IMMUNE RESPONSE TO SARS CoV2 INFECTION BY TLR3, TLR4 AND TLR7 GENE
EXPRESSION.
Abstract
Toll-like receptors (TLRs) may be involved both in the initial failure
of viral clearance and in the subsequent development of severe clinical
manifestations of COVID-19, essentially ARDS (acute respiratory distress
syndrome) with fatal respiratory failure. We present the gene expression
of TLR 3, 4, and 7 in nasopharyngeal total RNA samples from 150
individuals positive for SARS Cov2 (DET) by molecular techniques of
isothermal amplification (Neokit SA) and 152 SARS Cov2 non detectable
(ND) ambulatory and hospitalized patients with a non-defined respiratory
disease, and we compared with the symptomatology developed by all those
patients. We analyzed 4 cohorts: 1-SARS Cov2 genome detected patients
with severe to high symptomatology (n=107); 2-SARS Cov2 genome detected
patients low to mild symptomatology (n=43); 3-SARS Cov2 genome non
detected patients with severe to high symptomatology (n=109); and 4-SARS
Cov2 genome non detected patients low to mild symptomatology (n=41). Our
results not only contradict few previous study, it also corrects for
sample size bias, showing no significant differences of expression for
TLR3, TLR4 and TLR7 between SARS Cov2 DET and ND total cohort of
patients (Non Paired T –Test p Value>0.1). When compared
severity of symptoms -presence of symptoms from the COVID-19 12 WHO
diagnosis symptoms- and gene expression, here we found significant
positive correlation between severe symptomatology, and the number of
symptoms and death for TLR4 and TLR7 for both DET and ND COVID-19
patients. When the cohort was construct with low/middle and severe
symptoms, the Correlation Coefficient showed that expression of TLR4 and
TLR7 was significantly amplified in those ND patients with severe
symptomatology ( p Value= 0.00311) as well as for TLR3 in ND low
to mild symptoms cohort of patients. We also showed and discussed the
results obtained of these genes expression and the sex and age of
patients. In summary, our data suggest that although our innate immune
system with TLRs contributes to the elimination of viruses, it can also
be associated with harm to the host due to persistent inflammation and
tissue destruction. We confirmed that principally TLR4 and TLR7 could be
involved not only in the pathogenesis of COVID‐19 but also in other
respiratory diseases with same symptomatology. We agree with previous
studies that treatments focus on TLR4 and TLR7 expression in
inflammatory respiratory diseases could be a start point against severe
symptoms development.