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COMMENTARY
Adv Biomed Res 2022,  11:106

Does COVID-19 escalate aging process? A possible concern


1 Department of Infectious Diseases, Iranian Research Center of HIV and AIDS, Iranian Institute for Reduction of High Risk Behaviors, Tehran University of Medical Sciences, Tehran, Iran
2 Dental Unit, Islamic Azad University of Isfahan, Isfahan, Iran
3 Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA
4 Department of Physiology, School of Medicine, Applied Physiology Research Center, Cardiovascular Research Institute, Isfahan, Iran

Date of Submission02-Nov-2021
Date of Acceptance29-Dec-2021
Date of Web Publication28-Nov-2022

Correspondence Address:
Prof. Shaghayegh Haghjooy Javanmard
Department of Physiology, School of Medicine, Applied Physiology Research Center, Cardiovascular Research Institute, Isfahan
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/abr.abr_350_21

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  Abstract 


A key challenge after the COVID-19 pandemic will be managing the long-term sequelae for the millions of individuals who recover from the disease. Based on the available evidence, our hypothesis is that the SARS-CoV-2 pandemic and its long-term complications will lead to premature aging (in terms of health) of many people in the world. Obviously, to maintain appropriate public health and prevent poor health-care services, countries should think and plan about the health problems and the long-term consequences of SARS-CoV-2 after controlling the COVID-19 pandemic.

Keywords: Aging, complications, COVID-19


How to cite this article:
Tayeri K, Asadollahi K, Madani N, Haghjooy Javanmard S. Does COVID-19 escalate aging process? A possible concern. Adv Biomed Res 2022;11:106

How to cite this URL:
Tayeri K, Asadollahi K, Madani N, Haghjooy Javanmard S. Does COVID-19 escalate aging process? A possible concern. Adv Biomed Res [serial online] 2022 [cited 2023 Sep 26];11:106. Available from: https://www.advbiores.net/text.asp?2022/11/1/106/362024




  Introduction Top


COVID-19 disease is an emerging viral infection known primarily as a lung disease.[1] Until August 13, 2021, over 2.550 million people have been infected with the disease and more than 4,340,000 people died.

Despite advances in the production and distribution of various COVID-19 vaccines with different platforms, SARS-CoV-2 continues to spread worldwide for several reasons including inequality in access to vaccines, vaccine resistance among people, and developing new variants with poor response to vaccines.[2],[3],[4]

During COVID-19, various short-term and long-term symptoms may occur.[5] Although most patients completely recover, sometimes, long-term complications such as cardiovascular, pulmonary, renal, skin, neurological, and psychological problems occur which can last for weeks or months and potentially lead to some limitation in individual's life and health.[6]

Evidence from studies on other coronaviruses (SARS and MERS) reported long-term complications of survivors, including psychoneurological complications, weakness, and fatigue, until 24 months after infection.[7],[8] On the other hand, about 40% of people with SARS have had symptoms of chronic fatigue syndrome for more than 3.5 years after recovery.[9]


  Postacute Sequelae of Covid-19 Top


There are increasing studies on the persistence of symptoms, long-term consequences, and the occurrence of end-organ damage after recovery of COVID-19, called postacute sequelae of COVID-19 (PASC).[10] PASC means the persistence of symptoms for more than 3 weeks from the onset of disease, chronic/long COVID-19 indicates persistence of symptoms for more than 12 weeks.[8]

Many survivors need a multi-specialized team for posthospital care, which is recommended to set up postdischarge COVID-19 clinics.[11] The need for follow-up will be more important in high-risk patients, severe COVID-19, intensive care unit admitted, and underlying immunodeficiency.[3]


  Musculoskeletal Complications Top


Myalgia, muscle dysfunction, osteoporosis, and osteonecrosis have been reported as a complication in patients with moderate-to-severe SARS.[12] Preliminary studies have shown similar complications following COVID-19.[12],[13] Bone complications may also be due to long-term use or high doses of corticosteroids, which is one of the most common treatments in COVID-19, and appropriate nutrition should be considered during treatment.[13]


  Neuropsychological Complication Top


Various reports of direct nerve damage due to invasion of the SARS-CoV-2 have been reported,[14],[15] which can potentially lead to long-term neurological complications such as headache and dizziness.

