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Impact of intra-host immune adaptations on the evolution of SARS-CoV-2 S protein among individuals with SARS-CoV-2 infections in South Africa, 2020 to 2022
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  • Kathleen Subramoney,
  • Nkhensani Mtileni,
  • Ashlyn Davis,
  • Jennifer Giandhari,
  • Yeshnee Naidoo,
  • Yajna Ramphal,
  • Sureshnee Pillay,
  • Upasana Ramphal,
  • Houriiyah Tegally,
  • Eduan Wilkinson,
  • Andiswa Simane,
  • Bhaveshan Reddy,
  • Bonolo Mashishi,
  • Nonhlanhla Mbenenge,
  • Tulio de Oliveira,
  • Burtram Fielding,
  • Florette Treurnicht
Kathleen Subramoney
National Health Laboratory Service

Corresponding Author:[email protected]

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Nkhensani Mtileni
National Health Laboratory Service
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Ashlyn Davis
National Health Laboratory Service
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Jennifer Giandhari
University of KwaZulu-Natal Nelson R Mandela School of Medicine
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Yeshnee Naidoo
University of KwaZulu-Natal Nelson R Mandela School of Medicine
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Yajna Ramphal
University of KwaZulu-Natal Nelson R Mandela School of Medicine
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Sureshnee Pillay
University of KwaZulu-Natal Nelson R Mandela School of Medicine
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Upasana Ramphal
University of KwaZulu-Natal Nelson R Mandela School of Medicine
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Houriiyah Tegally
University of KwaZulu-Natal Nelson R Mandela School of Medicine
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Eduan Wilkinson
Stellenbosch University
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Andiswa Simane
National Health Laboratory Service
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Bhaveshan Reddy
National Health Laboratory Service
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Bonolo Mashishi
National Health Laboratory Service
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Nonhlanhla Mbenenge
National Health Laboratory Service
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Tulio de Oliveira
University of KwaZulu-Natal Nelson R Mandela School of Medicine
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Burtram Fielding
University of the Western Cape
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Florette Treurnicht
National Health Laboratory Service
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Abstract

Background Intra-host diversity studies are used to characterise mutational heterogeneity of SARS-CoV-2 infections to understand the impact of virus-host adaptations. This study investigated the frequency and diversity of the spike (S) protein mutations within SARS-CoV-2 infected South African individuals. Methods Single nucleotide polymorphism (SNP) assays and whole genome sequencing were performed on SARS-CoV-2 positive samples. Allele frequency (AF) was determined using TaqMan Genotyper software for SNP analysis and galaxy.eu for analysis of FASTQ reads. Results The SNP assays identified 5.3% (50/948) Delta cases with heterogeneity at delY144 (4%; 2/50), E484Q (6%; 3/50), N501Y (2%; 1/50) and P681H (88%; 44/50). Sequencing identified 9% (210/2381) cases with Beta, Delta, Omicron BA.1, BA.2.15, and BA.4 lineages with heterogeneity in the S protein. Heterogeneity was primarily identified at positions 19 (1.4%) with T19IR (AF 0.2-0.7), 371 (92.3%) with S371FP (AF 0.1-1.0), and 484 (1.9%) with E484AK (0.2-0.7), E484AQ (AF 0.4-0.5) and E484KQ (AF 0.1-0.4). Conclusion Mutations at heterozygous amino acid positions 19, 371 and 484 reduce recognition of neutralising antibodies, however the impact of the multiple substitutions at the same position is unknown. Therefore, we hypothesise that intra-host SARS-CoV-2 quasispecies with heterogeneity in the S protein facilitate competitive advantage of variants that can completely/partially evade host’s natural and vaccine-induced immune responses.