The effectiveness of COVID-19 vaccines has been demonstrated in Phase III clinical trials. However, whether this efficacy is replicated in clinical practice can only be derived from complementary, real-world studies.
The UK vaccination programme began in December 2020, and based on advice from the Joint Committee on Vaccination and Immunisation (JCVI), sought to target those at greatest risk of severe outcomes if infected, e.g., care home residents and their carers, individuals aged 80 years and over, as well as front-line healthcare workers. The overarching aim of the vaccination programme is to reduce the rate of hospitalisation and death, especially among the most vulnerable patients. In an effort to demonstrate the real-world effectiveness of the current vaccination programme, the publication of three prospective studies, based on experience with the Pfizer-BioNTech (BNT162b2) and Oxford-AstraZeneca (ChAdOx1) vaccines, would appear to support the observations seen in clinical trials.
The first was a prospective cohort study using the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) database (1) and looked at both the Pfizer-BioNTech (BNT162b2) and the Oxford-AstraZeneca (ChAdOx1) vaccines. The cohort included 5.4 million adults and the primary outcome was vaccine efficacy against hospital admission with COVID-19 as either the primary cause of the admission or an admission within 28 days of a positive PCR test from 8 December 2020 to 13 February 2021. Outcomes were stratified by time intervals post-vaccination as 7–13, 14–20, 21–27, 35–41 and > 42 days.
The overall vaccine efficacy recored in EAVE II was highest, at 84%, between 28–34 days post-vaccination but this reduced to 58% after more than 42 days. Both BNT162b2 and ChAdOx1 demonstrated peak efficacies although the latter appeared to be more efficacious (85% vs 94%, BNT162b2 vs ChAdOx1). The BNT162b2 efficacy reduced to 64% after more than 42 days although at the time of publication, similar efficacy date for the ChAdOx1 vaccine was not available. In terms of COVID-19-related hospitalisations, among those aged 18–64, there was an 85% reduction in the risk of being hospitalised 28– 34 days post vaccination (hazard ratio, HR = 0.15, 95% CI 0.07–0.32). However, in the most vulnerable group, those aged 80 years and over, the risk of hospitalisation between 28- and 34-days post-vaccination was reduced by 81% (HR = 0.19) and while overall vaccine efficacy reduced after 42 days, the reduction in risk reduction was minimal (HR = 0.20).
The second prospective study (2), the SARS-CoV-2 Immunity and reinfection Evaluation (SIREN), included a range of hospital staff, e.g., healthcare professionals and both support and administrative staff. Participants were categorised as “ever vaccinated” if they had at least one of the available vaccines between 8 December 2020 and 5 February 2021. They were further divided into those who were either positive (i.e., COVID-19 antibodies detected) or a prior history of COVID-19 infection or negative (no antibodies or history of infection). The primary outcome was a PCR-confirmed COVID-19 infection during follow-up for the negative group and a reinfection among the positive group. A total of 23,324 participants were followed-up which comprised 8203 (35%) who were assigned to the positive cohort and 15,121 (65%) to the negative group. The majority of participants were female (84%) and worked in a patient-facing role (86%) and all participants were followed for a maximum of 59 days after their first vaccine dose and 39 days after the second dose.
Among the whole cohort, 21 days after the first dose, vaccine efficacy was 70% and this increased to 85%, seven days after the second dose. In those assigned to the negative group, the efficacy was higher (72%), 21 days after the first dose but identical (85%) seven days after the second dose. The impact among the positive cohort was not calculated because this group already had 90% protection compared to the negative group. In addition, the majority of participants received the BNT162b2 vaccine and too few participants received the ChAdOx1 vaccine to investigate the its effectiveness.
Public Health England
The third and final study was undertaken by Public Health England,3 and this reported on the effectiveness of vaccines against symptomatic COVID-19 among those over 80 years of age. Data were available for 11,860 people and vaccine efficacy was estimated to be 57%, 28 days after the first dose, and this rose of 88%, 7 days after the second dose. The study also sought to examine the risk of hospitalisation and mortality in this age group and stratified this as either less or more than 14 days the first vaccine dose.
In unvaccinated patients (80 years and over), there were 8682 positive COVID-19 cases of which 15.3% were hospitalised. Among 1260 patients who tested positive for COVID-19 less than 14 days after vaccination, 14.8% were hospitalised. In contrast, of the 984 positive cases that occurred 14 or more days after vaccination, only 9% were hospitalised. What was more striking was the apparent reduction in the risk of death within 21 days of a positive COVID-19 test. For example, the comparative risks were 13.4% (unvaccinated), 10.8% (less than 14 days after vaccination) and 5.8% (14 or more days after first dose). In other words, if infected 14 or more days after vaccination, the risk of death was halved.
While these early results are encouraging, an important caveat is that the studies were observational in nature and thus subject to some level of bias and current levels of follow-up were relatively short. Nevertheless, the studies offer a valuable insight of the real-world effectiveness of the vaccines at both reducing the incidence of infection and in particular, driving down rates of hospitalisation. Further results are eagerly awaited, especially whether vaccination reduces transmission of the virus.
1. Vasileiou E et al. Effectiveness of first dose of COVID-19 vaccines against hospital admissions in Scotland: national prospective cohort study of 5.4 million people. 2021 https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3789264
2. Hall V et al. Effectiveness of BNT162b2 mRNA vaccine against infection and COVID-19 vaccine coverage in healthcare workers in England, multi-centre prospective cohort study (the SIREN study). 2021 https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3790399
3. Public Health England. PHE monitoring of the early impact and effectiveness of COVID-19 vaccination in England. https://www.gov.uk/government/publications/phe-monitoring-of-the-effectiveness-of-covid-19-vaccination