key: cord-0707811-hkzna9yj
authors: Batur, Elif Balevi; Korez, Muslu Kazim; Gezer, Ilknur Albayrak; Levendoglu, Funda; Ural, Onur
title: Musculoskeletal symptoms and relationship with laboratory findings in patients with COVID‐19
date: 2021-03-14
journal: Int J Clin Pract
DOI: 10.1111/ijcp.14135
sha: 95622ad8b3483b39c0362154e1ab6434419114b3
doc_id: 707811
cord_uid: hkzna9yj

AIM: To investigate the frequency of fatigue and musculoskeletal symptoms and their correlation with laboratory data in patients with COVID‐19. METHODS: This study included 80 patients hospitalised and treated for COVID‐19 in the infectious diseases clinic between March 2020 and May 2020. Data analysis was performed retrospectively from the hospital medical charts. Demographic data, clinical symptoms, and laboratory findings were noted. Clinical symptoms and correlations with laboratory results were assessed. Besides, an analysis of patients with and without chronic disease was performed for clinical symptoms and laboratory findings. RESULTS: The frequencies of myalgia and fatigue were 46.1% and 50%, respectively. In the laboratory data, there was a significant increase in creatinine kinase (CK) level and lymphocyte count in the patients with myalgia symptoms (P < .05). There were no other significant results in the laboratory data. Of the patients with chronic disease, it has been shown that hemoglobin levels were significantly decreased (P < .05), while D‐dimer was markedly increased (P < .05). CONCLUSION: The laboratory findings of COVID‐19‐related myalgia suggested that patients might have a risk of progressive muscle injury. Therefore, these patients should also be followed up in terms of the myopathic process.

Before the study, 250 patients were screened. Of these, 110 patients had incomplete data and 60 patients did not meet the inclusion criteria. In total 80 patients diagnosed with COVID-19 and hospitalised between March 2020 and May 2020 were included in this study. The data were obtained retrospectively from the hospital records. The patients were called by phone and the data were provided, in case of missing data. Patients' demographic characteristics, symptoms, and laboratory results were noted.

The frequency of symptoms and correlation with the laboratory data were examined. Before the study, approval was obtained from the institutional review board (No:2020/16) and the General Directorate of Health Services of the Republic of Turkey (No: 2020-06-16T10-26-57).

Criteria for inclusion in the study; Adult patients over 18 years of age, who meet the diagnosis and treatment criteria 14 defined for COVID-19 mentioned below: (a) clinical signs such as fever, fatigue, dry cough, dyspnea, and pneumonia findings in imaging, (b) the history of travel to the risky regions 14 days before symptoms start, (c) the history of close contact with the sick people, (d) the confirmation of diagnosis by the nucleic acid real time-polymerase chain reaction (RT-PCR) test. All patients' chronic diseases such as hypertension, diabetes, cardiovascular disease, chronic obstructive pulmonary disease, malignancy that may cause comorbidity were noted. Furthermore, the patients were divided into two groups according to the presence or absence of comorbidity, and their symptoms and correlations with laboratory findings were also examined. 

Of the 80 cases included in the study, 31 (38.8%) were female and 49 (61.1%) were male. The average age was 44.93 ± 15.55 and the most common symptoms were cough (61.3%), fatigue (50%), myalgia (46.3%), and fever (37.5%), respectively. Lung involvement was present in 38.8% of the patients. Hypertension (26.2%), diabetes (21.4%), and asthma (21.4%) were the most common accompanying comorbid diseases. Other demographic data of the patients are summarised in Table 1 .

When the laboratory data of the patients were examined, white blood cell count was normal in 77.5%. However, neutrophil, lymphocyte, and platelet counts were decreased in 11.3%, 12.5%, and 16.3% of the patients, respectively. High levels of neutrophil, lymphocyte, and platelet counts were 16.3%, 21.3%, and 2%, respectively. The C-reactive protein was high in 48.8% of patients, while the d-Dimer value was high in 40% of patients. Data on other laboratory data are given in Table 2 .

