Resistin and IL-15 as Predictors of Invasive Mechanical Ventilation in COVID-19 Pneumonia Irrespective of the Presence of Obesity and Metabolic Syndrome

Abstract

The cytokine signature present in COVID-19 could provide information on the pathogenic mechanisms of the disease and could identify possible prognostic biomarkers and possible therapeutic targets. In this longitudinal work, we studied the clinical and biochemical parameters and circulating cytokine levels of 146 patients at the time of admission for COVID-19 and 4-6 weeks later. The main objective of this study was to determine whether basal cytokines could be early prognostic biomarkers of COVID-19, and also to analyze the impact of comorbidities, such as obesity or metabolic syndrome (MS), in the cytokine profile. The levels of most inflammatory cytokines were elevated on admission in relation to the level that was reached 4-6 weeks later, except for IL-1β, which was lower on admission; these levels were irrespective of the presence of obesity or MS since the cytokine storm masks these inflammatory processes. Among the cytokines analyzed, those that correlated with a worse prognosis of COVID-19 were resistin, IL-6, IL-8, IL-15, MCP-1 and TNF-α. Specifically, resistin and IL-15 are the best early predictors of requiring invasive ventilation. Therefore, resistin and IL-15 should be included in the personalized treatment decision algorithm of patients with COVID-19.

Keywords: COVID-19; SARS-CoV-2; cytokines; metabolic syndrome; obesity; prediction.

Figure 1

Baseline circulating levels of cytokines of the whole cohort according to COVID-19 pneumonia severity. Serum levels of (A) resistin, (B) IL-6, (C) IL-8, (D) IL-15, (E) MCP-1 and (F) TNF-α in patients with mild, moderate or severe COVID-19 pneumonia. IL, interleukin; TNF-α, tumor necrosis factor alpha; MCP-1, monocyte chemoattractant protein 1. Data were presented as Median and IQR. * p < 0.05 and ** p < 0.001 were considered statistically significant by Mann–Whitney.

Figure 2

Classification and regression trees of the whole cohort of study were elaborated through CRT method for pneumonia categorization (no pneumonia, mild, moderate and severe). IL, interleukin.

Figure 3

Receiver operating characteristic (ROC) curve and Youden index for (A) resistin (n = 79, AUC CI95%: 0.64–0.85), (B) IL-8 (n = 78, AUC CI95%: 0.56–0.77), (C) IL-15 (n = 78, AUC CI95%: 0.59–0.80) and (D) combination of resistin, IL-8 and IL15 (n = 70, AUC CI95%: 0.60–0.82) for the prognosis of COVID-19 severity outcomes (need for mechanical ventilation). AUC, area under the curve; IL, interleukin; Y, Youden index; Se, sensitivity; Sp, Specificity.