Дисбаланс адипокинов и его роль в патогенезе новой коронавирусной инфекции

В обзоре обобщены и проанализированы результаты крупных зарубежных исследований, касающихся изучения роли адипокинового дисбаланса в развитии тяжелого течения и осложнений новой коронавирусной инфекции (COVID-19). Адипокины – биологически активные соединения, которые вырабатываются клетками жировой ткани и участвуют в регуляции обмена веществ и работы иммунной системы.

Известно, что ожирение является доказанным фактором риска тяжелого течения COVID-19 в связи с высокой гормональной и метаболической активностью висцеральной жировой ткани. Глубокое понимание патогенеза COVID-19 с позиций участия в нем адипокинового дисбаланса может лечь в основу разработки эффективных патогенетических подходов к профилактике тяжелого течения и осложнений новой коронавирусной инфекции.

1. Zhu N., Zhang D., Wang W., Li X., Yang B., Song J. et al. Novel coronavirus investigating and research team. A novel coronavirus from patients with pneumonia in China, 2019. N. Engl. J. Med. 2020;82(8):727–733. DOI: 10.1056/NEJMoa2001017.

2. Горошко Н.В., Пацала С.В., Емельянова Е.К. Смертность трудоспособного населения России в условиях пандемии COVID-19. Социальные аспекты здоровья населения. 2022;68(5):1. DOI: 10.21045/2071-5021-2022-68-5-1.

3. Каштанова Е.В., Шахтшнейдер Е.В., Кручинина М.В., Логвиненко И.И., Стрюкова Е.В., Рагино Ю.И. Биохимические, молекулярно-генетические и клинические аспекты COVID-2019. Бюллетень сибирской медицины. 2021;20(1):147–157. DOI: 10.20538/1682-0363-2021-1-147-157.

4. Trougakos I.P., Stamatelopoulos K., Terpos E., Tsitsilonis O.E., Aivalioti E., Paraskevis D. et al. Insights to SARS-CoV-2 life cycle, pathophysiology, and rationalized treatments that target COVID-19 clinical complications. J. Biomed. Sci. 2021;28(1):9. DOI: 10.1186/s12929-020-00703-5.

5. Беспалова И.Д., Бычков В.А., Калюжин В.В., Рязанцева Н.В., Медянцев Ю.А., Осихов И.А. и др. Качество жизни больных гипертонической болезнью с метаболическим синдромом: взаимосвязь с маркерами системного воспаления. Бюллетень сибирской медицины. 2013;12(6):5–11. DOI: 10.20538/1682-0363-2013-6-5-11.

6. Кытикова О.Ю., Антонюк М.В., Кантур Т.А., Новгородцева Т.П., Денисенко Ю.К. Распространенность и биомаркеры метаболического синдрома. Ожирение и метаболизм. 2021;8(3):302–312. DOI: 10.14341/omet12704.

7. Fahed G., Aoun L., Bou Zerdan M., Allam S., Bou Zerdan M., Bouferraa Y. et al. Metabolic syndrome: updates on pathophysiology and management in 2021. Int. J. Mol. Sci. 2022;(2):786. DOI: 10.3390/ijms23020786.

8. Petrilli C.M., Jones S.A., Yang J., Rajagopalan H., O’Donnell L., Chernyak Y. et al. Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York City: prospective cohort study. BMJ. 2020;369:m1966. DOI: 10.1136/bmj.m1966.

9. Huang C., Wang Y., Li X., Ren L., Zhao J., Hu Y. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506. DOI: 10.1016/S0140-6736(20)30183-5.

10. Denson J.L., Gillet A.S., Zu Y., Brown M., Pham T., Yoshida Y. et al. Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry Investigator Group. Metabolic Syndrome and Acute Respiratory Distress Syndrome in Hospitalized Patients with COVID-19. JAMA Netw. Open. 2021;4(12):e2140568. DOI: 10.1001/jamanetworkopen.2021.40568.

11. Lohia P., Kapur S., Benjaram S., Pandey A., Mir T., Seyoum B. Metabolic syndrome and clinical outcomes in patients infected with COVID-19: Does age, sex, and race of the patient with metabolic syndrome matter? J. Diabetes. 2021;13(5):420– 429. DOI: 10.1111/1753-0407.13157.

