Role of Sex and Age in Fatal Outcomes of COVID-19: Women and Older Centenarians Are More Resilient
Abstract
:1. Introduction
2. Have Women Been More Resilient Than Men?
3. Did Centenarians Die Less Than Remaining Older People?
4. Older Centenarians Were More Resistant to the SARS-CoV-2 Compared to Younger Centenarians?
5. Discussions
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
ACE2 | angiotensin II converting enzyme |
β-CoV | Betacoronavirus |
CFR | case fatality rate |
COVID-19 | Coronavirus disease 2019 |
H1N1 | hemagglutinin 1 and neuraminidase 1 |
IFN | Interferon |
RHS | Regional Health Services |
SARS-CoV-2 | severe acute respiratory syndrome coronavirus 2. |
TLR | Toll-like receptor |
TMPRSS2 | transmembrane serine protease 2 |
References
- Hu, B.; Guo, H.; Zhou, P.; Shi, Z.-L. Characteristics of SARS-CoV-2 and COVID-19. Nat. Rev. Microbiol. 2021, 19, 141–154, Erratum in Nat. Rev. Microbiol. 2022, 20, 315. [Google Scholar] [CrossRef] [PubMed]
- Pojero, F.; Candore, G.; Caruso, C.; Di Bona, D.; Groneberg, D.A.; Ligotti, M.E.; Accardi, G.; Aiello, A. The Role of Immunogenetics in COVID-19. Int. J. Mol. Sci. 2021, 22, 2636. [Google Scholar] [CrossRef] [PubMed]
- Zarulli, V.; Jones, J.A.B.; Oksuzyan, A.; Lindahl-Jacobsen, R.; Christensen, K.; Vaupel, J.W. Women live longer than men even during severe famines and epidemics. Proc. Natl. Acad. Sci. USA 2018, 115, E832–E840. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Franceschi, C.; Bonafè, M. Centenarians as a model for healthy aging. Biochem. Soc. Trans. 2003, 31, 457–461. [Google Scholar] [CrossRef]
- Caruso, C.; Passarino, G.; Puca, A.; Scapagnini, G. “Positive biology”: The centenarian lesson. Immun. Ageing 2012, 9, 5. [Google Scholar] [CrossRef] [Green Version]
- Caruso, C. (Ed.) Centenarians; Springer: Cham, Switzerland, 2019. [Google Scholar]
- Poulain, M.; Chambre, D.; Pes, G.M. Centenarians exposed to the Spanish flu in their early life better survived to COVID-19. Aging 2021, 13, 21855–21865. [Google Scholar] [CrossRef]
- Caruso, C.; Accardi, G.; Aiello, A.; Calabrò, A.; Ligotti, M.E.; Candore, G. Centenarians born before 1919 are resistant to COVID-19. Aging Clin. Exp. Res. 2023, 35, 217–220. [Google Scholar] [CrossRef]
- Scully, E.P.; Haverfield, J.; Ursin, R.L.; Tannenbaum, C.; Klein, S.L. Considering how biological sex impacts immune responses and COVID-19 outcomes. Nat. Rev. Immunol. 2020, 20, 442–447. [Google Scholar] [CrossRef]
- Pradhan, A.; Olsson, P.E. Sex differences in severity and mortality from COVID-19: Are males more vulnerable? Biol. Sex Differ. 2020, 11, 53. [Google Scholar] [CrossRef]
- Nasiri, M.J.; Haddadi, S.; Tahvildari, A.; Farsi, Y.; Arbabi, M.; Hasanzadeh, S.; Jamshidi, P.; Murthi, M.; Mirsaeidi, M. COVID-19 Clinical Characteristics, and Sex-Specific Risk of Mortality: Systematic Review and Meta-Analysis. Front. Med. 2020, 7, 459. [Google Scholar] [CrossRef]
- Caselli, G.; Egidi, V. Gender differences in COVID-19 cases and death rates in Italy. Ital. J. Gend. Specif. Med. 2020, 6, 96–99. [Google Scholar]
- Niessen, A.; Teirlinck, A.C.; McDonald, S.A.; van der Hoek, W.; van Gageldonk-Lafeber, R. RIVM COVID-19 epidemiology, sur-veillance group, Knol MJ. Sex differences in COVID-19 mortality in the Netherlands. Infection 2022, 50, 709–717. [Google Scholar] [CrossRef]
- Marcon, G.; Tettamanti, M.; Capacci, G.; Fontanel, G.; Spanò, M.; Nobili, A.; Forloni, G.; Franceschi, C. COVID-19 mortality in Lom-bardy: The vulnerability of the oldest old and the resilience of male centenarians. Aging 2020, 12, 15186–15195. [Google Scholar] [CrossRef]
