SlideShare ist ein Scribd-Unternehmen logo
1 von 77
Downloaden Sie, um offline zu lesen
京都府⽴医科⼤学 救急医療学教室
医療法⼈ 双樹会 よしき往診クリニック
宮本 雄気
Omicron・第6波に備える
〜何が分かっていて何が分かっていないか〜
2022年1⽉1⽇ 配布⽤
• オミクロンとは︖変異体は何が問題︖
• オミクロンの診断⽅法
• オミクロンの特徴① 再感染リスク
• オミクロンの特徴② ⼊院・重症化リスク
• オミクロンのワクチン効果(VE)について
• オミクロンに対する今後の予測
• オミクロンとは︖変異体は何が問題︖
• オミクロンの診断⽅法
• オミクロンの特徴① 再感染リスク
• オミクロンの特徴② ⼊院・重症化リスク
• オミクロンのワクチン効果(VE)について
• オミクロンに対する今後の予測
Extended Data Fig. 1
T
E
D
A
R
T
I
C
L
E
P
R
E
V
I
E
W
Nature Dec 23. 2021 doi: https://doi.org/10.1038/d41586-a021-03826-3
外界から気道などを通して
SARS-CoV-2が侵⼊する
スパイクタンパクの先端(RBD︓受容体結合ドメイン)と
ACE2受容体が結合してウイルスが侵⼊する
遺伝⼦と「殻」がそれぞれ増幅され
その後、組み⽴てを⾏う
増幅し組み⽴てられたウイルスは
外に放出される
変異株はスパイクタンパク(特に先端︓RBD)に変化があり
受容体にくっつきやすくなる︕
ロナプリーブ®(カシリビマブ・イムデビマブ)は
このスパイクタンパクの先端(RBD)に結合して
ACE2受容体にくっつけなくしてしまう
ゼビュディ®(ソトロビマブ)は
このスパイクタンパクの先端(RBD)以外の部位に
結合するためomicronにも効果がありそう
• オミクロンとは︖変異体は何が問題︖
• オミクロンの診断⽅法
• オミクロンの特徴① 再感染リスク
• オミクロンの特徴② ⼊院・重症化リスク
• オミクロンのワクチン効果(VE)について
• オミクロンに対する今後の予測
① L452R変異(デルタ変異体の検査)が陰性ならオミクロンと
判断する
② E484AとN501Yなど複数の変異の組み合わせて判断する
(オミクロンはE484A/N501Yが陽性・L452Rが陰性)
③ デルタ変異体で特徴的なS遺伝⼦が検出されなければ
(SGTF︓S gene target failure)オミクロンと判断する
① L452R変異(デルタ変異体の検査)が陰性ならオミクロンと
判断する
② E484AとN501Yなど複数の変異の組み合わせて判断する
(オミクロンはE484A/N501Yが陽性・L452Rが陰性)
③ デルタ変異体で特徴的なS遺伝⼦が検出されなければ
(SGTF︓S gene target failure)オミクロンと判断する
既存のキットで検査できるが少し雑な検査⽅法
(デルタ以外のほとんどの変異体で陰性になる)
地域の状況(ほぼ全てがデルタの場合など)に応じて有⽤
① L452R変異(デルタ変異体の検査)が陰性ならオミクロンと
判断する
② E484AとN501Yなど複数の変異の組み合わせて判断する
(オミクロンはE484A/N501Yが陽性・L452Rが陰性)
③ デルタ変異体で特徴的なS遺伝⼦が検出されなければ
(SGTF︓S gene target failure)オミクロンと判断する
確実性は⾼いが複数のプライマーを要し
時間と⼿間を要する可能性がある
① L452R変異(デルタ変異体の検査)が陰性ならオミクロンと
判断する
② E484AとN501Yなど複数の変異の組み合わせて判断する
(オミクロンはE484A/N501Yが陽性・L452Rが陰性)
③ デルタ変異体で特徴的なS遺伝⼦が検出されなければ
(SGTF︓S gene target failure)オミクロンと判断する
簡便だが
・アルファ変異体が陽性になる
・オミクロンの⼀部(BA.2)が陰性になる
などの問題あり
① L452R変異(デルタ変異体の検査)が陰性ならオミクロンと
判断する
② E484AとN501Yなど複数の変異の組み合わせて判断する
(オミクロンはE484A/N501Yが陽性・L452Rが陰性)
③ デルタ変異体で特徴的なS遺伝⼦が検出されなければ
(SGTF︓S gene target failure)オミクロンと判断する
ちなみに…
変異に伴うPCR検査の検出感度の低下はないとされている
(抗原検査は諸説あり︓FDAは低下あるかもしれないと
発表あり・WHOも今後の研究待ちの姿勢)
• オミクロンとは︖変異体は何が問題︖
• オミクロンの診断⽅法
• オミクロンの特徴① 再感染リスク
• オミクロンの特徴② ⼊院・重症化リスク
• オミクロンのワクチン効果(VE)について
• オミクロンに対する今後の予測
16 December 2021 Imperial College COVID-19 response team
Report 49: Growth, population distribution and immune escape of
Omicron in England+
Neil Ferguson1
, Azra Ghani, Anne Cori, Alexandra Hogan, Wes Hinsley, Erik Volz on behalf of the
Imperial College COVID-19 response team
WHO Collaborating Centre for Infectious Disease Modelling
MRC Centre for Global Infectious Disease Analysis, Jameel Institute, Imperial College London
1
Correspondence: neil.ferguson@imperial.ac.uk
https://www.imperial.ac.uk/media/imperial-college/medicine/mrc-gida/2021-12-22-COVID19-Report-49.pdf
preprint
16 December 2021 Imperial College COVID-19 response team
