effectiveness of bnt162b2 and chadox1 against sars cov 2 household transmission CORD-Papers-2022-06-02 (Version 1)

Title: Effectiveness of BNT162b2 and ChAdOx1 against SARS-CoV-2 household transmission - a prospective cohort study in England
Abstract: Background: The ability of SARS-CoV-2 vaccines to protect against infection and onward transmission determines whether immunisation can control global circulation. We estimated effectiveness of BNT162b2 and ChAdOx1 vaccines against acquisition and transmission of the Alpha and Delta variants in a prospective household study in England. Methods: Adult index cases in the community and their household contacts took oral-nasal swabs on days 1 3 and 7 after enrolment. Swabs were tested by RT-qPCR with genomic sequencing conducted on a subset. We used Bayesian logistic regression to infer vaccine effectiveness against acquisition and transmission adjusted for age vaccination history and variant. Findings: Between 2 February 2021 and 10 September 2021 213 index cases and 312 contacts were followed up. After excluding households lacking genomic proximity (N=2) or with unlikely serial intervals (N=16) 195 households with 278 contacts remained of whom 113 (41%) became PCR positive. Delta lineages were 4.6 times (95% Credible Interval: 1.5 - 20.1) more transmissible than Alpha; contacts older than 18 years were 2.0 times (1.4 - 3.3) more likely to acquire infection than children. Effectiveness of two doses of BNT162b2 against transmission of Delta was 31% (-3% 61%) and 42% (14% 69%) for ChAdOx1 similar to their effectiveness for Alpha. Protection against infection with Alpha was higher than for Delta 71% (12%95%) vs 24% (-2% 64%) respectively for BNT162b2 and 26% (-39% 73%) vs 14% (-5% 46%) respectively for ChAdOx1. Interpretation: BNT162b2 and ChAdOx1 reduce transmission of the Delta variant from breakthrough infections in the household setting though their protection against infection is low. Funding: This study was funded by the UK Health Security Agency (formerly Public Health England) as part of the COVID-19 response.
Published: 2021-11-24
DOI: 10.1101/2021.11.24.21266401
DOI_URL: http://doi.org/10.1101/2021.11.24.21266401
Author Name: Clifford S
Author link: https://covid19-data.nist.gov/pid/rest/local/author/clifford_s
Author Name: Waight P
Author link: https://covid19-data.nist.gov/pid/rest/local/author/waight_p
Author Name: Hackman J
Author link: https://covid19-data.nist.gov/pid/rest/local/author/hackman_j
Author Name: Hue S
Author link: https://covid19-data.nist.gov/pid/rest/local/author/hue_s
Author Name: Gower C M
Author link: https://covid19-data.nist.gov/pid/rest/local/author/gower_c_m
Author Name: Kirsebom F C
Author link: https://covid19-data.nist.gov/pid/rest/local/author/kirsebom_f_c
Author Name: Skarnes C
Author link: https://covid19-data.nist.gov/pid/rest/local/author/skarnes_c
Author Name: Letley L
Author link: https://covid19-data.nist.gov/pid/rest/local/author/letley_l
Author Name: Lopez Bernal J
Author link: https://covid19-data.nist.gov/pid/rest/local/author/lopez_bernal_j
Author Name: Andrews N
Author link: https://covid19-data.nist.gov/pid/rest/local/author/andrews_n
Author Name: Flasche S
Author link: https://covid19-data.nist.gov/pid/rest/local/author/flasche_s
Author Name: Miller E
Author link: https://covid19-data.nist.gov/pid/rest/local/author/miller_e
sha: 4b4f7ed61dd78894b167196805b6a8862efbfdc2
license: medrxiv
source_x: MedRxiv; WHO
source_x_url: https://www.who.int/
url: http://medrxiv.org/cgi/content/short/2021.11.24.21266401v1?rss=1 https://doi.org/10.1101/2021.11.24.21266401
has_full_text: TRUE
Keywords Extracted from Text Content: https://github.com/cmmid/hhSAR appendix HH007 non-household Delta HH003 BNT16b2 BNT162b2 286 UK HH006 SARS-CoV-2 ChAdOx1 Alpha UKHSA ChadOx1 adult contacts Oral Pillar 2 275 children medRxiv preprint after 2 BNT162b2 Pillar 2 medRxiv Vaccine Figure A4 UK Health Security Agency
