Skeletal muscle damage in the course of coronavirus disease (COVID-19) in a pediatric practice. Own supervision: a clinical case

Background. Coronavirus disease (COVID-19) pandemic is still at the heart of healthcare in Ukraine and over the world. The nervous system and other human organs and systems can be affected by pathogenic nature of SARS-CoV-2. We purposed to pay physicians’ attention to the diagnosis of skeletal muscle damage, in particular rhabdomyolysis, to avoid possible complications in COVID-19. Materials and methods. We have examined a group of children with skeletal muscle damage on the background of COVID-19 during 2020–2021. A clinical case from own practice has been presented in the article. Results and conclusions. The patient, a 15-year-old boy, developed general weakness, severe pain in the right thigh and hip joint, fever 33 days after the acute phase of coronavirus disease. The differential diagnosis was carried out between skeletal muscle damage and osteomyelitis. Diffuse connective tissue diseases, oncohematological disorders, and hepatitis were excluded on the basis of clinical data and examinations. The inflammatory changes in m.iliopsoas, m.obturatorius internus and m.piriformis with abscess formation identified during clinical examination and magnetic resonance imaging, along with high levels of blood transaminases indicated the development of rhabdomyolysis. The detected positive IgG to SARS-CoV-2 confirmed the association of this pathological condition with the previous acute phase of COVID-19. Signs of coagulopathy, anemia in the hemogram simultaneously with the clinical symptoms of rhabdomyolysis confirmed the systemic lesions in the course of coronavirus disease in the child. Timely assessment of clinical symptoms (general weakness, muscle pain) and levels of creatine phosphokinase, transaminases, electrolytes, creatinine, blood urea will help make an early diagnosis of rhabdomyolysis, prescribe adequate therapy and prevent the deve-lopment of severe complications.

Histopathological characteristics of cervical extensor tissue in patients with dropped head syndrome

Background To date, the histopathologic characteristics of dropped head syndrome (DHS) have not been reported sufficiently. The present study investigates the histopathology of biopsy specimens from the cervical paravertebral region in patients with DHS. Methods Histopathological parameters were evaluated in biopsy specimens of the cervical paravertebral soft tissue from 15 patients with DHS. Results Among the 15 cases of DHS examined, skeletal muscle was identified in 7 cases, all of which showed necrosis, microvessel proliferation and atrophy. The ligament was identified in 12 cases, 8 of which showed degeneration. The lag time between the onset of symptoms and the performance of a biopsy in all 8 cases, which showed degeneration was over 3 months. Microvessel proliferation in the ligament was observed in 1 of the 4 cases, in which the lag time between the onset of symptoms and the performance of a biopsy was less than 3 months (acute or subacute phase), and in 7 of the 8 cases, in which the lag time between the symptoms and the performance of a biopsy was over 3 months (chronic phase). Chronic inflammation in the ligament was identified in 1 of the 12 cases. Conclusions The identification of necrosis, microvessel proliferation, and atrophy in the skeletal muscle of patients with DHS and the presence of ligament degeneration and microvessel proliferation in the chronic but not acute or subacute phases may suggest that persistent skeletal muscle damage of the cervical paravertebral region causes subsequent ligament damage in patients with DHS.

From skeletal muscle damage and regeneration to the hypertrophy induced by exercise: What is the role of different macrophages subsets?

Macrophages are one of the top players when considering immune cells involved with tissue homeostasis. Recently, increasing evidence has demonstrated that these macrophages could also present two major subsets during tissue healing; proliferative macrophages (M1-like), which are responsible for increasing myogenic cell proliferation, and restorative macrophages (M2-like), which are accountable for the end of the mature muscle myogenesis. The participation and characterization of these macrophage subsets is critical during myogenesis, not only to understand the inflammatory role of macrophages during muscle recovery but also to create supportive strategies that can improve mass muscle maintenance. Indeed, most of our knowledge about macrophage subsets comes from skeletal muscle damage protocols, and we still do not know how these subsets can contribute to skeletal muscle adaptation. This narrative review aims to collect and discuss studies demonstrating the involvement of different macrophage subsets during the skeletal muscle damage/regeneration process, showcasing an essential role of these macrophage subsets during muscle adaptation induced by acute and chronic exercise programs.

