Clinical aspects, persistent symptoms, physical functionality, and quality of life 24 months after COVID-19

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Objective To evaluate the clinical, functional aspects, and quality of life post-COVID-19 recovery. Methods This study comprised 43 patients from São Luís, Maranhão, Brazil. Were collected manovacuometry, Fatigue Assessment Scale (FAS), Post-COVID-19 Functional Scale (PCFS), EuroQol-5D Quality of Life Questionnaire (EQ-5D-5L), and anthropometry. Results Predominated females, age of 55±12.3 years; 93.0% reported tiredness and fatigue. Women exhibited a higher percentage of normal maximum inspiratory pressure (MIP) (60.5%) and maximum expiratory pressure (MEP), moderate (36.8%). Moderate functional limitation was reported by 51.2%, and 48% experienced fatigue. The EQ-5D-5L averaged 60, with 46.5% at high cardiovascular risk based on waist-hip ratio, 16.3% identified as sarcopenic. Unsupervised machine learning correlated higher MIP and MEP with lower fatigue and sarcopenia. The main components in the multivariate analysis were: waist, hip, calf circumference and MIP. Conclusion Anthropometry negatively impact functionality and quality of life. Symptoms as fatigue, joint pain, and dyspnea, persisted approximately 24 months post-COVID-19. COVID-19 Long COVID Functionality Quality of life. Figures Figure 1 Figure 2 Figure 3 Figure 4 1 Introduction The viral disease caused by the novel coronavirus, SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), has led to significant morbidity and mortality worldwide since the initial cases were identified in Wuhan, China, in December 2019. In Brazil, COVID-19 (Coronavirus Disease 2019) has accounted for over 700,000 deaths. However, it’s noteworthy that the recovery rate surpasses 95% for most cases [ 1 , 2 ]. Despite the fact that the majority of these patients fully recover without any lasting effects, a notable proportion reports persistent health issues. The exact count of individuals experiencing lingering symptoms after the acute episode of COVID-19 remains unknown; however, it appears to be more prevalent among those with pre-existing comorbidities, advanced age, and obesity [ 3 ]. Among the main persistent complications found in these individuals after recovery from the disease include fatigue, dyspnea, reduced lung capacity, respiratory and peripheral muscle weakness, pain, among others that can impact functionality and decrease the quality of life of survivors [ 4 ]. This phase of the disease is classified as post-COVID-19 syndrome, that is, a set of clinical symptoms persistent beyond four weeks developed by individuals with a history of SARS-CoV-2 infection, as long as there is no other intercurrent process that could explain it. Them [ 5 ]. Studies indicate that a considerable portion of individuals recovering from COVID-19 exhibit low physical fitness and impaired performance in daily activities. This often leads to increased dependence on others for personal care adversely affecting their quality of life [ 6 ]. While these consequences are more pronounced in patients who experienced severe forms of the disease, Jacobson et al. [ 7 ] describe similar symptoms in both hospitalized and non-hospitalized patients 3 to 4 months post-diagnosis. Functional impairment was notably higher in hospitalized patients but also prevalent in those who did not require hospitalization during the acute phase of the disease. Previous studies with other coronaviruses, such as severe acute respiratory syndrome (SARS) in 2003 and Middle East Respiratory Syndrome (MERS) in mid-2012, highlighted persistent cardiovascular and muscular impairment with an impact on quality of life for up to 2 years after the symptom onset [ 8 ]. It is important to highlight that vaccination has proven effective in preventing SARS-CoV-2 infection, reducing the rates of death and hospitalization following COVID-19 illness. However, its efficacy in preventing the sequelae resulting from the disease, namely a significant reduction in persistent symptoms after the acute phase, has not been pronounced [ 9 ]. In this context, this study aims to assess the clinical, functional aspects, and quality of life in individuals’ post-recovery from COVID-19. 2 Methods 2.1 Study design and population This is a descriptive observational study applied to 43 individuals (35 women and 8 men) with post-COVID-19 syndrome in the Brazilian public network, diagnosed by the medical team with post-COVID-19 syndrome, clinically stable, immunized, hospitalized or not during the acute phase of the disease, with voluntary and consented participation, without distinction of race or ethnicity and who were in the process of rehabilitation. Patients were not included if they had a diagnosed cognitive impairment that prevented them from understanding the instructions presented and carrying them out safely, those under 18 years of age, presence of pre-COVID-19 symptoms, use of a tracheostomy, musculoskeletal and neurological conditions that prevented the performance of all stages of the study. 2.2 Instruments and procedures Patients were submitted to an anamnesis using an assessment questionnaire, containing clinical history of the disease, data such as sex, age, presence of comorbidities, persistent symptoms, immunization, among others. Respiratory muscle strength was assessed using manovacuometry. The analog manometer − 150/+150cmH20 from the Brazilian manufacturer VENTBRAS (São Paulo, SP, Brasil) was used, in which the patient took three measurements for each respiratory phase in a sitting position, with only the one with the highest value being considered [ 10 ]. We then assessed functionality using the Post Covid-19 Functional Scale (PCFS). This scale already has a validated measurement adaptation for the Brazilian population and its version presented content validity, reliability, internal consistency and convergent validity suitable for the functional assessment of individuals affected by COVID-19 [ 11 ]. Quality of life was measured using the EuroQol-5 Dimensions Questionnaire (EQ-5D-5L) score. Values closer to 0 correspond to the worst health status and closer to 100 indicate better health status [ 12 ]. It is worth noting that this questionnaire already has translation and cross-cultural validation into Brazilian Portuguese [ 13 ] and currently, this questionnaire is recommended in international guidelines for the initial assessment of patients undergoing post-COVID-19 rehabilitation [ 14 ]. The Fatigue Assessment Scale (FAS) was used to assess fatigue. This instrument consists of 10 items, answered on a five-point scale, ranging from 1 (Never) to 5 (Always) [ 15 ]. After its application, the values found in each item are added and the result is compared with the following reference values brought by the scale: below 22 there are no signs of fatigue, above 22 there are signs of fatigue, while above 35 there is the presence of intense fatigue [ 16 ]. In Brazil, this scale was adapted by Oliveira et al., [ 17 ] which provides evidence of their factorial validity and internal consistency. Cardiovascular risk was verified based on the waist-hip ratio (WHR), obtained by dividing the waist (cm) and hip (cm) perimeters [ 18 ]. To measure calf circumference, values below 33 cm in women and 34 cm in men were considered, characterizing reduced muscle mass [ 19 ]. 