Genetic epidemiology of variants associated with immune escape from global SARS-CoV-2 genomes

Jolly, Bani; Rophina, Mercy; Shamnath, Afra; Imran, Mohamed; Bhoyar, Rahul C.; Divakar, Mohit Kumar; Rojarani, Pallavali; Ranjan, Gyan; Sehgal, Paras; Chandrasekhar, Pulala; Afşar, Selim; Lakshmi, J Vijaya; Surekha, A.; Sivasubbu, Sridhar; Scaria, Vinod

doi:10.1101/2020.12.24.424332

Cited by 18 publications

(17 citation statements)

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“…The variant has previously been shown to emerge in vitro under selective pressure against the human monoclonal antibody C135 and show resistance to it [3] . The variant had a high prevalence of over 33% in the state of Andhra Pradesh [10] and has been reported previously in another case of SARS-CoV-2 reinfection from North India [1] . Phylogenetic analysis for the 2 isolates was done using all global genomes having the N440K variant, which includes 92 genomes from India sequenced in-house (BioProject ID: PRJNA655577).…”

Section: Dear Editorsupporting

confidence: 71%

Symptomatic reinfection of SARS-CoV-2 with spike protein variant N440K associated with immune escape

Rani¹,

Imran²,

Lakshmi³

et al. 2021

Preprint

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Here we describe a case of re-infection in an individual from South India characterized by whole genome sequencing of the virus isolated from both episodes. The analysis shows the presence of an immune escape variant N440K in the Spike protein in both episodes of infection. Incidentally, this variant was also found in a case of reinfection previously reported by us in a healthcare worker from North India

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Section: Dear Editorsupporting

confidence: 71%

Symptomatic reinfection of SARS-CoV-2 with spike protein variant N440K associated with immune escape

Rani¹,

Imran²,

Lakshmi³

et al. 2021

Preprint

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“…The lineage is characterized by the following amino acid replacements-nsp12-P323L(95.38%), S-D614G (93.85%), S-N440K (56.92%), ORF 3a-Q57H (90.77%), ORF 3a-E261*(81.54%), nsp3-T183I (81.54%), nsp16-L126F(80%), N-S2P (72.31%), ORF 8-S97I (72.31%) (Supplementary Table 9). The immune escape associated amino acid change, N440K has been reported from the states of Andhra Pradesh, Maharashtra, Telangana, and Karnataka, and is also associated with reinfection 24,36,44 . This change was found in 37/65 (56.92%) of the sequences clustering to B.1.36 (Supplementary Table 9).…”

Section: Discussionmentioning

confidence: 98%

“…They occurred singly or in pairs (N440K+F490S) (Fig 2). All nine amino acid changes, namely N440K, S477N, V483A, E484K/Q, F490S, S494L/P, N501Y are associated with immune escape 24,25 . Viruses with some of these amino acid changes were already known to be circulating in other parts of India 16,17,24 .…”

Section: Discussionmentioning

confidence: 99%

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Importation, circulation, and emergence of variants of SARS-CoV-2 in the South Indian State of Karnataka

