Strategies for expanding childhood vaccination in the Americas following the COVID-19 pandemic.

Objective: To provide an overview of the status of the childhood vaccination schedule in the Americas, outline program structures, and identify updated implementation strategies to improve vaccination coverage following the COVID-19 pandemic. Methods: A group of experts in pediatrics, epidemiology, vaccines, and global and public health discussed the current status of the childhood vaccination schedule in the Americas, describing the program structure and identifying new implementation strategies that have the potential to improve vaccination coverage in the post-pandemic context, after the challenges COVID-19 presented for more than two years. Results: The Americas currently face a high risk of resurgence of diseases that were previously controlled or eliminated. Therefore, it is important to find new strategies to educate citizens on the risks associated with lower vaccination rates, especially in children. Conclusions: New strategies along with strong mobilization of the population and advocacy by citizens are necessary to prevent antivaccination groups from gaining a stronger presence in the region and jeopardizing the credibility of the Expanded Program on Immunization.

Behavioral factors associated with multiple-type HPV genital infections: data from a cross-sectional study in young women in Brazil.

OBJECTIVES: To investigate the pattern of multiple human papillomavirus (HPV) infections and associated factors in young women who access the Brazilian public health care system to better understand the characteristics of multiple HPV infections, a critical issue in this era of multivalent vaccines. METHODS: This was a cross-sectional, multicenter study with sexually active unvaccinated women (16-25 years old) from 119 primary Brazilian healthcare centers between September 2016 and November 2017. Cervical samples were collected by trained health professionals, and HPV detection was performed in a central laboratory by Linear Array. RESULTS: Of the 5268 women, 33.00% (95% CI 31.07-34.92) had multiple infections. At least one type of high-risk HPV was present in 85.50% of all multiple infections. All HPV types were detected more frequently in association with other types than alone. Young individuals who were single or in a casual relationship and those who had more than one sexual partner in the past year were more likely to have multiple infections. CONCLUSIONS: In this work, a high rate of multiple HPV infections among unvaccinated young adults tended to increase due to certain risk factors. Such data can provide insight for decision makers in the development of public policies regarding HPV prevention.

Understanding the characteristics of multiple infections is critical in the era of HPV multivalent vaccines for the prevention of cervical carcinomas. Therefore, in this cross-sectional study, we aimed to investigate the pattern of multiple HPV infections and associated factors in 5,268 sexually active unvaccinated women (16­25 years old) who access the Brazilian public health care system. Cervical samples were collected by trained health professionals, and HPV detection was performed in a central laboratory by Linear Array. A total of 33.00% (95% CI 31.07­34.92) had multiple infections (60.43% of the HPV-positive sample). The number of HPV types in a multiple infection ranged from 2 to 14 different types. The viral types more frequently identified were HPV 16 and 52. All HPV types were detected more frequently in association with other types than alone. The incidence of multiple infections was 1.29 times higher in single than in married or cohabitating participants. Women who had two or more partners in the last year also had higher rates of multiple infections than those who had fewer than two sexual partners. In conclusion, a high prevalence of multiple infections prior to the national HPV immunization program was observed, especially with the increase in less safe behavior factors.

17DD Yellow Fever Revaccination and Heightened Long-Term Immunity in Populations of Disease-Endemic Areas, Brazil.

We evaluated the duration of neutralizing antibodies and the status of 17DD vaccine-specific T- and B-cell memory following primary and revaccination regimens for yellow fever (YF) in Brazil. We observed progressive decline of plaque-reduction neutralization test (PRNT) seropositivity and of the levels of effector memory CD4+ and CD8+ T cells, as well as interferon-γ+CD8+ T cells, 10 years after primary vaccination. Revaccination restored PRNT seropositivity as well as the levels of effector memory CD4+, CD8+, and interferon-γ+CD8+ T cells. Moreover, secondary or multiple vaccinations guarantee long-term persistence of PRNT positivity and cell-mediated memory 10 years after booster vaccination. These findings support the relevance of booster doses to heighten the 17DD-YF-specific immune response to guarantee the long-term persistence of memory components. Secondary or multiple vaccinations improved the correlates of protection triggered by 17DD-YF primary vaccination, indicating that booster regimens are needed to achieve efficient immunity in areas with high risk for virus transmission.

[Analysis of the Vaccine Adverse Event Reporting System in Brazil, 2014 to 2016Análisis del Sistema de Información de Vigilancia de Eventos Adversos Posvacunación en Brasil, 2014 a 2016]. / Análise do Sistema de Informação da Vigilância de Eventos Adversos Pós-Vacinação no Brasil, 2014 a 2016.

