Electronic supplementary material:

The online version of this article contains supplementary material.

© 2024 The Author(s) Cite as: Deng J, Qin C, Lee M, Lee Y, You M, Liu J. Effects of rehabilitation interventions
for old adults with long COVID: A systematic review and meta-analysis of randomised
controlled trials. J Glob Health 2024;14:05025.

Effects of rehabilitation interventions for

PAPERS
old adults with long COVID: A systematic
review and meta-analysis of randomised
controlled trials
Jie Deng1 , Background There is limited evidence on the effectiveness of the existing reha-
Chenyuan Qin1 , bilitation interventions for old adults with long coronavirus disease (COVID),
Minjung Lee2 , which is of particular concern among old adults.
Yubin Lee3 , Methods We systematically searched studies published in PubMed, EMBASE,
Myoungsoon You3,4 , Web of Science, Scopus, and Cochrane Library databases from their inception
Jue Liu1,5 to 15 November 2023. Randomised controlled trials (RCTs) compared rehabil-
itation interventions with other controls in old adults (mean/median age of 60
Department of Epidemiology and
1
or older) with long COVID were included. We performed a meta-analysis to
Biostatistics, School of Public compare the effects of the rehabilitation interventions with the common con-
Health, Peking University, Beijing,
China
trol group. Mean difference (MD) or standardised mean difference (SMD) with
Dental Research Institute, School
2 its 95% confidence intervals (CI) were used as summary statistics. Moreover,
of Dentistry, Seoul National subgroup analyses based on the intervention programmes, the severity of acute
University, Seoul, Republic of infection, and the age of participants were carried out.
Korea
Department of Public Health
3 Results A total of 11 RCTs involving 832 participants (64.37 ± 7.94 years, 52.2%
Sciences, Graduate School of were men) were included in the analysis. Compared with the control groups, re-
Public Health, Seoul National habilitation interventions significantly improved 6-minute walking test (6 MWT;
University, Seoul, Republic of MD = 15.77 metres (m), 95% CI = 5.40, 26.13, P < 0.01), 30-second sit-to-stand
Korea test (MD = 4.11 number of stands (n), 95% CI = 2.46, 5.76, P < 0.001), all aspects
Institute of Health and
4
of quality of life, independence in activities of daily living (SMD = 0.31, 95%
Environment, Seoul National
CI = 0.14, 0.48, P < 0.001), and relieved fatigue (SMD = −0.66, 95% CI = −1.13,
University, Seoul, Republic of
Korea −0.19, P < 0.01), depression (SMD = −0.89, 95% CI = −1.76, −0.02, P < 0.05) and
Institute for Global Health and
5 anxiety (SMD = −0.81, 95% CI = −1.58, −0.05, P < 0.05). However, the improve-
Development, Peking University, ment of hand grip strength and pulmonary function was not statistically sig-
Beijing, China nificant (P > 0.05). Subgroup analyses showed that improvements in 6 MWT,
fatigue, anxiety, and depression were more pronounced in old patients who
received exercise training, while those who received respiratory rehabilitation
had more pronounced improvements in pulmonary function and quality of life.
Conclusions Old adults with long COVID who underwent rehabilitation inter-
Correspondence to: ventions experienced significant improvement in functional capacity, fatigue,
Prof Jue Liu quality of life, independence in activities of daily living, and mental health out-
School of Public Health; Institute for comes compared with usual/standard care. These findings suggest that screen-
Global Health and Development, ing, management, and rehabilitation interventions for long COVID in older
Peking University
No.38, Xueyuan Road, Haidian adults should be strengthened to improve their complete health status and func-
District, Beijing tional status, thereby reducing the long-term disease burden caused by long
China COVID and fostering healthy aging during the post-pandemic era.
jueliu@bjmu.edu.cn

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 Deng et al.

