LABORATORY MARKERS FOR PREDICTING AGGRAVATION AND POOR PROGNOSIS IN PATIENTS WITH COVID-19

Abstract

Introduction: Covid-19 is an infectious disease with systemic involvement, which causes intense changes in the blood system, such as neutrophilia and lymphopenia, as well as changes in coagulation function and the concentration of acute phase proteins. Infected patients require laboratory follow-up to assist in clinical and therapeutic management. It is important to define efficient parameters to predict the clinical course of the disease, especially when the overall symptoms are becoming worse, in an attempt to anticipate therapeutic measures and to ensure the most appropriate assistance. Purpose: To correlate neutrophil and lymphocyte counts and their subtypes with the severity and outcome of patients with Covid-19. Materials and methods: Patients hospitalized for severe Covid-19, of both genders and without evidence of bacterial pneumonia, seen at the CHC-UFPR between April and June 2020, were included. Lymphocyte subpopulation analysis was performed by multiparametric flow cytometry (MFC) on whole blood sample using antibodies against CD45, CD3, CD4, CD8 and CD19. A BD FACSCanto™ II cytometer and Infinicyt™ 2.0 analysis software were used. ROC curve and other statistical relationships were performed with IBM SPSS™ v. 25 software. Results: Patients were divided as moderate (not intubated, n = 41) and severe (intubated, n = 35). From the median total leukocyte, neutrophil and lymphocyte counts and their subsets, we define the cutoff values with the highest correlation with hospital discharge. Patients with lymphocyte counts higher than 489/μL, CD4 counts higher than 326 and CD8 counts higher than 121 had a greater chance of evolving with a better prognosis (p < 0.001). Patients who had neutrophil-to-lymphocyte ratio (NLR) higher than 15.2 showed greater correlation with worse prognosis. Patients with lymphopenia below cutoff values are 40 to 55% more likely to be intubated and 50 to 63% to progress to death. Patients with NLR higher than 15.2 have 53.1% more chances of being intubated and 78.1% of evolving to death. Discussion: Laboratory evaluation is essential in the follow-up of patients with Covid-19. In addition to routinely used biochemical markers, cellular analysis can provide valuable information about the clinic and its progression. Lymphopenia and neutrophilia are common parameters in patients with severe disease, so NLR analysis presents itself as an objective scale for stratification of infected patients with a high correlation with possible outcomes. Associated with this, assessment of the immune profile with low levels of T-cells and especially low levels of positive CD4 cells has been associated with worse prognosis in patients with severe Covid-19. Conclusion: We conclude that analysis of the neutrophil/lymphocyte ratio routinely obtained from the complete blood count may provide relevant prognostic information for patients with Covid-19. In addition, flow cytometry analysis of CD4 and CD8 T-lymphocytes can complement the screening of patients with Covid-19 by providing information on the immune profile of the disease.