Interleukin-17, a salivary biomarker for COVID-19 severity

Abstract

Objectives: T-helper 17 cell-mediated response and their effector IL-17 cytokine induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a major cause of COVID-19 disease severity and death. Therefore, the study aimed to determine if IL-17 level in saliva mirrors its circulatory level and hence can be used as a non-invasive biomarker for disease severity.

Methods: Interleukin-17 (IL-17) level was evaluated by ELISA in saliva and blood of 201 adult COVID-19 patients with different levels of severity. The IL-17 saliva level was also associated with COVID-19 disease severity, and need for mechanical ventilation and/or death within 29 days after admission of severe COVID-19 patients.

Results: We found that IL-17 level in saliva of COVID-19 patients reflected its circulatory level. High IL-17 level in saliva was associated with COVID-19 severity (P<0.001), need for mechanical ventilation (P = 0.002), and/or death by 29 days (P = 0.002), after adjusting for patients' demographics, comorbidity, and COVID-19 serum severity markers such as D-Dimer, C-reactive protein, and ferritin.

Conclusion: We propose that saliva IL-17 level could be used as a biomarker to identify patients at risk of developing severe COVID-19.

Fig 1. Higher IL-17 level in saliva of severe COVID-19 patients.

(A) IL-17 mRNA levels in whole blood of COVID-19 patients with different severities. (B) IL-17 protein levels in plasma of COVID-19 patients with different severities. (C and D) IL-17 protein levels in saliva of COVID-19 patients with different severities and the associated ROC (receiver operating characteristic curve). (E-G) Correlation of IL-17 saliva level with serum levels of D-dimer, CRP (C-reactive protein), and ferritin of these patients. (H-K) TNFα and IL-1β protein levels in saliva of COVID-19 patients with different severities, and the associated ROCs. Specimens were collected from the following patients with COVID-19 (asymptomatic (n = 67), mild/moderate (n = 81), and severe (n = 53), as well as healthy controls (n = 50). Statistical test: Regression models were adjusted for demographics (age, gender, body mass index), comorbidity (diabetes mellitus) and severity markers of COVID-19 (CRP, D-dimer, and ferritin). ns: Non-significant, * P<0.05, *** P<0.001.

Fig 2. Increased IL-17 level in saliva of severe COVID-19 patients associated with higher need for mechanical ventilation and/or death by days 29.

Kaplan–Meier survival curves of the need for mechanical ventilation (A-C) and/or death (D-F), based on the IL-17, TNFα, and IL-1β cytokine levels in saliva of patients with severe COVID-19 (n = 53). Statistical test: Cox proportional models adjusted for patient’s demographics factors (age, gender, and body mass index), comorbidities (diabetes mellitus), and COVID-19 related severity serum markers (D-dimer, CRP, and ferritin), with significance indicated by P value of less than 0.05.