Abstract
Objective
The current study investigated the immune response of maternal coronavirus disease 2019 (COVID‐19) vaccination and vertical transmission of anti–severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) spike (S) and nucleocapsid (N) proteins.
Study design
This retrospective study included pregnant women in Bahrain Defense Force Hospital from March 2021 to September 2021 who were vaccinated with Sinopharm or Pfizer/BioNTech. Testing of anti‐N and ‐S levels from paired samples of maternal and umbilical cord blood was performed at the time of delivery. The immune response to vaccination, association with maternal and fetal factors, and vertical transmission of antibodies were studied.
Results
The current study included 79 pregnant women. The median gestational age for those vaccinated with Sinopharm was 28 weeks and those vaccinated with Pfizer was 31 weeks, with 100% of the vaccinated population generating antibodies and showing vertical transmission. The anti‐N and ‐S titers and interval frequencies varied in both vaccinations. The anti‐N and ‐S and transfer ratio statistically correlated with maternal age, gestational age at delivery, latency period, and birth weight of the neonates differently in both vaccines. In addition, the peak level of antibodies and transfer ratios varied.
Conclusion
Although variations are exhibited in both types of vaccination, the vaccinated pregnant population generated a significant level of anti‐N and ‐S and showed vertical transmission.
Keywords: anti–SARS‐CoV‐2, gestational age, latency period, maternal age, paired sample, spike and nucleocapsid proteins, transfer ratio, umbilical cord, vaccination
Synopsis
Although variations are exhibited in the type of COVID‐19 vaccination, the vaccinated pregnant population generated a significant level of anti‐N and ‐S and showed vertical transmission.
1. INTRODUCTION
The coronavirus disease 2019 (COVID‐19) pandemic created a global crisis, including the risk to pregnant women. The progression of the disease is not well‐known and the sequence of the virus and different strain mutations vary from region to region. Pregnant women infected with COVID‐19 are at risk for severe complications, 1 including maternal morbidity and mortality as well as adverse fetal outcome. The uncertainty of the disease is of concern in the pregnant population; therefore, vaccination for pregnant women may provide comfort among women in reproductive life. The study of maternal immunization is crucial to controlling the pandemic.
In February 2021, the Kingdom of Bahrain was the first Gulf Cooperation Council country to approve five COVID‐19 vaccines and encouraged pregnant women to receive either the Sinopharm or Pfizer/BioNTech vaccine. Vaccinations during pregnancy mount immunity and reduce maternal and neonatal morbidity and mortality. 2 Focus was given to improve immunity for the mother and baby in order to obtain a healthy outcome. Positive antibodies against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in the mother's serum and umbilical cord blood after vaccination raise the hope of immunity for pregnant women and newborns from COVID‐19; thus, vaccination shows protection of mother and baby from the pandemic.
2. MATERIALS AND METHODS
This retrospective study investigated the vaccination of a pregnant population between March 2021 and September 2021 at Bahrain Defense Force Hospital. The study design was approved by the ethical committee at the Research Centre in Bahrain Defense Force Hospital and the national COVID‐19 clinical research team. All data included were anonymized. Computerized medical records were reviewed with confidentiality. Demographic data such as maternal age and body mass index and newborn birth weight were collected. Analysis of anti‐SARS‐CoV‐2 spike (S) and anti‐SARS‐CoV‐2 nucleocapsid (N) in paired samples from mother's serum and cord blood was performed at the time of delivery to evaluate vertical transmission of immune response. The transfer ratio was calculated as cord blood antibody levels divided by maternal antibody levels. Antibody level and transfer ratio of both Sinopharm‐ and Pfizer‐vaccinated pregnant populations were correlated with maternal variables, newborn weight, gestational age at vaccination, gestational age at delivery, and latency period.
2.1. Inclusion criteria
Women not infected with COVID‐19 who received both doses of Sinopharm or Pfizer vaccine during pregnancy were included. Nasopharyngeal samples with polymerase chain reaction or SARS‐CoV‐2 GeneXpert and questionnaires were used to rule out the history of COVID‐19 infection in the study population before assessing antibody levels.