2.3 Statistical analysis Data was tabulated in Microsoft Office Excel (version 2016, Redmond, WA, USA) and analyzed in SPSS (version 21, Chicago, IL, USA). Data presentation was performed using the mean and standard deviation of parametric variables, median and range (minimum and maximum) in non-parametric and categorical variables, in absolute (n) and relative frequency (%). Normality was verified using the Shapiro-Wilk test. To investigate the relationships and patterns present in the data, we applied Principal Component Analysis (PCA), with subsequent creation of biplots to evaluate the distribution of observations and variables in the principal component space. These analyzes were stratified based on different groups of post-COVID symptoms and classifications related to muscle function, providing a comprehensive understanding of the associations present in the data. After indicating the main variables by PCA, we calculated the correlation matrix between the variables and visualized the correlation structure through a correlation graph according to the levels of fatigue and functionality. 3 Results The sample consisted of 43 participants, 35 females (81.4%) and 8 males (18.6%), with a mean age of 55 ± 12.3 years. The sociodemographic and clinical characteristics are described in Table 1 . Table 1 Sociodemographic characterization. Variables n % Gender Female 35 81.4 Male 8 18.6 Age (years) a 55.0 ± 12.3 Education Incomplete Elementary 6 14.0 Complete Elementary 2 4.7 Incomplete High School 1 2.3 Complete High School 18 41.9 Incomplete Graduation 3 7.0 Complete Graduation 13 30.2 Height (m) b 1.6 (1.4–1.8) Weight (kg) 71.0 ± 10.8 Year of COVID-19 diagnosis 2020 21 48.8 2021 17 39.5 2022 5 11.6 Vaccine (dose) 1 1 2.3 2 7 16.3 3 18 41.9 4 17 39.5 Form of treatment Required hospitalization (no ICU) 8 19.0 Did not require hospitalization 34 81.0 Comorbidities Hypertension 18 41.9 Diabetes 8 18.6 Neurological diseases 3 7.0 a Mean ± standard deviation; b Median (Minimum-Maximum). Using the Fatigue Assessment Scale (FAS), it was found that 48.8% of participants were fatigued and 18.6% had severe fatigue, however 32.6% did not manifest this symptom (Fig. 1 A). According to Fig. 1 B, which presents the Post Covid-19 Functional Scale (PCFS), after COVID-19, 51.2% of participants had moderate functional limitation (grade 3), 27.9% reported mild functional limitation (grade 2) and around 14.0% very mild functional limitation (grade 1). Therefore, the majority of participants presented some degree of functional impairment, which could have negative impacts on activities of daily living. The correlation matrix demonstrates significant associations between different characteristics, providing insights into the interdependence of the evaluated parameters (Fig. 2 A and Fig. 2 B). Noteworthy, for example, is the strong positive correlation between the waist and hip circumference (r = 0.81), weight and calf circumference (r = 0.577) and other significant correlations can be seen in Fig. 3 B. On the other hand, the negative correlation observed between the age and calf variables (r = -0.409) suggests an inverse association (Fig. 2 B). These results provide an initial understanding of the interactions present in the data, fundamental for the interpretation and deeper understanding of the phenomenon under study. Correlation analysis revealed patterns in the relationships between the studied variables. PCA revealed a unique visual representation of the structure underlying our multidimensional data (Fig. 2 C to Fig. 2 H). The generated biplots illustrate the distribution of observations and variables in the principal component space. Notably, nearby observations on the graph indicate similarities in terms of patterns, while the orientation of the variables indicates the relative contribution of each to the total variation. We observed that most variables tend to cluster in a specific region of the biplot, indicating a common trend in this subset of data. This approach provides a compact and informative view of the data structure, making it easier to interpret and identify underlying patterns. Furthermore, the main variables that contribute to the observed phenomenon are: waist circumference, calf circumference, hip circumference, body weight and MIP (maximum inspiratory pressure). The Figs. 4 and 5 describe the correlations of the variables indicated by the PCA stratified according to the fatigue and functionality classifications, respectively. 4 Discussion This study highlights the presence of fatigue, functional limitations and low quality of life scores in patients with more than two years post diagnosis to COVID-19. These manifestations were more present in individuals with anthropometric changes. Regarding our sample, the average age of 55 years, women and the presence of previous comorbidities such as Diabetes Mellitus and Arterial Hypertension stand out. These variables were also the most present in a Brazilian cohort carried out by Visconti et al. [ 20 ] with 88 adult patients monitored 2, 6 and 12 months after the onset of COVID-19 symptoms. Furthermore, they reported that more severe illness during hospitalization was associated with worse long-term outcomes. However, in the present study, the majority of participants did not require hospitalization and were more than 2 years post-recovery from COVID-19. Furthermore, it was seen that the persistence of symptoms after recovery from COVID-19 was more present in individuals with anthropometric changes. This is in line with Nakayama et al., [ 21 ] who report in their studies that obesity was associated with a 2.45 times greater chance (95% CI: 0.44; 1.34; p > 0.001) for developing persistent symptoms. Ota et al. [ 22 ] in their research with patients 6 months after recovery from the disease, showed that 50% of their sample reported that they often feel fatigue and that it is easier to get tired after activity today, when compared to the period before COVID-19. However, our findings have been around for longer than the aforementioned study, which demonstrates that there are still many patients in need of multidisciplinary assistance. Moreira et al. [ 23 ] report that individuals who underwent home treatment for COVID-19 had a MIP of 108.0 ± 63.79 cmH2O, higher than the predicted value of 10137 ± 14.41 cmH2O. Furthermore, these participants obtained a MEP (Maximum Expiratory Pressure) also higher than predicted, having an average of 134.0 ± 86.19 cmH2O, while the expected was 104.45 ± 18.15 cmH2O. However, Ricotta et al., [ 24 ] mention a decrease in MIP and MEP values in these individuals when compared to the values predicted by Neder et al. [ 25 ]. In our study, it can be seen that there was a predominance of greater impairment of MEP in both sexes. Furthermore, it is worth highlighting that in previous infections with other coronaviruses, such as SARS and MERS, lung and respiratory muscle strength were found to be compromised for months and even years after hospital