COVID-19 vaccine effectiveness against symptomatic SARS-CoV-2 infection and severe COVID-19 outcomes from Delta AY.4.2: Cohort and test-negative study of million individuals in Scotland

Abstract

The AY.4.2 variant, commonly known as “Delta plus”, is a sub-lineage of the Delta variant of concern (VOC). The first case of AY.4.2 confirmed by viral sequencing in Scotland occurred on June 8, 2021. By the week of October 18 to October 24, 2021, AY.4.2 was present in 11.3% of Delta cases in the UK [1]. As of October 25, 2021, AY.4.2 sequences had been uploaded to the Global initiative on sharing avian influenza data from 42 countries [2]. There was a total of 121 111 confirmed AY.4.2 cases in the UK by January 19, 2022 [3]. The rapid increase in the proportion of cases due to the AY.4.2 variant led the UK Health and Security Agency to designate it as a variant under investigation on October 20, 2021 [1]. There has been significant policy-making interest in the virulence of the AY.4.2 variant, as well as the effectiveness of existing vaccines against it. We aimed to investigate vaccine effectiveness (VE) against infection and hospitalisation/death due to the AY.4.2 variant. We are not aware of any other studies investigating this topic. We used the Scotland-wide Early Pandemic Evaluation and Enhanced Surveillance (EAVE-II) platform, which consists of linked primary care, secondary care, mortality, virological sequencing, and coronavirus disease 2019 (COVID-19) testing data for the population of Scotland. We carried out a test-negative design (TND) study of VE against symptomatic infection with AY.4.2. One of the main confounders in studies of this type is that propensity to be tested for COVID-19 may vary by vaccination status. The TND seeks to control for this by matching positive-testing individuals with negative-testing individuals. We also carried out a cohort study of VE against a composite outcome of COVID-19 hospitalisation or death using a Cox proportional hazards model. To isolate hospital admissions due to COVID-19 rather than with COVID-19, we restricted to individuals who tested positive in the community and were not in a hospital at the time of the test, and whose hospital admission was classed as an emergency.