Assessing the Impact of SARS-CoV-2 Lineages and Mutations on Patient Survival

Carlos Loucera; Javier Perez-Florido; Carlos S Casimiro-Soriguer; Francisco M Ortuño; Rosario Carmona; Gerrit Bostelmann; L Javier Martínez-González; Dolores Muñoyerro-Muñiz; Román Villegas; Jesus Rodriguez-Baño; Manuel Romero-Gomez; Nicola Lorusso; Javier Garcia-León; Jose M Navarro-Marí; Pedro Camacho-Martinez; Laura Merino-Diaz; Adolfo de Salazar; Laura Viñuela; The Andalusian Covid-Sequencing Initiative; Jose A Lepe; Federico Garcia; Joaquin Dopazo

doi:10.3390/v14091893

Assessing the Impact of SARS-CoV-2 Lineages and Mutations on Patient Survival

Viruses. 2022 Aug 27;14(9):1893. doi: 10.3390/v14091893.

Authors

Carlos Loucera^{1

2}, Javier Perez-Florido^{1

2}, Carlos S Casimiro-Soriguer^{1

2}, Francisco M Ortuño^{1

3}, Rosario Carmona¹, Gerrit Bostelmann¹, L Javier Martínez-González⁴, Dolores Muñoyerro-Muñiz⁵, Román Villegas⁵, Jesus Rodriguez-Baño^{2

6

7

8}, Manuel Romero-Gomez^{2

7

9}, Nicola Lorusso¹⁰, Javier Garcia-León¹¹, Jose M Navarro-Marí^{12

13}, Pedro Camacho-Martinez¹⁴, Laura Merino-Diaz¹⁴, Adolfo de Salazar^{8

15}, Laura Viñuela^{8

15}, The Andalusian Covid-Sequencing Initiative, Jose A Lepe^{2

8

15}, Federico Garcia^{8

13

15}, Joaquin Dopazo^{1

2

16}

Affiliations

¹ Bioinformatics Area, Andalusian Public Foundation Progress and Health-FPS, 41013 Sevilla, Spain.
² Institute of Biomedicine of Seville, IBiS, University Hospital Virgen del Rocío/CSIC/University of Seville, 41013 Sevilla, Spain.
³ Department of Computer Architecture and Computer Technology, University of Granada, 18011 Granada, Spain.
⁴ GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS Granada, 18016 Granada, Spain.
⁵ Subdirección Técnica Asesora de Gestión de la Información, Servicio Andaluz de Salud, 41001 Sevilla, Spain.
⁶ Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen Macarena, 41009 Sevilla, Spain.
⁷ Departamento de Medicina, Universidad de Sevilla, C. San Fernando, 4, 41004 Sevilla, Spain.
⁸ Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), ISCIII, 28029 Madrid, Spain.
⁹ Servicio de Aparato Digestivo, Hospital Universitario Virgen del Rocío, 41013 Sevilla, Spain.
¹⁰ Dirección General de Salud Pública, Consejería de Salud y Familias, Junta de Andalucía, 41020 Sevilla, Spain.
¹¹ Departamento de Metafísica y Corrientes Actuales de la Filosofía, Ética y Filosofía Política, Universidad de Sevilla, 41004 Sevilla, Spain.
¹² Servicio de Microbiología, Hospital Virgen de las Nieves, 18014 Granada, Spain.
¹³ Instituto de Investigación Biosanitaria, ibs.GRANADA, 18012 Granada, Spain.
¹⁴ Servicio de Microbiología, Unidad Clínica Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen del Rocío, 41013 Sevilla, Spain.
¹⁵ Servicio de Microbiología, Hospital Universitario San Cecilio, 18016 Granada, Spain.
¹⁶ FPS/ELIXIR-ES, Andalusian Public Foundation Progress and Health-FPS, 41013 Sevilla, Spain.

Abstract

Objectives: More than two years into the COVID-19 pandemic, SARS-CoV-2 still remains a global public health problem. Successive waves of infection have produced new SARS-CoV-2 variants with new mutations for which the impact on COVID-19 severity and patient survival is uncertain.

Methods: A total of 764 SARS-CoV-2 genomes, sequenced from COVID-19 patients, hospitalized from 19th February 2020 to 30 April 2021, along with their clinical data, were used for survival analysis.

Results: A significant association of B.1.1.7, the alpha lineage, with patient mortality (log hazard ratio (LHR) = 0.51, C.I. = [0.14,0.88]) was found upon adjustment by all the covariates known to affect COVID-19 prognosis. Moreover, survival analysis of mutations in the SARS-CoV-2 genome revealed 27 of them were significantly associated with higher mortality of patients. Most of these mutations were located in the genes coding for the S, ORF8, and N proteins.

Conclusions: This study illustrates how a combination of genomic and clinical data can provide solid evidence for the impact of viral lineage on patient survival.

Keywords: COVID-19; SARS-CoV-2; phylogeny; survival; virus genome.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

COVID-19*
Genome, Viral
Humans
Mutation
Pandemics
Phylogeny
SARS-CoV-2* / genetics

Supplementary concepts

SARS-CoV-2 variants

Grants and funding

This work was supported by Spanish Ministry of Science and Innovation (grant PID2020-117979RB-I00), the Instituto de Salud Carlos III (ISCIII), co-funded with European Regional Development Funds (ERDF) (grant IMP/00019), and has also been funded by Consejería de Salud y Familias, Junta de Andalucía (grants COVID-0012-2020 and PS-2020-342) and the postdoctoral contract of Carlos Loucera (PAIDI2020- DOC_00350), co-funded by the European Social Fund (FSE) 2014-2020. ELIXIR-CONVERGE—H2020 (871075).