SARS-CoV-2 vaccination is highly effective at reducing viral infection, hospitalization and death. However, vaccine breakthrough infections have been widely observed, raising the question of whether particular viral variants or viral mutations are associated with breakthrough. Here, we report analysis of 2621 surveillance isolates from people diagnosed with COVID-19 in the Delaware Valley in southeastern Pennsylvania, allowing rigorous comparison to 159 vaccine breakthrough case specimens. Our best estimate is a 3-fold enrichment for some lineages of delta among breakthroughs, and enrichment of a notable spike substitution, N501Y. We introduce statistical methods that should be widely useful for evaluating vaccine breakthroughs and other viral phenotypes.
Marques AD, Sherrill-Mix S, Everett JK, Reddy S, Hokama P, Roche AM, Hwang Y, Glascock A, Whiteside SA, Graham-Wooten J, Khatib LA, Fitzgerald AS, Moustafa AM, Bianco C, Rajagopal S, Helton J, Deming R, Denu L, Ahmed A, Kitt E, Coffin SE, Newbern C, Mell JC, Planet PJ, Badjatia N, Richards B, Wang ZX, Cannuscio CC, Strelau KM, Jaskowiak-Barr A, Cressman L, Loughrey S, Ganguly A, Feldman MD, Collman RG, Rodino KG, Kelly BJ, Bushman FD. (2022). SARS-CoV-2 Variants Associated with Vaccine Breakthrough in the Delaware Valley through Summer 2021. mBio