Literature DB >> 34713356

Long COVID: rheumatologic/musculoskeletal symptoms in hospitalized COVID-19 survivors at 3 and 6 months.

Fatih Karaarslan1, Fulya Demircioğlu Güneri2, Sinan Kardeş3.   

Abstract

OBJECTIVE: To document the detailed characteristics including severity, type, and locations of rheumatic and musculoskeletal symptoms along with other COVID-19 persistent symptoms in hospitalized COVID-19 survivors at 3 and 6 months.
METHODS: In this extension cohort study, two telephone surveys at 3 and 6 months following the hospitalization were carried out. In these telephone surveys, participants were asked regarding their symptoms through a previously designed standard questionnaire.
RESULTS: At 3 months, 89.0% of survivors had at least one symptom, 74.6% had at least one rheumatic and musculoskeletal symptom, and 82.1% had at least one other COVID-19 symptom. At 6 months, 59.6% of survivors had at least one symptom, 43.2% had at least one rheumatic and musculoskeletal symptom, and 51.2% had at least one other COVID-19 symptom. Regarding the rheumatic and musculoskeletal symptoms, 31.6% had fatigue, 18.6% had joint pain, and 15.1% had myalgia; and regarding the other-COVID-19-symptoms, 25.3% had dyspnea, 20.0% had hair loss, and 17.2% sweat at 6 months. In an adjusted model, female patients were more likely to have fatigue (OR: 1.99, 95% CI: 1.18-3.34), myalgia (3.00, 1.51-5.98), and joint pain (3.39, 1.78-6.50) at 6 months.
CONCLUSION: Approximately 3 in 5 patients had at least one symptom with ≈2 in 5 patients had at least one rheumatic and musculoskeletal symptom. Fatigue, joint pain, and myalgia were the most frequent rheumatic and musculoskeletal symptoms. Joint pain and myalgia were mostly widespread. This information guide rheumatologists to understand the nature and features of persistent rheumatic and musculoskeletal symptoms in hospitalized COVID-19 survivors and may contribute to better management of these individuals. Key Points • Approximately 3 in 5 patients had at least one symptom with ≈2 in 5 patients had at least one rheumatic and musculoskeletal symptom at 6 months • Fatigue, joint pain, and myalgia were the most frequent rheumatic and musculoskeletal symptoms followed by back pain, low back pain, and neck pain • Dyspnea, hair loss, and sweat were the most frequent other-COVID-19-symptoms.
© 2021. International League of Associations for Rheumatology (ILAR).

Entities:  

Keywords:  Fatigue; Joint pain; Long-haul COVID; Muscle pain; Post-acute COVID-19 syndrome; SARS-CoV-2

Mesh:

Year:  2021        PMID: 34713356      PMCID: PMC8553494          DOI: 10.1007/s10067-021-05942-x

Source DB:  PubMed          Journal:  Clin Rheumatol        ISSN: 0770-3198            Impact factor:   3.650


Introduction

Since the emergence in the late of 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread across the world leading an unexpected, large, and serious global pandemic [1-5]. By the 5th of July 2021, 182,319,261 confirmed cases of coronavirus disease 2019 (COVID-19), involving 3,954,324 deaths, have been identified worldwide according to the World Health Organization (WHO) [6]. Even though as COVID-19 vaccination becomes more available throughout the world and the COVID-19 infection/death rates are dropping, clinicians have still caring the COVID-19 survivors who were previously infected and recovered from acute infection and now experience a broad range of persistent symptoms, which are called as post-acute COVID-19 syndrome, long COVID, long-haul COVID, post-COVID condition, or post-acute sequelae of SARS-CoV-2 infection (PASC) [7, 8]. Several observational studies have recently evaluated the persistent symptoms in hospitalized COVID-19 survivors beyond 3 months [9-13]. Although some of these studies have partly described the persistent fatigue, myalgia, and joint pain in hospitalized COVID-19 survivors, they only reported their prevalence. In other words, the severity, type (local or widespread), and locations of persistent rheumatic and musculoskeletal symptoms have not been documented in detail. Thus, we aimed to document the detailed characteristics including severity, type, and locations of rheumatic and musculoskeletal symptoms along with other COVID-19 persistent symptoms in hospitalized COVID-19 survivors at 3 and 6 months. We also sought to evaluate whether an association exists between the presence of symptoms (i.e., fatigue, myalgia, joint pain) and age, sex, body mass index (BMI), and duration of hospital stay.

