Are Older People Really More Susceptible to SARS-CoV-2?
Open accessAbstract
Since the outbreak, COVID-19 has spread rapidly across the globe due to its high infectivity and lethality. Age appears to be one of the key factors influencing the status and progression of SARS-CoV-2 infection, as multiple reports indicated that the majority of COVID-19 infections and severe cases are elderly. Most people simply assume that the elderly are more susceptible to SARS-CoV-2 than the young, but the mechanism behind it is still open to question. The older and younger people are at similar risk of infection because their infection process is the same and they must be exposed to the virus first. However, whether they will get sick after exposure to the virus and how their disease progresses depend on their immune mechanisms. In older populations, inflammation and immune aging reduce their ability to resist SARS-CoV-2 infection. Meanwhile, under the influence of comorbidities, ACE2 receptor and various cytokines undergo corresponding changes, thus accelerating the entry, replication, and transmission of SARS-CoV-2 in the body, promoting disease progression, and leading to severe illness and even death. In addition, the relatively fragile mental state of the elderly can also affect their timely recovery from COVID-19. Therefore, once older people are infected with SARS-CoV-2, they are more prone to severe illness and death with a poor prognosis, and they should strengthen protection to avoid exposure to the virus.
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In early Alzheimer's disease, transporter dysfunction, specifically reduced expression of GLUT1 and LRP1, occurs prior to brain atrophy.
“Another early-stage feature is transporter dysfunction, specifically reduced expression of GLUT1 and LRP1 prior to brain atrophy [48, 49].”
From Targeted Nanoparticles for Drug Delivery Across the Blood–Brain Barrier in Early and Late Stages of Alzheimer's Disease: A Review (2026) · cites this paper as [49]
The section on older people with COVID-19 discusses mitochondrial dysfunction and immune responses, not early Alzheimer’s disease. Searches for GLUT1, LRP1, transporter dysfunction, and brain atrophy found no passage in our copy addressing the claimed sequence. (LLM, conf=0.76)
Experimental — accuracy not yet measuredIn advanced Alzheimer's disease, there is increased penetration of immune cells, including neutrophils, macrophages, and T lymphocytes, into the brain parenchyma.
“There is also increased penetration of immune cells, including neutrophils, macrophages, and T lymphocytes, into the brain parenchyma [48, 49].”
From Targeted Nanoparticles for Drug Delivery Across the Blood–Brain Barrier in Early and Late Stages of Alzheimer's Disease: A Review (2026) · cites this paper as [49]
The section “Older people infected with SARS-CoV-2 are more likely to develop disease” discusses age-related immune changes and neutrophil migration to sites of infection, not immune-cell entry into the brain. Searches for Alzheimer’s disease and brain-parenchyma penetration found no passage addressing increased entry of neutrophils, macrophages, or T lymphocytes in advanced Alzheimer’s disease. No page number was available for these passages. (LLM, conf=0.76)
Experimental — accuracy not yet measuredIn advanced Alzheimer's disease, transporter impairment worsens, notably with decreased P-glycoprotein activity.
“Furthermore, transporter impairment worsens, notably with decreased P-glycoprotein activity [49, 54].”
From Targeted Nanoparticles for Drug Delivery Across the Blood–Brain Barrier in Early and Late Stages of Alzheimer's Disease: A Review (2026) · cites this paper as [49]
The sections on older people and COVID-19 discuss immune aging and SARS-CoV-2 severity, not transporter function in advanced Alzheimer’s disease. Searches for P-glycoprotein activity and Alzheimer’s-related transporter impairment found no passage addressing the claim in our copy. (LLM, conf=0.77)
Experimental — accuracy not yet measuredIn advanced Alzheimer's disease, blood-brain barrier alterations are marked by progressive loss of tight junction proteins, namely decreased expression of occludin, claudin-5, and ZO-1.
“In advanced AD, BBB alterations are marked by the progressive loss of TJ proteins—namely, decreased expression of occludin, claudin-5, and ZO-1 [48, 49].”
