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In COVID-19, NLRP3 inflammasome genetic variants are associated with critical disease and these effects are partly mediated by the sickness symptom complex: a nomothetic network approach

In coronavirus disease (COVID-19), the nucleotide-binding domain, leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) inflammasome is activated in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Acute infections are accompanied by a sickness symptom...

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Autores principales: Maes, Michael, Tedesco Junior, Walton Luiz Del, Lozovoy, Marcell Alysson Batisti, Mori, Mayara Tiemi Enokida, Danelli, Tiago, Almeida, Elaine Regina Delicato de, Tejo, Alexandre Mestre, Tano, Zuleica Naomi, Reiche, Edna Maria Vissoci, Simão, Andréa Name Colado
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8752583/
https://www.ncbi.nlm.nih.gov/pubmed/35022530
http://dx.doi.org/10.1038/s41380-021-01431-4
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author Maes, Michael
Tedesco Junior, Walton Luiz Del
Lozovoy, Marcell Alysson Batisti
Mori, Mayara Tiemi Enokida
Danelli, Tiago
Almeida, Elaine Regina Delicato de
Tejo, Alexandre Mestre
Tano, Zuleica Naomi
Reiche, Edna Maria Vissoci
Simão, Andréa Name Colado
author_facet Maes, Michael
Tedesco Junior, Walton Luiz Del
Lozovoy, Marcell Alysson Batisti
Mori, Mayara Tiemi Enokida
Danelli, Tiago
Almeida, Elaine Regina Delicato de
Tejo, Alexandre Mestre
Tano, Zuleica Naomi
Reiche, Edna Maria Vissoci
Simão, Andréa Name Colado
author_sort Maes, Michael
collection PubMed
description In coronavirus disease (COVID-19), the nucleotide-binding domain, leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) inflammasome is activated in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Acute infections are accompanied by a sickness symptom complex (SSC) which is highly conserved and protects against infections and hyperinflammation. The aim of this study is to delineate the associations of COVID-19, SSC and NLPR3 rs10157379 T > C and NLPR3 rs10754558 C > G variants; and the protective role of SSC in SARS-CoV-2 infection. We recruited COVID-19 patients, 308 with critical, 63 with moderate and 157 with mild disease. Increased SSC protects against SARS, critical disease, and death due to COVID-19. Increasing age, male sex and rs10754558 CG significantly reduce SSC protection. The rs10157379 CT and rs10754558 GG genotypes are positively associated with SARS. Partial Least Squares analysis shows that a) 41.8% of the variance in critical COVID-19 symptoms is explained by SSC and oxygen saturation (inversely associated), inflammation, chest computed tomography abnormalities, increased body mass index, SARS and age (positively associated); and b) the effects of the NLRP3 rs10157379 and rs10754558 variants on critical COVID-19 are mediated via SSC (protective) and SARS (detrimental). SSC includes anosmia and dysgeusia, and maybe gastrointestinal symptoms. In conclusion, intersections among the rs10754558 variant, age, and sex increase risk towards critical COVID-19 by attenuating SSC. NLRP3 variants play an important role in SARS, and severe and critical COVID-19 especially in elderly male individuals with reduced SSC and with increased BMI, hypertension, and diabetes type 2.
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spelling pubmed-87525832022-01-12 In COVID-19, NLRP3 inflammasome genetic variants are associated with critical disease and these effects are partly mediated by the sickness symptom complex: a nomothetic network approach Maes, Michael Tedesco Junior, Walton Luiz Del Lozovoy, Marcell Alysson Batisti Mori, Mayara Tiemi Enokida Danelli, Tiago Almeida, Elaine Regina Delicato de Tejo, Alexandre Mestre Tano, Zuleica Naomi Reiche, Edna Maria Vissoci Simão, Andréa Name Colado Mol Psychiatry Article In coronavirus disease (COVID-19), the nucleotide-binding domain, leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) inflammasome is activated in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Acute infections are accompanied by a sickness symptom complex (SSC) which is highly conserved and protects against infections and hyperinflammation. The aim of this study is to delineate the associations of COVID-19, SSC and NLPR3 rs10157379 T > C and NLPR3 rs10754558 C > G variants; and the protective role of SSC in SARS-CoV-2 infection. We recruited COVID-19 patients, 308 with critical, 63 with moderate and 157 with mild disease. Increased SSC protects against SARS, critical disease, and death due to COVID-19. Increasing age, male sex and rs10754558 CG significantly reduce SSC protection. The rs10157379 CT and rs10754558 GG genotypes are positively associated with SARS. Partial Least Squares analysis shows that a) 41.8% of the variance in critical COVID-19 symptoms is explained by SSC and oxygen saturation (inversely associated), inflammation, chest computed tomography abnormalities, increased body mass index, SARS and age (positively associated); and b) the effects of the NLRP3 rs10157379 and rs10754558 variants on critical COVID-19 are mediated via SSC (protective) and SARS (detrimental). SSC includes anosmia and dysgeusia, and maybe gastrointestinal symptoms. In conclusion, intersections among the rs10754558 variant, age, and sex increase risk towards critical COVID-19 by attenuating SSC. NLRP3 variants play an important role in SARS, and severe and critical COVID-19 especially in elderly male individuals with reduced SSC and with increased BMI, hypertension, and diabetes type 2. Nature Publishing Group UK 2022-01-12 2022 /pmc/articles/PMC8752583/ /pubmed/35022530 http://dx.doi.org/10.1038/s41380-021-01431-4 Text en © The Author(s), under exclusive licence to Springer Nature Limited 2022 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Article
Maes, Michael
Tedesco Junior, Walton Luiz Del
Lozovoy, Marcell Alysson Batisti
Mori, Mayara Tiemi Enokida
Danelli, Tiago
Almeida, Elaine Regina Delicato de
Tejo, Alexandre Mestre
Tano, Zuleica Naomi
Reiche, Edna Maria Vissoci
Simão, Andréa Name Colado
In COVID-19, NLRP3 inflammasome genetic variants are associated with critical disease and these effects are partly mediated by the sickness symptom complex: a nomothetic network approach
title In COVID-19, NLRP3 inflammasome genetic variants are associated with critical disease and these effects are partly mediated by the sickness symptom complex: a nomothetic network approach
title_full In COVID-19, NLRP3 inflammasome genetic variants are associated with critical disease and these effects are partly mediated by the sickness symptom complex: a nomothetic network approach
title_fullStr In COVID-19, NLRP3 inflammasome genetic variants are associated with critical disease and these effects are partly mediated by the sickness symptom complex: a nomothetic network approach
title_full_unstemmed In COVID-19, NLRP3 inflammasome genetic variants are associated with critical disease and these effects are partly mediated by the sickness symptom complex: a nomothetic network approach
title_short In COVID-19, NLRP3 inflammasome genetic variants are associated with critical disease and these effects are partly mediated by the sickness symptom complex: a nomothetic network approach
title_sort in covid-19, nlrp3 inflammasome genetic variants are associated with critical disease and these effects are partly mediated by the sickness symptom complex: a nomothetic network approach
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8752583/
https://www.ncbi.nlm.nih.gov/pubmed/35022530
http://dx.doi.org/10.1038/s41380-021-01431-4
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