Abstract
Background:
The COVID-19 pandemic has highlighted a spectrum of long-term sequelae, with musculoskeletal symptoms being a substantial component of Post-Acute Sequelae of SARS-CoV-2 infection (PASC). This systematic review and meta-analysis aimed to evaluate the incidence and nature of musculoskeletal manifestations in individuals recovering from COVID-19.
Methods:
A systematic search across PubMed, Embase, and Web of Science was performed up to February 15, 2024, to identify studies reporting on musculoskeletal symptoms post-COVID-19. Observational studies which reported any musculoskeletal symptoms of PASC were included. Data were pooled using a random-effects model to calculate the incidence of symptoms, with subgroup analyses based on time since infection. Statistical analysis were conducted in R software (V 4.3).
Results:
Sixty-four studies were included, demonstrating a pooled prevalence of muscle pain at 28% (95% CI: 22%−35%), which increased to 25.9% (95% CI: 20.7%−31.7%) at 12 months post-infection. Joint pain showed a pooled prevalence of 14.8% (95% CI: 10.6%−20.2%), with no significant temporal change. Muscle weakness was observed in 12.9% (95% CI: 4.2%−32.9%) of patients. Notable heterogeneity was observed across studies (I2 > 89% for all symptoms).
Conclusion:
Musculoskeletal symptoms are prevalent in individuals with PASC, with muscle pain being the most common. The findings highlight the need for comprehensive clinical management and continuous research to create targeted treatments and revise care protocols as the pandemic evolves.
Introduction
The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged as a defining global health crisis of the early 21st century (, ). Initially recognized for its acute respiratory symptoms, the disease spectrum of COVID-19 has since expanded to reveal a multifaceted impact on human health, challenging the medical community's understanding of viral infections (). As the pandemic has progressed, it has become increasingly evident that COVID-19 is not merely a transient respiratory illness but a complex condition with the potential to cause persistent and multifarious health issues (). Among these, musculoskeletal manifestations represent a significant and debilitating consequence for a considerable number of individuals recovering from the infection (, ).
Musculoskeletal symptoms, including muscle pain, joint pain, and muscle weakness have been documented with alarming frequency among patients in the post-acute phase of COVID-19 (). These symptoms can persist for months beyond the initial infection, leading to a condition often called “long COVID” or post-acute sequelae of SARS-CoV-2 infection (PASC) (). The persistence of such symptoms has profound implications for individuals' quality of life, ability to return to work, and overall functional status. Furthermore, the broad spectrum of severity, from mild discomfort to severe impairment, underscores the need for a deeper understanding of these manifestations to inform patient management and rehabilitation strategies (–). The exact mechanisms underlying the musculoskeletal manifestations of PASC remain incompletely understood, but emerging evidence suggests a complex interplay of inflammatory, immunological, and possibly vascular factors (–). This complexity is compounded by the heterogeneity of patient experiences, with some individuals recovering fully from their acute infection without sequelae while others endure long-term disabilities. The variability in patient outcomes highlights the importance of identifying the prevalence, risk factors, and potential pathophysiological mechanisms contributing to the persistence of musculoskeletal symptoms (–).
Given the global scale of the pandemic and the significant number of individuals affected by COVID-19, understanding the long-term consequences of the disease is critical. A systematic review and meta-analysis of the musculoskeletal manifestations of post-acute sequelae of COVID-19 provides an opportunity to synthesize available evidence, offering a clearer picture of these conditions' prevalence and characteristics. By elucidating the extent and nature of musculoskeletal manifestations in PASC, this review aims to assess the type and incidence of musculoskeletal manifestation of PASC.
Methods
To investigate the musculoskeletal manifestations of the post-acute sequelae of COVID-19, a comprehensive systematic review and meta-analysis was conducted. The study protocol has been registered with PROSPERO, adhering to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines () (Supplementary Table S1).
Literature search
Initially, a detailed search strategy was developed to capture relevant studies published in several electronic databases, including PubMed, Embase, and Web of Science. The search was conducted using a combination of keywords and MeSH terms related to “COVID-19,” “SARS-CoV-2,” “musculoskeletal manifestations,” “post-acute sequelae,” and “long COVID.” To ensure a comprehensive retrieval of pertinent studies, no restrictions were placed on language, publication status, or study design. The search was carried out covering the period from the inception of each database until February 15 2024. The search strategy is given in Supplementary Table S2.