12. Mahamat-Saleh Y., Fiolet T., Rebeaud M.E., Mulot M., Guihur A., El Fatouhi D. et al. Diabetes, hypertension, body mass index, smoking and COVID-19-related mortality: a systematic review and meta-analysis of observational studies. BMJ Open. 2021;11(10):e052777. DOI: 10.1136/bmjopen-2021-052777.

13. Yang J.K., Feng Y., Yuan M.Y., Yuan S.Y., Fu H.J., Wu B.Y. et al. Plasma glucose levels and diabetes are independent predictors for mortality and morbidity in patients with SARS. Diabet. Med. 2006;23(6):623–628. DOI: 10.1111/j.1464-5491.2006.01861.x.

14. Barron E., Bakhai C., Kar P., Weaver A., Bradley D., Ismail H. et al. Associations of type 1 and type 2 diabetes with COVID-19-related mortality in England: a whole-population study. Lancet Diabetes Endocrinol. 2020;8(10):813–822. DOI: 10.1016/S2213-8587(20)30272-2.

15. Woolcott O.O., Castilla-Bancayan J.P. The effect of age on the association between diabetes and mortality in adult patients with COVID-19 in Mexico. Sci. Rep. 2021;11(1):8386. DOI: 10.1038/s41598-021-88014-z.

16. Silverii G.A., Monami M., Cernigliaro A., Vigneri E., Guarnotta V., Scondotto S. et al. Are diabetes and its medications risk factors for the development of COVID-19? Data from a population-based study in Sicily. Nutr. Metab. Cardiovasc. Dis. 2021;31(2):396–398. DOI: 10.1016/j.numecd.2020.09.028.

17. Zhang J., Kong W., Xia P., Xu Y., Li L., Li Q. et al. Impaired fasting glucose and diabetes are related to higher risks of complications and mortality among patients with coronavirus disease 2019. Front. Endocrinol. (Lausanne). 2020;11:525. DOI: 10.3389/fendo.2020.00525.

18. Lazarus G., Audrey J., Wangsaputra V.K., Tamara A., Tahapary D.L. High admission blood glucose independently predicts poor prognosis in COVID-19 patients: A systematic review and dose-response meta-analysis. Diabetes Res. Clin. Pract. 2021;171:108561. DOI: 10.1016/j.diabres.2020.108561.

19. Yang Y., Cai Z., Zhang J. Hyperglycemia at admission is a strong predictor of mortality and severe/critical complications in COVID-19 patients: a meta-analysis. Biosci. Rep. 2021;41(2):BSR20203584. DOI: 10.1042/BSR20203584.

20. Prattichizzo F., de Candia P., Nicolucci A., Ceriello A. Elevated HbA1c levels in pre-Covid-19 infection increases the risk of mortality: A sistematic review and meta-analysis. Diabetes Metab. Res. Rev. 2022;38(1):e3476. DOI: 10.1002/dmrr.3476.

21. Gallo G., Calvez V., Savoia C. Hypertension and COVID-19: current evidence and perspectives. High Blood Press Cardiovasc. Prev. 2022;29(2):115–123. DOI: 10.1007/s40292-022-00506-9.

22. Hu X., Chen D., Wu L., He G., Ye W. Declined serum high density lipoprotein cholesterol is associated with the severity of COVID-19 infection. Clin. Chim. Acta. 2020;510:105–110. DOI: 10.1016/j.cca.2020.07.015.

23. Fan J., Wang H., Ye G., Cao X., Xu X., Tan W. et al. Letter to the editor: low-density lipoprotein is a potential predictor of poor prognosis in patients with coronavirus disease 2019. Metabolism. 2020;107:154243. DOI: 10.1016/j.metabol.2020.154243.

24. Wei X., Zeng W., Su J., Wan H., Yu X., Cao X. et al. Hypolipidemia is associated with the severity of COVID-19. J. Clin. Lipidol. 2020;14(3):297–304. DOI: 10.1016/j.jacl.2020.04.008.

25. Minuzzi L.G., Seelaender M., Silva B.S.A., Cunha E.D.B.B., Deus M.C., Vasconcellos F.T.F. et al. COVID-19 outcome relates with circulating BDNF, according to patient adiposity and age. Front. Nutr. 2021;8:784429. DOI: 10.3389/fnut.2021.784429.

26. Liu Y., Pan Y., Yin Y., Chen W., Li X. Association of dyslipidemia with the severity and mortality of coronavirus disease 2019 (COVID-19): a meta-analysis. Virol. J. 2021;18(1):157. DOI: 10.1186/s12985-021-01604-1.

