Estudo dos polimorfismos nos genes das citocinas IL1β, IL6, IL18 e do inflamassoma NLRP1 e NLRP3 em pacientes convalescentes da covid- 19 e pacientes com diagnóstico de covid-19 no estado do Amazonas, Brasil

Abstract

Infection with the SARS-CoV-2 virus, known as coronavirus, can result in an asymptomatic condition, when the individual does not present clinical manifestations, or a clinical condition that can range from mild to serious complications. The findings in critically ill patients draw attention to lung damage associated with intense inflammation due to the production of inflammatory molecules, called cytokine storms, produced mainly by the innate immune system, and coagulation problems, due to a systemic inflammatory reaction (disseminated intravascular coagulation). In this way, we evaluated the polymorphisms of the cytokines IL1β, IL6, IL18, NLRP1 and NLRP3 inflammasomes, together with the immune response profile of convalescent patients from COVID-19 treated at the Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas and patients with COVID-19. 19 treated at the Getúlio Vargas University Hospital. It was possible to observe statistical differences between the genotypes and alleles of NLRP1 (rs35865013), NLRP3 (rs10754558), IL6 (rs1800795) and IL18 (rs1872384) of the control and convalescent groups, which could have some relationship with protection/risk to COVID- 19. And the AA and AG NLRP1 rs35865013 genotypes and the IL18 CG genotype of patients with COVID-19 may be related to protection against the disease. The cytokines IL1β and IL6 showed a higher serum concentration in patients with COVID-19, and when separated between high and Death groups, we found that patients who died had a high production of these cytokines. It is likely that this significant increase in IL1β and IL6 may have led to the final outcome of these patients. Patients with COVID-19 who presented the AT NLRP1 rs12150220 genotype had a higher concentration of IL1β when compared to patients with the TT genotype. Suggesting that patients with the AT genotype release a higher concentration of IL1β, consequently, a better innate immunity response against COVID-19. In the comparison of the genotypes AA/AT NLRP1 rs12150220, GG NLRP1 rs35865013, CT/TT NLRP3 rs10802502, CC NLRP3 rs10754558, CC IL1β rs16944 and GG/GC IL6 rs1800795 of patients with COVID-19 and convalescent patients in periods D30, D60 and D90, statistical differences were observed in the production of IL1β and IL6, where those with COVID-19 showed a higher concentration in the different genotypes. Our work highlights the importance of analyzing genetic variations in the NLRP1 and NLRP3 inflammasome genes as possible risk factors in the clinical evolution of COVID-19.