Acute Effects of Osteopathic Treatment in Long COVID-19 Patients with Fatigue Symptoms: A Randomized, Controlled Trial

<b>Background</b>: Persistent fatigue is among the most commonly reported symptoms in patients suffering from post-acute sequelae of SARS-CoV-2 infection (long COVID). Autonomic dysfunction, measurable via heart rate variability, has been implicated as a contributing factor. Osteopathic manipulative treatment is a manual therapeutic approach that targets autonomic balance and may offer a novel intervention for long COVID-related fatigue. <b>Methods</b>: In this single-blind, randomized controlled trial, 42 participants (mean age 51 ± 11 years; fatigue severity score: 31 ± 5 points) with long COVID and persistent fatigue ≥12 weeks post-infection were allocated to either a 45 min standardized osteopathic treatment (<i>n</i> = 21) or a sham-treatment group (<i>n</i> = 21). Heart rate variability was assessed using a 10 min resting electrocardiogram before intervention, immediately after, and again 48 h later. The analysis of heart rate variability encompassed time-domain indices, including the root mean square of successive differences, the standard deviation of normal-to-normal intervals, mean heart rate, and mean RR interval. Additionally, frequency-domain measures such as low-frequency, high-frequency, total power, and the LF/HF ratio were considered. <b>Results</b>: The osteopathy group showed a statistically significant increase in root mean square of successive differences post-treatment (<i>p</i> < 0.01), accompanied by a decrease in the stress index (<i>p</i> < 0.05) and an increase in the mean of the standard deviations of RR intervals (<i>p</i> < 0.05). Significant between-group differences were observed for mean heart rate and mean of RR intervals (<i>p</i> < 0.05). Frequency-domain measures also improved significantly from baseline in the intervention group. Outlier patterns suggest potential subgroup effects, possibly due to underlying dysautonomia. <b>Conclusions</b>: A single session of osteopathic treatment significantly enhanced short-term heart rate variability in long COVID patients with fatigue. These findings highlight the potential role of manual autonomic modulation as a supportive therapy in long COVID management. Further research is needed to assess the long-term effects and optimal treatment frequency of osteopathic manipulative treatment in this population.