Inclusion criteria
Studies were included if they reported on musculoskeletal symptoms in patients with post-acute sequelae of COVID-19. Observational studies of cross-sectional and cohort were included. Studies which reported acute symptoms of COVID-19 without reporting the PASC were excluded. Exclusion criteria encompassed studies that did not specifically address musculoskeletal outcomes, case reports, editorial comments, and reviews.
Screening
Following the search, all identified records were imported into a Nested-Knowledge software, where duplicates were removed. Two independent reviewers then screened the titles and abstracts of the remaining records for eligibility, using predefined inclusion and exclusion criteria. Any discrepancies between the two reviewers were resolved with the help of a third reviewer.
Data extraction
Eligible studies underwent a full-text review to confirm their suitability for inclusion in the meta-analysis. Data extraction was performed independently by two reviewers using a standardized form. The tagging function of Nested-Knowledge was used for extraction. Extracted information included study characteristics (e.g., author, year of publication, study design), participant demographics (e.g., age, gender), musculoskeletal manifestations reported. The quality of included studies was assessed using JBI tool.
Statistical analysis
Meta-analysis was to pool data from studies reporting similar outcomes, using random-effects models to account for between-study heterogeneity. The prevalence of each type of musculoskeletal symptoms, along with 95% confidence intervals, was calculated. Heterogeneity among studies was quantified using the I2 statistic (). Subgroup analyses were conducted based on the time point of assessment after getting initial COVID infection. Publication bias was assessed through Doi plots and LFK index (). All statistical analyses were performed using a R software version 4.3 (, ). A 95% prediction interval was calculated to provide a range within which the true effect size is expected to lie in similar future studies.
Results
Literature search
The systematic review began with the identification of 3,031 records through database and registry searches, broken down as follows: 857 from PubMed, 1,523 from Embase, and 651 from Web of Science. Before screening, duplicates were removed, totaling 1,079 records. After deduplication, 1,897 records were screened, and subsequently, 919 of these records were excluded. The remaining 257 full-text reports were assessed for eligibility. Of these, 193 were excluded due to the outcome not being of interest. Finally, 64 studies were included in the meta-analysis (Figure 1).
Figure 1
Characteristics of included studies
The summary of the included studies is given in Table 1. In total, 64 studies were encompassed in this synthesis, offering a broad overview of the clinical presentations associated with post-acute sequelae of COVID-19. These studies spanned numerous countries, with a majority conducted in 2023, indicating a concentrated effort to understand the long-term effects of the virus in recent times. The studies varied in design, with cohort studies being predominant, followed by cross-sectional studies, and a few retrospective cohort studies. The populations targeted were generally adult, with a few focusing on specific groups such as older adults with diabetes, health professionals, children, and patients with hypertension, showcasing the wide-reaching impact of COVID-19 across different demographic segments. Sample sizes across studies ranged from as few as 13 participants in a study involving football players in Italy to a significant cohort of 5,946 in Saudi Arabia, indicating the variance in the scale of these research efforts. The male percentage varied widely among studies, with some studies having a higher representation of male participants, like the study in Brazil with 70.9%, and others with a lower representation, such as 23.9% in a study from Saudi Arabia. Mean ages of participants spanned from as young as 12.1 years in a Turkish study on children to an older cohort with a mean age of 71 years in an Indian study, reflecting the diverse age range affected by post-COVID conditions. Musculoskeletal manifestations reported in these studies commonly included muscle pain and joint pain, with some studies also noting muscle weakness as a significant symptom. This indicates a consistent pattern of musculoskeletal issues in patients post-COVID infection, regardless of the country or population category. The quality assessment of studies is given in Supplementary Table S3.
