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Review 1: "Maternal Antibody Response and Transplacental Transfer Following SARS-CoV-2 Infection or Vaccination in Pregnancy"

Reviewers found the research meaningful for maternal antibody response and transplacental transfer among different SARS variants. However, authors could improve the research structure and evidence relating to patient samples, as it could play a key role in human diseases.

Published onMay 19, 2022
Review 1: "Maternal Antibody Response and Transplacental Transfer Following SARS-CoV-2 Infection or Vaccination in Pregnancy"
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key-enterThis Pub is a Review of
Maternal Antibody Response and Transplacental Transfer Following SARS-CoV-2 Infection or Vaccination in Pregnancy

AbstractBackgroundPregnant persons are at increased risk of severe COVID-19 and adverse obstetric outcomes. Understanding maternal antibody response and transplacental transfer after SARS-CoV-2 infection and COVID-19 vaccination is important to inform public health recommendations.MethodsThis prospective observational cohort study included 351 birthing individuals who had SARS-CoV-2 infection or COVID-19 vaccination during pregnancy. IgG and IgM to SARS-CoV-2 S1 receptor binding domain were measured in maternal and cord blood. Antibody levels and transplacental transfer ratios were compared across 1) disease severity for those with SARS-CoV-2 infection and 2) infection versus vaccination.FindingsThere were 252 individuals with SARS-CoV-2 infection and 99 who received COVID-19 vaccination during pregnancy. Birthing people with more severe SARS-CoV-2 infection category had higher maternal and cord blood IgG levels (p=0.0001, p=0.0001). Median IgG transfer ratio was 0.87-1.2. Maternal and cord blood IgG were higher after vaccination than infection (p=0.001, p=0.001). Transfer ratio was higher after 90 days in the vaccinated group (p<0.001). Modeling showed higher amplitude and half-life of maternal IgG following vaccination (p<0.0001). There were no significant differences by fetal sex.InterpretationCOVID-19 vaccination in pregnancy leads to higher and longer lasting maternal IgG levels, higher cord blood IgG, and higher transfer ratio after 90 days compared to SARS-CoV-2 infection. Greater infection severity leads to higher maternal and cord blood antibodies. Maternal IgG decreases over time following both vaccination and infection, reinforcing the importance of vaccination, even after infection, and vaccine boosters for pregnant patients.

RR:C19 Evidence Scale rating by reviewer:

  • Reliable. The main study claims are generally justified by its methods and data. The results and conclusions are likely to be similar to the hypothetical ideal study. There are some minor caveats or limitations, but they would/do not change the major claims of the study. The study provides sufficient strength of evidence on its own that its main claims should be considered actionable, with some room for future revision.




  • Overall well written and succinct

  • Within the results, it is unclear to me what type of vaccines patients received, assuming majority mRNA? Also, the results should include vaccinated cord blood transfer ratios.


  • To line: “COVID-19 vaccines include messenger RNA (mRNA) vaccines BNT162b2(Pfizer/BioNTech) and mRNA-1273 (Moderna) and viral vector vaccines such as J&J/Janssen.” The authors should specify the CDC's preference for mRNA vaccines.

  •  “Yet, few studies have addressed the duration of vaccine-induced antibody response in pregnancy or have compared vaccine-induced antibodies to natural infection in pregnancy.” This line should include proper citations of relevant studies.

  •  Again, it is unclear what type of vaccines the authors are analyzing, and I suggest changing the introduction.


  • Within the section on Maternal and infant antibodies, the last line says “antibody ratio calculated as infant divided by maternal.” Instead of infant, the authors should say cord. Similarly elsewhere in the text and in figures, the authors should specify “cord” rather than “infant.”

  • Could authors clarify IRB approval vs exempt vs..?

  • There is great analytic method to differentiate the severity of infection from latency from infection to delivery as they often occur together and are difficult to tease out


  • The racial differences in vaccination versus infection are striking.

  • Figures 1 -4 would benefit from the succinct explanation of the methods and main findings.


  • The authors note “The possibility that fetal sex modifies maternal antibody response or placental transfer is intriguing this is more than intriguing and has been well studied in the literature.” I would like to see the authors discuss their findings in the context of the sex differences in vaccine-induced immunity. The authors can reference PMID30547182 (Fischinger S, Semin Immunopathol, 2019).

  • Another limitation is that the manuscript did not analyze or present data on the crossover (ie how many vaccinated patients also had an infection), and should specify cord blood as a marker for neonatal levels but that correlates of protection have not been established.

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