- Couderc, A.L.; Correard, F.; Nouguerède, E.; Berbis, J.; Rey, D.; Daumas, A.; Villani, P. Centenarians in nursing homes during the COVID-19 pandemic. Aging 2021, 13, 6247–6257. [Google Scholar] [CrossRef]
- Gellert, P.; Kohl, R.; Jürchott, K.; Hering, C.; Gangnus, A.; Steinhagen-Thiessen, E.; Kuhlmey, A.; Schwinger, A. Centenarians from Long-Term Care Facilities and COVID-19-Relevant Hospital Admissions. J. Am. Med. Dir. Assoc. 2022, 23, 1117–1118. [Google Scholar] [CrossRef]
- Fulop, T.; Larbi, A.; Pawelec, G.; Khalil, A.; Cohen, A.A.; Hirokawa, K.; Witkowski, J.M.; Franceschi, C. Immunology of Aging: The Birth of Inflammaging. Clin. Rev. Allergy Immunol. 2021, 18, 1–14. [Google Scholar] [CrossRef]
- Alberts, S.C.; Archie, E.A.; Gesquiere, L.R.; Altmann, J.; James, W.; Vaupel, J.W.; Christensen, K. The Male-Female Health-Survival Paradox: A Comparative Perspective on Sex Differences in Aging and Mortality. In Committee on Population, Division of Behavioral and Social Sciences and Education; Weinstein, M., Lane, M.A., Eds.; National Research Council; Sociality, Hierarchy, Health: Comparative Biodemography: A Collection of Papers; National Academies Press: Washington, DC, USA, 2014; p. 15. [Google Scholar]
- Ostan, R.; Monti, D.; Franceschi, C. Sex Differences in Lifespan. Gender and longevity. Ital. J. Gend.-Specif. Med. 2015, 1, 10–14. [Google Scholar]
- Wang, H.Y.; Lv, X.; Du, J.; Kong, G.; Zhang, L. Age- and Gender-Specific Prevalence of Frailty and Its Outcomes in the Longevous Population: The Chinese Longitudinal Healthy Longevity Study. Front. Med 2021, 8, 719806. [Google Scholar] [CrossRef]
- Lio, D.; Scola, L.; Giarratana, R.M.; Candore, G.; Colonna-Romano, G.; Caruso, C.; Balistreri, C.R. SARS-CoV-2 infection the longevity study perspectives. Ageing Res. Rev. 2021, 67, 101299. [Google Scholar] [CrossRef]
- Guerini, F.R.; Cesari, M.; Arosio, B. Hypothetical COVID-19 protection mechanism: Hints from centenarians. Immun. Ageing 2021, 18, 15. [Google Scholar] [CrossRef]
- Cohen, A.A.; Kennedy, B.K.; Anglas, U.; Bronikowski, A.M.; Deelen, J.; Dufour, F.; Ferbeyre, G.; Ferrucci, L.; Franceschi, C.; Frasca, D.; et al. Lack of consensus on an aging biology paradigm? A global survey reveals an agreement to disagree, and the need for an interdisciplinary framework. Mech. Ageing Dev. 2020, 191, 111316. [Google Scholar] [CrossRef] [PubMed]
- Hardy, O.J.; Dubourg, D.; Bourguignon, M.; Dellicour, S.; Eggerickx, T.; Gilbert, M.; Sanderson, J.P.; Scohy, A.; Vandael, E.; Decroly, J.M. A world apart: Levels and determinants of excess mortality due to COVID-19 in care homes: The case of the Belgian region of Wallonia during the spring 2020 wave. Demogr. Res. 2021, 45, 1011–1040. [Google Scholar] [CrossRef]
- Aoki, Y.; Mehmet, S.C. The COVID-19 pandemic appears to have increased longevity in Japanese centenarians. Age Ageing 2021, 50, 1052–1053. [Google Scholar] [CrossRef] [PubMed]
- Borpujari, P. How Japan survived COVID-19. BMJ 2022, 376, o778. [Google Scholar] [CrossRef]
- Iwasaki, A.; Grubaugh, N.D. Why does Japan have so few cases of COVID-19? EMBO Mol. Med. 2020, 12, e12481. [Google Scholar] [CrossRef]
- Abbatecola, A.M.; Antonelli-Incalzi, R. Editorial: COVID-19 Spiraling of Frailty in Older Italian Patients. J. Nutr. Health Aging 2020, 24, 453–455. [Google Scholar] [CrossRef]
- Available online: https://www.menshealth.com/uk/health/a31728622/coronavirus-survivor-covid (accessed on 20 January 2022).
