COVID-19 related acute muscle loss linked to worse outcomes

Sarcopenia, which is defined as the loss of skeletal muscle that occurs during hospitalization from an acute illness, is associated with chronic disease and is largely responsible for the illness and deaths associated with these conditions. A new Journal of Cachexia, Sarcopenia and Muscle study investigates acute sarcopenia prevalence in coronavirus disease 2019 (COVID-19) patients and the outcomes of this complication. 

Study: Acute Skeletal Muscle Loss In SARS-Cov-2 Infection Contributes to Poor Clinical Outcomes In COVID-19 Patients. Image Credit: Stokkete / Shutterstock.com

Introduction

As of July 21, 2022, over 572 million people have been infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) worldwide, of which almost 6.4 million have died. In severe cases, COVID-19 can trigger a hyperinflammatory state or cytokine storm that ultimately causes multiple organ systems to fail.

Little is known about acute sarcopenia in COVID-19, despite the knowledge that it can cause clinical deterioration and increase the risk of death.

Some factors as to why COVID-19 causes sarcopenia include inflammation, the bedridden state in acute COVID-19 patients, poor appetite leading to a significantly reduced intake of food, and the use of certain medications like corticosteroids that cause muscle wasting.

Sarcopenia can subsequently cause or aggravate the fatigue and overall delay in recovery that is commonly reported in post-acute sequelae of COVID-19 (PASC). Moreover, sarcopenia increases the patients’ risk of severe illness and poor outcomes.

About the study

Earlier studies have demonstrated that loss of mass in the pectoralis and erector spinae muscles in patients with chronic obstructive pulmonary disease (COPD) causes adverse outcomes.

In the present study, the authors were interested in determining whether sarcopenia occurred acutely in COVID-19 and if the changing rate of muscle loss was a prognostic factor for death and other disease outcomes. To this end, the authors used computed tomogram (CT) scanning of the chest and/or abdomen to quantify muscle mass.

Patient data was acquired from a prospective registry of acute COVID-19 patients called the Cleveland Clinic COVID-19 Research Registry (CCCRR) from March 2020 to December 2020. Taken together, the ‘CT COVID cohort’ included 100 patients with two or more high-resolution chest CT scans taken at least three days apart, which allowed chest muscle thickness to be measured.

Other clinical, demographic, and laboratory test results were compared. Alcohol use was also quantified, as drinking increased during the pandemic and alcohol use contributed to sarcopenia.

Study findings

The CT COVID group had more underlying illnesses, heavier body mass, and more frequently reported shortness of breath, cough, and fever as compared to the COVID registry in general. The comorbidities included COPD, asthma, and congestive cardiac failure.

Furthermore, the CT COVID cohort was at an increased risk for intensive care unit (ICU) admission and mechanical ventilation at more than two and four times the risk, respectively but not of death. Disease severity was thus higher in this group, with most deaths due to respiratory failure and, subsequently, liver failure. Almost one in four patients in this group drank over five alcoholic drinks a week.

Laboratory findings showed elevated liver enzyme levels at admission as compared to prior tests.

Changes in muscle mass were apparent in the CT COVID group and to a minimal level in controls. The median change in pectoral muscle (PM) over a month was almost -3 cm² in these patients as compared to 0.06 cm² in controls. The corresponding changes in the erector spinae muscle (ESM) were almost 2 cm² and 0.06 cm², respectively.

Survivors and non-survivors in this group could not be predicted by age, body mass index (BMI), or sex, Conversely, a lower ESM area on the first CT and a lower final ESM area were associated with an increased risk of ICU admission. Over 80% of those admitted to the ICU died as compared to less than 50% of survivors.

Non-survivors also lost more PM mass. In fact, the percentage decline in PM mass predicted a five-fold increased risk of mortality and double the risk of ICU admission. With ESM reduction, mortality was unchanged; however, the risk of ICU admission increased eight-fold.

Those who drank five or more drinks each week exhibited a greater decline in PM but no association with ESM. PM and ESM reductions did not appear to correlate with each other.

Implications

PM reduction percentages were associated with death rates and ICU admission risk, while reduced ESM was associated with a higher risk of ICU admission. ESM is responsible for keeping the body upright against gravity; therefore, its atrophy may occur with debilitating illness or weakness, thus explaining why a low initial ESM predicts a poor outcome following COVID-19.

The study findings indicate dynamic deterioration in skeletal muscle mass occurred, especially in the PM, and was associated with several adverse outcomes. However, static measurements of ESM mass were correlated with higher mortality and an increased requirement for mechanical ventilation.

Taken together, different muscles respond in different ways to acute inflammation and varying methods must be used to capture such risk factors.

Future studies may be needed to compare static and dynamic measurements of muscle loss in COVID-19 and similar illnesses, as well as possible long-term consequences of sarcopenia. These may include features often associated with PASC, such as fatigue, difficulty breathing, joint pain, and reduced exercise tolerance.

The current study also shows that specific therapies may be required in heavy drinkers with sarcopenia in COVID-19 due to the association of alcohol consumption with liver impairment and muscle loss.

The relationship between alcohol use and increased risk of sarcopenia in COVID-19 patients is particularly concerning, as COVID-19 itself can cause liver injury due to direct invasion of cholangiocytes by SARS-CoV-2 and immunologic injury. Other mechanisms include hypoxia and elevated ferritin levels due to inflammation, along with the associated loss of appetite, nausea, and vomiting in acute COVID-19.

Patients on mechanical ventilation may suffer inadequate nutrition during the initial days, while the use of corticosteroids, which are often used to treat severe COVID-19, is known to promote muscle loss.

The CT COVID cohort in the current study represents a group of very sick people with inflamed lungs, which is unlike the general COVID population. However, the study findings demonstrated that non-COVID-19 patients who required two CT scans in the same period with a similar rate of ICU admission exhibited a lower rate of muscle loss. This was observed despite the presence of multiple medical conditions in this control cohort.

Future studies are needed to determine whether COVID-19 increases the risk for sarcopenia as compared with other severe respiratory infections.”

Monitoring these patients over longer periods will help delineate the underlying mechanisms and outcomes of sarcopenia in such cases.

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.”

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.