2.2. Exclusion criteria
Pregnant women with COVID‐19 during or before pregnancy, irrespective of vaccination, were excluded from the study. The women who received vaccination before pregnancy as well as women who received the first or second dose after delivery were also excluded from the study.
2.3. Statistical analysis
Continuous variables are represented as mean ± standard deviation or median (first quartile–third quartile), whereas categorical variables are represented as frequencies and percentages. Depending on the data requirements, independent t test and Mann–Whitney U‐test were used to compare the characteristics of Sinopharm and Pfizer vaccination groups. Pearson and Spearman correlations were used to assess the relationship between maternal factors, mother's antibodies, cord blood antibodies, and antibody transfer ratio. To assess associations between categorical variables, χ2 and Fisher exact tests were used. SPSS version 26.0 (IBM) and Minitab version 18 (Minitab, LLC) software were used to conduct all analyses. A P‐value <0.05 was considered statistically significant.
3. RESULTS
The analyses included a total of 79 women, 37 (46.8%) of whom were vaccinated with Sinopharm and 42 (53.2%) with Pfizer while pregnant. The patients' ages ranged from 19 to 42 years. Characteristics of Sinopharm and Pfizer vaccination groups are summarized in Table 1.
TABLE 1.
Demographic characteristics difference between patients with the Sinopharm and Pfizer vaccinations
| Sinopharm vaccination (n = 37) | Pfizer vaccination (n = 42) | P‐value | ||
|---|---|---|---|---|
| Mother's age, mean ± SD, y | 30 ± 6 | 28 ± 5 | 0.122 | |
| Body mass index, mean ± SD, kg/m2 | 32.53 ± 5.98 | 31.42 ± 6.03 | 0.435 | |
| Baby's birth weight, mean ± SD, g | 3207 ± 601 | 3116 ± 648 | 0.525 | |
| Gestational age, median (quartile 1–quartile 3), wk | 28 (23–32) | 31 (25–34) | 0.122 | |
| Delivery gestational age, median (quartile 1–quartile 3), wk | 39 (37–40) | 39 (38–40) | 0.562 | |
| Antibody levels (mother), median (quartile 1–quartile 3) | Antibody N (cutoff index) | 1.14 (0.61–5.19) | 0.09 (0.07–1.98) | <0.01* |
| Antibody S (U/ml) | 50.30 (11–311) | 1153.5 (463–4259) | <0.01* | |
| Antibody levels (cord blood), median (quartile 1–quartile 3) | Antibody N (cutoff index) | 1.37 (0.75–4.61) | 0.1 (0.06–2.89) | <0.01* |
| Antibody S (U/ml) | 50 (14.3–173) | 1484.5 (531–5418) | <0.01* | |
| Transfer ratio, median (quartile 1–quartile 3) | Antibody N | 1.09 (0.54–1.44) | 1 (0.94–1.2) | 0.898 |
| Antibody S | 0.94 (0.22–1.59) | 1.28 (0.92–1.63) | 0.153 | |
| Interval, median (quartile 1–quartile 3), d | 71 (56–111) | 62 (38–103) | 0.229 | |
Note: The P‐value was calculated using independent t test or Mann–Whitney test as appropriate. The interval for the vaccinated group is from the second dose.
Abbreviation: SD, standard deviation.
Significant P < 0.01 level.
The median gestational age at Sinopharm vaccination was 28 weeks and at Pfizer vaccination was 31 weeks on average. The antibodies N and S of mothers and cords differed statistically between the two vaccinations, with those with the Pfizer vaccination having significantly higher levels of antibody S for both mothers and babies and those in the Sinopharm vaccination group having higher levels of antibody N. The interval frequencies of antibodies from second dose are illustrated in Figures 1 and 2.
FIGURE 1.
(a) Interval frequencies of Sinopharm vaccination. (b) Interval frequencies of Pfizer vaccination.
FIGURE 2.
