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- 4. The new engl and jour nal of medicine notoriously variable because they use live virus to a reality of a safe, efficacious Covid-19 vaccine Figure 1. Traditional Vaccine Development Pathway. < < 10+ 100+ 1000+ 3–8 Yr 2–10 Yr 1–2 Yr Discovery and Target Validation Preclinical Stage Manufacturing Development Initial bioprocess, formulation, and analytics Phase I Safety Phase II Safety and immunogenicity Phase III Safety, efficacy, and regulatory approval Regulatory Review Clinical Assay Optimization (antibody) Innovative Clinical Trials Large sample size needed for safety and efficacy evaluation Translational medicine entry Dose Regimen Selection The new engl and jour nal of medicine notoriously variable because they use live virus to a reality of a safe, efficacious Covid- Figure 1. Traditional Vaccine Development Pathway. < < 10+ 100+ 1000+ 3–8 Yr 2–10 Yr 1–2 Y Discovery and Target Validation Preclinical Stage Manufacturing Development Initial bioprocess, formulation, and analytics Phase I Safety Phase II Safety and immunogenicity Phase III Safety, efficacy, and regulatory approval R Clinical Assay Optimization (antibody) Innovative Clinical Trials Large sample size needed for safety and efficacy evaluation Translational medicine entry Dose Regimen Selection w engl and jour nal of medicine y use live virus to a reality of a safe, efficacious Covid-19 vaccine ment Pathway. 10+ 100+ 1000+ 2–10 Yr 1–2 Yr g s, d Phase I Safety Phase II Safety and immunogenicity Phase III Safety, efficacy, and regulatory approval Regulatory Review linical Assay Optimization (antibody) Innovative Clinical Trials Large sample size needed for safety and efficacy evaluation Dose Regimen Selection 標的の発見 と検証 The new engl and jour nal of medicine because they use live virus to a reality of a safe, efficacious Covid-19 vaccine cine Development Pathway. 10+ 100+ 1000+ Yr 2–10 Yr 1–2 Yr Manufacturing Development nitial bioprocess, ormulation, and analytics Phase I Safety Phase II Safety and immunogenicity Phase III Safety, efficacy, and regulatory approval Regulatory Review Clinical Assay Optimization (antibody) Innovative Clinical Trials Large sample size needed for safety and efficacy evaluation onal entry Dose Regimen Selection 前臨床段階 The new engl and jour nal of medicine itional Vaccine Development Pathway. < < 10+ 100+ 1000+ 3–8 Yr 2–10 Yr 1–2 Yr reclinical Stage Manufacturing Development Initial bioprocess, formulation, and analytics Phase I Safety Phase II Safety and immunogenicity Phase III Safety, efficacy, and regulatory approval Regulatory Review Clinical Assay Optimization (antibody) Innovative Clinical Trials Large sample size needed for safety and efficacy evaluation Translational medicine entry Dose Regimen Selection 製造開発 The new engl and jour nal of medicine Figure 1. Traditional Vaccine Development Pathway. < < 10+ 100+ 1000+ 3–8 Yr 2–10 Yr 1–2 Yr Discovery and Target Validation Preclinical Stage Manufacturing Development Initial bioprocess, formulation, and analytics Phase I Safety Phase II Safety and immunogenicity