What is the Prevalence of Persistent Symptoms in Older Adults after Covid-19 Infection? A Cohort Study

Abbreviations

NHS: National Health Service; UK: United Kingdom; MMRC: Modified Medical Research Council; SD: Standard Deviation; EQ VAS: EQ-5D-5L Visual Analogue Scale; 6MWT: 6-Minute Walk Test.

Introduction

The United Kingdom (UK) National Health Service (NHS) has defined post-COVID-19 syndrome as unexplained and persistent signs or symptoms over 12 weeks, developed during or after COVID-19 infection [1]. The current 12- week window is based on the median duration of symptoms disappearing [2]. A systematic analysis reveals that, on average, 45% of COVID-19 survivors continue to experience at least one persistent symptom after a follow-up period of 126 days. Fatigue, disrupted sleep, and shortness of breath were widely prevalent symptoms reported across hospitalized, non-hospitalized, and mixed groups. Additionally, the significant occurrence of persistent symptoms after 12 weeks highlights the need for prioritizing Long Covid care within healthcare services and policy. It is essential to comprehend the different types of Long Covid and affected populations to enable tailored healthcare and prevent potential future service overwhelm [3].

In older people, the prevalence of post-COVID-19 syndrome is approximately 9.3% and the most common symptom reported 90 days after recovery was fatigue, followed by cough and breathlessness [4, 5, 6]. In addition, according to Sathyamurthy, et al. a significant proportion of older people also had a risk of anxiety (7.5%) and depression (12.2%) 90 days after recovery and discharge from the hospital [4]. Guo, et al. showed that old patients tend to have more complications than young patients during hospitalization, but with timely and effective treatment they could also achieve comparably good outcomes as young patients [5]. According to Mansell, et al. further research specifically targeting Long Covid in older patients group is necessary. This is crucial as Long Covid should be considered in the differential diagnosis of symptoms, ensuring equitable access to multidisciplinary care interventions aimed at enhancing their functional capacity and overall quality of life [7]. Based on the significant proportion of these symptoms in older adults, it is necessary to understand the long-term consequences and the impact they have on their lives.

From this, the high prevalence of long COVID among the elderly population indicates the need for clinical attention and resource allocation for long COVID among older adults. Then, more comprehensive and prospective long-term follow- up research is needed to investigate if the natural history and patterns of recovery from COVID-19 are different in older adults when compared to younger adults and to accurately estimate the prevalence among the older population because little is known about the long-term effect of long COVID among the older population [4, 6, 8, 9]. A comprehensive understanding of patient care needs beyond the acute phase will help in the development of infrastructure for COVID-19 clinics that will be equipped to provide specialist care for older people, integrated into the outpatient setting. From this, this study aims to assess the prevalence of persistent symptoms in older adults (65 years and over) infected with COVID-19 at 6-8 weeks following infection and at 6-12 months follow-up, and to compare this to the prevalence in younger adults (aged less than 65 years).

Methods

This is a cohort study using routinely collected data from the post-COVID service at Alfred Hospital in Melbourne, Australia. All patients managed by Alfred Health for COVID-19 were invited to complete standardized surveys at 6-8 weeks following infection, and 6-12 months later. A description of the service has previously been published [10]. The study was approved by the Ethics Committee of the Alfred Hospital (66/22) and the methodology was in line with Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) [11].

All patients admitted to the health service with a diagnosis of COVID-19 were identified using a standard report prepared by Alfred Health data analytics. Clinical staff in the post-COVID service use this list to contact all patients and invite them to participate in screening at 6-8 weeks following their admission. Patients included were over 18 years old, of both sexes and tested positive for COVID-19 Patients who declined the offer of follow-up from the Post COVID service or who were unable to complete screening questionnaires due to cognitive impairment or language barriers were excluded. It’s important to note that in Australia, an older adult is defined as an individual aged 65 years or older chronologically [12, 13].

All patients who agreed to receive follow-up from the post-COVID service were invited to complete standardized questionnaires via REDCap in order to identify the nature of ongoing symptoms and the services likely to be needed. Assessments and reassessments were taken place with completion of patient-reported outcomes via the REDCap system, but when patients could not access it, they were reached by phone. Routine follow-up using the same questionnaires was completed at 6-12 months after the first contact to quantify the proportion of patients with persistent symptoms.

Results

Between March 2020 and October 2023, 5471 individuals eligible through the post-COVID service were contacted and sent screening invitations (Figure 1). In total, 1181 patients returned the survey (21% of those eligible). Of these, 870 patients were younger adults (<65 years), and 311 were older adults (≥65 years). Compared to younger adults, older adults were more likely to be male and to have been hospitalized for COVID-19, and less likely to have been working prior to their infection (Table 1). After 6 to 12 months, 84 younger adults and 37 older adults responded to the follow-up.

