It Takes Two to Make a Thing Go Wrong

Seventy-three-year-old diabetic male was a high-risk transfer from Alaska for respiratory decompensation in the setting of progressive bulbar and proximal weakness. He was diagnosed with COVID-19 two months prior and viral mononucleosis 1 month prior to presentation. While the patient had a fall 3 months prior to presentation, and decreased mobility at home, there was abrupt onset of progressive upper/lower extremity weakness, dysphagia, and difficulties managing secretions 2 weeks prior to presentation. Initial exam was notable for MRC 3-4/5 proximal upper/lower extremity weakness, areflexia, and negative inspiratory force of 224 to 230 cm H20. A subtle periorbital heliotrope rash was documented. Lumbar puncture demonstrated albumino-cytologic dissociation (protein 142 mg/dL, 6 WBCs) and CK remained elevated (1930 U/L) despite intravenous hydration. Outside electrodiagnostic testing demonstrated a sensorimotor axonal neuropathy with questionable myopathic features on needle electromyography. Given concern for an inflammatory neuropathy and concomitant inflammatory myopathy, intravenous immunoglobulin 2G/kg and IV methylprednisolone 1G/day over 5 days was started. He was transferred for further diagnostic workup and supportive care 6 days after presentation and required intubation within 24 hours of admission. Exam showed progressive proximal and distal weakness of the extremities and general areflexia/hyporeflexia. Repeat electromyography confirmed a severe sensorimotor axonal polyneuropathy without acquired demyelinating features and normal repetitive nerve stimulation. While the patient could no longer activate muscles voluntarily, proximal muscles had increased spontaneous activity with predominant myotonia. Neuroaxis imaging was notable only for enhancement of the lumbar nerve roots. Combined vastus lateralis muscle biopsy and serologic testing confirmed a second pathologic process contributing to the patient's weakness. This case highlights the cooccurrence of 2 distinct neuropathological entities, with potential relation to a prior viral infection, and the importance of ancillary testing to guide treatment for acute causes of neuromuscular respiratory failure.

Post-Covid-19 peripheral muscle weakness is not associated with muscle ultrasound echogenicity or muscle thickness

Background: Peripheral muscle weakness has been observed in the post-acute phase of Covid-19 patients. However, it is unknown whether Covid-19 is associated with structural changes in skeletal muscles, like atrophy, inflammation or fibrosis. Aim(s): To examine whether peripheral muscle weakness in post-Covid-19 patients is associated with changes in muscle echogenicity and thickness. Method(s): Post-Covid-19 patients with objectified muscle weakness (isometric quadriceps maximal voluntary contraction (MVC) <lower limit of normal) at ~6 months after infection were cross-sectionally studied. Vastus lateralis (VL), rectus femoris (RF), tibialis anterior (TA) and gastrocnemius (GCM) were examined unilaterally using quantitative muscle ultrasound. Standardized scores (z-scores) of 2 were defined as limits of normal. Result(s): Fourteen post-Covid-19 patients were included (age 47+/-15y, 64% male, BMI 26+/-3 kg/m2). Median z-scores were determined for muscle thickness and echogenicity of VL (-1.0 [-1.3- -0.2], 0 [-0.2-1.1]), RF (-0.2 [-1.4-0.1], -0.2 [-1.3-0.6]), TA (0.1 [-0.8-0.6], 0.5 [-0.4-1.0]), and GCM (0.8 [0.1-1.0], -0.7 [-1.3- -0.1]), respectively. Thirteen patients had values within the limits of normal. One patient showed increased echogenicity of VL, but normal values for other muscles. There were significant moderate-to-strong correlations between MVC and muscle thickness of VL (r=0.670), RF (r=0.812), TA (r=0.593) and GCM (r=0.579), and between MVC and echogenicity of GCM (r=-0.588). Conclusion(s): In a cohort of post-Covid-19 patients with peripheral muscle weakness, standardized muscle ultrasound investigations did not show any evidence for structural abnormalities.

