Pathogenesis of influenza and SARS-CoV-2 co-infection at the extremes of age: decipher the ominous tales of immune vulnerability

doi:10.1007/s44307-025-00057-9

Review

. 2025 Jan 21;3(1):5.

doi: 10.1007/s44307-025-00057-9.

Pathogenesis of influenza and SARS-CoV-2 co-infection at the extremes of age: decipher the ominous tales of immune vulnerability

Kai-Lin Mai^{1

2

3}, Wei-Qi Pan³, Zheng-Shi Lin³, Yang Wang^{4

5}, Zi-Feng Yang^{6

7}

Affiliations

¹ Henan University College of Medicine, Kaifeng, 475004, China.
² School of Life Sciences, Henan University, Kaifeng, 475004, China.
³ National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.
⁴ National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China. wang_yang@gzlab.ac.cn.
⁵ Guangzhou National Laboratory, Guangzhou, 510005, China. wang_yang@gzlab.ac.cn.
⁶ National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China. jeffyah@163.com.
⁷ Guangzhou National Laboratory, Guangzhou, 510005, China. jeffyah@163.com.

PMID: 39883362
DOI: 10.1007/s44307-025-00057-9

Review

Pathogenesis of influenza and SARS-CoV-2 co-infection at the extremes of age: decipher the ominous tales of immune vulnerability

Kai-Lin Mai et al. Adv Biotechnol (Singap). 2025.

. 2025 Jan 21;3(1):5.

doi: 10.1007/s44307-025-00057-9.

Authors

Kai-Lin Mai^{1

2

3}, Wei-Qi Pan³, Zheng-Shi Lin³, Yang Wang^{4

5}, Zi-Feng Yang^{6

7}

Affiliations

¹ Henan University College of Medicine, Kaifeng, 475004, China.
² School of Life Sciences, Henan University, Kaifeng, 475004, China.
³ National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.
⁴ National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China. wang_yang@gzlab.ac.cn.
⁵ Guangzhou National Laboratory, Guangzhou, 510005, China. wang_yang@gzlab.ac.cn.
⁶ National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China. jeffyah@163.com.
⁷ Guangzhou National Laboratory, Guangzhou, 510005, China. jeffyah@163.com.

PMID: 39883362
DOI: 10.1007/s44307-025-00057-9

Abstract

The co-circulation of influenza and SARS-CoV-2 has led to co-infection events, primarily affecting children and older adults, who are at higher risk for severe disease. Although co-infection prevalence is relatively low, it is associated with worse outcomes compared to mono-infections. Previous studies have shown that the outcomes of co-infection depend on multiple factors, including viral interference, virus-host interaction and host response. Children and the elderly exhibit distinct patterns of antiviral response, which involve airway epithelium, mucociliary clearance, innate and adaptive immune cells, and inflammatory mediators. This review explores the pathogeneses of SARS-CoV-2 and influenza co-infection, focusing on the antiviral responses in children and the elderly. By comparing immature immunity in children and immune senescence in older adults, we aim to provide insights for the clinical management of severe co-infection cases.

Keywords: Co-infection; Immature immunity; Immunosenescence; Influenza; SARS-CoV-2.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: All authors approved the manuscript for the submission to this journal. Competing interests: The authors declare no competing interest.

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Zheng C, Jiang X, Yin Y, Dai Q, Tang S, Hu J, Bao C, Yang H, Peng Z. Zheng C, et al. Front Public Health. 2025 Apr 14;13:1555430. doi: 10.3389/fpubh.2025.1555430. eCollection 2025. Front Public Health. 2025. PMID: 40297024 Free PMC article.

