Tag: musculoskeletal system

Structural and functional impairments of skeletal muscle in patients with post-acute sequelae of SARS-CoV-2 infection

Abstract:

Background: Following acute COVID-19, a substantial proportion of patients showed symptoms and sequelae for several months, namely the post-acute sequelae of COVID-19 (PASC) syndrome. Major phenomena are exercise intolerance, muscle weakness and fatigue. We aimed to investigate the physiopathology of exercise intolerance in patients with PASC syndrome by structural and functional analyses of skeletal muscle.

Methods: At least 3 months after infection, non-hospitalized patients with PASC (n=11,ys:54±11; PASC) and patients without long-term symptoms (n=12,ys:49±9; CTRL) visited the laboratory on four non-consecutive days. Spirometry, lung diffusion capacity and quality of life were assessed at rest. Cardiopulmonary incremental exercise test was performed. Oxygen consumption (VO2) kinetics were determined by moderate-intensity exercises. Muscle oxidative capacity (k) was assessed by near-infrared spectroscopy. Histochemical analysis, O2 flux (JO2) by high-resolution respirometry, and quantification of key molecular markers of mitochondrial biogenesis and dynamics were performed in vastus lateralis biopsies.

Results: Pulmonary and cardiac functions were within normal range in all patients. VO2peak was lower in PASC than CTRL (24.7±5.0vs32.9±7.4mL*min-1*kg-1, respectively, P<.05). VO2 kinetics was slower in PASC than CTRL (41±12vs30±9s-1, P<.05). k was lower in PASC than CTRL (1.54±0.49vs2.07±0.51min-1, P<.05). Citrate synthase, PGC1alfa and JO2 for mitochondrial complex II were significantly lower in PASC vs CTRL (all P<.05).

Conclusion: In our cohort of patients with PASC, we showed limited exercise tolerance mainly due to “peripheral” determinants. Substantial reductions were observed for biomarkers of mitochondrial function, content, and biogenesis. PASC syndrome appears to negatively impact skeletal muscle function, although the disease is an heterogenous condition.

Source: Colosio M, Brocca L, Gatti M, Neri M, Crea E, Cadile F, Canepari M, Pellegrino MA, Polla B, Porcelli S, Bottinelli R. Structural and functional impairments of skeletal muscle in patients with post-acute sequelae of SARS-CoV-2 infection. J Appl Physiol (1985). 2023 Sep 7. doi: 10.1152/japplphysiol.00158.2023. Epub ahead of print. PMID: 37675472. https://journals.physiology.org/doi/abs/10.1152/japplphysiol.00158.2023 (Full text available as PDF file)

Myopathy as a cause of Long COVID fatigue: Evidence from quantitative and single fiber EMG and muscle histopathology

Highlights:

• Myopathic changes in qEMG and/or increased jitter in sfEMG were seen in 63% of 84 patients with Long COVID neuromuscular symptoms.

• Low quality of life score correlated with higher mean jitter values in sfEMG but not with qEMG measures.

• Electron microscopy showed damage of terminal nerves and motor endplate.Abstract:

Objective: To describe neurophysiological abnormalities in Long COVID and correlate quantitative electromyography (qEMG) and single fiber EMG (sfEMG) results to clinical scores and histopathology.

Methods: 84 patients with non-improving musculoskeletal Long COVID symptoms were examined with qEMG and sfEMG. Muscle biopsies were taken in a subgroup.

Results: Mean motor unit potential (MUP) duration was decreased in ≥1 muscles in 52% of the patients. Mean jitter was increased in 17% of the patients in tibialis anterior and 25% in extensor digitorum communis. Increased jitter was seen with or without myopathic qEMG. Low quality of life score correlated with higher jitter values but not with qEMG measures. In addition to our previously published mitochondrial changes, inflammation, and capillary injury, we show now in muscle biopsies damage of terminal nerves and motor endplate with abundant basal lamina material. At the endplate, axons were present but no vesicle containing terminals. The post-synaptic cleft in areas appeared atrophic with short clefts and coarse crests.

Conclusions: Myopathic changes are common in Long COVID. sfEMG abnormality is less common but may correlate with clinical scores. sfEMG changes may be due to motor endplate pathology.

Significance: These findings may indicate a muscle pathophysiology behind fatigue in Long COVID.