Phase III Safety, efficacy, and regulatory approval Regulatory Review Clinical Assay Optimization (antibody) Innovative Clinical Trials Large sample size needed for safety and efficacy evaluation Translational medicine entry Dose Regimen Selection 初期バイオプロセス 製剤化、分析 フェーズ 1 安全性 The new engl and jour nal of medicine notoriously variable because they use live virus to a reality of a safe, ef Figure 1. Traditional Vaccine Development Pathway. < < 10+ 100+ 3–8 Yr 2–10 Yr Discovery and Target Validation Preclinical Stage Manufacturing Development Initial bioprocess, formulation, and analytics Phase I Safety Phase II Safety and immunogenicity Sa re Clinical Assay Optimization (antibody) L ne e Translational medicine entry Dose Regimen Selection フェーズ 2 安全性および 免疫原性 The new engl and jour nal o notoriously variable because they use live virus to a realit Figure 1. Traditional Vaccine Development Pathway. < < 10+ 3–8 Yr 2– Discovery and Target Validation Preclinical Stage Manufacturing Development Initial bioprocess, formulation, and analytics Phase I Safety i Clinical Assay Optimization (antibody) Translational medicine entry Dose Regim Selectio The new engl and jour nal of m notoriously variable because they use live virus to a reality Figure 1. Traditional Vaccine Development Pathway. < < 10+ 3–8 Yr 2–10 Discovery and Target Validation Preclinical Stage Manufacturing Development Initial bioprocess, formulation, and analytics Phase I Safety imm Clinical Assay Optimization (antibody) Translational medicine entry Dose Regime Selection The new engl and jour notoriously variable because they use live virus to a Figure 1. Traditional Vaccine Development Pathway. < < 10+ 3–8 Yr Discovery and Target Validation Preclinical Stage Manufacturing Development Initial bioprocess, formulation, and analytics Phase I Safety Clinical Assay Optimization (antibody) Translational medicine entry Do フェーズ 3 安全性・有効性 規制当局の承認 The new engl and notoriously variable because they use live viru Figure 1. Traditional Vaccine Development Pathway. < < 3–8 Yr Discovery and Target Validation Preclinical Stage Manufacturing Development Initial bioprocess, formulation, and analytics Clinical Assay Optimization (antibody) Translational medicine entry 販売後調査 3-8年 2-10年 1-2年 The new engl and jour nal of medicine notoriously variable because they use live virus to a reality of a safe, efficacious Covid Figure 1. Traditional Vaccine Development Pathway. < < 10+ 100+ 1000+ 3–8 Yr 2–10 Yr 1–2 Discovery and Target Validation Preclinical Stage Manufacturing Development Initial bioprocess, formulation, and analytics Phase I Safety Phase II Safety and immunogenicity Phase III Safety, efficacy, and regulatory approval R Clinical Assay Optimization (antibody) Innovative Clinical Trials Large sample size needed for safety and efficacy evaluation Translational medicine entry Dose Regimen Selection トランスレーショナル 医療 The new engl and jour nal of medici notoriously variable because they use live virus to a reality of a safe Figure 1. Traditional Vaccine Development Pathway. < < 10+ 100+ 3–8 Yr 2–10 Yr Discovery and Target