Developing the foundation of real time assessment of COVID-19 accounting for heterogeneity and asymptomatic nature of infection

• Project/Area Number: 23K21519
• Project/Area Number (Other): 21H03198 (2021-2023)
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Multi-year Fund (2024); Single-year Grants (2021-2023)
• Section: 一般
• Review Section: Basic Section 58030:Hygiene and public health-related: excluding laboratory approach
• Research Institution: Kyoto University
• Principal Investigator: 西浦 博 京都大学, 医学研究科, 教授 (70432987)
• Project Period (FY): 2021-04-01 – 2026-03-31
• Project Status: Granted (Fiscal Year 2024)
• Budget Amount: ¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000); Fiscal Year 2025: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2024: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2023: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2021: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
• Keywords: 感染症 / 疫学 / 数理モデル / 予防医学 / 不顕性感染

Outline of Research at the Start

本研究は、COVID-19流行の観察データを使用して伝播の異質性や不顕性感染者が生み出す2次感染者数、および、ヒトの移動に伴う流行リスクを明示的に推定し、それを感染症対策の評価に役立てる数理モデリングプロジェクトである。倫理的理由から、隔離や接触者追跡調査をランダムに割り付けするができないため、観察研究成果を利用して後ろ向きに疫学データを分析し、そのデータに統計モデルを適用することで推定する。伝播ネットワークの再構築と分析に必要な分岐過程や多変量再生産方程式などのモデルで明らかにできることを体系的に整理し、モデル構造とモデル化に必要な想定を明らかにしつつ、基礎的方法論を確立する。

Outline of Annual Research Achievements

新型コロナウイルス感染症（COVID-19）流行で数理モデルを活用した分析を行ってきたが、評価の細部技術において様々な科学的問題が浮き彫りになった。本研究の目的は、リアルタイムの感染症流行評価のための数理モデルを活用した定量化方法を構築することである。交付期間内に次の3つの研究項目に取り組む： 特に令和3年度繰越では、(1) 職種別の実効再生産数推定（伝播ネットワークを利用した世界初の推定モデルの実装）、(2) 不顕性感染者の2次感染リスク推定手法の開発とクラスター対策の妥当性評価、(3) ヒト移動データとゲノム情報を駆使した移動に伴う流行リスクの定量化に取り組んだ。
異質性（感染者が同等にふるまわない性質）は流行対策を考案する上で鍵となる情報である。例えば、接待を伴う飲食業や居酒屋などで2次感染が多く、その他に大きな発声や頻回の呼吸回数を伴うライブハウスやフィットネスクラブ、医療機関や福祉施設などで患者の集団発生（クラスター）が頻発したのは2次感染の異質性と深く関与したものである。これまでの流行では、ある時刻に1人の感染者が生み出す2次感染者数の平均値を意味する実効再生産数の推定を通じて現状分析を行ってきたが、それは人口全体での平均値を推定するに留まってきた。例えば、職業別（接待飲食業、飲食業、医療・福祉、その他、のような区分）で行列を作り、同一職種内と異職種間のそれぞれで1人の特定種の感染者1人あたりが生み出す同/異職種の2次感染者数の平均値が時刻毎に十分に定量化されていれば、人口全体で接触の削減をせずに、限定的な職種や空間などで営業自粛や時間短縮などを行うことに繋がり、よりきめ細やかな流行対策をリアルタイムで実現することが可能となる。本研究では同分析の基盤づくりに取り組んだ。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

繰越の上で予定していた研究を進めることができた。

Strategy for Future Research Activity

今後、ヒトの移動を十分に取り入れた感染リスクの空間的拡大やその人口レベルでの影響に関する定量化に取り組む。感染症対策と経済活動の両立を目的としてGoToトラベルキャンペーンが実施された。その影響を定量化する観察研究が必要であることはもちろんだが、基礎的研究手法としてヒト移動の疫学的インパクトを未然に推定する方法が必要であった。加えて、海外とのヒトの往来を通じたリスクや関連したデータを利用することによるリスク評価は、その政策判断前に十分に検討されてこなかった。他方、国内で流行が拡大したウイルスのゲノム情報は既に一部公開されており、移入リスクや国別リスクの推定等は既に実装可能な状態にある。この定量化を実現すれば、予想される感染リスクに基づいた出入国の政策判断が可能となるだろう。

