High Levels of NfL, GFAP, TAU, and UCH-L1 as Potential Predictor Biomarkers of Severity and Lethality in Acute COVID-19.

Few studies showed that neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), total tubulin-associated unit (TAU), and ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) may be related to neurological manifestations and severity during and after SARS-CoV-2 infection. The objective of this work was to investigate the relationship among nervous system biomarkers (NfL, TAU, GFAP, and UCH-L1), biochemical parameters, and viral loads with heterogeneous outcomes in a cohort of severe COVID-19 patients admitted in Intensive Care Unit (ICU) of a university hospital. For that, 108 subjects were recruited within the first 5 days at ICU. In parallel, 16 mild COVID-19 patients were enrolled. Severe COVID-19 group was divided between "deceased" and "survivor." All subjects were positive for SARS-CoV-2 detection. NfL, total TAU, GFAP, and UCH-L1 quantification in plasma was performed using SIMOA SR-X platform. Of 108 severe patients, 36 (33.33%) presented neurological manifestation and 41 (37.96%) died. All four biomarkers - GFAP, NfL, TAU, and UCH-L1 - were significantly higher among deceased patients in comparison to survivors (p < 0.05). Analyzing biochemical biomarkers, higher Peak Serum Ferritin, D-Dimer Peak, Gamma-glutamyltransferase, and C-Reactive Protein levels were related to death (p < 0.0001). In multivariate analysis, GFAP, NfL, TAU, UCH-L1, and Peak Serum Ferritin levels were correlated to death. Regarding SARS-CoV-2 viral load, no statistical difference was observed for any group. Thus, Ferritin, NFL, GFAP, TAU, and UCH-L1 are early biomarkers of severity and lethality of SARS-COV-2 infection and may be important tools for therapeutic decision-making in the acute phase of disease.

Spatial-temporal distribution of incidence, mortality, and case-fatality ratios of coronavirus disease 2019 and its social determinants in Brazilian municipalities.

The COVID-19 pandemic caused impact on public health worldwide. Brazil gained prominence during the pandemic due to the magnitude of disease. This study aimed to evaluate the spatial-temporal dynamics of incidence, mortality, and case fatality of COVID-19 and its associations with social determinants in Brazilian municipalities and epidemiological week. We modeled incidence, mortality, and case fatality rates using spatial-temporal Bayesian model. "Bolsa Família Programme" (BOLSAFAM) and "proportional mortality ratio" (PMR) were inversely associated with the standardized incidence ratio (SIR), while "health insurance coverage" (HEALTHINSUR) and "Gini index" were directly associated with the SIR. BOLSAFAM and PMR were inversely associated with the standardized mortality ratio (SMR) and standardized case fatality ratio (SCFR). The highest proportion of excess risk for SIR and the SMR started in the North, expanding to the Midwest, Southeast, and South regions. The highest proportion of excess risk for the SCFR outcome was observed in some municipalities in the North region and in the other Brazilian regions. The COVID-19 incidence and mortality in municipalities that most benefited from the cash transfer programme and with better social development decreased. The municipalities with a higher proportion of non-whites had a higher risk of becoming ill and dying from the disease.

The effect of BCG vaccination on infection and antibody levels against SARS-CoV-2-The results of ProBCG: a multicenter randomized clinical trial in Brazil.

OBJECTIVES: Evatuate if Bacillus Calmette-Guérin (BCG) vaccine could be used as a tool against SARS-CoV-2 based on the concept of trained immunity. METHODS: A multicenter, double-blinded, randomized clinical trial recruited health care workers (HCWs) in Brazil. The incidence rates of COVID-19, clinical manifestations, absenteeism, and adverse events among HCWs receiving BCG vaccine (Moreau or Moscow strains) or placebo were compared. BCG vaccine-mediated immune response before and after implementing specific vaccines for COVID-19 (CoronaVac or COVISHIELD) was analyzed. Cox proportional hazard and linear mixed effect modeling were used. RESULTS: A total of 264 volunteers were included for analysis (BCG = 134 and placebo = 130). The placebo group presented a COVID-19 cumulative incidence of 0.75% vs 0.52% of BCG. The Moreau strain also presented a higher incidence rate (1.60% × 0.22%). BCG did not show a protective hazard ratio against COVID-19. In addition, the log (immunoglobulin G) level against SARS-CoV-2 presented a higher increase in the BCG group, whether or not participants had COVID-19, but also without statistical significance. CONCLUSION: Our results suggest that BCG has a tendency of protection against SARS-CoV-2 and higher immunoglobulin G levels than placebo. The clinical trial was registered at https://clinicaltrials.gov/ (NCT04659941).

Impacts of a delayed and slow-paced vaccination on cases and deaths during the COVID-19 pandemic: a modelling study.

