Mpox in Children and Adolescents during Multicountry Outbreak, 2022-2023.

The 2022-2023 mpox outbreak predominantly affected adult men; 1.3% of reported cases were in children and adolescents <18 years of age. Analysis of global surveillance data showed 1 hospital intensive care unit admission and 0 deaths in that age group. Transmission routes and clinical manifestations varied across age subgroups.

[Reregistration of the population residing in Foz do Iguaçu, Brazil, in compliance with the Primary Health Care PolicyReinscripción de la población residente en Foz do Iguaçu, Brasil, en cumplimiento de la Política de atención primaria de salud]. / Recadastramento da população residente em Foz do Iguaçu, Brasil, em atendimento à Política de Atenção Primária à Saúde.

Objective: To present the experience and results of the reregistration of residents in Foz do Iguaçu, a border town located in the state of Paraná, Brazil, to meet the guidelines of the national Primary Health Care (PHC) Policy and its new financing model (Programa Previne Brasil). Method: A scanning strategy (convenience sample) was used for data collection, with 52 263 households visited and 22 710 interviews conducted from September to November 2019. The interviews were conducted face-to-face by 54 community health workers. Data were collected on the household (ownership status, urban or rural location, type of household, construction material, availability of electrical and sewage networks, water supply and waste disposal). Demographic and health information on the residents was also collected. Results: The reregistration process revealed that most residents were home owners and lived in well-constructed homes, located mostly in urban areas, served by electricity, with access to water supply and garbage collection. Of the reregistered population, 52.8% were women, 62.5% were aged between 15 and 59 years and 60.0% declared themselves white. Among respondents aged 15 or over, 90.0% had completed elementary school. The main occupation was "formal salaried job". Additionally, 18.6% of the interviewees declared themselves to be hypertensive and 7.0%, diabetic. Conclusions: The reregistration process uncovered relevant information to support both PHC planning as well as social assistance, work and housing initiatives; it was also fundamental to define health care strategies in this border town during the COVID-19 pandemic.

Objetivo: Presentar la experiencia y los resultados de la reinscripción de la población residente en Foz do Iguaçu, un municipio fronterizo ubicado en el estado de Paraná (Brasil), en cumplimiento de las directrices de la Política de atención primaria de salud y su nuevo modelo de financiamiento (Programa Previne Brasil). Métodos: Utilizando una estrategia de barrido (muestreo de conveniencia) para la recolección de datos, se visitaron 52 263 hogares y se realizaron 22 710 entrevistas entre septiembre y noviembre de 2019. Las entrevistas fueron presenciales y estuvieron a cargo de 54 trabajadores comunitarios de salud. Se recopilaron datos sobre el hogar (régimen de propiedad de la vivienda, ubicación en una zona urbana o rural, tipo de vivienda, material de construcción, disponibilidad de redes de energía eléctrica y alcantarillado, abastecimiento de agua y eliminación de desechos) e información sobre la composición demográfica y la salud de los residentes. Resultados: La reinscripción reveló que los residentes eran propietarios de sus viviendas y que estas se encontraban ubicadas en zonas urbanas, estaban bien construidas y tenían servicios de energía eléctrica, abastecimiento de agua y recolección de basura. El 52,8% de la población registrada correspondió a mujeres, el 62,5% tenía entre 15 y 59 años y el 60,0% declaró que era de raza blanca. El 90,0% de los entrevistados mayores de 15 años había terminado la escuela primaria. La ocupación principal era "persona asalariada con carnet de trabajo". Además, el 18,6% de los entrevistados indicó que tenía hipertensión y el 7,0%, diabetes. Conclusiones: La reinscripción aportó información relevante para apoyar la planificación de la atención primaria de salud , así como las iniciativas en materia de asistencia social, trabajo y vivienda; también fue fundamental para definir las estrategias de atención de salud en ese municipio fronterizo durante la pandemia de COVID-19.

Zika Virus Transmission - Region of the Americas, May 15, 2015-December 15, 2016.