Validation Preclinical Stage Manufacturing Development Initial bioprocess, formulation, and analytics Phase I Safety Phase II Safety and immunogenic Clinical Assay Optimization (antibody) Translational medicine entry Dose Regimen Selection 臨床分析の 最適化 （抗体） The new engl and jo notoriously variable because they use live virus Figure 1. Traditional Vaccine Development Pathway. < < 1 3–8 Yr Discovery and Target Validation Preclinical Stage Manufacturing Development Initial bioprocess, formulation, and analytics Pha Sa Clinical Assay Optimization (antibody) Translational medicine entry 投与量・回数 の選別 Th notoriously variable becaus Figure 1. Traditional Vaccine De < < 3–8 Yr Discovery and Target Validation Preclinical Stage Manufa Develo Initial bio formulati analy Translational medicine entry 革新的臨床研究 安全性・有効性の評価のために 大規模なサンプルサイズが必要 DOI: 10.1056/NEJMe2025111
- 5. Classical platforms Next-generation platforms Whole-inactivated virus Example: Polio vaccine COVID-19: PiCoVacc in phase 1 clinical trials Viral vector Example: VSV-Ebola vaccine COVID-19: AZD1222, Ad5-nCoV in phase 1/2/3 clinical trials DNA Example: Not currently licensed COVID-19: INO-4800 in phase 1 clinical trials Live-attenuated virus Example: MMR vaccine COVID-19: in preclinical stage RNA Example: Not currently licensed COVID-19: mRNA-1273, BNT162 in phase 1/2 clinical trials Protein subunit Example: Seasonal influenza vaccine COVID-19: NVX-CoV2373 in phase 1/2 clinical trials Antigen-presenting cells Example: Not currently licensed COVID-19: LV-SMENP-DC, COVID-19/aAPC in phase 1/2 clinical trials Virus-like particle Example: Human papillomavirus vaccine COVID-19: in preclinical stage SARS-CoV-2 Nucleocapsid protein RNA Spike protein Fig. 1 | An overview of the different vaccine platforms in development against COVID-19. A schematic representation is shown of the classical vaccine Nature Materials volume 19, pages810‒812(2020) 全粒子不活化ワクチン 生ワクチン 蛋白サブユニットワクチン ウイルス様粒子ワクチン 例：ポリオワクチン 新型コロナワクチン： PiCoVacc(Phase I) 例：インフルエンザワクチン 新型コロナワクチン： VX-CoV2373(Phase I/II) 例：MMRワクチン 新型コロナワクチン： 臨床前試験 例：HPVワクチン 新型コロナワクチン： 臨床前試験 ウイルスベクターワクチン 例：VSV-エボラワクチン 新型コロナワクチン： AZD1222, Ad5- nCoV(Phase I/II/III) RNAワクチン 例：未承認 新型コロナワクチン： mRNA-1273, BNT162(Phase I/II) DNAワクチン 例：未承認 新型コロナワクチン： INO-4800(Phase I) 抗原提示細胞ワクチン 例：未承認 新型コロナワクチン： LV-SMENP-DC, COVID-19/ aAPC(Phase I/II) 古典的プラットフォーム 新世代プラットフォーム 新型コロナウイルス ヌクレオカプシ ドタンパク質 スパイクタンパク質
- 6. 10.1056/NEJMoa2034577 Lipid nanoparticle mRNA Spike protein (prefusion conformation) Ribosome CELL 2.4 0.5 脂質 ナノ粒子 細胞 リボソーム スパイク蛋白 DOI: 10.1056/NEJMoa2034577
- 7. Figure. Cumulative incidence curves for the first COVID-19 occurrence a 0.024 0.020 0.016 0.012 0.008 0.004 0.000 Cumulative Incidence of COVID-19 Occurrence 0 7 14 21 28 35 42 49 56 63 73 77 84 91 98 105 112 119 Days After Dose 1 Cumulative Incidence Rate, % 1st Dose 2nd Dose Placebo Vaccine A. Pfizer-BioNTech 0/21 314 0/21 258 Vaccine Placebo 21/21 230 25/21 170 37/21 054 55/20 970 39/20 481 73/20 366 41/19 314 97/19 209 42/18 377 123/18 218 42/17 702 143/17 578 43/17 186 166/17 025 44/15 464 192/15 290 47/14 038 212/13 876 48/12 169 235/11 994 48/9591 249/9471 49/6403 257/6294 49/3374 267/3301 50/1463 274/1449 50/398 275/398 50/0 275/0 At risk, n 1回目接種からの日数 新型コロナの累積患者発生率 1回目接種 2回目接種 プラセボ群 ワクチン接種群 95%減 https://doi.org/10.7326/M21-0111