In Brazil, vaccination has always cut across party political and ideological lines, which has delayed its start and brought the whole process into disrepute. Such divergences put the immunization of the population in the background and create additional hurdles beyond the pandemic, mistrust and scepticism over vaccines. We conduct a mathematical modelling study to analyse the impacts of late vaccination along with slowly increasing coverage, as well as how harmful it would be if part of the population refused to get vaccinated or missed the second dose. We analyse data from confirmed cases, deaths and vaccination in the state of Rio de Janeiro in the period between 10 March 2020 and 27 October 2021. We estimate that if the start of vaccination had been 30 days earlier, combined with efforts to drive vaccination rates up, about 31 657 deaths could have been avoided. In addition, the slow pace of vaccination and the low demand for the second dose could cause a resurgence of cases as early as 2022. Even when reaching the expected vaccination coverage for the first dose, it is still challenging to increase adherence to the second dose and maintain a high vaccination rate to avoid new outbreaks.

Fatores associados ao óbito em casos confirmados de COVID-19 no estado do Rio de Janeiro.

BACKGROUND: COVID-19 can occur asymptomatically, as influenza-like illness, or as more severe forms, which characterize severe acute respiratory syndrome (SARS). Its mortality rate is higher in individuals over 80 years of age and in people with comorbidities, so these constitute the risk group for severe forms of the disease. We analyzed the factors associated with death in confirmed cases of COVID-19 in the state of Rio de Janeiro. This cross-sectional study evaluated the association between individual demographic, clinical, and epidemiological variables and the outcome (death) using data from the Unified Health System information systems. METHODS: We used the extreme boosting gradient (XGBoost) model to analyze the data, which uses decision trees weighted by the estimation difficulty. To evaluate the relevance of each independent variable, we used the SHapley Additive exPlanations (SHAP) metric. From the probabilities generated by the XGBoost model, we transformed the data to the logarithm of odds to estimate the odds ratio for each independent variable. RESULTS: This study showed that older individuals of black race/skin color with heart disease or diabetes who had dyspnea or fever were more likely to die. CONCLUSIONS: The early identification of patients who may progress to a more severe form of the disease can help improve the clinical management of patients with COVID-19 and is thus essential to reduce the lethality of the disease.

Association between socio-environmental factors, coverage by family health teams, and rainfall in the spatial distribution of Zika virus infection in the city of Rio de Janeiro, Brazil, in 2015 and 2016.

BACKGROUND: Zika virus (ZIKV) infection caused outbreak in Brazil, in 2015 and 2016. Disorganized urban growth, facilitates the concentration of numerous susceptible and infected individuals. It is useful to understand the mechanisms that can favor the increase in ZIKV incidence, such as areas with wide socioeconomic and environmental diversity. Therefore, the study analyzed the spatial distribution of ZIKV in the city of Rio de Janeiro, Brazil, in 2015 and 2016, and associations between the incidence per 1000 inhabitants and socio-environmental factors. METHODS: The census tracts were used as the analytical units reported ZIKV cases among the city's inhabitants. Local Empirical Bayesian method was used to control the incidence rates' instability effect. The spatial autocorrelation was verified with Moran's Index and local indicators of spatial association (LISA). Spearman correlation matrix was used to indicate possible collinearity. The Ordinary Least Squares (OLS), Spatial Lag Model (SAR), and Spatial Error Model (CAR) were used to analyze the relationship between ZIKV and socio-environmental factors. RESULTS: The SAR model exhibited the best parameters: R2 = 0.44, Log-likelihood = - 7482, Akaike Information Criterion (AIC) = 14,980. In this model, mean income between 1 and 2 minimum wages was possible risk factors for Zika occurrence in the localities. Household conditions related to adequate water supply and the existence of public sewage disposal were associated with lower ZIKV cumulative incidence, suggesting possible protective factors against the occurrence of ZIKV in the localities. The presence of the Family Health Strategy in the census tracts was positively associated with the ZIKV cumulative incidence. However, the results show that mean income less than 1 minimum wage were negatively associated with higher ZIKV cumulative incidence. CONCLUSION: The results demonstrate the importance of socio-environmental variables in the dynamics of ZIKV transmission and the relevance for the development of control strategies.

[Evolution of CD4+ T-cell count among AIDS patients in socially unequal contexts]. / Evolução da contagem de células T CD4+ de portadores de AIDS em contextos socialmente desiguais.

This study analyzed the evolution in CD4+ T-cell count in AIDS patients in the city of Rio de Janeiro, Brazil, who were on highly active antiretroviral treatment (HAART) at the Municipal Health Centers in the Maré neighborhood, located in a large slum area, and in Copacabana, located in the city's more affluent South Side. Immediately prior to HAART, the median CD4+ T-lymphocyte count was 181 cells/mm(3) in Maré and 182 cells/mm(3) in Copacabana. After 24 weeks of HAART, the median count reached 302 and 315/mm3 in the two health centers, respectively. Following HAART, individuals with AIDS in Maré had 2.8 times the odds of not presenting an immune response as compared to cases in Copacabana (95%CI: 1.1-7.2). Slum residents from Maré had 3.7 the odds of not presenting an immune response as compared to slum residents from Copacabana (95%CI: 1.2-11.5). Males from Maré had 4.4 the odds of not presenting an immune response as compared to those from Copacabana (95%CI: 1.1-18.2). The results suggest a worse prognosis and higher case-fatality for AIDS patients from slums, independently of access to HAART.