Inflammasome genes polymorphisms are associated with progression to mechanical ventilation and death in a cohort of hospitalized COVID-19 patients in a reference hospital in Rio de Janeiro, Brazil

• Published in: Gene Vol. 865; p. 147325
• Main Authors: Neira-Goulart, Milena, de Sá, Nathalia Beatriz Ramos, Ribeiro-Alves, Marcelo, Perazzo, Hugo, Geraldo, Kim Mattos, Ribeiro, Maria Pia Diniz, Cardoso, Sandra Wagner, Grinsztejn, Beatriz, Veloso, Valdiléa G., Rodrigues Gomes, Larissa, Cazote, Andressa da Silva, de Almeida, Dalziza Victalina, Giacoia-Gripp, Carmem Beatriz Wagner, Côrtes, Fernanda Heloise, Morgado, Mariza Gonçalves
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 20-05-2023
• Subjects: Brazil - epidemiology; CARD Signaling Adaptor Proteins - genetics; COVID-19; COVID-19 - genetics; Genetic Predisposition to Disease; Genotype; Humans; Inflammasome single nucleotide polymorphisms (SNPs); Inflammasomes - genetics; Neoplasm Proteins - genetics; NLR Family, Pyrin Domain-Containing 3 Protein - genetics; Polymorphism, Single Nucleotide; Respiration, Artificial; Risk factors; Brazil; NF-kB; TMPRSS2; HR; MVS; IL-23; SAPS-III; Risk factors; COVID-19; CASP-1; PRR; SARS-CoV-2; MCP1; IFI16; SNPs; NLRP3; Th17; ARDS; WHO; IFNγ; CARD8; Inflammasome single nucleotide polymorphisms (SNPs); IL-4; IL-1β; IP-10; IL-1α; IL-6; ACE2; SOFA; AIM2; GSDM-D; DNA; IL-18; TLR7; CFTR; TLR3; TLRs; COPD
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2023.147325

•Inflammasome genetic variations influence the critical clinical course of COVID-19.•Carrying C allele of the NLRP3 rs10754558 variant increases progression to death.•NLRP3 ATGAG haplotype was associated with faster progression to MVS use or death.•Several NLRP3 haplotypes are associated with increased risk to death.
COVID-19 has a broad spectrum of clinical manifestations. We assessed the impact of single nucleotide polymorphisms (SNPs) of inflammasome genesas risk factors for progression toCOVID-19 critical outcomes, such as mechanical ventilation support (MVS) or death.The study included 451 hospitalized individuals followed up at the INI/FIOCRUZ, Rio de Janeiro, Brazil, from 06/2020 to 03/2021. SNPs genotyping was determined by Real-Time PCR. We analyzed risk factors for progression to MVS (n = 174[38.6 %]) or death (n = 175[38.8 %])as a result of COVID-19 by Cox proportional hazardmodels.Slower progression toMVSwas associated with allele G (aHR = 0.66;P = 0.005) or the genotype G/G (aHR = 0.391;P = 0.006) in the NLRP3 rs10754558 or the allele G (aHR = 0.309;P = 0.004) in the IL1βrs1143634, while C allele in the NLRP3 rs4612666 (aHR = 2.342;P = 0.006) or in the rs10754558 (aHR = 2.957;P = 0.005) were associated with faster progression to death. Slower progression to death was associated to allele G (aHR = 0.563;P = 0.006) or the genotype A/G (aHR = 0.537;P = 0.005) in the CARD8 rs6509365; the genotype A/C in the IFI16 rs1101996 (aHR = 0.569;P = 0.011); the genotype T/T (aHR = 0.394;P = 0.004) or allele T (aHR = 0.68;P = 0.006) in the NLRP3 rs4612666, and the genotype G/G (aHR = 0.326;P = 0.005) or allele G (aHR = 0,68;P = 0.014) in the NLRP3 rs10754558. Our results suggest that inflammasome genetic variations might influence the critical clinical course of COVID-19.