discharge, which agrees with our results in patients affected by SARS-CoV-2, in which persistent symptoms were seen for more than two years from the onset of the disease [ 8 ]. Schmidt et al. [ 26 ] used the PCFS to evaluate the functionality of individuals after COVID recovery and reported the presence of some functional limitation at 30 days, 3 months and 6 months in the proportions of 89.7%, 57.4% and 38 .2%, respectively. Furthermore, functional independence for personal care, mobility and self-care activities were evidenced in these individuals, which corroborates with our research. A cohort carried out by Kingery et al. [ 27 ] with 530 patients in a post-COVID-19 situation who had recovered from the disease for more than a year, showed that more than 35% of the participants had moderate limitations in carrying out activities of daily living, even in those who did not require hospitalization in the acute phase of the disease. We observed moderate functional limitation in 51.2% of individuals with an average age similar to the study above, however more than two years after recovery from the disease, in most cases. In addition, Nielsen et al. [ 28 ] reported that the daily lives of COVID-19 survivors were highly influenced by long-lasting symptoms. The majority of individuals had mild to moderate functional limitations, generating negative impacts on activities of daily living and quality of life. In this research, moderate functional limitations were observed, in most patients, which could have negative impacts on usual activities and quality of life. A systematic review demonstrated that COVID-19 survivors had reduced levels of physical function, activities of daily living, and health-related quality of life. Furthermore, incomplete recovery of physical function and performance in activities of daily living was observed 1 to 6 months after infection [ 29 ]. Regarding quality of life, our results in relation to pain/discomfort, mobility and usual activities are in line with the findings of Qorolli et al., [ 30 ] who described these domains as being among the most frequently reported by post-COVID-19 patients between 1 and 6 months after discharge. Furthermore, the least affected domain reported in our survey was self-care, which corresponds to existing literature. Similarly, Tarazona et al. [ 31 ] reported that 47.9% of individuals had problems in at least one of the dimensions of the EQ-5D-5L, even in patients who did not require hospital treatment during the infectious process, which corroborates our findings. However, the post-COVID-19 evaluation period was much shorter (between 1 and 3 months), whereas in our research, the majority of volunteers were more than two years after the onset of infection. Furthermore, research carried out by Walker et al. [ 32 ] in which they evaluated the impact of persistent COVID-19 symptoms on health-related quality of life (HRQoL), found that 51% of individuals reported losing ≥ 1 day of work in the last 4 weeks and 20% reported being unable to work. Another study carried out in China by Huang et al., [ 33 ] showed that 88% of individuals returned to work 12 months after recovering from the disease; however, 24% were unable to return to the same level of work before COVID-19. Regarding vaccination, Al-Aly et al. [ 34 ] report that individuals immunized against COVID-19 have a 15% less chance of suffering the persistent effects of the disease. However, the severity of the symptoms of sequelae did not change between those vaccinated and those not vaccinated, which is in line with our findings, given that our sample was all immunized. It is important to highlight that the conclusions that vaccination against SARS-CoV-2 does not protect against some persistent symptoms of COVID-19 should not obscure its importance in protecting against these outcomes, since the best way to prevent it is, in First, avoid SARS-CoV-2 infection [ 9 ]. This study has limitations as it was carried out in a single center and had a small sample size, which, in part, may be related to the remission period of the COVID-19 pandemic, where the number of Long COVID cases potentially decreased. Furthermore, it is worth highlighting that our sample was mostly made up of women, and this can be explained because women seek more health care than men, in addition to some studies have shown that women suffer from Long COVID more than men. The number of COVID-19 infections after the first diagnosis was not monitored, which may influence, to some degree, the prevalence of symptoms. However, our findings are important, as they expose the need to develop prevention strategies and interventions for the population studied. More research needs to be carried out with a larger number of patients 5 Conclusion It was evidenced that survivors of COVID-19, regardless of the clinical spectrum of the disease, showed a marked reduction in functionality and quality of life, especially in those with anthropometric changes. Furthermore, musculoskeletal disorders, presence of fatigue, joint pain and dyspnea were the main persistent symptoms. Therefore, understanding these aspects is necessary for an adequate approach to the main patient care needs beyond the acute phase, providing important information for individualized care within a multidisciplinary team, especially considering that the majority of those assessed had already recovered from COVID-19 for at least 24 months. Abbreviations SARS-CoV-2: Severe Acute Respiratory Syndrome Coronavirus 2; COVID-19: Coronavirus Disease 2019; SARS: Severe Acute Respiratory Syndrome; MERS: Middle East Respiratory Syndrome; CNS: National Health Council; PCFS: Post Covid-19 Functional Scale; EQ-5D-5L: EuroQol-5 Dimensions Questionnaire; FAS: Fatigue Assessment Scale; WHR: Waist-Hip Ratio; PCA: Principal Component Analysis; PCFS: Functional Status Scale; MIP: Maximum Inspiratory Pressure; MEP: Maximum Expiratory Pressure; EQ-5D-5L: EuroQol-5D Quality of Life Questionnaire. Declarations Funding The research was carried out with resources from the National Council for Scientific and Technological Development (CNPq) under grant process number 403457/2021-1. Conflicts of interest The authors declare that they have no conflict of interest. Data availability Data are available from the authors upon reasonable request. Ethics approval All procedures performed in studies involving human participants were under the ethical standards of the institutional, national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Ethics Committee of the Dom Bosco Higher Education Unit, with CAAE:59074522.9.0000.8707, opinion no. 5.571.687, on 9 th August 2022. Consent Informed consent was obtained in write from all participants included in the study. Authors' contributions MMS, FSdeSS, GBBL, TCSJ, DLB, PMSDS: Conception, work design, acquisition, analysis and interpretation of data; DLB, AVDF, HdeLC: data interpretation and substantial review; CENE, AVDF, HdeLC; conception, study design, data analysis and interpretation, review and final approval. References OPAS. Organização Pan-Americana da Saúde. Histórico da pandemia de COVID-19 - OPAS/OMS. https://www.paho.org/pt/covid19/historico-da-pandemia-covid-19. Accessed 02 Sept 2024. SUS. Sistema Único de Saúde. Coronavírus Brasil. https://covid.saude.gov.br/?snax_login_popup%3Fsnax_login_popup=forgot_password&mode=list. Accessed 02 Sept 2024. 