Generic placeholder image

Infectious Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5265
ISSN (Online): 2212-3989

Research Article

The Relationship between the Clinical Course of SARS-CoV-2 Infections and Expression of Bruton's Tyrosine Kinase

In Press, (this is not the final "Version of Record"). Available online 27 June, 2024
Author(s): Mitra Rezaei, Abdolreza Babamahmoodi*, Alireza Mirahmadi, Niloufar Bineshfar, Shima Mahmoudi*, Somayeh Ghadimi, Melika Valizadeh, Tannaz Malakouti, Fatemeh Talebian Taheri, Hadiseh Mohammadpour, Farinaz Nasr Azadani, Seyed Ali Ziai, Seyed Mohammad Poorhosseini and Majid Marjani
Published on: 27 June, 2024

Article ID: e270624231361

DOI: 10.2174/0118715265301312240529044923

Price: $95

Abstract

Objectives: The Bruton tyrosine kinase (BTK), an important element for the production of several inflammatory cytokines, may play a role in the pathogenesis of COVID-19. The aim of this study was to investigate the level of BTK gene expression in COVID-19 cases based on the severity and the outcome of the disease.

Methods: In this study, 33 hospitalized patients with COVID-19 were recruited and were divided into two groups based on the severity of the disease: "mild to moderate" and "severe to critical". A blood sample was taken from each patient, peripheral blood mononuclear cells (PBMCs) were extracted, and BTK gene expression was measured. The level of BTK gene expression was compared based on the demographic data, laboratory results, and the severity and outcome of the disease.

Results: Among 33 patients, 22 (66.7%) were male. Nearly half of the cases had at least one underlying disease. According to the severity of the disease, 12 patients were in the "mild to moderate" group, and 21 were in the "severe to critical" group; eight (24.2%) eventually died. Age, weight, and BMI had no significant relationship with BTK expression. BTK expression was significantly lower in "severe to critical" and ICU-admitted cases and in subjects with low O2 saturation. There was no significant difference in BTK expression between cured and dead patients (p=0.117).

Conclusion: BTK gene expression in PBMCs had an inverse relationship with the severity of the disease of COVID-19. However, no correlation between BTK expression and disease outcome was observed.

