Macrophage Migration Inhibitory Factor and Post-Discharge Inflammatory Profiles in Severe COVID-19: A Prospective Observational Study from Romania

TL;DR

This study shows that severe COVID-19 patients have prolonged inflammation after discharge, with high levels of MIF and other cytokines.

Contribution

The study identifies MIF as a potential marker for immune recovery and long-term immune dysregulation in severe COVID-19.

Findings

Severe COVID-19 patients had elevated MIF, IFN-γ, IL-17, and TNF-α at admission.

MIF and IFN-γ remained elevated in severe patients one month post-discharge.

Cytokine profiling could help identify patients at risk of long-term immune issues.

Abstract

Dysregulated cytokine responses are a hallmark of severe COVID-19; however, the persistence of these responses following hospital discharge remains inadequately understood. This study aimed to characterize the inflammatory profile of hospitalized COVID-19 patients in Mureș County, Romania, at the point of admission and one month post-discharge. We conducted a prospective observational study involving 68 patients with RT-PCR-confirmed SARS-CoV-2 infection, classified according to disease severity. Blood samples were collected at baseline and after one month. Macrophage migration inhibitory factor (MIF) levels were quantified using ELISA, while other cytokines, including MCP-1, IP-10, IFN-γ, IL-4, IL-10, IL-13, IL-17, and TNF-α, were measured via Luminex multiplex assays. Patients with severe disease exhibited significantly elevated levels of MIF, IFN-γ, IL-17, and TNF-α at admission (p < 0.0001). Although cytokine concentrations generally declined over time, patients with severe disease continued to display persistently elevated MIF (mean 31,035 pg/mL), IFN-γ, and TNF-α, indicative of ongoing inflammatory processes. Clinical parameters such as respiratory rate and oxygen saturation correlated with disease severity. These findings suggest that severe COVID-19 induces a prolonged inflammatory response, with MIF and IFN-γ remaining elevated beyond the acute phase. Cytokine profiling holds potential for improving prognostic assessments and identifying patients at risk of long-term immune dysregulation, with MIF emerging as a potential candidate marker for immune recovery and a possible target for therapy.

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