Effectiveness of BNT162b2 and ChAdOx1 nCoV-19 COVID-19 vaccination at preventing hospitalisations in people aged at least 80 years: a test-negative, case-control study

Second, we did not measure the effect of one dose in individuals who were not admitted to hospital with COVID-19, and there might be treatment bias where people of advanced age are not referred to hospital. This study provides vaccine effectiveness estimates in secondary care settings only, not including general practice or accident and emergency consultations which did not result in hospitalisation. Individuals who died before admission to hospital or who were otherwise not referred to hospital were not included in this study. Patients with severe disease seen in general practice or accident and emergency might have been included in this analysis (via referral), and biased results towards lower vaccine effectiveness. It is also possible that weak or moderate protection induced by vaccination could result in slower disease progression and longer intervals from symptom onset to hospitalisation for vaccinated individuals.

Third, sampling and processing might have resulted both in false positive and negative PCR results, which could have rendered the effectiveness estimates imprecise to some degree with uncertain direction and size of any such biases.

Fourth, the study cohort was predominantly White and the effectiveness of these vaccines might differ in individuals from other ethnic backgrounds. This study specifically excluded individuals with asymptomatic disease and cannot determine the effectiveness of one vaccine dose against asymptomatic disease or transmission.

Fifth, this analysis was done in one location on a small number of participants and, by necessity, over a short time period, which restricts the generalisability of the findings.

Sixth, we did not assess vaccine effectiveness against individual variants of SARS-CoV-2, and this was not being comprehensively tested on standard-of-care specimens during the study period. However, selective sequencing data indicate that almost all cases during the study period were B.1.1.7, with a small number of wild-type variants. Finally, although we controlled for time in our analysis, we cannot fully account for temporal changes due to background exposure to infection, prevalence of variants of concern, or rising rates of vaccine receipt with emerging differences in characteristics between vaccine recipients and non-recipients in the study age range. A larger, individually matched cohort study is required to control for these potential confounders better.

In summary, the findings of our case-control analysis will help to guide strategy development for the use of BNT162b2 and ChAdOx1 nCOV-19 vaccines in clinical practice and should reassure policy makers of the high value of deploying these vaccines, and the importance of administering two doses, in high-risk populations in whom incidence of severe disease and death from SARS-CoV-2 infection remains high.