key: cord-0298923-5zaw2iot
authors: Eyre, D. W.; Taylor, D.; Purver, M.; Chapman, D.; Fowler, T.; Pouwels, K.; Walker, A. S.; Peto, T. E.
title: The impact of SARS-CoV-2 vaccination on Alpha and Delta variant transmission
date: 2021-09-29
journal: nan
DOI: 10.1101/2021.09.28.21264260
sha: cf3f7268d65d43f9f39bc2de0aa87a19fea15911
doc_id: 298923
cord_uid: 5zaw2iot

Background Pre-Delta, vaccination reduced transmission of SARS-CoV-2 from individuals infected despite vaccination, potentially via reducing viral loads. While vaccination still lowers the risk of infection, similar viral loads in vaccinated and unvaccinated individuals infected with Delta question how much vaccination prevents onward transmission. Methods We performed a retrospective observational cohort study of contacts of SARS-CoV-2-infected index cases using contact testing data from England. We used multivariable logistic regression to investigate the impact of index case and contact vaccination on transmission, and how this varies with Alpha and Delta variants (classified using S-gene detection/calendar trends) and time since second vaccination. Results 51,798/139,164(37.2%) contacts tested were PCR-positive. Two doses of BNT162b2 or ChAdOx1 vaccines in Alpha variant index cases independently reduced PCR-positivity in contacts (aOR, adjusted odds ratio vs. unvaccinated=0.18[95%CI 0.12-0.29] and 0.37[0.22-0.63] respectively). The Delta variant attenuated vaccine-associated reductions in transmission: two BNT162b2 doses reduced Delta transmission (aOR=0.35[0.26-0.48]), more than ChAdOx1 (aOR=0.64[0.57-0.72]; heterogeneity p<0.001). Variation in viral load (Ct values) explained only a modest proportion of vaccine-associated transmission reductions. Transmission reductions declined over time since second vaccination, for Delta reaching similar levels to unvaccinated individuals by 12 weeks for ChAdOx1 and attenuating substantially for BNT162b2. Protection from vaccination in contacts also declined in the 3 months after second vaccination. Conclusions Vaccination reduces transmission of Delta, but by less than the Alpha variant. The impact of vaccination decreased over time. Factors other than PCR-measured viral load are important in vaccine-associated transmission reductions. Booster vaccinations may help control transmission together with preventing infections.

ChAdOx1 was less effective than BNT162b2 at preventing transmission after one ( is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint PCR-positivity after household contact with index cases aged ≥30 years and the lowest rates 208 following contact with index cases <20 years at work or education (Figure 2A ). Contacts in 209 their 30s, 40s and 70s had the highest rates of positive tests after household contact, while 210 contacts in their 20s had the highest rates after contact events outside their own home 211 ( Figure 2B ). Contacts of index cases of the opposite sex were more likely to test positive, 212 except for children where contacts of girls were more likely to test positive ( Figure 2C ). Male 213 contacts were more likely than female contacts to be infected outside the home ( Figure S2 ). 214 . CC-BY 4.0 International license It is made available under a perpetuity.

is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted September 29, 2021. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted September 29, 2021. ; https://doi.org/10.1101/2021.09.28.21264260 doi: medRxiv preprint vaccinated, but this needs further study. 262

We found that index cases infected with the Delta variant and vaccinated with BNT162b2 264 had lower odds of having PCR-positive contacts compared to index cases receiving 265 ChAdOx1, with potentially insufficient power to resolve differences for Alpha. Contacts is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint particularly if test-seeking behaviour is related to perceived vaccine efficacy, given non-292 specificity of many symptoms. 24 We did not have sufficient data to consider the impact of 293 previous infection status, which is also imperfectly ascertained in national testing programs. 294

It is likely that part of the explanation for the declines over time in the adjusted probability 295 of contacts testing positive ( Figure S4 ), is increasing prevalence of prior infection in the 296 unvaccinated group, along with changes in test seeking behaviour and the incidence of 297 other infections causing similar symptoms. 25 We also had to use SGTF and time as a proxy 298 for Alpha vs. Delta infection rather than sequencing, which means some low viral load Delta 299 infections with SGTF may have been misclassified as Alpha, however we restricted the time 300 period of our dataset to minimise this. As we considered all PCR results in contacts, not just 301 those tested with assays including an S-gene target, we could not assess SGTF concordance 302 as supporting evidence for transmission between case-contact pairs. Finally, we did not 303 have data to adjust for comorbidities; with clinically vulnerable individuals and healthcare 304 workers vaccinated earlier, this may have partly impacted some of our findings, particularly 305 on waning over time and differences by vaccine type. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted September 29, 2021. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint Figure 3 for trends with 407 time post-second vaccine. aOR, adjusted odds ratio, CI confidence interval. Adjustment made for contact event type; index case factors -age, 408 sex, and symptom status; contact factors -age, sex; local deprivation, local SARS-CoV-2 incidence and calendar time (see Table S4 is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted September 29, 2021. ; https://doi.org/10.1101/2021.09.28.21264260 doi: medRxiv preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted September 29, 2021. ; https://doi.org/10.1101/2021.09.28.21264260 doi: medRxiv preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted September 29, 2021. ; https://doi.org/10.1101/2021.09.28.21264260 doi: medRxiv preprint

14,066;10%), at events and activities (14,270;10%) and at work/education (13

Household Transmission of SARS-CoV-2 in England

Impact of BNT162b2 vaccination and isolation on 356

SARS-CoV-2 transmission in Israeli households: an observational study

Vaccination with BNT162b2 reduces 359 transmission of SARS-CoV-2 to household contacts in Israel

The indirect effect of mRNA-based Covid-19

Initial report of decreased SARS-CoV-2 viral 364 load after inoculation with the BNT162b2 vaccine

Transmission of COVID-19 in 282 clusters in 366

Spain: a cohort study

SARS-CoV-2 infectivity by viral load

Kinetics of SARS-CoV-2 Delta (B.1.617.2)Variant in Vaccinated and Unvaccinated Individuals

Virological and serological kinetics of SARS-CoV-2

Delta variant vaccine-breakthrough infections: a multi-center cohort study

SARS-CoV-2 variants of concern and variants under investigation 381 in England: Technical briefing 21

Basic principles of test-negative design in evaluating influenza 385 vaccine effectiveness

Understanding cycle threshold (Ct) in SARS-CoV-2 RT-PCR