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Legend: FAS: Fatigue Assessment Scale; mMRC: Modified Medical Research Council; EQ-5D: Euroqol-5D questionnaire; 6MWT: 6 meters walking test; HADS: Hospital Anxiety and Depression Scale questionnaire; IES-R: The Impact of Events Scale-Revised. Figure 1: Flowchart of the study.

Table 1 presents the prevalence and symptom comparison between younger adults and older adults at baseline. Older adults, compared to younger adults, had a lower prevalence of dyspnoea (mMRC: 21% vs. 31%, p<0.01), depression (HADS-D: 9% vs 26%, p<0.01), anxiety (HADS-A: 16% vs 36%, p<0.01), extreme fatigue (FAS: 9% vs 39%, p<0.01), and post-traumatic stress (IES-R: 12% vs 27%, p<0.01). In addition, older adults reported better quality of life compared to younger adults (EQ-5D-5L-VAS: 69±18 vs 57±22, p<0.01), and in specific domains related to usual activities (EQ-5D usual activities: 25% vs 45%, p<0.01), pain (EQ-5D pain: 29% vs 41%, p<0.01), and anxiety and depression (EQ-5D anxiety and depression: 21% vs 40%, p<0.01).

Legend: 30 STS: 30-second sit-to-stand; ICU: Intensive care unit; FEV1: Forced expiratory volume in 1 second; L: litres; FVC: Forced vital capacity; TLCO: Clinical Interpretation of Transfer Factor; 6MWT: 6 minutes walking test; SpO2: Oxygen saturation; HR: Heart rate; mMRC: Modified Medical Research Council; HADS: Hospital Anxiety and Depression Scale; FAS: Fatigue Assessment Scale; EQ-5D: Euroqol-5D questionnaire; IES-R: Impact of Events Scale-Revised. Table 1: Prevalence and comparison of symptoms between younger adults and older adults.

According to Table 2, older adults reported fewer changes in memory (p<0.01), concentration (p<0.01), slowed thinking (p<0.01), heightened agitation (p<0.01), thinking difficulties (p<0.01) and fewer difficulties that affected their ability to carry out daily activities (p<0.01) compared to younger adults. Older adults reported fewer symptoms of extreme fatigue (p<0.01), depression (p<0.01), anxiety (p<0.01), pain (p<0.01), post-traumatic stress disorder (p<0.01), and limitations in usual activities (p<0.01) compared to younger adults (Table 2).

Legend: PTSD: Post-traumatic stress disorder. Table 2: Comparison of the answers between younger adults and older adults.

The resolution of symptoms in younger adult and older adult respondents, over 6-12 months are presented in Table 3. There was a reduction in the proportion of younger adults reporting dyspnoea at 6-12 months compared to baseline (mMRC: 44% vs. 30%, p=0.04), with no changes in prevalence for other outcomes. At follow-up, older adults continued to report a lower prevalence of symptoms than younger adults for anxiety (HADS-A: 17% vs 36%, p=0.03), extreme fatigue (FAS: 9% vs 44%, p<0.01), and better quality of life (EQ- 5D-5L-VAS, 66±23 vs 56±21, p=0.03). Respondents to 6-12 month follow-up were more likely to report symptoms at baseline than those who did not respond, in both older and younger groups (Supplementary table).

Legend: mMRC: Modified Medical Research Council; HADS: Hospital Anxiety and Depression Scale; FAS: Fatigue Assessment Scale; EQ-5D: Euroqol-5D questionnaire; IES-R: Impact of Events Scale-Revised. Table 3: Comparison of symptoms between younger adults and older adults in baseline assessment and after 6 to 12 months of COVID-19 infection.

Discussion

This study reports the prevalence of persistent symptoms in older adults after COVID-19 infection. The results showed that older adults reported fewer symptoms of dyspnea, depression, anxiety, fatigue, post-traumatic stress, and demonstrated a better quality of life at 6-8 weeks following infection (baseline) compared to younger adults. Older adults also reported fewer changes in memory, concentration and thinking when compared to younger adults. When compared at 6-12 months follow-up, older adults continued to report fewer symptoms of anxiety and fatigue, and demonstrated a better quality of life compared to younger adults. There were no differences between older and younger adults for the proportion of patients reporting limitations to mobility, personal care or usual activities at 6-12 months follow-up.

