ABSTRACT
COVID-19 is the name of sickness headed by SARS-CoV-2, which gated the confinement restrictions since March 2020. At the beginning the S protein was identified as the "key" that enhances entering human body, due to its affinity with ACE2 receptor. ACE2 receptor is known to be expressed in a variety of tissues in a manner in which that location increases their infection-probabilities in exposure to this virus. The brain contains two regions where ACE2 is manly expressed: 1) The olfactory bulb which is thought to be involved in loss of smell and facilitating entering to the Central Nervous System, on the other hand 2) the brainstem keeps imbibed the Pre-Botzinger complex, a mediator of respiratory rhythm, showed its implications in oxygen depletion because of abnormal working of O2, and CO2 sensing chemoreceptors. In concern with PNS it is considered virus-nociceptors interaction as the most likely reason to muscular pain and headache. © 2022 Harvard University Law School. All rights reserved.
ABSTRACT
COVID-19 has aspects on its pathogenesis that still need elucidating and an analysis of clinical and immunogenetic factors in each cohort of patients is paramount to understanding how genetic variability can explain the multiple clinical spectra seen in patients infected with SARS-CoV-2. The aim of this study was to correlate the KIR polymorphism/HLA class I ligand interactions from patients and healthy subjects with either the susceptibility or severity to COVID-19. Genotyping of HLA-A, -B, -C and KIR genes were carried out from 459 symptomatic as well as 667 non-infected Spanish Caucasian individuals using Lifecodes HLA-SSO and KIR-SSO kits (ImmucorTM, USA) and analyzed in the Luminex in this uni-centre case-control study performed at the University Hospital of Salamanca, Spain. Comparative KIR gene analysis showed that KIR2DS4 was significantly more representative in healthy versus infected individuals. When comparing subgroups of infected patients, KIR2DS3 had a higher frequency in those who progressed to a more severity disease and yet with higher mortality rate. Three functional combinations were significant on univariate analysis: KIR2DL2/C1, KIR2DS2/C1, and KIR2DS3/C1. However, in the multivariate analysis, only the KIR2DL2/C1 interaction remained significant (OR = 15.2 (95% CI 1.5-147), p = 0.0189). Compared with the solo-clinical characteristics predictive model, that included well-known comorbidity variables such as hypertension, age, sex, diabetes, C-reactive protein, dyslipidemia, smoking, ferritin, and fibrinogen, the clinical-and-KIR-based model showed a better ability to discriminate between severe and nonsevere patients with higher sensitivity and specificity. Our results support a fundamental role of KIR/ligand interaction in the clinical course of COVID-19. Since the KIR2DL2 gene has a high frequency in Spain (60%), the analysis of the KIR2DL2/C1 in symptomatic patients who require hospitalization could be helpful to better determine their prognosis.