Diaphragm Muscle Weakness Might Explain Exertional Dyspnea 15 Months after Hospitalization for COVID-19.

Rationale: Dyspnea is often a persistent symptom after acute coronavirus disease (COVID-19), even if cardiac and pulmonary function are normal. Objectives: This study investigated diaphragm muscle strength in patients after COVID-19 and its relationship to unexplained dyspnea on exertion. Methods: Fifty patients previously hospitalized with COVID-19 (14 female, age 58 ± 12 yr, half of whom were treated with mechanical ventilation, and half of whom were treated outside the ICU) were evaluated using pulmonary function testing, 6-minute-walk test, echocardiography, twitch transdiaphragmatic pressure after cervical magnetic stimulation of the phrenic nerve roots, and diaphragm ultrasound. Diaphragm function data were compared with values from a healthy control group. Measurements and Main Results: Moderate or severe dyspnea on exertion was present at 15 months after hospital discharge in approximately two-thirds of patients. No significant pulmonary function or echocardiography abnormalities were detected. Twitch transdiaphragmatic pressure was significantly impaired in patients previously hospitalized with COVID-19 compared with control subjects, independent of initial disease severity (14 ± 8 vs. 21 ± 3 cm H2O in mechanically ventilated patients vs. control subjects [P = 0.02], and 15 ± 8 vs. 21 ± 3 cm H2O in nonventilated patients vs. control subjects [P = 0.04]). There was a significant association between twitch transdiaphragmatic pressure and the severity of dyspnea on exertion (P = 0.03). Conclusions: Diaphragm muscle weakness was present 15 months after hospitalization for COVID-19 even in patients who did not require mechanical ventilation, and this weakness was associated with dyspnea on exertion. The current study, therefore, identifies diaphragm muscle weakness as a correlate for persistent dyspnea in patients after COVID-19 in whom lung and cardiac function are normal. Clinical trial registered with www.clinicaltrials.gov (NCT04854863).

Longitudinal Analysis of Quadriceps Muscle Strength in Patients with Previous COVID-19 Hospitalization and in Patients with Post-Acute Sequelae following Mild COVID-19.

Muscle weakness is a prominent symptom in post-acute sequelae of COVID-19 (PASC). However, few studies have objectively and longitudinally assessed muscle strength after varying COVID-19 severity grades. This observational study aimed to explore the prevalence, determinants, and 1.5 years change of quadriceps muscle weakness in 98 patients discharged from COVID-19 hospitalization and in 50 patients with PASC following mild COVID-19. Isometric quadriceps maximal voluntary contraction (MVC) was assessed on a computerized dynamometer at three visits. Also, in a subgroup of 14 post-COVID-19 patients with quadriceps muscle weakness, muscle thickness and echo intensity were determined by muscle ultrasound of nine upper and lower extremity muscles. Muscle weakness was found in 59% of post-hospitalized patients and in 65% of those with PASC following mild COVID-19 at ~14 weeks after acute COVID-19. Whereas during ~1.5 years follow-up MVC modestly improved, muscle weakness prevalence remained unchanged. Hospital length of stay and diabetes mellitus were identified as possible predictors of muscle weakness following COVID-19 hospitalization. No predictors could be identified in those with PASC following mild COVID-19. Ultrasound outcomes revealed no large structural abnormalities. In conclusion, clinically relevant muscle weakness is common after COVID-19 and its long-term improvement is poor. Future studies with relevant control groups are warranted to confirm our data.

Intensive care unit-acquired weakness and the COVID-19 pandemic: A clinical review.

Patients with severe cases of coronavirus disease 2019 (COVID-19) often become critically ill requiring intensive care unit (ICU) management. These individuals are at risk for developing ICU-acquired weakness (ICUAW), a multifactorial condition in which polyneuropathy, myopathy, and/or disuse muscle atrophy result in motor weakness. This weakness is thought to contribute to the long-term functional disability frequently observed in survivors of critical illness. This review discusses the current evidence regarding the epidemiology, pathophysiology, evaluation, risk factors, and rehabilitation-specific management of ICUAW in patients with COVID-19. Because of the novelty of COVID-19, the exact prevalence of ICUAW is not well delineated among COVID-19 patients. However, ICUAW has been reported in this population with retrospective studies showing weakness occurring in up to 45.5% of patients with severe COVID-19. There are multiple risk factors for developing ICUAW among COVID-19 patients, including premorbid health status, sepsis, multiple organ failure, mechanical ventilation, immobilization, neuromuscular blockade, corticosteroid use, and glycemic control. ICUAW is more likely to occur after prolonged mechanical ventilation and long hospital stays and can be diagnosed with manual muscle and electrodiagnostic testing. Although the long-term sequela of COVID-19 after ICU stays is not fully studied, increasing evidence indicates significant risk for this population developing long-term functional impairments. Establishing postacute rehabilitation programs for COVID-19 survivors will be important for recovery of endurance, mobility, and function.

