To test whether genetic factors that may alter the function of nucleases are involved in the impaired NET degradation observed in pediatric COVID-19, we performed whole-genome sequencing association analysis (WGS) within a subset of patients and conducted variant association analysis for genes encoding enzymes or molecules involved in DNA degradation (DNASE1, DNASE1L3, DNASE1L1, DNASE1L2, DNASE2B, SERPINB1, three prime repair exonuclease 1 [TREX1], and TREX2). This evidence concerns the gene SERPINB1 and COVID-19.