Dynamic matching of oxygen uptake kinetics and muscle deoxygenation in post-COVID-19

Recent studies showed that post-COVID-19 patients with reduced pulmonary oxygen uptake (VO2p) kinetics, exhibited a lower peripheral oxygen extraction [lower C(a-v) O2 /Ca O2 ] rather than a central cardiac limitation (supernormal predicted exercisepeak cardiac output), opening further questions of what is impacting VO dynamics. We proposed to investigate the dynamic matching of VO2p , increase of heart rate (HR) and muscle deoxygenation (deoxy[Hb + Mb]) at the onset of heavy-exercise in post-COVID-19 patients. We expected to find a slowness of VO unrelated to circulatory impairment. 12 patients (90 days after onset of symptoms) were compared to 10 healthy controls. The VO rate of change, deoxy[Hb + Mb] in vastus lateralis (by near infrared spectroscopy) and HR were analyzed during a constant work-rate exercise test up to limit of tolerance (~70%peak work-rate). Post-COVID-19 patients had significantly slower VO2p kinetics than controls (Tau-VO2p 52+/-9 vs 40+/-11 seconds(s);p=0,001 and MRT-VO 70+/-12 vs 51+/-10 s;p<0,001). In contrast, t1/2 -HR was faster in patients (65+/-28 vs 85+/-20 s, p=0,04). Not only deoxy[Hb + Mb] dynamics were not accelerated compared to controls, suggesting normal muscle microvascular O2 delivery, but significantly slower (MRT-deoxy[Hb + Mb] 25+/-7 vs 20+/-2 s;p=0,02)(Figure 1). In conclusion, a sluggish on-exercise VO2p in these patients seems unrelated to central and peripheral circulatory adjustments. .

CASE REPORT of A HARD to TREAT DERMATOMYOSITIS after A COVID-19 INFECTION and SUBSEQUENT VACCINATION

Background: A 50 years old woman, a medical doctor, came to our department with symmetrical proximal muscular weakness, several months after Covid-19 infection and three weeks after a second dose of Covid-19 mRNA vaccine. The patient had no prior or family history of autoimmune diseases and take no medicines. In the past she undergone an operation for double-kidney with frequent urinary infections. Objective fndings have shown symmetrical proximal muscular weakness and classic sings of dermatomyositis-Gottron's papules, shawl and holster signs, periungual vasculitis. Objectives: We present a case of a 50 old woman with clinical and laboratory proven dermatomyositis, starting three weeks after a second dose of a Covid1-19 mRNA vaccine without other reasons. Methods: The laboratory tests showed elevated CPK, lactate dehydroge-nase, aspartate aminotransferase and alanine aminotransferase, high ANA-1:1280 and myositis specifc autoantibodies-anti-NXP2 and anti-Mi-2-beta. The electromyography showed myopathic changes and the muscle MRI-symmetrical edema of mm.obturator and mm.adductor brevis. We exclude diseases that may mimic infammatory myopathies. We made a cancer screening-whole body MRI, colonoscopy, gastroscopy, mammography and gynecological exam, immunoblot for detection of paraneoplastic syndrome-associated neuronal antibodies, with no detection of cancer. Muscle biopsy of m.vastus lateralis showed attenuating muscle infammation with advancing muscle atrophy and fbrosis. Results: The diagnose dermatomyositis was made according Bohan and Peter criteria and we start a high dose (1mg/kg/day) glucocorticoid therapy with good initial clinical and laboratory effect. Two months after starting a therapy muscle weakness worsened together with difficulty of swallowing. We excluded steroid myopathy after second EMG and lack of improvement when tapering the GS dose. Methotrexate 20 mg/weekly was added as a steroid sparing drug with good response, but was stopped because fare of pyelonephritis. Accordning to the opinion of dermatologist hydroxychloroquine was started for a couple of weeks, because of active skin manifestations. Muscle weakness worsened on the background of treatment, which was stopped. We started a therapy with intravenous immunoglobulins and considered therapy with cyclophosphamide or azathio-prine after urinary infection. Because the patient was infected for a second time with covid-19, although vaccine, we continued only with glucocorticoids and anti-osteoporotic therapy. Conclusion: The etiology and pathogenesis of infammatory myopathies are not fully clarifed so far. We speculate that the infection with Covid-19 as well as mRNA vaccine trigger infammatory myopathy and compromise the patient's immunity for poor treatment response with glucocorticoids and immunosuppres-sives. On the other hand advanced muscle atrophy and fbrosis within a short period show that suspected triggering factors could be a reason for difficult to treat such type of dermatomyiositis.