Materials and methods

Study design, setting, and ethical approval

We conducted an extension cohort study of our previously published investigation reporting 1-month results [14]. We carried out this study in a tertiary hospital, namely Gülhane Training and Research Hospital. We obtained an ethical approval for this extension study by the Ethic Committee of the Gülhane Scientific Researches, University of Health Sciences (2021/187). We obtained informed verbal consent to participate in the study at the beginning of the telephone interviews. We informed by Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) [15] in reporting our study and by standard recommendations [16] in reporting our results.

Study cohort

COVID-19 survivors who aged 18 to 70 years old and who had been discharged after hospital stay due to the acute COVID-19 infection anytime during the November 18, 2020, through January 30, 2021, were included. We included COVID-19 survivors who had been only treated in hospital ward unit; in other words, we excluded survivors who admitted/or were transferred to intensive care unit during their hospital stay.

Data gathering

One author (FK) carried out all telephone surveys at 3 and 6 months following the hospitalization. In these telephone surveys, participants were asked regarding their symptoms through a previously designed standard questionnaire. The following rheumatic and musculoskeletal symptoms were systematically gathered: fatigue, myalgia, joint pain, low back pain, back pain, and neck pain. The type (local, widespread) and locations of myalgia, and joint pain were asked as well. Additionally, the other COVID-19 symptoms were gathered: fever, cough, lack of appetite, dyspnea, diarrhea, sore throat, headache, dizziness, absence of taste, and absence of smell. We evaluated the severity of all these symptoms through a 5-point Likert-type scale.

Statistical analyses

We conducted the analysis with the use of the SPSS v. 21.0 (IBM, Armonk, NY). We analyzed the data and variables through descriptive statistical analyses and expressed the results either as mean ± standard deviation (SD) or number (%). We also tested whether there is an association between the presence of symptoms (i.e., fatigue, myalgia, joint pain) and age, sex, BMI, and duration of hospital stay at 6 months using generalized estimating equations by a selection of binary logistic regression models. The 95% confidence interval (CI) values that did not include 1 indicated statistical significance.

Results

Baseline characteristics

We included a total of 300 COVID-19 survivors in our previous publication presenting 1-month results [14]. At 3 months, there were 9 missing, and at 6 months, there were 6 additional missing survivors. The reasons of these 15 missings were dead (n = 2), could not be reached through telephone (n = 4), did not answer to telephone (n = 7), staying in intensive care unit at the time of assessment (n = 1), and abdominal hysterectomy with bilateral salpingo-oophorectomy (n = 1). We presented the baseline demographic and clinical features of the study cohort at 3 (n = 291) and 6 (n = 285) months in Table 1.
Table 1

Baseline characteristics of study population, which have data for 3- and 6-month follow-up

Parameter3 months (n = 291)6 months (n = 285)
Age, yrs52.54 ± 12.0352.32 ± 12.05
Male173 (59.5)172 (60.4)
Female118 (40.5)113 (39.6)
BMI, kg/m228.96 ± 4.7628.92 ± 4.77
Schooling grade
  Illiterate8 (2.7)8 (2.8)
  Primary101 (34.7)97 (34.0)
  Junior high31 (10.7)31 (10.9)
  High51 (17.5)51 (17.9)
  University100 (34.4)98 (34.4)
Employed126 (43.3)125 (43.9)
Alcohol usage
  Current users15 (5.2)15 (5.3)
  None276 (94.8)270 (94.7)
Smoking status
  Current smoker22 (7.6)22 (7.7)
  Nonsmoker220 (75.6)214 (75.1)
  Ex-smoker49 (16.8)49 (17.2)
Smoking, pack-years26.70 ± 15.9726.70 ± 15.97
Comorbidities
  At least one comorbidity190 (65.3)185 (64.9)
  Hypertension93 (32.0)88 (30.9)
  Diabetes mellitus83 (28.5)80 (28.1)
  Hyperlipidemia26 (8.9)25 (8.8)
  Coronary artery disease42 (14.4)40 (14.0)
  Thyroid diseases12 (4.1)12 (4.2)
  Asthma19 (6.5)19 (6.7)
  COPD6 (2.1)6 (2.1)
  Osteoarthritis8 (2.7)8 (2.8)
  Familial Mediterranean fever4 (1.4)4 (1.4)
  Rheumatoid arthritis5 (1.7)5 (1.7)
  Scleroderma1 (.4)1 (.4)
  Ankylosing spondylitis1 (.4)1 (.4)
  Psoriatic arthritis1 (.4)1 (.4)
  Sjogren syndrome1 (.4)1 (.4)
SARS-CoV-2 RT-PCR positive255 (87.6)249 (87.3)
SARS-CoV-2 infection chest CT scan findings263 (90.4)257 (90.1)
Duration from PCR test to hospitalization, days6.43 ± 3.456.42 ± 3.45
Duration of hospital stay, days7.63 ± 3.967.58 ± 3.95

