Cardiometabolic disorders in SARS-CoV-2 infection and post-covid syndrome

Since the end of 2019, the world has been gripped by a pandemic of a new coronavirus infection caused by SARS-CoV-2. From the first days, the international medical community has been actively studying the acute phase of this infection, but gradually the understanding has come that the number of people with long-term consequences, which can be of the most diverse, including multisystem nature, is increasing more and more. The review of the literature reflects current ideas about the short-term and long-term impact of infection with the SARS-CoV-2 virus on the development of electrolyte disorders and the course of cardiovascular pathology, including those that developed de novo. The debatable issues of definition, risk factors, pathogenesis, course of post-COVID syndrome are discussed with the introduction of the official term «states after COVID-19» and its interpretation, according to the World Health Organization definition proposed in the fall of 2021. Separately, the problems of cardiac arrhythmias are highlighted with an emphasis on atrial fibrillation and chronic heart failure, primarily diagnostic ones associated with non-specific dyspnea in such patients and a frequent increase in natriuretic peptides due to non-cardiac causes. It should be emphasized that information on the clinical outcomes, prognosis and pathogenesis of atrial fibrillation in COVID-19 remains controversial, which is due, on the one hand, to the influence of viremia, intoxication, and fever as obvious transient causes of this arrhythmia, and, on the other hand, to the longitudinal prothrombotic status characteristic of SARS-CoV-2 infection. It is known that the largest number of hospitalizations and deaths in the world associated with a new coronavirus infection occurs in elderly and senile people. The atypicality of the clinical picture, polymorbidity, polypharmacy, the presence of geriatric syndromes occupies a special place in the supervision of the gerontological contingent of patients, to which the authors of the review also draw the attention of clinicians.

1. Wu F., Zhao S., Yu B. et al. A new coronavirus associated with human respiratory disease in China // Nature. 2020; 579 (7798): 265-269. DOI: 10.1038/s41586-020-2008-3.

2. Wahlgren C., Divanoglou A., Larsson M. et al. Rehabilitation needs following COVID-19: Five-month post-discharge clinical follow-up of individuals with concerning self-reported symptoms // EClinicalMedicine, Published by the Lancet. Published online. 2021; 4. https://doi.org/10.1016/j.eclinm.2021.101219.

3. Chazova I. E., Blinova N. V., Nevzorova V. A. et al. Russian Medical Society for Arterial Hypertension Expert Consensus: Hypertension and COVID-19 // Systemic Hypertension. 2020; 17 (3): 35-41. https://doi.org/10.26442/2075082X.2020.3.200362/.

4. World Health Organization. Coronavirus disease 2019 (COVID-19). https://covid19.who.int/.

5. Tsygankova O. V., Nikolayev K. Yu., Fedorova Ye. L. i dr. Risk factors for cardiovascular diseases. A look at a woman // Ateroskleroz. 2014; 1: 44-55.

6. Tsygankova O. V., Nikolayev K. Yu., Fedorova Ye. L., Bondareva Z. G. The exchange of sex hormones in the body of a man through the prism of cardiovascular risk // Ateroskleroz i dislipidemii. 2014; 1 (14): 17-25.

7. Tsygankova O. V., Platonov D. Yu., Bondareva Z. G., Starichkov A. A. i dr. Ischemic disease in women: pathogenetic and pathomorphological features of the formation and clinical course // Problemy zhenskogo zdorov'ya. 2013; 4 (8): 50-59.

8. https://activ.euat.ru/ 10.01.2022 г. ID-исследования: идентификатор ClinicalTrials.gov: NCT04492384.

9. Arutyunov G. P., Tarlovskaya Е. I., Arutyunov A. G. on behalf of coauthors. Clinical features of post-COVID-19 period. Results of the international register «Dynamic analysis of comorbidities in SARS-CoV-2 survivors (AKTIV SARS-CoV-2)». Data from 6-month follow-up // Russian Journal of Cardiology. 2021; 26 (10): 4708. DOI: 10.15829/1560-4071-2021-4708.

10. Arutyunov G. P., Tarlovskaya E. I., Arutyunov A. G. et al. Analysis of influence of background therapy for comorbidities in the period before infection on the risk of the lethal COVID outcome. Data from the international ACTIV SARS-CoV-2 registry («Analysis of chronic non-infectious diseases dynamics after COVID-19 infection in adult patients SARS-CoV-2») // Kardiologiia. 2021; 61 (9): 20-32. DOI: 10.18087/cardio.2021.9.n1680.

