Jeroen Molinger ^1,2,3,4* John Whittle ⁵ Susie Cha ⁶ David Macleod ^4,7 Marat Fudim ^3,8 Luis Ulloa ⁷ Christina Barkauskas ⁹ Zachary R. Healy ⁹ Krista Haines ¹⁰ Rajan T. Gupta ^11,12 Mathieu van der Jagt ¹ Henrik Endeman ¹ Diederik Gommers ¹ Jan Bakker ^1,13 Paul Wischmeyer ²

• ¹ Intensive Care Adults, Erasmus Medical Center, Rotterdam, Netherlands
• ² Division of Critical Care, Department of Anesthesiology, School of Medicine, Duke University, Durham, United States
• ³ Division of Cardiology, Department of Medicine, School of Medicine, Duke University, Durham, United States
• ⁴ Human Pharmacology and Physiology Laboratory, School of Medicine, Duke University, Durham, United States
• ⁵ University College London Hospitals NHS Foundation Trust, London, United Kingdom
• ⁶ Independent researcher, Cerritos, United States
• ⁷ Department of Anesthesiology, School of Medicine, Duke University, Durham, United States
• ⁸ Duke Clinical Research Institute, School of Medicine, Duke University, Durham, North Carolina, United States
• ⁹ Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Surgery, School of Medicine, Duke University, Durham, United States
• ¹⁰ Division of Trauma, Acute and Critical Care, Department of Surgery, School of Medicine, Duke University, Durham, United States
• ¹¹ Department of Radiology, School of Medicine, Duke University, Durham, United States
• ¹² Duke Cancer Institute, School of Medicine, Duke University, Durham, United States
• ¹³ Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York City, United States

Introduction: The COVID-19 pandemic brought unprecedented challenges to healthcare systems worldwide, particularly the often challenging physical recovery from critical illness. Among the myriad complications faced by these patients, ICU-acquired weakness (ICU-AW) stands out due to its significant impact on patient outcomes. ICU-AW, characterized by skeletal muscle atrophy and weakness, is linked to critical illness polyneuropathy (CIN), myopathy (CIM), and muscle atrophy. Notably, fasciculations, or involuntary muscle twitches, have been observed in patients with ICU-AW, suggesting altered muscle fiber excitability. This study aimed to describe the pattern of fasciculations in critically ill mechanically ventilated COVID-19 patients, assess clinical features associated with fasciculations, and evaluate their prognostic significance. Methods: The study enrolled patients admitted to the Intensive Care Unit (ICU) with COVID-19 infection requiring intubation and mechanical ventilation. Quadriceps muscles were assessed using muscle skeletal (MSK) ultrasound and Phase Angle (PhA) through multifrequency segmental bioelectrical impedance analysis (MFBIA) every 72 hours. PhA is considered a marker of cell membrane integrity and function, with lower PhA values indicating reduced skeletal muscle quality and increased risk of sarcopenia. Fasciculations were classified based on their appearance and frequency. Results A total of 35 intubated patients were studied, with 15 patients (43%) displaying scattered fasciculations exclusively in the vastus intermedius muscles. Upon admission, the study found no significant difference in PhA between the fasciculation and non-fasciculation groups. However, PhA decreased significantly from admission to discharge ICU only in the fasciculation group. Patients with fasciculations exhibited higher mortality rates, though not statistically significant, and this correlated with prolonged ICU and hospital lengths of stay. Discussion This study is the first to report scattered fasciculations in the vastus intermedius muscles of multiple patients with SARS-CoV-2 infection identified with MSK ultrasound. The findings suggest that the combination of impaired muscle cellular function (PhA) and the onset of fasciculations could serve as a potential biomarker of adverse outcomes and ICU-related muscle dysfunction and muscle loss.