ABSTRACT
BACKGROUND: The prevalence and pathophysiological mechanisms of cognitive deficits (CD) Systemic Lupus Erythematosus (SLE) and Rheumatoid arthritis (RA) are very heterogeneous and poorly understood. We characterized CD in patients with SLE compared with RA patients and healthy controls. We compared the neuropsychological profile of SLE and RA with patients' oxidative/inflammatory biomarkers for CD. METHODS: We performed a cross-sectional study, including 50 SLE patients, 29 RA patients, and 32 healthy controls. SLEDAI and DAS28 assessed disease activity. SF-36 questionnaire and a battery of cognitive tests were applied to all participants. Blood samples were collected to determine IL-6, S100ß, myeloperoxidase (MPO), malondialdehyde and reduced glutathione (GSH) alterations. RESULTS: In the SLE group, higher GSH was associated with the absence of CD (With CD = 69 ± 49, Without CD = 112 ± 81, p = 0.030), while higher IL-6 was associated with the presence of CD in the RA group (With CD = 603 ± 173, Without CD = 431 ± 162, p = 0.032). Regarding specific cognitive domains, in SLE higher MPO was associated with poor performance in reasoning and abstraction (p = 0.039), higher IL-6 was associated with poor performance in inhibitory control and attention (p = 0.031), and higher GSH was associated with better performance in memory(p = 0.021). Higher SLEDAI was associated with poor performance in semantic fluency(p = 0.031), inhibitory control, and attention in the SLE group(p = 0.037). In the RA group, higher DAS-28 was associated with poor performance in executive functions(p = 0.016) and phonemic fluency (p = 0.003). CONCLUSION: SLE patients' disease activity, inflammatory state, and oxidative stress were associated with CD. In RA patients, CD was associated with disease activity and inflammatory state. These results encourage further studies with larger samples aiming to confirm oxidative stress parameters as biomarkers of CD in SLE patients.
Subject(s)
Arthritis, Rheumatoid , Cognitive Dysfunction , Lupus Erythematosus, Systemic , Humans , Cross-Sectional Studies , Interleukin-6 , Arthritis, Rheumatoid/complications , Lupus Erythematosus, Systemic/complications , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/etiology , Biomarkers , Oxidative StressABSTRACT
Infection with the SARS-CoV-2 virus can lead to neurological symptoms in the acute phase and in the Long COVID phase. These symptoms usually involve cognition, sleep, smell disorders, psychiatric manifestations, headache and others. This condition is more commonly described in young adults and women. This symptomatology can follow severe or mild cases of the disease. The importance of this issue resides in the high prevalence of neurological symptoms in the Long COVID phase, which entails significant morbidity in this population. In addition, such a condition is associated with high health care costs, with some estimates hovering around 3.7 trillion US dollars. In this review, we will sequentially describe the current knowledge about the most prevalent neurological symptoms in Long COVID, as well as their pathophysiology and possible biomarkers.
A infecção pelo vírus SARS-CoV-2 pode levar a sintomas neurológicos na fase aguda e na fase de COVID longa. Esses sintomas geralmente envolvem cognição, sono, distúrbios do olfato, manifestações psiquiátricas, dor de cabeça e outros. Esta condição é mais comumente descrita em adultos jovens e mulheres. A sintomatologia pode acompanhar casos graves ou leves da doença. A importância desta questão reside na elevada prevalência de sintomas neurológicos na fase de COVID longa, o que acarreta morbilidade significativa nesta população. Além disso, tal condição está associada a elevados custos de cuidados de saúde, com algumas estimativas em torno de 3,7 trilhões de dólares americanos. Nesta revisão, descrevemos sequencialmente o conhecimento atual sobre os sintomas neurológicos mais prevalentes na COVID longa, bem como sua fisiopatologia e possíveis biomarcadores.
