key: cord-0991961-y203109o
authors: Gray, G. E.; COLLIE, S.; Garrett, N.; Goga, A.; Champion, J.; Zylstra, M.; Reddy, T.; Yende, N.; Seocharan, I.; Takalani, A.; Sanne, I.; Mayat, F.; Odhiambo, J.; Bamford, L.; Moultrie, H.; Fairall, L.; Bekker, L.-G.
title: Vaccine effectiveness against hospital admission in South African health care workers who received a homologous booster of Ad26.COV2 during an Omicron COVID19 wave: Preliminary Results of the Sisonke 2 Study.
date: 2021-12-29
journal: nan
DOI: 10.1101/2021.12.28.21268436
sha: c5c5f39ab9adf11bff56553e12eb43c7dc60f033
doc_id: 991961
cord_uid: y203109o

Following the results of the ENSEMBLE 2 study, which demonstrated improved vaccine efficacy of a two-dose regimen of Ad26.COV.2 vaccine given 2 months apart, we expanded the Sisonke study which had provided single dose Ad26.COV.2 vaccine to almost 500 000 health care workers (HCW) in South Africa to include a booster dose of the Ad26.COV.2. Sisonke 2 enrolled 227 310 HCW from the 8 November to the 17 December 2021. Enrolment commenced before the onset of the Omicron driven fourth wave in South Africa affording us an opportunity to evaluate early VE in preventing hospital admissions of a homologous boost of the Ad26.COV.2 vaccine given 6-9 months after the initial vaccination in HCW. We estimated vaccine effectiveness (VE) of the Ad26.COV2.S vaccine booster in 69 092 HCW as compared to unvaccinated individuals enrolled in the same managed care organization using a test negative design. We compared VE against COVID19 admission for omicron during the period 15 November to 20 December 2021. After adjusting for confounders, we observed that VE for hospitalisation increased over time since booster dose, from 63% (95%CI 31-81%); to 84% (95% CI 67-92%) and then 85% (95% CI: 54-95%), 0-13 days, 14-27 days, and 1-2 months post-boost. We provide the first evidence of the effectiveness of a homologous Ad26.COV.2 vaccine boost given 6-9 months after the initial single vaccination series during a period of omicron variant circulation. This data is important given the increased reliance on the Ad26.COV.2 vaccine in Africa.

South Africa is in the middle of a fourth wave of the COVID19 pandemic, driven by Omicron, a new variant of concern that emerged in early November 2021, and has spread rapidly across the world. [1] [2] [3] [4] [5] Both in-vitro experiments and epidemiological data suggest that Omicron may reduce vaccine effectiveness (VE). [6] [7] [8] When the South African national vaccine roll-out faltered in We applied a test-negative design and data exclusion rules to obtain VE estimates 12 . Vaccine effectiveness estimates were obtained from the following formula: 1-odds of COVID19 admission amongst the vaccinated population, where the odds ratio was calculated using logistic regression, and adjusting for confounders of age (18-29, then 10-year age bands and then age 80+), sex, number of documented CDC risk factors (0,1,2,3+), surveillance week, period of prior documented infection (D614G:2020/03/01-2020/10/31, Beta:2020/11/01-2021/05/16, and Delta: 2021/05/17-2021/10/31), and geographic region (province). COVID19 related admission was a dependent variable, while vaccination status was included as an independent variable.

Vaccination status was analyzed in the following categories: not vaccinated; 0-6, 7-13, 14-27 days, and 1 to 2 months since second dose vaccination for Ad26. test results a random selection of three of those results were included. Finally, indeterminate test results, and test results for individuals younger than age 18 years were also excluded. We performed a sensitivity analysis using only COVID19 PCR results within the Gauteng province, given the geographical concentration of the Omicron variant in that province over the study period. Calculations were performed using R version 4.1.1

After adjusting for confounders, we observed that VE for hospitalisation increased over time since booster dose, from 63% (95%CI 31-81%); to 84% (95% CI 67-92%) and then 85% (95% CI: 54-95%), 0-13 days, 14-27 days, and 1-2 months post-boost (Table 2) . Preliminary data emanating from pseudovirus neutralization assays have shown the ability of Omicron to escape antibody neutralization after a single dose Ad26.COV.2 vaccine (Penny Moore, personal communication), thereby raising concerns about the impact that this variant will have on VE.

Our data demonstrates that a homologous boost given to HCW 6-9 months after the initial Ad26.COV.2 vaccine is protective against hospital admissions.

Our analysis has several limitations: overall follow up was short for Ad26.COV.2 vaccine boosts-median follow up since the boost was 8 days (IQR 5-11) for HCW (n=1 799) who received their boost within 0-13 days; 20 days (IQR 17-24) for those 14-27 days post boost (n= 2 514) and 32 days (IQR 29-34) for those who had been boosted for 1-2 months (n=823) which 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.

The copyright holder for this this version posted December 29, 2021. ; https://doi.org/10.1101/2021.12.28.21268436 doi: medRxiv preprint could impact overall VE. Omicron dominance was also increasing around the country over this time but started from a low Delta variant base in Gauteng and quickly became the dominant variant in that province and around the country, and as such similar results in Gauteng are reassuring; in addition, as we did not have access to the national EVDS some of the control individuals after late August may have been vaccinated leading to a potential underestimation of VE.

We provide the first evidence of the effectiveness of a homologous Ad26.COV.2 vaccine boost given 6-9 months after the initial single vaccination series during a period of omicron variant circulation. We have demonstrated that VE for hospital admissions increased over time up to at least 1-2 months post-boost. This increase in VE is consistent with other studies that have evaluated the Ad26COV.2 vaccine, showing consistency in protection against severe disease over time, indicative that protection against severe disease may be due to cellular immunity and immune memory rather than neutralizing antibodies 9,11,12 . This data is important given the increased reliance on the Ad26.COV.2 vaccine in Africa. and Abeda Williams from Janssen, Johnson and Johnson who facilitated and provided the investigational product. We also wish to acknowledge our regulator, SAHPRA as well as the Health Research Ethics Committees who provided guidance and oversight. 

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. 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.

The copyright holder for this this version posted December 29, 2021. ; https://doi.org/10.1101/2021.12.28.21268436 doi: medRxiv preprint

How South African Researchers Identified the Omicron Variant of COVID. The New Yorker

Heavily mutated Omicron variant puts scientists on alert. Nature Magazine. 2021

Classification of Omicron (B.1.1.529): SARS-CoV-2 Variant of Concern

Omicron strain spreads with the doubling time of 3.2-3.6 days in South Africa province of Gauteng that achieved herd immunity to Delta variant

Here's what Omicron can tell us about how COVID-19 variants are discovered

Omicron likely to weaken COVID vaccine protection

Reduced Neutralization of SARS-CoV-2

Omicron Variant by

SARS-CoV-2 Omicron has extensive but incomplete escape of Pfizer BNT162b2 elicited neutralization and requires ACE2 for infection

Total Tests between 15 November and 20 December 2021 for J&J dose 2 and unvaccinated population

The authors wish to thank the Health Care Workers who participated in the Sisonke Study.Appreciation to the clinical research site investigators, the study staff and teams and the support staff at the SAMRC. We are deeply grateful for the assistance of Paul Stoffels, Johan van Hoof