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AbstractObjectiveTo estimate the effectiveness of the inactivated whole virus vaccine, CoronaVac (Sinovac Biotech), against symptomatic covid-19 in the elderly population of São Paulo state, Brazil during widespread circulation of the gamma variant.DesignTest negative case-control study.SettingCommunity testing for covid-19 in São Paulo state, Brazil.Participants43 774 adults aged ≥70 years who were residents of São Paulo state and underwent reverse transcription polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 from 17 January to 29 April 2021. 26 433 cases with symptomatic covid-19 and 17 622 test negative controls with covid-19 symptoms were formed into 13 283 matched sets, one case with to up to five controls, according to age, sex, self-reported race, municipality of residence, previous covid-19 status, and date of RT-PCR test (±3 days).InterventionVaccination with a two dose regimen of CoronaVac.Main outcome measuresRT-PCR confirmed symptomatic covid-19 and associated hospital admissions and deaths.ResultsAdjusted vaccine effectiveness against symptomatic covid-19 was 24.7% (95% confidence interval 14.7% to 33.4%) at 0-13 days and 46.8% (38.7% to 53.8%) at ≥14 days after the second dose. Adjusted vaccine effectiveness against hospital admissions was 55.5% (46.5% to 62.9%) and against deaths was 61.2% (48.9% to 70.5%) at ≥14 days after the second dose. Vaccine effectiveness ≥14 days after the second dose was highest for the youngest age group (70-74 years)—59.0% (43.7% to 70.2%) against symptomatic disease, 77.6% (62.5% to 86.7%) against hospital admissions, and 83.9% (59.2% to 93.7%) against deaths—and declined with increasing age.ConclusionsVaccination with CoronaVac was associated with a reduction in symptomatic covid-19, hospital admissions, and deaths in adults aged ≥70 years in a setting with extensive transmission of the gamma variant. Vaccine protection was, however, low until completion of the two dose regimen, and vaccine effectiveness was observe to decline with increasing age among this elderly population.

A two-dose regimen of the Oxford-AstraZeneca (ChAdOx1) Covid-19 vaccine with an inter-dose interval of three months has been implemented in many countries with restricted vaccine supply. However, there is limited evidence for the effectiveness of ChAdOx1 by dose in elderly populations in countries with high prevalence of the Gamma variant of SARS-CoV-2. Here, we estimate ChAdOx1 effectiveness by dose against the primary endpoint of RT-PCR-confirmed Covid-19, and secondary endpoints of Covid-19 hospitalization and Covid-19-related death, in adults aged ≥60 years during an epidemic with high Gamma variant prevalence in São Paulo state, Brazil using a matched, test-negative case-control study. Starting 28 days after the first dose, effectiveness of a single dose of ChAdOx1 is 33.4% (95% CI, 26.4–39.7) against Covid-19, 55.1% (95% CI, 46.6–62.2) against hospitalization, and 61.8% (95% CI, 48.9–71.4) against death. Starting 14 days after the second dose, effectiveness of the two-dose schedule is 77.9% (95% CI, 69.2–84.2) against Covid-19, 87.6% (95% CI, 78.2–92.9) against hospitalization, and 93.6% (95% CI, 81.9–97.7) against death. Completion of the ChAdOx1 vaccine schedule affords significantly increased protection over a single dose against mild and severe Covid-19 outcomes in elderly individuals during widespread Gamma variant circulation. Here, the authors investigate the effectiveness of the Oxford-AstraZeneca (ChAdOx1) vaccine during extensive Gamma variant SARS-CoV-2 circulation in São Paulo state, Brazil, and find that a two-dose regime is more effective than one dose against mild to severe Covid-19 outcomes in older adults.

AbstractObjectiveTo estimate the change in odds of covid-19 over time following primary series completion of the inactivated whole virus vaccine CoronaVac (Sinovac Biotech) in São Paulo State, Brazil.DesignTest negative case-control study.SettingCommunity testing for covid-19 in São Paulo State, Brazil.ParticipantsAdults aged ≥18 years who were residents of São Paulo state, had received two doses of CoronaVac, did not have a laboratory confirmed SARS-CoV-2 infection before vaccination, and underwent reverse transcription polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 from 17 January to 14 December 2021. Cases were matched to test negative controls by age (in 5 year bands), municipality of residence, healthcare worker status, and epidemiological week of RT-PCR test.Main outcome measuresRT-PCR confirmed symptomatic covid-19 and associated hospital admissions and deaths. Conditional logistic regression was adjusted for sex, number of covid-19 associated comorbidities, race, and previous acute respiratory illness.ResultsFrom 202 741 eligible people, 52 170 cases with symptomatic covid-19 and 69 115 test negative controls with covid-19 symptoms were formed into 43 257 matched sets. Adjusted odds ratios of symptomatic covid-19 increased with time since completion of the vaccination series. The increase in odds was greater in younger people and among healthcare workers, although sensitivity analyses suggested that this was in part due to bias. In addition, the adjusted odds ratios of covid-19 related hospital admission or death significantly increased with time compared with the odds 14-41 days after series completion: from 1.25 (95% confidence interval 1.04 to 1.51) at 70-97 days up to 1.94 (1.41 to 2.67) from 182 days onwards.ConclusionsSignificant increases in the risk of moderate and severe covid-19 outcomes occurred three months after primary vaccination with CoronaVac among people aged 65 and older. These findings provide supportive evidence for the implementation of vaccine boosters in these populations who received this inactivated vaccine. Studies of waning should include analyses designed to uncover common biases.

