Influence of vaccination status and sarcopenia on the need for physical rehabilitation in patients infected with SARS-CoV-2

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Objectives: The aim of this study was to investigate the influence of vaccination status and post-COVID sarcopenia on the need for physical rehabilitation in patients infected with SARS-CoV-2. Methodology: A case-control study was carried out in the city of Ouro Preto, Brazil, which has a centralized public health system. The cases were patients of the city’s post-COVID clinic who underwent rehabilitation, and the controls were COVID-19 patients randomly selected from the population who did not need rehabilitation. Directed acyclic graph (DAG) and logistic regression were used to analyze the data. Results: The presence of post-COVID sarcopenia increased the chances of needing rehabilitation (OR 2.14), along with age over 60 (OR 4.26) and hospitalization during the acute phase of the disease (OR 16.7). Vaccination with three or more doses reduces the need for rehabilitation (OR 0.1), while the presence of comorbidities increases the need for it (OR 4.18). Conclusion: It is important for health care systems to be prepared for the rehabilitation needs of post-COVID patients. Our results reinforce the importance of vaccination in reducing the sequelae of COVID-19 and the need for greater attention in the post-Covid phase to older people and those with prior comorbidities, as well as to patients who have been hospitalized and who have post-COVID musculoskeletal symptoms. SARS-CoV-2 COVID-19 Vaccine Sarcopenia Comorbidity Figures Figure 1 Figure 2 1. Introduction On May 5, 2023, the World Health Organization declared the end of the Public Health Emergency of International Concern for COVID-19 [ 1 ]. However, global concerns have emerged regarding post-COVID-19 conditions, also known as long COVID, post-COVID syndrome or post-acute COVID-19. This condition manifests itself through a wide variety of signs and symptoms, including fatigue, headache, attention disorders, hair loss and dyspnea, in addition to neurological and musculoskeletal changes, such as neuropathy, muscle weakness, severe hypoxemia, anxiety and/or depression, significant weight loss and cardiovascular complications [ 2 – 4 ]. The World Health Organization defines long COVID as a syndrome that affects individuals with confirmed SARS-CoV-2 infection, with onset of symptoms up to three months after the acute phase of the disease and with no other attributable cause. It is estimated that between 10% and 20% of infected people develop persistent symptoms [ 5 ]. Individuals who had COVID-19 may experience a reduction in functional capacity, compromising quality of life and long-term survival. The pandemic has posed ongoing challenges to public health, requiring professionals to manage the physical and psychosocial sequelae of survivors [ 6 ]. Among the main complications, sarcopenia stands out, characterized by the loss of muscle mass and strength [ 7 ], often related to physical inactivity, prolonged immobility, and nutritional deficiencies [ 8 , 9 ], and further aggravated by neurological symptoms and neuromuscular damage [ 10 – 12 ]. In this context, continuous monitoring of individuals who have overcome the acute phase of the disease is essential to reduce the risk of complications and mortality [ 6 ]. COVID-19 vaccines play an essential role not only in preventing infection, but also in reducing severe complications and the need for rehabilitation [ 13 ], in addition to contributing to the prevention of post-COVID conditions, such as sarcopenia, which are essential for long-term recovery [ 14 ]. Recent evidence reinforces that vaccination reduces both the incidence and severity of persistent symptoms, favoring better clinical outcomes [ 15 ]. Despite this, many patients develop functional sequelae, requiring specific rehabilitation approaches. Rehabilitation can be defined as the process of restoring functionality and autonomy after illness or injury, may involve pharmacological, physical, and behavioral interventions [ 16 ]. In the post-COVID-19 context, rehabilitation has proven to be fundamental for recovery, promoting improved functional capacity, increased muscle strength, reduced fatigue, and psychosocial reestablishment [ 17 , 18 ]. Structured rehabilitation programs have shown efficacy in reducing musculoskeletal and neurological sequelae associated with long COVID [ 19 ], making their early integration essential to minimize functional impact and improve patients' quality of life in the long term. This study aimed to investigate the influence of vaccination status and post-COVID sarcopenia on the need for physical rehabilitation in patients infected with SARS-CoV-2. This information can aid in planning actions of the health systems by evaluating how post-COVID can impact the care process. 2. Material and methods 2.1. Study design A case-control study was conducted in the city of Ouro Preto, MG, Brazil, which has a robust public health system. The cases were patients from the city’s post-COVID clinic who required physical rehabilitation. This clinic, which served patients referred by community health centers, was the city's reference center for post-COVID complaints where the post-COVID rehabilitation resources were centralized. Controls were patients diagnosed with COVID-19 who did not require physical rehabilitation. These controls were selected from COVID-19 notification databases provided by the city's health surveillance service. The selection was aleatory and proportional to the prevalence of infection within the coverage area of ​​each of the city’s community health centers, ensuring sample representativeness. Controls were contacted to schedule an interview that was conducted at their local community health center. If a patient refused to participate, the next person on the list was invited. The cases and controls were interviewed and from the data obtained it was possible to investigate the effect of vaccination status and post-COVID sarcopenia on the need for functional rehabilitation in patients affected by COVID-19. 2.2. Power of the study With a total of 54 cases and 230 controls, based on a 95% confidence interval, with an exposure among cases of 52 to 59% and controls of 37 to 79%, the power of the study was 84% for the evaluation of the sarcopenia variable and 97% for vaccination status in influencing the need for rehabilitation. 2.3. Study Area The city of Ouro Preto is located in the state of Minas Gerais, in southeastern Brazil. The estimated population in 2020 was 74,558 inhabitants and as of 30/05/2023 17,309 cases of COVID-19 had been reported and 142 deaths. In March 2020, when an international health emergency of global importance was established, the Ouro Preto Health Department opened a COVID-19 temporary hospital with 50 adult and pediatric beds, establishing a centralized point-of-entry for respiratory syndromes, to better control transmission and monitor positive cases, with a counter-referral protocol for the territory. In the waning phase of the pandemic, as of April 2021, the Ouro Preto Health Department established a specialized post-acute clinic for individuals with post-COVID complaints. Patients seen at the clinic were referred by the community health centers and, after a multi-professional evaluation, it was determined the need for physical rehabilitation (physiotherapy, occupational therapy and/or speech therapy), cognitive rehabilitation, and/or specialized medical care. 2.4. Data Collection Data was collected using an electronic form using the KoBoToolbox tool. The WHO 2021 recommendation was chosen to classify the forms of presentation of COVID-19 as asymptomatic (no clinical symptoms), mild (no pneumonia and no indication for oxygen therapy), moderate (clinical signs of non-severe pneumonia and no indication for oxygen therapy), severe (clinical signs of severe pneumonia and indication for oxygen therapy) and critical (severe acute respiratory syndrome, with complications and orotracheal intubation) [ 20 ]. Next, a clinical and pharmacological history of the SARS-CoV-2 infection was recorded in the questionnaire (form of presentation of the disease, need for hospitalization, use of oxygen, drug treatment for the acute phase, among others), sociodemographic characteristics (gender, self-declared race/ethnicity, occupation, marital status and education), pre-existing comorbidities (diabetes, hypertension, cardiovascular diseases, obesity, mental disorders, chronic obstructive pulmonary disease [COPD], asthma, chronic kidney disease, among others), lifestyle and behavioral habits (use of alcohol, tobacco products, other illicit drugs and physical activity), vaccination status at the time of infection (number of doses administered until the infection), presence or absence of post-COVID-19 changes and need for rehabilitation due to sequelae of the infection. For the purposes of this study, the exposure variable 'sarcopenia' was assessed using the Clinical-Functional Vulnerability Index (IVCF-20), a validated instrument for screening functional frailty in the elderly, with a sensitivity greater than 90% for detecting frail individuals [ 21 ]. The IVCF-20 covers dimensions such as mobility, activities of daily living, cognition, mood, and comorbidities, allowing a broad functional assessment, which is particularly relevant in the post-COVID-19 context. Although it is a self-reported instrument, its application is recommended in recent post-COVID-19 management guidelines due to its ability to detect functional vulnerabilities early [ 22 ]. In addition, the assessment of sarcopenia was confirmed by the analysis of the case records. Post-COVID-19 sarcopenia was considered present if the research participant answered “yes” to at least one of the following questions: Has any health professional diagnosed you with sarcopenia after the COVID-19 infection? After COVID-19, did you experience significant weight loss, unintentional weight loss, accompanied by loss of strength, a feeling of lack of energy, balance and physical performance to perform activities such as walking, climbing stairs or getting out of bed? The outcome variable, need for physical rehabilitation, was measured based on a positive response to rehabilitation with a physical therapist, occupational therapist and/or speech therapist. To mitigate possible recall bias, we triangulated medical records to validate the diagnoses and treatments reported by the participants, thus ensuring accuracy of the data. For cases in which the participant had difficulty recalling, we sought to interview caregivers or family members involved in the patient's care, reinforcing the reliability of the information. 