. 2020;5(26):16292–16298. doi: 10.1021/acsomega.0c02125
63. Violi F., Oliva A., Cangemi R., Ceccarelli G., Pignatelli P., Carnevale R., Cammisotto V., Lichtner M., Alessandri F., De Angelis M., … Mastroianni C.M. Nox2 activation in COVID-19. Redox Biol. 2020;36:101655. doi: 10.1016/j.redox.2020.101655
64. Lei Y., Zhang J., Schiavon C.R., He M., Chen L., Shen H., Zhang Y., Yin Q., Cho Y., Andrade L., … Shyy J.Y. SARS-CoV-2 spike protein impairs endothelial function via downregulation of ACE 2. Circ. Res. 2021;128(9):1323–1326. doi: 10.1161/CIRCRESAHA.121.318902
65. Suhail S., Zajac J., Fossum C., Lowater H., McCracken C., Severson N., Laatsch B., Narkiewicz-Jodko A., Johnson B., Liebau J., Bhattacharyya S., Hati S. Role of oxidative stress on SARS-CoV (SARS) and SARS-CoV-2 (COVID-19) infection: a review. Protein J. 2020;39(6):644–656. doi: 10.1007/s10930-02009935-8
66. Chang R., Mamun A., Dominic A., Le N.T. SARS-CoV-2 mediated endothelial dysfunction: the potential role of chronic oxidative stress. Front. Physiol. 2021;11:605908. doi: 10.3389/fphys.2020.605908
67. Vassiliou A.G., Zacharis A., Keskinidou C., Jahaj E., Pratikaki M., Gallos P., Dimopoulou I., Kotanidou A., Orfanos S.E. Soluble angiotensin converting enzyme 2 (ACE2) Is upregulated and soluble endothelial nitric oxide synthase (eNOS) is downregulated in COVID-19-induced acute respiratory distress syndrome (ARDS). Pharmaceuticals (Basel). 2021;14(7):695. doi: 10.3390/ph14070695
68. Pincemail J., Cavalier E., Charlier C., Cheramy– Bien J., Brevers E., Courtois A., Fadeur M., Meziane S., Le Goff C., Misset B., … Rousseau A.F. Oxidative stress status in COVID-19 patients hospitalized in intensive care unit for severe pneumonia. A pilot study. Antioxidants. 2021;10(2):257. doi: 10.3390/antiox10020257
69. Zhang J., Rao X., Li Y., Zhu Y., Liu F., Guo G., Luo G., Meng Z., De Backer D., Xiang H., Peng Z.Y. High-dose vitamin C infusion for the treatment of critically ill COVID-19. Res. Sq. 2020;100:e25876. doi: 10.21203/rs.3.rs-52778/v1+
70. Mehri F., Rahbar A.H., Ghane E.T., Souri B., Esfahani M. Changes in oxidative markers in COVID-19 patients. Arch. Med. Res. 2021;52(8):843–849. doi: 10.1016/j.arcmed.2021.06.004
71. Saleh M.G., Chang L., Liang H., Ryan M.C., Cunningham E., Garner J., Wilson E., Levine A.R., Kottilil S., Ernst T. Ongoing oxidative stress in individuals with post-acute sequelae of COVID-19. NeuroImmune Pharm. Ther. 2022;2(2):89–94. doi: 10.1515/nipt-2022-0006
72. Muhammad Y., Kani Y.A., Iliya S., Muhammad J.B., Binji A., El-Fulaty Ahmad A., Kabir M.B., Umar Bindawa K., Ahmed A. Deficiency of antioxidants and increased oxidative stress in COVID-19 patients: a cross-sectional comparative study in Jigawa, Northwestern Nigeria. SAGE Open Med. 2021;9:2050312121991246. doi: 10.1177/2050312121991246
73. Khan N., Singla M., Samal S., Lodha R., Medigeshi G.R. Respiratory syncytial virus-induced oxidative stress leads to an increase in labile zinc pools in lung epithelial cells. mSphere. 2020;5:e00447–e004420. doi: 10.1128/mSphere.00447-20
74. Ao G., Li J., Yuan Y., Wang Y., Nasr B., Bao M., Gao M., Qi X. Intravenous vitamin C use and risk of severity and mortality in COVID-19: A systematic review and meta-analysis. Nutr. Clin. Pract. 2022;37(2):274–281. doi: 10.1002/ncp.10832
75. Kow C.S., Hasan S.S., Ramachandram D.S. The effect of vitamin C on the risk of mortality in patients with COVID-19: a systematic review and metaanalysis of randomized controlled trials. Inflammopharmacology. 2023;31(6):3357–3362. doi: 10.1007/s10787-023-01200-5
76. Atefi N., Goodarzi A., Riahi T., Khodabandehloo N., Talebi Taher M., Najar Nobari N., Seirafianpour F., Mahdi Z., Baghestani A., Valizadeh R. Evaluation of the efficacy and safety of oral N-acetylcysteine in patients with COVID-19 receiving the routine antiviral and hydroxychloroquine protocol: A randomized controlled clinical trial. Immun. Inflamm. Dis. 2023;11(11):e1083. doi: 10.1002/iid3.1083
77. Paraskevas T., Kantanis A., Karalis I., Michailides C., Karamouzos V., Koniari I., Pierrakos C., Velissaris D. N-acetylcysteine efficacy in patients hospitalized with COVID-19 pneumonia: a systematic review and meta-analysis. Rom. J. Intern. Med. 2023;61(1):41–52. doi: 10.2478/rjim-2023-0001
78. Afaghi S., Moghimi N., Malekpour Alamdari N., Rahimi F.S., Irilouzadian R., Esmaeili Tarki F., Moghimi M., Besharat S., Salehi Omran H., Karimi A. N-acetylcysteine as adjuvant therapy for hospitalized COVID-19 patients: A single-center prospective cohort study. Caspian J. Intern. Med. 2023;14(3):543–552. doi: 10.22088/cjim.14.3.553
79. Pilia E., Alborino E., Covello R.D. Does melatonin reduce mortality in COVID-19? Ann. Med. Surg. (Lond.). 2022:78:103817. doi: 10.1016/j.amsu.2022.103817
80. Huang P.Y., Wu J.Y., Liu T.H., Tsai Y.W., Chen P.T., Liao C.T., Toh H.S. The clinical efficacy of melatonin in the treatment of patients with COVID-19: a systematic review and meta-analysis of ran-
Рецензия
Просмотров:
138
JATS XML
Послать статью по эл. почте 