Clinical Profile and Risk Factors for Severe COVID-19 in Hospitalized Patients from Rio de Janeiro, Brazil: Comparison between the First and Second Pandemic Waves.

Since COVID-19 was declared a pandemic, Brazil has become one of the countries most affected by this disease. A year into the pandemic, a second wave of COVID-19 emerged, with a rapid spread of a new SARS-CoV-2 lineage of concern. Several vaccines have been granted emergency-use authorization, leading to a decrease in mortality and severe cases in many countries. However, the emergence of SARS-CoV-2 variants raises the alert for potential new waves of transmission and an increase in pathogenicity. We compared the demographic and clinical data of critically ill patients infected with COVID-19 hospitalized in Rio de Janeiro during the first and second waves between July 2020 and October 2021. In total, 106 participants were included in this study; among them, 88% had at least one comorbidity, and 37% developed severe disease. Disease severity was associated with older age, pre-existing neurological comorbidities, higher viral load, and dyspnea. Laboratory biomarkers related to white blood cells, coagulation, cellular injury, inflammation, renal, and liver injuries were significantly associated with severe COVID-19. During the second wave of the pandemic, the necessity of invasive respiratory support was higher, and more individuals with COVID-19 developed acute hepatitis, suggesting that the progression of the second wave resulted in an increase in severe cases. These results can contribute to understanding the behavior of the COVID-19 pandemic in Brazil and may be helpful in predicting disease severity, which is a pivotal for guiding clinical care, improving patient outcomes, and defining public policies.

Molecular mimicry between Zika virus and central nervous system inflammatory demyelinating disorders: the role of NS5 Zika virus epitope and PLP autoantigens / Mimetismo molecular entre o vírus Zika e os distúrbios inflamatórios desmielinizantes do sistema nervoso central: o papel do epítopo NS5 do vírus Zika e dos autoantígenos PLP

Abstract Background Evidence indicates a strong link between Zika virus (ZikV) and neurological complications. Acute myelitis, optic neuritis, polyneuropathy, and encephalomyelitis that mimic inflammatory idiopathic demyelination disorders (HDD) after ZikV infection have been reported in Brazil. Objective The present study aims to investigate the possible occurrence of molecular mimicry between ZikV antigens and Multiple Sclerosis (MS) autoantigens, the most frequent HDD of the central nervous system (CNS). Methods A retrospective cohort study with 305 patients admitted due to suspected arbovirus infection in Rio de Janeiro was performed, all subjects were submitted to neurological examination, and a biological sample was collected for serologic and molecular diagnostic. Bioinformatics tools were used to analyze the peptides shared between ZikV antigens and MS autoantigens. Results Of 305 patients, twenty-six were positive for ZikV and 4 presented IDD patterns found in MS cases. Sequence homology comparisons by bioinformatics approach between NS5 ZikV and PLP MS protein revealed a homology of 5/6 consecutive amino acids (CSSVPV/CSAVPV) with 83% identity, deducing a molecular mimicry. Analysis of the 3D structures revealed a similar conformation with alpha helix presentation. Conclusions Molecular mimicry between NS5 Zika virus antigen and PLP MS autoantigens emerge as a possible mechanism for IDD spectrum in genetically susceptible individuals.

Resumo Antecedentes Evidências indicam uma forte ligação entre o vírus Zika (ZikV) e complicações neurológicas. Mielite aguda, neurite óptica, polineuropatia e encefalomielite que mimetizam distúrbios inflamatórios de desmielinização idiopáticos (DDII) após infecção por ZikV têm sido relatadas no Brasil. Obejtivo O presente estudo tem como objetivo investigar a possível ocorrência de mimetismo molecular entre antígenos do ZikV e autoantígenos da Esclerose Múltipla (EM), a DDII mais frequente do sistema nervoso central (SNC). Métodos Foi realizado um estudo de coorte retrospectivo com 305 pacientes internados por suspeita de infecção por arbovirus no Rio de Janeiro, todos os indivíduos foram submetidos a exame neurológico e coleta de amostra biológica para diagnóstico sorológico e molecular. Ferramentas de bioinformática foram usadas para analisar os peptídeos compartilhados entre antígenos do ZikV e autoantígenos da EM. Resultados Dos 305 pacientes, vinte e seis foram positivos para ZikV e 4 apresentaram padrão IDD encontrado em casos de EM. As comparações de homologia de sequência por abordagem de bioinformática entre a proteína NS5 ZikV e PLP EM revelaram uma homologia de 5/6 aminoácidos consecutivos (CSSVPV/CSAVPV) com 83% de identidade, deduzindo um mimetismo molecular. A análise das estruturas 3D revelou uma conformação semelhante com apresentação em alfa-hélice. Conclusões O mimetismo molecular entre o antígeno NS5 do vírus Zika e o autoantígeno PLP da EM surge como um possível mecanismo para o espectro IDD em indivíduos geneticamente suscetíveis.

Exome-Wide Search for Genes Associated With Central Nervous System Inflammatory Demyelinating Diseases Following CHIKV Infection: The Tip of the Iceberg.