2.5. Data analysis Descriptive analyses of absolute and relative frequencies were carried out and the chi-square technique was used to compare the characteristics of cases and controls. These analyses were performed using Stata software version 18. To select the set of covariates to be included in the multivariate model, two causality models based on directed acyclic graphs (DAGs) were developed to guide the analysis. The DAG was used to select a minimum and sufficient set of adjustment and confounding variables based on a backdoor criterion. The variables considered sufficient (S) are a set of variables chosen to block all non-causal pathways linking the exposure to the outcome. A minimum selection was made, since the inclusion of unnecessary variables not only increases the risk of collision bias, but also reduces the accuracy of the estimates. Backdoor criteria are non-causal, non-blocked pathways that link exposure to the outcome [ 23 , 24 ]. A theoretical causality model was developed to guide the analysis of the total effect of COVID-19 vaccination (exposure variable) on the need for physical rehabilitation (outcome variable). With the DAG, it was possible to identify the causal effect based on the variables: age, gender, vaccination status at the time of the COVID-19 infection, hospitalization in the acute phase, use of oxygen, musculoskeletal symptoms in the post-COVID period, form of presentation in the acute phase, post-COVID sarcopenia, comorbidities prior to the acute phase and the assumptions contained in the diagram. The selection of variables included in the directed acyclic graph (DAG) was based on well-established theoretical knowledge from the scientific literature, considering previously identified causal relationships among the variables of interest [ 25 , 26 ]. Variables functioning as confounders, mediators, and colliders were incorporated based on epidemiological evidence and the clinical plausibility of the observed associations. In the causal structure diagram (CSD), causal connections were established between the variables, represented by arrows. Each variable was represented by a circle, and the colors used have different meanings. The DAG assessing the association between vaccination status and rehabilitation enabled the selection of the covariates that were included in the multivariate logistic regression model (Fig. 1 ). The minimum and sufficient adjustment suggested was: presence of previous comorbidity at the time of the infection and age. A second model was developed to guide the analysis of the total effect of post-COVID sarcopenia (exposure variable) on the need for physical rehabilitation (outcome variable) (Fig. 2 ). In this model, the minimum and sufficient adjustment suggested was: hospitalization in the acute phase, physical activity at the time of infection, age and gender. The online software Dagitty was used to carry out these DAG analyses and Stata version 18 for the multivariate analyses. 3. Results 3.1. Participants' characteristics Among the 120 patients being monitored at the post-COVID outpatient clinic, 99 agreed to participate in the study and, of these, 54 needed physical rehabilitation and were included as cases. The control group consisted of 230 people who were randomly selected and did not require rehabilitation. It was observed that the case and control groups differed in terms of age, form of presentation of COVID-19, hospitalization in the acute phase, use of oxygen by mask/catheter and/or invasive mechanical ventilation, COVID-19 vaccination status, types of vaccines administrated, use of chronic medications at the time of infection, presence of prior comorbidity and post-COVID hospitalization (Table 1 S). With regards to behavioral variables, the practice of physical activity and the use of tobacco products at the time of the infection also differentiated the case and control groups (Table 2S). 3.2. Association between vaccination status with the rehabilitation Multivariate analysis showed that people aged 60 or over were 4.48 (95% CI 1.68 −11.93) times more likely to undergo rehabilitation compared to younger people (reference category: >= 18 years and < than 45 years old). The presence of comorbidities in the acute phase of COVID-19 increased the chances of rehabilitation by 4.18 (95% CI 1.85 − 9.42) times. Vaccination status at the time of SARS-CoV-2 infection, in individuals with 3 doses or more of COVID-19 vaccine, was a protective factor (OR 0.1; 95% CI 0.04 − 0.26), i.e. vaccination with 3 doses or more conferred 90% protection against the need for rehabilitation (Table 1 ). 3.3. Association between Post-COVID sarcopenia with the rehabilitation Multivariate analysis showed that people aged 60 and over were 4.26 times more likely to be rehabilitated than people aged between 18 and 45. In addition, hospitalization during the acute phase of COVID-19 increases the chances of needing rehabilitation by 16.7 times and post-COVID sarcopenia increases the chances of rehabilitation by 2.14 times (Table 1 ). Table 1 Causal association between vaccination status and post-COVID sarcopenia with the need for physical rehabilitation after COVID-19, Ouro Preto, Brazil, 2023. Variables Need for rehabilitation 1st Model * 2nd Model # OR (CI95%) p OR (CI95%) p 3 doses or more of vaccine vs. not vaccinated 0.10 (0.04 − 0.26) < 0.001 - - Presence vs. absence of sarcopenia - - 2.14 (1.02–4.53) 0.045 * Model 1 - Association between vaccination status with the rehabilitation, adjusted by age and presence of previous comorbity; # Model 2 - Association between Post-COVID sarcopenia with the rehabilitation, adjusted by age and hospitalization in the acute phase. Models 1 and 2 were derived from the directed acyclic graphs (DAGs) depicted in Figs. 1 and 2 , respectively. 4. Discussion In this study, two causal relationships proposed by two different DAG models were assessed: one between the need for physical rehabilitation and vaccination status, and the other between rehabilitation and sarcopenia in the post-COVID period. In the first relationship, it was observed that receiving three or more vaccine doses reduces the likelihood of needing rehabilitation. In the second analysis, the presence of sarcopenia was associated with an increased need for rehabilitation. The first multivariate analysis showed that individuals aged 60 years or older had a 4.48-fold higher chance (95% CI: 1.68–11.93) of being referred for rehabilitation, compared with those aged 18–45 years. This finding was confirmed in the second multivariate analysis, in which individuals in this age group remained 4.26-fold more likely to require rehabilitation. In addition, hospitalization during the acute phase of COVID-19 increased the odds of rehabilitation by 16.7-fold, and the presence of post-COVID sarcopenia increased this chance by 2.14-fold. It is important to highlight that these associations were observed after adjusting for variables in the models, providing greater robustness to the results by minimizing potential confounding factors. These data corroborate the existing literature, which recognizes advanced age, disease severity, and loss of muscle mass and strength as critical factors for worsening functional capacity in COVID-19 survivors [ 27 , 28 ]. Vaccination against COVID-19 has shown to be highly effective in protecting against severe forms of the disease and its long-term complications. Studies demonstrate that vaccines significantly reduce the risk of hospitalization, intensive care unit admissions, and death [ 29 – 31 ]. In addition, vaccinated individuals are less likely to develop COVID complications, such as cardiovascular and thromboembolic diseases [ 32 , 33 ]. Vaccination also reduces the risk of post-COVID syndrome depending on the number of doses administered [ 34 , 35 ]. Full vaccination, especially with two or more doses of mRNA vaccines such as Pfizer-BioNTech and Moderna, significantly reduces the incidence of long-term complications requiring rehabilitation [ 34 , 36 ]. The efficacy of the vaccines, especially after booster doses, is notable in preventing hospitalizations and severe complications associated with SARS-CoV-2 infection, particularly in the Omicron BA.4 and BA.5 variants, which have a greater capacity for immune evasion [ 13 ]. Patients who contracted COVID-19 but were vaccinated tend to recover more quickly and efficiently, with a reduced need for extensive rehabilitation programs [ 37 ]. Therefore, the continuation of vaccination and the promotion of booster doses are essential to ensure safety and effective recovery for the population. In the present study, the control group primarily received doses of combined vaccines that included the Pfizer-BioNTech (mRNA) vaccine in their regimen, which may have reduced the need for rehabilitation among these individuals. Previous research has shown that the Pfizer-BioNTech (mRNA) vaccine helps prevent the need for rehabilitation post-COVID-19 [ 34 , 36 ]. However, it is important to emphasize that all vaccine manufacturers provide protection against severe cases, hospitalization, post-COVID symptoms, the need for rehabilitation, and death. Most of the patients assessed at the post-COVID clinic had at least one comorbidity, with systemic arterial hypertension being the most frequent, followed by obesity or overweight and type 2 diabetes mellitus. Several studies have shown that overweight, obesity, hypertension and previous type 2 diabetes increase the risk of long COVID-19 [ 38 – 41 ]. On the other