Assessing the impact of SARS-CoV-2 lineages and mutations on patient survival (preprint)

After more than two years of 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 whose impact on COVID-19 severity and patient survival is uncertain. A total of 764 SARS-CoV-2 genomes sequenced from COVID-19 patients, hospitalized from 19th February 2020 to 30st April 2021, along with their clinical data, were used for survival analysis. 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 rendered 27 of them significantly associated with higher mortality of patients. Most of these mutations were located in the S, ORF8 and N proteins. This study illustrates how a combination of genomic and clinical data provide solid evidence on the impact of viral lineage on patient survival.

From partial to whole genome imputation of SARS-CoV-2 for epidemiological surveillance (preprint)

The current SARS-CoV-2 pandemic has emphasized the utility of viral whole genome sequencing in the surveillance and control of the pathogen. An unprecedented ongoing global initiative is increasingly producing hundreds of thousands of sequences worldwide. However, the complex circumstances in which viruses are sequenced, along with the demand of urgent results, causes a high rate of incomplete and therefore useless, sequences. However, viral sequences evolve in the context of a complex phylogeny and therefore different positions along the genome are in linkage disequilibrium. Therefore, an imputation method would be able to predict missing positions from the available sequencing data. We developed impuSARS, an application that includes Minimac, the most widely used strategy for genomic data imputation and, taking advantage of the enormous amount of SARS-CoV-2 whole genome sequences available, a reference panel containing 239,301 sequences was built. The impuSARS application was tested in a wide range of conditions (continuous fragments, amplicons or sparse individual positions missing) showing great fidelity when reconstructing the original sequences. The impuSARS application is also able to impute whole genomes from commercial kits covering less than 20% of the genome or only from the Spike protein with a precision of 0.96. It also recovers the lineage with a 100% precision for almost all the lineages, even in very poorly covered genomes (< 20%). Imputation can improve the pace of SARS-CoV-2 sequencing production by recovering many incomplete or low-quality sequences that would be otherwise discarded. impuSARS can be incorporated in any primary data processing pipeline for SARS-CoV-2 whole genome sequencing.