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

Loucera, Carlos; Pérez-Florido, Javier; Casimiro-Soriguer, Carlos S.; Guzman, Francisco M. Ortuño; Carmona, Rosario; Bostelmann, Gerrit; Martínez-González, Luis Javier; Muñoyerro-Muñiz, Dolores; Villegas, R.; Romero‐Gómez, Manuel; Lorusso, Nicola; García-León, Francisco Javier; Navarro-Marí, José María; Camacho‐Martínez, Pedro; Merino-Díaz, Laura; Salazar, Adolfo de; Viñuela, Laura; Lepe, José Antonio; García, Federico; Dopazo, Joaquı́n

doi:10.1101/2022.07.07.22277353

Cited by 3 publications

(4 citation statements)

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“…Parallel mutations in multiple independent lineages and variants have been observed (Dorp et al 2020), which may indicate convergent evolution, 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 pressure in the nucleocapsid and spike genes (Benvenuto et al 2020).…”

Section: Introductionmentioning

confidence: 97%

“…2020), 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 & Mandal 2020; Loucera et al . 2022)).…”

Section: Introductionmentioning

confidence: 99%

“…2020), which may indicate convergent evolution, 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).…”

Section: Introductionmentioning

confidence: 99%

“…Particularly interesting are those changes increasing viral fitness (Dorp et al 2020;Holmes et al 2021;Zhou et al 2020), 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 & 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.…”

Section: Introductionmentioning

confidence: 99%

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

Oliver

Bernaola‐Galván

Perfectti

et al. 2021

Preprint

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In the brief time since the outbreak of the COVID-19 pandemic, and despite its proofreading mechanism, the SARS-CoV-2 coronavirus has accumulated a significant amount of genetic variability through recombination and mutation events. To test evolutionary trends that could inform us on the adaptive process of the virus to its human host, we summarize all this variability in the Sequence Compositional Complexity (SCC), a measure of genome heterogeneity that captures the mutational and recombinational changes accumulated by a nucleotide sequence along time. Despite the brief time elapsed, we detected many differences in the number and length of compositional domains, as well as in their nucleotide frequencies, in more than 12,000 high-quality coronavirus genomes from across the globe. These differences in SCC are phylogenetically structured, as revealed by significant phylogenetic signal. Phylogenetic ridge regression shows that SCC followed a generalized decreasing trend along the ongoing process of pathogen evolution. In contrast, SCC evolutionary rate increased with time, showing that it accelerates toward the present. In addition, a low rate set of genomes was detected in all the genome groups, suggesting the existence of a stepwise distribution of rates, a strong indication of selection in favor of different dominant strains. Coronavirus variants reveal an exacerbation of this trend: non-significant SCC regression, low phylogenetic signal and, concomitantly, a threefold increase in the evolutionary rate. Altogether, these results show an accelerated decline of genome heterogeneity along with the SARS-CoV-2 pandemic expansion, a process that might be related to viral adaptation to the human host, perhaps paralleling the transformation of the current pandemic to epidemic.

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Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Oliver

Bernaola‐Galván

Perfectti

et al. 2021

Preprint

View full text Add to dashboard Cite

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Molecular and Clinical Epidemiology of SARS-CoV-2 Infection among Vaccinated and Unvaccinated Individuals in a Large Healthcare Organization from New Jersey