(a) Paired mothers and cords with Sinopharm Antibody‐N. (b) Paired mothers and cords with Sinopharm Antibody‐S.
Antibody intervals frequency of Sinopharm vaccination group from the second dose were highest within 61 to 71 and 111 to 121 days, whereas intervals from Pfizer vaccination were highest within 34 to 44 and 54 to 64 days as shown in Figure 1a,b.
The correlation of maternal factors with mother's and cord blood antibodies in the Sinopharm and Pfizer vaccination groups are presented in Table 2.
TABLE 2.
Correlation between maternal factors with Sinopharm and Pfizer vaccinations of mother and cord blood antibodies
| Mother antibody N | Mother antibody S | Cord antibody N | Cord antibody S | |
|---|---|---|---|---|
| Mother and cord blood with Sinopharm vaccination | ||||
| Mother's age | r = −0.112 | r = −0.201 | r = −0.085 | r = −0.209 |
| P = 0.521 | P = 0.247 | P = 0.656 | P = 0.268 | |
| Body mass index | r = 0.093 | r = −0.118 | r = 0.091 | r = 0.136 |
| P = 0.608 | P = 0.512 | P = 0.638 | P = 0.481 | |
|
Baby's birth weight |
r = 0.245 | r = 0.037 | r = 0.215 | r = 0.257 |
| P = 0.155 | P = 0.834 | P = 0.245 | P = 0.162 | |
| Gestational age | rs = 0.112 | rs = −0.048 | rs = 0.011 | rs = 0.155 |
| P = 0.523 | P = 0.786 | P = 0.953 | P = 0.404 | |
| Gestational age at delivery | rs = −0.054 | rs = −0.068 | rs = −0.018 | rs = 0.052 |
| P = 0.756 | P = 0.700 | P = 0.922 | P = 0.782 | |
| Interval | rs = −0.113 | rs = 0.100 | rs = 0.024 | rs = −0.135 |
| P = 0.520 | P = 0.567 | P = 0.900 | P = 0.470 | |
| Mother and cord blood with Pfizer vaccination | ||||
| Mother's age | r = 0.046 | r = −0.331 | r = 0.117 | r = −0.316 |
| P = 0.778 | P = 0.037* | P = 0.484 | P = 0.053 | |
| Body mass index | r = 0.211 | r = −0.179 | r = 0.213 | r = −0.118 |
| P = 0.203 | P = 0.283 | P = 0.220 | P = 0.500 | |
| Baby's birth weight | r = −0.036 | r = −0.061 | r = 0.037 | r = −0.053 |
| P = 0.827 | P = 0.708 | P = 0.827 | P = 0.752 | |
| Gestational age | rs = 0.181 | rs = 0.235 | rs = 0.288 | rs = 0.079 |
| P = 0.265 | P = 0.144 | P = 0.079 | P = 0.638 | |
| Gestational age at delivery | rs = 0.035 | rs = −0.305 | rs = −0.054 | rs = −0.142 |
| P = 0.832 | P = 0.056 | P = 0.746 | P = 0.397 | |
| Interval | rs = −0.269 | rs = −0.360 | rs = −0.398 | rs = −0.092 |
| P = 0.093 | P = 0.023* | P = 0.013* | P = 0.582 | |
Note: The P‐value was calculated using Pearson correlation and Spearman correlation as appropriate.
Significant P < 0.05 level.
In the Pfizer vaccination group, the mother's antibody S had a weak negative correlation with age and interval. The cord's antibody N from the Pfizer vaccination group had a weak negative correlation with the interval. No statistically significant correlation was found among the Sinopharm vaccination group. Mother antibodies N and S had a statistically significant correlation with cord antibodies N and S in both the Sinopharm and Pfizer vaccination groups. Correlations between maternal factors and antibodies transfer ratio of both vaccination groups are presented in Table 3.
TABLE 3.
