Table 2.
Characteristics of Relevant Studies
| Author, Year Country | Sample Size (Male/Female) | Hospitalization | Type of Study | Time Point(s) | MSK Pain Type and Prevalence at Follow-Up(s) | Pain Characterizations and Location | Risk Factors | Hypothesized Mechanisms |
|---|---|---|---|---|---|---|---|---|
|
Adnan et al (2021)27 Pakistan |
55 (35–20) | No | Cross-sectional study | Not clear | Myalgia and Arthralgia (63.63%) in male (36.36%) in female |
Back ache 45.45% Knee joint 18.18% Mixed 18.18% Hip joint 9.09% Ankle joint 5.45% |
The prevalence of Myalgia and Arthralgia increase with aging and was higher in the lower socio-economic status. | Not available |
|
Bai et al (2021)28 Italy |
377 (240–137) | Yes | Prospective cohort study | Median of 6 weeks from symptom onset | Musculoskeletal pain 21.2% | Joint pain or myalgia No, ever (57%) Ongoing (21.2%) Resolved (19.6%) Unknown (2.1%) |
Female gender, older age and active smoking were associated with long COVID syndrome, but not severity of the acute disease. | Not available |
|
Bellan et al (2021)89 Italy |
200 (122/78) | Yes | Prospective longitudinal study | Baseline, 17 weeks and 52 weeks. | Arthralgia/myalgia Baseline (19.3%) At week 17 (6.5%) At week 52 (21.9%) |
Not available | Not available | Not available |
|
Bileviciute-ljungar et al (2022)31 Sweden |
100 (18/82) | No (90%) Yes (10%) |
Cross-sectional study | A mean of 47 weeks since the start of the infection. | Head/face 27% Throat/neck 5% Shoulder/arms 5% Chest 16% Legs 12% Pain sites varied 15% |
The mean value of pain intensity during the last week was 4.4/10 75% reported generalized pain. |
Comorbidities Wealthy middle-aged women |
Not available |
|
Carfì et al (2020)90 Italy |
143 (90/53) | Yes | Case series | Mean of 7 weeks after onset of the first COVID-19 symptoms | Arthralgia 27.3% | Not available | Not available | Not available |
|
Carvalho-Soares et al (2021)26 Brazil |
46 (21/25) | Yes | Controlled cross-sectional study | Mean 16 week after hospital discharge | De novo pain 65.2% De novo chronic pain 19.6% Location of de novo pain: Head and neck 66.7% Upper limbs 16.7% Thorax and/or abdomen 16.7% Dorsal and/or low back 46.7% Lower limbs 36.7% Widespread pain 23.3% |
COVID-19 pain was more frequently located in the head/neck and lower limbs Frequency of de novo pain: <15 days/month 13.3% ≥ 15 days/month 50% Trend of de novo pain after discharge: Improved 17.2% Unchanged 44.8% Worsened 0% Not informed 37.9% |
Not available | Not available |
|
Carvalho-Schneider et al (2021)36 France |
150 (66/84) | Yes | Prospective cohort study | 1 week, 4 weeks and 8.5 Weeks | Chest pain Onset (14%) Day 30 (18%) Day 60 (13.1%) Arthralgia Onset (-) Day 30 (9.8%) Day 60 (16.3%) |
Not available | Not available | Not available |
|
Ferna ´ndez-de-las-Pen ~as et al (2021)38 Spain |
738 Patients reporting myalgia at admission (n=369) (176/193) Control: Patients without myalgia at admission (n=369) (176/193) |
Yes | Case-control study | A mean of 31 weeks after hospital discharge | Overall prevalence of MSK post-covid pain of 38%, 31 weeks post-discharge -With myalgia group (42.5%) -without myalgia group (34.5%) |
Musculoskeletal pain Locations (Cervical spine, Thorax-chest, Lumbar spine, Widespread pain, Upper extremity, Shoulder area, Wrist-elbow, Lower extremity, Hip region, Knee) |
Presence of myalgia at the onset of SARS-cov-2 and hospital admission | Prolonged inflammatory response associated with Covid-19 (cytokine mediated), viral neurotropic properties, Lead to hyperexcitability of peripheral and central nervous systems (nociplastic pain), Emotional and social factors (psychosocial mechanisms) |
|
Galal et al (2021)91 Egypt |
430 (156/274) | Yes | Cross-sectional study | Follow-up mean 5 weeks | Myalgia 60% Arthralgia 57.2% |
Not available | Not available | Not available |
|
Goërtz et al (2020)32 Netherlands |
2113 (310/1803) | 112 hospitalized 2001 non-hospitalized |
Cross-sectional study | Mean 11 weeks | Myalgia (36%) Pain between shoulder blades (33%) Arthralgia (22%) |
Not available | Not available | Not available |
|
Graham et al (2021)44 USA |
100 (30/70) (n=50 lab. +ve PCR Control n=50 -ve PCR) |
No | Prospective study | Baseline and an average of 20 weeks after symptom onset | Myalgia Overall 55% +ve 60% -ve 50% Pain other than chest Overall 43% +ve 40% -ve 46% |
