key: cord-0696551-8dmyve1b authors: Bakılan, Fulya; Gökmen, İsmail Güneş; Ortanca, Burcu; Uçan, Anıl; Eker Güvenç, Şebnem; Şahin Mutlu, Fezan; Gökmen, Hatice Merve; Ekim, Ayşe title: Musculoskeletal symptoms and related factors in postacute COVID‐19 patients date: 2021-08-18 journal: Int J Clin Pract DOI: 10.1111/ijcp.14734 sha: 29ae661562ecd43307b6c9fd61ae0028603a29f4 doc_id: 696551 cord_uid: 8dmyve1b AIM: There is a lack of an overview of the factors associated with postacute COVID‐19 musculoskeletal symptoms. The aims of this study were as follows: 1‐ to evaluate the most frequent admission symptoms and the frequency of musculoskeletal symptoms in postacute COVID‐19 patients; and 2‐ to determine the related factors with the postacute COVID‐19 musculoskeletal symptoms. METHODS: A total of 280 postacute COVID‐19 patients (183 females, 97 males) were enrolled and divided into two groups: 1‐ patients whose musculoskeletal symptoms initiated with or were aggravated by COVID‐19 (n = 240); and 2‐ patients whose musculoskeletal symptoms did not change with COVID‐19 (n = 40). The variables were demographic and treatment data, symptoms on admission, postacute COVID‐19 symptoms, laboratory results (complete blood count, erythrocyte sedimentation rate, C‐reactive protein, ferritin and d‐dimer), chest computed tomography findings and symptoms during acute COVID‐19. RESULTS: Most of the patients have fatigue (71.8%), spine pain (70.7%) and myalgia (60.7%). The most common pain region was the back (30.4%). The frequency of dyspnoea was 30%, cough 18.5% and chest pain 10.7%. Having any chronic disease (P = .031), the duration of hospital stay (P = .016), frequency of back pain during acute COVID‐19 (P = .018), tomography findings and d‐dimer (P = .035) levels were significantly higher, and lymphocyte (P = .024) levels were significantly lower in the patients whose symptoms began with or were aggravated by COVID‐19. CONCLUSION: Back pain was the most frequent symptom on admission. The most common postacute COVID‐19 musculoskeletal symptoms were fatigue, spine pain and myalgia. Lower lymphocyte and higher d‐dimer levels, the presence of COVID‐19 findings in tomography and back pain during acute COVID‐19 infection, higher duration of hospital stay and having chronic diseases were related to post‐COVID‐19 musculoskeletal symptoms. COVID-19 leads to long-term effects in multiple biological systems, including the musculoskeletal system. These long-term effects are said to result from "post acute COVID-19". In recent guidelines, postacute COVID-19 patients, who have persistent symptoms, have been divided into two groups: (i) 4-12 weeks after the onset of acute COVID-19: ongoing symptomatic COVID-19 patients, and This retrospective cross-sectional study was carried out with the records of 280 postacute COVID-19 patients who were admitted to the PMR outpatient clinic between December 2020 and May 2021. The inclusion criteria were being 18 years or older, and having COVID-19 treatment (home quarantine/hospital/intensive care unit) according to a positive polymerase chain reaction (PCR) test in a nasopharyngeal + oropharyngeal swab or chest CT. Patients who have both negative PCR test and chest CT, patients who did not have recorded musculoskeletal symptoms (admission symptoms and musculoskeletal symptoms such as fatigue and spine/joint/muscle pain/ numbness) in patients files and also acute COVID-19 patients whose symptoms have started less than 1 month previously were excluded. The typical findings of the chest CT were as follows: bilateral, multifocal and peripheral ground glass opacities with/without con- The symptoms of all patients on admission to outpatient clinics were recorded, including local or radicular back/lower back/neck pain, fatigue, myalgia, knee/hip/ankle/foot pain, shoulder/elbow/ wrist/hand pain, chest pain and numbness. Furthermore, all patients have musculoskeletal symptom records in detail, including fatigue, spine pain, myalgia, arthralgia and numbness. Neck/back/lower back pain, both radiating or not, was accepted as spine pain. Widespread myalgia was accepted as pain in more than one site (shoulder girdle, arm, thigh and lower leg). Joint pain in any joint was accepted as arthralgia and also the region of joint pain was recorded. The presence of numbness was also recorded. Moreover, it was also recorded whether these musculoskeletal symptoms have begun with or been infection were recorded from the patient files, including cough, fever, dyspnoea, chest pain, loss of smell and taste, sore throat, headache as well as no