Chikungunya virus (CHIKV) is a re-emergent arbovirus that causes a disease characterized primarily by fever, rash and severe persistent polyarthralgia, although <1% of cases develop severe neurological manifestations such as inflammatory demyelinating diseases (IDD) of the central nervous system (CNS) like acute disseminated encephalomyelitis (ADEM) and extensive transverse myelitis. Genetic factors associated with host response and disease severity are still poorly understood. In this study, we performed whole-exome sequencing (WES) to identify HLA alleles, genes and cellular pathways associated with CNS IDD clinical phenotype outcomes following CHIKV infection. The cohort includes 345 patients of which 160 were confirmed for CHIKV. Six cases presented neurological manifestation mimetizing CNS IDD. WES data analysis was performed for 12 patients, including the CNS IDD cases and 6 CHIKV patients without any neurological manifestation. We identified 29 candidate genes harboring rare, pathogenic, or probably pathogenic variants in all exomes analyzed. HLA alleles were also determined and patients who developed CNS IDD shared a common signature with diseases such as Multiple sclerosis (MS) and Neuromyelitis Optica Spectrum Disorders (NMOSD). When these genes were included in Gene Ontology analyses, pathways associated with CNS IDD syndromes were retrieved, suggesting that CHIKV-induced CNS outcomesmay share a genetic background with other neurological disorders. To our knowledge, this study was the first genome-wide investigation of genetic risk factors for CNS phenotypes in CHIKV infection. Our data suggest that HLA-DRB1 alleles associated with demyelinating diseases may also confer risk of CNS IDD outcomes in patients with CHIKV infection.

Neurological signs described at the Federal University of Rio de Janeiro: connecting the past to the future.

OBJECTIVE: The Federal University of Rio de Janeiro (UFRJ) is one of the pillars of Brazilian Medicine and, in Neurology, has always shown prominence, with notable professors such as Antônio Austregésilo and Deolindo Couto. Historically, practitioners of the UFRJ Medical School have discovered neurological signs that, although used in medical and academic practice, have never been published. Our aim was to bring these signs to the forefront so that they become properly recognized and studied. METHODS: We conducted our search by questioning 49 professors and physicians by e-mail about neurological signs that they remembered having had contact with at UFRJ. RESULTS: We report on the unpublished pillow sign in progressive supranuclear palsy; the Brazilian sandal sign in functional or malingering patients; the dermographism sign in acute meningitis; the reverse forearm rolling sign in functional palsies; the cycling maneuver in parkinsonian syndromes and the Sá Cavalcanti sign, a Babinski equivalent. We have also recollected the following published signs for their historical relevance: the Austregésilo sign (Antônio Austregésilo), another Babinski equivalent; the digiti quinti rolling sign in subtle palsies (Péricles Maranhão) and the digiti quinti sign in hemiplegic migraine (Maurice Vincent). These signs are easily reproduced and have potential clinical applicability, deserving to be more thoroughly studied. CONCLUSIONS: Through a qualitative methodology, we have identified six original unpublished neurological signs known by the academic community, establishing the contribution of these individuals to the expansion of neurological semiology.

Neurological signs described at the Federal University of Rio de Janeiro: connecting the past to the future / Sinais neurológicos descritos na Universidade Federal do Rio de Janeiro: conectando o passado ao futuro

ABSTRACT The Federal University of Rio de Janeiro (UFRJ) is one of the pillars of Brazilian Medicine and, in Neurology, has always shown prominence, with notable professors such as Antônio Austregésilo and Deolindo Couto. Historically, practitioners of the UFRJ Medical School have discovered neurological signs that, although used in medical and academic practice, have never been published. Objective Our aim was to bring these signs to the forefront so that they become properly recognized and studied. Methods We conducted our search by questioning 49 professors and physicians by e-mail about neurological signs that they remembered having had contact with at UFRJ. Results We report on the unpublished pillow sign in progressive supranuclear palsy; the Brazilian sandal sign in functional or malingering patients; the dermographism sign in acute meningitis; the reverse forearm rolling sign in functional palsies; the cycling maneuver in parkinsonian syndromes and the Sá Cavalcanti sign, a Babinski equivalent. We have also recollected the following published signs for their historical relevance: the Austregésilo sign (Antônio Austregésilo), another Babinski equivalent; the digiti quinti rolling sign in subtle palsies (Péricles Maranhão) and the digiti quinti sign in hemiplegic migraine (Maurice Vincent). These signs are easily reproduced and have potential clinical applicability, deserving to be more thoroughly studied. Conclusions Through a qualitative methodology, we have identified six original unpublished neurological signs known by the academic community, establishing the contribution of these individuals to the expansion of neurological semiology.

RESUMO A Universidade Federal do Rio de Janeiro é um dos pilares da Medicina brasileira. Na Neurologia sempre se destacou com notáveis professores, como Antônio Austregésilo e Deolindo Couto. Historicamente, professores da Faculdade de Medicina da UFRJ descreveram sinais neurológicos que, embora utilizados na prática médica e acadêmica, nunca foram publicados. Objetivo Fazer ressurgir sinais clínicos neurológicos nunca antes publicados, para que possam ser devidamente reconhecidos e estudados. Métodos Quarenta e nove professores e médicos foram contactados por e-mail. Dez responderam questionário semi-estruturado acerca de sinais neurológicos conhecidos pelos profissionais, porém nunca publicados. Resultados Foram relatados: 1- Sinal do Travesseiro - na Paralisia Supranuclear Progressiva; 2- Sinal da sandália- nos pacientes funcionais ou simuladores; 3- Sinal do dermografismo- nas meningites agudas da infância; 4- Sinal do rolamento reverso do antebraço- nas paralisias funcionais; 5- Manobra do pedalar- nas síndromes parkinsonianas; 6- Sinal de Sá Cavalcanti- um sucedâneo de Babinski. Revisamos também os seguintes sinais publicados, por sua relevância histórica: o sinal Austregésilo, outro sucedâneo de Babinski; sinal do rolamento do quinto dedo- nas paralisias sutis e o sinal do quinto dedo- na enxaqueca hemiplégia. Conclusão Por meio de metodologia qualitativa, identificamos seis sinais neurológicos inéditos originais. Esses sinais são de fácil reprodutibilidade e têm aplicabilidade clínica potencial, merecendo estudos adicionais.