Correlation between maternal factors with Sinopharm and Pfizer vaccinations of antibodies transfer ratio
| Sinopharm vaccination | Pfizer vaccination | |||
|---|---|---|---|---|
| Anti‐N transfer ratio | Anti‐S transfer ratio | Anti‐N transfer ratio | Anti‐S transfer ratio | |
| Mother's age | r = −0.187 | r = −0.007 | r = 0.007 | r = −0.275 |
| P = 0.282 | P = 0.966 | P = 0.965 | P = 0.086 | |
| Body mass index | r = −0.236 | r = −0.167 | r = −0.131 | r = −0.187 |
| P = 0.187 | P = 0.353 | P = 0.431 | P = 0.260 | |
| Baby's birth weight | r = 0.366 | r = 0.013 | r = 0.134 | r = 0.307 |
| P = 0.031* | P = 0.941 | P = 0.410 | P = 0.054 | |
| Gestational age | rs = −0.263 | rs = 0.004 | rs = 0.353 | rs = 0.009 |
| P = 0.127 | P = 0.982 | P = 0.026* | P = 0.958 | |
| Gestational age at delivery | rs = 0.414 | rs = 0.452 | rs = 0.085 | rs = 0.355 |
| P = 0.013* | P = 0.006** | P = 0.602 | P = 0.025* | |
| Interval | rs = 0.411 | rs = 0.168 | rs = −0.320 | rs = 0.180 |
| P = 0.014* | P = 0.334 | P = 0.044* | P = 0.266 | |
Note: The P‐value was calculated using Pearson correlation and Spearman correlation as appropriate.
Significant P < 0.05 level
Significant P < 0.01 level.
Transfer ratio of antibody N from the Sinopharm vaccination group had a moderate positive correlation with baby's birth weight, gestational age at delivery, and the interval, whereas antibody S transfer ratio had a moderate positive correlation with gestational age at delivery. Transfer ratio of antibody N from the Pfizer vaccination group had a weak positive correlation with gestational age and weak negative correlation with the interval, whereas antibody S had a weak positive correlation with gestational age at delivery, as shown in Table 3.
The transfer ratio was divided into two categories: <1 and ≥1. In the Sinopharm vaccination group, 54.3% had anti‐N transfer ratios ≥1 and 45.7% had anti‐S transfer ratios ≥1. In the Pfizer vaccination group, 27.5% had an anti‐N transfer ratio <1 and 72.5% had an anti‐S transfer ratio ≥1. Frequencies of transfer ratios <1 and ≥1 stratified by maternal factors for both vaccination groups are shown in Table 4.
TABLE 4.
Frequencies and association of maternal factors with antibody transfer ratios of Sinopharm and Pfizer vaccinations
| Anti‐N transfer ratio | P‐value | Anti‐S transfer ratio | P‐value | ||||
|---|---|---|---|---|---|---|---|
| <1 | ≥1 | <1 | ≥1 | ||||
| Mothers and cord blood with Sinopharm vaccination | |||||||
| Mother's age, y | 18–25 | 5 (50.0) | 5 (50.0) | 0.239 | 7 (70.0) | 3 (30.0) | 0.216 |
| 26–35 | 5 (31.3) | 11 (68.8) | 6 (37.5) | 10 (62.5) | |||
| >35 | 6 (66.7) | 3 (33.3) | 6 (66.7) | 3 (33.3) | |||
| Body mass index, kg/m2 | 18.5–25 (normal) | 1 (25.0) | 3 (75.0) | 0.847 | 1 (25.0) | 3 (75.0) | 0.847 |