Data are prevalence (%) or mean ± standard deviation. BMI body mass index, COPD chronic obstructive pulmonary disease, CT computed tomography, RT-PCR reverse transcriptase–polymerase chain reaction, SARS-CoV-2 severe acute respiratory syndrome coronavirus 2

Baseline characteristics of study population, which have data for 3- and 6-month follow-up Data are prevalence (%) or mean ± standard deviation. BMI body mass index, COPD chronic obstructive pulmonary disease, CT computed tomography, RT-PCR reverse transcriptase–polymerase chain reaction, SARS-CoV-2 severe acute respiratory syndrome coronavirus 2

Symptoms at 3 months

At 3 months, 89.0% of survivors had at least one symptom (in other words, 11.0% had no symptoms), 74.6% had at least one rheumatic and musculoskeletal symptom, and 82.1% had at least one other-COVID-19-symptom. Regarding the rheumatic and musculoskeletal symptoms, 59.5% had fatigue, 40.6% had myalgia, and 39.2% had joint pain. Regarding the other COVID-19 symptoms, 46.1% had hair loss, 45.0% had dyspnea, and 26.8% had sweat (Tables 2 and 3, Fig. 1).
Table 2

Prevalence of symptoms at 3 and 6 months

Parameter3 months6 months
At least one symptom259 (89.0)170 (59.6)
At least one rheumatic/musculoskeletal symptom217 (74.6)123 (43.2)
Fatigue173 (59.45)90 (31.58)
Myalgia118 (40.55)43 (15.09)
Joint pain114 (39.18)53 (18.59)
Low back pain72 (24.74)32 (11.23)
Back pain92 (31.62)41 (14.39)
Neck pain60 (20.62)27 (9.47)
At least one other COVID-19 symptom239 (82.1)146 (51.2)
Fever8 (2.75)1 (0.35)
Cough40 (13.75)16 (5.61)
Lack of appetite19 (6.53)6 (2.11)
Dyspnea131 (45.02)72 (25.26)
Diarrhea18 (6.19)8 (2.81)
Sore throat38 (13.06)19 (6.67)
Headache71 (24.40)27 (9.47)
Dizziness55 (18.90)16 (5.61)
Absence of taste24 (8.25)11 (3.86)
Absence of smell37 (12.71)15 (5.26)
Sweat78 (26.80)49 (17.19)
Hair loss134 (46.05)57 (20.00)

Data are prevalence (%)

Table 3

Severity of symptoms at 3 and 6 months

Parameter3 months6 months
Fatigue
  None118 (40.5)195 (68.4)
  Mild62 (21.3)60 (21.1)
  Moderate80 (27.5)21 (7.4)
  Severe25 (8.6)8 (2.8)
  Very severe6 (2.1)1 (.4)
Myalgia
  None173 (59.5)242 (84.9)
  Mild35 (12.0)22 (7.7)
  Moderate55 (18.9)15 (5.3)
  Severe24 (8.2)6 (2.1)
  Very severe4 (1.4)0
Joint pain
  None177 (60.8)232 (81.4)
  Mild34 (11.7)25 (8.8)
  Moderate57 (19.6)22 (7.7)
  Severe21 (7.2)6 (2.1)
  Very severe2 (.7)0
Low back pain
  None219 (75.3)253 (88.8)
  Mild27 (9.3)14 (4.9)
  Moderate34 (11.7)15 (5.3)
  Severe9 (3.1)1 (.4)
  Very severe2 (.7)2 (.7)
Back pain
  None199 (68.4)244 (85.6)
  Mild36 (12.4)23 (8.1)
  Moderate40 (13.7)17 (6.0)
  Severe14 (4.8)1 (.4)
  Very severe2 (.7)0
Neck pain
  None231 (79.4)258 (90.5)
  Mild25 (8.6)17 (6.0)
  Moderate20 (6.9)7 (2.5)
  Severe14 (4.8)3 (1.1)
  Very severe1 (.3)0
Fever
  None283 (97.3)284 (99.6)
  Mild6 (2.1)1 (.4)
  Moderate1 (.3)0
  Severe1 (.3)0
  Very severe
Cough
  None251 (86.3)269 (94.4)
  Mild26 (8.9)12 (4.2)
  Moderate10 (3.4)4 (1.4)
  Severe4 (1.4)0
  Very severe00
Lack of appetite
  None272 (93.5)279 (97.9)
  Mild7 (2.4)3 (1.1)
  Moderate10 (3.4)3 (1.1)
  Severe2 (.7)0
  Very severe00
Dyspnea
  None160 (55.0)213 (74.7)
  Mild58 (19.9)52 (18.2)
  Moderate58 (19.9)17 (6.0)
  Severe14 (4.8)3 (1.1)
  Very severe1 (.3)0
Diarrhea
  None273 (93.8)277 (97.2)
  Mild6 (2.1)7 (2.5)
  Moderate10 (3.4)1 (.4)
  Severe2 (.7)0
  Very severe00
Sore throat
  None253 (86.9)266 (93.7)
  Mild30 (10.3)14 (4.9)
  Moderate5 (1.7)4 (1.4)
  Severe2 (.7)0
  Very severe1 (.3)0
Headache
  None220 (75.6)258 (90.5)
  Mild31 (10.7)22 (7.7)
  Moderate23 (7.9)3 (1.1)
  Severe13 (4.5)2 (.7)
  Very severe4 (1.4)0
Dizziness
  None236 (81.1)269 (94.4)
  Mild26 (8.9)14 (4.9)
  Moderate23 (7.9)1 (.4)
  Severe5 (1.7)1 (.4)
  Very severe1 (.3)0
Absence of taste
  None267 (91.8)274 (96.1)
  Mild3 (1.0)5 (1.8)
  Moderate12 (4.1)4 (1.4)
  Severe7 (2.4)1 (.4)
  Very severe2 (.7)1 (.4)
Absence of smell
  None254 (87.3)270 (94.7)
  Mild9 (3.1)6 (2.1)
  Moderate14 (4.8)5 (1.8)
  Severe8 (2.7)3 (1.1)
  Very severe6 (2.1)1 (.4)
Sweat
  None213 (73.2)236 (82.8)
  Mild20 (6.9)19 (6.7)
  Moderate22 (7.6)11 (3.9)
  Severe20 (6.9)19 (6.7)
  Very severe16 (5.5)0
Hair loss
  None157 (54.0)228 (80.0)
  Mild17 (5.8)38 (13.3)
  Moderate26 (8.9)7 (2.5)
  Severe25 (8.6)10 (3.5)
  Very severe66 (22.7)2 (.7)

