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Objective: To report clinical and electroneuromyographic (ENMG) characteristics of patients affected by severe COVID-19 infection, evaluated for muscular weakness.Materials and Methods: ENMGs performed for evaluation of diffuse weakness in patients who could not be discharged from semi-intensive care COVID unit because of difficulties in ventilation weaning were reviewed. Patients with severe COVID-19 infection who had undergone endotracheal intubation and able to co-operate were considered. ENMG protocol was focused on neurophysiological items that excluded or confirmed critical illness polyneuropathy (CIP), myopathy (CIM), or polyneuromyopathy (CIPM). Standardized clinical evaluation was performed using Medical Research Council (MRC) sum score.Results: Eight patients were included in the study. All presented known risk factors for intensive care unit-acquired weakness (ICU-AW), and none of them had history of underlying neuromuscular disorders. ENMG findings were normal in two patients, while only two patients had an altered MRC sum score (< 48). Neuromuscular involvement was diagnosed in 6/8 patients (75%): 2 had CIP, 1 had possible CIM, 1 had CIPM, while 1 patient, with clinically evident weakness but equivocal ENMG findings, was classified as ICU-AW. Finally, 1 patient was diagnosed with acute demyelinating neuropathy. Patients with neuromuscular involvement were those with longer intubation duration and higher levels of IL-6 at admission.Conclusion: Neuromuscular complications are frequent in severe COVID-19 and cannot be excluded by MRC sum scores above 48. Standardized ENMG is helpful in guiding diagnosis when clinical evaluation is not reliable or possible. Elevated IL-6 at admission may be a predictor biomarker of ICU-AW in COVID-19. [ABSTRACT FROM AUTHOR]

(1) Background: Female sex is considered a risk factor for Intensive Care Unit-Acquired Weakness (ICUAW). The aim is to investigate sex-specific aspects of skeletal muscle metabolism in the context of ICUAW. (2) Methods: This is a sex-specific sub-analysis from two prospectively conducted trials examining skeletal muscle metabolism and advanced muscle activating measures in critical illness. Muscle strength was assessed by Medical Research Council Score. The insulin sensitivity index was analyzed by hyperinsulinemic-euglycemic (HE) clamp. Muscular metabolites were studied by microdialysis. M. vastus lateralis biopsies were taken. The molecular analysis included protein degradation pathways. Morphology was assessed by myocyte cross-sectional area (MCSA). Multivariable linear regression models for the effect of sex on outcome parameters were performed. (3) Results: n = 83 (♂n = 57, 68.7%; ♀n = 26, 31.3%) ICU patients were included. ICUAW was present in 81.1%♂ and in 82.4%♀ at first awakening (p = 0.911) and in 59.5%♂ and in 70.6%♀ at ICU discharge (p = 0.432). Insulin sensitivity index was reduced more in women than in men (p = 0.026). Sex was significantly associated with insulin sensitivity index and MCSA of Type IIa fibers in the adjusted regression models. (4) Conclusion: This hypothesis-generating analysis suggests that more pronounced impairments in insulin sensitivity and lower MCSA of Type IIa fibers in critically ill women may be relevant for sex differences in ICUAW. [ABSTRACT FROM AUTHOR]

Background: The pathophysiology of intensive care unit-acquired weakness (ICU-AW), which affects peripheral nerves, limb muscles and respiratory muscles, is complex and incompletely understood. This illustrates the need for an ICU-AW animal model. However, a translatable and easily applicable ICU-AW animal model does not exist. The objective of this study was to investigate whether induction of a S. pneumoniae sepsis could serve as a model for ICU-AW., Methods: A total of 24 C57BL/6J mice were infected intranasally with viable S. pneumoniae . Control mice (n=8) received intranasal saline and mice of the blank group (n=4) were not inoculated. Ceftriaxone was administered at 24 h (n=8) or at 48h after inoculation (n=8), or as soon as mice lost 10% of their body weight (n=8). The primary endpoint, in vivo grip strength, was measured daily. At the end of the experiment, at 120 h after inoculation, electrophysiological recordings were performed and diaphragm muscle was excised to determine ex vivo muscle fiber strength and myosin/action ratio., Results: Grip strength over time was similar between experimental and control groups and electrophysiological recordings did not show signs of ICU-AW. Diaphragm fiber contractility measurements showed reduced strength in the group that received ceftriaxone at 48 h after S. pneumoniae inoculation., Conclusions: Ex vivo diaphragm weakness, but no in vivo limb weakness was found in the S. pneumoniae mouse model in which severe illness was induced. This does not reflect the full clinical picture of ICU-AW as seen in humans and as such this model did not fulfill our predefined requirements. However, this model may be used to study inflammation induced diaphragmatic weakness., Competing Interests: Conflicts of Interest: Prof. IN van Schaik received departmental honoraria for serving on scientific advisory boards and a steering committee for CSL-Behring. The other authors have no conflicts of interest to declare.