Research Products

• [Journal Article] Estimating infection fatality risk and ascertainment bias of COVID-19 in Osaka, Japan from February 2020 to January 2022 (2023)
  • Author(s): Zhang Tong、Nishiura Hiroshi
  • Journal Title: Scientific Reports Volume: 13 Issue: 1
  • DOI: 10.1038/s41598-023-32639-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Letter to the Editor: Knowledge gap in assessing the risk of a human pandemic via mammals’ infection with highly pathogenic avian influenza A(H5N1) (2023)
  • Author(s): Nishiura Hiroshi、Kayano Taishi、Hayashi Katsuma、Kobayashi Tetsuro、Okada Yuta
  • Journal Title: Eurosurveillance Volume: 28 Issue: 9
  • DOI: 10.2807/1560-7917.es.2023.28.9.2300134
  • Peer Reviewed / Open Access
• [Journal Article] Identifying High-Risk Events for COVID-19 Transmission: Estimating the Risk of Clustering Using Nationwide Data (2023)
  • Author(s): Ueda Minami、Hayashi Katsuma、Nishiura Hiroshi
  • Journal Title: Viruses Volume: 15 Issue: 2 Pages: 456-456
  • DOI: 10.3390/v15020456
  • Peer Reviewed / Open Access
• [Journal Article] Epidemiological Associations between Rabies Vaccination and Dog Owner Characteristics (2023)
  • Author(s): Amemiya Yuri、Inoue Satoshi、Maeda Ken、Nishiura Hiroshi
  • Journal Title: Vaccines Volume: 11 Issue: 2 Pages: 352-352
  • DOI: 10.3390/vaccines11020352
  • Peer Reviewed / Open Access
• [Journal Article] Projecting the COVID-19 immune landscape in Japan in the presence of waning immunity and booster vaccination (2023)
  • Author(s): Sasanami Misaki、Fujimoto Marie、Kayano Taishi、Hayashi Katsuma、Nishiura Hiroshi
  • Journal Title: Journal of Theoretical Biology Volume: 559 Pages: 111384-111384
  • DOI: 10.1016/j.jtbi.2022.111384
  • Peer Reviewed / Open Access
• [Journal Article] Seasonal transmission dynamics of varicella in Japan: The role of temperature and school holidays (2022)
  • Author(s): Suzuki Ayako、Nishiura Hiroshi
  • Journal Title: Mathematical Biosciences and Engineering Volume: 20 Issue: 2 Pages: 4069-4081
  • DOI: 10.3934/mbe.2023190
  • Peer Reviewed / Open Access
• [Journal Article] COVID-19 cases with a contact history: A modeling study of contact history-stratified data in Japan (2022)
  • Author(s): Zhang Tong、Nishiura Hiroshi
  • Journal Title: Mathematical Biosciences and Engineering Volume: 20 Issue: 2 Pages: 3661-3676
  • DOI: 10.3934/mbe.2023171
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Protection against SARS-CoV-2 BA.4 and BA.5 subvariants via vaccination and natural infection: A modeling study (2022)
  • Author(s): Okada Yuta、Kayano Taishi、Anzai Asami、Zhang Tong、Nishiura Hiroshi
  • Journal Title: Mathematical Biosciences and Engineering Volume: 20 Issue: 2 Pages: 2530-2543
  • DOI: 10.3934/mbe.2023118
  • Peer Reviewed / Open Access
• [Journal Article] Basic reproduction number of the COVID-19 Delta variant: Estimation from multiple transmission datasets (2022)
  • Author(s): Ueda Minami、Kobayashi Tetsuro、Nishiura Hiroshi
  • Journal Title: Mathematical Biosciences and Engineering Volume: 19 Issue: 12 Pages: 13137-13151
  • DOI: 10.3934/mbe.2022614
  • Peer Reviewed / Open Access
• [Journal Article] Time-dependent risk of COVID-19 death with overwhelmed health-care capacity in Japan, 2020?2022 (2022)
  • Author(s): Hayashi Katsuma、Nishiura Hiroshi
  • Journal Title: BMC Infectious Diseases Volume: 22 Issue: 1 Pages: 22-933
  • DOI: 10.1186/s12879-022-07929-8
  • Peer Reviewed / Open Access
• [Journal Article] Correlation between times to SARS-CoV-2 symptom onset and secondary transmission undermines epidemic control efforts (2022)
  • Author(s): Linton Natalie M.、Akhmetzhanov Andrei R.、Nishiura Hiroshi
  • Journal Title: Epidemics Volume: 41 Pages: 100655-100655
  • DOI: 10.1016/j.epidem.2022.100655
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Decrease in overdispersed secondary transmission of COVID-19 over time in Japan (2022)
