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Review 1: "Adverse effects and antibody titers in response to the BNT162b2 mRNA COVID-19 vaccine in a prospective study of healthcare workers"

This preprint investigates antibody titer and whether titer correlates with a variety of parameters, including age, weight, sex, and post-vaccine symptom severity. Reviewers deem date reliable with only minor revision to data analysis.

Published onAug 04, 2021
Review 1: "Adverse effects and antibody titers in response to the BNT162b2 mRNA COVID-19 vaccine in a prospective study of healthcare workers"
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key-enterThis Pub is a Review of
Adverse effects and antibody titers in response to the BNT162b2 mRNA COVID-19 vaccine in a prospective study of healthcare workers

AbstractBackgroundmRNA COVID-19 vaccines are playing a key role in controlling the COVID-19 pandemic. The relationship between post-vaccination symptoms and strength of antibody responses is unclear.ObjectiveTo determine whether adverse effects caused by vaccination with the Pfizer/BioNTech BNT162b2 vaccine are associated with the magnitude of vaccine-induced antibody levels.DesignSingle center, prospective, observational cohort study.SettingParticipants worked at Walter Reed National Military Medical Center and were seen monthly at the Naval Medical Research Center Clinical Trials Center.ParticipantsGenerally healthy adults that were not severely immunocompromised, had no history of COVID-19, and were seronegative for SARS-CoV-2 spike protein prior to vaccination.MeasuresSeverity of vaccine-associated symptoms was obtained through participant completed questionnaires. Testing for IgG antibodies against SARS-CoV-2 spike protein and receptor binding domain was conducted using microsphere-based multiplex immunoassays.Results206 participants were evaluated (69.4% female, median age 41.5 years old). We found no correlation between vaccine-associated symptom severity scores and vaccine-induced antibody titers one month after vaccination. We also observed that 1) post-vaccination symptoms were inversely correlated with age and weight and more common in women, 2) systemic symptoms were more frequent after the second vaccination, 3) high symptom scores after first vaccination were predictive of high symptom scores after second vaccination, and 4) older age was associated with lower titers.LimitationsStudy only observes antibody responses and consists of healthy participants.ConclusionsLack of post-vaccination symptoms following receipt of the BNT162b2 vaccine does not equate to lack of vaccine-induced antibodies one month after vaccination. This study also suggests that it may be possible to design future mRNA vaccines that confer robust antibody responses with lower frequencies of vaccine-associated symptoms.FundingThis study was executed by the Infectious Disease Clinical Research Program (IDCRP), a Department of Defense (DoD) program executed by the Uniformed Services University of the Health Sciences (USUHS) through a cooperative agreement by the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. (HJF). This project has been funded by the Defense Health Program, U.S. DoD, under award HU00012120067. Project funding for JHP was in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The funding bodies have had no role in the study design or the decision to submit the manuscript for publication.

RR:C19 Evidence Scale rating by reviewer:

  • Potentially informative. The main claims made are not strongly justified by the methods and data, but may yield some insight. The results and conclusions of the study may resemble those from the hypothetical ideal study, but there is substantial room for doubt. Decision-makers should consider this evidence only with a thorough understanding of its weaknesses, alongside other evidence and theory. Decision-makers should not consider this actionable unless the weaknesses are clearly understood and there is other theory and evidence to further support it.



The research in this article is very meaningful, but there are still some issues that need to be explored in-depth.

1. The article lacks a PBS blank control group, and thus could not explain whether the adverse reaction is caused by the vaccination method or the vaccine antigen.

2. Compared with primary immunization, the adverse reactions increased after the booster immunization, but the manuscript does not explain why it increased. Regarding the increase of adverse reactions and antibody titers after booster immunity, does booster immunity induce a stronger immune response, thus enhancing adverse reactions and antibody titers?

3. As mentioned in the article, there is no relationship between antibody titers and adverse reactions, and there may be a correlation between T cell reactions and adverse reactions. The author should provide references for this statement in the discussion.

4. Whether the participants drink alcohol or use other drugs after vaccination also has an impact on the adverse reactions of the vaccine.

5. The adverse reactions shown in the article have more inflammatory reactions, such as redness and swelling at the injection site, whole-body fever, lymphadenopathy, etc. The article also mentions the role of IL-6 and other inflammatory factors in this process. Are there test results for these cytokines to further explain how the adverse reactions are produced?

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