Data are prevalence (%)

Fig. 1

Severity of rheumatic/musculoskeletal symptoms and other COVID-19 symptoms at 3 and 6 months. Data are percentage

Prevalence of symptoms at 3 and 6 months Data are prevalence (%) Severity of symptoms at 3 and 6 months Data are prevalence (%) Severity of rheumatic/musculoskeletal symptoms and other COVID-19 symptoms at 3 and 6 months. Data are percentage

Symptoms at 6 months

At 6 months, 59.6% of survivors had at least one symptom (in other words, 40.4% had no symptoms), 43.2% had at least one rheumatic and musculoskeletal symptom, and 51.2% had at least one other COVID-19 symptom. Regarding the rheumatic and musculoskeletal symptoms, 31.6% had fatigue, 18.6% had joint pain, and 15.1% had myalgia. Regarding the other COVID-19 symptoms, 25.3% had dyspnea, 20.0% had hair loss, and 17.2% sweat (Tables 2 and 3, Fig. 1).

Location of arthralgia and myalgia at 6 months

Joint pain and myalgia were widespread (64.2% and 69.8%, respectively); if regional, joint pain was mostly in the knee, foot–ankle, and shoulder, and myalgia was mostly in the lower leg, arm, and shoulder girdle (Table 4).
Table 4

Location of myalgia and arthralgia symptoms at 3 and 6 months

Parameter3 months6 months
Myalgia
  Present118 (100.0)43 (100.0)
  Widespread74 (62.7)30 (69.8)
  Regional44 (37.3)13 (30.2)
  Shoulder girdle6 (13.6)2 (15.4)
  Arm13 (29.5)2 (15.4)
  Upper leg00
  Lower leg25 (56.8)9 (69.2)
Joint pain
  Present114 (100.0)53 (100.0)
  Widespread68 (59.6)34 (64.2)
  Regional46 (40.4)19 (35.8)
  Shoulder8 (17.0)4 (21.1)
  Elbow1 (2.1)0
  Hand-wrist3 (6.4)1 (5.3)
  Hip8 (17.0)2 (10.5)
  Knee15 (31.9)6 (31.6)
  Foot–ankle11 (23.4)6 (31.6)

Data are frequency (percentage)

Location of myalgia and arthralgia symptoms at 3 and 6 months Data are frequency (percentage)

Regression analyses results

In an adjusted model, female patients were more likely to have fatigue (OR: 1.99, 95% CI: 1.18–3.34), myalgia (3.00, 1.51–5.98), and joint pain (3.39, 1.78–6.50) at 6 months, whereas no association was observed between age/BMI/duration of hospital stay and fatigue/myalgia/joint pain (Table 5).
Table 5

