26th August 2021, Dr Chee L Khoo
The Delta variant, first identified in India in December 2020, spread rapidly throughout a mostly unvaccinated country and caused massive numbers of cases, hospitalisations, and deaths. It’s now responsible for the outbreaks spreading across the world. This includes countries that have high vaccination rates. In the UK, the Delta variant has spread rapidly. Since March 2021 Delta has become the predominant variant in the US and has caused an expansive wave of new infections, especially in the Southeastern US in places where community vaccination rates are low. The effectiveness of BNT162b2, ChAdOx1, and mRNA-1273 vaccines against new SARS-CoV-2 infections need to undergo continuous re-evaluation, given the increasingly dominant Delta variant.
We are used to rely on randomised controlled trials (RCTs) to inform us on effectiveness of drugs (or vaccines) but with such a rapid moving front with Covid-19, RCTs are hard to come by. We have to rely on real world data but real-world data on vaccine effectiveness against Delta infections are currently limited. A test-negative case-control study compared symptomatic Covid-19 cases with symptomatic but test negative cases in the UK suggested that the effectiveness after one BNT162b2 (i.e. Pfizer’s Comirnaty vaccine) or ChAdOx1 (i.e. AstraZeneca vaccine) vaccination was lower against symptomatic infection with Delta (31%) than Alpha (49%) (1). Reductions in effectiveness against infection with Delta versus Alpha were smaller following two doses of either vaccine.
In a most recent study, individuals living in randomly selected private households across the UK were surveyed to assess the effectiveness of the BNT162b2, ChAdOx1, and mRNA-1273 (Moderna’s mRNA) vaccines against the newer variants of Covid-19 (2). RT-PCR tests were performed following a pre-determined schedule, irrespective of symptoms, vaccination and prior infection. They assessed vaccine effectiveness based on overall RT-PCR positivity, and split according to self-reported symptoms, viral load as measured by cycle threshold (Ct) value (lower reading means high viral load), from 1 December 2020 (start of vaccination rollout) to 16 May 2021, when Alpha dominated, and from 17 May 2021 to 1 August 2021 when Alpha was replaced by Delta.
Overall vaccine effectiveness (VE)
The results from this large community surveillance study show that vaccination with two doses of
BNT162b2 or ChAdOx1 significantly reduces the risk of new PCR-positive SARS-CoV-2 infections.
However, whereas the two vaccines provided similar benefits when Alpha was dominant, benefits from two ChAdOx1 doses are reduced with Delta but was not statistically significant (79% vs 67%, p=0.023). VE was also reduced with two BNT162b2 doses with Delta although the reduction was also not statistically significant (80% vs 57% p=0.23). Whereas the two vaccines provided similar benefits when Alpha was dominant, benefits from two ChAdOx1 doses are reduced with Delta more than two BNT162b2 doses.
Symptomatic vs asymptomatic patients
Benefits from both vaccines are greater in symptomatic PCR-positive patients versus asymptomatic PCR-positive patients and in patients with high versus low viral burden but the difference in effectiveness is smaller with Delta for both vaccines.
In patients who had prior Covid-19 infection, VE against new PCR-positives was significantly larger compared to those vaccinated without prior infection – 88% vs 68% with two ChAdOx1 vaccinations and 93% vs 85% with BNT162b2 vaccinations.
BNT162b2 vs ChAdOx1
In the Delta-dominant period, VE against new PCR-positives amongst those aged 18-64 years was significantly lower for ChAdOx1 versus BNT162b2 after one vaccination and after two vaccinations (p=0.001 and p<0.0001, respectively).
Two ChAdOx1 vaccinations were as good in preventing new PCR-positives as protection from previous natural infection without vaccination whereas two BNT162b2 vaccinations afforded greater protection.
In the initial few months BNT162b2 were more effective than ChAdOx1 but they became more similar by ~4-5 months after the second dose due to more rapid waning of effectiveness with BNT162b2, particularly against infections with high viral load (Ct<30) and in those patients with symptoms. In those 18 to 64 years, VE of BNT162b2 against new PCR-positives reduced by 22% for every 30 days from second vaccination (p=0.007). Reductions were numerically smaller for ChAdOx1 (change -7% per 30 days) and not statistically significant (p=0.15).
Further, vaccine effectiveness did not depend on the interval between first and second vaccinations (<9 weeks versus ≥9 weeks) for either vaccines.
Vaccine effectiveness was also generally higher at younger ages. For example, VE after the second BNT162b2 dose was 90% for those aged 18-34 years versus 77% for those aged 35-64 years (p=0.0001); and was 73% versus 54% respectively, for ChAdOx1 (p=0.002).
During the Alpha dominated era, viral load reduced with increasing time from the first dose and was the lowest 2 weeks after the second dose. However, during the Delta dominated era, the reduction in viral load post vaccination was attenuated especially with the ChAdOx1 vaccines. With Delta, infections occurring following two vaccinations had similar peak viral burden to those in unvaccinated individuals with potential implications for onward transmission risk, given the strong association between peak Ct and infectivity34. However, the degree to which this might translate into increased transmissibility is unclear.
Vaccination reduced symptomatic and asymptomatic infections in this study. There were no data presented on effect of vaccination on hospitalisations with the Delta variant. A cohort analysis of the national health care datasets from Scotland also suggested reduced effectiveness against infection with Delta versus Alpha following two doses of either vaccine (3). However, they found no evidence that effectiveness on hospital admissions among those first testing positive was reduced with Delta versus Alpha but the number of admissions were too small to make a statistical conclusion.
In summary, this large study both vaccines significantly reduce SARS-CoV-2 infections aftertwo doses. Although vaccine effectiveness was similar between ChAdOx1 and BNT162b2 vaccines when infections were mainly of the Alpha variant, reduction in VE was numerically lower with ChAdOx1 than with BNT162b2 when the infections were mainly of the Delta variant.
Both vaccines showed greater benefit in patients who had previous SARS-CoV-2 infections, were symptomatic, had higher viral load and were younger.
While BNT162b2 vaccination provided better VE initially compared with ChAdOx1 vaccination, the VE of BNT162b2 vaccine had a tendency to wane faster than ChAdOx1 vaccine although VE were equivalent by 4-5 months after the second dose of vaccination.
It appears that both vaccines still protect against hospitalisations and severe disease from the Delta variant despite reduction in vaccine effectiveness against contracting the disease.
- Lopez Bernal, J. et al. Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant. N Engl J Med, doi:10.1056/NEJMoa2108891 (2021).
- Pouwels K, Pritchard E, Matthews P, et al. Impact of Delta on viral burden and vaccine effectiveness against new SARS-CoV-2 infections in the UK. https://www.ndm.ox.ac.uk/files/coronavirus/covid-19-infection-survey/finalfinalcombinedve20210816.pdf Accessed 20th August 2021.
- Sheikh, A. et al. SARS-CoV-2 Delta VOC in Scotland: demographics, risk of hospital admission, and vaccine effectiveness. Lancet 397, 2461-2462, doi:10.1016/S0140-6736(21)01358-1 (2021).