The objective of this retrospective study was to identify biochemical parameters and CT characteristics associated with ARDS covid-related or death. The need to identify early clinical markers of covid severity is compelling.
Obesity has been identified as risk factor for hypoventilation syndrome in Intensive Care Unit (ICU) patients (19) and for respiratory failure in patients with ARDS (20).
Obesity is also associated with chronic inflammation and visceral adipose tissue is capable of secreting inflammatory mediators such as IL-6, TNF, INF gamma, IL1 beta (21-23). Moreover, in patients with obesity and diabetes, the expression of Angiotensin-converting enzyme 2(ACE2), the functional receptor for SARS-CoV-2, is upregulatedin adipocytes and turns adipose tissue into a potentialtarget and viral reservoir. This may explain why the excess of VAT anddiabetes are potential empowering factors for COVID-19infection (24).
Some reports showed as CT-based quantification of VAT and upper abdominal circumference in routine chest CTs were associated toworse clinical outcome in patients withSars-CoV-2 infection and asEAT closely correlated with abdominal visceral adiposity and metabolic risk factors (25-26).
Some authors have investigated the association between EAT and Covid-19 severity showing how epicardial fat measured in terms of thickness at the level of the right coronary artery origin on the axial plane (8,25) was similar among the groups of COVID-19 severity.
Other authors, using a fully automated, three-dimensional measurement of epicardial fat, which gives a better estimate of visceral deposits, have shown that EAT volume and attenuation were associated with the quantitative burden of Covid 19 pneumonia and that both parameters independently predicted clinical deterioration or death (9,27).
In our study, using a semiautomatic three-dimensional EAT volume quantification system, a significantly higher value of EAT volume was observed in the ARDS/death group and it was a strong independent predictor of negative outcome. It was also interesting to note when our sample was stratified based on the severity of ARDS (mild, moderate and severe), EAT volume showed a progressive increase in parallel with the degree of ARDS. Infact, not only P/F at baseline but also P/F nadir was positively correlated with EAT.
The lack of difference in EAT attenuation between the two groups and among patients with different degrees of ARDS, could be probably explained by the attenuation calculated exclusively on a ROI of 6 mm.
The role of EAT as a viral reservoir and cytokine storm amplification site, could explain not only a worsening of lung function, but also the clinical deterioration up to multiorgan failure and death, through a direct/paracrine and indirect/systemic effect (27-30).
Interestingly, our study showed that EAT volume correlated with metabolic parameters, in particular with blood glucose.
We found that fasting glucose was higher in the ARDS/death group and that fasting glucose at admission, had a trend as independent risk factor for ARDS or death. This data could be confirmed by increasing the sample size.
This was in line with previous reports highlighting that admission hyperglycemiawas a strong predictor of radiographic findings of ARDS (15)and that not only diabetes but alsoinfection-related hyperglycemiaat admission were associated with higher risks of adverse outcomes among patients with COVID-19 (31).
Further studies are needed to evaluate both the role of tight glycemic control in the outcome of Covid-19 pneumonia and the possibility of modifying EAT with target therapies to prevent the outbreak of the immune response.
Our study has some limitations. First, the nature of this study was retrospective and only selected biochemical and clinical parameters were available. Second, we didn’t have the possibility of applying cardio-synchronization software to the CT acquisition.Third, the epicardial fat attenuation was calculated on a 6 mm ROI which did not allow an average estimate of the whole EAT attenuation.
Some strengths should also be emphasized. First our sample size was larger than in other studies. Second, we were able to obtain the BMI of about half of the patients, despite the critical health and isolation conditions that prevented the physical examination of the patients, which allowed a preliminary anthropometric comparison between the two groups, even if we were unable to include this obesity measure in our multivariable model. Third,the same decision-making protocol for hospitalization and treatment for all patients made the samplehomogeneous in the severity of COVID-19 pneumonia or in hospital outcomes.Fourth, chest CT indications and acquisition protocols were standardized. Fifth, the semiautomatic quantification of the epicardial fat volume and the positioning of the ROI for the estimation of tissue attenuation were performed by the same operator.
In conclusion, we found that EAT was correlated strictly with inflammatory markers, as C-reactive protein and fibrinogen and fasting blood glucose. Our findings suggest that hyperglycemia in hospitalized patients should be adequately treated in patients with or without diabetes and that both blood glucose and EAT, as measurable and modifiable targets, could be included in a risk score for patients hospitalized withCovid-related pneumonia, in order topredict a worst prognosis and improve the therapeutic approach.
Indirect parameters of inflammation, such as hyperglycemiaand EAT, easily obtained by chest CT in patients with suspicion of COVID-19, could allow the early identification of subjects at greater risk of developing severe complications.