Table 5.
Primary, Secondary and Exploratory Objectives, Endpoints and Analyses
| Objectives | Endpoints | Analyses | |
|---|---|---|---|
| Primary | 1. Immunogenicity: To describe kinetics and durability of maternal serum antibodies following receipt of COVID-19 vaccine in individuals vaccinated during pregnancy, by vaccine type and platform. | • Geometric Mean Titer (GMT) of serum immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) and neutralizing (Neut) antibodies after vaccination and up to 12 months after delivery, by vaccine type and platforma | • Geometric Mean Titers (GMTs) and 95% Confidence Intervals (CIs) will be calculated in Group 1. Plots such as reverse cumulative distributions or longitudinal presentations of GMTs will be presented. |
| 2. Immunogenicity: To describe the transplacental antibody transfer of SARS-CoV-2 antibodies among individuals vaccinated during pregnancy, overall and by vaccine type and platform. | • GMT and ratio of cord blood to maternal serum IgG ELISA and Neut antibodies overall and by vaccine type and platform. | • GMTs and ratio of cord blood to maternal serum and 95% CIs will be calculated in Group 1. | |
| 3. Immunogenicity: To describe kinetics and durability of serum SARS-CoV-2 antibodies in infants of mothers vaccinated during pregnancy, by vaccine type and platform. | • GMT of serum IgG ELISA and Neut antibodies at birth (cord blood) and at approximately 2 and 6 months of age in all infants, by vaccine type and platform. | • GMTs and 95% CIs will be calculated in Group 3. Plots such as reverse cumulative distributions or longitudinal presentations of GMTs will be presented. | |
| Secondary | 1. Safety: To describe pregnancy outcomes in individuals who receive COVID-19 vaccine during pregnancy or postpartum, and their infants, by vaccine type and platform. | • Frequency of maternal and infant outcomes vs. background rates in the US, overall and by vaccine type and platform. | • A comparison of frequencies to background rates will be reported in Groups 1–4 (no formal statistical testing). |
| 2. Immunogenicity: To evaluate immune responses and durability of antibodies in individuals who received different COVID-19 vaccines during pregnancy or postpartum compared to non-pregnant populations of women of childbearing age and to a correlate of protection (if available), by vaccine type and platform. | • GMT of serum IgG ELISA and Neut antibodies after vaccination in pregnancy or postpartum vs. mean titers achieved by non-pregnant participants in clinical trials and to a correlate of protection if available, by vaccine type and platform. | • One sample t-tests will be done in Group 1. | |
| 3. Immunogenicity: To assess the effect of gestational age at vaccination (trimester of gestation), maternal age, health and risk status, on immune responses and durability of antibodies in individuals who receive different COVID-19 vaccines during pregnancy or post-partum, by vaccine type and platform. | • GMT of serum IgG ELISA and Neut antibodies after vaccination in pregnancy by gestational age at vaccination (trimester of gestation) and interval between vaccination and delivery, by vaccine type and platform. GMT of serum IgG ELISA and Neut antibodies after vaccination in pregnancy or postpartum by maternal age, health status, and risk status (e.g., occupation, priority vaccination group) overall and by vaccine type and platform. | • GMTs and 95% CIs will be calculated for Group 1 by strata. Student’s t-tests and linear regression (controlling for potential confounders) will be used to compare strata. | |
| 4. Immunogenicity: To describe the transplacental antibody transfer of SARS-CoV-2 antibodies among individuals vaccinated during pregnancy, by gestational age at vaccination, by interval from vaccination to delivery and maternal age, health and risk status, overall and by vaccine type and platform. |
• GMT and ratio of cord blood to maternal serum IgG ELISA and Neut antibodies at delivery by gestational age at vaccination (trimester of gestation) and interval between vaccination and delivery, overall and by vaccine type and platform. • GMT and ratio of cord blood to maternal serum IgG ELISA and Neut antibodies at delivery by maternal age, health status, and risk status, overall and by vaccine type and platform. |
• GMTs and ratios of cord blood to maternal serum and 95% CIs will be presented for Group 1 by strata. Student’s t-tests and linear regression (controlling for potential confounders) will be used to compare strata. | |
| 5. Immunogenicity: To describe the kinetics of SARS-CoV-2 antibodies in breast milk of mothers who received vaccine during pregnancy or postpartum, overall and by vaccine type and platform. | • GMT of IgG and immunoglobulin A (IgA) ELISA and Neut antibodies in breast milk at approximately 2 weeks, and 2, 6, and 12 months postpartum, in individuals vaccinated during pregnancy or postpartum, overall and by vaccine type and platform. | • GMTs and 95% CIs will be calculated in Group 1. Plots such as reverse cumulative distributions or longitudinal presentations of GMTs will be presented. | |
| 6. Immunogenicity: To describe the kinetics and durability of maternal serum antibodies following receipt of COVID-19 vaccine in individuals vaccinated postpartum, by vaccine type and platform. | • Postpartum individuals: GMT of serum IgG ELISA and Neut SARS-CoV-2 antibodies pre- and/or post-vaccination, and at approximately 2, 6, and 12 months after delivery, overall, and by vaccine type and platform. | • GMTs and 95% CIs will be calculated in Group 3. Plots such as reverse cumulative distributions or longitudinal presentations of GMTs will be presented. | |
| 7. Immunogenicity: To describe the kinetics and durability of serum SARS-CoV-2 antibodies in infants of individuals vaccinated postpartum, by vaccine type and platform. | • GMT of serum IgG ELISA and Neut antibodies at approximately 2 and 6 months of age in infants of postpartum individuals, overall and by vaccine type and platform. | • GMTs and 95% CIs will be calculated in Group 4. Plots such as reverse cumulative distributions or longitudinal presentations of GMTs will be presented. | |
| Exploratory | 1. To describe the effectiveness of COVID-19 vaccines against maternal COVID-19 infection during pregnancy and postpartum. | • Incidence of laboratory confirmed COVID-19 and severity of disease during study participation assessed through passive surveillance in individuals vaccinated during pregnancy or postpartum vs. rates in unvaccinated population of women of childbearing age, overall and by vaccine type and platform. | • Incidence rates and 95% CIs will be calculated in Groups 1 and 3. |
| 2. To describe the effectiveness of maternal antibodies to provide protection against SARS-CoV-2 infection/symptomatic disease/severity in infants in the first 12 months of life. | • Incidence of laboratory confirmed COVID-19 and severity of disease during study participation assessed through passive surveillance in infants of individuals vaccinated in pregnancy or postpartum vs. background rates in infants of unvaccinated population, overall and by vaccine type and platform. | • Incidence rates and 95% CIs will be calculated in Groups 2 and 4. | |
| 3. To describe the effectiveness of breast milk antibodies to provide protection against SARS-CoV-2 infection/symptomatic disease/severity in infants in the first 12 months of life. |
• Incidence of laboratory confirmed COVID-19 and severity of disease during study participation through passive surveillance in breastfed infants vs. not breastfed infants, by vaccine type and platform. • Incidence of laboratory confirmed COVID-19 and severity of disease during study participation through passive surveillance in breastfed infants of individuals vaccinated during pregnancy vs. postpartum, overall and by vaccine type and platform. |
• Incidence rates and 95% CIs will be calculated in Groups 2 and 4. |
Abbreviations: GMT Geometric Mean Titer, IgG immunoglobulin G, ELISA enzyme-linked immunosorbent assay, Neut neutralizing, IgA immunoglobulin A
aPregnant individuals: pre- and/or post-vaccination, at delivery, and at approximately 2, 6, and 12 months postpartum