elderly – American ME and CFS Society

Risk Factors for Long COVID in Older Adults

Abstract:

As time has passed following the COVID-19 pandemic, individuals infected with SARS-CoV-2 have gradually exhibited a variety of symptoms associated with long COVID in the postacute phase of infection. Simultaneously, in many countries worldwide, the process of population aging has been accelerating. Within this context, the elderly population has not only become susceptible and high-risk during the acute phase of COVID-19 but also has considerable risks when confronting long COVID.

Elderly individuals possess specific immunological backgrounds, and during the process of aging, their immune systems can enter a state known as “immunosenescence”. This further exacerbates “inflammaging” and the development of various comorbidities in elderly individuals, rendering them more susceptible to long COVID. Additionally, long COVID can inflict both physical and mental harm upon elderly people, thereby reducing their overall quality of life. Consequently, the impact of long COVID on elderly people should not be underestimated.

This review seeks to summarize the infection characteristics and intrinsic factors of older adults during the COVID-19 pandemic, with a focus on the physical and mental impact of long COVID. Additionally, it aims to explore potential strategies to mitigate the risk of long COVID or other emerging infectious diseases among older adults in the future.

Source: Hu Y, Liu Y, Zheng H, Liu L. Risk Factors for Long COVID in Older Adults. Biomedicines. 2023; 11(11):3002. https://doi.org/10.3390/biomedicines11113002 https://www.mdpi.com/2227-9059/11/11/3002 (Full text)

From aging to long COVID: exploring the convergence of immunosenescence, inflammaging, and autoimmunity

Abstract:

The process of aging is accompanied by a dynamic restructuring of the immune response, a phenomenon known as immunosenescence. This mini-review navigates through the complex landscape of age-associated immune changes, chronic inflammation, age-related autoimmune tendencies, and their potential links with immunopathology of Long COVID. Immunosenescence serves as an introductory departure point, elucidating alterations in immune cell profiles and their functional dynamics, changes in T-cell receptor signaling, cytokine network dysregulation, and compromised regulatory T-cell function.

Subsequent scrutiny of chronic inflammation, or “inflammaging,” highlights its roles in age-related autoimmune susceptibilities and its potential as a mediator of the immune perturbations observed in Long COVID patients. The introduction of epigenetic facets further amplifies the potential interconnections.

In this compact review, we consider the dynamic interactions between immunosenescence, inflammation, and autoimmunity. We aim to explore the multifaceted relationships that link these processes and shed light on the underlying mechanisms that drive their interconnectedness. With a focus on understanding the immunological changes in the context of aging, we seek to provide insights into how immunosenescence and inflammation contribute to the emergence and progression of autoimmune disorders in the elderly and may serve as potential mediator for Long COVID disturbances.

Source: Müller L, Di Benedetto S. From aging to long COVID: exploring the convergence of immunosenescence, inflammaging, and autoimmunity. Front Immunol. 2023 Oct 24;14:1298004. doi: 10.3389/fimmu.2023.1298004. PMID: 37942323; PMCID: PMC10628127. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10628127/ (Full text)

Long COVID in the Older Adult and Vitamin D

Abstract:

Background: The coronavirus COVID-19 strain that emerged in December 2019 continues to produce a widespread and seemingly intractable negative impact on health and longevity and life quality in all parts of the world, especially, among older adults with chronic health conditions.

Objectives: The first aim of this updated review article was to examine, summarize, synthesize, and report on the research base concerning the possible use of vitamin D in the realm of the recently emergent syndrome termed long or post-acute COVID-19 disease. A second was to establish any health associated preventive and intervention recommendations for the older adult with long COVID-19 manifestations, who may yet be susceptible to future COVID-19 variant infections and others.

Methods: To examine the association between vitamin D and long COVID-19 illness manifestations, articles responding to several key words entered into leading data bases were examined: These included the terms: Vitamin D, Long/Post-Acute COVID-19 and/or COVID-19. Databases employed were PUBMED, PubMed Central and Google Scholar. All relevant articles were carefully examined and those meeting the review criteria were carefully read, and described in narrative form.

Results: Data reveal some possible benefits may accrue in the context of COVID-19 illness prevention and rehabilitation by efforts to ensure optimal vitamin D serum levels among high risk, vitamin D deficient, and chronically challenged post-acute COVID-19 older adults.

