A Cross-Sectional Analysis of Muscular and Joint Symptoms in COVID-19 Patients: Insights From Syria
Conditions: Musculoskeletal Pain, COVID-19
Sponsor: Syrian Private University

A Cross-Sectional Analysis of Muscular and Joint Symptoms in
COVID-19 Patients: Insights from Syria.
Introduction:
Since its emergence in 2020, Coronavirus Disease 2019 (COVID-19) has radically
transformed lifestyles and exerted immense pressure on public health infrastructures
worldwide1. Not merely confined to respiratory ailments, COVID-19 exhibits a plethora
of manifestations, notably in the musculoskeletal system. Such symptoms can linger for
weeks or even months, predominantly in severe and critical cases of the infection [1-3].
The underlying mechanisms behind the virus's adverse effects on muscle tissue can be
attributed to two prevailing hypotheses. The first proposes a direct binding of the virus to
the ACE2 receptor on muscle cell surfaces, leading to muscle weakness. The second
postulates that the heightened inflammatory response triggered by the virus adversely
impacts musculoskeletal tissues. This reaction releases cytokines, which can induce
multi-organ injuries, manifesting chiefly as fatigue and myalgia [4-6]. Additionally,
factors like prolonged immobilization during illness or pre-existing autoimmune,
neuromuscular, and muscular conditions might exacerbate musculoskeletal symptoms
[4-6].
Musculoskeletal symptoms and their disparities among sexes are areas warranting more
attention. Although males present an increased risk of severe COVID-19 outcomes and
higher infectivity rates than females
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9149780/], women with severe
symptoms have demonstrated elevated levels of IgG antibodies against SARS-CoV-2 and
a stronger early-phase antibody
response[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9149780/]. Moreover, female
gender associates significantly with the long COVID syndrome
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8575536/]. Nevertheless, another study
observed comparable symptoms and comorbidities between the genders
[https://www.frontiersin.org/articles/10.3389/fpubh.2020.00152/full]. These disparities
could arise from various socio-health determinants like smoking habits or mask-wearing
compliance and biological factors, given the well-established differences in the immune
systems of both sexes.
Numerous studies have documented an array of musculoskeletal symptoms in COVID-19
patients. Fatigue, which can be enduring, arthralgia, arthritis, myalgia, myositis,
rhabdomyolysis, and myopathy are among the most commonly reported. These

symptoms can profoundly affect patients' quality of life, potentially triggering anxiety
and depression[4,7-9].
Regrettably, only a handful of laboratory and imaging techniques delve into the
musculoskeletal ramifications of COVID-19. Yet, their insights are invaluable. These
findings play a pivotal role in the assessment, diagnosis, and prognosis of
musculoskeletal manifestations, subsequently guiding the therapeutic journey[10-11].
It is worth noting that drugs such as corticosteroids, colchicine, and hydroxychloroquine,
which find utility in the treatment of COVID-19, might be double-edged swords. Their
potential side effects, including myalgia, myopathies, myositis, and arthralgia, can mimic
the very symptoms of COVID-19, necessitating judicious clinical discernment[12-13].
Empirical data has shed light on the prominence of muscle symptoms among hospitalized
patients during SARS-CoV-2's acute phase. Manifestations like myalgia, evident muscle
wasting, myopathy, rhabdomyolysis, and elevated serum CK levels were more frequent
among severe cases. Conversely, a minor 5.12% to 2.36% of mild COVID-19 cases
reported fatigue, myalgia, and weakness [14-16]. A review of available literature
identified thirteen studies that highlighted persistent muscle-related symptoms, even in
non-hospitalized individuals with milder infection variants. These primarily include
fatigue, deteriorated quality of life, prolonged arthralgia, and persistent myalgia [17-19].
Therefore, this research endeavors to explore the recurrent effects of COVID-19
infections on the musculoskeletal symptoms both during and post-infection among the
Syrian population. Additionally, we seek to investigate any disparities in these
musculoskeletal symptoms between males and females. Through this inquiry, we aim to
bridge gaps in understanding and provide insights to better manage and treat affected
individuals.
Methods:
Study Design and Rationale:
This was a cross-sectional study conducted between June and October 2022 at
Al-Mouassa University Hospital, Damascus, Syria. The rationale for employing a
cross-sectional design was twofold: it permitted an assessment of musculoskeletal
manifestations in COVID-19 patients at a singular, crucial time point - both during their
infection and post-infection. Moreover, given the rapidly evolving nature of the
COVID-19 pandemic, this design enabled timely data collection, essential for generating
hypotheses about musculoskeletal symptoms' underlying mechanisms or potential

