nmpЖурнал им. Н.В. Склифосовского «Неотложная медицинская помощь»Russian Sklifosovsky Journal "Emergency Medical Care"2223-90222541-8017“N.V. Sklifosovsky Research Institute for Emergency Medicine”10.23934/2223-9022-2021-10-2-248-258nmp-1152Research ArticleНОВОЕ О COVID-19NEW ABOUT COVID-19COVID-19 и сердечно-сосудистая система. Часть II. Постковидный синдромCOVID-19 and Cardiovascular System. Part II. Post-COVID Syndromehttps://orcid.org/0000-0002-9738-1801ИванниковА. А.IvannikovA. A.

клинический ординатор по специальности «кардиология», 

129090, Москва, Б. Сухаревская пл., д. 3

Cardiology Clinical Resident,

3 B. Sukharevskaya square, Moscow, 129090

ivannikov_a95@mail.ruhttps://orcid.org/0000-0002-4940-9574ЭсауленкоА. Н.EsaulenkoA. N.

клинический ординатор по специальности «кардиология», 

129090, Москва, Б. Сухаревская пл., д. 3

Cardiology Clinical Resident, 

3 B. Sukharevskaya square, Moscow, 129090

aesaulenko95@mail.ruhttps://orcid.org/0000-0002-4831-7977ВасильченкоМ. К.VasilchenkoM. K.

клинический ординатор по специальности «кардиология»,

129090, Москва, Б. Сухаревская пл., д. 3

Cardiology Clinical Resident,

3 B. Sukharevskaya square, Moscow, 129090

maryvasil25@mail.ruhttps://orcid.org/0000-0002-6229-8629АлиджановаХ. Г.AlidzhanovaKh. G.

доктор медицинских наук, старший преподаватель учебного центра,

129090, Москва, Б. Сухаревская пл., д. 3

Doctor of Medical Sciences, Senior Lecturer,

3 B. Sukharevskaya square, Moscow, 129090

doctorhafiza@mail.ruhttps://orcid.org/0000-0003-3292-8789ПетриковС. С.PetrikovS. S.

член-корреспондент РАН, доктор медицинских наук, директор,

129090, Москва, Б. Сухаревская пл., д. 3

Сorresponding Member of RAS, Doctor of Medical Sciences, Director,

3 B. Sukharevskaya square, Moscow, 129090

petrikovss@sklif.mos.ruГБУЗ «Научно-исследовательский институт скорой помощи им. Н.В. Склифосовского ДЗМ», Учебный центрРоссияN.V. Sklifosovsky Research Institute for Emergency Medicine of the Moscow Healthcare Department, Training centerRussian Federation202120082021102248258Copyright © Иванников А.А., Эсауленко А.Н., Васильченко М.К., Алиджанова Х.Г., Петриков С.С., 20212021Иванников А.А., Эсауленко А.Н., Васильченко М.К., Алиджанова Х.Г., Петриков С.С.Ivannikov A.A., Esaulenko A.N., Vasilchenko M.K., Alidzhanova K.G., Petrikov S.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.jnmp.ru/jour/article/view/1152

Долгосрочный прогноз состояния пациентов, перенесших COVID-19, остается до конца не изученным. Рассмотрены данные о распространенности постковидного синдрома (ПКС), основных симптомах, особенностях течения, а также механизмах его развития и связь с коморбидностью. Поражение легких, сердца, мозга и других систем требует мультидисциплинарного ведения пациентов с ПКС. 

ong-term consequences of COVID-19 remain the subject of active research interest. In this article the Post-COVID-19 syndrome (PCS) main features and symptoms are considered, its incidence and link with comorbidity is presented and the possible mechanisms are discussed. Due to the damage COVID-19 has on lungs, heart, brain and other systems, patients with PCS require multidisciplinary management. 