Conclusion: More rigorous and carefully construed research efforts to examine vitamin D implications and its moderating or mediating role in averting or mitigating long COVID-19 health complications are strongly warranted.

Source: Ray Marks (2023) Long COVID in the Older Adult and Vitamin D. J Gerontol Geriatr Med 9: 155. https://www.heraldopenaccess.us/openaccess/long-covid-in-the-older-adult-and-vitamin-d (Full text)

Long COVID burden and risk factors in 10 UK longitudinal studies and electronic health records

Abstract:

The frequency of, and risk factors for, long COVID are unclear among community-based individuals with a history of COVID-19. To elucidate the burden and possible causes of long COVID in the community, we coordinated analyses of survey data from 6907 individuals with self-reported COVID-19 from 10 UK longitudinal study (LS) samples and 1.1 million individuals with COVID-19 diagnostic codes in electronic healthcare records (EHR) collected by spring 2021. Proportions of presumed COVID-19 cases in LS reporting any symptoms for 12+ weeks ranged from 7.8% and 17% (with 1.2 to 4.8% reporting debilitating symptoms). Increasing age, female sex, white ethnicity, poor pre-pandemic general and mental health, overweight/obesity, and asthma were associated with prolonged symptoms in both LS and EHR data, but findings for other factors, such as cardio-metabolic parameters, were inconclusive.

Source: Thompson EJ, Williams DM, Walker AJ, Mitchell RE, Niedzwiedz CL, Yang TC, Huggins CF, Kwong ASF, Silverwood RJ, Di Gessa G, Bowyer RCE, Northstone K, Hou B, Green MJ, Dodgeon B, Doores KJ, Duncan EL, Williams FMK; OpenSAFELY Collaborative, Steptoe A, Porteous DJ, McEachan RRC, Tomlinson L, Goldacre B, Patalay P, Ploubidis GB, Katikireddi SV, Tilling K, Rentsch CT, Timpson NJ, Chaturvedi N, Steves CJ. Long COVID burden and risk factors in 10 UK longitudinal studies and electronic health records. Nat Commun. 2022 Jun 28;13(1):3528. doi: 10.1038/s41467-022-30836-0. PMID: 35764621; PMCID: PMC9240035. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9240035/ (Full text)

Neuropsychological measures of “Long COVID-19 Fog” in older subjects

Abstract:

Covid-19 is known to impact older people more severely and to cause a number of persistent symptoms during the recovery phase, including cognitive and neurological ones. We investigated the cognitive and neurological features of 100 elderly patients with confirmed diagnosis of Covid-19 evaluated in the post-acute phase through a direct neuropsychological evaluation consisting on Mini Mental State Examination and other 8 neuropsychological tests. Overall, a total of 33 subjects were found to perform at a level considered to be pathological; more specifically, 33%, 23% and 20% failed on Trial Making, Digit Span Backwards and Frontal Evaluation Battery tests respectively.

Source: Alessandra Lauria, Angelo Carfì, Francesca Benvenuto, Giulia Bramato, Francesca Ciciarello, Sara Rocchi, Elisabetta Rota, Andrea Salerno, Leonardo Stella, Marcello Tritto, Antonella Di Paola, Cristina Pais, Matteo Tosato, Delfina Janiri, Gabriele Sani, Francesco Cosimo Pagano, Massimo Fantoni, Roberto Bernabei, Francesco Landi, Alessandra Bizzarro. Neuropsychological measures of “Long COVID-19 Fog” in older subjects. Clinics in Geriatric Medicine, 2022. ISSN 0749-0690, https://doi.org/10.1016/j.cger.2022.05.003. (Full text available as PDF file)

A call to action to enhance understanding of long COVID in long-term care home residents

Letter to the editor:

The COVID-19 pandemic has highlighted significant vulnerabilities in the long-term care (LTC) sector, with widespread outbreaks and high rates of mortality in LTC homes (including nursing homes and assisted living facilities). In Canada, where our team is based, 81% of all COVID-19 deaths in the first wave of the pandemic were among LTC residents.¹ By the end of 2020, there had been ~44,000 COVID-19 cases and 9200 related deaths among residents in Canadian LTC homes.² Although most LTC residents survived acute COVID-19 infection, this does not mean they escaped the lasting impacts of long COVID. There are few studies investigating COVID-19 survivorship, including long COVID prevalence, management, and outcomes among LTC residents.