OBJECTIVE: To describe the characteristics of vaccine adverse events (VAE) reports in the online VAE Reporting System (VAE-RS) after 2 years of operation. METHOD: A descriptive analysis of VAE reports entered into the VAE-RS between July 2014 and June 2016 was performed. RESULTS: During the study period, 24 732 VAE were reported. Of 5 570 Brazilian municipalities, 2 571 (46.2%) reported at least one VAE; however, only 1 622 (6.6%) reports had been completed/closed at the end of the study period. Of these, 89.9% referred to mild VAE. Among the completed reports, 19.7% did not provide information on "type of medical care provided," and 98.7% had no information regarding laboratory tests. Systemic neurological symptoms were the most frequent serious VAE among closed reports (59.5% of serious signs/symptoms). Concerning age, the highest VAE reporting coefficients were recorded for children aged ≤ 4 years. CONCLUSION: The VAE-RS is useful to monitor immunization safety. However, municipal services must increase adherence to the system and perform the required investigation and reporting of VAE, with timely and adequate completion of the VAE-RS form. Knowledge regarding VAE can be used in the daily routine of surveillance services, improving the safety of immunobiological agents.

OBJETIVO: Describir las características de las notificaciones de eventos adversos posvacunación (EAPV) en el Sistema de Información de Vigilancia de EAPV (SI-EAPV, un sistema en línea, durante los primeros 2 años de ejecución del sistema. MÉTODO: Se realizó un estudio descriptivo de los registros de EAPV notificados en el SI-EAPV entre julio de 2014 y junio de 2016. RESULTADOS: Durante el período del estudio, se registraron 24 732 notificaciones. De 5 570 municipios brasileños, 2 571 (46,2%) notificaron algún EAPV. Sin embargo, solamente 1 622 (6,6%) notificaciones estaban cerradas al momento del estudio; de ellas, el 89,9% no presentó gravedad. Respecto a las notificaciones cerradas, en el 19,7% no fue anotada la variable "atención médica" y el 98,7% no presentó registro de exámenes de laboratorio. Entre los eventos adversos graves cerrados, las manifestaciones clínicas sistémicas neurológicas fueron las más frecuentes, representado el 59,5% de los signos y síntomas. En cuanto a la edad, los mayores coeficientes de notificación se registraron entre los menores de 4 años. CONCLUSIÓN: El SI-EAPV es útil para el monitoreo de la seguridad de las vacunas. Sin embargo, los municipios necesitan ampliar la adhesión al sistema, así como realizar las investigaciones y notificaciones de los EAPV, llenando la ficha de notificación de forma adecuada y oportuna. El conocimiento sobre EAPV puede ser aplicado en la práctica de los servicios de vigilancia en salud, mejorando la seguridad en la utilización de los productos inmunobiológicos.

Risk analysis for the reintroduction and transmission of measles in the post-elimination period in the Americas.

OBJECTIVE: To propose and test a model for analyzing municipalities' level of risk of reintroduction and transmission of the measles virus in the post-elimination period in the Americas. METHODS: An ecological-analytical study was conducted using data on the measles epidemic that occurred in 2013-2015 in northeastern Brazil. The variables for analysis were selected after an extensive review of scientific literature on the risk of importation of measles cases. A univariate analysis considering the presence or absence of confirmed cases of measles in 184 municipalities in the state of Ceará, Brazil, was carried out to evaluate the association between the dependent variable and 23 independent variables, grouped into four categories: 1) characteristics of the municipalities; 2) quality indicators for immunization programs and epidemiological surveillance; 3) organizational structure for the public health response; and 4) selected impact indicators. A P value < 0.05 was considered significant. All variables with P < 0.200 were analyzed using multivariate logistic regression. Based on the results, the municipalities were categorized by four levels of risk ("low," "medium," "high," and "very high"). RESULTS: The model sensitivity was 95% for concordance between municipalities classified as "high risk" and "very high risk" and those that had an epidemic between 2013 and 2015 in Ceará. Of the 38 municipalities that had an epidemic, 76% (29/38) were classified as "high risk" and "very high risk"; 146 municipalities did not report cases (P < 0.0002). CONCLUSIONS: Given the imminent risk of reintroduction of measles circulation in the post-elimination period in the Americas, this model may be useful in identifying areas at greater risk for reintroduction and continued transmission of measles. Knowledge of vulnerable areas could trigger appropriate surveillance and monitoring to prevent sustained transmission.