| 26–30 (overweight) | 5 (41.7) | 7 (58.3) | 7 (58.3) | 5 (41.7) | |||
| 31–35 (obese grade 1) | 4 (66.7) | 2 (33.3) | 4 (66.7) | 2 (33.3) | |||
| 36–40 (obese grade 2) | 4 (44.4) | 5 (55.6) | 5 (55.6) | 4 (44.4) | |||
| >40 (obese grade 3) | 1 (50.0) | 1 (50.0) | 1 (50.0) | 1 (50.0) | |||
| Sex | Male | 7 (43.8) | 9 (56.3) | 0.830 | 9 (56.3) | 7 (43.8) | 0.830 |
| Female | 9 (47.4) | 10 (52.6) | 10 (52.6) | 9 (47.4) | |||
| Baby's weight, g | <2500 | 3 (100) | 0 (0.0) | 0.031* | 3 (100) | 0 (0.0) | 0.211 |
| 2500–3500 | 10 (52.6) | 9 (47.4) | 11 (57.9) | 8 (42.1) | |||
| >3500 | 3 (23.1) | 10 (76.9) | 5 (38.5) | 8 (61.5) | |||
| Delivery gestational age, wk | ≤37 weeks | 8 (72.7) | 3 (27.3) | 0.030* | 9 (81.8) | 2 (18.2) | 0.027* |
| >37 weeks | 8 (33.3) | 16 (66.7) | 10 (41.7) | 14 (58.3) | |||
| Interval | 0–50 | 5 (62.5) | 3 (37.5) | 0.307 | 4 (50.0) | 4 (50.0) | 0.826 |
| 51–100 | 8 (53.3) | 7 (46.7) | 9 (60.0) | 6 (40.0) | |||
| 101–150 | 3 (27.3) | 8 (72.7) | 6 (54.5) | 5 (45.5) | |||
| >150 | 0 (0.0) | 1 (100) | 0 (0.0) | 1 (100) | |||
| Mothers and cord blood with Pfizer vaccination | |||||||
| Mother's age, y | 18–25 | 2 (15.4) | 11 (84.6) | 0.186 | 1 (7.7) | 12 (92.3) | 0.084 |
| 26–35 | 6 (27.3) | 16 (72.7) | 9 (40.9) | 13 (59.1) | |||
| >35 | 3 (60.0) | 2 (40.0) | 1 (20.0) | 4 (80.0) | |||
| Body mass index, kg/m2 | <18.5 (underweight) | 0 (0.0) | 1 (100) | 0.695 | 0 (0.0) | 1 (100) | 0.149 |
| 18.5–25 (normal) | 1 (50.0) | 1 (50.0) | 1 (50.0) | 1 (50.0) | |||
| 26–30 (overweight) | 5 (33.3) | 10 (66.7) | 2 (13.3) | 13 (86.7) | |||
| 31–35 (obese grade 1) | 2 (16.7) | 10 (83.3) | 4 (33.3) | 8 (66.7) | |||
| 36–40 (obese grade 2) | 2 (33.3) | 4 (66.7) | 4 (66.7) | 2 (33.3) | |||
| >40 (obese grade 3) | 1 (50.0) | 1 (50.0) | 0 (0.0) | 2 (100) | |||
| Sex | Male | 4 (21.1) | 15 (78.9) | 0.385 | 7 (36.8) | 12 (63.2) | 0.208 |
| Female | 7 (33.3) | 14 (66.7) | 4 (19.0) | 17 (81.0) | |||
| Baby's weight, g | <2500 | 3 (75.0) | 1 (25.0) | 0.009** | 3 (75.0) | 1 (25.0) | 0.043* |
| 2500–3500 | 3 (12.0) | 22 (88.0) | 7 (28.0) | 18 (72.0) | |||
| >3500 | 5 (45.5) | 6 (54.5) | 1 (9.1) | 10 (90.9) | |||
| Delivery gestational age, wk | ≤37 weeks | 4 (44.4) | 5 (55.6) | 0.227 | 5 (55.6) | 4 (44.4) | 0.083 |
| >37 weeks | 7 (22.6) | 24 (77.4) | 6 (19.4) | 25 (80.6) | |||
| Interval | 0–50 | 3 (23.1) | 10 (76.9) | 0.569 | 6 (46.2) | 7 (53.8) | 0.353 |
| 51–100 | 4 (28.6) | 10 (71.4) | 3 (21.4) | 11 (78.6) | |||
| 101–150 | 3 (25.0) | 9 (75.0) | 2 (16.7) | 10 (83.3) | |||
| >150 | 1 (100) | 0 (0.0) | 0 (0.0) | 1 (100) | |||
Note: Values are presented as number (percentage).*Significant P < 0.05. The P‐value was calculated using χ2 test and Fisher exact test as appropriate.