There has been increasing recognition and research on post-acute sequelae of COVID-19 (PASC), commonly known as long COVID. PASC is a complex and poorly defined syndrome with several possible mechanisms (e.g., viral persistence, immune dysregulation, autoimmunity).³ It involves diverse, persistent, and sometimes disabling symptoms lasting for weeks to months following acute COVID-19 infection (e.g., fatigue, shortness of breath, malaise, cough, pain, brain fog).⁴

Long COVID research is challenged by several factors. First, there is a lack of a globally standardized clinical case definition for long COVID. Some definitions,⁴ but not all, recognize several phases of long COVID, such as ongoing symptomatic COVID-19 (4 to 12 weeks) and post COVID-19 syndrome (≥12 weeks).⁵ Variations across definitions can inadvertently exclude groups with possible atypical presentation and different clusters of symptoms, such as in older adult and pediatric populations. Second, there lacks consensus on the onset and duration of long COVID symptoms and phases, as well as on the symptoms associated with long COVID. In fact, some studies identify more than 200 different symptoms.⁶ This hampers health professionals’ ability to diagnose and treat persons experiencing long-term sequelae of COVID-19, which also hinders clinical research on long COVID in particular.

Another shortcoming of long COVID research has been the exclusion of older adults – especially the oldest old (80+ years), those with multiple complex comorbidities, frailty, disability, dementia, and impaired immune function, which are characteristic of LTC residents. Challenges in studying this population include distinguishing between long COVID as a clinical entity separate from anticipated decline when recovering from acute illness, and intersecting mechanisms of advanced aging, pre-existing conditions, and long COVID. One of the few studies⁷ in older adults found that COVID-19 survivors (65+ years) had a higher risk of new or persistent clinical sequelae compared to non-infected older adults. Furthermore, older adult COVID-19 survivors only had increased risk differences of select sequelae (i.e., respiratory failure, dementia, and post-viral fatigue) compared to a group of older adults with viral lower respiratory tract illness.

Emerging, although limited, research in LTC residents has investigated symptoms, clinical outcomes, and wellbeing of COVID-19 survivors.^8–10 However, these studies lack consideration of long COVID in their design and interpretation, such as the etiology, symptoms, and follow-up periods consistent with the current evidence on long COVID. The only study⁸ to our knowledge on COVID-19 disease trajectories in LTC residents found widespread, prolonged symptoms regardless of symptom severity, but neglected to assess differences in the acute COVID-19 infection versus long COVID phases. COVID-19 survivors in LTC have been found to have poorer outcomes related to malnutrition, weight loss, and frailty compared to non-infected residents.^9, 10 Studies have also attributed physical and cognitive decline and depressive symptoms among COVID-19 survivors to the isolation and loneliness due to protective measures in LTC.⁹

Research design and interpretation of long COVID outcomes for LTC residents require special consideration of their complex comorbidities and diverse physical, psychological, and social care needs (e.g., communication impairments that limit self-reporting of symptoms, long COVID symptoms being attributed to pre-existing conditions).⁵ There is also a need to explore the impact and possible further exacerbation of policies and practices that were enacted in LTC homes during the pandemic. Given the waves of COVID-19 and its variants, it is also important to consider the impacts of policies and practices at different junctures in time, such as visitation restrictions and pre-vaccinations and boosters for LTC residents.

We make a call to action to the research community to rapidly address the dearth of research about long COVID among residents in LTC homes. The knowledge gaps and challenges outlined above emphasize the need for research to inform guidelines for long COVID management in this unique care context. This must be addressed in a timely fashion considering the ongoing COVID-19 outbreaks in LTC homes and the immense challenges currently faced by the LTC sector.

Source: Sorensen JM, Crooks VA, Freeman S, Carroll S, Davison KM, MacPhee M, Berndt A, Walls J, Mithani A. A call to action to enhance understanding of long COVID in long-term care home residents. J Am Geriatr Soc. 2022 May 14. doi: 10.1111/jgs.17889. Epub ahead of print. PMID: 35567575. https://agsjournals.onlinelibrary.wiley.com/doi/10.1111/jgs.17889 (Full text)

The long-COVID-19 in older adults: facts and conjectures

The coronavirus disease-19 (COVID-19) has greatly affected the overall health of the elderly population through direct biological (infection-related) and indirect psychosocial (quarantine- and isolation-related) effects. Because the severe form of COVID-19 most frequently targets this population, the prevalence of long-term sequelae is expected to rise consequentially in people ≥ 65 years old. The prominent neuropsychiatric consequences of COVID-19 and the cognitive frailty seen in older adults can both have a negative impact on their mental health.

