Risk factors of COVID-19: immunological aspects
DOI: 10.32364/2587-6821-2023-7-11-5
T.V. Glazanova, E.R. Shilova, I.E. Pavlova
Russian Research Institute of Hematology and Transfusiology of the Federal Medical Biological Agency of Russia, St. Petersburg, Russian Federation
Recent studies devoted to the patterns of the COVID-19 course in patients of various groups indicate a significant role of the immunity state in the disease development. Risk groups of severe disease course, including senile age, obesity and immunodeficiency conditions, have been identified. Research is underway to identify the genetic predisposition to SARS-CoV-2 infection and determine the poor prognosis in COVID-19. The presented article examines the immunological aspects of pathological conditions associated with an unfavorable prognosis of COVID-19. A complex immune response (including both innate immune mechanisms and an adaptive systemic response) develops in response to SARS-CoV-2 infection. The key mechanism of multisystem organ failure is a hyperimmune reaction with the development of a systemic inflammatory response, the so-called "cytokine storm", and the characteristics of the immune response largely determine the disease severity. In this regard, the immune response characteristics in patients at risk are of particular interest, including studies concerning the immunological aspects of a more severe disease course depending on age, the history of obesity, diabetes mellitus and other pathological conditions, as well as various genetic factors, which is the subject of active study at present.
Keywords: immune system, COVID-19, SARS-CoV-2, risk factors, obesity, oncological diseases, genetic predisposition, immune response.
For citation: Glazanova T.V., Shilova E.R., Pavlova I.E. Risk factors of COVID-19: immunological aspects. Russian Medical Inquiry. 2023;7(11):751–758 (in Russ.). DOI: 10.32364/2587-6821-2023-7-11-5.
About the authors:
Tatiana V. Glazanova — Dr. Sc. (Med.), Head of the Research Laboratory of Immunology, Russian Research Institute of Hematology and Transfusiology of the Federal Medical Biological Agency of Russia; 16, 2nd Sovetskaya str., St. Petersburg, 191024, Russian Federation; ORCID iD 0000-0002-1022-8127.
Elena R. Shilova — C. Sc. (Med.), Leading Researcher at the Research Laboratory of Immunology, Russian Research Institute of Hematology and Transfusiology of the Federal Medical Biological Agency of Russia; 16, 2nd Sovetskaya str., St. Petersburg, 191024, Russian Federation; ORCID iD 0000-0002-9253-6181.
Irina E. Pavlova — Dr. Sc. (Med.), Chief Researcher of the Research Laboratory of Immunology, Russian Research Institute of Hematology and Transfusiology of the Federal Medical Biological Agency of Russia; 16, 2nd Sovetskaya str., St. Petersburg, 191024, Russian Federation; ORCID iD 0000-0001-7756-4902.
Contact information: Tatiana V. Glazanova, e-mail: tatyana-glazanova@yandex.ru.
Financial Disclosure: no authors have a financial or property interest in any material or method mentioned.
There is no conflict of interests.
Received 10.03.2023.
Revised 04.04.2023.
Accepted 27.04.2023.
References
1. Mohn K.G., Bredholt G., Zhou F. et al. Durable T-cellular and humoral responses in SARS-CoV-2 hospitalized and community patients. PloS One. 2022;17(2):e0261979. DOI: 10.1371/journal.pone.0261979.
2. Хавинсон В.Х., Кузник Б.И. Осложнения у больных COVID-19. Предполагаемые механизмы коррекции. Клиническая медицина. 2020;98(4):256–265. DOI: 10.30629/0023-2149-2020-98-4-256-265. [Khavinson V.K., Kuznik B.I. Complications in COVID-19 patients. Suggested mechanisms of correction. Clinical Medicine (Russian Journal). 2020;98(4):256–265 (in Russ.)]. DOI: 10.30629/0023-2149-2020-98-4-256-265.
3. Mather M.W., Jardine L., Talks B. et al. Complexity of immune responses in COVID-19. Semin Immunol. 2021;55:101545. DOI: 10.1016/j.smim.2021.101545.
4. Болевич C.Б., Болевич С.С. Комплексный механизм развития СOVID-19. Сеченовский вестник. 2020;11(2):50–61. DOI: 10.47093/2218-7332.2020.11.2.50-61. [Bolevich S.B., Bolevich S.S. Complex mechanism of development of СOVID-19. Sechenovskiy vestnik. 2020;11(2):50–61 (in Russ.)]. DOI: 10.47093/2218-7332.2020.11.2.50-61.
5. Sette A., Crotty S. Adaptive immunity to SARS-CoV-2 and COVID-19. Cell. 2021;184(4):861–880. DOI: 10.1016/j.cell.2021.01.007.