References

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1. Aleebrahim-Dehkordi E, Molavi B, Mokhtari M, Deravi N, Fathi M, Fazel T, et al. T helper type (Th1/Th2) responses to SARS-CoV-2 and influenza A (H1N1) virus: from cytokines produced to immune responses. Transpl Immunol. 2022;70:101495. https://doi.org/10.1016/j.trim.2021.101495 . - DOI - PubMed

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[1] Achdout H, Vitner EB, Politi B, Melamed S, Yahalom-Ronen Y, Tamir H, et al. Increased lethality in influenza and SARS-CoV-2 coinfection is prevented by influenza immunity but not SARS-CoV-2 immunity. Nat Commun. 2021;12(1):5819. https://doi.org/10.1038/s41467-021-26113-1 . - DOI - PubMed - PMC

[2] Achdout H, Vitner EB, Politi B, Melamed S, Yahalom-Ronen Y, Tamir H, et al. Increased lethality in influenza and SARS-CoV-2 coinfection is prevented by influenza immunity but not SARS-CoV-2 immunity. Nat Commun. 2021;12(1):5819. https://doi.org/10.1038/s41467-021-26113-1 . - DOI - PubMed - PMC

[3] Adams K, Tastad KJ, Huang S, Ujamaa D, Kniss K, Cummings C, et al. Prevalence of SARS-CoV-2 and influenza coinfection and clinical characteristics among children and adolescents aged <18 years who were hospitalized or died with influenza - United States, 2021–22 influenza season. MMWR Morb Mortal Wkly Rep. 2022;71(50):1589–96. https://doi.org/10.15585/mmwr.mm7150a4 . - DOI - PubMed - PMC

[4] Adams K, Tastad KJ, Huang S, Ujamaa D, Kniss K, Cummings C, et al. Prevalence of SARS-CoV-2 and influenza coinfection and clinical characteristics among children and adolescents aged <18 years who were hospitalized or died with influenza - United States, 2021–22 influenza season. MMWR Morb Mortal Wkly Rep. 2022;71(50):1589–96. https://doi.org/10.15585/mmwr.mm7150a4 . - DOI - PubMed - PMC

[5] Agrawal A, Gupta S. Impact of aging on dendritic cell functions in humans. Ageing Res Rev. 2011;10(3):336–45. https://doi.org/10.1016/j.arr.2010.06.004 . - DOI - PubMed

[6] Agrawal A, Gupta S. Impact of aging on dendritic cell functions in humans. Ageing Res Rev. 2011;10(3):336–45. https://doi.org/10.1016/j.arr.2010.06.004 . - DOI - PubMed

[7] Aksoy E, Albarani V, Nguyen M, Laes J-F, Ruelle J-L, De Wit D, et al. Interferon regulatory factor 3-dependent responses to lipopolysaccharide are selectively blunted in cord blood cells. Blood. 2007;109(7):2887–93. - DOI - PubMed

[8] Aksoy E, Albarani V, Nguyen M, Laes J-F, Ruelle J-L, De Wit D, et al. Interferon regulatory factor 3-dependent responses to lipopolysaccharide are selectively blunted in cord blood cells. Blood. 2007;109(7):2887–93. - DOI - PubMed

[9] Aleebrahim-Dehkordi E, Molavi B, Mokhtari M, Deravi N, Fathi M, Fazel T, et al. T helper type (Th1/Th2) responses to SARS-CoV-2 and influenza A (H1N1) virus: from cytokines produced to immune responses. Transpl Immunol. 2022;70:101495. https://doi.org/10.1016/j.trim.2021.101495 . - DOI - PubMed

[10] Aleebrahim-Dehkordi E, Molavi B, Mokhtari M, Deravi N, Fathi M, Fazel T, et al. T helper type (Th1/Th2) responses to SARS-CoV-2 and influenza A (H1N1) virus: from cytokines produced to immune responses. Transpl Immunol. 2022;70:101495. https://doi.org/10.1016/j.trim.2021.101495 . - DOI - PubMed

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Pathogenesis of influenza and SARS-CoV-2 co-infection at the extremes of age: decipher the ominous tales of immune vulnerability

Affiliations

Pathogenesis of influenza and SARS-CoV-2 co-infection at the extremes of age: decipher the ominous tales of immune vulnerability

Authors

Affiliations

Abstract

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