Association between the presence of symptoms (i.e., fatigue, myalgia, joint pain) and age, sex, BMI, and duration of hospital stay at 6 months

ParameterFatigueMyalgiaJoint pain
Crude ORAdjusted ORCrude ORAdjusted ORCrude ORAdjusted OR
Age

1.02 (0.99–1.04)

P: 0.104

1.02 (0.99–1.04)

P: 0.186

1.03 (0.99–1.06)

P: 0.081

1.02 (0.99–1.05)

P: 0.223

1.05 (1.02–1.08)

P: 0.001

1.04 (1.01–1.08)

P: 0.004

Female sex

2.14 (1.28–3.55)

P: 0.003

1.99 (1.18–3.34)

P: 0.010

3.06 (1.56–5.99)

P: 0.001

3.00 (1.51–5.98)

P: 0.002

3.47 (1.86–6.47)

P: < 0.001

3.39 (1.78–6.50)

P: < 0.001

BMI

1.06 (1.01–1.12)

P: 0.035

1.05 (0.99–1.11)

P: 0.109

1.04 (0.97–1.11)

P: 0.277

1.02 (0.95–1.08)

P: 0.616

1.04 (0.98–1.11)

P: 0.161

1.02 (0.96–1.08)

P: 0.584

Duration of hospital stay

1.00 (0.94–1.07)

P: 0.986

0.99 (0.93–1.07)

P: 0.87

1.05 (0.97–1.13)

P: 0.219

1.04 (0.96–1.13)

P: 0.325

1.05 (0.98–1.13)

P: 0.217

1.03 (0.94–1.12)

P: 0.566

We performed generalized estimating equations by a selection of binary logistic regression models. In adjusted analyses of age, sex, BMI, and duration of hospital stay, the remaining 3 parameters were controlled in the models. BMI body mass index, OR Odds ratio

Association between the presence of symptoms (i.e., fatigue, myalgia, joint pain) and age, sex, BMI, and duration of hospital stay at 6 months 1.02 (0.99–1.04) P: 0.104 1.02 (0.99–1.04) P: 0.186 1.03 (0.99–1.06) P: 0.081 1.02 (0.99–1.05) P: 0.223 1.05 (1.02–1.08) P: 0.001 1.04 (1.01–1.08) P: 0.004 2.14 (1.28–3.55) P: 0.003 1.99 (1.18–3.34) P: 0.010 3.06 (1.56–5.99) P: 0.001 3.00 (1.51–5.98) P: 0.002 3.47 (1.86–6.47) P: < 0.001 3.39 (1.78–6.50) P: < 0.001 1.06 (1.01–1.12) P: 0.035 1.05 (0.99–1.11) P: 0.109 1.04 (0.97–1.11) P: 0.277 1.02 (0.95–1.08) P: 0.616 1.04 (0.98–1.11) P: 0.161 1.02 (0.96–1.08) P: 0.584 1.00 (0.94–1.07) P: 0.986 0.99 (0.93–1.07) P: 0.87 1.05 (0.97–1.13) P: 0.219 1.04 (0.96–1.13) P: 0.325 1.05 (0.98–1.13) P: 0.217 1.03 (0.94–1.12) P: 0.566 We performed generalized estimating equations by a selection of binary logistic regression models. In adjusted analyses of age, sex, BMI, and duration of hospital stay, the remaining 3 parameters were controlled in the models. BMI body mass index, OR Odds ratio

