Effectiveness of COVID-19 vaccines against the Omicron (B.1.1.529) variant of concern

Abstract Background A rapid increase in cases due to the SARS-CoV-2 Omicron (B.1.1.529) variant in highly vaccinated populations has raised concerns about the effectiveness of current vaccines. Methods We used a test-negative case-control design to estimate vaccine effectiveness (VE) against symptomatic disease caused by the Omicron and Delta variants in England. VE was calculated after primary immunisation with two BNT162b2 or ChAdOx1 doses, and at 2+ weeks following a BNT162b2 booster. Results Between 27 November and 06 December 2021, 581 and 56,439 eligible Omicron and Delta cases respectively were identified. There were 130,867 eligible test-negative controls. There was no effect against Omicron from 15 weeks after two ChAdOx1 doses, while VE after two BNT162b2 doses was 88.0% (95%CI: 65.9 to 95.8%) 2-9 weeks after dose 2, dropping to between 34 and 37% from 15 weeks post dose 2.From two weeks after a BNT162b2 booster, VE increased to 71.4% (95%CI: 41.8 to 86.0%) for ChAdOx1 primary course recipients and 75.5% (95%CI: 56.1 to 86.3%) for BNT162b2 primary course recipients. For cases with Delta, VE was 41.8% (95%CI: 39.4-44.1%) at 25+ weeks after two ChAdOx1 doses, increasing to 93.8% (95%CI: 93.2-94.3%) after a BNT162b2 booster. With a BNT162b2 primary course, VE was 63.5% (95%CI: 61.4 to 65.5%) 25+ weeks after dose 2, increasing to 92.6% (95%CI: 92.0-93.1%) two weeks after the booster. Conclusions Primary immunisation with two BNT162b2 or ChAdOx1 doses provided no or limited protection against symptomatic disease with the Omicron variant. Boosting with BNT162b2 following either primary course significantly increased protection.

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Effectiveness of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines on covid-19 related symptoms, hospital admissions, and mortality in older adults in England: test negative case-control study

BMJ ◽

10.1136/bmj.n1088 ◽

2021 ◽

pp. n1088

Author(s):

Jamie Lopez Bernal ◽

Nick Andrews ◽

Charlotte Gower ◽

Chris Robertson ◽

Julia Stowe ◽

...

Keyword(s):

Case Control Study ◽

Case Control ◽

Vaccine Effectiveness ◽

Symptomatic Disease ◽

Emergency Hospital Admission ◽

Negative Case ◽

Control Study ◽

Underlying Risk ◽

Reduced Risk

Abstract Objective To estimate the real world effectiveness of the Pfizer-BioNTech BNT162b2 and Oxford-AstraZeneca ChAdOx1-S vaccines against confirmed covid-19 symptoms (including the UK variant of concern B.1.1.7), admissions to hospital, and deaths. Design Test negative case-control study. Setting Community testing for covid-19 in England. Participants 156 930 adults aged 70 years and older who reported symptoms of covid-19 between 8 December 2020 and 19 February 2021 and were successfully linked to vaccination data in the National Immunisation Management System. Interventions Vaccination with BNT162b2 or ChAdOx1-S. Main outcome measures Primary outcomes were polymerase chain reaction confirmed symptomatic SARS-CoV-2 infections, admissions to hospital for covid-19, and deaths with covid-19. Results Participants aged 80 years and older vaccinated with BNT162b2 before 4 January 2021 had a higher odds of testing positive for covid-19 in the first nine days after vaccination (odds ratio up to 1.48, 95% confidence interval 1.23 to 1.77), indicating that those initially targeted had a higher underlying risk of infection. Vaccine effectiveness was therefore compared with the baseline post-vaccination period. Vaccine effects were noted 10 to 13 days after vaccination, reaching a vaccine effectiveness of 70% (95% confidence interval 59% to 78%), then plateauing. From 14 days after the second dose a vaccination effectiveness of 89% (85% to 93%) was found compared with the increased baseline risk. Participants aged 70 years and older vaccinated from 4 January (when ChAdOx1-S delivery commenced) had a similar underlying risk of covid-19 to unvaccinated individuals. With BNT162b2, vaccine effectiveness reached 61% (51% to 69%) from 28 to 34 days after vaccination, then plateaued. With ChAdOx1-S, effects were seen from 14 to 20 days after vaccination, reaching an effectiveness of 60% (41% to 73%) from 28 to 34 days, increasing to 73% (27% to 90%) from day 35 onwards. On top of the protection against symptomatic disease, a further 43% (33% to 52%) reduced risk of emergency hospital admission and 51% (37% to 62%) reduced risk of death was observed in those who had received one dose of BNT162b2. Participants who had received one dose of ChAdOx1-S had a further 37% (3% to 59%) reduced risk of emergency hospital admission. Follow-up was insufficient to assess the effect of ChAdOx1-S on mortality. Combined with the effect against symptomatic disease, a single dose of either vaccine was about 80% effective at preventing admission to hospital with covid-19 and a single dose of BNT162b2 was 85% effective at preventing death with covid-19. Conclusion Vaccination with either one dose of BNT162b2 or ChAdOx1-S was associated with a significant reduction in symptomatic covid-19 in older adults, and with further protection against severe disease. Both vaccines showed similar effects. Protection was maintained for the duration of follow-up (>6 weeks). A second dose of BNT162b2 was associated with further protection against symptomatic disease. A clear effect of the vaccines against the B.1.1.7 variant was found.

