Expression of Serum Immune Inflammatory Factors in Children with Suppurative Tonsillitis Caused by Adenovirus Infection and Its Correlation with Adenovirus Pneumonia
Abstract
Adenovirus infection is a common cause of pediatric respiratory disease, often misdiagnosed as a bacterial infection. This study compared immune-inflammatory markers in children with adenovirus- vs bacterial-induced suppurative tonsillitis and evaluated their correlation with adenovirus pneumonia.
A retrospective study of 275 children (145 with adenovirus, 130 with bacterial infections) admitted to The First People’s Hospital of Changde, China (January–June 2019), was conducted. Laboratory markers (white blood cell [WBC] count, C-reactive protein [CRP], serum amyloid A [SAA], procalcitonin [PCT], heparin-binding protein [HBP], tumor necrosis factor-alpha [TNF-α], and interleukin 6 [IL-6]) were analyzed. Adenovirus cases were stratified by pneumonia status (58 with pneumonia, 87 without pneumonia) via chest computed tomography.
Compared with the bacterial group, the adenovirus group had lower WBC counts (14.97 [1.37] vs 18.86 [2.65] ×109/L), CRP levels (15.26 [3.44] vs 26.36 [3.18] mg/L), and PCT levels (15.06 [2.12] vs 42.53 [4.58] ng/L) but higher SAA levels (216.75 [39.23] vs 136.55 [28.66] mg/L). Among children with adenovirus, those with pneumonia had elevated SAA (236.39 [38.67] vs 203.65 [33.95] mg/L), HBP (44.30 [8.93] vs 35.62 [6.77] ng/mL), TNF-α (731.52 [99.21] vs 604.21 [95.53] ng/L), and IL-6 (96.86 [17.63] vs 76.55 [15.50] ng/L) levels. A combination of SAA, HBP, TNF-α, and IL-6 predicted pneumonia with an area under the curve of 0.927 (sensitivity, 87.93%; specificity, 88.51%).
SAA, HBP, TNF-α, and IL-6 are strongly associated with adenovirus pneumonia, and their combined measurement improves diagnostic accuracy.
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27. Ren J. Advances in combination therapy for gastric cancer: integrating targeted agents and immunotherapy. Adv Clin Pharmacol Ther. 2024;1(1):1–15.
28. Shi T, Zhao X, Zhang X, Meng L, Li D, Liu X, et al. Immediate and long-term changes in the epidemiology, infection spectrum, and clinical characteristics of viral and bacterial respiratory infections in Western China after the COVID-19 outbreak: a modeling study. Arch Virol. 2023;168(4):120.
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31. Zou S, Liu J, Yang Z, Xiao D, Cao D. SAA and CRP are potential indicators in distinction and severity assessment for children with influenza. Int J Infect Dis. 2021;108:357–62.
32. Kawka M, Płocińska R, Płociński P, Pawełczyk J, Słomka M, Gatkowska J, et al. The functional response of human monocyte-derived macrophages to serum amyloid A and Mycobacterium tuberculosis infection. Front Immunol. 2023;14:1238132.
33. Li J, Wei J, Xu Z, Jiang C, Li M, Chen J, et al. Cytokine/chemokine expression is closely associated with disease severity of human adenovirus infections in immunocompetent adults and predicts disease progression. Front Immunol. 2021;12:691879.
34. Abouelasrar Salama S, Gouwy M, Van Damme J, Struyf S. The turning away of serum amyloid A biological activities and receptor usage. Immunology. 2021;163(2):115–27.
35. Paulsson M, Thelaus L, Riesbeck K, Qvarfordt I, Smith ME, Lindén A, et al. Heparin-binding protein in lower airway samples as a biomarker for pneumonia. Respir Res. 2021;22(1):174.
36. Meng Y, Zhang L, Huang M, Sun G. Blood heparin-binding protein and neutrophil-to-lymphocyte ratio as indicators of the severity and prognosis of community-acquired pneumonia. Respir Med. 2023;208:107144.
37. Del Valle DM, Kim-Schulze S, Huang HH, Beckmann ND, Nirenberg S, Wang B, et al. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat Med. 2020;26(10):1636–43.
38. Hou Y, Liu J, Li Y, Chen F. Study on the changes and significance of immune state and cytokines in children with adenovirus pneumonia. Evid Based Complement Alternat Med. 2022;2022:2419454.
