Limited role of regulatory T cells during acute Theiler virus-induced encephalitis in resistant C57BL/6 mice

Background: Theiler's murine encephalomyelitis virus (TMEV) infection represents a commonly used infectious animal model to study various aspects of the pathogenesis of multiple sclerosis (MS). In susceptible SJL mice, dominant activity of Foxp3+ CD4+ regulatory T cells (Tregs) in the CNS partly contributes to viral persistence and progressive demyelination. On the other hand, resistant C57BL/6 mice rapidly clear the virus by mounting a strong antiviral immune response. However, very little is known about the role of Tregs in regulating antiviral responses during acute encephalitis in resistant mouse strains. Methods: In this study, we used DEREG mice that express the diphtheria toxin (DT) receptor under control of the foxp3 locus to selectively deplete Foxp3+ Tregs by injection of DT prior to infection and studied the effect of Treg depletion on the course of acute Theiler's murine encephalomyelitis (TME). Results: As expected, DEREG mice that are on a C57BL/6 background were resistant to TMEV infection and cleared the virus within days of infection, regardless of the presence or absence of Tregs. Nevertheless, in the absence of Tregs we observed priming of stronger effector T cell responses in the periphery, which subsequently resulted in a transient increase in the frequency of IFNγ-producing T cells in the brain at an early stage of infection. Histological and flow cytometric analysis revealed that this transiently increased frequency of brain-infiltrating IFNγ-producing T cells in Treg-depleted mice neither led to an augmented antiviral response nor enhanced inflammation-mediated tissue damage. Intriguingly, Treg depletion did not change the expression of IL-10 in the infected brain, which might play a role for dampening the inflammatory damage caused by the increased number of effector T cells. Conclusion: We therefore propose that unlike susceptible mice strains, interfering with the Treg compartment of resistant mice only has negligible effects on virus-induced pathologies in the CNS. Furthermore, in the absence of Tregs, local anti-inflammatory mechanisms might limit the extent of damage caused by strong anti-viral response in the CNS

Prevalence, predictors, and patient-reported outcomes of long COVID in hospitalized and non-hospitalized patients from the city of São Paulo, Brazil

BackgroundRobust data comparing long COVID in hospitalized and non-hospitalized patients in middle-income countries are limited.MethodsA retrospective cohort study was conducted in Brazil, including hospitalized and non-hospitalized patients. Long COVID was diagnosed at 90-day follow-up using WHO criteria. Demographic and clinical information, including the depression screening scale (PHQ-2) at day 30, was compared between the groups. If the PHQ-2 score is 3 or greater, major depressive disorder is likely. Logistic regression analysis identified predictors and protective factors for long COVID.ResultsA total of 291 hospitalized and 1,118 non-hospitalized patients with COVID-19 were included. The prevalence of long COVID was 47.1% and 49.5%, respectively. Multivariable logistic regression showed female sex (odds ratio [OR] = 4.50, 95% confidence interval (CI) 2.51–8.37), hypertension (OR = 2.90, 95% CI 1.52–5.69), PHQ-2 > 3 (OR = 6.50, 95% CI 1.68–33.4) and corticosteroid use during hospital stay (OR = 2.43, 95% CI 1.20–5.04) as predictors of long COVID in hospitalized patients, while female sex (OR = 2.52, 95% CI 1.95–3.27) and PHQ-2 > 3 (OR = 3.88, 95% CI 2.52–6.16) were predictors in non-hospitalized patients.ConclusionLong COVID was prevalent in both groups. Positive depression screening at day 30 post-infection can predict long COVID. Early screening of depression helps health staff to identify patients at a higher risk of long COVID, allowing an early diagnosis of the condition

Longer-term effectiveness of a heterologous coronavirus disease 2019 (COVID-19) vaccine booster in healthcare workers in Brazil

Abstract Objective: To compare the long-term vaccine effectiveness between those receiving viral vector [Oxford-AstraZeneca (ChAdOx1)] or inactivated viral (CoronaVac) primary series (2 doses) and those who received an mRNA booster (Pfizer/BioNTech) (the third dose) among healthcare workers (HCWs). Methods: We conducted a retrospective cohort study among HCWs (aged ≥18 years) in Brazil from January 2021 to July 2022. To assess the variation in the effectiveness of booster dose over time, we estimated the effectiveness rate by taking the log risk ratio as a function of time. Results: Of 14,532 HCWs, coronavirus disease 2019 (COVID-19) was confirmed in 56.3% of HCWs receiving 2 doses of CoronaVac vaccine versus 23.2% of HCWs receiving 2 doses of CoronaVac vaccine with mRNA booster (P < .001), and 37.1% of HCWs receiving 2 doses of ChAdOx1 vaccine versus 22.7% among HCWs receiving 2 doses of ChAdOx1 vaccine with mRNA booster (P < .001). The highest vaccine effectiveness with mRNA booster was observed 30 days after vaccination: 91% for the CoronaVac vaccine group and 97% for the ChAdOx1 vaccine group. Vacine effectiveness declined to 55% and 67%, respectively, at 180 days. Of 430 samples screened for mutations, 49.5% were SARS-CoV-2 delta variants and 34.2% were SARS-CoV-2 omicron variants. Conclusions: Heterologous COVID-19 vaccines were effective for up to 180 days in preventing COVID-19 in the SARS-CoV-2 delta and omicron variant eras, which suggests the need for a second booster