11. Lopez-Leon S., Wegman-Ostrosky T., Perelman C. et al. More than 50 long-term effects of COVID-19: a systematic review and meta-analysis // Sci Rep. 2021; 11 (1): 16144. DOI: 10.1038/s41598-021-95565-8.

12. Michelen M., Manoharan L., Elkheir N. et al. Characterising long COVID: a living systematic review // BMJ Global Health. 2021; 6: e005427. DOI: 10.1136/bmjgh-2021-005427.

13. Cabrera Martimbianco A. L., Pacheco R. L., Bagattini Â. M., Riera R. Frequency, signs and symptoms, and criteria adopted for long COVID-19: A systematic review // Int J Clin Pract. 2021; 75: e14357. https://doi.org/10.1111/ijcp.14357.

14. Seeherman S., Suzuki Y. J. 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/ijms22041659.

15. Zhang L., Li C., Zhou Y. et al. 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.2020.04.08.

16. Liu W.-D., Chang S.-Y., Wang J. T. 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.2020.03.063.

17. Shin Jie Yong. Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments // Infectious Diseases. 2021; 10 (53): 737-754. https: //doi.org/10.1080/23744235.2021.1924397.

18. Belotserkovskaya Yu. G., Romanovskikh A. G., Smirnov I. P. et al. Long COVID-19 // Consilium Medicum. 2021; 23 (3): 261-268. DOI: 10.26442/20751753.2021.3.200805.

19. Dixit N. M., Churchill A., Nsair A., Hsu J. J. Post-Acute COVID-19 Syndrome and the cardiovascular system: What is known? // American Heart Journal Plus: Cardiology Research and Practice. 2021; 5: 100025. DOI: 10.1016/j.ahjo.2021.100025.

20. Arévalos V., Ortega-Paz L., Fernandez-Rodríguez D. et al. Long-term effects of coronavirus disease 2019 on the cardiovascular system, CV COVID registry: A structured summary of a study protocol // PLoS One. 2021; 16 (7): e0255263. DOI: 10.1371/journal.pone.0255263.

21. Cassar M. P., Tunnicliffe E. M., Petousi N. et al. Symptom Persistence Despite Improvement in Cardiopulmonary Health – Insights from longitudinal CMR, CPET and lung function testing postCOVID-19 // EClinicalMedicine, Published by the Lancet. 2021. https://doi.org/10.1016/j.eclinm.2021.1011592589-5370/.

22. Raveendran A. V., Jayadevan R., Sashidharan S. Long COVID: An overview // Diabetes Metab Syndr. 2021; 15 (3): 869-875. DOI: 10.1016/j.dsx.2021.04.007.

23. Michelen M., Manoharan L., Elkheir N. et al. Characterising long COVID: a living systematic review // BMJ Global Health. 2021; 6: e005427. DOI: 10.1136/bmjgh-2021-005427.

24. World Health Organization. A clinical case definition of post COVID-19 condition by a Delphi consensus. 6 October 2021. https://covid19.who.int/.

25. Polyakova O. A., Ostroumova O. D., Mironova E. V. et al. Prospects for the use of a fixed combination of bisoprolol and amlodipine in the treatment of patients with post-covid syndrome // Meditsinskiy sovet = Medical Council. 2021; (14): 23-34. https://doi.org/10.21518/2079-701X-2021-14-23-34.

26. Karpov Y. A., Komissarenko I. A. Cardiovascular System Damage in SARSCoV- 2 Infection. Role of β-blockers and Calcium Channel Blockers // Atm spherA. 2020. 4: 3-11. DOI: 10.24412/2076-4189-2020-1231.

27. Salamanna F., Veronesi F., Martini L., Landini M. P., Fini M. Post-COVID-19 Syndrome: The Persistent Symptoms at the Post-viral Stage of the Disease. A Systematic Review of the Current Data // Front. Med. 2021; 8: 653516. DOI: 10.3389/fmed.2021.653516.

28. Ståhlberg M., Reistam U., Fedorowski A. et al. Post-COVID-19 Tachycardia Syndrome: A Distinct Phenotype of Post-Acute COVID-19 Syndrome // The American Journal of Medicine. 2021; 134: 1451−1456. https://doi.org/10.1016/j.amjmed.2021.07.004.

