Pathogenetic approaches to the correction of vascular homeostasis in patients with COVID-19: A review

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Abstract

The adverse outcomes in patients with COVID-19 in the initial phase of the disease are often due to the development of cytokine storm, endothelial dysfunction, shifts in the hemostasis system, microangiopathy, angiocentric inflammation, and pathological angiogenesis, which require targeted therapy. Unfortunately, to date, there is still no drug with proven high efficacy. This review is to analyse the literature data on the pathogenesis of vascular homeostasis lesions and possible ways to correct the existing shifts in patients with COVID-19. When the oxygen content in the tissue decreases, one of the most important mechanisms of adaptation is the activation of the succinate oxidase pathway, but under conditions of prolonged hypoxia and intoxication, the succinate reserve is rapidly depleted. That is why exogenous of succinic acid can enhance the adaptive capabilities of the organism and improve the prognosis in patients with COVID-19. Succinic acid preparations contribute to normalization of energy exchange and reduction of oxidative stress, especially in combination with inosine, nicotinamide and riboflavin and are widely used in clinical practice in various nosological forms. Taking into account the analysis of data on the mechanisms of clinical effects of succinate-containing preparations, this group of drugs can be considered as promising with regard to the correction of vascular disorders in COVID-19.

About the authors

Andrey A. Shuldyakov

Razumovsky Saratov State Medical University

Author for correspondence.
Email: shuldaykov@mail.ru
ORCID iD: 0000-0002-3009-9262