hand, Thompson et al. (2022) found no association between the presence of hypertension or diabetes and prolonged COVID-19 symptoms [ 39 ]. Due to the large number of patients with different comorbidities, this variable remained in the model as an adjustment variable. This study also shows that the presence of post-COVID sarcopenia is associated with the need for rehabilitation. As a result of the clinical manifestations of the disease, a significant proportion of patients required hospitalization and were subjected to invasive procedures to ensure the maintenance of physiological functions essential to life. During the hospitalization, these individuals often experience a decline in their physiological health and, in many cases, undergo a series of physical changes. It has been observed that hospitalized patients who experience muscle or joint pain during COVID-19 had a significant reduction in functional capacity [ 42 ], even when undergoing physiotherapy during their hospitalization [ 43 ]. Muscle atrophy due to prolonged immobilization is a common consequence in patients who face long periods of inactivity, such as those hospitalized due to COVID-19, since muscle deterioration is a complication that sets in quickly [ 44 ]. Loss of muscle mass during hospitalization can delay recovery and increase the risk of long-term complications, such as persistent muscle weakness and functional disability [ 45 ]. Prolonged bed restriction due to hospitalization is also associated with a drastic increase in systemic inflammation, typical of COVID-19, and are important catabolic stimuli that can intensify the loss of muscle mass [ 46 – 48 ]. Post-COVID sarcopenia is exacerbated by chronic inflammation and decreased physical activity, creating a vicious cycle that further accelerates muscle loss and reduces functionality [ 8 , 49 , 50 ]. The cause of sarcopenia is complex and multifactorial, including endocrine and metabolic abnormalities, and has a strong link with low-grade systemic inflammation in the elderly, reduced protein synthesis and regeneration, increased apoptosis and protein breakdown [ 51 ]. Interleukin-6 (IL-6), an inflammatory marker associated with obesity, metabolic syndrome, atherosclerotic diseases, inflammatory autoimmune diseases, and heart failure, has been shown to correlate with muscle strength and function. In chronic diseases among older adults, IL-6 appears to play a significant role in the reduction of functional capacity, suggesting that its dysregulation may be a precursor to the development of sarcopenia [ 52 , 53 ]. These findings highlight the importance of implementing early rehabilitation programs after hospital discharge to improve functionality, enhance quality of life, and reduce hospital readmissions [ 54 ]. In addition to the methodology used in the present study, other diagnostic methods for sarcopenia and frailty include grip strength [ 55 , 56 ], isometric contraction of the vastus lateralis muscle [ 57 ], bioelectrical impedance [ 58 ], and magnetic resonance imaging, considered the gold standard for assessing muscle quality and quantity [ 59 ]. The COVID-19 pandemic required the rapid adaptation of health services, especially in the rehabilitation sectors. A study in Italy described the restructuring of a hospital rehabilitation unit to meet new demand, highlighting the need for structural and operational adjustments [ 60 ]. In addition, another study suggested the importance of reorganizing care flows and implementing safety protocols to ensure continuity of care and minimize functional losses in post-COVID-19 patients [ 61 ]. Furthermore, Iannaccone et al. (2020) demonstrated that rehabilitation units for COVID-19 patients had costs approximately twice as high as conventional units, highlighting the need for specific investments to ensure the sustainability of rehabilitation services in the face of new demands [ 62 ]. Both models were adjusted by age, since age is associated with the explanatory and outcome variable. With advancing age there is a progressive decline in the body's functional capacities, leading to greater vulnerability to health problems and frailty [ 63 ]. Older patients have more severe symptoms of the infection, leading to a longer post-COVID period. This may be related to pre-existing comorbidities and the elderly patient's own physiological condition [ 64 ], reinforcing the need for greater adherence of this population to vaccination against COVID-19, to avoid a greater risk of functional weakness and sequelae [ 65 ]. This study has some limitations, as the retrospective nature of the questions could lead to a recall bias. However, we believe that this bias was minimal, as the information was obtained within one or two years of the infection and, due to the great repercussions of the pandemic, people were generally aware of their symptoms. In addition, the assessment of sarcopenia was based on self-report, which may also introduce bias, but was complemented by the analysis of the case records, confirming the formal indication for rehabilitation by clinical evaluation. Despite the variation in the definition of sarcopenia in different studies, the use of IVCF-20 ensured greater standardization and generalization of the results [ 21 ]. 5. Conclusion Our results show the importance of encouraging vaccination against COVID-19, as it helps to reduce the need for physical rehabilitation after COVID-19. In addition, our results highlight the importance of healthcare professionals paying closer attention to patients with post-COVID sarcopenia as it increases the need for rehabilitation. Declarations Acknowledgments: We would like to thank the staff of the Ouro Preto Health Department post-COVID clinic for their support in this study. Ethics approval and consent to participate: This study was approved by the Ethics Committee of the Federal University of Ouro Preto (CAAE: 54298221.9.0000.5150) in accordance with Resolution nº 466, of december 12, 2012. The researchers adhered to the Declaration of Helsinki in carrying out the research. All the patients who agreed to participate in the study signed an informed consent form. Funding: No external funding. Competing interests: The authors declare no competing interests. Data availability: The data for this study are not publicly available to protect the privacy of the participants. However, they can be made available by the corresponding author upon reasonable request. Code availability: Not applicable. Authors’ contributions: T.O., B.B.S, M.C., A.B.S., and W.C.V., conceived the idea for the study. T.O., C.C.R.G.B., A.M.G., S.C.M, were involved in data collection. T.O., R.V.D., B.B.S., L.A.A.M.J., M.C., A.B.R., W.C.V., were involved in data Cleaning and analysis, writing the first draft, review and editing. T.O., W.C.V., B.B.S., L.A.A.M.J., M.C., were involved in statistical analysis and review. T.O., W.C.V. were involved in the overall study coordination. All authors provided technical inputs to the manuscript and approved the final version of the paper. 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BMJ. 2023;383:e076990.https://doi.org/10.1136/bmj-2023-076990. Gao P, Liu J, Liu M. Effect of COVID-19 Vaccines on Reducing the Risk of Long COVID in the Real World: A Systematic Review and Meta-Analysis. Int J Environ Res Public Health. 2022;19.https://doi.org/10.3390/ijerph191912422. Ceban F, Kulzhabayeva D, Rodrigues NB, Di Vincenzo JD, Gill H, Subramaniapillai M, et al. COVID-19 vaccination for the prevention and treatment of long COVID: A systematic review and meta-analysis. Brain Behav Immun. 2023;111:211-29.https://doi.org/10.1016/j.bbi.2023.03.022. Ayoubkhani D, Bermingham C, Pouwels KB, Glickman M, Nafilyan V, Zaccardi F, et al. Trajectory of long covid symptoms after covid-19 vaccination: community based cohort study. BMJ. 2022;377:e069676.https://doi.org/10.1136/bmj-2021-069676. Subramanian A, Nirantharakumar K, Hughes S, Myles P, Williams T, Gokhale KM, et al. Symptoms and risk factors for long COVID in non-hospitalized adults. Nat Med. 2022;28:1706-14.https://doi.org/10.1038/s41591-022-01909-w. Thompson EJ, Williams DM, Walker AJ, Mitchell RE, Niedzwiedz CL, Yang TC, et al. Long COVID burden and risk factors in 10 UK longitudinal studies and electronic health records. Nat Commun. 2022;13:3528.https://doi.org/10.1038/s41467-022-30836-0. Tleyjeh IM, Saddik B, AlSwaidan N, AlAnazi A, Ramakrishnan RK, Alhazmi D, et al. Prevalence and predictors of Post-Acute COVID-19 Syndrome (PACS) after hospital discharge: A cohort study with 4 months median follow-up. PLoS One. 2021;16:e0260568.https://doi.org/10.1371/journal.pone.0260568. Su Y, Yuan D, Chen DG, Ng RH, Wang K, Choi J, et al. Multiple early factors anticipate post-acute COVID-19 sequelae. Cell. 2022;185:881-95 e20.https://doi.org/10.1016/j.cell.2022.01.014. Du HW, Fang SF, Wu SR, Chen XL, Chen JN, Zhang YX, et al. Six-month follow-up of functional status in discharged patients with coronavirus disease 2019. BMC Infect Dis. 2021;21:1271.https://doi.org/10.1186/s12879-021-06970-3. Belli S, Balbi B, Prince I, Cattaneo D, Masocco F, Zaccaria S, et al. Low physical functioning and impaired performance of activities of daily life in COVID-19 patients who survived hospitalisation. Eur Respir J. 2020;56.https://doi.org/10.1183/13993003.02096-2020. Russell AP. Molecular regulation of skeletal muscle mass. Clin Exp Pharmacol Physiol. 2010;37:378-84.https://doi.org/10.1111/j.1440-1681.2009.05265.x. Sagarra-Romero L, Vinas-Barros A. COVID-19: Short and Long-Term Effects of Hospitalization on Muscular Weakness in the Elderly. Int J Environ Res Public Health. 2020;17.https://doi.org/10.3390/ijerph17238715. Cao X. COVID-19: immunopathology and its implications for therapy. Nat Rev Immunol. 