Myopathy as a cause of Long COVID fatigue: Evidence from quantitative and single fiber EMG and muscle histopathology
Jane Agergaard, Benjamin Yamin Ali Khan, Thomas Engell-Sørensen, Berit Schiøttz-Christensen, Lars Østergaard, Eva Kildall Hejbøl, Henrik Daa Schrøder, Henning Andersen, Jakob Udby Blicher, Thomas Holm Pedersen, Thomas Harbo, Hatice Tankişi, Anders Lehmann Dahl Pedersen, Andreas Fløe, Benjamin Yamin Ali Khan, Berit Schiøttz-Christensen, Cagla Cömert, Christoffer Laustsen, Elisabeth Bendstrup, Grégory Wood, Hans Erik Bøtker, Hatice Tankişi, Henning Andersen, Jane Agergaard, Johan Palmfeldt, Kristoffer Skaalum, Lars Østergaard, Line K. Vibholm, Martin Mølhave, Rikke Katrine Jentoft Olsen, Sofie E. Jørgensen, Steen Hvitfeldt Poulsen, Steffen Leth, Søren Sperling Haugen, Thomas Harbo, Trine H. Mogensen, William Mølgaard Ullahammer, Wonyong Kim
Abstract
OBJECTIVE: To describe neurophysiological abnormalities in Long COVID and correlate quantitative electromyography (qEMG) and single fiber EMG (sfEMG) results to clinical scores and histopathology. METHODS: 84 patients with non-improving musculoskeletal Long COVID symptoms were examined with qEMG and sfEMG. Muscle biopsies were taken in a subgroup. RESULTS: Mean motor unit potential (MUP) duration was decreased in ≥ 1 muscles in 52 % of the patients. Mean jitter was increased in 17 % of the patients in tibialis anterior and 25 % in extensor digitorum communis. Increased jitter was seen with or without myopathic qEMG. Low quality of life score correlated with higher jitter values but not with qEMG measures. In addition to our previously published mitochondrial changes, inflammation, and capillary injury, we show now in muscle biopsies damage of terminal nerves and motor endplate with abundant basal lamina material. At the endplate, axons were present but no vesicle containing terminals. The post-synaptic cleft in areas appeared atrophic with short clefts and coarse crests. CONCLUSIONS: Myopathic changes are common in Long COVID. sfEMG abnormality is less common but may correlate with clinical scores. sfEMG changes may be due to motor endplate pathology. SIGNIFICANCE: These findings may indicate a muscle pathophysiology behind fatigue in Long COVID.