Report 49: Growth, population distribution and immune escape of
Omicron in England+
Neil Ferguson1
, Azra Ghani, Anne Cori, Alexandra Hogan, Wes Hinsley, Erik Volz on behalf of the
Imperial College COVID-19 response team
WHO Collaborating Centre for Infectious Disease Modelling
MRC Centre for Global Infectious Disease Analysis, Jameel Institute, Imperial College London
1
Correspondence: neil.ferguson@imperial.ac.uk
UKHSAとNHSのデータを⽤いたイングランドの情報
オミクロンはデルタと⽐較して
再感染のオッズ⽐︓5.41(95%CI: 4.87-6.00)
ワクチン未接種の場合: 6.36 接種済の場合: 5.02
preprint
• オミクロンとは︖変異体は何が問題︖
• オミクロンの診断⽅法
• オミクロンの特徴① 再感染リスク
• オミクロンの特徴② ⼊院・重症化リスク
• オミクロンのワクチン効果(VE)について
• オミクロンに対する今後の予測
[Preprint] medRxiv Dec. 21, 2021 doi: https://doi.org/10.1101/2021.12.21.21268116
preprint
南アフリカのNational dataを⽤いた研究
査読前論⽂だが、問題点さえ理解できていれば
実際の臨床に⼗分適⽤できる
[Preprint] medRxiv Dec. 21, 2021 doi: https://doi.org/10.1101/2021.12.21.21268116
preprint
今までのCrude Dataの問題点
・南アフリカの感染初期は若者が多かったので
重症化率が低いのではないかという懸念
・ワクチン接種の影響が考慮されていない可能性
・重症化には1-2週間を要するためオミクロンの
流⾏初期は重症化を過⼩評価してた可能性
[Preprint] medRxiv Dec. 21, 2021 doi: https://doi.org/10.1101/2021.12.21.21268116
preprint
<研究デザイン①>
SGTFあり(オミクロン疑い)
vs
SGTFなし(最近のデルタ︖)
(10⽉1⽇〜11⽉30⽇の患者だけを抽出)
preprint
<研究デザイン①>
SGTFあり(オミクロン疑い)
vs
SGTFなし(最近のデルタ︖)
⼊院率︓
オミクロン疑い 2.5%(261/10,547)
最近のデルタ︖ 12.8%(121/948)
調整後オッズ⽐︓0.2 (95%CI 0.1-0.3)
preprint
<研究デザイン①>
SGTFあり(オミクロン疑い)
vs
SGTFなし(最近のデルタ)
⼊院率︓
SGTFあり 2.5% (261/10,547)
SGTFなし 12.8% (121/948)
調整後オッズ⽐︓0.2 (95%CI 0.1-0.3)
以下の項⽬で調整を⾏った
年齢・性別・併存疾患の有無・居住地(州)
私⽴/公⽴病院・診断から⼊院までの⽇数
COVID-19罹患歴の有無・ワクチン接種の有無
preprint
<研究デザイン①>
SGTFあり(オミクロン疑い)
vs
SGTFなし(最近のデルタ)
⼊院率︓
SGTFあり 2.5% (261/10,547)
SGTFなし 12.8% (121/948)
調整後オッズ⽐︓0.2 (95%CI 0.1-0.3)
この論⽂でわかったこと①(私⾒あり)
⼊院の閾値は国や地域、時期によって様々だが…
・少なくとも同じ時期のSGTFあり/なしで⽐較しているので
⼊院の閾値は⼤きく変わらないだろう
・つまりオミクロンは⼊院に⾄る患者が少ない可能性が⾼い︕
preprint
<研究デザイン①>
⼊院患者382⼈中、12⽉21⽇までに転帰の分かっている
患者(退院 or 死亡)317⼈を対象に重症化率を⽐較した
(つまり12⽉21⽇時点でまだ⼊院している患者をすべて
除外していることに注意する)
preprint
<研究デザイン①>
⼊院患者382⼈中、12⽉21⽇までに転帰の分かっている
患者(退院 or 死亡)317⼈を対象に重症化率を⽐較した
(つまり12⽉21⽇時点でまだ⼊院している患者をすべて
除外していることに注意する)
重症化の定義︓
酸素投与・ICU⼊室・⼈⼯呼吸器管理・ECMO装着
→酸素投与だけでも「重症」となってしまうことに注意︕
preprint
<研究デザイン①>
⼊院患者382⼈中、12⽉21⽇までに転帰の分かっている
患者(退院 or 死亡)317⼈を対象に重症化率を⽐較した
(つまり12⽉21⽇時点でまだ⼊院している患者をすべて
除外していることに注意する)
⼊院患者の重症化率︓
SGTFあり 21%(42/204: 57⼈除外)
SGTFなし 40%(45/113: 8⼈除外)
調整後オッズ⽐︓0.7 (95%CI 0.3-1.4)
preprint
<研究デザイン①>
⼊院患者382⼈中、12⽉21⽇までに転帰の
分かった患者317⼈を対象に重症⽐較した
⼊院患者の重症化率︓
SGTFあり 21%(42/204: 57⼈除外)
SGTFなし 40%(45/113: 8⼈除外)
調整後オッズ⽐︓0.7 (95%CI 0.3-1.4)
ちなみに除外した患者(つまりまだ⼊院している患者)が
全員重症化したと仮定すると…
SGTFあり 38%(99/261)vs SGTFなし 44%(53/121)
preprint
<研究デザイン①>
⼊院患者382⼈中、12⽉21⽇までに転帰の
分かった患者317⼈を対象に重症⽐較した
⼊院患者の重症化率︓
SGTFあり 21%(42/204: 57⼈除外)
SGTFなし 40%(45/113: 8⼈除外)
調整後オッズ⽐︓0.7 (95%CI 0.3-1.4)
この論⽂でわかったこと②(私⾒あり)
・除外患者が多く少し信頼性には⽋けるが…
・⼊院に⾄ってしまった患者の中での重症化率は