Table 1
| Author | Publication year | Country | Design | Population category | Total sample | Male % | Mean age | Musculoskeletal manifestations |
|---|---|---|---|---|---|---|---|---|
| Al-Husinat (36) | 2022 | Jordan | Cross-sectional study | General | 495 | 33.5 | 30.5 | Muscle pain, muscle weakness |
| Alkwai (37) | 2022 | Saudi Arabia | Cross-sectional study | General | 213 | 23.9 | NA | Muscle weakness |
| Asadi-Pooya (38) | 2021 | Iran | Retrospective cohort study | General | 2,685 | 50.9 | 52 | Joint pain, muscle pain |
| Babicki (39) | 2023 | Poland | Cohort study | General | 801 | 34.7 | 53.5 | Joint pain, muscle pain |
| Bhandari (40) | 2023 | India | Cohort study | General | 3,840 | 60.7 | 46.89 | Muscle pain |
| Buttery (41) | 2021 | UK | Cross-sectional study | General | 1,865 | 21.1 | 34.5 | Muscle weakness |
| Chathoth (42) | 2023 | India | Cross-sectional study | General | 938 | 56.5 | 41.5 | Joint pain, muscle pain |
| Chudzik (43) | 2022 | Poland | Cohort study | General | 218 | 31.0 | 45.74 | Muscle pain |
| Dagher (44) | 2023 | USA | Cohort study | Cancer patients | 188 | NA | 54.5 | Muscle pain |
| Daitch (45) | 2022 | Israel, Switzerland, Spain, and Italy | Cohort study | Older adults | 2,333 | 50.9 | 51.25 | Joint pain, muscle pain |
| de Oliveira (46) | 2022 | Brazil | Cross-sectional study | General | 369 | 50.3 | 58 | Joint pain, muscle pain |
| di Filippo (47) | 2023 | Italy | Cross-sectional study | General | 50 | 56 | 61.5 | Joint pain, muscle pain |
| Duwel (48) | 2023 | Aruba | Retrospective cohort study | General | 222 | 53.1 | 58.1 | Joint pain, muscle pain |
| El Otmani (49) | 2022 | Morocco | Case control study | health professionals | 118 | 28.8 | 33.25 | Muscle pain |
| Emecen (50) | 2023 | Turkey | Cohort study | General | 5,610 | 48 | 44.75 | Muscle pain |
| Ercegovac (51) | 2022 | Serbia | Cross-sectional study | General | 167 | 59.8 | 55.9 | Joint pain |
| Fernández-de-Las-Peñas (52) | 2022 | Denmark | Cohort study | General | 1,969 | NA | 61 | Joint pain, muscle pain |
| Freire (53) | 2022 | Brazil | Cohort study | General | 822 | 53.1 | 56 | Muscle pain |
| Garout (54) | 2022 | Saudi Arabia | Cross-sectional study | General | 744 | 49.2 | 33 | Muscle pain |
| Gasnier (55) | 2022 | France | Cross-sectional study | General | 177 | 40.5 | 57.2 | Muscle weakness |
| Gattoni (56) | 2022 | Italy | Retrospective cohort study | Football players | 13 | 100 | 23.9 | Joint pain, muscle pain |
| Ghosn (57) | 2023 | France | Cohort study | General | 737 | 64.4 | 61 | Joint pain |
| Gonzalez-Aumatell (58) | 2022 | Spain | Cohort study | General | 50 | 34 | 14.1 | Joint pain, muscle pain, muscle weakness |
| Guadalupe Gutiérrez-Canales (59) | 2022 | Mexico | Cohort study | General | 206 | 37.3 | 30.9 | Joint pain, muscle pain |
| Hendrickson (60) | 2023 | USA | Cross-sectional study | General | 284 | 33 | 45.2 | Joint pain |
| Huang (61) | 2022 | China | Cohort study | General | 1,192 | 53.7 | 56.75 | Joint pain, muscle pain |
| Karaarslan () | 2022 | Turkey | Cohort study | General | 291 | 59.4 | 52.54 | Joint pain, muscle weakness |
| Karaarslan (62) | 2021 | Turkey | Cohort study | General | 300 | 59.6 | 52.58 | Joint pain, muscle pain |
| Kayaaslan (63) | 2021 | Turkey | Cohort study | General | 1,007 | 54 | 45 | Muscle pain |
| Kenny (64) | 2022 | Ireland | Cohort study | General | 233 | 25.7 | 44 | Joint pain, muscle pain |
| Magnavita (65) | 2023 | Italy | Cross-sectional study | Occupational cohorts | 164 | 25 | 48.71 | Muscle pain |
