ABSTRACT
Introduction Elevated soluble urokinase Plasminogen Activator Receptor (suPAR) is a biomarker associated with adverse outcomes. We aimed to investigate the associations among plasma suPAR levels (testing the cut-offs <=4 and >=6 ng/mL that supports patient discharge/hospitalisation, respectively) with other biomarkers such as PCR, PCT, IL-6 and with sex, age, discharge/death and WHO disease severity in patients tested positive for SARS-CoV-2. Methods We performed an observational cohort study of 99 patients (37 females, 62 males) presenting with COVID-19 symptoms at Department of Infectous and Critical Care of our Hospital in April 2020. Plasma suPAR was measured using suPARnostic kit (Virogates, Denmark), an immunoturbidimetric method on Abbott Alinity i platform. Patients were followed for development of mechanical ventilation, mortality or discharged. Statistical analysis was performed using Principal Component Analysis (PCA) that can be applied to datasets to obtain a simplified model for stratifying patients by reducing the number of variables. PCA weights the variables according to their relative importance. This method, in our case, can aid in determining key variables in management of patients affected by SARS-CoV-2. Results The mean age was 58 years;women had a higher concentration average of suPAR (8.9 vs 8.3 ng/mL) but the subdivision by sex did not determine any clustering. All variables showed a positive correlation with disease severity, better with IL-6 and suPAR (IL-6=25.3%, suPAR=24%, age=16.4%, PCT=15.4%, PCR=17.2%), allowing a subdivision of 3 groups (severe/ critic: IL-6=227.65 pg/mL, suPAR=9.26 ng/mL;moderate: IL-6=48.1 pg/mL, suPAR=7.35 ng/mL, paucisymptomatic: IL-6=3.7 pg/mL, suPAR=2.78 ng/mL). Combining the variables and discharge/death outcome showed positive correlation although this did not result any clear clustering (n.78 discharged: IL-6=214 pg/mL, suPAR=8.23 ng/mL;n.14 dead: IL-6=286 pg/mL, suPAR=11.31 ng/mL). Discussion Our data show that suPAR levels increase as the disease worsens. Statistical analyses demonstrated that suPAR levels are positively correlated with age and IL-6 levels. Therefore, further evaluation of suPAR plasma levels in different symptoms of COVID-19 patients could still provide important indications for early admission and treatment.
ABSTRACT
Background: The use of cytokine-blocking agents has been proposed to modulate the inflammatory response in patients with COVID-19. Tocilizumab and anakinra were included in the local protocol as an optional treatment in critically ill patients with acute respiratory distress syndrome (ARDS) by SARS-CoV-2 infection. This cohort study evaluated the effects of therapy with cytokine blocking agents on in-hospital mortality in COVID-19 patients requiring mechanical ventilation and admitted to intensive care unit. Methods: The association between therapy with tocilizumab or anakinra and in-hospital mortality was assessed in consecutive adult COVID-19 patients admitted to our ICU with moderate to severe ARDS. The association was evaluated by comparing patients who received to those who did not receive tocilizumab or anakinra and by using different multivariable Cox models adjusted for variables related to poor outcome, for the propensity to be treated with tocilizumab or anakinra and after patient matching. Results: Sixty-six patients who received immunotherapy (49 tocilizumab, 17 anakinra) and 28 patients who did not receive immunotherapy were included. The in-hospital crude mortality was 30,3% in treated patients and 50% in non-treated (OR 0.77, 95% CI 0.56-1.05, p=0.069). The adjusted Cox model showed an association between therapy with immunotherapy and in-hospital mortality (HR 0.40, 95% CI 0.19-0.83, p=0.015). This protective effect was further confirmed in the analysis adjusted for propensity score, in the propensity-matched cohort and in the cohort of patients with invasive mechanical ventilation within 2 hours after ICU admission. Conclusions: Although important limitations, our study showed that cytokine-blocking agents seem to be safe and to improve survival in COVID-19 patients admitted to ICU with ARDS and the need for mechanical ventilation.