Hyperinflammatory Immune Response in COVID-19: Host Genetic Factors in Pyrin Inflammasome and Immunity to Virus in a Spanish Population from Majorca Island
The hyperinflammatory response caused by SARS-CoV-2 infection contributes to its severity, and many critically ill patients show features of cytokine storm (CS) syndrome. We investigated, by next-generation sequencing, 24 causative genes of primary immunodeficiencies whose defect predisposes to CS....
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| Format: | Article |
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MDPI AG
2023-09-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/9/2548 |
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| author | Natalia Martínez-Pomar Vanesa Cunill Marina Segura-Guerrero Elisabet Pol-Pol Danilo Escobar Oblitas Jaime Pons Ignacio Ayestarán Patricia C. Pruneda Inés Losada Nuria Toledo-Pons Mercedes García Gasalla Joana Maria Ferrer Balaguer |
| author_facet | Natalia Martínez-Pomar Vanesa Cunill Marina Segura-Guerrero Elisabet Pol-Pol Danilo Escobar Oblitas Jaime Pons Ignacio Ayestarán Patricia C. Pruneda Inés Losada Nuria Toledo-Pons Mercedes García Gasalla Joana Maria Ferrer Balaguer |
| author_sort | Natalia Martínez-Pomar |
| collection | DOAJ |
| description | The hyperinflammatory response caused by SARS-CoV-2 infection contributes to its severity, and many critically ill patients show features of cytokine storm (CS) syndrome. We investigated, by next-generation sequencing, 24 causative genes of primary immunodeficiencies whose defect predisposes to CS. We studied two cohorts with extreme phenotypes of SARS-CoV-2 infection: critical/severe hyperinflammatory patients (H-P) and asymptomatic patients (AM-risk-P) with a high risk (older age) to severe COVID-19. To explore inborn errors of the immunity, we investigated the presence of pathogenic or rare variants, and to identify COVID-19 severity-associated markers, we compared the allele frequencies of common genetic polymorphisms between our two cohorts. We found: 1 H-P carries the likely pathogenic variant c.887-2 A>C in the <i>IRF7</i> gene and 5 H-P carries variants in the <i>MEFV</i> gene, whose role in the pathogenicity of the familial Mediterranean fever (FMF) disease is controversial. The common polymorphism analysis showed three potential risk biomarkers for developing the hyperinflammatory response: the homozygous haplotype rs1231123A/A-rs1231122A/A in <i>MEFV</i> gene, the <i>IFNAR2</i> p.Phe8Ser variant, and the <i>CARMIL2</i> p.Val181Met variant. The combined analysis showed an increased risk of developing severe COVID-19 in patients that had at least one of our genetic risk markers (odds ratio (OR) = 6.2 (95% CI) (2.430–16.20)). |
| first_indexed | 2024-03-10T23:00:06Z |
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| id | doaj.art-3ebc29bcdc924933843a4a2ed7708723 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T23:00:06Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-3ebc29bcdc924933843a4a2ed77087232023-11-19T09:42:52ZengMDPI AGBiomedicines2227-90592023-09-01119254810.3390/biomedicines11092548Hyperinflammatory Immune Response in COVID-19: Host Genetic Factors in Pyrin Inflammasome and Immunity to Virus in a Spanish Population from Majorca IslandNatalia Martínez-Pomar0Vanesa Cunill1Marina Segura-Guerrero2Elisabet Pol-Pol3Danilo Escobar Oblitas4Jaime Pons5Ignacio Ayestarán6Patricia C. Pruneda7Inés Losada8Nuria Toledo-Pons9Mercedes García Gasalla10Joana Maria Ferrer Balaguer11Immunology Department, Hospital Universitari Son Espases, 07120 Palma de Mallorca, SpainImmunology Department, Hospital Universitari Son Espases, 07120 Palma de Mallorca, SpainImmunology Department, Hospital Universitari Son Espases, 07120 Palma de Mallorca, SpainImmunology Department, Hospital Universitari Son Espases, 07120 Palma de Mallorca, SpainImmunology Department, Hospital Universitari Son Espases, 07120 Palma de