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

Introduction Bacillus Calmette-Guérin (BCG) vaccine was considered as a tool against SARS-CoV-2 based on the concept of trained immunity, which could be useful against emerging pathogens. Methods A multicenter double-blinded randomized clinical trial recruited health care workers (HCW) in Brazil. The incidence rates of COVID-19, clinical manifestations, absenteeism, and adverse events among HCW 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 CovishieldTM) was analyzed. Cox proportional hazard and linear mixed effect modelling were used. Results 264 volunteers were included for analysis (BCG=134 and placebo=130). Placebo group presented a COVID-19 cumulative incidence of 0.75% versus 0.52% of BCG. Moreau strain also presented a higher incidence rate (1.60% x 0.22%). BCG did not show a protective hazard ratio against COVID-19. In addition, the log(IgG) 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 a BCG's tendency of protection against SARS-CoV-2 and higher IgG levels when compared to placebo. The clinical trial was registered at https://clinicaltrials.gov/ (NCT04659941).

Host genetic susceptibility underlying SARS-CoV-2-associated Multisystem Inflammatory Syndrome in Brazilian Children.

BACKGROUND: Multisystem Inflammatory Syndrome in Children (MIS-C) is a life-threatening complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which manifests as a hyper inflammatory process with multiorgan involvement in predominantly healthy children in the weeks following mild or asymptomatic coronavirus disease 2019 (COVID-19). However, host monogenic predisposing factors to MIS-C remain elusive. METHODS: Herein, we used whole exome sequencing (WES) on 16 MIS-C Brazilian patients to identify single nucleotide/InDels variants as predisposition factors associated with MIS-C. RESULTS: We identified ten very rare variants in eight genes (FREM1, MPO, POLG, C6, C9, ABCA4, ABCC6, and BSCL2) as the most promising candidates to be related to a higher risk of MIS-C development. These variants may propitiate a less effective immune response to infection or trigger the inflammatory response or yet a delayed hyperimmune response to SARS-CoV-2. Protein-Protein Interactions (PPIs) among the products of the mutated genes revealed an integrated network, enriched for immune and inflammatory response mechanisms with some of the direct partners representing gene products previously associated with MIS-C and Kawasaki disease (KD). In addition, the PPIs direct partners are also enriched for COVID-19-related gene sets. HLA alleles prediction from WES data allowed the identification of at least one risk allele in 100% of the MIS-C patients. CONCLUSIONS: This study is the first to explore host MIS-C-associated variants in a Latin American admixed population. Besides expanding the spectrum of MIS-C-associated variants, our findings highlight the relevance of using WES for characterising the genetic interindividual variability associated with COVID-19 complications and ratify the presence of overlapping/convergent mechanisms among MIS-C, KD and COVID-19, crucial for future therapeutic management.

Seroprevalence of IgG and IgM anti-SARS-CoV-2 among voluntary blood donors in Rio de Janeiro, Brazil

Background: In Brazil, mathematical models for derivingestimates and projections of COVID-19 cases have been developed without data on asymptomatic SARS-CoV-2 infection. We estimated the seroprevalence of antibodies to SARS-CoV-2 among blood donors in the State of Rio de Janeiro. Methods: Data were collected on 2,857 blood donors from April 14 to 27, 2020. We report the crude prevalence of antibodies to SARS-CoV-2, the weighted prevalence by the total state population, and adjusted prevalence estimates for test sensitivity and specificity. To establish the correlates of SARS-CoV-2 prevalence, we used logistic regression models. The analysis included period and site of blood collection, sociodemographic characteristics, and place of residence. Results: The proportion of SARS-Cov-2 positive tests without any adjustment was 4.0% (95% CI 3.3-4.7%), and the weighted prevalence was 3.8% (95% CI 3.1-4.5%). Further adjustment by test sensitivity and specificity produced lower estimates, 3.6% (95% CI 2.7-4.4%) and 3.3% (95% CI 2.6-4.1%), respectively. The variable most significantly associated with the crude prevalence was the period of blood collection: the later the period, the higher the prevalence. Regarding socio-demographic characteristics, the younger the blood donors, the higher the prevalence, and the lower the educational level, the higher the odds of a positive SARS-Cov-2 antibody. Similar results were found for the weighted prevalence. Discussion: Although our findings resulted from a convenience sample, they match some basic premises: the increasing trend over time, since the epidemic curve in the state is still on the rise;the higher prevalence among the youngest who are more likely to circulate;and the higher prevalence among the less educated as they have more difficulties in following the social distancing recommendations. Despite the study limitations, it is possible to infer that protective levels of natural herd immunity to SARS-CoV-2 are far from being reached in Rio de Janeiro. (AU)

Seroprevalence of anti-SARS-CoV-2 among blood donors in Rio de Janeiro, Brazil.

