We identified for the first time a protective subset of LDNs with high expression of PI3. PI3 is a serine proteinase inhibitor targeting proteinase 3 that participates in tissue injury.38 PI3 has also been reported to reduce the amounts of active IL-1β from extracellular pro-IL-1β cleaved by proteinase 3.39 Single nucleotide polymorphisms (SNPs) in the PI3 gene or low PI3 plasma levels show an association with the increased risk of ARDS,27,40 suggesting that PI3 can play a protective role in controlling the progression of COVID-19. This evidence concerns the gene IL1B and COVID-19.