Association of TLR7 Variants with Secondary Bacterial Pneumonia in COVID-19 Patients
TLR7 Variants and Secondary Bacterial Pneumonia in COVID-19
DOI:
https://doi.org/10.54393/pjhs.v7i3.3655Keywords:
Covid-19, Genetic Variants, Innate Immunity, Interferon Pathway, TLR7Abstract
Variations in the TLR7 gene have been linked to impaired immune signaling, which may increase a person's risk of developing secondary infections and developing severe COVID-19. Objectives: To investigate the relationship between variations in the TLR7 gene and the prevalence of co-infections and secondary bacterial pneumonia among hospitalized COVID-19. Methods: A case-control study was a hospital-based study done among 200 RT-PCR-confirmed COVID-19 patients. The secondary bacterial pneumonia (SBP) was determined as another type of clinical deterioration that appeared over 48 hours of admission and was proven by radiological infiltrates and the increase of inflammatory factors; the microbiological confirmation was viewed as supportive but not obligatory. Hardy-Weinberg equilibrium of the female control group was checked, and the genotype was determined with the help of Taqman SNP assays. Results: The average age of the participants was 45.6 ± 12.3 years, and 60 percent of them were men. Among the SBP cases, 85% had microbiological confirmation, while 15% fulfilled predefined clinical, radiological, and inflammatory marker–based criteria for SBP despite negative cultures. Hence, pathogens in SBP cases were Klebsiella pneumoniae 25%, as well as Staphylococcus aureus 35%. Conclusions: TLR7 gene polymorphisms were substantially linked to a roughly three-fold higher risk of secondary bacterial pneumonia in this cohort of hospitalized COVID-19 adults, ages 18 to 65. These results imply that bacterial superinfection may be predisposed by compromised TLR7-mediated antiviral innate responses.
References
Feldman C and Anderson R. The Role of Co-Infections and Secondary Infections in Patients With COVID-19. Pneumonia. 2021 Apr; 13(1): 5. doi: 10.1186/s41479-021-00083-w. DOI: https://doi.org/10.1186/s41479-021-00083-w
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. The Lancet. 2020 Feb; 395(10223): 497-506. doi: 10.1016/S0140-6736(20)30183-5. DOI: https://doi.org/10.1016/S0140-6736(20)30183-5
Xu X, Yu C, Qu J, Zhang L, Jiang S, Huang D et al. Imaging and Clinical Features of Patients with 2019 Novel Coronavirus SARS-Cov-2. European Journal of Nuclear Medicine and Molecular Imaging. 2020 May; 47(5): 1275-1280. doi: 10.1007/s00259-020-04735-9. DOI: https://doi.org/10.1007/s00259-020-04735-9
Zhu X, Yuan W, Shao J, Huang K, Wang Q, Yao S et al. Risk Factors for Mortality in Patients Over 70 Years Old with COVID-19 in Wuhan at the Early Break: Retrospective Case Series. BioMed Center Infectious Diseases. 2021 Aug; 21(1): 821. doi: 10.1186/s12879-021-06450-8. DOI: https://doi.org/10.1186/s12879-021-06450-8
Lansbury L, Lim B, Baskaran V, Lim WS. Co-Infections in People with COVID-19: A Systematic Review and Meta-Analysis. Journal of Infection. 2020 Aug; 81(2): 266-275. doi: 10.1016/j.jinf.2020.05.046. DOI: https://doi.org/10.1016/j.jinf.2020.05.046
Wang C, Khatun MS, Ellsworth CR, Chen Z, Islamuddin M, Nisperuza Vidal AK et al. Deficiency of Tlr7 and Irf7 in Mice Increases the Severity Of COVID-19 Through the Reduced Interferon Production. Communications Biology. 2024 Sep; 7(1): 1162. doi: 10.1038/s42003-024-06872-5. DOI: https://doi.org/10.1038/s42003-024-06872-5
Schultze JL and Aschenbrenner AC. COVID-19 and the Human Innate Immune System. Cell. 2021 Apr; 184(7): 1671-1692. doi: 10.1016/j.cell.2021.02.029. DOI: https://doi.org/10.1016/j.cell.2021.02.029
Spiering AE and de Vries TJ. Why Females Do Better: The X Chromosomal TLR7 Gene-Dose Effect in COVID-19. Frontiers in Immunology. 2021 Nov; 12: 756262. doi: 10.3389/fimmu.2021.756262. DOI: https://doi.org/10.3389/fimmu.2021.756262
Gokhale NS, Smith JR, Van Gelder RD, Savan R. RNA Regulatory Mechanisms that Control Antiviral Innate Immunity. Immunological Reviews. 2021 Nov; 304(1): 77-96. doi: 10.1111/imr.13019. DOI: https://doi.org/10.1111/imr.13019
Van der Made CI, Netea MG, van der Veerdonk FL, Hoischen A. Clinical Implications of Host Genetic Variation and Susceptibility to Severe or Critical COVID-19. Genome Medicine. 2022 Aug; 14(1): 96. doi: 10.1186/s13073-022-01100-3. DOI: https://doi.org/10.1186/s13073-022-01100-3
Zhang Q, Bastard P, Cobat A, Casanova JL. Human Genetic and Immunological Determinants of Critical COVID-19 Pneumonia. Nature. 2022 Mar; 603(7902): 587-598.