Introduction of sequential inactivated polio vaccine-oral polio vaccine schedule for routine infant immunization in Brazil's National Immunization Program.

In August 2012, the Brazilian Ministry of Health introduced inactivated polio vaccine (IPV) as part of sequential polio vaccination schedule for all infants beginning their primary vaccination series. The revised childhood immunization schedule included 2 doses of IPV at 2 and 4 months of age followed by 2 doses of oral polio vaccine (OPV) at 6 and 15 months of age. One annual national polio immunization day was maintained to provide OPV to all children aged 6 to 59 months. The decision to introduce IPV was based on preventing rare cases of vaccine-associated paralytic polio, financially sustaining IPV introduction, ensuring equitable access to IPV, and preparing for future OPV cessation following global eradication. Introducing IPV during a national multivaccination campaign led to rapid uptake, despite challenges with local vaccine supply due to high wastage rates. Continuous monitoring is required to achieve high coverage with the sequential polio vaccine schedule.

Comprehensive landscape of neutralizing antibody and cell-mediated response elicited by the 1/5 fractional dose of 17DD-YF primary vaccination in adults.

The present study aimed at evaluating the YF-specific neutralizing antibody profile besides a multiparametric analysis of phenotypic/functional features of cell-mediated response elicited by the 1/5 fractional dose of 17DD-YF vaccine, administered as a single subcutaneous injection. The immunological parameters of each volunteer was monitored at two time points, referred as: before (Day 0) [Non-Vaccinated, NV(D0)] and after vaccination (Day 30-45) [Primary Vaccinees, PV(D30-45)]. Data demonstrated high levels of neutralizing antibodies for PV(D30-45) leading to a seropositivity rate of 93%. A broad increase of systemic soluble mediators with a mixed profile was also observed for PV(D30-45), with IFN-γ and TNF-α presenting the highest baseline fold changes. Integrative network mapping of soluble mediators showed increased correlation numbers in PV(D30-45) as compared to NV(D0) (532vs398). Moreover, PV(D30-45) exhibited increased levels of Terminal Effector (CD45RA+CCR7-) CD4+ and CD8+ T-cells and Non-Classical memory B-cells (IgD+CD27+). Dimensionality reduction of Mass Cytometry data further support these findings. A polyfunctional cytokine profile (TNF-α/IFN-γ/IL-10/IL-17/IL-2) of T and B-cells was observed upon in vitro antigen recall. Mapping and kinetics timeline of soluble mediator signatures for PV(D30-45) further confirmed the polyfunctional profile upon long-term in vitro culture, mediated by increased levels of IFN-γ and TNF-α along with decreased production of IL-10. These findings suggest novel insights of correlates of protection elicited by the 1/5 fractional dose of 17DD-YF vaccine.

Immune response induced by standard and fractional doses of 17DD yellow fever vaccine.

The re-emergence of yellow fever (YF) urged new mass vaccination campaigns and, in 2017, the World Health Organization approved the use of the fractional dose (FD) of the YF vaccine due to stock shortage. In an observational cross-sectional investigation, we have assessed viremia, antibodies, soluble mediators and effector and memory T and B-cells induced by primary vaccination of volunteers with FD and standard dose (SD). Similar viremia and levels of antibodies and soluble markers were induced early after immunization. However, a faster decrease in the latter was observed after SD. The FD led to a sustained expansion of helper T-cells and an increased expression of activation markers on T-cells early after vaccination. Although with different kinetics, expansion of plasma cells was induced upon SD and FD immunization. Integrative analysis reveals that FD induces a more complex network involving follicular helper T cells and B-cells than SD. Our findings substantiate that FD can replace SD inducing robust correlates of protective immune response against YF.

Racial inequalities in child vaccination and barriers to vaccination in Brazil among live births in 2017 and 2018: an analysis of a retrospective cohort of the first two years of life.

