Advertisement

The link between nutritional status and outcomes in COVID-19 patients in ICU: Is obesity or sarcopenia the real problem?

      Keywords

      Obesity is frequent among COVID-19 patients and data indicate that this condition is associated with poor outcomes [
      • Hendren NS
      • de Lemos JA
      • Ayers C
      • et al.
      Association of body mass index and age with morbidity and mortality in patients hospitalized with COVID-19: results from the American Heart Association COVID-19 Cardiovascular Disease Registry.
      ]. Nutritional status, in particular in COVID-19 patients in intensive care unit (ICU), was often assessed by the calculation of body mass index (BMI) classes, allowing to indicate the presence/absence of overweight or obesity [
      • Moonen HPFX
      • van Zanten FJL
      • Driessen L
      • et al.
      Association of bioelectric impedance analysis body composition and disease severity in COVID-19 hospital ward and ICU patients: the BIAC-19 study.
      ]. However, scanty information is available on body composition in COVID-19 patients in ICU [
      • Moonen HPFX
      • van Zanten FJL
      • Driessen L
      • et al.
      Association of bioelectric impedance analysis body composition and disease severity in COVID-19 hospital ward and ICU patients: the BIAC-19 study.
      ] and, more importantly, on patient's muscularity. In fact, most of the studies conducted in these patients indicate a high prevalence of increased adiposity (based on high visceral adipose tissue by computed tomography - CT) that seems to be able to predict the severity of the disease [
      • Yang Y
      • Ding L
      • Zou X
      • et al.
      Visceral adiposity and high intramuscular fat deposition independently predict critical illness in patients with SARS-CoV-2.
      ,
      • Battisti S
      • Pedone C
      • Napoli N
      • et al.
      Computed tomography highlights increased visceral adiposity associated with critical illness in COVID-19.
      ]. Obesity was shown to predict COVID-19 severity also among young patients [
      • Deng M
      • Qi Y
      • Deng L
      • et al.
      Obesity as a potential predictor of disease severity in young COVID-19 patients: a retrospective study.
      ].
      In ICU (not COVID-19 patients), recent evidences showed that low skeletal muscle mass as assessed by CT, was a risk factor for reduced survival in mechanically ventilated patients, revealing that BMI was not an independent predictor of mortality when muscularity was considered [
      • Weijs PJ
      • Looijaard WG
      • Dekker IM
      • et al.
      Low skeletal muscle area is a risk factor for mortality in mechanically ventilated critically ill patients.
      ].
      In addition, low Skeletal Muscle Area (SMA) and low skeletal muscle radiodensity, indicating loss of muscle quality, were associated with increased infections in non-COVID-19 patients in ICU [
      • Dusseaux MM
      • Antoun S
      • Grigioni S
      • et al.
      Skeletal muscle mass and adipose tissue alteration in critically ill patients.
      ].
      Therefore, by the present exploratory study we aimed to describe,in ICU COVID-19 patients the status of muscularity, assessing SMA and skeletal muscle index (SMI), and its association(s) with complications and mortality during the ICU stay.

      Patients enrollment, clinical parameters and outcomes

      We enrolled critical patients with a diagnosis of COVID-19 performed by nasopharyngeal or oropharyngeal swab (positive real-time reverse-transcriptase polymerase chain reaction - RT-PCR) and byCTscan admitted in the ICU of Sant'Andrea Hospital, Sapienza University of Rome, Italy in the period between March and May 2020. The local ethics committee approved the study and decided that consent could be waived in the context of the pandemic.
      We recorded clinical characteristics, including comorbidities and laboratory findings at admission. We also collected data about complications, including acute kidney injury, bleedings and thromboembolic events (pulmonary embolism, acute myocardial infarction, line clotted, deep venous thrombosis), as well as mortality during the ICU hospitalization. All the patients received the same standard therapy according to Italian recommendation (www.aifa.gov.it).

      Nutritional status and muscularity assessment

      We collected data about anthropometry, including waist and arm circumference, body mass index (kg/m2). We assessed the presence of metabolic syndrome according to the criteria of International Diabetes Federation (2006).
      For each patient, by CT images we obtained axial slices at the level of the third lumbar vertebrae (L3) and we estimated the SMA (cm2), which includes psoas, paraspinal and abdominal wall muscles. The SMI (cm2/m2) was calculated dividing SMA (cm2) by height of the patient expressed in m2. All the CT images were analyzed in a separate workstation, using Osirix Lite DICOM Viewer (version 11.0.3, Geneva, Switzerland).
      Patients characteristics were shown as mean ± standard deviation and median with 25th and 75th percentiles for continuous normally and non-normally distributed variables. Categorical variables were described as number (%). To analyze differences between groups we used the two-tailed t-test or Mann-Whitney according to normal or non-normal distribution. Also, to compare patients with lower vs higher muscle mass, we used as cutoff values the sex-specific median of SMA and SMI.
      Pearson's chi-square test was used to establish association between categorical variables. A p-value < 0.05 was considered statistically significant.