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Influenza vaccine effectiveness against influenza A in children based on the results of various rapid influenza tests in the 2018/19 season

PLoS ONE ◽

10.1371/journal.pone.0249005 ◽

2021 ◽

Vol 16 (3) ◽

pp. e0249005

Author(s):

Masayoshi Shinjoh ◽

Norio Sugaya ◽

Yoshio Yamaguchi ◽

Ichiro Ookawara ◽

Yuji Nakata ◽

...

Keyword(s):

Confidence Interval ◽

Influenza Vaccine ◽

Diagnostic Tests ◽

Influenza A ◽

Control Design ◽

Case Control ◽

Vaccine Effectiveness ◽

Test Results ◽

Negative Case ◽

Influenza A H1n1

During influenza epidemics, Japanese clinicians routinely conduct rapid influenza diagnostic tests (RIDTs) in patients with influenza-like illness, and patients with positive test results are treated with anti-influenza drugs within 48 h after the onset of illness. We assessed the vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) in children (6 months–15 years old, N = 4243), using a test-negative case-control design based on the results of RIDTs in the 2018/19 season. The VE against influenza A(H1N1)pdm and A(H3N2) was analyzed separately using an RIDT kit specifically for detecting A(H1N1)pdm09. The adjusted VE against combined influenza A (H1N1pdm and H3N2) and against A(H1N1)pdm09 was 39% (95% confidence interval [CI], 30%–46%) and 74% (95% CI, 39%–89%), respectively. By contrast, the VE against non-A(H1N1)pdm09 influenza A (presumed to be H3N2) was very low at 7%. The adjusted VE for preventing hospitalization was 56% (95% CI, 16%–77%) against influenza A. The VE against A(H1N1)pdm09 was consistently high in our studies. By contrast, the VE against A(H3N2) was low not only in adults but also in children in the 2018/19 season.

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Influenza vaccine effectiveness in adults 65 years and older, Denmark, 2015/16 – a rapid epidemiological and virological assessment

Eurosurveillance ◽

10.2807/1560-7917.es.2016.21.14.30189 ◽

2016 ◽

Vol 21 (14) ◽

Cited By ~ 16

Author(s):

Hanne Dorthe Emborg ◽

Tyra Grove Krause ◽

Lene Nielsen ◽

Marianne Kragh Thomsen ◽

Claus Bohn Christiansen ◽

...

Keyword(s):

Influenza Vaccine ◽

Influenza A ◽

Control Design ◽

Case Control ◽

Vaccine Effectiveness ◽

Influenza B ◽

Trivalent Influenza Vaccine ◽

Negative Case ◽

Influenza A H1n1 ◽

Genetic Subgroup

In Denmark, both influenza A(H1N1)pdm09 and influenza B co-circulated in the 2015/16 season. We estimated the vaccine effectiveness (VE) of the trivalent influenza vaccine in patients 65 years and older using the test-negative case–control design. The adjusted VE against influenza A(H1N1)pdm09 was 35.0% (95% confidence interval (CI): 11.1–52.4) and against influenza B 4.1% (95% CI: −22.0 to 24.7). The majority of influenza A(H1N1)pdm09 circulating in 2015/16 belonged to the new genetic subgroup subclade 6B.1.

