Molecular signature of COVID-19 prior to its exacerbation by multi-omics survey
Tomoyuki Suzuki, Yoshihiro Kita, Keisuke Yanagida, Kenji Maeda, Tomomi Hashidate-Yoshida, Hiroki Nakanishi, Takayo Ohto-Nakanishi, Junko Terada-Hirashima, Yoshie Tsujimoto, Masayuki Hojo, Hiroaki Mitsuya, Takao Shimizu, Hideo Shindou
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic due to its high transmissibility and ability to evade innate immune responses. Comprehensive characterization of the disease is essential for elucidating its pathophysiology and clinical progression. In this study, we performed multi-omics analyses of plasma samples collected from SARS-CoV-2-positive patients prior to clinical deterioration of coronavirus disease 2019 (COVID-19).
Introduction
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has affected billions of people worldwide. Patients with COVID-19 exhibited higher in-hospital mortality rates (~1–2%) compared to those with influenza virus infections [1–3].
Materials and method
Human subjects and sample collection
Between January 1, 2020, and December 31, 2020, patients diagnosed with SARS-CoV-2 infection by polymerase chain reaction (PCR) testing were admitted to the National Center for Global Health and Medicine (NCGM), Tokyo, Japan. A total of 399 individuals were enrolled in a prospective observational study which was approved by Institutional Review Board of NCGM (NCGM-G-003472-00).
Results
Study design
The goal of this study was to identify molecular features associated with early-stage exacerbation of COVID-19 by analyzing plasma samples collected from SARS-CoV-2-positive patients at the time of hospital admission, prior to the development of severe disease. We adopted NIH guidelines to define severe cases who had SpO₂ < 94% on room air and required supplemental oxygen.
Discussion
In this study, we revealed multi-omics alterations in plasma between “stable” and “progressive” COVID-19 patients prior to disease exacerbation. The samples were collected in Japan between January and December 2020, during which the predominant circulating strains were B.1.1, B.1.1.284, and B.1.1.214 lineages [46,47]. The clinical manifestations observed in this study may partly reflect the SARS-CoV-2 lineages circulating during the study period.
Acknowledgments
We would like to express our gratitude to Human Metabolome Technologies, Inc. (HMT) and NEC Solution Innovators, Ltd. for their cooperation in the analytical measurements. We are grateful for the constructive comments from K. Waku (Teikyo University), S. Morioka, N. Iwamoto, S. Saito (Japan Institute for Health Security).
Citation: Suzuki T, Kita Y, Yanagida K, Maeda K, Hashidate-Yoshida T, Nakanishi H, et al. (2026) Molecular signature of COVID-19 prior to its exacerbation by multi-omics survey. PLoS One 21(7): e0352423. https://doi.org/10.1371/journal.pone.0352423
Editor: Jon M. Jacobs, Pacific Northwest National Laboratory, UNITED STATES OF AMERICA
Received: January 14, 2026; Accepted: June 10, 2026; Published: July 22, 2026
Copyright: © 2026 Suzuki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data underlying the findings of this study are available in Zenodo at https://doi.org/10.5281/zenodo.17527930. The repository includes the raw data and R scripts used to generate the results reported in this article.
Funding: This work was supported by the Japan Agency for Medical Research and Development (AMED)-CREST (grant number JP22gm0910011 to H.S.), and the Japan Institute for Health Security (JIHS) Intramural Research Fund (22T001 to H.S., 24A1013 to H.S., and 24A2011 to H.S. and Y.K.). T.S. was supported by the Japan Agency for Medical Research and Development (AMED) (grant number 20fk0108255 to T.S.) and the Takeda Science Foundation. The funder provided support in the form of salaries for authors (H.N. and T.O.-N.), but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘Author Contributions’ section.
Competing interests: The authors declare that H.N. and T.O.-N. are affiliated by Lipidome Lab Co., Ltd. This commercial affiliation did not influence the study design, data collection and analysis, decision to publish, or preparation of the manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
