Severity of omicron variant of concern and effectiveness of vaccine boosters against symptomatic disease in Scotland (EAVE II): a national cohort study with nested test-negative design

Aziz Sheikh* (Corresponding Author), Steven Kerr, Mark Woolhouse, Jim McMenamin, Chris Robertson, EAVE II Collaborators, Colin Richard Simpson, Tristan Millington, Ting Shi, Utkarsh Agrawal, Safraj Shahul Hameed, Elliott Hall, Igor Rudan, Syed Ahmar Shah, Lewis Ritchie, Sarah Stock, Colin McCowan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

106 Citations (Scopus)
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Summary Background Since its emergence in November, 2021, in southern Africa, the SARS-CoV-2 omicron variant of concern (VOC) has rapidly spread across the world. We aimed to investigate the severity of omicron and the extent to which booster vaccines are effective in preventing symptomatic infection. Methods In this study, using the Scotland-wide Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) platform, we did a cohort analysis with a nested test-negative design incident case-control study covering the period Nov 1–Dec 19, 2021, to provide initial estimates of omicron severity and the effectiveness of vaccine boosters against symptomatic disease relative to 25 weeks or more after the second vaccine dose. Primary care data derived from 940 general practices across Scotland were linked to laboratory data and hospital admission data. We compared outcomes between infection with the delta VOC (defined as S-gene positive) and the omicron VOC (defined as S-gene negative). We assessed effectiveness against symptomatic SARS-CoV-2 infection, with infection confirmed through a positive RT-PCR. Findings By Dec 19, 2021, there were 23 840 S-gene-negative cases in Scotland, which were predominantly among those aged 20–39 years (11 732 [49·2%]). The proportion of S-gene-negative cases that were possible reinfections was more than ten times that of S-gene-positive cases (7·6% vs 0·7%; p
Original languageEnglish
Pages (from-to)959-966
Number of pages8
JournalThe Lancet Infectious Diseases
Issue number7
Early online date22 Jun 2022
Publication statusPublished - Jul 2022

Bibliographical note

This study is part of the EAVE II project. EAVE II is funded by the MRC (MC_PC_19075) with the support of BREATHE—The Health Data Research Hub for Respiratory Health (MC_PC_19004), which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. This research is part of the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (MC_PC_20058). Additional support has been provided through Public Health Scotland, the Scottish Government Director General Health and Social Care, and the University of Edinburgh. The original EAVE project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme (11/46/23). The views expressed are those of the authors and not necessarily those of the NIHR, the Department of Health and Social Care, or the UK Government. We thank Dave Kelly from Albasoft (Inverness, UK) for his support with making primary care data available, and Wendy Inglis-Humphrey, Vicky Hammersley, and Laura Brook (University of Edinburgh, Edinburgh, UK) for their support with project management and administration.

Data Availability Statement

A data dictionary covering the datasets used in this study can be found at All code used in this study is publicly available at The data used to undertake this analysis are not publicly available because they are based on deidentified national clinical records. These data are available, subject to approval by the NHS Scotland Public Benefit and Privacy Panel, by application through the Scotland National Safe Haven (


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