OBJECTIVE: To describe timely vaccination completion and obstacles in the first 24 months of life in Brazil, examining associations with maternal race/skin color. METHODS: Study participants were 37,801 children born in 2017 and 2018 included in the National Immunization Coverage Survey. We calculated prevalence and 95% confidence intervals for timely vaccine completeness and obstacles at 5, 12 and 24 months of life, according to maternal race/skin color. Associations were analyzed using logistic regression. RESULTS: 7.2% (95%CI 6.3;8.2) of mothers faced difficulties in taking their children to be vaccinated, and 23.4% (95%CI 21.7;25.1) were not vaccinated when taken. These proportions were 75% (95%CI 1.25;2.45) and 97% (95%CI 1.57;2.48) higher, respectively, among Black mothers. At least one vaccination was delayed among 49.9% (95%CI 47.8;51.9) and 61.1% (95%CI 59.2;63.0) of children by 5 and 12 months, respectively. These rates were higher among Black/mixed race mothers. CONCLUSION: There are racial inequalities in both the obstacles faced and in vaccination rates in Brazil. MAIN RESULTS: Marked racial inequalities were found in the obstacles to vaccination of children under 24 months in Brazil and to timely vaccination at 5 months and in the first year of life. IMPLICATIONS FOR SERVICES: Racial inequalities in the occurrence of vaccination shortcomings in health services, in the objective restrictions faced by families in taking their children to vaccination centers and in incomplete vaccination in a timely manner need to be addressed by the Brazilian National Health System. PERSPECTIVES: Equal public policies to address barriers to vaccination and qualification of health services need to be implemented. Studies need to deepen understanding of the structural determinants that lead to racial disparities.

Description of vaccination coverage and hesitancy obtained by epidemiological survey of children born in 2017-2018, in Belo Horizonte and Sete Lagoas, Minas Gerais, Brazil.

OBJECTIVE: To describe vaccination coverage and hesitation for the basic children's schedule in Belo Horizonte and Sete Lagoas, Minas Gerais state, Brazil. METHODS: Population-based epidemiological surveys performed from 2020 to 2022, which estimated vaccine coverage by type of immunobiological product and full schedule (valid and ministered doses), according to socioeconomic strata; and reasons for vaccination hesitancy. RESULTS: Overall coverage with valid doses and vaccination hesitancy for at least one vaccine were, respectively, 50.2% (95%CI 44.1;56.2) and 1.6% (95%CI 0.9;2.7), in Belo Horizonte (n = 1,866), and 64.9% (95%CI 56.9;72.1) and 1.0% (95%CI 0.3;2.8), in Sete Lagoas (n = 451), with differences between socioeconomic strata. Fear of severe reactions was the main reason for vaccination hesitancy. CONCLUSION: Coverage was identified as being below recommended levels for most vaccines. Disinformation should be combated in order to avoid vaccination hesitancy. There is a pressing need to recover coverages, considering public health service access and socioeconomic disparities. MAIN RESULTS: Vaccination coverage of children up to 4 years old was 50.2% in Belo Horizonte, and 64.9% in Sete Lagoas. Fear of severe reactions and believing that vaccination against eradicated diseases is unnecessary were the main reasons for vaccination hesitancy. IMPLICATIONS FOR SERVICES: Recovery of high vaccination coverage among children, considering public health service access conditions and socioeconomic inequities. Acting on reasons for hesitancy that can assist in targeting actions. PERSPECTIVES: The multifactorial context of vaccination hesitancy demands the development of health education strategies to raise awareness about child immunization.

Effect of 10-valent pneumococcal vaccine on pneumonia among children, Brazil.

Pneumonia is most problematic for children in developing countries. In 2010, Brazil introduced a 10-valent pneumococcal conjugate vaccine (PCV10) to its National Immunization Program. To assess the vaccine's effectiveness for preventing pneumonia, we analyzed rates of hospitalization among children 2-24 months of age who had pneumonia from all causes from January 2005 through August 2011. We used data from the National Hospitalization Information System to conduct an interrupted time-series analysis for 5 cities in Brazil that had good data quality and high PCV10 vaccination coverage. Of the 197,975 hospitalizations analyzed, 30% were for pneumonia. Significant declines in hospitalizations for pneumonia were noted in Belo Horizonte (28.7%), Curitiba (23.3%), and Recife (27.4%) but not in São Paulo and Porto Alegre. However, in the latter 2 cities, vaccination coverage was less than that in the former 3. Overall, 1 year after introduction of PCV10, hospitalizations of children for pneumonia were reduced.

Vaccination coverage in children in the period before and during the COVID-19 pandemic in Brazil: a time series analysis and literature review.