OBJECTIVE To estimate the seroprevalence of antibodies to SARS-CoV-2 among blood donors in the state of Rio de Janeiro, Brazil. METHODS Data were collected on 2,857 blood donors from April 14 to 27, 2020. This study reports crude prevalence of antibodies to SARS-CoV-2, population weighted prevalence for the state, and prevalence adjusted for test sensitivity and specificity. Logistic regression models were used to establish the correlates of SARS-CoV-2 prevalence. For the analysis, we considered collection period and site, sociodemographic characteristics, and place of residence. RESULTS The proportion of positive tests for SARS-Cov-2, without any adjustment, was 4.0% (95%CI 3.3-4.7%), and the weighted prevalence was 3.8% (95%CI 3.1-4.5%). We found lower estimates after adjusting for test sensitivity and specificity: 3.6% (95%CI 2.7-4.4%) for the non-weighted prevalence, and 3.3% (95%CI 2.6-4.1%) for the weighted prevalence. Collection period was the variable most significantly associated with crude prevalence: the later the period, the higher the prevalence. Regarding sociodemographic characteristics, the younger the blood donor, the higher the prevalence, and the lower the education level, the higher the odds of testing positive for SARS-Cov-2 antibody. We found similar results for weighted prevalence. CONCLUSIONS Our findings comply with some basic premises: the increasing trend over time, as the epidemic curve in the state is still on the rise; and the higher prevalence among both the youngest, for moving around more than older age groups, and the less educated, for encountering more difficulties in following social distancing recommendations. Despite the study limitations, we may infer that Rio de Janeiro is far from reaching the required levels of herd immunity against SARS-CoV-2.

Seroprevalence of anti-SARS-CoV-2 among blood donors in Rio de Janeiro, Brazil

ABSTRACT OBJECTIVE To estimate the seroprevalence of antibodies to SARS-CoV-2 among blood donors in the state of Rio de Janeiro, Brazil. METHODS Data were collected on 2,857 blood donors from April 14 to 27, 2020. This study reports crude prevalence of antibodies to SARS-CoV-2, population weighted prevalence for the state, and prevalence adjusted for test sensitivity and specificity. Logistic regression models were used to establish the correlates of SARS-CoV-2 prevalence. For the analysis, we considered collection period and site, sociodemographic characteristics, and place of residence. RESULTS The proportion of positive tests for SARS-Cov-2, without any adjustment, was 4.0% (95%CI 3.3-4.7%), and the weighted prevalence was 3.8% (95%CI 3.1-4.5%). We found lower estimates after adjusting for test sensitivity and specificity: 3.6% (95%CI 2.7-4.4%) for the non-weighted prevalence, and 3.3% (95%CI 2.6-4.1%) for the weighted prevalence. Collection period was the variable most significantly associated with crude prevalence: the later the period, the higher the prevalence. Regarding sociodemographic characteristics, the younger the blood donor, the higher the prevalence, and the lower the education level, the higher the odds of testing positive for SARS-Cov-2 antibody. We found similar results for weighted prevalence. CONCLUSIONS Our findings comply with some basic premises: the increasing trend over time, as the epidemic curve in the state is still on the rise;and the higher prevalence among both the youngest, for moving around more than older age groups, and the less educated, for encountering more difficulties in following social distancing recommendations. Despite the study limitations, we may infer that Rio de Janeiro is far from reaching the required levels of herd immunity against SARS-CoV-2.

Seroprevalence of IgG and IgM anti-SARS-CoV-2 among voluntary blood donors in Rio de Janeiro, Brazil

Background: In Brazil, mathematical models for derivingestimates and projections of COVID-19 cases have been developed without data on asymptomatic SARS-CoV-2 infection. We estimated the seroprevalence of antibodies to SARS-CoV-2 among blood donors in the State of Rio de Janeiro. Methods: Data were collected on 2,857 blood donors from April 14 to 27, 2020. We report the crude prevalence of antibodies to SARS-CoV-2, the weighted prevalence by the total state population, and adjusted prevalence estimates for test sensitivity and specificity. To establish the correlates of SARS-CoV-2 prevalence, we used logistic regression models. The analysis included period and site of blood collection, sociodemographic characteristics, and place of residence. Results: The proportion of SARS-Cov-2 positive tests without any adjustment was 4.0% (95% CI 3.3-4.7%), and the weighted prevalence was 3.8% (95% CI 3.1-4.5%). Further adjustment by test sensitivity and specificity produced lower estimates, 3.6% (95% CI 2.7-4.4%) and 3.3% (95% CI 2.6-4.1%), respectively. The variable most significantly associated with the crude prevalence was the period of blood collection: the later the period, the higher the prevalence. Regarding socio-demographic characteristics, the younger the blood donors, the higher the prevalence, and the lower the educational level, the higher the odds of a positive SARS-Cov-2 antibody. Similar results were found for the weighted prevalence. Discussion: Although our findings resulted from a convenience sample, they match some basic premises: the increasing trend over time, since the epidemic curve in the state is still on the rise;the higher prevalence among the youngest who are more likely to circulate;and the higher prevalence among the less educated as they have more difficulties in following the social distancing recommendations. Despite the study limitations, it is possible to infer that protective levels of natural herd immunity to SARS-CoV-2 are far from being reached in Rio de Janeiro. (AU)