Mood, behavioral, and cognitive disorders have also been reported for several months after COVID-19, even could be due to physical distance and fear from a fatal disease.[16] COVID-19 was considered a stigmatized diseases and lead to a lot of frustration. Various studies have shown that COVID-19 survivors may have higher risk for depression, anxiety, posttraumatic stress disorder, and drug use. Given the number of worldwide patients, such potential complications could pose a global mental health crisis.[8]

Stroke is a known acute neurological complication of COVID-19.[17] Several studies have shown that the incidence of stroke could increase in the recovery period of COVID-19 in age groups <50 years. In a case series, the median time to acute stroke after positive SARS-CoV-2 serological test was about 54.5 days (0–130 days). It seems that in the future, a history of COVID-19 will be considered a risk factor for stroke, especially in young people.[18],[19] COVID-19 can be a modifier of the onset, feature, and outcome of a stroke.[20]


  Cardiopulmonary Complication Top


Long-term cardiac complications such as myocarditis and cardiac arrhythmias are a known consequence of COVID-19 disease and can happen in different age groups.[8]

Pulmonary abnormalities of COVID-19 such as interstitial thickening, persistent pulmonary fibrosis, decreased diffusion capacity for carbon monoxide, and decreased respiratory muscle strength can persistent up to 1–3 months after discharge from hospital.[21],[22]


  Diabetes Top


Diabetes was initially considered a risk factor for severe COVID-19 disease, but it seems the high prevalence of diabetes in the general population led to this perception. COVID-19 may be a trigger for diabetes in some people.[23],[24],[25],[26]

According to the current evidence, it seems some COVID-19 survivors will need chronic disease care in the future, and preventive measures must be taken to provide the necessary health infrastructure to deliver health services for survivors with physical and mental health problems.[27]


  Covid-19 and Aging Top


Physical pain and bone problems, chronic obstructive pulmonary disease, diabetes, cardiovascular complications, depression and psychiatric disorders, amnesia, and Alzheimer's are some of the complications that often affect the elderly.[28] In 2020, the number of people over 60 in the world was more than children under five. Between 2015 and 2050, the proportion of the world's population over the age of 60 will double from 12% to 22%.

By 2050, more than 80% of older people are expected to live in low- and middle-income countries. All countries must prepare their health systems to face with old age health problems[29] and must be ready to provide health-care services to a population suffering from chronic complications and aging.

A key challenge after the COVID-19 pandemic will be managing the long-term sequelae for the millions of individuals who recover from the disease.[8]

Studies have shown that COVID-19 is associated with the amplified inflammatory response, leading to the “cytokine storm,” potentially leading to severe multisystem end-organ damage.[30] Cytokine dysregulation has known to have a role in the attenuation of the immune system at older age.[31] Moreover, remodeling of the cytokine expression pattern, with an increasing propensity toward a pro-inflammatory phenotype has been called “inflammaging.” “Inflammaging” is associated with several common age-related diseases, including atherosclerosis, diabetes, Alzheimer's disease, rheumatoid arthritis, and cancer.[32]

In addition to the acute inflammatory response, it seems that chronic inflammation also has a key role in the clinical outcomes of COVID-19 and its long-term consequences.[33],[34]

COVID-19 showed the vulnerability of aging populations to emerging diseases and highlighted the importance of immunosenescence and inflammaging, which may have a role in vulnerability to severe COVID-19 outcomes in older adults.[35]

Previous studies showed that various signaling pathways activated by inflammation and stress converge with nuclear factor (NF)-κB signaling, which is a chief controller of the immune response, and inflammatory cascade.[36] Aging is associated with impaired immune homeostasis and dysregulated NF-κB signaling.[37]

Therefore, aging and age-related diseases after pandemic have posed a major public health catastrophe worldwide. However, there is not enough evidence about the underlying molecular pathways related with aging as a consequence of COVID-19.[38]

Inflammation and oxidative stress are known as two major mechanisms for aging and age-related diseases.[39] Telomere shortening is a hallmark and major determinant of biological aging. Immune system activation, tissue damage, and following cell replication lead to telomere attrition during COVID-19 which can accelerate cellular senescence and aging.[40]

Inflammation associated with telomere-driven cellular senescence can limit the tissue regenerative capacity by compromising the function of tissue-specific stem and progenitor cells and accelerated aging.[41] Accumulation of senescent cells can be responsible for organ failure due to depletion of the organ's renewal capacity that is associated with aging. Telomeres can be considered a memento of previous cell divisions and DNA damage.[42]