Long-Term Evolution of Malnutrition and Loss of Muscle Strength after COVID-19: A Major and Neglected Component of Long COVID-19.

Post-acute consequences of COVID-19, also termed long COVID, include signs and symptoms persisting for more than 12 weeks with prolonged multisystem involvement; most often, however, malnutrition is ignored. METHOD: The objective was to analyze persistent symptoms, nutritional status, the evolution of muscle strength and performance status (PS) at 6 months post-discharge in a cohort of COVID-19 survivors. RESULTS: Of 549 consecutive patients hospitalized for COVID-19 between 1 March and 29 April 2020, 23.7% died and 288 patients were at home at D30 post-discharge. At this date, 136 of them (47.2%) presented persistent malnutrition, a significant decrease in muscle strength or a PS ≥ 2. These patients received dietary counseling, nutritional supplementation, adapted physical activity guidance or physiotherapy assistance, or were admitted to post-care facilities. At 6 months post-discharge, 91.0% of the 136 patients (n = 119) were evaluated and 36.0% had persistent malnutrition, 14.3% complained of a significant decrease in muscle strength and 14.9% had a performance status > 2. Obesity was more frequent in patients with impairment than in those without (52.8% vs. 31.0%; p = 0.0071), with these patients being admitted more frequently to ICUs (50.9% vs. 31.3%; p = 0.010). Among those with persistent symptoms, 10% had psychiatric co-morbidities (mood disorders, anxiety, or post-traumatic stress syndrome), 7.6% had prolonged pneumological symptoms and 4.2% had neurological symptoms. CONCLUSIONS: Obese subjects as well as patients who have stayed in intensive care have a higher risk of functional loss or undernutrition 6 months after a severe COVID infection. Malnutrition and loss of muscle strength should be considered in the clinical assessment of these patients.

Guillain-Barré syndrome after COVID-19 in Japan.

We report the first case of Guillain-Barré syndrome (GBS) associated with SARS-CoV-2 infection in Japan. A 54-year-old woman developed neurological symptoms after SARS-CoV-2 infection. We tested for various antiganglioside antibodies, that had not been investigated in previous cases. The patient was diagnosed with GBS based on neurological and electrophysiological findings; no antiganglioside antibodies were detected. In previous reports, most patients with SARS-CoV-2-infection-related GBS had lower limb predominant symptoms, and antiganglioside antibody tests were negative. Our findings support the notion that non-immune abnormalities such as hyperinflammation following cytokine storms and microvascular disorders due to vascular endothelial damage may lead to neurological symptoms in patients with SARS-CoV-2 infection. Our case further highlights the need for careful diagnosis in suspected cases of GBS associated with SARS-CoV-2 infection.

[Weakness as a complication of COVID-19 in critically ill patients: clinical features and prognostic factors in a case series]. / Debilidad como complicación del paciente crítico por COVID-19: características clínicas y factores pronósticos en una serie de casos.

INTRODUCTION: Weakness is a frequent complication in those critically ill due to COVID-19. This study describes its characteristics and the factors that can condition and predict it. PATIENTS AND METHODS: We conducted a prospective, descriptive, observational study of patients admitted to the intensive care unit (ICU) due to COVID-19 between April and May 2020 with muscle weakness. A motor balance equal to or lower than 3/5 according to the modified Medical Research Council muscle strength scale was considered to be severe clinical impairment. Altogether 25 analytical studies, 16 neurophysiological studies and one muscle biopsy were performed, with a telephone follow-up at one month, a comparative analysis between the groups with and without severe compromise, and determination of cut-off points for analytical parameters to predict severe involvement using ROC curves. RESULTS: The sample consisted of 25 patients with a mean age of 58 years (standard deviation ± 9). The median length of stay in the ICU was 27.5 days. All the electromyograms exhibited a myogenic pattern and 75% also showed neuropathy. The group with severe clinical involvement had higher levels of D-dimer (p = 0.08), lactate dehydrogenase (p = 0.03) and interleukin-6 (p = 0.10), and the combination of the alteration of any two of these three parameters predicted severe involvement with a sensitivity of 100% and a specificity of 76.9%. At one month of follow-up, 36% were unable to walk autonomously and 92% continued with muscle weakness. CONCLUSIONS: Weakness in severe COVID-19 patients has a major clinical impact. Its early detection and study by means of predictors of its development may allow for better management. The absence in some cases of classical risk factors for ICU-acquired weakness suggests a different pathophysiology.

