Acute skeletal muscle loss in SARS-CoV-2 infection contributes to poor clinical outcomes in COVID-19 patients

Abstract

Background: Chronic disease causes skeletal muscle loss that contributes to morbidity and mortality. There are limited data on the impact of dynamic muscle loss on clinical outcomes in COVID-19. We hypothesized that acute COVID-19-related muscle loss (acute sarcopenia) is associated with adverse outcomes.

Methods: A retrospective analysis of a prospective clinical registry of COVID-19 patients was performed in consecutive hospitalized patients with acute COVID-19 (n = 95) and compared with non-COVID-19 controls (n = 19) with two temporally unique CT scans. Pectoralis muscle (PM), erector spinae muscle (ESM) and 30 day standardized per cent change in cross sectional muscle area were quantified. Primary outcomes included mortality and need for intensive care unit (ICU) admission. Multivariate linear and logistic regression were performed. Cox proportional hazard ratios were generated for ICU admission or mortality for the per cent muscle loss standardized to 30 days.

Results: The COVID-19 CT scan cohort (n = 95) had an average age of 63.3 ± 14.3 years, comorbidities including COPD (28.4%) and diabetes mellitus (42.1%), and was predominantly Caucasian (64.9%). The proportion of those admitted to the ICU was 54.7%, with 10.5% requiring tracheostomy and overall mortality 16.8%. Median duration between CT scans was 32 days (IQR: 16-63 days). Significant reductions in median per cent loss was noted for PM (-2.64% loss [IQR: -0.28, -5.47] in COVID-19 vs. -0.06 loss [IQR: -0.01, -0.28] in non-COVID-19 CT controls, P < 0.001) and ESM (-1.86% loss [IQR: -0.28, -5.47] in COVID-19 vs. -0.06 loss [IQR: -0.02, -0.11]) in non-COVID-19 CT controls, P < 0.001). Multivariate linear regression analysis of per cent loss in PM was significantly associated with mortality (-10.8% loss [95% CI: -21.5 to -0.19]) and ICU admission (-11.1% loss [95% CI: -19.4 to -2.67]), and not significant for ESM. Cox proportional hazard ratios demonstrated greater association with ICU admission (adj HR 2.01 [95% CI: 1.14-3.55]) and mortality (adj HR 5.30 [95% CI: 1.19-23.6]) for those with significant per cent loss in PM, and greater association with ICU admission (adj HR 8.22 [95% CI: 1.11-61.04]) but not mortality (adj HR 2.20 [95% CI: 0.70-6.97]) for those with significant per cent loss in ESM.

Conclusions: In a well-characterized cohort of 95 hospitalized patients with acute COVID-19 and two temporally distinct CT scans, acute sarcopenia, determined by standardized reductions in PM and ESM, was associated with worse clinical outcomes. These data lay the foundation for evaluating dynamic muscle loss as a predictor of clinical outcomes and targeting acute sarcopenia to improve clinical outcomes for COVID-19.

Keywords: Acute sarcopenia; COVID-19; Erector spinae muscle area; Standardized reduction; pectoralis muscle area.

Figure 1

Flow chart of patients included from the COVID‐19 registry. Of the 75 782 patients who tested positive for COVID‐19 in the CCCRR between March 2020 and December 2020, 12 524 were hospitalized, 2343 had at least one CT of the chest during their hospital stay, and 95 met our inclusion criteria of having two CT scans of the chest at least 3 days apart during or after their hospital stay.

Figure 2

Representative computed tomography (CT) scans at thoracic level used to determine muscle area in patients with COVID‐19. (A) Representative CT image utilizing lung windows demonstrates evidence of COVID‐19 related bilateral pneumonia. (B) Representative CT image for pectoralis muscle and erector spinae muscle imaging from the initial CT scan are shaded. Skeletal muscle CSAs are measured in cm². (C) Representative CT image for pectoralis muscle and erector spinae muscles from the subsequent CT scan are shaded. Skeletal muscle mass CSAs are measured in cm².

Figure 3

Mortality and ICU admission outcomes for patients with COVID‐19 who had decreased muscle area. (A) Cox proportional hazards ratio for mortality and ICU admission patients with COVID‐19 as determined by percentage change in pectoralis major (PM) and erector spinae (ES) muscle area. The cutoff value for PM and ESM areas corresponds to the optimum cutoff determined by a receiver operating characteristic curve based on sensitivity and specificity in this cohort for the standardized rate of muscle loss. The Cox proportional hazard ratio and P‐values for the optimum cutoff are presented. Optimum cutoffs are defined in the corresponding panel using Youden's optimal cutpoint criteria. (B) Receiver operating characteristic curves for per cent change in PM or ESM area.