- Gerontology Wiki. Available online: https://gerontology.fandom.com/wiki/Julia_Van_Hool (accessed on 20 January 2022).
- Gerontology Wiki. Available online: https://gerontology.fandom.com/wiki/Iris_Estay (accessed on 20 January 2022).
- De Castro, M.V.; Silva, M.V.R.; Naslavsky, M.S.; Scliar, M.O.; Nunes, K.; Passos-Bueno, M.R.; Castelli, E.C.; Magawa, J.Y.; Adami, F.L.; Moretti, A.I.S.; et al. The oldest unvaccinated COVID-19 survivors in South America. Immun. Ageing 2022, 19, 57. [Google Scholar] [CrossRef]
- Available online: https://www.reuters.com/business/healthcare-pharmaceuticals/europes-oldest-person-117-year-old-french-nun-survives-covid-19-2021-02-09 (accessed on 20 January 2022).
- Fulop, T.; Larbi, A.; Pawelec, G.; Cohen, A.A.; Provost, G.; Khalil, A.; Lacombe, G.; Rodrigues, S.; Desroches, M.; Hirokawa, K.; et al. Immunosenescence and Altered Vaccine Efficiency in Older Subjects: A Myth Difficult to Change. Vaccines 2022, 10, 607. [Google Scholar] [CrossRef]
- Hoffmann, M.; Kleine-Weber, H.; Schroeder, S.; Krüger, N.; Herrler, T.; Erichsen, S.; Schiergens, T.S.; Herrler, G.; Wu, N.H.; Nitsche, A.; et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell 2020, 181, 271–280.e8. [Google Scholar] [CrossRef]
- Van der Sluis, R.M.; Cham, L.B.; Gris-Oliver, A.; Gammelgaard, K.R.; Pedersen, J.G.; Idorn, M.; Ahmadov, U.; Hernandez, S.S.; Cémalovic, E.; Godsk, S.H.; et al. TLR2 and TLR7 mediate distinct immunopathological and antiviral plasmacytoid dendritic cell responses to SARS-CoV-2 infection. EMBO J. 2022, 41, e109622. [Google Scholar]
- Baratchian, M.; McManus, J.M.; Berk, M.P.; Nakamura, F.; Mukhopadhyay, S.; Xu, W.; Erzurum, S.; Drazba, J.; Peterson, J.; Klein, E.A.; et al. Androgen regulation of pulmonary AR, TMPRSS2 and ACE2 with implications for sex-discordant COVID-19 outcomes. Sci. Rep. 2021, 11, 11130. [Google Scholar] [CrossRef]
- Berghöfer, B.; Frommer, T.; Haley, G.; Fink, L.; Bein, G.; Hackstein, H. TLR7 ligands induce higher IFN-alpha production in females. J. Immunol. 2006, 177, 2088–2096. [Google Scholar] [CrossRef] [Green Version]
- Horowitz, J.E.; Kosmicki, J.A.; Damask, A.; Sharma, D.; Roberts, G.H.L.; Justice, A.E.; Banerjee, N.; Coignet, M.V.; Yadav, A.; Leader, J.B.; et al. Genome-wide analysis provides genetic evidence that ACE2 influences COVID-19 risk and yields risk scores associated with severe disease. Nat. Genet. 2022, 54, 382–392. [Google Scholar] [CrossRef]
- Ligotti, M.E.; Pojero, F.; Accardi, G.; Aiello, A.; Caruso, C.; Duro, G.; Candore, G. Immunopathology and Immunosenescence, the Immunological Key Words of Severe COVID-19. Is There a Role for Stem Cell Transplantation? Front. Cell Dev. Biol. 2021, 9, 725606. [Google Scholar] [CrossRef]
- Bektas, A.; Schurman, S.H.; Franceschi, C.; Ferrucci, L. A public health perspective of aging: Do hyper-inflammatory syndromes such as COVID-19, SARS, ARDS, cytokine storm syndrome, and post-ICU syndrome accelerate short- and long-term in-flammaging? Immun. Ageing 2020, 17, 23. [Google Scholar] [CrossRef]
- Schurz, H.; Salie, M.; Tromp, G.; Hoal, E.G.; Kinnear, C.J.; Möller, M. The X chromosome and sex-specific effects in infectious disease susceptibility. Hum. Genom. 2019, 13, 2. [Google Scholar] [CrossRef] [Green Version]
