Background: The most severe forms of COVID-19 are associated with excessive production of proinflammatory cytokines which causes the consequent macrophage activation syndrome[1]. In this regard, the inflammasome, a multiprotein complex that triggers a strong systemic inflammation, influences the clinical outcome of COVID-19[2].

Objectives: To determine whether NLRP1, IL1? and IL18, inflamasome related-genes, constitute severity loci for COVID-19.

Methods: 377 COVID-19 patients with mild (n=72), moderate (n=84), severe (n=100) and critical (n=121) infection were included. Polymorphisms within NLRP1 (rs878329, rs4790797, rs2670660, rs6502867, rs12150220, rs8182532 and rs385076), IL1? (rs1143634 and rs16944) and IL18 (rs187238 and rs194618) were genotyped.

Results: An increase of IL18 CA haplotype frequency in COVID-19 patients with mild infection compared to those with severe and critical infection was disclosed (OR[95% CI]=0.38[0.16-0.91] and 0.41[0.18-0.95], respectively, p<0.05 in all the cases). IL18 GC haplotype frecuency was higher in COVID-19 patients with mild infection than those with severe disease (0.57[0.34-0.97], p<0.05). No differences were found in haplotype frequencies between COVID-19 patients with mild infection and those with moderate, several or critical infection when NLRP1 and IL1? were analyzed. Similar results were observed when genotype and allele frequencies of NLRP1, IL1? and IL18 were evaluated.

Conclusions: IL18 may be involved in the inflammasome signaling that predispose COVID-19 patients to suffer more serious forms of the disease.

References:[1]Annu Rev Med.2023;74:321-337;[2]J Exp Med.2021;218(3):e20201707

Personal funds,VP-C:PI18/00042(ISCIII-ERDF);MSM-G:TRANSVAL22/01(IDIVAL);RL-M: CPII21/00004(ISCIII-ESF).