Total Psoas Area and Psoas Density Assessment in COVID-19 Patients Using CT Imaging – Could Muscle Mass Alteration During Intensive Care Hospitalization be Determined?

Since its debut, as reported by the first published studies, COVID-19 has been linked to life-threatening conditions that needed vital assistance and admission to the intensive care unit (ICU) [1,2]. Although the medical picture of those diagnosed with COVID-19 appeared to be heterogeneous [3], a large group of patients experienced severe COVID-19 infection prompting life-saving treatments such as non-invasive ventilation (NIV), invasive mechanical ventilation (IMV), vasopressors, extracorporeal membrane oxygenation, and renal replacement therapy [4]. Considering acute respiratory failure (ARF) the indicator for fulminant COVID-19 disease, supportive care of hypoxic distress was the principal part of the therapy [3,4]. Therefore, skeletal muscle-related problems were situated on a secondary level. However, skeletal muscle is a core element in an organism’s health due to its ability to keep energy balance and homeostasis. About 45–50% of the body’s mass consists of skeletal muscle, which is essential for physical activity, oxygen consumption, energy metabolism, storage, and turnover [5]. For instance, patients with acute COVID-19 viral infection may suffer from mild to severe acute myopathy [6,7]. Additionally, many patients with prolonged hospitalization [8], are characterized by a greater probability prone of critical illness myopathy (CIM) or intensive care unit-acquired weakness (ICUAW) [9]. Nonetheless, skeletal muscle changes rooted in low muscle strength, low muscle quantity, and low physical performance represent the attributes of sarcopenia. Despite various techniques used to estimate muscle mass or muscle quantity, computed tomography (CT) is accepted as the gold standard for non-invasive evaluation [10]. Doctors may assess muscle area and density in various patients who have previously had CT imaging. This analysis is essential for aiding doctors in dividing patients for additional issues and mortality. Only a few researchers have investigated this issue [11].

The methods pattern for the present study design considered the guidelines for reporting observational studies, The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement (Table 1).

Study participants

The screening included critically ill adult patients. Inclusion criteria were patients ≥ 18 years of age admitted in the ICU for at least 24 hours, positively tested for SARS-COV2 by real-time polymerase chain reaction (RT-PCR), and who had two eligible CT scans for psoas analysis. Non-critically ill patients, or those tested negative for SARS-COV2, minors, pregnant women, patients hospitalized for less than 24 hours in the ICU or those with non-eligible CT scans for psoas analysis were excluded. The final cohort included twenty-two patients, for whom data was collected from the electronic medical records (Hipocrate3 Concept) (Figure 1).

Fig.1.

Psoas CT evaluation

Two radiologists with at least two years of experience each evaluated the scans. Radiologists were unaware of the clinical progress and results of the patients. Patients with two psoas examinations were included in the study group to observe the musculoskeletal changes. The patients were lying supine and the CT images were evaluated in the abdominal window. Psoas muscle area and density (HU) were measured at the level of the third lumbar vertebrae (Figure 2). Picture Archiving and Communicating System (PACS) and RadiAnt DICOM Viewer were used for data analysis.

Fig. 2.

Patients’ characteristics, details about admission status, inflammatory markers, and metabolic response are summarized in Table 2. Out of 22 patients included, one-third were male (36.4%), with a mean age of 71.09±10.57 years old. All patients had an emergency criterion to be admitted to the ICU and half of them were admitted for ARF. Used as a prognostic tool for early clinical decompensation, qCSI identified patients at risk of critical respiratory illness in the next 24 hours (qCSI≥7 points). At the same time, CHOSEN score (<29 points) and modified CHOSEN score (<19 points), used as predictors of suitability for discharge, identified patients not apt to be discharged. Median LOS in hospital was 18 days and median LOS in ICU was 11 days. When admitted to the ICU 50% of the patients needed IMV and during hospitalization, the percentage increased by 30%. During the ICU stay, the majority received IMV for more than 96 hours. Laboratory results identified white blood count (WBC) values of 12.307±8.4211/μL, neutrophilia 10.381±7.924/μL, and lymphopenia 0.958±0.783/μL and high values of CRP= 106.810 (5.660–353.300) mg/L. Elevated neutrophil to lymphocytes ratio (NLR)= 10.537 (3.758–66.631), platelets to lymphocytes ratio (PLR) = 382.907 (59.644–1184.2100), and SII= 2361.589 (474.000–42981.947) showed an imbalance in inflammatory status. The metabolic response identified normal values for creatinine of 1.025 (0.140–8.160) mg/dL and glucose of 149.136±73.879 mg/dL in critical care settings.

Minor and not statistically significant differences (p> 0.05) were noticed regarding the right and the left total psoas area (TPA) and HU when comparing the results of the two radiologists (Table 3). Further analysis included the mean results of the two radiologists for each CT scan evaluation. As shown in Table 4., it is noticed that the right TPA decreased by −0.12 cm² and the left TPA decreased by −0.59 cm². Changes were observed in the right psoas HU by −4.24 HU and in the left psoas HU by −3.99 HU. There are no statistically significant differences, and this evidence is also sustained by the box plots comparing alterations over time (Figure 3).

Fig. 3.

