Prevalence, Pattern and Functional Outcome of Post COVID-19 Syndrome in Older Adults

Introduction COVID-19 pandemic has been shown to produce high infection rates, significant morbidity and mortality among older adults. A significant proportion of people who have recovered from acute COVID-19 illness seem to suffer from post COVID-19 syndrome. Post COVID-19 syndrome is thought to be a multisystem disease involving physical, functional, mental and psychological domains. This analysis tries to estimate the prevalence, pattern and functional outcomes of post COVID-19 syndrome in hospitalized older adults. Methods A prospective cohort study was done on 279 older adults who were discharged from our centre between August 1st, 2020 and November 30th 2020. Information was collected through a telephonic interview after 90 days of discharge from the hospital using a standard questionnaire by a trained physician. Collected data were analyzed with IBM SPSS Statistics for Windows, Version 23.0 (IBM Corp., Armonk, NY). Results After 90 days of recovery, the most common symptoms prevalent in the study population were fatigue (8.9%) followed by cough (4.3%), breathlessness (1.8%), dizziness (1.4%), myalgia (1.1%), loss of smell and taste (0.8%) and chest discomfort (0.7%). The prevalence of risk of anxiety in the study population after 90 days of recovery was 7.5% while that of risk of depression was 12.2%. After 90 days of recovery, 66 (23.6%) patients reported the presence of at least one clinical feature while 9.3% had two or more clinical features. On comparing the mean activities of daily living (ADL) 5.58 (.795) and mean instrumental activities of daily living (IADL) 5.84 (1.49) before the illness and 90 days following recovery there was no statistical difference for the study population. Conclusion The prevalence of post COVID-19 syndrome in older adults is about 9.3%. The most common symptoms reported by older adults after 90 days following recovery were fatigue followed by cough and breathlessness. Most older adults retained their baseline functional status after 90 days of recovery from acute COVID-19.


Introduction
The COVID-19 pandemic, which began in December 2019, has produced high infection rates as well as significant morbidity and mortality among older adults [1][2][3]. Immune senescence and age-related immune remodeling might be the reason for this vulnerability [4]. Six months into the pandemic, reports of persisting symptoms and long-term morbidity in COVID-19 survivors have been published across the world [5][6][7][8][9][10][11][12][13]. Most of the cases have symptoms that persist from the time of acute clinical illness, whereas some cases have symptoms that appear even after recovery [5,7] from acute COVID-19 and can also be intermittent [7]. Residual organ damage, persistence of systemic inflammation, the effects of hospitalization, and associated comorbidities might be the contributing factors for this [5,14]. Slowly, researchers have started using the term "long COVID-19 syndrome" or "post-COVID-19 syndrome" for these protracted symptoms following virological recovery of COVID-19 [7,8,10,12,[14][15][16][17][18]. Post-COVID-19 syndrome is thought to be a multisystem disease [6,7,14,18], involving physical (breathlessness, fatigue, and anosmia), functional (reduced activity), mental (cognitive impairment), and psychological (anxiety and depression) domains [7,8,9,11,13,16,19,20]. Nevertheless, the precise definition or the duration of post-COVID-19 syndrome remains unclear [7,10,14,16,18]. Moreover, the prevalence of various symptoms of post-COVID-19 syndrome, the features of the study population, and the timing of analysis have varied across the study settings [14,18]. In December 2020, guidelines from the National Institute of Health and Care Excellence suggested a temporal criterion of 12 weeks (approximately three months) for defining post-COVID-19 syndrome [15]. Studies have shown that this syndrome affects a significant proportion of recovered COVID-19 patients, independent of their age, clinical severity, and laboratory features [6,[12][13][14]18,19]. However, an earlier comprehensive review suggested that post-COVID-19 syndrome is likely to occur more among women and older adults [7,18]. Data in the older adults are lacking, yet it is essential for providing appropriate post-COVID-19 rehabilitation in this vulnerable age group. This study aimed to analyze a cohort of older adults hospitalized with COVID-19 for the presence, prevalence, and patterns of post-COVID-19 syndrome alongside their functional outcomes 90 days after their recovery and discharge from the hospital.