OBJECTIVE: To evaluate the behavior of VCR and VCH, per municipality and per vaccines offered at the NVC, to identify priority areas for intervention. METHODS: Descriptive study of a time series, using secondary data and accompanied by a narrative review of the literature evaluating VCR and VCH. Vaccines offered to children under one year and to those aged one year in the pre-pandemic period of COVID-19 (2015 to 2019) were selected and compared to those offered during the pandemic period (2020 and 2021). RESULTS AND DISCUSSIONS: The decrease in VCR and VCH is a process that precedes the COVID-19 pandemic but was intensified during this period. In 2021, the VCR was around 70% for most vaccines. This phenomenon encompasses the entire country; however, it is more intense in the states/municipalities located in the north and northeast regions, suggesting greater difficulty in accessing health services. CONCLUSIONS: Low and heterogeneous VCR requires the adoption of practices that were previously implemented, establishing partnerships with governmental and non-governmental institutions, with adequate communication, active search for non-compliance and non-adherence to the regular vaccination program, adopting intra- and extramural vaccination strategies, to reverse the current situation and reduce the risk of recurrence of diseases that have been already controlled and eliminated.

The effectiveness of COVID-19 vaccines in Latin America, 2021: a multicenter regional case-control study.

Background: As of September 2022, nearly 1.3 billion doses of COVID-19 vaccine products have been administered in Latin America and the Caribbean, where 27% of global COVID-19 deaths have occurred. This study aimed to estimate the effectiveness of COVID-19 vaccines against lab-confirmed COVID-19 related hospitalizations and deaths among adults in Argentina, Brazil, Chile, and Colombia. Methods: Using a test-negative case control design, we evaluated the effectiveness of a primary vaccination series considering six COVID-19 vaccine products (Sputnik V, mRNA-1273, CoronaVac, ChAdOx1, BNT162b2, Ad26.COV2.S) against lab-confirmed COVID-19 hospitalizations and deaths among 83,708 hospitalized adults from February-December, 2021. Data from hospitalization records, COVID surveillance, and vaccination registries were used. Vaccine effectiveness was estimated using logistic regression ((1-OR) x 100). Findings: The average age of participants was 56.7 (SD = 17.5), and 45,894 (54.8%) were male. Adjusted VE (aVE) estimates for full vaccination against hospitalization were 82% for mRNA-1273 (95% confidence interval (CI) = -30 to 98%), 76% (71%-81%) for BNT162b2, 65% (61-68%) for ChAdOx1, 57% (10-79%) for Sputnik V, 53% (50-56%) for CoronaVac, and 46% (23-62%) for Ad26.COV2.S. Estimates, particularly for CoronaVac, varied by variant. Decreasing aVE was estimated as age increased, particularly for CoronaVac and ChAdOx1. aVE estimates against death were generally higher, with 100% (CI not estimated) for mRNA-1273, 82% (69-90%) for BNT162b2, 73% (69-77%) for ChAdOx1, 65% (60-67%) for CoronaVac, 38% (-75 to 78%) for Sputnik V, 6% (-58 to 44%) for Ad26.COV2.S. Interpretation: Primary series vaccination with available COVID-19 vaccine products was effective against COVID-19 hospitalization and mortality. Effectiveness varied by product and declined with increasing age. Funding: This study was funded by the Pan-American Health Organization (PAHO, World Health Organization (WHO)). PAHO convened and led the study implementation.

Half dose ChAdOx1 nCoV-19 vaccine was equivalent to full doses to reduce moderate and severe COVID-19 cases.

Objectives: Previously, we presented the effectiveness of ChAdOx1 nCoV-19 half-dose (HD) immunization for preventing new COVID-19 cases. Here, we evaluated the administration of an HD of ChAdOx1 nCoV-19 in the primary immunization protocol (up to two doses) in reducing moderate and severe cases, hospitalizations, and deaths when compared to the administration of full doses (FD) after a long-term follow-up. Methods: We evaluated data from 29,469 participants between January 2021 and November 2022 who received an HD or FD vaccine and crossed this information with their medical records to identify those who developed moderate or severe cases. All participants were classified into four groups according to their immunization status and followed 500 days after the last vaccine administration. Results: The propensity-score matching analysis indicates that the administration of the two HDs of ChAdOx1 nCoV-19 was equivalent to the use of two FDs to reduce moderate and severe COVID-19 cases. The relative risk of being infected and developing moderate or severe conditions after the administration of at least one HD or FD was similar 150 or 500 days after the administration of the immunizers. Conclusion: Administering two HDs can be used safely as a cost-effective alternative to the primary immunization protocol.

Timeline kinetics of protective immunity to SARS-CoV-2 upon primary vaccination and humoral response to variants after booster dose.

New variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged, imposing the need for periodic booster doses. However, whether booster doses should be applied to the entire population or groups, and the booster doses interval, remains unclear. In this study, we evaluated humoral reactivity kinetics from before the first dose to 180 days after the third booster dose in different schedules in a well-controlled health worker cohort. Among the 2,506 employees, the first 500 vaccinated health workers were invited to participate. The third booster dose was administered 8 months after the first dose. Among the invited participants, 470 were included in the study; 258 received inactivated vaccine CoronaVac (VAC group) and 212 received viral vector vaccine ChAdOx1 (AZV group). The groups were homogeneous in terms of age and sex. 347 participants were followed up after the booster dose with AZV or BNT162b2 (Pfizer, BNT group): 63 with VAC/AZV, 117 with VAC/BNT, 72 with the AZV/AZV and 95 with AZV/BNT schedules. Blood samples were collected immediately before, 28 days after each dose and 180 days after the primary vaccination and booster dose. Anti-SARS-CoV-2 antibodies were measured by chemiluminescence and plaque reduction neutralization test (PRNT). Plasma immune mediators were quantified using a multiplex immunoassay. Geometric mean of antibodies increased 28 days after the second dose with 100 % seroconversion rate in both groups and decreased 180 days after the first dose. In the baseline-seropositive VAC group, the levels of plasma immune mediators increased after the second dose. Booster dose was applied at 4-6 months after the primary vaccination. Heterologous booster in VAC or AZV primary vaccinees were effective maintaining the titers of anti-SARS-CoV-2 antibodies even after 6 months of follow-up. The heterologous schedule induced higher and stable antibody reactivity, even after 180 days, protecting to ancestral (Wuhan), Delta, and Omicron variants.

National Vaccine Coverage Survey 2020: methods and operational aspects.

OBJECTIVE: The national vaccination coverage survey on full vaccination at 12 and 24 months of age was carried out to investigate drops in coverage as of 2016. METHODS: A sample of 37,836 live births from the 2017 or 2018 cohorts living in capital cities, the Federal District, and 12 inner cities with 100 thousand inhabitants were followed for the first 24 months through vaccine record cards. Census tracts stratified according to socioeconomic levels had the same number of children included in each stratum. Coverage for each vaccine, full vaccination at 12 and 24 months and number of doses administered, valid and timely, were calculated. Family, maternal and child factors associated with coverage were surveyed. The reasons for not vaccinating analyzed were: medical contraindications, access difficulties, problems with the program, and vaccine hesitancy. RESULTS: Preliminary results showed that less than 1% of children were not vaccinated, full coverage was less than 75% at all capitals and the Federal District, vaccines requiring more than one dose progressively lost coverage, and there were inequalities among socioeconomic strata, favorable to the highest level in some cities and to the lowest in others. CONCLUSION: There was an actual reduction in full vaccination in all capitals and the Federal District for children born in 2017 and 2018, showing a deteriorating implementation of the National Immunization Program from 2017 to 2019. The survey did not measure the impacts of the COVID-19 pandemic, which may have further reduced vaccination coverage.

The SARS-CoV-2 vaccination campaign in Brazil and the invisibility of science evidences. / A campanha de vacinação contra o SARS-CoV-2 no Brasil e a invisibilidade das evidências científicas.

This paper reflects on the vaccination campaign against COVID-19 in Brazil in light of the consideration of scientific evidence in the decision-making process. Brazil has one of the largest and most complete vaccination programs in the world, the National Immunization Program (Programa Nacional de Imunizações or PNI). Unfortunately, in the current context, with the political interference of the federal government, the PNI lost its role in conducting the vaccination campaign against COVID-19. Despite being a vaccination campaign with a lot of potential and one of the most accepted by the population among countries in the world, it presented many problems and left several gaps in the Brazilian scenario. In this sense, it is essential that the quality scientific evidence produced during this period can guide a constant remodeling of the vaccination strategy. Four points deserve to be highlighted: 1) the interval between doses; 2) the interchangeability between vaccines; 3) vaccination in children and adolescentes; and 4) the need for better evidence to define the vaccination strategy in certain groups and age groups.