  • Author(s): Miyama Takeshi、Jung Sung-mok、Nishiura Hiroshi
  • Journal Title: Epidemiology and Infection Volume: 150 Pages: 1-29
  • DOI: 10.1017/s0950268822001789
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Go To Travel campaign and the geographic spread of COVID-19 in Japan (2022)
  • Author(s): Anzai Asami、Jung Sung-mok、Nishiura Hiroshi
  • Journal Title: BMC Infectious Diseases Volume: 22 Issue: 1
  • DOI: 10.1186/s12879-022-07799-0
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Human monkeypox disease (MPX) (2022)
  • Author(s): Nishiura H, et al.
  • Journal Title: Infezioni in Medicina Volume: 30 Issue: 3
  • DOI: 10.53854/liim-3003-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Doubling time of infectious diseases (2022)
  • Author(s): Anzai Asami、Nishiura Hiroshi
  • Journal Title: Journal of Theoretical Biology Volume: 554 Pages: 111278-111278
  • DOI: 10.1016/j.jtbi.2022.111278
  • Peer Reviewed / Open Access
• [Journal Article] Age-specific hospitalization risk of primary and secondary respiratory syncytial virus infection among young children (2022)
  • Author(s): Nakajo Ko、Nishiura Hiroshi
  • Journal Title: International Journal of Infectious Diseases Volume: 124 Pages: 14-20
  • DOI: 10.1016/j.ijid.2022.09.008
  • Peer Reviewed / Open Access
• [Journal Article] Quantifying the future risk of dengue under climate change in Japan (2022)
  • Author(s): Hayashi Katsuma、Fujimoto Marie、Nishiura Hiroshi
  • Journal Title: Frontiers in Public Health Volume: 10
  • DOI: 10.3389/fpubh.2022.959312
  • Peer Reviewed / Open Access
• [Journal Article] Number of averted COVID-19 cases and deaths attributable to reduced risk in vaccinated individuals in Japan (2022)
  • Author(s): Kayano Taishi、Sasanami Misaki、Kobayashi Tetsuro、Ko Yura K.、Otani Kanako、Suzuki Motoi、Nishiura Hiroshi
  • Journal Title: The Lancet Regional Health - Western Pacific Volume: 28 Pages: 100571-100571
  • DOI: 10.1016/j.lanwpc.2022.100571
  • Peer Reviewed / Open Access
• [Journal Article] Estimating relative generation times and reproduction numbers of Omicron BA.1 and BA.2 with respect to Delta variant in Denmark (2022)
  • Author(s): Ito Kimihito、Piantham Chayada、Nishiura Hiroshi
  • Journal Title: Mathematical Biosciences and Engineering Volume: 19 Issue: 9 Pages: 9005-9017
  • DOI: 10.3934/mbe.2022418
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Baseline scenarios of heat-related ambulance transportations under climate change in Tokyo, Japan (2022)
  • Author(s): Fujimoto Marie、Nishiura Hiroshi
  • Journal Title: PeerJ Volume: 10 Pages: e13838-e13838
  • DOI: 10.7717/peerj.13838
  • Peer Reviewed / Open Access
• [Journal Article] Response to COVID-19 during the Tokyo Olympic Games: Did we properly assess the risk? (2022)
  • Author(s): Jung Sung-mok、Hayashi Katsuma、Kayano Taishi、Nishiura Hiroshi
  • Journal Title: Epidemics Volume: 40 Pages: 100618-100618
  • DOI: 10.1016/j.epidem.2022.100618
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Assessing Public Health and Social Measures Against COVID-19 in Japan From March to June 2021 (2022)
  • Author(s): Hayashi Katsuma、Kayano Taishi、Anzai Asami、Fujimoto Marie、Linton Natalie、Sasanami Misaki、Suzuki Ayako、Kobayashi Tetsuro、Otani Kanako、Yamauchi Masato、Suzuki Motoi、Nishiura Hiroshi
  • Journal Title: Frontiers in Medicine Volume: 9
  • DOI: 10.3389/fmed.2022.937732
  • Peer Reviewed / Open Access
• [Journal Article] Age-Dependent Effects of COVID-19 Vaccine and of Healthcare Burden on COVID-19 Deaths, Tokyo, Japan (2022)
  • Author(s): Ko Yura K.、Murayama Hiroaki、Yamasaki Lisa、Kinoshita Ryo、Suzuki Motoi、Nishiura Hiroshi
  • Journal Title: Emerging Infectious Diseases Volume: 28 Issue: 9 Pages: 1777-1784
  • DOI: 10.3201/eid2809.220377
  • Peer Reviewed / Open Access