From Targeted Nanoparticles for Drug Delivery Across the Blood–Brain Barrier in Early and Late Stages of Alzheimer's Disease: A Review (2026) · cites this paper as [49]
The section on older people infected with SARS-CoV-2 discusses immune aging and COVID-19, not blood-brain barrier changes in advanced Alzheimer’s disease. Searches of our full-text copy for Alzheimer’s disease, tight junctions, occludin, claudin-5, and ZO-1 found no passage addressing the claim. (LLM, conf=0.76)
Experimental — accuracy not yet measuredIn advanced Alzheimer's disease, widespread leakage and deposition of blood-derived proteins such as fibrinogen, thrombin, and albumin are observed.
“Simultaneously, widespread leakage and deposition of blood-derived proteins such as fibrinogen, thrombin, and albumin are observed [49, 55].”
From Targeted Nanoparticles for Drug Delivery Across the Blood–Brain Barrier in Early and Late Stages of Alzheimer's Disease: A Review (2026) · cites this paper as [49]
The section “Older people with COVID-19 are more likely to become severe” (page unavailable) discusses cytokine storms and microvascular clotting, not advanced Alzheimer’s disease or deposition of blood-derived proteins. Searches for fibrinogen, thrombin, albumin, and Alzheimer’s disease found no passage addressing the claim in our copy. (LLM, conf=0.77)
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“Improved mitochondrial activity in older people can be used as a preventive therapy to improve immune response and reduce mortality from respiratory diseases [49].”
BackgroundRole of Neuroimmunomodulation in Aging
la Fuente, M. D. (2008) · Neuroimmunomodulation · doi:10.1159/000156465 · Cited by 61 · see citing works
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Bernabeu‐Wittel, M., Ternero-Vega, J. E., Díaz-Jiménez, P., Guzmán, C. C., Nieto‐Martín, M. D., Moreno-Gaviño, L., Delgado, J., Rincón‐Gómez, M., Giménez, L., Navarro-Amuedo, M. D., et al. (2020) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2020.104240 · Cited by 46 · cited 1× · see citing works
“COVID-19 has a devastating effect on older people [56].”
Chitinase 3-like-1 is a therapeutic target that mediates the effects of aging in COVID-19
Kamle, S., Ma, B., He, C. H., Akosman, B., Zhou, Y., Lee, C.-M., El‐Deiry, W. S., Huntington, K. E., Liang, O. D., Machan, J. T., et al. (2021) · JCI Insight · doi:10.1172/jci.insight.148749 · Cited by 43 · cited 1× · see citing works
“Moreover, CH3L1 is an effective SARS-CoV-2 stimulator that acts on human body through ACE2 receptor, and this induction is the main mechanism by which aging aggravates the COVID-19 disease [52].”
BackgroundAge, Complexity, and Crisis - A Prescription for Progress in Pandemic.
Aronson, L. (2020) · New England Journal of Medicine · doi:10.1056/nejmp2006115 · Cited by 41 · cited 1×
“The close link between advanced age and a higher risk of severe illness from COVID-19 is one of the most compelling information [11-12].”
BackgroundShin, J. H., Gao, Y., Moore, J. H., Bolick, D. T., Kolling, G. L., Wu, M., & Warren, C. A. (2017) · The Journal of Infectious Diseases · doi:10.1093/infdis/jix414 · Cited by 33 · cited 1× · see citing works
“Aging and Disease • Volume 13, Number 5, October 2022 1341 homeostasis and keeps the body healthy [23], but the function of the immune active cells of human body will gradually decline with age [24].”
BackgroundAll Nations Must Prioritize the COVID-19 Vaccination Program for Elderly Adults Urgently
Chakraborty, C., Sharma, A. R., Bhattacharya, M., Agoramoorthy, G., & Lee, S. (2021) · Aging and Disease · doi:10.14336/ad.2021.0426 · Cited by 14 · cited 1× · see citing works
“The majority of COVID-19 infected, and critically ill patients are elderly [6], and about 50% are over 60 years old [7].”
BackgroundImmune-related adverse events of immune checkpoint inhibitors
Tadano, H., & Torigoe, T. (2017) · Japanese Journal of Clinical Immunology · doi:10.2177/jsci.40.102 · Cited by 11 · cited 1× · see citing works
“For examples, hyperglycemia can increase the plasma osmotic pressure, as well as inhibit the chemotactic activity, phagocytosis and intracellular killing of leukocytes, thereby reducing the body’s resistance to infection and weakening the reaction ability to the invasion of viruses [38].”