Extracted Text Content in Record: First 5000 Characters:Introduction 38 secondary attack rates (SARs). For such the SARs were sampled during the MCMC sampling, for 107 each combination of variant and case and contact vaccine status (1 or 2 doses for each product) 108 and age group, against a baseline of that case-contact pair and variant in the absence of any 109 vaccination. 110 Lineage 111 cases and contacts, with pseudo-absences generated to simulate the time of infecting exposure. 135 Comparison is made for each combination of vaccine product, number of doses, and variant 136 against the corresponding unvaccinated group. Details of this modelling can be found in the 137 Identification of non-household transmission 139 As per the study design, the index case for each household was by default considered to be the 140 individual who presented for Pillar 2 testing. To reduce the risk of misclassification bias we 141 excluded from the analyses all households where both the index case and an infected household 142 contact were symptomatic and the index case's symptoms appeared more than two days after the 143 contact's symptoms. 144 To further reduce the potential for misclassification bias, a phylogenetic approach was used to 145 identify apparent secondary cases in the household who were in fact infected elsewhere. If none 146 of the sequences from a contact clustered with at least one of the sequences from the household's 147 index case, then this was considered as evidence for an infection acquired outside of the 148 household; therefore, the contact was excluded from the downstream analysis. Details of the 149 phylogenetic approach can be found in the Appendix. 150 Role of funding source 151 The study sponsors had no role in the collection, analysis, and interpretation of data; in the 152 writing of the report; and in the decision to submit the paper for publication 153 By September 10th, 2021, a total of 213 index cases and 312 contacts had been recruited and met 155 the criteria for inclusion at that time. Two contacts were removed due to lack of genomic 156 proximity (outlined below), which resulted in the removal of each of their households as there The phylogeny provided evidence that in two households the contact of the recruited index case 195 had acquired infection elsewhere (Figure 1 , households HH002 and HH007). Five households 196 that did not form unique clusters in the phylogeny did not meet the exclusion criteria: in two a 197 sequence from an index case did not cluster with the remaining household sequences but another 198 sequence from the same index case did (HH004 and HH006) while the other three households 199 did not have sufficient bootstrap support to be a part of a cluster (HH001, HH003, and 200 HH005). Of the remaining households, 72 (91%), formed unique, household-specific clusters 201 All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Either one or two doses of BNT162b2 provide a protective effect against infection from a 213 symptomatic index case with Alpha variant SARS-CoV-2 with a vaccine effectiveness of 53%, 214 (95% credible interval: 7%, 83%) and 71% (95% CrI: 12%, 95%), respectively (Table 1, Figure A4 ). against infection with the Delta variant was lower than against Alpha and was similar to the 217 effectiveness offered by ChAdOx1 to either variant (Table A5 ) which, after two doses, had 218 effectiveness against Alpha of 26% (-39%, 73%) and against Delta of 14% (-5%, 46%). 219 We estimate that the effectiveness of one and two doses of BNT162b2 against onward 220 transmission if infected with the Alpha variant was 26% (-11%, 54%) and 57% (5%, 85%) and for 221 Delta variant one and two doses reduce transmission by 9% (-16%, 49%) and 37% (4%, 65%). RRs 222 for the protective effect of BNT162b2 over ChAdOx1 for one and two doses of against both 223 Alpha and Delta variants indicate that at 95% credibility there is no difference between the 224 effectiveness of the two vaccine products (Table A5) . Specifically, two doses of ChAdOx1 reduce 225 transmission from an Alpha variant case by 35% (-26%, 74%) and from a Delta variant case by 226 42% (14%, 69%). 227 Table 1 : Median vaccine effectiveness (VE) and 95% credible intervals for infection protection 228 All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. has an SAR of 30% (13%, 57%). SARs for each combination of contact and case age, vaccine 245 history and variant lineage are given in the appendix (Figures A5, A6) . Notably, the reduced 246 susceptibility to infection of (unvaccinated) under-18s results in SARs which are no greater
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