- 8. 感染予防効果 発症予防効果 男性 91% 88% 女性 93% 96% 16∼39歳 94% 99% 40∼69歳 90% 90% 70歳以上 95% 98% 基礎疾患なし 91% 93% 基礎疾患1∼2つ 95% 95% 基礎疾患3つ以上 86% 89% 肥満 95% 98% 2型糖尿病 91% 91% 高血圧 93% 95% N Engl J Med 2021;384:1412-23. イスラエルにおけるmRNAワクチンの予防効果
- 9. https://twitter.com/CDCgov/status/1380181175474393091/photo/1 ワクチンの副反応 痛み 発赤 腫れ だるさ 頭痛 寒気 筋肉痛 発熱 吐き気
- 10. 迷走神経反射 アナフィラキシー 発熱・腫脹など（自然免疫） IV型アレルギー ウイルス・菌の増殖（生ワクチン） 自己免疫 接種後の時間 接種 30分 4時間 1日 2日 5日 10日 28日 数ヶ月 想定される副反応
- 11. 0 20 40 60 80 100 接種部位 の痛み だるさ 頭痛 筋肉痛 寒気 発熱 接種部位 の腫れ 関節痛 吐き気 13.9 21.2 26.7 25.2 26.7 41.6 41.9 50 74.8 7 7.1 6.8 7.4 7 17.2 25.6 28.6 67.7 1回目の接種 2回目の接種 % ファイザー社新型コロナワクチンの 1回目・2回目の接種後1週間以内にみられた 局所/ 全身性副反応 COVID-19 vaccine safety update Advisory Committee on Immunization Practices (ACIP) January 27, 2021
- 12. 5000人に1人 ペニシリン 20万人に1人 mRNAワクチン 一般的なワクチン 100万人に1人 アナフィラキシー反応が起こる頻度 COVID-19 vaccine safety update Advisory Committee on Immunization Practices (ACIP) January 27, 2021 を元に筆者作成
- 14. 名称 開発元 BNT162b2 ファイザー/ビオンテック mRNA-1273 モデルナ ChAdOx1 nCoV-19/AZD1222 アストラゼネカ/オックス フォード大学 プラットフォーム mRNA 複製不能チンパンジー アデノウイルスベクター 接種スケジュール 3週間間隔で2回 4週間間隔で2回 4∼12週間間隔で2回 発症予防効果 95% 94% 70% 重症化予防 ワクチン接種群 1：非接 種群 9 ワクチン接種群 0：非接 種群 30 ワクチン接種群0：非接種 群 2 変異株への有 効性(B.1.351) 軽度低下 大きく低下 保存条件 超低温冷凍庫（-80∼-60°C） 冷蔵（2∼8°C）で最大5日間 冷凍庫（-25∼-15°C） 冷蔵（2∼8°C）で最大30日間 冷蔵（2∼8°C） 頻度の高い副反応 ▪ 接種部位の腫れ・ 痛 ▪ 全身症状（発熱、悪寒、 怠感、筋肉痛、頭痛） ▪ 接種部位の腫れ・ 痛 ▪ 全身症状（発熱、悪寒、 怠感、筋肉痛、頭痛） 稀な副反応と 起こしやすい人 アナフィラキシー（約20万 人に１人） アナフィラキシーの既往、 アレルギー歴、女性 アナフィラキシー（約35万 人に１人） アナフィラキシーの既往、 アレルギー歴、女性 ワクチン誘発性免疫性血栓 性血小板減少症（約10万人 に1人） 50歳未満の女性 禁忌 （接種できない人） ポリエチレングリコール（PEG）アレルギー mRNA接種後のアナフィラキシー アストラゼネカワクチン接 種後のアナフィラキシー https://doi.org/10.7326/M21-0111
- 15. /S0140-6736(21)01238-1 1 We were all involved in drafting, reviewing, and writing the final manuscript. Consent for publication was obtained from the patient. Declaration of interests We declare no competing interests. © 2021 Elsevier Ltd. All rights reserved. Figure: Vaccine-induced immune thrombotic thrombocytopenia (A) Contrast-enhanced MRI shows bilateral hypointense thrombi in the parauterine venous plexus (arrows). (B) Contrast-enhanced CT pulmonary angiography shows a subsegmental embolus in the posterior–basal segment of the right lower lobe (arrows). A B SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia treated with immunoglobulin and argatroban Katharina Guetl,Thomas Gary, Reinhard B Raggam, Johannes Schmid, AlbertWölfler, Marianne Brodmann A 50-year-old woman attended our emergency department with a 3-day history of severe back pain and a severe headache. 