Cross-reactive immunity against SARS-CoV-2 N protein in Central and West Africa precedes the COVID-19 pandemic.

Early predictions forecasted large numbers of severe acute respiratory syndrome coronavirus (SARS-CoV-2) cases and associated deaths in Africa. To date, Africa has been relatively spared. Various hypotheses were postulated to explain the lower than anticipated impact on public health in Africa. However, the contribution of pre-existing immunity is yet to be investigated. In this study, the presence of antibodies against SARS-CoV-2 spike (S) and nucleocapsid (N) proteins in pre-pandemic samples from Africa, Europe, South and North America was examined by ELISA. The protective efficacy of N specific antibodies isolated from Central African donors was tested by in vitro neutralization and in a mouse model of SARS-CoV-2 infection. Antibodies against SARS-CoV-2 S and N proteins were rare in all populations except in Gabon and Senegal where N specific antibodies were prevalent. However, these antibodies failed to neutralize the virus either in vitro or in vivo. Overall, this study indicates that cross-reactive immunity against SARS-CoV-2 N protein was present in Africa prior to the pandemic. However, this pre-existing humoral immunity does not impact viral fitness in rodents suggesting that other human immune defense mechanisms could be involved. In Africa, seroprevalence studies using the N protein are over-estimating SARS-CoV-2 circulation.

Depression and anxiety in patients with multiple sclerosis treated with interferon-beta or fingolimod: Role of indoleamine 2,3-dioxygenase and pro-inflammatory cytokines.

Depression/anxiety (D/A) occurs in up to 50% of multiple sclerosis (MS) patients. Proinflammatory cytokines induce classical symptoms of depression. Activation of the inflammatory response also triggers production of indoleamine 2,3-dioxygenase (IDO), which catabolizes tryptophan, the amino acid precursor of serotonin and melatonin. It has been suggested that IDO is the link between the immune and serotonergic systems. This study aimed to quantify the levels of IDO and pro-inflammatory and anti-inflammatory cytokines in patients with MS and depression, according to treatment with interferon-beta (IFN-ß) or fingolimod. The study inclusion criteria were age 18-60 years and a clinical and radiological diagnosis of MS. One hundred and thirty-two patients diagnosed by McDonald's criteria and followed up at Brasília District Hospital, Brazil, with relapsing-remitting MS were identified as potential study participants. Thirty-five of these patients were identified to be receiving treatment with fingolimod or IFN-ß and to have a diagnosis of D/A. IDO and pro-inflammatory and anti-inflammatory cytokine levels were compared between these 35 patients and 18 healthy controls. The level of IL-10 (an anti-inflammatory cytokine) was lower in both the fingolimod-treated (P â€‹< â€‹0.001) and IFN-ß-treated (P â€‹< â€‹0.01) patient groups than in the control group. IFN-ß-treated patients showed increased IDO expression and decreased inflammatory cytokine levels. In contrast, fingolimod-treated patients showed significantly decreased expression of IDO and significantly increased levels of proinflammatory cytokines produced by innate immune cells, including tumor necrosis factor-alpha and interleukin-6. The agents used to treat MS maintain symptoms of D/A in patients with MS via different mechanisms.

From Charcot's descriptions to the current understanding of neuropsychiatric symptoms in multiple sclerosis.

Neuropsychiatric disorders in multiple sclerosis have been known since the original clinicopathological description by Charcot in the late nineteenth century. Charcot, in the last decades of his life, became involved in the field of neuropsychiatry. This produced a battle between rival schools in the era that still echoes to this day. Charcot's intuition, including the line of thought of Babinski, one of his most famous disciples, was that there was a connection between mood disorders and many of the diseases of the nervous system. Medicine's concern with establishing a relationship between mood disorders and disease stems from the ancient and middle ages with references found in the Hippocratic doctrine. However, it was only in the second half of the nineteenth and early twentieth century, with Charcot's discoveries, that this discussion was established in a structured way, laying the foundations of neuropsychiatry.

