SARS COV2 HOST IMMUNE RESPONSE AND CLINICAL MANIFESTATIONS: TLR3, TLR4 AND TLR7.

MARTINEZ MARIGNAC V.; OERTLIN, G; GHILINI, DANIEL; FLEISCHMAN, ERIKA; RICHARD, SILVINA

Encuentro; REUNION ANUAL DE BIOCIENCIAS Y SOCIEDAD ARGENTINA DE INVESTIGACION CLINICA SAIC.; 2022

Toll-like receptors (TLRs) may be involved in the initial failure of viral clearance and in the subsequent development of fatal clinical manifestations of severe COVID-19,essentially ARDS (acute respiratory distress syndrome).Here we characterized the expression of TLR 3, 4, and 7 in nasopharyngeal total RNA samples from 150 individuals positive for Covid19 by Neokit SA and 150 non detectable ambulatory patients; we compared with the symptomatology developed.Weanalyzed 4 cohorts: Viral genome detected patients with severe to highsymptomatology(n=107);Viral genome detected patients without or lowsymptomatology(n=43);Viral genome non detected patients with severe to highsymptomatology(n=109); andViral genome non detected patients without or lowsymptomatology(n=41).We showed significant differences of expression for TLR4 between detected and non-detected patients with severe or non-severe symptoms (Non Paired T?test pValue=0.04; and pValue=0.04).TLR3 showed significant differences between non detected and detected patients with severe symptoms(Non Paired T-test; pValue=0.003).The expression of TLR7 was not significant different between cohorts however when compared by Spearman?s CorrelationCoefficient there was a significant positive correlation between severity of symptoms in those patients without covid19 infection. The same significant positive correlation was observed for TLR4 and severe symptoms in no covid19 patients by Spearman?s and Point-Biserial Correlation.On average all detected patients expressed these genes in a same way as non-detected patients with severe symptoms, been TLR4 the significant higher expressed gene in all patients with severe symptoms;we confirmed that the immune response can be associated with harm to the host due to persistent inflammation and tissue destruction; we confirmed TLR4 gene expression involvement in the pathogenesis of COVID‐19 as well as other respiratory diseases;we suggest that effort must be done to focus therapies on TLR4 expression in inflammatory respiratory diseases.