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Background Post-COVID-19 syndrome is characterized by diverse symptoms and abnormalities that persist beyond 12 weeks from the onset of acute COVID-19. Severity disease has been associated with more musculoskeletal alterations such as muscle weakness, dyspnea, and distance walking. The aim was to evaluate the impact of invasive mechanical ventilation (IMV) on body composition and investigate risk factors associated with sarcopenia in post-COVID-19 patients three months after moderate or severe COVID-19 infections. Methods Cross-sectional study. 530 patients with PCR-confirmed diagnoses of moderate to severe COVID-19, > 18 years old, oxygen saturation ≤ 93%, PaO2/FiO2 ratio < 300, who required hospitalization and were discharged were included. We excluded those who died before the follow-up visit, declined to participate, or could not be contacted. Results The mean age was 53.79 ± 12.90 years. IMV subjects had lower phase angle and handgrip strength and higher impedance index, frequency of low muscle mass, and low muscle strength than those without IMV. The risk factors of sarcopenia were > 60 years of age, diabetes, obesity, IMV, and prolonged hospital stay. The multivariate model showed that age > 60 years (OR: 4.91, 95% CI: 2.26–10.63), obesity (OR: 3.73, 95% CI: 1.21–11.54), and interaction between prolonged length of hospital stay and IMV (OR: 2.92; 95% CI: 1.21–7.02) were related to a higher risk of sarcopenia. Conclusion Obesity and the interaction between prolonged length of hospital stay and IMV are associated with a higher risk of sarcopenia at 3 months after severe or moderate COVID-19 infection.

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