Laboratory parameters predicting mortality of adult in-patients with COVID-19 associated cytokine release syndrome treated with high-dose tocilizumab

Abstract

Large randomized clinical trials in severe Coronavirus Disease 2019 (COVID-19) patients have proven efficacy of intravenous tocilizumab. Our aim was to describe the laboratory parameters predicting in-hospital mortality of patients with tocilizumab administration in COVID-19 associated cytokine release syndrome (CRS).We evaluated high-dose (8 mg/kg) intravenous tocilizumab administration in severe and critically ill COVID-19 adult patients fulfilling predefined strict CRS criteria. A single-centre, prospective, observational cohort study was carried out among consecutive adult (≥18 years of age) in-patients with COVID-19 between April 1 and December 31, 2020. The primary endpoint was 28-day all-cause mortality. The changes in laboratory parameters from baseline on day 7 and 14 after administration of tocilizumab were analysed.In total, 1801 patients were admitted to our centre during the study period. One hundred and six patients received tocilizumab, and among them 62 (58.5%) required intensive care unit admittance while 25 (23.6%) deceased. At day 7 after tocilizumab administration, inflammatory markers (CRP, IL-6, ferritin) and lactate dehydrogenase (LDH) values were significantly lower among survivors. Subsequently, at day 14, differences of IL-6 and LDH levels has become more pronounced between subgroups. Restoration of absolute lymphocyte count (ALC) by day 7 and 14 was insufficient among patients who died.In our cohort, administration of high-dose tocilizumab for COVID-19 patients with CRS demonstrated clinical and sustained biochemical parameter improvement in 76.4%. In this patient population high and increasing LDH, IL-6, and low ALC levels had a predictive role for mortality.

Predictors of poor outcome in tocilizumab treated patients with Sars-CoV-2 related severe respiratory failure: A multicentre real world study

“…Literature evidence shows that poor outcome is associated with persistence of high biomarkers values after Tocilizumab administration. Lakatos B et al, in a one hundred and six sample size study on COVID-19 patients treated with Tocilizumab, reported that patients who died had higher values of IL-6 and LDH and insufficient restoration of lymphocytes count at 7 and 14 days after Tocilizumab administration compared with survivors [35] . A lot of evidence shows that different phenotypes of COVID-19 patients with different inflammatory and immune response, mortality risk and response to respiratory support exist [4] , [36] , [37] .…”

Application of Machine Learning in Hospitalized Patients with Severe COVID-19 Treated with Tocilizumab

“…Therefore, monitoring these parameters during hospitalisation of the patient on tocilizumab treatment would be the key to see if there is a beneficial response or, on the contrary, an increased risk of mortality. The scientific evidence concludes that a poor outcome is associated with persistently high biomarker values over time after tocilizumab administration, such as LDH, IL-6 and low absolute lymphocyte counts [ 56 ]. To circumvent this problem, and due to the large subject-to-subject variability in response to anti-inflammatory treatment for COVID-19, personalized strategies are being developed, guided by rapid cytokine assays, such as the digital immunoassay, which allows rapid “real-time” cytokine monitoring [ 57 ].…”

Trends of thrombo-inflammation biomarkers after Tocilizumab predict treatment failure better than scores in patients with severe SARS-CoV2 related respiratory failure

“…To tail treatment on single patient based on his or her inflammatory status could improve the rate of success, as highlighted by Levi M in a recent issue of European Journal of Internal Medicine [2] . Evidence shows that the response to TCZ in this context is associated with restoration of thrombo-inflammation biomarkers after its administration [3] , while persistence of high biomarkers after TCZ administration seems to be associated with poor outcome [4] . Recently, Emre Eskazan A. et al.…”