[1]
Tal S, Spectre G, Kornowski R, Perl L. Venous thromboembolism complicated with COVID-19: What do we know so far? Acta Haematol 2020; 143(5): 417-24.
[http://dx.doi.org/10.1159/000508233] [PMID: 32396903]
[2]
Mahmoudi S, Rezaei M, Mansouri N, Marjani M, Mansouri D. Immunologic features in coronavirus disease 2019: Functional exhaustion of T cells and cytokine storm. J Clin Immunol 2020; 40(7): 974-6.
[http://dx.doi.org/10.1007/s10875-020-00824-4] [PMID: 32648027]
[3]
Mohammadpour H, Ziai A, Sadr M, Rezaei M, Marjani M, Tabarsi P. A novel coronavirus disease (COVID-19): A review of host cell signaling pathways. Tanaffos 2020; 19(2): 108-11.
[PMID: 33262797]
[4]
Ghazizadeh Esslami G, Mamishi S, Pourakbari B, Mahmoudi S. Systematic review and meta‐analysis on the serological, immunological, and cardiac parameters of the multisystem inflammatory syndrome (MIS‐C) associated with SARS‐CoV‐2 infection. J Med Virol 2023; 95(7): e28927.
[http://dx.doi.org/10.1002/jmv.28927] [PMID: 37436781]
[5]
McDonald C, Xanthopoulos C, Kostareli E. The role of Bruton’s tyrosine kinase in the immune system and disease. Immunology 2021; 164(4): 722-36.
[http://dx.doi.org/10.1111/imm.13416] [PMID: 34534359]
[6]
López-Herrera G, Vargas-Hernández A, González-Serrano ME, et al. Bruton’s tyrosine kinase—an integral protein of B cell development that also has an essential role in the innate immune system. J Leukoc Biol 2013; 95(2): 243-50.
[http://dx.doi.org/10.1189/jlb.0513307] [PMID: 24249742]
[7]
Weber ANR, Bittner Z, Liu X, Dang TM, Radsak MP, Brunner C. Bruton’s tyrosine kinase: An emerging key player in innate immunity. Front Immunol 2017; 8: 1454.
[http://dx.doi.org/10.3389/fimmu.2017.01454] [PMID: 29167667]
[8]
Ye B, Zhou C, Guo H, Zheng M. Effects of BTK signalling in pathogenic microorganism infections. J Cell Mol Med 2019; 23(10): 6522-9.
[http://dx.doi.org/10.1111/jcmm.14548] [PMID: 31397086]
[9]
Roschewski M, Lionakis MS, Sharman JP, et al. Inhibition of Bruton tyrosine kinase in patients with severe COVID-19. Sci Immunol 2020; 5(48): eabd0110.
[http://dx.doi.org/10.1126/sciimmunol.abd0110] [PMID: 32503877]
[10]
Rezaei M, Babamahmoodi A, Marjani M. Bruton’s tyrosine kinase: A promising target for the treatment of COVID-19. Tanaffos 2020; 19(2): 85-8.
[PMID: 33262793]
[11]
Rezaei M, Barati S, Babamahmoodi A, Dastan F, Marjani M. The possible role of bruton tyrosine kinase inhibitors in the treatment of COVID-19: A review. Curr Ther Res Clin Exp 2022; 96: 100658.
[http://dx.doi.org/10.1016/j.curtheres.2021.100658] [PMID: 34931090]
[12]
Coronavirus disease 2019 (COVID-19) treatment guidelines. 2023. Available from: https://www.covid19treatmentguidelines.nih.gov/ cited March 31, 2023.
[13]
McGonagle D, Sharif K, O’Regan A, Bridgewood C. The role of cytokines including interleukin-6 in COVID-19 induced pneumonia and macrophage activation syndrome-like disease. Autoimmun Rev 2020; 19(6): 102537.
[http://dx.doi.org/10.1016/j.autrev.2020.102537] [PMID: 32251717]
[14]
Borczuk AC, Yantiss RK. The pathogenesis of coronavirus-19 disease. J Biomed Sci 2022; 29(1): 87.
[http://dx.doi.org/10.1186/s12929-022-00872-5] [PMID: 36289507]
[15]
Samelson LE. Immunoreceptor signaling. Cold Spring Harb Perspect Biol 2011; 3(12): a011510.
[http://dx.doi.org/10.1101/cshperspect.a011510] [PMID: 22134888]
[16]
Liu Y. Bruton’s Tyrosine Kinase: Structure and Functions. Expression and Mutations 2013.
[17]
Du Z, Lovly CM. Mechanisms of receptor tyrosine kinase activation in cancer. Mol Cancer 2018; 17(1): 58.
[http://dx.doi.org/10.1186/s12943-018-0782-4] [PMID: 29455648]
[18]
Mohamed AJ, Yu L. Bäckesjö CM, et al. Bruton’s tyrosine kinase (Btk): Function, regulation, and transformation with special emphasis on the PH domain. Immunol Rev 2009; 228(1): 58-73.
[http://dx.doi.org/10.1111/j.1600-065X.2008.00741.x] [PMID: 19290921]
[19]
Treon SP, Castillo JJ, Skarbnik AP, et al. The BTK inhibitor ibrutinib may protect against pulmonary injury in COVID-19–infected patients. Blood 2020; 135(21): 1912-5.
[http://dx.doi.org/10.1182/blood.2020006288] [PMID: 32302379]
[20]
Reda G, Noto A, Cassin R, et al. Reply to “CLL and COVID-19 at the hospital clinic of Barcelona: An interim report” Analysis of six hematological centers in lombardy. Leukemia 2020; 34(9): 2531-2.
[http://dx.doi.org/10.1038/s41375-020-0966-y] [PMID: 32753689]
[21]
Scarfò L, Chatzikonstantinou T, Rigolin GM, et al. COVID-19 severity and mortality in patients with chronic lymphocytic leukemia: A joint study by ERIC, the European Research Initiative on CLL, and CLL Campus. Leukemia 2020; 34(9): 2354-63.
[http://dx.doi.org/10.1038/s41375-020-0959-x] [PMID: 32647324]
[22]
Thibaud S, Tremblay D, Bhalla S, Zimmerman B, Sigel K, Gabrilove J. Protective role of Bruton tyrosine kinase inhibitors in patients with chronic lymphocytic leukaemia and COVID‐19. Br J Haematol 2020; 190(2): e73-6.
[http://dx.doi.org/10.1111/bjh.16863] [PMID: 32433778]
[23]
Gomes AMC, Farias GB, Trombetta AC, et al. Phenotype of BTK ‐lacking myeloid cells during prolonged COVID ‐19 and upon convalescent plasma. Eur J Haematol 2023; 110(2): 209-12.
[http://dx.doi.org/10.1111/ejh.13881] [PMID: 36208028]
[24]
Soresina A, Moratto D, Chiarini M, et al. Two X‐linked agammaglobulinemia patients develop pneumonia as COVID‐19 manifestation but recover. Pediatr Allergy Immunol 2020; 31(5): 565-9.
[http://dx.doi.org/10.1111/pai.13263] [PMID: 32319118]
[25]
An S, Li Y, Lin Y, et al. Genome-wide profiling reveals alternative polyadenylation of innate immune-related mRNA in patients With COVID-19. Front Immunol 2021; 12: 756288.
[http://dx.doi.org/10.3389/fimmu.2021.756288] [PMID: 34777369]
[26]
Gandhi RT, Lynch JB, del Rio C. Mild or moderate COVID-19. N Engl J Med 2020; 383(18): 1757-66.
[http://dx.doi.org/10.1056/NEJMcp2009249] [PMID: 32329974]
[27]
Berlin DA, Gulick RM, Martinez FJ. Severe Covid-19. N Engl J Med 2020; 383(25): 2451-60.
[http://dx.doi.org/10.1056/NEJMcp2009575] [PMID: 32412710]
[28]
Wang F, Nie J, Wang H, et al. Characteristics of peripheral lymphocyte subset alteration in COVID-19 pneumonia. J Infect Dis 2020; 221(11): 1762-9.
[http://dx.doi.org/10.1093/infdis/jiaa150] [PMID: 32227123]
[29]
Claude L, Martino F, Hermand P, et al. Platelet caspase‐1 and Bruton tyrosine kinase activation in patients with COVID‐19 is associated with disease severity and reversed in vitro by ibrutinib. Res Pract Thromb Haemost 2022; 6(8): e12811.
[http://dx.doi.org/10.1002/rth2.12811] [PMID: 36514346]
[30]
Park A, Iwasaki A. Type I and type III interferons – Induction, signaling, evasion, and application to combat COVID-19. Cell Host Microbe 2020; 27(6): 870-8.
[http://dx.doi.org/10.1016/j.chom.2020.05.008] [PMID: 32464097]
[31]
Florence JM, Krupa A, Booshehri LM, Davis SA, Matthay MA, Kurdowska AK. Inhibiting Bruton’s tyrosine kinase rescues mice from lethal influenza-induced acute lung injury. Am J Physiol Lung Cell Mol Physiol 2018; 315(1): L52-8.
[http://dx.doi.org/10.1152/ajplung.00047.2018] [PMID: 29516781]

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy