Impact of the first year of COVID-19 vaccination strategy in Brazil: an ecological study.

OBJECTIVES: No consensus exists about the best COVID-19 vaccination strategy to be adopted by low-income and middle-income countries. Brazil adopted an age-based calendar strategy to reduce mortality and the burden on the healthcare system. This study evaluates the impact of the vaccination campaign in Brazil on the progression of the reported COVID-19 deaths. METHODS: This ecological study analyses the dynamic of vaccination coverage and COVID-19 deaths in hospitalised adults (≥20 years) during the first year of the COVID-19 vaccination roll-out (January to December 2021) using nationwide data (DATASUS). We stratified the adult population into 20-49, 50-59, 60-69 and 70+ years. The dynamic effect of the vaccination campaign on mortality rates was estimated by applying a negative binomial regression. The prevented and possible preventable deaths (observed deaths higher than expected) and potential years of life lost (PYLL) for each age group were obtained in a counterfactual analysis. RESULTS: During the first year of COVID-19 vaccination, 266 153 517 doses were administered, achieving 91% first-dose coverage. A total of 380 594 deaths were reported, 154 091 (40%) in 70+ years and 136 804 (36%) from 50-59 or 20-49 years. The mortality rates of 70+ decreased by 52% (rate ratio [95% CI]: 0.48 [0.43-0.53]) in 6 months, whereas rates for 20-49 were still increasing due to low coverage (52%). The vaccination roll-out strategy prevented 59 618 deaths, 53 088 (89%) from those aged 70+ years. However, the strategy did not prevent 54 797 deaths, 85% from those under 60 years, being 26 344 (45%) only in 20-49, corresponding to 1 589 271 PYLL, being 1 080 104 PYLL (68%) from those aged 20-49 years. CONCLUSION: The adopted aged-based calendar vaccination strategy initially reduced mortality in the oldest but did not prevent the deaths of the youngest as effectively as compared with the older age group. Countries with a high burden, limited vaccine supply and young populations should consider other factors beyond the age to prioritise who should be vaccinated first.

What we talk about when we talk about COVID-19 vaccination campaign impact: a narrative review.

Background: The lack of precise definitions and terminological consensus about the impact studies of COVID-19 vaccination leads to confusing statements from the scientific community about what a vaccination impact study is. Objective: The present work presents a narrative review, describing and discussing COVID-19 vaccination impact studies, mapping their relevant characteristics, such as study design, approaches and outcome variables, while analyzing their similarities, distinctions, and main insights. Methods: The articles screening, regarding title, abstract, and full-text reading, included papers addressing perspectives about the impact of vaccines on population outcomes. The screening process included articles published before June 10, 2022, based on the initial papers' relevance to this study's research topics. The main inclusion criteria were data analyses and study designs based on statistical modelling or comparison of pre- and post-vaccination population. Results: The review included 18 studies evaluating the vaccine impact in a total of 48 countries, including 32 high-income countries (United States, Israel, and 30 Western European countries) and 16 low- and middle-income countries (Brazil, Colombia, and 14 Eastern European countries). We summarize the main characteristics of the vaccination impact studies analyzed in this narrative review. Conclusion: Although all studies claim to address the impact of a vaccination program, they differ significantly in their objectives since they adopt different definitions of impact, methodologies, and outcome variables. These and other differences are related to distinct data sources, designs, analysis methods, models, and approaches.

Primary healthcare protects vulnerable populations from inequity in COVID-19 vaccination: An ecological analysis of nationwide data from Brazil.

Background: There is limited information on the inequity of access to vaccination in low-and-middle-income countries during the COVID-19 pandemic. Here, we described the progression of the Brazilian immunisation program for COVID-19, and the association of socioeconomic development with vaccination rates, considering the potential protective effect of primary health care coverage. Methods: We performed an ecological analysis of COVID-19 immunisation data from the Brazilian National Immunization Program from January 17 to August 31, 2021. We analysed the dynamics of vaccine coverage in the adult population of 5,570 Brazilian municipalities. We estimated the association of human development index (HDI) levels (low, medium, and high) with age-sex standardised first dose coverage using a multivariable negative binomial regression model. We evaluated the interaction between the HDI and primary health care coverage. Finally, we compared the adjusted monthly progression of vaccination rates, hospital admission and in-hospital death rates among HDI levels. Findings: From January 17 to August 31, 2021, 202,427,355 COVID-19 vaccine doses were administered in Brazil. By the end of the period, 64·2% of adults had first and 31·4% second doses, with more than 90% of those aged ≥60 years with primary scheme completed. Four distinct vaccine platforms were used in the country, ChAdOx1-S/nCoV-19, Sinovac-CoronaVac, BNT162b2, Ad26.COV2.S, composing 44·8%, 33·2%, 19·6%, and 2·4% of total doses, respectively. First dose coverage differed between municipalities with high, medium, and low HDI (Median [interquartile range] 72 [66, 79], 68 [61, 75] and 63 [55, 70] doses per 100 people, respectively). Municipalities with low (Rate Ratio [RR, 95% confidence interval]: 0·87 [0·85-0·88]) and medium (RR [95% CI]: 0·94 [0·93-0·95]) development were independently associated with lower vaccination rates compared to those with high HDI. Primary health care coverage modified the association of HDI and vaccination rate, improving vaccination rates in those municipalities of low HDI and high primary health care coverage. Low HDI municipalities presented a delayed decrease in adjusted in-hospital death rates by first dose coverage compared to high HDI locations. Interpretation: In Brazil, socioeconomic disparities negatively impacted the first dose vaccination rate. However, the primary health care mitigated these disparities, suggesting that the primary health care coverage guarantees more equitable access to vaccines in vulnerable locations. Funding: This work is part of the Grand Challenges ICODA pilot initiative, delivered by Health Data Research UK and funded by the Bill & Melinda Gates Foundation and the Minderoo Foundation. This study was supported by the National Council for Scientific and Technological Development (CNPq), the Coordination for the Improvement of Higher Education Personnel (CAPES) - Finance Code 001, Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro (FAPERJ) and the Pontifical Catholic University of Rio de Janeiro.

Predicting drug sensitivity of cancer cells based on DNA methylation levels.

Cancer cell lines, which are cell cultures derived from tumor samples, represent one of the least expensive and most studied preclinical models for drug development. Accurately predicting drug responses for a given cell line based on molecular features may help to optimize drug-development pipelines and explain mechanisms behind treatment responses. In this study, we focus on DNA methylation profiles as one type of molecular feature that is known to drive tumorigenesis and modulate treatment responses. Using genome-wide, DNA methylation profiles from 987 cell lines in the Genomics of Drug Sensitivity in Cancer database, we used machine-learning algorithms to evaluate the potential to predict cytotoxic responses for eight anti-cancer drugs. We compared the performance of five classification algorithms and four regression algorithms representing diverse methodologies, including tree-, probability-, kernel-, ensemble-, and distance-based approaches. We artificially subsampled the data to varying degrees, aiming to understand whether training based on relatively extreme outcomes would yield improved performance. When using classification or regression algorithms to predict discrete or continuous responses, respectively, we consistently observed excellent predictive performance when the training and test sets consisted of cell-line data. Classification algorithms performed best when we trained the models using cell lines with relatively extreme drug-response values, attaining area-under-the-receiver-operating-characteristic-curve values as high as 0.97. The regression algorithms performed best when we trained the models using the full range of drug-response values, although this depended on the performance metrics we used. Finally, we used patient data from The Cancer Genome Atlas to evaluate the feasibility of classifying clinical responses for human tumors based on models derived from cell lines. Generally, the algorithms were unable to identify patterns that predicted patient responses reliably; however, predictions by the Random Forests algorithm were significantly correlated with Temozolomide responses for low-grade gliomas.

App-based symptom tracking to optimize SARS-CoV-2 testing strategy using machine learning.

BACKGROUND: Tests are scarce resources, especially in low and middle-income countries, and the optimization of testing programs during a pandemic is critical for the effectiveness of the disease control. Hence, we aim to use the combination of symptoms to build a predictive model as a screening tool to identify people and areas with a higher risk of SARS-CoV-2 infection to be prioritized for testing. MATERIALS AND METHODS: We performed a retrospective analysis of individuals registered in "Dados do Bem," a Brazilian app-based symptom tracker. We applied machine learning techniques and provided a SARS-CoV-2 infection risk map of Rio de Janeiro city. RESULTS: From April 28 to July 16, 2020, 337,435 individuals registered their symptoms through the app. Of these, 49,721 participants were tested for SARS-CoV-2 infection, being 5,888 (11.8%) positive. Among self-reported symptoms, loss of smell (OR[95%CI]: 4.6 [4.4-4.9]), fever (2.6 [2.5-2.8]), and shortness of breath (2.1 [1.6-2.7]) were independently associated with SARS-CoV-2 infection. Our final model obtained a competitive performance, with only 7% of false-negative users predicted as negatives (NPV = 0.93). The model was incorporated by the "Dados do Bem" app aiming to prioritize users for testing. We developed an external validation in the city of Rio de Janeiro. We found that the proportion of positive results increased significantly from 14.9% (before using our model) to 18.1% (after the model). CONCLUSIONS: Our results showed that the combination of symptoms might predict SARS-Cov-2 infection and, therefore, can be used as a tool by decision-makers to refine testing and disease control strategies.

Characterisation of the first 250,000 hospital admissions for COVID-19 in Brazil: a retrospective analysis of nationwide data.

BACKGROUND: Most low-income and middle-income countries (LMICs) have little or no data integrated into a national surveillance system to identify characteristics or outcomes of COVID-19 hospital admissions and the impact of the COVID-19 pandemic on their national health systems. We aimed to analyse characteristics of patients admitted to hospital with COVID-19 in Brazil, and to examine the impact of COVID-19 on health-care resources and in-hospital mortality. METHODS: We did a retrospective analysis of all patients aged 20 years or older with quantitative RT-PCR (RT-qPCR)-confirmed COVID-19 who were admitted to hospital and registered in SIVEP-Gripe, a nationwide surveillance database in Brazil, between Feb 16 and Aug 15, 2020 (epidemiological weeks 8-33). We also examined the progression of the COVID-19 pandemic across three 4-week periods within this timeframe (epidemiological weeks 8-12, 19-22, and 27-30). The primary outcome was in-hospital mortality. We compared the regional burden of hospital admissions stratified by age, intensive care unit (ICU) admission, and respiratory support. We analysed data from the whole country and its five regions: North, Northeast, Central-West, Southeast, and South. FINDINGS: Between Feb 16 and Aug 15, 2020, 254 288 patients with RT-qPCR-confirmed COVID-19 were admitted to hospital and registered in SIVEP-Gripe. The mean age of patients was 60 (SD 17) years, 119 657 (47%) of 254 288 were aged younger than 60 years, 143 521 (56%) of 254 243 were male, and 14 979 (16%) of 90 829 had no comorbidities. Case numbers increased across the three 4-week periods studied: by epidemiological weeks 19-22, cases were concentrated in the North, Northeast, and Southeast; by weeks 27-30, cases had spread to the Central-West and South regions. 232 036 (91%) of 254 288 patients had a defined hospital outcome when the data were exported; in-hospital mortality was 38% (87 515 of 232 036 patients) overall, 59% (47 002 of 79 687) among patients admitted to the ICU, and 80% (36 046 of 45 205) among those who were mechanically ventilated. The overall burden of ICU admissions per ICU beds was more pronounced in the North, Southeast, and Northeast, than in the Central-West and South. In the Northeast, 1545 (16%) of 9960 patients received invasive mechanical ventilation outside the ICU compared with 431 (8%) of 5388 in the South. In-hospital mortality among patients younger than 60 years was 31% (4204 of 13 468) in the Northeast versus 15% (1694 of 11 196) in the South. INTERPRETATION: We observed a widespread distribution of COVID-19 across all regions in Brazil, resulting in a high overall disease burden. In-hospital mortality was high, even in patients younger than 60 years, and worsened by existing regional disparities within the health system. The COVID-19 pandemic highlights the need to improve access to high-quality care for critically ill patients admitted to hospital with COVID-19, particularly in LMICs. FUNDING: National Council for Scientific and Technological Development (CNPq), Coordinating Agency for Advanced Training of Graduate Personnel (CAPES), Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro (FAPERJ), and Instituto de Salud Carlos III.