「現時点でデルタと⽐べて⾼いとも低いとも⾔えない」
preprint
<研究デザイン②>
SGTFあり(オミクロン疑い)
vs
4-11⽉のデルタ あ
⼊院患者の重症化率︓
SGTFあり 23%(53/244)
4-11⽉のデルタ 63%(496/793)
調整後オッズ⽐︓0.3 (95%CI 0.2-0.5)
preprint
<研究デザイン②>
SGTFあり(オミクロン疑い)
vs
4-11⽉のデルタ あ
preprint
<研究デザイン②>
SGTFあり(オミクロン疑い)
vs
4-11⽉のデルタ株
⼊院患者の重症化率︓
SGTFあり 23%(53/244)
4-11⽉のデルタ 63%(496/793)
調整後オッズ⽐︓0.3 (95%CI 0.2-0.5)
この論⽂でわかったこと③(私⾒あり)
・もしかするとデルタより重症化しにくいかも
・ただし11⽉以降の⼊院の閾値と4-11⽉の⼊院の閾値が
違うかもしれないのでこの結果だけで判断するのは早計かも
・⼊院中にて除外された患者が105名いることに注意
preprint
<研究デザイン②>
SGTFあり(オミクロン疑い)
vs
4-11⽉のデルタ株
⼊院患者の重症化率︓
SGTFあり 23%(53/244)
4-11⽉のデルタ 63%(496/793)
調整後オッズ⽐︓0.3 (95%CI 0.2-0.5)
この論⽂でわかったこと③(私⾒あり)
・仮に除外された105名がすべてSGTFありと仮定し
(しかもその可能性は⾼い)さらにその患者がすべて酸素
吸⼊など重症化の条件に当てはまると仮定すると…
→65%(158/244)でデルタの重症化と変わらない結果に
preprint
[Preprint] medRxiv Dec. 21, 2021 doi: https://doi.org/10.1101/2021.12.21.21268116
preprint
この論⽂の⽋点は…
①SGTFがすべてのオミクロンを検出できない(BA.2とい
うタイプは⾒逃される)
→ただし全オミクロンの0.1%程度という説あり
②除外患者(⼊院中の患者)が多く、結果がひっくり返る
可能性が残っている
→査読中にこの結果が追加される可能性もある︖
③⽇本で⾔うところの「中等症」も重症に含まれるので
重症化した患者のどれくらいが⽇本で⾔う「重症」
なのかが分からない
[Preprint] medRxiv Dec. 21, 2021 doi: https://doi.org/10.1101/2021.12.21.21268116
preprint
ということでこの(査読前)論⽂で分かったことは…
[Preprint] medRxiv Dec. 21, 2021 doi: https://doi.org/10.1101/2021.12.21.21268116
preprint
この論⽂から分かったこと…
・SGTFあり(オミクロン疑い)はSGTFなしと
⽐較して⼊院の割合はおそらく低くなるだろう
・⼊院患者における重症化の割合についてはまだ
なんとも⾔えない段階
(差がない可能性も結構残っている)
[Preprint] medRxiv Dec. 21, 2021 doi: https://doi.org/10.1101/2021.12.21.21268116
preprint
https://www.research.ed.ac.uk/en/publications/severity-of-omicron-variant-of-concern-and-vaccine-effectiveness-
preprint
https://www.research.ed.ac.uk/en/publications/severity-of-omicron-variant-of-concern-and-vaccine-effectiveness-
preprint
スコットランドのNational dataを⽤いた査読前論⽂
SGTFなし(デルタ etc.)のデータから⼊院患者数を予測し
SGTFあり(オミクロン疑い)の実際の⼊院患者数と⽐較
(例︓予測では100⼈だったけど実際は30⼈しか⼊院
しなかったので、リスクとしては30%程度と考える)
https://www.research.ed.ac.uk/en/publications/severity-of-omicron-variant-of-concern-and-vaccine-effectiveness-
preprint
Table 3: Observed vs expected analysis for risk of hospital admission by S gene status
S Gene Status N
Person
Years
Hospital
Admissions
Expected
Admissions
Observed/
Expected LCL UCL
All cases
linking into
the EAVE
II dataset
S Positive 119100 4375.1 856 856.9 1 0.93 1.07
S Negative 22205 413.4 15 46.6 0.32 0.19 0.52
Weak S
Positive 2199 57.3 7 6.9 1.02 0.45 2
Other 990 33.8 * * 0.79 0.26 1.88
Unknown 1647 58.2 14 14.8 0.94 0.54 1.54
All cases S Positive 126464 4643.5 967 903.7 1.07 1 1.14
S Negative 23830 443.1 18 50.1 0.36 0.22 0.56
Weak S
Positive 2384 62.1 9 7.5 1.2 0.59 2.19
Other 1080 36.5 * * 0.71 0.24 1.69
Unknown 1813 63.3 17 16.1
1.05
0.64 1.65
All cases
followed up
for at least 7
days
S Positive 102765 4096.2 824 824.9 1 0.93 1.07
S Negative 4111 140.2 7 21.2 0.33 0.15 0.65
Weak S
Positive 995 37.5 7 5.3 1.32 0.59 2.59
