<scp>IL</scp>‐25 and Periostin Serum Concentrations May Be Associated With <scp>COVID</scp>‐19 Severity and Recovery
Authors: Anna Zaleska, Adrian Gajewski, Anna Dor‐Wojnarowska, Anna Radlińska, Marta Rorat, Maciej Chałubiński
Journal: Allergy (2024)

SARS-CoV-2 infection is associated with a robust inflammatory response, called the 'cytokine storm', in patients with severe or lethal COVID-19 [1]. IL-25 is expressed in human airways and guts, and it induces T2 responses within barrier tissues. It may affect ILC2, T helper 2 (Th2) cells, eosinophils, basophils, mast cells and bronchial epithelium. Periostin is released at sites of injury, and it is responsible for tissue repair, fibrosis and angiogenesis, thus supporting the tissue remodelling. Eotaxin (CCL11) is produced by eosinophils, T and B cells, epithelial and endothelial cells, fibroblasts and smooth muscle cells. It affects mostly mast cells, eosinophils and Th2 cells. The role of T2 cytokines in COVID-19 have not been widely studied [2, 3]. The aim of this study was to assess whether T2 cytokine serum levels, including IL-4,5,13,25,33, TSLP, periostin and eotaxin, may be associated with COVID-19 severity. For this reason, we analysed 51 patients with moderate (n = 16) and severe (n = 35) COVID-19, admitted to three Medical COVID-19 Centres in Wrocław, Poland. Clinical characteristics, comorbidities and treatment are placed in the supplementary section (Table S1, Appendix S1). Patients were assessed on the first (V1) and eigth day of hospitalisation (V2), and then on Days 40–50 (V3). In severe COVID-19, the percentage of lung inflammatory changes in CT scans, CRP, fibrinogen and ferritin was significantly higher with concomitant eosinopenia and lymphopenia on the V1 as compared to the moderate group (Table 1). Eosinopenia is a risk factor for severe outcomes of COVID-19. First, severe COVID-19 patients had significantly higher IL-25 levels as compared to the moderate group (Figure 1A). Moreover, there was a positive correlation between IL-25 levels and changes in CT scans (R = 0.47, p < 0.001), fibrinogen (R = 0.3, p < 0.05) and ferritin (R = 0.29, p < 0.05) concentrations (Figure 1B, Table S2). IL-25 overproduction was observed in COVID-19 patients, and it was shown to suppress an immunity against respiratory viruses. IL-25 has been proposed as a marker of severe COVID-19 and its poor prognosis [4]. We did not observe any differences in periostin, eotaxin and TSLP concentrations between groups. Second, both IL-25 and periostin concentrations were elevated on V1 and later significantly decreased (Figure 1A). Periostin decreased already on Day 8, while IL-25 decreased only on V3. High periostin levels were detected in both mild/moderate and severe cases [5]. Higher TNF-α, IL-5, IL-6, IL-10, MCP-1, IP-10 and eotaxin concentrations were noted in severe COVID-19 as compared to mild cases. Notably, concentrations of IL-4,5,13 and TSLP, which may be engaged in lung fibrosis in COVID-19, remained unchanged in our patients. Third, decreases in IL-25 and periostin concentrations on Days 40–50 were accompanied by decreases in laboratory inflammatory markers to normal values, including CRP, fibrinogen and D-dimers (Table 1). These data suggest that the decrease in IL-25 and periostin may be associated with the recovery from COVID-19. Additionally, we observed the increase in eotaxin levels on V2 in severe COVID-19 patients (Figure 1A). Initially, eotaxin concentrations negatively correlated with CRP (R = −0.34, p < 0.05), fibrinogen (R = −0.35, p < 0.05) and D-dimers (R = −0.33, p < 0.05) levels (Figure 1B, Table S2). On the other hand, Nazarinia D. et al. showed that elevations in eotaxin levels correlated with disease severity. Determination of eotaxin may be helpful in the early prediction of the COVID-19 severity and follow-up [6]. This study exhibited several limitation. First, a limited number of patients were included. Second, there was no healthy control group. However, the aim of the study was to compare moderate-to-severe COVID-19 patients. To sum up: IL-25 may become a candidate for a potential biomarker of COVID-19 severity. Decreases in IL-25 and periostin serum concentrations may reflect the clinical recovery from COVID-19 and serve potential prognostic factors. However, the confirmation of their clinical significance needs further studies. The authors declare no conflicts of interest. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. Appendix S1. Table S1. Table S2. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.