2020;20:269-70.https://doi.org/10.1038/s41577-020-0308-3. Meftahi GH, Jangravi Z, Sahraei H, Bahari Z. The possible pathophysiology mechanism of cytokine storm in elderly adults with COVID-19 infection: the contribution of "inflame-aging". Inflamm Res. 2020;69:825-39.https://doi.org/10.1007/s00011-020-01372-8. Puthucheary ZA, Rawal J, McPhail M, Connolly B, Ratnayake G, Chan P, et al. Acute skeletal muscle wasting in critical illness. JAMA. 2013;310:1591-600.https://doi.org/10.1001/jama.2013.278481. de Moura PH, de Souza H, Brandao DC, Barros C, Correia M, Reinaux C, et al. Mapping peripheral and abdominal sarcopenia acquired in the acute phase of COVID-19 during 7 days of mechanical ventilation. Sci Rep. 2023;13:3514.https://doi.org/10.1038/s41598-023-29807-2. Aguiar GB, Dourado KF, Andrade MIS, Domingos Junior IR, Barros-Neto JA, Vasconcelos SML, et al. Frequency and factors associated with sarcopenia prediction in adult and elderly patients hospitalized for COVID-19. Exp Gerontol. 2022;168:111945.https://doi.org/10.1016/j.exger.2022.111945. Curcio F, Ferro G, Basile C, Liguori I, Parrella P, Pirozzi F, et al. Biomarkers in sarcopenia: A multifactorial approach. Exp Gerontol. 2016;85:1-8.https://doi.org/10.1016/j.exger.2016.09.007. Hanberg JS, Rao VS, Ahmad T, Chunara Z, Mahoney D, Jackson K, et al. Inflammation and cardio-renal interactions in heart failure: a potential role for interleukin-6. Eur J Heart Fail. 2018;20:933-4.https://doi.org/10.1002/ejhf.963. Maggio M, Guralnik JM, Longo DL, Ferrucci L. Interleukin-6 in aging and chronic disease: a magnificent pathway. J Gerontol A Biol Sci Med Sci. 2006;61:575-84.https://doi.org/10.1093/gerona/61.6.575. Aquim EE, Bernardo WM, Buzzini RF, Azeredo NSG, Cunha LSD, Damasceno MCP, et al. Brazilian Guidelines for Early Mobilization in Intensive Care Unit. Rev Bras Ter Intensiva. 2019;31:434-43.https://doi.org/10.5935/0103-507X.20190084. Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyere O, Cederholm T, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019;48:16-31.https://doi.org/10.1093/ageing/afy169. Bohannon RW. Grip Strength: An Indispensable Biomarker For Older Adults. Clin Interv Aging. 2019;14:1681-91.https://doi.org/10.2147/CIA.S194543. Bäckman E, Johansson V, Häger B, Sjöblom P, Henriksson K. Isometric muscle strength and muscular endurance in normal persons aged between 17 and 70 years. Journal of Rehabilitation Medicine. 1995;27:109-17. Clark BC, Rutkove S, Lupton EC, Padilla CJ, Arnold WD. Potential Utility of Electrical Impedance Myography in Evaluating Age-Related Skeletal Muscle Function Deficits. Front Physiol. 2021;12:666964.https://doi.org/10.3389/fphys.2021.666964. Huber FA, Del Grande F, Rizzo S, Guglielmi G, Guggenberger R. MRI in the assessment of adipose tissues and muscle composition: how to use it. Quant Imaging Med Surg. 2020;10:1636-49.https://doi.org/10.21037/qims.2020.02.06. Bush TL. The epidemiology of cardiovascular disease in postmenopausal women. Ann N Y Acad Sci. 1990;592:263-71; discussion 334-45.https://doi.org/10.1111/j.1749-6632.1990.tb30338.x. Miranda V. Sarcopenia e fatores de risco: como minimizar os prejuízos durante a quarentena? Accessed in: https://pebmedcombr/sarcopenia-e-fatores-de-risco-como-minimizar-os-prejuizos-durante-a-quarentena/#:~:text=Em%20pacientes%20com%20baixo%20IMC,gr%C3%A3os%20refinados%20refrigerantes%20e%20cerveja. 2020. Barbosa IR, Galvão MHR, Souza TAd, Gomes SM, Medeiros AdA, Lima KCd. Incidência e mortalidade por COVID-19 na população idosa brasileira e sua relação com indicadores contextuais: um estudo ecológico. Revista Brasileira de Geriatria e Gerontologia. 2020;23:e200171.https://doi.org/10.1590/1981-22562020023.200171 Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5097803","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":446407078,"identity":"44c6990e-a028-4534-b767-9700f4d42106","order_by":0,"name":"Taciana Oliveira","email":"","orcid":"","institution":"Universidade Federal de Ouro Preto, Minas Gerais","correspondingAuthor":false,"prefix":"","firstName":"Taciana","middleName":"","lastName":"Oliveira","suffix":""},{"id":446407079,"identity":"bf74a66f-9f91-4cd1-883a-0c6304b325b5","order_by":1,"name":"Carla Carneiro Rola Gomes Barbosa","email":"","orcid":"","institution":"Universidade Federal de Ouro Preto, Minas Gerais","correspondingAuthor":false,"prefix":"","firstName":"Carla","middleName":"Carneiro Rola Gomes","lastName":"Barbosa","suffix":""},{"id":446407080,"identity":"fa3ad5c6-4f88-4cc3-9be1-546f5cfc7222","order_by":2,"name":"Aline Magalhães-Gonçalves","email":"","orcid":"","institution":"Universidade Federal de Ouro Preto, Minas Gerais","correspondingAuthor":false,"prefix":"","firstName":"Aline","middleName":"","lastName":"Magalhães-Gonçalves","suffix":""},{"id":446407081,"identity":"9e211342-e166-460e-b41f-00bdeb985fd7","order_by":3,"name":"Rafael Vieira-Duarte","email":"","orcid":"","institution":"Universidade Federal de Ouro Preto, Minas Gerais","correspondingAuthor":false,"prefix":"","firstName":"Rafael","middleName":"","lastName":"Vieira-Duarte","suffix":""},{"id":446407082,"identity":"8aef0522-120c-4294-8118-311fe5c7da0a","order_by":4,"name":"Sara Custódio Martins","email":"","orcid":"","institution":"Universidade Federal de Ouro Preto, Minas Gerais","correspondingAuthor":false,"prefix":"","firstName":"Sara","middleName":"Custódio","lastName":"Martins","suffix":""},{"id":446407083,"identity":"084d9675-9fbd-429a-9a98-9f44a5cc0df2","order_by":5,"name":"Breno Bernardes-Souza","email":"","orcid":"","institution":"University of Miami","correspondingAuthor":false,"prefix":"","firstName":"Breno","middleName":"","lastName":"Bernardes-Souza","suffix":""},{"id":446407084,"identity":"af04a3ea-1fc2-4b2e-a47a-a919bb4f0417","order_by":6,"name":"Luiz Antônio Alves Menezes-Júnior","email":"","orcid":"","institution":"Universidade Federal de Ouro Preto, Minas Gerais","correspondingAuthor":false,"prefix":"","firstName":"Luiz","middleName":"Antônio Alves","lastName":"Menezes-Júnior","suffix":""},{"id":446407085,"identity":"dcb40b47-0802-4886-b9fd-979e93bbafd8","order_by":7,"name":"Mariângela Carneiro","email":"","orcid":"","institution":"Universidade Federal de Minas Gerais","correspondingAuthor":false,"prefix":"","firstName":"Mariângela","middleName":"","lastName":"Carneiro","suffix":""},{"id":446407086,"identity":"599965ba-81d5-4c88-912a-76e8b8e2a2d4","order_by":8,"name":"Alexandre Barbosa Reis","email":"","orcid":"","institution":"Universidade Federal de Ouro Preto, Minas Gerais","correspondingAuthor":false,"prefix":"","firstName":"Alexandre","middleName":"Barbosa","lastName":"Reis","suffix":""},{"id":446407087,"identity":"fb6bae6c-0810-4494-be4b-3759bd0859ac","order_by":9,"name":"Wendel Coura-Vital","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8ElEQVRIiWNgGAWjYJACCYYCMM34gMEGzDBgYGwgpMUATDMbMKSRqIVNgigtBsd7D974YGAnZ3D78LNqngSbPAb25m0SjDvu4dZy5lyy5QyDZGODc2lmt3kS0ooZeI6VSTCeKcapxexGjpk0j8GBxA1nGMxu8/44nNggkWMmwdiWgFvL/Tdm0n/AWti/FfMkALXIvyGg5QaPmTQDWAuPGTNYiwQPfi32Z3KMLXuAfpE8w1MsOQfoFzaetGKLxDO4tUi2nzG88aPCTo7vDPvGD2+AIcbPfnjjjY87cGvBAAlsYJJ4DSQqHgWjYBSMgpEBAE1dUKozeXM1AAAAAElFTkSuQmCC","orcid":"","institution":"Universidade Federal de Ouro Preto, Minas Gerais","correspondingAuthor":true,"prefix":"","firstName":"Wendel","middleName":"","lastName":"Coura-Vital","suffix":""}],"badges":[],"createdAt":"2024-09-16 13:42:41","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5097803/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5097803/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12982-025-01051-1","type":"published","date":"2025-11-04T15:56:55+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":90012124,"identity":"1688998e-8bce-4111-a9f2-9f5af4a51c86","added_by":"auto","created_at":"2025-08-27 10:59:34","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":200286,"visible":true,"origin":"","legend":"\u003cp\u003eDirected acyclic graph evaluating the association between vaccination status and the need for rehabilitation. The variable in the green rectangle is the exposure variable, while the variable in blue with the letter I is the outcome variable. Green arrows are causal paths between explanatory variables and outcome variables, black arrows are non-causal and unbiased paths, pink arrows are biased paths and the pink variables are antecedents of the outcome and exposure variables and the blue variables are antecedents of the outcome variable\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5097803/v1/9fd3f8f2a2df36c47cbbbf1c.png"},{"id":90012125,"identity":"1b79133f-a890-4260-b4fa-cd143891795f","added_by":"auto","created_at":"2025-08-27 10:59:34","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":157409,"visible":true,"origin":"","legend":"\u003cp\u003eDirected acyclic graph testing the association between sarcopenia and the need for rehabilitation. The variable in the green rectangle is the exposure variable, while the variable in blue with the letter I is the outcome variable. Green arrows are causal paths between explanatory variables and outcome variables, black arrows are non-causal and unbiased paths, pink arrows are biased paths and the pink variables are antecedents of the outcome and exposure variables and the blue variables are antecedents of the outcome variable\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-5097803/v1/f912660d061b54c9ee990708.png"},{"id":95563928,"identity":"9b7159c1-6583-4fd6-8e22-d6f05ddac72c","added_by":"auto","created_at":"2025-11-10 16:04:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":994735,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5097803/v1/9e856b5c-2d05-45e7-9d6e-2af6823ddbe3.pdf"},{"id":90012662,"identity":"97341c24-f3f7-4b69-beb9-284afb96053b","added_by":"auto","created_at":"2025-08-27 11:07:34","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":24401,"visible":true,"origin":"","legend":"","description":"","filename":"SuplemmentaryTables.docx","url":"https://assets-eu.researchsquare.com/files/rs-5097803/v1/07a30eb63dbfec8b7e1dfcb1.