Saliva as Alternative Specimen for Measuring Inflammatory Markers Interleukins (IL10, IL-4, and IL-1β) in Association with Disease Severity among COVID-19 Patients

Abstract

Background: Saliva is a specimen that is easily collected by non-invasive means and does not require well-trained staff; it could be helpful in measuring inflammatory markers to determine COVID-19 severity. The aim of this study was to investigate saliva as an alternative specimen for measuring inflammatory markers IL-10, IL-4, and IL-1β among COVID-19 patients in relation to disease severity. Methods and Results: This cross-sectional study was conducted among COVID-19 patients in a fever clinic, isolated hotels, and hospitals providing care for positive COVID-19 patients and in public health centers for negative control patients in Jeddah, Saudi Arabia. A total of 151 subjects participated in this study, including 101 patients with COVID-19 and 50 healthy controls. Patients with COVID-19 were categorized according to the severity of their symptoms into mild (n=50) and severe cases (n=51). The salivary concentrations of IL-4, IL-10, and IL-1β were measured using sandwich MyBioSource ELISA Test Kits. The age of the study population ranged from 19 to 70 years old, with a mean age of 43.3±13.0 years. The distribution of the study population showed that more of the patients were men (65[64.4%]) than women (36[35.6%]) (P=0.004). The frequency of severe infection in men was higher than in women (35[68.6%] and 16[31.4%], respectively, P=0.008). The group of severe cases was significantly older than the group of mild cases (47.9±11.03 years and 38.64±13.82 years, respectively, P=0.0007). The volume of saliva was the smallest in severe COVID-19, compared to mild cases and controls (P=0.0000 in all cases). The salivary levels of IL-4, IL-10, and IL-1β were greater in the severe cases than in mild cases and controls (46.14±11.61 pg/mL, 12.86±1.99 pg/mL, and 27.45±11.47 pg/mL versus 19.31±5.72 pg/mL, 7.96±2.12 pg/mL, and 6.59±1.90 pg/mL, respectively; P=0.0000 in all cases). The salivary levels of IL-4 and IL-10 in mild cases were greater than in controls (19.31±5.72 pg/mL and 7.96±2.12 pg/mL versus 15.30±4.36 pg/mL and 6.02±0.89 pg/mL, respectively; P=0.0329 and P=0.000, respectively), but salivary IL-1β levels in mild cases did not differ from controls (6.59±1.90 pg/mL vs. 6.03±2.28 pg/mL, P=0.9129). Conclusion: Saliva could be used as an alternative sample in measuring IL-10, IL-4, and IL-1β with the suggestion of using IL-10 and IL-4 as markers for predicting disease severity.