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Published, Version of Record (VoR)CC BY V4.0, Open
Preprint
SARS-CoV-2 variants associated with vaccine breakthrough in the Delaware Valley through summer 2021
medRxiv : the preprint server for health sciences
17 Nov 2021
PMID: 34704098
Abstract
The severe acute respiratory coronavirus-2 (SARS-CoV-2) is the cause of the global outbreak of COVID-19. Evidence suggests that the virus is evolving to allow efficient spread through the human population, including vaccinated individuals. Here we report a study of viral variants from surveillance of the Delaware Valley, including the city of Philadelphia, and variants infecting vaccinated subjects. We sequenced and analyzed complete viral genomes from 2621 surveillance samples from March 2020 to September 2021 and compared them to genome sequences from 159 vaccine breakthroughs. In the early spring of 2020, all detected variants were of the B.1 and closely related lineages. A mixture of lineages followed, notably including B.1.243 followed by B.1.1.7 (alpha), with other lineages present at lower levels. Later isolations were dominated by B.1.617.2 (delta) and other delta lineages; delta was the exclusive variant present by the last time sampled. To investigate whether any variants appeared preferentially in vaccine breakthroughs, we devised a model based on Bayesian autoregressive moving average logistic multinomial regression to allow rigorous comparison. This revealed that B.1.617.2 (delta) showed three-fold enrichment in vaccine breakthrough cases (odds ratio of 3; 95% credible interval 0.89-11). Viral point substitutions could also be associated with vaccine breakthroughs, notably the N501Y substitution found in the alpha, beta and gamma variants (odds ratio 2.04; 95% credible interval of 1.25-3.18). This study thus provides a detailed picture of viral evolution in the Delaware Valley and a geographically matched analysis of vaccine breakthroughs; it also introduces a rigorous statistical approach to interrogating enrichment of viral variants.
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Details
- Title
- SARS-CoV-2 variants associated with vaccine breakthrough in the Delaware Valley through summer 2021
- Creators
- Andrew D Marques - Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PAScott Sherrill-Mix - Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PAJohn Everett - Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PAShantan Reddy - Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PAPascha Hokama - Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PAAoife M Roche - University of PennsylvaniaYoung Hwang - University of PennsylvaniaAbigail Glascock - Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PASamantha A WhitesideJevon Graham-WootenLayla A KhatibAyannah S FitzgeraldAhmed M Moustafa - Division of Gastroenterology, Hepatology & Nutrition, Children's Hospital of Philadelphia, Philadelphia, PAColleen Bianco - Division of Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, PASwetha Rajagopal - Division of Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, PAJenna Helton - Division of COVID-19 Containment, Philadelphia Department of Public Health, Philadelphia, PARegan Deming - Division of Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, PALidiya Denu - Division of Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, PAEimear Kitt - Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PASusan E Coffin - Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PAClaire Newbern - Philadelphia Department of Public HealthJosh Chang Mell - Drexel UniversityPaul J Planet - University of PennsylvaniaNitika Badjatia - Molecular & Genomic Pathology Laboratory, Thomas Jefferson University Hospital, Philadelphia, PABonnie Richards - Jefferson Occupational Health Network for Employees and Students (JOHN), Thomas Jefferson University, Philadelphia, PAZi-Xuan Wang - Department of Anatomy, Pathology, and Cell Biology, Thomas Jefferson University Hospital, Philadelphia, PACarolyn C Cannuscio - Department of Family Medicine and Community Health, University of Pennsylvania, Philadelphia, PAKatherine M Strelau - Department of Family Medicine and Community Health, University of Pennsylvania, Philadelphia, PAAnne Jaskowiak-BarrLeigh CressmanSean LoughreyArupa Ganguly - Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PAMichael D Feldman - Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PARonald G CollmanKyle G Rodino - Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PABrendan J KellyFrederic D Bushman - Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
- Publication Details
- medRxiv : the preprint server for health sciences
- Publisher
- American Physical Society (APS); United States
- Resource Type
- Preprint
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Other Identifier
- 991021864305904721