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Nat Med. 2022;28(7):1461–7. https://doi.org/10.1038/s41591-022-01840-0 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-5242403","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":370118646,"identity":"4ac6f17c-569e-4af0-a821-870581871ce0","order_by":0,"name":"Marcos Moreno Salgado","email":"","orcid":"","institution":"Federal University of Maranhão","correspondingAuthor":false,"prefix":"","firstName":"Marcos","middleName":"Moreno","lastName":"Salgado","suffix":""},{"id":370118647,"identity":"3586944b-3c25-4e5b-94eb-0d4b577369b1","order_by":1,"name":"Flaviana Santos de Sousa Silva","email":"","orcid":"","institution":"Federal University of Maranhão","correspondingAuthor":false,"prefix":"","firstName":"Flaviana","middleName":"Santos de Sousa","lastName":"Silva","suffix":""},{"id":370118648,"identity":"111af042-01b4-44b6-8fa3-5645640ba0bd","order_by":2,"name":"Giérisson Brenno Borges Lima","email":"","orcid":"","institution":"Federal University of Maranhão","correspondingAuthor":false,"prefix":"","firstName":"Giérisson","middleName":"Brenno Borges","lastName":"Lima","suffix":""},{"id":370118649,"identity":"549226f7-c1ad-4e21-aa58-00f460cd677c","order_by":3,"name":"Tailane Cristina Sousa Jansen","email":"","orcid":"","institution":"Federal University of Maranhão","correspondingAuthor":false,"prefix":"","firstName":"Tailane","middleName":"Cristina Sousa","lastName":"Jansen","suffix":""},{"id":370118650,"identity":"22f07194-ecc3-49f4-a98b-21774b3d52f3","order_by":4,"name":"Daniel Lago Borges","email":"","orcid":"","institution":"Presidente Dutra University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Daniel","middleName":"Lago","lastName":"Borges","suffix":""},{"id":370118651,"identity":"b634352c-c881-4c38-a178-b99b487b48b4","order_by":5,"name":"Pollyanna Maria Santos Diniz Salgado","email":"","orcid":"","institution":"Hospital do Servidor Estadual","correspondingAuthor":false,"prefix":"","firstName":"Pollyanna","middleName":"Maria Santos Diniz","lastName":"Salgado","suffix":""},{"id":370118652,"identity":"748b2e6f-7796-4ab7-ba42-4e791a94f95d","order_by":6,"name":"Almir Vieira Dibai Filho","email":"","orcid":"","institution":"Federal University of Maranhão","correspondingAuthor":false,"prefix":"","firstName":"Almir","middleName":"Vieira Dibai","lastName":"Filho","suffix":""},{"id":370118653,"identity":"f2c8a5fb-52cd-4e7e-a9ff-94b73c002ece","order_by":7,"name":"Hugo de Luca Correa","email":"","orcid":"","institution":"Catholic University of Brasilia","correspondingAuthor":false,"prefix":"","firstName":"Hugo","middleName":"de Luca","lastName":"Correa","suffix":""},{"id":370118654,"identity":"3899a10e-4532-4aa4-bdac-d3e6331c4e23","order_by":8,"name":"Carlos Eduardo Neves Amorim","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA30lEQVRIie3PMQrCMBSA4ReEuihdU4T2BIKh4KKHqRR08QAOIpVCewMRFO/g0rkS6BR0FboYvICj3XyKBRdjRof8Q0iGj/cCYDL9a8HrbEQAM7DxZukSgkSAE2kRqAlJNIi94sVNTsGzN4elrHacdtPcus4UhJbjcD3KgK2Po9hvZ5z2RdBkQjWmnPqAJABBkg7J+KKfB9Zzu695NfGQONUWp5wuatKrSQ8JbUdIzj+mMPwLEsr2gsR+q5ggkSlTEbcMOamyoeeKxkHe5wNcLCykiryjnw+iAUwmk8mk7AH120y0tY08OAAAAABJRU5ErkJggg==","orcid":"","institution":"Federal University of Maranhão","correspondingAuthor":true,"prefix":"","firstName":"Carlos","middleName":"Eduardo Neves","lastName":"Amorim","suffix":""}],"badges":[],"createdAt":"2024-10-11 00:08:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5242403/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5242403/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":67470543,"identity":"fb072625-e965-4ff5-bee0-ac6c0199dae8","added_by":"auto","created_at":"2024-10-25 11:28:50","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":42277,"visible":true,"origin":"","legend":"\u003cp\u003eFatigue Assessment Scale (FAS) and Functional Status Scale (PCFS)\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5242403/v1/d2c2b572660310c23242a4c4.png"},{"id":67470547,"identity":"3c0ab65a-ebd3-488d-b1e2-ccec5f7cb2b6","added_by":"auto","created_at":"2024-10-25 11:28:50","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":385015,"visible":true,"origin":"","legend":"\u003cp\u003eExploratory data analysis\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-5242403/v1/240aea744a963a498d20fc68.png"},{"id":67470545,"identity":"bbbb13ea-e38c-4442-be61-e75e85a6509f","added_by":"auto","created_at":"2024-10-25 11:28:50","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":767270,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation of the most important variables indicated by the PCA according to the fatigue classification\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-5242403/v1/36d5cce10f9e7ac6075255fd.png"},{"id":67470546,"identity":"cb4f07c7-0311-47cb-a68a-e6b5e250e247","added_by":"auto","created_at":"2024-10-25 11:28:50","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":710773,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation of the most important variables indicated by the PCA according to the functionality classification\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-5242403/v1/0a0e1feda17951a1d1c23aa8.png"},{"id":69570355,"identity":"93926f13-7887-4bf6-91e7-ce92b8ea2df9","added_by":"auto","created_at":"2024-11-21 18:39:33","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1957431,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5242403/v1/6a5e7540-ae55-4e82-9fb1-00c7b89d27de.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical aspects, persistent symptoms, physical functionality, and quality of life 24 months after COVID-19","fulltext":[{"header":"1 Introduction","content":"\u003cp\u003eThe viral disease caused by the novel coronavirus, SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), has led to significant morbidity and mortality worldwide since the initial cases were identified in Wuhan, China, in December 2019. In Brazil, COVID-19 (Coronavirus Disease 2019) has accounted for over 700,000 deaths. However, it\u0026rsquo;s noteworthy that the recovery rate surpasses 95% for most cases [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDespite the fact that the majority of these patients fully recover without any lasting effects, a notable proportion reports persistent health issues. The exact count of individuals experiencing lingering symptoms after the acute episode of COVID-19 remains unknown; however, it appears to be more prevalent among those with pre-existing comorbidities, advanced age, and obesity [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAmong the main persistent complications found in these individuals after recovery from the disease include fatigue, dyspnea, reduced lung capacity, respiratory and peripheral muscle weakness, pain, among others that can impact functionality and decrease the quality of life of survivors [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis phase of the disease is classified as post-COVID-19 syndrome, that is, a set of clinical symptoms persistent beyond four