Materials And Methods
This study included patients at least 65 years old who were hospitalized with acute COVID-19 and were discharged in a stable condition after recovery between August 1, 2020 and November 30, 2020. COVID-19 was confirmed in these patients using nasopharyngeal swab real-time polymerase chain reaction testing. Patients were clinically categorized as either mild to moderate illness (M/M) or severe to critical illness (S/C) [21]. Mild illness was defined as having any of the various signs and symptoms of COVID-19 but without shortness of breath, dyspnea, or abnormal chest imaging. Moderate illness was defined as having evidence of lower respiratory disease during clinical assessment or imaging and with oxygen saturation (SpO2) ≥ 94% on room air at sea level. Severe illness was defined as having SpO2 < 94% on room air at sea level. Critical illness was defined as having respiratory failure, septic shock, and/or multiple organ dysfunction [21].
A telephone interview was attempted using a standard questionnaire (Appendix 1) by a trained physician 90 days from the date of discharge. Patients who responded within five days (i.e., from day 91 to 96 postdischarge) after a maximum of five attempts and completed the interview were included in the analysis. Non-responders due to various reasons, patients who died before the survey, and patients who developed significant medical illness (such as aphasia) before the survey, which precluded them from completing the interview, were all excluded from the study. Out of 335 cases in the study period, 47 did not respond because of various reasons (not willing to participate, not answering the call, etc.), four died within 90 days after discharge, and five were unable to complete the interview due to medical illness. Finally, 279 eligible older adults were included in our analysis ( Figure 1).

FIGURE 1: Patient flow chart
The questionnaire (Supplementary Questionnaire 1) was composed of details regarding the following: symptoms persisting and present at the end of 90 days; comorbidities present during hospitalization; KATZ index of independence in activities of daily living (ADL) [22], scores and LAWTONS instrumental activities of daily living (IADL) [23], scored before the illness and 90 days after discharge from the hospital; mental status screening using the Short Portable Mental Status Questionnaire (SPMSQ) [24]; screening for depression using a 5-item version of the Geriatric Depression Scale [25]; and screening for anxiety using a short form of the Geriatric Anxiety Inventory [26].
Because the concept and components of post-COVID-19 syndrome were in the evolving stage at the start of this study, SPMSQ was conducted only for patients who presented with altered mentation upon hospital admission.
The collected data were analyzed with IBM SPSS Statistics for Windows, Version 23.0 (IBM Corp., Armonk, NY). In the descriptive statistics frequency analysis, categorical variables were described as percentages, whereas continuous variables were described as mean ± standard deviation (SD). Unpaired sample t-test was used to find significant differences between the bivariate samples among independent groups. Chi-square test was used to find significance in categorical data. Similarly, if the expected cell frequency is <5 in 2 × 2 tables, then Fisher's exact test was used. Statistical significance was set at p < .05.
As per the government regulations, this study has been registered with the Clinical Trial Registry of India (CTRI) (ref no. CTRI/2020/11/029264). The study was approved by the Sri Ramachandra Institute of Higher Education and Research (SRIHER) institutional ethics committee, ref. no IEC-NI/20/SEP/75/70(COVID19).
Male n (%) Female n (%) P-value M/M n (%) S/C n (%) P-value Total n (%)   In comparing the prevalence of persisting symptoms between clinical severity groups, cough was significantly more prevalent in the S/C group versus the M/M group (6.9% vs. 2.5%, respectively) ( Table 2).
Ironically, the prevalence of persistent breathlessness was higher in the M/M group than in the S/C group (1.8% vs. 1.7%, respectively) ( Table 2 and Figure 1). There was no difference in the prevalence of the other symptoms between the groups.
On the basis of the screening questionnaire, 90 days after recovery, the prevalence of anxiety risk was 7.5%, whereas that of depression risk was 12.2% ( Table 2). There was no statistical difference in the prevalence of anxiety and depression risks between men and women. However, the prevalence of depression risk was significantly more (17.2% vs. 8.6%) in the S/C group than in the M/M group 90 days after recovery (p = 0.0219) ( Table 2). There was no significant difference in the prevalence of risk of anxiety between the two groups (6.7% vs. 8.6%) ( Table 2).
Regarding the presence of clinical features, 90 days after recovery, 66 (23.6%) patients reported the presence of at least one clinical feature. Among these 66 patients, only 26 (9.3%) had two or more clinical features ( Table 3). The prevalence of post-COVID-19 syndrome (two or more clinical features) was significantly high among S/C patients (14% vs. 6%) when compared with M/M patients (p = 0.50) ( Table 3).
Despite these similarities, many earlier studies conducted on post-COVID-19 hospitalized patients have reported a very high frequency of symptoms, with >50% of patients reporting at least one symptom [8,9,11,13,19]. The lesser prevalence of symptoms in our study could be because most of the earlier studies analyzed a heterogeneous population with a smaller sample size. An application-based COVID-19 symptom study showed that the frequency of post-COVID-19 symptoms declines over time, with the prevalence of symptomatic patients decreasing from 13% to 2.3% at four to 12 weeks post-recovery, respectively [7]. Hence, the decreased prevalence of symptoms in our study is understandable, because we analyzed patients 90 days after recovery, in contrast to earlier studies that had follow-up periods of <60 days [8,9,11,13,19].
Anxiety and depression have been recognized as a part of post-COVID-19 syndrome by many authors [8,14,20,29], but these have been reported with varying rates [8]. A recent review has estimated the prevalence of anxiety and depression to be between 23% and 26% among post-COVID patients [14], and another study reported the prevalence of anxiety and depression to be 29.6% and 26.8%, respectively [20].
Our study showed far less prevalence of anxiety and depression (7.5% and 12.2%, respectively) in older adults after recovery from acute COVID-19 ( Table 2 and Figure 2). This could be due to our larger sample size and longer follow-up period, especially because most of the earlier studies did their analysis within eight weeks of recovery.
When comparing the clinical features between the clinical severity groups, S/C patients were more likely to have persistent cough and breathlessness along with a higher risk of depression (P = 0.0219) 90 days after recovery from acute illness compared with M/M patients ( Table 2 and Figure 1).
The prevalence of post-COVID-19 syndrome has widely varied between reports. In a recent review [18], the prevalence rate varied widely between 4.7% and 80%, with the temporal criteria for analysis varying between two and 24 weeks. In another report [14], the prevalence was as high as 80% in hospitalized patients, compared with non-hospitalized patients at 10%, with the overall prevalence estimated to be 10%. In a Mediterranean cohort study [12], the incidence of post-COVID-19 syndrome (defined as the presence of at least one symptom) was 58.2% in cases with severe pneumonia, compared with 37% in cases without pneumonia.
Our study defined post-COVID-19 syndrome as the presence of at least two clinical features >12 weeks postrecovery [15]; its overall presence was approximately 9.3% among older adults in our study ( Table 3). This lower prevalence could be due to the better sample size and longer follow-up period because the prevalence of post-COVID-19 syndrome decreases over time [7]. Comparing patients by clinical severity, post-COVID-19 syndrome was significantly higher in the S/C group than in the M/M group. This is in line with an earlier cohort study [13] that showed that patients with severe pneumonia had a higher incidence of post-COVID syndrome.
The functional status of patients after recovery from acute COVID-19 is expected to be poor because of various reasons like fatigue, myalgia, and breathlessness [5,[7][8][9]19]. So far, the functional status of older adults after recovery from COVID-19 has not been objectively assessed. In our analysis of 279 patients, there was no significant difference in mean ADL and IADL before the illness and at 90 days after recovery ( Table  4). Therefore, it can be said that older adults regained their near-baseline function status 90 days after recovery from acute COVID-19.

