Ukrainian Journal of Perinatology and Pediatrics. 2023. 1(93): 118-122; doi 10.15574/PP.2023.93.118
Matviyenko I. M., Ignatova T. B.
SI «Institute of Pediatrics, Obstetrics and Gynecology named after academician O.M. Lukyanova of the NAMS of Ukraine», Kyiv

For citation: Matviyenko IM, Ignatova TB. (2023). Long-term consequences of the coronavirus infection: review of scientific sources. Ukrainian Journal of Perinatology and Pediatrics. 1(93): 118-122; doi 10.15574/PP.2023.93.118.
Article received: Jan 09, 2023. Accepted for publication: Mar 13, 2023.

Data on the disease of COVID-19, given in the open literature sources, shows the presence of long-term consequences after this infection, especially in cohorts of patients with chronic pathology. More and more published data indicates that long-term clinical symptoms are also observed in cohorts of children.
Purpose – to study the disorders of endothelial function in patients after COVID-19 based on the analysis of data from current clinical studies
Thus, according to the results of the CLoCk study, it was found that among children infected with SARS-CoV-2, 52.2% reported about one or more symptoms after 4 weeks, and 37.7% observed at least one symptom for 12 weeks or longer. At the same time, fatigue and headache were most common symptoms among children after three months after coronavirus infection. Older children (12-17 years old) showed such symptoms as «brain fog» (11.3% – cognitive dysfunction, problems with memory and concentration) and bad mood (15.6%). Official data from the UK Office for National Statistics show that 9.8% of children aged 2-11 and 13.0% aged 12-16 had at least 1 symptom that lasted for 5 weeks after COVID-19.
Conclusions. The results of current clinical trials show endothelial dysfunction as the consequences of infection, which arises as a result of direct coronavirus invasion, and could be the basis of microvascular damage and microcirculatory thrombosis, which leads to the development of systemic manifestations and long term consequences, regardless of age.
No conflict of interests was declared by the authors.
Keywords: endothelial disfunction, disorders of endothelial function, complication, coronavirus infection, COVID-19, SARS-COV-2.
REFERENCES

1. Ahmed S, Zimba O, Gasparyan AY. (2020, Jul 11). Thrombosis in Coronavirus disease 2019 (COVID-19) through the prism of Virchow's triad. Clinical Rheumatology. 39: 2529-2543. https://doi.org/10.1007/s10067-020-05275-1; PMid:32654082 PMCid:PMC7353835

2. Alharthy A, Faqihi F, Memish ZA, Karakitsos D. (2020). Fragile Endothelium and Brain Dysregulated Neurochemical Activity in COVID-19. ACS Chemical Neuroscience. 11 (15): 2159-2162. https://doi.org/10.1021/acschemneuro.0c00437; PMid:32786343 PMCid:PMC7393674

3. Berg SK, Palm P, Nygaard U et al. (2022). Long COVID symptoms in SARS-CoV-2-positive children aged 0-14 years and matched controls in Denmark (LongCOVIDKidsDK): a national, cross-sectional study. Lancet Child Adolesc Health. 6 (4): 240-248. https://doi.org/10.1016/S2352-4642(22)00004-9; PMid:35143771

4. Bi X, Su Z, Yan H et al. (2020). Prediction of severe illness due to COVID-19 based on an analysis of initial fibrinogen to albumin ratio and platelet count. Platelets. 31; 5: 1-6. https://doi.org/10.1080/09537104.2020.1760230; PMid:32367765 PMCid:PMC7212543

5. Bonetti PO, Pumper GM et al. (2004). Noninvasive Identification of Patients With Early Coronary Atherosclerosis by Assessment of Digital Reactive Hyperemia. Journal of the American College of Cardiology. 44: 11. https://doi.org/10.1016/j.jacc.2004.08.062; PMid:15582310

6. Bradley VC, Kuriwaki S, Isakov M et al. (2020). Unrepresentative big surveys significantly overestimate US vaccine uptake. Nature. 600: 695-700. https://doi.org/10.1038/s41586-021-04198-4; PMid:34880504 PMCid:PMC8653636

7. CDC. (2021). Multisystem inflammatory syndrome (MIS-C). Information for Pediatric Healthcare Providers. (last accessed 25.06.2021). URL: https://www.cdc.gov/mis/index.html.