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Evaluating Real-World COVID-19 Vaccine Effectiveness Using a Test-Negative Case-Control Design

10.1101/2022.01.06.22268726 ◽

2022 ◽

Author(s):

Matthew W Reynolds ◽

Alex Secora ◽

Alice Joules ◽

Lisa Albert ◽

Emma Brinkley ◽

...

Keyword(s):

Real World ◽

Odds Ratio ◽

Severe Symptom ◽

Control Design ◽

Case Control ◽

Vaccine Effectiveness ◽

Test Results ◽

Community Based ◽

Negative Case ◽

Modified Test

It is important to assess the extent to which the real-world effectiveness of marketed vaccines is consistent with that observed in the clinical trials, and to characterize how well vaccines prevent COVID-19 symptoms. We conducted a modified test-negative design (TND) to evaluate the RW effectiveness of three COVID-19 vaccines by leveraging data from an on-going, US community-based registry. Vaccine effectiveness was examined in two ways: considering cases who (1) tested positive for COVID-19 (695 cases, 1,786 controls) and who (2) tested positive with at least one moderate/severe COVID-19 symptom (165 cases, 2,316 controls). Any vaccination (full or partial) was associated with a 95% reduction in the odds of having a positive COVID-19 test [adjusted odds ratio (aOR) = 0.05 (95% confidence interval (CI): 0.04, 0.06)]. Full vaccination was associated with an aOR of 0.03 (95% CI: 0.03, 0.05) while partial vaccination had an aOR of 0.08 (95% CI: 0.06, 0.12). Any vaccination was associated with a 71% reduction in the odds of testing positive and having at least one moderate/severe symptom (aOR=0.29 (95% CI: 0.20, 0.40)). High effectiveness was observed across all three vaccine manufacturers both for prevention of positive COVID-19 test results and prevention of moderate/severe COVID-19 symptoms.

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Effectiveness of CoronaVac in the setting of high SARS-CoV-2 P.1 variant transmission in Brazil: A test-negative case-control study

10.1101/2021.04.07.21255081 ◽

2021 ◽

Author(s):

Matt Hitchings ◽

Otavio T. Ranzani ◽

Mario S.S. Torres ◽

Silvano Barbosa de Oliveira ◽

Maria Almiron ◽

...

Keyword(s):

Case Control Study ◽

Conditional Logistic Regression ◽

Case Control ◽

Vaccine Effectiveness ◽

Rt Pcr ◽

Fold Reduction ◽

Negative Case ◽

Health Organization ◽

Negative Controls ◽

Control Study

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant P.1 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 P.1 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 P.1 accounted for 75% of genotyped SARS-CoV-2 samples at the peak of its epidemic. Information from electronic surveillance databases was used to select cases of RT-PCR-confirmed SARS-CoV-2 infection and matched test-negative controls from 19 January, 2021 to 25 March, 2021. We used conditional logistic regression to estimate the effectiveness in reducing the odds of primary and secondary outcomes of, respectively, symptomatic and any SARS-CoV-2 infection. Findings Among 53,176 HCWs, 46,884 (88%) received at least one dose of CoronaVac and 2,656 (5%) underwent RT-PCR testing from 19 January, 2021 to 25 March, 2021. Of 2,797 RT-PCR tests, 776 (28%) were positive. 393 and 135 case-control pairs with and without, respectively, symptomatic illness were selected for the matched analyses. Vaccination with at least one dose was associated with a 0.50-fold reduction (adjusted vaccine effectiveness, 49.6%; 95% CI, 11.3 - 71.4) in the odds of symptomatic SARS-CoV-2 infection during the period 14 days or more after receiving the first dose. Estimated vaccine effectiveness of at least one dose against any SARS-CoV-2 infection was 35.1% (95% CI, -6.6 - 60.5) in the same time period. Interpretation Administration of at least one dose of CoronaVac showed effectiveness against symptomatic SARS-CoV-2 infection in the setting of epidemic P.1 transmission, underscoring the need to increase vaccination efforts in response to the spread of this variant in Brazil and globally. Funding Pan American Health Organization; Fundação Oswaldo Cruz (Fiocruz); Municipal Health Secretary of Manaus