Clinical study on the efficacy and safety of arginine administered orally in association with other active ingredients for the prevention and treatment of sarcopenia in patients with COVID-19-related pneumonia

Aim of the study: In order to evaluate the efficacy of oral supplementation with 3 g of arginine in the prevention and treatment of sarcopenia in patients with COVID-19-related pneumonia, we conducted a parallel randomized study comparing it with standard therapy alone. Materials and Methods: Patients on standard therapy plus supplementation were compared with a control group of 40 patients, all hospitalized at the sub-intensive care unit, with a clinical diagnosis of SARS-CoV-2 infection and COVID-19 pneumonia. Muscle strength was assessed with the handgrip test and muscle ultrasound. Results: Arginine-supplemented patients had an average grip strength of 23.5 at the end of hospitalization compared with 22.5 in the untreated group with less reduction, showing statistical significance (p<0.001). In the same way, the thickness of the vastus lateralis quadriceps femoris muscle measured at the end of hospitalization showed less reduction on ultrasound, with a higher average value in the group receiving treatment than in the group of patients without supplementation (p<0.001). Upon discharge there was a 58.40% reduction in ventilation days. Conclusions: We believe that nutritional support with this arginine- based supplement was essential to the improved muscular and respiratory performance of these patients, which was demonstrated by the reduction in the need for respiratory support. This study suggests greater attention is needed in the assessment, prevention and treatment of sarcopenia and malnutrition in COVID patients undergoing non-invasive ventilation.

Neuromuscular electrical stimulation prevents the skeletal muscle weakness in patients with severe COVID-19 associated with sepsis and septic shock: a case series

Introduction: Neuromuscular electrical stimulation (NMES) results on muscle strength and functionality in patients with severe coronavirus disease 2019 (COVID-19) associated with sepsis and septic shock are unknown. Methods: Patients with severe COVID-19 associated with sepsis or septic shock were selected. The NMES intervention was performed on 7 consecutive days in a daily session of 40 min (frequency of 100 Hz and a pulse of 350 μs). Electrodes were positioned in the vastus medialis and vastus lateralis muscles, and inguinal region. The outcome measures were the femoris cross-sectional area (RF-CSA), thickness of the anterior compartment of the quadriceps muscle, rectus femoris echogenicity, International Classification of Functioning, Disability, and Health (ICF)-muscle strength, Physical Function ICU Test-scored (PFIT-s), Morton Mobility Index (DEMMI), and the Surgical Intensive Care Unit Optimal Mobilization Score (SOMS). The patients were evaluated on days 1, 5, and 8. Results: The RF-CSA area decreased significantly (- 16.9%;p < 0.05) from days 1 to 8, but showed maintenance of the thickness of the anterior compartment of the quadriceps muscle (- 3.20%;p = 0.3) from days 1 to 8. These patients showed a reduction of 2.1% per day in the rectus femoris cross-sectional area and 0.3% per day in the thickness of the anterior compartment of the quadriceps muscle during 8 days. Patients showed maintenance of the echogenicity (1.3%;p = 0.8) from days 1 to 8 with an increase of 0.16% per day. All patients showed an increase in the MRC score and reduction of the ICF-muscle strength, meaning improved muscle strength from days 1 to 8 (p < 0.05). The PFIT-s increased from days 1 to 5 and improved until day 8 compared to day 5 (p < 0.05). DEMMI and SOMS scores increased on day 8 compared to days 1 and 5 (p < 0.05). Conclusions: NMES showed a protective effect on muscle strength and improve the functionality of patients with several COVID-19 associated with sepsis and septic shock.