10 days earlier she had received the first dose of vaccine against SARS-CoV-2—ChAdOx1 nCoV-19 (AstraZeneca). The patient had no significant medical history—specifically no personal or family history of venous thromboembolism. She was not pregnant, she did not take an oral contraceptive, and did not have a hormone-eluting intrauterine device in situ. On examination, the patient was afebrile, her peripheral oxygen saturation was 99% (with a 21% fraction of inspired oxygen), blood pressure was 130/80 mm Hg, heart rate was 80 beats per min, and body-mass index was 20 kg/m². She had no obvious haematomas or petechial haemorrhages; she reported no chest pain, shortness of breath, swelling, redness, pallor, or cold in any limb. Laboratory investigations showed a severe thrombo- cytopenia of 27×10⁹ per L (normal 140–440). 3 days earlier it had been 163×10⁹ per L. Serum D-dimer concentration was significantly elevated at greater than 33 mg/L (normal <0·5), fibrinogen concentration was 121 mg/dL (normal 210–400), coagulation factor XIII activity was 63% (normal >70%), and both prothrombin time and activated partial thromboplastin time (aPTT) were normal. Haemoglobin concentration was 10·8 g/dL pelvic region—including bilateral thrombi in the parauterine venous plexus, a superficial vein of the left gluteus maximus muscle, and left presacral and lumbar veins (figure; appendix). CT pulmonary angiography showed a subsegmental embolus in the posterior–basal right lower lobe (figure). CT cerebral venography and compression ultrasound of both legs showed no abnormalities—neither cerebral venous sinus thrombosis nor deep vein thrombosis. We assumed the diagnosis was a vaccine-induced immune thrombotic thrombocytopenia and administered high-dose intravenous immunoglobulin (IVIG) followed by a second dose 24 h later, together with dexamethasone 40 mg orally for 4 days to avoid allergic reactions to IVIG. Simultaneously, anticoagulant therapy with intravenous argatroban—a direct thrombin inhibitor—was started at a dose of 2 μg per kg bodyweight per min; the dose was adjusted to obtain a steady state aPTT of between 1·5 to three times baseline. The patient’s condition rapidly improved; her pain subsided and her platelet count reached 91×10⁹ per L 48 h after starting treatment. Additionally, concentrations of fibrinogen and coagulation factor XIII also steadily increased as D-dimer concentrations dropped (appendix). After 4 days, we switched argatroban to oral dabigatran Publ June http S014 Divis (K Gu R B R M Br of H of In (AW Gene of Ra Med Graz Corr DrTh Angi Inter Univ Aust thom See O アストラゼネカ社のワクチン接種後に血栓症を起こした事例が海外で報告されている。 ヘパリン起因性血小板減少症（HIT）によく似ており、脳静脈洞、門脈・脾静脈・肝静脈などに血 栓が見られること、そして多くが50歳未満の女性であることが特徴。 このワクチンを誘因とした血栓性血小板減少症の発生率は、10万回の接種につき、おそらく1例 程度と見積もられている。 DOI:https://doi.org/10.1016/S0140-6736(21)01238-1
- 18. BRIEF COMMUNICATION https://doi.org/10.1038/s41591-021-01407-5 Mass vaccination has the potential to curb the current COVID- 19 pandemic by protecting individuals who have been vacci- nated against the disease and possibly lowering the likelihood of transmission to individuals who have not been vaccinated. The high effectiveness of the widely administered BNT162b vaccine from Pfizer–BioNTech in preventing not only the dis- ease but also infection with SARS-CoV-2 suggests a potential for a population-level effect, which is critical for disease erad- ication. However, this putative effect is difficult to observe, especially in light of highly