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Stratification of viral shedding patterns in saliva of COVID-19 patients

Hyeongki Park, Raiki Yoshimura, View ORCID ProfileShoya Iwanami, Kwang Su Kim, Keisuke Ejima, View ORCID ProfileNaotoshi Nakamura, View ORCID ProfileKazuyuki Aihara, Yoshitsugu Miyazaki, Takashi Umeyama, Ken Miyazawa, Takeshi Morita, Koichi Watashi, View ORCID ProfileChristopher B. Brooke, View ORCID ProfileRuian Ke, View ORCID ProfileShingo Iwami, Taiga Miyazaki
doi: https://doi.org/10.1101/2024.01.30.578034
Hyeongki Park
1interdisciplinary Biology Laboratory (iBLab), Division of Natural Science, Graduate School of Science, Nagoya University, Nagoya, Japan
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Raiki Yoshimura
1interdisciplinary Biology Laboratory (iBLab), Division of Natural Science, Graduate School of Science, Nagoya University, Nagoya, Japan
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Shoya Iwanami
1interdisciplinary Biology Laboratory (iBLab), Division of Natural Science, Graduate School of Science, Nagoya University, Nagoya, Japan
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Kwang Su Kim
1interdisciplinary Biology Laboratory (iBLab), Division of Natural Science, Graduate School of Science, Nagoya University, Nagoya, Japan
2Department of Science System Simulation, Pukyong National University, Busan, South Korea
3Department of Mathematics, Pusan National University, Busan, South Korea
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Keisuke Ejima
4Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
5The Tokyo Foundation for Policy Research, Tokyo, Japan
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Naotoshi Nakamura
1interdisciplinary Biology Laboratory (iBLab), Division of Natural Science, Graduate School of Science, Nagoya University, Nagoya, Japan
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Kazuyuki Aihara
6International Research Center for Neurointelligence, The University of Tokyo Institutes for Advanced Study, The University of Tokyo, Tokyo, Japan
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Yoshitsugu Miyazaki
7Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Tokyo, Japan
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Takashi Umeyama
7Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Tokyo, Japan
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Ken Miyazawa
7Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Tokyo, Japan
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Takeshi Morita
8Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo, Japan
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Koichi Watashi
8Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo, Japan
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Christopher B. Brooke
9Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL, USA
10Department of Statistics, University of Illinois at Urbana-Champaign, Urbana, IL, USA
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Ruian Ke
11Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM, USA
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  • ORCID record for Ruian Ke
Shingo Iwami
1interdisciplinary Biology Laboratory (iBLab), Division of Natural Science, Graduate School of Science, Nagoya University, Nagoya, Japan
6International Research Center for Neurointelligence, The University of Tokyo Institutes for Advanced Study, The University of Tokyo, Tokyo, Japan
12Institute of Mathematics for Industry, Kyushu University, Fukuoka, Japan
13Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto, Japan
14Interdisciplinary Theoretical and Mathematical Sciences Program (iTHEMS), RIKEN, Saitama, Japan
15NEXT-Ganken Program, Japanese Foundation for Cancer Research (JFCR), Tokyo, Japan
16Science Groove Inc., Fukuoka, Japan
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  • ORCID record for Shingo Iwami
  • For correspondence: [email protected] [email protected]
Taiga Miyazaki
17Division of Respirology, Rheumatology, Infectious Diseases, and Neurology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
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  • For correspondence: [email protected] [email protected]
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Abstract

Living with COVID-19 requires continued vigilance against the spread and emergence of variants of concern (VOCs). Rapid and accurate saliva diagnostic testing, alongside basic public health responses, is a viable option contributing to effective transmission control. Nevertheless, our knowledge regarding the dynamics of SARS-CoV-2 infection in saliva is not as advanced as our understanding of the respiratory tract. Here we analyzed longitudinal viral load data of SARS-CoV-2 in saliva samples from 144 patients with mild COVID-19 (a combination of our collected data and published data). Using a mathematical model, we successfully stratified infection dynamics into three distinct groups with clear patterns of viral shedding: viral shedding durations in the three groups were 11.5 days (95% CI: 10.6 to 12.4), 17.4 days (16.6 to 18.2), and 30.0 days (28.1 to 31.8), respectively. Surprisingly, this stratified grouping remained unexplained despite our analysis of 47 types of clinical data, including basic demographic information, clinical symptoms, results of blood tests, and vital signs. Additionally, we quantified the expression levels of 92 micro-RNAs in a subset of saliva samples, but these also failed to explain the observed stratification, although the mir-1846 level may have been weakly correlated with peak viral load. Our study provides insights into SARS-CoV-2 infection dynamics in saliva, highlighting the challenges in predicting the duration of viral shedding without indicators that directly reflect an individual’s immune response, such as antibody induction. Given the significant individual heterogeneity in the kinetics of saliva viral shedding, identifying biomarker(s) for viral shedding patterns will be crucial for improving public health interventions in the era of living with COVID-19.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted February 02, 2024.
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Stratification of viral shedding patterns in saliva of COVID-19 patients
Hyeongki Park, Raiki Yoshimura, Shoya Iwanami, Kwang Su Kim, Keisuke Ejima, Naotoshi Nakamura, Kazuyuki Aihara, Yoshitsugu Miyazaki, Takashi Umeyama, Ken Miyazawa, Takeshi Morita, Koichi Watashi, Christopher B. Brooke, Ruian Ke, Shingo Iwami, Taiga Miyazaki
bioRxiv 2024.01.30.578034; doi: https://doi.org/10.1101/2024.01.30.578034
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Stratification of viral shedding patterns in saliva of COVID-19 patients
Hyeongki Park, Raiki Yoshimura, Shoya Iwanami, Kwang Su Kim, Keisuke Ejima, Naotoshi Nakamura, Kazuyuki Aihara, Yoshitsugu Miyazaki, Takashi Umeyama, Ken Miyazawa, Takeshi Morita, Koichi Watashi, Christopher B. Brooke, Ruian Ke, Shingo Iwami, Taiga Miyazaki
bioRxiv 2024.01.30.578034; doi: https://doi.org/10.1101/2024.01.30.578034

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