It has been shown that the consecutive low-grade inflammation seen in COVID-19 patients after acute phase may result in a constant cycle of inflammation-induced organ injury and injury-induced inflammation.[43]

Telomere shortening due to oxidative damage is another reason for an increased rate of telomere loss. Indeed, increase in reactive oxygen species production is interconnected to cellular senescence by induction of the p53 expression, which can then result in the inhibition of autophagy. This effect initiates mitochondrial dysfunction, and leads to cellular senescence.[44]

It has been suggested that cellular senescence is involved in the increased death rate of COVID-19 patients.[45]

As discussed above, it seems many aging comorbidities and pathophysiologic mechanisms are similar between aging and long COVID. Further studies are needed to clarify the complex pathophysiologic mechanisms involved in inflammaging and cellular senescence to combat COVID-19-associated aging and age-related disorders.


  Conclusion Top


Due to the extent of COVID-19 and the involvement of different age groups, especially young and middle-aged, and because of the long-term complications of COVID-19, which causes some kind of complications similar to the elderly in people (such as joint bone problems, chronic obstructive pulmonary disease, diabetes, cardiovascular complications, depression and psychiatric disorders, amnesia, and Alzheimer's) in the coming years, we believe the events similar to aging complications are expected to occur at younger ages. Therefore, the health system will be faced with higher load of aging complications than expected. In other words, the number of people who will potentially suffer from complications similar to old age will be much higher than the estimated number of elderly people at that time.

Based on the available evidence, our hypothesis is that the SARS-CoV-2 pandemic and its long-term complications will lead to premature aging (in terms of health) of many people in the world.

Obviously, to maintain appropriate public health and prevent poor health-care services, countries should think and plan about the health problems and the long-term consequences of SARS-CoV-2 after controlling the COVID-19 pandemic.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Yuki K, Fujiogi M, Koutsogiannaki S. COVID-19 pathophysiology: A review. Clin Immunol 2020;215:108427.  Back to cited text no. 1
    
2.
Tregoning JS, Flight KE, Higham SL, Wang Z, Pierce BF. Progress of the COVID-19 vaccine effort: Viruses, vaccines and variants versus efficacy, effectiveness and escape. Nat Rev Immunol 2021;21:626-36.  Back to cited text no. 2
    
3.
Goldman E. How the unvaccinated threaten the vaccinated for COVID-19: A Darwinian perspective. Proc Natl Acad Sci U S A 2021;118:e2114279118.  Back to cited text no. 3
    
4.
Black M, Ford J, Lee A. Vaccination against COVID-19 and inequalities – Avoiding making a bad situation worse. Public Health Pract (Oxf) 2021;2:100101.  Back to cited text no. 4
    
5.
Groff D, Sun A, Ssentongo AE, Ba DM, Parsons N, Poudel GR, et al. Short-term and long-term rates of postacute sequelae of SARS-CoV-2 infection: A systematic review. JAMA Netw Open 2021;4:e2128568.  Back to cited text no. 5
    
6.
Long-Term Effect of COVID-19, CDC; Nov, 13 2020. https://stacks.cdc.gov/view/cdc/97204  Back to cited text no. 6
    
7.
Ngai JC, Ko FW, Ng SS, To KW, Tong M, Hui DS. The long-term impact of severe acute respiratory syndrome on pulmonary function, exercise capacity and health status. Respirology 2010;15:543-50.  Back to cited text no. 7
    
8.
Del Rio C, Collins LF, Malani P. Long-term health consequences of COVID-19. JAMA 2020;324:1723-4.  Back to cited text no. 8
    
9.
Lam MH, Wing YK, Yu MW, Leung CM, Ma RC, Kong AP, et al. Mental morbidities and chronic fatigue in severe acute respiratory syndrome survivors: Long-term follow-up. Arch Intern Med 2009;169:2142-7.  Back to cited text no. 9
    
10.
Proal AD, VanElzakker MB. Long COVID or Post-acute Sequelae of COVID-19 (PASC): An overview of biological factors that may contribute to persistent symptoms. Front Microbiol 2021;12:698169.  Back to cited text no. 10
    