29. Kunal S., Madan M., Tarke C. et al. Emerging spectrum of post-COVID-19 syndrome // Postgrad Med J Epub ahead of print: [please include Day Month Year]. DOI: 10.1136/postgradmedj-2020-139585.

30. Deshmukh V., Motwani R., Kumar A. et al. Histopathological observations in COVID-19: a systematic review // J Clin Pathol. 2021; 74 (2): 76-83. DOI: 10.1136/jclinpath-2020-206995.

31. Roshdy A., Zaher S., Fayed H., Coghlan J. G. COVID-19 and the Heart: A Systematic Review of Cardiac Autopsies // Front Cardiovasc Med. 2021; 7: 626975. DOI: 10.3389/fcvm.2020.626975.

32. Ramadan M. S., Bertolino L., Zampino R. et al. Cardiac sequelae after coronavirus disease 2019 recovery: a systematic review // Clin Microbiol Infect. 2021; 27 (9): 1250-1261. DOI: 10.1016/j.cmi.2021.06.015.

33. Utkina E. A., Afanasyeva O. I., Pokrovsky S. N. C-reactive protein: pathogenetic characteristics and possible therapeutic target // Russian Journal of Cardiology. 2021; 26 (6): 4138. (In Russ.) DOI: 10.15829/1560-4071-2021-4138.

34. Zhou F., Yu T., Du R. et al. Clinical course and risk factors for mortality of adult in patients with COVID-19 in Wuhan, China: a retrospective cohort study // Lancet. 2020; 395 (10229): 1054-1062. DOI: 10.1016/S0140-6736(20)30566-3.

35. Hendren N. S., Drazner M. H., Bozkurt B., Cooper L. T. Jr. Description and proposed management of the acute COVID19 cardiovascular syndrome // Circulation. 2020; 141 (23): 1903-1914. DOI: 10.1161/CIRCULATIONAHA.120.047349.

36. Bubnova M. G., Aronov D. M. COVID-19 and сardiovascular diseases: from epidemiology to rehabilitation // Pul’monologiya. 2020; 30 (5): 688-699 (in Russ.). DOI: 10.18093/0869-0189-2020-30-5-688-699.

37. Tkacheva O. N., Kotovskaya Yu., Runihina N. K. et al. Comprehensive geriatric assessment in elderly and senile patients with cardiovascular diseases. Expert opinion of the Russian Association of Gerontologists and Geriatricians // Kardiologiia. 2021; 61 (5): 71-78. DOI: 10.18087/cardio.2021.5.n1349.

38. Deer R. R., Rock M. A., Vasilevsky N. et al. Characterizing Long COVID: Deep Phenotype of a Complex Condition // EBioMedicine. Published by the Lancet. November 2021; 25; 74: 103722. DOI: 10.1016/j.ebiom.2021.103722.

39. Peixun Zhang, Jia Li, Huixin Liu et al. Long-term bone and lung consequences associated with hospital-acquired severe acute respiratory syndrome: a 15-year follow-up from a prospective cohort study // Bone Research. 2020; 8: 8.

40. Wu Q., Zhou L., Sun X. et al. Altered Lipid Metabolism in Recovered SARS Patients Twelve Years after Infection // Sci Rep. 2017; 7 (1): 9110.

41. Blagova O. V., Kogan E. A., Lutokhina Y. A. et al. Subacute and chronic postcovid myoendocarditis: clinical presentation, role of coronavirus persistence and autoimmune mechanisms // Kardiologiia. 2021; 61 (6): 11-27. DOI: 10.18087/cardio.2021.6.n1659.

42. Dorward D. A., Russell C. D., Um I. H. et al. Tissue-Specific Immunopathology in Fatal COVID-19 // American Journal of Respiratory and Critical Care Medicine. 2021; 203 (2): 192-201. DOI: 10.1164/rccm.202008-3265OC.

43. McGonagle D., Kearney M. F., O’Regan A. et al. Therapeutic implications of ongoing alveolar viral replication in COVID-19 // The Lancet Rheumatology. Published online December 1, 2021. https://doi.org/10.1016/S2665-9913(21)00322-2.

44. Gushchina O. I., Lozhkina N. G. Cardiovascular diseases in combination with SARS-CoV-2 viral infection: cours and forecast // Ateroscleroz. 2021; 17 (3): 97-105. (In Russ.) DOI: 10.52727/2078-256Х-2021-3-97-105.