To explore the behavioral, neurological, and psychosocial consequences of COVID-19, we conducted separate studies on different populations of older adult people residing in Lombardy – the Italian epicenter of the first pandemic wave in spring 2020. In one study, we found that behavioral changes (i.e., delirium) were a frequent symptom of COVID-19, manifesting at disease onset and preceding the typical symptoms in about 1/3 (36.8%) of cases, particularly in patients with neurocognitive disorders (NCD), such as dementia (major-NCD) or mild cognitive impairment (mild-NCD). Delirium was also associated with short-term mortality and potential long-term cognitive sequelae (Poloni et al., 2020).

To uncover the neuropathology underlying behavioral changes and their possible effects over time, we compared 9 brains of elderly patients who had died of COVID-19 (with and without dementia) with 6 brains from age-matched non-COVID controls. The main finding was an excessive innate immune response, represented by microglial hyperactivation. Although we observed severe inflammatory changes especially in the brainstem, we did not find neuropathological evidence suggestive of SARS-CoV-2 replication in the brain (Gagliardi et al., 2021; Poloni et al., 2021).

In a study evaluating the psychosocial consequences of the lockdown due to the pandemic (Carlos et al., 2021), we observed that those with mild-moderate dementia were unable to cope and adapt to the life changes caused by the restrictions and consequently suffered from depression and cognitive decline. Before COVID, patients with dementia normally engaged in habitual daily activities. The disruption of said routines, the inability to engage in new activities, and the incapability to use modern technologies all triggered psychological distress and some degree of cognitive and motor regression (Figure 1A). Although lockdown (the sternest form of quarantine in history) protected them from COVID-19, the social seclusion and the inability to access primary care treatment – aggravated by an unprepared and unequipped primary care health sector – caused further complications (Carlos et al., 2021). Moreover, the general effects of the pandemic in terms of loss of “individual freedom”, economic crisis, and mass media conditioning should not be overlooked due to their possible impact on mental health.

Source: Poloni, Tino Emanuele; Medici, Valentina; Zito, Antonio; Carlos, Arenn Faye The long-COVID-19 in older adults, Neural Regeneration Research: December 2022 – Volume 17 – Issue 12 – p 2679-2681 doi: 10.4103/1673-5374.339483 https://journals.lww.com/nrronline/Fulltext/2022/12000/The_long_COVID_19_in_older_adults__facts_and.27.aspx (Full text)

Increased HDAC in association with decreased plasma cortisol in older adults with chronic fatigue syndrome

Abstract:

Hypocortisolism is a frequent finding in individuals with chronic fatigue syndrome (CFS) with other research findings implying potential dysregulation of glucocorticoid signaling. Glucocorticoid signaling is under the influence of several pathways, several of which are of interest in the study of CFS. Oxidative stress and decreased antioxidant capacity are known to disrupt the hypothalamic-pituitary-adrenal (HPA) axis (Epel et al., 2004) and the presence of histone deacetylases (HDAC) could also impact glucocorticoid signaling.

The intent of this pilot study was to investigate the relationship among oxidative stress elements, select HDAC’s (2/3) and glucocorticoid receptor signaling in an elderly sample with CFS. Findings suggest increased histone deacetylase activity, lower total antioxidant power, in the context of decreased plasma cortisol and increased plasma dehydroepiandrosterone concomitant with decreased expression of the encoding gene for the glucocorticoid receptor. These findings support the presence of HPA axis dysregulation in elderly individuals with CFS.

Source: Jason L, Sorenson M, Sebally K, Alkazemi D, Lerch A, Porter N, Kubow S. Increased HDAC in association with decreased plasma cortisol in older adults with chronic fatigue syndrome. Brain Behav Immun. 2011 Nov;25(8):1544-7. doi: 10.1016/j.bbi.2011.04.007. Epub 2011 Apr 28. https://www.ncbi.nlm.nih.gov/pubmed/21549189