fluctuating spatiotemporal epi- demic dynamics. Here, by analyzing vaccination records and test results collected during the rapid vaccine rollout in a large population from 177 geographically defined communities, we find that the rates of vaccination in each community are asso- ciated with a substantial later decline in infections among a cohort of individuals aged under 16!years, who are unvacci- nated. On average, for each 20!percentage points of individu- als who are vaccinated in a given population, the positive test fraction for the unvaccinated population decreased approxi- mately twofold. These results provide observational evidence that vaccination not only protects individuals who have been data. Capitalizing on differences in vaccination rates among geographically distinct communities, and on the availability of an unvaccinated bystander cohort of individuals below 16years of age for whom the vaccine was not authorized in the first stages of vac- cine rollouts, we asked whether and to what extent the fraction of patients vaccinated in each community affects the risk of infection in an unvaccinated cohort of individuals under 16years old within this same community. We focused our analysis on the vaccination rates and test results of 177 distinct communities with a presumed low rate of natural immunization as inferred by a low fraction of individu- als infected with SARS-CoV-2. We retrieved the vaccination dates and test results, from 9December2020 to 9March2021, of mem- bers of Maccabi Healthcare Services (MHS), Israel’s second larg- est healthcare maintenance organization. We defined geographical communities based on residence codes, and identified 246 commu- nities that each comprised a sufficient number of tests and people (Methods). As both vaccination and natural infection could render individuals immunized, thereby possibly conferring protection to unvaccinated individuals, high infection rates could mask the effect of vaccination-induced immunity. To minimize the confounding Community-level evidence for SARS-CoV-2 vaccine protection of unvaccinated individuals Oren Milman1,5 , Idan Yelin! !1,5 , Noga Aharony1 , Rachel Katz2 , Esma Herzel2 , Amir Ben-Tov! !2,3 , Jacob Kuint2,3 , Sivan Gazit! !2 , Gabriel Chodick! !2,3 , Tal Patalon! !2 and Roy Kishony! !1,4 177の地域・集団を対象にワクチン接種率と感染者との関連を調査した研究による と、ワクチン接種率が高い地域では、接種を受けた人だけでなく、接種していない 16歳未満も感染者が減っていた。 接種率が20％上がるごとに、ワクチンを受けていない集団の新型コロナの感染が約2 倍減少したとのことで、これらの結果は、ワクチン接種が、接種を受けた人を守るだ けでなく、その地域の未接種者をも保護することを示している。 https://doi.org/10.1038/s41591-021-01407-5
- 19. F COMMUNICATION NATURE MED 30 1 4 0 1 8 3 2 4 7 3 4 1 3 5 6 3 0 8 2 7 7 2 1 0 2 2 3 2 2 0 1 1 3 1 0 4 9 0 4 5 4 7 4 6 2 2 1 2 5 6 7 7 1 3 1 4 4 2 5 6 3 6 3 7 1 3 3 1 2 8 1 5 1 1 1 4 3 0 2 3 4 3 7 2 6 8 2 8 5 29 28 27 26 25 24 23 Ct Mean Ct, days 1–11 Mean Ct, days 12–37 RdRp gene 1 28 21 35 7 14 Days after first vaccine dose ecreased SARS-CoV-2 viral load after 12 d post-vaccination. Mean Ct values of the RdRp gene for positive tests after vaccination are plot vaccination day in which the sample was taken. The dashed line on day 21 indicates inoculation with the second dose. The number of pos ts for each day is indicated below (in total, n!=!4,938). Black error bars and green or magenta shading indicate the standard error of the m 初回接種からの日数 Threshold Cycle（Ct） 平均Ct値、発症後1∼11日 平均Ct値、発症後12∼37日 陽性人数 https://doi.org/10.1038/s41591-021-01316-7
