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      Reinfection rate and disease severity of the BA.5 Omicron SARS-CoV-2 lineage compared to previously circulating variants of concern in the Canary Islands (Spain)

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          ABSTRACT

          The emergence of the Omicron SARS-CoV-2 variant of concern has changed the COVID-19 scenario as this variant is characterized by high transmissibility and immune evasion ability. To evaluate the impact of this variant on the Canary Islands (Spain) population, we determined the reinfection rates and disease severity associated with the Omicron sublineages and the previously circulating variants of concern. We performed a retrospective observational study on 21,745 SARS-CoV-2 viral genomes collected from December 2020 to July 2022 in the Canary Islands (Spain). We compared the reinfection rates between lineages using pairwise proportion and Fisher’s exact tests. To assess disease severity, we studied the association of Alpha, Delta, BA.1, BA.2, BA.5, and other risk factors on 28-day hospital mortality using logistic regression and Cox proportional hazard models. We observed 127 bona fide reinfection cases throughout the study period. We found that BA.5 had the highest reinfection rate compared to other lineages (vs. Delta p = 2.89 × 10 −25; vs. BA.1 p = 5.17 × 10 −11; vs. BA.2 p = 0.002). Among the 1,094 hospitalized patients, multivariate logistic regression showed that Alpha (Odds Ratio [OR] =  0.45, 95% Confidence Interval [CI] =  0.23-0.87, p = 0.02), BA.2 (OR =   0.38, 95% CI = 0.22-0.63, p = 1.91 × 10 −4), and BA.5 (OR =  0.30, 95% CI = 0.16-0.55, p = 1.05 × 10 −4) had lower 28-day hospital mortality compared to Delta. These results were confirmed by using Cox proportional hazard models. Omicron lineages, and in particular BA.5, were associated with higher reinfection rates and lower disease severity (28-day hospital mortality) than previously circulating variants of concern.

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          BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection

          Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages BA.2.12.1, BA.4 and BA.5 exhibit higher transmissibility than the BA.2 lineage 1 . The receptor binding and immune-evasion capability of these recently emerged variants require immediate investigation. Here, coupled with structural comparisons of the spike proteins, we show that BA.2.12.1, BA.4 and BA.5 (BA.4 and BA.5 are hereafter referred collectively to as BA.4/BA.5) exhibit similar binding affinities to BA.2 for the angiotensin-converting enzyme 2 (ACE2) receptor. Of note, BA.2.12.1 and BA.4/BA.5 display increased evasion of neutralizing antibodies compared with BA.2 against plasma from triple-vaccinated individuals or from individuals who developed a BA.1 infection after vaccination. To delineate the underlying antibody-evasion mechanism, we determined the escape mutation profiles 2 , epitope distribution 3 and Omicron-neutralization efficiency of 1,640 neutralizing antibodies directed against the receptor-binding domain of the viral spike protein, including 614 antibodies isolated from people who had recovered from BA.1 infection. BA.1 infection after vaccination predominantly recalls humoral immune memory directed against ancestral (hereafter referred to as wild-type (WT)) SARS-CoV-2 spike protein. The resulting elicited antibodies could neutralize both WT SARS-CoV-2 and BA.1 and are enriched on epitopes on spike that do not bind ACE2. However, most of these cross-reactive neutralizing antibodies are evaded by spike mutants L452Q, L452R and F486V. BA.1 infection can also induce new clones of BA.1-specific antibodies that potently neutralize BA.1. Nevertheless, these neutralizing antibodies are largely evaded by BA.2 and BA.4/BA.5 owing to D405N and F486V mutations, and react weakly to pre-Omicron variants, exhibiting narrow neutralization breadths. The therapeutic neutralizing antibodies bebtelovimab 4 and cilgavimab 5 can effectively neutralize BA.2.12.1 and BA.4/BA.5, whereas the S371F, D405N and R408S mutations undermine most broadly sarbecovirus-neutralizing antibodies. Together, our results indicate that Omicron may evolve mutations to evade the humoral immunity elicited by BA.1 infection, suggesting that BA.1-derived vaccine boosters may not achieve broad-spectrum protection against new Omicron variants.
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            Assignment of Epidemiological Lineages in an Emerging Pandemic Using the Pangolin Tool