доктор медицинских наук, профессор, зав. кафедры инфекционных болезней

Russian Federation, Saratov

Anna N. Smagina

Razumovsky Saratov State Medical University

Email: shuldaykov@mail.ru
ORCID iD: 0000-0001-5139-2188

кандидат медицинских наук, доцент кафедры инфекционных болезней

Russian Federation, Saratov

Kristina Kh. Ramazanova

Razumovsky Saratov State Medical University

Email: shuldaykov@mail.ru
ORCID iD: 0000-0002-5249-4888

кандидат медицинских наук, доцент кафедры инфекционных болезней

Russian Federation, Saratov

Elena P. Lyapina

Razumovsky Saratov State Medical University

Email: shuldaykov@mail.ru
ORCID iD: 0000-0001-6116-0567

доктор медицинских наук, профессор кафедры инфекционных болезней

Russian Federation, Saratov

Yusef R. Chabbarov

Razumovsky Saratov State Medical University

Email: shuldaykov@mail.ru
ORCID iD: 0000-0002-1872-2154

студент 6-го курса лечебного факультета

Russian Federation, Saratov

Natalia A. Sheshina

Razumovsky Saratov State Medical University

Email: shuldaykov@mail.ru
ORCID iD: 0009-0003-2279-5430

ассистент кафедры инфекционных болезней

Russian Federation, Saratov

Alena A. Zhuk

Razumovsky Saratov State Medical University

Email: shuldaykov@mail.ru
ORCID iD: 0000-0002-5236-0871

ординатор кафедры инфекционных болезней

Russian Federation, Saratov

References

  1. Meini S, Giani T, Tascini C. Intussusceptive angiogenesis in COVID-19: Hypothesis on the significance and focus on the possible role of FGF2. Mol Biol Rep. 2020;47(10):8301-4. doi: 10.1007/s11033-020-05831-7
  2. Basta G. Direct or indirect endothelial damage? An unresolved question. EBioMedicine. 2021;64:103215. doi: 10.1016/j.ebiom.2021.103215
  3. Kandhaya-Pillai R, Yang X, Tchkonia T, et al. TNF-α/IFN-γ synergy amplifies senescence-associated inflammation and SARS-COV-2 receptor expression via hyper-activated JAK/STAT1. Aging Cell. 2022;21(6):e13646. doi: 10.1111/acel.13646
  4. Xu SW, Ilyas I, Weng JP. Endothelial dysfunction in COVID-19: An overview of evidence, biomarkers, mechanisms and potential therapies. Acta Pharmacol Sin. 2023;44(4):695-709. doi: 10.1038/s41401-022-00998-0
  5. Scioli MG, Storti G, D'Amico F, et al. Oxidative stress and new pathogenetic mechanisms in endothelial dysfunction: Potential diagnostic biomarkers and therapeutic targets. J Clin Med. 2020;9(6):1995. doi: 10.3390/jcm9061995
  6. Tarnawski AS, Ahluwalia A. Endothelial cells and blood vessels are major targets for COVID-19-induced tissue injury and spreading to various organs. World J Gastroenterol. 2022 Jan 21;28(3):275-289. doi: 10.3748/wjg.v28.i3.275
  7. Sfera A, Osorio C, Zapata Martín Del Campo CM, et al. Endothelial senescence and chronic fatigue syndrome, a COVID-19 based hypothesis. Front Cell Neurosci. 2021;15:673217. doi: 10.3389/fncel.2021.673217
  8. Iba T, Connors JM, Levy JH. The coagulopathy, endotheliopathy, and vasculitis of COVID-19. Inflamm Res. 2020;69(12):1181-9. doi: 10.1007/s00011-020-01401-6
  9. Janaszak-Jasiecka A, Siekierzycka A, Płoska A, et al. Endothelial dysfunction driven by hypoxia – the influence of oxygen deficiency on NO bioavailability. Biomolecules. 2021;11(7):982. doi: 10.3390/biom11070982
  10. Xu S, Ilyas I, Little PJ, et al. Endothelial dysfunction in atherosclerotic cardiovascular diseases and beyond: From mechanism to pharmacotherapies. Pharmacol Rev. 2021;73(3):924-67. doi: 10.1124/pharmrev.120.000096
  11. Fodor A, Tiperciuc B, Login C, et al. 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
  12. Montiel V, Lobysheva I, Gérard L, et al. Oxidative stress-induced endothelial dysfunction and decreased vascular nitric oxide in COVID-19 patients. EBioMedicine. 2022;77:103893. doi: 10.1016/j.ebiom.2022.103893