The pandemic of coronavirus disease 2019 (COVID-19) has posed a significant impact on global public
health, particularly old adults who were more vulnerable to severe illness and complications following
COVID-19 infection [1]. Although survivors recovered from the acute phase of COVID-19, many of them
were facing various ongoing symptoms, which were defined as post-COVID-19 condition (PCC) or long
COVID, impacted functioning and activities of daily living, encompassing physical, psychological, and cog-
nitive functions [2,3]. A scoping review of 50 studies suggested that long COVID was a heterogeneous con-
dition, with a spectrum of over 100 reported symptoms, the incidence of which ranged from 10 to 80% [4].
Long COVID has emerged as an important public health issue that could increase the existing burden of
diseases and health care resources globally [5].
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Long COVID is of particular concern among older adults. Previous studies showed that older patients faced
an increased risk of morbidity and mortality due to COVID-19, and were at a higher risk of long COVID com-
pared to younger patients [1,6]. Besides, COVID-19 might worsen or trigger chronic conditions commonly
found in older people, such as cardiovascular diseases, respiratory diseases, neurodegenerative conditions,
and functional decline [1]. Furthermore, lockdowns and other restrictions, as well as the possibility of los-
ing a spouse or loved one during the pandemic, may also contribute to the mental and physical decline of
older persons [1]. Aging present is a growing problem globally. According to the World Health Organization
(WHO), the number of people aged 60 years and older was one billion in 2019 and will increase to 1.4 bil-
lion by 2030 [7]. The older population bears an additional burden in the face of long COVID, and the size
of older people affected by long COVID is enormous if estimated by the prevalence rate of 10–80%, which
could pose a great burden to the health care system [4]. Thus, a critical consideration is necessary for the
management and rehabilitation of long COVID in the aged population, which would also help foster healthy
aging during the pandemic towards a Decade of Healthy Ageing (2021–2030) [8].
Effective rehabilitation interventions for long COVID are critical, especially in the elderly, a high-risk popu-
lation. The conclusions of existing studies on rehabilitation interventions for long COVID were inconsistent.
According to previous reviews, rehabilitation interventions for patients with long COVID encompassed a
range of approaches such as respiratory exercises, aerobic training, strength exercises, psychological sup-
port, medicine treatment, etc. [9–11]. The latest systematic review with meta-analysis (1244 participants
of 14 trials; median (interquartile range (IQR)) age, 50 (47–56) years) suggested that rehabilitation inter-
ventions were associated with improvements in functional exercise capacity, dyspnoea, and quality of life,
with a high probability of improvement compared with the current standard care [9]. However, most of the
existing studies assessing the effectiveness of rehabilitation interventions for long COVID were targeted at
the general population, and very limited high-quality evidence has specifically addressed the rehabilitation
interventions for old adults recovering from COVID-19. McCarthy et al. conducted a systematic review and
meta-analysis (570 older adults of 12 studies) and the results showed that multidisciplinary rehabilitation
may result in improved functional outcomes on discharge from rehabilitation units/centres for older adults
with COVID-19, but the limitation is that no trial studies were included in this review and none of the in-
cluded studies followed up patients after discharge or reported on long term effects of COVID-19 on dis-
charge from rehabilitation units [10]. Therefore, enhancing research to provide high-quality evidence on
rehabilitation interventions for older adults with long COVID is essential.
Rehabilitation interventions for old adults played a crucial role in addressing challenges posed by long
COVID. The general aim of geriatric rehabilitation is to improve the complete health status and functional
status of older patients and to prevent and treat the physical, functional, and psychological impairments re-
sulting from COVID-19 [12]. Therefore, these questions should be considered and addressed: what are the
existing rehabilitation interventions for old adults with long COVID? Compared to standard care, some re-
habilitation interventions have shown symptomatic and functional improvements in the general population
with long COVID, however, what are the effects of these existing interventions for old adults, a specific and
vulnerable group? There is a paucity of evidence on these questions. Therefore, we conducted a systematic re-
view and meta-analysis of the existing randomised controlled trials (RCTs), aimed to comprehensively sum-
marise the pattern and effectiveness of current rehabilitation interventions for old adults with long COVID.

METHODS
Search strategy
We searched studies published in PubMed, EMBASE, Web of Science, Scopus and Cochrane Library data-
bases from their inception to 15 November 2023 without language restrictions. We used a search strategy
with a combination of Medical Subject Headings (MeSH) terms and key terms (words in the title, keywords

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 Rehabilitation intervention for long COVID in old adults

or abstract of the manuscript) to identify potential studies. Examples of the keywords we used were the fol-
lowing terms: (‘long covid’ OR ‘post covid’ OR ‘long-covid’ OR ‘post-covid’ OR ((‘long-term’ OR ‘post-acute’
OR ‘sequela’ OR ‘sequala’) AND (‘SARS-CoV-2’ OR ‘COVID-19’))) AND (‘rehabilitation’ OR ‘recovery’ OR
‘management’ OR ‘telehealth’ OR ‘exercise’ OR ‘training’ OR ‘therapy’ OR ‘medicine’ OR ‘physical’) AND
(‘randomized controlled trial’ OR ‘clinical trial’ OR ‘intervention’ OR ‘RCT’). The detailed search strategy
is shown in Appendix 1 in the Online Supplementary Document. Furthermore, we manually examined
the reference lists of the studies included to identify any additional studies not found during the electronic
search. We used EndNoteX9.3.3 (Thomson Research Soft, Stanford, USA) to manage records.
This study was strictly performed according to the Preferred Reporting Items for Systematic Reviews and

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Meta-Analyses (PRISMA) which is shown in Appendix 2 in the Online Supplementary Document. [13].
The protocol of this study has been registered in the PROSPERO database (CRD42023412605).

Inclusion and exclusion criteria

We included RCTs that compared rehabilitation interventions such as respiratory rehabilitation, aerobic
training, exercise training, and other rehabilitation programmes with either placebo, usual care, or control
in old adults (with a mean or median age of 60 or older) with long COVID. No limitations were imposed re-
garding the presence of comorbidities or concurrent medication use during the rehabilitation programmes.
The following studies were excluded: (1) irrelevant to the subject of the systematic review and meta-anal-
ysis; (2) insufficient data that cannot be addressed after contacting the authors; (3) duplicate studies; (4)
non-RCT studies, qualitative researches, reviews, editorials, conference papers, case reports or animal ex-
periments; or (5) the age of participants less than 60 years. Studies were identified by two investigators in-
dependently following the criteria above, while discrepancies were solved by consensus or with a senior
research team member.

