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      Vaccine effectiveness of heterologous CoronaVac plus BNT162b2 in Brazil

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          Abstract

          There is considerable interest in the waning of effectiveness of coronavirus disease 2019 (COVID-19) vaccines and vaccine effectiveness (VE) of booster doses. Using linked national Brazilian databases, we undertook a test-negative design study involving almost 14 million people (~16 million tests) to estimate VE of CoronaVac over time and VE of BNT162b2 booster vaccination against RT–PCR-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe COVID-19 outcomes (hospitalization or death). Compared with unvaccinated individuals, CoronaVac VE at 14–30 d after the second dose was 55.0% (95% confidence interval (CI): 54.3–55.7) against confirmed infection and 82.1% (95% CI: 81.4–82.8) against severe outcomes. VE decreased to 34.7% (95% CI: 33.1–36.2) against infection and 72.5% (95% CI: 70.9–74.0) against severe outcomes over 180 d after the second dose. A BNT162b2 booster, 6 months after the second dose of CoronaVac, improved VE against infection to 92.7% (95% CI: 91.0−94.0) and VE against severe outcomes to 97.3% (95% CI: 96.1−98.1) 14–30 d after the booster. Compared with younger age groups, individuals 80 years of age or older had lower protection after the second dose but similar protection after the booster. Our findings support a BNT162b2 booster vaccine dose after two doses of CoronaVac, particularly for the elderly.

          Abstract

          A test-negative case–control analysis of data from Brazil shows that vaccine effectiveness against SARS-CoV-2 infection and severe COVID-19 outcomes declines after two doses of CoronaVac but increases after a booster dose of the BNT162b2 vaccine.

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            Waning Immune Humoral Response to BNT162b2 Covid-19 Vaccine over 6 Months

            Background Despite high vaccine coverage and effectiveness, the incidence of symptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been increasing in Israel. Whether the increasing incidence of infection is due to waning immunity after the receipt of two doses of the BNT162b2 vaccine is unclear. Methods We conducted a 6-month longitudinal prospective study involving vaccinated health care workers who were tested monthly for the presence of anti-spike IgG and neutralizing antibodies. Linear mixed models were used to assess the dynamics of antibody levels and to determine predictors of antibody levels at 6 months. Results The study included 4868 participants, with 3808 being included in the linear mixed-model analyses. The level of IgG antibodies decreased at a consistent rate, whereas the neutralizing antibody level decreased rapidly for the first 3 months with a relatively slow decrease thereafter. Although IgG antibody levels were highly correlated with neutralizing antibody titers (Spearman’s rank correlation between 0.68 and 0.75), the regression relationship between the IgG and neutralizing antibody levels depended on the time since receipt of the second vaccine dose. Six months after receipt of the second dose, neutralizing antibody titers were substantially lower among men than among women (ratio of means, 0.64; 95% confidence interval [CI], 0.55 to 0.75), lower among persons 65 years of age or older than among those 18 to less than 45 years of age (ratio of means, 0.58; 95% CI, 0.48 to 0.70), and lower among participants with immunosuppression than among those without immunosuppression (ratio of means, 0.30; 95% CI, 0.20 to 0.46). Conclusions Six months after receipt of the second dose of the BNT162b2 vaccine, humoral response was substantially decreased, especially among men, among persons 65 years of age or older, and among persons with immunosuppression.
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              Waning Immunity after the BNT162b2 Vaccine in Israel