45. Recommendations for the management of patients with coronavirus infection COVID-19 in the acute phase and with post-covid syndrome in the outpatient setting / Ed. prof. Vorobieva P. A. // Problemy standartizatsii v zdravookhranenii. 2021; 7-8: 3-96. https://doi.org/10.26347/1607-2502202107-08003-096.

46. Martynov A. I., Gorelov A. V., Malyavin A. G. i dr. Methodological recommendations «Peculiarities of the course of Long-COVID infection. Therapeutic and rehabilitation measures» (approved at the XVI National Congress of Therapists on November 18, 2021).

47. Onder G., Rezza G., Brusaferro S. Case-fatality rate and characteristics of patients dying in relation to COVID-19 in Italy // JAMA. 2020; 323 (18): 1775-1776. DOI: 10.1001/jama.2020.4683

48. Yakhontov D. A., Khidirova L. D., Zenin S. A. Assessment of some clinical pathogenetic interactions in patients with atrial fibrillation in combination with the arterial hypertension and extracardiac pathology // Journal of Siberian Medical Sciences. 2019; (2): 29-37. https://doi.org/10.31549/2542-1174-2019-2-29-37.

49. Serezhina Ye. K., Obrezan A. G. Atrial fibrillation associated with novel coronavirus infection: mechanisms and therapeutic approaches. 2021; 2 (9): 14-20. DOI: https://doi.org/10.33029/2309-1908-2021-9-2-14-20.

50. Ming-yue Chen, Fang-ping Xiao, Kuai L. et al. Outcomes of atrial fibrillation in patients with COVID-19 pneumonia: A systematic review and metaanalysis // American Journal of Emergency Medicine. 2021; 50: 661-669. https://doi.org/10.1016/j.ajem.2021.09.050.

51. Khidirova L. D., Yakhontov D. A. Assessment of progression of atrial fibrillation in middle-aged individuals with hypertension in combination with comorbid extracardial diseases // Medical alphabet. 2019; 2 (30): 23-27. (In Russ.) https://doi.org/10.33667/2078-5631-2019-2-30(405)-23-27.

52. Kanorskii S. G. Atrial fibrillation in old age: risk management and features of the use of direct oral anticoagulants // Kardiologiia. 2021; 61 (6): 79-87. DOI: 10.18087/cardio.2021.6.n1627.

53. Lippi G., Plebani M., Henry B. M. et al. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis // Clin Chim Acta. 2020; 506: 145-148. DOI: 10.1016/j.cca.2020.03.022. Epub 2020 Mar 13. PMID: 32178975; PMCID: PMC7102663.

54. Korompoki E., Gavriatopoulou M., Fotiou D. et al. Late-onset hematological complications post COVID-19: An emerging medical problem for the hematologist // Am J Hematol. 2021; 1-10. DOI: 10.1002/ajh.26384.

55. Chen W., Li Z., Wang P. et al. Delayed-phase thrombocytopenia in patients with coronavirus disease 2019 (COVID-19) // Br J Haematol. 2020; 190 (2): 179-184. DOI: 10.1111/bjh.16885.

56. Tsiberkin A. I., Golovatyuk K. А., Bykova E. S. et al. Hypokalemia and the renin-angiotensinaldosterone system activity in COVID-19 patients // Arterial’naya gipertenziya (Arterial hypertension). 2021; 27 (4): 457-463. (In Russ.) https://doi.org/10.18705/1607-419X-2021-27-4-457-463.

57. Chen D., Li X., Song Q. et al. Assessment of hypokalemia and clinical characteristics in patients with coronavirus disease 2019 in Wenzhou, China // JAMA Netw Open. 2020; 3 (6): e2011122. DOI: 10.1001/jamanetworkopen.2020.11122.

58. Alnafiey M. O., Alangari A. M., Alarifi A. M., Abushara A. Persistent Hypokalemia post SARS-coV-2 infection, is it a life-long complication? Case report // Ann Med Surg (Lond). 2021; 62: 358-361. DOI: 10.1016/j.amsu.2021.01.049. Epub 2021 Jan 27. PMID: 33527042; PMCID: PMC7839393.

59. Noori M., Nejadghaderi S. A., Sullman M. J. M. et al. How SARS-CoV-2 might affect potassium balance via impairing epithelial sodium channels? // Mol Biol Rep. 2021; 48 (9): 6655-6661. DOI: 10.1007/s11033-021-06642-0. Epub 2021 Aug 15. PMID: 34392451; PMCID: PMC8364628.