            The response of the global virus genomics community to the SARS-CoV-2 pandemic has been unprecedented, with significant advances made towards the ‘real-time’ generation and sharing of SARS-CoV-2 genomic data. The rapid growth in virus genome data production has necessitated the development of new analytical methods that can deal with orders of magnitude more genomes than previously available. Here we present and describe pangolin (Phylogenetic Assignment of Named Global Outbreak Lineages), a computational tool that has been developed to assign the most likely lineage to a given SARS-CoV-2 genome sequence according to the Pango dynamic nomenclature scheme described in Rambaut et al. (2020). To date, nearly two million virus genomes have been submitted to the web-application implementation of pangolin, which has facilitated the SARS-CoV-2 genomic epidemiology and provided researchers with access to actionable information about the pandemic’s transmission lineages.
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              Increased risk of SARS-CoV-2 reinfection associated with emergence of Omicron in South Africa

              Here, we provide two methods for monitoring reinfection trends in routine surveillance data to identify signatures of changes in reinfection risk and apply these approaches to data from South Africa’s SARS-CoV-2 epidemic to date. While we found no evidence of increased reinfection risk associated with circulation of Beta (B.1.351) or Delta (B.1.617.2) variants, we find clear, population-level evidence to suggest immune evasion by the Omicron (B.1.1.529) variant in previously infected individuals in South Africa. Reinfections occurring between 01 November 2021 and 31 January 2022 were detected in individuals infected in all three previous waves, and there has been an increase in the risk of having a third infection since mid-November 2021.
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                Author and article information

                Journal
                Emerg Microbes Infect
                Emerg Microbes Infect
                Emerging Microbes & Infections
                Taylor & Francis
                2222-1751
                1 May 2023
                2023
                1 May 2023
                : 12
                : 1
                : 2202281
                Affiliations
                [a ]Research Unit , Hospital Universitario N. S. de Candelaria , Santa Cruz de Tenerife, Spain
                [b ] Genomics Division, Instituto Tecnológico y de Energías Renovables , Santa Cruz de Tenerife, Spain
                [c ]Servicio de Microbiología, Hospital Universitario N. S. de Candelaria , Santa Cruz de Tenerife, Spain
                [d ]Laboratorio de Inmunología Celular y Viral, Unidad de Farmacología, Facultad de Medicina, Universidad de La Laguna , San Cristóbal de La Laguna, Spain
                [e ]CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III , Madrid, Spain
                [f ]Facultad de Ciencias de la Salud, Universidad Fernando Pessoa Canarias , Las Palmas de Gran Canaria, Spain
                Author notes
                [CONTACT ] Carlos Flores cflores@ 123456ull.edu.es Research Unit, Hospital Universitario N. S. de Candelaria , 38010 Santa Cruz de Tenerife, Spain
                Genomics Division, Instituto Tecnológico y de Energías Renovables , 38600 Santa Cruz de Tenerife, Spain
                CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III , 28029 Madrid, Spain
                Facultad de Ciencias de la Salud, Universidad Fernando Pessoa Canarias , 35450 Las Palmas de Gran Canaria, Spain
                [†]

                Equal contribution

                Supplemental data for this article can be accessed online at https://doi.org/10.1080/22221751.2023.2202281.

                Author information
                https://orcid.org/0000-0001-5352-069X
                Article
                2202281
                10.1080/22221751.2023.2202281
                10155628
                37039029
                4ff3d4c0-6008-40cf-ad03-a6f547c810f7
                © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.

                History
                Page count
                Figures: 5, Tables: 1, Equations: 0, References: 20, Pages: 8
                Categories
                Coronaviruses
                Research Article

                sars-cov-2,variants of concern,omicron lineage,reinfection,disease severity

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