key: cord-0275469-3sm8sxmt
authors: Ranzani, O. T.; Silva, A. A. B.; Peres, I. T.; Antunes, B. B. P.; Gonzaga-da-Silva, T. W.; Soranz, D. R.; Cerbino-Neto, J.; Hamacher, S.; Bozza, F. A.
title: One-dose ChAdOx1 nCoV-19 Vaccine Effectiveness Against Symptomatic COVID-19 in a vulnerable community in Rio de Janeiro, Brazil: test-negative design study
date: 2021-10-20
journal: nan
DOI: 10.1101/2021.10.16.21265095
sha: e4e91aeb2f68c46f6e09094fede9a10a1c0d4817
doc_id: 275469
cord_uid: 3sm8sxmt

We conducted a test-negative study design at the community "Complexo da Maré", the largest group of favelas in Rio de Janeiro, Brazil, when Gamma and Delta were the predominant variants circulating. We estimated 42.4% (95% CI, 24.6, 56.0) protection against symptomatic COVID-19 after 21 days of one dose of ChAdOx1.

Several studies have reported the disproportionate impact COVID-19 is having on vulnerable communities [1] [2] [3] . This impact is due to the perpetuated social, economic and health inequities.

Recently, inequity in access to vaccines has become a global issue [4] . Large populations in low-and middle-income countries (LMIC) live in slums or favelas, densely populated urban areas with deteriorated or incomplete infrastructure, but with a high risk of infectious disease transmission, limited access to health services or even vaccination.

Although the effectiveness of COVID-19 vaccines has been addressed in several articles from high income countries, studies that estimate vaccine effectiveness in neighborhoods such as favelas are lacking. We estimated the vaccine effectiveness of one dose of ChAdOx1 nCoV-19 (AstraZeneca/Oxford, hereafter ChAdOx1) vaccine against symptomatic COVID-19 using a test-negative design in the population of a large vulnerable community ("Complexo da Maré") in Rio de Janeiro, Brazil. METHODS "Complexo da Maré" is the largest group of favelas in Rio de Janeiro's city, composed by 16 favelas with 140,000 residents [5], 54% of the population aged ≤30 years, and low HDI (0.686, 123rd out of Rio's 126 neighbourhoods) in 2010 [6] . From the beginning of the pandemic until 14 September 2021, the region presented high rates of positive cases (6,416/100,000) and deaths (267/100,000) [7]. Since July 2020, a community broad testing strategy became available at the "Complexo da Maré" after an effort of civil society, NGOs and local community [8] . The testing was free of any charge and available on tents located in three different regions in Maré. There have been 193 RT-PCR tests per 1,000 inhabitants since the beginning of the campaign. During the study period, Gamma was the prevalent Variant of Concern in Rio de 4 Janeiro and Delta became dominant after July 2021 [9] . This study was approved by the National Research Ethics Committee (IRB/CONEP) (CAAE -49726921.6.0000.5248).

The COVID-19 vaccination campaign for Rio's general population started on January 17, 2021, according to an age-based strategy. The vaccination campaign in "Complexo da Maré" initially followed the Rio's city strategy, and by the end of July 2021, only 38% of Maré residents had received a first dose (53,084) and 13% a second or single dose (19, 203) We used a test-negative design to estimate the vaccine effectiveness of ChAdOx1 first dose, against symptomatic COVID-19. We linked the community-program testing database with the vaccination campaign database using a unique identifier (CPF, Cadastro de Pessoas Físicas). Overall, we followed the methodology reported elsewhere [10] . The description of inclusion/exclusion criteria is shown in eFigure 1. Briefly, we selected all RT-PCR (positive and negative tests) from symptomatic individuals, defined as presenting at least one symptom, from RT-PCRs sampled within 10 days of symptoms onset [11] . We excluded individuals with a previous positive RT-PCR, and those with a negative and subsequent positive test in the following 14 days. In a secondary analysis, we also included RT-PCR tests from asymptomatic individuals.

We estimated the vaccine effectiveness as 1-OR from logistic regression models. Our primary outcome was effectiveness against symptomatic COVID-19 after 21 days of the first . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted October 20, 2021. ; https://doi.org/10.1101/2021.10.16.21265095 doi: medRxiv preprint dose of ChAdOx1. RT-PCR tests sampled after the second dose were excluded. We adjusted by time of epidemic using a restricted cubic spline on day of the year, and subsequently adjusted by age (restricted cubic spline), sex, self-reported race, Maré residence (three different regions -north, center and south), occupation, whether the RT-PCR was from routine testing or spontaneous walking, and for six chronic comorbidities. We evaluated the interaction between effectiveness and the age groups divided by the median of the symptomatic population (≤35 years; >35 years). We conducted four sensitivity analyses: 1) Excluding test-negative cases that reported taste/smell alterations [11] ; 2) Expanding the time groups after the first dose until 56 days; 3) Analyzing symptomatic and asymptomatic cases, and 4) Analyzing only asymptomatic cases. We have missing data only for self-reported race (15%) and chronic comorbidities (<1%).