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A probability model for evaluating the bias and precision of influenza vaccine effectiveness estimates from case-control studies

Epidemiology and Infection ◽

10.1017/s0950268814002179 ◽

2014 ◽

Vol 143 (7) ◽

pp. 1417-1426 ◽

Cited By ~ 25

Author(s):

M. HABER ◽

Q. AN ◽

I. M. FOPPA ◽

D. K. SHAY ◽

J. M. FERDINANDS ◽

...

Keyword(s):

Influenza Vaccine ◽

Medical Care ◽

Randomized Clinical Trials ◽

Probability Model ◽

Control Design ◽

Case Control ◽

Vaccine Effectiveness ◽

Case Control Studies ◽

Respiratory Illnesses ◽

Study Designs

SUMMARYAs influenza vaccination is now widely recommended, randomized clinical trials are no longer ethical in many populations. Therefore, observational studies on patients seeking medical care for acute respiratory illnesses (ARIs) are a popular option for estimating influenza vaccine effectiveness (VE). We developed a probability model for evaluating and comparing bias and precision of estimates of VE against symptomatic influenza from two commonly used case-control study designs: the test-negative design and the traditional case-control design. We show that when vaccination does not affect the probability of developing non-influenza ARI then VE estimates from test-negative design studies are unbiased even if vaccinees and non-vaccinees have different probabilities of seeking medical care against ARI, as long as the ratio of these probabilities is the same for illnesses resulting from influenza and non-influenza infections. Our numerical results suggest that in general, estimates from the test-negative design have smaller bias compared to estimates from the traditional case-control design as long as the probability of non-influenza ARI is similar among vaccinated and unvaccinated individuals. We did not find consistent differences between the standard errors of the estimates from the two study designs.

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Case-Control Study of Rotavirus Vaccine Effectiveness Compared to Test-Negative Controls or Hospital Controls

Journal of Epidemiology ◽

10.2188/jea.je20180054 ◽

2019 ◽

Vol 29 (8) ◽

pp. 282-287 ◽

Cited By ~ 4

Author(s):

Kaoru Araki ◽

Megumi Hara ◽

Chisato Shimanoe ◽

Yuichiro Nishida ◽

Muneaki Matsuo ◽

...

Keyword(s):

Case Control Study ◽

Case Control ◽

Vaccine Effectiveness ◽

Rotavirus Vaccine ◽

Negative Controls ◽

Control Study

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Evaluation of Influenza Vaccine Effectiveness Among Young Children Receiving Consecutive Versus Nonconsecutive Vaccination During Influenza A(H3N2)-Predominant Seasons

Journal of the Pediatric Infectious Diseases Society ◽

10.1093/jpids/piaa080 ◽

2020 ◽

Author(s):

Suchitra Rao ◽

Angela Moss ◽

Molly M Lamb ◽

Edwin J Asturias

Keyword(s):

Influenza Vaccine ◽

Influenza A ◽

Care Setting ◽

Case Control ◽

Vaccine Effectiveness ◽

Urgent Care ◽

Control Analysis ◽

Negative Case ◽

Case Control Analysis ◽

Urgent Care Setting

Abstract A test-negative case-control analysis of 1478 children aged 6 months to 8 years of age seeking care at an emergency/urgent care setting with influenza like illness during the 2016-17 and 2018-19 (H3N2 predominant) influenza seasons demonstrated that influenza vaccine effectiveness did not vary significantly by the prior seasons’ vaccination status. Clinical Trials Registration NCT02979626.

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“I-MOVE” towards monitoring seasonal and pandemic influenza vaccine effectiveness: lessons learnt from a pilot multi-centric case-control study in Europe, 2008-9

Eurosurveillance ◽

10.2807/ese.14.44.19388-en ◽

2009 ◽

Vol 14 (44) ◽

Cited By ~ 1

Author(s):

E Kissling ◽

M Valenciano ◽

J M Falcão ◽

A Larrauri ◽

K Widgren ◽

...