| Martino (66) | 2022 | Italy | Cohort study | General | 64 | 64 | 66.75 | Joint pain |
| Mateu (67) | 2023 | Spain | Cohort study | General | 341 | 30.2 | 47.9 | Joint pain, muscle pain |
| Maestre-Muñiz (68) | 2021 | Spain | Cross-sectional study | General | 543 | 50.6 | 65.1 | Muscle pain, muscle weakness |
| Muñoz-Corona (69) | 2022 | Mexico | Cohort study | General | 141 | 59.5 | 52.24 | Joint pain, muscle pain |
| Naik (70) | 2021 | India | Cohort study | General | 1,234 | 69.3 | 41.6 | Muscle pain |
| Sathyamurthy (71) | 2021 | India | Cohort study | General | 279 | 36 | 71 | Muscle pain |
| Paradowska-Nowakowska (72) | 2023 | Poland | Cross-sectional study | General | 471 | 42.8 | 63.94 | Muscle pain |
| Polese (73) | 2023 | Brazil | Cohort study | General | 31 | 70.9 | 53.6 | Muscle pain |
| Rass (74) | 2022 | Germany | Cohort study | General | 81 | 59.2 | 54.75 | Muscle pain |
| Román-Montes (75) | 2023 | Mexico | Cross-sectional study | General | 246 | 54.8 | 52.5 | Muscle pain |
| Romero (76) | 2023 | Colombia | Cross-sectional study | General | 1,047 | 37.2 | 46.25 | Joint pain, muscle pain |
| Sansone (77) | 2022 | Italy | Cohort study | General | 247 | 35.6 | 48.1 | Joint pain, muscle pain |
| Seang (78) | 2022 | Brazil | Cohort study | General | 31 | 70.9 | 53.6 | Muscle pain |
| Senjam (79) | 2022 | India | Cross-sectional study | General | 257 | 56.4 | 34.75 | Joint pain, muscle pain |
| Serrano (80) | 2023 | Colombia | Retrospective cohort study | General | 135 | 70.3 | 61.75 | Muscle weakness, muscle pain |
| Shivani (81) | 2022 | Pakistan | Cohort study | General | 4,638 | 53.7 | 43 | Muscle pain |
| Soh (82) | 2022 | South Korea | Cross-sectional study | General | 147 | 53 | 52 | Joint pain, muscle pain |
| Sousa (83) | 2023 | Brazil | Cross-sectional study | Older adults with diabetes | 54 | 29.6 | 68.2 | Muscle pain |
| Sykes (84) | 2023 | UK | Cohort study | General | 144 | 62.5 | 62 | Muscle pain |
| Tajer (85) | 2023 | Latin America | Cross-sectional study | Health professionals | 3,642 | 35.8 | 47.8 | Muscle pain |
| Talhari (86) | 2023 | Brazil | Ambidirectional cohort study | General | 190 | 41 | 41.5 | Joint pain, muscle pain, muscle weakness |
| Tejerina (87) | 2022 | Spain | Cohort study | General | 29 | 37.9 | 45.25 | Muscle pain |
| Tleyjeh (88) | 2022 | Saudi Arabia | Cross-sectional study | General | 5,946 | 64.4 | 35.75 | Joint pain, muscle pain |
| Tracy (89) | 2024 | USA | Cohort study | General | 52 | 42.3 | 57.9 | Muscle weakness |
| Vaira (90) | 2022 | Italy | Cross-sectional study | General | 431 | 23.6 | 38.4 | Joint pain, muscle pain |
| Wan (91) | 2023 | Malaysia | Retrospective cohort study | General | 452 | 54.2 | 23.75 | Joint pain, muscle pain |
| Wang (92) | 2023 | China | Cross-sectional study | General | 1,546 | 50 | 57.93 | Muscle pain |
| Wieteska-Mia, (93) | 2023 | Poland | Cohort study | Hypertension patients | 69 | 31.8 | 50 | Muscle pain |
| Wong (94) | 2023 | China | Cross-sectional study | General | 2,712 | 40 | NA | Joint pain, muscle pain |
| Wose Kinge (95) | 2022 | South Africa | Cross-sectional study | Frontline workers | 62 | 24.1 | 35.25 | Joint pain, muscle pain |
| Yaksi (96) | 2022 | Turkey | Retrospective cohort study | General | 86 | 45.3 | 65.7 | Muscle pain |
| Yildirim Arslan (97) | 2023 | Turkey | Cohort study | children | 200 | 33.3 | 12.1 | Joint pain |
| Zayet (98) | 2021 | France | Retrospective cohort study | General | 354 | 37 | 49.6 | Joint pain, muscle pain |
Characteristics of included studies.
