Post-vaccination COVID-19: A case-control study and genomic analysis of 119 breakthrough infections in partially vaccinated individuals.
2021
BACKGROUND: Post-vaccination infections challenge the control of the COVID-19 pandemic. METHODS: We matched 119 cases of post-vaccination SARS-CoV-2 infection with BNT162b2 mRNA, or ChAdOx1 nCOV-19, to 476 unvaccinated patients with COVID-19 (Sept 2020-March 2021), according to age and sex. Differences in 60-day all-cause mortality, hospital admission, and hospital length of stay were evaluated. Phylogenetic, single nucleotide polymorphism (SNP) and minority variant allele (MVA) full genome sequencing analysis was performed. RESULTS: 116/119 cases developed COVID-19 post first vaccination dose (median 14 days, IQR 9 - 24 days). Overall, 13/119 (10â9%) cases and 158/476 (33â2%) controls died (p<0.001), corresponding to 4â5 number needed to treat (NNT). Multivariably, vaccination was associated with 69â3% (95%CI 45â8 - 82â6) relative risk (RR) reduction in mortality. Similar results were seen in subgroup analysis for patients with infection onset ≥14 days after first vaccination (RR reduction 65â1%, 95%CI 27â2 - 83â2, NNT 4â5), and across vaccine subgroups (BNT162b2: RR reduction 66%, 95%CI 34â9 - 82â2, NNT 4â7, ChAdOx1: RR reduction 78â4%, 95%CI 30â4 - 93â3, NNT 4â1). Hospital admissions (OR 0â80, 95%CI 0â51 - 1â28), and length of stay (-1â89 days, 95%CI -4â57 - 0â78) were lower for cases, while Ct values were higher (30â8 versus 28â8, p = 0.053). B.1.1.7 was the predominant lineage in cases (100/108, 92.6%) and controls (341/446, 76.5%). Genomic analysis identified one post-vaccination case harboring the E484K vaccine escape mutation (B.1.525 lineage). CONCLUSIONS: Previous vaccination reduces mortality when B.1.1.7 is the predominant lineage. No significant lineage-specific genomic changes during phylogenetic, SNP and MVA analysis were detected.
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