IL 33 Correlates With COVID-19 Severity, Radiographic and Clinical Finding

Abstract

Objective: The increased level of interleukin (IL)-33 is considered as a predictor of severe coronavirus disease 2019 (COVID-19) infection, but its role at different stages of the disease is still unclear. Our goal was to analyze the correlation of IL-33 and other innate immunity cytokines with disease severity.Methods: In this study, 220 patients with COVID-19 were included and divided into two groups, mild/moderate and severe/critical. The value of the cytokines, clinical, biochemical, radiographic data was collected and their correlation with disease severity was analyzed.Results: Most patients in the severe/critical group were male (81.8%) and older (over 64.5 years). We found a statistically significant difference (p < 0.05) in these two groups between clinical features (dyspnea, dry cough, fatigue, and auscultatory findings); laboratory [(neutrophil count, lymphocyte count, monocyte count, hemoglobin, plasma glucose, urea, creatinine, total bilirubin (TBIL), direct bilirubin (DBIL), aspartate aminotransferase (AST), albumin (ALB), lactate dehydrogenase (LDH), creatinine kinase (CK), D-dimer, C-reactive protein (CRP), procalcitonin (PCT), Fe, and Ferritin)], arterial blood gases (oxygen saturation-Sa02, partial pressure of oxygen -p02), and chest X-rays (CXR) lung findings (p = 0.000). We found a significantly higher serum concentration (p < 0.05) of TNF-α, IL-1β, IL-6, IL-12, IL-23, and IL-33 in patients with COVID-19 with severe disease. In the milder stage of COVID-19, a positive correlation was detected between IL-33 and IL-1β, IL-12 and IL-23, while a stronger positive correlation between the serum values of IL-33 and TNF-α, IL-1β, IL-6, and IL-12 and IL-23 was detected in patients with COVID-19 with severe disease. A weak negative correlation (p < 0.05) between pO2 and serum IL-1β, IL-12, and IL-33 and between SaO2 and serum IL-33 was noted. The positive relation (p < 0.05) between the serum values of IL-33 and IL-12, IL-33 and IL-6, and IL-6 and IL-12 is proven.Conclusion: In a more progressive stage of COVID-19, increased IL-33 facilitates lung inflammation by inducing the production of various innate proinflammatory cytokines (IL-1β, IL-6, TNF-α, IL-12, and IL-23) in several target cells leading to the most severe forms of the disease. IL-33 correlates with clinical parameters of COVID-19 and might represent a promising marker as well as a therapeutic target in COVID-19.

Biochemical, Biophysical, and Immunological Characterization of Respiratory Secretions in Severe SARS-CoV-2 (COVID-19) Infections

“…Hadjadj et al reported that plasma levels of IFN-α2 decreased with disease severity, but were not significantly different compared to healthy controls (71). Our results are different from a plasma study which reported higher IL33 in severe COVID-19 cohort but our findings are consistent with a nasopharynx study (70, 72). IL-13 was also not significantly different from healthy controls in our samples, in contrast to a previous report (56).…”

Biochemical, biophysical, and immunological characterization of respiratory secretions in severe SARS-CoV-2 infections

“…Hadjadj et al reported that plasma levels of IFN-α2 decreased with disease severity but were not significantly different compared to healthy controls (71). Our results are different from a plasma study that reported higher IL-33 in a cohort with severe COVID-19, but our findings are consistent with a nasopharynx study (70,72). IL-13 was also not significantly different from healthy controls in our samples, in contrast to a previous report (56).…”

The role of IL-1 family of cytokines and receptors in pathogenesis of COVID-19

“…In one of the first studies, Burke H et al revealed increased levels of the IL-33 as a significant predictive marker of adverse outcome in COVID-19 patients [ 205 ]. Following observations similarly demonstrated its elevated levels that were correlated with clinical and radiographic parameters of the disease and established its positive correlation with TNF-α, IL-1β, IL-6, IL-12, and IL-23 levels and its negative correlation with O2 saturation of the COVID-19 patients [ 206 , 207 ] (Table 1 ). Additionally, elevated levels of the IL-33 together with IL-18 were coupled with higher concentrations of the renal toxicity markers such as glutathione S-transferase (GST) and osteopontin in COVID-19 patients, which confers its putative interference in multi-systemic damages of the SARS-CoV-2 infection [ 208 ].…”