Zika virus, a mosquito-borne flavivirus that can cause rash with fever, emerged in the Region of the Americas on Easter Island, Chile, in 2014 and in northeast Brazil in 2015 (1). In response, in May 2015, the Pan American Health Organization (PAHO), which serves as the Regional Office of the Americas for the World Health Organization (WHO), issued recommendations to enhance surveillance for Zika virus. Subsequently, Brazilian investigators reported Guillain-Barré syndrome (GBS), which had been previously recognized among some patients with Zika virus disease, and identified an association between Zika virus infection during pregnancy and congenital microcephaly (2). On February 1, 2016, WHO declared Zika virus-related microcephaly clusters and other neurologic disorders a Public Health Emergency of International Concern.* In March 2016, PAHO developed case definitions and surveillance guidance for Zika virus disease and associated complications (3). Analysis of reports submitted to PAHO by countries in the region or published in national epidemiologic bulletins revealed that Zika virus transmission had extended to 48 countries and territories in the Region of the Americas by late 2016. Reported Zika virus disease cases peaked at different times in different areas during 2016. Because of ongoing transmission and the risk for recurrence of large outbreaks, response efforts, including surveillance for Zika virus disease and its complications, and vector control and other prevention activities, need to be maintained.

Disseminating information on acute public health events globally: experiences from the WHO's Disease Outbreak News.

WHO works, on a daily basis, with countries globally to detect, prepare for and respond to acute public health events. A vital component of a health response is the dissemination of accurate, reliable and authoritative information. The Disease Outbreak News (DON) reports are a key mechanism through which WHO communicates on acute public health events to the public. The decision to produce a DON report is taken on a case-by-case basis after evaluating key criteria, and the subsequent process of producing a DON report is highly standardised to ensure the robustness of information. DON reports have been published since 1996, and up to 2022 over 3000 reports have been published. Between 2018 and 2022, the most frequently published DON reports relate to Ebola virus disease, Middle East respiratory syndrome, yellow fever, polio and cholera. The DON web page is highly visited with a readership of over 2.6 million visits per year, on average. The DON report structure has evolved over time, from a single paragraph in 1996 to a detailed report with seven sections currently. WHO regularly reviews the DON report process and structure for improvements. In the last 25 years, DON reports have played a unique role in rapidly disseminating information on acute public health events to health actors and the public globally. They have become a key information source for the global public health response to the benefit of individuals and communities.

Technology transfer during the COVID-19 pandemic: report on the first face-to-face practical training course in Brazil.

MAIN RESULTS: Technology transfer can take place at large events, as long as safety protocols are strictly enforced. It is important to disseminate, at these events, the concepts of the Responsible Research and Innovation (RRI). Implications for services: Face-to-face training course is fundamental for training public health professionals. Technology transfer between research institutions and health services results in updating and improving health system performance. PERSPECTIVES: Based on the success of the reported technology transfer, a new module will be incorporated into the next edition of VEME (Panama 2022), entitled Virus Evolution to Public Health Policy Makers. The objective of this report was to describe the first face-to-face course aimed at training public health professionals in performing real-time genomic surveillance during the pandemic period. Experience report on a theoretical-practical course focusing on genomic research and surveillance, including mobile sequencing technologies, bioinformatics, phylogenetics and epidemiological modeling. There were 162 participants in the event and it was the first major face-to-face training course conducted during the COVID-19 epidemic in Brazil. No cases of SARS-CoV-2 infection was detected among the participants at the end of the event, suggesting the safety and effectiveness of all safety measures adopted. The results of this experience suggest that it is possible to conduct professional training safely during pandemics, as long as all safety protocols are followed.

Description of the first global outbreak of mpox: an analysis of global surveillance data.

