tetano
Editor, Senior Moderator
Immun Inflamm Dis
. 2022 Nov;10(11):e712.
doi: 10.1002/iid3.712.
Exploratory analysis of interleukin-38 in hospitalized COVID-19 patients
Dennis M de Graaf[SUP] 1 2 [/SUP], Lisa U Teufel[SUP] 1 [/SUP], Aline H de Nooijer[SUP] 1 [/SUP], Adriaan J van Gammeren[SUP] 3 [/SUP], Antonius A M Ermens[SUP] 3 [/SUP], Ildikó O Gaál[SUP] 4 [/SUP], Tania O Crișan[SUP] 4 [/SUP], Frank L van de Veerdonk[SUP] 1 [/SUP], Mihai G Netea[SUP] 1 5 [/SUP], Charles A Dinarello[SUP] 1 2 [/SUP], Leo A B Joosten[SUP] 1 4 [/SUP], Rob J W Arts[SUP] 1 [/SUP], Radboudumc Center for Infectious Diseases COVID-19 Study Group
Affiliations
Abstract
Introduction: A major contributor to coronavirus disease 2019 (COVID-19) progression and severity is a dysregulated innate and adaptive immune response. Interleukin-38 (IL-38) is an IL-1 family member with broad anti-inflammatory properties, but thus far little is known about its role in viral infections. Recent studies have shown inconsistent results, as one study finding an increase in circulating IL-38 in COVID-19 patients in comparison to healthy controls, whereas two other studies report no differences in IL-38 concentrations.
Methods: Here, we present an exploratory, retrospective cohort study of circulating IL-38 concentrations in hospitalized COVID-19 patients admitted to two Dutch hospitals (discovery n = 148 and validation n = 184) and age- and sex-matched healthy subjects. Plasma IL-38 concentrations were measured by enzyme-linked immunosorbent assay, disease-related proteins by proximity extension assay, and clinical data were retrieved from hospital records.
Results: IL-38 concentrations were stable during hospitalization and similar to those of healthy control subjects. IL-38 was not associated with rates of intensive care unit admission or mortality. Only in men in the discovery cohort, IL-38 concentrations were positively correlated with hospitalization duration. A positive correlation between IL-38 and the inflammatory biomarker d-dimer was observed in men of the validation cohort. In women of the validation cohort, IL-38 concentrations correlated negatively with thrombocyte numbers. Furthermore, plasma IL-38 concentrations in the validation cohort correlated positively with TNF, TNFRSF9, IL-10Ra, neurotrophil 3, polymeric immunoglobulin receptor, CHL1, CD244, superoxide dismutase 2, and fatty acid binding protein 2, and negatively with SERPINA12 and cartilage oligomeric matrix protein.
Conclusions: These data indicate that IL-38 is not associated with disease outcomes in hospitalized COVID-19 patients. However, moderate correlations between IL-38 concentrations and biomarkers of disease were identified in one of two cohorts. While we demonstrate that IL-38 concentrations are not indicative of COVID-19 severity, its anti-inflammatory effects may reduce COVID-19 severity and should be experimentally investigated.
Keywords: COVID-19; SARS-CoV-2; interleukin-38; retrospective cohort study.
. 2022 Nov;10(11):e712.
doi: 10.1002/iid3.712.
Exploratory analysis of interleukin-38 in hospitalized COVID-19 patients
Dennis M de Graaf[SUP] 1 2 [/SUP], Lisa U Teufel[SUP] 1 [/SUP], Aline H de Nooijer[SUP] 1 [/SUP], Adriaan J van Gammeren[SUP] 3 [/SUP], Antonius A M Ermens[SUP] 3 [/SUP], Ildikó O Gaál[SUP] 4 [/SUP], Tania O Crișan[SUP] 4 [/SUP], Frank L van de Veerdonk[SUP] 1 [/SUP], Mihai G Netea[SUP] 1 5 [/SUP], Charles A Dinarello[SUP] 1 2 [/SUP], Leo A B Joosten[SUP] 1 4 [/SUP], Rob J W Arts[SUP] 1 [/SUP], Radboudumc Center for Infectious Diseases COVID-19 Study Group
Affiliations
- PMID: 36301025
- DOI: 10.1002/iid3.712
Abstract
Introduction: A major contributor to coronavirus disease 2019 (COVID-19) progression and severity is a dysregulated innate and adaptive immune response. Interleukin-38 (IL-38) is an IL-1 family member with broad anti-inflammatory properties, but thus far little is known about its role in viral infections. Recent studies have shown inconsistent results, as one study finding an increase in circulating IL-38 in COVID-19 patients in comparison to healthy controls, whereas two other studies report no differences in IL-38 concentrations.
Methods: Here, we present an exploratory, retrospective cohort study of circulating IL-38 concentrations in hospitalized COVID-19 patients admitted to two Dutch hospitals (discovery n = 148 and validation n = 184) and age- and sex-matched healthy subjects. Plasma IL-38 concentrations were measured by enzyme-linked immunosorbent assay, disease-related proteins by proximity extension assay, and clinical data were retrieved from hospital records.
Results: IL-38 concentrations were stable during hospitalization and similar to those of healthy control subjects. IL-38 was not associated with rates of intensive care unit admission or mortality. Only in men in the discovery cohort, IL-38 concentrations were positively correlated with hospitalization duration. A positive correlation between IL-38 and the inflammatory biomarker d-dimer was observed in men of the validation cohort. In women of the validation cohort, IL-38 concentrations correlated negatively with thrombocyte numbers. Furthermore, plasma IL-38 concentrations in the validation cohort correlated positively with TNF, TNFRSF9, IL-10Ra, neurotrophil 3, polymeric immunoglobulin receptor, CHL1, CD244, superoxide dismutase 2, and fatty acid binding protein 2, and negatively with SERPINA12 and cartilage oligomeric matrix protein.
Conclusions: These data indicate that IL-38 is not associated with disease outcomes in hospitalized COVID-19 patients. However, moderate correlations between IL-38 concentrations and biomarkers of disease were identified in one of two cohorts. While we demonstrate that IL-38 concentrations are not indicative of COVID-19 severity, its anti-inflammatory effects may reduce COVID-19 severity and should be experimentally investigated.
Keywords: COVID-19; SARS-CoV-2; interleukin-38; retrospective cohort study.