Can hydrophilic coated catheters be beneficial for the public healthcare system in Brazil? - A cost-effectiveness analysis in patients with spinal cord injuries

ABSTRACT Introduction Detrusor sphincter dyssynergia affects 70% to 80% of all spinal cord injury patients, resulting in increased risk of urinary tract infections (UTIs) and potential exposure to antimicrobial resistance. In Brazil, local guidelines recommend intermittent catheterization as the best method for bladder emptying, and two catheter types are available: the conventional uncoated PVC and the hydrophilic coated catheters. Objective To evaluate the cost-effectiveness of two types of catheters for intermittent catheterization from the perspective of the Brazilian public healthcare system. Materials and Methods A Markov model was used to evaluate cost-effectiveness in those with spinal cord injuries. A primary analysis was conducted on all possible adverse events, and a secondary analysis was performed with urinary tract infections as the only relevant parameter. The results were presented as cost per life years gained (LYG), per quality-adjusted life years (QALY) and per number of urinary tract infections (UTIs) avoided. Results The base scenario of all adverse events shows a cost-effective result of hydrophilic coated catheters compared to uncoated PVC catheters at 57,432 BRL (Brazilian Reais) per LYG and 122,330 BRL per QALY. The secondary scenario showed that the use of hydrophilic coated catheters reduces the total number of UTIs, indicating that an additional cost of hydrophilic coated catheters of 31,240 BRL over a lifetime will reduce lifetime UTIs by 6%. Conclusions Despite the higher unit value, the use of hydrophilic coated catheters is a cost-effective treatment from the perspective of the Brazilian public healthcare system

Burden and cost of multiple sclerosis in Brazil.

BackgroundThe objective of this study was to estimate costs to society and patients' quality of life (QoL) at all levels of disease severity (measured with the Expanded Disability Status Scale, EDSS) in Brazil.MethodsThe study was part of an international, cross-sectional burden-of-illness study carried out in collaboration with national MS patient organizations. All information was collected directly from patients using a validated questionnaire. Direct costs were estimated both from societal and payer perspectives, while total costs are presented as societal costs.ResultsThe survey included 694 patients (response rate 21%; mean age 40.8 years). 95% of patients were of working age, and around half were working. The mean EDSS score was 3.2 (62.5% of patients with EDSS ConclusionsThis study included a population with relatively mild and early disease, with a majority of patients with relapsing disease and thus on DMD treatment. It is not possible to conclude directly on the total cost of MS in Brazil. Nevertheless, resource quantities used, QoL and MS symptoms are very similar to what was seen in the European survey

Evaluation of cost-effectiveness from the funding body’s point of view of ultrasound-guided central venous catheter insertion compared with the conventional technique

RESUMO Objetivo: Avaliar o custo-efetividade da inserção de cateter venoso central guiada por ultrassonografia em tempo real, em comparação com a técnica tradicional, que é baseada na técnica de reparos anatômicos externos, sob a perspectiva da fonte pagadora. Métodos: Uma simulação teórica, baseada em dados de literatura internacional foi aplicada ao contexto brasileiro, ou seja, ao Sistema Único de Saúde (SUS). Foi estruturada uma árvore de decisão, que apresentava as duas técnicas para inserção de cateter venoso central: ultrassonografia em tempo real versus reparos anatômicos externos. As probabilidades de falha e complicações foram extraídas de uma busca nas bases PubMed e Embase, e os valores associados ao procedimento e às complicações foram extraídos de pesquisa de mercado e do Departamento de Informática do Sistema Único de Saúde (DATASUS). Cada alternativa de passagem do cateter venoso central teve um custo calculado por meio do seguimento de cada um dos possíveis caminhos da árvore de decisão. A razão de custo-efetividade incremental foi calculada considerando-se a divisão do custo incremental médio da técnica de ultrassonografia em tempo real comparada à técnica de reparos anatômicos externos pelo benefício incremental médio, em termos de complicações evitadas. Resultados: O custo final médio avaliado pela árvore de decisão, considerando a incorporação da ultrassonografia em tempo real e a redução de custo por diminuição de complicações, para a técnica de reparos anatômicos externos foi de R$262,27 e, para ultrassonografia em tempo real, de R$187,94. O custo incremental final foi de -R$74,33 por cateter venoso central. A razão de custo-efetividade incremental foi -R$2.494,34 por pneumotórax evitado. Conclusão: A inserção de cateter venoso central com auxílio de ultrassonografia em tempo real esteve associada à diminuição da taxa de falhas e complicações, além de hipoteticamente reduzir custos na perspectiva da fonte pagadora, no caso o SUS