6. Liu C., Martins A.J., Lau W.W. et al. Time-resolved systems immunology reveals a late juncture linked to fatal COVID-19. Cell. 2021;184(7):1836–1857.e22. DOI: 10.1016/j.cell.2021.02.018.
7. Rydyznski-Moderbacher C., Ramirez S.I., Dan J.M. et al. Antigen-specific adaptive immunity to SARS-Cov-2 in acute COVID-19 and associations with age and disease severity. Cell. 2020;183(4):996–1012.e19. DOI: 10.1016/j.cell.2020.09.038.
8. Zhou F., Yu T., Du R. et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054–1062. DOI: 10.1016/S0140-6736(20)30566-3.
9. Bernardes J.P., Mishra N., Tran F. et al. Longitudinal multi-omics analyses identify responses of megakaryocytes, erythroid cells, and plasmablasts as hallmarks of severe COVID-19. Immunity. 2020;53(6):1296–1314.e9. DOI: 10.1016/j.immuni.2020.11.017.
10. Chen J., Lau Y.F., Lamirande E.W. et al. Cellular immune responses to severe acute respiratory syndrome coronavirus (SARS-CoV) infection in senescent BALB/c mice: CD4+T cells are important in control of SARS-CoV infection. J Virol. 2010;84(3):1289–1301. DOI: 10.1128/JVI.01281-09.
11. Zheng H.Y., Zhang M., Yang C.X. et al. Elevated exhaustion levels and reduced functional diversity of T cells in peripheral blood may predict severe progression in COVID-19 patients. Cell Mol Immunol. 2020;17(5):541–543. DOI: 10.1038/s41423-020-0401-3.
12. Delanghe J.R., De Buyzere M.L., Speeckaert M.M. C3 and ACE1 polymorphisms are more important confounders in the spread and outcome of COVID-19 in comparison with ABO polymorphism. Eur J Prev Cardiol. 2020;27(12):1331–1332. DOI: 10.1177/2047487320931305.
13. Fang S., Wang H., Lu L. et al. Decreased complement C3 levels are associated with poor prognosis in patients with COVID-19: a retrospective cohort study. Int Immunopharmacol. 2020;89(Pt A):107070. DOI: 10.1016/j.intimp.2020.107070.
14. Jamilloux Y., Henry T., Belot A. et al. Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions. Autoimmun Rev. 2020;19(7):102567. DOI: 10.1016/j.autrev.2020.102567.
15. Hong K.-H., Choi J.-P., Hong S.-H. et al. Predictors of mortality in Middle East respiratory syndrome (MERS). Thorax. 2018;73(3):286–289. DOI: 10.1136/thoraxjnl-2016-209313.
16. Dessie Z.G., Zewotir T. Mortality-related risk factors of COVID-19: a systematic review and meta-analysis of 42 studies and 423,117 patients. BMC Infect Dis. 2021;21:855. DOI: 10.1186/s12879-021-06536-3.
17. Wang D., Hu B., Hu C. et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;17;323(11):1061–1069. DOI: 10.1001/jama.2020.1585.
18. Wang K., Zuo P., Liu Y. et al. Clinical and laboratory predictors of in-hospital mortality in 305 patients with COVID-19: a cohort study in Wuhan, China. Clin Infect Dis. 2020;71(16):2079–2088. DOI: 10.1093/cid/ciaa538.
19. Yoneyama M., Kikuchi M., Natsukawa T. et al. The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol. 2004;5(7):730–737. DOI: 10.1038/ni1087.
20. Pourgheysari B., Khan N., Best D. et al. The cytomegalovirus-specific CD4+ T-cell response expands with age and markedly alters the CD4+ T-cell repertoire. J Virol. 2007;81(14):7759–7765. DOI: 10.1128/JVI.01262-06.
21. Goronzy J.J., Weyand C.M. Successful and maladaptive T cell aging. Immunity. 2017;46(3):364–378. DOI: 10.1016/j.immuni.2017.03.010.
22. Xu H., Barnes G.T., Yang Q. et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest. 2003;112(12):1821–1830. DOI: 10.1172/JCI19451.
23. Weisberg S.P., McCann D., Desai M. et al. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003;112(12):1796–1808. DOI: 10.1172/JCI19246.
24. Демидова Т.Ю., Волкова Е.В., Грицкевич Е.Ю. Ожирение и COVID-19: фатальная связь. Инфекционные болезни: новости, мнения, обучение. 2020;9(3):25–32. DOI: 10.33029/2305-3496-2020-9-3S-25-32. [Demidova T.Yu., Volkova Е.V., Grickevich Е.Yu. Obesity and COVID-19: a fatal link. Infectious Diseases: News, Opinions, Training. 2020;9(3):25–32 (in Russ.)]. DOI: 10.33029/2305-3496-2020-9-3S-25-32.