      Patient's characteristics

      We collected data from 25 patients (56% male) with a confirmed diagnosis of COVID-19 presenting with a median age of 67 years (IQR 60; 78). The mean BMI (kg/m2) was 28.8 ± 4.8 and the prevalence of overweight and obesity was 44% (11/25) and 32% (8/25), respectively. None of the patients presented with a BMI below 18.5. The prevalence of metabolic syndrome was 56% (14/25).
      The most common comorbidities were hypertension (52%), diabetes (16%) and chronic kidney disease (8%) (Table 1).
      Table 1Patient's characteristics
      ParameterTotal Participants (n = 25)Low muscularity
      Muscularity (SMI) available in 24 out of 25 patients
      (n = 12)
      High muscularity
      Muscularity (SMI) available in 24 out of 25 patients
      (n = 12)
      patients with low muscularity (below the sex-specific median value of SMI) vs patients with high muscularity (over the sex-specific median value of SMI)
      p-value
      Survivors (n = 18)Non-Survivors (n = 7)
      survivors vs non-survivors.
      p-value
      Age, y67 (60; 78)67 (58; 71)67 (62; 78)0.42264 (59; 68)78 (70; 79.5)0.034
      Male, (%)14 (56)7 (58)7 (58)>0.999 (50)5 (71)0.332
      Hemoglobin, g/dL12.9 ± 2.012.3 ± 2.213.5 ± 1.70.13812.5 ± 2.214.0 ± 0.70.081
      White blood cell count, /μL9590 ± 48549955 ± 42698625 ± 52240.5028462 ± 416412492 ± 56090.061
      Lymphocyte count, /μL720 (550; 1130)740 (430; 1200)710 (595; 1110)0.760695 (467.5; 890)1200 (720; 1410)0.174
      Neutrophil count, /μL8066 ± 46708980 (6725; 10600)5890 (4870; 7538)0.2157063 ± 356310643 ± 63640.085
      Neutrophil-Lymphocyte Ratio8.52 (5.25; 16.02)11.65 (5.45; 17.34)6.22 (5.06; 11.18)0.4019.34 (5.55; 14.33)5.79 (4.86; 19.19)0.976
      Albumin, g/dL3.2 ± 0.53.2 ± 0.43.3 ± 0.60.4793.2 ± 0.53.3 ± 0.60.667
      CRP, mg/dl15.6 (9.4; 19.2)15.3 (12.4; 19.3)14.8 (8.9; 19.8)0.84118.1 (11.6; 19.5)12.3 (7.4; 16.8)0.263
      Orotracheal Intubation, (%)15 (60)7 (58)7 (58)>0.998 (44)7 (100)0.020
      Anthropometric and body composition indices
      BMI, kg/m228.8 ± 4.829.4 ± 5.728.3 ± 4.00.58928.98 ± 5.4728.20 ± 2.750.724
      BMI  25, (%)19 (76)8 (67)10 (83)0.34612 (67)7 (100)0.137
      BMI 18.5–24.9, (%)6 (24)4 (33)2 (17)0.3466 (33)0 (0)0.137
      Waist circumference, cm113 ± 23117 ± 26112 ± 210.603117 ± 25103 ± 130.191
      Arm circumference, cm31 ± 431 ± 331 ± 40.91331 ± 431 ± 30.808
      SMA, cm271 (61.75; 77.25)62 (54; 71)78 (71; 98)0.00171 (62.5; 76.25)72.5 (64.25; 77)0.741
      SMI, cm2/m224.86 (23.36; 25.69)22.99 (20.44; 24.12)25.78 (25.35; 33.81)<0.000125 (22.63; 25.4)25 (24.08; 25.86)0.667
      Comorbidities
      Hypertension, (%)13 (52)7 (58)5 (42)0.4148 (44)5 (71)0.225
      Diabetes, (%)4 (16)2 (17)2 (17)>0.993 (17)1 (14)0.884
      Chronic kidney disease, (%)2 (8)1 (8)1 (8)>0.991 (6)1 (14)0.470
      Complications
      Acute kidney injury, %5 (20)2 (17)2 (17)>0.990 (0)5 (71)0.0004
      Embolic events, %6 (24)5 (71)1 (8)0.0593 (17)3 (43)0.169
      Bleedings, %4 (16)4 (33)0 (0)0.2713 (17)1 (14)0.884
      Abbreviations. CRP, C-reactive protein; BMI, body mass index; SMA, skeletal muscle area, SMI, skeletal muscle index
      Data are shown as mean ± standard deviation and median (interquartile range) for nonnormally distributed variables.
      low asterisk Muscularity (SMI) available in 24 out of 25 patients
      § patients with low muscularity (below the sex-specific median value of SMI) vs patients with high muscularity (over the sex-specific median value of SMI)
      # survivors vs non-survivors.
      Fourteen out of 25 patients (56%) had at least 1 comorbidity and 5 patients (20%) had 2 or more comorbidities. Clinical characteristics of the participants are summarized in Table 1.