Data extraction
The following data was extracted from the eligible studies: (1) basic information about the studies, includ-
ing the publication year, authors, study conducting time, and country; (2) characteristics of participants
(sample size, age, sex ratio, comorbidity, severity in acute infection et al.), intervention programmes, con-
trol, and outcomes. Data extraction was conducted by two investigators independently. As for missing or
unclear data, try to solve it by consulting with panel members or contacting the corresponding authors to
gain the original data.

Outcomes
The primary outcome was functional capacity, mainly measured with the 6-minute walking test (6MWT,
metre (m)). Secondary outcomes included functional capacity (assessed by 30-second sit-to-stand test (30
seconds STS, number of stands(n) and hand grip strength (HGS, kg)), pulmonary function (measured by the
forced expiratory volume in one second/forced vital capacity (FEV1/FVC, %)), fatigue, quality of life, inde-
pendence in activities of daily living, anxiety, and depression. Fatigue was assessed by the Fatigue Severity
Scale (FSS), which consisted of nine questions that measured the patient’s perception of how fatigue affects
their daily activities, with the higher score, the more fatigue [14]. Quality of life was assessed through the
Short Form 36 Health Survey Questionnaire (SF-36), which consisted of eight domains, including physi-
cal functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and
mental health [15]. Scores for each domain ranged from 0 to 100, and higher scores indicated better quality
of life. Independence in activities of daily living was assessed through the Functional Independence Mea-
sure (FIM), Katz Index of Independence in Tasks of Everyday Living (KATZ), and Barthel Index (BI). De-
pression was assessed by the Hamilton Anxiety and Depression Scale (HADS) and Self-rating Depression
Scale (SDS) [16,17]. Anxiety was assessed by the HADS and Self-rating Anxiety Scale (SAS) [16,18]. All of
the primary and secondary outcomes were assessed at the earliest available time point after the completion
of the rehabilitation programme.

Quality assessment
Two independent investigators used the Cochrane Collaboration’s tool to assess the risk of bias [19]. The in-
cluded RCTs were classified as low, unclear, or high risk of bias from comprehensive evaluation from seven
dimensions, including random sequence generation, allocation concealment, blinding of participants and
personnel, incomplete outcome data, selective reporting, and other biases. Discrepancies were resolved with
a senior research team member.

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 Deng et al.

Statistical analysis
Mean (standard deviation (SD)) was used to describe variables with normal distribution, median (IQR) was
used to describe variables with skewed distribution, and number (percentage) was used to describe cate-
gorical variables.
We performed meta-analyses to compare the effects of the rehabilitation interventions with the common
control group (i.e. placebo, usual care, et al.). For continuous outcomes measured by the same scale in all
studies, the summary result was presented as a difference in mean (MD) with its 95% confidence intervals
(CI). It estimated the amount by which the experimental intervention changed the outcome on average com-
pared with the comparator intervention. When the studies assessed the same outcome, but measured it in
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a variety of ways (for example, some studies measured depression but used different psychometric scales),
the standardised mean difference (SMD) with its 95% CI was used as a summary statistic [20].
I-square (I2) statistic was used to assess the inter-study heterogeneity: I2≤50% represented low to moder-
ate heterogeneity, while I2≥50% represented substantial heterogeneity [20]. If there was no significant het-
erogeneity observed, a fixed-effects model was used, otherwise, a random-effects model, which considered
variation across studies and could better deal with heterogeneity, was used to estimate the pooled effect
size. Moreover, the literature review indicates that different interventions vary in rehabilitation effective-
ness and importance in clinical practice [11,21–23]. Additionally, different ages and the severity of acute
infection might also impact the demands and effectiveness of rehabilitation in older adults. Therefore, sub-
group analyses were carried out by the intervention programmes (exercise training, respiratory rehabilita-
tion, and others), the severity of acute infection (non-severe and severe/critical), and the mean age of par-
ticipants (60–65 and >65 years old).
Egger’s test was used to assess the potential publication bias for continuous outcomes. A two-sided P < 0.10
was considered evidence of publication bias [24]. If publication bias was observed, sensitivity analysis was
performed using the trimming and filling method to assess the effect of publication bias. If the pooled ef-
fect size and its 95% CI did not change significantly before and after trimming and filling, it suggested that
the effect of publication bias was not significant and the meta-analysis results were robust [25]. All analyses
were conducted in Stata version 15.0 (Stata Corp, Texas, USA).

RESULTS
Characteristics of included studies
In the original literature retrieval, a total of 3738 potential records were identified up to 15 December 2023.
After the removal of 1232 duplicates, we carried out title and abstract screening of 2506 articles and left
191 articles screened for full-text review. Eventually, based on the exclusion and inclusion criteria, 11 arti-
cles were eligible and included in this meta-analysis and systematic review [26–36]. The literature retrieval
flowchart is shown in Figure 1.
In brief, the majority of the included studies
were conducted in Asia (two in Saudi Arabia,
one in China, one in Kazakhstan, and one in
Turkey) [28,29,32,34,35], three in Europe (one
each in Poland, Italy, and Portugal) [26,30,36],
two in Africa (all in Egypt) [27,31], and one in
South America (Brazil) [33]. More details about
the characteristics of the included studies are
shown in Table S1 in the Online Supplemen-
tary Document.