Analysis of COVID-19 under-reporting in Brazil. / Análise da subnotificação de COVID-19 no Brasil.

OBJECTIVE: To estimate the reporting rates of coronavirus disease 2019 (COVID-19) cases for Brazil as a whole and states. METHODS: We estimated the actual number of COVID-19 cases using the reported number of deaths in Brazil and each state, and the expected case-fatality ratio from the World Health Organization. Brazil's expected case-fatality ratio was also adjusted by the population's age pyramid. Therefore, the notification rate can be defined as the number of confirmed cases (notified by the Ministry of Health) divided by the number of expected cases (estimated from the number of deaths). RESULTS: The reporting rate for COVID-19 in Brazil was estimated at 9.2% (95%CI 8.8% - 9.5%), with all the states presenting rates below 30%. São Paulo and Rio de Janeiro, the most populated states in Brazil, showed small reporting rates (8.9% and 7.2%, respectively). The highest reporting rate occurred in Roraima (31.7%) and the lowest in Paraiba (3.4%). CONCLUSION: The results indicated that the reporting of confirmed cases in Brazil is much lower as compared to other countries we analyzed. Therefore, decision-makers, including the government, fail to know the actual dimension of the pandemic, which may interfere with the determination of control measures.

Progression of confirmed COVID-19 cases after the implementation of control measures. / Progressão dos casos confirmados de COVID-19 após implantação de medidas de controle.

OBJECTIVE: To analyse the measures adopted by countries that have shown control over the transmission of coronavirus disease 2019 (COVID-19) and how each curve of accumulated cases behaved after the implementation of those measures. METHODS: The methodology adopted for this study comprises three phases: systemizing control measures adopted by different countries, identifying structural breaks in the growth of the number of cases for those countries, and analyzing Brazilian data in particular. RESULTS: We noted that China (excluding Hubei Province), Hubei Province, and South Korea have been effective in their deceleration of the growth rates of COVID-19 cases. The effectiveness of the measures taken by these countries could be seen after 1 to 2 weeks of their application. In Italy and Spain, control measures at the national level were taken at a late stage of the epidemic, which could have contributed to the high propagation of COVID-19. In Brazil, Rio de Janeiro and São Paulo adopted measures that could be effective in slowing the propagation of the virus. However, we only expect to see their effects on the growth of the curve in the coming days. CONCLUSION: Our results may help decisionmakers in countries in relatively early stages of the epidemic, especially Brazil, understand the importance of control measures in decelerating the growth curve of confirmed cases.

Análise da subnotificação de COVID-19 no Brasil / Analysis of COVID-19 under-reporting in Brazil

RESUMO Objetivo: Estimar as taxas de notificação de casos de doença pelo coronavírus 2019 (COVID-19) para o Brasil em geral e em todos os estados. Métodos: Estimamos o número real de casos de COVID-19 utilizando o número de óbitos notificados no Brasil e em cada estado e a proporção entre casos e letalidade, conforme a Organização Mundial da Saúde. A proporção entre casos e letalidade prevista para o Brasil foi também ajustada segundo a pirâmide de idade populacional. Assim, a taxa de notificações pode ser definida como o número de casos confirmados (informados pelo Ministério da Saúde) dividido pelo número de casos previstos (estimado a partir do número de óbitos). Resultados: A taxa de notificação de COVID-19 no Brasil foi estimada em 9,2% (IC95%: 8,8% - 9,5%), sendo que, em todos os estados, as taxas encontradas foram inferiores a 30%. São Paulo e Rio de Janeiro, os estados mais populosos do país, mostraram baixas taxas de notificação (8,9% e 7,2%, respectivamente). A taxa de notificação mais alta ocorreu em Roraima (31,7%) e a mais baixa na Paraíba (3,4%). Conclusão: Os resultados indicam que a notificação de casos confirmados no Brasil é muito abaixo da encontrada em outros países que avaliamos. Assim, os responsáveis pela tomada de decisões, inclusive os governos, não têm conhecimento da real dimensão da pandemia, o que pode prejudicar a determinação das medidas de controle.