Dengue is a substantial public health challenge in tropical regions, and is considered a global health threat owing to its expanding geographical range and increasing incidence as a result of climate change. Despite the availability of tetravalent dengue vaccines, real-world evidence on their effectiveness is scarce. We aimed to evaluate the vaccine effectiveness of the dengue vaccine TAK-003 in adolescents during the 2024 dengue outbreak in the state of São Paulo, Brazil. This test-negative, case–control study was conducted among adolescents aged 10–14 years in São Paulo state, Brazil, from Feb 20 to Dec 31, 2024. Cases were defined as individuals with acute febrile illness and virologically confirmed dengue, and controls as individuals with acute febrile illness who tested negative for dengue; in both groups, confirmation was based on NS1 antigen or RT-PCR testing within 5 days of symptom onset. Data were obtained from the national surveillance databases for dengue and the São Paulo State Secretary of Health vaccination registry. We used mixed-effects logistic regression models to estimate vaccine effectiveness against symptomatic, virologically confirmed dengue and against hospitalisation with dengue after one or two doses of the vaccine. Of 128 358 potentially eligible tests, 92 621 were included in the analysis: 43 873 from cases and 48 748 from controls. Adjusted vaccine effectiveness was 50·2% (95% CI 45·0–54·9) for the first dose and 61·7% (39·9–75·6) for the second dose against symptomatic dengue, and 67·5% (95% CI 43·4–81·3) for the first dose against hospitalisation with dengue. Protection against symptomatic disease began 14 days after the first dose (67·4% [57·2–75·1] at 14–27 days), but declined to 49·7% (30·4–63·6) after 90 days from the first dose. Sensitivity analyses showed the robustness of these findings, although estimates for the second dose were limited by the small number of events observed. TAK-003 was effective against symptomatic dengue and hospitalisation with dengue in adolescents during a large outbreak caused predominantly by dengue virus serotypes 1 and 2. These findings underscore the importance of real-world evidence in guiding dengue vaccination strategies, particularly in high-transmission settings and during emergency response use. National Council for Scientific and Technological Development. For the Portuguese translation of the abstract see Supplementary Materials section.

In this paper by Ranzani and colleagues (BMJ 2021;374:n2015, doi:10.1136/bmj.n2015, published 20 August 2021), author Edlaine Faria de Moura Villela should have been shown affiliated with address 5 [not 6], the Disease Control Coordination of the São Paulo State Department of Health, São Paulo, Brazil.

Over 400 million people are estimated to be at risk of acquiring dengue virus (DENV). Despite efforts to mitigate the impact of DENV epidemics, the virus remains a public health problem in the Americas: more than one million DENV cases were reported in the continent between January and July 2019 DENV was first detected in Brazil in 1982, and Brazil has reported 88% (1,127,244 cases) of all DENV cases in the Americas during 2019 to date. São Paulo state in the southeast of Brazil has reported nearly half of all DENV infections in the country. Here we characterised the genetic diversity of DENV strains circulating in São Paulo state in 2019, at the epicentre of the ongoing DENV epidemic. Using portable nanopore sequencing we generated 20 new DENV genome sequences from viremic patients with suspected dengue infection residing in two of the most-affected municipalities, Araraquara and São José do Rio Preto. We conducted a comprehensive phylogenetic analysis with 1,630 global DENV strains to better understand the evolutionary history of the DENV lineages that currently circulate in the region. The new outbreak strains were classified as DENV2 genotype III (American/Asian genotype). Notably, phylogenetic analysis indicated that the 2019 outbreak is the result of a novel DENV lineage that was recently introduced to Brazil from the Caribbean region. Our genetic analysis further indicates that the introduction and onwards spread of the outbreak lineage (named here DENV2-III lineage 4) indicates a new DENV2 lineage replacement in Brazil. Molecular clock analyses suggest that DENV2-III lineage 4 was introduced to Brazil in or around early 2014. Our study describes the early detection of a newly introduced and rapidly-expanding DENV2 virus lineage in Brazil.