Construct and criterion validity of muscle ultrasonography for assessment of skeletal muscle in patients recovering from COVID-19

Abstract

Background: The purpose was to investigate the content, construct, and criterion validity of muscle ultrasound in a mixed cohort of participants recovering from mild and critical COVID-19. Methods: A secondary analysis of a prospective cross-sectional study was conducted on data obtained from a battery of muscle and physical function assessments including a muscle biopsy and muscle ultrasonography (US). Rectus femoris (RF) muscle thickness (mT), quadricep complex (QC) mT, RF muscle cross-sectional area (CSA) using 2D freeform trace and estimated from Feret's diameter, and RF echo intensity (EI) were assessed with US. Muscle fiber CSA, fiber type, protein content in muscle fibers, extracellular matrix content (ECM; wheat-germ agglutin), and percent area of collagen in ECM (picrosirius red) were examined from vastus lateralis muscle biopsies. Spearman rho correlations (r) were performed to assess validity of ultrasound parameters. Results: Thirty-three individuals participated including 11 patients surviving critical COVID-19, 15 individuals recovering from mild-COVID, and 7 controls. There were several significant correlations between RF mT, QC mT, RF CSA, and RF EI with age, comorbid burden, body-mass index, and measures of muscle strength, muscle power, and physical function (range r = 0.35-0.83). RF Feret's CSA correlated to CSA of type II muscle fibers (r = 0.41, p = 0.022) and the average size of all muscle fibers (r = 0.39, p = 0.031). RF EI was correlated with collagen in muscle ECM (r = 0.53, p = 0.003) and protein content in muscle tissue (r = -0.52, p = 0.012). Conclusion: Muscle size and quality measured using US has moderate content and construct validity, and to lesser extent, fair to moderate criterion validity in a mixed cohort of individuals recovering from COVID. Muscle ultrasound quality (EI) appears to be sensitive at detecting muscle dysfunction as it is associated with strength, power, physical function, and collagen distribution in a mixed group of individuals recovering from COVID-19.

Keywords: ICU-acquired weakness; critical illness; muscle dysfunction; muscle ultrasound; muscle wasting; post-intensive care syndrome; skeletal muscle.

FIGURE 1

Relationship between rectus femoris echo intensity derived from ultrasonography and picrosirius red staining of muscle fibers. Panel (A) representative images of picrosirius red (SR+) area in muscle biopsy from a healthy community dwelling individual and an individual 9-months post critical COVID-19 (scale bar: 500 μm); Panel (B) Rectus femoris muscle EI is correlated with SR+ (r = 0.52, p = 0.003) in the combined cohort, with statistical significance attenuated in the critical illness group (r = 0.53, p = 0.194, red). Healthy community dwelling (n = 7) = white circles; mild COVID (n = 15) = blue circles; and critical COVID (n = 9) = red circles.

FIGURE 2

Relationship between US parameters and selected muscle strength and physical function testing. Panel (A) Rectus femoris muscle thickness is correlated with knee extensor strength, quadriceps force production, (r = 0.689, p < 0.001). Panel (B) Quadriceps complex thickness (rectus femoris and vastus intermedius thickness—VC) had moderate positive correlation with lower-extremity muscle power (r = 0.48, p = 0.005). Panel (C) RF 2D free-form CSA had positive moderate correlations with performance on 6 MWT (r = 0.72, p < 0.001). Panel (D,E) Rectus femoris Feret’s Diameter CSA is fair to moderately correlated with average CSA of muscle fibers from biopsy tissue (Panel D, r = 0.389, p = 0.031) and lower-extremity muscle power (Panel E, r = 0.585, p < 0.001). Panel (F) RF EI had negative strong correlation with performance on 6 MWT (r = −0.823, p < 0.001). Healthy community dwelling (n = 7) = white circles; mild COVID (n = 15) = blue circles; and critical COVID (n = 11 except Panel D n = 9) = red circles.