Detecting time-evolving phenotypic components of adverse reactions against BNT162b2 SARS-CoV-2 vaccine via non-negative tensor factorization
Kei Ikeda,
Taka-Aki Nakada,
Takahiro Kageyama,
Shigeru Tanaka,
Naoki Yoshida,
Tetsuo Ishikawa,
Yuki Goshima,
Natsuko Otaki,
Shingo Iwami,
Teppei Shimamura,
Toshibumi Taniguchi,
Hidetoshi Igari,
Hideki Hanaoka,
Koutaro Yokote,
Koki Tsuyuzaki,
Hiroshi Nakajima,
Eiryo Kawakami
Affiliations
Kei Ikeda
Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
Taka-Aki Nakada
Department of Emergency and Critical Care Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
Takahiro Kageyama
Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
Shigeru Tanaka
Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
Naoki Yoshida
Artificial Intelligence Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
Tetsuo Ishikawa
Advanced Data Science Project (ADSP), RIKEN Information R&D and Strategy Headquarters, Yokohama, Kanagawa 230-0045, Japan
Yuki Goshima
Advanced Data Science Project (ADSP), RIKEN Information R&D and Strategy Headquarters, Yokohama, Kanagawa 230-0045, Japan
Natsuko Otaki
Artificial Intelligence Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
Shingo Iwami
Interdisciplinary Biology Laboratory (iBLab), Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya, Aichi 464-8602, Japan; Institute of Mathematics for Industry, Kyushu University, Fukuoka 819-0395, Japan; Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Sakyo Ward, Kyoto 606-8501, Japan; Interdisciplinary Theoretical and Mathematical Sciences Program (iTHEMS), RIKEN, Wako, Saitama 351-0198, Japan; NEXT-Ganken Program, Japanese Foundation for Cancer Research (JFCR), Koto Ward, Tokyo 135-8550, Japan; Science Groove Inc., Fukuoka 810-0041, Japan
Teppei Shimamura
Division of Systems Biology, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan
Toshibumi Taniguchi
Department of Infectious Diseases, Chiba University Hospital, Chiba University, Chiba 260-8670, Japan
Hidetoshi Igari
Department of Infectious Diseases, Chiba University Hospital, Chiba University, Chiba 260-8670, Japan; Chiba University Hospital COVID-19 Vaccine Center, Chiba University, Chiba 260-8670, Japan
Hideki Hanaoka
Clinical Research Centre, Chiba University Hospital, Chiba University, Chiba 260-8670, Japan
Koutaro Yokote
Department of Endocrinology, Hematology and Gerontology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
Koki Tsuyuzaki
Laboratory for Bioinformatics Research, RIKEN Center for Biosystems Dynamics Research, Wako, Saitama 351-0198, Japan
Hiroshi Nakajima
Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; Chiba University Hospital COVID-19 Vaccine Center, Chiba University, Chiba 260-8670, Japan; Corresponding author
Eiryo Kawakami
Artificial Intelligence Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; Advanced Data Science Project (ADSP), RIKEN Information R&D and Strategy Headquarters, Yokohama, Kanagawa 230-0045, Japan; NEXT-Ganken Program, Japanese Foundation for Cancer Research (JFCR), Koto Ward, Tokyo 135-8550, Japan; Institute for Advanced Academic Research (IAAR), Chiba University, Chiba 260-8670, Japan; Corresponding author
Summary: Symptoms of adverse reactions to vaccines evolve over time, but traditional studies have focused only on the frequency and intensity of symptoms. Here, we attempt to extract the dynamic changes in vaccine adverse reaction symptoms as a small number of interpretable components by using non-negative tensor factorization. We recruited healthcare workers who received two doses of the BNT162b2 mRNA COVID-19 vaccine at Chiba University Hospital and collected information on adverse reactions using a smartphone/web-based platform. We analyzed the adverse-reaction data after each dose obtained for 1,516 participants who received two doses of vaccine. The non-negative tensor factorization revealed four time-evolving components that represent typical temporal patterns of adverse reactions for both doses. These components were differently associated with background factors and post-vaccine antibody titers. These results demonstrate that complex adverse reactions against vaccines can be explained by a limited number of time-evolving components identified by tensor factorization.