Our findings suggest that older adults generally have better outcomes following COVID-19 infection than younger adults, and contrary to our expectation, experienced a lower symptom burden. These findings are similar to a systematic review [30] which reported the prevalence of symptoms by age (<60 years old and ≥60 years old), where the prevalence of some symptoms in <60 years old was higher than that in ≥60 years old, as found in our results. In older adults, the process of inflammaging, together with immunosuppression or immunosenescence, creates the perfect situation to increase the risk of poor evolution after COVID-19 infection [31, 32, 33]. However, according to current evidence, [32, 34] due to the decompensation of underlying chronic diseases that can mimic clinical manifestations of COVID-19, older adults have a different clinical presentation than younger adults, characterized by more atypical and fewer typical symptoms. In addition, symptoms of Long Covid might be difficult to distinguish from those perceived to be due to ageing, particularly in older people with comorbidities and potential side-effects from polypharmacy [7]. Shanbehzadeh, et al. [34] emphasized that persistent symptoms like fatigue and pain depend on various factors, including cognitive, physiological, and psychological aspects, rather than solely age. Sathyamurthy, et al. [4] found that most older adults retained their baseline functional status after 90 days of recovery from acute COVID-19. In this context, older age was not an independent predictor [34, 35]. These studies support the results of this study, in which, older adults reported fewer symptoms than younger adults.

The COVID-19 pandemic significantly impacted work, study, finances, socialization, and the availability of social support, even in developed countries with sophisticated infrastructure [36, 37]. These diverse factors might have influenced different age groups, potentially affecting their symptoms and well-being. For example, digital tools successfully addressed various pandemic-related challenges in which older adults, who often encounter difficulties accessing and utilizing technology, did not enjoy the same advantages as younger generations [38]. Although, according to an Australian scoping review, [39] mental health problems (i.e. psychological distress, anxiety, depression, poor well- being) increased during the COVID pandemic in young people, those with fewer socio-economic resources and those with pre-existing mental health conditions. These results support our findings, as younger adults reported more symptoms of depression, anxiety, and post-traumatic stress compared to older adults. In addition Castell-Alcalá, et al. [40] affirmed that confinement due to the COVID-19 pandemic was not associated with a worsening of physical function, cognition, depressive mood, and quality of life in pre-frail elderly individuals over 70 years of age. Wróblewska, et al. [41] concluded that the better the functional state of a senior and the support received from relatives, the lower the severity of depression and the lower the quality of a senior’s life, especially in terms of mental state, the greater the negative impact on his/her well-being in isolation. Schäfer, et al. [42] in their systematic review and meta-analysis, illustrated minor declines in mental health among older adults during the initial phases of the pandemic. These findings challenge prior assertions that older adults are uniquely susceptible to adverse mental health outcomes.

In relation to quality of life (QoL), our results showed that older adults demonstrated a better QoL at 6-8 weeks following infection (baseline) compared to younger adults, particularly in the domains of usual activities, pain (EQ- 5D pain), and anxiety and depression (EQ-5D anxiety and depression). At 6-12 months follow-up, older adults continued to demonstrate a superior QoL in comparison to younger adults and there were no differences in the proportion of patients reporting limitations to mobility, personal care or usual activities. According to Salci, et al. [43] the high level of QoL following infection was associated with white race, home ownership, fewer hours of daily screen time, lack of musculoskeletal and anxiety symptoms and no changes to work conditions. The results are in line with our study, as younger adults reported more symptoms and reduced QoL because had to reduce their working hours, and presented more pain and anxiety symptoms in comparison to older adults. In addition, Moens, et al. [44] showed that on the different dimensions of the EQ-5D, in which 89.58% of the post-COVID-19 infected persons reported some or extreme pain, 82.45% indicated some or serious limitations when performing usual activities and 42.59% indicated anxiety/depression. Self-care was preserved in most post- COVID-19 infected persons, as we found in our study. The pandemic disrupted not only social contacts of the general population, but also induced fear, stress, financial concerns, and worries about health, eventually leading to a lower QoL [44].

Conclusion

Older adults reported fewer symptoms of dyspnea, depression, anxiety, fatigue, and post-traumatic stress, and demonstrated a better quality of life at 6-8 weeks following COVID-19 infection compared to younger adults. When compared at 6-12 months follow-up, older adults continued to report fewer symptoms of anxiety and fatigue, and demonstrated a better quality of life compared to younger adults. Further research is needed to understand the persistent symptoms in these populations and the best strategies for treatment according to different age groups.

Declarations

Authors’ Contributions: The study was conceived by AH, MO and ABS. Data were collected by TM, MC, JBeaman, DF, LW, JBuchanan, JU, NL, CM, KF, and JBondarenko. Data were analysed by MO and AH. MO and MH wrote the manuscript. All authors critically reviewed the manuscript and approved submission of the final version. Funding Statement: This study is supported by a research grant by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior- Brasil (CAPES - 001). Conflict of Interest Disclosure: The authors reported no potential conflict of interest. Data Availability Statement: The data are not publicly available due to privacy or ethical restrictions. Ethics Approval Statement: This study was approved by the Ethics Committee of the Alfred Hospital (66/22).