- Fricke-Galindo, I.; Martínez-Morales, A.; Chávez-Galán, L.; Ocaña-Guzmán, R.; Buendía-Roldán, I.; Pérez-Rubio, G.; Hernán-dez-Zenteno, R.J.; Verónica-Aguilar, A.; Alarcón-Dionet, A.; Aguilar-Duran, H.; et al. IFNAR2 relevance in the clinical outcome of individuals with severe COVID-19. Front. Immunol. 2022, 13, 949413. [Google Scholar] [CrossRef]
- Nakanishi, T.; Pigazzini, S.; Degenhardt, F.; Cordioli, M.; Butler-Laporte, G.; Maya-Miles, D.; Bujanda, L.; Bouysran, Y.; Niemi, M.E.; Palom, A.; et al. Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mor-tality. J. Clin. Investig. 2021, 131, e152386. [Google Scholar] [CrossRef]
- Plebani, M.; Lippi, G. Sex and gender differences in COVI-19: A narrative review. Ital. J. Gend.-Specif. Med. 2022, 8, 105–111. [Google Scholar]
- Caruso, C.; Accardi, G.; Virruso, C.; Candore, G. Sex, gender and immunosenescence: A key to understand the different lifespan between men and women? Immun. Ageing 2013, 10, 20. [Google Scholar] [CrossRef] [Green Version]
- Aiello, A.; Farzaneh, F.; Candore, G.; Caruso, C.; Davinelli, S.; Gambino, C.M.; Ligotti, M.E.; Zareian, N.; Accardi, G. Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention. Front. Immunol. 2019, 10, 2247. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Caruso, C.; Ligotti, M.E.; Accardi, G.; Aiello, A.; Candore, G. An immunologist’s guide to immunosenescence and its treatment. Expert Rev. Clin. Immunol. 2022, 18, 961–981. [Google Scholar] [CrossRef] [PubMed]
- Aiello, A.; Ligotti, M.E.; Garnica, M.; Accardi, G.; Calabrò, A.; Pojero, F.; Arasanz, H.; Bocanegra, A.; Blanco, E.; Chocarro, L.; et al. How Can We Improve Vaccination Response in Old People? Part I: Targeting Immunosenescence of Innate Immunity Cells. Int. J. Mol. Sci. 2022, 23, 9880. [Google Scholar] [CrossRef] [PubMed]
- Candore, G.; Balistreri, C.R.; Colonna-Romano, G.; Lio, D.; Listì, F.; Vasto, S.; Caruso, C. Gender-related immune-inflammatory factors, age-related diseases, and longevity. Rejuvenation Res. 2010, 13, 292–297. [Google Scholar] [CrossRef] [PubMed]
- Moldenhauer, L.M.; Jin, M.; Wilson, J.J.; Green, E.S.; Sharkey, D.J.; Salkeld, M.D.; Bristow, T.C.; Hull, M.L.; Dekker, G.A.; Robertson, S.A. Regulatory T Cell Proportion and Phenotype Are Altered in Women Using Oral Contraception. Endocrinology 2022, 163, bqac098. [Google Scholar] [CrossRef]
- Oertelt-Prigione, S. The influence of sex and gender on the immune response. Autoimmun. Rev. 2012, 11, A479–A485. [Google Scholar] [CrossRef]
- Nielsen, J.; Nørgaard, S.K.; Lanzieri, G.; Vestergaard, L.S.; Moelbak, K. Sex-differences in COVID-19 associated excess mortality is not exceptional for the COVID-19 pandemic. Sci. Rep. 2021, 11, 20815. [Google Scholar] [CrossRef]
- Tadiri, C.P.; Gisinger, T.; Kautzy-Willer, A.; Kublickiene, K.; Herrero, M.T.; Raparelli, V.; Pilote, L.; Norris, C.M. GOING-FWD Con-sortium. The influence of sex and gender domains on COVID-19 cases and mortality. CMAJ 2020, 192, E1041–E1045. [Google Scholar] [CrossRef]
