Genome Sequencing of the SARS-CoV-2 Delta (B.1.617.2) Variant of Concern Detected in Bangladesh.
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ABSTRACT:
SUBMITTER: Banu TA
PROVIDER: S-EPMC8638595 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The continuous transmission and evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has required that diagnostic capabilities be constantly monitored and updated as new variants emerge and prior variants disappear. Although whole genome sequencing provides full characterisation of SARS-CoV-2 directly from patient samples, this has limited throughput and requires sufficient resources. To enhance screening for circulating variants, we designed a rapid in-house RT-PCR assay to target a spike mutation (D950N) in Delta variants, which is not detected in the remaining variants of concern (VOCs). Assay sensitivity for detecting Delta variants was 93% and specificity was 100% using a sequenced sample bank of several lineages. As the D950N mutation is prevalent in >95% of the global Delta variant sequences deposited in GISAID, this assay has the potential to provide rapid results to determine if the samples are presumptively Delta variants and can support clinicians in timely clinical decision-making for effective treatments and surveillance.
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Project description:Vaccines are proving to be highly effective in controlling hospitalisation and deaths associated with SARS-CoV-2 infection but the emergence of viral variants with novel antigenic profiles threatens to diminish their efficacy. Assessment of the ability of sera from vaccine recipients to neutralise SARS-CoV-2 variants will inform the success of strategies for minimising COVID19 cases and the design of effective antigenic formulations. Here, we examine the sensitivity of variants of concern (VOCs) representative of the B.1.617.1 and B.1.617.2 (first associated with infections in India) and B.1.351 (first associated with infection in South Africa) lineages of SARS-CoV-2 to neutralisation by sera from individuals vaccinated with the BNT162b2 (Pfizer/BioNTech) and ChAdOx1 (Oxford/AstraZeneca) vaccines. Across all vaccinated individuals, the spike glycoproteins from B.1.617.1 and B.1.617.2 conferred reductions in neutralisation of 4.31 and 5.11-fold respectively. The reduction seen with the B.1.617.2 lineage approached that conferred by the glycoprotein from B.1.351 (South African) variant (6.29-fold reduction) that is known to be associated with reduced vaccine efficacy. Neutralising antibody titres elicited by vaccination with two doses of BNT162b2 were significantly higher than those elicited by vaccination with two doses of ChAdOx1. Fold decreases in the magnitude of neutralisation titre following two doses of BNT162b2, conferred reductions in titre of 7.77, 11.30 and 9.56-fold respectively to B.1.617.1, B.1.617.2 and B.1.351 pseudoviruses, the reduction in neutralisation of the delta variant B.1.617.2 surpassing that of B.1.351. Fold changes in those vaccinated with two doses of ChAdOx1 were 0.69, 4.01 and 1.48 respectively. The accumulation of mutations in these VOCs, and others, demonstrate the quantifiable risk of antigenic drift and subsequent reduction in vaccine efficacy. Accordingly, booster vaccines based on updated variants are likely to be required over time to prevent productive infection. This study also suggests that two dose regimes of vaccine are required for maximal BNT162b2 and ChAdOx1-induced immunity.
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Project description:Natural and experimental SARS-CoV-2 infection in pets has been widely evidenced since the beginning of the COVID-19 pandemic. Among the numerous affected animals, cats are one of the most susceptible species. However, little is known about viral pathogenicity and transmissibility in the case of variants of concern (VOCs) in animal hosts, such as the B.1.617.2 (Delta) variant first detected in India. Here, we have identified the B.1.617.2 (Delta) VOC in a cat living with a COVID-19 positive owner. The animal presented mild symptoms (sneezing) and a high viral load was detected in the oropharyngeal swab, suggesting that an active infection was occurring in the upper respiratory tract of the cat. Transmission from the owner to the cat occurred despite the human being fully vaccinated against SARS-CoV-2. This study documents the first detection of B.1.165.2 VOC in a cat in Spain and emphasizes the importance of performing active surveillance and genomic investigation on infected animals.
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Project description:The B.1.617.2 (Delta) variant of concern is causing a new wave of infections in many countries. In order to better understand the changes of the SARS-CoV-2 mutation at the genetic level, we selected six mutations in the S region of the Delta variant compared with the native SARS-CoV-2 and get the conductance information of these six short RNA oligonucleotides groups by construct RNA: DNA hybrids. The electronic characteristics are investigated by the combination of density functional theory and non-equilibrium Green's function formulation with decoherence. We found that conductance is very sensitive to small changes in virus sequence. Among the 6 mutations in the Delta S region, D950N shows the largest change in relative conductance, reaching a surprising 4104.75%. These results provide new insights into the Delta variant from the perspective of its electrical properties. This may be a new method to distinguish virus variation and possess great research prospects.
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Project description:The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era.
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Project description:Several cases of naturally infected dogs with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported despite the apparently low susceptibility of this species. Here, we document the first reported case of infection caused by the Delta (B.1.617.2) variant of concern (VOC) in a dog in Spain that lived with several household members suffering from Coronavirus Infectious Disease 2019 (COVID-19). The animal displayed mild digestive and respiratory clinical signs and had a low viral load in the oropharyngeal swab collected at the first sampling. Whole-genome sequencing indicated infection with the Delta variant, coinciding with the predominant variant during the fifth pandemic wave in Spain. The dog seroconverted, as detected 21 days after the first sampling, and developed neutralizing antibodies that cross-neutralized different SARS-CoV-2 variants. This study further emphasizes the importance of studying the susceptibility of animal species to different VOCs and their potential role as reservoirs in the context of COVID-19.