ABSTRACT
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). OBJECTIVE: To analyze the epidemiology of OD and its relationship with APOE polymorphisms in a cohort of Long-COVID patients. METHODS: We conducted a prospective cohort study with patients followed in a post-COVID neurological outpatient clinic, with OD being defined as a subjective reduction of olfactory function after infection, and persistent OD being defined when the complaint lasted more than 3 months after the COVID-19 infection resolution. This cross-sectional study is part of a large research with previously reported data focusing on the cognitive performance of our sample. RESULTS: The final sample comprised 221 patients, among whom 186 collected blood samples for APOE genotyping. The persistent OD group was younger and had a lower hospitalization rate during the acute phase of the disease (p < 0.001). Furthermore, the APOE variant E4 allele frequency was lower in this group (p = 0.035). This study evaluated OD in an outpatient population with COVID-19. In the current literature on this disease, anosmia is associated with better clinical outcomes and the E4 allele is associated with worse outcomes. CONCLUSION: Our study provides new information to these correlations, suggesting APOE E4 as a protective factor for OD.
ANTECEDENTES: A disfunção olfatória (DO) é uma manifestação frequente da doença do coronavírus 2019 (COVID-19). A apolipoproteína E (APOE) é uma proteína que interage com o receptor da enzima conversora de angiotensina, essencial para a entrada viral na célula. Publicações anteriores sugeriram um possível papel da APOE na gravidade da COVID-19. Até onde sabemos, nenhuma publicação encontrou associações significativas entre a gravidade dessa doença, DO e polimorfismos da APOE (E2, E3 e E4). OBJETIVO: Analisar a epidemiologia da DO e sua relação com os polimorfismos do gene APOE em uma coorte de pacientes com COVID longa. MéTODOS: Um estudo de coorte prospectiva com pacientes acompanhados em ambulatório neurológico pós-COVID, com DO sendo definida como uma redução subjetiva da função olfativa após a infecção e a DO persistente sendo definida quando a queixa durou mais de 3 meses após a resolução da infecção por COVID-19. Este estudo transversal é parte de uma pesquisa maior com dados anteriormente relatados, focando na performance cognitiva dos pacientes. RESULTADOS: Foram selecionados 221 pacientes para esse estudo, dos quais 186 haviam coletado amostras de sangue para genotipagem APOE. O grupo DO persistente foi mais jovem e apresentou menor taxa de internação na fase aguda da doença (p < 0,001). Além disso, a frequência do alelo E4 da APOE foi menor nesse grupo (p = 0,035). Este estudo avaliou a DO em uma população com COVID longa. Na literatura atual sobre essa doença, a anosmia está associada a melhores desfechos clínicos e o alelo E4 está associado a piores desfechos. CONCLUSãO: Nosso estudo acrescenta novas informações a essas correlações, sugerindo a APOE E4 como um fator de proteção para DO.
Subject(s)
Alleles , COVID-19 , Olfaction Disorders , Humans , COVID-19/complications , Male , Female , Middle Aged , Prospective Studies , Olfaction Disorders/genetics , Cross-Sectional Studies , Apolipoprotein E4/genetics , Aged , Adult , Protective Factors , Apolipoproteins E/genetics , Polymorphism, Genetic , SARS-CoV-2 , Genotype , Post-Acute COVID-19 SyndromeABSTRACT
Introduction: Few 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. Methods: This 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. Results: The 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. Discussion: Hospitalized 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.
ABSTRACT
ABSTRACT. Infection with the SARS-CoV-2 virus can lead to neurological symptoms in the acute phase and in the Long COVID phase. These symptoms usually involve cognition, sleep, smell disorders, psychiatric manifestations, headache and others. This condition is more commonly described in young adults and women. This symptomatology can follow severe or mild cases of the disease. The importance of this issue resides in the high prevalence of neurological symptoms in the Long COVID phase, which entails significant morbidity in this population. In addition, such a condition is associated with high health care costs, with some estimates hovering around 3.7 trillion US dollars. In this review, we will sequentially describe the current knowledge about the most prevalent neurological symptoms in Long COVID, as well as their pathophysiology and possible biomarkers.