BACKGROUND: In May 2022, several countries with no history of sustained community transmission of mpox (formerly known as monkeypox) notified WHO of new mpox cases. These cases were soon followed by a large-scale outbreak, which unfolded across the world, driven by local, in-country transmission within previously unaffected countries. On July 23, 2022, WHO declared the outbreak a Public Health Emergency of International Concern. Here, we aim to describe the main epidemiological features of this outbreak, the largest reported to date. METHODS: In this analysis of global surveillance data we analysed data for all confirmed mpox cases reported by WHO Member States through the global surveillance system from Jan 1, 2022, to Jan 29, 2023. Data included daily aggregated numbers of mpox cases by country and a case reporting form (CRF) containing information on demographics, clinical presentation, epidemiological exposure factors, and laboratory testing. We used the data to (1) describe the key epidemiological and clinical features of cases; (2) analyse risk factors for hospitalisation (by multivariable mixed-effects binary logistic regression); and (3) retrospectively analyse transmission trends. Sequencing data from GISAID and GenBank were used to analyse monkeypox virus (MPXV) genetic diversity. FINDINGS: Data from 82 807 cases with submitted CRFs were included in the analysis. Cases were primarily due to clade IIb MPXV (mainly lineage B.1, followed by lineage A.2). The outbreak was driven by transmission among males (73 560 [96·4%] of 76 293 cases) who self-identify as men who have sex with men (25 938 [86·9%] of 29 854 cases). The most common reported route of transmission was sexual contact (14 941 [68·7%] of 21 749). 3927 (7·3%) of 54 117 cases were hospitalised, with increased odds for those aged younger than 5 years (adjusted odds ratio 2·12 [95% CI 1·32-3·40], p=0·0020), aged 65 years and older (1·54 [1·05-2·25], p=0·026), female cases (1·61 [1·35-1·91], p<0·0001), and for cases who are immunosuppressed either due to being HIV positive and immunosuppressed (2·00 [1·68-2·37], p<0·0001), or other immunocompromising conditions (3·47 [1·84-6·54], p=0·0001). INTERPRETATION: Continued global surveillance allowed WHO to monitor the epidemic, identify risk factors, and inform the public health response. The outbreak can be attributed to clade IIb MPXV spread by newly described modes of transmission. FUNDING: WHO Contingency Fund for Emergencies. TRANSLATIONS: For the French and Spanish translations of the abstract see Supplementary Materials section.

Global public health intelligence: World Health Organization operational practices.

Early warning and response are key to tackle emerging and acute public health risks globally. Therefore, the World Health Organization (WHO) has implemented a robust approach to public health intelligence (PHI) for the global detection, verification and risk assessment of acute public health threats. WHO's PHI operations are underpinned by the International Health Regulations (2005), which require that countries strengthen surveillance efforts, and assess, notify and verify events that may constitute a public health emergency of international concern (PHEIC). PHI activities at WHO are conducted systematically at WHO's headquarters and all six regional offices continuously, throughout every day of the year. We describe four interlinked steps; detection, verification, risk assessment, and reporting and dissemination. For PHI operations, a diverse and interdisciplinary workforce is needed. Overall, PHI is a key feature of the global health architecture and will only become more prominent as the world faces increasing public health threats.

Potential predictors in neonaticide: the impact of the circumstances of pregnancy.

This study aims to evaluate the psychosocial factors of neonaticide, especially the circumstances before delivery, the relationships of the pregnant women, and their social environment awareness of women's pregnancy. This nationwide study was register-based, comprising all known neonaticides in Austria and Finland between 1995 and 2005. Cases (n = 28) were obtained by screening the death certificates from coroner's departments and by analyzing them along with all further available reports. Few women (17.9 %, 5/28) admitted their pregnancy to others. Although most (16/28) offenders were in a relationship, the partner had knowledge of the pregnancy in only three cases. The main motive for negation of the pregnancy (named in 60.8 % of cases) was fear of abandonment/negative response from others. The fertility rate among the women was high, but half of those with children had lost the custody of them. In neonaticide, the lack of awareness surrounding offenders' pregnancy, as well as the awareness of social environment, is more relevant than any other social variable.

Effectiveness of an inactivated Covid-19 vaccine with homologous and heterologous boosters against Omicron in Brazil.

