General immunologic reactivity of patients with COVID-19 and its relation to gene polymorphism, severity of clinical course of the disease and combination with comorbidities

Автор(и)

DOI:

https://doi.org/10.26641/2307-0404.2024.3.313570

Ключові слова:

COVID-19, immunological reactivity, immune resistance, genotype, comorbidities

Анотація

The aim of the study is to identify and evaluate the general immunological reactivity of patients with COVID-19 and its relationship with gene polymorphism, severity of the clinical course of the disease and combination with comorbidities. A cohort study was conducted involving 204 patients with COVID-19 diagnosed with community-acquired pneumonia of mild, moderate, and severe degrees who also had comorbidities: endocrinopathies (46 patients), cardiovascular diseases (82 patients), and comorbidities of the ENT organs, connective tissue, gastrointestinal tract, chronic kidney disease (CKD), which were grouped into the group "other comorbidities (76 patients). Among the patients there were 51.97% (106) women and 48.03% (98) men. The average age of patients was 55.93±8.75 years. The polymorphism of the NOS3 (rs2070744), FGB (rs1800790) and TMPRSS2 (rs12329760) genes was determined by real-time polymerase chain reaction (qualitative determination). The overall immunological reactivity was detected and evaluated based on the analysis of 14 integral leukocyte indices: leukocyte shift index, absolute leukocyte count/erythrocyte sedimentation rate (ESR) ratio index, lymphocyte-granulocyte index, lymphocyte index, immunological resistance and reactivity index, and others. The overall immunological reactivity of the body of patients with coronavirus infection increases in the presence of the wild-type T-allele of the eNOS gene (rs2070744) in the patient's genotype, especially the CC genotype, by 21.98-57.89% (p≤0.029-0.001), against the background of a decrease in the index of nonspecific reactivity and the ratio of agranulocytes to ESR – by 23.0 (p=0.039) and 15.74% (p=0.044), indicating the onset of specific immunological reactions in the active infectious process. Carriers of the mutational A-allele of the FGB gene (rs1800790) and the TT genotype of the TMPRSS2 gene (rs12329760) showed higher immune reactivity and resistance, which was significantly confirmed by the level of increase in immune reactivity by 6.31-17.21% (p=0.007) and 22.05-35.78% (p≤0.06-0.004), respectively, against the background of a slightly higher rate of allergy (especially in owners of the AG genotype of the FGB gene – by 68.18%, PAG=0.017), a higher ratio of agranulocytes and ESR – by 18.30-21.84% (p≤0.008-0.007) and 19.46-31.07% (p=0.023), with a higher ratio of lymphocytes and eosinophils – by 13.35-19.20% (p≤0.002-0.001). The influence of the wild-type T-allele of the eNOS gene (rs2070744), the A-allele of the FGB gene (rs1800790) and the TT genotype of the TMPRSS2 gene (rs12329760) on the immunological reactivity of the body of a patient with coronavirus infection was revealed.

Посилання

Azkur AK, Akdis M, Azkur D, Sokolowska M, van de Veen W, Brüggen MC, et al. Immune response to SARS‐CoV‐2 and mechanisms of immunopathological changes in COVID‐19. Allergy. 2020 Jul;75(7):1564-81. doi: https://doi.org/10.1111/all.14364

Paces J, Strizova Z, Danie SM, Cerny J. COVID-19 and the immune system. Physiological research. 2020;69(3):379. doi: https://doi.org/10.33549/physiolres.934492

Shi Y, Wang Y, Shao C, Huang J, Gan J, Huang X, et al. COVID-19 infection: the perspectives on immune responses. Cell Death & Differentiation. 2020;27(5):1451-4. doi: https://doi.org/10.1038/s41418-020-0530-3

Siracusano G, Pastori C, Lopalco L. Humoral immune responses in COVID-19 patients: a window on the state of the art. Frontiers in immunology. 2020;11:551868. doi: https://doi.org/10.3389/fimmu.2020.01049

Mortaz E, Tabarsi P, Varahram M, Folkerts G, Adcock IM. The immune response and immunopathology of COVID-19. Frontiers in immunology. 2020;11:558378. doi: https://doi.org/10.3389/fimmu.2020.02037

