The Relationship Between COVID-19 Disease Severity and Zonulin Levels

Muhammed Okuyucu; Demet Yalcin Kehribar; Mustafa Çapraz; Aylin Çapraz; Mustafa Arslan; Zülfinaz Betül Çelik; Büşra Usta; Asuman Birinci; Metin Ozgen

doi:10.7759/cureus.28255

The Relationship Between COVID-19 Disease Severity and Zonulin Levels

Cureus. 2022 Aug 22;14(8):e28255. doi: 10.7759/cureus.28255. eCollection 2022 Aug.

Authors

Muhammed Okuyucu¹, Demet Yalcin Kehribar¹, Mustafa Çapraz², Aylin Çapraz³, Mustafa Arslan⁴, Zülfinaz Betül Çelik⁵, Büşra Usta⁶, Asuman Birinci⁶, Metin Ozgen⁷

Affiliations

¹ Internal Medicine, Ondokuz Mayıs University Faculty of Medicine, Samsun, TUR.
² Internal Medicine, Amasya University Sabuncuoğlu Şerefeddin Education and Research Hospital, Amasya, TUR.
³ Pulmonary Medicine, Amasya University Sabuncuoğlu Şerefeddin Education and Research Hospital, Amasya, TUR.
⁴ Infectious Diseases, Amasya University Sabuncuoğlu Şerefeddin Education and Research Hospital, Amasya, TUR.
⁵ Medical Biology, Samsun University Faculty of Medicine, Samsun, TUR.
⁶ Medical Microbiology, Ondokuz Mayıs University Faculty of Medicine, Samsun, TUR.
⁷ Rheumatology, Ondokuz Mayıs University Faculty of Medicine, Samsun, TUR.

Abstract

Introduction Zonulin is a protein that plays a role in the reversible regulation of epithelial permeability. As zonulin is released in large amounts into the intestinal lumen, it disrupts the integrity of the tight junctions and causes continuous migration of antigens to the submucosa. Consequently, it can trigger inflammatory processes and severe immune reactions. In severe cases, SARS-CoV-2 may have a major impact on the clinical manifestations of the disease by directly or indirectly affecting intestinal cells and triggering systemic inflammation. Therefore, our study aimed to investigate the role of one of the possible mediators, zonulin, in the severity of the COVID-19 infection. Methods Thirty COVID-19 patients and 35 healthy controls were included in the study. Blood samples were taken from the patients on the 1st, 4th, and 8th days of hospitalization. Serum zonulin levels were determined by enzyme-linked immunosorbent assay (ELISA). Complete blood count (white blood cell [WBC], neutrophil, lymphocyte, and platelet), biochemical parameters (serum lactic acid dehydrogenase [LDH], erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], D-dimer, ferritin, fibrinogen levels) were determined and chronic systemic disease states of the patients were assessed. Results Serum zonulin levels were notably higher in the healthy control group compared to the patient group (p=0.003). Although there was an increase in the zonulin values by time in hospitalization, this rising was not significant. Conversely, ESR and CRP levels were significantly higher in the patient group (p<0.001). There was no significant difference between the two groups regarding gender, age, and WBC counts. Conclusion The serum zonulin levels of COVID-19 patients with the mild clinical course were lower than the healthy control group. Moreover, serum zonulin levels were not correlated with ESR, CRP, and other inflammation markers. Our results suggest that low serum zonulin levels in COVID-19 patients might represent a mild disease course.

Keywords: covid patients; covid-19; inflammation; inflammatory markers; zonulin.