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Challenges in Estimating the Effectiveness of 2 Doses of COVID-19 Vaccine Beyond 6 Months in England
This paper discusses the challenges in estimating long-term (>6 months) vaccine effectiveness in observational data, primarily due to high uptake of a subsequent third vaccine dose.
Summary
Understanding how the effectiveness of coronavirus disease 2019 (COVID-19) vaccine changes over time and in response to new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is crucial to scheduling subsequent doses. In a previous study, Horne et al. quantified vaccine effectiveness (VE) over 6 consecutive 4-week periods from 2 weeks to 26 weeks after the second dose. Waning of hazard ratios (HRs) when comparing vaccinated persons with unvaccinated persons was approximately log-linear over time and was consistent across COVID-19–related outcomes and risk-based subgroups. To investigate waning beyond 26 weeks and in the era of the Omicron variant, we extended follow-up to the earliest of 50 weeks after the second dose or March 31, 2022.
We found that it is challenging to estimate the long-term effectiveness of 2 COVID-19 vaccine doses in populations in which uptake of a third dose was high. These challenges also affect investigations of VE against the Omicron variant, whose emergence coincided with rapid uptake of third doses and of incremental effectiveness of a third dose against the second dose.
- Elsie Horne, Will Hulme, Ruth Keogh, Tom Palmer, Elizabeth Williamson, Edward Parker, Venexia Walker, Rochelle Knight, Yinghui Wei, Kurt Taylor, Louis Fisher, Jess Morley, Amir Mehrkar, Iain Dillingham, Seb Bacon, Ben Goldacre, Jonathan Sterne