In contrast, SP family (SPI1, adjusted P = 1 × 10−320; SPIB1, adjusted P = 1 × 10−295), CEBP family (CEBPD, adjusted P = 1 × 10−270; CEBPE, adjusted P = 1 × 10−248) and AP2 family (JUN, adjusted P = 1 × 10−101; FOS, adjusted P = 1 × 10−51) motifs are prominently more activated in severe COVID-19 risk variant-enriched cells. Here, SPI1 is linked to COVID-19.