Muscle pain
We performed meta-analysis to assess the incidence of muscle pain in individuals with PASC. The random-effects model yielded a pooled prevalence rate of 28% for muscle pain (95% CI: 22%−35%), with substantial heterogeneity (I2 = 100%, Tau2 = 0.0717). The prediction interval ranged expansively from 0.0 to 80%, suggesting that future research may encounter a similarly wide spectrum of muscle pain incidence among PASC patients (Figure 2).
Figure 2
The subgroup analysis of muscle pain incidence in PASC based on different time points post-COVID-19 infection reveals distinct prevalence rates correlating with the duration post-infection. The analysis stratifies the data into two subgroups: the 3–6 months post-infection period and the point at 12 months post-infection. For the subgroup of 3–6 months post-infection, the meta-analysis reports a pooled prevalence of muscle pain at 17.4% (95% CI: 12.8%−22.1%). This suggests that within this time frame, on average, approximately one in six individuals may experience muscle pain as a symptom of PASC with high heterogeneity (I2 = 99.6%). In contrast, the subgroup representing 12 months post-infection demonstrates a pooled prevalence of 25.9% (95% CI: 20.7%−31.7%; Figure 3).
Figure 3
Joint pain
We performed a meta-analysis for joint pain incidence in PASC. The pooled prevalence rate for joint pain is observed at 14.8% (95% CI: 10.6%−20.2%), suggesting that on average, about one in seven individuals may experience joint pain as a sequela of COVID-19 infection. A high level of heterogeneity (I2 = 98%, Tau2 = 0.8425) among the studies was noted. The prediction interval, ranging from 2.5 to 54.1%, suggests that in a similar study context, the prevalence of joint pain could be expected to fall within this wide range (Figure 4).
Figure 4
We performed subgroup analysis for joint pain based on the time point of assessment after the initial COVID-19 diagnosis. For the first subgroup, encompassing 3–6 months post-infection, the pooled prevalence of joint pain is 17.2% (95% CI: 12.1%−25.4%). The substantial heterogeneity observed (I2 = 89%) suggests significant variability in joint pain reporting across the included studies. In the 6–12 months post-infection subgroup, the data show a pooled prevalence of 10.7% (95% CI: 7.5%−15.1%) with high heterogeneity (I2 = 90; Figure 5).
Figure 5
Muscle weakness
In the PASC, muscle weakness has been identified as a significant symptom affecting a considerable proportion of individuals. The pooled prevalence rate for muscle weakness is determined to be 12.9% (95% CI: 4.2%−32.9%, Tau2 = 2.31). This indicates that more than one in ten individuals may experience muscle weakness as a post-infection sequela, although there is a notable range in the confidence interval, suggesting variability in the symptom's manifestation. The heterogeneity present in the meta-analysis is significant, with an I2 value of 97%, reflecting considerable differences in the prevalence rates reported by the individual studies (Figure 6).
Figure 6
Publication bias
The evaluation of publication bias across different musculoskeletal symptoms PASC of COVID-19 infection using Doi plots has produced varied results, each with distinct implications for the interpretation of meta-analytic data (Figure 7). For muscle pain, a pronounced asymmetry was detected with an LFK index of 5.28, substantially exceeding the threshold of 2 and suggesting the potential overrepresentation of studies with positive results. This could imply an overestimation of the actual effect size due to the underrepresentation of smaller or non-significant studies, thereby introducing a cautionary note in interpreting the pooled prevalence figures. Conversely, the analysis of joint pain studies indicated an asymmetry in the opposite direction with an LFK index of −2.78. This negative value may indicate a relative underestimation of effect sizes in smaller studies that have been published despite demonstrating weaker effects. Such asymmetry does not necessarily point to selective publication based on positive findings but suggests that conservative results from smaller studies are present in the literature. Nonetheless, the negative index highlights the need for careful interpretation and suggests the possibility of other biases or unaccounted heterogeneity influencing the results. The assessment for muscle weakness revealed an LFK index of 0.14, which falls within the acceptable range for symmetry and suggests no significant publication bias in the meta-analysis. The balanced representation of studies provides confidence in the pooled effect size estimate, supporting the reliability of the reported prevalence of muscle weakness.