Keyword(s):

Influenza Vaccine ◽

Functional Status ◽

Pandemic Influenza ◽

Pooled Analysis ◽

Case Control ◽

Vaccine Effectiveness ◽

Age Group ◽

Case Control Studies ◽

Statistical Heterogeneity ◽

Negative Controls

Within I-MOVE (European programme to monitor seasonal and pandemic influenza vaccine effectiveness (IVE)) five countries conducted IVE pilot case-control studies in 2008-9. One hundred and sixty sentinel general practitioners (GP) swabbed all elderly consulting for influenza-like illness (ILI). Influenza confirmed cases were compared to influenza negative controls. We conducted a pooled analysis to obtain a summary IVE in the age group of ≥65 years. We measured IVE in each study and assessed heterogeneity between studies qualitatively and using the I2 index. We used a one-stage pooled model with study as a fixed effect. We adjusted estimates for age-group, sex, chronic diseases, smoking, functional status, previous influenza vaccinations and previous hospitalisations. The pooled analysis included 138 cases and 189 test-negative controls. There was no statistical heterogeneity (I2=0) between studies but ILI case definition, previous hospitalisations and functional status were slightly different. The adjusted IVE was 59.1% (95% CI: 15.3-80.3%). IVE was 65.4% (95% CI: 15.6-85.8%) in the 65-74, 59.6% (95% CI: -72.6 -90.6%) in the age group of ≥75 and 56.4% (95% CI: -0.2-81.3%) for A(H3). Pooled analysis is feasible among European studies. The variables definitions need further standardisation. Larger sample sizes are needed to achieve greater precision for subgroup analysis. For 2009-10, I-MOVE will extend the study to obtain early IVE estimates in groups targeted for pandemic H1N1 influenza vaccination.

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Vaccine effectiveness and duration of protection of Comirnaty, Vaxzevria and Spikevax against mild and severe COVID-19 in the UK

10.1101/2021.09.15.21263583 ◽

2021 ◽

Author(s):

Nick Andrews ◽

Elise Tessier ◽

Julia Stowe ◽

Charlotte Gower ◽

Freja Kirsebom ◽

...

Keyword(s):

Severe Disease ◽

Vaccine Effectiveness ◽

Real World Data ◽

Post Vaccination ◽

Symptomatic Disease ◽

Negative Case ◽

The Uk ◽

Comorbidity Status ◽

Duration Of Protection ◽

Over Time

Background COVID-19 vaccines have been used for 9 months in the UK. Real world data have demonstrated the vaccines to be highly effective against COVID-19, severe disease and death. Here, we estimate vaccine effectiveness over time since the second dose of Comirnaty, Vaxzevria and Spikevax in England. Methods We used a test-negative case-control design to estimate vaccine effectiveness against symptomatic disease, hospitalisation and mortality by age, comorbidity status and over time after the second dose to investigate waning separately for Alpha and Delta variants. Results Vaccine effectiveness against symptomatic disease peaked in the early weeks after the second dose and then fell to 47.3 (95% CI 45 to 49.6) and 69.7 (95% CI 68.7 to 70.5) by 20+ weeks against the Delta variant for Vaxzevria and Comirnaty, respectively. Waning of vaccine effectiveness was greater for 65+ year-olds compared to 40-64 year-olds. Vaccine effectiveness fell less against hospitalisations to 77.0 (70.3 to 82.3) and 92.7 (90.3 to 94.6) beyond 20 weeks post-vaccination and 78.7 (95% CI 52.7 to 90.4) and 90.4 (95% CI 85.1 to 93.8) against death for Vaxzevria and Comirnaty, respectively. Greater waning was observed among 65+ year-olds in a clinically extremely vulnerable group and 40-64-year olds with underlying medical conditions compared to healthy adults. Conclusions We observed limited waning in vaccine effectiveness against hospitalisation and death more than 20 weeks post-vaccination with Vaxzevria or Comirnaty. Waning was greater in older adults and those in a clinical risk group, suggesting that these individuals should be prioritised for booster doses.

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