A Prospective, Cross-Sectional Study of Tear Cytokines to Assess Ocular Surface Immune Response in COVID-19 Patients in a Tertiary Care Referral Centre: First Report from the Asia-Pacific Region

Purpose To compare systemic (serum) and local (tear) cytokine profiles in COVID-19 patients across varying disease severities and durations.Methods This prospective, cross-sectional study evaluated four cohorts (n = 30 each): healthy controls, “mild,” “moderate,” and “severe” COVID-19. Baseline tear and blood samples were collected. Target cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ, and TNF) were quantified. Group comparisons across disease severities and duration (1–7; 8–14; >15 days) were assessed (omnibus Kruskal–Wallis H tests and post-hoc Dunn’s tests with Bonferroni correction). Linear regression mapped serum-to-tear concentration correlations.Results Systemically, serum IL-6 (p < 0.001) and TNF (p = 0.003) were significantly elevated in COVID-19 patients, while serum IL-4 was suppressed (p < 0.001). Global group variations existed for tear IL-6 (H = 9.49, p = 0.023) and tear IL-10 (H = 12.95, p = 0.005); post-hoc testing revealed significant elevations in “severe” cases (mean rank 72.63 for IL-6; 75.13 for IL-10) compared to “mild” cases (48.42 for IL-6; 47.72 for IL-10). No significant differences occurred for IL-2, IL-17A, or IFN-γ (p > 0.05). Temporally, serum IL-4 (p = 0.041), serum IL-17A (p = 0.043), and tear IL-17A (p = 0.019) showed significant duration shifts. Correlations were moderately positive for IFN-γ (r = .390, R2 = .152), TNF (r = .387, R2 = .150), and IL-10 (r = .344, R2 = .118). Six (6.7%) COVID-19 patients had positive conjunctival RT-PCR swabs.Conclusion Localised ocular surface cytokine expression partially mirrored systemic COVID-19 immune response. Tear TNF and IL-4 matched systemic profiles, while tear IL-6 and IL-10 displayed unique trends with selective peaks in “severe” cohorts. Non-invasive tear assays are viable tools for studying localized inflammatory profiles.