Influence of Interferon Gamma Gene rs2430561 Variant on Complicated Course of Pneumonia in Patients with COVID-19

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Abstract

Background: Pneumonia is one of the most common complications of the course of COVID-19. Interferon-γ (IFN-γ) is an essential cytokine for lung defense against intracellular and extracellular pathogens. Since the rs2430561 variant of the IFNG gene, which encodes IFN-γ, affects the production of IFN-γ, it can potentially be associated with a severe course of COVID-19.

Objective: The aim of our research was to determine the impact of the rs2430561 variant of the IFNG gene on the propensity of patients to develop and experience a severe course of COVID-19-related pneumonia.

Methods: The study included 117 patients with a complicated course of COVID-19- associated pneumonia, who were hospitalized in the intensive care unit. All patients received a standard clinical and laboratory evaluation and course of treatment for COVID- 19. IFNG gene variants were determined by PCR method. For comparisons, we used clinical and laboratory indicators from the inpatients’ medical records, which reflected the course of the patient's disease, taking into account the rs2430561 variants of the IFNG gene.

Results: In the group of patients, the following genotype frequencies were found: TT – 18.8%, TA – 52.1%, and AA – 29.1%. The results showed that AA genotype carriers had essentially higher SpO2/FiO2 ratio (p=0.043). High base excess rates were present in patients with the TT genotype (p=0.047). It was found that patients with the T allele (whether homozygous or heterozygous state) had significantly higher concentrations of such electrolytes as potassium and sodium (p=0.016 and p=0.004, respectively).

Сonclusion: In patients with COVID-19, the rs2430561 variant of the IFNG gene is linked to a complicated course of pneumonia. Certainly, this finding requires further research.