27. Zuin M., Rigatelli G., Bilato C., Cervellati C., Zuliani G., Roncon L. Dyslipidaemia and mortality in COVID-19 patients: a meta-analysis. QJM. 2021;114(6):390–397. DOI: 10.1093/qjmed/hcab071.

28. Louie J.K., Acosta M., Samuel M.C., Schechter R., Vugia D.J., Harriman K. et al. California Pandemic (H1N1) Working Group. A novel risk factor for a novel virus: obesity and 2009 pandemic influenza A (H1N1). Clin. Infect. Dis. 2011;52(3):301–312. DOI: 10.1093/cid/ciq152.

29. Martín V., Castilla J., Godoy P., Delgado-Rodríguez M., Soldevila N., Fernández-Villa T. et al. Grupo de Trabajo del Proyecto CIBERESP de Casos y Controles sobre la Gripe Pandémica, España. High Body Mass Index as a Risk Factor for Hospitalization Due to Influenza: A Case-Control Study. Arch. Bronconeumol. 2016;52(6):299–307. DOI: 10.1016/j.arbres.2015.11.006.

30. Díaz E., Rodríguez A., Martin-Loeches I., Lorente L., Del Mar Martín M., Pozo J.C. et al. H1N1 SEMICYUC Working Group. Impact of obesity in patients infected with 2009 influenza A(H1N1). Chest. 2011;139(2):382–386. DOI: 10.1378/chest.10-1160.

31. Simonnet A., Chetboun M., Poissy J., Raverdy V., Noulette J., Duhamel A. et al. LICORN and the Lille COVID-19 and Obesity study group. High Prevalence of Obesity in Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Requiring Invasive Mechanical Ventilation. Obesity (Silver Spring). 2020;28(7):1195–1199. DOI: 10.1002/oby.22831.

32. Biscarini S., Colaneri M., Ludovisi S., Seminari E., Pieri T.C., Valsecchi P. et al. The obesity paradox: Analysis from the SMAtteo COvid-19 REgistry (SMACORE) cohort. Nutr. Metab. Cardiovasc. Dis. 2020;30(11):1920–1925. DOI: 10.1016/j.numecd.2020.07.047.

33. Bellini B., Cresci B., Cosentino C., Profili F., Bartolacci S., Scoccimarro D. et al. Obesity as a risk factor for hospitalization in COronaVirus Disease-19 (COVID-19) patients: analysis of the Tuscany regional database. Nutr. Metab. Cardiovasc. Dis. 2021;31(3):769–773. DOI: 10.1016/j.numecd.2020.11.030.

34. Van der Voort P.H.J., Moser J., Zandstra D.F., Muller Kobold A.C., Knoester M., Calkhoven C.F. et al. Leptin levels in SARS-CoV-2 infection related respiratory failure: A cross-sectional study and a pathophysiological framework on the role of fat tissue. Heliyon. 2020;6(8):e04696. DOI: 10.1016/j.heliyon.2020.e04696.

35. Andersen A.L., Gribsholt S.B., Pedersen L., Thomsen R.W., Benfield T.L., Søgaard O. et al. The impact of age and obesity on outcomes among patients hospitalized with COVID-19 in Denmark: A nationwide cohort study. Obes. Sci. Pract. 2023;9(4):355–363. DOI: 10.1002/osp4.659.

36. Huang Y., Lu Y., Huang Y.M., Wang. M., Ling W., Sui Y. et al. Obesity in patients with COVID-19: a systematic review and meta-analysis. Metabolism. 2020;113:154378. DOI: 10.1016/j.metabol.2020.154378.

37. Tilg H., Moschen A.R. Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat. Rev. Immunol. 2006;6:772–783. DOI: 10.1038/nri1937.

38. Hornung F., Rogal J., Loskill P., Löffler B., Deinhardt-Emmer S. The inflammatory profile of obesity and the role on pulmonary bacterial and viral infections. Int. J. Mol. Sci. 2021;22(7):3456. DOI: 10.3390/ijms22073456.

39. Klok M.D., Jakobsdottir S., Drent M.L. The role of leptin and ghrelin in the regulation of food intake and body weight in humans: A review. Obes. Rev. Off. J. Int. Assoc. Study Obes. 2007;8:21–34. DOI: 10.1111/j.1467-789X.2006.00270.x.

