key: cord-0842728-05pv2w38
authors: Buchan, S. A.; Nguyen, L.; Wilson, S. E.; Kitchen, S. A.; Kwong, J.
title: Vaccine effectiveness of BNT162b2 against Omicron and Delta outcomes in adolescents
date: 2022-04-07
journal: nan
DOI: 10.1101/2022.04.07.22273319
sha: 348bbbcae02adf461f089919928e73b3d45b9562
doc_id: 842728
cord_uid: 05pv2w38

Introduction Data on vaccine effectiveness (VE) against Omicron in adolescents are limited. We estimated 2-dose and 3-dose VE against Omicron and Delta in adolescents aged 12-17 years in Ontario, Canada. Methods We conducted a test-negative design study among SARS-CoV-2-tested adolescents aged 12-17 years between November 22, 2021 (date of first Omicron detection) and March 6, 2022; we assessed Delta outcomes prior to January 2, 2022. We used multivariable logistic regression to compare the odds of vaccination in cases to symptomatic test-negative controls and calculated VE as 1-adjusted odds ratio. Results VE was lower against symptomatic Omicron infection than against Delta and decreased more rapidly over time, from 51% (95%CI, 38-61%) in the 7-59 days following a second dose to 29% (95%CI, 17-38%) after 180 days, compared to 97% (95%CI, 94-99%) and 90% (95%CI, 79-95%) for the same intervals against symptomatic Delta infection. Overall, 2-dose VE against severe outcomes caused by Omicron was 85% (95%CI, 74-91%) [≥]7 days following a second dose and estimates were similar over time. VE against symptomatic Omicron infection was 62% (95%CI, 49-72%) [≥]7 days following a third dose. Discussion Two-dose VE against symptomatic Omicron infection wanes over time in adolescents. While lower than observed against Delta, protection against severe outcomes appears to be maintained over time. A third dose substantially improves protection against Omicron infection, but 3-dose VE is only moderate at approximately 60% in the early period following vaccination and the duration of this protection is unknown.

There are limited data on vaccine effectiveness (VE) against Omicron in adolescents. In Ontario, Canada, most vaccinated adolescents completed their primary series of BNT162b2 during summer 2021; third dose eligibility (6 months following a second dose) expanded to those aged 12-17 years in February 2022. We estimated 2-dose and 3-dose VE against Omicron and Delta for this age group.

We conducted a test-negative design among individuals aged 12-17 years and SARS-CoV-2-tested between November 22, 2021 (date of first Omicron detection) and March 6, 2022 using methods detailed elsewhere. 1, 2 We assessed Delta outcomes prior to January 2, 2022. We linked and analyzed laboratory, vaccination, reportable disease, and health administrative data for the entire eligible population at ICES. We estimated VE against symptomatic infection and severe outcomes (i.e., hospitalization or death) over time since second or third dose receipt for both Omicron and Delta, which were defined using a combination of whole genome sequencing and S-gene target failure results, and dates (Supplementary Table 1 ). 2 In a sensitivity analysis, we estimated VE against symptomatic Omicron infection before and after restrictions to PCR test eligibility. We used multivariable logistic regression to compare the odds of vaccination in cases to symptomatic test-negative controls and calculated VE as 1-adjusted odds ratio.

ICES is a prescribed entity under Ontario's Personal Health Information Protection Act (PHIPA). Section 45 of PHIPA authorizes ICES to collect personal health information, without consent, for the purpose of analysis or compiling statistical information with respect to the management of, evaluation or monitoring of, the allocation of resources to or planning for all or part of the health system. Projects that use data collected by ICES under section 45 of PHIPA, and use no other data, are exempt from REB review. The use of the data in this project is authorized under section 45 and approved by ICES' Privacy and Legal Office.

We included 9,902 Omicron cases and 502 Delta cases (Supplementary Table 2 ). For the Omicron analyses, 91% of tested subjects had received two doses and 1.3% had received three doses (Supplementary Table 3 ). VE was lower against symptomatic Omicron infection than against Delta and decreased more rapidly over time, from 51% (95%CI, 38-61%) in the 7-59 days following a second dose to 29% (95%CI, 17-38%) after 180 days, compared to 97% (95%CI, 94-99%) and 90% (95%CI, 79-95%) for the same intervals against symptomatic Delta infection (Figure 1, Supplementary Table 4) . Overall, 2-dose VE against severe outcomes due to Omicron was 85% (95%CI, 74-91%) ≥ 7 days following a second dose and estimates were similar over time. Although we were unable to assess 3-dose VE against severe Omicron outcomes or any Delta outcomes due to small numbers, VE against symptomatic Omicron infection was 62% (95%CI, 49-72%) ≥ 7 days following a third dose. Results against symptomatic Omicron infection were similar before and after changes to test eligibility criteria (Supplementary Table 5 and Supplementary Figure 1 ).

VE against symptomatic Omicron infection wanes over time in adolescents given 2-doses of BNT162b2 and was higher following a third dose. While lower than observed against Delta, protection against severe outcomes appears to be maintained over time. The declining VE against infection is similar to results from England, where VE against Omicron and Delta in adolescents aged 16-17 years decreased from 76% and 93% after 7-13 days to 23% and 84% ≥ 70 days post second dose, respectively. 3 In the US, 2-dose VE against Omicron hospitalization for those aged 12-15 and 16-17 years was 92% and 94% after 14-149 days compared to 73% and 88% after ≥ 150 days, respectively. 4 This difference in VE over time since second dose was not statistically significant, whereas declines in VE against emergency department (ED) visits were. VE against ED visits increased following a third dose in those aged 16-17 years. 4 Limitations of this study included an inability to classify some specimens using SGTF or sequencing, changes to test eligibility over the study period, and potential unmeasured confounding between vaccinated and unvaccinated individuals. These results can inform third dose recommendations in adolescents, as 2-dose protection against symptomatic Omicron infection is relatively low and wanes over time, whereas protection of a second dose against severe outcomes is higher. A third dose substantially improves protection against Omicron infection in adolescents, but 3-dose VE is only moderate at approximately 60% in the early period following vaccination and the duration of this protection is unknown. Understanding the impact of a third dose on improved protection against severe outcomes will be important.

