The closer to the Europe Union headquarters, the higher risk of COVID-19? Cautions regarding ecological studies of COVID-19

Several ecological studies of the coronavirus disease 2019 (COVID-19) have reported correlations between group-level aggregated exposures and COVID-19 outcomes. While some studies might be helpful in generating new hypotheses related to COVID-19, results of such type of studies should be interpreted with cautions. To illustrate how ecological studies and results could be biased, we conducted an ecological study of COVID-19 outcomes and the distance to Brussels using European country-level data. We found that, the distance was negatively correlated with COVID-19 outcomes; every 100 km away from Brussels was associated with approximately 6% to 17% reductions (all P<0.01) in COVID-19 cases and deaths in Europe. Without cautions, such results could be interpreted as the closer to the Europe Union headquarters, the higher risk of COVID-19 in Europe. However, these results are more likely to reflect the differences in the timing of and the responding to the outbreak, etc . between European countries, rather than the ‘effect’ of the distance to Brussels itself. Associations observed at the group level have limitations to reflect individual-level associations – the so-called ecological fallacy. Given the public concern over COVID-19, ecological studies should be conducted and interpreted with great cautions, in case the results would be mistakenly understood.