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. 2024 Jul 30:12:1406315.
doi: 10.3389/fpubh.2024.1406315. eCollection 2024.

Group of longitudinal adverse event patterns after the fourth dose of COVID-19 vaccination with a latent class analysis

Chika Yamamoto  1 , Yurie Kobashi  1   2 , Takeshi Kawamura  3   4 , Yoshitaka Nishikawa  2 , Hiroaki Saito  1   5 , Fumiya Oguro  2 , Tianchen Zhao  1 , Morihito Takita  1 , Toyoaki Sawano  6 , Akihiko Ozaki  7 , Toshiki Abe  1 , Naomi Ito  1 , Yudai Kaneko  4   8 , Aya Nakayama  3 , Masatoshi Wakui  9 , Tatsuhiko Kodama  4 , Masaharu Tsubokura  1   2   10
Affiliations

Group of longitudinal adverse event patterns after the fourth dose of COVID-19 vaccination with a latent class analysis

Chika Yamamoto et al. Front Public Health. .

Abstract

Introduction: Vaccination has been implemented as a useful measure to combat the COVID-19 pandemic. However, there is a tendency for individuals to avoid vaccination due to the possibility of adverse events, making it important to investigate the relationship between COVID-19 vaccines and their adverse events. This study explored longitudinal adverse event patterns and factors that influence adverse events following the second to fourth doses of the COVID-19 vaccine through a latent class analysis.

Methods: Participants were recruited from the Fukushima Prefecture and included individuals who had completed four doses of the COVID-19 mRNA vaccine. This study utilized data from questionnaire surveys and blood collection conducted between September 2021 and November 2022. In the questionnaire, factors such as sex, age, medical history, medication, type of vaccine administered, and adverse events following vaccination were recorded. Additionally, in the blood data, serological tests [IgG(S)] and cellular immune responses (T-spot) were measured. Descriptive statistics, latent class analysis, multivariable logistic regression, and multiple regression analyses were performed to identify the longitudinal adverse event patterns and influencing factors. By analyzing adverse events over time, we identified two distinct groups: those less prone to experiencing adverse events (Group 1) and those more susceptible (Group 2) to latent class analysis.

Results: A total of 1,175 participants were included after excluding those without any adverse events. The median age of the participants in Group 1 was 70 years, and in Group 2 it was 51 years. The proportion of female participants was 298 in Group 1 and 353 in Group 2. Patients in Group 2 were significantly younger (p < 0.001) and more likely to be female (p < 0.001) than those in Group 1. Furthermore, the median IgG(S) value after the fourth vaccination was 3,233 AU/mL in Group 1 and 4,059.39 AU/mL in Group 2. The median T-spot value was 15.4 in Group 1 and 28.5 in Group 2. Group 2 showed significantly higher IgG(S) and T-spot values after the fourth vaccination (p < 0.001).

Discussion: Our findings suggest that factors other than age, particularly sex and a history of allergies, significantly influence the likelihood of experiencing adverse events. Groups categorized by latent class analysis for longitudinal adverse events are expected to be valuable for optimizing vaccination strategies and formulating public health measures.

Keywords: COVID-19; Fukushima cohort; adverse events; latent class analysis; vaccination.

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Conflict of interest statement

YKa was hired by Medical & Biological Laboratories Co. (MBL, Tokyo, Japan). MBL imported the test materials used in the study. YKa participated in the testing process; however, he did not engage in the research design and analysis. YKo and MTs received a grant from the Pfizer Health Research Foundation for research that was not associated with this study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flowchart of inclusion and exclusion criteria for the study participants. A total of 2,527 subjects from the Fukushima Cohort Study participated in up to five blood draws and answered questionnaires between September 2021 and November 2022; those who received the fourth dose of COVID-19 vaccine (n = 1,466) were enrolled and those with no documented adverse effects after the second, third or fourth vaccine doses (n = 291) were excluded. A total of 1,175 individuals were ultimately included in the study.
Figure 2
Figure 2
Group of latent class analysis. The figure shows group classification results based on latent class analysis of the study participants’ adverse events.
See this image and copyright information in PMC

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Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This study was composed of two parts. The first part involved the collection of blood samples from study subjects and the acquisition of data. The second part analyzes the data and discusses the findings to compile the paper. The first part was primarily funded by the Japan Agency for Medical Research and Development (AMED) under the funding title “Development of Vaccines for the Novel Coronavirus Disease,” with a budget from Grant No. JP21nf0101638. The second part of the study was supported by Moderna, Inc. Additionally, this work was supported by JSPS KAKENHI Grant Number 23H00503, and by Medical & Biological Laboratories Co., Ltd. and Shenzhen YHLO Biotech Co., Ltd., the distributor and manufacturer of the antibody measurement system (iFlash 3000). This research was also supported by grants from the Kowa Co. and Research Center for Advanced Science and Technology at the University of Tokyo. It is important to note that none of the funding bodies are related in any capacity. The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication.

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