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 (preprint)

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 Research in Context Evidence before this study We searched PubMed for articles published from inception of the pandemic until April 3, 2021, with no language restrictions, using the search terms “P.1” AND “vaccine” AND “SARS-CoV-2”. Additionally, we searched for “CoronaVac” AND “SARS-CoV-2”. Early studies have found plasma from convalescent COVID-19 patients and sera from vaccinated individuals have reduced neutralisation of the SARS-CoV-2 variant, Gamma or P.1, compared with strains isolated earlier in the pandemic. Pfizer BNT162b2 mRNA, Oxford-AstraZeneca ChAdOx1, and CoronaVac are the only vaccines for which such data has been published to date. No studies reported effectiveness of any vaccine on reducing the risk of infection or disease among individuals exposed to P.1 or in settings of high P.1 transmission. Added value of this study This study finds that vaccination with CoronaVac was 49.4% (95% CI 13.2 to 71.9) effective at preventing COVID-19 in a setting with likely high prevalence of the Gamma Variant of Concern. However, an analysis of effectiveness by dose was underpowered and failed to find significant effectiveness of the two-dose schedule of CoronaVac (estimated VE 37.1%, 95% CI -53.3 to 74.2). Implications of all the available evidence These findings are suggestive for the effectiveness of CoronaVac in healthcare workers in the setting of widespread P.1 transmission but must be strengthened by observational studies in other settings and populations. Based on this evidence, there is a need to implement sustained non-pharmaceutical interventions even as vaccination campaigns continue.

SARS-CoV-2 Seroprevalence and Associated Factors in Manaus, Brazil: Baseline Results from the DETECTCoV-19 Cohort Study (preprint)

Background: Manaus located in the Brazilian rainforest has twice experienced a health system collapse due to the SARS-CoV-2 pandemic. However, little is known about which groups among the general population have been more affected. Methods: A convenience sampling strategy via online advertising recruited 3046 adults. Sociodemographic characteristics, COVID-19-related symptoms, COVID-19 testing, self-medication and prescribed medications were recorded. Serum anti-SARS-CoV-2 nucleocapsid IgG antibodies were measured with an ELISA. Prevalence ratios (PR) were obtained using cluster-corrected and adjusted Poisson’s regression models.Results: A crude positivity rate among asymptomatic and symptomatic individuals, was estimated at 29.10%, with a maximum seroprevalence of 41.53% corrected by test characteristics and an antibody decay rate of 27%. Regression models demonstrated a strong association towards marginalized low-income and vulnerable residents with limited health access. Presence of a COVID-19 case (PR 1.39, 1.24-1.57) or death (PR 2.14, 1.74-2.62) in a household increased greatly the risk of other household members acquiring infection. SARS-CoV-2 seroprevalence was higher among those who self-medicated to prevent infection (PR 1.36, 1.27-1.46). Conclusions: A disproportionate social and economic disparity was observed among the study participants. The syndemic nature of COVID-19 in the Amazon region needs differential policies and urgent solutions to control the ongoing pandemic.

SARS-CoV-2 Seroprevalence and Associated Factors in Manaus, Brazil: Baseline Results from the DETECTCoV-19 Cohort Study (preprint)

Background: Twice city of Manaus located in the Brazilian rainforest, has experienced a health system collapse due to the SARS-CoV-2 pandemic. However, little is known about which groups among the general population have been more affected. In this report, we present the overall prevalence of SARS-CoV-2 infection and associated factors from the DETECTCoV-19 cohort. Methods: A convenience sampling strategy via online advertising recruited 3046 adults. Sociodemographic characteristics, COVID-19-related symptoms, COVID-19 testing, self-medication and prescribed medications were recorded. Serum anti-SARS-CoV-2 nucleocapsid IgG antibodies were measured with an in-house ELISA. Prevalence ratios (PR) were obtained using cluster-corrected and adjusted Poisson’s regression models. Findings: A crude positivity rate among asymptomatic and symptomatic individuals, was estimated at 29·10%, with a maximum seroprevalence of 41·53% corrected by test characteristics and an antibody decay rate of 27%. Regression models demonstrated a strong association towards marginalized low-income and vulnerable residents with limited health access. Presence of a COVID-19 case (PR 1·39, 1·24-1·57) or death (PR 2·14, 1·74-2·62) in a household increased greatly the risk of other household members acquiring infection. SARS-CoV-2 seroprevalence was higher among those who self-medicated to prevent infection (PR 1·36, 1·27-1·46). Interpretation: High SARS-CoV-2 seropositivity reveals a much burdensome scenario than estimations based on confirmed COVID-19 cases in Manaus. Overall, prevalence of SARS-CoV-2 antibody response demonstrated a disproportionate social and economic disparity among the study participants. The syndemic nature of COVID-19 in the Amazon region needs differential policies and urgent solutions to control the pandemic. Funding: Research was funded by Ministry of Education (MEC), Brazil. BBS, IVPF, ROS, ARCB and WBSS received scholarship from CAPES. DSSS, TBNM, MFF and NOC received scholarship from FAPEAMDeclaration of Interests: The authors declare no conflict of interest.Ethics Approval Statement: The research ethics committee of Federal University of Amazonas (UFAM) approved this study (CAAE:34906920·4·0000·5020) in accordance with Brazilian law