40. Ahima R.S., Flier J.S. Leptin. Annu. Rev. Physiol. 2000;62:413–437. DOI: 10.1146/annurev.physiol.62.1.413.

41. Zakrzewska K.E., Cusin I., Sainsbury A., Rohner-Jeanrenaud F., Jeanrenaud B. Glucocorticoids as counterregulatory hormones of leptin: Toward an understanding of leptin resistance. Diabetes. 1997;46:717–719. DOI: 10.2337/diab.46.4.717.

42. Беспалова И.Д. Лептин как индуктор воспаления и окислительного стресса при метаболическом синдроме. Бюллетень сибирской медицины. 2014;13(1):20–26. DOI: 10.20538/1682-0363-2014-1-20-26.

43. Беспалова И.Д., Калюжин В.В., Мурашев Б.Ю., Осихов И.А., Кощавцева Ю.И., Тетенева А.В., Романов Д.С., Страшкова У.М. Субпопуляционный состав и прооксидантная активность клеток висцеральной жировой ткани пациенток с метаболическим синдромом. Сибирский журнал клинической и экспериментальной медицины. 2022;37(3):114–120. DOI: 10.29001/2073-8552-2022-37-3-114-120.

44. Perrotta F., Scialò F., Mallardo M., Signoriello G., D’Agnano V., Bianco A. et al. Adiponectin, leptin, and resistin are dysregulated in patients infected by SARS-CoV-2. Int. J. Mol. Sci. 2023;24(2):1131. DOI: 10.3390/ijms24021131.

45. Wang J., Xu Y., Zhang X., Wang S., Peng Z., Guo J. et al. Leptin correlates with monocytes activation and severe condition in COVID-19 patients. JLB. 2021;110(1):9–20. DOI: 10.1002/JLB.5HI1020-704R.

46. Larsson A., Lipcsey M., Hultström M., Frithiof R., Eriksson M. Plasma leptin is increased in intensive care patients with COVID-19-an investigation performed in the PronMed-Cohort. Biomedicines. 2021;10(1):4. DOI: 10.3390/biomedicines10010004.

47. Sulicka-Grodzicka J., Surdacki A., Surmiak M., Sanak M., Wizner B., Sydor W. et al. Chemerin as a potential marker of resolution of inflammation in COVID-19 infection. Biomedicines. 2022;10(10):2462. DOI: 10.3390/biomedicines10102462.

48. Di Filippo L., De Lorenzo R., Sciorati C., Capobianco A., Lorè N.I., Giustina A. et al. Adiponectin to leptin ratio reflects inflammatory burden and survival in COVID-19. Diabetes Metab. 2021;47(6):101268. DOI: 10.1016/j.diabet.2021.101268.

49. Beltrão F.E.L., Beltrão D.C.A., Carvalhal G., Beltrão F.N.L., de Aquino I.M., Brito T.D.S. et al. Low muscle mass and high visceral fat mass predict mortality in patients hospitalized with moderate-to-severe COVID-19: a prospective study. Endocr. Connect. 2022;11(10):e220290. DOI: 10.1530/EC22-0290.

50. Беспалова И.Д., Рязанцева Н.В., Калюжин В.В., Осихов И.А., Мурашев Б.Ю., Медянцев Ю.А. и др. Гендерные особенности взаимосвязи гормональной активности жировой ткани и провоспалительного статуса при гипертонической болезни с метаболическим синдромом. Бюллетень сибирской медицины. 2014;13(5):12–19. DOI: 10.20538/1682-0363-2014-5-12-19.

51. Coelho M., Oliveira T., Fernandes R. Biochemistry of adipose tissue: An endocrine organ. Arch. Med. Sci. 2013;9:191. DOI: 10.5114/aoms.2013.33181.

52. Lenz A., Diamond F.B. Jr. Obesity: The hormonal milieu. Curr. Opin. Endocrinol. Diabetes Obes. 2008;15:9–20. DOI: 10.1097/MED.0b013e3282f43a5b.

53. Lago F., Gómez R., Gómez-Reino J.J., Dieguez C., Gualillo O. Adipokines as novel modulators of lipid metabolism. Trends Biochem. Sci. 2009;34:500–510. DOI: 10.1016/j.tibs.2009.06.008.