ABSTRACT Objective: To estimate the reporting rates of coronavirus disease 2019 (COVID-19) cases for Brazil as a whole and states. Methods: We estimated the actual number of COVID-19 cases using the reported number of deaths in Brazil and each state, and the expected case-fatality ratio from the World Health Organization. Brazil's expected case-fatality ratio was also adjusted by the population's age pyramid. Therefore, the notification rate can be defined as the number of confirmed cases (notified by the Ministry of Health) divided by the number of expected cases (estimated from the number of deaths). Results: The reporting rate for COVID-19 in Brazil was estimated at 9.2% (95%CI 8.8% - 9.5%), with all the states presenting rates below 30%. São Paulo and Rio de Janeiro, the most populated states in Brazil, showed small reporting rates (8.9% and 7.2%, respectively). The highest reporting rate occurred in Roraima (31.7%) and the lowest in Paraiba (3.4%). Conclusion: The results indicated that the reporting of confirmed cases in Brazil is much lower as compared to other countries we analyzed. Therefore, decision-makers, including the government, fail to know the actual dimension of the pandemic, which may interfere with the determination of control measures.

Progressão dos casos confirmados de COVID-19 após implantação de medidas de controle / Progression of confirmed COVID-19 cases after the implementation of control measures

RESUMO Objetivo: Analisar as medidas adotadas por países que demonstraram controle sobre a transmissão da doença pelo novo coronavírus 2019 (COVID-19) e também como cada curva de casos acumulados se comportou após a implantação dessas medidas. Métodos: A metodologia adotada para este estudo compreendeu três fases: sistematização das medidas de controle adotadas por diferentes países, identificação dos pontos de inflexão na curva do crescimento do número de casos nesses países e análise específica dos dados brasileiros. Resultados: Observamos que China (excluindo-se Hubei), Hubei e Coreia do Sul foram eficazes na desaceleração das taxas de crescimento dos casos de COVID-19. A eficácia das medidas tomadas por esses países pode ser observada após 1 ou 2 semanas de sua aplicação. Na Itália e Espanha, foram tomadas medidas de controle em nível nacional em uma fase tardia da epidemia, o que pode ter contribuído para a elevada propagação da COVID-19. No Brasil, Rio de Janeiro e São Paulo adotaram medidas que podem ter sido eficazes na redução da rapidez da propagação do vírus, entretanto, só temos expectativa de ver seus efeitos no crescimento da curva nos próximos dias. Conclusão: Nossos resultados podem ajudar os responsáveis pela tomada de decisões em países em estágios relativamente precoces da epidemia, especialmente no Brasil, a compreenderem a importância das medidas de controle para desaceleração da curva de crescimento de casos confirmados.

ABSTRACT Objective: To analyse the measures adopted by countries that have shown control over the transmission of coronavirus disease 2019 (COVID-19) and how each curve of accumulated cases behaved after the implementation of those measures. Methods: The methodology adopted for this study comprises three phases: systemizing control measures adopted by different countries, identifying structural breaks in the growth of the number of cases for those countries, and analyzing Brazilian data in particular. Results: We noted that China (excluding Hubei Province), Hubei Province, and South Korea have been effective in their deceleration of the growth rates of COVID-19 cases. The effectiveness of the measures taken by these countries could be seen after 1 to 2 weeks of their application. In Italy and Spain, control measures at the national level were taken at a late stage of the epidemic, which could have contributed to the high propagation of COVID-19. In Brazil, Rio de Janeiro and São Paulo adopted measures that could be effective in slowing the propagation of the virus. However, we only expect to see their effects on the growth of the curve in the coming days. Conclusion: Our results may help decisionmakers in countries in relatively early stages of the epidemic, especially Brazil, understand the importance of control measures in decelerating the growth curve of confirmed cases.