A common variant close to the “tripwire” linker region of NLRP1 contributes to severe COVID-19

Objective and design The heterogeneity of response to SARS-CoV-2 infection is directly linked to the individual genetic background. Genetic variants of inflammasome-related genes have been pointed as risk factors for several inflammatory sterile and infectious disease. In the group of inflammasome receptors, NLRP1 stands out as a good novel candidate as severity factor for COVID-19 disease. Methods To address this question, we performed an association study of NLRP1 , DPP9 , CARD8 , IL1B , and IL18 single nucleotide variants (SNVs) in a cohort of 945 COVID-19 patients. Results The NLRP1 p.Leu155His in the linker region, target of viral protease, was significantly associated to COVID-19 severity, which could contribute to the excessive cytokine release reported in severe cases. Conclusion Inflammasome genetic background contributes to individual response to SARS-CoV-2.