ABSTRACT
Fractional dose is an important strategy to increase access to vaccines. This study evaluated the effectiveness, safety, and immunogenicity of half dose of ChAdOx1 nCoV-19 vaccine. A non-inferiority non-randomized controlled trial compared a half dose of ChAdOx1 nCoV-19 with the full dose, with an interval of 8 to 10 weeks, in individuals aged 18-49 years. The primary endpoints were the incidence rate of new cases/1,000 person-year at 90 days after 14 days of the second dose, confirmed by RT-PCR and new cases registered at SUS National Health Surveillance Database (e-SUS VS). The anti-SARS-CoV-2 spike (S) protein receptor binding domain (RBD) by chemiluminescence and the neutralizing antibodies by plaque reduction neutralization test (PRNT) were titrated. The soluble biomarkers were quantified with a multiplex immunoassay. Follow-up was 90 days after 14 days of the second dose. A total of 29,598 individuals were vaccinated. After exclusion, 16,570 individuals who received half a dose and 6,402 who received full doses were analyzed. The incidence of new cases confirmed by RT-PCR of half dose was non-inferior to full dose (23.7 vs. 25.7 cases per 1,000 persons-year [coefficient group -0.09 CI95%(-0.49 to 0.31)], even after adjusting for age and sex. There were no deaths or hospitalization after immunization of either group. Immunogenicity was evaluated in a subsample (N=558) compared to 154 healthcare workers who received a full dose. The seroconversion rate in seronegative individuals at baseline half dose was 99.8%, similar to that of the full dose (100%). Geometric mean concentration (95% CI; BAU/mL) were half dose = 188 (163-217) and full dose = 529 (423-663) (p < 0.001). In seropositive subjects at baseline (pre-immune individuals), the first dose induced very high and similar IgG-S in half dose 1,359 (1,245-1,483) and full dose 1,354 (1,048-1,749) BAU/mL. A half dose induced a high increase in plasma chemokines, pro-inflammatory/regulatory cytokines, and growth factors. The frequency of adverse events was similar. No serious adverse events or deaths were reported. A half dose of ChAdOx1 nCoV-19 is as effective, safe, and immunogenic as the full dose. The immune response in pre-immune (seropositive in the baseline) individuals indicates that the half dose may be a booster dose schedule.
Subject(s)
COVID-19 Vaccines , COVID-19 , ChAdOx1 nCoV-19 , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , HumansABSTRACT
The impact of COVID-19 vaccination in the elderly has received relatively little attention, particularly in a scenario predominated by the gamma variant. The aim of this study was to assess vaccination coverage and its relationship to changes in the pattern of COVID-19 hospitalizations and deaths in the elderly in Manaus, Amazonas State, Brazil. This was an ecological study with Brazilian Ministry of Health data on hospitalizations and deaths, assessing vaccination coverage based on a two-dose regimen, in addition to two vaccination regimens associated with a significant protective effect, one partial (35 days or more after the first dose of the Oxford/AstraZeneca vaccine) and the other complete (14 days or more after the second dose of the Sinovac-CoronaVac vaccine). Based on the date of initial symptoms, patterns of COVID-19 hospitalizations and deaths were assessed comparatively in elderly 60-69 years and 70 years or more in two groups of Epidemiological Weeks (EW) in 2020 (unvaccinated) and 2021 (vaccinated). Hospitalization and death rates were estimated with Poisson regression. In the groups 60-69 and 70 years or more, vaccination coverage rates were 41.8% and 54.8%, as well as 53.5% and 90.1%, in the EW groups 18-20/2021 and 21-23/2021, respectively. Both EW groups in 2021 showed a substantial change in the patterns of COVID-19 hospitalizations and deaths, with an increase in the risk of hospitalization and death in unvaccinated younger individuals and an important reduction in vaccinated elderly, especially those 60-69 years of age, besides overall reductions of 62% (95%CI: 52-69) and 63% (95%CI: 43-75) in hospitalization and death rates, respectively. Our results emphasize the importance of mass vaccination, especially during an epidemic such as in Manaus, marked by high circulation of the gamma variant.