Not available | Not available | Not available |
|
Havervall et al (2021)92 Sweden |
323 (55/268) | No | Cross-sectional study | At the 34-week follow-up Participants reported symptoms ≥8, ≥17 and ≥34 weeks |
Myalgia/Arthralgia ≥8 weeks (2.2%) ≥17 weeks (1.9%) ≥34 weeks (0.6%) |
Not available | Not available | Not available |
|
Horwitz et al (2021)93 USA |
126 (75/51) | Yes | Prospective observational study | 4 weeks and 26 weeks post-hospital discharge | Muscle/body ache (38%) Arthralgia (33%) Chest pain (21%) |
Not available | Not available | Not available |
|
Huang et al (2021)61 China |
1276 (681/595) | Yes | Ambi-directional cohort study | 26 weeks and 52 weeks after symptoms onset. | Myalgia 26 weeks (3%) 52 weeks (4%) Arthralgia 26 weeks (11%) 52 weeks (12%) Chest pain 26 weeks (5%) 52 weeks (7%) |
Not available | Not available | Not available |
|
Iqbal et al (2021)41 Pakistan |
158 (71/87) | No | Cross-sectional study | Mean of 5 weeks since recovery (from acute phase) | Arthralgia (47.5%) Chest pain (35.4%) |
Not available | Not available | Not available |
|
Jacobs et al (2020)94 Italy |
183 (112/71) | Yes | Prospective cohort study | Baseline and 5 weeks post-hospitalization | Myalgia 51% Arthralgia 54.7% |
Not available | Not available | Not available |
|
Jacobson et al (2021)33 USA |
118 (63/55) | Hospitalized n=22 Non-hospitalized n=96 |
Cross-sectional study | Median of 17 weeks | Myalgia Total 17.9% Hospitalized 22.7% Non-hospitalized 16.8% Chest pain Total 13.7% Hospitalized 9.1% Non-hospitalized 14.7% |
Not available | Not available | Not available |
|
Kamal et al (2020)95 Egypt |
287 (103/184) | Yes | Cross-sectional study | Median of 8.5 weeks | Arthralgia (31.4%) Chest pain (28.9%) |
Not available | Not available | Not available |
|
Karaarslan et al (2022)30 Turkey |
285 (172/173) | Yes | Prospective cohort study | 13 weeks and 26 weeks following the hospitalization. | Myalgia 13 weeks (40.55%) 26 weeks (15.09%) Arthralgia 13 weeks (39.18%) 26 weeks (18.59%) Low back pain 13 weeks (24.74%) 26 weeks (11.23%) Back pain 13 weeks (31.62%) 26 weeks (14.39%) Neck pain 13 weeks (20.62%) 26 weeks (9.47%) |
Severity, type, and locations of rheumatic and musculoskeletal symptoms Arthralgia and myalgia were mostly widespread (64.2% and 69.8%, respectively); if regional, arthralgia was mostly in the knee, foot-ankle, and shoulder, and myalgia was mostly in the lower leg, arm, and shoulder girdle. |
Female patients were more likely to have myalgia and joint pain at 26 weeks. | Immune response and pro-inflammatory cytokines generated after infection/direct invasion/injury of musculoskeletal cells by SARS-cov-2 through the angiotensin-converting enzyme 2 (ACE2) receptor Cellular invasion by SARS-COV-2, inflammatory and the immune response, and sequelae of post-critical illness, transforming growth factor beta (TGF-β) overexpression causing a prolonged state of immunosuppression and fibrosis |
|
Leite et al (2021)34 Brazil |
1696 (745/951) | Yes | Cross-sectional study | 4 weeks after hospital discharge | Pain Total (28.5) 26.4%-30.8% ICU (33.9) 29.0%-39.1% Ward (27.1) 24.7%-29.6% |
Not available | Not available | Not available |
|
Leth et al (2021)37 Denmark |
49 (21/28) | Yes | Prospective longitudinal study | Baseline, 6 weeks, and 12 weeks | Myalgia Baseline (47%) 6 weeks (16%) 12 weeks (35%) Chest pain Baseline (17%) 6 weeks (10%) 12 weeks (20%) |
Not available | Not available | Not available |
|
Lu et al (2020)35 China |
60 (34/26) | Yes | Prospective study | Baseline and 13 weeks after hospital discharge | Myalgia At acute stage (15%) At follow-up (25%) |
Not available | Not available | Not available |
|
Magdy et al (2021)39 Egypt |
90 45 patients with post-COVID pain (15/30) 45 recovered from COVID-19 without pain (16/29) |
Yes | Case-control study | Recovery duration 8.5 weeks | VAS [median] 8 (6–9) Frequency (days per week) 7 (3–7) Site of pain: Hands and feet (20%) Arms and legs (66.7%) Radicular (13.3%) |
Pain character (n=45) Burning (33.3%) Painful cold (13.3%) Electric shock (37.8%) Burning and electric shock (11.1%) Burning and painful cold (4.4%) Associated symptoms: Tingling (15.6%) Numbness (42.2%) Itching (8.9%) Pins and needles (13.3%) Numbness and itching (4.4%) Numbness and pins and needles (8.9%) Pins, needles and tingling (2.2%) Pins, needles, numbness and tingling (4.4%) Hypothesia to touch (68.9%) Hypothesia to prick (31.1%) Allodynia: Yes (37.8%) No (62.2%) |