COVID-19постковидный синдромкоморбидностьCOVID-19postcovid syndromecomorbidityReferencesNIHR Themed Review: Living with Covid19. October 2020. Available at: https://evidence.nihr.ac.uk/themedreview/living-with-covid19/ [Accessed April 08, 2021] https://doi.org/10.3310/themedreview_41169NIHR Themed Review: Living with Covid19. October 2020. Available at: https://evidence.nihr.ac.uk/themedreview/living-with-covid19/ [Accessed Apr 08, 2021] https://doi.org/10.3310/themedreview_41169O’Sullivan O. Long-term sequelae following previous coronavirus epidemics. Clin Med (Lond). 2021;21(1):e68–e70. PMID: 33144403 https://doi.org/10.7861/clinmed.2020-0204O’Sullivan O. Long-term sequelae following previous coronavirus epidemics. Clin Med (Lond). 2021;21(1):e68–e70. PMID: 33144403 https://doi.org/10.7861/clinmed.2020-0204Ahmed H, Patel K, Greenwood DC, Halpin S, Lewthwaite P, Salawu A, et al. Long-term clinical outcomes in survivors of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronavirus outbreaks after hospitalisation or ICU admission: a systematic review and meta-analysis. J Rehabil Med. 2020;52(5): jrm00063. PMID: 32449782 https://doi.org/10.2340/16501977-2694Ahmed H, Patel K, Greenwood DC, Halpin S, Lewthwaite P, Salawu A, et al. Long-term clinical outcomes in survivors of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronavirus outbreaks after hospitalisation or ICU admission: a systematic review and meta-analysis. J Rehabil Med. 2020;52(5): jrm00063. PMID: 32449782 https://doi.org/10.2340/16501977-2694Iqbal A, Iqbal K, Arshad Ali S, Azim D, Farid E, Baig MD, et al. The COVID-19 Sequelae: A Cross-Sectional Evaluation of Post-recovery Symptoms and the Need for Rehabilitation of COVID-19 Survivors. Cureus. 2021;13(2):e13080. PMID: 33680620 https://doi.org/10.7759/cureus.13080Iqbal A, Iqbal K, Arshad Ali S, Azim D, Farid E, Baig MD, et al. The COVID-19 Sequelae: A Cross-Sectional Evaluation of Post-recovery Symptoms and the Need for Rehabilitation of COVID-19 Survivors. Cureus. 2021;13(2):e13080. PMID: 33680620 https://doi.org/10.7759/cureus.13080Raveendran AV. Long COVID-19: Challenges in the diagnosis and proposed diagnostic criteria. Diabetes Metab Syndr. 2021;15(1):145– 146. PMID: 33341598 https://doi.org/10.1016/j.dsx.2020.12.025Raveendran AV. Long COVID-19: Challenges in the diagnosis and proposed diagnostic criteria. Diabetes Metab Syndr. 2021;15(1):145– 146. PMID: 33341598 https://doi.org/10.1016/j.dsx.2020.12.025Sonnweber T, Sahanic S, Pizzini A, Luger A, Schwabl C, Sonnweber B, et al. Cardiopulmonary recovery after COVID-19 – an observational prospective multi-center trial. Eur Respir J. 2020 Dec 10:2003481. PMID: 33303539 https://doi.org/10.1183/13993003.03481-2020 Online ahead of printSonnweber T, Sahanic S, Pizzini A, Luger A, Schwabl C, Sonnweber B, et al. Cardiopulmonary recovery after COVID-19–an observational prospective multi-center trial. Eur Respir J. 2020 Dec 10:2003481. PMID: 33303539 https://doi.org/10.1183/13993003.03481-2020 Online ahead of printMoreno-Pérez O, Merino E, Leon-Ramirez JM, Andres M, Ramos JM, Arenas-Jiménez J, et al. Post-acute COVID-19 syndrome. Incidence and risk factors: A Mediterranean cohort study. J Infect. 2021;82(3):378–383. PMID: 33450302 https://doi.org/10.1016/j.jinf.2021.01.004Moreno-Pérez O, Merino E, Leon-Ramirez JM, Andres M, Ramos JM, Arenas-Jiménez J, et al. Post-acute COVID-19 syndrome. Incidence and risk factors: A Mediterranean cohort study. J Infect. 2021;82(3):378–383. PMID: 33450302 https://doi.org/10.1016/j.jinf.2021.01.004Carfì A, Bernabei R, Landi F, Gemelli Against COVID-19 Post-Acute Care Study Group. Persistent symptoms in patients after acute Covid-19. JAMA. 2020;324(6):603–605. PMID: 32644129 https://doi.org/10.1001/jama.2020.12603Carfì A, Bernabei R, Landi F, Gemelli Against COVID-19 Post-Acute Care Study Group. Persistent symptoms in patients after acute COVID-19. JAMA. 2020;324(6):603–605. PMID: 32644129 https://doi.org/10.1001/jama.2020.12603Oronsky B, Larson C, Hammond TC, Oronsky A, Kesari S, Lybeck M, et al. A Review of Persistent Post-COVID Syndrome (PPCS). Clin Rev Allergy Immunol. 2021 Feb 20:1–9. PMID: 33609255 https://doi.org/10.1007/ s12016-021-08848-3 Online ahead of print.Oronsky B, Larson C, Hammond TC, Oronsky A, Kesari S, Lybeck M, et al. A Review of Persistent Post-COVID Syndrome (PPCS). Clin Rev Allergy Immunol. 2021 Feb 20:1–9. PMID: 33609255 https://doi.org/10.1007/s12016-021-08848-3 Online ahead of print.Wang F, Kream RM, Stefano GB. Long-term respiratory and neurological sequelae of COVID-19. Med Sci Monit. 