Increasing Levels of Macrophage Migration Inhibitory Factor (MIF) in COVID-19 Infection and Its Pathophysiological Role; Though a Defined Cut-off Value Might Be Clinically Misleading

Abstract

Background: The serious outbreak of coronavirus disease 2019 (COVID-19) has provoked deep concern throughout the world. The pathophysiologic network leading to severe conditions has still unsolved gaps. Considered a pleiotropic, multifaceted cytokine, macrophage migration inhibitory factor (MIF) has distinct functions, which seem to stand at the edge of distinct known mechanisms involving in COVID-19 pathogenesis. Additionally, MIF is a key mediator of acute respiratory distress syndrome and lung injury. Objectives: The current study aimed to evaluate the serum levels of MIF in COVID-19 patients, particularly in severe cases. Methods: This case control study was performed on the sera of 60 randomly selected COVID-19 patients as case group and 30 randomly selected healthy individuals as control group during November 2020 till April 2021 at Mashhad University of Medical Sciences. The case group included 30 outpatients with mild disease and 30 hospitalized severe subjects. A commercial enzyme-linked immunosorbent assay was utilized to measure serum MIF. Data were analyzed using SPSS version 16 with student t-test and chi-squared test considering a P < 0.05 as statistical significance level. Results: There was no statistical difference between two groups regarding demographic variables. According to the obtained data, significantly higher MIF levels were observed in the affected subjects than the healthy individuals, particularly in severe COVID-19 subjects (severe: 65.31 ± 6.2 ng/mL, mild: 40.45 ± 6.6 ng/mL, healthy: 20.63 ± 6.1 ng/mL P < 0.0001). The receiver operating characteristic (ROC curve) drawn for the present study illustrates that MIF amounts differentiate COVID-19 severe and mild cases with high accuracy (90.8%) (sensitivity:86.6%, specificity:96.6%). Conclusions: There might be an association between MIF concentration with respiratory failure and disease exacerbation due to COVID-19 infection. Therefore, MIF can act as a marker of clinical severity for COVID 19 infection. However, due to variations in MIF amounts a definite cut-off value might be specific to the study and should be considered with caution. MIF is supposed to be one of the most important cytokines in COVID-19 pathogenesis and might be a target for therapeutic approaches with MIF inhibitors in possible upcoming disease peaks.