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Influence of vaccination status and sarcopenia on the need for physical rehabilitation in patients infected with SARS-CoV-2","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eOn May 5, 2023, the World Health Organization declared the end of the Public Health Emergency of International Concern for COVID-19 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. However, global concerns have emerged regarding post-COVID-19 conditions, also known as long COVID, post-COVID syndrome or post-acute COVID-19. This condition manifests itself through a wide variety of signs and symptoms, including fatigue, headache, attention disorders, hair loss and dyspnea, in addition to neurological and musculoskeletal changes, such as neuropathy, muscle weakness, severe hypoxemia, anxiety and/or depression, significant weight loss and cardiovascular complications [\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The World Health Organization defines long COVID as a syndrome that affects individuals with confirmed SARS-CoV-2 infection, with onset of symptoms up to three months after the acute phase of the disease and with no other attributable cause. It is estimated that between 10% and 20% of infected people develop persistent symptoms [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Individuals who had COVID-19 may experience a reduction in functional capacity, compromising quality of life and long-term survival. The pandemic has posed ongoing challenges to public health, requiring professionals to manage the physical and psychosocial sequelae of survivors [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Among the main complications, sarcopenia stands out, characterized by the loss of muscle mass and strength [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], often related to physical inactivity, prolonged immobility, and nutritional deficiencies [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], and further aggravated by neurological symptoms and neuromuscular damage [\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In this context, continuous monitoring of individuals who have overcome the acute phase of the disease is essential to reduce the risk of complications and mortality [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCOVID-19 vaccines play an essential role not only in preventing infection, but also in reducing severe complications and the need for rehabilitation [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], in addition to contributing to the prevention of post-COVID conditions, such as sarcopenia, which are essential for long-term recovery [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Recent evidence reinforces that vaccination reduces both the incidence and severity of persistent symptoms, favoring better clinical outcomes [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Despite this, many patients develop functional sequelae, requiring specific rehabilitation approaches. Rehabilitation can be defined as the process of restoring functionality and autonomy after illness or injury, may involve pharmacological, physical, and behavioral interventions [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In the post-COVID-19 context, rehabilitation has proven to be fundamental for recovery, promoting improved functional capacity, increased muscle strength, reduced fatigue, and psychosocial reestablishment [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Structured rehabilitation programs have shown efficacy in reducing musculoskeletal and neurological sequelae associated with long COVID [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], making their early integration essential to minimize functional impact and improve patients' quality of life in the long term.\u003c/p\u003e \u003cp\u003eThis study aimed to investigate the influence of vaccination status and post-COVID sarcopenia on the need for physical rehabilitation in patients infected with SARS-CoV-2. This information can aid in planning actions of the health systems by evaluating how post-COVID can impact the care process.\u003c/p\u003e"},{"header":"2. Material and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Study design\u003c/h2\u003e \u003cp\u003eA case-control study was conducted in the city of Ouro Preto, MG, Brazil, which has a robust public health system. The cases were patients from the city\u0026rsquo;s post-COVID clinic who required physical rehabilitation. This clinic, which served patients referred by community health centers, was the city's reference center for post-COVID complaints where the post-COVID rehabilitation resources were centralized. Controls were patients diagnosed with COVID-19 who did not require physical rehabilitation. These controls were selected from COVID-19 notification databases provided by the city's health surveillance service. The selection was aleatory and proportional to the prevalence of infection within the coverage area of ​​each of the city\u0026rsquo;s community health centers, ensuring sample representativeness. Controls were contacted to schedule an interview that was conducted at their local community health center. If a patient refused to participate, the next person on the list was invited.\u003c/p\u003e \u003cp\u003eThe cases and controls were interviewed and from the data obtained it was possible to investigate the effect of vaccination status and post-COVID sarcopenia on the need for functional rehabilitation in patients affected by COVID-19.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2. Power of the study\u003c/h2\u003e \u003cp\u003eWith a total of 54 cases and 230 controls, based on a 95% confidence interval,\u003c/p\u003e \u003cp\u003ewith an exposure among cases of 52 to 59% and controls of 37 to 79%, the\u003c/p\u003e \u003cp\u003epower of the study was 84% for the evaluation of the sarcopenia variable and 97% for vaccination status in influencing the need for rehabilitation.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3. Study Area\u003c/h2\u003e \u003cp\u003eThe city of Ouro Preto is located in the state of Minas Gerais, in southeastern Brazil. The estimated population in 2020 was 74,558 inhabitants and as of 30/05/2023 17,309 cases of COVID-19 had been reported and 142 deaths.\u003c/p\u003e \u003cp\u003eIn March 2020, when an international health emergency of global importance was established, the Ouro Preto Health Department opened a COVID-19 temporary hospital with 50 adult and pediatric beds, establishing a centralized point-of-entry for respiratory syndromes, to better control transmission and monitor positive cases, with a counter-referral protocol for the territory. In the waning phase of the pandemic, as of April 2021, the Ouro Preto Health Department established a specialized post-acute clinic for individuals with post-COVID complaints. Patients seen at the clinic were referred by the community health centers and, after a multi-professional evaluation, it was determined the need for physical rehabilitation (physiotherapy, occupational therapy and/or speech therapy), cognitive rehabilitation, and/or specialized medical care.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4. Data Collection\u003c/h2\u003e \u003cp\u003eData was collected using an electronic form using the KoBoToolbox tool. The WHO 2021 recommendation was chosen to classify the forms of presentation of COVID-19 as asymptomatic (no clinical symptoms), mild (no pneumonia and no indication for oxygen therapy), moderate (clinical signs of non-severe pneumonia and no indication for oxygen therapy), severe (clinical signs of severe pneumonia and indication for oxygen therapy) and critical (severe acute respiratory syndrome, with complications and orotracheal intubation) [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Next, a clinical and pharmacological history of the SARS-CoV-2 infection was recorded in the questionnaire (form of presentation of the disease, need for hospitalization, use of oxygen, drug treatment for the acute phase, among others), sociodemographic characteristics (gender, self-declared race/ethnicity, occupation, marital status and education), pre-existing comorbidities (diabetes, hypertension, cardiovascular diseases, obesity, mental disorders, chronic obstructive pulmonary disease [COPD], asthma, chronic kidney disease, among others), lifestyle and behavioral habits (use of alcohol, tobacco products, other illicit drugs and physical activity), vaccination status at the time of infection (number of doses administered until the infection), presence or absence of post-COVID-19 changes and need for rehabilitation due to sequelae of the infection.\u003c/p\u003e \u003cp\u003eFor the purposes of this study, the exposure variable 'sarcopenia' was assessed using the Clinical-Functional Vulnerability Index (IVCF-20), a validated instrument for screening functional frailty in the elderly, with a sensitivity greater than 90% for detecting frail individuals [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. The IVCF-20 covers dimensions such as mobility, activities of daily living, cognition, mood, and comorbidities, allowing a broad functional assessment, which is particularly relevant in the post-COVID-19 context. Although it is a self-reported instrument, its application is recommended in recent post-COVID-19 management guidelines due to its ability to detect functional vulnerabilities early [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. In addition, the assessment of sarcopenia was confirmed by the analysis of the case records.\u003c/p\u003e \u003cp\u003ePost-COVID-19 sarcopenia was considered present if the research participant answered \u0026ldquo;yes\u0026rdquo; to at least one of the following questions: Has any health professional diagnosed you with sarcopenia after the COVID-19 infection? After COVID-19, did you experience significant weight loss, unintentional weight loss, accompanied by loss of strength, a feeling of lack of energy, balance and physical performance to perform activities such as walking, climbing stairs or getting out of bed? The outcome variable, need for physical rehabilitation, was measured based on a positive response to rehabilitation with a physical therapist, occupational therapist and/or speech therapist.\u003c/p\u003e \u003cp\u003eTo mitigate possible recall bias, we triangulated medical records to validate the diagnoses and treatments reported by the participants, thus ensuring accuracy of the data. For cases in which the participant had difficulty recalling, we sought to interview caregivers or family members involved in the patient's care, reinforcing the reliability of the information.