Discussion

We showed that approximately 3 in 5 patients had at least one symptom with approximately 2 in 5 patients had at least one rheumatic and musculoskeletal symptom and just over than half of the patients had at least one other COVID-19 symptom at 6 months. Fatigue (approximately 1 in 3), joint pain (approximately 1 in 5), and myalgia (approximately 1 in 7 patients) were the most frequent rheumatic and musculoskeletal symptoms. Joint pain and myalgia were mostly widespread. Dyspnea (approximately 1 in 4), hair loss (approximately 1 in 5), and sweat (approximately 1 in 6) were the most frequent other COVID-19 symptoms. Furthermore, female patients were more likely to have fatigue, myalgia, and joint pain at 6 months. In the literature, some observational studies investigated the persistent symptoms in hospitalized COVID-19 survivors beyond 3 months [9-13]. Ghosn and colleagues analyzed 1137 hospitalized survivors (of which 288 admitted to the intensive care unit) and found that 60% had at least one symptom at 6 months, most frequently fatigue, dyspnea, joint pain, and muscle pain [11]. Peghin and colleagues evaluated 599 survivors (outpatients, n = 442; hospital ward unit, n = 134; the intensive care unit, n = 23) and reported that 52% of hospital ward unit survivors had post-COVID-19 syndrome at 6 months [12]. Our data at 6 months showed that 59.6% of survivors had at least one symptom, in consistent with previous two studies [11, 12]. Garrigues and colleagues assessed 120 survivors through telephone surveys after a mean of 111 days after admission either to the hospital ward unit (n = 96) or to the intensive care unit (n = 24) and documented that 54.2% had fatigue, 39.6% had dyspnea, 14.6% had cough, 14.6% had anosmia, and 9.4% had ageusia in the hospital ward unit group [9]. González-Hermosillo and colleagues assessed 130 survivors through telephone surveys and reported that 46.9% had fatigue, 43.8% joint pain, 42.3% had dyspnea, 36.2% muscle pain, 6.9% had anosmia, and 5.4% had ageusia at 6 months [10]. Fortini and colleagues assessed 59 survivors after a median of 123 days after discharge from the hospital ward unit and observed that 42.4% had fatigue, 37.3% had dyspnea, 16.9% had ageusia, 15.2% had anosmia, 11.9% had cough, 8.5% joint pain, and 8.5% myalgia [13]. In those earlier investigations, generally fatigue and dyspnea were the most frequent symptoms. In our study, fatigue (approximately 1 in 3) and dyspnea (approximately 1 in 4) were the two most common symptoms as well. Also, we showed that joint pain and myalgia were each observed in approximately one-sixth of patients, and back pain, low back pain, and neck pain were each observed in approximately one-tenth of patients. With regard to the other COVID-19 symptoms, hair loss and sweat were each observed in approximately one-fifth of patients with less frequently, headache, sore throat, dizziness, cough, absence of smell, lack of appetite, absence of taste, diarrhea, lack of appetite, and fever. Considering the broad range of symptoms, multidisciplinary teams involving rheumatologists should provide a care for COVID-19 survivors. In a study evaluating severe fatigue on 239 COVID-19 patients confirmed by PCR/CT, it was shown that severe fatigue lasted 12–23 weeks after the initial symptoms of the disease. It has been stated that the prevalence of long-term persistence of severe fatigue is high [17]. In another study, excessive fatigue persisted in 26 (33.3%) of 78 patients at 3-month follow-up and in 9 (39.1%) of 23 patients at 6-month follow-up [18]. In our study, severe/very severe fatigue was present in 10.7% of patients at 3 months and 3.2% at 6 months. We showed that female patients were more likely to have fatigue, myalgia, and joint pain at 6 months. This finding was consistent with two previous studies [11, 12], which showed an association of female sex and post-COVID symptoms. Our study provides information on association of female sex with rheumatic/musculoskeletal symptoms, therefore, extends the results of previous studies. In the recent review, possible mechanisms that predominantly contribute to post-acute COVID-19 symptoms were listed as cellular invasion by SARS-COV-2, inflammatory and the immune response, and sequelae of post-critical illness [19]. Also, transforming growth factor beta (TGF-β) overexpression causing a prolonged state of immunosuppression and fibrosis was proposed as a unifying hypothesis mechanism for persistent post-COVID syndrome [20]. However, further research is warranted to elaborate the pathophysiologic mechanisms of wide spectrum of manifestations including rheumatologic/musculoskeletal involvement of post-COVID syndrome.

Limitations and strengths

We must acknowledge the limitations of our study. As we only included COVID-19 survivors who had been treated in hospital ward unit, our results are not generalizable to outpatient survivors or to those who admitted to intensive care unit. Also, it was an uncontrolled cohort study, the results would have been better interpreted if a comparative group who were hospitalized for other reasons than COVID-19 could exist. Furthermore, some factors such as medicines patients used might contribute to developing symptoms; however, the study did not investigate these factors. On the other hand, our study has several strengths. It was a prospective study with a relatively long-term follow-up period.

Conclusion

Approximately 3 in 5 patients had at least one symptom with ≈2 in 5 patients had at least one rheumatic and musculoskeletal symptom and just over than half of the patients had at least one other COVID-19 symptom at 6 months. Fatigue, joint pain, and myalgia were the most frequent rheumatic and musculoskeletal symptoms. Joint pain and myalgia were mostly widespread. Dyspnea, hair loss, and sweat were the most frequent other COVID-19 symptoms. Furthermore, female patients were more likely to have fatigue, myalgia, and joint pain at 6 months. This information guide rheumatologists to understand the nature and features of persistent rheumatic and musculoskeletal symptoms in hospitalized COVID-19 survivors and may translate into improved management of such individuals with persistent symptoms who had recovered from acute COVID-19 infection.

