Harris E, Most. COVID-19 deaths worldwide were among older people. JAMA. 2023;329:704.

PubMed  Google Scholar 

López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: an expanding universe. Cell. 2023;186:243–78.

PubMed  Google Scholar 

Lo Tartaro D, Neroni A, Paolini A, Borella R, Mattioli M, Fidanza L, et al. Molecular and cellular immune features of aged patients with severe COVID-19 pneumonia. Commun Biol. 2022;5:590.

CAS  PubMed  PubMed Central  Google Scholar 

Schuliga M, Read J, Knight DA. Ageing mechanisms that contribute to tissue remodeling in lung disease. Ageing Res Rev. 2021;70:101405.

CAS  PubMed  Google Scholar 

Chow RD, Majety M, Chen S. The aging transcriptome and cellular landscape of the human lung in relation to SARS-CoV-2. Nat Commun. 2021;12:4.

CAS  PubMed  PubMed Central  Google Scholar 

Chait M, Yilmaz MM, Shakil S, Ku AW, Dogra P, Connors TJ et al. Immune and epithelial determinants of age-related risk and alveolar injury in fatal COVID-19. JCI Insight. 2022;7.

Song T-Z, Zheng H-Y, Han J-B, Jin L, Yang X, Liu F-L, et al. Delayed severe cytokine storm and immune cell infiltration in SARS-CoV-2-infected aged Chinese rhesus macaques. Zool Res. 2020;41:503–16.

CAS  PubMed  PubMed Central  Google Scholar 

Zheng H-Y, He X-Y, Li W, Song T-Z, Han J-B, Yang X, et al. Pro-inflammatory microenvironment and systemic accumulation of CXCR3 + cell exacerbate lung pathology of old rhesus macaques infected with SARS-CoV-2. Signal Transduct Target Ther. 2021;6:328.

CAS  PubMed  PubMed Central  Google Scholar 

Speranza E, Purushotham JN, Port JR, Schwarz B, Flagg M, Williamson BN, et al. Age-related differences in immune dynamics during SARS-CoV-2 infection in rhesus macaques. Life Sci Alliance. 2022;5:e202101314.

CAS  PubMed  PubMed Central  Google Scholar 

Erjefält JS, de Souza Xavier Costa N, Jönsson J, Cozzolino O, Dantas KC, Clausson C-M, et al. Diffuse alveolar damage patterns reflect the immunological and molecular heterogeneity in fatal COVID-19. EBioMedicine. 2022;83:104229.

PubMed  PubMed Central  Google Scholar 

de Souza Xavier Costa N, Ribeiro Júnior G, do Nascimento ECT, de Brito JM, Antonangelo L, Faria CS, et al. COVID-19 induces more pronounced extracellular matrix deposition than other causes of ARDS. Respir Res. 2023;24:281.

PubMed  PubMed Central  Google Scholar 

Gasparini A. Comorbidity: an R package for computing comorbidity scores. J Open Source Softw. 2018;3:648.

Google Scholar 

Quan H, Sundararajan V, Halfon P, Fong A, Burnand B, Luthi J-C, et al. Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Med Care. 2005;43:1130–9.

PubMed  Google Scholar 

Charlson M, Szatrowski TP, Peterson J, Gold J. Validation of a combined comorbidity index. J Clin Epidemiol. 1994;47:1245–51.

CAS  PubMed  Google Scholar 

Duarte-Neto AN, Monteiro RAA, Silva LFF, Malheiros DMAC, Oliveira EP, Theodoro‐Filho J et al. Pulmonary and systemic involvement in COVID‐19 patients assessed with ultrasound‐guided minimally invasive autopsy. Histopathology [Internet]. 2020;77:186–97. Available from: https://onlinelibrary.wiley.com/doi/https://doi.org/10.1111/his.14160

Giugni FR, Aiello VD, Faria CS, Pour SZ, Cunha M dos, Giugni P. Understanding yellow fever-associated myocardial injury: an autopsy study. EBioMedicine. 2023;96:104810.

PubMed  PubMed Central  Google Scholar 

Phillips SP, Carver LF. Greatest risk factor for death from COVID-19: older age, chronic disease burden, or place of residence?? Descriptive analysis of Population-Level Canadian data. Int J Environ Res Public Health. 2023;20:7181.

PubMed  PubMed Central  Google Scholar 

Dessie ZG, Zewotir T. Mortality-related risk factors of COVID-19: a systematic review and meta-analysis of 42 studies and 423,117 patients. BMC Infect Dis. 2021;21:855.

CAS  PubMed  PubMed Central  Google Scholar 

Ramasamy S, Subbian S. Erratum for Ramasamy and subbian, critical determinants of cytokine storm and type I interferon response in COVID-19 pathogenesis. Clin Microbiol Rev. 2021;34.

Panda A, Qian F, Mohanty S, van Duin D, Newman FK, Zhang L, et al. Age-Associated decrease in TLR function in primary human dendritic cells predicts influenza vaccine response. J Immunol. 2010;184:2518–27.

CAS  PubMed  Google Scholar 

Volkova M, Zhang Y, Shaw AC, Lee PJ. The role of Toll-like receptors in Age-Associated lung diseases. J Gerontol Biol Sci Med Sci. 2012;67A:247–53.

CAS  Google Scholar 

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. Commun Biol. 2024;7:1162.

CAS  PubMed  PubMed Central  Google Scholar 

Lazear HM, Schoggins JW, Diamond MS. Shared and distinct functions of type I and type III interferons. Immunity. 2019;50:907–23.

