Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 lineages circulating in Brazil

Abstract

Several COVID-19 vaccines have shown good efficacy in clinical trials, but there remains uncertainty about the efficacy of vaccines against different variants. Here, we investigate the efficacy of ChAdOx1 nCoV-19 (AZD1222) against symptomatic COVID-19 in a post-hoc exploratory analysis of a Phase 3 randomised trial in Brazil (trial registration ISRCTN89951424). Nose and throat swabs were tested by PCR in symptomatic participants. Sequencing and genotyping of swabs were performed to determine the lineages of SARS-CoV-2 circulating during the study. Protection against any symptomatic COVID-19 caused by the Zeta (P.2) variant was assessed in 153 cases with vaccine efficacy (VE) of 69% (95% CI 55, 78). 49 cases of B.1.1.28 occurred and VE was 73% (46, 86). The Gamma (P.1) variant arose later in the trial and fewer cases (N = 18) were available for analysis. VE was 64% (-2, 87). ChAdOx1 nCoV-19 provided 95% protection (95% CI 61%, 99%) against hospitalisation due to COVID-19. In summary, we report that ChAdOx1 nCoV-19 protects against emerging variants in Brazil despite the presence of the spike protein mutation E484K.

Fig. 1. CONSORT Flow diagram.

Flow chart showing; the number of participants randomised and vaccinated with ChAdOx1 nCoV-19 or control vaccines; the number of participants included in the primary efficacy analysis and reasons for exclusion; the number of participants receiving vaccines after unblinding; and cases occurring after unblinding. Feb 28, 2021 was the data cut-off date for this analysis and events occurring after this date are not included in the data set for analysis.

Fig. 2. Distribution of SARS-CoV-2 lineages from nose/throat swabs over time.

a Stacked bar chart of cases of NAAT + SARS-CoV-2 each week during the study, with lineage assigned by sequencing or genotyping where available. b Stacked bar chart of cases of NAAT + SARS-CoV-2 each week during the study, by study site, with lineage assigned by sequencing or genotyping where available. The 6 study sites are are: Sao Paulo, Rio de Janeiro, Salvador, Santa Maria, and Porto Alegre. (see map of sites in Supplementary Fig. 3). X-axis labels show calendar year and week number. Numbers above the x-axis show the number of cases of NAAT + SARS-CoV-2 that occurred in the study during that week. Swabs were available for sequencing and genotyping only if participants were tested at a study site laboratory and the study sample was stored. An early sample from August 2020 was assigned to Gamma (P.1) to the presence of the K417T mutation. Phylogeographic analyses suggest emergence of the dominant P.1 lineage in November 2020, with a most recent common ancestor of all P.1-like (K417T) viruses estimated at August 2020. As low viral load of this sample in our dataset precluded sequencing, we were unable to further refine its phylogenetic lineage. Therefore it is plausible that this sample was a precursor to likely ‘true’ Gamma (P.1) or a spontaneous K417T mutation. In keeping with national surveillance data, multiple instances of Gamma (P.1) samples were observed in our data from January 2021.

Fig. 3. Viral Load in nose and throat swabs by SARS-CoV-2 lineage.

Box plot of viral load (IU/mL) from NAAT + SARS-CoV-2 cases in Brazil, in vaccinated and control participants combined. Lineages were assigned by sequencing and genotyping. Number of cases included in the analysis are shown below each box. Boxes show the median and 25th to 75th percentile range (bounds of the boxes) and whiskers to the last data point within 1.5 x interquartile range from the 25th or 75th percentile. Kruskal-Wallis test across all four groups: two-sided p = 0.0002. Different colours represent different lineages as labelled on the x-axis.