Depression, Azithromycin use, moderate and severe COVID-19 are independent predictors of persistent post-COVID-19 pain. Serum NFL may serve as a potential biomarker for persistent neuropathic pain after COVID-19. | Direct neuro- invasive potential of SARS-cov-2. And massive release of pro- inflammatory mediators (cytokine storm) The higher the chance of exposure to the injurious effect of the virus, either through a longer duration of the COVID-19 infection or the severity of the infection, the greater the likelihood of pain. Both depression and neuropathic pain may arise from a common underlying inflammatory process induced by the cytokine storm. |
|
Mahmud et al (2021)96 Bangladesh |
355 (207/148) N=162 with post-covid syndrome (symptomatic) N=193 no post-covid symptoms |
Yes | Prospective cohort study | 4 weeks after clinical improvement | Myalgia Total (0.6%) Symptomatic (1.2%) Arthralgia Total (1.4%) Symptomatic (4.8%) Chest pain Total (0.8%) Symptomatic (1.8%) |
Not available | Not available | Not available |
|
Mohiuddin Chowdhury et al (2021)25 Bangladesh |
313 (251/62) | Yes (n=62) No (n=251) |
Prospective multicenter cross-sectional study | 4 weeks following recovery. | Arthralgia (0.6%) Mild body ache (0.3%) Back pain (0.3%) |
Not available | Not available | Not available |
|
Moradian et al (2020)97 Iran |
200 (160/40) | Yes | Cross-sectional study | 6 weeks after discharge | Myalgia 8% | Not available | Not available | Not available |
|
Moreno-Perez et al (2021)98 Spain |
277 (146/131) | Severe (hospitalized) Mild (hospital follow-up) |
Prospective covid study | 8–12 weeks | Myalgias-arthralgias 19.6% | Not available | Not available | Not available |
|
Ong et al (2021)66 Singapore |
288 (243/45) | Yes | Prospective longitudinal multicenter cohort study | 4 weeks, 12 weeks, and 25 weeks post-symptom onset | Myalgia at 12 weeks or 25 weeks (22.7%) | Not available | Not available | Not available |
|
Stavem et al (2021)99 Norway |
451 (198/253) | No | Cross-sectional study | 6–26 weeks after symptom onset | Arthralgia (9%) Myalgia (8.5%) |
Not available | Not available | Not available |
|
Sykes et al (2021)42 UK |
134 (88/46) Ward-based n=107 ICU n=27 |
Yes | Cross-sectional study | Median of 16 weeks | Myalgia Total 51.5% Ward-based 49.5% ICU 59.3% |
Not available | Not available | Not available |
|
Taquet et al (2021)40 USA |
273,618 (121,461/152,157) | No | Retrospective cohort study | From 1 day to 26 weeks post-diagnosis From 13 weeks to 26 weeks post-diagnosis |
Myalgia From 1 day to 26 weeks (3.24%) From 13 weeks to 26 weeks (1.54%) Pain From 1 day to 26 weeks (11.60%) From 13 weeks to 26 weeks (7.19%) |
Not available | Females were significantly more likely to have myalgia **p < 0.01/Patients with more severe illnesses (as proxied by hospitalization, ITU admission, or leukocytosis) were less likely to have myalgia/myalgia was more common in women and in younger patients, and notably so in those who had been less acutely ill | Not available |
|
Venturelli et al (2021)100 Italy |
767 (515/252) | Yes | Cross-sectional study | Median of 11.5 weeks after discharge | Myalgia Female (3.6%) Male (3.9%) Chest pain Female (3.6%) Male (2.9%) |
Not available | Not available | Not available |
|
Wahlgren et al (2022)29 Sweden |
158 (97/61) | Yes | Descriptive ambidirectional cohort study | 21 weeks | Pain (34.8%) Neuropathic type pain (5.1%) Nociceptive type pain (31.0%) Headache (17.7%) Pain in extremities (10.1%) Generalized pain (3.8%) Trunk (2.5%) |
34.8% reported new or aggravated pain. Nociceptive-type pain was considerably more common than neuropathic-type pain For nociceptive pain, headache was the most common pain localization. |
Not available | Not available |
|
Xiong et al (2021)101 China |
538 (245/293) | Yes | Retrospective cohort study | 12 weeks | Arthralgia 7.6% Myalgia 4.5% Chest pain 12.3% |
Not available | Not available | Not available |
|
Zhou et al (2021)102 China |
89 (46/43) | Yes | Longitudinal study | 3 weeks after discharge | Myalgia and arthralgia (2.2%) | Not available | Not available | Not available |