Mediavilla,

Lozy,

Lee

et al. 2023

Viruses

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New Jersey was among the first states impacted by the COVID-19 pandemic, with one of the highest overall death rates in the nation. Nevertheless, relatively few reports have been published focusing specifically on New Jersey. Here we report on molecular, clinical, and epidemiologic observations, from the largest healthcare network in the state, in a cohort of vaccinated and unvaccinated individuals with laboratory-confirmed SARS-CoV-2 infection. We conducted molecular surveillance of SARS-CoV-2-positive nasopharyngeal swabs collected in nine hospitals from December 2020 through June 2022, using both whole genome sequencing (WGS) and a real-time RT-PCR screening assay targeting spike protein mutations found in variants of concern (VOCs) within our region. De-identified clinical data were obtained retrospectively, including demographics, COVID-19 vaccination status, ICU admission, ventilator support, mortality, and medical history. Statistical analyses were performed to identify associations between SARS-CoV-2 variants, vaccination status, clinical outcomes, and medical risk factors. A total of 5007 SARS-CoV-2-positive nasopharyngeal swabs were successfully screened and/or sequenced. Variant screening identified three predominant VOCs, including Alpha (n = 714), Delta (n = 1877), and Omicron (n = 1802). Omicron isolates were further sub-typed as BA.1 (n = 899), BA.2 (n = 853), or BA.4/BA.5 (n = 50); the remaining 614 isolates were classified as “Other”. Approximately 31.5% (1577/5007) of the samples were associated with vaccine breakthrough infections, which increased in frequency following the emergence of Delta and Omicron. Severe clinical outcomes included ICU admission (336/5007 = 6.7%), ventilator support (236/5007 = 4.7%), and mortality (430/5007 = 8.6%), with increasing age being the most significant contributor to each (p < 0.001). Unvaccinated individuals accounted for 79.7% (268/336) of ICU admissions, 78.3% (185/236) of ventilator cases, and 74.4% (320/430) of deaths. Highly significant (p < 0.001) increases in mortality were observed in individuals with cardiovascular disease, hypertension, cancer, diabetes, and hyperlipidemia, but not with obesity, thyroid disease, or respiratory disease. Significant differences (p < 0.001) in clinical outcomes were also noted between SARS-CoV-2 variants, including Delta, Omicron BA.1, and Omicron BA.2. Vaccination was associated with significantly improved clinical outcomes in our study, despite an increase in breakthrough infections associated with waning immunity, greater antigenic variability, or both. Underlying comorbidities contributed significantly to mortality in both vaccinated and unvaccinated individuals, with increasing risk based on the total number of comorbidities. Real-time RT-PCR-based screening facilitated timely identification of predominant variants using a minimal number of spike protein mutations, with faster turnaround time and reduced cost compared to WGS. Continued evolution of SARS-CoV-2 variants will likely require ongoing surveillance for new VOCs, with real-time assessment of clinical impact.

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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

Goller,

Ziemann,

Kohler

et al. 2024

Viruses

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The Omicron variants BA.1, BA.2, and BA.5 caused several waves of SARS-CoV-2 in Germany in 2022. In this comparative study, public health data on SARS-CoV-2 infections from Mecklenburg-Western Pomerania, Germany, between January and October 2022 were examined retrospectively using Pearson’s chi-squared tests and Fisher’s exact tests for testing for statistical significance. Compared to BA.5 infections, BA.1 and BA.2 infections affected younger individuals aged up to 19 years significantly more often, whereas BA.5 infections occurred significantly more frequently in patients between 40 and 59 years of age when compared to BA.1 and BA.2. Infections with all three variants predominantly caused flu-like symptoms; nevertheless, there were significant differences between the reported symptoms of BA.1, BA.2, and BA.5 infections. Especially, the symptoms of ‘fever’, ‘severe feeling of sickness’, ‘loss of taste’, and ‘loss of smell’ were significantly more often present in patients with BA.5 infections compared to BA.1 and BA.2 cases. Additionally, BA.2 and BA.5 cases reported significantly more often the symptoms of ‘runny nose’ and ‘cough’ than BA.1-infected cases. Our findings indicate remarkable differences in the clinical presentations among the sub-lineages, especially in BA.5 infections. Furthermore, the study demonstrates a powerful tool to link epidemiological data with genetic data in order to investigate their potential impact on public health.

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

Cited by 3 publications

References 53 publications

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

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

Molecular and Clinical Epidemiology of SARS-CoV-2 Infection among Vaccinated and Unvaccinated Individuals in a Large Healthcare Organization from New Jersey

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

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