15 July 2020

This summary document discusses the inclusion of individuals from risk groups into COVID-19 vaccine efficacy trials and some challenges posed. Pregnant women and children are not considered within the scope of this paper. Demonstration of vaccine efficacy in a pandemic situation is time critical so that a potentially efficacious vaccine can be deployed for use during the pandemic. While those included in COVID-19 vaccine efficacy trials should be recruited strategically to demonstrate vaccine efficacy at the earliest possible time, such trials should include adequate representation of those at higher risk of severe disease who are likely to be the initial target population for vaccination post approval.

Risk factors for severe COVID-19 include, but are not limited to, older age, diabetes, obesity, and cardiovascular and pulmonary diseases. Older adults should be appropriately represented, and relaxing trial exclusion criteria to allow inclusion of those with co-morbidities will enable critical data to be obtained to better characterize the benefit-risk profile in those most at risk of severe COVID-19. The challenge for vaccine developers is to balance the risk of disease with the risk of infection. If strict non-pharmaceutical interventions (NPI) including shielding at home, are implemented to protect the most vulnerable individuals from SARS-CoV-2 exposure, those at highest risk of severe disease may be at low risk for infection.

Socioeconomic deprivation is an independent risk factor for both infection and disease. Of all risk factors, socioeconomic deprivation appears least affected by NPIs and is unique in that its relative contribution to COVID-19 mortality has been suggested to increase over time. This risk group is anticipated to remain at high risk of infection due to their social and occupational circumstances. Individuals in this group might be less able to comply with social distancing and shielding policies as they are more likely to live in densely populated areas and larger family units, and are less likely to work from home.

Some groups at high risk of severe COVID-19 disease, including those on immunosuppressive therapy, may need to be excluded from specific trials, such as those using live-attenuated viral vaccines. Considering the theoretical possibility of vaccine-mediated enhanced disease, vulnerable individuals at high risk of severe COVID-19 should only be included in trials if preclinical data show an adequate immune response, including Th1/Th2 balance, and there is sufficient safety data from individuals at lower risk of severe disease.