Systemically Administered Homing Peptide Targets Dystrophic Lesions and Delivers Transforming Growth Factor-β (TGFβ) Inhibitor to Attenuate Murine Muscular Dystrophy Pathology

Muscular dystrophy is a progressively worsening and lethal disease, where accumulation of functionality-impairing fibrosis plays a key pathogenic role. Transforming growth factor-β1 (TGFβ1) is a central signaling molecule in the development of fibrosis in muscular dystrophic humans and mice. Inhibition of TGFβ1 has proven beneficial in mouse models of muscular dystrophy, but the global strategies of TGFβ1 inhibition produce significant detrimental side effects. Here, we investigated whether murine muscular dystrophy lesion-specific inhibition of TGFβ1 signaling by the targeted delivery of therapeutic decorin (a natural TGFβ inhibitor) by a vascular homing peptide CAR (CARSKNKDC) would reduce skeletal muscle fibrosis and pathology and increase functional characteristics of skeletal muscle. We demonstrate that CAR peptide homes to dystrophic lesions with specificity in two muscular dystrophy models. Recombinant fusion protein consisting of CAR peptide and decorin homes selectively to sites of skeletal muscle damage in mdxDBA2/J and gamma-sarcoglycan deficient DBA2/J mice. This targeted delivery reduced TGFβ1 signaling as demonstrated by reduced nuclear pSMAD staining. Three weeks of targeted decorin treatment decreased both membrane permeability and fibrosis and improved skeletal muscle function in comparison to control treatments in the mdxD2 mice. These results show that selective delivery of decorin to the sites of skeletal muscle damage attenuates the progression of murine muscular dystrophy.

Importance of Nutrient Availability and Metabolism for Skeletal Muscle Regeneration

Skeletal muscle is fundamentally important for quality of life. Deterioration of skeletal muscle, such as that observed with advancing age, chronic disease, and dystrophies, is associated with metabolic and functional decline. Muscle stem/progenitor cells promote the maintenance of skeletal muscle composition (balance of muscle mass, fat, and fibrotic tissues) and are essential for the regenerative response to skeletal muscle damage. It is increasing recognized that nutrient and metabolic determinants of stem/progenitor cell function exist and are potential therapeutic targets to improve regenerative outcomes and muscle health. This review will focus on current understanding as well as key gaps in knowledge and challenges around identifying and understanding nutrient and metabolic determinants of skeletal muscle regeneration.

Neurological Manifestations of COVID-19

The year 2020 started with the news of a novel coronavirus, severe acute respiratory syndrome corona virus 2(SARS-CoV2), induced disease in China which was termed as coronavirus disease 2019 (COVID-19). This viralinfection soon became pandemic and affected millions of people all over the world. The virus preferentiallyaffects respiratory system causing dry cough and fever, but has the tendency to spread to different organs in the body leading to multiple organ failure. Recent evidences show that corona virus can invade nervous system and damage it. This review is based on different articles and case reports that provide an evidence of neuro-virulent nature of COVID-19 and its consequences. The neuro-invasive property of the virus is divided into threecategories i) Central Nervous System (CNS) manifestations, ii) Peripheral Nervous System (PNS) manifestationsand iii) Skeletal Muscle damage. Headache and dizziness were observed to be common symptoms for CNS,whereas loss of smell and taste for PNS damage due to COVID-19. The aim of this review is, to develop anunderstanding of the devastating effects of COVID-19 on nervous system for the early recognition of virusinduced damage. This information can be used for the development of better therapeutic strategies.

Histopathological characteristics of cervical extensor tissue in patients with dropped head syndrome

Background To date, the histopathologic characteristics of dropped head syndrome (DHS) have not been reported sufficiently. The present study investigates the histopathology of biopsy specimens from the cervical paravertebral region in patients with DHS. Methods Histopathological parameters were evaluated in biopsy specimens of the cervical paravertebral soft tissue from 15 patients with DHS. Results Among the 15 cases of DHS examined, skeletal muscle was identified in 7 cases, all of which showed necrosis, microvessel proliferation and atrophy. The ligament was identified in 12 cases, 8 of which showed degeneration. The lag time between the onset of symptoms and the performance of a biopsy in all 8 cases, which showed degeneration was over 3 months. Microvessel proliferation in the ligament was observed in 1 of the 4 cases, in which the lag time between the onset of symptoms and the performance of a biopsy was less than 3 months (acute or subacute phase), and in 7 of the 8 cases, in which the lag time between the symptoms and the performance of a biopsy was over 3 months (chronic phase). Chronic inflammation in the ligament was identified in 1 of the 12 cases. Conclusions The identification of necrosis, microvessel proliferation, and atrophy in the skeletal muscle of patients with DHS and the presence of ligament degeneration and microvessel proliferation in the chronic but not acute or subacute phases may suggest that persistent skeletal muscle damage of the cervical paravertebral region causes subsequent ligament damage in patients with DHS.