The dataset from this study is held securely in coded form at ICES. While legal data sharing agreements between ICES and data providers (e.g., healthcare organizations and government) prohibit ICES from making the dataset publicly available, access may be granted to those who meet pre-specified criteria for confidential access, available at www.ices.on.ca/DAS (email: das@ices.on.ca).

The full dataset creation plan and underlying analytic code are available from the authors upon request, understanding that the computer programs may rely upon coding templates or macros that are unique to ICES and are therefore either inaccessible or may require modification. . 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 April 7, 2022.

Estimates of vaccine effectiveness a against symptomatic infection or severe outcomes (hospitalization or death) caused by Omicron or Delta b during the period of November 22, 2021 to March 6, 2022, by time since latest dose a Vaccine effectiveness estimates adjusted for: age, sex, public health unit region of residence, comorbidities, influenza vaccination status during the 2019/2020 and/or 2020/2021 influenza seasons, positive test >90 days before index date, week of testing, and neighbourhood-level information on median household income, proportion of the working population employed as non-health essential workers, mean number of persons per dwelling, and proportion of the population who self-identify as a visible minority. b Delta outcomes were restricted to January 2, 2022 or prior due to small numbers and limited circulation after that date.

. 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 April 7, 2022. ; WGS: whole genome sequencing; SGTF: S-gene target failure a Delta outcomes were restricted to January 2, 2022 or prior due to small numbers and limited circulation after that date.

. 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 April 7, 2022. Week of test i . 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 April 7, 2022. Percentage of people in the area working in the following occupations: sales and service occupations; trades, transport and equipment operators and related occupations; natural resources, agriculture, and related production occupations; and occupations in manufacturing and utilities. Census counts for people are randomly rounded up or down to the nearest number divisible by 5, which causes some minor imprecision. g Range of persons per dwelling. h Percentage of people in the area who self-identified as a visible minority. Census counts for people are randomly rounded up or down to the nearest number divisible by 5, which causes some minor imprecision. i Delta outcomes were restricted to January 2, 2022 or prior due to small numbers and limited circulation.

. 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 April 7, 2022. . 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 April 7, 2022. ;

Week of test Comorbidities include asthma, diabetes, immunocompromising conditions due to underlying diseases or therapy, autoimmune diseases, active cancer, or pediatric complex chronic conditions. d The sum of counts does not equal the column total because of individuals with missing information (≤1.0%) for this characteristic. e Household income quintile has variable cut-off values in each city/Census area to account for cost of living. A dissemination area (DA) being in quintile 1 means it is among the lowest 20% of DAs in its city by income.

f Percentage of people in the area working in the following occupations: sales and service occupations; trades, transport and equipment operators and related occupations; natural resources, agriculture, and related production occupations; and occupations in manufacturing and utilities. Census counts for people are randomly rounded up or down to the nearest number divisible by 5, which causes some minor imprecision. g Range of persons per dwelling. h Percentage of people in the area who self-identified as a visible minority. Census counts for people are randomly rounded up or down to the nearest number divisible by 5, which causes some minor imprecision.

. 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 April 7, 2022. Household income quintile has variable cut-off values in each city/Census area to account for cost of living. A dissemination area (DA) being in quintile 1 means it is among the lowest 20% of DAs in its city by income.

f Percentage of people in the area working in the following occupations: sales and service occupations; trades, transport and equipment operators and related occupations; natural resources, agriculture, and related production occupations; and occupations in manufacturing and utilities. Census counts for people are randomly rounded up or down to the nearest number divisible by 5, which causes some minor imprecision. g Range of persons per dwelling. h Percentage of people in the area who self-identified as a visible minority. Census counts for people are randomly rounded up or down to the nearest number divisible by 5, which causes some minor imprecision.

. 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 April 7, 2022. ; https://doi.org/10.1101/2022.04.07.22273319 doi: medRxiv preprint Supplementary Figure 1. Estimates of vaccine effectiveness a against symptomatic infection caused by Omicron during the period November 22, 2021 to March 6, 2022, by time since latest dose, before and after PCR testing restrictions a Vaccine effectiveness estimates adjusted for: age, sex, public health unit region of residence, comorbidities, influenza vaccination status during the 2019/2020 and/or 2020/2021 influenza seasons, positive test >90 days before index date, week of testing, and neighbourhood-level information on median household income, proportion of the working population employed as non-health essential workers, mean number of persons per dwelling, and proportion of the population who self-identify as a visible minority.

. 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 April 7, 2022. ; https://doi.org/10.1101/2022.04.07.22273319 doi: medRxiv preprint

Effectiveness of BNT162b2 and mRNA-1273 covid-19 vaccines against symptomatic SARS-CoV-2 infection and severe covid-19 outcomes in Ontario, Canada: test negative design study

Effectiveness of COVID-19 vaccines against Omicron or Delta symptomatic infection and severe outcomes

We would like to acknowledge Public Health Ontario for access to vaccination data from COVaxON, case-level data from CCM and COVID-19 laboratory data, as well as assistance with data interpretation. We also thank the