Calprotectin as prognostic marker in COVID-19 patients

Introduction: Calprotectin plays an important role in the inflammatory response and its levels were significantly increased in patients with various inflammatory and autoimmune conditions. Calprotectin is located in the cytosol of neutrophils and is released after their activation. The aim of the study was to evaluate the prognostic role of serum circulating calprotectin in COVID-19 patients. Patients and Methods: We retrospectively analyzed data about 195 COVID-19 adult patients, 10 of which resulting in a fatal outcome. Circulating calprotectin and C-reactive protein (CRP) levels were measured with the ACHITECT i2000R System (Abbott Laboratories, Wiesbaden, Germany). Complete blood count was obtained by a standard method on ADVIA 2120 Hematology System (Siemens Healthcare). Result(s): Calprotectin levels and neutrophil counts were higher in patients with a fatal outcome respect to surviving patients: 4.26 (2.01-9.84) vs 1.28 (0.54-3.60) with p=0.006 and 20.26 (8.29-30.26) vs 6.57 (4.74-9.38) with p=0.002.Calprotectin levels correlated with levels CRP (Spearman coefficient 0.354, p<0.001) and neutrophil count (Spearman coefficient 0.350, p<0.001). Both high calprotectin levels and high neutrophil counts were associated with death at multivariate analysis.Multivariate analysis revealed the association with death of both calprotectin levels and neutrophil count, with an odds ratio (OR) higher for calprotectin levels 1.843 (1.292-2.630)p=0.001. ROC curve analysis of calprotectin levels revealed a good discriminating power toward survival with an AUC=0.759 (p=0.0004). The best cut-off value for calprotectin was 1.66 mg/L with a sensitivity of 90% and specificity of 58.9%. To test the prognostic value of this cut-off of calprotectin levels toward the exitus, a Kaplan-Meier analysis was performed. Log-rank test revealed a statistical difference in terms of survival between the two groups (p< 0.0005). Conclusion(s): Calprotectin levels higher than 1.66 mg/L are a predictor of mortality and can be used as a prognostic marker in patients with COVID-19. Calprotectin levels were more efficient in the outcome evaluation than other inflammatory markers, probably because it represents a marker of neutrophil activation.

Diabetes and COVID-19: The potential role of mTOR.

Diabetes is the most frequent comorbidity among patients with COVID-19. COVID-19 patients with diabetes have a more severe prognosis than patients without diabetes. However, the etiopathogenetic mechanisms underlying this more unfavorable outcome in these patients are not clear. Probably the etiopathogenetic mechanisms underlying diabetes could represent a favorable substrate for a greater development of the inflammatory process already dysregulated in COVID-19 with a more severe evolution of the disease. In the attempt to shed light on the possible etiopathogenetic mechanisms, we wanted to evaluate the possible role of mTOR (mammalian Target Of Rapamycin) pathway in this context. We searched the PubMed and Scopus databases to identify articles involving diabetes and the mTOR pathway in COVID-19. The mTOR pathway could be involved in this etiopathogenetic mechanism, in particular, the activation and stimulation of this pathway could favor an inflammatory process that is already dysregulated in itself, while its inhibition could be a way to regulate this dysregulated inflammatory process. However, much remains to be clarified about the mechanisms of the mTOR pathway and its role in COVID-19. The aim of this review is to to understand the etiopathogenesis underlying COVID-19 in diabetic patients and the role of mTOR pathway in order to be able to search for new weapons to deal with this disease.