              Background In December 2020, Israel began a mass vaccination campaign against coronavirus disease 2019 (Covid-19) by administering the BNT162b2 vaccine, which led to a sharp curtailing of the outbreak. After a period with almost no cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, a resurgent Covid-19 outbreak began in mid-June 2021. Possible reasons for the resurgence were reduced vaccine effectiveness against the delta (B.1.617.2) variant and waning immunity. The extent of waning immunity of the vaccine against the delta variant in Israel is unclear. Methods We used data on confirmed infection and severe disease collected from an Israeli national database for the period of July 11 to 31, 2021, for all Israeli residents who had been fully vaccinated before June 2021. We used a Poisson regression model to compare rates of confirmed SARS-CoV-2 infection and severe Covid-19 among persons vaccinated during different time periods, with stratification according to age group and with adjustment for possible confounding factors. Results Among persons 60 years of age or older, the rate of infection in the July 11–31 period was higher among persons who became fully vaccinated in January 2021 (when they were first eligible) than among those fully vaccinated 2 months later, in March (rate ratio, 1.6; 95% confidence interval [CI], 1.3 to 2.0). Among persons 40 to 59 years of age, the rate ratio for infection among those fully vaccinated in February (when they were first eligible), as compared with 2 months later, in April, was 1.7 (95% CI, 1.4 to 2.1). Among persons 16 to 39 years of age, the rate ratio for infection among those fully vaccinated in March (when they were first eligible), as compared with 2 months later, in May, was 1.6 (95% CI, 1.3 to 2.0). The rate ratio for severe disease among persons fully vaccinated in the month when they were first eligible, as compared with those fully vaccinated in March, was 1.8 (95% CI, 1.1 to 2.9) among persons 60 years of age or older and 2.2 (95% CI, 0.6 to 7.7) among those 40 to 59 years of age; owing to small numbers, the rate ratio could not be calculated among persons 16 to 39 years of age. Conclusions These findings indicate that immunity against the delta variant of SARS-CoV-2 waned in all age groups a few months after receipt of the second dose of vaccine.
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                Author and article information

                Contributors
                viviane.boaventura@fiocruz.br
                Journal
                Nat Med
                Nat Med
                Nature Medicine
                Nature Publishing Group US (New York )
                1078-8956
                1546-170X
                9 February 2022
                9 February 2022
                2022
                : 28
                : 4
                : 838-843
                Affiliations
                [1 ]LIB and LEITV Laboratories, Instituto Gonçalo Moniz, Salvador, Brazil
                [2 ]GRID grid.8399.b, ISNI 0000 0004 0372 8259, Universidade Federal de Bahia (UFBA), ; Salvador, Brazil
                [3 ]GRID grid.8756.c, ISNI 0000 0001 2193 314X, MRC/CSO Social and Public Health Sciences Unit, , University of Glasgow, ; Glasgow, UK
                [4 ]GRID grid.508718.3, Public Health Scotland, ; Glasgow, UK
                [5 ]Center of Data and Knowledge Integration for Health (CIDACS), Instituto Gonçalo Moniz, Salvador, Brazil
                [6 ]GRID grid.8991.9, ISNI 0000 0004 0425 469X, London School of Hygiene and Tropical Medicine, ; London, UK
                [7 ]GRID grid.11984.35, ISNI 0000000121138138, Department of Mathematics and Statistics, , University of Strathclyde, ; Glasgow, UK
                [8 ]GRID grid.7632.0, ISNI 0000 0001 2238 5157, Núcleo de Medicina Tropical, , Universidade de Brasília, Escola Fiocruz de Governo, ; Fiocruz, Brazil
                [9 ]GRID grid.412211.5, ISNI 0000 0004 4687 5267, Universidade do Estado do Rio de Janeiro, ; Rio de Janeiro, Brazil
                [10 ]GRID grid.4305.2, ISNI 0000 0004 1936 7988, Usher Institute, , University of Edinburgh, ; Edinburgh, UK
                Author information
                http://orcid.org/0000-0003-4534-2509
                http://orcid.org/0000-0001-6593-9092
                http://orcid.org/0000-0001-7858-9650
                http://orcid.org/0000-0001-7639-2627
                http://orcid.org/0000-0002-4797-908X
                http://orcid.org/0000-0001-8967-536X
                http://orcid.org/0000-0003-1169-1436
                http://orcid.org/0000-0002-9938-7852
                http://orcid.org/0000-0001-7022-3056
                http://orcid.org/0000-0002-7241-6844
                Article
                1701
                10.1038/s41591-022-01701-w
                9018414
                35140406
                51b2b7f5-cd85-428f-9fd1-6b55a3a04371
                © The Author(s) 2022

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 3 December 2021
                : 14 January 2022
                Funding
                Funded by: NRS Senior Clinical Fellowship (SCAF/15/02), the Medical Research Council (MC_UU_00022/2) and the Scottish Government Chief Scientist Office (SPHSU17).
                Funded by: Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant ref MC_PC_20058).
                Funded by: Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro - E-26/210.180/2020
                Funded by: "Fazer o bem faz bem" programme
                Funded by: UK Research and Innovation (grant ref MC_PC_20058
                Categories
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                © The Author(s), under exclusive licence to Springer Nature America, Inc. 2022

                Medicine
                epidemiology,outcomes research
                Medicine
                epidemiology, outcomes research

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