From Sinopharm vaccination group, baby's birth weight of >3500 g had a high prevalence with anti‐N transfer ratios of ≥1. Gestational age at delivery had a statistically significant association with anti‐N and anti‐S transfer ratios with the pre‐term delivery having a high prevalence with anti‐transfer ratios of <1 and delivery at >37 weeks having a high prevalence with anti‐transfer ratios of ≥1. From Pfizer vaccination group, baby's birth weight had a statistically significant association with anti‐N and anti‐S transfer ratios with baby's birth weight <2500 g having a high prevalence with anti‐transfer ratios of <1 and those with birth weight >2500 g having a high prevalence with anti‐transfer ratios of ≥1 as represented in Table 4. Antibodies N & S of mothers and cords in both vaccinations are represented as pairs in Figures 2 and 3.
FIGURE 3.
(a) Paired mothers and cords Pfizer Antibody‐N. (b) Paired mothers and cords Pfizer Antibody‐S.
Antibodies N and S of both Sinopharm‐ and Pfizer‐vaccinated mothers as well as antibody transfer ratios with relation to interval are illustrated in Figure 4.
FIGURE 4.
(a) Comparison between antibody N of Sinopharm vaccinated mothers and cords. (b) Comparison between antibody S of Sinopharm vaccinated mothers and cords. (c) Comparison between antibody N of Pfizer vaccinated mothers and cords. (d) Comparison between antibody S of Pfizer vaccinated mothers and cords. (e) Comparison between antibody's transfer ratios of Sinopharm vaccinated mothers and Cord blood. (f) Comparison between antibody's transfer ratios of Pfizer vaccinated mothers and Cord blood.
Mothers and cord blood Antibodies‐N levels peaked at 21 days after the second dose and then gradually decreases over time. Both mothers and cord blood Antibodies‐N were at their lowest levels starting from 108 days after the second dose, as shown in Figure 4a. All mothers and cord blood Antibodies‐S were between (0.4–1200) Antibody level after the second dose, only one mother had a high Antibody level after 116 days (Figure 4b).
Mothers and cord blood Antibodies‐N were between (0.05–40) Antibody levels after the second dose, after 36 days both a mother and her cord peaked at (72.1, 149) Antibody levels respectively, (Figure 4c). From 14–142 days following the second dose, mothers and cord blood Antibodies‐S varied between (1192–25000 COI) levels as shown in (Figure 4d).
Sinopharm transfer ratios N&S ranged between (0–2.7) Antibody levels after the second dose, transfer Ratio‐S peaked at 74 Antibody level after 95 days from the second dose (Figure 4e). Pfizer transfer ratios N&S ranged between (0–2) Antibody levels after the second dose, transfer Ratio‐N peaked at 10.75 after 21 days, and at 13.7 after 60 days from the second dose as shown in Figure 4f.
4. DISCUSSION
Pregnant women are at increased risk of viral infections, including COVID‐19, because of immunological changes during pregnancy. 3 As the severity of the disease increases with pregnancy, preventive actions are vital for mother and baby. Apart from precautionary measures, such as hand washing, mask wearing, and maintaining social distance, the availability of vaccines promoted interest in mothers, with recommendations getting stronger.
Immunological effects of the vaccine increased expectations in the pregnant population to protect them from COVID‐19. Khoury et al. 4 demonstrated neutralizing antibody levels against COVID‐19 and protective effects. Coronavirus vaccination helps in producing antibodies, reactionary changes in cellular immunity, and memory cells that may help to protect individuals from the disease. 5 The immunological induction of the COVID‐19 messenger RNA vaccine and the umbilical cord transfer of antibodies were explained by Collier et al. 6 In our study population, the maternal age range was 19 to 41 years, with a mean body mass index of 32.53 kg/m2 for the Sinopharm and 31.43 kg/m2 for the Pfizer populations. Participants received their first dose of vaccine at 26 weeks and the second dose at 28 to 31 weeks, on average. The study by Gray et al., and the mean age of the vaccinated pregnant population was 34.1 and 23.2 weeks of gestation, when the first dose was received. 7 Our study Antibody intervals frequency of Sinopharm vaccination group from the second dose were highest within 61 to 71 and 111 to 121 days, whereas intervals from Pfizer vaccination were highest within 34 to 44 and 54 to 64 days (Figure 1a,b).