weeks developed by individuals with a history of SARS-CoV-2 infection, as long as there is no other intercurrent process that could explain it. Them [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eStudies indicate that a considerable portion of individuals recovering from COVID-19 exhibit low physical fitness and impaired performance in daily activities. This often leads to increased dependence on others for personal care adversely affecting their quality of life [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWhile these consequences are more pronounced in patients who experienced severe forms of the disease, Jacobson et al. [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] describe similar symptoms in both hospitalized and non-hospitalized patients 3 to 4 months post-diagnosis. Functional impairment was notably higher in hospitalized patients but also prevalent in those who did not require hospitalization during the acute phase of the disease. Previous studies with other coronaviruses, such as severe acute respiratory syndrome (SARS) in 2003 and Middle East Respiratory Syndrome (MERS) in mid-2012, highlighted persistent cardiovascular and muscular impairment with an impact on quality of life for up to 2 years after the symptom onset [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIt is important to highlight that vaccination has proven effective in preventing SARS-CoV-2 infection, reducing the rates of death and hospitalization following COVID-19 illness. However, its efficacy in preventing the sequelae resulting from the disease, namely a significant reduction in persistent symptoms after the acute phase, has not been pronounced [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In this context, this study aims to assess the clinical, functional aspects, and quality of life in individuals\u0026rsquo; post-recovery from COVID-19.\u003c/p\u003e"},{"header":"2 Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Study design and population\u003c/h2\u003e \u003cp\u003eThis is a descriptive observational study applied to 43 individuals (35 women and 8 men) with post-COVID-19 syndrome in the Brazilian public network, diagnosed by the medical team with post-COVID-19 syndrome, clinically stable, immunized, hospitalized or not during the acute phase of the disease, with voluntary and consented participation, without distinction of race or ethnicity and who were in the process of rehabilitation.\u003c/p\u003e \u003cp\u003ePatients were not included if they had a diagnosed cognitive impairment that prevented them from understanding the instructions presented and carrying them out safely, those under 18 years of age, presence of pre-COVID-19 symptoms, use of a tracheostomy, musculoskeletal and neurological conditions that prevented the performance of all stages of the study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Instruments and procedures\u003c/h2\u003e \u003cp\u003ePatients were submitted to an anamnesis using an assessment questionnaire, containing clinical history of the disease, data such as sex, age, presence of comorbidities, persistent symptoms, immunization, among others.\u003c/p\u003e \u003cp\u003eRespiratory muscle strength was assessed using manovacuometry. The analog manometer \u0026minus;\u0026thinsp;150/+150cmH20 from the Brazilian manufacturer VENTBRAS (S\u0026atilde;o Paulo, SP, Brasil) was used, in which the patient took three measurements for each respiratory phase in a sitting position, with only the one with the highest value being considered [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWe then assessed functionality using the Post Covid-19 Functional Scale (PCFS). This scale already has a validated measurement adaptation for the Brazilian population and its version presented content validity, reliability, internal consistency and convergent validity suitable for the functional assessment of individuals affected by COVID-19 [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eQuality of life was measured using the EuroQol-5 Dimensions Questionnaire (EQ-5D-5L) score. Values closer to 0 correspond to the worst health status and closer to 100 indicate better health status [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. It is worth noting that this questionnaire already has translation and cross-cultural validation into Brazilian Portuguese [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] and currently, this questionnaire is recommended in international guidelines for the initial assessment of patients undergoing post-COVID-19 rehabilitation [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe Fatigue Assessment Scale (FAS) was used to assess fatigue. This instrument consists of 10 items, answered on a five-point scale, ranging from 1 (Never) to 5 (Always) [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. After its application, the values found in each item are added and the result is compared with the following reference values brought by the scale: below 22 there are no signs of fatigue, above 22 there are signs of fatigue, while above 35 there is the presence of intense fatigue [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In Brazil, this scale was adapted by Oliveira et al., [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] which provides evidence of their factorial validity and internal consistency.\u003c/p\u003e \u003cp\u003eCardiovascular risk was verified based on the waist-hip ratio (WHR), obtained by dividing the waist (cm) and hip (cm) perimeters [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. To measure calf circumference, values below 33 cm in women and 34 cm in men were considered, characterizing reduced muscle mass [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Statistical analysis\u003c/h2\u003e \u003cp\u003eData was tabulated in Microsoft Office Excel (version 2016, Redmond, WA, USA) and analyzed in SPSS (version 21, Chicago, IL, USA). Data presentation was performed using the mean and standard deviation of parametric variables, median and range (minimum and maximum) in non-parametric and categorical variables, in absolute (n) and relative frequency (%). Normality was verified using the Shapiro-Wilk test.\u003c/p\u003e \u003cp\u003eTo investigate the relationships and patterns present in the data, we applied Principal Component Analysis (PCA), with subsequent creation of biplots to evaluate the distribution of observations and variables in the principal component space. These analyzes were stratified based on different groups of post-COVID symptoms and classifications related to muscle function, providing a comprehensive understanding of the associations present in the data. After indicating the main variables by PCA, we calculated the correlation matrix between the variables and visualized the correlation structure through a correlation graph according to the levels of fatigue and functionality.\u003c/p\u003e \u003c/div\u003e"},{"header":"3 Results","content":"\u003cp\u003eThe sample consisted of 43 participants, 35 females (81.4%) and 8 males (18.6%), with a mean age of 55\u0026thinsp;\u0026plusmn;\u0026thinsp;12.3 years. The sociodemographic and clinical characteristics are described in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eSociodemographic characterization.