prolonged effects. This study protocol received approval from the Ethical Committee of
the Mouassat Hospital. Furthermore, in line with the Helsinki Declaration, all participants
rendered written informed consent before their involvement.
Study Population and Sampling:
A total of 1039 participants, all aged above 18 years and residing in Damascus, were
recruited. The recruitment combined online survey dissemination and field recruitment to
mitigate potential biases. Online, 625 participants completed the questionnaire after it
was shared on various websites and social media platforms. For field recruitment, 414
participants were approached at Al-Mouassa University Hospital outpatients clinics and
at Faculty of Medicine, Damascus University. After a thorough explanation of the study's
objectives, willing patients were provided an online survey link and monitored during
completion.
Inclusion and Exclusion Criteria:
Inclusion: Participants aged ≥18 years with a prior COVID-19
infection or suspicious COVID-19 infection and currently
residing in Damascus.
Exclusion: Participants below 18 years, those unwilling to give consent, individuals with
joint surgery history, pregnant women, or those who had taken immunosuppressive drugs
before the study.
Data Collection:
The primary tool was an adapted questionnaire based on the study 'Musculoskeletal
symptoms and related factors in post-acute COVID-19 patients [20]. This questionnaire
underwent modifications to tailor it to our participants, specifically emphasizing clarity
and comprehension. Though budget constraints restricted laboratory tests such as PCR,
CRP, and WBC, the adapted questionnaire captured inflammation-related symptoms,
such as musculoskeletal swelling and pain. Comprehensive, interviewer-administered
questionnaires solicited data on demographic, social, clinical, and behavioral aspects,
alongside specifics like vaccination status, musculoskeletal symptoms during and post
COVID-19 infection, and rheumatoid disease status.
Outcome Measures:
The primary outcome measure of this study was the prevalence and nature of
musculoskeletal manifestations in individuals with past COVID-19 infections. Secondary

outcome measures included factors influencing these manifestations, such as vaccination
status, and potential associations with conditions like osteoporosis
Statistical Analysis
Data were analyzed using IBM SPSS Statistics 28.0.0.0. Continuous variables were
depicted as both means with standard deviations and medians with their respective
ranges. Categorical variables were presented in terms of frequencies and associated
percentages.
For the comparison of categorical variables, the Chi-Square test was utilized. Continuous
variables were evaluated using the Mann-Whitney U test to determine significant
differences between groups. A threshold of p < 0.05 was set for statistical significance.
Findings were systematically organized and exhibited in tables or graphical
representations as deemed fitting.
Results:
Demographics and Clinical Characteristics of the Participants:
The demographic distribution, summarized in Table 1, elucidated certain distinctive
trends in our study population. Of the 1,039 participants, 613 (59.0%) were females, and
426 (41.0%) were males. The age range spanned 18 to 78 years, with a similar median
age observed in females (25 years) compared to males (24 years); this difference was
statistically significant (p=0.018). Most participants resided in urban areas, accounting
for 82.8% of the total, with no significant gender-wise disparity noted. When evaluating
marital status, a striking difference was evident: a larger proportion of males (78.4%)
were single compared to females (67.2%), and this difference was statistically significant
(p<0.001).
Turning our attention to the participants' COVID-19 experiences, the majority had
encountered the infection once (60.6%). The recurrence of infections did not significantly
differ between genders. Interestingly, the severity of the first infection revealed that a vast
majority, 85.2%, experienced low severity, but a significant difference was noted in the
distribution between males and females (p=0.018). Males appeared to exhibit a higher
prevalence of asymptomatic cases during their first infection (13.4%) than females
(8.0%) (Table 1).