Key Points

Approximately 3 in 5 patients had at least one symptom with ≈2 in 5 patients had at least one rheumatic and musculoskeletal symptom at 6 months

Fatigue, joint pain, and myalgia were the most frequent rheumatic and musculoskeletal symptoms followed by back pain, low back pain, and neck pain

• Dyspnea, hair loss, and sweat were the most frequent other-COVID-19-symptoms

  15 in total

1.  Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration.

Authors:  Jan P Vandenbroucke; Erik von Elm; Douglas G Altman; Peter C Gøtzsche; Cynthia D Mulrow; Stuart J Pocock; Charles Poole; James J Schlesselman; Matthias Egger
Journal:  Epidemiology       Date:  2007-11       Impact factor: 4.822

2.  Prevalence of joint-specific osteoarthritis and joint pain in British Columbia, Canada.

Authors:  Jacek A Kopec; Allison J Heath; Eric C Sayre; Jolanda Cibere; Linda C Li; Carlo A Marra; Ran R Liu; John M Esdaile
Journal:  Rheumatol Int       Date:  2021-10-29       Impact factor: 3.580

3.  Postdischarge rheumatic and musculoskeletal symptoms following hospitalization for COVID-19: prospective follow-up by phone interviews.

Authors:  Fatih Karaarslan; Fulya Demircioğlu Güneri; Sinan Kardeş
Journal:  Rheumatol Int       Date:  2021-05-12       Impact factor: 2.631

4.  Public interest in musculoskeletal symptoms and disorders during the COVID-19 pandemic : Infodemiology study.

Authors:  Sinan Kardeş; Anıl Erdem; Hatice Gürdal
Journal:  Z Rheumatol       Date:  2021-03-29       Impact factor: 1.530

5.  The impact of COVID-19 on familial Mediterranean fever: a nationwide study.

Authors:  Zafer Günendi; Fatma Gül Yurdakul; Hatice Bodur; Ahmet Kıvanç Cengiz; Ülkü Uçar; Hasan Fatih Çay; Nesrin Şen; Yaşar Keskin; Gülcan Gürer; Meltem Alkan Melikoğlu; Duygu Altıntaş; Hülya Deveci; Merve Baykul; Kemal Nas; Remzi Çevik; Ali Yavuz Karahan; Murat Toprak; Sertaç Ketenci; Mehmet Nayimoğlu; İlhan Sezer; Ali Nail Demir; Hilal Ecesoy; Mehmet Tuncay Duruöz; Ozan Volkan Yurdakul; Ayşe Banu Sarıfakıoğlu; Şebnem Ataman
Journal:  Rheumatol Int       Date:  2021-05-25       Impact factor: 2.631

6.  COVID-19: persistence of symptoms and lung alterations after 3-6 months from hospital discharge.

Authors:  Alberto Fortini; Arianna Torrigiani; Serena Sbaragli; Aldo Lo Forte; Andrea Crociani; Paolo Cecchini; Giulia Innocenti Bruni; Antonio Faraone
Journal:  Infection       Date:  2021-06-06       Impact factor: 7.455

7.  Post-Acute COVID-19 Symptoms, a Potential Link with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A 6-Month Survey in a Mexican Cohort.

Authors:  J Antonio González-Hermosillo; Jhanea Patricia Martínez-López; Sofía Antonieta Carrillo-Lampón; Dayanara Ruiz-Ojeda; Sharon Herrera-Ramírez; Luis M Amezcua-Guerra; María Del Rocío Martínez-Alvarado
Journal:  Brain Sci       Date:  2021-06-08

8.  Post-discharge persistent symptoms and health-related quality of life after hospitalization for COVID-19.

Authors:  Eve Garrigues; Paul Janvier; Yousra Kherabi; Audrey Le Bot; Antoine Hamon; Hélène Gouze; Lucile Doucet; Sabryne Berkani; Emma Oliosi; Elise Mallart; Félix Corre; Virginie Zarrouk; Jean-Denis Moyer; Adrien Galy; Vasco Honsel; Bruno Fantin; Yann Nguyen
Journal:  J Infect       Date:  2020-08-25       Impact factor: 6.072

9.  COVID-19 pandemic in Japan.

Authors:  Olga Amengual; Tatsuya Atsumi
Journal:  Rheumatol Int       Date:  2020-11-17       Impact factor: 2.631

10.  African League Against Rheumatism (AFLAR) preliminary recommendations on the management of rheumatic diseases during the COVID-19 pandemic.