TITLE: Debilidad como complicación del paciente crítico por COVID-19: características clínicas y factores pronósticos en una serie de casos.Introducción. La debilidad es una complicación frecuente en el enfermo crítico por COVID-19. Se describen sus características, y los factores que pueden condicionarla y predecirla. Pacientes y métodos. Estudio observacional descriptivo prospectivo con pacientes ingresados en la unidad de cuidados intensivos (UCI) por COVID-19 entre abril y mayo de 2020 con debilidad muscular. Se consideró una afectación clínica grave un equilibrio motor igual o inferior a 3/5 según la escala de fuerza muscular modificada del Medical Research Council. Se han realizado 25 estudios analíticos, 16 estudios neurofisiológicos y una biopsia muscular; seguimiento telefónico al mes; análisis comparativo entre los grupos con y sin afectación grave, y determinación de puntos de corte de parámetros analíticos para predecir afectación grave mediante curvas ROC. Resultados. Se incluyó a 25 pacientes con 58 años (desviación estándar ± 9) de edad media. La mediana de estancia en la UCI fue de 27,5 días. Todos los electromiogramas mostraban un patrón miógeno y el 75%, también una neuropatía. El grupo con afectación clínica grave tenía mayores niveles de dímero-D (p = 0,08), lactato deshidrogenasa (p = 0,03) e interleucina 6 (p = 0,10), y la combinación de la alteración de dos cualquiera de estos tres parámetros pronosticaba la afectación grave con una sensibilidad del 100% y una especificidad del 76,9%. Al mes de seguimiento, el 36% no podía deambular autónomamente y el 92% seguía con debilidad muscular. Conclusiones. La debilidad en el enfermo por COVID-19 grave tiene una repercusión clínica importante. Su detección y estudio precoces mediante predictores de su desarrollo pueden permitir un mejor manejo. La ausencia en algunos casos de los factores de riesgo clásicos para la debilidad adquirida en la UCI sugiere una fisiopatología diferente.

Clinical and neurophysiological characterization of muscular weakness in severe COVID-19.

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.

A 64-Year-Old Man With Multifocal Infiltrates.

CASE PRESENTATION: A 64-year-old previously healthy man presented with 8 weeks of progressive dyspnea on exertion and cough. Prior to presentation, the patient was able to bicycle > 60 miles per week and work full-time in a home improvement store. He was up-to-date with age-appropriate cancer screening and immunizations, and home medications included famotidine for reflux and nonsteroidal antiinflammatories for osteoarthritis, both as-needed. He had no significant respiratory exposure, aside from previous work as an electrician. His symptoms began in mid-February 2020 amid the coronavirus disease 2019 pandemic, although he had no known exposure to the virus.

Challenges in diagnosing hydroxychloroquine myopathy during the COVID-19 pandemic.

Hydroxychloroquine is being used for COVID-19 symptoms and in clinical trials, but can cause a toxic myopathy that leads to muscle weakness. A review of skeletal muscle biopsies from patients with hydroxychloroquine myopathy gives pointers of steps that can be taken to diagnose this toxic myopathy early and help differentiate it from COVID-19-related muscle weakness.

Neuromuscular involvement in COVID-19 critically ill patients.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) has a high incidence of intensive care admittance due to the severe acute respiratory syndrome (SARS). Intensive care unit (ICU)-acquired weakness (ICUAW) is a common complication of ICU patients consisting of symmetric and generalised weakness. The aim of this study was to determine the presence of myopathy, neuropathy or both in ICU patients affected by COVID-19 and whether ICUAW associated with COVID-19 differs from other aetiologies. METHODS: Twelve SARS CoV-2 positive patients referred with the suspicion of critical illness myopathy (CIM) or polyneuropathy (CIP) were included between March and May 2020. Nerve conduction and concentric needle electromyography were performed in all patients while admitted to the hospital. Muscle biopsies were obtained in three patients. RESULTS: Four patients presented signs of a sensory-motor axonal polyneuropathy and seven patients showed signs of myopathy. One muscle biopsy showed scattered necrotic and regenerative fibres without inflammatory signs. The other two biopsies showed non-specific myopathic findings. CONCLUSIONS: We have not found any distinctive features in the studies of the ICU patients affected by SARS-CoV-2 infection. SIGNIFICANCE: Further studies are needed to determine whether COVID-19-related CIM/CIP has different features from other aetiologies. Neurophysiological studies are essential in the diagnosis of these patients.