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

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.

Clinical Manifestations of Infections with the Omicron Sub-Lineages BA.1, BA.2, and BA.5: A Retrospective Follow-Up Analysis of Public Health Data from Mecklenburg-Western Pomerania, Germany

“…Throughout the study period, the genetic diversity of the sub-lineages exhibited a steady increase, although specific details are not presented in this paper. Distinct mutations in the Omicron genome have the potential to alter the behavior and characteristics of the virus, consequently impacting its spread and affecting patient outcomes [ 8 , 9 , 10 , 31 ]. For example, the BA.2 descendant BA.2.12.1 has developed a neutralization escape mechanism affecting both vaccinated individuals and those infected with BA.1 or BA.2, potentially leading to an increased infection rate and the manifestation of more symptoms [ 32 ].…”

“…The transmissibility and immune escape of SARS-CoV-2 variants are caused by specific mutations that can alter the virus behavior and thus influence the spread, clinical severity, and clinical presentation of the virus [ 7 , 8 , 9 , 10 ]. Compared to other pre-Omicron variants, such as ‘Delta’, the Omicron BA.1 and BA.2 sub-lineages showed a higher transmissibility but less severe symptoms [ 11 , 12 , 13 ].…”

Nanomaterials to combat SARS-CoV-2: Strategies to prevent, diagnose and treat COVID-19

“…WGS and genome-wide association studies (GWAS) have been used to identify host genetic factors that predict COVID-19 severity and patient survival. In this regard, it was of special interest the GWAS analysis associating inborn errors of immunity (i.e., mainly INF and TLR genes and associated pathways) with severe COVID-19 (Bastard et al, 2020;Chung et al, 2020;Ellinghaus et al, 2020;Grasselli et al, 2020; The-Covid-Host-Genetics-Initiative, 2020; Al Kaabi et al, 2021;Alcoba-Florez et al, 2021;Bastard et al, 2021;Castano-Jaramillo et al, 2021;Fallerini et al, 2021; Frontiers in Bioengineering and Biotechnology frontiersin.org Niemi Pairo-Castineira et al, 2021;Tan et al, 2021;Karlsen, 2022;Loucera et al, 2022;Oh and Shin, 2022). In these critically ill patients, the SARS-CoV-2 infection have generally been diagnosed mainly by specific and sensitive retrotranscription and quantitative polymerase chain reaction (RT-qPCR) technique (COVID-19-Host-Genetics-Initiative, 2021) (Figure 4A).…”

Adaptive trends of sequence compositional complexity over pandemic time in the SARS-CoV-2 coronavirus

“…Particularly interesting are those changes increasing viral fitness (Dorp et al , 2020; Garvin et al , 2020; Zhou et al , 2020; Holmes et al , 2021), such as mutations giving rise to epitope loss and antibody escape mechanisms. These have mainly been found in evolved variants isolated from Europe and the Americas, and have critical implications for SARS-CoV-2 fitness (transmission, pathogenesis, and immune interventions (Gupta and Mandal, 2020; Loucera et al , 2022)). Some studies have shown that SARS-CoV-2 is acquiring mutations more slowly than expected for neutral evolution, suggesting that purifying selection is the dominant mode of evolution, at least during the initial phase of the pandemic time course.…”

“…Parallel mutations in multiple independent lineages and variants have been observed (Dorp et al ., 2020), which may indicate convergent evolution (Cooper, 2021), and are of particular interest in the context of adaptation of SARS-CoV-2 to the human host. Survival analysis of mutations in the SARS-CoV-2 genome revealed 27 of them were significantly associated with higher mortality of patients (Loucera et al ., 2022). Other authors have reported some sites under positive selection pressure in the nucleocapsid and spike genes (Benvenuto et al ., 2020).…”