Authors:  Richard Oluyinka Akintayo; Rachid Bahiri; Yasser El Miedany; Hakeem Olaosebikan; Asgar Ali Kalla; Adewale Olukayode Adebajo; Angela Nyangore Migowa; Samy Slimani; Ouma Devi Koussougbo; Ben Abdelghani Kawther; Akpabio Akanimo Akpabio; Imad Ghozlani; Dzifa Dey; Waleed A Hassan; Nimmisha Govind; Kavita Makan; Abdelgaffar Mohamed; Eugene Kalman Genga; Mohamed Khattry Ahmed Ghassem; Mohamed Mortada; Wafa Hamdi; Moudjib O Wabi; Mohammed Tikly; Madeleine Ngandeu-Singwe; Christian Scott
Journal:  Clin Rheumatol       Date:  2020-09-02       Impact factor: 2.980

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  17 in total

1.  Sequelae of COVID-19 among previously hospitalized patients up to 1 year after discharge: a systematic review and meta-analysis.

Authors:  Tianqi Yang; Michael Zhipeng Yan; Xingyi Li; Eric H Y Lau
Journal:  Infection       Date:  2022-06-24       Impact factor: 7.455

Review 2.  The Impact of Long COVID-19 on Muscle Health.

Authors:  Montserrat Montes-Ibarra; Camila L P Oliveira; Camila E Orsso; Francesco Landi; Emanuele Marzetti; Carla M Prado
Journal:  Clin Geriatr Med       Date:  2022-03-21       Impact factor: 3.529

Review 3.  Skeletal Muscle and COVID-19: The Potential Involvement of Bioactive Sphingolipids.

Authors:  Elisabetta Meacci; Federica Pierucci; Mercedes Garcia-Gil
Journal:  Biomedicines       Date:  2022-05-04

4.  DMARD disruption, rheumatic disease flare, and prolonged COVID-19 symptom duration after acute COVID-19 among patients with rheumatic disease: A prospective study.

Authors:  Michael Di Iorio; Claire E Cook; Kathleen M M Vanni; Naomi J Patel; Kristin M D'Silva; Xiaoqing Fu; Jiaqi Wang; Lauren C Prisco; Emily Kowalski; Alessandra Zaccardelli; Lily W Martin; Grace Qian; Tiffany Y-T Hsu; Zachary S Wallace; Jeffrey A Sparks
Journal:  Semin Arthritis Rheum       Date:  2022-05-18       Impact factor: 5.431

5.  Evaluation of Muscle Mass and Stiffness with Limb Ultrasound in COVID-19 Survivors.

Authors:  Sarah Damanti; Marta Cilla; Bruno Tuscano; Rebecca De Lorenzo; Giuseppina Manganaro; Aurora Merolla; Giacomo Pacioni; Chiara Pomaranzi; Valeria Tiraferri; Sabina Martinenghi; Giordano Vitali; Emanuele Bosi; Caterina Conte; Andrea Giustina; Moreno Tresoldi; Patrizia Rovere Querini
Journal:  Front Endocrinol (Lausanne)       Date:  2022-02-17       Impact factor: 5.555

6.  DMARD disruption, disease flare, and prolonged symptom duration after acute COVID-19 among participants with rheumatic disease: A prospective study.

Authors:  Michael Di Iorio; Claire E Cook; Kathleen M M Vanni; Naomi J Patel; Kristin M D'Silva; Xiaoqing Fu; Jiaqi Wang; Lauren C Prisco; Emily Kowalski; Alessandra Zaccardelli; Lily W Martin; Grace Qian; Tiffany Y-T Hsu; Zachary S Wallace; Jeffrey A Sparks
Journal:  medRxiv       Date:  2022-02-09

Review 7.  Post-acute Sequelae in COVID-19 Survivors: an Overview.

Authors:  Adekunle Sanyaolu; Aleksandra Marinkovic; Stephanie Prakash; Anne Zhao; Vyshnavy Balendra; Nafees Haider; Isha Jain; Teodora Simic; Chuku Okorie
Journal:  SN Compr Clin Med       Date:  2022-04-06

Review 8.  The Short- and Long-Term Clinical, Radiological and Functional Consequences of COVID-19.

Authors:  Yang Gao; Wei-Quan Liang; Yi-Ran Li; Jian-Xing He; Wei-Jie Guan
Journal:  Arch Bronconeumol       Date:  2022-04-13       Impact factor: 6.333

Review 9.  COVID-19 in Joint Ageing and Osteoarthritis: Current Status and Perspectives.

Authors:  Marianne Lauwers; Manting Au; Shuofeng Yuan; Chunyi Wen
Journal:  Int J Mol Sci       Date:  2022-01-10       Impact factor: 5.923

10.  Global Trends and Research Hotspots in Long COVID: A Bibliometric Analysis.

Authors:  Hongxia Jin; Lu Lu; Haojun Fan
Journal:  Int J Environ Res Public Health       Date:  2022-03-21       Impact factor: 3.390

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