Expanding repertoire of SARS-CoV-2 deletion mutations contributes to evolution of highly transmissible variants

A. J. Venkatakrishnan, Praveen Anand, Patrick J. Lenehan, Pritha Ghosh, Rohit Suratekar, Eli Silvert, Colin Pawlowski, Abhishek Siroha, Dibyendu Roy Chowdhury, John C. O’Horo, Joseph D. Yao, Bobbi S. Pritt, Andrew P. Norgan, Ryan T. Hurt, Andrew D. Badley, John Halamka, Venky Soundararajan

Research output: Contribution to journalArticlepeer-review


The emergence of highly transmissible SARS-CoV-2 variants and vaccine breakthrough infections globally mandated the characterization of the immuno-evasive features of SARS-CoV-2. Here, we systematically analyzed 2.13 million SARS-CoV-2 genomes from 188 countries/territories (up to June 2021) and performed whole-genome viral sequencing from 102 COVID-19 patients, including 43 vaccine breakthrough infections. We identified 92 Spike protein mutations that increased in prevalence during at least one surge in SARS-CoV-2 test positivity in any country over a 3-month window. Deletions in the Spike protein N-terminal domain were highly enriched for these ‘surge-associated mutations’ (Odds Ratio = 14.19, 95% CI 6.15–32.75, p value = 3.41 × 10–10). Based on a longitudinal analysis of mutational prevalence globally, we found an expanding repertoire of Spike protein deletions proximal to an antigenic supersite in the N-terminal domain that may be one of the key contributors to the evolution of highly transmissible variants. Finally, we generated clinically annotated SARS-CoV-2 whole genome sequences from 102 patients and identified 107 unique mutations, including 78 substitutions and 29 deletions. In five patients, we identified distinct deletions between residues 85–90, which reside within a linear B cell epitope. Deletions in this region arose contemporaneously on a diverse background of variants across the globe since December 2020. Overall, our findings based on genomic-epidemiology and clinical surveillance suggest that the genomic deletion of dispensable antigenic regions in SARS-CoV-2 may contribute to the evasion of immune responses and the evolution of highly transmissible variants.

Original languageEnglish (US)
Article number257
JournalScientific reports
Issue number1
StatePublished - Dec 2023

ASJC Scopus subject areas

  • General


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