Other 748 29.5 * * 0.64 0.18 1.7
Unknown 1336 52.8 10 14.1 0.71 0.36 1.25
All cases
aged 20-59
S Positive 68035 2489.4 575 575.6 1 0.92 1.08
S Negative 17302 322.9 15 34.4 0.44 0.25 0.7
SGTFありの22,205⼈(413.4⼈年︓観察期間)のうち
予測していた⼊院数は46.6例だったにも関わらず、
実際は15例の⼊院であった
→予測の0.32倍(95%CI 0.19-0.52)
https://www.research.ed.ac.uk/en/publications/severity-of-omicron-variant-of-concern-and-vaccine-effectiveness-
preprint
Table 3: Observed vs expected analysis for risk of hospital admission by S gene status
S Gene Status N
Person
Years
Hospital
Admissions
Expected
Admissions
Observed/
Expected LCL UCL
All cases
linking into
the EAVE
II dataset
S Positive 119100 4375.1 856 856.9 1 0.93 1.07
S Negative 22205 413.4 15 46.6 0.32 0.19 0.52
Weak S
Positive 2199 57.3 7 6.9 1.02 0.45 2
Other 990 33.8 * * 0.79 0.26 1.88
Unknown 1647 58.2 14 14.8 0.94 0.54 1.54
All cases S Positive 126464 4643.5 967 903.7 1.07 1 1.14
S Negative 23830 443.1 18 50.1 0.36 0.22 0.56
Weak S
Positive 2384 62.1 9 7.5 1.2 0.59 2.19
Other 1080 36.5 * * 0.71 0.24 1.69
Unknown 1813 63.3 17 16.1
1.05
0.64 1.65
All cases
followed up
for at least 7
days
S Positive 102765 4096.2 824 824.9 1 0.93 1.07
S Negative 4111 140.2 7 21.2 0.33 0.15 0.65
Weak S
Positive 995 37.5 7 5.3 1.32 0.59 2.59
Other 748 29.5 * * 0.64 0.18 1.7
Unknown 1336 52.8 10 14.1 0.71 0.36 1.25
All cases
aged 20-59
S Positive 68035 2489.4 575 575.6 1 0.92 1.08
S Negative 17302 322.9 15 34.4 0.44 0.25 0.7
・⼊院患者の多くは20-59歳
・60歳以上の⼊院患者は存在しなかった
https://www.research.ed.ac.uk/en/publications/severity-of-omicron-variant-of-concern-and-vaccine-effectiveness-
preprint
Table 3: Observed vs expected analysis for risk of hospital admission by S gene status
S Gene Status N
Person
Years
Hospital
Admissions
Expected
Admissions
Observed/
Expected LCL UCL
All cases
linking into
the EAVE
II dataset
S Positive 119100 4375.1 856 856.9 1 0.93 1.07
S Negative 22205 413.4 15 46.6 0.32 0.19 0.52
Weak S
Positive 2199 57.3 7 6.9 1.02 0.45 2
Other 990 33.8 * * 0.79 0.26 1.88
Unknown 1647 58.2 14 14.8 0.94 0.54 1.54
All cases S Positive 126464 4643.5 967 903.7 1.07 1 1.14
S Negative 23830 443.1 18 50.1 0.36 0.22 0.56
Weak S
Positive 2384 62.1 9 7.5 1.2 0.59 2.19
Other 1080 36.5 * * 0.71 0.24 1.69
Unknown 1813 63.3 17 16.1
1.05
0.64 1.65
All cases
followed up
for at least 7
days
S Positive 102765 4096.2 824 824.9 1 0.93 1.07
S Negative 4111 140.2 7 21.2 0.33 0.15 0.65
Weak S
Positive 995 37.5 7 5.3 1.32 0.59 2.59
Other 748 29.5 * * 0.64 0.18 1.7
Unknown 1336 52.8 10 14.1 0.71 0.36 1.25
All cases
aged 20-59
S Positive 68035 2489.4 575 575.6 1 0.92 1.08
S Negative 17302 322.9 15 34.4 0.44 0.25 0.7
この論⽂からわかったこと(私⾒あり)
・南アフリカの論⽂と同様に⼊院リスクは1/3程度
・ただしこちらの論⽂は⼊院患者数が少なくて正確に
評価できているのかは不明
https://www.imperial.ac.uk/media/imperial-college/medicine/mrc-gida/2021-12-22-COVID19-Report-50.pdf