Characteristics of the participants

A total of 832 participants were included in the
analysis (64.37 ± 7.94 years, 52.2% were men).
301 (36.18%) participants from 5 studies were
discharged from the intensive care unit (ICU)
after experiencing a severe/critical course of
Figure 1. Flowchart for study selection. COVID-19 infection [26,30,33,35,36]. Two

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 Rehabilitation intervention for long COVID in old adults

studies included 232 (27.88%) discharged patients from general wards [29,34], and four studies included
299 (35.94%) participants whose hospitalisation status was unclear [27,28,31,32]. A total of 371 (44.59%)
participants from five studies were all ≥60 years old [27,28,31,32,34]. The age criteria for participants in
three studies was <60 years [29,33,36], and in three studies was not specified, but the average age of all of
them was >60 years [26,30,35]. The characteristics of the participants are shown in Table S1 in the Online
Supplementary Document.

Characteristics of rehabilitation interventions

The most common rehabilitation interventions were exercise training, including aerobic exercises (231 par-

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ticipants from five records) [27,28,30,32], home-based exercise training programme (50 participants from
one study) [33], and exercises on the rehabilitation robot (81 participants from one study) [26]. Intervention
for 210 participants from three studies was respiratory rehabilitation [34–36]. Other rehabilitation inter-
ventions included acupuncture (160 participants from one study) and photobiomodulation treatment (100
participants from one study) [29,31].

Outcomes
Functional capacity
Three outcome variables were used to assess the functional capacity (Table 1, Figure 2). Meta-analysis re-
sults showed that compared with the control groups, rehabilitation interventions significantly improved 6
MWT (MD = 15.77 m, 95% CI = 5.40, 26.13, P < 0.01). Subgroup analyses showed that this improvement was
more pronounced in participants who received exercise training intervention (MD = 19.84 m, 95% CI = 8.13,
31.56, P < 0.01), experienced a non-severe course of COVID-19 infection (MD = 22.36 m, 95% CI = 10.58,
34.13, P < 0.01), and averaged between 60–65 years of age (MD = 19.01 m, 95% CI = 8.05, 29.96, P < 0.001)
(Table S2 in the Online Supplementary Document).
Rehabilitation interventions were associated with the improvement of 30 seconds STS (MD = 4.11 n, 95%
CI = 2.46, 5.76, P < 0.001), which was more pronounced in participants with non-severe infection (MD = 5.22
n, 95% CI = 3.72, 6.72, P < 0.001) and who aged 60–65 years (MD = 5.05 n, 95% CI = 2.89, 7.22, P < 0.01)
(Table S3 in the Online Supplementary Document).
The pooled MD of HGS was not significant (MD = 1.67 kg, 95% CI = −0.84, 4.18, P > 0.05). But subgroup anal-
ysis showed that rehabilitation interventions significantly improved HGS among participants with severe/

Table 1. Comparison of treatment outcomes of rehabilitation between intervention and control groups
Trials/ Participants,
Outcome variables MD (95% CI) P-value I2 (%) P-heterogeneity
records, No. No.
Functional capacity
6-min walk test, m 6 387 15.77 (5.40, 26.13) 0.003 78.5 <0.001
30 s sit-to-stand test, n 6 250 4.11 (2.46, 5.76) <0.001 89.9 <0.001
Hand grip strength, kg 7 404 1.67 (−0.84, 4.18) 0.193 88.7 <0.001
Pulmonary function
FEV1/FVC, % 3 164 3.45 (−1.43, 8.33) 0.166 85.1 0.001
Fatigue 4 222 −0.66 (−1.13, −0.19)* 0.006 62.9 0.044
Quality of life
Physical functioning 5 260 11.41 (5.59, 17.24) <0.001 96.8 <0.001
Bodily pain 5 260 8.48 (4.99, 11.97) <0.001 90.9 <0.001
General health 5 260 7.98 (4.29, 11.67) <0.001 90.5 <0.001
Role-physical 5 260 7.13 (3.72, 10.54) <0.001 90.2 <0.001
Vitality 5 260 8.19 (4.20, 12.18) <0.001 87.4 <0.001
Social functioning 5 260 7.09 (3.59, 10.59) <0.001 88.0 <0.001
Mental health 5 260 5.61 (2.88, 8.34) <0.001 85.3 <0.001
Role-emotional 5 260 7.51 (3.15, 11.86) 0.001 90.5 <0.001
Independence in activities of daily living 6 516 0.31 (0.13, 0.48)* <0.001 0.0 0.581
Depression and anxiety
Depression 4 210 −0.89 (−1.76, −0.02)* 0.046 88.5 <0.001
Anxiety 4 210 −0.81 (−1.58, −0.05)* 0.038 85.4 <0.001
CI – confidence interval, FEV1/FVC – forced expiratory volume in one second/forced vital capacity, MD – difference in mean
*Using standard mean difference (SMD) as pooled effect size.

