ABSTRACT
We read the recent review article by Marta Kopanska et al. [...].
Subject(s)
Acetylcholinesterase/metabolism , COVID-19/metabolism , Cytokine Release Syndrome/metabolism , Receptors, Nicotinic/metabolism , SARS-CoV-2/metabolism , Acetylcholine/metabolism , Antiviral Agents/therapeutic use , COVID-19/prevention & control , COVID-19/virology , Caffeine/therapeutic use , Cytokine Release Syndrome/virology , Humans , Muscle, Skeletal/metabolism , Muscle, Skeletal/virology , Myasthenia Gravis/metabolism , Myasthenia Gravis/virology , Nicotine/therapeutic use , Protein Binding , SARS-CoV-2/drug effects , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/metabolism , Vagus Nerve/metabolism , Vagus Nerve/virologyABSTRACT
The ability of the ribonucleic acid (RNA) to self-replicate, combined with a unique cocktail of chemical properties, suggested the existence of an RNA world at the origin of life. Nowadays, this hypothesis is supported by innovative high-throughput and biochemical approaches, which definitively revealed the essential contribution of RNA-mediated mechanisms to the regulation of fundamental processes of life. With the recent development of SARS-CoV-2 mRNA-based vaccines, the potential of RNA as a therapeutic tool has received public attention. Due to its intrinsic single-stranded nature and the ease with which it is synthesized in vitro, RNA indeed represents the most suitable tool for the development of drugs encompassing every type of human pathology. The maximum effectiveness and biochemical versatility is achieved in the guise of non-coding RNAs (ncRNAs), which are emerging as multifaceted regulators of tissue specification and homeostasis. Here, we report examples of coding and ncRNAs involved in muscle regeneration and discuss their potential as therapeutic tools. Small ncRNAs, such as miRNA and siRNA, have been successfully applied in the treatment of several diseases. The use of longer molecules, such as lncRNA and circRNA, is less advanced. However, based on the peculiar properties discussed below, they represent an innovative pool of RNA biomarkers and possible targets of clinical value.
Subject(s)
MicroRNAs/metabolism , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , RNA, Messenger/metabolism , RNA, Untranslated/genetics , Regeneration , Animals , Biomarkers/metabolism , COVID-19 , Homeostasis , Humans , Mice , Muscle, Skeletal/virology , Myocardium/metabolism , Origin of Life , RNA, Circular , RNA, Long Noncoding/genetics , RNA, Small Interfering/metabolism , RNA, Small Untranslated/genetics , RNA, Viral/metabolism , SARS-CoV-2/geneticsSubject(s)
Betacoronavirus , Coronavirus Infections/virology , Muscle, Skeletal/virology , Muscular Diseases/virology , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/virology , Angiotensin-Converting Enzyme 2 , COVID-19 , Coronavirus Infections/pathology , Disease Susceptibility , Humans , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , Muscular Diseases/metabolism , Muscular Diseases/pathology , Pandemics , Pneumonia, Viral/pathology , Respiration Disorders/metabolism , Respiration Disorders/pathology , Respiration Disorders/virology , Respiratory Muscles/metabolism , Respiratory Muscles/pathology , Respiratory Muscles/virology , SARS-CoV-2ABSTRACT
OBJECTIVE: To explore the spectrum of skeletal muscle and nerve pathology of patients who died after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and to assess for direct viral invasion of these tissues. METHODS: Psoas muscle and femoral nerve sampled from 35 consecutive autopsies of patients who died after SARS-CoV-2 infection and 10 SARS-CoV-2-negative controls were examined under light microscopy. Clinical and laboratory data were obtained by chart review. RESULTS: In SARS-CoV-2-positive patients, mean age at death was 67.8 years (range 43-96 years), and the duration of symptom onset to death ranged from 1 to 49 days. Four patients had neuromuscular symptoms. Peak creatine kinase was elevated in 74% (mean 959 U/L, range 29-8,413 U/L). Muscle showed type 2 atrophy in 32 patients, necrotizing myopathy in 9, and myositis in 7. Neuritis was seen in 9. Major histocompatibility complex-1 (MHC-1) expression was observed in all cases of necrotizing myopathy and myositis and in 8 additional patients. Abnormal expression of myxovirus resistance protein A (MxA) was present on capillaries in muscle in 9 patients and in nerve in 7 patients. SARS-CoV-2 immunohistochemistry was negative in muscle and nerve in all patients. In the 10 controls, muscle showed type 2 atrophy in all patients, necrotic muscle fibers in 1, MHC-1 expression in nonnecrotic/nonregenerating fibers in 3, MxA expression on capillaries in 2, and inflammatory cells in none, and nerves showed no inflammatory cells or MxA expression. CONCLUSIONS: Muscle and nerve tissue demonstrated inflammatory/immune-mediated damage likely related to release of cytokines. There was no evidence of direct SARS-CoV-2 invasion of these tissues. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that muscle and nerve biopsies document a variety of pathologic changes in patients dying of coronavirus disease 2019 (COVID-19).
