Occurrence of SARS-CoV-2 viremia is associated with genetic variants of genes related to COVID-19 pathogenesis

Emilia Roy-Vallejo; Sara Fernández De Córdoba-Oñate; Pablo Delgado-Wicke; Ana Triguero-Martínez; Nuria Montes; Rosa Carracedo-Rodríguez; Nelly Zurita-Cruz; Ana Marcos-Jiménez; Amalia Lamana; José María Galván-Román; Gonzalo Villapalos García; Pablo Zubiaur; Marianela Ciudad; Laura Rabes; Marta Sanz; Carlos Rodríguez; Almudena Villa; Jesús Álvarez Rodríguez; Celeste Marcos; Julia Hernando; Paula Díaz-Fernández; Francisco Abad; Ignacio de Los Santos; Diego A Rodríguez Serrano; Rosario García-Vicuña; Carmen Suárez Fernández; Rosa P Gomariz; Cecilia Muñoz-Calleja; Elena Fernández-Ruiz; Isidoro González-Álvaro; Laura Cardeñoso; PREDINMUN-COVID Group; Ana Barrios; Jesús Sanz; Pedro Casado; Ángela Gutiérrez; Azucena Bautista; Pilar Hernández; Nuria Ruiz Giménez; Berta Moyano; Paloma Gil; María Jesús Delgado; Pedro Parra; Beatriz Sánchez; Carmen Sáez; Marta Fernández Rico; Cristina Arévalo Román; Santos Castañeda; Irene Llorente; Eva G Tomero; Noelia García Castañeda; Miren Uriarte; Leticia Fontán García-Rodrigo; Diego Domingo García; Teresa Alarcón Cavero; María Auxiliadora Semiglia Chong; Ainhoa Gutiérrez Cobos; Francisco Sánchez-Madrid; Enrique Martín Gayo; Ildefonso Sánchez-Cerrillo; Pedro Martínez-Fleta; Celia López-Sanz; Ligia Gabrie; Luciana Del Campo Guerola; Reyes Tejedor; Julio Ancochea; Elena García Castillo; Elena Ávalos; Ana Sánchez-Azofra; Tamara Alonso; Carolina Cisneros; Claudia Valenzuela; Francisco Javier García Pérez; Rosa María Girón; Javier Aspa; Celeste Marcos; M Del Perpetuo Socorro Churruca; Enrique Zamora; Adrián Martínez; Mar Barrio Mayo; Rosalina Henares Espi; Rosa Méndez; David Arribas; Marta Chicot Llano; Begoña González; Begoña Quicios; Pablo Patiño; Marina Trigueros; Cristina Dominguez Peña; David Jiménez Jiménez; Pablo Villamayor; Alfonso Canabal; Rafael de la Cámara; Javier Ortiz; Isabel Iturrate

doi:10.3389/fmed.2023.1215246

Occurrence of SARS-CoV-2 viremia is associated with genetic variants of genes related to COVID-19 pathogenesis

Front Med (Lausanne). 2023 Sep 22:10:1215246. doi: 10.3389/fmed.2023.1215246. eCollection 2023.

Authors

Emilia Roy-Vallejo^{1

2}, Sara Fernández De Córdoba-Oñate³, Pablo Delgado-Wicke⁴, Ana Triguero-Martínez^{2

3}, Nuria Montes^{2

3}, Rosa Carracedo-Rodríguez⁴, Nelly Zurita-Cruz⁵, Ana Marcos-Jiménez^{2

6}, Amalia Lamana⁷, José María Galván-Román^{1

2}, Gonzalo Villapalos García^{2

8}, Pablo Zubiaur^{2

8}, Marianela Ciudad¹, Laura Rabes¹, Marta Sanz¹, Carlos Rodríguez¹, Almudena Villa¹, Jesús Álvarez Rodríguez¹, Celeste Marcos⁹, Julia Hernando¹⁰, Paula Díaz-Fernández^{2

6}, Francisco Abad^{2

8

11}, Ignacio de Los Santos^{1

2

12}, Diego A Rodríguez Serrano¹³, Rosario García-Vicuña^{2

3}, Carmen Suárez Fernández^{1

2

14}, Rosa P Gomariz⁷, Cecilia Muñoz-Calleja^{2

6

14}, Elena Fernández-Ruiz^{2

4

14}, Isidoro González-Álvaro^{2

3}, Laura Cardeñoso^{2

5}; PREDINMUN-COVID Group; Ana Barrios^{1

2

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14}, Jesús Sanz^{1

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14}, Pedro Casado^{1

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14}, Ángela Gutiérrez^{1

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14}, Azucena Bautista^{1

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14}, Pilar Hernández^{1

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14}, Nuria Ruiz Giménez^{1

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14}, Berta Moyano^{1

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14}, Paloma Gil^{1

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14}, María Jesús Delgado^{1

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14}, Pedro Parra^{1

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14}, Beatriz Sánchez^{1

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14}, Carmen Sáez^{1

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14}, Marta Fernández Rico^{1

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14}, Cristina Arévalo Román^{1

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14}, Santos Castañeda^{1

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14}, Irene Llorente^{1

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14}, Eva G Tomero^{1

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14}, Noelia García Castañeda^{1

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14}, Miren Uriarte^{1

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14}, Leticia Fontán García-Rodrigo^{1

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14}, Diego Domingo García^{1

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14}, Teresa Alarcón Cavero^{1

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14}, María Auxiliadora Semiglia Chong^{1

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14}, Ainhoa Gutiérrez Cobos^{1

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14}, Francisco Sánchez-Madrid^{1

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14}, Enrique Martín Gayo^{1

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14}, Ildefonso Sánchez-Cerrillo^{1

