SARS-CoV-2 Variants Associated with Vaccine Breakthrough in the Delaware Valley through Summer 2021

Area of Science:

• Virology
• Epidemiology
• Genomics

Background:

• Severe acute respiratory coronavirus-2 (SARS-CoV-2) causes COVID-19 and evolves for efficient human transmission.
• Vaccine breakthrough infections are observed, prompting investigation into specific viral variants or mutations associated with them.

Purpose of the Study:

• To analyze SARS-CoV-2 viral variants in the Delaware Valley from March 2020 to September 2021.
• To compare viral genomes from surveillance samples with those from vaccine breakthrough cases.
• To identify specific variants and mutations enriched in vaccine breakthrough infections.

Main Methods:

• Sequencing and analysis of 2621 complete viral genomes from surveillance samples.
• Comparison with 159 genome sequences from vaccine breakthrough cases.
• Application of Bayesian autoregressive moving average logistic multinomial regression for variant enrichment analysis.

Main Results:

• SARS-CoV-2 lineages evolved from B.1 to B.1.1.7 (alpha) and predominantly B.1.617.2 (delta) over the study period.
• The B.1.617.2 (delta) variant showed a 3-fold enrichment in vaccine breakthrough cases (OR 3; 95% CI 0.89-11).
• The N501Y substitution was associated with a 2.04-fold enrichment in vaccine breakthroughs (95% CI 1.25-3.18).

Conclusions:

• The study provides an overview of SARS-CoV-2 evolution and vaccine breakthroughs in the Delaware Valley.
• Delta lineages and the N501Y mutation are associated with increased odds of vaccine breakthrough infections.
• The statistical methods introduced can be valuable for evaluating viral phenotypes like vaccine breakthroughs.