Coronavirus (COVID-19) vaccine certification: evidence paper

Annex B – Vaccine effectiveness

Vaccine effectiveness against Delta in UK

• Vaccine Effectiveness Expert Panel (VEEP), published on 14 September 2021 the consensus view of vaccine effectiveness for different vaccines and doses and outcomes, which was reached on 27 August 2021^[242]. The values presented in the table below are the consensus judgement of the Vaccine Effectiveness Expert Panel for Delta, they also published a table for Alpha (not shown here). The panel considers a wide range of domestic and international data, and draws a conclusion as to the most accurate values, given the data. Green shows high confidence (Evidence from studies is consistent and comprehensive), Orange shows medium confidence (Evidence is emerging but may be inconsistent requires further analysis) and Red shows low confidence (Little evidence is available at present and results are inconclusive).

• REal-time Assessment of Community Transmission (REACT-1) - the UK study analysed swabs taken by nearly 100,000 people in England between 24 June 2021 and 12 July 2021, 100% of which were Delta variant. Based on the findings the researchers estimated that "fully vaccinated people in this testing round had between around 50% to 60% reduced risk of infection, including asymptomatic infection, compared to unvaccinated people. In addition, double vaccinated people were less likely than unvaccinated people to test positive after coming into contact with someone who had COVID-19 (3.84% vs 7.23%)"^{[243] [244]}.
• Office for National Statistics COVID-19 Infection Survey is a large survey of randomly selected private households across the UK, where RT-PCR tests were performed following a schedule, irrespective of symptoms, vaccination

and prior infection. It found a lower risk of new PCR-positive infections in those vaccinated with two doses of Pfizer/BioNTech or Oxford/AstraZeneca vaccines. Two doses of either kind of vaccine offers at least as good protection as those who have built natural immunity following a previous COVID-19 infection and have not been vaccinated. However, reported vaccine effectiveness against the Delta variant was reduced in comparison with the Alpha variant (Pfizer/BioNTech 88% for Delta versus 94% for Alpha and for Oxford/AstraZeneca 67% versus 75%, respectively)^{[245] [246]}.

• The EAVE II study undertook cohort analysis of the population in Scotland and reported 'Risk of COVID-19 hospital admission was approximately doubled in those with the Delta VOC when compared to the Alpha VOC, with risk of admission particularly increased in those with five or more relevant comorbidities. Both the Oxford–AstraZeneca and Pfizer–BioNTech COVID-19 vaccines were effective in reducing the risk of SARS-CoV-2 infection and COVID-19 hospitalisation in people with the Delta VOC, but these effects on infection appeared to be diminished when compared to those with the Alpha VOC'^[247].
• Greater risk of disease (8 fold increase), hospitalisation (25 fold increase) and death (25 fold increase) between unvaccinated in comparison with vaccinated Americans was also reported by the Centers for Disease Control and Prevention (CDC)^[248]. The study also showed that breakthrough cases of Delta have roughly 10 fold increase in viral load compared to Alpha and other lineages.

Vaccine effectiveness against transmission of Delta.

As shown in the section above on vaccine effectiveness against Delta in the UK there are no direct studies looking at how effective vaccination is at reducing transmission of Delta in breakthrough infections or from people infected but without symptoms. Ct values are a measure of viral load, where the lower the Ct value, the higher the viral load and therefore Ct values can be an indication of how infectious a person is and how likely transmission could occur. Delta cases have a higher viral load compared to alpha^{[249] [250] [251] [252] [253] [254]} and Delta is more transmissible than Alpha^[255].

Vaccination reduced the rate of transmission of the Alpha variant^{[256] [257] [258] [259] [260] [261]}. However, it is important not to generalize what has been seen in other variants to Delta, as vaccination may not have the same protective effect against transmission^[262]. Some studies are summarised below that compare Ct value in vaccinated versus unvaccinated people, as a proxy for viral load and infectiousness:

• Office for National Statistics COVID-19 Infection Survey found that with Delta, infections occurring following two vaccinations had similar peak viral burden to those in unvaccinated individuals^{[263] [264]} . Sarah Walker, professor of medical statistics and epidemiology at the University of Oxford and chief investigator of the study, "We don't yet know how much transmission can happen from people who get COVID-19 after being vaccinated—for example, they may have high levels of virus for shorter periods of time". "But the fact that they can have high levels of virus suggests that people who aren't yet vaccinated may not be as protected from the Delta variant as we hoped. This means it is essential for as many people as possible to get vaccinated—both in the UK and worldwide."^[265]
• REACT-1 study found a difference in viral load between vaccinated and non-vaccinated people with a positive PCR test, with a median Ct value in vaccinated participants at 27.6 (25.5, 29.7) compared with unvaccinated at 23.1 (20.3, 25.8). However, when the Ct threshold for positivity was reduced, representing strong positives with greater infectiousness, the difference between medians for vaccinated and unvaccinated individuals became smaller. The REACT-1 study analysed swab-positivity data from round 12 (between 20 May and 7 June 2021) and round 13 (between 24 June and 12 July 2021) with swabs sent to non-overlapping random samples of the population ages 5 years and over in England^[266].
• A PHE study found similar Ct values in unvaccinated and vaccinated people for

all cases with Delta, where Ct data was available, since the 14 June 2021. The study uses NHS tests and trace data^[267]. The majority of cases would be symptomatic at the time of testing.

• Luo et al., "Infection with the SARS-CoV-2 Delta Variant is Associated with Higher Infectious Virus Loads Compared to the Alpha Variant in both Unvaccinated and Vaccinated Individuals" found no significant differences in Ct value between vaccinated and unvaccinated people for both alpha and Delta variant in cases from the National Capital Region, USA. However, Alpha variant breakthrough vaccinated individuals had higher viral loads at the start of the infection than later (a mean Ct value of 20.75 within the first 5 days vs 26.45 after 5 days). A similar analysis was not possible for the Delta variant breakthrough infections due to the infrequent positives after 5 days of symptoms in the study^[268].
• Griffin et al, "SARS-CoV-2 Infections and Hospitalizations Among Persons Aged ≥16 Years, by Vaccination Status - Los Angeles County, California, USA, from May 1 to July 25, 2021" found that by July, when Delta was dominant, there were no differences in median Ct values detected among specimens from fully vaccinated, partially vaccinated, and unvaccinated persons by gene targets^[269].
• A US Centers for Disease Control and Prevention (CDC) report, detailed that following large public gatherings in a town in Massachusetts, nearly three-quarters of the 469 new COVID-19 cases were in vaccinated people. Both vaccinated and unvaccinated individuals had comparably low PCR Ct values, indicating high viral loads, and of the 133 samples sequenced, 90% were identified as Delta^[270].
• Riemersma et al., compared RT-PCR cycle threshold (Ct) data from 699 swab specimens collected in Wisconsin USA, from 29 June to .31 July 2021. They found low Ct values (<25) in both vaccinated (68%) and non-vaccinated (63%) individuals, regardless of symptoms^[271].
• Chia et al., report a small study of 218 with delta infection in Singapore and found that Ct values were similar between both vaccinated and unvaccinated groups at diagnosis, but viral loads decreased faster in vaccinated individuals^[272].

• Christensen et al., sequenced the genomes of 12,221 SARS-CoV-2 from samples acquired March 15, 2021 through August 26, 2021 in Houston and found a similar median Ct value for vaccinated and unvaccinated patients with COVID-19 caused by Delta variants^[273].
• Ke et al., found that in a small study of SARS-CoV-2 infection in 23 individuals the duration of virus shedding and symptoms was shorter in vaccinated people compared to unvaccinated people^[274].