2020;26:e928996. PMID: 33177481 https://doi.org/10.12659/MSM.928996Wang F, Kream RM, Stefano GB. Long-term respiratory and neurological sequelae of COVID-19. Med Sci Monit. 2020;26:e928996. PMID: 33177481 https://doi.org/10.12659/MSM.928996Mendelson M, Nel J, Blumberg L, Madhi SA, Dryden M, Stevens W, et al. Long-COVID: An evolving problem with an extensive impact. S Afr Med J. 2020;111(1):10–12. PMID: 33403997 https://doi.org/10.7196/ SAMJ.2020.v111i11.15433Mendelson M, Nel J, Blumberg L, Madhi SA, Dryden M, Stevens W, et al. Long-COVID: An evolving problem with an extensive impact. S Afr Med J. 2020;111(1):10–12. PMID: 33403997 https://doi.org/10.7196/SAMJ.2020.v111i11.15433Venkatesan P. NICE guideline on long COVID. Lancet Respir Med. 2021;9(2):129. PMID: 33453162 https://doi.org/10.1016/S2213-2600(21)00031-XVenkatesan P. NICE guideline on long COVID. Lancet Respir Med. 2021;9(2):129. PMID: 33453162 https://doi.org/10.1016/S2213-2600(21)00031-XMahase E. Long covid could be four different syndromes, review suggests. BMJ. 2020;371:m3981. PMID: 33055076 https://doi.org/10.1136/bmj. m3981 14. Garg P, Arora U, Kumar A, Wig N. The “post-COVID” syndrome: how deep is the damage? J Med Virol. 2021;93(2):673–674. PMID: 32852801 https://doi.org/10.1002/jmv.26465Mahase E. Long covid could be four different syndromes, review suggests. BMJ. 2020;371:m3981. PMID: 33055076 https://doi.org/10.1136/bmj.m3981Greenhalgh T, Knight M, A’Court C, Buxton M, Husain L. Management of post-acute Covid-19 in primary care. BMJ. 2020;370:m3026. PMID: 32784198 https://doi.org/10.1136/bmj.m3026Garg P, Arora U, Kumar A, Wig N. The “post-COVID” syndrome: how deep is the damage? J Med Virol. 2021;93(2):673–674. PMID: 32852801 https://doi.org/10.1002/jmv.26465Willi S, Lüthold R, Hunt A, Hänggi NV, Sejdiu D, Scaff C, et al. COVID19 Sequelae in adults aged less than 50 years: A Systematic Review. Travel Med Infect Dis. 2021;40:101995. PMID: 33631340 https://doi.org/10.1016/j.tmaid.2021.101995Greenhalgh T, Knight M, A’Court C, Buxton M, Husain L. Management of post-acute Covid-19 in primary care. BMJ. 2020;370:m3026. PMID: 32784198 https://doi.org/10.1136/bmj.m3026Kamal M, Abo Omirah M, Hussein A, Saeed H. Assessment and characterisation of post-COVID-19 manifestations. Int J Clin Pract. 2020 Sep 29:e13746. PMID: 32991035 https://doi.org/10.1111/ijcp.13746 Online ahead of printWilli S, Lüthold R, Hunt A, Hänggi NV, Sejdiu D, Scaff C, et al. COVID19 Sequelae in adults aged less than 50 years: A Systematic Review. Travel Med Infect Dis. 2021;40:101995. PMID: 33631340 https://doi.org/10.1016/j.tmaid.2021.101995Zhao YM, Shang YM, Song WB, Li QQ, Xie H, Xu QF, et al. Followup study of the pulmonary function and related physiological characteristics of COVID-19 survivors three months after recovery. EClinicalMedicine. 2020;25:100463. PMID: 32838236 https://doi.org/10.1016/j.eclinm.2020.100463Kamal M, Abo Omirah M, Hussein A, Saeed H. Assessment and characterisation of post-COVID-19 manifestations. Int J Clin Pract. 2020 Sep 29:e13746. PMID: 32991035 https://doi.org/10.1111/ijcp.13746 Online ahead of printvan den Borst B, Peters JB, Brink M, Schoon Y, Bleeker-Rovers CP, Schers H, et al. Comprehensive health assessment three months after recovery from acute COVID-19. Clin Infect Dis. 2020 Nov 21:ciaa1750. PMID: 33220049 https://doi.org/10.1093/cid/ciaa1750 Online ahead of print.Zhao YM, Shang YM, Song WB, Li QQ, Xie H, Xu QF, et al. Followup study of the pulmonary function and related physiological characteristics of COVID-19 survivors three months after recovery. EClinicalMedicine. 2020;25:100463. PMID: 32838236 https://doi.org/10.1016/j.eclinm.2020.100463Huang C, Huang L, Wang Y, Li X, Ren L, Gu X, et al. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet. 2021;397(10270):220–232. PMID: 33428867 https://doi.org/10.1016/S0140-6736(20)32656-8van den Borst B, Peters JB, Brink M, Schoon Y, Bleeker-Rovers CP, Schers H, et al. Comprehensive health assessment three months after recovery from acute COVID-19. Clin Infect Dis. 2020 Nov 21:ciaa1750. PMID: 33220049 https://doi.org/10.1093/cid/ciaa1750 Online ahead of print.Seeherman S, Suzuki YJ. Suzuki Viral Infection and Cardiovascular Disease: Implications for the Molecular Basis of COVID-19 Pathogenesis. Int J Mol Sci. 2021;22(4):1659. PMID: 33562193 https://doi.org/10.3390/ijms22041659Huang C, Huang L, Wang Y, Li X, Ren L, Gu X, et al. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet. 2021;397(10270):220–232. PMID: 33428867 https://doi.org/10.1016/S0140-6736(20)32656-8Simmonds P, Williams S, Harvala H. Understanding the outcomes of COVID-19–does the current model of an acute respiratory infection really fit? J Gen Virol. 