BackgroundElderly Patient Care: A New Reality of the SARS-CoV-2 Pandemic
Jankowska-Polańska, B., Sarzyńska, K., Pytel, A., Izbiański, D., Gaweł-Dąbrowska, D., & Knysz, B. (2021) · Aging and Disease · doi:10.14336/ad.2021.0222 · Cited by 7 · cited 1× · see citing works
“Studies have found that advanced age is an independent risk factor for COVID-19 mortality and severe infection [35], and elderly patients with comorbid diseases account for a large proportion of severe and fatal patients [36].”
BackgroundWillschke, H., Wochele‐Thoma, T., Atanasov, A. G., Klager, E., Haslinger, C., Kletečka-Pulker, M., Laxar, D., Ay, C., Öhlinger, T., Kimberger, O., et al. (2021) · Aging and Disease · doi:10.14336/ad.2021.0217 · Cited by 1 · cited 1× · see citing works
“Since its outbreak, COVID-19 has spread rapidly and enveloped most of the world [3] and has seriously affected people’s daily life and work due to its strong infectivity and widespread.”
Background
Flagged first, then by citations
2 of the 68 references couldn’t be matched to a known paper.
Research works printed but not linked: 4
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Kochman, U., Sitka, H., Kuźniar, J., Czaja, M., Kozubek, P., Beszłej, J. A., & Leszek, J. (2026) · Molecular Neurobiology · doi:10.1007/s12035-025-05417-z · Cited by 60 · see citing works
The immune mechanism of the nasal epithelium in COVID-19–related olfactory dysfunction
Chen, S., & Wang, S. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1045009 · Cited by 16 · see citing works
Rousogianni, E., Perlepe, G., Boutlas, S., Rapti, G. G., Gouta, E., Mpaltopoulou, E., Mpaltopoulos, G., Papagiannis, D., Exadaktylos, A., Gourgoulianis, K., et al. (2025) · Scientific Reports · doi:10.1038/s41598-025-19236-8 · Cited by 16
Wastewater-Based Surveillance of SARS-CoV-2 and Modeling of COVID-19 Infection Trends
Wang, W., Li, R.-Y., Chen, S., Chen, L., Jiang, Y., Xiang, J.-J., Wu, J., Li, J., Chen, Z.-W., & Wu, C.-C. (2025) · Tropical Medicine and Infectious Disease · doi:10.3390/tropicalmed10090264 · Cited by 11
“This is likely due to a combination of factors, including shorter incubation periods, faster disease progression, and lower healthcare-seeking delays in older adults [48].”
Self-citationAging During the Pandemic: Untangling the Complexities of COVID-19 and Geriatric Care
Su, K., & Jin, K.-L. (2023) · Aging and Disease · doi:10.14336/ad.2023.0405 · Cited by 11
Suicide among the young population and the urgency of public health policies
Guimarães, R. M., Moreira, M. R., & Costa, N. D. R. (2024) · The Lancet Regional Health - Americas · doi:10.1016/j.lana.2024.100793 · Cited by 7
“7 As a consequence, some families tried to protect this age group, preserving them with social distancing, 8 placing the younger population in several front – line activities, exposing them to a dangerous situation for exposure to the previously unknown virus.”
BackgroundSârbu, F., Oprea, V. D., Tatu, A. L., Drima, E. P., Ștefănescu, C., Nechita, A., Onose, G., & Romila, A. (2022) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2022.11424 · Cited by 7 · see citing works
Humoral and Cellular Immune Response Elicited by the BNT162b2 COVID-19 Vaccine Booster in Elderly
Gasperina, D. D., Veronesi, G., Castelletti, C. M., Varchetta, S., Ottolini, S., Mele, D., Ferrari, G., Shaik, A. K. B., Celesti, F., Dentali, F., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241813728 · Cited by 6 · see citing works
“The elderly are more susceptible to SARS-CoV2 infections than younger individuals due to age and overall reduced function of the immune system [18–20].”