8. Colantuoni A, Martini R, Caprari P et al. (2020). COVID-19 Sepsis and Microcirculation Dysfunction Front. Physiol. 11: 747. https://doi.org/10.3389/fphys.2020.00747; PMid:32676039 PMCid:PMC7333313

9. Data and analysis from Census 2021. (2021). COVID-19 Schools Infection Survey, England: Prevalence of ongoing symptoms following coronavirus (COVID-19) infection in school pupils and staff: July 2021. Statistical bulletin. URL: https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/bulletins/covid19schoolsinfectionsurveyenglandprevalenceofongoingsymptomsfollowingcoronaviruscovid19infectioninschoolpupilsan dstaff/july2021 (last accessed 28.09.2021).

10. Davies P, Evans C, Kanthimathinathan HK et al. (2020). Intensive care admissions of children with paediatric inflammatory multisystem syndrome temporally associated with SARS- CoV-2 (PIMS-TS) in the UK: a multicentre observational study. Lancet Child Adolesc Health. 4 (9): 669-677. https://doi.org/10.1016/S2352-4642(20)30215-7; PMid:32653054

11. De Andrade SA, de Souza DA, Torres AL et al. (2022). Pathophysiology of COVID-19: Critical Role of Hemostasis Front. Cell. Infect. Microbiol, Sec. Clinical Microbiology. 12: 896972. https://doi.org/10.3389/fcimb.2022.896972; PMid:35719336 PMCid:PMC9205169

12. Del Turco S, Vianello A, Ragusa R et al. (2020). COVID-19 and cardiovascular consequences: Is the endothelial dysfunction the hardest challenge? Thromb. Res. 196: 143-151. https://doi.org/10.1016/j.thromres.2020.08.039; PMid:32871306 PMCid:PMC7451195

13. Endemann DH, Schiffrin EL. (2004). Endothelial dysfunction. Journal of the American Society of Nephrology. 15 (8): 1983-1992. https://doi.org/10.1097/01.ASN.0000132474.50966.DA; PMid:15284284

14. Fraga-Silva RA, Pinheiro SVB, Gonçalves ACC et al. (2008). The antithrombotic effect of angiotensin-(1-7) involves mas-mediated NO release from platelets. Mol Med. 14: 28-35. https://doi.org/10.2119/2007-00073.Fraga-Silva; PMid:18026570 PMCid:PMC2078558

15. Gao Y-P, Zhou W, Huang P-N et al. (2022). Persistent Endothelial Dysfunction in Coronavirus Disease-2019 Survivors Late After Recovery. Front. Med. 9: 809033. https://doi.org/10.3389/fmed.2022.809033; PMid:35237624 PMCid:PMC8882598

16. Gewaltig MT, Kojda G. (2002). Vasoprotection by nitric oxide: mechanisms and therapeutic potential. Cardiovasc Res. 55 (2): 250-260. https://doi.org/10.1016/S0008-6363(02)00327-9; PMid:12123764

17. Gustafson D, Raju S, Wu R et al. (2020). Overcoming barriers: The endothelium as a linchpin of coronavirus disease 2019 pathogenesis? Arteriosclerosis, Thrombosis, and Vascular Biology. 40 (8): 1818-1829. https://doi.org/10.1161/ATVBAHA.120.314558; PMid:32510978 PMCid:PMC7370857

18.Han H, Yang L, Liu R et al. (2020). Prominent changes in blood coagulation of patients with SARS-CoV-2 infection. Clin Chem Lab Med. 58: 1116-1120. https://doi.org/10.1515/cclm-2020-0188; PMid:32172226