22 December 2021 Imperial College COVID-19 response team
Report 50: Hospitalisation risk for Omicron cases in England
Neil Ferguson1
, Azra Ghani, Wes Hinsley and Erik Volz on behalf of the Imperial College COVID-19 response
team
WHO Collaborating Centre for Infectious Disease Modelling
MRC Centre for Global Infectious Disease Analysis, Jameel Institute, Imperial College London
1
Correspondence: neil.ferguson@imperial.ac.uk
https://www.imperial.ac.uk/media/imperial-college/medicine/mrc-gida/2021-12-22-COVID19-Report-50.pdf
22 December 2021 Imperial College COVID-19 response team
Report 50: Hospitalisation risk for Omicron cases in England
Neil Ferguson1
, Azra Ghani, Wes Hinsley and Erik Volz on behalf of the Imperial College COVID-19 response
team
WHO Collaborating Centre for Infectious Disease Modelling
MRC Centre for Global Infectious Disease Analysis, Jameel Institute, Imperial College London
1
Correspondence: neil.ferguson@imperial.ac.uk
UKHSAとNHSのデータを⽤いたイングランドの情報
SGTFなし(デルタ etc.)と⽐較して
SGTFあり(オミクロン疑い)は
1泊以上の⼊院のリスクが41%(95%CI: 37-45%)減少
(0泊の⼊院も含めると20-25%減少)
• オミクロンとは︖変異体は何が問題︖
• オミクロンの診断⽅法
• オミクロンの特徴① 再感染リスク
• オミクロンの特徴② ⼊院・重症化リスク
• オミクロンのワクチン効果(VE)について
• オミクロンに対する今後の予測
[Epub ahead of print, 2021 Dec 29]. N Engl J Med. 2021;10.1056/NEJMc2119270.
C or r e sp ondence
The new engl and jour nal of medicine
Effectiveness of BNT162b2 Vaccine against
Omicron Variant in South Africa
To the Editor: In early November 2021, the
B.1.1.529 (omicron) variant was first identified
in South Africa and has rapidly become the domi-
nant variant in Gauteng province, where a third
wave of coronavirus disease 2019 (Covid-19) driv-
en by the B.1.617.2 (delta) variant had largely
subsided. As of November 15, the omicron variant
was being detected in more than 75% of Covid-19–
positive tests that were sequenced in South Africa1
(Figs. S1 and S2 in the Supplementary Appendix,
available with the full text of this letter at
ated with the omicron variant during the period
from November 15 to December 7 in South Africa,
which we dubbed a proxy for dominance of the
omicron variant (omicron proxy period), against
estimates of vaccine effectiveness between Sep-
tember 1 and October 30, when the delta variant
was dominant (comparator period).
In our study, we used a test-negative design
and data-exclusion rules to obtain estimates of
vaccine effectiveness4
(Table S1), according to the
following formula: 1−odds ratio for Covid-19
[Epub ahead of print, 2021 Dec 29]. N Engl J Med. 2021;10.1056/NEJMc2119270.
<研究デザイン>
11⽉15⽇時点で南アフリカでは75%がオミクロン
→11⽉15⽇〜12⽉7⽇までの感染者を
オミクロンと仮定してワクチン効果を推定
(ワクチンはファイザー2回接種に限定して調査)
年齢・性別・重症化リスク因⼦・過去の感染歴
感染したタイミング(週)・居住地(州)
で交絡を調整した
[Epub ahead of print, 2021 Dec 29]. N Engl J Med. 2021;10.1056/NEJMc2119270.
