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.

Prevalence and clinical implications of abnormal body composition phenotypes in patients with COVID-19: a systematic review

“…Included articles were published between 2020 and 2022. Two studies reported data from both the first and second COVID-19 wave ( 41 , 42 ) and 4 studies investigated changes over time in body composition ( 43 , 44 , 45 , 46 ).…”

“…The relationship between mortality and body composition abnormalities was investigated in 36 studies ( 4 , 37 , 40 , 42 , 43 , 46 , 47 , 48 , 50 , 53 , 54 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 70 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 ) ( Figure 3 , Supplementary Table 4 ). Out of 24 of these studies, 12 showed that skeletal muscle mass assessed by either CT ( 43 , 47 , 50 , 56 , 61 , 77 , 78 , 80 , 86 , 88 ) or US ( 42 , 46 ) was negatively associated with in-hospital mortality and 30-day mortality ( 4 , 40 , 42 , 43 , 46 , 47 , 50 , 53 , 54 , 56 , 57 , 58 , 60 , 61 ,…”

“…The relationship between body composition abnormalities and ICU admission in patients with COVID-19 was evaluated in 24 studies ( 37 , 43 , 46 , 48 , 49 , 50 , 52 , 55 , 56 , 57 , 71 , 73 , 78 , 80 , 84 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 ) ( Figure 3 , Supplementary Table 4 ). Among 16 studies assessing muscle mass ( 37 , 43 , 46 , 49 , 50 , 55 , 56 , 57 , 78 , 80 , 84 , 87 , 88 , 89 , 93 , 95 ), 4 using CT ( 43 , 50 , 55 , 88 ) and 1 using US ( 46 ) found that low muscle mass was related to a greater likelihood of being admitted to the ICU. Using BIA, FFM ( 49 , 89 ), ALST ( 37 ), LST and SMI ( 89 ) were unrelated to ICU admission in 3 of 4 studies ( 37 , 49 , 89 , 93 ).…”

“…Thirty-seven studies investigated the relationship between body composition abnormalities and MV or severe COVID-19 ( 4 , 6 , 20 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 47 , 50 , 51 , 54 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 74 , 78 , 81 , 82 , 83 , 85 , 87 , 88 , 89 , 92 , 93 , 94 , 96 , 97 , 98 ) ( Figure 3 , Supplementary Table 4 ). Twenty-one of these studies assessed muscle mass using CT ( 4 , 40 , 41 , 43 , 47 , 50 , 51 , 54 , 57 , 58 , 61 , 62 , 63 , 64 , 78 , 81 , 83 , 87 , 88 , 97 , 98 ) and 2 by US ( 42 , 44 ). Low muscle mass by CT was inversely related to greater disease severity and/or need for intubation in 6 studies ( 47 , 50...…”

Hot water immersion as a potential substitute for strength training during the COVID-19 pandemic

“…For example, in rats which were re-ambulated following 7 days of immobilization, soleus muscle regrowth was 20% greater in animals that had their rectal temperature raised to 41°C–41.5°C for 30 min every second day for 7 days compared to non-heated animals ( Selsby et al, 2007 ). Given that severe forms of COVID-19 are associated with muscle wasting ( Attaway et al, 2022 ), the findings of Selsby et al (2007) are highly relevant in the context of rehabilitation of those COVID-19 survivors who cannot exercise.…”