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Interleukin-18 and COVID-19.

ABSTRACT: Vulnerability to coronavirus disease (COVID)-19 varies due to differences in interferon gamma (IFNγ) immunity. We investigated whether a key modifiable interferon precursor, interleukin-18, was related to COVID-19, overall and by severity, using Mendelian randomisation. We used four established genome-wide significant genetic predictors of interleukin-18 applied to the most recent genome-wide association study of COVID-19 (June 2021) to obtain Mendelian randomisation inverse variance weighted estimates by severity, i.e. any (cases = 112 612, non-cases = 2 474 079), hospitalised (cases = 24 274, non-cases = 2 061 529) and very severe (cases = 8779, non-cases = 1 001 875) COVID-19. To be comprehensive, we also conducted an exploratory analysis for IFNγ and two related cytokines with less well-established genetic predictors, i.e. interleukin-12 and interleukin-23. Genetically predicted interleukin-18 was associated with lower risk of any COVID-19 (odds ratio (OR) 0.96 per standard deviation, 95% confidence interval (0.94-0.99, P-value 0.004)) and of very severe COVID-19 (OR 0.88, 95% CI 0.78-0.999, P-value 0.048). Sensitivity analysis and a more liberal genetic instrument selection gave largely similar results. Few genome-wide significant genetic predictors were available for IFNγ, interleukin-12 or interleukin-23, and no associations with COVID-19 were evident. Interleukin-18 could be a modifiable target to prevent COVID-19 and should be further explored in an experimental design.

SUBMITTER: Schooling CM

PROVIDER: S-EPMC8755530 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Interleukin-18 Is a Potential Biomarker to Discriminate Active Adult-Onset Still's Disease From COVID-19.

Project description:BackgroundHyperinflammation with dysregulated production of galectins and cytokines may develop in COVID-19 or adult-onset Still's disease (AOSD). Given the similar clinical features in both diseases, it is necessary to identify biomarkers that can differentiate COVID-19 from AOSD. However, the related data remain scarce currently.MethodsIn this cross-sectional study, plasma levels of galectin-3, galectin-9, and soluble TIM-3 (sTIM-3) were determined by ELISA in 55 COVID-19 patients (31 non-severe and 24 severe), 23 active AOSD patients, and 31 healthy controls (HC). The seropositivity for SARS-CoV-2 was examined using an immunochromatographic assay, and cytokine profiles were determined with the MULTIPLEX platform.ResultsSignificantly higher levels of galectin-3, galectin-9, IL-1β, IL-1Ra, IL-10, IFN-α2, IL-6, IL-18, and TNF-α were observed in severe COVID-19 and active AOSD patients compared with HC (all p<0.001). AOSD, but not COVID-19, showed significantly higher IFN-γ and IL-17A compared with HC (both p<0.01). Moreover, active AOSD patients had 68-fold higher IL-18 levels and 5-fold higher ferritin levels than severe COVID-19 patients (both p<0.001). IL-18 levels at the cut-off value 190.5pg/mL had the highest discriminative power for active AOSD and severe COVID-19, with AUC 0.948, sensitivity 91.3%, specificity 95.8%, and accuracy of 91.5% (p<0.005). Multivariate regression analysis revealed IL-18 as a significant predictor of active AOSD (p<0.05).ConclusionActive AOSD patients share features of hyperinflammation and cytokine storm with severe COVID-19 patients but possess a distinct cytokine profile, including elevated IL-18, IL-6, IFN-γ, and IL-17A. IL-18 is a potential discriminator between AOSD and COVID-19 and may significantly predict active AOSD.

| S-EPMC8343229 | biostudies-literature

Cohort survey of healthcare workers with COVID-19 infection

Project description: Not available

| S-BSST563 | biostudies-other

Proteomic blood profiling in mild, severe and critical COVID-19 patients

Project description: Not available

| S-BSST416 | biostudies-other

Covid-19

Project description:Host

| PRJEB62576 | ENA

Covid-19

Project description:SARS-CoV2 sequences from Finland

| PRJEB42396 | ENA

Structural basis for antagonism of human interleukin 18 by poxvirus interleukin 18-binding protein.