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14}, Pedro Martínez-Fleta^{1

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14}, Celia López-Sanz^{1

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14}, Ligia Gabrie^{1

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14}, Luciana Del Campo Guerola^{1

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14}, Reyes Tejedor^{1

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14}, Julio Ancochea^{1

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14}, Elena García Castillo^{1

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14}, Elena Ávalos^{1

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14}, Ana Sánchez-Azofra^{1

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14}, Tamara Alonso^{1

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14}, Carolina Cisneros^{1

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14}, Claudia Valenzuela^{1

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14}, Francisco Javier García Pérez^{1

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14}, Rosa María Girón^{1

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14}, Javier Aspa^{1

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14}, Celeste Marcos^{1

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14}, M Del Perpetuo Socorro Churruca^{1

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14}, Enrique Zamora^{1

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14}, Adrián Martínez^{1

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14}, Mar Barrio Mayo^{1

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14}, Rosalina Henares Espi^{1

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14}, Rosa Méndez^{1

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14}, David Arribas^{1

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14}, Marta Chicot Llano^{1

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14}, Begoña González^{1

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14}, Begoña Quicios^{1

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14}, Pablo Patiño^{1

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14}, Marina Trigueros^{1

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14}, Cristina Dominguez Peña^{1

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14}, David Jiménez Jiménez^{1

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14}, Pablo Villamayor^{1

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14}, Alfonso Canabal^{1

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14}, Rafael de la Cámara^{1

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14}, Javier Ortiz^{1

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14}, Isabel Iturrate^{1

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14}

Affiliations

¹ Internal Medicine Department, Hospital Universitario La Princesa, Madrid, Spain.
² Instituto de Investigación Sanitaria La Princesa (IIS-IP), Madrid, Spain.
³ Rheumathology Department, Hospital Universitario La Princesa, Madrid, Spain.
⁴ Molecular Biology Unit, Hospital Universitario La Princesa, Madrid, Spain.
⁵ Microbiology Department, Hospital Universitario La Princesa, Madrid, Spain.
⁶ Immunology Department, Hospital Universitario La Princesa, Madrid, Spain.
⁷ Cell Biology Department, Facultad de Biología, Universidad Complutense, Madrid, Spain.
⁸ Clinical Pharmacology Department, Hospital Universitario La Princesa, Instituto Teófilo Hernando, Universidad Autónoma de Madrid (UAM), Madrid, Spain.
⁹ Pneumology Department, Hospital Universitario La Princesa, Madrid, Spain.
¹⁰ Anesthesiology Department, Hospital Universitario La Princesa, Madrid, Spain.
¹¹ Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
¹² Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.
¹³ Intensive Care Unit, Hospital Universitario La Princesa, Madrid, Spain.
¹⁴ Universidad Autónoma de Madrid (UAM), Madrid, Spain.

Abstract

Introduction: SARS-CoV-2 viral load has been related to COVID-19 severity. The main aim of this study was to evaluate the relationship between SARS-CoV-2 viremia and SNPs in genes previously studied by our group as predictors of COVID-19 severity.

Materials and methods: Retrospective observational study including 340 patients hospitalized for COVID-19 in the University Hospital La Princesa between March 2020 and December 2021, with at least one viremia determination. Positive viremia was considered when viral load was above the quantifiable threshold (20 copies/ml). A total of 38 SNPs were genotyped. To study their association with viremia a multivariate logistic regression was performed.

Results: The mean age of the studied population was 64.5 years (SD 16.6), 60.9% patients were male and 79.4% white non-Hispanic. Only 126 patients (37.1%) had at least one positive viremia. After adjustment by confounders, the presence of the minor alleles of rs2071746 (HMOX1; T/T genotype OR 9.9 p < 0.0001), rs78958998 (probably associated with SERPING1 expression; A/T genotype OR 2.3, p = 0.04 and T/T genotype OR 12.9, p < 0.0001), and rs713400 (eQTL for TMPRSS2; C/T + T/T genotype OR 1.86, p = 0.10) were associated with higher risk of viremia, whereas the minor alleles of rs11052877 (CD69; A/G genotype OR 0.5, p = 0.04 and G/G genotype OR 0.3, p = 0.01), rs2660 (OAS1; A/G genotype OR 0.6, p = 0.08), rs896 (VIPR1; T/T genotype OR 0.4, p = 0.02) and rs33980500 (TRAF3IP2; C/T + T/T genotype OR 0.3, p = 0.01) were associated with lower risk of viremia.

Conclusion: Genetic variants in HMOX1 (rs2071746), SERPING1 (rs78958998), TMPRSS2 (rs713400), CD69 (rs11052877), TRAF3IP2 (rs33980500), OAS1 (rs2660) and VIPR1 (rs896) could explain heterogeneity in SARS-CoV-2 viremia in our population.

Keywords: COVID-19; SARS-CoV-2; genetic variants; single nucleotide polymorphism (SNPs); viremia.

Copyright © 2023 Roy-Vallejo, Fernández de Córdoba-Oñate, Delgado-Wicke, Triguero-Martínez, Montes, Carracedo-Rodríguez, Zurita-Cruz, Marcos-Jiménez, Lamana, Galván-Román, Villapalos García, Zubiaur, Ciudad, Rabes, Sanz, Rodríguez, Villa, Rodríguez, Marcos, Hernando, Díaz-Fernández, Abad, de los Santos, Rodríguez Serrano, García-Vicuña, Suárez Fernández, P. Gomariz, Muñoz-Calleja, Fernández-Ruiz, González-Álvaro Cardeñoso and the PREDINMUN-COVID Group.