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Review 2: "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 18, 2022
Review 2: "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.



Please comment on how the threshold of positive antibody detection was set for >1 cutoff? I.e. what were controls/standards used to calibrate this cutoff?

The comparisons of Infected patients vs. vaccinated patients as a whole may be too much of an oversimplification of two cohorts that have great variability concerning where they are in the timing of
their vaccination time-course and where they are with respect to latency since infection. Given the known variability within the population, it is hard to accept comparison at the cohort level. Figure 4, which addresses the latency variable, seems to be a better comparison and visualization of the data. It is striking, however, just how many infected patients have such a low antibody response irrespective of latency. Is this finding something that you expected?

We know that symptoms are not the most accurate measure of onset of infection or SARS-CoV-2 infection. Given that you have RT-PCR testing data, could you reanalyze the latency in comparison to
time elapsed since the positive test result to see how the population falls?

Graphs utilizing LOESS should include a 95% confidence interval so that variability in the data is clear for the reader. For example, there are a lot of moderate and mild cases with high antibody levels, so it would be nice to see if they are outliers.

It was a bit difficult to connect the results section to relevant data findings quickly. It would be useful to reference figures and associated panels (A, B, or C, etc.) following each finding in the text.

I recommend including p-values on plots to make it easier for the reader to delineate which comparisons are significant vs. not significant (especially for figures 1 and 3) so the figures can stand independently.

Figure legends would benefit from being expanded on with more detail which would again be helpful for comprehension and allow the figures to stand more independently.

There is a potential typo in the methods section. In the first paragraph of ‘Statistical analysis: SARS-CoV-2 severity,’ the authors write, “locally weighted smoothing (LOESS) smoothing was applied for regression analysis..”

For mentions of median “(IQR),” The IQR should only be one number. Based on the text, assuming it is (Q1-Q3)?

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