Figure 7
Meta-regression
We conducted a meta-regression analysis to examine the effects of moderators, including mean age, sample size, country, study design, and percentage of male participants, on the prevalence of diabetes in prison populations. No significant effects of these moderators were observed. The results of the meta-regression are presented in Supplementary Table S5.
Discussion
This systematic review and meta-analysis have synthesized available evidence regarding the incidence of musculoskeletal symptoms in individuals with PASC. Our findings indicate that musculoskeletal manifestations, specifically muscle pain, joint pain, and muscle weakness, are prevalent symptoms experienced by a significant proportion of patients recovering from COVID-19. The pooled incidence of muscle pain was 24.1%, suggesting that nearly a quarter of individuals post-COVID-19 may experience this symptom. Interestingly, the incidence seemed to increase at 12 months post-infection, indicating a possibility of persisting or late-onset muscle pain in PASC. Joint pain was reported with a pooled prevalence of 14.8%, a less frequent but still significant symptom affecting patients in the long term. The lack of significant differences in prevalence between the 3–6 months and 6–12 months subgroups suggests that joint pain may manifest consistently over time post-infection. Muscle weakness, though less prevalent at 12.9%, is another notable symptom that may profoundly impact the functional recovery of individuals.
The clinical implications of these findings are profound. Healthcare providers managing the PASC of COVID-19 patients should be cognizant of the high likelihood of musculoskeletal symptoms, which can substantially hinder patients' recovery and quality of life (, ). The relatively high incidence of muscle pain and its increase over time underscores the need for pain management and rehabilitation strategies to be integrated into long COVID care protocols (). Given the persistence of joint pain across time frames, clinicians should also consider long-term management plans for joint health, possibly incorporating anti-inflammatory treatments, physical therapy, and lifestyle modifications tailored to reduce pain and improve joint function. The impact of muscle weakness on functional ability may require targeted physical rehabilitation strategies, including strength training and occupational therapy, to assist patients in regaining their pre-infection levels of function and independence (, ). Understanding the scope of these symptoms can help in the allocation of appropriate resources for long COVID clinics and rehabilitation services. It may also inform public health messaging and patient education, preparing individuals for possible long-term sequelae following COVID-19 infection and emphasizing the importance of seeking care when needed. The development of specific guidelines for the assessment and management of PASC-associated musculoskeletal symptoms would be beneficial. Such guidelines would help standardize care, improve patient outcomes, and could be informed by ongoing research into the pathophysiological mechanisms underlying these persistent symptoms. Additionally, the psychological impact of chronic musculoskeletal pain should not be overlooked, and appropriate mental health support services should be made available to patients struggling with the long-term consequences of COVID-19 ().
The high heterogeneity observed in our meta-analyses suggests substantial variability across studies, potentially limiting the generalizability of our pooled prevalence estimates for PASC. To explore this, we conducted a meta-regression analyzing moderators including mean age, gender distribution, geographic location, study design, and percentage of male participants, but no significant effects were identified. Data limitations precluded further analysis of other potential moderators. The high heterogeneity shows challenges in applying these findings to diverse populations or clinical guidelines. Future research should prioritize standardized reporting and larger, more diverse studies to better elucidate sources of variability and enhance the applicability of PASC prevalence estimates.
Future studies must prioritize longitudinal cohort designs that track the evolution of musculoskeletal symptoms from the acute phase of COVID-19 to the chronic phase, delineating their trajectory and identifying predictors of long-term disability. Concurrently, mechanistic studies should delve into the biological underpinnings of PASC, unraveling the inflammatory, immunological, and vascular factors that contribute to the persistence of musculoskeletal manifestations. The establishment of standardized diagnostic criteria will harmonize research efforts and enhance the comparability of findings across studies (). Research should also appraise the effectiveness of multidisciplinary management strategies that integrate pharmacological and non-pharmacological interventions to support the holistic recovery of PASC patients (). Investigating the health system's response to PASC will shed light on the efficacy of existing healthcare pathways, including the role of long COVID clinics and rehabilitation services (, ). Additionally, incorporating a global health perspective will ensure research is inclusive, capturing the experiences of diverse populations across varying socioeconomic and geographical contexts. As the COVID-19 landscape evolves with new variants and vaccination updates, it is crucial to integrate these changes into ongoing research (). This will help assess their impact on the incidence, severity, and recovery trajectory of PASC, ensuring that findings remain relevant and responsive to the current state of the pandemic. The creation of registry databases for PASC can serve as a comprehensive repository for global data, aiding real-time analysis and informing public health policies (33–35). Research outcomes should be translated into public health initiatives and educational programs that empower patients and inform the broader community about the long-term consequences of COVID-19. By addressing these focused research priorities, we can better grasp the complexities of PASC and work toward more effective interventions and policies that alleviate the burden of long-term sequelae on individuals and healthcare systems. This forward-looking research agenda will facilitate a concerted and informed response to the ongoing challenges of the COVID-19 pandemic.