2021;102(3). PMID: 33331810 https://doi.org/10.1099/jgv.0.001545Seeherman S, Suzuki YJ. Suzuki Viral Infection and Cardiovascular Disease: Implications for the Molecular Basis of COVID-19 Pathogenesis. Int J Mol Sci. 2021;22(4):1659. PMID: 33562193 https://doi.org/10.3390/ijms22041659Biradar V, Moran JL. SIRS, Sepsis and Multiorgan Failure. In: Fitridge R, Thompson M, (eds). Mechanisms of vascular disease: a reference book for vascular specialists. Adelaide (AU): Barr Smith Press; 2011. p. 315–330.Simmonds P, Williams S, Harvala H. Understanding the outcomes of COVID-19–does the current model of an acute respiratory infection really fit? J Gen Virol. 2021;102(3). PMID: 33331810 https://doi.org/10.1099/jgv.0.001545Walton AH, Muenzer JT, Rasche D, Boomer JS, Sato B, Brownstein BH, et al Reactivation of multiple viruses in patients with sepsis. PLoS One. 2014;9(2):e98819. PMID: 24919177 https://doi.org/10.1371/journal.pone.0098819 eCollection 2014.Biradar V, Moran JL. SIRS, Sepsis and Multiorgan Failure. In: Fitridge R, Thompson M, (eds). Mechanisms of vascular disease: a reference book for vascular specialists. Adelaide (AU): Barr Smith Press; 2011. p. 315–330.Liu W-D, Chang S-Y, Wang J-T, Tsai M-J, Hung C-C, Hsu CL, et al. Prolonged virus shedding even after seroconversion in a patient with COVID-19. J Infect. 2020;81(2):318–356.PMID: 32283147 https://doi.org/10.1016/j.jinf.2020.03.063Walton AH, Muenzer JT, Rasche D, Boomer JS, Sato B, Brownstein BH, et al. Reactivation of multiple viruses in patients with sepsis. PLoS One. 2014;9(2):e98819. PMID: 24919177 https://doi.org/10.1371/journal.pone.0098819 eCollection 2014.Zhang L, Li C, Zhou Y, Wang B, Zhang J. Persistent viral shedding lasting over 60 days in a mild COVID-19 patient with ongoing positive SARS-CoV-2. Quant Imaging Med Surg. 2020;10(5):1141–1144. PMID: 32489935 https://doi.org/10.21037/qims.2020.04.08Liu W-D, Chang S-Y, Wang J-T, Tsai M-J, Hung C-C, Hsu CL, et al. Prolonged virus shedding even after seroconversion in a patient with COVID-19. J Infect. 2020;81(2):318–356. PMID: 32283147 https://doi.org/10.1016/j.jinf.2020.03.063Molina LP, Chow SK, Nickel A, Love JE. Prolonged detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in an obstetric patient with antibody seroconversion. Obstet Gynecol. 2020;136(4):838–841. PMID: 32701763 https://doi.org/10.1097/AOG.0000000000004086Zhang L, Li C, Zhou Y, Wang B, Zhang J. Persistent viral shedding lasting over 60 days in a mild COVID-19 patient with ongoing positive SARS-CoV-2. Quant Imaging Med Surg. 2020;10(5):1141–1144. PMID: 32489935 https://doi.org/10.21037/qims.2020.04.08Xu K, Cai H, Shen Y, Ni Q, Chen Y, Hu S, et al. Management of COVID-19: the Zhejiang experience. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2020;49(2):147–157. PMID: 32391658 https://doi.org/10.3785/j.issn.1008-9292.2020.02.02Molina LP, Chow SK, Nickel A, Love JE. Prolonged detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in an obstetric patient with antibody seroconversion. Obstet Gynecol. 2020;136(4):838–841. PMID: 32701763 https://doi.org/10.1097/AOG.0000000000004086Yong SJ. Persistent Brainstem Dysfunction in Long-COVID: A Hypothesis. ACS Chem Neurosci. 2021;12(4):573–580. PMID: 33538586 https://doi.org/10.1021/acschemneuro.0c00793Xu K, Cai H, Shen Y, Ni Q, Chen Y, Hu S, et al. Management of COVID-19: the Zhejiang experience. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2020;49(2):147–157. PMID: 32391658 https://doi.org/10.3785/j.issn.1008-9292.2020.02.02Steyers CM 3rd, Miller FJ Jr. Endothelial dysfunction in chronic inflammatory diseases. Int J Mol Sci. 2014;15(7):11324–11349. PMID: 24968272 https://doi.org/10.3390/ijms150711324Yong SJ. Persistent Brainstem Dysfunction in Long-COVID: A Hypothesis. ACS Chem Neurosci. 2021;12(4):573–580. PMID: 33538586 https://doi.org/10.1021/acschemneuro.0c00793Malyszko J. Mechanism of endothelial dysfunction in chronic kidney disease. Clin Chim Acta. 2010;411(19–20):1412–1420. PMID: 20598675 https://doi.org/10.1016/j.cca.2010.06.019Steyers CM 3rd, Miller FJ Jr. Endothelial dysfunction in chronic inflammatory diseases. Int J Mol Sci. 2014;15(7):11324–11349. PMID: 24968272 https://doi.org/10.3390/ijms150711324Bermejo-Martin JF, Almansa R, Torres A, González-Rivera M, Kelvin DJ. COVID-19 as a cardiovascular disease: the potential role of chronic endothelial dysfunction. Cardiovasc Res. 2020;116(10):e132–e133. PMID: 32420587 https://doi.org/10.1093/cvr/cvaa140Malyszko J. Mechanism of endothelial dysfunction in chronic kidney disease. Clin Chim Acta. 2010;411(19–20):1412–1420. PMID: 20598675 https://doi.org/10.1016/j.cca.2010.06.019Poredos P, Jezovnik MK. Endothelial dysfunction and venous thrombosis. Angiology. 