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SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion.

ABSTRACT: 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.

SUBMITTER: Mlcochova P

PROVIDER: S-EPMC8566220 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion.

Mlcochova Petra P Kemp Steven A SA Dhar Mahesh Shanker MS Papa Guido G Meng Bo B Ferreira Isabella A T M IATM Datir Rawlings R Collier Dami A DA Albecka Anna A Singh Sujeet S Pandey Rajesh R Brown Jonathan J Zhou Jie J Goonawardane Niluka N Mishra Swapnil S Whittaker Charles C Mellan Thomas T Marwal Robin R Datta Meena M Sengupta Shantanu S Ponnusamy Kalaiarasan K Radhakrishnan Venkatraman Srinivasan VS Abdullahi Adam A Charles Oscar O Chattopadhyay Partha P Devi Priti P Caputo Daniela D Peacock Tom T Wattal Chand C Goel Neeraj N Satwik Ambrish A Vaishya Raju R Agarwal Meenakshi M Mavousian Antranik A Lee Joo Hyeon JH Bassi Jessica J Silacci-Fegni Chiara C Saliba Christian C Pinto Dora D Irie Takashi T Yoshida Isao I Hamilton William L WL Sato Kei K Bhatt Samir S Flaxman Seth S James Leo C LC Corti Davide D Piccoli Luca L Barclay Wendy S WS Rakshit Partha P Agrawal Anurag A Gupta Ravindra K RK

Nature 20210906 7883

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)<sup>1</sup>. 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. Seru ...[more]

PMID: 34488225

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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.

Project description:The emergence of the B.1.617.2 (Delta) variant of the severe acute syndrome coronavirus (SARS-CoV-2) that emerged in 2019 (COVID-19), resulted in a surge of cases in India and has expanded and been detected across the world, including in the United States. The B.1.617.2 (Delta) variant has been seen to be twice more transmissible coupled with potential increases in disease severity and immune escape. As a result, case numbers and hospitalisations are once again on the rise in the USA. On 16 July 2021, the Centers for Disease Control and Prevention (CDC) reported a 7-day average 69.3% increase in new cases and a 35% increase in hospitalisations. Although the gold standard for SARS-CoV-2 variants identification remains genomic sequencing, this approach is not accessible to many clinical laboratories. The main goal of this study was to validate and implement the detection of the B.1.617.2 (Delta) variant utilising an open reverse transcription polymerase chain reaction (RT-PCR) platform by explicitly detecting the S-gene target failure (SGTF) corresponding to the deletion of two amino acids (ΔE156/ΔF157) characteristic of B.1.617.2 (Delta) variant. This approach was conceived as a rapid screening of B.1.617.2 (Delta) variant in conjunction with CDC's recommended N1 (nucleocapsid gene), N2, and RP (human RNase P) genes, as a pre-screening tool prior to viral genomic sequencing. We assessed 4,937 samples from 5 July to 5 September 2021. We identified the B.1.617.2 (Delta) variant in 435 of 495 positive samples (87.8%); the additional positive samples (7 samples, 1.4%) were found to belong to the B.1.1.7 (Alpha, UK) lineage and the remaining 53 samples (10.7%) were reported as 'other' lineages. Whole genome sequencing of 46 randomly selected samples validated the strains identified as positive and negative for the B.1.617.2 (Delta) variant and confirmed the S gene deletion in addition to B.1.617.2 characteristic mutations including L452R, T478K, P681R and D950N located in the spike protein. This modality has been used as routine testing at the Riverside University System Health (RUHS) Medical Center as a method for detection of B.1.617.2 (Delta) to pre-screen samples before genome sequencing. The assay can be easily implemented in clinical laboratories, most notably those with limited economic resources and access to genomic platforms.

Dataset Information

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion.

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SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion.

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