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Figure 2. Forest plot of effects of rehabilitation interventions for old adults with long COVID in functional capacity and pulmonary
function, compared to usual/standard care. Panel A. Effects in 6-minute walk test. Panel B. Effects in 30-second sit-to-stand test. Pan-
el C. Effects in hand grip strength. Panel D. Effects in FEV1/FVC. CI – confidence interval, COVID – coronavirus disease, FEV1/FVC
– forced expiratory volume in one second/forced vital capacity, MD – difference in mean.

critical acute infection (MD = 1.81 kg, 95% CI = 0.42, 3.19, P < 0.05) and aged over 65 years (MD = 2.53kg,
95% CI = 1.29, 3.78, P < 0.001) (Table S4 in the Online Supplementary Document).

Pulmonary function
The pooled MD of FEV1/FVC was not significant (MD = 3.45%, 95% CI = −1.43%, 8.33%, P > 0.05) (Table
1, Figure 2). But subgroup analysis showed that compared with control groups, rehabilitation interven-
tions significantly improved pulmonary function among participants who received respiratory rehabilita-
tion (MD = 6.24%, 95% CI = 3.16%, 9.32%, P < 0.001), with non-severe acute infection (MD = 6.92%, 95%
CI = 4.07%, 9.77%, P < 0.001) and aged over 65 years (MD = 6.92%, 95% CI = 4.07%, 9.77%), P < 0.001) (Ta-
ble S5 in the Online Supplementary Document).

Fatigue
Fatigue was measured by the FSS, and the higher the score, the more severe the fatigue was. Thus, decreased
scores indicated improvement in fatigue. Compared with the control group, rehabilitation interventions were
associated with the alleviation of fatigue (SMD = −0.66, 95% CI = −1.13, −0.19, P < 0.01) (Table 1, Figure 3).
Subgroup analysis showed that fatigue alleviated more significantly in participants who received exercise
training rehabilitation intervention, whose mean age was over 65 years, and who had severe/critical acute
infection (Table S6 in the Online Supplementary Document).

Quality of life
Results of meta-analysis suggested that compared to the control group, participants in the rehabilita-
tion interventions group showed significant improvement in all domains of the SF-36: physical func-
tioning (MD = 11.41 points, 95% CI = 5.59, 17.24, on the 100-point SF-36 subscale for physical function-
ing), bodily pain (MD = 8.48 points, 95% CI = 4.99, 11.97, on the 100-point SF-36 subscale for bodily
pain), general health (MD = 7.98 points, 95% CI = 4.29, 11.67, on the 100-point SF-36 subscale for general
health perception), role-physical (MD = 7.13 points, 95% CI = 3.72, 10.54, on the 100-point SF-36 sub-
scale for role limitation due to physical health), vitality (MD = 8.19 points, 95% CI = 4.20, 12.18, on the
100-point SF-36 subscale for vitality), social functioning (MD = 7.09 points, 95% CI = 3.59, 10.59, on the

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 Rehabilitation intervention for long COVID in old adults

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Figure 3. Forest plot of effects of rehabilitation interventions for old adults with long COVID in independence in ac-
tivities of daily living, fatigue, depression, and anxiety, compared to usual/standard care. CI – confidence interval,
COVID – coronavirus disease, SMD – standard mean difference.

100-point SF-36 subscale for social functioning), mental health (MD = 5.61 points, 95% CI = 2.88, 8.34,
on the 100-point SF-36 subscale for perceived mental health), and role-emotional (MD = 7.51 points, 95%
CI = 3.15, 11.86, on the 100-point SF-36 subscale for role limitation due to mental health), all P-value
<0.01 (Table 1, Figure 4).
Subgroup analyses showed that the respiratory rehabilitation intervention group improved better than the
exercise training intervention group in all domains of quality of life, and the mean age >65 group was bet-
ter than the 60–65 group. In contrast, improvements in all domains of quality of life varied across severity
in the acute infection phase. More details about the results of subgroup analyses are shown in Table S7 in
the Online Supplementary Document.

Independence in activities of daily living, depression, and anxiety

Compared with the control group, rehabilitation interventions were associated with the improvement of in-
dependence in activities of daily living (SMD = 0.31, 95% CI = 0.13, 0.48, P < 0.001) (Table 1, Figure 3). De-
pression and anxiety were both measured by different psychometric scales and the higher the score, the more
severe the anxiety/depression was. Thus, decreased scores indicated alleviation of anxiety/depression. Relief
was observed in both depression (SMD = −0.89, 95% CI = −1.76, −0.02, P < 0.05) and anxiety (SMD = −0.81,
95% CI = −1.58, −0.05, P < 0.05) for participants in the rehabilitation intervention group compared to the
comparison group (Table 1). Subgroup analysis showed that both anxiety and depression alleviated more
significantly in participants who received exercise training rehabilitation intervention and those with non-se-
vere acute infection (Table S8–9 in the Online Supplementary Document).

