Negative correlation between ACE2 gene expression levels and loss of taste in a cohort of COVID-19 hospitalized patients: New clues to long-term cognitive disorders

Abstract

In early 2020, one of the most prevalent symptoms of SARS-CoV-2 infection was the loss of smell (anosmia), found in 60-70% of all cases. Anosmia used to occur early, concomitantly with other symptoms, and often persisted after recovery for an extended period, sometimes for months. In addition to smell disturbance, COVID-19 has also been associated with loss of taste (ageusia). The latest research suggests that SARS-CoV-2 could spread from the respiratory system to the brain through receptors in sustentacular cells localized to the olfactory epithelium. The virus invades human cells via the obligatory receptor, angiotensin-converting enzyme II (ACE2), and a priming protease, TMPRSS2, facilitating viral penetration. There is an abundant expression of both ACE2 and TMPRSS2 in sustentacular cells. In this study, we evaluated 102 COVID-19 hospitalized patients, of which 17.60% presented anosmia and 9.80% ageusia. ACE1, ACE2, and TMPRSS2 gene expression levels in nasopharyngeal tissue were obtained by RT-qPCR and measured using ΔCT analysis. ACE1 Alu287bp association was also evaluated. Logistic regression models were generated to estimate the effects of variables on ageusia and anosmia Association of ACE2 expression levels with ageusia. was observed (OR: 1.35; 95% CI: 1.098-1.775); however, no association was observed between TMPRSS2 and ACE1 expression levels and ageusia. No association was observed among the three genes and anosmia, and the Alu287bp polymorphism was not associated with any of the outcomes. Lastly, we discuss whetherthere is a bridge linking these initial symptoms, including molecular factors, to long-term COVID-19 health consequences such as cognitive dysfunctions.

Prevalence of Olfactory Dysfunction with the Omicron Variant of SARS-CoV-2: A Systematic Review and Meta-analysis

“…Omicron’s Hyposmia vs. UGT2A1 Risk Allele Frequency Initially, it was thought that differences in expression levels or in genetic variation of the virus entry proteins, ACE2 and TMPRSS2, may be host factors that contribute to population differences in COVID’s olfactory dysfunction [11,12]. However, this hypothesis appears to be inconsistent with recent data [14], and it is now thought that the host factor most likely is an odorant-metabolizing enzyme, a glycosyltransferase that is encoded by the UGT2A1/A2 locus, based on a recent genome-wide association study showing significant ethnic differences in the frequency of the risk allele at this locus [13].…”

“…It is possible that host factors also contribute to the population differences in COVID’s olfactory dysfunction [7,11-13]. Such host factors, besides age and gender, are apparently not due to differences in expression levels or in genetic variation of the virus entry proteins, ACE2 and TMPRSS2, as was initially assumed [11,12,14], but rather may be due to genetic variation and the frequency of risk alleles of an odorant-metabolizing enzyme, a glycosyltransferase that is encoded by the UGT2A1/A2 locus [13]. This enzyme is abundantly expressed in sustentacular support cells of the olfactory epithelium of vertebrates [15,16], including humans [17-20].…”

Olfactory and gustatory dysfunction, evaluation and the impact on quality of life among COVID-19 patients: a multi-centre study

“…ACE2 has many genetic variants that might also be a another reason for the difference in prevalence of chemosensory dysfunction among different ethnicity as pointed out by Lechien et al 3 as these variants found to differ in frequency between Asian and European population 27 . However, recent research indicates that differences in ACE2 expression levels among populations do not correspond with infection or chemosensory dysfunction and cannot account for the observed phenotypes 26 , 32 , 33 , 46 . Instead, a genome-wide association study carried out with a large sample size has identified the UGT2A1/A2 locus as the genetic locus related to the difference in anosmia prevalence among various populations 47 .…”