Electrophysiological Neuromuscular Alterations and Severe Fatigue Predict Long-Term Muscle Weakness in Survivors of COVID-19 Acute Respiratory Distress Syndrome

Background: Long-term weakness is common in survivors of COVID-19–associated acute respiratory distress syndrome (CARDS). We longitudinally assessed the predictors of muscle weakness in patients evaluated 6 and 12 months after intensive care unit discharge with in-person visits.Methods: Muscle strength was measured by isometric maximal voluntary contraction (MVC) of the tibialis anterior muscle. Candidate predictors of muscle weakness were follow-up time, sex, age, mechanical ventilation duration, use of steroids in the intensive care unit, the compound muscle action potential of the tibialis anterior muscle (CMAP-TA-S100), six-minute walk test, severe fatigue, depression and anxiety, post-traumatic stress disorder, cognitive assessment, and body mass index. We also compared the clinical tools currently available for the evaluation of muscle strength (handgrip strength, Medical Research Council sum score) and electrical neuromuscular function (simplified peroneal nerve test [PENT]) with more objective and robust measures of force (MVC) and electrophysiological evaluation of the neuromuscular function of the tibialis anterior muscle (CMAP-TA-S100) for its essential role in ankle control.Findings: MVC improved at 12 months compared with 6 months. CMAP-TA-S100 (P = 0.016) and the presence of severe fatigue (P = 0.036) were independent predictors of MVC. MVC was strongly associated with handgrip strength, whereas CMAP-TA-S100 was strongly associated with PENT.Interpretation: Electrical neuromuscular abnormalities and severe fatigue are independently associated with reduced MVC and can be used to predict the risk of long-term muscle weakness in CARDS survivors.Trial Registration: The present study was registered at ClinicalTrial.gov (NCT: NCT04608994).Funding: Italian Ministry of University and Research.Declaration of Interest: We declare no competing interests.Ethical Approval: The Ethics Committee of Brescia approved this study (study title: The PIC syndrome: follow-up of the intensive care patient – approval number: NP3369 – approval date: December 11, 2018) and written informed consent was obtained from all participants (or substitute decision-makers) before data collection. The study was carried out according to the declaration of Helsinki of 1975 and the EU GCP-ICH Guidelines.