• [Journal Article] Age-Dependent Risks of COVID-19 Putatively Caused by Variant Alpha in Japan (2022)
  • Author(s): Kayano Taishi、Hayashi Katsuma、Kobayashi Tetsuro、Nishiura Hiroshi
  • Journal Title: Frontiers in Public Health Volume: 10 Pages: 837970-837970
  • DOI: 10.3389/fpubh.2022.837970
  • Peer Reviewed / Open Access
• [Journal Article] Prioritizing COVID-19 vaccination. Part 2: Real-time comparison between single-dose and double-dose in Japan (2022)
  • Author(s): Kobayashi Tetsuro、Nishiura Hiroshi
  • Journal Title: Mathematical Biosciences and Engineering Volume: 19 Issue: 7 Pages: 7410-7424
  • DOI: 10.3934/mbe.2022350
  • Peer Reviewed / Open Access
• [Journal Article] Prioritizing COVID-19 vaccination. Part 1: Final size comparison between a single dose and double dose (2022)
  • Author(s): Kobayashi Tetsuro、Nishiura Hiroshi
  • Journal Title: Mathematical Biosciences and Engineering Volume: 19 Issue: 7 Pages: 7374-7387
  • DOI: 10.3934/mbe.2022348
  • Peer Reviewed / Open Access
• [Journal Article] Monitoring the COVID-19 immune landscape in Japan (2022)
  • Author(s): Sasanami Misaki、Kayano Taishi、Nishiura Hiroshi
  • Journal Title: International Journal of Infectious Diseases Volume: 122 Pages: 300-306
  • DOI: 10.1016/j.ijid.2022.06.005
  • Peer Reviewed / Open Access
• [Journal Article] Epidemiology of coronavirus disease 2019 (COVID-19) in Japan during the first and second waves (2022)
  • Author(s): Kinoshita Ryo, Jung Sung-mok, Kobayashi Tetsuro, Akhmetzhanov Andrei R., Nishiura Hiroshi
  • Journal Title: Mathematical Biosciences and Engineering Volume: 19 Issue: 6 Pages: 6088-6101
  • DOI: 10.3934/mbe.2022284
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Transmission dynamics of varicella before, during and after the COVID-19 pandemic in Japan: a modelling study (2022)
  • Author(s): Suzuki Ayako、Nishiura Hiroshi
  • Journal Title: Mathematical Biosciences and Engineering Volume: 19 Issue: 6 Pages: 5998-6012
  • DOI: 10.3934/mbe.2022280
  • Peer Reviewed / Open Access
• [Journal Article] High population burden of Omicron variant (B.1.1.529) is associated with the emergence of severe hepatitis of unknown etiology in children (2022)
  • Author(s): Nishiura Hiroshi、Jung Sung-mok、Hayashi Katsuma
  • Journal Title: International Journal of Infectious Diseases Volume: 122 Pages: 30-32
  • DOI: 10.1016/j.ijid.2022.05.028
  • Peer Reviewed / Open Access
• [Journal Article] The number of COVID-19 clusters in healthcare and elderly care facilities averted by vaccination of healthcare workers in Japan, February?June 2021 (2022)
  • Author(s): Sasanami Misaki、Kyoto University School of Public Health, Yoshida-Konoe, Sakyo, Kyoto 606-8601, Japan、Kayano Taishi、Nishiura Hiroshi
  • Journal Title: Mathematical Biosciences and Engineering Volume: 19 Issue: 3 Pages: 2762-2773
  • DOI: 10.3934/mbe.2022126
  • Peer Reviewed / Open Access
• [Journal Article] Estimating the transmissibility of SARS-CoV-2 VOC 202012/01 in Japan using travel history information (2022)
  • Author(s): Kayano Taishi、Kyoto University School of Public Health, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan、Nishiura Hiroshi
  • Journal Title: Mathematical Biosciences and Engineering Volume: 19 Issue: 3 Pages: 2750-2761
  • DOI: 10.3934/mbe.2022125
  • Peer Reviewed / Open Access
• [Presentation] Monitoring the COVID-19 immune landscape (2022)
  • Author(s): 西浦博
  • Organizer: ICID2022-International Congress on Infectious Diseases
  • Int'l Joint Research
• [Presentation] Monitoring the COVID-19 immune landscape in Japan (2022)
  • Author(s): 西浦博
  • Organizer: 20th International Congress for Tropical Medicine and Malaria (ICTMM2020)
  • Int'l Joint Research
• [Presentation] 新型コロナウイルス感染症の中期および長期のリスク分析 (2022)
  • Author(s): 西浦博
  • Organizer: 第81回日本公衆衛生学会総会、山梨、2022/10/7
  • Invited