Regarding the diagnostic approaches for COVID-19, the most common method for both
genders was based on symptom presentation (62.5%), with no significant differences
observed in the utilization of rapid tests or PCR. As for the vaccination status against
COVID-19, slightly over half of the participants, 55.2%, had been vaccinated, with males
(56.3%) having a marginal lead over females (54.5%), though this difference was not
statistically significant (Table 1).
Table 1: Demographic characteristics of the participants
Female
(n=613)
Male
(n=426)
Total
(n=1039)
P-Value
Age
Median
(Range)
25 (18-78)
24 (18-77)
24 (18–78)
0.018*
Mean ± SD
29.4 ± 11.2
29.0 ± 12.9
29.27 ± 11.9
Residual
area
Rural
112 (18.3%)
67 (15.7%)
179 (17.2%)
NS
City
501 (81.7%)
359 (84.3%)
860 (82.8%)
Social
Status
Single
412 (67.2%)
334 (78.4%)
746 (71.8%)
<0.001*
Married
181 (29.5%)
80 (18.8%)
261 (25.1%)
Divorced
10 (1.6%)
9 (2.1%)
19 (1.8%)
Widow
10 (1.6%)
3 (0.7%)
13 (1.3%)
Number of
times of
COVID-19
Infections
Once
376 (61.3%)
254 (59.6%)
630 (60.6%)
NS
Twice
171 (27.9%)
132 (31.0%)
303 (29.2%)
Three
times
52 (8.5%)
28 (6.6%)
80 (7.7%)
More than
that
14 (2.3%)
12 (2.8%)
26 (2.5%)

COVID-19
infection
Now
Yes
16 (2.6%)
15 (3.5%)
31 (3.0%)
NS
No
581 (94.8%)
407 (95.5%)
988 (95.1%)
Maybe
16 (2.6%)
4 (0.9%)
20 (1.9%)
Severity of
the First
infections
Low
534 (87.1%)
251 (82.4%)
885 (85.2%)
0.018*
Severe
30 (4.9%)
18 (4.2%)
48 (4.6%)
No
symptoms
49 (8.0%)
57 (13.4%)
106 (10.2%)
The
severity of
the
symptoms
in
recurrent
infections
Lower
117 (19.1%)
107 (25.1%)
224 (21.6%)
NS
More
severe
59 (9.6%)
48 (11.3%)
107 (10.3%)
Same
82 (13.4%)
49 (11.5%)
131 (12.6%)
Only one
infection
355 (57.9%)
222 (251%)
577 (55.5%)
COVID-19
diagnostic
way
Rapid test
79 (12.9%)
65 (15.3%)
144 (13.9%)
NS
PCR
154 (25.1%)
93 (21.6%)
246 (23.7%)
Symptoms
380 (62.0%)
269 (63.1%)
649 (62.5%)
Taken
COVID-19
vaccines
Yes
334 (54.5%)
240 (56.3%)
574 (55.2%)
NS
No
279 (45.5%)
186 (43.7%)
465 (44.8%)

