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

Overview

Journal Viruses

Publisher MDPI

Specialty Microbiology

Date 2022 Sep 23

PMID 36146700

Authors

Carlos Loucera

Javier Perez-Florido

Carlos S Casimiro-Soriguer

Francisco M Ortuno

Rosario Carmona

Gerrit Bostelmann

L Javier Martinez-Gonzalez

Dolores Munoyerro-Muniz

Roman Villegas

Jesus Rodriguez-Bano

Manuel Romero-Gomez

Nicola Lorusso

Javier Garcia-Leon

Jose M Navarro-Mari

Pedro Camacho-Martinez

Laura Merino-Diaz

Adolfo De Salazar

Laura Vinuela

The Andalusian Covid-Sequencing Initiative

Jose A Lepe

Federico Garcia

Joaquin Dopazo

Affiliations

Soon will be listed here.

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.

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References

Thorne L, Bouhaddou M, Reuschl A, Zuliani-Alvarez L, Polacco B, Pelin A . Evolution of enhanced innate immune evasion by SARS-CoV-2. Nature. 2021; 602(7897):487-495. PMC: 8850198. DOI: 10.1038/s41586-021-04352-y. View

Ellinghaus D, Degenhardt F, Bujanda L, Buti M, Albillos A, Invernizzi P . Genomewide Association Study of Severe Covid-19 with Respiratory Failure. N Engl J Med. 2020; 383(16):1522-1534. PMC: 7315890. DOI: 10.1056/NEJMoa2020283. View

Tegally H, Wilkinson E, Giovanetti M, Iranzadeh A, Fonseca V, Giandhari J . Detection of a SARS-CoV-2 variant of concern in South Africa. Nature. 2021; 592(7854):438-443. DOI: 10.1038/s41586-021-03402-9. View

Degenhardt F, Ellinghaus D, Juzenas S, Lerga-Jaso J, Wendorff M, Maya-Miles D . Detailed stratified GWAS analysis for severe COVID-19 in four European populations. Hum Mol Genet. 2022; 31(23):3945-3966. PMC: 9703941. DOI: 10.1093/hmg/ddac158. View

Huddleston J, Hadfield J, Sibley T, Lee J, Fay K, Ilcisin M . Augur: a bioinformatics toolkit for phylogenetic analyses of human pathogens. J Open Source Softw. 2021; 6(57). PMC: 8237802. DOI: 10.21105/joss.02906. View

Sterne J, Murthy S, Diaz J, Slutsky A, Villar J, Angus D . Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis. JAMA. 2020; 324(13):1330-1341. PMC: 7489434. DOI: 10.1001/jama.2020.17023. View

Tegally H, Wilkinson E, Lessells R, Giandhari J, Pillay S, Msomi N . Sixteen novel lineages of SARS-CoV-2 in South Africa. Nat Med. 2021; 27(3):440-446. DOI: 10.1038/s41591-021-01255-3. View

Elbe S, Buckland-Merrett G . Data, disease and diplomacy: GISAID's innovative contribution to global health. Glob Chall. 2019; 1(1):33-46. PMC: 6607375. DOI: 10.1002/gch2.1018. View

Austin P . Variance estimation when using inverse probability of treatment weighting (IPTW) with survival analysis. Stat Med. 2016; 35(30):5642-5655. PMC: 5157758. DOI: 10.1002/sim.7084. View

10.

Volz E, Mishra S, Chand M, Barrett J, Johnson R, Geidelberg L . Assessing transmissibility of SARS-CoV-2 lineage B.1.1.7 in England. Nature. 2021; 593(7858):266-269. DOI: 10.1038/s41586-021-03470-x. View

11.

Dai W, Zhang B, Jiang X, Su H, Li J, Zhao Y . Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease. Science. 2020; 368(6497):1331-1335. PMC: 7179937. DOI: 10.1126/science.abb4489. View

12.

Hajage D, Chauvet G, Belin L, Lafourcade A, Tubach F, De Rycke Y . Closed-form variance estimator for weighted propensity score estimators with survival outcome. Biom J. 2018; 60(6):1151-1163. DOI: 10.1002/bimj.201700330. View

13.

Graham R, Baric R . Recombination, reservoirs, and the modular spike: mechanisms of coronavirus cross-species transmission. J Virol. 2009; 84(7):3134-46. PMC: 2838128. DOI: 10.1128/JVI.01394-09. View

14.

Toyoshima Y, Nemoto K, Matsumoto S, Nakamura Y, Kiyotani K . SARS-CoV-2 genomic variations associated with mortality rate of COVID-19. J Hum Genet. 2020; 65(12):1075-1082. PMC: 7375454. DOI: 10.1038/s10038-020-0808-9. View

15.

. An integrated national scale SARS-CoV-2 genomic surveillance network. Lancet Microbe. 2020; 1(3):e99-e100. PMC: 7266609. DOI: 10.1016/S2666-5247(20)30054-9. View

16.

Dopazo J, Maya-Miles D, Garcia F, Lorusso N, Calleja M, Pareja M . Implementing Personalized Medicine in COVID-19 in Andalusia: An Opportunity to Transform the Healthcare System. J Pers Med. 2021; 11(6). PMC: 8226500. DOI: 10.3390/jpm11060475. View

17.

Elliott P, Eales O, Steyn N, Tang D, Bodinier B, Wang H . Twin peaks: The Omicron SARS-CoV-2 BA.1 and BA.2 epidemics in England. Science. 2022; 376(6600):eabq4411. PMC: 9161371. DOI: 10.1126/science.abq4411. View

18.

Araf Y, Akter F, Tang Y, Fatemi R, Parvez M, Zheng C . Omicron variant of SARS-CoV-2: Genomics, transmissibility, and responses to current COVID-19 vaccines. J Med Virol. 2022; 94(5):1825-1832. PMC: 9015557. DOI: 10.1002/jmv.27588. View

19.

Zhou S, Butler-Laporte G, Nakanishi T, Morrison D, Afilalo J, Afilalo M . A Neanderthal OAS1 isoform protects individuals of European ancestry against COVID-19 susceptibility and severity. Nat Med. 2021; 27(4):659-667. DOI: 10.1038/s41591-021-01281-1. View

20.

Tang J, Tambyah P, Hui D . Emergence of a new SARS-CoV-2 variant in the UK. J Infect. 2020; 82(4):e27-e28. PMC: 7834693. DOI: 10.1016/j.jinf.2020.12.024. View