25. Sattar N., McInnes I.B., McMurray J.J.V. Obesity is a risk factor for severe COVID-19 infection: Multiple Potential Mechanisms. Circulation. 2020;142(1):4–6. DOI: 10.1161/CIRCULATIONAHA.120.047659.
26. Budu-Aggrey A., Brumpton B., Tyrrell J. et al. Evidence of a causal relationship between body mass index and psoriasis: a mendelian randomization study. PLoS Med. 2019;16:e1002739. DOI: 10.1371/journal.pmed.1002739.
27. Романцова Т.И., Сыч И.П. Иммунометаболизм и метавоспаление при ожирении. Ожирение и метаболизм. 2019;16(4):3–17. DOI: 14341/omet12218. [Romantsova T.I., Sych Y.P. Immunometabolism and Metainflammation in Obesity. Obesity and Metabolism. 2019;16(4):3–17 (in Russ.)]. DOI: 14341/omet12218.
28. Cai S., Liao W., Chen S. et al. Association between obesity and clinical prognosis in patients infected with SARS-CoV-2. Infect Dis Poverty. 2020;9(1):80. DOI: 10.1186/s40249-020-00703-5.
29. Халимов Ю.Ш., Агафонов П.В., Киреева Е.Б. Ожирение и COVID-19: инсайты двух пандемий. Журнал инфектологии. 2022;14(2):27–38. DOI: 10.22625/2072-6732-2022-14-2-27-38. [Khalimov Yu.S., Agafonov P.V., Kireeva E.B. Obesity and COVID-19: insights from two pandemics. Journal of Infectology. 2022;14(2):27–38 (in Russ.)]. DOI: 10.22625/2072-6732-2022-14-2-27-38.
30. Гусова З.Р., Воробьев С.В., Хрипун И.А. и др. О роли цитокинов в патогенезе метаболических нарушений и андрогенного дефицита у мужчин с ожирением и метаболическим синдромом. Фундаментальные исследования. 2014;10(6):1227–1233. (Электронный ресурс.) URL: https://fundamental-research.ru/ru/article/view?id=36021) (дата обращения: 08.11.2022). [Gusova Z.R., Vorobev S.V., Khripun I.A. Role of cytokines in the pathogenesis of metabolic disorders and androgen deficiency in men with obesity and metabolic syndrome. Fundamental research. 2014;10(6):1227–1233. URL: https://fundamental-research.ru/ru/article/view?id=36021 (access date: 08.11.2022) (in Russ.)].
31. Tamara A., Tahapary D.L. Obesity as a predictor for a poor prognosis of COVID-19: A systematic review. Diabetes Metab Syndr. 2020;14(4):655–659. DOI: 10.1016/j.dsx.2020.05.020.
32. Барсуков И.А., Демина А.А. Ожирение и инсулинорезистентность: механизмы развития и пути коррекции. РМЖ. 2021;2:26–30. [Barsukov I.A., Demina A.A. Obesity and insulin resistance: pathogenesis and ways of correction. RMJ. 2021;2:26–30 (in Russ.)].
33. Поддубная И.В., Тумян Г.С., Трофимова О.П. и др. Особенности ведения онкогематологических пациентов в условиях пандемии COVID-19. Современная онкология. 2020;22(3):45–58. DOI: 10.26442/18151434.2020.3.200152. [Poddubnaya I.V., Tumian G.S., Trofimova O.P. et al. Features of management of oncohematological patients in the context of the COVID-19 pandemic. Journal of Modern Oncology. 2020;22(3):45–58 (in Russ.)]. DOI: 10.26442/18151434.2020.3.200152.
34. Mato A., Roeker L., Lamanna N. et al. Outcomes of COVID-19 in patients with CLL: a multicenter international experience. Blood. 2020;136(10):1134–1143. DOI: 10.1182/blood.2020006965.
35. Lee C., Shah M., Hoyos D. et al. Prolonged SARS-CoV-2 infection in patients with lymphoid malignancies. Cancer Discov. 2022;12(1):62–73. DOI: 10.1158/2159-8290.CD-21-1033.
36. Бубнова Л.Н., Павлова И.Е., Беркос А.С. и др. Особенности распределения групп аллелей HLA-А*, B*, DRB1* среди лиц, перенесших COVID-19. Медицинская иммунология. 2021;23(3):523–532. DOI: 10.15789/1563-0625-DPO-2334. [Bubnova L.N., Pavlova I.E., Berkos A.S. et al. Distribution patterns of HLA-A*, B*, DRB1* allele groups among persons who underwent COVID-19. Medical Immunology (Russia). 2021;23(3):523–532 (in Russ.)]. DOI: 10.15789/1563-0625-DPO-2334.
