AUTHOR=Markovic Sofija Sekulic , Jovanovic Marina , Gajovic Nevena , Jurisevic Milena , Arsenijevic Nebojsa , Jovanovic Marina , Jovanovic Milan , Mijailovic Zeljko , Lukic Snezana , Zornic Nenad , Vukicevic Vladimir , Stojanovic Jasmina , Maric Veljko , Jocic Miodrag , Jovanovic Ivan 

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

JOURNAL=Frontiers in Medicine

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.749569

DOI=10.3389/fmed.2021.749569

ISSN=2296-858X

ABSTRACT=<p><bold>Objective:</bold> 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.</p><p><bold>Methods:</bold> 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.</p><p><bold>Results:</bold> Most patients in the severe/critical group were male (81.8%) and older (over 64.5 years). We found a statistically significant difference (<italic>p</italic> &lt; 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-Sa0<sub>2</sub>, partial pressure of oxygen -p0<sub>2</sub>), and chest X-rays (CXR) lung findings (<italic>p</italic> = <italic>0</italic>.000). We found a significantly higher serum concentration (<italic>p</italic> &lt; 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 (<italic>p</italic> &lt; 0.05) between pO<sub>2</sub> and serum IL-1β, IL-12, and IL-33 and between SaO<sub>2</sub> and serum IL-33 was noted. The positive relation (<italic>p</italic> &lt; 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.</p><p><bold>Conclusion:</bold> 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.</p>