  13. Alam MS, Czajkowsky DM. 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
  14. Veenith T, Martin H, Le Breuilly M, et al. High generation of reactive oxygen species from neutrophils in patients with severe COVID-19. Sci Rep. 2022;12(1):10484. doi: 10.1038/s41598-022-13825-7
  15. Tong M, Jiang Y, Xia D, et al. Elevated expression of serum endothelial cell adhesion molecules in COVID-19 patients. J Infect Dis. 2020;222(6):894-8. doi: 10.1093/infdis/jiaa349
  16. Chang R, Mamun A, Dominic A, Le NT. SARS-CoV-2 mediated endothelial dysfunction: The potential role of chronic oxidative stress. Front Physiol. 2021;11:605908. doi: 10.3389/fphys.2020.605908
  17. Jahani M, Dokaneheifard S, Mansouri K. Hypoxia: A key feature of COVID-19 launching activation of HIF-1 and cytokine storm. J Inflamm (Lond). 2020;17:33. doi: 10.1186/s12950-020-00263-3
  18. Abbasifard M, Khorramdelazad H. The bio-mission of interleukin-6 in the pathogenesis of COVID-19: A brief look at potential therapeutic tactics. Life Sci. 2020;257:118097. doi: 10.1016/j.lfs.2020.118097
  19. Desai TR, Leeper NJ, Hynes KL, Gewertz BL. Interleukin-6 causes endothelial barrier dysfunction via the protein kinase C pathway. J Surg Res. 2002;104(2):118-23. doi: 10.1006/jsre.2002.6415
  20. Didion S. Cellular and oxidative mechanisms associated with interleukin-6 signaling in the vasculature. Int J Mol Sci. 2017;18(12):2563. doi: 10.3390/ijms18122563
  21. Kang S, Kishimoto T. Interplay between interleukin-6 signaling and the vascular endothelium in cytokine storms. Exp Mol Med. 2021;53(7):1116-23. doi: 10.1038/s12276-021-00649-0
  22. Potje SR, Costa TJ, Fraga-Silva TFC, et al. Heparin prevents in vitro glycocalyx shedding induced by plasma from COVID-19 patients. Life Sci. 2021;276:119376. doi: 10.1016/j.lfs.2021.119376
  23. Du Preez HN, Aldous C, Hayden MR, et al. Pathogenesis of COVID-19 described through the lens of an undersulfated and degraded epithelial and endothelial glycocalyx. FASEB J. 2022;36(1):e22052. doi: 10.1096/fj.202101100RR
  24. Targosz-Korecka M, Kubisiak A, Kloska D, et al. Endothelial glycocalyx shields the interaction of SARS-CoV-2 spike protein with ACE2 receptors. Sci Rep. 2021;11(1):12157. doi: 10.1038/s41598-021-91231-1
  25. Stahl K, Gronski PA, Kiyan Y, et al. Injury to the endothelial glycocalyx in critically ill patients with COVID-19. Am J Respir Crit Care Med. 2020;202(8):1178-81. doi: 10.1164/rccm.202007-2676LE
  26. Vollenberg R, Tepasse P-R, Ochs K, et al. Indications of persistent glycocalyx damage in convalescent COVID-19 patients: A prospective multicenter study and hypothesis. Viruses. 2021;13(11):2324. doi: 10.3390/v13112324
  27. Зарубина И.В. Современные представления о патогенезе гипоксии и ее фармакологической коррекции. Обзоры по клинической фармакологии и лекарственной терапии. 2011;9(3):31-48 [Zarubina IV. Modern view on pathogenesis of hypoxia and its pharmacological corection. Obzory po Klinicheskoi Farmakologii i Lekarstvennoi Terapii. 2011;9(3):31-48 (In Russian)].
  28. Тихонова Е.О., Ляпина Е.П., Шульдяков А.А., Сатарова С.А. Использование препаратов, содержащих сукцинат, в клинике инфекционных болезней. Терапевтический архив. 2016;11:121-7 [Tihonova EO, Lyapina EP, Shul’dyakov AA, Satarova SA. Use of succinate-containing agents in the treatment of infectious diseases. Terapevticheskii Arkhiv. 2016;11:121-7 (In Russian)]. doi: 10.17116/terarkh20168811121-127
  29. Евглевский А.А., Рыжкова Г.Ф., Евглевская Е.П., и др. Биологическая роль и метаболическая активность янтарной кислоты. Вестник Курской государственной сельскохозяйственной академии. 2013;9:67-9 [Evglevskii AA, Ryzhkova GF, Evglevskaia EP, et al. Biologicheskaia rol' i metabolicheskaia aktivnost' iantarnoi kisloty. Vestnik Kurskoi Gosudarstvennoi Sel'skokhoziaistvennoi Akademii. 2013;9:67-9 (In Russian)].