The effectiveness of inactivated vaccines (VE) against symptomatic and severe COVID-19 caused by omicron is unknown. We conducted a nationwide, test-negative, case-control study to estimate VE for homologous and heterologous (BNT162b2) booster doses in adults who received two doses of CoronaVac in Brazil in the Omicron context. Analyzing 1,386,544 matched-pairs, VE against symptomatic disease was 8.6% (95% CI, 5.6-11.5) and 56.8% (95% CI, 56.3-57.3) in the period 8-59 days after receiving a homologous and heterologous booster, respectively. During the same interval, VE against severe Covid-19 was 73.6% (95% CI, 63.9-80.7) and 86.0% (95% CI, 84.5-87.4) after receiving a homologous and heterologous booster, respectively. Waning against severe Covid-19 after 120 days was only observed after a homologous booster. Heterologous booster might be preferable to individuals with completed primary series inactivated vaccine.

Outbreak caused by the SARS-CoV-2 Omicron variant in the psychiatric ward of a general hospital in Brazil.

BACKGROUND: An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant was detected in the psychiatric ward of a general hospital in Brasília, Brazil. METHODS: We report the investigation, clinical outcomes, viral sequencing, and control measures applied to outbreak containment. RESULTS: The overall attack rate was 95% (23/24) in a period of 13 days. Among the cases, 78% (18/23) were vaccinated and 17% (4/23) required intensive care. The Omicron variant was isolated from the 19 sequenced samples. CONCLUSIONS: The findings highlight the potential harm that highly transmissible variants may generate among hospitalized populations, particularly those with comorbidities.

Change in covid-19 risk over time following vaccination with CoronaVac: test negative case-control study.

OBJECTIVE: To 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. DESIGN: Test negative case-control study. SETTING: Community testing for covid-19 in São Paulo State, Brazil. PARTICIPANTS: Adults 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 MEASURES: RT-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. RESULTS: From 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. CONCLUSIONS: Significant 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.

Replacement of the Gamma by the Delta variant in Brazil: Impact of lineage displacement on the ongoing pandemic.

The coronavirus disease 2019 (COVID-19) epidemic in Brazil was driven mainly by the spread of Gamma (P.1), a locally emerged variant of concern (VOC) that was first detected in early January 2021. This variant was estimated to be responsible for more than 96 per cent of cases reported between January and June 2021, being associated with increased transmissibility and disease severity, a reduction in neutralization antibodies and effectiveness of treatments or vaccines, and diagnostic detection failure. Here we show that, following several importations predominantly from the USA, the Delta variant rapidly replaced Gamma after July 2021. However, in contrast to what was seen in other countries, the rapid spread of Delta did not lead to a large increase in the number of cases and deaths reported in Brazil. We suggest that this was likely due to the relatively successful early vaccination campaign coupled with natural immunity acquired following prior infection with Gamma. Our data reinforce reports of the increased transmissibility of the Delta variant and, considering the increasing concern due to the recently identified Omicron variant, argues for the necessity to strengthen genomic monitoring on a national level to quickly detect the emergence and spread of other VOCs that might threaten global health.

Importance of animal/human health interface in potential Public Health Emergencies of International Concern in the Americas.

This study analyzed the importance of zoonoses and communicable diseases common to man and animals as potential Public Health Emergencies of International Concern to build an evidence base for future efforts to reduce risk of infection at the animal/human health interface. The events recorded in the World Health Organization (WHO) Event Management System (EMS) database for the Americas during the 18 months since the implementation of the 2005 revised version of WHO's International Health Regulations (15 June 2007-31 December 2008) were the main source for this analysis. Of the 110 events recorded by the EMS for the Americas during the study period, 86 were classified as communicable diseases-77 (70.0%) "within the animal/human health interface," 9 (8.2%) "not common to man and animals," 16 (14.5%) "syndromes with unknown etiologies," and 8 (7.3%) "product-related/ other." Of the 77 events within the animal/human health interface, 48 were "substantiated" (the presence of hazard was confirmed and/or human cases occurred clearly in excess of normal expectancy). These results confirm previous research and underscore the importance of the animal/human health interface as well as inter-sectoral collaboration.

