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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 Pan  3 , Zheng-Shi Lin  3 , Yang Wang  4   5 , Zi-Feng Yang  6   7
Affiliations
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). .

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.

Figures

Fig. 1
Fig. 1
Characteristics of host antiviral responses in upper respiratory tract (A and B), lower respiratory tract and peripheral blood (C and D) in children and older adults, respectively. A and B, the upper respiratory tracts of children are characterized by narrowed airway lumens and mucus hypersecretion; while older adults have aging-related epithelial damages. Dotted black boxes illustrate the distinct receptor patterns of SARS-CoV-2 and influenza in the upper airway of children and older adults. C and D, alterations in immune cell functions and cytokine responses that may contribute to severe immunopathology in children and older adults during pulmonary viral infections. Abbreviations: SA, sialic acid; ACE2, angiotensin-converting enzyme II; Neu, neutrophils; NET, neutrophil extracellular traps; ROS, reactive oxygen species; AM, alveolar macrophages; NK, natural killer cells; Mo/MΦ, monocytes/macrophages; DC, dendritic cells
See this image and copyright information in PMC

References

    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. 10.1038/s41467-021-26113-1. - DOI - PMC - PubMed
    1. 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. 10.15585/mmwr.mm7150a4. - DOI - PMC - PubMed
    1. Agrawal A, Gupta S. Impact of aging on dendritic cell functions in humans. Ageing Res Rev. 2011;10(3):336–45. 10.1016/j.arr.2010.06.004. - DOI - PMC - PubMed
    1. 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
    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. 10.1016/j.trim.2021.101495. - DOI - PMC - PubMed

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