results
er dur
the co
Dur
vaccin
interva
ported
measu
differe
when t
hospit
Thu
saw a
BNT16
agains
presum
ant as
of vaccine effectiveness should be viewed as conservative since unvaccinated controls m
cinated persons. On the basis of the number of Discovery Health patients who had been
2021, the rate of misclassification of unvaccinated controls was estimated to be no more
Table 2. Effectiveness of Two Doses of BNT162b2 Vaccine before and during
Proxy Omicron Period.*
Variable
Vaccine Effectiveness
(95% CI)
Comparator
Period
Proxy Omicron
Period
%
Overall estimate 93 (90–94) 70 (62–76)
Sensitivity analyses of PCR results
Patients with S-gene target failure — 69 (48–81)
Patients in Gauteng province — 70 (59–78)
Patients with Covid-19 symptoms — 50 (35–62)
* The overall estimates of vaccine effectiveness were calculated according to a
test-negative design after adjustment for confounders. The three sensitivity
analyses included the results of polymerase-chain-reaction (PCR) tests show-
[Epub ahead of print, 2021 Dec 29]. N Engl J Med. 2021;10.1056/NEJMc2119270.
results
er dur
the co
Dur
vaccin
interva
ported
measu
differe
when t
hospit
Thu
saw a
BNT16
agains
presum
ant as
of vaccine effectiveness should be viewed as conservative since unvaccinated controls m
cinated persons. On the basis of the number of Discovery Health patients who had been
2021, the rate of misclassification of unvaccinated controls was estimated to be no more
Table 2. Effectiveness of Two Doses of BNT162b2 Vaccine before and during
Proxy Omicron Period.*
Variable
Vaccine Effectiveness
(95% CI)
Comparator
Period
Proxy Omicron
Period
%
Overall estimate 93 (90–94) 70 (62–76)
Sensitivity analyses of PCR results
Patients with S-gene target failure — 69 (48–81)
Patients in Gauteng province — 70 (59–78)
Patients with Covid-19 symptoms — 50 (35–62)
* The overall estimates of vaccine effectiveness were calculated according to a
test-negative design after adjustment for confounders. The three sensitivity
analyses included the results of polymerase-chain-reaction (PCR) tests show-
オミクロン⾮流⾏期のVEは93%(95%CI: 90-94%)
オミクロン流⾏期のVEは70%(95%CI: 62-76%)
[Epub ahead of print, 2021 Dec 29]. N Engl J Med. 2021;10.1056/NEJMc2119270.
results
er dur
the co
Dur
vaccin
interva
ported
measu
differe
when t
hospit
Thu
saw a
BNT16
agains
presum
ant as
of vaccine effectiveness should be viewed as conservative since unvaccinated controls m
cinated persons. On the basis of the number of Discovery Health patients who had been
2021, the rate of misclassification of unvaccinated controls was estimated to be no more
Table 2. Effectiveness of Two Doses of BNT162b2 Vaccine before and during
Proxy Omicron Period.*
Variable
Vaccine Effectiveness
(95% CI)
Comparator
Period
Proxy Omicron
Period
%
Overall estimate 93 (90–94) 70 (62–76)
Sensitivity analyses of PCR results
Patients with S-gene target failure — 69 (48–81)
Patients in Gauteng province — 70 (59–78)
Patients with Covid-19 symptoms — 50 (35–62)
* The overall estimates of vaccine effectiveness were calculated according to a
test-negative design after adjustment for confounders. The three sensitivity
analyses included the results of polymerase-chain-reaction (PCR) tests show-
感度分析①︓SGTFありを計測した場合 VE69%
感度分析②︓流⾏地の患者のみを対象 VE70%
感度分析③︓症状のある⼊院患者を対象 VE50%
[Epub ahead of print, 2021 Dec 29]. N Engl J Med. 2021;10.1056/NEJMc2119270.
results
er dur
the co
Dur
vaccin
interva
ported
measu
differe
when t
hospit
Thu
saw a
BNT16
agains
presum
ant as
of vaccine effectiveness should be viewed as conservative since unvaccinated controls m
cinated persons. On the basis of the number of Discovery Health patients who had been
2021, the rate of misclassification of unvaccinated controls was estimated to be no more
Table 2. Effectiveness of Two Doses of BNT162b2 Vaccine before and during
Proxy Omicron Period.*
Variable
Vaccine Effectiveness
(95% CI)
Comparator
Period
Proxy Omicron
Period
%
Overall estimate 93 (90–94) 70 (62–76)
Sensitivity analyses of PCR results
Patients with S-gene target failure — 69 (48–81)
Patients in Gauteng province — 70 (59–78)
Patients with Covid-19 symptoms — 50 (35–62)
* The overall estimates of vaccine effectiveness were calculated according to a
test-negative design after adjustment for confounders. The three sensitivity
analyses included the results of polymerase-chain-reaction (PCR) tests show-
この論⽂の著者の意⾒としては…
・思ったより悪くないのでは︖
・ブースター接種でさらに良い結果が得られる可能性も
[Epub ahead of print, 2021 Dec 29]. N Engl J Med. 2021;10.1056/NEJMc2119270.
