Baseline transmission of target pathogen in population (i.e., exposure) and its seasonality | Known | Rapidly changing; seasonality unknown | Social distancing and other public health interventions | Flexible trial designs to ensure adequate numbers of end points (infections or hospital admissions); determination of potential confounding by nonvaccine prevention measures |
Population level of pre-existing immunity to target pathogen (i.e., susceptibility) | Known | Rapidly changing | Paucity of seroepidemiologic data; accuracy of serologic tests; unclear extent and duration of protection from natural immunity | Baseline serologic testing of participants in efficacy trials |
Differential susceptibility of subpopulations to infection or disease | Known | Emerging | Numerous risk factors identified, but older adults at highest risk of severe disease; young children rarely have complications and may be less susceptible to infection; antibody-dependent enhancement | Evaluation of vaccine efficacy and end points in older adults and other high-risk groups; close monitoring and prolonged follow-up for possible antibody-dependent enhancement in all trials |