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"3\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003en\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e%\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGender\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e81.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge (years) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e55.0\u0026thinsp;\u0026plusmn;\u0026thinsp;12.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEducation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIncomplete Elementary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eComplete Elementary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIncomplete High School\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eComplete High School\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIncomplete Graduation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eComplete Graduation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHeight (m) \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.6 (1.4\u0026ndash;1.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWeight (kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e71.0\u0026thinsp;\u0026plusmn;\u0026thinsp;10.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYear of COVID-19 diagnosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e48.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVaccine (dose)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eForm of treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRequired hospitalization (no ICU)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDid not require hospitalization\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e81.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eComorbidities\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHypertension\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiabetes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNeurological diseases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\"\u003e\u003csup\u003ea\u003c/sup\u003e Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation; \u003csup\u003eb\u003c/sup\u003e Median (Minimum-Maximum).\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eUsing the Fatigue Assessment Scale (FAS), it was found that 48.8% of participants were fatigued and 18.6% had severe fatigue, however 32.6% did not manifest this symptom (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eA). According to Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eB, which presents the Post Covid-19 Functional Scale (PCFS), after COVID-19, 51.2% of participants had moderate functional limitation (grade 3), 27.9% reported mild functional limitation (grade 2) and around 14.0% very mild functional limitation (grade 1). Therefore, the majority of participants presented some degree of functional impairment, which could have negative impacts on activities of daily living.\u003c/p\u003e\n\u003cp\u003eThe correlation matrix demonstrates significant associations between different characteristics, providing insights into the interdependence of the evaluated parameters (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eA and Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eB). Noteworthy, for example, is the strong positive correlation between the waist and hip circumference (r\u0026thinsp;=\u0026thinsp;0.81), weight and calf circumference (r\u0026thinsp;=\u0026thinsp;0.577) and other significant correlations can be seen in Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eB. On the other hand, the negative correlation observed between the age and calf variables (r = -0.409) suggests an inverse association (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eB). These results provide an initial understanding of the interactions present in the data, fundamental for the interpretation and deeper understanding of the phenomenon under study. Correlation analysis revealed patterns in the relationships between the studied variables.\u003c/p\u003e\n\u003cp\u003ePCA revealed a unique visual representation of the structure underlying our multidimensional data (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eC to Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eH). The generated biplots illustrate the distribution of observations and variables in the principal component space. Notably, nearby observations on the graph indicate similarities in terms of patterns, while the orientation of the variables indicates the relative contribution of each to the total variation. We observed that most variables tend to cluster in a specific region of the biplot, indicating a common trend in this subset of data. This approach provides a compact and informative view of the data structure, making it easier to interpret and identify underlying patterns. Furthermore, the main variables that contribute to the observed phenomenon are: waist circumference, calf circumference, hip circumference, body weight and MIP (maximum inspiratory pressure).\u003c/p\u003e\n\u003cp\u003eThe Figs. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e and 5 describe the correlations of the variables indicated by the PCA stratified according to the fatigue and functionality classifications, respectively.\u003c/p\u003e"},{"header":"4 Discussion","content":"\u003cp\u003eThis study highlights the presence of fatigue, functional limitations and low quality of life scores in patients with more than two years post diagnosis to COVID-19. These manifestations were more present in individuals with anthropometric changes. Regarding our sample, the average age of 55 years, women and the presence of previous comorbidities such as Diabetes Mellitus and Arterial Hypertension stand out. These variables were also the most present in a Brazilian cohort carried out by Visconti et al. [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] with 88 adult patients monitored 2, 6 and 12 months after the onset of COVID-19 symptoms. Furthermore, they reported that more severe illness during hospitalization was associated with worse long-term outcomes. However, in the present study, the majority of participants did not require hospitalization and were more than 2 years post-recovery from COVID-19.\u003c/p\u003e \u003cp\u003eFurthermore, it was seen that the persistence of symptoms after recovery from COVID-19 was more present in individuals with anthropometric changes. This is in line with Nakayama et al., [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] who report in their studies that obesity was associated with a 2.45 times greater chance (95% CI: 0.44; 1.34; p\u0026thinsp;\u0026gt;\u0026thinsp;0.001) for developing persistent symptoms.\u003c/p\u003e \u003cp\u003eOta et al. [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] in their research with patients 6 months after recovery from the disease, showed that 50% of their sample reported that they often feel fatigue and that it is easier to get tired after activity today, when compared to the period before COVID-19. However, our findings have been around for longer than the aforementioned study, which demonstrates that there are still many patients in need of multidisciplinary assistance.