Subject(s)
COVID-19/pathology , Muscle, Skeletal/pathology , Peripheral Nerves/pathology , Adult , Aged , Aged, 80 and over , Autopsy , COVID-19/immunology , COVID-19/virology , Female , Humans , Male , Middle Aged , Muscle, Skeletal/immunology , Muscle, Skeletal/virology , Peripheral Nerves/immunology , Peripheral Nerves/virologyABSTRACT
Anticoagulation plays a major role in reducing the risk of systematic thrombosis in patients with severe COVID-19. Serious hemorrhagic complications, such as intracranial hemorrhage, have also been recognized. However, intra-abdominal hemorrhage is under-recognized because of its rare occurrence, despite high mortality. Here, we discuss two cases of spontaneous iliopsoas hematoma (IPH) likely caused by anticoagulants during the clinical course of COVID-19. We also explored published case reports to identify clinical characteristics of IPH in COVID-19 patients. The use of anticoagulants may increase the risk of lethal IPH among COVID-19 patients becsuse of scarce data on optimal dosage and adequate monitoring of anticoagulant effects. Rapid diagnosis and timely intervention are crucial to ensure good patient outcomes.
Subject(s)
Abscess/virology , COVID-19/complications , Hematoma/diagnosis , Hematoma/virology , Muscle, Skeletal/pathology , Abscess/classification , Abscess/diagnosis , Aged , Anticoagulants/adverse effects , Antiviral Agents/therapeutic use , Blood Coagulation , COVID-19/diagnostic imaging , Fatal Outcome , Hematoma/classification , Hematoma/drug therapy , Humans , Male , Middle Aged , Muscle, Skeletal/virology , Severity of Illness Index , Thigh/pathology , Tomography, X-Ray Computed , Treatment Outcome , COVID-19 Drug TreatmentABSTRACT
Autopsies represent medical procedures through which the causes of patients' deaths are determined or, through tissue sampling and microscopic examination of slides in usual stains or special tests, one can offer the basis for understanding the physiopathological mechanisms that contribute to the patients' death Histological findings of tissue samples from patients who have died of COVID-19 have been mainly orientated to lung, heart, liver, kidney damage with a small percent of them following other organs, but none has, to our knowledge, studied skeletal muscle.
Subject(s)
COVID-19/pathology , Muscle, Skeletal/pathology , Muscle, Skeletal/virology , Necrosis , Autopsy , Creatine Kinase/blood , Endothelium, Vascular/pathology , Fatal Outcome , Humans , Inflammation , Ischemia/pathology , Kidney Tubules/pathology , Male , Middle Aged , Muscle, Skeletal/immunology , Tissue DistributionABSTRACT
The role of skeletal muscle mass in modulating immune response and supporting metabolic stress has been increasingly confirmed. Patients with sarcopenia, characterized by reduced muscle mass and muscle strength, were reported to have poor immune response and metabolic stress when facing acute infection, major surgeries, and other attacks. Based on empirical data, patients with sarcopenia are speculated to have increased infection rates and dismal prognoses amid the current 2019 novel coronavirus disease (COVID-19) epidemic. COVID-19 infection also aggravates sarcopenia because of the increased muscle wasting caused by systematic inflammation and the reduced physical activity and inadequate nutrient intake caused by social isolation. Notably, the interventions targeting skeletal muscle are anticipated to break the vicious circle and benefit the treatment of both conditions. We recommend sarcopenia assessment for populations with advanced age, inactivity, chronic disease, cancers, and nutritional deficiency. Patients with sarcopenia and COVID-19 infection need intensive care and aggressive treatments. The provision of at-home physical activities together with protein supplementation is anticipated to reverse sarcopenia and promote the prevention and treatment of COVID-19. The recommended protocols on nutritional support and physical activities are provided in detail.
Subject(s)
COVID-19/therapy , Nutritional Support , SARS-CoV-2 , Sarcopenia/therapy , Sarcopenia/virology , COVID-19/complications , COVID-19/virology , Exercise/physiology , Humans , Inflammation , Muscle Strength/physiology , Muscle, Skeletal/virology , Wasting Syndrome/virologySubject(s)
COVID-19/pathology , Muscle, Skeletal/pathology , Muscular Diseases/pathology , Muscular Diseases/virology , Biopsy , Fatal Outcome , Female , Humans , Inclusion Bodies, Viral/pathology , Inclusion Bodies, Viral/ultrastructure , Microscopy, Electron, Transmission , Middle Aged , Muscle, Skeletal/ultrastructure , Muscle, Skeletal/virology , SARS-CoV-2ABSTRACT
The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been predominantly a respiratory manifestation. Currently, with evolving literature, neurological signs are being increasingly recognized. Studies have reported that SARS-CoV-2 affects all aspects of the nervous system including the central nervous system (CNS), peripheral nervous system (PNS) and the muscular system as well. Not all patients have reverse transcription-polymerase chain reaction positive for the virus in the cerebrospinal fluid, and diagnosing the association of the virus with the myriad of neurological manifestations can be a challenge. It is important that clinicians have a high-index of suspicion for COVID-19 in patients presenting with new-onset neurological symptoms. This will lead to early diagnosis and specific management. Further studies are desired to unravel the varied neurological manifestations, treatment, outcome and long-term sequel in COVID-19 patients.