60. Noori M., Nejadghaderi S. A., Sullman M. J. M. et al. Epidemiology, prognosis and management of potassium disorders in Covid-19 // Rev Med Virol. 2022; 32 (1): e2262. DOI: 10.1002/rmv.2262. Epub 2021 2 июня. PMID: 34077995; PMCID: PMC8209915.

61. Ebzeeva E. Y., Ostroumova O. D., Krotkova I. F. et al. Electrolyte deficiency after the novel coronavirus infection and post-COVID asthenia // Russian Medical Inquiry. 2021; 5 (5): 245-251. DOI: 10.32364/2587-6821-2021-5-5-245-251.

62. Büyükcam F., Calık M., Erkuran M. K., Akay H. Hypokalemia and muscle paralysis after low-dose methylprednisolone // Am J Emerg Med. 2011; 29 (5): 573.e1-573.e2. DOI: 10.1016/j.ajem.2010.05.008.

63. Singh Rehan H., Hotha P. Antimicrobial Agents-induced Hypokalemia: A Possible Causality Association // Indian J Crit Care Med. 2019; 23 (4): 175-177. DOI: 10.5005/jpjournals-10071-23148.

64. Bader F., Manla Y., Atallah B., Starling R. C. Heart failure and COVID-19 // Heart Failure Reviews. 2021; 26: 1-10.

65. Yonas E., Alwi I., Pranata R. et al. Effect of heart failure on the outcome of COVID-19 - A meta-analysis and systematic review // Am J Emerg Med. 2021; 46: 204-211. DOI: 10.1016/j.ajem.2020.07.009.

66. Temporary guidelines of the Ministry of Health of the Russian Federation on the prevention, diagnosis and treatment of a new coronavirus infection (COVID-19). Version 14, 12/27/2021. 1-232.

67. Evans R. A., McAuley H., Harrison E. M., et al. Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): a UK multicentre, prospective cohort study // Lancet Respiratory Medicine. 2021; 9: 1275-1287. Published Online October 7, 2021. https://doi.org/10.1016/S2213-2600(21)00383-0.

68. Shlyakho E. V., Konradi A. O., Arutyunov G. P. et al. Guidelines for the diagnosis and treatment of circulatory diseases in the context of the COVID-19 pandemic // Russian Journal of Cardiology. 2020; 25 (3): 3801. (In Russ.) DOI: 10.15829/1560-4071-2020-3-3801.

69. Yang C., Jin Z. An acute respiratory infection runs into the most common noncommunicable epidemic ‒ COVID-19 and Cardiovascular Diseases // JAMA Cardiology. 2020; 25. DOI: 10.1001/jamacardio.2020.0934.

70. Arutyunov A. G., Seferovic P., Bakulin I. G. et al. Rehabilitation after COVID-19. Resolution of the International Expert Council of the Eurasian Association of Therapists and the Russian Society of Cardiology // Russian Journal of Cardiology. 2021; 26 (9): 4694. (In Russ.) DOI: 10.15829/1560-4071-2021-469.

71. World Health Organization. Global strategy and action plan on ageing and health. Geneva: World Health Organization; 2017.

72. Larina V. N. Modern vision on the problem of chronic heart failure in the older persons // Russian Journal of Geriatric Medicine. 2021; 1 (5): 65-75. DOI: 10.37586/2686-8636-1-2021-65-75.

73. Kamenskaya O. V., Loginova I. Y., Klinkova A. S. et al. Clinical observations of COVID-19 infection in patients with chronic thromboembolic pulmonary hypertension // Kardiologiia. 2021; 61 (6): 28-34. DOI: 10.18087/cardio.2021.6.n1564.

74. Tkacheva O. N., Kotovskaya Y. V., Aleksanyan L. A. et al. Novel coronavirus infection SARS-CoV-2 in elderly and senile patients: prevention, diagnosis and treatment. Expert Position Paper of the Russian Association of Gerontology and Geriatrics // Cardiovascular Therapy and Prevention. 2020; 19 (3): 2601. (In Russ.) DOI: 10.15829/1728-8800-2020-2601.

75. Clinical recommendations of the Ministry of Health of the Russian Federation. Senile asthenia. 2020. 1-88.

76. Klimenko V. S., Vlasova N. V., Cherepenina N. L. Evaluation of long-term consequences of COVID-19 in an elderly patient according to ECG Holter monitoring (clinical observation). 2021; 16: 5-187. https://doi.org/10.17116/Cardiobulletin2021160225.