Vaccine Distribution among Participants
Delving into the types of COVID-19 vaccines received by the participants, Table 2
illustrates a diverse range of choices. AstraZeneca and Pfizer emerged as the most
preferred vaccines, accounting for 31% and 30.3% of the vaccinated participants,
respectively. Other vaccines like Sputnik and Sputnik Light were also fairly common,
with uptake rates of 11.7% and 12.4% respectively. Notably, 12.0% of the participants
reported having received two different types of vaccines.
Table 2: Types of Vaccines
AstraZeneca
178 (31%)
Johnson
28 (4.9%)
Moderna
32 (5.6%)
Pfizer
174 (30.3%)
Sinopharm
53 (9.2%)
Sinovac
27 (4.7%)
Sputnik
67 (11.7%)
Sputnik light
71 (12.4%)
Not known
16 (2.8%)
2 different
types
69 (12.0%)

Muscular and Joint Symptoms by Sex
Table 3 presents a comprehensive comparison of muscle and joint symptoms among the
participants, segmented by sex. During their COVID-19 infection, muscle-related
symptoms were prominent among both genders, with 71.6% of females and 73.0% of
males reporting them. Specifically, muscle pain was the dominant symptom, reported by
70.4% of the symptomatic females and 66.9% of the symptomatic males. Malaise and
fatigue were also non significant, affecting 27.6% of the symptomatic females and 30.9%
of the symptomatic males. A smaller fraction experienced an inability to perform certain
movements, at 7.7% for females and 5.8% for males.
As for joint-related symptoms during the infection, 38.5% of females and 42.0% of males
reported experiencing them. Of these, joint pain was overwhelmingly the most prevalent
complaint, reported by 90.7% of symptomatic females and 88.8% of symptomatic males.
Limitations in joint movement were described by 15.7% of symptomatic females and
19.6% of symptomatic males. Swelling and tenderness of joints were relatively less
common but were still observed in 7.2% of symptomatic females and 8.9% of
symptomatic males.
Interestingly, post-infection muscle symptoms were reported by approximately 30% of
both genders, with both groups equally experiencing muscle pain (59.4%). Similarly,
malaise and fatigue post-infection were reported by 55.1% of symptomatic females and
54.7% of symptomatic males. Joint symptoms post-infection were found in 19.9% of
females and 19.2% of males, with joint pain being the most common complaint.
Table 3: Muscle and joints symptoms among the participants compared by sex
Female
(n=613)
Male
(n=426)
Total
(n=1039)
P-Value
Symptom
s during
the
Muscles Symptoms
439
(71.6%)
311
(73.0%)
750
(72.2%)
NS

COVID
infections
1)
Muscle
Pain
309
(70.4%)
208
(66.9%)
517
(68.9%)
NS
2)
Malaise
and Fatigue
121
(27.6%)
96
(30.9%)
217
(28.9%)
NS
3)
Inability
to do some
movement
34 (7.7%)
18 (5.8%)
5.2 (6.9%)
NS
Joint Symptoms
236
(38.5%)
179
(42.0%)
415
(39.9%)
NS
1)
Joint
swallow and
tenderness
17 (7.2%)
16 (8.9%)
33 (8.0%)
NS
2)
Joint Pain
214
(90.7%)
159
(88.8%)
373
(89.9%)
NS
3)
Limitation
in joint
movement
37
(15.7%)
35
(19.6%)
72 (17.3%)
NS
Symptom
s Post
COVID
infections
Muscles Symptoms
175
(30.5%)
295
(30.0%)
315
(30.3%)
NS
1)
Muscle
Pain
111
(59.4%)
76
(59.4%)
187
(59.4%%)
NS
2)
Malaise
and Fatigue
103
(55.1%)
70
(54.7%)
173
(54.9%)
NS
3)
Inability to
do some
movement
19
(10.2%)
11 (8.6%)
30 (9.5%)
NS
Joint Symptoms
122
(19.9%)
82
(19.2%)
204
(19.6%)
NS
1)
Joint
swallow and
tenderness
12 (9.8%)
12
(14.6%)
24 (11.8%)
NS