Ravindran R, McReynolds C, Yang J, Hammock BD, Ikram A, Ali A, et al. Immune response dynamics in COVID-19 patients to SARS-CoV-2 and other human coronaviruses. PloS one. 2021;16(7):e0254367. doi: https://doi.org/10.1371/journal.pone.0254367

Boechat JL, Chora I, Morais A, Delgado L. The immune response to SARS-CoV-2 and COVID-19 immunopathology–current perspectives. Pulmonology. 2021;27(5):423-37. doi: https://doi.org/10.1016/j.pulmoe.2021.03.008

Jafarzadeh A, Jafarzadeh S, Nozari P, Mokhtari P, Nemati M. Lymphopenia an important immunological abnormality in patients with COVID‐19: possible mechanisms. Scandinavian journal of immunology. 2021;93(2):e12967. doi: https://doi.org/10.1111/sji.12967

Oliveira DS, Medeiros NI, Gomes JA. Immune response in COVID-19: What do we currently know? Microbial pathogenesis. 2020;148:104484. doi: https://doi.org/10.1016/j.micpath.2020.104484

Sydorchuk lP, Syrota BS, Sydorchuk AR, Gerush OV, Muzyka NY, Sheremet MI, et al. Clinical markers of immune disorders in the pathogenesis of Escherichia coli enteritis. Arch Balk Med Union. 2019;54(1):89-96. doi: https://doi.org/10.31688/ABMU.2019.54.1.12

Moody R, Wilson K, Flanagan KL, Jaworowski A, Plebanski M. Adaptive immunity and the risk of autoreactivity in COVID-19. International journal of molecular sciences. 2021;22(16):8965. doi: https://doi.org/10.3390/ijms22168965

Schön MP, Berking C, Biedermann T, Buhl T, Erpenbeck L, Eyerich K, et al. COVID‐19 and immunological regulations-from basic and translational aspects to clinical implications. JDDG: Journal der Deutschen Dermatologischen Gesellschaft. 2020;18(8):795-807. doi: https://doi.org/10.1111/ddg.14169

Elshazli RM, Toraih EA, Elgaml A, El-Mowafy M, El-Mesery M, Amin MN, Diagnostic and prognostic value of hematological and immunological markers in COVID-19 infection: A meta-analysis of 6320 patients. PloS one. 2020;15(8):e0238160. doi: https://doi.org/10.1371/journal.pone.0238160

Sydorchuk A, Sydorchuk L, Gutnitska A, Vasyuk V, Tkachuk O, Dzhuryak V, et al. The role of NOS3 (rs2070744) and GNB3 (rs5443) genes’ polymorphisms in endothelial dysfunction pathway and carotid intima-media thickness in hypertensive patients. General Physiology & Biophysics. 2023;42(2):179-90. doi: https://doi.org/10.4149/gpb_2022060

[Protocol "Provision of medical assistance for the treatment of coronavirus disease (COVID-19)". Approved by the Order of the Ministry of Health of Ukraine of April 2, 2020 No. 762 (as amended by the Order of the Ministry of Health of Ukraine of May 17, 2023 No. 913)]. [Internet]. 2023 [cited 2024 Mar 2024]. Ukrainian. Available from: https://moz.gov.ua/uploads/9/46447-dn_913_17052023_dod.pdf

[Medical care standards "Coronavirus disease (COVID-19)". Approved by Order No. 722 of the Ministry of Health of Ukraine dated March 28, 2020]. [Internet]. 2020 [cited 2024 Mar 2024]. Ukrainian. Available from: https://www.dec.gov.ua/wp/content/uploads/2022/02/2020_722_standart_covid_19.pdf

CDC 24/7: saving lives, protecting people. Prevention Actions to Use at All COVID-19 Community Levels [Internet]. Center for Disease Control and Prevention. 2023 [cited 2024 Mar 2024]. Available from: https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/prevention.html