  30. Оковитый С.В., Заплутанов В.А., Смагина А.Н., Суханов Д.С. Антигипоксанты в современной клинической практике. Клиническая медицина. 2012;9:63-8 [Okovity SV, Sukhanov DS, Zaplutanov VA, Smagina АN. Antihypoxants in current clinical practice. Klinicheskaia Meditsina. 2012;9:63-8 (In Russian)].
  31. Голубев Р.В., Смирнов А.В. Расширение представлений о механизмах действия сукцинатсодержащих диализирующих растворов. Нефрология. 2017;21(1):19-24 [Golubev RV, Smirnov AV. Expanding the frontiers of succinate-containing dialysate’s effects. Nephrology (Saint-Petersburg). 2017;21(1):19-24 (In Russian)]. doi: 10.24884/1561-6274-2017-21-1-19-24
  32. Новиков В.Е., Левченкова О.С. Новые направления поиска лекарственных средств с антигипоксической активностью и мишени для их действия. Экспериментальная и клиническая фармакология. 2013;76(5):37-47 [Novikov VE, Levchenkova OS. Promising directions of search for antihypoxants and targets of their action. Eksperimental'naia i Klinicheskaia Farmakologiia. 2013;76(5):37-47 (In Russian)].
  33. Скрипченко Н.В., Егорова Е.С. Применение цитофлавина в комплексной терапии нейроинфекций у детей. Журнал неврологии и психиатрии им. С.С. Корсакова. 2011;111(9):28-31 [Skripchenko NV, Egorova ES. Cytoflavin in the complex treatment of neuroinfections in children. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2011;111(9):28-31 (In Russian)].
  34. Semenza GL. Hypoxia-inducible factor 1 and cardiovascular disease. Annu Rev Physiol. 2014;76:39-56. doi: 10.1146/annurev-physiol-021113-170322
  35. Карташова Е.А., Сарвилина И.В. Влияние Цитофлавина на молекулярные механизмы ремоделирования миокарда и сосудистой стенки у пациентов с систолической артериальной гипертензией. Кардиология и сердечно-сосудистая хирургия. 2018;11(5):40 6 [Kartashova EA, Sarvilina IV. The influence of Cytoflavin on molecular mechanisms of myocardial and vascular wall remodeling in patients with sistolic arterial hypertension. Kardiologiya i Serdechno-Sosudistaya Khirurgiya. 2018;11(5):40 6 (In Russian)]. doi: 10.17116/kardio20181105140
  36. Малишевская Т.Н., Киселева Т.Н., Филиппова Ю.Е., и др. Состояние антиоксидантного статуса и липидного спектра крови у пациентов с разными вариантами течения первичной открытоугольной глаукомы. Офтальмология. 2020;17(4):761-70 [Malishevskaya TN, Kiseleva TN, Filippova YuE, et al. Аntioxidant Status and Lipid Metabolism in Patients with Different Forms of Primary Open-Angle Glaucoma Progression. Ophthalmology in Russia. 2020;17(4):761-70 (In Russian)]. doi: 10.18008/1816-5095-2020-4-761-770
  37. Белова Л.А., Машин В.В., Колотик-Каменева О.Ю., и др. Влияние терапии препаратом цитофлавин на состояние церебральной гемодинамики при различных стадиях гипертонической болезни. Журнал неврологии и психиатрии им. С.С. Корсакова. 2017;117(7):28 35 [Belova LA, Mashin VV, Kolotik-Kameneva OIu, et al. The influence of Cytoflavin therapy on the cerebral hemodynamics in patients with various stages of hypertensive disease. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2017;117(7):28 35 (In Russian)]. doi: 10.17116/jnevro20171177128-35
  38. Скрипко В.Д., Чурпий И.К., Михайлойко И.Я., и др. Включение Цитофлавина в комлексном лечении синдрома диабетической стопы с признаками медиакальциноза сосудов нижних конечностей. Хирургия. Журнал им. Н.И. Пирогова. 2018;(10):69 72 [Skripko VD, Churpiy IK, Mykhailoiko IYa, et al. Cytophlavin inclusion in complex treatment of diabetic foot syndrome with signs of lower limb blood vessels medicalcinosis. Pirogov Russian Journal of Surgery = Khirurgiya. Zurnal im. N.I. Pirogova. 2018;(10):69 72 (In Russian)]. doi: 10.17116/hirurgia201810169