O presente texto trata de refletir sobre a campanha de vacinação contra COVID-19 no Brasil à luz da consideração das evidências científicas no processo de tomada de decisão. O Brasil possui um dos maiores e mais completos programas de vacinação do mundo, o Programa Nacional de Imunizações (PNI). Infelizmente, no contexto atual, com as interferências políticas do governo federal, o PNI perdeu seu protagonismo na condução da campanha de vacinação contra a COVID-19. Apesar de ser uma campanha de vacinação com muito potencial e uma das mais aceitas pela população entre os países no mundo, apresentou muitos problemas e deixou diversas lacunas no cenário brasileiro. Nesse sentido, é fundamental que as evidências científicas de qualidade produzidas nesse período possam guiar uma remodelagem constante da estratégia de vacinação. Quatro pontos merecem ser destacados: 1) o intervalo entre as doses; 2) a intercambialidade entre vacinas; 3) a vacinação em adolescentes; e 4) a necessidade de melhores evidências para definir a estratégia de vacinação em certos grupos e faixas etárias.

[Changes in the pattern of COVID-19 hospitalizations and deaths after substantial vaccination of the elderly in Manaus, Amazonas State, Brazil]. / Mudanças no padrão de internações e óbitos por COVID-19 após substancial vacinação de idosos em Manaus, Amazonas, Brasil.

The impact of COVID-19 vaccination in the elderly has received relatively little attention, particularly in a scenario predominated by the gamma variant. The aim of this study was to assess vaccination coverage and its relationship to changes in the pattern of COVID-19 hospitalizations and deaths in the elderly in Manaus, Amazonas State, Brazil. This was an ecological study with Brazilian Ministry of Health data on hospitalizations and deaths, assessing vaccination coverage based on a two-dose regimen, in addition to two vaccination regimens associated with a significant protective effect, one partial (35 days or more after the first dose of the Oxford/AstraZeneca vaccine) and the other complete (14 days or more after the second dose of the Sinovac-CoronaVac vaccine). Based on the date of initial symptoms, patterns of COVID-19 hospitalizations and deaths were assessed comparatively in elderly 60-69 years and 70 years or more in two groups of Epidemiological Weeks (EW) in 2020 (unvaccinated) and 2021 (vaccinated). Hospitalization and death rates were estimated with Poisson regression. In the groups 60-69 and 70 years or more, vaccination coverage rates were 41.8% and 54.8%, as well as 53.5% and 90.1%, in the EW groups 18-20/2021 and 21-23/2021, respectively. Both EW groups in 2021 showed a substantial change in the patterns of COVID-19 hospitalizations and deaths, with an increase in the risk of hospitalization and death in unvaccinated younger individuals and an important reduction in vaccinated elderly, especially those 60-69 years of age, besides overall reductions of 62% (95%CI: 52-69) and 63% (95%CI: 43-75) in hospitalization and death rates, respectively. Our results emphasize the importance of mass vaccination, especially during an epidemic such as in Manaus, marked by high circulation of the gamma variant.

A avaliação do impacto da vacinação contra a COVID-19 em idosos é escassa, sobretudo em um cenário com predomínio da variante Gama. O objetivo deste estudo foi avaliar a cobertura vacinal e sua relação com mudanças no padrão de internações e óbitos por COVID-19 em idosos de Manaus, Amazonas, Brasil. Este é um estudo ecológico com dados de internações e óbitos do Ministério da Saúde que avaliou a cobertura vacinal, mediante esquema com duas doses, além de dois regimes de vacinação associados a significativo efeito protetor, um parcial (35 ou mais dias após a primeira dose da vacina Oxford/AstraZeneca) e outro completo (14 dias ou mais após a segunda dose da vacina Sinovac-CoronaVac). A partir da data dos primeiros sintomas, padrões de internação e óbito por COVID-19 foram avaliados, comparativamente, em idosos de 60-69 e de 70 anos ou mais, em dois grupos de Semanas Epidemiológicas (SE) de 2020 (não vacinados) e 2021 (vacinados). Taxas de internação e óbito foram estimadas pelo modelo Poisson. Entre 60-69 anos e naqueles com 70 anos ou mais, a cobertura por vacina foi 41,8% e 54,8%, bem como 53,5% e 90,1% nos grupos de SE 18-20/2021 e 21-23/2021, respectivamente. Em ambos os grupos de SE de 2021, observou-se substancial mudança nos padrões de internações e óbitos por COVID-19, com aumento no risco de internação e óbito nos mais jovens não vacinados, e importante redução no número de idosos vacinados, sobretudo naqueles com 60-69 anos, além de redução global de 62% (IC95%: 52-69) e 63% (IC95%: 43-75) nas taxas de internação e óbitos, respectivamente. Nossos resultados reforçam a importância da vacinação em massa, especialmente em contexto epidêmico como o de Manaus, marcado por elevada circulação da variante Gama.