\u003c/p\u003e \u003cp\u003eMoreira et al. [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] report that individuals who underwent home treatment for COVID-19 had a MIP of 108.0\u0026thinsp;\u0026plusmn;\u0026thinsp;63.79 cmH2O, higher than the predicted value of 10137\u0026thinsp;\u0026plusmn;\u0026thinsp;14.41 cmH2O. Furthermore, these participants obtained a MEP (Maximum Expiratory Pressure) also higher than predicted, having an average of 134.0\u0026thinsp;\u0026plusmn;\u0026thinsp;86.19 cmH2O, while the expected was 104.45\u0026thinsp;\u0026plusmn;\u0026thinsp;18.15 cmH2O. However, Ricotta et al., [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] mention a decrease in MIP and MEP values in these individuals when compared to the values predicted by Neder et al. [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. In our study, it can be seen that there was a predominance of greater impairment of MEP in both sexes.\u003c/p\u003e \u003cp\u003eFurthermore, it is worth highlighting that in previous infections with other coronaviruses, such as SARS and MERS, lung and respiratory muscle strength were found to be compromised for months and even years after hospital discharge, which agrees with our results in patients affected by SARS-CoV-2, in which persistent symptoms were seen for more than two years from the onset of the disease [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSchmidt et al. [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] used the PCFS to evaluate the functionality of individuals after COVID recovery and reported the presence of some functional limitation at 30 days, 3 months and 6 months in the proportions of 89.7%, 57.4% and 38 .2%, respectively. Furthermore, functional independence for personal care, mobility and self-care activities were evidenced in these individuals, which corroborates with our research.\u003c/p\u003e \u003cp\u003eA cohort carried out by Kingery et al. [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] with 530 patients in a post-COVID-19 situation who had recovered from the disease for more than a year, showed that more than 35% of the participants had moderate limitations in carrying out activities of daily living, even in those who did not require hospitalization in the acute phase of the disease. We observed moderate functional limitation in 51.2% of individuals with an average age similar to the study above, however more than two years after recovery from the disease, in most cases.\u003c/p\u003e \u003cp\u003eIn addition, Nielsen et al. [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] reported that the daily lives of COVID-19 survivors were highly influenced by long-lasting symptoms. The majority of individuals had mild to moderate functional limitations, generating negative impacts on activities of daily living and quality of life. In this research, moderate functional limitations were observed, in most patients, which could have negative impacts on usual activities and quality of life.\u003c/p\u003e \u003cp\u003eA systematic review demonstrated that COVID-19 survivors had reduced levels of physical function, activities of daily living, and health-related quality of life. Furthermore, incomplete recovery of physical function and performance in activities of daily living was observed 1 to 6 months after infection [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Regarding quality of life, our results in relation to pain/discomfort, mobility and usual activities are in line with the findings of Qorolli et al., [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] who described these domains as being among the most frequently reported by post-COVID-19 patients between 1 and 6 months after discharge. Furthermore, the least affected domain reported in our survey was self-care, which corresponds to existing literature. Similarly, Tarazona et al. [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] reported that 47.9% of individuals had problems in at least one of the dimensions of the EQ-5D-5L, even in patients who did not require hospital treatment during the infectious process, which corroborates our findings. However, the post-COVID-19 evaluation period was much shorter (between 1 and 3 months), whereas in our research, the majority of volunteers were more than two years after the onset of infection.\u003c/p\u003e \u003cp\u003eFurthermore, research carried out by Walker et al. [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] in which they evaluated the impact of persistent COVID-19 symptoms on health-related quality of life (HRQoL), found that 51% of individuals reported losing\u0026thinsp;\u0026ge;\u0026thinsp;1 day of work in the last 4 weeks and 20% reported being unable to work. Another study carried out in China by Huang et al., [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] showed that 88% of individuals returned to work 12 months after recovering from the disease; however, 24% were unable to return to the same level of work before COVID-19.\u003c/p\u003e \u003cp\u003eRegarding vaccination, Al-Aly et al. [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e] report that individuals immunized against COVID-19 have a 15% less chance of suffering the persistent effects of the disease. However, the severity of the symptoms of sequelae did not change between those vaccinated and those not vaccinated, which is in line with our findings, given that our sample was all immunized. It is important to highlight that the conclusions that vaccination against SARS-CoV-2 does not protect against some persistent symptoms of COVID-19 should not obscure its importance in protecting against these outcomes, since the best way to prevent it is, in First, avoid SARS-CoV-2 infection [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis study has limitations as it was carried out in a single center and had a small sample size, which, in part, may be related to the remission period of the COVID-19 pandemic, where the number of Long COVID cases potentially decreased. Furthermore, it is worth highlighting that our sample was mostly made up of women, and this can be explained because women seek more health care than men, in addition to some studies have shown that women suffer from Long COVID more than men. The number of COVID-19 infections after the first diagnosis was not monitored, which may influence, to some degree, the prevalence of symptoms. However, our findings are important, as they expose the need to develop prevention strategies and interventions for the population studied. More research needs to be carried out with a larger number of patients\u003c/p\u003e"},{"header":"5 Conclusion","content":"\u003cp\u003eIt was evidenced that survivors of COVID-19, regardless of the clinical spectrum of the disease, showed a marked reduction in functionality and quality of life, especially in those with anthropometric changes. Furthermore, musculoskeletal disorders, presence of fatigue, joint pain and dyspnea were the main persistent symptoms. Therefore, understanding these aspects is necessary for an adequate approach to the main patient care needs beyond the acute phase, providing important information for individualized care within a multidisciplinary team, especially considering that the majority of those assessed had already recovered from COVID-19 for at least 24 months.