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Spatiotemporal Components of Adverse Reactions Against BNT162b2 mRNA SARS-CoV-2 Vaccine Reflect Different Immunological Processes

15 Pages Posted: 12 Aug 2021

See all articles by Kei Ikeda

Kei Ikeda

Chiba University - Department of Allergy and Clinical Immunology

Taka-Aki Nakada

Chiba University - Department of Allergy and Clinical Immunology

Takahiro Kageyama

Chiba University - Department of Allergy and Clinical Immunology

Shigeru Tanaka

Chiba University - Department of Allergy and Clinical Immunology

Naoki Yoshida

Chiba University - Artificial Intelligence Medicine

Tetsuo Ishikawa

RIKEN Information R&D and Strategy Headquarters - Advanced Data Science Project (ADSP)

Yuki Goshima

RIKEN Information R&D and Strategy Headquarters - Advanced Data Science Project (ADSP)

Toshibumi Taniguchi

Chiba University - Department of Infectious Diseases

Hidetoshi Igari

Chiba University - Division of Infection Control

Hideki Hanaoka

Chiba University - Clinical Research Center

Koutaro Yokote

Chiba University - Department of Endocrinology, Hematology and Gerontology; Chiba University - Division of Diabetes, Metabolism and Endocrinology; Chiba University - Department of Clinical Cell Biology and Medicine

Hiroshi Nakajima

Chiba University Hospital COVID-19 Vaccine Center

Eiryo Kawakami

Chiba University - Artificial Intelligence Medicine

More...

Abstract

Background: Reactogenicity of vaccines can derive from different immunological processes and is composed of a range of symptoms with varying time courses. This study aimed to decompose complex adverse reactions against the BNT162b2 SARS-CoV-2 vaccine into spatiotemporal patterns and clarify their associations with external information. 

Methods: We recruited healthcare workers who were receiving the BNT162b2 mRNA SARS-CoV-2 vaccine in the Chiba University Hospital vaccination program. We collected information on adverse reactions every day after each dose using a smartphone/web-based platform. Information for immediate reactions was collected specifically on the vaccination day. We determined the serum anti-SARS-CoV-2S antibody titers after the 2nd dose. We employed non-negative tensor factorization to decompose the serial reactogenicity information into components. Associations of these tensor components with external information were analyzed using a generalized linear model and a generalized additive model. 

Findings: We analyzed 1,774 participants who received two doses of vaccine. Tensor decomposition revealed four components that represented spatiotemporal patterns of adverse reactions. The original reactogenicity data were well explained by these four tensor components with minimal errors. One component, which represented diverse and severe symptoms that occurred early after the 2nd dose, was significantly associated with post-vaccination antibody titers, suggesting the involvement of acquired immunity. On the other hand, the other three components were not significantly associated with antibody titers. These four components were differently associated with immediate reactions and background factors such as demographics, habits, comorbidities, and medications. 

Interpretation: Complex adverse reactions against vaccines can be explained by a limited number of spatiotemporal components identified by tensor decomposition. Our data indicate that these components reflect distinct underlying immunological processes. 

Funding: This study was supported by a donation to Chiba University Hospital, the Future Medicine Founds at Chiba University, a JST Moonshot R&D Grant, a JST CREST Grant, and Japan AMED Grants.

Declaration of Interest: None to declare.

Ethical Approval: The study procedures for sample collection and those for analyses were approved by Chiba University Ethics Committee on February 24th, 2021 (No. HS202101-03) and April 21st, 2021 (No. HS202104-01), respectively.

Suggested Citation

Ikeda, Kei and Nakada, Taka-Aki and Kageyama, Takahiro and Tanaka, Shigeru and Yoshida, Naoki and Ishikawa, Tetsuo and Goshima, Yuki and Taniguchi, Toshibumi and Igari, Hidetoshi and Hanaoka, Hideki and Yokote, Koutaro and Nakajima, Hiroshi and Kawakami, Eiryo, Spatiotemporal Components of Adverse Reactions Against BNT162b2 mRNA SARS-CoV-2 Vaccine Reflect Different Immunological Processes. Available at SSRN: https://ssrn.com/abstract=3903937 or http://dx.doi.org/10.2139/ssrn.3903937

Kei Ikeda

Chiba University - Department of Allergy and Clinical Immunology

Japan

Taka-Aki Nakada

Chiba University - Department of Allergy and Clinical Immunology ( email )

Japan

Takahiro Kageyama

Chiba University - Department of Allergy and Clinical Immunology

Japan

Shigeru Tanaka

Chiba University - Department of Allergy and Clinical Immunology ( email )

Japan

Naoki Yoshida

Chiba University - Artificial Intelligence Medicine ( email )

Chiba
Japan

Tetsuo Ishikawa

RIKEN Information R&D and Strategy Headquarters - Advanced Data Science Project (ADSP) ( email )

Japan

Yuki Goshima

RIKEN Information R&D and Strategy Headquarters - Advanced Data Science Project (ADSP) ( email )

Japan

Toshibumi Taniguchi

Chiba University - Department of Infectious Diseases ( email )

Japan

Hidetoshi Igari

Chiba University - Division of Infection Control ( email )

Chiba
Japan

Hideki Hanaoka

Chiba University - Clinical Research Center ( email )

1-8-1 Inohana, Chuo-ku
Chiba City, 260-8677
Japan

Koutaro Yokote

Chiba University - Department of Endocrinology, Hematology and Gerontology ( email )

Japan

Chiba University - Division of Diabetes, Metabolism and Endocrinology ( email )

1-8-1 Inohana
Chuo-ku, Chiba City
Chiba, 260-8677
Japan

Chiba University - Department of Clinical Cell Biology and Medicine ( email )

1-8-1 Inohana
Chuo-ku
Chiba City, Chiba 260-8670
Japan

Hiroshi Nakajima

Chiba University Hospital COVID-19 Vaccine Center ( email )

Chiba
Japan

Eiryo Kawakami (Contact Author)

Chiba University - Artificial Intelligence Medicine ( email )

Chiba
Japan

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