OVID-19 is a severe acute respiratory infection (SARI) that emerged in early December 2019 in Wuhan, China 1. The outbreak was declared a public health emergency of international concern by the World Health Organization on 30 January 2020. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an enveloped, single-stranded positive-sense RNA virus that belongs to the Betacoronavirus genus and Coronaviridae family 2. SARS-CoV-2 is closely related genetically to bat-derived SARS-like coronaviruses 3. Human-to-human transmission occurs primarily via respiratory droplets and direct contact, similar to human influenza viruses, SARS-CoV and Middle East respiratory syndrome coronavirus 4. The most commonly reported clinical symptoms are fever, dry cough, fatigue, dyspnoea, anosmia, ageusia, or some combination of these 1,4,5. As of 16 June 2020, more than 7.9 million cases have been confirmed worldwide, resulting in 434,796 deaths 6. Brazil declared COVID-19 a national public health emergency on 3 February 2020 7. After the development of a national emergency plan and the early establishment of molecular diagnostic facilities across Brazil's network of public health laboratories, the country reported its first confirmed COVID-19 case on 25 February 2020, in a traveller returning to São Paulo from northern Italy 8. São Paulo is the largest city in South America and no other Brazilian city receives a greater proportion of international flights 9. Currently, Brazil has one of the fastest-growing COVID-19 epidemics in the world, now accounting for 1,864,681 cases and 72,100 deaths, comprising over 55% of the total number of reported cases in Latin America and the Caribbean (as of 14 July 2020) 6. About 21% of Latin American and Caribbean populations are estimated to be at risk of severe COVID-19 illness 10. The region has been experiencing large outbreaks, with growing epidemics in Brazil,

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.

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 Cr...