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Project description:Competition assays were conducted in vitro and in vivo to examine how the Delta (B.1.617.2) variant displaced the prototype Washington/1/2020 (WA/1) strain. While WA/1 virus exhibited a moderately increased proportion compared to that in the inoculum following co-infection in human respiratory cells, Delta variant possessed a substantial in vivo fitness advantage as this virus becoming predominant in both inoculated and contact animals. This work identifies critical traits of the Delta variant that likely played a role in it becoming a dominant variant and highlights the necessities of employing multiple model systems to assess the fitness of newly emerged SARS-CoV-2 variants.
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Project description:Here, we report the identification and coding-complete genome sequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains obtained from patients with COVID-19. The strains identified belong to variant of concern B.1.617.2 and variant of interest B.1.617.1.
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Project description:BackgroundThe Delta variant (Pango lineage B.1.617.2) is one of the most significant and aggressive variants of SARS-CoV-2. To the best of our knowledge, this is the first paper specifically studying pulmonary morphopathology in COVID-19 caused by the B.1.617.2 Delta variant.MethodsThe study included 10 deceased patients (40-83 years) with the COVID-19 Delta variant. The necrotic lung fragments were obtained either by biopsy (six cases) or autopsy (four cases). Tissue samples were subjected to virology analysis for identification of the SARS-CoV-2 variant, histopathology, and immunohistochemistry (anti-SARS coronavirus mouse anti-virus antibody).ResultsVirology analysis identified B.1.617.2 through genetic sequencing in eight cases, and in two cases, specific mutations of B.1.617.2 were identified. Macroscopically, in all autopsied cases, the lung had a particular appearance, purple in color, with increased consistency on palpation and abolished crepitations. Histopathologically, the most frequently observed lesions were acute pulmonary edema (70%) and diffuse alveolar damage at different stages. The immunohistochemical examination was positive for proteins of SARS-CoV-2 in 60% of cases on alveolocytes and in endothelial cells.ConclusionsThe histopathological lung findings in the B.1.617.2 Delta variant are similar to those previously described in COVID-19. Spike protein-binding antibodies were identified immunohistochemically both on alveolocytes and in the endothelial cells, showing the potential of indirect damage from thrombosis.
| S-EPMC9961426 | biostudies-literature
Project description:ImportanceThe Delta variant (B.1.617.2) is estimated to be more transmissible than previous strains of SARS-CoV-2, especially among children and adolescents. However, to our knowledge, there are no reports confirming this to date.ObjectiveTo gain a better understanding of the association of age with susceptibility to the Delta variant of SARS-CoV-2.Design, setting, and participantsThis decision analytic model used an age-structured compartmental model using the terms symptom onset (S), exposure (E), infectious (I), and quarantine (Q) (SEIQ) to estimate the age-specific force of infection, combining age-specific contact matrices and observed distribution of periods between each stage of infection (E to I [ie, latent period], I given S, and S to Q [ie, diagnostic delay]) developed in a previous contact tracing study. A bayesian inference method was used to estimate the age-specific force of infection (S to E) and, accordingly, age-specific susceptibility. The age-specific susceptibility during the third wave (ie, before Delta, from October 15 to December 22, 2020, when the COVID-19 vaccination campaign was not yet launched) and the fourth wave (ie, the Delta-driven wave, from June 27 to August 21, 2021) in Korea were compared. As vaccine uptake increased, individuals who were vaccinated were excluded from the susceptible population in accordance with vaccine effectiveness against the Delta variant. This nationwide epidemiologic study included individuals who were diagnosed with COVID-19 during the study period in Korea. Data were analyzed from September to November 2021.ExposuresAge group during the third wave (ie, before Delta) and fourth wave (ie, Delta-driven) of the COVID-19 pandemic in South Korea.Main outcomes and measuresAge-specific susceptibility during the third and fourth waves was estimated.ResultsAmong 106 866 confirmed COVID-19 infections (including 26 597 infections and 80 269 infections during the third and fourth waves of COVID-19 in Korea, respectively), a significant difference in age-specific susceptibility to the Delta vs pre-Delta variant was found in the younger age group. After adjustment for contact pattern and vaccination status, the increase in susceptibility to the Delta vs pre-Delta variant was estimated to be highest in the group aged 10 to 15 years, approximately doubling (1.92-fold increase [95% CI, 1.86-fold to 1.98-fold]), whereas in the group aged 50 years or more, susceptibility to the Delta vs pre-Delta variant remained stable at an approximately 1-fold change (eg, among individuals aged 50-55 years: 0.997-fold [95% CI, 0.989-fold to 1.001-fold).Conclusions and relevanceIn this study, the Delta variant of SARS-CoV-2 was estimated to propagate more easily among children and adolescents than pre-Delta strains, even after adjusting for contact pattern and vaccination status.
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