Source: Jane Agergaard, Benjamin Yamin Ali Khan, Thomas Engell-Sørensen, Berit Schiøttz-Christensen, Lars Østergaard, Eva K. Hejbøl, Henrik D. Schrøder, Henning Andersen, Jakob Blicher, Thomas Holm Pedersen, Thomas Harbo, Hatice Tankisi,
Myopathy as a cause of Long COVID fatigue: Evidence from quantitative and single fiber EMG and muscle histopathology,
Clinical Neurophysiology, 2023, ISSN 1388-2457, https://doi.org/10.1016/j.clinph.2023.01.010.
https://www.sciencedirect.com/science/article/pii/S1388245723000196 (Full text)

Musculoskeletal complications in long COVID-19: A systematic review

Abstract:

Background: Coronavirus disease 2019 (COVID-19) has crippled humanity since early 2020. Various sequelae of COVID-19 have been reported in different body systems. Musculoskeletal symptoms are widely reported during COVID-19 infection, but musculoskeletal complications in long COVID-19 are underreported. However, post-COVID-19 survivors have reported complaints of persisting or new-onset fatigue, myalgia, arthralgia, arthritis, muscle weakness, etc in clinical practice. The well-known detrimental effects of steroids on the musculoskeletal system coupled with their over-the-counter availability can also be anticipated since they were the cornerstone of life-saving management in this pandemic.

Aim: To determine the musculoskeletal complications in long COVID.

Methods: We performed a systematic review of ‘systematic reviews and meta-analyses’.

Results: Of the 63 articles screened, 24 articles were included. Two articles specifically discussed children and adolescents. One article discussed rehabilitation intervention. No article addressed rehabilitation of musculoskeletal issues in long COVID-19 in particular. Fatigue was the most common musculoskeletal complication.

Conclusion: Fatigue is found to be very common along with myalgia and arthralgia. There were no studies on rehabilitation intervention in musculoskeletal complications specifically. Considering the lacuna in literature and the needs of the current situation, further studies are warranted to standardize effective rehabilitation interventions in musculoskeletal complications. More homogenous studies are needed. Studies on functional impairment due to musculoskeletal involvement are essential.

Source: Swarnakar R, Jenifa S, Wadhwa S. Musculoskeletal complications in long COVID-19: A systematic review. World J Virol. 2022 Nov 25;11(6):485-495. doi: 10.5501/wjv.v11.i6.485. PMID: 36483107; PMCID: PMC9724204. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9724204/ (Full text)

Musculoskeletal symptoms in patients with Long COVID: A cross-sectional study on Iranian patients

Abstract:

Background and objectives: Latest studies have revealed that an increasing number of Corona Virus Disease of 2019 (COVID-19) patients may continue to feel symptoms after the acute phase. This study aimed to evaluate the prevalence of musculoskeletal symptoms after the acute phase of COVID-19 and its associated factors.

Methods: We designed a cross-sectional study from January 2021 to April 2021. An online questionnaire was designed and sent to patients who had recovered from COVID-19. The questionnaire contained questions on participants’ demographic characteristics, COVID-19 course at its acute phase, and musculoskeletal symptoms after recovering from COVID-19. Musculoskeletal symptoms associations with patients’ characteristic and COVID-19 course was evaluated.

Result: 239 patients, including 72 (30.1%) males and 167 (69.9%) females with a mean age of 37.96 years (SD=11.19), were included in the study. 98.74% of our patients had experienced at least one musculoskeletal symptom after recovering from COVID-19, and the most common symptom was fatigue, as 91.2% of participants experienced this symptom, followed by myalgia, headache, and low back pain. High BMI, hospitalization, and ICU admission were associated with a higher risk of musculoskeletal symptoms.

Conclusion: This study indicated a high prevalence of persistent musculoskeletal symptoms among patients who recovered from COVID-19. Modifiable factors, such as BMI, can be targeted to reduce the prevalence of musculoskeletal symptoms in COVID-19 survivors and reduce its burden.

Source: Azadvari M, Haghparast A, Nakhostin-Ansari A, Emami Razavi SZ, Hosseini M. Musculoskeletal symptoms in patients with Long COVID: A cross-sectional study on Iranian patients. Heliyon. 2022 Aug 11:e10148. doi: 10.1016/j.heliyon.2022.e10148. Epub ahead of print. PMID: 35971463; PMCID: PMC9367176. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9367176/ (Full text)

Clinical Characteristics and Mechanisms of Musculoskeletal Pain in Long COVID

Abstract:

Objective: Musculoskeletal (MSK) pain is being increasingly reported by patients as one of the most common persistent symptoms in post-COVID-19 syndrome or Long COVID. However, there is a lack of understanding of its prevalence, characteristics, and underlying pathophysiological mechanisms. The objective of this review is to identify and describe the features and characteristics of MSK pain in Long COVID patients.