Mallorca, SpainImmunology Department, Hospital Universitari Son Espases, 07120 Palma de Mallorca, SpainHealth Research Institute of the Balearic Islands (IdISBa), 07120 Palma de Mallorca, SpainDreamgenics, 33011 Oviedo, SpainHealth Research Institute of the Balearic Islands (IdISBa), 07120 Palma de Mallorca, SpainHealth Research Institute of the Balearic Islands (IdISBa), 07120 Palma de Mallorca, SpainHealth Research Institute of the Balearic Islands (IdISBa), 07120 Palma de Mallorca, SpainImmunology Department, Hospital Universitari Son Espases, 07120 Palma de Mallorca, SpainThe hyperinflammatory response caused by SARS-CoV-2 infection contributes to its severity, and many critically ill patients show features of cytokine storm (CS) syndrome. We investigated, by next-generation sequencing, 24 causative genes of primary immunodeficiencies whose defect predisposes to CS. We studied two cohorts with extreme phenotypes of SARS-CoV-2 infection: critical/severe hyperinflammatory patients (H-P) and asymptomatic patients (AM-risk-P) with a high risk (older age) to severe COVID-19. To explore inborn errors of the immunity, we investigated the presence of pathogenic or rare variants, and to identify COVID-19 severity-associated markers, we compared the allele frequencies of common genetic polymorphisms between our two cohorts. We found: 1 H-P carries the likely pathogenic variant c.887-2 A>C in the <i>IRF7</i> gene and 5 H-P carries variants in the <i>MEFV</i> gene, whose role in the pathogenicity of the familial Mediterranean fever (FMF) disease is controversial. The common polymorphism analysis showed three potential risk biomarkers for developing the hyperinflammatory response: the homozygous haplotype rs1231123A/A-rs1231122A/A in <i>MEFV</i> gene, the <i>IFNAR2</i> p.Phe8Ser variant, and the <i>CARMIL2</i> p.Val181Met variant. The combined analysis showed an increased risk of developing severe COVID-19 in patients that had at least one of our genetic risk markers (odds ratio (OR) = 6.2 (95% CI) (2.430–16.20)).https://www.mdpi.com/2227-9059/11/9/2548hyperinflammatory immune responsePyrinCOVID-19primary immunodeficiencycytokine stormgenetic markers |
| spellingShingle | Natalia Martínez-Pomar Vanesa Cunill Marina Segura-Guerrero Elisabet Pol-Pol Danilo Escobar Oblitas Jaime Pons Ignacio Ayestarán Patricia C. Pruneda Inés Losada Nuria Toledo-Pons Mercedes García Gasalla Joana Maria Ferrer Balaguer Hyperinflammatory Immune Response in COVID-19: Host Genetic Factors in Pyrin Inflammasome and Immunity to Virus in a Spanish Population from Majorca Island Biomedicines hyperinflammatory immune response Pyrin COVID-19 primary immunodeficiency cytokine storm genetic markers |
| title | Hyperinflammatory Immune Response in COVID-19: Host Genetic Factors in Pyrin Inflammasome and Immunity to Virus in a Spanish Population from Majorca Island |
| title_full | Hyperinflammatory Immune Response in COVID-19: Host Genetic Factors in Pyrin Inflammasome and Immunity to Virus in a Spanish Population from Majorca Island |
| title_fullStr | Hyperinflammatory Immune Response in COVID-19: Host Genetic Factors in Pyrin Inflammasome and Immunity to Virus in a Spanish Population from Majorca Island |
| title_full_unstemmed | Hyperinflammatory Immune Response in COVID-19: Host Genetic Factors in Pyrin Inflammasome and Immunity to Virus in a Spanish Population from Majorca Island |
| title_short | Hyperinflammatory Immune Response in COVID-19: Host Genetic Factors in Pyrin Inflammasome and Immunity to Virus in a Spanish Population from Majorca Island |
| title_sort | hyperinflammatory immune response in covid 19 host genetic factors in pyrin inflammasome and immunity to virus in a spanish population from majorca island |
| topic | hyperinflammatory immune response Pyrin COVID-19 primary immunodeficiency cytokine storm genetic markers |
| url | https://www.mdpi.com/2227-9059/11/9/2548 |
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