results
er dur
the co
Dur
vaccin
interva
ported
measu
differe
when t
hospit
Thu
saw a
BNT16
agains
presum
ant as
of vaccine effectiveness should be viewed as conservative since unvaccinated controls m
cinated persons. On the basis of the number of Discovery Health patients who had been
2021, the rate of misclassification of unvaccinated controls was estimated to be no more
Table 2. Effectiveness of Two Doses of BNT162b2 Vaccine before and during
Proxy Omicron Period.*
Variable
Vaccine Effectiveness
(95% CI)
Comparator
Period
Proxy Omicron
Period
%
Overall estimate 93 (90–94) 70 (62–76)
Sensitivity analyses of PCR results
Patients with S-gene target failure — 69 (48–81)
Patients in Gauteng province — 70 (59–78)
Patients with Covid-19 symptoms — 50 (35–62)
* The overall estimates of vaccine effectiveness were calculated according to a
test-negative design after adjustment for confounders. The three sensitivity
analyses included the results of polymerase-chain-reaction (PCR) tests show-
実際、この論⽂では接種からの⽇数を考慮されてないので
もしかするとVEはさらに過⼩評価されている可能性も…︖
16 December 2021 Imperial College COVID-19 response team
Report 49: Growth, population distribution and immune escape of
Omicron in England+
Neil Ferguson1
, Azra Ghani, Anne Cori, Alexandra Hogan, Wes Hinsley, Erik Volz on behalf of the
Imperial College COVID-19 response team
WHO Collaborating Centre for Infectious Disease Modelling
MRC Centre for Global Infectious Disease Analysis, Jameel Institute, Imperial College London
1
Correspondence: neil.ferguson@imperial.ac.uk
https://www.imperial.ac.uk/media/imperial-college/medicine/mrc-gida/2021-12-22-COVID19-Report-49.pdf
preprint
16 December 2021 Imperial College COVID-19 response team
Report 49: Growth, population distribution and immune escape of
Omicron in England+
Neil Ferguson1
, Azra Ghani, Anne Cori, Alexandra Hogan, Wes Hinsley, Erik Volz on behalf of the
Imperial College COVID-19 response team
WHO Collaborating Centre for Infectious Disease Modelling
MRC Centre for Global Infectious Disease Analysis, Jameel Institute, Imperial College London
1
Correspondence: neil.ferguson@imperial.ac.uk
再掲(再感染の項で取り上げ)ですがVEについても記載あり
ファイザー2回接種(平均140⽇経過)のVEは19%
ファイザーブースター接種14⽇経過後のVEは77%
preprint
https://www.research.ed.ac.uk/en/publications/severity-of-omicron-variant-of-concern-and-vaccine-effectiveness-
preprint
https://www.research.ed.ac.uk/en/publications/severity-of-omicron-variant-of-concern-and-vaccine-effectiveness-
preprint
スコットランドのデータを⽤いた査読前論⽂(再掲)
SGTFなし(デルタ etc)と
SGTFあり(オミクロン疑い)のVEを⽐較
ワクチンの種別(Pfizer・Moderna・AZ)は検討されてない
https://www.research.ed.ac.uk/en/publications/severity-of-omicron-variant-of-concern-and-vaccine-effectiveness-
preprint
この論⽂からわかったこと①
2回接種後6ヶ⽉以上経過した場合のVEは
SGTFの有無に関わらず0だった…︕
https://www.research.ed.ac.uk/en/publications/severity-of-omicron-variant-of-concern-and-vaccine-effectiveness-
preprint
この論⽂からわかったこと②
ブースター接種後2週間経過した場合のVEは
16-49歳・SGTFあり︓56%(95%CI: 51-60%)
50歳以上・SGTFあり︓57%(95%CI: 52-62%)
https://www.research.ed.ac.uk/en/publications/severity-of-omicron-variant-of-concern-and-vaccine-effectiveness-
preprint
この論⽂からわかったこと③
ブースター接種後2週間経過した場合のVEは
16-49歳・SGTFなし︓83%(95%CI: 81-84%)
50歳以上・SGTFなし︓88%(95%CI: 86-89%)
C or r e sp ondence
The new engl and jour nal of medicine
Effectiveness of BNT162b2 Vaccine against
Omicron Variant in South Africa
To the Editor: In early November 2021, the
B.1.1.529 (omicron) variant was first identified
in South Africa and has rapidly become the domi-
nant variant in Gauteng province, where a third
wave of coronavirus disease 2019 (Covid-19) driv-
en by the B.1.617.2 (delta) variant had largely
subsided. As of November 15, the omicron variant
was being detected in more than 75% of Covid-19–
positive tests that were sequenced in South Africa1
(Figs. S1 and S2 in the Supplementary Appendix,
available with the full text of this letter at
NEJM.org). On November 26, the World Health
Organization declared omicron a variant of con-
cern. In a study of live-virus neutralization as-
says, omicron was shown to escape antibody
neutralization by the BNT162b2 messenger RNA
vaccine (Pfizer–BioNTech).2
Thus, data were
needed regarding the effectiveness of the current
vaccines against the omicron variant in prevent-
ing hospitalization for Covid-19.
