Protection against SARS-CoV-2 after vaccination against Covid-19 and prior infection

Study population

Demographics of participants at baseline and vaccination status as of September 21, 2021.

A total of 44,546 participants were enrolled between June 18, 2020 and April 23, 2021, from 135 sites across the UK; 35,768 met the inclusion criteria for this analysis (Fig. S1). The characteristics of the participants are presented in Table 1; most participants were female (84%) and the median age was 46 years (interquartile range, 36 to 54). Table S2 presents a comparison of these characteristics with those of the national population.

At the start of the analysis, we assigned 26,280 participants to the previously uninfected cohort and 9,488 to the previously infected cohort. Participants in the previously infected cohort were more likely than those in the previously uninfected cohort to be male, younger, black, Asian, or ethnic minority, to work in clinical roles (e.g., be doctors, nurses or paramedics). professionals), and to report more frequent exposure to patients with Covid-19 (Table 1).

At the end of the analysis, 94.9% of participants had received two doses of vaccine: 78.5% had received BNT162b2 vaccine with a long interval between doses, 8.6% had received BNT162b2 vaccine with a short interval between doses and 7.8% had received the ChAdOx1 nCoV-19 vaccine (Table 1 and Figure S2). We identified no major demographic differences among participants by vaccination schedule (Table S3).

The length of follow-up varied by participant, with a total of 7,482,388 participant person-days, including 998,270 unvaccinated participants and 6,430,118 vaccinated participants (from the date of the first dose). A total of 62,291 PCR tests were performed during the “unvaccinated follow-up period,” which included pre-vaccination follow-up time in participants who were vaccinated during the analysis period and total follow-up time in those who remained unvaccinated at the end of the analysis. A total of 427,951 PCR tests were performed during the analysis period in which participants were vaccinated (i.e. the “vaccinated follow-up period”). The mean test interval was 16 days during the unvaccinated period and 15 days during the vaccinated period. In the previously uninfected cohort, 358,346 tests (mean testing interval, 14.8 days) were performed, and 131,896 tests were performed in the previously infected cohort (mean testing interval, 14.3 days).

Primary outcome

The primary outcome was PCR-confirmed SARS-CoV-2 infection. Primary infections were noted in 2,747 participants during follow-up, and reinfections were seen in 210, with cases peaking in late December 2020, declining in March and April 2021, and increasing in May 2021, a trend that mirrored national trends (Fig.S3). At 14 days before or after the date of the positive PCR test, among participants with primary infections, 1673 (61%) reported symptoms related to Covid-19, 368 (13%) reported other symptoms, 118 ( 4%) reported no symptoms, and 588 (21%) did not provide symptom data. In contrast, among participants with reinfections, 71 (34%) reported symptoms related to Covid-19, 42 (20%) reported other symptoms, 45 (21%) reported no symptoms and 52 (25%) did not provide data. on the symptoms. A total of 357 participants (13%) with a primary infection reported a hospital visit for symptoms related to Covid-19, compared to 18 (9%) of those with a reinfection.

Vaccine efficacy against primary infection

Incidence of SARS-CoV-2 infection and effectiveness of Covid-19 vaccines against symptomatic and asymptomatic infection in participants without prior SARS-CoV-2 infection, December 7, 2020 through September 21, 2021. Adjusted vaccine efficacy over time in previously uninfected participants, by vaccine type and dosing interval.

The adjusted vaccine efficacy of two doses of the BNT162b2 vaccine against coronavirus disease 2019 (Covid-19) with a long interval between doses (panel A), of the BNT162b2 vaccine with a short interval between doses (panel B) and of the ChAdOx1 nCoV-19 vaccine is shown. with short dose intervals and long dose intervals combined (group C) in participants without previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Data are for the period from December 7, 2020 to September 21, 2021. Bars 𝙸 indicate 95% confidence intervals.

Among participants without a history of SARS-CoV-2 infection, two doses of BNT162b2 vaccine given with a long interval between doses were associated with an 85% decreased risk of infection (95% confidence interval [CI]72-92) (i.e. adjusted vaccine efficacy during the first 2 months after the development of the full immune response, 14-73 days after the second dose) (Table 2 and S4 and Figure 1). Over time, the adjusted vaccine efficacy declined but remained high, at 68% (95% CI, 54 to 77), 134 to 193 days after the second dose. At a median of 201 days (interquartile range, 197 to 205) after the second dose, we observed evidence of diminished protection, with an adjusted vaccine efficacy of 51% (95% CI, 22 to 69).

A similar trend was observed in participants who received a second dose of BNT162b2 vaccine with a short interval between doses, with high protection at 14 to 73 days (adjusted vaccine efficacy, 89%; 95% CI, 78 to 94 ) which decreased to 53% (95% CI, 28 to 69) at a median of 238 days (interquartile range, 220 to 249) after the second dose. We found no significant difference between BNT162b2 vaccine participants who had a long interval and those who had a short interval between doses in protection after the second dose, with a relative risk of infection of 1, 34 (95% CI, 0.58 to 3.10) at 14 to 73 days with the use of the short interval as the reference group.

The adjusted efficacy of two doses of the ChAdOx1 nCoV-19 vaccine was 58% (95% CI, 23 to 77) 14 to 73 days after the second dose. Efficacy did not differ significantly with longer time periods after the second dose, with overlapping confidence intervals of vaccine efficacy reflecting the small number of participants with data used to calculate this estimate (Table 2 and Figure 1). From 14 to 73 days after the second dose, the BNT162b2 vaccine with a short interval between doses was 74% more effective (95% CI, 36 to 89) and the BNT162b2 vaccine with a long interval between doses was 65% more effective. effective (95% CI, 21 to 85) than the ChAdOx1 nCoV-19 vaccine. The model’s Wald chi-square test was 371.46 (31 degrees of freedom), with Akaike’s information criterion of 15,367.

Durability of protection after primary infection

Incidence of SARS-CoV-2 reinfection and efficacy of the BNT162b2 vaccine against symptomatic and asymptomatic reinfection in participants with prior SARS-CoV-2 infection, December 7, 2020 through September 21, 2021. Protection against reinfection with SARS-CoV-2 up to 18 months after primary infection.

Data are for the period from December 7, 2020 to September 21, 2021, for BNT162b2 and ChAdOx1 nCoV-19 vaccines and with all dosing intervals. The bars 𝙸 indicate 95% confidence intervals.

A total of 6169 participants from the previously infected cohort were followed during the unvaccinated follow-up period and up to 1 year after primary infection. These participants were primarily infected in the spring of 2020 and were followed in the period before the emergence of the delta variant (B.1.617.2). The risk of reinfection in these participants was 86% lower (95% CI, 81 to 89) than the risk of primary infection in unvaccinated participants in the previously uninfected cohort (Table 3 and Figure 2). There was evidence of a considerable decline in protection over one year after infection, with a reduction of 69% (95% CI, 38 to 84); protection during the first year after infection was 54% (95% CI, 3 to 78) greater than after more than a year.

Durability of protection conferred by infection and vaccination

In the previously infected cohort, with unvaccinated participants from the previously uninfected cohort as the reference group (Table 3 and Figure 2), a beneficial enhancement of acquired immunity against infection was apparent, with a combined protection of more than 90% after vaccination (after the first and second doses). Decline in protection was not observed more than one year after infection or more than 6 months after vaccination. The model’s Wald chi-square was 789.68 (30 degrees of freedom), with Akaike’s information criterion of 14,841.

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