2. Kulanayake S, Tikoo SK. Adenovirus core proteins: structure and function. Viruses. 2021;13(3):481.
3. Mao NY, Zhu Z, Zhang Y, Xu WB. Current status of human adenovirus infection in China. World J Pediatr. 2022;18(8):533–7.
4. Liu MC, Xu Q, Li TT, Wang T, Jiang BG, Lv CL, et al. Prevalence of human infection with respiratory adenovirus in China: a systematic review and meta-analysis. PLoS Negl Trop Dis. 2023;17(2)\:e0011151.
5. Shieh WJ. Human adenovirus infections in pediatric population - an update on clinico-pathologic correlation. Biomed J. 2022;45(1):38–49.
6. Gu J, Su QQ, Zuo TT, Chen YB. Adenovirus diseases: a systematic review and meta-analysis of 228 case reports. Infection. 2021;49(1):1–13.
7. Cheng FJ, Lyu J, Wang LX, Xie YM. Potential efficacy and safety of Xiyanping injection as adjuvant therapy in treatment of suppurative acute tonsillitis: a meta-analysis, trial sequential analysis, and certainty of evidence. Front Pharmacol. 2024;15:1327856.
8. Smith KL, Hughes R, Myrex P. Tonsillitis and tonsilloliths: diagnosis and management. Am Fam Physician. 2023;107(1):35–41.
9. Klug TE, Greve T, Hentze M. Complications of peritonsillar abscess. Ann Clin Microbiol Antimicrob. 2020;19(1):32.
10. Matsuda K, Migueles SA, Huang J, Bolkhovitinov L, Stuccio S, Griesman T, et al. A replication-competent adenovirus-vectored influenza vaccine induces durable systemic and mucosal immunity. J Clin Invest. 2021;131(5)\:e143033.
11. Wallace R, Bliss CM, Parker AL. The immune system - a double-edged sword for adenovirus-based therapies. Viruses. 2024;16(6):928.
12. Perry SS, Brice DC, Sakr AA, Kandeil A, DeBeauchamp J, Ghonim M, et al. Modulation of cytokeratin and cytokine/chemokine expression following influenza virus infection of differentiated human tonsillar epithelial cells. J Virol. 2025;99(6)\:e0146024.
13. Liu Y, Shen Y, Wei B. The clinical risk factors of adenovirus pneumonia in children based on the logistic regression model: correlation with lactate dehydrogenase. Int J Clin Pract. 2022;2022:3001013.
14. Wen S, Lin Z, Zhang Y, Lv F, Li H, Zhang X, et al. The epidemiology, molecular, and clinical of human adenoviruses in children hospitalized with acute respiratory infections. Front Microbiol. 2021;12:629971.
15. Vashisht R, Mirzai S, Koval C, Duggal A. Adenovirus-associated acute respiratory distress syndrome: need for a protocol-based approach. Indian J Crit Care Med. 2020;24(5):367–8.
16. Correction to: Genome and proteomic analysis of risk factors for fatal outcome in children with severe community-acquired pneumonia caused by human adenovirus 7. J Med Virol. 2024;96(1)\:e29364.
17. Lin F, Zhou Q, Li W, Xiao W, Li S, Liu B, et al. A prediction model for acute respiratory distress syndrome in immunocompetent adults with adenovirus-associated pneumonia: a multicenter retrospective analysis. BMC Pulm Med. 2023;23(1):431.
18. Biserni GB, Scarpini S, Dondi A, Biagi C, Pierantoni L, Masetti R, et al. Potential diagnostic and prognostic biomarkers for adenovirus respiratory infection in children and young adults. Viruses. 2021;13(9):1706.
19. Stein M, Shapira M, Bamberger E, Chistyakov I, Dumov D, Srugo I, et al. BV score differentiates viral from bacterial-viral co-infection in adenovirus PCR positive children. Front Pediatr. 2022;10:990750.
20. El-Fakharany EM, Abu-Serie MM, Habashy NH, El-Deeb NM, Abu-Elreesh GM, Zaki S, et al. Inhibitory effects of bacterial silk-like biopolymer on herpes simplex virus type 1, adenovirus type 7 and hepatitis C virus infection. J Funct Biomater. 2022;13(1):24.
21. Moracas C, Poeta M, Grieco F, Tamborino A, Moriondo M, Stracuzzi M, et al. Bacterial-like inflammatory response in children with adenovirus leads to inappropriate antibiotic use: a multicenter cohort study. Infection. 2024. doi:10.1007/s15010-024-02094-6.