      Indices of muscularity

      We assessed muscle mass in 24 out of 25 patients because in one patient the CT scan images presented insufficient quality for the analyses.
      The median SMA (cm2) was 71 (IQR 61.75; 77.25), whereas the SMI median value (cm2/m2) was 24.86 (IQR 23.36; 25.69).
      No differences in terms of SMA and SMI were observed between males (median SMA 73.5; median SMI 24.5) and females (median SMA 67.5; median SMI 25.3 (p = 0.197; p = 0.542, respectively). Moreover, for both muscle measurements, we did not find difference between overweight/obese patients (median SMA 70.5; median SMI 25.31) compared to those with normal BMI (median SMA 73; median SMI 24.3) (p = 0.912; p = 0.416, respectively), as well as between patients with or without metabolic syndrome (p = 0.099; p = 0.646, respectively) or between those with one vs those with two or more comorbidities (p = 0.952; p = 0.818, respectively). No correlation was found between age and both SMA (p = 0.48) and SMI (p = 0.24).
      Based on previous cutoffs in critical care for low muscle mass – SMA (cm2) (110 for females and 170 for males) [
      • Weijs PJ
      • Looijaard WG
      • Dekker IM
      • et al.
      Low skeletal muscle area is a risk factor for mortality in mechanically ventilated critically ill patients.
      ] and SMI (cm2/m2) (42.0, independently by sex) [
      • Ng CC
      • Lee ZY
      • Chan WY
      • et al.
      Low muscularity as assessed by abdominal computed tomography on intensive care unit admission is associated with mortality in a critically ill Asian Population.
      ], all the patients of our cohort (100%) could be classified as sarcopenic.

      Association between complications, mortality and indices of muscularity

      The median duration of the ICU stay was 12 days (IQR 5; 26). The complications observed were thromboembolic events in 6 out of 25 (24%), bleedings in 4 out of 25 (16%) and acute kidney injury in 5 out of 25 (20%).
      The number and type of complications were not associated with the presence of overweight (BMI 25–29.9) and/or obesity (BMI 30).
      Considering the small number of participants, to verify differences in terms of complications according to lower muscularity vs higher muscularity, we used the SMA and SMI sex-specific median values.
      Patients presenting with these two muscle measurements below the median (SMA below 67.5 for females and 73.5 for males and SMI below 25.31 for females and 24.46 for males) showed one or more complications more frequently than those with SMA and SMI values over the median (p = 0.04). Seven out of 25 patients died (28%) during the hospitalization. No differences were found in terms of SMA, SMI and BMI classes between survivors and non-survivors (Table 1).
      No association was present between low muscularity (SMA and SMI below the sex-specific median) and the number of deaths.