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 Deng et al.
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Figure 4. Forest plot of effects of rehabilitation interventions for old adults with long COVID in quality of life, com-
pared to usual/standard care. CI – confidence interval, COVID – coronavirus disease, MD – difference in mean.

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 Rehabilitation intervention for long COVID in old adults

Risk of bias
Figure 5 summarises the risk of bias of included studies based on the Cochrane criteria. For performance
bias, six studies were graded as having a high risk, as the personnel and participants were not blinded. One
study was graded as having a high risk of detection bias because the outcome assessment was not blinded.
Two studies were graded as having a high risk of reporting bias because of selective reporting. Overall, the
risk of all types of bias was low except for performance bias.

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Figure 5. Risk of bias. Panel A. Risk of bias summary: review authors’ judgements about each risk of bias item for
each included study. Panel B. Risk of bias graph: review authors’ judgements about each risk of bias item presented
as percentages across all included studies.

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 Deng et al.

The results of Egger’s test showed that publication bias was not observed for all outcome variables (P > 0.1)
except HGS and fatigue (P < 0.1) (Table S10 in the Online Supplementary Document). Sensitivity analysis
by trimming and filling method showed that the MD of HGS was 1.67 kg (95% CI = −0.84, 4.18) before and
0.22 kg (95% CI = 0.03, 1.77) after trimming and filling, and the SMD of fatigue was −0.66 (95% CI = −1.13,
0.19) both before and after trimming and filling. The pooled effect sizes and their 95% CIs did not change
significantly (Table S11 in the Online Supplementary Document). The application of the trimming and
filling method demonstrated that the effect sizes for HGS and fatigue remained relatively stable after ac-
counting for potential publication bias, which suggested that the observed publication bias had a minimal
impact and the meta-analysis results are robust and reliable.
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DISCUSSION
This systematic review and meta-analysis of the existing RCTs aimed to comprehensively summarise the
pattern and effectiveness of current rehabilitation interventions for old adults aged over 60 years with long
COVID. A total of 11 studies involving 832 participants (64.37 ± 7.94 years old) were included in the anal-
ysis. Our results showed that old adults who underwent rehabilitation interventions experienced great im-
provement in functional capacity, quality of life, independence in activities of daily living, and alleviation
in fatigue, depression and anxiety outcomes compared with those who received usual or standard care.
To our knowledge, up to now, this study is the first systematic review and meta-analysis of RCTs in this
important field. By consolidating the available evidence, this study will provide valuable evidence-based
information for health care professionals, policymakers, and researchers to make informed decisions re-
garding implementing effective rehabilitation strategies for old adults with long COVID. Ultimately, the
findings of this study would help improve the care and outcomes for this vulnerable population, and con-
tribute to their overall health and well-being, thereby reducing the burden on medical resources and the
health care system.
Regarding the components of rehabilitation programmes for old adults, the results of this review showed
that the most common was exercise training with aerobic exercise [27,28,30,32,33], followed by pulmonary
rehabilitation programmes including respiratory muscle training, cough exercise, diaphragmatic training,
stretching exercise, and home exercise, etc. [34–36]. As some patients experienced muscle strength loss
after discharge from the hospital, rehabilitation robot-assisted exercise training has also been observed to
be effective [26]. Some rehabilitation measures were outside the scope of our review, such as nutraceuticals
and dietary supplements, and Tosato et al. suggested that bioactive foods, supplements, and nutraceuticals
might be used for the management of long-term COVID-19 clinical sequelae [37].
Our results are consistent with the findings of several previous studies reviewing the general population,
in which rehabilitation interventions significantly improved the functional capacity [9,11,38–40], fatigue
[40], quality of life [9,38–40], and mental health [38,40] of patients with long COVID compared with
usual care, but differ in that we focused on a special group of older adults. In Torres et al.’s meta-anal-
ysis (age range: 18–75 years old), there was a significant difference in the 6 MWT (MD = 51.69 m, 95%
CI = 36.99, 66.38, P < 0.001) [11], whereas this value was 15.77 m (95% CI = 5.40, 26.13, P < 0.01) in our
study, suggesting that rehabilitation interventions might be more effective in younger people. The rela-
tionship between rehabilitation interventions and improvement in pulmonary function is highly hetero-
geneous across reviews [9,11,38,39,41,42]. In this study, we found no difference between rehabilitation
interventions and standard/usual care in pulmonary function assessed by the FEV1/FVC (MD = 3.45%,
95% CI = −1.43%, 8.33%, P > 0.05), which is in line with the review results of by Pouliopoulou et al. (me-
dian (IQR) age = 50 (47–56) years; assessed by FEV1 and FVC) [9]. In addition, non-significant results
for pulmonary function improvement were also observed in a review conducted by AL-Mhanna and his
colleagues targeting pulmonary rehabilitation among the general population [41]. However, in Torres et
al.’s review (age range: 18–75 years), rehabilitation interventions improved pulmonary function (assessed
by FEV1 (MD = 3.49%, 95% CI = 1.25%, 5.73%, P = 0.002)) significantly compared with the control group
[11], the same as a meta-analysis among general age of Yang et al. [43]. Therefore, the results should also
be interpreted with caution as different reviews were of variable quality and included literature with short
follow-up or low quality.
Subgroup analyses showed that in terms of functional capacity, exercise training was more significant in
improving the 6 MWT, whereas pulmonary rehabilitation was more effective in improving HGS. It is sug-
gested that different interventions such as exercise training and pulmonary rehabilitation should be com-
bined to improve functional capacity more comprehensively in older adults with long COVID. In addition,