- Yu, X.; Tsibane, T.; McGraw, P.A.; House, F.S.; Keefer, C.J.; Hicar, M.D.; Tumpey, T.M.; Pappas, C.; Perrone, L.A.; Martinez, O.; et al. Neu-tralizing antibodies derived from the B cells of 1918 influenza pandemic survivors. Nature 2008, 455, 532–536. [Google Scholar] [CrossRef] [Green Version]
- Restifo, N. Flu: The Story of the Great Influenza Pandemic of 1918 and the Search for the Virus that Caused It. Nat. Med. 2000, 6, 12–13. [Google Scholar] [CrossRef]
- Almond, D. Is the 1918 Influenza pandemic over? Long-term effects of in utero influenza exposure in the post-1940 US popu-lation. J. Polit Econ. 2006, 114, 672–712. [Google Scholar] [CrossRef] [Green Version]
- Mazumder, B.; Almond, D.; Park, K.; Crimmins, E.M.; Finch, C.E. Lingering prenatal effects of the 1918 influenza pandemic on cardiovascular disease. J. Dev. Orig. Health Dis. 2010, 1, 26–34. [Google Scholar] [CrossRef] [Green Version]
- Ogasawara, K. The long-run effects of pandemic influenza on the development of children from elite backgrounds: Evidence from industrializing Japan. Econ. Hum. Biol. 2018, 31, 125–137. [Google Scholar] [CrossRef]
- Mantovani, A.; Netea, M.G. Trained Innate Immunity, Epigenetics, and COVID-19. N. Engl. J. Med. 2020, 383, 1078–1080. [Google Scholar] [CrossRef]
- Debisarun, P.A.; Gössling, K.L.; Bulut, O.; Kilic, G.; Zoodsma, M.; Liu, Z.; Oldenburg, M.; Rüchel, N.; Zhang, B.; Xu, C.J.; et al. Induction of trained immunity by influenza vaccination-impact on COVID-19. PLoS Pathog. 2021, 17, e1009928. [Google Scholar] [CrossRef]
- Rijkers, G.T.; van Overveld, F.J. The “original antigenic sin” and its relevance for SARS-CoV-2 (COVID-19) vaccination. Clin. Immunol. Commun. 2021, 1, 13–16. [Google Scholar] [CrossRef]
- Ligotti, M.E.; Aiello, A.; Accardi, G.; Aprile, S.; Bonura, F.; Bulati, M.; Gervasi, F.; Giammanco, G.M.; Pojero, F.; Zareian, N.; et al. Analysis of T and NK cell subsets in the Sicilian population from young to supercentenarian: The role of age and gender. Clin. Exp. Immunol. 2021, 205, 198–212. [Google Scholar] [CrossRef]
- Biagi, E.; Franceschi, C.; Rampelli, S.; Severgnini, M.; Ostan, R.; Turroni, S.; Consolandi, C.; Quercia, S.; Scurti, M.; Monti, D.; et al. Gut Microbiota and Extreme Longevity. Curr. Biol. 2016, 26, 1480–1485. [Google Scholar] [CrossRef]
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Caruso, C.; Marcon, G.; Accardi, G.; Aiello, A.; Calabrò, A.; Ligotti, M.E.; Tettamanti, M.; Franceschi, C.; Candore, G. Role of Sex and Age in Fatal Outcomes of COVID-19: Women and Older Centenarians Are More Resilient. Int. J. Mol. Sci. 2023, 24, 2638. https://doi.org/10.3390/ijms24032638
Caruso C, Marcon G, Accardi G, Aiello A, Calabrò A, Ligotti ME, Tettamanti M, Franceschi C, Candore G. Role of Sex and Age in Fatal Outcomes of COVID-19: Women and Older Centenarians Are More Resilient. International Journal of Molecular Sciences. 2023; 24(3):2638. https://doi.org/10.3390/ijms24032638
Chicago/Turabian StyleCaruso, Calogero, Gabriella Marcon, Giulia Accardi, Anna Aiello, Anna Calabrò, Mattia Emanuela Ligotti, Mauro Tettamanti, Claudio Franceschi, and Giuseppina Candore. 2023. "Role of Sex and Age in Fatal Outcomes of COVID-19: Women and Older Centenarians Are More Resilient" International Journal of Molecular Sciences 24, no. 3: 2638. https://doi.org/10.3390/ijms24032638