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

Abstract

Background

The impact of body composition (BC) abnormalities on COVID-19 outcomes remains to be determined.

Objectives

We summarized the evidence on BC abnormalities and their relationship with adverse clinical outcomes in patients with COVID-19.

Methods

A systematic search was conducted up until 26 September, 2022 for observational studies using BC techniques to quantify skeletal muscle mass (or related compartments), muscle radiodensity or echo intensity, adipose tissue (AT; or related compartments), and phase angle (PhA) in adults with COVID-19. Methodological quality of studies was assessed using the Newcastle-Ottawa Scale. A synthesis without meta-analysis was conducted to summarize the prevalence of BC abnormalities and their significant associations with clinical outcomes.

Results

We included 62 studies (69.4% low risk of bias) with 12–1138 participants, except 3 studies with ≤490,301 participants. Using CT and different cutoff values, prevalence ranged approximately from 22% to 90% for low muscle mass, 12% to 85% for low muscle radiodensity, and 16% to 70% for high visceral AT. Using BIA, prevalence of high FM was 51%, and low PhA was 22% to 88%. Mortality was inversely related to PhA (3/4 studies) and positively related to intra- and intermuscular AT (4/5 studies), muscle echo intensity (2/2 studies), and BIA-estimated FM (2/2 studies). Intensive care unit (ICU) admission was positively related to visceral AT (6/7 studies) and total AT (2/3 studies). Disease severity and hospitalization outcomes were positively related to intra- and intermuscular AT (2/2 studies). Inconsistent associations were found for the rest of the BC measures and hospitalization outcomes.

Conclusions

Abnormalities in BC were prevalent in patients with COVID-19. Although conflicting associations were observed among certain BC abnormalities and clinical outcomes, higher muscle echo intensity (reflective of myosteatosis) and lower PhA were more consistently associated with greater mortality risk. Likewise, high intra- and intermuscular AT and visceral AT were associated with mortality and ICU admission, respectively.

This trial was registered at PROSPERO as CRD42021283031.

Introduction

COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has a wide spectrum of clinical manifestations, ranging from asymptomatic to severely symptomatic. Advanced age and comorbid conditions, such as obesity, diabetes mellitus, hypertension, and cardiovascular or respiratory system diseases, have been associated with severe or lethal COVID-19 [1]. Body composition (BC) may also play a role in COVID-19 severity. Evidence suggests that individuals with abnormal BC phenotypes—including low muscle mass, low muscle radiodensity (reflective of myosteatosis), and/or excess adiposity—may be at higher risk for greater disease severity and death [[2], [3], [4]]. However, although BC is a better predictor of health outcomes than BMI [5,6], its assessment during and after COVID-19 hospitalization has been particularly difficult in such an overburdened clinical scenario [7].

SARS-CoV-2 infection directly contributes to muscle loss and myosteatosis through increased production of proinflammatory cytokines, leading to muscle protein breakdown and/or inhibition of protein synthesis [[8], [9], [10]] (Figure 1). Prolonged bed rest and hospital stay (>2 wk) are also associated with reduced muscle mass in critical care [11,12]. This can be extrapolated to COVID-19 and might contribute to worse clinical course and long-term sequelae [13,14]. Patients with COVID-19 discharged from the intensive care unit (ICU) may experience an especially challenging post-acute functional recovery, requiring specific rehabilitation strategies [15].

Obesity [using BMI as a proxy of high adipose tissue (AT)] is a risk factor for developing severe COVID-19 [16]. Thus, AT content and distribution may also predict COVID-19 prognosis [3,17]. Excess visceral adipose tissue (VAT), which is highly metabolically active, is detrimental to several health aspects. VAT secretes inflammatory mediators that may amplify the cytokine storm triggered by SARS-CoV-2, thereby possibly contributing to disease severity [[18], [19], [20]].

In view of the above-mentioned literature, this systematic review aimed to summarize the evidence on the prevalence of BC abnormalities in COVID-19. We also investigated the relationship between BC phenotypes and adverse outcomes, including mortality, ICU admission, mechanical ventilation (MV), disease severity, hospitalization, and length of stay (LOS), among others.