The current coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has resulted in over 125 million cases and 2.7 million deaths. The virus has disproportionately affected the elderly and those with underlying health problems. In particular, a large percentage of deaths in Europe and North America has been in Long-Term Care Facilities (LTCF) residents, albeit they make up less than one percent of the population.
A new preprint released on the medRxiv* server deals with the effect of two widely used vaccines in eliciting humoral immunity against the virus in this group. These are the Oxford/AstraZeneca viral-vectored vaccine (ChAdOx1 nCoV-19), and the Pfizer/BioNTech’s messenger RNA-based vaccine (BNT162b2). Both express the viral spike antigen, and both are currently being employed in the UK’s vaccination program.
In clinical trials, both showed efficacy above 62%, with the latter going as high as 95%. Since these trials excluded older and frailer individuals, vaccine efficacy in this group is largely unknown. Real-world data is emerging from vaccine rollouts, but is again not specifically directed at this population.
Anticipating their efficacy in LTCF residents, the UK already put this group on its high-priority group for vaccination.
The current study aimed especially to examine the efficacy of protection against SARS-CoV-2 infection, both its extent and the duration, after a single dose of either vaccine. This is in view of the recent decision made by the UK government to extend the interval between the two doses of the vaccine from the three weeks and four weeks, recommended by the respective manufacturers, to 12 weeks.
This policy is intended to cover as much of the most vulnerable population with a single dose of the vaccine, driven by the rapid spread of the highly transmissible UK B.1.1.7 variant within the general population, and especially within the LTCFs, beginning in November 2020.
The VIVALDI study is a prospective study that began in May 2020 to explore the spread and outcomes of, and immune response to, SARS-CoV-2 within LTCF staff and residents aged 65 years or more.
The study included over 10,000 LTCF residents, with a median age of 86 years. About 70% were female, and 11% had a history of prior infection.
Approximately 88% had received one or two doses of either vaccine, 67% the Pfizer and 33% the Oxford vaccine. About 900 received two doses at a median interval of nine weeks. Regular testing for the infection is in place for all LTCF residents in the UK, and has been since June 2020, using polymerase chain reaction (PCR)-based assays of nasopharyngeal swabs. This has been used to test LTCF residents monthly, and in case a cluster of cases was detected, all residents were tested twice, with an interval of one week.
Positive tests led to the exclusion of such individuals from testing for the subsequent 90 days unless new symptoms of the infection arose, though symptoms are unreliable in this group.
What were the results?
There were about 1.6 PCR tests per person per month, for a total of over 36,000 results in about 671,000 person-days. Of 1.335 positive PCR results, 85% were from routine testing, with a crude infection rate of 20 per 10,000 person-days at risk overall.
Compared to a rate of 21 in the unvaccinated group, the rate dropped to about ten at 28-34 days, and nine at 35-48 days after vaccination in the vaccinated group. After adjusting for age, sex, local infection rates, history of prior infection, and other factors, the effect of vaccination was observed to be significant only after 28-34 days.
At this time point, the adjusted risk of infection was reduced by 56%, and at 35-48 days, by 62%.
Significant differences in risk between the vaccinated and unvaccinated groups were not observed at 49 or more days following vaccination, but in those with prior infection, the risk dropped by 80%.
The vaccines also appeared to reduce the risk of contagion. The mean cycle threshold values was 27 among positive PCR results from the unvaccinated group and in the vaccine recipients up to 27 days post-vaccination, on average. After this period, the mean Ct was 31.
Early Oxford vaccine efficacy?
When analyzed separately, there was a reduced risk of PCR-positivity among those who received the Oxford vaccine but not the Pfizer vaccine in the early post-vaccination period (0-13 days). The reduction was by about half over this period.
Thus, by day 28, the risk of infection following the first dose of the Oxford vaccine was reduced by 67%, but this was not observed with the Pfizer vaccine.
However, this could be because the LTCF residents had a lower ongoing risk of infection after being vaccinated, as assessed by the guidelines for deferring the second dose of the vaccine.
These guidelines came into effect towards the end of 2020. Since the Oxford vaccine was rolled out later than the Pfizer, a larger proportion of LTCF residents would have been assessed for risk-based deferral of vaccines, allowing single-dose vaccine efficacy to be evaluated. This aspect could not be examined due to the lack of data on deferral decisions.
Effect of prior infection
Overall, the risk of becoming PCR positive was lower in unvaccinated residents with a history of prior infection relative to those without a history of infection, by approximately 80%. The magnitude of reduction was not increased in the former group by a single dose of vaccination at any point.
The efficacy of a single dose of the Pfizer vaccine in this population is controversial, since a single Danish study indicated a lack of effectiveness. In that study, the second dose was administered at a mean of 24 days from the first, which may not have allowed protective effects to set in, as indicated by the current findings.
What are the implications?
Thus, a single dose of either vaccine was associated with a significant reduction of risk of positive PCR tests for the virus, from 28 days onwards, which remained observable for at least seven weeks.
This supports the UK guidelines for deferring the second dose in order to achieve optimal coverage of the vulnerable population. The effect extends beyond the prevention of symptomatic disease to reducing transmission itself, as well as the total incidence of infection.
In the real world, the risk of infection was significantly reduced in both groups. If unvaccinated people among the LTCF residents are excluded from the analysis, the vaccine efficacy increases to 76% at 35-48 days.
The reduction in transmissibility is supported by the higher Ct values found at 28 days or more after the first dose, which indicates that those who contract the infection despite being vaccinated are less likely to transmit the virus to others.
This adds to the early real-world experience of vaccine efficacy with the Oxford vaccine, even though only one dose of each vaccine was evaluated. It also provides evidence for vaccine efficacy in older adults.
The findings support the earlier figure of 64% vaccine efficacy against asymptomatic and symptomatic infection at 22-90 days, in adults over 70 years, after one dose of the vaccine. This data was obtained from the pooled results of earlier clinical trials with the Oxford vaccine.
More research is required to assess the effectiveness of the second dose, as well as the overall efficacy of the vaccine against both infection and transmission. This will help shape vaccination protocols for this high-risk population, and the nature of intervention required to protect them against future waves of infection.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.