Our review has some limitations. The significant heterogeneity observed across may have impacted the pooled estimates. This may undermine the reliability and generalizability of our pooled prevalence estimates for specific clinical or public health applications. The potential for publication bias, particularly in studies reporting on muscle pain, introduces a degree of uncertainty into our findings. Despite conducting a meta-regression to explore potential moderators, including mean age, gender distribution, geographic location, study design, and percentage of male participants, no significant effects were identified, likely due to limited data availability. The temporal relationship between COVID-19 infection and the onset of musculoskeletal symptoms was also challenging to ascertain due to the reliance on self-reported data and the retrospective nature of many studies. These limitations, along with the lack of consistent reporting on COVID-19 severity and vaccination status, restrict our ability to fully elucidate symptom trajectories and may reduce the applicability of our findings to specific clinical or public health contexts.
The evolving nature of the COVID-19 pandemic, with new variants emerging and changing patterns of infection and immunity, may influence the incidence and presentation of PASC, including musculoskeletal manifestations. Therefore, these findings must be viewed as a snapshot in time, with the need for ongoing research to update and confirm these results as the pandemic continues to unfold.
Conclusion
Musculoskeletal symptoms such as muscle pain, joint pain and muscle weakness are common in PASC. The persistent nature of these symptoms demands not only immediate clinical attention but also a sustained research effort to understand and mitigate their long-term impacts. As the pandemic evolves, continuous updating of clinical guidelines and patient management approaches will be essential to address the needs of those suffering from PASC.
Statements
Data availability statement
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
Author contributions
AV: Visualization, Writing – original draft, Conceptualization, Methodology. SN: Formal analysis, Validation, Visualization, Writing – review & editing. HS: Conceptualization, Formal analysis, Software, Validation, Writing – review & editing. AU: Writing – review & editing, Data curation, Investigation, Methodology. MS: Writing – original draft, Data curation, Methodology, Conceptualization, Formal analysis. RS: Writing – review & editing, Conceptualization, Methodology, Data curation. RM: Supervision, Software, Writing – review & editing, Validation. AJ: Writing – original draft, Writing – review & editing. NA: Data curation, Methodology, Validation, Writing – review & editing. AR: Writing – review & editing, Methodology, Formal analysis, Data curation. UA: Conceptualization, Supervision, Software, Writing – original draft, Data curation.
Funding
The author(s) declare that no financial support was received for the research and/or publication of this article.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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Supplementary material
The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fpubh.2025.1662953/full#supplementary-material
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Summary
Keywords
post-acute sequelae of SARS-CoV-2 infection, muscle pain, joint pain, muscle weakness, long COVID, good health and well being
Citation
Verma A, Naidu SV, Sulthana H, Ullah A, Shabil M, Sah R, Mehta R, Jan A, Ain NU, Rahim A and Abu Nahla U (2025) Musculoskeletal manifestations in post-acute sequelae of SARS-CoV-2 infection: a systematic review and meta-analysis. Front. Public Health 13:1662953. doi: 10.3389/fpubh.2025.1662953
Received
09 July 2025
Accepted
29 August 2025
Published
19 September 2025
Volume
13 - 2025
Edited by
Chutian Zhang, Northwest A&F University, China
Reviewed by
Duy-Thai Nguyen, NICVB, Vietnam
Camelia Corina Pescaru, University of Medicine and Pharmacy “Victor Babes” Timisoara, Romania
Updates
Copyright
© 2025 Verma, Naidu, Sulthana, Ullah, Shabil, Sah, Mehta, Jan, Ain, Rahim and Abu Nahla.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Ursula Abu Nahla Uabunahla@gmail.comAsif Jan asif.research1@gmail.com
Disclaimer
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