Risk Factors for Death Among 120,804 Hospitalized Patients with Confirmed COVID-19 in São Paulo, Brazil.

São Paulo is a state in Brazil with one of the highest numbers of confirmed and severe cases of coronavirus disease (COVID-19), with an incidence of 294 hospitalizations per 100,000 inhabitants. We report the clinical characteristics and outcomes of 120,804 hospitalized patients with confirmed COVID-19 from February 26 to October 10, 2020, in São Paulo. Characteristics of patients who died and survived were compared using a survival analysis. The median age was 60 years (interquartile range [IQR], 47-72), 67,821 (56.1%) were men, and 61,659 (51.0%) were white. Most hospitalized patients (79,812; 66.1%) reported one or more comorbidities, 41,708 (34.5%) hospitalized patients were admitted to intensive care units, and 33,079 (27.4%) died. Men (hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.18-1.25), elderly individuals (HR, 3.85; 95% CI, 3.68-4.02), and patients with chronic cardiovascular disease including hypertension (HR, 1.05; 95% CI, 1.02-1.08), chronic lung disease (HR, 1.38; 95% CI, 1.31-1.45), diabetes mellitus (HR, 1.14; 95% CI, 1.11-1.18), and chronic neurological disease (HR, 1.48; 95% CI, 1.41-1.55) were at higher risk for death from COVID-19.

Restructuring of emergency services to COVID-19 in Brazil: a space-time analysis from February to August 2020. / Reestruturação dos serviços de emergência à COVID-19 no Brasil: uma análise espaço-temporal, fevereiro a agosto de 2020.

OBJECTIVE: To explore the reorganization of the health system in response to the COVID-19 pandemic. METHODS: We conducted an ecological, descriptive-exploratory study with analysis of spatio-temporal clusters by epidemiological week in Brazilian municipalities. Secondary data sources were used, from the National Health Establishment Registry (April 2020) and on COVID-19 cases, February to August 2020. Intensive Care Units (ICU) availability was overlaid on incidence and mortality hot spots in order to assess expanded access in critical regions. RESULTS: Of the 5,570 municipalities analyzed, 54% were identified as incidence hot spots and 31% as mortality hot spots. Of the municipalities in incidence hot spots and with scarce access, 28% were covered by ICU expansion, while with regard to mortality 14% were covered. CONCLUSION: The opening of new beds was not able to provide broad coverage for critical regions and could be optimized with the use of spatial analysis techniques.

Change in COVID-19 risk over time following vaccination with CoronaVac: A testnegative case-control study.

OBJECTIVE: To 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. DESIGN: Test negative case-control study. SETTING: Community testing for covid-19 in São Paulo state, Brazil. PARTICIPANTS: Adults aged 18-120 years who were residents of São Paulo state, without a previous laboratory-confirmed covid-19 infection, who received only two doses of CoronaVac, and underwent reverse transcription polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 from 17 January to 30 September 2021. MAIN OUTCOME MEASURES: RT-PCR-confirmed symptomatic covid-19 and associated hospital admissions and deaths. Cases were pair-matched to test-negative controls by age (in 5-year bands), municipality of residence, healthcare worker (HCW) status, and date of RT-PCR test (±3 days). Conditional logistic regression was adjusted for sex, number of covid-19-associated comorbidities, race, and previous acute respiratory infection. RESULTS: From 137,820 eligible individuals, 37,929 cases with symptomatic covid-19 and 25,756 test-negative controls with covid-19 symptoms were formed into 37,929 matched pairs. Adjusted odds ratios of symptomatic covid-19 increased with time since series completion, and this increase was greater in younger individuals, and among HCWs compared to non-HCWs. Adjusted odds ratios of covid-19 hospitalisation or death were significantly increased from 98 days since series completion, compared to individuals vaccinated 14-41 days previously: 1.40 (95% confidence interval 1.09 to 1.79) from 98-125 days, 1.55 (1.16 to 2.07) from 126-153 days, 1.56 (1.12 to 2.18) from 154-181 days, and 2.12 (1.39-3.22) from 182 days. CONCLUSIONS: In the general population of São Paulo state, Brazil, an increase in odds of moderate and severe covid-19 outcomes was observed over time following primary series completion with CoronaVac.