Manohar P, Loh B, Nachimuthu R, Hua X, Welburn SC, Leptihn S. Secondary Bacterial Infections in Patients with Viral Pneumonia. Frontiers in Medicine. 2020 Aug; 7: 420. doi: 10.3389/fmed.2020.00420. DOI: https://doi.org/10.3389/fmed.2020.00420
Liu S, Yu C, Tu Q, Zhang Q, Fu Z, Huang Y et al. Bacterial Co-Infection in COVID-19: A Call to Stay Vigilant. PeerJ. 2024 Sep; 12: 18041. doi: 10.7717/peerj.18041. DOI: https://doi.org/10.7717/peerj.18041
Devi P, Kumari P, Yadav A, Tarai B, Budhiraja S, Shamim U et al. Longitudinal Study Across SARS-CoV-2 Variants Identifies Transcriptionally Active Microbes (Tams) Associated with Delta Severity. Iscience. 2023 Oct; 26(10): 1-20. doi: 10.1016/j.isci.2023.107779. DOI: https://doi.org/10.1016/j.isci.2023.107779
Mustafa ZU, Saleem MS, Ikram MN, Salman M, Butt SA, Khan S et al. Co-Infections and Antimicrobial Use Among Hospitalized COVID-19 Patients in Punjab, Pakistan: Findings from a Multicenter, Point Prevalence Survey. Pathogens And Global Health. 2022 Oct; 116(7): 421-427. doi: 10.1080/20477724.2021.1999716. DOI: https://doi.org/10.1080/20477724.2021.1999716
Palmer CS. Innate Metabolic Responses Against Viral Infections. Nature Metabolism. 2022 Oct; 4(10): 1245-1259. doi: 10.1038/s42255-022-00652-3. DOI: https://doi.org/10.1038/s42255-022-00652-3
Boos J, van der Made CI, Ramakrishnan G, Coughlan E, Asselta R, Löscher BS et al. Stratified Analyses Refine the Association Between TLR7 Rare Variants and Severe COVID-19. Human Genetics and Genomics Advances. 2024 Oct; 5(4): 1-12.
Van Der Made CI, Simons A, Schuurs-Hoeijmakers J, Van Den Heuvel G, Mantere T, Kersten S et al. Presence of Genetic Variants Among Young Men with Severe COVID-19. Jama. 2020 Aug; 324(7): 663-673. doi: 10.1001/jama.2020.13719. DOI: https://doi.org/10.1001/jama.2020.13719
Fung B, Gopez A, Servellita V, Arevalo S, Ho C, Deucher A et al. Direct Comparison of SARS-CoV-2 Analytical Limits of Detection Across Seven Molecular Assays. Journal of Clinical Microbiology. 2020 Aug; 58(9): 10-128. doi: 10.1128/JCM.01535-20. DOI: https://doi.org/10.1128/JCM.01535-20
Bengoechea JA, Bamford CG. SARS‐CoV‐2, Bacterial Co‐Infections, and Antimicrobial Resistance: The Deadly Trio In COVID‐19. European Molecular Biology Organization Molecular Medicine. 2020 Jul; 12(7): 12560. doi: 10.15252/emmm.202012560. DOI: https://doi.org/10.15252/emmm.202012560
Martínez-Gómez LE, Martínez-Armenta C, Medina-Luna D, Ordoñez-Sánchez ML, Tusie-Luna T, Ortega-Peña S et al. Implication of Myddosome Complex Genetic Variants in the Outcome Severity of COVID-19 Patients. Journal of Microbiology, Immunology and Infection. 2023 Oct; 56(5): 939-950. doi: 10.1016/j.jmii.2023.06.002. DOI: https://doi.org/10.1016/j.jmii.2023.06.002
Alseoudy MM, Elgamal M, Abdelghany DA, Borg AM, El-Mesery A, Elzeiny D et al. Prognostic Impact of Toll-Like Receptors Gene Polymorphism on Outcome of COVID-19 Pneumonia: A Case-Control Study. Clinical Immunology. 2022 Feb; 235: 108929. doi: 10.1016/j.clim.2022.108929. DOI: https://doi.org/10.1016/j.clim.2022.108929
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