37. Трошина Е.А., Юкина М.Ю., Нуралиева Н.Ф., Мокрышева Н.Г. Роль генов системы HLA: от аутоиммунных заболеваний до COVID-19. Проблемы эндокринологии. 2020;4(66):9–15. DOI: 10.14341/probl12470. [Troshina E.A., Yukina M.Yu., Nuralieva N.F., Mokrysheva N.G. The role of HLA genes: from autoimmune diseases to COVID-19. Problems of Endocrinology. 2020;66(4):9–15 (in Russ.)]. DOI: 10.14341/probl12470.
38. Nguyen A., David J.K., Maden S.K. et al. Human leukocyte antigen susceptibility map for SARS-CoV-2. J Virol. 2020;94(13):e00510–20. DOI: 10.1128/JVI.00510-20.
39. Adhiahet A.H., Abdullah M.H., Alsudani M.Y. et al. Association between ABO blood groups and susceptibility to COVID-19: profile of age and gender in Iraqi patients. Egyptian Journal of Medical Human Genetics. 2020;21:76. DOI: 10.1186/s43042-020-00115-y.
40. Zhao J., Yang Y., Huang H.-P. et al. Relationship between the ABO Blood Group and the COVID-19 Susceptibility. MedRxiv. 2020.03.11.20031096. Preprint. DOI: 10.1101/2020.03.11.20031096.
41. Rodríguez Y., Novelli L., Rojas M. et al. Autoinflammatory and autoimmune conditions at the crossroad of COVID-19. J Autoimmun. 2020;114:102506. DOI: 10.1016/j.jaut.2020.102506.
42. Zhang Q., Bastard P., Liu Z. et al. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science. 2020;370(6515):eabd4570. DOI: 10.1126/science.abd4570.
43. Solanich X., Rigo-Bonnin R., Gumucio V.D. et al. Pre-existing autoantibodies neutralizing high concentrations of type I interferons in almost 10% of COVID-19 patients admitted to intensive care in Barcelona. J Clin Immunol. 2021;41(8):1733–1744. DOI: 10.1007/s10875-021-01136-x.
44. Abdullah M., Chai P.-S., Chong M.-Y. et al. Gender effect on in vitro lymphocyte subset levels of healthy individuals. Cell Immunol. 2012;272(2):214–219. DOI: 10.1016/j.cellimm.2011.10.009.
45. Ding T., Zhang J., Wang T. et al. A multi-hospital study in Wuhan, China: protective effects of non-menopause and female hormones on SARS-CoV-2 infection. MedRxiv. March 2020. Preprint. DOI: 10.1101/2020.03.26.20043943.
46. Scully E.P., Haverfield J., Ursin R.L. et al. Considering how biological sex impacts immune responses and COVID-19 outcomes. Nat Rev Immunol. 2020;20(7):442–447. DOI: 10.1038/s41577-020-0348-8.
47. Parohan M., Yaghoubi S., Seraji A. et al. Risk factors for mortality in patients with Coronavirus disease 2019 (COVID-19) infection: a systematic review and meta-analysis of observational studies. Aging Male. 2020;23(5):1416–1424. DOI: 10.1080/13685538.2020.1774748.
48. Van der Made C.I., Simons A., Schuurs-Hoeijmakers J. et al. Presence of Genetic Variants Among Young Men With Severe COVID-19. JAMA. 2020;324(7):663–673. DOI: 10.1001/jama.2020.13719.
49. Tvito A., Ronson A., Ghosheh R. et al. Anti-CD20 monoclonal antibodies inhibit seropositive response to Covid-19 vaccination in non-Hodgkin lymphoma patients within 6 months after treatment. Exp Hematol. 2022;107:20–23. DOI: 10.1016/j.exphem.2021.12.396.
50. Tamariz-Amador L.E., Battaglia A., Maia C. et al. Immune biomarkers to predict SARS-CoV-2 vaccine effectiveness in patients with hematological malignancies. Blood Cancer J. 2021;11(12):202. DOI: 10.1038/s41408-021-00594-1.
51. Chung D., Shah G., Devlin S.L. et al. Disease- and Therapy-Specific Impact on Humoral Immune Responses to COVID-19 Vaccination in Hematologic Malignancies. Blood Cancer Discov. 2021;2(6):568–576. DOI: 10.1158/2643-3230.BCD-21-0139.
52. Woodruff M., Ramonell R., Haddad N. et al. Dysregulated naïve B cells and de novo autoreactivity in severe COVID-19. Nature. 2022;611:139–147. DOI: 10.1038/s41586-022-05273-0.
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