RESUMO. A infecção pelo vírus SARS-CoV-2 pode levar a sintomas neurológicos na fase aguda e na fase de COVID longa. Esses sintomas geralmente envolvem cognição, sono, distúrbios do olfato, manifestações psiquiátricas, dor de cabeça e outros. Esta condição é mais comumente descrita em adultos jovens e mulheres. A sintomatologia pode acompanhar casos graves ou leves da doença. A importância desta questão reside na elevada prevalência de sintomas neurológicos na fase de COVID longa, o que acarreta morbilidade significativa nesta população. Além disso, tal condição está associada a elevados custos de cuidados de saúde, com algumas estimativas em torno de 3,7 trilhões de dólares americanos. Nesta revisão, descrevemos sequencialmente o conhecimento atual sobre os sintomas neurológicos mais prevalentes na COVID longa, bem como sua fisiopatologia e possíveis biomarcadores.
ABSTRACT
Abstract 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). Objective To analyze the epidemiology of OD and its relationship with APOE polymorphisms in a cohort of Long-COVID patients. Methods We conducted a prospective cohort study with patients followed in a post-COVID neurological outpatient clinic, with OD being defined as a subjective reduction of olfactory function after infection, and persistent OD being defined when the complaint lasted more than 3 months after the COVID-19 infection resolution. This cross-sectional study is part of a large research with previously reported data focusing on the cognitive performance of our sample. Results The final sample comprised 221 patients, among whom 186 collected blood samples for APOE genotyping. The persistent OD group was younger and had a lower hospitalization rate during the acute phase of the disease (p < 0.001). Furthermore, the APOE variant E4 allele frequency was lower in this group (p = 0.035). This study evaluated OD in an outpatient population with COVID-19. In the current literature on this disease, anosmia is associated with better clinical outcomes and the E4 allele is associated with worse outcomes. Conclusion Our study provides new information to these correlations, suggesting APOE E4 as a protective factor for OD.
Resumo Antecedentes A disfunção olfatória (DO) é uma manifestação frequente da doença do coronavírus 2019 (COVID-19). A apolipoproteína E (APOE) é uma proteína que interage com o receptor da enzima conversora de angiotensina, essencial para a entrada viral na célula. Publicações anteriores sugeriram um possível papel da APOE na gravidade da COVID-19. Até onde sabemos, nenhuma publicação encontrou associações significativas entre a gravidade dessa doença, DO e polimorfismos da APOE (E2, E3 e E4). Objetivo Analisar a epidemiologia da DO e sua relação com os polimorfismos do gene APOE em uma coorte de pacientes com COVID longa. Métodos Um estudo de coorte prospectiva com pacientes acompanhados em ambulatório neurológico pós-COVID, com DO sendo definida como uma redução subjetiva da função olfativa após a infecção e a DO persistente sendo definida quando a queixa durou mais de 3 meses após a resolução da infecção por COVID-19. Este estudo transversal é parte de uma pesquisa maior com dados anteriormente relatados, focando na performance cognitiva dos pacientes. Resultados Foram selecionados 221 pacientes para esse estudo, dos quais 186 haviam coletado amostras de sangue para genotipagem APOE. O grupo DO persistente foi mais jovem e apresentou menor taxa de internação na fase aguda da doença (p < 0,001). Além disso, a frequência do alelo E4 da APOE foi menor nesse grupo (p = 0,035). Este estudo avaliou a DO em uma população com COVID longa. Na literatura atual sobre essa doença, a anosmia está associada a melhores desfechos clínicos e o alelo E4 está associado a piores desfechos. Conclusão Nosso estudo acrescenta novas informações a essas correlações, sugerindo a APOE E4 como um fator de proteção para DO.