symptoms and any musculoskeletal symptoms such as muscle, lower back, back and/or joint pain. Moreover, concomitant What's known? • The majority of postacute COVID-19 patients have at least one symptom. • Fatigue was the most common symptom in postacute COVID-19 patients. • This study described the factors associated with postacute COVID-19 musculoskeletal symptoms. • The most frequent admission symptom to physical medicine and rehabilitation outpatient clinic was back pain. • The presence of lower lymphocyte, higher d-dimer levels, presence of COVID-19 in chest computed tomography and back pain during acute COVID-19 infection, higher duration of hospital stay and having chronic diseases, all seem to contribute to postacute COVID-19 musculoskeletal symptoms. respiratory tract symptoms in the post-COVID-19 period, such as cough, dyspnoea and chest pain, were also recorded. Ethics approval was received from the local ethics committee (date: 30.03.21, decision number: 04). The distribution of each continuous variable was tested for normality using the Shapiro-Wilk test. Non-normally distributed variables were compared using the Mann-Whitney U-test and expressed as median values (25%-75%). Normally distributed variables were performed using the t-test and they were expressed as mean ± standard deviation. Categorical variables are expressed as frequencies and percentages and they were compared using the Chi-square test. A P-value of <.05 was considered significant. All analyses were performed using the SPSS version 22.0 software (SPSS Inc, Chicago, IL, USA). All patients have at least one musculoskeletal symptom. The most common admission symptom was back pain (28.6%). All admission symptoms are given in Table 1 . Table 2 . The patients were divided into two groups: (i) patients whose musculoskeletal symptoms began with or were aggravated by COVID-19 (n = 240), and (ii) patients whose musculoskeletal symptoms did not change with COVID-19 (n = 40). Comparison of demographic and treatment parameters of these two groups showed that age, body mass index, smoking, employment status, education level, duration of symptoms, using vitamin supplements (vitamin D and/or vitamin C and/or zinc), anticoagulant treatment, the duration after the onset of COVID-19 symptoms and places of treatment were all similar. However, the frequency of any chronic disease (P = .031) and the duration of the treatment in hospital (P = .016) were higher in those patients whose symptoms began with or were aggravated by COVID-19. The duration of home quarantine was 10 days in all patients who were treated at home. When patients were evaluated in terms of drug treatment, the musculoskeletal symptoms began with or were aggravated by COVID-19 in 3 (30%) of 10 patients who refused to use any drug and in 216 (90%) of 241 patients who used favipiravir, as well as in 8 (80%) of 10 patients who used hydroxychloroquine ( Table 3) . showed that only back pain (P = .018) was significantly higher in patients whose musculoskeletal symptoms began with or were aggravated by COVID-19. On the other hand, the asymptomatic rate was significantly higher (P = .046) in patients whose symptoms did not change with COVID-19. A total of 206 of the patients have chest CTs, and the presence of COVID-19 findings in tomography were significantly higher in patients whose musculoskeletal symptoms began with or were aggravated by COVID-19 (P = .048). A total of 182 of all the patients have laboratory findings during the infection. When the patients were evaluated in terms of laboratory parameters, only the lymphocyte count (P = .024) was significantly lower, whose musculoskeletal symptoms began with or were aggravated by COVID-19 (Table 4 ). All the respiratory tract symptoms of the patients were found to have begun with their COVID-19 infection. The comparison of the frequency of respiratory tract symptoms between the groups showed that the frequency of dyspnoea (P = .015) and any respiratory tract symptom (P = .014) was significantly higher in patients whose musculoskeletal symptoms began with or were aggravated by COVID-19. However, the frequency of cough and chest pain was similar between the groups (Table 5 ). To the best of our knowledge, this is the first study that describes how factors such as disease symptoms and laboratory and chest CT related to postacute COVID-19 musculoskeletal symptoms. To evaluate these related factors, comparison was made between patients whose musculoskeletal symptoms began with or were aggravated by COVID-19 and patients whose musculo- The results of the present study support these pathophysiologic mechanisms with lower lymphocyte and higher d-dimer levels in patients whose musculoskeletal symptoms began with or were aggravated by COVID-19. The reduction in lymphocytes is related to the consumption of lymphocytes in inflamed regions while fighting against COVID-19. 