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5. Data analysis\u003c/h2\u003e \u003cp\u003eDescriptive analyses of absolute and relative frequencies were carried out and the chi-square technique was used to compare the characteristics of cases and controls. These analyses were performed using Stata software version 18.\u003c/p\u003e \u003cp\u003eTo select the set of covariates to be included in the multivariate model, two causality models based on directed acyclic graphs (DAGs) were developed to guide the analysis. The DAG was used to select a minimum and sufficient set of adjustment and confounding variables based on a backdoor criterion. The variables considered sufficient (S) are a set of variables chosen to block all non-causal pathways linking the exposure to the outcome. A minimum selection was made, since the inclusion of unnecessary variables not only increases the risk of collision bias, but also reduces the accuracy of the estimates. Backdoor criteria are non-causal, non-blocked pathways that link exposure to the outcome [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eA theoretical causality model was developed to guide the analysis of the total effect of COVID-19 vaccination (exposure variable) on the need for physical rehabilitation (outcome variable). With the DAG, it was possible to identify the causal effect based on the variables: age, gender, vaccination status at the time of the COVID-19 infection, hospitalization in the acute phase, use of oxygen, musculoskeletal symptoms in the post-COVID period, form of presentation in the acute phase, post-COVID sarcopenia, comorbidities prior to the acute phase and the assumptions contained in the diagram. The selection of variables included in the directed acyclic graph (DAG) was based on well-established theoretical knowledge from the scientific literature, considering previously identified causal relationships among the variables of interest [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Variables functioning as confounders, mediators, and colliders were incorporated based on epidemiological evidence and the clinical plausibility of the observed associations. In the causal structure diagram (CSD), causal connections were established between the variables, represented by arrows. Each variable was represented by a circle, and the colors used have different meanings. The DAG assessing the association between vaccination status and rehabilitation enabled the selection of the covariates that were included in the multivariate logistic regression model (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The minimum and sufficient adjustment suggested was: presence of previous comorbidity at the time of the infection and age.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eA second model was developed to guide the analysis of the total effect of post-COVID sarcopenia (exposure variable) on the need for physical rehabilitation (outcome variable) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). In this model, the minimum and sufficient adjustment suggested was: hospitalization in the acute phase, physical activity at the time of infection, age and gender. The online software Dagitty was used to carry out these DAG analyses and Stata version 18 for the multivariate analyses.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.1. Participants' characteristics\u003c/h2\u003e \u003cp\u003eAmong the 120 patients being monitored at the post-COVID outpatient clinic, 99 agreed to participate in the study and, of these, 54 needed physical rehabilitation and were included as cases. The control group consisted of 230 people who were randomly selected and did not require rehabilitation. It was observed that the case and control groups differed in terms of age, form of presentation of COVID-19, hospitalization in the acute phase, use of oxygen by mask/catheter and/or invasive mechanical ventilation, COVID-19 vaccination status, types of vaccines administrated, use of chronic medications at the time of infection, presence of prior comorbidity and post-COVID hospitalization (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003eS). With regards to behavioral variables, the practice of physical activity and the use of tobacco products at the time of the infection also differentiated the case and control groups (Table\u0026nbsp;2S).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.2. Association between vaccination status with the rehabilitation\u003c/h2\u003e \u003cp\u003eMultivariate analysis showed that people aged 60 or over were 4.48 (95% CI 1.68 \u0026minus;11.93) times more likely to undergo rehabilitation compared to younger people (reference category: \u0026gt;= 18 years and \u0026lt;\u0026thinsp;than 45 years old). The presence of comorbidities in the acute phase of COVID-19 increased the chances of rehabilitation by 4.18 (95% CI 1.85 \u0026minus; 9.42) times. Vaccination status at the time of SARS-CoV-2 infection, in individuals with 3 doses or more of COVID-19 vaccine, was a protective factor (OR 0.1; 95% CI 0.04 \u0026minus; 0.26), i.e. vaccination with 3 doses or more conferred 90% protection against the need for rehabilitation (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.3. Association between Post-COVID sarcopenia with the rehabilitation\u003c/h2\u003e \u003cp\u003eMultivariate analysis showed that people aged 60 and over were 4.26 times more likely to be rehabilitated than people aged between 18 and 45. In addition, hospitalization during the acute phase of COVID-19 increases the chances of needing rehabilitation by 16.7 times and post-COVID sarcopenia increases the chances of rehabilitation by 2.14 times (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCausal association between vaccination status and post-COVID sarcopenia with the need for physical rehabilitation after COVID-19, Ouro Preto, Brazil, 2023.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003eNeed for rehabilitation\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e1st Model\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e2nd Model\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR (CI95%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOR (CI95%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3 doses or more of vaccine vs. not vaccinated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.10 (0.04 \u0026minus;\u0026thinsp;0.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresence vs. absence of sarcopenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.14 (1.02\u0026ndash;4.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.045\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e* Model 1 - Association between vaccination status with the rehabilitation, adjusted by age and presence of previous comorbity; # Model 2 - Association between Post-COVID sarcopenia with the rehabilitation, adjusted by age and hospitalization in the acute phase. Models 1 and 2 were derived from the directed acyclic graphs (DAGs) depicted in Figs.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, respectively.\u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eIn this study, two causal relationships proposed by two different DAG models were assessed: one between the need for physical rehabilitation and vaccination status, and the other between rehabilitation and sarcopenia in the post-COVID period. In the first relationship, it was observed that receiving three or more vaccine doses reduces the likelihood of needing rehabilitation. In the second analysis, the presence of sarcopenia was associated with an increased need for rehabilitation.\u003c/p\u003e \u003cp\u003eThe first multivariate analysis showed that individuals aged 60 years or older had a 4.48-fold higher chance (95% CI: 1.68\u0026ndash;11.93) of being referred for rehabilitation, compared with those aged 18\u0026ndash;45 years. This finding was confirmed in the second multivariate analysis, in which individuals in this age group remained 4.26-fold more likely to require rehabilitation. In addition, hospitalization during the acute phase of COVID-19 increased the odds of rehabilitation by 16.7-fold, and the presence of post-COVID sarcopenia increased this chance by 2.14-fold. It is important to highlight that these associations were observed after adjusting for variables in the models, providing greater robustness to the results by minimizing potential confounding factors. These data corroborate the existing literature, which recognizes advanced age, disease severity, and loss of muscle mass and strength as critical factors for worsening functional capacity in COVID-19 survivors [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eVaccination against COVID-19 has shown to be highly effective in protecting against severe forms of the disease and its long-term complications. Studies demonstrate that vaccines significantly reduce the risk of hospitalization, intensive care unit admissions, and death [\u003cspan additionalcitationids=\"CR30\" citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. In addition, vaccinated individuals are less likely to develop COVID complications, such as cardiovascular and thromboembolic diseases [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Vaccination also reduces the risk of post-COVID syndrome depending on the number of doses administered [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Full vaccination, especially with two or more doses of mRNA vaccines such as Pfizer-BioNTech and Moderna, significantly reduces the incidence of long-term complications requiring rehabilitation [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. The efficacy of the vaccines, especially after booster doses, is notable in preventing hospitalizations and severe complications associated with SARS-CoV-2 infection, particularly in the Omicron BA.4 and BA.5 variants, which have a greater capacity for immune evasion [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Patients who contracted COVID-19 but were vaccinated tend to recover more quickly and efficiently, with a reduced need for extensive rehabilitation programs [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. Therefore, the continuation of vaccination and the promotion of booster doses are essential to ensure safety and effective recovery for the population.