La evaluación del impacto de la vacunación contra la COVID-19 en ancianos es escasa, sobre todo en un escenario con predominio de la variante Gamma. El objetivo de este estudio fue evaluar la cobertura de vacunación y su relación con cambios en el patrón de internamientos y óbitos por COVID-19 en ancianos de Manaos, Amazonas, Brasil. Este es un estudio ecológico con datos de internamientos y óbitos del Ministerio de Salud, que evaluó la cobertura de vacunación, mediante un esquema con dos dosis, además de dos regímenes de vacunación, asociados a un significativo efecto protector, uno parcial (35 o más días tras la primera dosis de la vacuna Oxford/AstraZeneca) y otro completo (14 días o más tras la segunda dosis de la vacuna Sinovac-CoronaVac). A partir de los datos de los primeros síntomas, se evaluaron patrones de internamiento y óbito por COVID-19, comparativamente, en ancianos de 60-69 y de 70 años o más, en dos grupos de Semanas Epidemiológicas (SE) de 2020 (no vacunados) y 2021 (vacunados). Se estimaron tasas de internamiento y óbito mediante el modelo Poisson. Entre 60-69 años y en aquellos con 70 años o más, la cobertura por vacuna fue 41,8% y 54,8%, así como 53,5% y 90,1% en los grupos de SE 18-20/2021 y 21-23/2021, respectivamente. En ambos grupos de SE de 2021, se observó un cambio sustancial en los patrones de internamiento y óbitos por COVID-19, con un aumento en el riesgo de internamiento y óbito en los más jóvenes no vacunados e importante reducción en los ancianos vacunados, sobre todo en aquellos con 60-69 años, además de una reducción global de 62% (IC95%: 52-69) y 63% (IC95%: 43-75) en las tasas de internamiento y óbitos, respectivamente. Nuestros resultados refuerzan la importancia de la vacunación en masa, especialmente en un contexto epidémico como el de Manaos, marcado por una elevada circulación de la variante Gamma.

Effectiveness, safety, and immunogenicity of half dose ChAdOx1 nCoV-19 COVID-19 Vaccine: Viana project.

Fractional dose is an important strategy to increase access to vaccines. This study evaluated the effectiveness, safety, and immunogenicity of half dose of ChAdOx1 nCoV-19 vaccine. A non-inferiority non-randomized controlled trial compared a half dose of ChAdOx1 nCoV-19 with the full dose, with an interval of 8 to 10 weeks, in individuals aged 18-49 years. The primary endpoints were the incidence rate of new cases/1,000 person-year at 90 days after 14 days of the second dose, confirmed by RT-PCR and new cases registered at SUS National Health Surveillance Database (e-SUS VS). The anti-SARS-CoV-2 spike (S) protein receptor binding domain (RBD) by chemiluminescence and the neutralizing antibodies by plaque reduction neutralization test (PRNT) were titrated. The soluble biomarkers were quantified with a multiplex immunoassay. Follow-up was 90 days after 14 days of the second dose. A total of 29,598 individuals were vaccinated. After exclusion, 16,570 individuals who received half a dose and 6,402 who received full doses were analyzed. The incidence of new cases confirmed by RT-PCR of half dose was non-inferior to full dose (23.7 vs. 25.7 cases per 1,000 persons-year [coefficient group -0.09 CI95%(-0.49 to 0.31)], even after adjusting for age and sex. There were no deaths or hospitalization after immunization of either group. Immunogenicity was evaluated in a subsample (N=558) compared to 154 healthcare workers who received a full dose. The seroconversion rate in seronegative individuals at baseline half dose was 99.8%, similar to that of the full dose (100%). Geometric mean concentration (95% CI; BAU/mL) were half dose = 188 (163-217) and full dose = 529 (423-663) (p < 0.001). In seropositive subjects at baseline (pre-immune individuals), the first dose induced very high and similar IgG-S in half dose 1,359 (1,245-1,483) and full dose 1,354 (1,048-1,749) BAU/mL. A half dose induced a high increase in plasma chemokines, pro-inflammatory/regulatory cytokines, and growth factors. The frequency of adverse events was similar. No serious adverse events or deaths were reported. A half dose of ChAdOx1 nCoV-19 is as effective, safe, and immunogenic as the full dose. The immune response in pre-immune (seropositive in the baseline) individuals indicates that the half dose may be a booster dose schedule.