A avaliação do impacto da vacinação contra a COVID-19 em idosos é escassa, sobretudo em um cenário com predomínio da variante Gama. O objetivo deste estudo foi avaliar a cobertura vacinal e sua relação com mudanças no padrão de internações e óbitos por COVID-19 em idosos de Manaus, Amazonas, Brasil. Este é um estudo ecológico com dados de internações e óbitos do Ministério da Saúde que avaliou a cobertura vacinal, mediante esquema com duas doses, além de dois regimes de vacinação associados a significativo efeito protetor, um parcial (35 ou mais dias após a primeira dose da vacina Oxford/AstraZeneca) e outro completo (14 dias ou mais após a segunda dose da vacina Sinovac-CoronaVac). A partir da data dos primeiros sintomas, padrões de internação e óbito por COVID-19 foram avaliados, comparativamente, em idosos de 60-69 e de 70 anos ou mais, em dois grupos de Semanas Epidemiológicas (SE) de 2020 (não vacinados) e 2021 (vacinados). Taxas de internação e óbito foram estimadas pelo modelo Poisson. Entre 60-69 anos e naqueles com 70 anos ou mais, a cobertura por vacina foi 41,8% e 54,8%, bem como 53,5% e 90,1% nos grupos de SE 18-20/2021 e 21-23/2021, respectivamente. Em ambos os grupos de SE de 2021, observou-se substancial mudança nos padrões de internações e óbitos por COVID-19, com aumento no risco de internação e óbito nos mais jovens não vacinados, e importante redução no número de idosos vacinados, sobretudo naqueles com 60-69 anos, além de redução global de 62% (IC95%: 52-69) e 63% (IC95%: 43-75) nas taxas de internação e óbitos, respectivamente. Nossos resultados reforçam a importância da vacinação em massa, especialmente em contexto epidêmico como o de Manaus, marcado por elevada circulação da variante Gama.
La evaluación del impacto de la vacunación contra la COVID-19 en ancianos es escasa, sobre todo en un escenario con predominio de la variante Gamma. El objetivo de este estudio fue evaluar la cobertura de vacunación y su relación con cambios en el patrón de internamientos y óbitos por COVID-19 en ancianos de Manaos, Amazonas, Brasil. Este es un estudio ecológico con datos de internamientos y óbitos del Ministerio de Salud, que evaluó la cobertura de vacunación, mediante un esquema con dos dosis, además de dos regímenes de vacunación, asociados a un significativo efecto protector, uno parcial (35 o más días tras la primera dosis de la vacuna Oxford/AstraZeneca) y otro completo (14 días o más tras la segunda dosis de la vacuna Sinovac-CoronaVac). A partir de los datos de los primeros síntomas, se evaluaron patrones de internamiento y óbito por COVID-19, comparativamente, en ancianos de 60-69 y de 70 años o más, en dos grupos de Semanas Epidemiológicas (SE) de 2020 (no vacunados) y 2021 (vacunados). Se estimaron tasas de internamiento y óbito mediante el modelo Poisson. Entre 60-69 años y en aquellos con 70 años o más, la cobertura por vacuna fue 41,8% y 54,8%, así como 53,5% y 90,1% en los grupos de SE 18-20/2021 y 21-23/2021, respectivamente. En ambos grupos de SE de 2021, se observó un cambio sustancial en los patrones de internamiento y óbitos por COVID-19, con un aumento en el riesgo de internamiento y óbito en los más jóvenes no vacunados e importante reducción en los ancianos vacunados, sobre todo en aquellos con 60-69 años, además de una reducción global de 62% (IC95%: 52-69) y 63% (IC95%: 43-75) en las tasas de internamiento y óbitos, respectivamente. Nuestros resultados refuerzan la importancia de la vacunación en masa, especialmente en un contexto epidémico como el de Manaos, marcado por una elevada circulación de la variante Gamma.