9 This reduction has also been shown to be associated with poor outcomes. 10, 11 In addition, hyperinflammation seems to contribute to COVID-19-related coagulopathy, and microthrombosis was reported to occur in almost every system, including the musculoskeletal system. 12 Not only lower lymphocyte levels but also elevated levels of d-dimer are related to poor outcomes 13 and this elevation may be related to this coagulopathy patients. 5 In our study, the most common region of pain was the back (30%) and back pain was also the most frequent symptom on admission to the PMR outpatient clinic. Furthermore, back pain in acute COVID-19 was found to be related to postacute COVID-19 musculoskeletal symptoms. Gender and ethnic differences may be the reason for these different results: in our study, 65% of patients were women, whereas 30% of patients were women in the Bangladesh study. In another study in Turkey, phone interviews were conducted with 300 COVID-19 patients (60% male) after hospitalisation (intensive care unit patients were excluded): 72% of these patients have at least one symptom, while most complaints regarding the musculoskeletal system were fatigue (44%), back pain (22.7%), arthralgia (22%), myalgia (21%) and lower back pain (16%) after 1 month. 4 These frequencies were lower than in our study, and the methodology used was also different. Our study's population was predominantly female and also includes patients who were treated in an intensive care unit. In addition, the population consisted of patients admitted to the PMR outpatient clinic with at least one musculoskeletal symptom after COVID-19. The frequencies recorded in the present study were, thus, higher than those in the other Turkish study. On the other hand, similar to our study, Karaarslan et al 4 also reported that back pain was the most common form of pain, the knee was the most common site of joint pain and that fatigue was the most common symptom. In acute COVID-19 infections, the most common complaints regarding the musculoskeletal system are fatigue and myalgia. 15 In addition, these complaints seem to continue after acute COVID-19. Consistent with the results of our study, many other studies have reported that fatigue is commonly seen after recovery from TA B L E 3 Comparison of demographic parameters and treatment characteristics between the patients whose musculoskeletal symptoms initiated or were aggravated with COVID-19 and the patients whose musculoskeletal symptoms did not change with COVID-19 infection. [2] [3] [4] 7 Perrin et al 16 In a recently metadata analysis, an ongoing adaptation to COVID-19 evolution showed statistically higher virulence and/or TA B L E 4 Comparison of the findings during the period of COVID-19 infection between the patients whose musculoskeletal symptoms initiated or were aggravated with COVID-19 and the patients whose musculoskeletal symptoms did not change with COVID-19 The relationship between musculoskeletal and respiratory tract symptoms in post-COVID-19 period viral infectivity. 18 This analysis showed that we will continue to fight both with COVID-19 and long-term consequences. It is necessary to develop quick therapeutics that inhibit this infection; also, vaccination of people could control the COVID-19 outbreak. 19 The study included patients who were admitted to PMR clinic with at least one musculoskeletal symptom: for this reason, our results cannot be generalised to all postacute COVID-19 patients. Another limitation of our study was the lack of the antibiotic and glucocorticoid intake, invasive ventilation records and laboratory records in postacute period. Further studies are needed to determine the frequency of musculoskeletal symptoms after COVID-19 in the general population. The present study showed that musculoskeletal symptoms were more frequent than respiratory tract symptoms in postacute COVID-19 patients. Specialists in the musculoskeletal field should be a part of multidisciplinary teams. The most frequent symptom on admission to the PMR outpatient clinic was back pain and the most common musculoskeletal symptoms were fatigue, spine pain and myalgia. Each of these was present in more than three-fifths of postacute COVID-19 patients. 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