Immunological reaction to SARS‐CoV‐2 infection generates antibodies to viral proteins N and S1 (subunit of spike protein) or RBD (receptor binding domain). Immunoassays that detect IgG, IgM, and IGA are generated in response to the vaccine's immune reaction. 8 , 9 The concept of immune response was adapted for vaccination and intensely implemented. The immune response to spike protein or RBD in the vaccinated population showed a potential role in the defense against COVID‐19, not anti‐N. 9 However, presence of any antibodies against N/S/RBD were suggestive of previous COVID‐19 infection. 10 , 11 When we compare antibodies between vaccines, the Sinopharm vaccine showed statistically significantly higher levels of anti‐N than the Pfizer vaccine, whereas anti‐S levels were higher in the Pfizer group than the Sinopharm group (Table 1). Further studies on individual vaccine immune response in relation to viral proteins N and S1 could likely answer this hypothesis.
Regarding the association between the immune responses to vaccination and maternal, fetal, and clinical factors, the anti‐SARS‐CoV‐2 S and N titers did not have any association with maternal body mass index, newborn birth weight, gestational age at vaccination, or gestational age at delivery. This could explain the immunological reaction of every individual as varied. However, in the Pfizer vaccination group, the mothers' antibody S had a weak negative correlation with maternal age and interval, and the cords' antibody N had a weak negative correlation with interval. The antibody titer decreased with the longer interval. On the other hand, the population who received Sinopharm did not show any association, as individual response to different types of vaccination also differed.
In the current study, however, the transfer ratio of anti‐N and anti‐S did not show a significant association with maternal characteristics. Newborn and clinical factors varied in relation to the type of vaccinations.
All together, the antibody titer did not show the significant relationship with gestational age at vaccination, but the transfer ratio showed correlations with the gestational period. However, the anti‐S transfer ratio of both types of vaccinations positively significantly correlated with the latency period, as it is increased with prolonged interval of gestational week, which could offer immunological protection to mother and baby at the third trimester as well as at the time of delivery, with the peak transfer at 60 and 93 days after the second dose (Figure 4e,f). Anti‐N of Sinopharm positively correlated with interval, which is increased with the interval and anti‐N of Pfizer negatively correlated with the interval, which is decreased with the latency period. When we divided the transfer ratio of antibodies into <1 and ≥1, in the Sinopharm vaccination group, the baby's birth weight of >3500 g had a high prevalence with anti‐N transfer ratios of ≥1, and in the Pfizer group, the baby's birth weight of >2500 g had a high prevalence with anti‐N and ‐S transfer ratios of ≥1, which demonstrate the relationship of larger birth weight and higher transfer of antibodies. Similarly, higher transfer was demonstrated with the term babies than the preterm babies in the Sinopharm vaccine group. Prahl et al. 12 demonstrated the importance of timing of maternal vaccination in vertical transmission of antibodies. Prathama and et al. 13 explained the elevated antibody responses and transfer ratio with prolonged interval from the vaccination.