We generated 20 multiple imputed datasets using the standard procedure for multiple imputation using chained equation. We summarized the estimates and generated 95% confidence intervals using the Rubin's rules. All analyses were conducted in R statistical software version 4.0.3.

Between Jan 17, 2021, and Sept 14, 2021, there were 15,771 RT-PCR tests in the community.

After the inclusion/exclusion criteria (e- Figure 1 ), we analyzed 9,197 RT-PCR tests for the testnegative design. Overall, 36% of tests were from asymptomatic individuals. The test positivity was 20.6% (1211/5890) for symptomatic and 5.9% (195/3307) for asymptomatic cases (eFigure 2 and 3).

The general characteristics of the analyzed population for symptomatic cases is shown in eTable 1. The mean age was 38 ± 13 years, 65% of females and 41% of Brown/Pardo selfreported color. There were small proportion of individuals with chronic comorbidities, being most . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted October 20, 2021. ;

6 common obesity (9%) followed by cardiovascular disease (7%). Two-hundred and ten (3.6%) of individuals were healthcare workers. The median time between vaccination and RT-PCR testing among vaccinated was 36 [p25-p75: 20-60] days. The characteristics of the sample for asymptomatic and symptomatic and asymptomatic cases are shown in eTable 2 and eTable 3.

Vaccine effectiveness of one dose of ChAdOx1 is shown in Table 1 

We observed a vaccine effectiveness of 42% against symptomatic COVID-19 after a single dose of ChAdOx1 in a vulnerable population in Rio de Janeiro, Brazil, in a period of mixed Gamma and Delta dominance.

Our estimate is in accordance with previous evaluations for vaccine effectiveness of the first dose of ChAdOx1 in the context of Gamma or Delta [12, 13] . We observed the vaccine effectiveness increased up to 58.6% (28.0, 76.2) during 42-55 days of the first dose, which has . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted October 20, 2021. ; 7 been reported [12] and a decrease afterwards. We can hypothesize that this decrease might occur because of some factors, such limited power to evaluate vaccine effectiveness at this time window and increase on the dominance of Delta.

There is limited evidence for vaccine effectiveness against infection. We aimed to evaluate it combining asymptomatic cases in the estimates. The estimates are comparable to the protection against symptomatic cases, as previously reported [13] . However, the limited sample size resulting in low number of events among asymptomatic cases, shifts the estimate of the combined analysis towards symptomatic cases. Our analyses only with asymptomatic cases, although with large imprecision, shows a potential for effectiveness against asymptomatic infection. A detailed analysis on symptoms, such as a follow-up on those asymptomatic at RT-PCR collection or active surveys regarding symptoms, could help on understanding vaccine effectiveness against infection.

Our study has some limitations. First, we could not evaluate second dose effectiveness and waning because of the vaccination campaign and enough follow-up. Second, data on genome sequencing from all test-positives was not available. However, our study analyzed data in a period of high transmission rates of the Gamma and Delta variants in the community. Third, we could not evaluate the vaccine effectiveness for preventing COVID-19 hospitalizations or severe outcomes. Finally, although we excluded previous confirmed infections, it is expected that the community has a high attack rate and so the unvaccinated could have an unmeasured protection level, underestimating the vaccine effectiveness.

One-dose of ChAdOx1 was effective on reducing symptomatic COVID-19 in using data from a community surveillance program, where there was a broad testing strategy without any cost to an overall young vulnerable population in a group of favelas in Brazil.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted October 20, 2021. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted October 20, 2021. Flowchart ...................................................................................................... .................................................................................................................. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted October 20, 2021. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted October 20, 2021. * 2 missing values for each comorbidity. Data as N (%) unless differently reported . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted October 20, 2021. * Adjusted by day of the year of RT-PCR testing (restricted cubic spline); ^ Adjusted by age (restricted cubic spline), sex, cardiovascular disease, respiratory disease, obesity, diabetes mellitus, immunosuppressed status (includes cancer), liver disease, occupation, region of residence, self-reported race, reason of testing, and day of the year of RT-PCR testing using a restricted cubic spline.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted October 20, 2021. * Adjusted by day of the year of RT-PCR testing (restricted cubic spline); ^ Adjusted by age (restricted cubic spline), sex, cardiovascular disease, respiratory disease, obesity, diabetes mellitus, immunosuppressed status (includes cancer), liver disease, occupation, region of residence, self-reported race, reason of testing, and day of the year of RT-PCR testing using a restricted cubic spline.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted October 20, 2021. ; https://doi.org/10.1101/2021.10.16.21265095 doi: medRxiv preprint

Sociodemographic factors associated with COVID-19 in-hospital mortality in Brazil