Hyperinflammatory Immune Response in COVID-19: Host Genetic Factors in Pyrin Inflammasome and Immunity to Virus in a Spanish Population from Majorca Island

Martínez-Pomar, Natalia; Cunill, Vanesa; Segura-Guerrero, Marina; Pol-Pol, Elisabet; Escobar Oblitas, Danilo; Pons, Jaime; Ayestarán, Ignacio; Pruneda, Patricia C.; Losada, Inés; Toledo-Pons, Nuria; García Gasalla, Mercedes; Ferrer Balaguer, Joana Maria

doi:10.3390/biomedicines11092548

Open AccessArticle

Hyperinflammatory Immune Response in COVID-19: Host Genetic Factors in Pyrin Inflammasome and Immunity to Virus in a Spanish Population from Majorca Island

by

Natalia Martínez-Pomar

^1,2,*,

Vanesa Cunill

^1,2

,

Marina Segura-Guerrero

^1,2,

Elisabet Pol-Pol

^1,2,

Danilo Escobar Oblitas

^1,2,

Jaime Pons

^1,2,

Ignacio Ayestarán

^2,3,

Patricia C. Pruneda

⁴,

Inés Losada

^2,5,

Nuria Toledo-Pons

^2,6,

Mercedes García Gasalla

^2,7 and

Joana Maria Ferrer Balaguer

^1,2

¹

Immunology Department, Hospital Universitari Son Espases, 07120 Palma de Mallorca, Spain

²

Health Research Institute of the Balearic Islands (IdISBa), 07120 Palma de Mallorca, Spain

³

Intensive Care Unit (ICU), Hospital Universitari Son Espases, 07120 Palma de Mallorca, Spain

⁴

Dreamgenics, 33011 Oviedo, Spain

⁵

Internal Medicine, Hospital Universitari Son Llàtzer, 07198 Palma de Mallorca, Spain

⁶

Pneumology Department, Hospital Universitari Son Espases, 07120 Palma de Mallorca, Spain

⁷

Internal Medicine, Hospital Universitari Son Espases, 07120 Palma de Mallorca, Spain

^*

Author to whom correspondence should be addressed.

Biomedicines 2023, 11(9), 2548; https://doi.org/10.3390/biomedicines11092548

Submission received: 21 July 2023 / Revised: 31 August 2023 / Accepted: 5 September 2023 / Published: 16 September 2023

(This article belongs to the Special Issue Disease Biomarkers in Immunomediated Diseases)

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Abstract

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 IRF7 gene and 5 H-P carries variants in the MEFV 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 MEFV gene, the IFNAR2 p.Phe8Ser variant, and the CARMIL2 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)).

Keywords: hyperinflammatory immune response; Pyrin; COVID-19; primary immunodeficiency; cytokine storm; genetic markers

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MDPI and ACS Style

Martínez-Pomar, N.; Cunill, V.; Segura-Guerrero, M.; Pol-Pol, E.; Escobar Oblitas, D.; Pons, J.; Ayestarán, I.; Pruneda, P.C.; Losada, I.; Toledo-Pons, N.; et al. Hyperinflammatory Immune Response in COVID-19: Host Genetic Factors in Pyrin Inflammasome and Immunity to Virus in a Spanish Population from Majorca Island. Biomedicines 2023, 11, 2548. https://doi.org/10.3390/biomedicines11092548

AMA Style

Martínez-Pomar N, Cunill V, Segura-Guerrero M, Pol-Pol E, Escobar Oblitas D, Pons J, Ayestarán I, Pruneda PC, Losada I, Toledo-Pons N, et al. Hyperinflammatory Immune Response in COVID-19: Host Genetic Factors in Pyrin Inflammasome and Immunity to Virus in a Spanish Population from Majorca Island. Biomedicines. 2023; 11(9):2548. https://doi.org/10.3390/biomedicines11092548

Chicago/Turabian Style

Martínez-Pomar, Natalia, Vanesa Cunill, Marina Segura-Guerrero, Elisabet Pol-Pol, Danilo Escobar Oblitas, Jaime Pons, Ignacio Ayestarán, Patricia C. Pruneda, Inés Losada, Nuria Toledo-Pons, and et al. 2023. "Hyperinflammatory Immune Response in COVID-19: Host Genetic Factors in Pyrin Inflammasome and Immunity to Virus in a Spanish Population from Majorca Island" Biomedicines 11, no. 9: 2548. https://doi.org/10.3390/biomedicines11092548

APA Style

Martínez-Pomar, N., Cunill, V., Segura-Guerrero, M., Pol-Pol, E., Escobar Oblitas, D., Pons, J., Ayestarán, I., Pruneda, P. C., Losada, I., Toledo-Pons, N., García Gasalla, M., & Ferrer Balaguer, J. M. (2023). Hyperinflammatory Immune Response in COVID-19: Host Genetic Factors in Pyrin Inflammasome and Immunity to Virus in a Spanish Population from Majorca Island. Biomedicines, 11(9), 2548. https://doi.org/10.3390/biomedicines11092548

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Hyperinflammatory Immune Response in COVID-19: Host Genetic Factors in Pyrin Inflammasome and Immunity to Virus in a Spanish Population from Majorca Island

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