- 20. REVIEW ARTICLE | FOCUS NATURE MEDICINE Viral load Detection unlikely PCR positive PCR negative Fatigue Decline in quality of life Muscular weakness Joint pain Dyspnea Cough Persistent oxygen requirement Anxiety/depression Sleep disturbances PTSD Cognitive disturbances (brain fog) Headaches Palpitations Chest pain Thromboembolism Chronic kidney disease Hair loss Nasopharyngeal After symptom onset Viral isolation from respiratory tract SARS-CoV-2 exposure Before symptom onset Week 2 Week 3 Week 4 Week 12 6 months Week 1 Week –1 Week –2 Acute COVID-19 Post-acute COVID-19 Subacute/ongoing COVID-19 Chronic/post-COVID-19 Fig. 1 | Timeline of post-acute COVID-19. Acute COVID-19 usually lasts until 4!weeks from the onset of symptoms, beyond which replication-competent SARS-CoV-2 has not been isolated. Post-acute COVID-19 is defined as persistent symptoms and/or delayed or long-term complications beyond 4!weeks from the onset of symptoms. The common symptoms observed in post-acute COVID-19 are summarized. REVIEW ARTICLE | FOCUS NATURE MEDICINE 急性期 後遺症 亜急性期 / 急性期症状の遷延 慢性期 PCR陽性 PCR陰性 潜伏期 怠感 生活の質の低下 筋力低下 関節痛 呼吸苦 咳嗽 遷延する酸素需要 不安/抑うつ 睡眠障害 PTSD 認知機能障害 頭痛 動悸 胸痛 血栓塞栓症 慢性腎臓病 脱毛 1週目 2週目 3週目 4週目 1週前 2週前 12週目 6ヶ月 鼻咽頭 Detection unlikely PCR positive PCR negative Fatigue Decline in quality of Muscular weaknes Joint pain Dyspnea Cough Persistent oxygen requir Anxiety/depressio Sleep disturbance PTSD Cognitive disturbances (b Headaches Palpitations Chest pain Thromboembolism Chronic kidney dise Hair loss Nasopharyngeal After symptom onset Viral isolation from respiratory tract RS-CoV-2 exposure Before symptom onset Week 2 Week 3 Week 4 Week 12 Week 1 Week –1 Week –2 Acute COVID-19 Post-acute COVID-19 Subacute/ongoing COVID-19 Chroni PCR ウイルス培養 発症後 発症前 ウイルス 曝露 ウイルス量 https://doi.org/10.1038/s41591-021-01283-z
- 21. Miyazato Y, Morioka S, et al. OFID accepted. 発症60日後も嗅覚障害（19%）、呼吸苦（18%）、 だるさ（16%）、咳（8%)、味覚障害(5%)が持続 発症120日後も呼吸苦（11%）、嗅覚障害（10%）、 だるさ（10%）、咳（6%）、味覚異常（2%）が持続 Open Forum Infectious Diseases, ofaa507 症状 咳 味覚障害 嗅覚障害 呼吸苦 怠感 痰 咳 だるさ 痰 味覚障害 呼吸苦 嗅覚障害 発症からの日数 頻度(%) 0 50 100 150 200
- 22. 脱毛 Miyazato Y, Morioka S, et al. OFID accepted. 新型コロナの遅発性の症状としての脱毛 全体約2割の人でみられた 症状持続期間は平均76日 コロナ発症時には全くみられないが、 発症後30日くらいから出現し、発症後120日くらいまでみられる Open Forum Infectious Diseases, ofaa507 発症からの日数 頻度(%) 0 50 100 150 200
- 23. 新型 コ ロ ナ 感染後 の 脱毛 の 経過 2020 2021 3月 4月 5月 6月 8月 1月 3月 コ ロ ナ 感染 退院 脱毛 に 気 づ く 脱毛 が 回復 し 始 め る 40代 男性 軽症の新型コロナ患者 ⇐ 感染から3ヶ月後 1年後 Suzuki T, Kutsuna S, Saito S, et al. Int J Infect Dis. 2021.
- 24. R ACE2 activity and semen quality parameters in the COVID-19 and control (CON) g ± S.D. † P < 0.05, significantly different from baseline values. *P < 0.05, significan 精子の数 ベ ー ス ラ イ ン 1 0 日 後 2 0 日 後 3 0 日 後 4 0 日 後 5 0 日 後 6 0 日 後 新型コロナ患者 比較対象の健常者 Reproduction . 2021 Mar;161(3):319-331.