Methods: The narrative review involved a literature search of the following online databases: MEDLINE (OVID), EMBASE (OVID), CINAHL, PsyclNFO, and Web of Science (December 2019 to February 2022). We included observational studies that investigated the prevalence, characteristics, risk factors and mechanisms of MSK pain in Long COVID. After screening and reviewing the initial literature search results, a total of 35 studies were included in this review.

Results: The overall reported prevalence of MSK pain in Long COVID ranged widely from 0.3% to 65.2%. The pain has been reported to be localized to a particular region or generalized and widespread. No consistent pattern of progression of MSK pain symptoms over time was identified. Female gender and higher BMI could be potential risk factors for Long COVID MSK pain, but no clear association has been found with age and ethnicity. Different pathophysiological mechanisms have been hypothesized to contribute to MSK pain in Long COVID including increased production of proinflammatory cytokines, immune cell hyperactivation, direct viral entry of neurological and MSK system cells, and psychological factors.

Conclusion: MSK pain is one of the most common symptoms in Long COVID. Most of the current literature on Long COVID focuses on reporting the prevalence of persistent MSK pain. Studies describing the pain characteristics are scarce. The precise mechanism of MSK pain in Long COVID is yet to be investigated. Future research must explore the characteristics, risk factors, natural progression, and underlying mechanisms of MSK pain in Long COVID.

Source: Khoja O, Silva Passadouro B, Mulvey M, Delis I, Astill S, Tan AL, Sivan M. Clinical Characteristics and Mechanisms of Musculoskeletal Pain in Long COVID. J Pain Res. 2022 Jun 17;15:1729-1748. doi: 10.2147/JPR.S365026. PMID: 35747600; PMCID: PMC9212788. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9212788/ (Full text)

What Do We Need to Know About Musculoskeletal Manifestations of COVID-19?: A Systematic Review

Abstract:

»: COVID-19 is a disease that is challenging science, health-care systems, and humanity. An astonishingly wide spectrum of manifestations of multi-organ damage, including musculoskeletal, can be associated with SARS-CoV-2.

»: In the acute phase of COVID-19, fatigue, myalgia, and arthralgia are the most common musculoskeletal symptoms.

»: Post-COVID-19 syndrome is a group of signs and symptoms that are present for >12 weeks. The associated musculoskeletal manifestations are fatigue, arthralgia, myalgia, new-onset back pain, muscle weakness, and poor physical performance.

»: Data on COVID-19 complications are growing due to large absolute numbers of cases and survivors in these 2 years of the pandemic. Additional musculoskeletal manifestations encountered are falls by the elderly, increased mortality after hip fracture, reduced bone mineral density and osteoporosis, acute sarcopenia, rhabdomyolysis, Guillain-Barré syndrome, muscle denervation atrophy, fibromyalgia, rheumatological disease triggering, septic arthritis, adhesive capsulitis, myositis, critical illness myopathy, onset of latent muscular dystrophy, osteonecrosis, soft-tissue abscess, urticarial vasculitis with musculoskeletal manifestations, and necrotizing autoimmune myositis.

»: A wide range of signs and symptoms involving the musculoskeletal system that affect quality of life and can result in a decrease in disability-adjusted life years. This powerful and unpredictable disease highlights the importance of multimodality imaging, continuing education, and multidisciplinary team care to support preventive measures, diagnosis, and treatment.

Source: Pires RE, Reis IGN, Waldolato GS, Pires DD, Bidolegui F, Giordano V. What Do We Need to Know About Musculoskeletal Manifestations of COVID-19?: A Systematic Review. JBJS Rev. 2022 Jun 3;10(6). doi: 10.2106/JBJS.RVW.22.00013. PMID: 35658089. https://pubmed.ncbi.nlm.nih.gov/35658089/

Relationship between musculoskeletal symptoms and blood markers of oxidative stress in patients with chronic fatigue syndrome

Abstract:

In 21 patients with chronic fatigue syndrome (CFS) versus 20 normal subjects, we investigated the oxidant/antioxidant balance and its correlation with muscle symptoms. Patients versus controls showed significantly: lower Lag Phase and Vitamin E (Vit E) concentrations in plasma and low-density lipoproteins (LDL), higher LDL thiobarbituric acid reactive substances (TBARS), higher fatigue and lower muscle pain thresholds to electrical stimulation.

A significant direct linear correlation was found between fatigue and TBARS, thresholds and Lag Phase, thresholds and Vit E in plasma and LDL. A significant inverse linear correlation was found between fatigue and Lag Phase, fatigue and Vit E, thresholds and TBARS. Increased oxidative stress and decreased antioxidant defenses are related to the extent of symptomatology in CFS, suggesting that antioxidant supplementation might relieve muscle symptoms in the syndrome.

