Aspectos clínicos e moleculares associados aos sintomas de anosmia e ageusia em pacientes com COVID-19

Abstract

The infection caused by the SARS-CoV-2 virus, known as Coronavirus disease 2019 (COVID-19), presents a diverse clinical spectrum, from asymptomatic cases and mild clinical manifestations, to moderate and critical conditions, suggesting that the involvement of genetic and environmental factors may be associated with both its natural outcome and aspects associated with the virus itself. SARS-CoV-2 belongs to the genus Betacoronavirus, and has a positive-stranded RNA genome. approximately 30,000 bases long. Its genomic structure encodes the following proteins: structural Spike (S), Membrane (M), Envelope (E) and Nucleocapsid (N) and other non-structural ones. Protein S is responsible for the interaction of the virus with the host cell ACE2 receptor and the process of virus penetration. Mutations in this region can alter the transmissibility of the virus, as well as lead to changes in symptoms and alter the effectiveness of vaccines. Among the frequently reported symptoms are those of a chemosensitive nature, such as loss of smell (anosmia) and loss of taste (ageusia). In this dissertation, we aimed to understand the reason for the frequency variation of anosmia and ageusia throughout the pandemic and to characterize the molecular components, exploring the expression levels of (ACE1, ACE2 e TMPRSS2) genes related to the interaction of the virus with the host, analyzing the anosmia and ageusia outcomes in individuals infected with SARS-CoV-2. By using SIVEP-Gripe database, we performed an observational analysis involving 14,450 patients in the city of Betim/MG. The frequency of anosmia and ageusia fluctuated throughout the pandemic, with a approximately reduction of 7% of these outcomes in the second half of 2021. Co-occurrence of all reported symptoms (abdominal pain, fatigue, fever, cough, sore throat, dyspnea, respiratory distress, change in saturation, diarrhea, vomiting) with anosmia and ageusia was observed. It was observed that five pre-existing comorbidities (heart disease, hematological disease, asthma, diabetes and obesity) are associated with the chance of both outcomes and that neurological disease was only associated with anosmia and kidney disease only associated with ageusia. We further explored the expression levels of some genes and the outcomes of anosmia and ageusia. We evaluated 102 patients hospitalized with COVID-19, of which 17.60% had anosmia and 9.80% ageusia. Expression levels of ACE1, ACE2 and TMPRSS2 genes in nasopharyngeal tissue were obtained by RT-qPCR and measured using ΔCT analysis. The ACE1 Alu 287bp 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). The results suggest a possible bridge linking these early symptoms, including molecular factors, to the long-term health consequences of COVID-19, such as cognitive dysfunctions. Gene expression studies exploring new genes are important to elucidate the outcomes of anosmia and ageusia. Furthermore, the observational data are informative and full of interactions and biases, presenting real evidence about the clinical characteristics of the disease over time. Thus, they become important to identify potential effects and the impact of variants on clinical and epidemiological aspects of COVID-19.