2)
Joint Pain
90
(73.8%)
65
(79.3%)
155
(76.0%)
NS
3)
Limitation
in joint
movement
18
(14.8%)
11
(13.4%)
29 (14.2%)
NS
The revised Table 4 showcases the prevalence of specific joint afflictions experienced
during COVID-19 infections, broken down by gender. The knee joint was the most
commonly affected for both females (22.9%) and males (28.5%). For females, the
subsequent most commonly affected joints were the shoulder (13.1%) and hip (16.9%).
For males, the hip (19.0%) and feet (11.7%) followed the knee in prevalence. It is
noteworthy that across all joint types, the differences in prevalence between females and
males were not statistically significant, as indicated by the non-significant p-values.
Table 4: Prevalence of Specific Joint Afflictions During COVID-19 Infection
by Sex
Female
(n=236)
Male
(n=179)
Total
(n=415)
P-Value
Joint Type
Hip
40 (16.9%)
34 (19.0%)
74 (17.8%)
NS
Knee
54 (22.9%)
51 (28.5%)
105
(25.3%)
NS
Elbow
12 (5.1%)
12 (6.7%)
14 (5.8%)
NS
Feet
24 (10.2%)
21 (11.7%)
45 (10.8%)
NS
Shoulder
31 (13.1%)
23 (12.8%)
54 (13.0%)
NS
Neck
19 (8.1%)
14 (7.8%)
33 (7.9%)
NS
Ankle
18 (7.6%)
16 (8.9%)
34 (8.2%)
NS
Sex-Specific Overview of Joint Symptomatology in COVID Cases:

Table 5 presents a detailed breakdown of joint symptom characteristics observed during
COVID-19 infections, segmented by gender and the entire cohort. Regarding the number
of joints affected, a vast majority of participants, 74.0% overall, reported no joint
afflictions. When joints were affected, 7.1% of the participants experienced issues in one
joint, with 13.1% reporting afflictions in fewer than four joints, and 5.8% mentioning
issues in more than four joints. The prevalence of these symptoms was fairly consistent
between both genders, as indicated by the non-significant p-values.
As for the duration of the joint pain, 5.5% of the participants suffered for more than 6
months, while 30.3% reported pain lasting less than 6 months. Again, the distribution of
durations was comparable between females and males. Additionally, 5.7% of the
participants had associated rheumatoid diseases, with a slightly higher prevalence in
males (6.8%) than in females (4.9%). Lastly, 3.3% of the entire group had been diagnosed
with osteoporosis following the COVID vaccine, with a slightly higher incidence in
males (3.5%) compared to females (3.1%). Across all metrics discussed, the differences
between males and females did not attain statistical significance.
Table 5: Comparison of Joint Symptoms' Duration and Related Diseases by
Sex
Female
(n=613)
Male
(n=426)
Total
(n=1039)
P-Value
Number of
Joints
affected
One Joint
42 (6.9%)
32 (7.5%)
74 (7.1%)
NS
Less Than
4
80 (13.1%)
56 (13.1%)
136 (13.1%)
More Than
4
34 (5.5%)
26 (6.1%)
60 (5.8%)
No Joints
457 (74.6%)
312 (73.2%)
769 (74.0%)
Duration
of Joint
Pain
More than
6 months
33 (5.2%)
25 (5.9%)
58 (5.5%)
NS

