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Background Olfactory dysfunction (OD) represents a frequent manifestation of the coronavirus disease 2019 (COVID-19). Apolipoprotein E (APOE) is a protein that interacts with the angiotensin-converting enzyme receptor, essential for viral entry into the cell. Previous publications have suggested a possible role of APOE in COVID-19 severity. As far as we know, no publications found significant associations between this disease's severity, OD, and APOE polymorphisms (E2, E3, and E4).

APOE ε4 polymorphism has been recently described as a possible association with cognitive deficits in COVID-19 patients. This research aimed to establish the correlation between COVID-19 and cognitive impairment, and the APOE gene polymorphism among outpatients. We performed a cross-sectional study with confirmed COVID-19 patients and neurological symptoms that persisted for more than three months from onset. APOE genotypes were determined. The final number of patients included in this study was 219, of which 186 blood samples were collected for APOE genotyping, evaluated 4.5 months after COVID-19. Among the participants, 143 patients (65.3%) reported memory impairment symptoms as their primary concern. However, this complaint was objectively verified through screening tests (Addenbrooke Cognitive Examination-Revised and Mini-Mental State Examination) in only 36 patients (16.4%). The group experiencing cognitive decline exhibited a higher prevalence of the APOE ε4 allele than the normal group (30.8% vs. 16.4%, respectively, p = 0.038). Furthermore, the APOE ε4 allele and anxiety symptoms remained significant after multivariate analysis. This study assessed an outpatient population where cognitive changes were the primary complaint, even in mild cases. Moreover, the ε4 allele, sleep disorders, and anxiety symptoms were more frequent in the cognitive decline group.

IntroductionFew studies have objectively evaluated cognitive deficits after the acute phase of COVID-19 disease. Moreover, the role of apolipoprotein E (APOE) genotypes in cognitive decline in patients with COVID-19 has not been evaluated yet.MethodsThis cross-sectional study was conducted in confirmed cases of COVID-19 patients with neurological symptoms that persisted for more than 3 months from the onset. We determined APOE genotypes.ResultsThe final sample consisted of 141 patients. The most frequent APOE genotype was E3/E3 (N = 95; 67.3%). In total, 93 patients (65.9%) had memory impairment symptoms as the main complaint, objectively confirmed through screening tests in 25 patients (17.7%). Patients with cognitive impairment had a lower frequency of anosmia than the normal and subjective cognitive decline (SCD) groups (p = 0.005). In addition, depression was recurrent in the cognitive impairment group and the SCD group (p = 0.046). Cognitive impairment was significantly more frequent in hospitalized patients and those with a lower education level. Cognitive status was not associated with APOE genotypes.DiscussionHospitalized patients had more severe infection with a greater possibility of systemic complications, greater inflammatory response, and prolonged hospitalization, which could impact cognitive performance. Cognitive impairment in patients with COVID-19 does not necessarily involve specific APOE polymorphisms. However, psychiatric disorders may also be responsible for cognitive complaints. Cognitive complaints are frequent in patients with COVID-19, even after the acute phase of the disease and in mild cases. Hospitalized participants and depressed patients may have a higher risk of cognitive impairment. APOE genotypes or haplotypes may not significantly play a role in COVID-19 cognitive impairment.