ABSTRACT
A 55-year-old male patient presented to our outpatient clinic with complaints of dark urine and fatigue. The laboratory parameters were as follows: alanine aminotransferase 821 IU/L, aspartate aminotransferase 1042 IU/L, alkaline phosphatase 412 IU/L gamma-glutamyl transferase 268 IU/L and the complete urinalysis revealed hematuria, while other laboratory parameters were normal. The patient's abdominal ultrasonography (USG) and Doppler USG showed no pathological finding. Hepatitis and the other serologies were negative. The patient, who did not exhibit any symptoms of Coronavirus disease-2019 (COVID-19) initially, exhibited bilateral opacities in the middle zones on chest X-ray taken after the development of fever and dyspnea on the third day of hospitalization. The computed tomography scan revealed segmental consolidation across the subpleural regions, mostly in the middle zones, and was evaluated to be consistent with COVID-19. COVID-19 treatment was planned for the patient whose nasopharyngeal swab tested positive for severe acute respiratory syndrome-Coronavirus-2.
ABSTRACT
Background: Due to the pleiotropic cytokine interleukin-6 (IL-6) plays a pivotal role in the pathogenesis of COVID-19, tocilizumab, an inhibitor of the IL-6 receptors, was considered as an attractive therapeutic option. When the infamma-tion cascade is excessive and therapy is delayed, the efforts for suppression of infammation does not necessarily reduce mortality in all cases. Besides, early using anti-cytokine therapy may lead to both increased cost and risks including iatrogenic immunosuppression (1). Defning of patients who will beneft from tocilizumab and determining optimal timing of tocilizumab will prevent drug-related side effects and increased costs due to unnecessary drug use. Objectives: To investigate the reliability of pre-treatment levels of prognostic nutritional index (PNI), C-reactive protein/albumin ratio (CAR), systemic immune-in-fammatory index (SII), IL-6, lactate dehydrogenase (LDH) as a treatment response biomarker in hospitalized COVID-19 patients who administered tocilizumab. Methods: One hundred thirty three COVID-19 patients received tocilizumab were included. The end-points of treatment effectiveness were evaluated with the rate of death and emerging need for mechanical ventilation at 28 days of hospitalization. To determine independent mortality risk factors, multivariate logistic regression analyzes were performed for statistically different variables among groups that were statistically different in univariate analysis. The capacity of IL-6, CAR, PNI, SII and LDH values in predicting of tocilizumab response in COVID-19 patients were analyzed using receiver operating characteristic (ROC) curve analysis. Results: 34 (25.56%) patients died after tocilizumab therapy. Patients who improved after tocilizumab were signifcantly younger and had signifcantly lower IL-6, LDH, SII, CAR and higher PNI than patients who died. In univariate analyses, mortality was signifcantly associated with age, IL-6, LDH, PNI, SII, CAR and CRP. In multivariate analysis, age (OR:1.070, 95%CI:1.019-1.124, p:0.007) and LDH (OR:1.006, 95CI%:1.003-1.010, p<0.001) were found to be independent predictors of mortality after tocilizumab therapy. To identify of tocilizumab response in COVID-19 patients, IL6 had the highest area under curve (AUC) value (AUC:0.782, 95%CI:0694-0.870), followed by LDH (AUC:0.761, 95%CI:0.661-0.861), PNI (AUC:0.696, 95%CI:0.584-807), SII (AUC:0.671, 95%CI:0.551-0.790), CAR (AUC:0.682, 95%CI:0.578-0.786) and CRP (AUC:0.643, 95%CI:0.535-0.751). Predictive performance of infammatory biomarkers in the prediction of mortality after tocilizumab therapy was presented in Table 1. Conclusion: Although the patients with signifcantly lower IL-6, LDH, SII, CAR and higher PNI levels improved after tocilizumab therapy, only serum LDH levels and age were found to be as independent predictors of mortality. To specify the optimal time interval and the patients who will beneft from tocilizumab, these biomarkers may be used.