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GDF-15 AS A PREDICTOR of MORTALITY in COVID-19: IMPLICATIONS for TREATMENT
Topics in Antiviral Medicine ; 30(1 SUPPL):77-78, 2022.
Article in English | EMBASE | ID: covidwho-1880028
ABSTRACT

Background:

A cytokine storm drives the pathogenesis of severe COVID-19 and has therefore prompted the use of cytokine/transduction pathway inhibitors in the treatment of disease. However, numerous markers with different mechanisms of action have been linked to mortality, complicating the understanding of disease pathogenesis and the elaboration of therapeutic strategies.

Methods:

Retrospective study on COVID-19 hospitalized subjects in the acute phase of disease. A broad range of cytokines (CD25, IL-18, TNF-α, TNF RI, TNF RII, GDF-15, IL-7, LIF, IL-6, CHITINASE3-LIKE1, RAGE and Pentraxin-3) was assessed on plasma samples (Luminex, ELISA) collected upon hospitalization. Subjects were divided into two groups according to their clinical in-hospital death (Survivors S;Non-Survivors NS). Comparisons between groups were performed by Fisher's exact test or Mann-Whitney U test as appropriate. The association between each variable and mortality was analysed through univariate and multiple logistic regression models. Subsequently, survival analysis was conducted with Cox proportional hazard models.

Results:

77 hospitalised Covid-19 patients were enrolled 42 S and 35 NS (Figure 1A). As expected, in the NS group we found a higher proportion of subjects with fever and dyspnoea upon admission, development of ARDS and need of PEEP respiratory support (Figure 1A). NS also displayed significantly higher blood neutrophils/lymphocytes, C-reactive protein, LDH and procalcitonin as well as lower PaO2/FiO2 and peripheral O2 saturation values at admission (Figure 1A). In keeping with these findings, CD25, IL-18, IL-6, TNF-α, TNFRI, TNFRII, GDF-15, IL-7, LIF and Chitinase3-Like1, Pentraxin-3 and RAGE were significantly higher in NS than S (Figure 1B) and were associated to mortality in univariate regression models. In the multivariate regression model GDF-15 and fever were the two more relevant features associated with mortality (Figure 1C). In the survival analysis GDF-15 was the strongest predictor of mortality (HR 2,26, 1,55-3,31;p<0,01 reference group bottom quartile Figure 1D, E).

Conclusion:

Our in-depth characterization of the cytokine storm demonstrates that GDF-15 is an independent predictor of Covid-19 mortality. Given the reported increase of this cytokine with age and its possible mechanistic role in various pathological conditions, our findings suggest that GDF-15 signalling pathway inhibitors may be included as possible therapeutic candidates for Covid-19.
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Collection: Databases of international organizations Database: EMBASE Type of study: Prognostic study Language: English Journal: Topics in Antiviral Medicine Year: 2022 Document Type: Article

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Collection: Databases of international organizations Database: EMBASE Type of study: Prognostic study Language: English Journal: Topics in Antiviral Medicine Year: 2022 Document Type: Article