Artika IM, Dewi YP, Nainggolan IM, Siregar JE, Antonjaya U. Real-Time Polymerase Chain Reaction: Current Techniques, Applications, and Role in COVID-19 Diagnosis. Genes (Basel). 2022 Dec 16;13(12):2387. doi: https://doi.org/10.3390/genes13122387

Usul E, Şan İ, Bekgöz B, Şahin A. Role of hematological parameters in COVID-19 patients in the emergency room. Biomark Med. 2020 Sep;14(13):1207-15. doi: https://doi.org/10.2217/bmm-2020-0317

Dwivedi AK. How to write statistical analysis section in medical research. J Investig Med. 2022 Dec;70(8):1759-70. doi: https://doi.org/10.1136/jim-2022-002479

Yuan X, Huang W, Ye B, Chen C, Huang R, Wu F, et al. Changes of hematological and immunological parameters in COVID-19 patients. Int J Hematol. 2020 Oct;112(4):553-9. doi: https://doi.org/10.1007/s12185-020-02930-w

Birindelli S, Tarkowski MS, Gallucci M, Schiu-ma M, Covizzi A, Lewkowicz P, et al. Definition of the immune parameters related to COVID-19 severity. Fron-tiers in Immunology. 2022;13:850846. doi: https://doi.org/10.3389/fimmu.2022.850846

Qin R, He L, Yang Z, Jia N, Chen R, Xie J, et al. Identification of parameters representative of immune dysfunction in patients with severe and fatal COVID-19 infection: a systematic review and meta-analysis. Clinical Reviews in Allergy & Immunology. 2023;64(1):33-65. doi: https://doi.org/10.1007/s12016-021-08908-8

Chatterjee S, Nalla LV, Sharma M, Sharma N, Singh AA, Malim FM, et al. Association of COVID-19 with comorbidities: an update. ACS Pharmacology & Translational Science. 2023;6(3):334-54. doi: https://doi.org/10.1021/acsptsci.2c00181

Kamyshnyi A, Krynytska I, Matskevych V, Marushchak M, Lushchak O. Arterial hypertension as a risk comorbidity associated with COVID-19 pathology. International journal of hypertension. 2020 Dec 4:2020:8019360. doi: https://doi.org/10.1155/2020/8019360

Fishchuk L, Rossokha Z, Pokhylko V, Cherniavska Y, Dubitska O, Vershyhora V, et al. NOS3 (rs61722009) gene variants testing in prediction of COVID-19 pneumonia severity. Nitric Oxide. 2023;134:44-8. doi: https://doi.org/10.1016/j.niox.2023.04.002

Stopsack KH, Mucci LA, Antonarakis ES, Nelson PS, Kantoff PW. TMPRSS2 and COVID-19: Serendipity or Opportunity for Intervention? Cancer discovery. 2020;10(6):779-82. doi: https://doi.org/10.1158/2159-8290.CD-20-0451

Rezaei-Tavirani M, Nejad MR, Arjmand B, Tavirani SR, Razzaghi M, Mansouri V. Fibrinogen dysregulation is a prominent process in fatal conditions of COVID-19 infection; a proteomic analysis. Archives of Academic Emergency Medicine. 2021;9(1):e26. doi: https://doi.org/10.22037/aaem.v9i1.1128

Sur S, Khatun M, Steele R, Isbell TS, Ray R, Ray RB. Exosomes from COVID-19 patients carry tenascin-C and fibrinogen-β in triggering inflammatory signals in cells of distant organ. International Journal of Molecular Sciences. 2021;22(6):3184. doi: https://doi.org/10.3390/ijms22063184

##submission.downloads##

Опубліковано

2024-10-16

Як цитувати

1.
Sokolenko M, Sydorchuk L, Sokolenko L, Sokolenko A. General immunologic reactivity of patients with COVID-19 and its relation to gene polymorphism, severity of clinical course of the disease and combination with comorbidities. Med. perspekt. [інтернет]. 16, Жовтень 2024 [цит. за 05, Листопад 2024];29(3):108-17. доступний у: https://journals.uran.ua/index.php/2307-0404/article/view/313570

Номер

Розділ

КЛІНІЧНА МЕДИЦИНА