Impact of vitamin D levels on mortality in older covid-19 vaccinated patients
Ceolin, C., Vergadoro, M., Simonato, C., Cazzavillan, S., Papa, M. V., Trapella, G. S., Marzio, B. D., Sermasi, R., Zanforlini, B. M., Curreri, C., et al. (2025) · BMC Geriatrics · doi:10.1186/s12877-025-05873-1 · Cited by 4 · see citing works
“Age-related factors, such as the aging immune system, increased comorbidities, and physiological changes, have rendered old people the most vulnerable victims of this pandemic, with significantly high mortality rates reported within this population [3].”
D'Aversa, E., Antonica, B., Grisafi, M., Asselta, R., Paraboschi, E., Passaro, A., Volpato, S., Remelli, F., Castellazzi, M., Marra, A., et al. (2026) · Diagnostics · doi:10.3390/diagnostics16040583 · Cited by 4
“Scientific evidence suggests that people older than 65 years have a greater risk of developing severe forms of COVID-19 [74].”
Foláyan, M. O., Zúñiga, R. A. A., Aly, N. M., Ellakany, P., Ezechi, O., Gaffar, B. O., Ibigbami, O. I., Idigbe, I. E., Ishabiyi, A. O., Khader, Y. S., et al. (2025) · Frontiers in Public Health · doi:10.3389/fpubh.2025.1550719 · Cited by 4 · see citing works
Eijk, L. E. V.-V., Ertugrul, I., Upasani, V., Wold, K., Vincenti-González, M., Veloo, A., Bourgonje, A., Pantano, D., Gard, L., de Boer, G. C., et al. (2024) · Journal of Medical Virology · doi:10.1002/jmv.70125 · Cited by 3
Lee, B., Bae, G. E., Jeong, I. H., Kim, J., Kwon, M., Kim, J., Kim, B., Lee, J.-W., Nam, J.-H., Huh, H. J., et al. (2024) · The Journal of Applied Laboratory Medicine · doi:10.1093/jalm/jfae014 · Cited by 3 · see citing works
EpidemicKabu a new method to identify epidemic waves and their peaks and valleys
Ruiz, L., Ruales, A. A., Cardozo, O. M. M., Barengo, N., Garcia, J., & Valencia, P. (2024) · medRxiv · doi:10.1101/2024.03.11.24304124 · Cited by 3
“We assume that the total population of each country represents the total population susceptible to the SARS-CoV-2 [22,23].”
BackgroundRationale for combined therapies in severe-to-critical COVID-19 patients
Gonzaga, A., Andreu, E., Blasco, L., Meseguer, R., Al‐Akioui‐Sanz, K., Soria-Juan, B., Sanjuan-Gimenez, J. C., Ferreras, C., Tejedo, J. R., López‐Lluch, G., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1232472 · Cited by 3 · see citing works
“Elder patients with comorbidities typically have severe to critical COVID-19 (13, 14).”
BackgroundLi, H., Wang, Y., Li, X., Wang, S., Feng, X., Xiao, X., & Li, Y. (2023) · Journal of Diabetes · doi:10.1111/1753-0407.13448 · Cited by 4 · see citing works
“28 31 Those who had lower antibody response after receiving the COVID-19 vaccine were recommended to further receive the vaccine to enhance immunity.”
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“Given the complex interplay between HIV status, immunological responses, advancing age, and comorbid conditions, there remains considerable uncertainty regarding the comparative susceptibility of older individuals with HIV to the Omicron variant in comparison to their HIV-negative peers (17, 26).”
Aldahhan, R. A., & El-Sheikh, A. A. (2025) · Translational Research in Anatomy · doi:10.1016/j.tria.2025.100411
The underlying mechanism behind the different outcomes of COVID-19 in children and adults
Shang, Z., Huang, L., & Qin, S. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1440169 · Cited by 1 · see citing works
“These comprehensive alterations collectively weaken the host immune response to viral invasion (42).”
Zhang, X. Z., Wong, P. H. H., Lai, K. S., Yang, B., Song, M., Li, J., & Ung, C. O. L. (2024) · Vaccines · doi:10.3390/vaccines12080933 · Cited by 1 · see citing works
“Once infected, they often develop severe symptoms [27].”