Less than 6
months
185 (30.2%)
130 (30.5%)
315 (30.3%)
Rheumatoid Diseases
30 (4.9%)
29 (6.8%)
59 (5.7%)
NS
Have you been
diagnosed with
osteoporosis after the
COVID vaccine
19 (3.1%)
15 (3.5%)
34 (3.3%)
NS
Discussion:
The study, involving 1,039 participants, unveiled distinct demographic trends and
COVID-19 experiences, with 59.0% females and significant gender-based differences in
marital status. Urban residency was predominant, and 60.6% encountered COVID-19
once. Symptom-based diagnostics and vaccination (55.2%) favored AstraZeneca and
Pfizer. Muscular and joint symptoms, prevalent during and post-COVID, showed no
significant gender differences, and knee joints were most commonly affected.
AstraZeneca and Pfizer dominated vaccine distribution. Despite these observations, the
differences in symptom presentation and prevalence between genders did not attain
statistical significance in most metrics. This comprehensive insight into the clinical
progression of COVID-19 and its aftermath among our cohort provides a foundation for
further discussions on symptom management and long-term care.
Despite these observations, the differences in symptom presentation and prevalence
between genders did not attain statistical significance in most metrics. This
comprehensive insight into the clinical progression of COVID-19 and its aftermath
among our cohort provides a foundation for further discussions on symptom management
and long-term care.
Hold significant implications for the broader landscape of public health in the
post-pandemic era. The high occurrence of musculoskeletal symptoms, especially in the
context of COVID-19, underscores the necessity for a comprehensive understanding of
the enduring effects on the Syrian population. The study's thorough examination of
gender-specific manifestations yields crucial insights for tailoring healthcare strategies.

Muscle and joint symptoms, prevalent both during and after COVID-19 infection, can
profoundly impact individuals' quality of life, potentially resulting in prolonged
discomfort and hindering daily activities. The study's acknowledgment of comparable
prevalence between genders, despite minor variations, underscores the importance of
inclusive health interventions. The identified differences in marital status and urban
residence provide nuanced socio-demographic insights into the distribution and
experiences of COVID-19 within the Syrian population. The varied distribution of
COVID-19 vaccines, with AstraZeneca and Pfizer emerging as predominant choices,
furnishes valuable information for healthcare planning and resource allocation. We found
in this study that arthralgia and myalgia were to be the most common musculoskeletal
manifestation during and post covid which is consistent with a study focused on
Mechanisms of Musculoskeletal Pain in Long COVID(22).
Studies investigating the association between gender and musculoskeletal symptoms
yielded mixed results. While a study in Iran found no sex differences [23], a study in
Turkey reported higher prevalence in females [24], which aligns with our study, where
the females were more symptomatic , but the difference did not reach statistical
significance. This inconsistency might be due to methodological variations, including
unequal sample sizes and potential confounders such as age, BMI, and education levels.
Existing literature proposes two dominant hypotheses: the direct binding of the virus to
ACE2 receptors on muscle cells, inducing muscle weakness, and an inflammatory
response that adversely affects musculoskeletal tissues, and this goes along with the A
Narrative Review Article (25).
This heightened inflammatory reaction may lead to multi-organ injuries, manifesting in
symptoms like fatigue, myalgia, and joint pain. Furthermore, factors such as prolonged
immobilization during illness or pre-existing autoimmune, neuromuscular, and muscular
conditions could potentially intensify musculoskeletal symptoms.
The cross-sectional design of the study inherently restricts its capacity to establish
causation or unveil the dynamic evolution of musculoskeletal symptoms over time. The
utilization of a convenience sample, amalgamating online survey distribution and field
recruitment, may introduce selection biases. The study predominantly depends on
self-reported data, potentially leading to recall bias and subjective interpretations of
symptoms.

Conclusion
The study highlights a significant prevalence of musculoskeletal symptoms both during
and after COVID-19 infection, with notable complaints such as muscle pain, joint pain,
and fatigue. Importantly, these symptoms exhibit persistence post-infection, underscoring
the need for sustained attention to comprehend their long-term impact on affected
individuals. The dominance of AstraZeneca and Pfizer in Syria's vaccine landscape
underscores the importance of understanding not only infection-related symptoms but
also the potential musculoskeletal repercussions associated with different vaccines. In the
face of the pandemic's repercussions on a global scale, this research advocates for a
comprehensive approach to post-COVID-19 care in Syria, urging consideration not solely
of respiratory complications but also of musculoskeletal symptoms, acknowledging their
prevalence and potential contribution to long-term morbidity.
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