54. Bray G.A., Clearfield M.B., Fintel D.J., Nelinson D.S. Overweight and obesity: The pathogenesis of cardiometabolic risk. Clin. Cornerstone. 2009;9:30–42. DOI: 10.1016/S1098-3597(09)80003-3.

55. Yamauchi T., Kadowaki T. Adiponectin receptor as a key player in healthy longevity and obesity-related diseases. Cell Metab. 2013;17:185–196. DOI: 10.1016/j.cmet.2013.01.001.

56. De Oliveira Leal V., Mafra D. Adipokines in obesity. Clin. Chimica Acta. 2013;419:87–94. DOI: 10.1016/j.cca.2013.02.003.

57. Hosogai N., Fukuhara A., Oshima K., Miyata Y., Tanaka S., Segawa K. et al. Adipose tissue hypoxia in obesity and its impact on adipocytokine dysregulation. Diabetes. 2007;56:901– 911. DOI: 10.2337/db06-0911.

58. Ouchi N., Kihara S., Funahashi T., Matsuzawa Y., Walsh K. Obesity, Adiponectin and vascular inflammatory disease. Curr. Opin. Lipidol. 2003;14:561–566. DOI: 10.1097/00041433-200312000-00003.

59. Anandaraj A.A., Syed Ismail P.M., Namis S.M., Bajnaid Y.J., Shetty S.B., Almutairi K.M. Association of selected adipocytokines and inflammatory markers on body mass index in type 2 diabetes patients in Saudi Arabia and as risk factors to cardiovascular disease. Curr. Diabetes Rev. 2017;13:330–335. DOI: 10.2174/1573399812666160614014254.

60. Caterino M., Gelzo M., Sol S., Fedele R., Annunziata A., Calabrese C. et al. Dysregulation of lipid metabolism and pathological inflammation in patients with COVID-19. Sci. Rep. 2021;11(1):2941. DOI: 10.1038/s41598-021-82426-7.

61. De Nooijer A.H., Kooistra E.J., Grondman I., Janssen N.A.F., Joosten L.A.B., van de Veerdonk F.L. et al. RCI-COVID-19 study group. Adipocytokine plasma concentrations reflect influence of inflammation but not body mass index (BMI) on clinical outcomes of COVID-19 patients: A prospective observational study from the Netherlands. Clin. Obes. 2023;13(2):e12568. DOI: 10.1111/cob.12568.

62. Ryrsø C.K., Dungu A.M., Hegelund M.H., Jensen A.V., Sejdic A., Faurholt-Jepsen D. et al. Body composition, physical capacity, and immuno-metabolic profile in community-acquired pneumonia caused by COVID-19, influenza, and bacteria: a prospective cohort study. Int. J. Obes. (London). 2022;46(4):817–824. DOI: 10.1038/s41366-021-01057-0.

63. Kearns S.M., Ahern K.W., Patrie J.T., Horton W.B., Harris T.E., Kadl A. Reduced adiponectin levels in patients with COVID-19 acute respiratory failure: A case-control study. Physiol. Rep. 2021;9(7):e14843. DOI: 10.14814/phy2.14843.

64. Flikweert A.W., Kobold A.C.M., van der Sar-van der Brugge S., Heeringa P., Rodenhuis-Zybert I.A., Bijzet J. et al. Circulating adipokine levels and COVID-19 severity in hospitalized patients. Int. J. Obes. (London). 2023;47(2):126–137. DOI: 10.1038/s41366-022-01246-5.

65. Hindsberger B., Lindegaard B., Rabøl Andersen L., Bastrup Israelsen S., Pedersen L., Bela Szecsi P. et al. Circulating adiponectin levels are inversely associated with mortality and respiratory failure in patients hospitalized with COVID-19. Int. J. Endocrinol. 2023;2023:4427873. DOI: 10.1155/2023/4427873.

66. Park H.K., Ahima R.S. Resistin in rodents and humans. Diabetes Metab. J. 2013;37:404–414. DOI: 10.4093/dmj.2013.37.6.404.

67. Schwartz D.R., Lazar M.A. Human resistin: Found in translation from mouse to man. Trends Endocrinol. Metab. 2011;22:259–265. DOI: 10.1016/j.tem.2011.03.005.

68. Bokarewa M., Nagaev I., Dahlberg L., Smith U., Tarkowski A. Resistin, an adipokine with potent proinflammatory properties. J. Immunol. 2005;174:5789–5795. DOI: 10.4049/jimmunol.174.9.5789.