\u003c/p\u003e \u003cp\u003eIn the present study, the control group primarily received doses of combined vaccines that included the Pfizer-BioNTech (mRNA) vaccine in their regimen, which may have reduced the need for rehabilitation among these individuals. Previous research has shown that the Pfizer-BioNTech (mRNA) vaccine helps prevent the need for rehabilitation post-COVID-19 [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. However, it is important to emphasize that all vaccine manufacturers provide protection against severe cases, hospitalization, post-COVID symptoms, the need for rehabilitation, and death.\u003c/p\u003e \u003cp\u003eMost of the patients assessed at the post-COVID clinic had at least one comorbidity, with systemic arterial hypertension being the most frequent, followed by obesity or overweight and type 2 diabetes mellitus. Several studies have shown that overweight, obesity, hypertension and previous type 2 diabetes increase the risk of long COVID-19 [\u003cspan additionalcitationids=\"CR39 CR40\" citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. On the other hand, Thompson et al. (2022) found no association between the presence of hypertension or diabetes and prolonged COVID-19 symptoms [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. Due to the large number of patients with different comorbidities, this variable remained in the model as an adjustment variable.\u003c/p\u003e \u003cp\u003eThis study also shows that the presence of post-COVID sarcopenia is associated with the need for rehabilitation. As a result of the clinical manifestations of the disease, a significant proportion of patients required hospitalization and were subjected to invasive procedures to ensure the maintenance of physiological functions essential to life. During the hospitalization, these individuals often experience a decline in their physiological health and, in many cases, undergo a series of physical changes. It has been observed that hospitalized patients who experience muscle or joint pain during COVID-19 had a significant reduction in functional capacity [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e], even when undergoing physiotherapy during their hospitalization [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. Muscle atrophy due to prolonged immobilization is a common consequence in patients who face long periods of inactivity, such as those hospitalized due to COVID-19, since muscle deterioration is a complication that sets in quickly [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. Loss of muscle mass during hospitalization can delay recovery and increase the risk of long-term complications, such as persistent muscle weakness and functional disability [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. Prolonged bed restriction due to hospitalization is also associated with a drastic increase in systemic inflammation, typical of COVID-19, and are important catabolic stimuli that can intensify the loss of muscle mass [\u003cspan additionalcitationids=\"CR47\" citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e]. Post-COVID sarcopenia is exacerbated by chronic inflammation and decreased physical activity, creating a vicious cycle that further accelerates muscle loss and reduces functionality [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e, \u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]. The cause of sarcopenia is complex and multifactorial, including endocrine and metabolic abnormalities, and has a strong link with low-grade systemic inflammation in the elderly, reduced protein synthesis and regeneration, increased apoptosis and protein breakdown [\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eInterleukin-6 (IL-6), an inflammatory marker associated with obesity, metabolic syndrome, atherosclerotic diseases, inflammatory autoimmune diseases, and heart failure, has been shown to correlate with muscle strength and function. In chronic diseases among older adults, IL-6 appears to play a significant role in the reduction of functional capacity, suggesting that its dysregulation may be a precursor to the development of sarcopenia [\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e, \u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e]. These findings highlight the importance of implementing early rehabilitation programs after hospital discharge to improve functionality, enhance quality of life, and reduce hospital readmissions [\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e]. In addition to the methodology used in the present study, other diagnostic methods for sarcopenia and frailty include grip strength [\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e, \u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e], isometric contraction of the vastus lateralis muscle [\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e], bioelectrical impedance [\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e], and magnetic resonance imaging, considered the gold standard for assessing muscle quality and quantity [\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe COVID-19 pandemic required the rapid adaptation of health services, especially in the rehabilitation sectors. A study in Italy described the restructuring of a hospital rehabilitation unit to meet new demand, highlighting the need for structural and operational adjustments [\u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e]. In addition, another study suggested the importance of reorganizing care flows and implementing safety protocols to ensure continuity of care and minimize functional losses in post-COVID-19 patients [\u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e]. Furthermore, Iannaccone et al. (2020) demonstrated that rehabilitation units for COVID-19 patients had costs approximately twice as high as conventional units, highlighting the need for specific investments to ensure the sustainability of rehabilitation services in the face of new demands [\u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBoth models were adjusted by age, since age is associated with the explanatory and outcome variable. With advancing age there is a progressive decline in the body's functional capacities, leading to greater vulnerability to health problems and frailty [\u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e63\u003c/span\u003e]. Older patients have more severe symptoms of the infection, leading to a longer post-COVID period. This may be related to pre-existing comorbidities and the elderly patient's own physiological condition [\u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e], reinforcing the need for greater adherence of this population to vaccination against COVID-19, to avoid a greater risk of functional weakness and sequelae [\u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e65\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis study has some limitations, as the retrospective nature of the questions could lead to a recall bias. However, we believe that this bias was minimal, as the information was obtained within one or two years of the infection and, due to the great repercussions of the pandemic, people were generally aware of their symptoms. In addition, the assessment of sarcopenia was based on self-report, which may also introduce bias, but was complemented by the analysis of the case records, confirming the formal indication for rehabilitation by clinical evaluation. Despite the variation in the definition of sarcopenia in different studies, the use of IVCF-20 ensured greater standardization and generalization of the results [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eOur results show the importance of encouraging vaccination against COVID-19, as it helps to reduce the need for physical rehabilitation after COVID-19. In addition, our results highlight the importance of healthcare professionals paying closer attention to patients with post-COVID sarcopenia as it increases the need for rehabilitation.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments:\u0026nbsp;\u003c/strong\u003eWe would like to thank the staff of the Ouro Preto Health Department post-COVID clinic for their support in this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u0026nbsp;\u003c/strong\u003eThis study was approved by the Ethics Committee of the Federal University of Ouro Preto (CAAE: 54298221.9.0000.5150) in accordance with Resolution nº 466, of december 12, 2012. The researchers adhered to the Declaration of Helsinki in carrying out the research. All the patients who agreed to participate in the study signed an informed consent form.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eNo external funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e The authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability:\u0026nbsp;\u003c/strong\u003eThe data for this study are not publicly available to protect the privacy of the participants. However, they can be made available by the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCode availability:\u0026nbsp;\u003c/strong\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors’ contributions:\u0026nbsp;\u003c/strong\u003eT.O., B.B.S, M.C., A.B.S., and W.C.V., conceived the idea for the study. T.O., C.C.R.G.B., A.M.G., S.C.M, were involved in data collection. T.O., R.V.D., B.B.S., L.A.A.M.J., M.C., A.B.R., W.C.V., were involved in data Cleaning and analysis, writing the first draft, review and editing. T.O., W.C.V., B.B.S., L.A.A.M.J., M.C., were involved in statistical analysis and review. T.O., W.C.V. were involved in the overall study coordination. All authors provided technical inputs to the manuscript and approved the final version of the paper.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWorld Health Organization (WHO). Coronavirus disease (COVID-19) pandemic. Accessed in: https://wwwwhoint/europe/emergencies/situations/covid-19 2022.