Our study population received the second dose of vaccination at around 28 to 31 weeks of gestation. All of patients produced antibodies and significantly transferred to the fetus in variable ranges according to the individual immune response. The level of anti‐N and ‐S in the Sinopharm group as well as in the Pfizer group peaked differently and declined. However, the level of anti‐S in the Pfizer group sustained from 14 to 142 days with the highest level of 25 000 U/ml in cord blood. In the Sinopharm group, anti‐S varied in the range of 0.4 to 1200, with one mother having the highest antibody level of 16 800 after 116 days (Figure 4a–d). All of the women who received vaccination in the study group were provided protection from the COVID‐19 infection until delivery. A study by Kugelman et al. 14 explains second‐trimester vaccination and the immunological responses as well as the vertical transmission of antibodies. A similar study by Matsui 15 reported that second‐trimester vaccination generated a higher transfer ratio. Gill et al. 16 reported vertical transmission of anti‐SARS‐CoV‐2 after Pfizer in the last trimester. Sahin et al. 17 emphasized BNT162b1 and the likely protection against the virus. The span of protection in relation to the level of antibodies as well as the type of vaccination require further studies.
In the current study, the vaccinated population had a different range of maternal anti‐S and ‐N titer in both types of vaccines with the efficient vertical transmission and ranges relatively proportionate to most of the cord blood level (Figures 2 and 3). Although we could not elicit any relationship for the difference in titer, generation of immunological response and transfer of antibodies could be potentially individualized. Atyeo et al. 18 described the process of placental transfer to a variation in the levels of antibody. Gray et al. 7 illustrated the immune response following COVID‐19 vaccine and vertical transmission. Future studies of the placental mechanism may yield more clarity. Nir et al. 19 reported vertical transmission of SARS‐CoV‐2 IgG after the BNT162b2 messenger RNA vaccine as well as the association between the mother and cord blood antibody levels. Prahl et al. 12 explained the duration for the antibody production and vertical transmission and the study showed there was no statistical significance between maternal and cord blood antibodies. The immune response of COVID‐19 vaccination along with the vertical transmission could provide protection to pregnant women as well as neonates from COVID‐19 infection.
5. CONCLUSION
Invariably, all pregnant women who received vaccination for COVID‐19 generated antibodies in various ranges, and the antibodies significantly transferred to the fetus. The level of antibodies in the cord blood are substantially comparable to the level in most of the mother's serum. The variation in immune response and placental transfer could be individualized. The level of anti‐N and anti‐S and the association between maternal, fetal, and clinical factors varied between the Sinopharm and Pfizer vaccination groups. The transfer ratios of antibodies were higher in larger and term babies than in smaller and preterm babies. The latency period had positive correlation with the transfer ratio of anti‐S. However, the longer interval showed a decline in the titer as well as the transfer ratio, following the peak level. This supports the notion that mid‐trimester vaccination could be the ideal period for vaccination in the pregnant population to provide optimal protection to mother and neonate from COVID‐19 infection. While recommending vaccination, the safety profile of the vaccine also should be considered.
AUTHOR CONTRIBUTIONS
A.S. designed the study; drafted and wrote the manuscript; interpreted the data; and performed acquisition, analysis, and review of the final version. H.M.A., O.E.T., M.S.K., and F.K.B. collected data; contributed to the design of the study; drafted the manuscript; interpreted the data; and performed acquisition, analysis, and review of the final version. B.D. supervised the study; contributed to the design of the study; drafted the manuscript; interpreted the data; and performed acquisition, analysis, and review of the final version. All authors gave their approval for the final version of this paper to be published.
CONFLICT OF INTEREST
The authors report no conflicts of interest.
ACKNOWLEDGMENTS
The authors would like to thank the Royal Bahrain Defense Force Hospital, The Crown Prince Centre for Training and Medical Research, and the national COVID‐19 clinical research team for the technical support and study material. Our thanks to Fatima Buzaid and Shaima Khalid for their contribution to data analysis, and to our laboratory, biochemistry section in charge, Maha AL‐Ayadhi, for contribution of the immunoassay.
Sunder A, Taha OE, Keshta MS, Bughamar FK, Darwish B. COVID‐19 vaccinations in pregnancy: Save mother and baby from COVID‐19 pandemic. Int J Gynecol Obstet. 2022;00:1‐10. doi: 10.1002/ijgo.14532
DATA AVAILABILITY STATEMENT
Research data are not shared.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
Research data are not shared.