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. Author manuscript; available in PMC: 2023 Dec 1.
Published in final edited form as: Nat Microbiol. 2022 Nov 10;7(12):1996–2010. doi: 10.1038/s41564-022-01262-1

Fig. 3. Analyses of D29 ID50 titer as a correlate of risk and as a correlate of protection.

Fig. 3.

Analyses were performed in baseline SARS-CoV-2 seronegative per-protocol vaccine recipients. (A) Covariate-adjusted cumulative incidence of COVID-19 by 54 days post D29 by D29 ID50 titer above a threshold. The blue dots are point estimates at each COVID-19 primary endpoint linearly interpolated by solid black lines; the gray shaded area is pointwise 95% confidence intervals (CIs). The estimates and CIs were adjusted using the assumption that the true threshold-response is nonincreasing. The upper boundary of the green shaded area is the estimate of the reverse cumulative distribution function (CDF) of D29 ID50 titer. The vertical red dashed line is the D29 ID50 threshold above which no COVID-19 endpoints occurred (in the time frame of 1 to 54 days post D29). (B) Covariate-adjusted cumulative incidence of COVID-19 by 54 days post D29 by D29 ID50 titer, estimated using (solid purple line) a Cox model or (solid blue line) a nonparametric method. Each point on the curve represents the covariate-adjusted cumulative COVID-19 incidence at the given D29 ID50 titer value. The dotted black lines indicate bootstrap point-wise 95% CIs. The upper and lower horizontal gray lines are the overall cumulative incidence of COVID-19 from 1 to 54 days post D29 in placebo and vaccine recipients, respectively. (C) Vaccine efficacy (solid purple line) by D29 ID50 titer, estimated using a Cox proportional hazards implementation of Gilbert et al.44 Each point on the curve represents the vaccine efficacy at the given D29 ID50 titer value. The dashed black lines indicate bootstrap point-wise 95% CIs. Vaccine efficacy (solid blue line) by Day 29 ID50 titer, estimated using a nonparametric implementation of Gilbert et al.44 (described in the SAP). The blue shaded area represents the 95% CIs. In (B) and (C), the green histogram is an estimate of the density of Day 29 ID50 titer and the horizontal gray line is the overall vaccine efficacy from 1 to 54 days post D29, with the dotted gray lines indicating the 95% CIs. Baseline covariates adjusted for were baseline risk score and geographic region. LLOQ, limit of quantitation. In (B, C), curves are plotted over the range from LLOQ/2 to the 97.5th percentile = 96.3 IU50/ml.