69. Khera A.V., Qamar A., Murphy S.A., Cannon C.P., Sabatine M.S., Rader D.J. On-Statin Resistin, Leptin, and Risk of Recurrent Coronary Events After Hospitalization for an Acute Coronary Syndrome (from the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 Study). Am. J. Cardiol. 2015;116:694–698. DOI: 10.1016/j.amjcard.2015.05.038.

70. Bik W., Ostrowski J., Baranowska-Bik A., Wolinska-Witort E., Bialkowska M., Martynska L. et al. Adipokines and genetic factors in overweight or obese but metabolically healthy Polish women. Neuroendocrinol. Lett. 2010;31:497–506.

71. Telle-Hansen V., Halvorsen B., Dalen K., Narverud I., Wesseltoft-Rao N., Granlund L. et al. Altered expression of genes involved in lipid metabolism in obese subjects with unfavourable phenotype. Genes Nutr. 2013;8:425–434. DOI: 10.1007/s12263-012-0329-z.

72. Ebihara T., Matsumoto H., Matsubara T., Togami Y., Nakao S., Matsuura H. et al. Resistin associated with cytokines and endothelial cell adhesion molecules is related to worse outcome in COVID-19. Front. Immunol. 2022;13:830061. DOI: 10.3389/fimmu.2022.830061.

73. Perpiñan C., Bertran L., Terra X., Aguilar C., Binetti J., Lopez-Dupla M. et al. On Behalf Of Covid-Study Group. Resistin and IL-15 as Predictors of Invasive Mechanical Ventilation in COVID-19 Pneumonia Irrespective of the Presence of Obesity and Metabolic Syndrome. J. Pers. Med. 2022;12(3):391. DOI: 10.3390/jpm12030391.

74. Meizlish M.L., Pine A.B., Bishai J.D., Goshua G., Nadelmann E.R., Simonov M. et al. A neutrophil activation signature predicts critical illness and mortality in COVID-19. Blood Adv. 2021;5(5):1164–1177. DOI: 10.1182/bloodadvances.2020003568.

75. Zabel B.A., Allen S.J., Kulig P., Allen J.A., Cichy J., Handel T.M. et al. Chemerin activation by serine proteases of the coagulation, fibrinolytic, and inflammatory cascades. J. Biol. Chem. 2005;280:34661–34666. DOI: 10.1074/jbc.M504868200.

76. Treeck O., Buechler C., Ortmann O. Chemerin and cancer. Int. J. Mol. Sci. 2019;20:3750. DOI: 10.3390/ijms20153750.

77. Buechler C., Feder S., Haberl E.M., Aslanidis C. Chemerin isoforms and activity in obesity. Int. J. Mol. Sci. 2019;20:1128. DOI: 10.3390/ijms20051128.

78. Ernst M.C., Sinal C.J. Chemerin: At the crossroads of inflammation and obesity. Trends Endocrinol. Metab. 2010;21:660– 667. DOI: 10.1016/j.tem.2010.08.001.

79. Rourke J.L., Dranse H.J., Sinal C.J. Towards an integrative approach to understanding the role of chemerin in human health and disease. Obes. Rev. 2013;14:245–262. DOI: 10.1111/obr.12009.

80. Yoshimura T., Oppenheim J.J. Chemerin reveals its chimeric nature. J. Exp. Med. 2008;205:2187–2190. DOI: 10.1084/jem.20081736

81. Bondue B., Wittamer V., Parmentier M. Chemerin and its receptors in leukocyte trafficking, inflammation and metabolism. Cytokine Growth Factor Rev. 2011;22:331–338. DOI: 10.1016/j.cytogfr.2011.11.004.

82. Kukla M., Menżyk T., Dembiński M., Winiarski M., Garlicki A., Bociąga-Jasik M. et al. Anti-inflammatory adipokines: chemerin, vaspin, omentin concentrations and SARS-CoV-2 outcomes. Sci. Rep. 2021;11(1):21514. DOI: 10.1038/s41598-021-00928-w.

83. Lavis P., Morra S., Orte Cano C., Albayrak N., Corbière V., Olislagers V. et al. Chemerin plasma levels are increased in COVID-19 patients and are an independent risk factor of mortality. Front. Immunol. 2022 13: 41663. DOI: 10.3389/fimmu.2022.941663.