Abstract

Mortality in critically ill coronavirus disease 2019 (COVID-19) patients is high and pharmacological treatment strategies remain limited. Early-stage predictive biomarkers are needed to identify patients with a high risk of severe clinical courses and to stratify treatment strategies. Macrophage migration inhibitory factor (MIF) was previously described as a potential predictor for the outcome of critically ill patients and for acute respiratory distress syndrome (ARDS), a hallmark of severe COVID-19 disease. This prospective observational study evaluates the predictive potential of MIF for the clinical outcome after severe COVID-19 infection. Plasma MIF concentrations were measured in 36 mechanically ventilated COVID-19 patients over three days after intensive care unit (ICU) admission. Increased compared to decreased MIF was significantly associated with aggravated organ function and a significantly lower 28-day survival (sequential organ failure assessment (SOFA) score; 8.2 ± 4.5 to 14.3 ± 3, p = 0.009 vs. 8.9 ± 1.9 to 12 ± 2, p = 0.296; survival: 56% vs. 93%; p = 0.003). Arterial hypertension was the predominant comorbidity in 85% of patients with increasing MIF concentrations (vs. decreasing MIF: 39%; p = 0.015). Without reaching significance, more patients with decreasing MIF were able to improve their ARDS status (p = 0.142). The identified association between an early MIF response, aggravation of organ function and 28-day survival may open future perspectives for biomarker-based diagnostic approaches for ICU management of COVID-19 patients.

Highlights

  • Until now, the coronavirus disease 2019 (COVID-19) pandemic has caused more than 2.1 million death worldwide and more than 100 million cases in total [1]

  • We evaluated the severity of the acute respiratory distress syndrome (ARDS) represented by the Horowitz quotient (HQ), the changes in global organ function, represented by the sequential organ failure assessment (SOFA) score, the need for Extracorporeal Membrane Oxygenation (ECMO), or RRT, respectively, dialysis over 14 days, as well as preexisting conditions of the included COVID-19 patients

  • Overall, circulating plasma migration inhibitory factor (MIF) concentrations were determined from 36 COVD-19 patients on the 1st and the 3rd day during the intensive care unit (ICU) stay

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Summary

Introduction

The coronavirus disease 2019 (COVID-19) pandemic has caused more than 2.1 million death worldwide and more than 100 million cases in total (update28 January 2021) [1]. The coronavirus disease 2019 (COVID-19) pandemic has caused more than 2.1 million death worldwide and more than 100 million cases in total In Germany, mortality rates are high and the daily growing number of around 20,000–30,000 new cases during fall 2020 brought even intensive care unit (ICU) with large capacities to their limit. 2 (SARS-CoV-2) infections, and 20% of those hospitalized, experience severe symptoms necessitating intensive care treatment [2]. The most common symptoms in hospitalized patients are fever (70–90%), dry cough (60–86%), shortness of breath (53–80%) [3], and the development of endothelial dysfunction and organ failure, that requires prolonged ICU treatment [4]. In particular the need for ICU treatment in cases of severe disease is related to high in-hospital mortality rates [5,6]

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