Strengths and limitations
To the best of our knowledge, this is the first study of post-COVID-19 syndrome exclusively conducted on older adults with appropriate temporal criteria. Only 14% (47) of patients were non-responders during the follow-up survey. Moreover, unlike earlier studies, we included psychiatric sequelae and functional status in our analysis.
However, our study also has limitations. First, this was only a single-center study conducted during the first wave of COVID-19 in India. Mental status screening was performed during follow-up only for patients who presented with altered mentation during admission. Last, some parts of the questionnaire used for the interview are subject to recall bias.

Conclusions
The prevalence of post-COVID-19 syndrome in the elderly is approximately 9.3%. The most common symptom reported 90 days after recovery was fatigue, followed by cough and breathlessness. A significant proportion of the elderly had a risk of anxiety and depression 90 days after recovery and discharge from the hospital. Older adults seem to regain their baseline functional status in terms of ADL and IADL 90 days after recovery from COVID-19. However, because this was a single-center study conducted during the first wave of COVID-19, more comprehensive and multi-centric studies are required to accurately estimate the prevalence of post-COVID-19 syndrome. Because approximately 23.6% of patients had at least one symptom persisting 90 days after recovery, it is important to establish appropriate follow-up protocols such as setting up post-COVID-19 clinics to address the needs of this vulnerable population.

Appendices
Supplementary Questionnaire 1 Newly developed persisting -NOT present during admission but developed after discharge and still persisting Newly developed resolved -NOT present during admission, but developed after discharge and resolved now. (0 points) Needs partial or total help with feeding or requires parenteral feeding.