2018;69(7):564–567. PMID: 28954526 https://doi.org/10.1177/0003319717732238Bermejo-Martin JF, Almansa R, Torres A, González-Rivera M, Kelvin DJ. COVID-19 as a cardiovascular disease: the potential role of chronic endothelial dysfunction. Cardiovasc Res. 2020;116(10):e132–e133. PMID: 32420587 https://doi.org/10.1093/cvr/cvaa140Kang S, Narazaki M, Metwally H, Kishimoto T. Historical overview of the interleukin-6 family cytokine. J Exp Med. 2020;217(5):e20190347. PMID: 32267936 https://doi.org/10.1084/jem.20190347Poredos P, Jezovnik MK. Endothelial dysfunction and venous thrombosis. Angiology. 2018;69(7):564–567. PMID: 28954526 https://doi.org/10.1177/0003319717732238Minciullo PL, Catalano A, Mandraffino G, Casciaro M, Crucitti A, Maltese G, Inflammaging and anti-inflammaging: the role of cytokines in extreme longevity. Arch Immunol Ther Exp (Warsz). 2016;64(2):111– 126. PMID: 26658771 https://doi.org/10.1007/s00005-015-0377-3Kang S, Narazaki M, Metwally H, Kishimoto T. Historical overview of the interleukin-6 family cytokine. J Exp Med. 2020;217(5):e20190347. PMID: 32267936 https://doi.org/10.1084/jem.20190347Reiss AB, Siegart NM, De Leon J. Interleukin-6 in atherosclerosis: atherogenic or atheroprotective? Clin Lipidology. 2017;12(1):14–23. https://doi.org/10.1080/17584299.2017.1319787Minciullo PL, Catalano A, Mandraffino G, Casciaro M, Crucitti A, Maltese G, Inflammaging and anti-inflammaging: the role of cytokines in extreme longevity. Arch Immunol Ther Exp (Warsz). 2016;64(2):111– 126. PMID: 26658771 https://doi.org/10.1007/s00005-015-0377-3Kälsch AI, Scharnagl H, Kleber ME, Windpassinger C, Sattler W, Leipe J, et al. Long- and short-term association of low-grade systemic inflammation with cardiovascular mortality in the LURIC study. Clin Res Cardiol. 2020;109(3):358–373. PMID: 31263995 https://doi.org/10.1007/s00392-019-01516-9Reiss AB, Siegart NM, De Leon J. Interleukin-6 in atherosclerosis: atherogenic or atheroprotective? Clin Lipidology. 2017;12(1):14–23. https://doi.org/10.1080/17584299.2017.1319787Fanola CL, Morrow DA, Cannon CP, Jarolim P, Lukas MA, Bode C, et al. Interleukin-6 and the risk of adverse outcomes in patients after an acute coronary syndrome: observations from the SOLID-TIMI 52 (stabilization of plaque using darapladib — thrombolysis in myocardial infarction 52) trial. J Am Heart Assoc. 2017;6(10):e005637. PMID: 29066436 https://doi.org/10.1161/JAHA.117.005637Kälsch AI, Scharnagl H, Kleber ME, Windpassinger C, Sattler W, Leipe J, et al. Long- and short-term association of low-grade systemic inflammation with cardiovascular mortality in the LURIC study. Clin Res Cardiol. 2020;109(3):358–373. PMID: 31263995 https://doi.org/10.1007/s00392-019-01516-9Gager GM, Biesinger B, Hofer F, Winter MP, Hengstenberg C, Jilma B, et al. Interleukin-6 level is a powerful predictor of long-term cardiovascular mortality in patients with acute coronary syndrome. Vascul Pharmacol. 2020;135:106806. PMID: 33035661 https://doi.org/10.1016/j.vph.2020.106806Fanola CL, Morrow DA, Cannon CP, Jarolim P, Lukas MA, Bode C, et al. Interleukin-6 and the risk of adverse outcomes in patients after an acute coronary syndrome: observations from the SOLID-TIMI 52 (stabilization of plaque using darapladib — thrombolysis in myocardial infarction 52) trial. J Am Heart Assoc. 2017;6(10):e005637. PMID: 29066436 https://doi.org/10.1161/JAHA.117.005637Coomes EA, Haghbayan H. Interleukin-6 in COVID-19: a systematic review and meta-analysis. Rev Med Virol. 2020;30(6):1–9. PMID: 32845568 https://doi.org/10.1002/rmv.2141Gager GM, Biesinger B, Hofer F, Winter MP, Hengstenberg C, Jilma B, et al. Interleukin-6 level is a powerful predictor of long-term cardiovascular mortality in patients with acute coronary syndrome. Vascul Pharmacol. 2020;135:106806. PMID: 33035661 https://doi.org/10.1016/j.vph.2020.106806Price J, Lord JM, Harrison P. Inflammaging and platelet hyperreactivity: a new therapeutic target. J Thromb Haemost. 2020;18(1):3–5. PMID: 31894663 https://doi.org/10.1111/jth.14670Coomes EA, Haghbayan H. Interleukin-6 in COVID-19: a systematic review and meta-analysis. Rev Med Virol. 2020;30(6):1–9. PMID: 32845568 https://doi.org/10.1002/rmv.2141Wassmann S, Nickenig G. The role of the AT1 receptor in the cardiovascular continuum. Eur Heart J Suppl. 