Lung expression of genes encoding SARS-CoV-2 cell entry molecules and antiviral restriction factors: interindividual differences are associated with age and germline variants

Germline variants in genes involved in SARS-CoV-2 cell entry (i.e.ACE2andTMPRSS2) may influence the susceptibility to infection, as may polymorphisms in genes involved in the innate host response to viruses (e.g. APOBEC3 family). We searched for polymorphisms acting, in lung tissue, as expression quantitative trait loci (eQTLs) for 15 candidate COVID-19 susceptibility genes, selected for their roles in virus cell entry and host antiviral responses. No significant eQTLs were identified forACE2andTMPRSS2genes, whose expression levels did not associate with either sex or age of the 408 patients whose non-diseased lung tissue was analyzed. Instead, we identified sevencis-eQTLs (FDR<0.05) forAPOBEC3DandAPOBEC3G(rs139296, rs9611092, rs139331, rs8177832, rs17537581, rs61362448, and rs738469). The genetic control of the expression of APOBEC3 genes, which encode enzymes that interfere with virus replication, may explain interindividual differences in risk or severity of viral infections. Future studies should investigate the role of host genetics in COVID-19 patients using a genome-wide approach, to identify other genes whose expression levels are associated with susceptibility to SARS-CoV-2 infection or COVID-19 severity.