Efficacy of vaccination against severe COVID-19 in relation to Delta variant and time since second dose

  

View ORCID ProfilePaul M McKeigue,  View ORCID ProfileDavid A McAllister, Sharon J Hutchinson, Chris Robertson, Diane Stockton,  View ORCID ProfileHelen M Colhoun, for the PHS COVID-19 Epidemiology and Research Cell

doi: https://doi.org/10.1101/2021.09.12.21263448

This article is a preprint and has not been peer-reviewed [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2021.09.12.21263448v1.full.pdf

Abstract

Objectives To investigate: (1) whether vaccine efficacy against severe COVID-19 has decreased since Delta became the predominant variant; (2) whether efficacy wanes with time since second dose.

Design Matched case-control study.

Setting Population of Scotland from 1 December 2020 to 19 August 2021.

Main outcome measure Severe COVID-19, defined as cases with entry to critical care or fatal outcome.

Results Efficacy of vaccination against severe COVID-19 decreased in May 2021 coinciding with the replacement of the B.1.1.7 (Alpha) by the B.1.617.2 (Delta) variant in Scotland, but this decrease was reversed over the next month. In the most recent time window, the efficacy of two doses against severe COVID-19 was 91% (95 percent CI 86% to 95%) for the AstraZeneca product and 92% (95 percent CI 85% to 95%) for mRNA (Pfizer or Moderna) products. Against the broader category of hospitalised or fatal COVID-19, efficacy in this time window was slightly lower: 88% (95 percent CI 85% to 90%) for the AstraZeneca product, 91% (95 percent CI 88% to 93%) for mRNA vaccines. Efficacy against COVID-19 declined rapidly in the first two months since second dose but more slowly thereafter. For hospitalised or fatal COVID-19 the model best supported by the data was one in which efficacy was the sum of a rapidly waning effect with half-life of 17 (95% CI 9 to 39) days and a time-invariant efficacy of 83%.

Conclusions These results are reassuring with respect to concerns that efficacy against severe COVID-19 might have fallen since the Delta variant became predominant. Although there is considerable uncertainty attached to any extrapolation into the future, these results suggest that the rapid early waning of efficacy against hospitalised COVID-19 after the second dose tapers off within a few months. This weakens the rationale for policies based on delivering booster doses to the entire population, rather than to vulnerable individuals for focused protection.

Competing Interest Statement

HC receives research support and honoraria and is a member of advisory panels or speaker bureaus for Sanofi Aventis, Regeneron, Novartis, Novo-Nordisk and Eli Lilly. HC receives or has recently received non-binding research support from AstraZeneca and Novo-Nordisk. SH received honoraria from Gilead.

Funding Statement

No external funding was received for this work. HC is supported by an endowed chair from the AXA Research Foundation.

https://www.medrxiv.org/content/10.1101/2021.09.12.21263448v1