Graphical Abstract

[1]
Vicini S, Bellini D, Iannarelli A, et al. Pneumonia Frequency and Severity in Patients With Symptomatic COVID-19: Impact of mRNA and Adenovirus Vector Vaccines. AJR Am J Roentgenol 2022; 219(5): 752-61.
[http://dx.doi.org/10.2214/AJR.22.27843] [PMID: 35642761]
[2]
Lei D, Lancaster JR Jr, Joshi MS, et al. Activation of alveolar macrophages and lung host defenses using transfer of the interferon-gamma gene. Am J Physiol Lung Cell Mol Physiol 1997; 272(5): L852-9.
[http://dx.doi.org/10.1152/ajplung.1997.272.5.L852] [PMID: 9176248]
[3]
Smith NLD, Denning DW. Clinical implications of interferon‐ γ genetic and epigenetic variants. Immunology 2014; 143(4): 499-511.
[http://dx.doi.org/10.1111/imm.12362] [PMID: 25052001]
[4]
Schroder K, Hertzog PJ, Ravasi T, Hume DA. Interferon-γ An overview of signals, mechanisms and functions. J Leukoc Biol 2004; 75(2): 163-89.
[http://dx.doi.org/10.1189/jlb.0603252] [PMID: 14525967]
[5]
dbSNP – NCBI [Internet]. Nih.gov. 2019. Available from: https://www.ncbi.nlm.nih.gov/snp/
[6]
Pravica V, Perrey C, Stevens A, Lee JH, Hutchinson IV. A single nucleotide polymorphism in the first intron of the human IFN-γ gene. Hum Immunol 2000; 61(9): 863-6.
[http://dx.doi.org/10.1016/S0198-8859(00)00167-1] [PMID: 11053629]
[7]
Zhang Q, Song J, Yu J, et al. Polymorphism of IFN-γ+874T/A associated with production of IFN-γ affects human papillomavirus susceptibility in rural women from Luohe, Henan, China. OncoTargets Ther 2018; 11: 4339-44.
[http://dx.doi.org/10.2147/OTT.S161544] [PMID: 30100739]
[8]
Álvarez GI, Pino HDRE, Barbero AM, et al. Association of IFN-γ +874 A/T SNP and hypermethylation of the -53 CpG site with tuberculosis susceptibility. Front Cell Infect Microbiol 2023; 13: 1080100.
[http://dx.doi.org/10.3389/fcimb.2023.1080100] [PMID: 36743307]
[9]
Nie W, Meng L, Wang X, Xiu Q. Interferon-gamma +874A/T polymorphism is associated with asthma risk: A meta-analysis. J Investig Allergol Clin Immunol 2014; 24(5): 324-30.
[PMID: 25345302]
[10]
Trajkov D, Stojkovikj MJ, Petlichkovski A, et al. Association of cytokine gene polymorphisms with chronic obstructive pulmonary disease in Macedonians. Iran J Allergy Asthma Immunol 2009; 8(1): 31-42.
[PMID: 19279357]
[11]
Peddireddy V, Badabagni SP, Sulthana S, Kolla VK, Gundimeda SD, Mundluru H. Association of TNFα−308, IFNγ+874, and IL10−1082 gene polymorphisms and the risk of non-small cell lung cancer in the population of the South Indian state of Telangana. Int J Clin Oncol 2016; 21(5): 843-52.
[http://dx.doi.org/10.1007/s10147-016-0972-2] [PMID: 27282611]
[12]
Balzanelli M, Distratis P, Lazzaro R, et al. Analysis of gene single nucleotide polymorphisms in COVID-19 disease highlighting the susceptibility and the severity towards the infection. Diagnostics 2022; 12(11): 2824.
[http://dx.doi.org/10.3390/diagnostics12112824] [PMID: 36428884]
[13]
Dhabaan AAN, Alwan MH. Polymorphisms of IFN-γ T/A +874 gene and relationship with COVID 19 in Iraqi population. IOP conference series. University of Al-Qadisiyah, Iraq 2021; 790: 012049.
[http://dx.doi.org/10.1088/1755-1315/790/1/012049]
[14]
Approval of the protocol “Providing medical assistance for treatment Coronavirus disease (COVID-19)” [Internet]. Official web portal of the Parliament of Ukraine. Available from: https://zakon.rada.gov.ua/rada/show/v0762282-20#n6851
[15]
Ahmed AA, Rasheed Z, Salem T, Dhubaibi AMS, Robaee AAA, Alzolibani AA. TNF-α − 308 G/A and IFN-γ + 874 A/T gene polymorphisms in Saudi patients with cutaneous leishmaniasis. BMC Med Genet 2020; 21(1): 104.
[http://dx.doi.org/10.1186/s12881-020-01043-9] [PMID: 32404058]
[16]
Minchenko ZM, Dmytrenko OO, Liubarets TF, et al. Complex analysis of the role of cytokine gene polymorphisms as prognostic factor of the risk of plasma cell myeloma in persons suffered after the Chornobyl NPP accident. Probl Radiac Med Radiobiol 2022; 27: 374-84.
[http://dx.doi.org/10.33145/2304-8336-2022-27-374-384] [PMID: 36582102]
[17]
da Silva RS, Ju E, Meng W, et al. Broad Severe Acute Respiratory Syndrome Coronavirus 2 Cell Tropism and Immunopathology in Lung Tissues From Fatal Coronavirus Disease 2019. J Infect Dis 2021; 223(11): 1842-54.
[http://dx.doi.org/10.1093/infdis/jiab195] [PMID: 33837392]
[18]
Zanza C, Romenskaya T, Manetti AC, et al. Cytokine storm in COVID-19: Immunopathogenesis and therapy. Medicina 2022; 58(2): 144.
[http://dx.doi.org/10.3390/medicina58020144] [PMID: 35208467]
[19]
Raković TN, Whitfield JR. Between immunomodulation and immunotolerance: The role of IFNγ in SARS-CoV-2 disease. Cytokine 2021; 146: 155637.
[http://dx.doi.org/10.1016/j.cyto.2021.155637] [PMID: 34242899]
[20]
Karki R, Sharma BR, Tuladhar S, Williams EP, Zalduondo L, Samir P, et al. Synergism of TNF-α and IFN-γ Triggers Inflammatory Cell Death, Tissue Damage, and Mortality in SARS-CoV-2 Infection and Cytokine Shock Syndromes. Cell 2021; 184(1): 149-68.
[http://dx.doi.org/10.1016/j.cell.2020.11.025]
[21]
Lucas C, Wong P, Klein J, et al. Longitudinal analyses reveal immunological misfiring in severe COVID-19. Nature 2020; 584(7821): 463-9.
[http://dx.doi.org/10.1038/s41586-020-2588-y] [PMID: 32717743]
[22]
Melo BD, Payant NBE, Liu WC, et al. Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19. Cell 2020; 181(5): 1036-1045.e9.
[http://dx.doi.org/10.1016/j.cell.2020.04.026] [PMID: 32416070]
[23]
Khalaj AJ, Sterky FH, Sclip A, et al. Deorphanizing FAM19A proteins as pan-neurexin ligands with an unusual biosynthetic binding mechanism. J Cell Biol 2020; 219(9): e202004164.
[http://dx.doi.org/10.1083/jcb.202004164] [PMID: 32706374]
[24]
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.
[http://dx.doi.org/10.1126/science.abd4570] [PMID: 32972995]
[25]
Bonaventura A, Mumoli N, Mazzone A, et al. Correlation of SpO2/FiO2 and PaO2/FiO2 in patients with symptomatic COVID-19: An observational, retrospective study. Intern Emerg Med 2022; 17(6): 1769-75.
[http://dx.doi.org/10.1007/s11739-022-02981-3] [PMID: 35460432]
[26]
Roozeman JP, Mazzinari G, Serpa Neto A, et al. Prognostication using SpO2/FiO2 in invasively ventilated ICU patients with ARDS due to COVID-19 – Insights from the PRoVENT-COVID study. J Crit Care 2022; 68: 31-7.
[http://dx.doi.org/10.1016/j.jcrc.2021.11.009] [PMID: 34872014]
[27]
Alfano G, Fontana F, Mori G, et al. Acid base disorders in patients with COVID-19. Int Urol Nephrol 2022; 54(2): 405-10.
[http://dx.doi.org/10.1007/s11255-021-02855-1] [PMID: 34115260]
[28]
Amin A, Moon R, Agiro A, et al. In-hospital mortality, length of stay, and hospitalization cost of COVID-19 patients with and without hyperkalemia. Am J Med Sci 2022; 364(4): 444-53.
[http://dx.doi.org/10.1016/j.amjms.2022.04.029] [PMID: 35490703]
[29]
Hirsch JS, Uppal NN, Sharma P, et al. Prevalence and outcomes of hyponatremia and hypernatremia in patients hospitalized with COVID-19. Nephrol Dial Transplant 2021; 36(6): 1135-8.
[http://dx.doi.org/10.1093/ndt/gfab067] [PMID: 33724428]
[30]
Gadotti AC, Deus CM, Telles JP, et al. IFN-γ is an independent risk factor associated with mortality in patients with moderate and severe COVID-19 infection. Virus Res 2020; 289: 198171.
[http://dx.doi.org/10.1016/j.virusres.2020.198171] [PMID: 32979474]