Transmission, pathogenesis and immunogenicity of SARS-CoV-2 in frontline healthcare workers: a national longitudinal cohort of 1320 participants

We want to know how many and which doctors and nurses have been infected with the virus (SARS-Cov2) that causes COVID-19 with or without symptoms. We have been collecting blood from 1320 healthcare workers on a weekly basis during the pandemic. We are analysing blood for antibodies against the virus. We will continue to measure their blood 10 times up to 6 months after the lockdown is lifted.

This study will also allow us to know how the levels of antibodies in blood change over time and which of the antibodies are able to fight the virus. We will investigate whether individual characteristics, including genetics, age, sex, ethnicity, affect the length of time for which antibodies remain in blood at high enough levels to fight the virus.
Among the doctors and nurses in our study we have people who have had a severe infection, others who have had mild symptoms and many with no symptoms. We will put all this information together to work out how healthcare workers develop antibodies against the virus and if this is affected by the severity of the symptoms is important. We will measure proteins and gene expression to identify how to effectively vaccinate and treat healthcare workers.

This multi-disciplinary national consortium seeks to maximise the research impact of a unique resource of 26,000 serial serum samples (16,000 collected) from 1320 healthcare workers (HCWs). Comprising sequential (weekly) serum, and DNA/RNA. This unique cohort provides a rare opportunity for analysis of the genetics and immunology of SARS-Cov2 seroconversion.

The study objectives are to assess:

1) Baseline prior coronavirus exposure, immunity and cross reactivity of antibody assays to other strains
2) Incidence of HCWs seroconversion over time, across sites and the relationship to hospital exposures, and community transmission rates
3) Proportion of seroconverters achieve neutralizing antibodies (Nabs) responses, dual lab validation of Nabs assays, and Nabs potency and durability
4) Effect of HLA haplotypes, severity of symptoms of COVID-19 and levels of T-cell and B-cell activation cytokines to antibody titres and NAbs
5) Antibody titers correlate with severity of illness of SARS-Cov2 infection, baseline antibodies to other human coronavirus types and other demographic factors,

These data answer prioritized research questions surrounding mechanism and severity of disease in high risk cohorts. The results will be used in spatial population modelling work to inform public health policy and vaccination strategies for this and future pandemics. Mechanistic work will characterise anti-spike protein, anti-nucleocapsid, Nabs, Vitamin D, HLA haplotype and immune cell function relationships to symptoms, demographic characteristics and COVID burden in hospitals.

The data generated will provide information to understand the mechanistic basis underpinning the development of lasting humoral immunity to SARS-Cov2 and relationships to known high risk groups.