Background: Although it is known that mortality due to COVID-19 increases progressively with age, the probability of dying from this serious infection among the oldest-old population is little known, and controversial data are found in literature.

Methods: We examine the mortality by year and month of birth of Belgians who had turned 100 during the current COVID-19 pandemic and whose birth fell on the years around the end the First World War and the outbreak of the H1N1 "Spanish flu" pandemic.

Findings: The COVID-19 mortality of the "older" centenarians is significantly lower than that of "younger" centenarians, and this difference between the two groups reaches a maximum on August 1, 1918 as the discriminating cut-off date of birth. Having excluded the plausible impact of the end of WWI it becomes clear that this date corresponds to the time of reporting the first victims of the Spanish flu pandemic in Belgium.

Interpretation: In this study, the striking temporal coincidence between the outbreak of the Spanish flu epidemic and the birth of the cohorts characterized by greater fragility towards COVID-19 in 2020 strongly suggests a link between exposure to 1918 H1N1 pandemic influenza and resistance towards 2020 SARS-Cov-2. It can be speculated that the lifetime persistence of cross-reactive immune mechanisms has enabled centenarians exposed to the Spanish flu to overcome the threat of COVID-19 a century later.