2004;6(Suppl_H):h3–h9. https://doi.org/10.1093/eurheartj/6.suppl_h.h3Price J, Lord JM, Harrison P. Inflammaging and platelet hyperreactivity: a new therapeutic target. J Thromb Haemost. 2020;18(1):3–5. PMID: 31894663 https://doi.org/10.1111/jth.14670Schmieder RE. Endothelial dysfunction: how can one intervene at the beginning of the cardiovascular continuum? J Hypertens Suppl. 2006;24(2):S31–35. PMID: 16601559 https://doi.org/10.1097/01.hjh.0000220101.57896.cdWassmann S, Nickenig G. The role of the AT1 receptor in the cardiovascular continuum. Eur Heart J Suppl. 2004;6(Suppl_H):h3–h9. https://doi.org/10.1093/eurheartj/6.suppl_h.h3Benigni A, Cassis P, Remuzzi G. Angiotensin II revisited: new roles in inflammation, immunology and aging. EMBO Mol Med. 2010;2(7):247– 257. PMID: 20597104 https://doi.org/10.1002/emmm.201000080Schmieder RE. Endothelial dysfunction: how can one intervene at the beginning of the cardiovascular continuum? J Hypertens Suppl. 2006;24(2):S31–35. PMID: 16601559 https://doi.org/10.1097/01.hjh.0000220101.57896.cdCheng ZJ, Vapaatalo H, Mervaala E. Angiotensin II and vascular inflammation. Med Sci Monit. 2005;11(6):RA194–205. PMID: 15917731Benigni A, Cassis P, Remuzzi G. Angiotensin II revisited: new roles in inflammation, immunology and aging. EMBO Mol Med. 2010;2(7):247– 257. PMID: 20597104 https://doi.org/10.1002/emmm.201000080Soro-Paavonen A, Gordin D, Forsblom C, Rosengard-Barlund M, Waden J, Thorn L, et al. Circulating ACE2 activity is increased in patients with type 1 diabetes and vascular complications. J Hypertens. 2012;30(2):375– 383. PMID: 22179088 https://doi.org/10.1097/hjh.0b013e32834f04b6Cheng ZJ, Vapaatalo H, Mervaala E. Angiotensin II and vascular inflammation. Med Sci Monit. 2005;11(6):RA194–205. PMID: 15917731Sardu C, Gambardella J, Morelli MB, Wang X, Marfella R, Santulli G. Hypertension, thrombosis, kidney failure, and diabetes: is COVID-19 an endothelial disease? A comprehensive evaluation of clinical and basic evidence. J Clin Med. 2020;9(5):1417. PMID: 32403217 https://doi.org/10.3390/jcm9051417Soro-Paavonen A, Gordin D, Forsblom C, Rosengard-Barlund M, Waden J, Thorn L, et al. Circulating ACE2 activity is increased in patients with type 1 diabetes and vascular complications. J Hypertens. 2012;30(2):375– 383. PMID: 22179088 https://doi.org/10.1097/hjh.0b013e32834f04b6Amenta EM, Spallone A, Rodriguez-Barradas MC, El Sahly HM, Atmar RL, Kulkarni PA. Postacute COVID-19: An Overview and Approach to Classification. Open Forum Infect Dis. 2020;7(12):ofaa509. PMID: 33403218 https://doi.org/10.1093/ofid/ofaa509Sardu C, Gambardella J, Morelli MB, Wang X, Marfella R, Santulli G. Hypertension, thrombosis, kidney failure, and diabetes: is COVID-19 an endothelial disease? A comprehensive evaluation of clinical and basic evidence. J Clin Med. 2020;9(5):1417. PMID: 32403217 https://doi.org/10.3390/jcm9051417Ng WH, Tipih T, Makoah NA, Vermeulen JG, Goedhals D, Sempa JB, et al. Comorbidities in SARS-CoV-2 Patients: a Systematic Review and MetaAnalysis. mBio. 2021;12(1):e03647–20. PMID: 33563817 https://doi.org/10.1128/mBio.03647-20Amenta EM, Spallone A, Rodriguez-Barradas MC, El Sahly HM, Atmar RL, Kulkarni PA. Postacute COVID-19: An Overview and Approach to Classification. Open Forum Infect Dis. 2020;7(12):ofaa509. PMID: 33403218 https://doi.org/10.1093/ofid/ofaa509Shah W, Hillman T, Playford ED, Hishmeh L. Managing the long-term effects of covid-19: summary of NICE, SIGN, and RCGP rapid guideline. BMJ. 2021;372:n136. PMID: 33483331 https://doi.org/10.1136/bmj. n136Ng WH, Tipih T, Makoah NA, Vermeulen JG, Goedhals D, Sempa JB, et al. Comorbidities in SARS-CoV-2 Patients: a Systematic Review and MetaAnalysis. mBio. 2021;12(1):e03647–20. PMID: 33563817 https://doi.org/10.1128/mBio.03647-20Nalbandian A, Sehgal K, Gupta A, Madhavan MV, McGroder C, Stevens JS, et al. Post-acute COVID-19 syndrome. Nat Med. 2021 Mar 22. PMID: 33753937 https://doi.org/10.1038/s41591-021-01283-z Online ahead of print.Shah W, Hillman T, Playford ED, Hishmeh L. Managing the long-term effects of covid-19: summary of NICE, SIGN, and RCGP rapid guideline. BMJ. 2021;372:n136. PMID: 33483331 https://doi.org/10.1136/bmj. n136Girard TD, Ware LB, Bernard GR, Pandharipande PP, Thompson JL, Shintani AK, et al. Associations of markers of inflammation and coagulation with delirium during critical illness. Intensive Care Med. 2012;38(12):1965–1973. PMID: 22903241 https://doi.org/10.1007/s00134-012-2678-xNalbandian A, Sehgal K, Gupta A, Madhavan MV, McGroder C, Stevens JS, et al. Post-acute COVID-19 syndrome. Nat Med. 2021 Mar 22. PMID: 33753937 https://doi.org/10.1038/s41591-021-01283-z Online ahead of print.Baumgart M, Snyder HM, Carrillo MC, Fazio S, Kim H, Johns H. Summary of the evidence on modifiable risk factors for cognitive decline and dementia: a population-based perspective. Alzheimers Dement. 