Stratification of Clinically Vulnerable People for COVID-19 Risk Using Antibody Testing (STRAVINSKY)

Background: Although the COVID-19 vaccination program has proved extraordinarily successful, clinically vulnerable (CV) patients remain at risk of SARS-CoV-2 infection, severe COVID-19 and death. Coordinating large (inter)national studies, we have previously identified patients who make sub-optimal immune responses to COVID-19 vaccines, and those at highest risk of severe COVID-19. Although the precise immune correlates of protection against severe COVID19 are not defined, recent emerging data in patient groups suggests that the serological response to vaccination is a critical determinant in COVID-19 outcomes. Disease cohorts may be particularly informative in defining correlates of protection, as vaccine immune responses are heterogeneous such that correlations of these with disease outcomes is possible. The challenge/aims: Previous government advice to CV patients has recommended shielding, and early, repeat COVID-19 vaccination. The provision of ongoing advice is challenging since robust, evidence describing COVID-19 outcomes following additional boosters, the emergence of omicron variants, and the deployment of bivalent vaccines is lacking. Furthermore, QCOVID (a population study of health care records) has identified additional risk factors that enhance COVID-19 risk, with uncertainty as to whether this relates to vaccine responsiveness. We aim to use SARS-CoV-2 antibody testing to quantify COVID-19 risk, enabling clinicians/DHSC to provide on-going targeted advice over the next two years. Methodology: We will conduct a) a retrospective meta-analysis of existing data with the aim of refining CV groups for future follow up; b) a prospective arm of 3000 CV patients. For the retrospective study, we will collate existing data from national studies, including a minimal dataset of key characteristics and vaccine responsiveness. A meta-analysis will refine those disease groups with reduced or heterogeneous antibody levels compared to healthy controls. Groups with antibody levels comparable to age- and sex-matched healthy controls will be excluded from the prospective study. A multicentre prospective, observational cohort study will assess the predictive value of post COVID-19 vaccine serology in CV patients, including disease groups with baseline low/no antibodies (predicted using existing data, QCOVID4, the report from the Independent Advisory Group for COVID-19 medicines and refined following our retrospective analysis). A healthy control group will be provided by the UKRI funded PITCH2 consortium. Serological responses to bivalent vaccines will be correlated with COVID-19 clinical outcomes after infection with omicron lineage and emerging variants. Participants will be remotely sampled (n=2,600) with dried blood spots posted to a central laboratory, facilitating the recruitment of participants with diverse ethnic and socio-economic status. Additional blood and nasal secretions will be collected in 400 participants for immune assessment should serology fail to predict clinical outcomes. Three follow up visits will capture COVID-19 vaccine responses through to 2024. Significant outputs: We will establish if antibody testing can identify CV individuals at greatest risk of severe COVID-19 infection, and if possible, define serological thresholds for COVID-19 risk. We will improve the understanding of COVID-19 risk in CV individuals to inform future clinical care and guidance.