      Discussion

      Our study confirmed, in a small cohort of COVID-19 patients in ICU, a high prevalence of overweight and obesity, as well as a high percentage of individuals affected by metabolic syndrome (more than 50%). Moreover, in line with previous larger evidences [
      • Gupta S
      • Hayek SS
      • Wang W
      • et al.
      Factors associated with death in critically ill patients with coronavirus disease 2019 in the US.
      ], the most common comorbidity in our cohort was represented by essential hypertension. It has been well established that nutritional status represents a clinically relevant aspect to be assessed in ICU to stratify the risk of complications and mortality, independently by other factors including BMI and sex [
      • Weijs PJ
      • Looijaard WG
      • Dekker IM
      • et al.
      Low skeletal muscle area is a risk factor for mortality in mechanically ventilated critically ill patients.
      ]. In addition, in critical care, as well as in chronic diseases (e.g. cancer, chronic kidney disease, cirrhosis, etc.), body weight and BMI appear not accurate to reflect nutritional status [
      • Weijs PJ
      • Looijaard WG
      • Dekker IM
      • et al.
      Low skeletal muscle area is a risk factor for mortality in mechanically ventilated critically ill patients.
      ], in particular in small cohorts of patients such as ours. In this light, body composition analysis adds important information, specifically regarding low muscle mass assessed by CT, known to be a negative predictor of survival in ICU [
      • Ng CC
      • Lee ZY
      • Chan WY
      • et al.
      Low muscularity as assessed by abdominal computed tomography on intensive care unit admission is associated with mortality in a critically ill Asian Population.
      ].
      Our data showed that SMA and SMI, both indices of muscularity, were low when compared to the available data obtained among healthy individuals and more importantly in critically ill patients [
      • Weijs PJ
      • Looijaard WG
      • Dekker IM
      • et al.
      Low skeletal muscle area is a risk factor for mortality in mechanically ventilated critically ill patients.
      ,
      • Ng CC
      • Lee ZY
      • Chan WY
      • et al.
      Low muscularity as assessed by abdominal computed tomography on intensive care unit admission is associated with mortality in a critically ill Asian Population.
      ]. Our results indicate that these indices were not different between patients with normal BMI vs those with higher BMI ( 25) and between males and females. Also, considering the emergency setting of the COVID-19 pandemic and therefore the limited clinical information obtained by the relatives, we did not have information regarding patient's unintentional body weight loss, which is a well-known factor related to low muscle mass and higher in-hospital mortality [
      • Barazzoni R
      • Sulz I
      • Schindler K
      • et al.
      nutritionDay Research Group. a negative impact of recent weight loss on in-hospital mortality is not modified by overweight and obesity.
      ].
      Unfortunately, due to the small number of participants we did not have the power to detect an association between low muscularity and death. However, we were able to find an association between low muscle mass (defined with SMI and SMA values below the sex-specific median) and the presence of at least one complication during ICU stay. This observation appears a novel one, suggesting the importance of changes in nutritional status and body composition (muscle mass), beyond BMI, and outcomes in critically COVID-19 patients.
      Our study has several limitations including the small number of COVID-19 cases, the lack of a control group (non-COVID-19 critically ill patients) and the absence of an analysis of the changes of muscle mass overtime, although our aim was to assess muscularity in a cross-sectional setting. We did not assess adiposity which may have added information regarding outcomes.
      In conclusion, our study although exploratory, suggests the importance of the evaluation of muscle mass in COVID-19 patients in ICU to better stratify the risk of complications, and likely mortality, and to implement nutritional strategies in this setting. Larger trials are mandatory to confirm our initial results.

      Author Contributions

      AM and DA were responsible for the development of the research. AM, GI performed statistical analyses and contributed to the interpretation of the findings. AM wrote the paper. VR, CC performed images analysis. DA and MR collected the data. MM contributed to the manuscript revision and interpretation of the data.

      Funding

      This research received no specific grant from any funding agency, commercial or not-for-profit sectors.

      Declaration of Competing Interests

      The authors declare no conflict of interest.

      References

        • Hendren NS
        • de Lemos JA
        • Ayers C
        • et al.
        Association of body mass index and age with morbidity and mortality in patients hospitalized with COVID-19: results from the American Heart Association COVID-19 Cardiovascular Disease Registry.
        Circulation. 2020; (Epub ahead of print 17 November 2020)https://doi.org/10.1161/CIRCULATIONAHA.120.051936
        • Moonen HPFX
        • van Zanten FJL
        • Driessen L
        • et al.
        Association of bioelectric impedance analysis body composition and disease severity in COVID-19 hospital ward and ICU patients: the BIAC-19 study.
        Clin Nutr. 2020; 5614 (S0261-): 30551-30553
        • Yang Y
        • Ding L
        • Zou X
        • et al.
        Visceral adiposity and high intramuscular fat deposition independently predict critical illness in patients with SARS-CoV-2.
        Obesity (Silver Spring). 2020; 28: 2040-2048
        • Battisti S
        • Pedone C
        • Napoli N
        • et al.
        Computed tomography highlights increased visceral adiposity associated with critical illness in COVID-19.
        Diab Care. 2020; 43: e129-e130
        • Deng M
        • Qi Y
        • Deng L
        • et al.
        Obesity as a potential predictor of disease severity in young COVID-19 patients: a retrospective study.
        Obesity (Silver Spring). 2020; 28: 1815-1825
        • Weijs PJ
        • Looijaard WG
        • Dekker IM
        • et al.
        Low skeletal muscle area is a risk factor for mortality in mechanically ventilated critically ill patients.
        Crit Care. 2014; 18: R12
        • Dusseaux MM
        • Antoun S
        • Grigioni S
        • et al.
        Skeletal muscle mass and adipose tissue alteration in critically ill patients.
        PLoS One. 2019; 14e0216991
        • Ng CC
        • Lee ZY
        • Chan WY
        • et al.
        Low muscularity as assessed by abdominal computed tomography on intensive care unit admission is associated with mortality in a critically ill Asian Population.
        JPEN J Parenter Enteral Nutr. 2020; 44: 425-433
        • Gupta S
        • Hayek SS
        • Wang W
        • et al.
        Factors associated with death in critically ill patients with coronavirus disease 2019 in the US.
        JAMA Intern Med. 2020; 180 (J): 1-12
        • Barazzoni R
        • Sulz I
        • Schindler K
        • et al.
        nutritionDay Research Group. a negative impact of recent weight loss on in-hospital mortality is not modified by overweight and obesity.
        Clin Nutr. 2020; 39: 2510-2516