2015;11(6):718–726. PMID: 26045020 https://doi.org/10.1016/j.jalz.2015.05.016Girard TD, Ware LB, Bernard GR, Pandharipande PP, Thompson JL, Shintani AK, et al. Associations of markers of inflammation and coagulation with delirium during critical illness. Intensive Care Med. 2012;38(12):1965–1973. PMID: 22903241 https://doi.org/10.1007/s00134-012-2678-xRobertson DA, Savva GM, Kenny RA. Frailty and cognitive impairment— a review of the evidence and causal mechanisms. Ageing Res Rev. 2013;12(4):840–851. PMID: 23831959 https://doi.org/10.1016/j.arr.2013.06.004Baumgart M, Snyder HM, Carrillo MC, Fazio S, Kim H, Johns H. Summary of the evidence on modifiable risk factors for cognitive decline and dementia: a population-based perspective. Alzheimers Dement. 2015;11(6):718–726. PMID: 26045020 https://doi.org/10.1016/j.jalz.2015.05.016Nordvig AS, Rimmer KT, Willey JZ, Thakur KT, Boehme AK, Vargas WS, et al. Potential neurological manifestations of COVID-19. Neurol Clin Pract. 2020 June 30. Available at: https://cp.neurology.org/content/early/2020/06/30/CPJ.0000000000000897/ [Accessed April 08, 2021] https://doi.org/10.1212/CPJ.0000000000000897Robertson DA, Savva GM, Kenny RA. Frailty and cognitive impairment— a review of the evidence and causal mechanisms. Ageing Res Rev. 2013;12(4):840–851. PMID: 23831959 https://doi.org/10.1016/j.arr.2013.06.004Garrigues E, Janvier P, Kherabi Y, Le Bot A, Hamon A, Gouze H, et al. Post-discharge persistent symptoms and health-related quality of life after hospitalization for COVID-19. J Infect. 2020;81(6):e4–e6. PMID: 32853602 https://doi.org/10.1016/j.jinf.2020.08.029Nordvig AS, Rimmer KT, Willey JZ, Thakur KT, Boehme AK, Vargas WS, et al. Potential neurological manifestations of COVID-19. Neurol Clin Pract. 2020 June 30. Available at: https://cp.neurology.org/content/early/2020/06/30/CPJ.0000000000000897/ [Accessed Apr 08, 2021] https://doi.org/10.1212/CPJ.0000000000000897Junhua M, Zhang Q, Gong X, Li L, Zhang Z, Wang J, et al. Analysis of psychological and sleep state of medical stuff with novel coronavirus pneumonia. Herald Med. 2020;39(3):345–349. https://doi.org/10.3870/j.issn.1004-0781.2020.03.017Garrigues E, Janvier P, Kherabi Y, Le Bot A, Hamon A, Gouze H, et al. Post-discharge persistent symptoms and health-related quality of life after hospitalization for COVID-19. J Infect. 2020;81(6):e4–e6. PMID: 32853602 https://doi.org/10.1016/j.jinf.2020.08.029Geriatric Medicine Research Collaborative. Delirium is prevalent in older hospital inpatients and associated with adverse outcomes: results of a prospective multi-centre study on World Delirium Awareness Day. BMC Med. 2019;17(1):229. PMID: 31837711 https://doi.org/10.1186/s12916-019-1458-7Junhua M, Zhang Q, Gong X, Li L, Zhang Z, Wang J, et al. Analysis of psychological and sleep state of medical stuff with novel coronavirus pneumonia. Herald Med. 2020;39(3):345–349. https://doi.org/10.3870/ j.issn.1004-0781.2020.03.017Steardo L, Steardo L, Zorec R, Verkhratsky A. Neuroinfection may contribute to pathophysiology and clinical manifestations of COVID19. Acta Physiol (Oxf). 2020;229(3):e13473. PMID: 32223077 https://doi.org/10.1111/apha.13473Geriatric Medicine Research Collaborative. Delirium is prevalent in older hospital inpatients and associated with adverse outcomes: results of a prospective multi-centre study on World Delirium Awareness Day. BMC Med. 2019;17(1):229. PMID: 31837711 https://doi.org/10.1186/s12916-019-1458-7Mcloughlin BC, Miles A, Webb TE, Knopp P, Eyres C, Fabbri A, et al. Functional and cognitive outcomes after COVID-19 delirium. Eur Geriatr Med. 2020;11(5):857–862. PMID: 32666303 https://doi.org/10.1007/s41999-020-00353-8Steardo L, Steardo L, Zorec R, Verkhratsky A. Neuroinfection may contribute to pathophysiology and clinical manifestations of COVID19. Acta Physiol (Oxf). 2020;229(3):e13473. PMID: 32223077 https://doi.org/10.1111/apha.13473Safavynia SA, Arora S, Pryor KO, García PS. An update on postoperative delirium: clinical features, neuropathogenesis, and perioperative management. Curr Anesthesiol Rep. 2018;8(3):252–262. PMID: 30555281Mcloughlin BC, Miles A, Webb TE, Knopp P, Eyres C, Fabbri A, et al. Functional and cognitive outcomes after COVID-19 delirium. Eur Geriatr Med. 2020;11(5):857–862. PMID: 32666303 https://doi.org/10.1007/s41999-020-00353-8Safavynia SA, Goldstein PA. The role of neuroinflammation in postoperative cognitive dysfunction: moving from hypothesis to treatment. Front Psychiatry. 