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 Rehabilitation intervention for long COVID in old adults

we observed better improvement of functional capacity in old adults who were non-severe during acute in-
fection and aged 60–65 years, which is in accordance with the expected results. Regarding lung function,
better improvement was observed in older adults who received pulmonary rehabilitation, were non-severe
during acute infections, and were older than 65 years old. In addition, quality of life was improved more
significantly in older adults who received pulmonary rehabilitation, had severe/critical acute infections,
and were older than 65 years old. This indicates that rehabilitation interventions, especially pulmonary re-
habilitation, are effective in improving patients’ quality of life and organic function even in the presence of
severe/critical infections or older age, which further emphasises the importance of rehabilitation interven-
tions for older adults with long COVID.

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Because of the multi-organ involvement and diverse presentation of COVID-19 as well as age-related issues
like frailty, cognitive impairments, and multimorbidity, treating older post-acute COVID-19 patients is high-
ly challenging [12]. Multidisciplinary rehabilitation plays an important role in the older population, wheth-
er it is for COVID-19 or other disorders such as debilitation [12,44–46]. The European Geriatric Medicine
Society (EuGMS) provided detailed guidance on the management of post-acute COVID-19 patients in geri-
atric rehabilitation, advising personalised treatment regimes for older patients through multidisciplinary
rehabilitation [12]. A review by McCarthy et al. showed that multidisciplinary team rehabilitation for older
adults with COVID-19 in acute or post-acute inpatient hospital settings resulted in significant improvement
in function [10]. An interdisciplinary team could include Physicians, Nurses, Physiotherapists, Occupational
Therapists, Dietitians, Speech and Language Therapists, Psychologists, Social Workers, etc., who play their
respective roles [12]. For example, Physicians evaluate patients’ physical conditions and manage symptoms;
Physiotherapists develop and guide physical training programmes to help improve muscle strength and
motor function; Occupational therapists assist in restoring ability to daily living activities, such as the rec-
ommendation and use of assistive devices; Respiratory Therapists provide respiratory training guidance to
improve respiratory function; Dietitians develop nutritional plans to manage weight loss, muscle wasting,
and overall nutritional conditions; Psychologists provide psychological support and treatment to address
psychological problems such as anxiety and depression; and Social workers help navigate social services,
support systems, and provide resources to patients and their families [12]. Through the collaboration of an
interdisciplinary team, a personalised treatment regime will be formulated and adjusted promptly accord-
ing to the condition of patient. In addition, in the process of multidisciplinary rehabilitation, publicity and
education for patients and their family members should be strengthened, and active family participation
and community support should also be encouraged, such as the establishment of family support groups
[47]. Since health care resources are often limited and strained, it is expected to explore more accessible and
cost-effective rehabilitation programmes in the older population under the guidance of a multidisciplinary
team, to alleviate the pressure on medical resources. In addition, due to the vulnerability of the older pop-
ulation, we thus recommend that any rehabilitation intervention should follow the principle of safety to
avoid additional injuries to them.
This study included RCTs from multiple countries and regions around the world, and such geographic di-
versity enhances the broad applicability of the findings. However, cultural contexts and health care system
differences in different regions may affect the implementation and effectiveness of rehabilitation interven-
tions for old adults with long COVID. For one thing, cultural beliefs and attitudes towards rehabilitation and
health care might influence old adults’ participation and treatment adherence in different cultural contexts
[48,49]. For another, the availability and level of medical resources, as well as the structure of health care
systems, vary from region to region, which might also affect the type, intensity and outcome of rehabilita-
tion interventions [50]. For example, developed countries usually have better health care infrastructure and
resources, with higher standards and quality of rehabilitation services, making it easier for older adults to
access specialised rehabilitation services. While in some developing countries, medical resources might be
mainly concentrated in cities and less in rural areas, which might lead to disparities in rehabilitation out-
comes between urban and rural areas [51]. Therefore, future research on rehabilitation interventions for
older adults with long COVID should further consider the impact of cultural and health care system differ-
ences to ensure the effectiveness and applicability of interventions.