From Charcot's descriptions to the current understanding of neuropsychiatric symptoms in multiple sclerosis / Das descrições de Charcot à compreensão atual dos sintomas neuropsiquiátricos na esclerose múltipla

ABSTRACT Neuropsychiatric disorders in multiple sclerosis have been known since the original clinicopathological description by Charcot in the late nineteenth century. Charcot, in the last decades of his life, became involved in the field of neuropsychiatry. This produced a battle between rival schools in the era that still echoes to this day. Charcot's intuition, including the line of thought of Babinski, one of his most famous disciples, was that there was a connection between mood disorders and many of the diseases of the nervous system. Medicine's concern with establishing a relationship between mood disorders and disease stems from the ancient and middle ages with references found in the Hippocratic doctrine. However, it was only in the second half of the nineteenth and early twentieth century, with Charcot's discoveries, that this discussion was established in a structured way, laying the foundations of neuropsychiatry.

RESUMO Os distúrbios neuropsiquiátricos na esclerose múltipla são conhecidos desde a descrição clínico-patológica original de Charcot no final do século XIX. Charcot nas últimas décadas de sua vida se envolveu no campo da neuropsiquiatria. Isso produziu uma batalha de escolas rivais na época que ainda ecoa até hoje. A intuição de Charcot, incluindo a linha de pensamento de Babinski, um de seus discípulos mais famosos, foi a teoria correta da conexão entre os transtornos do humor e muitas das doenças do sistema nervoso. A preocupação da Medicina em estabelecer uma relação entre transtornos do humor e doenças vem das idades antiga e média, com referências encontradas na doutrina hipocrática. No entanto, foi apenas na segunda metade do século XIX e início do século XX que, com as descobertas de Charcot essa discussão foi realizada de maneira estruturada, estabelecendo os fundamentos da neuropsiquiatria.

Validation of the Brazilian version of the patient-determined disease steps scale in persons with multiple sclerosis.

OBJECTIVE: The present study translated and adapted the Brazilian version of the Patient-Determined Disease Steps (PDDS) scale and tested its validity and reproducibility in Brazilian persons with multiple sclerosis (MS). METHODS: The PDDS underwent translation and back-translation procedures for producing a Brazilian Portuguese version of the PDDS (PDDS/BR). Sixty-three patients with MS (48 females) completed the PDDS/BR and underwent a neurological examination for generation of Expanded Disability Status Scale (EDSS) scores. Participants further performed the following tests: Timed 25-Foot Walk (T25FW), Timed Up and Go (TUG), six-minute walk test (6MWT), Nine Hole Peg (9HPT), and Symbol Digit Modalities Test (SDMT). Construct validity of PDDS/BR scores was determined by Spearman correlation with EDSS, and comparison of correlations between PDDS/BR and EDSS with the functional tests. We examined overall correct classification of disability categories (i.e., mild, moderate, or severe disability) by the PDDS/BR in relation to the EDSS. Test-retest reproducibility of PDDS/BR scores was examined in a subsample of 31 participants after 15 days. RESULTS: There was a strong relationship between the PDDS/BR and EDSS scores (ρ = 0.723, p < 0.05). The correlations with TUG, T25FW, 6MWT, and 9HPT were comparable for the PDDS/BR and EDSS scores. Overall correct classification of disability categories by the PDDS/BR was 79.3%. Results indicated excellent test-retest reproducibility for the PDDS/BR (Intraclass Correlation Coefficient= 0.911, 95% CI: 0.685-0.918). CONCLUSION: The PDDS/BR scores provide a valid and reliable assessment of mobility disability and may be used by researchers and neurologists to assess disability status in Brazilians with MS.

Knee flexor strength and balance control impairment may explain declines during prolonged walking in women with mild multiple sclerosis.

BACKGROUND: Physiological factors such as muscle weakness and balance could explain declines in walking distance by multiple sclerosis (MS) patients. The purpose of this study was to characterize levels and examine associations among decline in walking distance, balance and muscular strength in women with mild MS. METHODS: Participants included 28 women with mild relapsing-remitting MS and 21 women without MS. We executed the 6-min walk test (6MWT) to verify declines in walking distance. Isokinetic knee flexion (KF) and extension (KE) muscle strength was measured using a dynamometer. Balance was quantified using a force platform, with eyes open and closed, on a rigid and foam surface. RESULTS: The MS patients presented declines in walking, lower KF muscle strength, and worse balance than controls. KF strength and balance correlated with walking in the MS group. The KF strength explained differences between groups in walking. The KF strength and balance presented as predictors of walking slowing down in the 6MWT, in mild MS. CONCLUSION: Women with mild MS have strength impairment of knee flexor muscles and balance control impairment that may explain walking related motor fatigability during prolonged walking.