\u003c/li\u003e\n\u003cli\u003eNogueira I, Fontoura F, Carvalho C. Recomenda\u0026ccedil;\u0026otilde;es para avalia\u0026ccedil;\u0026atilde;o e reabilita\u0026ccedil;\u0026atilde;o p\u0026oacute;s-COVID-19. 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Multiple early factors anticipate post-acute COVID-19 sequelae. Cell. 2022;185:881-95 e20.https://doi.org/10.1016/j.cell.2022.01.014.\u003c/li\u003e\n\u003cli\u003eDu HW, Fang SF, Wu SR, Chen XL, Chen JN, Zhang YX, et al. Six-month follow-up of functional status in discharged patients with coronavirus disease 2019. BMC Infect Dis. 2021;21:1271.https://doi.org/10.1186/s12879-021-06970-3.\u003c/li\u003e\n\u003cli\u003eBelli S, Balbi B, Prince I, Cattaneo D, Masocco F, Zaccaria S, et al. Low physical functioning and impaired performance of activities of daily life in COVID-19 patients who survived hospitalisation. Eur Respir J. 2020;56.https://doi.org/10.1183/13993003.02096-2020.\u003c/li\u003e\n\u003cli\u003eRussell AP. Molecular regulation of skeletal muscle mass. Clin Exp Pharmacol Physiol. 2010;37:378-84.https://doi.org/10.1111/j.1440-1681.2009.05265.x.\u003c/li\u003e\n\u003cli\u003eSagarra-Romero L, Vinas-Barros A. COVID-19: Short and Long-Term Effects of Hospitalization on Muscular Weakness in the Elderly. Int J Environ Res Public Health. 2020;17.https://doi.org/10.3390/ijerph17238715.\u003c/li\u003e\n\u003cli\u003eCao X. COVID-19: immunopathology and its implications for therapy. Nat Rev Immunol. 2020;20:269-70.https://doi.org/10.1038/s41577-020-0308-3.\u003c/li\u003e\n\u003cli\u003eMeftahi GH, Jangravi Z, Sahraei H, Bahari Z. The possible pathophysiology mechanism of cytokine storm in elderly adults with COVID-19 infection: the contribution of \u0026quot;inflame-aging\u0026quot;. Inflamm Res. 2020;69:825-39.https://doi.org/10.1007/s00011-020-01372-8.\u003c/li\u003e\n\u003cli\u003ePuthucheary ZA, Rawal J, McPhail M, Connolly B, Ratnayake G, Chan P, et al. Acute skeletal muscle wasting in critical illness. JAMA. 2013;310:1591-600.https://doi.org/10.1001/jama.2013.278481.\u003c/li\u003e\n\u003cli\u003ede Moura PH, de Souza H, Brandao DC, Barros C, Correia M, Reinaux C, et al. Mapping peripheral and abdominal sarcopenia acquired in the acute phase of COVID-19 during 7 days of mechanical ventilation. Sci Rep. 2023;13:3514.https://doi.org/10.1038/s41598-023-29807-2.\u003c/li\u003e\n\u003cli\u003eAguiar GB, Dourado KF, Andrade MIS, Domingos Junior IR, Barros-Neto JA, Vasconcelos SML, et al. Frequency and factors associated with sarcopenia prediction in adult and elderly patients hospitalized for COVID-19. Exp Gerontol. 2022;168:111945.https://doi.org/10.1016/j.exger.2022.111945.\u003c/li\u003e\n\u003cli\u003eCurcio F, Ferro G, Basile C, Liguori I, Parrella P, Pirozzi F, et al. Biomarkers in sarcopenia: A multifactorial approach. Exp Gerontol. 2016;85:1-8.https://doi.org/10.1016/j.exger.2016.09.007.\u003c/li\u003e\n\u003cli\u003eHanberg JS, Rao VS, Ahmad T, Chunara Z, Mahoney D, Jackson K, et al. Inflammation and cardio-renal interactions in heart failure: a potential role for interleukin-6. Eur J Heart Fail. 2018;20:933-4.https://doi.org/10.1002/ejhf.963.\u003c/li\u003e\n\u003cli\u003eMaggio M, Guralnik JM, Longo DL, Ferrucci L. Interleukin-6 in aging and chronic disease: a magnificent pathway. J Gerontol A Biol Sci Med Sci. 2006;61:575-84.https://doi.org/10.1093/gerona/61.6.575.\u003c/li\u003e\n\u003cli\u003eAquim EE, Bernardo WM, Buzzini RF, Azeredo NSG, Cunha LSD, Damasceno MCP, et al. Brazilian Guidelines for Early Mobilization in Intensive Care Unit. Rev Bras Ter Intensiva. 2019;31:434-43.https://doi.org/10.5935/0103-507X.20190084.\u003c/li\u003e\n\u003cli\u003eCruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyere O, Cederholm T, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019;48:16-31.https://doi.org/10.1093/ageing/afy169.\u003c/li\u003e\n\u003cli\u003eBohannon RW. Grip Strength: An Indispensable Biomarker For Older Adults. Clin Interv Aging. 2019;14:1681-91.https://doi.org/10.2147/CIA.S194543.\u003c/li\u003e\n\u003cli\u003eB\u0026auml;ckman E, Johansson V, H\u0026auml;ger B, Sj\u0026ouml;blom P, Henriksson K. Isometric muscle strength and muscular endurance in normal persons aged between 17 and 70 years. Journal of Rehabilitation Medicine. 1995;27:109-17.\u003c/li\u003e\n\u003cli\u003eClark BC, Rutkove S, Lupton EC, Padilla CJ, Arnold WD. Potential Utility of Electrical Impedance Myography in Evaluating Age-Related Skeletal Muscle Function Deficits. Front Physiol. 2021;12:666964.https://doi.org/10.3389/fphys.2021.666964.\u003c/li\u003e\n\u003cli\u003eHuber FA, Del Grande F, Rizzo S, Guglielmi G, Guggenberger R. MRI in the assessment of adipose tissues and muscle composition: how to use it. Quant Imaging Med Surg. 2020;10:1636-49.https://doi.org/10.21037/qims.2020.02.06.\u003c/li\u003e\n\u003cli\u003eBush TL. The epidemiology of cardiovascular disease in postmenopausal women. Ann N Y Acad Sci. 1990;592:263-71; discussion 334-45.https://doi.org/10.1111/j.1749-6632.1990.tb30338.x.\u003c/li\u003e\n\u003cli\u003eMiranda V. Sarcopenia e fatores de risco: como minimizar os preju\u0026iacute;zos durante a quarentena? Accessed in: https://pebmedcombr/sarcopenia-e-fatores-de-risco-como-minimizar-os-prejuizos-durante-a-quarentena/#:~:text=Em%20pacientes%20com%20baixo%20IMC,gr%C3%A3os%20refinados%20refrigerantes%20e%20cerveja. 2020.\u003c/li\u003e\n\u003cli\u003eBarbosa IR, Galv\u0026atilde;o MHR, Souza TAd, Gomes SM, Medeiros AdA, Lima KCd. Incid\u0026ecirc;ncia e mortalidade por COVID-19 na popula\u0026ccedil;\u0026atilde;o idosa brasileira e sua rela\u0026ccedil;\u0026atilde;o com indicadores contextuais: um estudo ecol\u0026oacute;gico. Revista Brasileira de Geriatria e Gerontologia. 2020;23:e200171.https://doi.org/10.1590/1981-22562020023.200171 \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"discover-public-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Discover Public Health](https://link.springer.com/journal/12982)","snPcode":"12982","submissionUrl":"https://submission.springernature.com/new-submission/12982/3","title":"Discover Public Health","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"SARS-CoV-2, COVID-19, Vaccine, Sarcopenia, Comorbidity","lastPublishedDoi":"10.21203/rs.3.rs-5097803/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5097803/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e The effects of COVID-19 are not restricted to the acute phase of the disease, and complications are common after the infection has resolved.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjectives:\u003c/strong\u003e The aim of this study was to investigate the influence of vaccination status and post-COVID sarcopenia on the need for physical rehabilitation in patients infected with SARS-CoV-2.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethodology:\u003c/strong\u003e A case-control study was carried out in the city of Ouro Preto, Brazil, which has a centralized public health system. The cases were patients of the city’s post-COVID clinic who underwent rehabilitation, and the controls were COVID-19 patients randomly selected from the population who did not need rehabilitation. Directed acyclic graph (DAG) and logistic regression were used to analyze the data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e The presence of post-COVID sarcopenia increased the chances of needing rehabilitation (OR 2.14), along with age over 60 (OR 4.26) and hospitalization during the acute phase of the disease (OR 16.7). Vaccination with three or more doses reduces the need for rehabilitation (OR 0.1), while the presence of comorbidities increases the need for it (OR 4.18).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e It is important for health care systems to be prepared for the rehabilitation needs of post-COVID patients. Our results reinforce the importance of vaccination in reducing the sequelae of COVID-19 and the need for greater attention in the post-Covid phase to older people and those with prior comorbidities, as well as to patients who have been hospitalized and who have post-COVID musculoskeletal symptoms.\u003c/p\u003e","manuscriptTitle":"Influence of vaccination status and sarcopenia on the need for physical rehabilitation in patients infected with SARS-CoV-2","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-27 10:59:29","doi":"10.21203/rs.3.rs-5097803/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-04-22T14:02:26+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-02-26T09:06:51+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"1647259849499587713493507839595639156","date":"2025-02-26T06:46:29+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-12-09T06:35:04+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-10-23T20:45:32+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-10-23T05:01:13+00:00","index":"","fulltext":""},{"type":"submitted","content":"Discover Public Health","date":"2024-10-20T20:53:56+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"discover-public-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Discover Public Health](https://link.springer.com/journal/12982)","snPcode":"12982","submissionUrl":"https://submission.springernature.com/new-submission/12982/3","title":"Discover Public Health","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"09c3edc3-ec25-4e33-9551-7129d69ef22e","owner":[],"postedDate":"August 27th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-11-10T15:59:18+00:00","versionOfRecord":{"articleIdentity":"rs-5097803","link":"https://doi.org/10.1186/s12982-025-01051-1","journal":{"identity":"discover-public-health","isVorOnly":false,"title":"Discover Public Health"},"publishedOn":"2025-11-04 15:56:55","publishedOnDateReadable":"November 4th, 2025"},"versionCreatedAt":"2025-08-27 10:59:29","video":"","vorDoi":"10.1186/s12982-025-01051-1","vorDoiUrl":"https://doi.org/10.1186/s12982-025-01051-1","workflowStages":[]},"version":"v1","identity":"rs-5097803","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5097803","identity":"rs-5097803","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}