19. Horodkova YuV, Kurochkin MIu, Davydova AH, Podlianova OI. (2022). Klinichni proiavy urazhennia sertsevo-sudynnoi systemy u ditei yak naslidok perenesenoi koronavirusnoi khvoroby (COVID-19) (klinichnyi vypadok). Zaporizkyi medychnyi zhurnal. 3 (132): 375-380. https://doi.org/10.14739/2310-1210.2022.3.251076

20. Jung F, Krüger-Genge A, Franke RP et al. (2020). COVID-19 and the endothelium. Clin. Hemorheol. Microcirc. 75 (1): 7-11. https://doi.org/10.3233/CH-209007; PMid:32568187 PMCid:PMC7458498

21. Kholboiev SB, Yusupov ShA, Yuldashova NE. (2021). Rezultaty sposterezhennia za osobamy, yaki perenesly COVID-19, na pervynnii lantsi okhorony zdorov'ia. Infektsiini khvoroby. 1 (103): 18-22. https://doi.org/10.11603/1681-2727.2021.1.11948

22. Kovalenko SV. (2020). Dosvid zastosuvannia metodiv syndromno-patohenetychnoi terapii pry pnevmonii, sprychynenii COVID-19, v umovakh pulmonolohichnoho viddilennia. Medychna hazeta «Zdorov'ia Ukrainy 21 storichchia». 13-14: 481-482.

23. Koyama Y. (2013). Endothelin systems in the brain: Involvement in pathophysiological responses of damaged nerve tissues. Biomolecular Concepts. 4 (4): 335-347. https://doi.org/10.1515/bmc-2013-0004; PMid:25436584

24. Lapi D, Stornaiuolo M, Sabatino L et al. (2020). The pomace extract taurisolo protects rat brain from ischemia-reperfusion injury. Front. Cell. Neurosci. 14: 3. https://doi.org/10.3389/fncel.2020.00003; PMid:32063837 PMCid:PMC6997812

25. Lytvyn HO, Stasiv MV. (2022). Pandemiia COVID-19 tryvalistiu u dva roky: problemni pytannia pediatrii ta shliakhy yikh vyrishennia. Infektsiini khvoroby. 108: 58-72.

26. Magro C, Mulvey JJ, Berlin D, Nuovo G, Salvatore S, Harp J, Baxter-Stoltzfus A, Laurence J. (2020). Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: a report of five cases. Transl Res. 220: 1-13. https://doi.org/10.1016/j.trsl.2020.04.007; PMid:32299776 PMCid:PMC7158248

27. Maier CL, Truong AD, Auld SC et al. (2020). COVID-19-associated hyperviscosity: a link between inflammation and thrombophilia? Lancet. 395 (10239): 1758-1759. https://doi.org/10.1016/S0140-6736(20)31209-5; PMid:32464112

28. Marchetti M. (2020). COVID-19-driven endothelial damage: complement, HIF-1, and ABL2 are potential pathways of damage and targets for cure. Ann. Hematol. 99: 1701-1707. https://doi.org/10.1007/s00277-020-04138-8; PMid:32583086 PMCid:PMC7312112

29. Marder W, Khalatbari S, Myles JD et al. (2011, Sep). Interleukin 17 as a novel predictor of vascular function in rheumatoid arthritis. Ann Rheum Dis. 70 (9): 1550-1555. https://doi.org/10.1136/ard.2010.148031; PMid:21727237 PMCid:PMC3151670

30. McGonagle D, O'Donnell JS, Sharif K et al. (2020). Immunemechanisms of pulmonary intravascular coagulopathy in COVID-19 pneumonia. Lancet Rheumatol. 2: e437-e445. https://doi.org/10.1016/S2665-9913(20)30121-1; PMid:32835247

31. McGonagle D, Sharif K, O'Regan A, Bridgewood C. (2020). The role of cytokines including Interleukin-6 in COVID-19 induced pneumonia and macrophage activation syndrome-like disease. Autoimmun Rev. 19 (6): 102537. https://doi.org/10.1016/j.autrev.2020.102537; PMid:32251717 PMCid:PMC7195002