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eSARS-CoV-2: Severe Acute Respiratory Syndrome Coronavirus 2; COVID-19: Coronavirus Disease 2019; SARS: Severe Acute Respiratory Syndrome; MERS: Middle East Respiratory Syndrome; CNS: National Health Council; PCFS: Post Covid-19 Functional Scale; EQ-5D-5L: EuroQol-5 Dimensions Questionnaire; FAS: Fatigue Assessment Scale; WHR: Waist-Hip Ratio; PCA: Principal Component Analysis; PCFS: Functional Status Scale; MIP: Maximum Inspiratory Pressure; MEP: Maximum Expiratory Pressure; EQ-5D-5L: EuroQol-5D Quality of Life Questionnaire.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe research was carried out with resources from the National Council for Scientific and Technological Development (CNPq) under grant process number 403457/2021-1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData are available from the authors upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll procedures performed in studies involving human participants were under the ethical standards of the institutional, national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Ethics Committee of the Dom Bosco Higher Education Unit, with CAAE:59074522.9.0000.8707, opinion no.\u0026nbsp;5.571.687, on 9\u003csup\u003eth\u003c/sup\u003e August 2022. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained in write from all participants included in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMMS, FSdeSS, GBBL, TCSJ, DLB, PMSDS: Conception, work design, acquisition, analysis and interpretation of data; DLB, AVDF, HdeLC: data interpretation and substantial review; CENE, AVDF, HdeLC; conception, study design, data analysis and interpretation, review and final approval.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eOPAS. Organiza\u0026ccedil;\u0026atilde;o Pan-Americana da Sa\u0026uacute;de. 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Res Soc Dev. 2023;12(2):e27312240235\u0026ndash;e27312240235. https://doi.org/10.33448/rsd-v12i2.40235.\u003c/li\u003e\n\u003cli\u003eMoreira NGR, Licurci M das GB, Nogueira DV, Fagundes AA, Costa MS. Comparison of respiratory mechanics and muscle performance between individuals cured from SARS-CoV-2 with home and hospital treatment. Res Soc Dev. 2022;11(5):e58011527816\u0026ndash;e58011527816. https://doi.org/10.33448/rsd-v11i5.27816.\u003c/li\u003e\n\u003cli\u003eRicotta ACG, Nunes GB, Almeida AF de, Gonzaga FMG, Licurci MGB, Nogueira DV. Post-Covid effects on respiratory mechanics, pulmonary function, response to physical exercise and quality of life. Res Soc Dev. 2022;11(15):e324111537053\u0026ndash;e324111537053. https://doi.org/10.33448/rsd-v11i15.37053\u003c/li\u003e\n\u003cli\u003eNeder JA, Andreoni S, Lerario MC, Nery LE. Reference values for lung function tests: II. Maximal respiratory pressures and voluntary ventilation. Braz J Med Biol Res. 1999;32:719\u0026ndash;27. https://doi.org/10.1590/S0100-879X1999000600007.\u003c/li\u003e\n\u003cli\u003eSchmidt D, Margarites AG, Alvarenga LPKB, Paesi PM, Friedman G, Sbruzzi G. Post\u0026ndash;COVID-19 Intensive Care Unit-Acquired Weakness Compromises Long-Term Functional Status. Phys Ther. 2023;103(12):pzad117. https://doi.org/10.1177/11795476221106759.\u003c/li\u003e\n\u003cli\u003eKingery JR, Safford MM, Martin P, Lau JD, Rajan M, Wehmeyer GT, Li HA, Alshak MN, Jabri A, Kofman A, Babu CS, Benitez EK, Palacardo F, Das IG, Kaylor K, Woo KM, Roberts NL, Rahiel S, Gali V, Han L, Lee J, Roszkowska N, Kim YE, Bakshi S, Hogan C, McNairy M, Pinheiro LC, Goyal P. Health status, persistent symptoms, and effort intolerance one year after acute COVID-19 infection. 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BMJ Open. 2023;13(6):e069217. https://doi.org/10.1136/bmjopen-2022-069217\u003c/li\u003e\n\u003cli\u003eHuang C, Huang L, Wang Y, Li X, Ren L, Gu X, Kang L, Guo L, Liu M, Zhou X, Luo J, Huang Z, Tu S, Zhao Y, Chen L, Xu D, Li Y, Li C, Peng L, Li Y, Xie W, Cui D, Shang L, Fan G, Xu J, Wang G, Wang Y, Zhong J, Wang C, Wang J, Zhang D, Cao B. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. The Lancet. 2023;401(10393):e21\u0026ndash;33. https://doi.org/10.1016/S0140-6736(23)00810-3\u003c/li\u003e\n\u003cli\u003eAl-Aly Z, Bowe B, Xie Y. Long COVID after breakthrough SARS-CoV-2 infection. Nat Med. 2022;28(7):1461\u0026ndash;7. https://doi.org/10.1038/s41591-022-01840-0\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"COVID-19, Long COVID, Functionality, Quality of life.","lastPublishedDoi":"10.21203/rs.3.rs-5242403/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5242403/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction\u003c/strong\u003e Patients affected by SARS-CoV-2 may experience sequelae and symptoms such as fatigue, abnormalities in lung function and decreased quality of life scores.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e To evaluate the clinical, functional aspects, and quality of life post-COVID-19 recovery.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods \u003c/strong\u003eThis study comprised 43 patients from São Luís, Maranhão, Brazil. Were collected manovacuometry, Fatigue Assessment Scale (FAS), Post-COVID-19 Functional Scale (PCFS), EuroQol-5D Quality of Life Questionnaire (EQ-5D-5L), and anthropometry.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e Predominated females, age of 55±12.3 years; 93.0% reported tiredness and fatigue. Women exhibited a higher percentage of normal maximum inspiratory pressure (MIP) (60.5%) and maximum expiratory pressure (MEP), moderate (36.8%). Moderate functional limitation was reported by 51.2%, and 48% experienced fatigue. The EQ-5D-5L averaged 60, with 46.5% at high cardiovascular risk based on waist-hip ratio, 16.3% identified as sarcopenic. Unsupervised machine learning correlated higher MIP and MEP with lower fatigue and sarcopenia. The main components in the multivariate analysis were: waist, hip, calf circumference and MIP.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e Anthropometry negatively impact functionality and quality of life. Symptoms as fatigue, joint pain, and dyspnea, persisted approximately 24 months post-COVID-19.\u003c/p\u003e","manuscriptTitle":"Clinical aspects, persistent symptoms, physical functionality, and quality of life 24 months after COVID-19","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-25 11:28:45","doi":"10.21203/rs.3.rs-5242403/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d90e95d4-1c8b-4abd-a0db-9dd28a301458","owner":[],"postedDate":"October 25th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-11-21T18:39:08+00:00","versionOfRecord":[],"versionCreatedAt":"2024-10-25 11:28:45","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5242403","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5242403","identity":"rs-5242403","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}