11.
Hall J, Myall K, Lam JL, Mason T, Mukherjee B, West A, et al. Identifying patients at risk of post-discharge complications related to COVID-19 infection. Thorax 2021;76:408-11.  Back to cited text no. 11
    
12.
Disser NP, De Micheli AJ, Schonk MM, Konnaris MA, Piacentini AN, Edon DL, et al. Musculoskeletal consequences of COVID-19. J Bone Joint Surg Am 2020;102:1197-204.  Back to cited text no. 12
    
13.
Vaishya R, Jain VK, Iyengar KP. Musculoskeletal manifestations of COVID-19. J Clin Orthop Trauma 2021;17:280-1.  Back to cited text no. 13
    
14.
Cosentino G, Todisco M, Hota N, Della Porta G, Morbini P, Tassorelli C, et al. Neuropathological findings from COVID-19 patients with neurological symptoms argue against a direct brain invasion of SARS-CoV-2: A critical systematic review. Eur J Neurol 2021;28:3856-65.  Back to cited text no. 14
    
15.
Scoppettuolo P, Borrelli S, Naeije G. Neurological involvement in SARS-CoV-2 infection: A clinical systematic review. Brain Behav Immun Health 2020;5:100094.  Back to cited text no. 15
    
16.
Zubair AS, McAlpine LS, Gardin T, Farhadian S, Kuruvilla DE, Spudich S. Neuropathogenesis and Neurologic Manifestations of the Coronaviruses in the Age of Coronavirus Disease 2019: A Review. JAMA Neurol 2020;77:1018-27.  Back to cited text no. 16
    
17.
Siow I, Lee KS, Zhang JJ, Saffari SE, Ng A, Young B. Stroke as a neurological complication of COVID-19: A systematic review and meta-analysis of incidence, outcomes and predictors. J Stroke Cerebrovasc Dis 2021;30:105549.  Back to cited text no. 17
    
18.
Tu TM, Seet CY, Koh JS, Tham CH, Chiew HJ, De Leon JA, et al. Acute ischemic stroke during the convalescent phase of asymptomatic COVID-2019 infection in Men. JAMA Netw Open 2021;4:e217498.  Back to cited text no. 18
    
19.
Fifi JT, Mocco J. COVID-19 related stroke in young individuals. Lancet Neurol 2020;19:713-5.  Back to cited text no. 19
    
20.
Perry RJ, Smith CJ, Roffe C, Simister R, Narayanamoorthi S, Marigold R, et al. Characteristics and outcomes of COVID-19 associated stroke: A UK multicentre case-control study. J Neurol Neurosurg Psychiatry 2021;92:242-8.  Back to cited text no. 20
    
21.
Blanco JR, Cobos-Ceballos MJ, Navarro F, Sanjoaquin I, Arnaiz de Las Revillas F, Bernal E, et al. Pulmonary long-term consequences of COVID-19 infections after hospital discharge. Clin Microbiol Infect 2021;27:892-6.  Back to cited text no. 21
    
22.
Zhao YM, Shang YM, Song WB, Li QQ, Xie H, Xu QF, et al. Follow-up study of the pulmonary function and related physiological characteristics of COVID-19 survivors three months after recovery. EClinicalMedicine 2020;25:100463.  Back to cited text no. 22
    
23.
Mallapaty S. Evidence suggests the coronavirus might trigger diabetes. Nature 2020;583:16-7.  Back to cited text no. 23
    
24.
Rubino F, Amiel SA, Zimmet P, Alberti G, Bornstein S, Eckel RH, et al. New-onset diabetes in COVID-19. N Engl J Med 2020;383:789-90.  Back to cited text no. 24
    
25.
Ma RC, Holt RI. COVID-19 and diabetes. Diabetic Medicine. 2020 May 1.  Back to cited text no. 25
    
26.
Atkinson MA, Powers AC. Distinguishing the real from the hyperglycaemia: Does COVID-19 induce diabetes? Lancet Diabetes Endocrinol 2021;9:328-9.  Back to cited text no. 26
    
27.
Nalbandian A, Sehgal K, Gupta A, Madhavan MV, McGroder C, Stevens JS, Cook JR, Nordvig AS, Shalev D, Sehrawat TS, Ahluwalia N. Post-acute COVID-19 syndrome. Nature Med 2021;27:601-15.  Back to cited text no. 27
    