  39. Михайлова Е.В., Чудакова Т.К. Грипп у детей. Гематологические показатели интоксикации, детоксикационная терапия. Экспериментальная и клиническая фармакология. 2015;78(5):33-6 [Mikhailova EV, Chudakova TK. Influenza in children: hematological indices of intoxication and detoxification therapy. Eksperimental'naia i Klinicheskaia Farmakologiia. 2015;78(5):33-6 (In Russian)]. doi: 10.30906/0869-2092-2015-78-5-33-36
  40. Орлов Ю.П., Говорова Н.В., Корпачева О.В., и др. О возможности использования препаратов группы сукцинатов в условиях гипоксии при COVID-19. Общая реаниматология. 2021;17(3):78-98 [Orlov YuP, Govorova NV, Korpacheva OV, et al. On the possibility of using succinate in hypoxia developing in COVID-19. General Reanimatology. 2021;17(3):78-98 (In Russian)]. doi: 10.15360/1813-9779-2021-3-78-98
  41. Шаповалов К.Г., Цыденпилов Г.А., Лукьянов С.А., и др. Перспективы применения сукцинатов при тяжелом течении новой коронавирусной инфекции. Экспериментальная и клиническая фармакология. 2020;83:40-3 [Shapovalov KG, Cydenpilov GA, Luk'yanov SA, et al. Prospects for the use of succinates in treating severe course of new coronavirus infection. Eksperimental'naia i Klinicheskaia Farmakologiia. 2020;83:40-3 (In Russian)] doi: 10.30906/0869-2092-2020-83-10-40-43
  42. Орлов Ю.П. Митохондриальная дисфункция как проблема критических состояний. Роль сукцинатов. миф или реальность завтрашнего дня? Антибиотики и химиотерапия. 2019;64(7-8):63-8 [Orlov YuP. Mitochondrial dysfunction as a problem of critical conditions. The role of succinates, myth or reality of tomorrow? Antibiotiki i Khimioterapiya. 2019;64(7-8):63-8 (In Russian)]. doi: 10.24411/0235-2990-2019-10046
  43. Екушева Е.В., Войтенков В.Б., Ризаханова О.А. Эффективность применения Цитофлавина в комплексной терапии пациентов с COVID-19. Журнал неврологии и психиатрии им. С.С. Корсакова. 2021;121(12):33 39 [Ekusheva EV, Voitenkov VB, Rizakhanova OA. The effectiveness of cytoflavin in complex therapy of patients with the coronavirus infection COVID-19. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2021;121(12):33 9 (In Russian)]. doi: 10.17116/jnevro202112112133
  44. Путилина М.В., Теплова Н.В., Баирова К.И., и др. Эффективность и безопасность Цитофлавина при реабилитации больных с постковидным синдромом: результаты проспективного рандомизированного исследования ЦИТАДЕЛЬ. Журнал неврологии и психиатрии им. С.С. Корсакова. 2021;121(10):45 51 [Putilina MV, Teplova NV, Bairova KI, et al. The result of prospective randomized study CITADEL – the efficacy and safety of drug cytoflavin in postcovid rehabilitation. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2021;121(10):45 51. (In Russian)]. doi: 10.17116/jnevro202112110145
  45. Филиппова Н.В., Шульдяков А.А., Еремин В.И., Барыльник Ю.Б., Рамазанова К.Х., Смагина А.Н., Шешина Н.А., Жук А.А. Реабилитация пациентов, перенесших COVID-19 с легкими (додементными) когнитивными расстройствами. Современные проблемы науки и образования. 2023;2 [Filippova NV, SHul’dyakov AA, Eremin VI, et al. Rehabilitation of COVID-19 patients with mild (pre-dement) cognitive disorders. Modern Problems of Science and Education. 2023;2 (In Russian)]. doi: 10.17513/spno.32564
  46. Симутис И.С., Бояринов Г.А., Юрьев М.Ю., и др. Возможности коррекции гипервоспаления при COVID-19. Антибиотики и химиотерапия. 2021;66(3-4):40-8 [Simutis IS, Boyarinov GA, Yuriev MYu, et al. Possibilities of hyperinflammation correction in COVID-19. Antibiot i Khimioter. 2021;66(3-4):40-8 (In Russian)]. doi: 10.24411/0235-2990-2021-66-3-4-40-48

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