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INFLAMMASOME GENETIC VARIANTS ARE ASSOCIATED WITH PROTECTION TO CLINICAL SEVERITY OF COVID-19 AMONG PATIENTS FROM RIO DE JANEIRO, BRAZIL
Variantes genéticas do inflamassoma
Proteção
Gravidade clínica
Pacientes
Rio de Janeiro
Inflammasome Genetic Variants
Protection
Clinical Severity of COVID-19
Patients
Rio de Janeiro, Brazil
Author
Affilliation
Abstract
COVID-19 has a broad spectrum of clinical manifestations, from asymptomatic or mild/moderate symptoms to severe symptoms
and death. The mechanisms underlying its clinical evolution are still unclear. Upon SARS-CoV-2 infection, host factors, such as
the inflammasome system, are activated by the presence of the virus inside host cells. The search for COVID-19 risk factors is of
relevance for clinical management. In this study, we investigated the impact of inflammasome single-nucleotide polymorphisms
(SNPs) in SARS-CoV-2-infected individuals with distinct severity profiles at clinical presentation. Patients were divided into two
groups according to disease severity at clinical presentation based on the WHO Clinical Progression Scale. Group 1 included
patients with mild/moderate disease (WHO< 6; n = 76), and group 2 included patients with severe/critical COVID-19
(WHO≥ 6; n = 357). Inpatients with moderate to severe/critical profiles were recruited and followed-up at Hospital Center for
COVID-19 Pandemic – National Institute of Infectology (INI)/FIOCRUZ, RJ, Brazil, from June 2020 to March 2021. Patients
with mild disease were recruited at Oswaldo Cruz Institute (IOC)/FIOCRUZ, RJ, Brazil, in August 2020. Genotyping of 11
inflammasome SNPs was determined by real-time PCR. Protection and risk estimation were performed using unconditional
logistic regression models. Significant differences in NLRP3 rs1539019 and CARD8 rs2043211 were observed between the two
groups. Protection against disease severity was associated with the A/A genotype (ORadj = 0:36; P = 0:032), allele A
(ORadj = 0:93; P = 0:010), or carrier-A (ORadj = 0:45; P = 0:027) in the NLRP3 rs1539019 polymorphism; A/T genotype
(ORadj = 0:5; P = 0:045), allele T (ORadj = 0:93; P = 0:018), or carrier-T (ORadj = 0:48; P = 0:029) in the CARD8 rs2043211
polymorphism; and the A-C-G-C-C (ORadj = 0:11; P = 0:018), A-C-G-C-G (ORadj = 0:23; P = 0:003), C-C-G-C-C (ORadj = 0:37;
P = 0:021), and C-T-G-A-C (ORadj = 0:04; P = 0:0473) in NLRP3 genetic haplotype variants. No significant associations were
observed for the other polymorphisms. To the best of our knowledge, this is the first study demonstrating an association
between CARD8 and NLRP3 inflammasome genetic variants and protection against COVID-19 severity, contributing to the
discussion of the impact of inflammasomes on COVID-19 outcomes.
Keywords in Portuguese
COVID-19Variantes genéticas do inflamassoma
Proteção
Gravidade clínica
Pacientes
Rio de Janeiro
Keywords
COVID-19Inflammasome Genetic Variants
Protection
Clinical Severity of COVID-19
Patients
Rio de Janeiro, Brazil
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