The lymphocyte count of patients with myalgia symptoms was significantly higher than those without myalgia symptoms (χ 2 = 9.368, P = .008). Similarly, creatine kinase levels in patients with myalgia symptoms were significantly higher than those without myalgia (χ 2 = 14.424, P < .001). No statistically significant relationship was found between other laboratory findings and myalgia symptoms (P > .05) ( Table 3) .

When the laboratory data of patients with and without comorbidity were compared, a statistically significant difference was found in hemoglobin, d-Dimer, and ferritin levels (P < .05) ( Table 4 ). There were no differences in myalgia and fatigue symptoms between the groups (P values for myalgia and fatigue were .249 and .999, respectively).

In this study, we found a 46.3% frequency for myalgia, which was one of the most common complaints in patients hospitalised for COVID-19. This result was in line with some studies in the literature. [15] [16] [17] In these studies myalgia frequencies were 52%, 55%, and 42%, respectively. We found fatigue frequency, which was also one of the most common symptoms, as 50% in our study. This rate was the same as in the study by Chen et al in the literature. 18 However, currently, the frequency of myalgia and other symptoms in the COVID-19 positive patients were variable in the literature. The Note: Data were presented as mean ± SS (min-max) and frequency (n) in percent (%).

Abbreviations: COPD, chronic obstructive pulmonary disease; SD, standard deviation. In our laboratory data, white blood cell, lymphocyte, and neutrophil counts were within normal limits in most patients. Still, the elevated lymphocyte counts were higher in patients with myalgia.

This finding might suggest that lymphocytosis leads to immune cell activation and overexpression of proinflammatory cytokines associated with myalgia. In contrast to our study, Huang et al showed mostly lymphopenia in patients. However, the correlation of this condition with myalgia was not evaluated in Huang et al's study. 17 In another study, because of the inflammatory cascade of the disease, it was strongly recommended to examine the relationship between laboratory data and musculoskeletal complaints. 13 To the best of our knowledge, this is the first study examining the correlation with the symptoms of myalgia and fatigue and laboratory results in COVID-19

patients.

Another parameter that we detected in patients with myalgia symptoms is the high creatinine kinase (CK) levels. As it is well known, CK is released into the blood in cases where the striped muscle cells are damaged and membrane integrity changes. As a result, elevated CK is closely related to the intensity of striated muscle damage. 23, 24 In a study, it was reported that myalgia with elevated CK is common in both moderate and severe cases and may cause a real myopathic injury. The cause of myalgia in COVID-19 may be because of muscle damage caused by the action of released cytokines.

TNF-alpha released during COVID-19 infection may cause musculoskeletal symptoms. 6, 7 Apart from this, in another study conducted in China, the most emphasised cytokine was IL-6, and it was stated that it might be responsible for the cytokine storm that can be seen during the course of the disease. 25 Since there was no kit for IL-6, we did not evaluate the IL-6 levels in this study and can be assessed in future studies.

Our study suggested that hemoglobin values were lower in the group of patients with chronic diseases than those without chronic diseases and d-Dimer values were higher in the chronic diseases group. This finding was in the same line with a study in the literature, and attention has been drawn to the elevated value of d-Dimer and low hemoglobin in patients with chronic disease. 17 The reason

for this may be that these patients are at a more advanced age and are prone to coagulation caused by their additional diseases. In this study, ferritin levels were also evaluated and it was observed that ferritin levels were not normal in the group with chronic conditions.

However, since the number of patients was not sufficient, we could not make definitive judgements about ferritin levels. In our study, we did not find any difference between patients with and without chronic disease in terms of symptoms. 

In our study, we showed that COVID-19 caused a high rate of myalgia and additionally caused CK elevation in the laboratory. The increase of CK in these patients should be a caution about muscle damage and extremely higher values may indicate the progressive myopathic process.

The authors report no conflicts of interest. Note: Data were presented in frequency (n) as percentages (%).

P values were calculated using Exact test for cases where the expected frequency was less than 20% in the case of Fisher's exact test and 2 × 3 in the case-squareness correction chi-square.

*P < .05 is statistically significant.

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