Project description:Human interleukin-18 (hIL-18) is a cytokine that plays an important role in inflammation and host defense against microbes. Its activity is regulated in vivo by a naturally occurring antagonist, the human IL-18-binding protein (IL-18BP). Functional homologs of human IL-18BP are encoded by all orthopoxviruses, including variola virus, the causative agent of smallpox. They contribute to virulence by suppressing IL-18-mediated immune responses. Here, we describe the 2.0-A resolution crystal structure of an orthopoxvirus IL-18BP, ectromelia virus IL-18BP (ectvIL-18BP), in complex with hIL-18. The hIL-18 structure in the complex shows significant conformational change at the binding interface compared with the structure of ligand-free hIL-18, indicating that the binding is mediated by an induced-fit mechanism. EctvIL-18BP adopts a canonical Ig fold and interacts via one edge of its beta-sandwich with 3 cavities on the hIL-18 surface through extensive hydrophobic and hydrogen bonding interactions. Most of the ectvIL-18BP residues that participate in these interactions are conserved in both human and viral homologs, explaining their functional equivalence despite limited sequence homology. EctvIL-18BP blocks a putative receptor-binding site on IL-18, thus preventing IL-18 from engaging its receptor. Our structure provides insights into how IL-18BPs modulate hIL-18 activity. The revealed binding interface provides the basis for rational design of inhibitors against orthopoxvirus IL-18BP (for treating orthopoxvirus infection) or hIL-18 (for treating certain inflammatory and autoimmune diseases).

| S-EPMC2634891 | biostudies-literature

TCR Rep-Seq of COVID-19 affected individuals

Project description:5'RACE-based TCR repertoire sequencing from peripheral blood

2024-09-26 | E-MTAB-13593 | biostudies-arrayexpress

Repurposing Interleukin-6 Inhibitors to Combat COVID-19.

Project description:Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is a pandemic with major implications across the world. One of the most frequent causes of death from SARS-CoV-2 is fatal pneumonia from coronavirus disease 2019 (COVID-19), which is associated with the development of acute respiratory distress syndrome (ARDS). To date (as of April 2, 2020), other than supportive measures, there are no efficient therapeutic options for COVID-19-related ARDS, although the US Food and Drug Administration recently granted emergency authorization for the use of hydroxychoroquine/chloroquine for this indication (which is usually given with azithromycin). Although the pathogenesis for ARDS is under investigation, one of the major culprits is considered to be cytokine storm, especially from interleukin 6 (IL-6) release. Herein, we review potential use of IL-6 inhibitors, several of which are approved for other disease conditions, as potential novel treatment for the management of COVID-19-related ARDS.

| S-EPMC8221576 | biostudies-literature

Interleukin-1 blocking agents for treating COVID-19.

Project description: Not available

| S-EPMC8791232 | biostudies-literature

Decreased memory B cells frequencies in COVID-19 Delta variant vaccine breakthrough infection

Project description:The SARS-CoV-2 Delta (B.1.617.2) variant is capable of infecting vaccinated persons. An open question remains as to whether deficiencies in specific vaccine-elicited immune responses result in susceptibility to vaccine breakthrough infection. We investigated 55 vaccine breakthrough infection cases (mostly Delta) in Singapore, comparing them against 86 vaccinated close contacts who did not contract infection. Vaccine breakthrough cases showed lower memory B cell frequencies against SARS-CoV-2 receptor binding domain (RBD). Compared to plasma antibodies, antibodies secreted by memory B cells retained a higher fraction of neutralizing properties against the Delta variant. Inflammatory cytokines including IL-1β and TNF were lower in vaccine breakthrough infections than primary infection of similar disease severity, underscoring the usefulness of vaccination in preventing inflammation. This report highlights the importance of memory B cells against vaccine breakthrough, and suggests that lower memory B cell levels may be a correlate of risk for Delta vaccine breakthrough infection.

| S-SCDT-EMM-2021-15227 | biostudies-other

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