Table 2. Covariate-adjusted hazard ratio of COVID-19 (A) across D29 antibody marker tertiles or (B) per 10-fold increase in D29 quantitative marker.
Analysis based on baseline SARS-CoV-2 seronegative per-protocol vaccine recipients in the case-cohort set. Baseline covariates adjusted for: baseline risk score, geographic region.
| A. | |||||||||
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| D29 Immunologic Marker | Tertile* | No. Cases/No. At-Risk** | Attack Rate | Hazard Ratio (Across Tertiles) | P-Value (2-sided) | Overall P-Value¶ | FDR-Adjusted P-Value† | FWER-Adjusted P-Value† | |
| Point Est. | 95% CI | ||||||||
| Anti Spike IgG (BAU/ml) | Low | 55/6,098 | 0.0090 | 1 | N/A | N/A | 0.498 | 0.499 | 0.493 |
| Medium | 44/6,141 | 0.0072 | 0.75 | (0.42, 1.32) | 0.316 | ||||
| High | 41/6,158 | 0.0067 | 0.75 | (0.42, 1.32) | 0.316 | ||||
| Anti RBD IgG (BAU/ml) | Low | 58/6,082 | 0.0095 | 1 | N/A | N/A | 0.162 | 0.189 | 0.255 |
| Medium | 41/6,186 | 0.0066 | 0.63 | (0.35, 1.12) | 0.118 | ||||
| High | 41/6,129 | 0.0067 | 0.61 | (0.34, 1.09) | 0.095 | ||||
| Pseudovirus-nAb ID50 (IU50/ml) | Low | 87/7,884 | 0.0110 | 1 | N/A | N/A | 0.003 | 0.015 | 0.011 |
| Medium | 23/4,442 | 0.0052 | 0.46 | (0.24, 0.86) | 0.016 | ||||
| High | 30/6,071 | 0.0049 | 0.41 | (0.22, 0.75) | 0.004 | ||||
| Placebo | 378/18,116 | 0.0209 | |||||||
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| B. | |||||||||
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| D29 Immunologic Marker | No. Cases/No. At-Risk** | Hazard Ratio (Per 10-fold Increase) | P-Value (2-sided) | FDR-Adjusted P-Value† | FWER-Adjusted P-Value† | ||||
| Point Est. | 95% CI | ||||||||
| Anti Spike IgG (BAU/ml) | 140/18,395 | 0.69 | (0.41, 1.16) | 0.162 | 0.189 | 0.255 | |||
| Anti RBD IgG (BAU/ml) | 140/18,395 | 0.59 | (0.33, 1.06) | 0.079 | 0.150 | 0.144 | |||
| Pseudovirus-nAb ID50 (IU50/ml) | 140/18,395 | 0.49 | (0.29, 0.81) | 0.006 | 0.015 | 0.016 | |||
BAU, binding antibody units/ml; CI, confidence interval; FDR, false discovery rate; FWER, family-wise error rate; RBD, receptor binding domain; ID50, 50% inhibitory dilution titer.
Tertiles: Spike IgG: Low is < 23 BAU/ml, Medium is 23 to 59 BAU/ml, High is > 59 BAU/ml; RBD IgG: Low is < 23 BAU/ml, Medium is 23 to 52 BAU/ml, High is > 52 BAU/ml; ID50: Low is < 1.4 IU50/ml, Medium is 1.4 to 9.1 IU50/ml, High is > 9.1 IU50/ml.
No. at-risk = estimated number in the population for analysis, i.e. baseline SARS-CoV-2 seronegative per-protocol vaccine recipients not experiencing the COVID-19 endpoint or with evidence of SARS-CoV-2 infection through D29; no. cases = numbers of this cohort with an observed COVID-19 endpoint (with onset ≥ 1 day post D29 and ≥ 28 days post vaccination). The total count across all tertiles for each marker (140) differs from the case numbers in Fig. 1 (92) because the former number is the estimated number of all vaccine breakthrough cases within each tertile including ones without D1, D29 antibody marker data.
The overall p-value is from a generalized Wald test of whether the hazard rate of COVID-19 differed across the Low, Medium, and High subgroups.
q-value and FWER are computed over the set of p-values both for quantitative markers and categorical markers using the Westfall and Young permutation method (10000 replicates).