 

Source: Vecchiet J, Cipollone F, Falasca K, Mezzetti A, Pizzigallo E, Bucciarelli T, De Laurentis S, Affaitati G, De Cesare D, Giamberardino MA. Relationship between musculoskeletal symptoms and blood markers of oxidative stress in patients with chronic fatigue syndrome. Neurosci Lett. 2003 Jan 2;335(3):151-4. http://www.ncbi.nlm.nih.gov/pubmed/12531455

 

Abnormalities of carnitine metabolism in chronic fatigue syndrome

Abstract:

Carnitine may be involved in the pathogenesis of the chronic fatigue syndrome (CFS). However, no information about the cellular metabolism of carnitine in CFS patients is currently available. Therefore, we aimed to measure the levels of carnitine (total, free and short-chain) in both peripheral blood lymphocytes (PBLs) and sera from patients with CFS.

The serum levels of total, free and short-chain were comparable in CFS patients, considered as the whole group, to those in healthy control subjects, even though a trend indicating slightly reduced serum concentrations of free carnitine was observed in male patients with CFS. In contrast, the concentrations of total, free and short-chain carnitine in PBLs from patients with CFS were significantly lower than in cells from healthy controls.

Our study indicates that patients with CFS require exogenous carnitine supplementation. The low carnitine concentrations in PBLs from patients with CFS probably reflect the carnitine deficiency occurring in other tissues, including the skeletal muscles. The low cellular concentrations of carnitines may help to explain both the immunological abnormalities and the impaired energy metabolism in skeletal muscles.

 

Source: Majeed T, de Simone C, Famularo G, Marcellini S, Behan PO. Abnormalities of carnitine metabolism in chronic fatigue syndrome. Eur J Neurol. 1995 Nov;2(5):425-8. doi: 10.1111/j.1468-1331.1995.tb00151.x. http://www.ncbi.nlm.nih.gov/pubmed/24283722

 

Silicone breast implant–associated musculoskeletal manifestations

Abstract:

Three hundred consecutive women with silicone breast implants (SBI), referred to the arthritis clinic with a variety of musculoskeletal complaints, were evaluated for the presence of underlying connective tissue disease. A complete history and physical examination were performed, as well as laboratory testing for C-reactive protein, rheumatoid factor; and autoantibody determination by indirect immunofluorescence and immunodiffusion.

The group mean age was 44.4 years (range 25-69), the mean time from initial implant surgery to appearance of symptoms was 6.8 years (range: 6m-19y) and 83.3% of women studied had clinical manifestations highly suggestive of an underlying connective tissue disorder. Fifty-four percent met criteria for fibromyalgia and/or chronic fatigue syndrome, distinct connective tissue diseases was detected in 11%, undifferentiated connective tissue disease or human adjuvant disease was found in 10.6%, and a variety of disorders such as angioneurotic oedema, frozen shoulder, multiple sclerosis-like syndrome were present.

Several other miscellaneous conditions including recurrent unexplained low grade fever, hair loss, skin rash, sicca symptoms, Raynaud’s phenomenon, carpal tunnel syndrome, memory loss, headaches, chest pain, and shortness of breath were also seen accompanying specific and non-specific conditions. Seventy percent of patients who underwent explanation of the implants reported improvement of their systemic symptomatology.

A significant proportion of SBI patients referred for rheumatic evaluation have clinical manifestations highly suggestive of an underlying connective tissue disease. Furthermore, improvement of their symptomatology follows explanation of the implants in over half of the patients.

 

Source: Cuellar ML, Gluck O, Molina JF, Gutierrez S, Garcia C, Espinoza R. Silicone breast implant–associated musculoskeletal manifestations. Clin Rheumatol. 1995 Nov;14(6):667-72. http://www.ncbi.nlm.nih.gov/pubmed/8608686

 

Rheumatic fever and disorders of the musculoskeletal system

Abstract:

New information provided on the pathogenesis and management of rheumatic fever is of current interest. Invasive disease by group A streptococci has been shown to be due to production of toxin A. The natural history and immunopathologic basis for chronic Lyme arthritis are reported. Attention is drawn to pyomyositis and clinical presentation of chronic fatigue syndrome in children. Patients with Sweet’s syndrome often have antineutrophil cytoplasmic autoantibodies. Biopsy specimens of panniculitis should be taken to aid treatment. Long-term outcome in chronic osteomyelitis is favorable; recommendations on the rational use of imaging have been reported.

 

Source: Coovadia HM. Rheumatic fever and disorders of the musculoskeletal system. Curr Opin Rheumatol. 1992 Oct;4(5):718-24. http://www.ncbi.nlm.nih.gov/pubmed/1419508