Effectiveness of the CoronaVac vaccine in older adults during a gamma variant associated epidemic of covid-19 in Brazil: test negative case-control study.

OBJECTIVE: To 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. DESIGN: Test negative case-control study. SETTING: Community testing for covid-19 in São Paulo state, Brazil. PARTICIPANTS: 43 774 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). INTERVENTION: Vaccination with a two dose regimen of CoronaVac. MAIN OUTCOME MEASURES: RT-PCR confirmed symptomatic covid-19 and associated hospital admissions and deaths. RESULTS: Adjusted 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. CONCLUSIONS: Vaccination 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.

Effectiveness of CoronaVac among healthcare workers in the setting of high SARS-CoV-2 Gamma variant transmission in Manaus, Brazil: A test-negative case-control study.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, Gamma, emerged in the city of Manaus in late 2020 during a large resurgence of coronavirus disease (COVID-19), and has spread throughout Brazil. The effectiveness of vaccines in settings with widespread Gamma variant transmission has not been reported. METHODS: We performed a matched test-negative case-control study to estimate the effectiveness of an inactivated vaccine, CoronaVac, in healthcare workers (HCWs) in Manaus, where the Gamma variant accounted for 86% of genotyped SARS-CoV-2 samples at the peak of its epidemic. We performed an early analysis of effectiveness following administration of at least one vaccine dose and an analysis of effectiveness of the two-dose schedule. The primary outcome was symptomatic SARS-CoV-2 infection. FINDINGS: For the early at-least-one-dose and two-dose analyses the study population was, respectively, 53,176 and 53,153 HCWs residing in Manaus and aged 18 years or older, with complete information on age, residence, and vaccination status. Among 53,153 HCWs eligible for the two-dose analysis, 47,170 (89%) received at least one dose of CoronaVac and 2,656 individuals (5%) underwent RT-PCR testing from 19 January, 2021 to 13 April, 2021. Of 3,195 RT-PCR tests, 885 (28%) were positive. 393 and 418 case-control pairs were selected for the early and two-dose analyses, respectively, matched on calendar time, age, and neighbourhood. Among those who had received both vaccine doses before the RT-PCR sample collection date, the average time from second dose to sample collection date was 14 days (IQR 7-24). In the early analysis, vaccination with at least one dose was associated with a 0.50-fold reduction (adjusted vaccine effectiveness (VE), 49.6%, 95% CI 11.3 to 71.4) in the odds of symptomatic SARS-CoV-2 infection during the period 14 days or more after receiving the first dose. However, we estimated low effectiveness (adjusted VE 36.8%, 95% CI -54.9 to 74.2) of the two-dose schedule against symptomatic SARS-CoV-2 infection during the period 14 days or more after receiving the second dose. A finding that vaccinated individuals were much more likely to be infected than unvaccinated individuals in the period 0-13 days after first dose (aOR 2.11, 95% CI 1.36-3.27) suggests that unmeasured confounding led to downward bias in the vaccine effectiveness estimate. INTERPRETATION: Evidence from this test-negative study of the effectiveness of CoronaVac was mixed, and likely affected by bias in this setting. Administration of at least one vaccine dose showed effectiveness against symptomatic SARS-CoV-2 infection in the setting of epidemic Gamma variant transmission. However, the low estimated effectiveness of the two-dose schedule underscores the need to maintain non-pharmaceutical interventions while vaccination campaigns with CoronaVac are being implemented. FUNDING: Fundação Oswaldo Cruz (Fiocruz); Municipal Health Secretary of Manaus; Fundação de Vigilância em Saúde do Amazonas.