Along with these results, AUC-ROC for psoas area and IMV duration (Figure 4) and outcome (Figure 6), respectively AUC for psoas HU and IMV duration (Figure 5) and outcome (Figure 6) were placed side by side. Regarding AUC-ROC for psoas area and IMV duration, an AUC-ROC near 1 was obtained for right psoas area (AUC-ROC= 0.929, 95% CI= 0.741–0.994, p= 0.0001) and left psoas area (AUC-ROC= 0.833, 95% CI= 0.621–0.954, p=0.0001) and IMV duration of 24–96 hours (Table 5). As to AUC-ROC for psoas HU and >96 hours of IMV, the results were AUC-ROC= 0.715, 95% CI= 0.491–0.882, p= 0.049 for the right psoas muscle and AUC-ROC= 0.623, 95% CI= 0.399–0.814, p= 0.31 for the left psoas muscle (Table 6). With reference to AUC-ROC and outcome, it is underlined that AUCROC is close to 0.5 value, for both the psoas area and HU, indicating that the model had no class separation capacity (Table 7).

Fig. 4.

Fig. 5.

Fig. 6.

Assessing possible correlations between LOS in hospital and in ICU with psoas area and HU, for the first CT scan performed, it is shown a positive coefficient correlation (0.417) and statistically significant (p= 0.02) with regard to the LOS in ICU and right psoas HU, and a positive coefficient correlation (0.666) and statistically significant (p= 0.01) with regard to the LOS in ICU and left psoas HU (Table 8). Other than those findings, no other correlations were verified.

In the long run, it was found that 48% of patients may gain ICU-AW ^[15]. Critically ill patients may lose more than 15% of their muscle mass over one week and 2% per day in the first week of admission, which could lead to negative long-term repercussions, as underlined in one of the most recent systematic reviews and meta-analyses by Fazzini et al. [15,16]. Typically, ICU-AW is assessed by ultrasound and CT [15].

In our study, we analyzed two CT scans performed during the hospitalization and we compared TPA and psoas HU over a period (Figure 3). Firstly, good reliability in both psoas measurements was demonstrated by the two blinded radiologists. With minor mean differences in right and left TPA and psoas HU, no statistically significant differences were noticed (p>0.05) (Table 3.) Secondly, the dynamic decrease was detected in TPA (right TPA= −0.12cm², p= 0.88; left TPA= −0.59cm², p= 0.56) and in psoas HU (right psoas HU= −4.24, p=0.17; left psoas HU= −3.99, p= 0.17), but not statistically significant as exposed in Table 4.

Furthermore, AUC-ROC for psoas area and IMV was calculated, classifying patients <24 hours of IMV, 24–96 hours of IMV, and > 96 hours of IMV. As shown in Table 5, a statistically significant result was found for patients ventilated for a maximum of 96 hours, as follows for the right psoas area was obtained: criterion >0.275, AUC-ROC= 0.929, 95%CI= 0.741–0.994, p= 0.0001 and for the left psoas area: was obtained criterion >0.307, AUC-ROC= 0.833, 95%CI= 0.621–0.954, p= 0.0001. As both the right and left psoas AUC-ROC is near one, it suggests a good reserve regarding this period of IMV (Figure 4).

Boutin et al. has analyzed sarcopenia imaging implications. As a follow, it has been shown that there is a strong association between CT-derived values from a single CT slice and whole-body adipose tissue and skeletal muscle [17]. Of great significance is that a CT scan can be used to assess the presence of intramuscular fat: “A threshold range of 29 to 150 HU is commonly used to define the muscle, whereas adipose tissue typically ranges from − 30 to − 190 Hounsfield units” ^[17,18]. Even if there is no statistically significant evidence, our study results identified for both A and B investigators that right psoas HU and left psoas HU are in the range that defines the muscle (Table 3.). Assessing the same intervals of IMV as for the TPA, regarding psoas HU, the following results were found for >96 h of IMV: for the right psoas HU, criterion ≤−4.12, AUC-ROC= 0.715, 95%CI= 0.491–0.882, p= 0.049; for the left psoas HU, criterion ≤−4.27, AUC-ROC= 0.623, 95%CI=0.399–0.814, p= 0.31. In this situation, as AUC-ROC is close to 0.5, the model had a dissatisfactory separation capacity for IMV >96 hours (Figure 5)

Regarding the clinical presentation of COVID-19, it is complemented by multiple extrapulmonary manifestations, despite the disease’s notable respiratory complications. Subjects suffering from moderate to severe SARS-CoV-2 infection acknowledged signs of muscular impairment, reduced capacity for physical activity, and fatigue [19]. Moreover, among SARS-CoV-2 critically ill patients, acute sarcopenia was identified as a side effect [20]. We analyzed correlations between psoas changes and LOS in hospital and in ICU. Positive coefficient correlation was found for left psoas on the first CT scan (correlation coefficient= 0.362, p= 0.09 for the LOS in Hospital; correlation coefficient= 0.666, p= 0.01 for the LOS in ICU). Nonetheless, AUC-ROC for negative outcome was evaluated (Figure 6). Only six patients were discharged from the hospital. The curves show poor separation capacity for the negative outcome (death), for both TPA and psoas HU (AUC-ROC close to 0.5).

In conclusion, our study suggested that over a short period the psoas muscle area and the psoas HU decline for both the left and the right sight in adult COVID-19 patients in ICU conditions. It was not noticed a statistically significant difference regarding the results of TPA and HU comparing the two CT scans in dynamics. Although more than two-thirds of the patients had a negative outcome, it was not possible to demonstrate an association between the SARS-COV2 infection and psoas muscle impairment. These findings highlight the need for further larger investigations.