BackgroundOberste, M., Asenova, T., Ernst, A., Shah‐Hosseini, K., Schnörch, N., Buess, M., Rosenberger, K. D., Kossow, A., Dewald, F., Neuhann, F., et al. (2024) · BMC Public Health · doi:10.1186/s12889-024-17958-4 · Cited by 2 · see citing works
“Infectious disease studies suggest that a greater propensity to inflammation, an aged immune system and changes in the cytokine profile are associated with this higher susceptibility to severe outcomes in old age [34].”
BackgroundJakovljević, D., Pavlovic, A. P. P., Ilic, A., Trpkovic, S., Videnović, N., Filipović, M., Đukić, S., Zdravković, R., Milanović, M., & Aleksandar, J. (2026) · COVID · doi:10.3390/covid6080141
“…prevalence of cardiovascular risk factors and unhealthy behaviors such as smoking [1,5,16,26–28 , Older age was strongly associated with IHCA, consistent with previous studies identifying advanced age as one of the strongest predictors of severe COVID-19 and poor clinical outcomes [13,26,34].”
Dlamini, M., Msolo, L., Nontongana, N., Ebomah, K. E., & Okoh, A. (2026) · Food and Environmnetal Virology · doi:10.1007/s12560-026-09688-0
Hussein, R. M., Alwan, A. H., & Fadhil, H. Y. (2025) · Medical Journal of Babylon · doi:10.4103/mjbl.mjbl_1551_23
Bolijn, R., Spijkerman, A. M. W., Galenkamp, H., Blokstra, A., Coyer, L., Boyd, A. C., Prins, M., & Stronks, K. (2024) · PLoS ONE · doi:10.1371/journal.pone.0311196
das Chagas, R. R., Freitas, H. R., & Cardozo, S. (2024) · medRxiv · doi:10.1101/2024.09.08.24313185
“The mental state of the elderly can also impact their recovery 15 .”
BackgroundCancer Care During the COVID-19 Pandemic: A Retrospective Study From a Najran Oncology Center
Badheeb, A., Musallam, S. H., Alyami, A., Almakrami, A. H., Al-Swedan, A. D., Ahmed, F., Badheeb, M., Aedh, A. I., Obied, H., Seada, I., et al. (2024) · Cureus · doi:10.7759/cureus.63252
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Grimsley, E. A., Torikashvili, J. V., Janjua, H. M., Read, M. D., Kothari, A. N., Verhagen, N. B., Pietrobon, R. S., Kuo, P. C., Rogers, M. P., Wilcox, A. B., et al. (2023) · JTCVS Open · doi:10.1016/j.xjon.2023.09.020 · Cited by 1 · see citing works
Xiao, J., Liang, C., Zhang, L., Li, J., & Liu, S. (2023) · Aging and Disease · doi:10.14336/ad.2023.0406
- Authors
- Zhang, S., Yang, Z., Li, Z.-N., Chen, Z.-L., Yue, S.-J., Fu, R.-J., Xu, D.-Q., Zhang, S., & Tang, Y.-P.
- Affiliations
- Beijing University of Chinese Medicine (CN)
- Shaanxi University of Chinese Medicine (CN)
- Shaanxi Administration of Traditional Chinese Medicine (CN)
- Corresponding author
- Chen, Zhen-Lin
- Tang, Yu-Ping
- Venue
- Aging and disease
- Publisher
- Aging and Disease
- Published
- 2022
- Volume
- 13
- Issue
- 5
- Pages
- 1336
- ISSN
- 2152-5250 (ISSN-L)
- PMC
- PMC9466979
- OpenAlex
- W4295560399
- Cited by
- 39
- References
- 68
- Citations by year
- 2026: 3 · 2025: 12 · 2024: 14 · 2023: 9 · 2022: 1
- FWCI
- 4.40
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Aging and Disease (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81974584, 81974522, 2019-YL10, 2019ZDLSF04-05)
- Shaanxi University of Chinese Medicine (2019-YL10)
- Key Research and Development Projects of Shaanxi Province (2019ZDLSF04-05)
- Topics
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Physical Sciences › Mathematics › Modeling and Simulation › COVID-19 epidemiological studies
- Keywords
- SARS-CoV-2, COVID-19 pandemic, older adults, age-related susceptibility, immunosenescence, inflammation, comorbidities, ACE2 receptor, cytokines, disease progression, mental health, prognosis
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