A genomewide association study involving 1980 patients with Covid-19 and severe disease (defined as respiratory failure) has been conducted at seven hospitals in the Italian and Spanish epicenters of the SARS-CoV-2 pandemic in Europe.

The study detected cross-replicating associations with rs11385942 at locus 3p21.31 and with rs657152 at locus 9q34.2, which were significant at the genomewide level in the meta-analysis of the two case–control panels.

The association signal at locus 3p21.31 comprised six genes (SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6, and XCR1). The risk allele GA of rs11385942 is associated with reduced expression of CXCR6 and increased expression of SLC6A20, and LZTFL1 is strongly expressed in human lung cells. It found that the frequency of the risk allele of the lead variant at 3p21.31 (rs11385942) was higher among patients who received mechanical ventilation than among those who received oxygen supplementation only in both the main meta-analysis.

At locus 9q34.2 the association signal coincided with the ABO blood group locus. There is a higher risk among persons with blood group A than among patients with other blood groups and a protective effect for blood group O as compared with the other blood groups.