CAS  PubMed  PubMed Central  Google Scholar 

King C, Sprent J. Dual nature of type I interferons in SARS-CoV-2-Induced inflammation. Trends Immunol. 2021;42:312–22.

CAS  PubMed  PubMed Central  Google Scholar 

Galani IE, Triantafyllia V, Eleminiadou E-E, Koltsida O, Stavropoulos A, Manioudaki M, et al. Interferon-λ mediates Non-redundant Front-Line antiviral protection against influenza virus infection without compromising host fitness. Immunity. 2017;46:875–e8906.

CAS  PubMed  Google Scholar 

Goritzka M, Durant LR, Pereira C, Salek-Ardakani S, Openshaw PJM, Johansson C. Alpha/Beta interferon receptor signaling amplifies early Proinflammatory cytokine production in the lung during respiratory syncytial virus infection. J Virol. 2014;88:6128–36.

PubMed  PubMed Central  Google Scholar 

Goritzka M, Makris S, Kausar F, Durant LR, Pereira C, Kumagai Y, et al. Alveolar macrophage–derived type I interferons orchestrate innate immunity to RSV through recruitment of antiviral monocytes. J Exp Med. 2015;212:699–714.

CAS  PubMed  PubMed Central  Google Scholar 

Gilbert C, Lefeuvre C, Preisser L, Pivert A, Soleti R, Blanchard S et al. Age-Related expression of IFN-λ1 versus IFN-I and Beta-Defensins in the nasopharynx of SARS-CoV-2-Infected individuals. Front Immunol. 2021;12.

Krämer B, Knoll R, Bonaguro L, ToVinh M, Raabe J, Astaburuaga-García R, et al. Early IFN-α signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19. Immunity. 2021;54:2650–e266914.

PubMed  PubMed Central  Google Scholar 

Lee JS, Park S, Jeong HW, Ahn JY, Choi SJ, Lee H et al. Immunophenotyping of COVID-19 and influenza highlights the role of type I interferons in development of severe COVID-19. Sci Immunol. 2020;5.

Bagheri-Hosseinabadi Z, Rezazadeh Zarandi E, Mirabzadeh M, Amiri A, Abbasifard M. mRNA expression of toll-like receptors 3, 7, 8, and 9 in the nasopharyngeal epithelial cells of coronavirus disease 2019 patients. BMC Infect Dis. 2022;22:448.

CAS  PubMed  PubMed Central  Google Scholar 

Bekeredjian-Ding IB, Wagner M, Hornung V, Giese T, Schnurr M, Endres S, et al. Plasmacytoid dendritic cells control TLR7 sensitivity of Naive B cells via type I IFN. J Immunol. 2005;174:4043–50.

PubMed  Google Scholar 

Sirén J, Pirhonen J, Julkunen I, Matikainen S, IFN-α Regulates. TLR-Dependent gene expression of IFN-α, IFN-β, IL-28, and IL-29. J Immunol. 2005;174:1932–7.

PubMed  Google Scholar 

Wang Y, Wang Q, He F, Qiao N, Li X, Wei L, et al. Age-dependent decrease of Circulating T follicular helper cells correlates with disease severity in elderly patients with COVID-19. Clin Immunol. 2024;266:110329.

CAS  PubMed  Google Scholar 

Frasca D, Blomberg BB. Aging affects human B cell responses. J Clin Immunol. 2011;31:430–5.

PubMed  PubMed Central  Google Scholar 

Mebratu YA, Soni S, Rosas L, Rojas M, Horowitz JC, Nho R. The aged extracellular matrix and the profibrotic role of senescence-associated secretory phenotype. Am J Physiology-Cell Physiol. 2023;325:C565–79.

CAS  Google Scholar 

Mauad T, Duarte-Neto AN, da Silva LFF, de Oliveira EP, de Brito JM, do, Nascimento ECT et al. Tracking the time course of pathological patterns of lung injury in severe COVID-19. Respir Res. 2021;22.

Goplen NP, Cheon IS, Sun J. Age-Related Dynamics of Lung-Resident Memory CD8 + T Cells in the Age of COVID-19. Front Immunol [Internet]. 2021;12. Available from: https://www.frontiersin.org/articles/https://doi.org/10.3389/fimmu.2021.636118/full

Wang T, Dai H, Wan N, Moore Y, Dai Z. The role for monocyte chemoattractant Protein-1 in the generation and function of memory CD8 + T cells. J Immunol. 2008;180:2886–93.

CAS  PubMed  Google Scholar 

Korobova ZR, Arsentieva NA, Totolian AA. Macrophage-Derived chemokine MDC/CCL22: an ambiguous finding in COVID-19. Int J Mol Sci. 2023;24:13083.

CAS  PubMed  PubMed Central  Google Scholar 

Idda ML, McClusky WG, Lodde V, Munk R, Abdelmohsen K, Rossi M, et al. Survey of senescent cell markers with age in human tissues. Aging. 2020;12:4052–66.

CAS  PubMed  PubMed Central  Google Scholar 

Triana-Martinez F, Pierantoni A, Graca D, Bergo V, Emelyanov A, Grigorash BB et al. p16 High immune cell - controlled disease tolerance as a broad defense and healthspan extending strategy. 2024.

Wang S, Yao X, Ma S, Ping Y, Fan Y, Sun S, et al. A single-cell transcriptomic landscape of the lungs of patients with COVID-19. Nat Cell Biol. 2021;23:1314–28.