2019;9:752. PMID: 30705643 https://doi.org/10.3389/fpsyt.2018.00752Safavynia SA, Arora S, Pryor KO, García PS. An update on postoperative delirium: clinical features, neuropathogenesis, and perioperative management. Curr Anesthesiol Rep. 2018;8(3):252–262. PMID: 30555281Goërtz YMJ, Van Herck M, Delbressine JM, Vaes AW, Meys R, Machado FVC,et al. Persistent symptoms 3 months after a SARS-CoV-2 infection: the post-COVID-19 syndrome? ERJ Open Res. 2020;6(4):00542–2020. PMID: 33257910 https://doi.org/10.1183/23120541.00542-2020Safavynia SA, Goldstein PA. The role of neuroinflammation in postoperative cognitive dysfunction: moving from hypothesis to treatment. Front Psychiatry. 2019;9:752. PMID: 30705643 https://doi.org/10.3389/fpsyt.2018.00752Вербовой А.Ф., Цанава И.А., Вербовая Н.И. Медицина XXI века: в фокусе коморбидность. Университетская медицина Урала. 2017;3(2):27–31.Goërtz YMJ, Van Herck M, Delbressine JM, Vaes AW, Meys R, Machado FVC, et al. Persistent symptoms 3 months after a SARS-CoV-2 infection: the post-COVID-19 syndrome? ERJ Open Res. 2020;6(4):00542–2020. PMID: 33257910 https://doi.org/10.1183/23120541.00542-2020Sanyaolu A, Okorie C, Marinkovic A, Patidar R, Younis K, Desai P, et al. Comorbidity and its Impact on Patients with COVID-19. SN Compr Clin Med. 2020 Jun 25:1–8. PMID: 32838147 https://doi.org/10.1007/s42399-020-00363-4 Online ahead of print.Verbovoy AF, Tsanava IA, Verbovaya NI. Meditsina XXI veka: v fokuse komorbidnost’. Universitetskaya meditsina Urala. 2017;3(2):27–31. (in Russ.)Pranata R, Supriyadi R, Huang I, Permana H, Lim MA, Yonas E, et al. The association between chronic kidney disease and new onset renal replacement therapy on the outcome of COVID-19 patients: a metaanalysis. Clin Med Insights Circ Respir Pulm Med. 2020;14:11795484209 59165. PMID: 32994700 https://doi.org/10.1177/1179548420959165Sanyaolu A, Okorie C, Marinkovic A, Patidar R, Younis K, Desai P, et al. Comorbidity and its Impact on Patients with COVID-19. SN Compr Clin Med. 2020 Jun 25:1–8. PMID: 32838147 https://doi.org/10.1007/s42399-020-00363-4 Online ahead of print.Kunutsor SK, Laukkanen JA. Renal complications in COVID-19: a systematic review and meta-analysis. Ann Med. 2020;52(7):345–353. PMID: 32643418 https://doi.org/10.1080/07853890.2020.1790643Pranata R, Supriyadi R, Huang I, Permana H, Lim MA, Yonas E, et al. The association between chronic kidney disease and new onset renal replacement therapy on the outcome of COVID-19 patients: a metaanalysis. Clin Med Insights Circ Respir Pulm Med. 2020;14:11795484209 59165. PMID: 32994700 https://doi.org/10.1177/1179548420959165Муркамилов И.Т., Айтбаев К.А., Фомин В.В., Муркамилова Ж.А., Сабиров И.С., Райимжанов З.Р. и др. Провоспалительные цитокины у больных с хронической болезнью почек: в фокусе Интерлейкин-6. Архивъ внутренней медицины. 2019;(6):428–433. https://doi.org/10.20514/2226-6704-2019-9-6-428-433Kunutsor SK, Laukkanen JA. Renal complications in COVID-19: a systematic review and meta-analysis. Ann Med. 2020;52(7):345–353. PMID: 32643418 https://doi.org/10.1080/07853890.2020.1790643Fernández-de-Las-Peñas C, Palacios-Ceña D, Gómez-Mayordomo V, Cuadrado ML, Florencio LL. Defining Post-COVID Symptoms (PostAcute COVID, Long COVID, Persistent Post-COVID): An Integrative Classification. Int J Environ Res Public Health. 2021;18(5):2621. PMID: 33807869 https://doi.org/10.3390/ijerph18052621Murkamilov IT, Aitbae KA, Fomin VV, Murkamilova ZA, Sabirov IS, Rayimzhanov ZR, et al. Pro-inflammatory cytokines in patients with chronic kidney disease: interleukin-6 in focus. The Russian Archives of Internal Medicine. 2019;9(6):428–433. https://doi.org/10.20514/2226- 6704-2019-9-6-428-433Fernández-de-Las-Peñas C, Palacios-Ceña D, Gómez-Mayordomo V, Cuadrado ML, Florencio LL. Defining Post-COVID Symptoms (PostAcute COVID, Long COVID, Persistent Post-COVID): An Integrative Classification. Int J Environ Res Public Health. 2021;18(5):2621. PMID: 33807869 https://doi.org/10.3390/ijerph18052621Fernández-de-Las-Peñas C, Palacios-Ceña D, Gómez-Mayordomo V, Cuadrado ML, Florencio LL. Defining Post-COVID Symptoms (PostAcute COVID, Long COVID, Persistent Post-COVID): An Integrative Classification. Int J Environ Res Public Health. 2021;18(5):2621. PMID: 33807869 https://doi.org/10.3390/ijerph18052621

The authors declare that there are no conflicts of interest present.