- 27. 2021年5月29日時点 の情報に基づき作成 VOC 202012/01 （B.1.1.7） 501Y.V2 (B.1.351) P.1 B.1.617 最初に見つかった国 イギリス 南アフリカ共和国 ブラジル インド 感染力 ↑ ↑ ↑ ↑ 重症度 ↑ ? ? ↑ 再感染リスク増加 ワクチン効果低下 ☓ ○ ○ ○ WHO situation report 11 Mayに基づき発表者作成
- 28. Fung TS, Liu DX. 2019. Annu. Rev. Microbiol. 73:529-57. より改変 中和抗体 標的細胞 【E484K変異ウイルス】 SARS-CoV-2 （E484K変異ウイルス） 中和抗体がE484K変異ウイルスに結合しにくくなる ↓ 感染出来る可能性が高くなる ウイルス受容体 （ACE2） 中和抗体 Fung TS, Liu DX. 2019. Annu. Rev. Microbiol. 73:529-57. より改変 疫）からの逃避とは？ Fung TS, Liu DX. 2019. Annu. Rev. Microbiol. 73:529-57. より改変 和抗体：病原体と細胞の結合を阻害する抗体 標的細胞 【中和抗体が存在する】 和抗体が存在しない】 ウイルスは受容体に結合可能 ↓ 感染が成立する 中和抗体がウイルスに結合することにより ウイルスは受容体に結合出来ない ↓ 感染が成立しない 【E484K変異ウイルス】 中和抗体がE484K変異ウイルスに結合しにくくなる ↓ 従来のウイルス 中和活性が結合し細胞侵入を阻害 免疫逃避を持つ変異ウイルス 中和活性が結合しにくくなり感染が成立しやすくなる 東京医科歯科大学大学院医歯学総合研究科ウイルス制御学分野 武内寛明先生のプレスリリースより
- 29. Table 1. Vaccine Effectiveness against Infection and against Disease in Qatar. Type of Infection or Disease PCR-Positive Persons PCR-Negative Persons Effectiveness (95% CI)* Vaccinated Unvaccinated Vaccinated Unvaccinated number of persons percent Infection PCR-confirmed infection with the B.1.1.7 variant† After one dose 892 18,075 1241 17,726 29.5 (22.9–35.5) ≥14 days after second dose 50 16,354 465 15,939 89.5 (85.9–92.3) PCR-confirmed infection with the B.1.351 variant‡ After one dose 1329 20,177 1580 19,926 16.9 (10.4–23.0) ≥14 days after second dose 179 19,396 698 18,877 75.0 (70.5–78.9) Disease§ Severe, critical, or fatal disease caused by the B.1.1.7 variant After one dose 30 468 61 437 54.1 (26.1–71.9) ≥14 days after second dose 0 401 20 381 100.0 (81.7–100.0) Severe, critical, or fatal disease caused by the B.1.351 variant After one dose 45 348 35 358 0.0 (0.0–19.0) ≥14 days after second dose 0 300 14 286 100.0 (73.7–100.0) Severe, critical, or fatal disease caused by any SARS-CoV-2 After one dose 139 1,966 220 1,885 39.4 (24.0–51.8) ≥14 days after second dose 3 1,692 109 1,586 97.4 (92.2–99.5) * Vaccine effectiveness was estimated with the use of a test-negative case–control study design,2 with persons found positive by polymerase- chain-reaction (PCR) testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serving as cases in the analysis and those DOI: 10.1056/NEJMc2104974
- 30. • 新型コロナワクチンはCOVID-19終息のための希望の光 • mRNAワクチンは「ぱねえ効果」を持ち、感染予防、重症化予防 の効果がある • 副反応の頻度は高く事前に説明が必要 • 感染そのものを防ぐ効果があり、自身だけでなく感染から周りの 人を守るためにもワクチンは有効 新型コロナワクチンまとめ