28.
Jaul E, Barron J. Age-related diseases and clinical and public health implications for the 85years old and over population. Front Public Health 2017;5:335.  Back to cited text no. 28
    
29.
Available from: https://www.who.int/news-room/fact-sheets/detail/ageing-and-health. [Last accessed on 2021 Jun 08].  Back to cited text no. 29
    
30.
Coperchini F, Chiovato L, Croce L, Magri F, Rotondi M. The cytokine storm in COVID-19: An overview of the involvement of the chemokine/chemokine-receptor system. Cytokine Growth Factor Rev 2020;53:25-32.  Back to cited text no. 30
    
31.
Rea IM, Gibson DS, McGilligan V, McNerlan SE, Alexander HD, Ross OA. Age and age-related diseases: Role of inflammation triggers and cytokines. Front Immunol 2018;9:586.  Back to cited text no. 31
    
32.
Franceschi C, Garagnani P, Parini P, Giuliani C, Santoro A. Inflammaging: A new immune-metabolic viewpoint for age-related diseases. Nat Rev Endocrinol 2018;14:576-90.  Back to cited text no. 32
    
33.
Buicu AL, Cernea S, Benedek I, Buicu CF, Benedek T. Systemic inflammation and COVID-19 mortality in patients with major noncommunicable diseases: Chronic coronary syndromes, diabetes and obesity. J Clin Med 2021;10:1545.  Back to cited text no. 33
    
34.
Bektas A, Schurman SH, 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 inflammaging? Immun Ageing 2020;17:23.  Back to cited text no. 34
    
35.
Chen Y, Klein SL, Garibaldi BT, Li H, Wu C, Osevala NM, et al. Aging in COVID-19: Vulnerability, immunity and intervention. Ageing Res Rev 2021;65:101205.  Back to cited text no. 35
    
36.
Freund A, Orjalo AV, Desprez PY, Campisi J. Inflammatory networks during cellular senescence: Causes and consequences. Trends Mol Med 2010;16:238-46.  Back to cited text no. 36
    
37.
Garschall K, Flatt T. The interplay between immunity and aging in Drosophila. F1000Res 2018;7:160.  Back to cited text no. 37
    
38.
Koff WC, Williams MA. COVID-19 and immunity in aging populations – A new research agenda. N Engl J Med 2020;383:804-5.  Back to cited text no. 38
    
39.
Liguori I, Russo G, Curcio F, Bulli G, Aran L, Della-Morte D, et al. Oxidative stress, aging, and diseases. Clin Interv Aging 2018;13:757-72.  Back to cited text no. 39
    
40.
Mahmoodpoor A, Sanaie S, Roudbari F, Sabzevari T, Sohrabifar N, Kazeminasab S. Understanding the role of telomere attrition and epigenetic signatures in COVID-19 severity. Gene 2022;811:146069.  Back to cited text no. 40
    
41.
de Magalhães JP, Passos JF. Stress, cell senescence and organismal ageing. Mech Ageing Dev 2018;170:2-9.  Back to cited text no. 41
    
42.
Zhang J, Rane G, Dai X, Shanmugam MK, Arfuso F, Samy RP, et al. Ageing and the telomere connection: An intimate relationship with inflammation. Ageing Res Rev 2016;25:55-69.  Back to cited text no. 42
    
43.
Nikolich-Zugich J, Knox KS, Rios CT, Natt B, Bhattacharya D, Fain MJ. SARS-CoV-2 and COVID-19 in older adults: What we may expect regarding pathogenesis, immune responses, and outcomes. Geroscience 2020;42:505-14.  Back to cited text no. 43
    
44.
Cordani M, Butera G, Pacchiana R, Masetto F, Mullappilly N, Riganti C, et al. Mutant p53-associated molecular mechanisms of ROS regulation in cancer cells. Biomolecules 2020;10:361.  Back to cited text no. 44
    
45.
Malavolta M, Giacconi R, Brunetti D, Provinciali M, Maggi F. Exploring the relevance of senotherapeutics for the current SARS-CoV-2 emergency and similar future global health threats. Cells 2020;9:909.  Back to cited text no. 45
    




 

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Abstract
Introduction
Postacute Sequel...
Musculoskeletal ...
Neuropsychologic...
Cardiopulmonary ...
Diabetes
Covid-19 and Aging
Conclusion
References

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