Strengths and limitations

Although several systematic reviews or meta-analyses of rehabilitation for patients with long COVID have
emerged, the limitations of the currently published evidence are the lack of analyses of the specific popu-
lation of the elderly as they focused primarily on the general population [9,11,38,39,41–43,52], and most
included studies of which were observational studies [53]. To our knowledge, this study is the first system-

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 Deng et al.

atic review and meta-analysis of rehabilitation interventions for old patients with long COVID which only
included RCTs. Our review identified eleven randomised controlled trials of a wide range of common re-
habilitation measures, such as exercise training and respiratory rehabilitation, and assessed a full range of
outcomes. As in previous reviews [10,11,43,53], heterogeneity between studies/trials was unavoidable, so
we conducted subgroup analyses to explore sources of heterogeneity and to compare the effects of different
rehabilitation interventions, as well as the effectiveness of rehabilitation interventions in old populations
with different ages and acute phase severity. The low risk of bias and very little publication bias further
supported the robustness and accuracy of our results. In addition, we used a comprehensive search strat-
egy and searched all relevant sources to retrieve all potential eligible randomised clinical trials. Therefore,
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this study could provide valuable high-quality evidence for the field of rehabilitation interventions for old
adults with long COVID.
However, there are also some limitations to this study. First, because of the very limited RCTs examining
rehabilitation interventions in older populations, we used the restriction of “median or mean age greater
than 60 years” as a definition and inclusion criterion for older populations to capture more available stud-
ies. Some participants younger than 60 years old might have been included in the analyses, which might
impact our results to some extent. Therefore, we performed subgroup analyses of participants’ ages to as-
sess the robustness of the results. Future RCTs of rehabilitation of long COVID targeting older adults, a
high-risk population, should be designed to provide more high-quality evidence. In addition, comorbid-
ity is an important consideration for rehabilitation outcomes in older adults, we summarised the charac-
teristics of comorbidity of the included participants but did not analyse this factor due to the limitation of
original data, suggesting that future research should further explore the impact of comorbidity on the ef-
fectiveness of rehabilitation interventions in older adults to better guide the clinical practice. Furthermore,
due to the specific features of rehabilitation intervention programmes, it was difficult to blind study par-
ticipants, whose expectations might affect the perception of intervention effects. So performance bias was
unavoidable and might lead to an overestimation of the true effects of the rehabilitation interventions. To
address this bias, future research could use more objective outcome measures, thereby mitigating the im-
pact of participants’ expectations on outcomes. Also, blinding of therapists and outcome assessors could
help control bias. Finally, given the complexity of long COVID, it is critical to explore all potential reha-
bilitation programmes including medicine intervention. However, none of the included studies researched
this programme among older adults, which highlights a gap in the current research. Future research should
pay attention to integrating medicinal interventions, such as anti-inflammatory drugs and supplements,
to evaluate their effectiveness in combination with other interventions for old adults with long COVID
[54,55]. Such a comprehensive approach could provide deeper insights into the best practices for managing
long COVID in older adults and help to develop more effective, multifaceted rehabilitation programmes. In
summary, it is emphasised that there is an urgent need for RCTs with larger sample sizes, rigorous meth-
odologies and comprehensive interventions to address the knowledge gaps mentioned above among old
adults with long COVID in future research.

Implications for clinical practice and policy-making

These results highlight the importance of effective screening programmes to detect long COVID timely
among old adults. Early referral to a multidisciplinary rehabilitation team to develop a personalised reha-
bilitation plan based on the physical condition and specific demands of the old adults, with regular assess-
ments and adjustments, to maximise the effectiveness of the intervention. Besides, training and education
of health care workers should be strengthened to draw their attention to long COVID and to understand the
best practices for managing long COVID in old adults. Furthermore, comorbidities might not only increase
the risk of developing long COVID in older adults, but also affect rehabilitation outcomes by increasing med-
ical complexity and demands of rehabilitation [56–58]. Among older adults long COVID, the effectiveness
of rehabilitation interventions might be somewhat restricted due to comorbidities, suggesting that individ-
ual comorbidities should be taken into account in clinical practice and further research.
For policy-making, it is important to further support research on the rehabilitation of old adults with long
COVID by ensuring the allocation of adequate funding and resources and encouraging the exploration of
innovative rehabilitation methods. Furthermore, there is a necessity to formulate national or international
rehabilitation guidelines to provide standardised care and management guidance for old adults with long
COVID. Finally, public health campaigns should also be conducted to increase public awareness of long
COVID rehabilitation.

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 Rehabilitation intervention for long COVID in old adults

CONCLUSIONS
Long COVID is of particular concern among old adults. Our finding showed that over-60-year-old adults
with long COVID who underwent rehabilitation interventions experienced great improvement in function-
al capacity, quality of life, independence in activities of daily living, and alleviation in fatigue, depression
and anxiety outcomes compared with those who received usual or standard care. These findings provide
valuable implications for clinical practice and policy-making, suggesting that screening and management
of long COVID among older adults should be strengthened. Formulating individualised rehabilitation pro-
grammes through multidisciplinary management to improve the complete health status and functional sta-
tus of older patients, thereby reducing the long-term disease burden caused by long COVID and fostering

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healthy aging during the post-pandemic era.

Data availability: All data used in this manuscript can be found in the online versions of the studies that were accessed.
Our data synthesis of these manuscripts is available upon reasonable request.
Funding: This work was supported by the National Natural Science Foundation of China (No.7221101017 and
No.72122001).
Authorship contributions: JD and JL were responsible for the conception and design of the study; JD and CQ per-
formed data acquisition; JD performed data analyses; JD and JL interpreted the results; JD drafted the manuscript; and
all authors critically revised the manuscript and approved the final version.
Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the
corresponding author) and disclose no relevant interests.
Additional material
Online Supplementary Document

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