Pattabiraman

Prasad

George

et al. 2021

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As the pandemic of COVID-19 caused by the coronavirus SARS-CoV-2 continues, the selection of genomic variants which can influence how the pandemic progresses is of growing concern. Of particular concern, are those variants that carry mutations/amino acid changes conferring higher transmission, more severe disease, re-infection, and immune escape. These can broadly be classified as Variants of Concern (VOCs). VOCs have been reported from several parts of the world- UK (lineage B.1.1.7), South Africa (lineage B.1.351) and, Brazil (lineage P.1/B.1.1.28). The conditions that contribute to the emergence of VOCs are not well understood. International travel remains an important means of spread. To track importation, spread, and the emergence of variants locally; we sequenced whole genomes of SARS-CoV-2 from international travellers (n=75) entering Karnataka, a state in South India, between Dec 22, 2020- Jan 31, 2021, and from positive cases in the city of Bengaluru (n=108), between Nov 22, 2020- Jan 22, 2021. The resulting 176 SARS-CoV-2 genomes could be classified into 34 lineages, that were either imported (73/176) or circulating (103/176) in this time period. The lineage B.1.1.7 (a.k.a the UK variant) was the major lineage imported into the state (24/73, 32.9%), followed by B.1.36 (20/73, 27.4%) and B.1 (14/73, 19.2%). We identified B.1.36 (45/103; 43.7%), B.1 (26/103; 25.2%), B.1.1.74 (5/103; 4.9%) and B.1.468 (4/103; 3.9%) as the major variants circulating in Bengaluru city. A distinct clade within the B.1.36 lineage was associated with a local outbreak. Analysis of the complete genomes predicted multiple amino acid replacements in the Spike protein. In total, we identified nine amino acid changes (singly or in pairs) in the Receptor Binding Domain of the Spike protein. Of these, the amino acid replacement N440K was found in 37/65 (56.92%) sequences in the B.1.36 lineage. The E484K amino acid change which is present in both VOCs, B.1.351 and P.1/B.1.1.28, was found in a single circulating virus in the B.1.36 lineage. This study highlights the introduction of VOCs by travel and the local circulation of viruses with amino acid replacements in the Spike protein. These were spread across lineages, suggesting that multiple paths can lead to the emergence of VOCs, this, in turn, highlights the need to sequence and limit outbreaks of SARS-CoV-2 locally. Our data support the use of concentrated and continued genomic surveillance of SARS-CoV-2 to direct public health measures, suggest revisions to vaccines, and serve as an early warning system to prepare for a surge in COVID-19 cases.

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“…Name Frequency 40 ). The immune escape associated amino acid change, N440K has been reported from the states of Andhra Pradesh, Maharashtra, Telangana, and Karnataka, and is also associated with reinfection 24,36,45 . This change was found in 37/65 (56.92%) of the sequences clustering to B.1.36 (extended data, Supplementary Table 7 40 ).…”

Section: Srnomentioning

confidence: 98%

Importation, circulation, and emergence of variants of SARS-CoV-2 in the South Indian state of Karnataka

et al. 2021

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Background: As the coronavirus disease 2019 (COVID-19) pandemic continues, the selection of genomic variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) associated with higher transmission, more severe disease, re-infection, and immune escape are a cause for concern. Such variants have been reported from the UK (B.1.1.7), South Africa (B.1.351) and, Brazil (P.1/B.1.1.28). We performed this study to track the importation, spread, and emergence of variants locally. Methods: We sequenced whole genomes of SARS-CoV-2 from international travellers (n=75) entering Karnataka, South India, between Dec 22, 2020 and Jan 31, 2021, and from positive cases in the city of Bengaluru (n=108), between Nov 22, 2020- Jan 22, 2021, as well as a local outbreak. We present the lineage distribution and analysis of these sequences. Results: Genomes from the study group into 34 lineages. Variant B.1.1.7 was introduced by international travel (24/73, 32.9%). Lineage B.1.36 and B.1 formed a major fraction of both imported (B.136: 20/73, 27.4%; B.1: 14/73, 19.2%), and circulating viruses (B.1.36: 45/103; 43.7%, B.1: 26/103; 25.2%). The lineage B.1.36 was also associated with a local outbreak. We detected nine amino acid changes, previously associated with immune escape, spread across multiple lineages. The N440K change was detected in 45/162 (27.7%) of the sequences. Conclusions: Our data support the idea that variants of concern spread by travel. Viruses with amino acid replacements associated with immune escape are already circulating. It is critical to check transmission and monitor changes in SARS-CoV-2 locally.

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Genetic epidemiology of variants associated with immune escape from global SARS-CoV-2 genomes

Cited by 18 publications

References 8 publications

Symptomatic reinfection of SARS-CoV-2 with spike protein variant N440K associated with immune escape

Symptomatic reinfection of SARS-CoV-2 with spike protein variant N440K associated with immune escape

Importation, circulation, and emergence of variants of SARS-CoV-2 in the South Indian State of Karnataka

Importation, circulation, and emergence of variants of SARS-CoV-2 in the South Indian state of Karnataka

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