32. Molteni E, Sudre CH, Canas LS et al. (2021). Illness duration and symptom profile in symptomatic UK school-aged children tested for SARS-CoV-2. Lancet Child Adolesc Health. 5: 708-718. https://doi.org/10.1016/S2352-4642(21)00198-X; PMid:34358472

33. Osmanov IM, Spiridonova E, Bobkova P et al. (2021). Risk factors for long COVID in previously hospitalised children using the ISARIC Global follow-up protocol: A prospective cohort study. Eur Respir J. 59 (2): 2101341. https://doi.org/10.1183/13993003.01341-2021; PMid:34210789 PMCid:PMC8576804

34. Page AV, Liles WC. (2013). Biomarkers of endothelial activation/dysfunction in infectious diseases. Virulence. 4 (6): 507-516. https://doi.org/10.4161/viru.24530; PMid:23669075 PMCid:PMC5359744

35. Panigada M, Bottino N, Tagliabue P et al. (2020). Hypercoagulability of COVID-19 patients in intensive care unit: A report of thromboelastography findings and other parameters of hemostasis. JTH. 18 (7): 1738-1742. https://doi.org/10.1111/jth.14850; PMid:32302438 PMCid:PMC9906150

36. Pober JS, Sessa WC. (2007). Evolving functions of endothelial cells in inflammation. Nat Rev Immunol. 7: 803-815. https://doi.org/10.1038/nri2171; PMid:17893694

37. Pons S, Fodil S, Azoulay E, Zafrani L. (2020). The vascular endothelium: The cornerstone of organ dysfunction in severe SARS-CoV-2 infection. Critical Care. 24 (353): 1-8. https://doi.org/10.1186/s13054-020-03062-7; PMid:32546188 PMCid:PMC7296907

38. Rajendran P, Rengarajan T, Thangavel J et al. (2013). The vascular endothelium and human diseases. Int. J. Biol. Sci. 9 (10): 1057-1069. https://doi.org/10.7150/ijbs.7502; PMid:24250251 PMCid:PMC3831119

39. Ranucci M, Ballotta A, Di Dedda U et al. (2020). The procoagulant pattern of patients with COVID-19 acute respiratory distress syndrome. J Thromb Haemost. 18 (7): 1747-1751. https://doi.org/10.1111/jth.14854; PMid:32302448 PMCid:PMC9906332

40. Risitano AM, Mastellos DC, Huber-Lang M et al. (2020). Complement as a target in COVID-19? Nat Rev Immunol.20:343-344. https://doi.org/10.1038/s41577-020-0320-7; PMid:32327719 PMCid:PMC7187144

41. Sagaydachniy АА. (2018, Sep). Reactive hyperemia test: methods of analysis, mechanisms of reaction and prospects. Regional Blood Circulation and Microcirculation. 3: 5-22. https://doi.org/10.24884/1682-6655-2018-17-3-5-22

42. Stephenson T, Shafran R, De Stavola B et al. (2021). Long COVID and the mental and physical health of children and young people: national matched cohort study protocol (the CLoCk study). BMJ Open. 11 (8): e052838. https://doi.org/10.1136/bmjopen-2021-052838; PMid:34446502 PMCid:PMC8392739

43. Urano T, Suzuki Y. (2012). Accelerated fibrinolysis and its propagation on vascular endothelial cells by secreted and retained tPA. J Biomed Biotechnol: 208108. https://doi.org/10.1155/2012/208108; PMid:23118500 PMCid:PMC3478939

44. Varga Z, Flammer A, Steiger P et al. (2020). Endothelial cell infection and endotheliitis in COVID-19. The Lancet. 395 (2): 1417-1418. https://doi.org/10.1016/S0140-6736(20)30937-5; PMid:32325026

45. Wright FL, Vogler TO, Moore EE et al. (2020). Fibrinolysis shutdowncorrelates to thromboembolic events in severe COVID-19 infection. J Am Coll Surg. https://doi.org/10.1016/j.jamcollsurg.2020.05.007; PMid:32422349 PMCid:PMC7227511