22. Chen Q, Lin L, Zhang N, Yang Y. Adenovirus and Mycoplasma pneumoniae co-infection as a risk factor for severe community-acquired pneumonia in children. Front Pediatr. 2024;12:1337786.
23. Wang L, Guo H, Li J, He S, Yang G, Li E. Adenovirus is prevalent in juvenile polyps and correlates with low vitamin D receptor expression. Pediatr Res. 2022;91(7):1703–8.
24. Gómez de Oña C, Alvarez-Argüelles ME, Rojo-Alba S, Casares H, Arroyo M, Rodríguez J, et al. Alterations in biochemical markers in adenovirus infection. Transl Pediatr. 2021;10(5):1248–58.
25. Root-Bernstein R, Huber J, Ziehl A. Complementary sets of autoantibodies induced by SARS-CoV-2, adenovirus and bacterial antigens cross-react with human blood protein antigens in COVID-19 coagulopathies. Int J Mol Sci. 2022;23(19):11486.
26. Marquez-Martinez S, Vijayan A, Khan S, Zahn R. Cell entry and innate sensing shape adaptive immune responses to adenovirus-based vaccines. Curr Opin Immunol. 2023;80:102282.
27. Ren J. Advances in combination therapy for gastric cancer: integrating targeted agents and immunotherapy. Adv Clin Pharmacol Ther. 2024;1(1):1–15.
28. Shi T, Zhao X, Zhang X, Meng L, Li D, Liu X, et al. Immediate and long-term changes in the epidemiology, infection spectrum, and clinical characteristics of viral and bacterial respiratory infections in Western China after the COVID-19 outbreak: a modeling study. Arch Virol. 2023;168(4):120.
29. Li F, Kong S, Xie K, Zhang Y, Yan P, Zhao W. High ratio of C-reactive protein/procalcitonin predicts Mycoplasma pneumoniae infection among adults hospitalized with community acquired pneumonia. Scand J Clin Lab Invest. 2021;81(1):65–71.
30. Ashrafizadeh M. Cell death mechanisms in human cancers: molecular pathways, therapy resistance and therapeutic perspective. J Cancer Biomol Ther. 2024;1(1):17–40.
31. Zou S, Liu J, Yang Z, Xiao D, Cao D. SAA and CRP are potential indicators in distinction and severity assessment for children with influenza. Int J Infect Dis. 2021;108:357–62.
32. Kawka M, Płocińska R, Płociński P, Pawełczyk J, Słomka M, Gatkowska J, et al. The functional response of human monocyte-derived macrophages to serum amyloid A and Mycobacterium tuberculosis infection. Front Immunol. 2023;14:1238132.
33. Li J, Wei J, Xu Z, Jiang C, Li M, Chen J, et al. Cytokine/chemokine expression is closely associated with disease severity of human adenovirus infections in immunocompetent adults and predicts disease progression. Front Immunol. 2021;12:691879.
34. Abouelasrar Salama S, Gouwy M, Van Damme J, Struyf S. The turning away of serum amyloid A biological activities and receptor usage. Immunology. 2021;163(2):115–27.
35. Paulsson M, Thelaus L, Riesbeck K, Qvarfordt I, Smith ME, Lindén A, et al. Heparin-binding protein in lower airway samples as a biomarker for pneumonia. Respir Res. 2021;22(1):174.
36. Meng Y, Zhang L, Huang M, Sun G. Blood heparin-binding protein and neutrophil-to-lymphocyte ratio as indicators of the severity and prognosis of community-acquired pneumonia. Respir Med. 2023;208:107144.
37. Del Valle DM, Kim-Schulze S, Huang HH, Beckmann ND, Nirenberg S, Wang B, et al. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat Med. 2020;26(10):1636–43.
38. Hou Y, Liu J, Li Y, Chen F. Study on the changes and significance of immune state and cytokines in children with adenovirus pneumonia. Evid Based Complement Alternat Med. 2022;2022:2419454.
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| Adenovirus infections Cytokines Inflammatory Pediatrics Suppurative tonsillitis Viral pneumonia | ||
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How to Cite
1.
Lei D, Liu Y, Liu M. Expression of Serum Immune Inflammatory Factors in Children with Suppurative Tonsillitis Caused by Adenovirus Infection and Its Correlation with Adenovirus Pneumonia. Iran J Allergy Asthma Immunol. 2025;:1-11.