Using data from Discovery Health, a South
African managed care organization, we estimated
the vaccine effectiveness of two doses of the
BNT162b2 vaccine (i.e., full vaccination) against
hospitalization for Covid-19 caused by the omi-
cron variant by analyzing data sets that included
the results of polymerase-chain-reaction (PCR)
assays, preauthorization admission data, a full
history of members’ medical records, registrations
regarding chronic diseases, and data regarding
body-mass index to obtain the number of Covid-19
risk factors per patient, according to the guide-
lines of the Centers for Disease Control and Pre-
vention (CDC).3
Vaccination status was deter-
ated with the omicron variant during the period
from November 15 to December 7 in South Africa,
which we dubbed a proxy for dominance of the
omicron variant (omicron proxy period), against
estimates of vaccine effectiveness between Sep-
tember 1 and October 30, when the delta variant
was dominant (comparator period).
In our study, we used a test-negative design
and data-exclusion rules to obtain estimates of
vaccine effectiveness4
(Table S1), according to the
following formula: 1−odds ratio for Covid-19
hospitalization in the vaccinated population, where
the odds ratio was calculated with the use of logis-
tic regression after adjustment for confounders
of age, sex, previous Covid-19 infection, surveil-
lance week, geographic location, and the number
of CDC risk factors. In this analysis, Covid-19
hospitalization was a dependent variable, and vac-
cination status was included as an independent
variable.
We then performed three sensitivity analyses
on different subsets of data during the omicron
proxy period. First, we performed PCR tests show-
ing S-gene target failure as an indication of omi-
cron infection. Second, we included only PCR re-
sults obtained from patients in Gauteng province,
given the geographic concentration of the omi-
cron variant during the study period. Third, we
limited PCR test results to those obtained from
patients who had been hospitalized (e.g., respi-
ratory medical admissions), with the latter used
as a proxy for identifying tests among a symp-
tomatic population (Table S4).
We analyzed 133,437 PCR test results that had
16 December 2021 Imperial College COVID-19 response team
Report 49: Growth, population distribution and immune escape of
Omicron in England+
Neil Ferguson1
, Azra Ghani, Anne Cori, Alexandra Hogan, Wes Hinsley, Erik Volz on behalf of the
Imperial College COVID-19 response team
WHO Collaborating Centre for Infectious Disease Modelling
MRC Centre for Global Infectious Disease Analysis, Jameel Institute, Imperial College London
1
Correspondence: neil.ferguson@imperial.ac.uk
+.
Updated 20-12-2021 to: (a) correct accidental transposition of S+ and S- columns in Table 3; (b) correct incorrect
total S+ and S- numbers given on page 5; (c) correct the labelling of the 18-20 age band in Table 1; (d) clarify that
VE analysis excluded reinfections; (e) provide separate estimates of the reinfection relative risk for vaccinated
and unvaccinated cases; (f) add a comment on page 5 that the crude ratios of hospitalisations to cases give no
information on severity on their own due to the differences in the age distribution of Omicron and Delta cases.
C or r e sp ondence
The new engl and jour nal of medicine
Effectiveness of BNT162b2 Vaccine against
Omicron Variant in South Africa
To the Editor: In early November 2021, the
B.1.1.529 (omicron) variant was first identified
in South Africa and has rapidly become the domi-
nant variant in Gauteng province, where a third
wave of coronavirus disease 2019 (Covid-19) driv-
en by the B.1.617.2 (delta) variant had largely
subsided. As of November 15, the omicron variant
was being detected in more than 75% of Covid-19–
positive tests that were sequenced in South Africa1
(Figs. S1 and S2 in the Supplementary Appendix,
available with the full text of this letter at
NEJM.org). On November 26, the World Health
Organization declared omicron a variant of con-
cern. In a study of live-virus neutralization as-
says, omicron was shown to escape antibody
neutralization by the BNT162b2 messenger RNA
vaccine (Pfizer–BioNTech).2
Thus, data were
needed regarding the effectiveness of the current
vaccines against the omicron variant in prevent-
ing hospitalization for Covid-19.
Using data from Discovery Health, a South
African managed care organization, we estimated
the vaccine effectiveness of two doses of the
BNT162b2 vaccine (i.e., full vaccination) against
hospitalization for Covid-19 caused by the omi-
cron variant by analyzing data sets that included
the results of polymerase-chain-reaction (PCR)
assays, preauthorization admission data, a full
history of members’ medical records, registrations
regarding chronic diseases, and data regarding
body-mass index to obtain the number of Covid-19
risk factors per patient, according to the guide-
lines of the Centers for Disease Control and Pre-
vention (CDC).3
Vaccination status was deter-
ated with the omicron variant during the period
from November 15 to December 7 in South Africa,
which we dubbed a proxy for dominance of the
omicron variant (omicron proxy period), against
estimates of vaccine effectiveness between Sep-
tember 1 and October 30, when the delta variant
was dominant (comparator period).
In our study, we used a test-negative design
and data-exclusion rules to obtain estimates of
vaccine effectiveness4
(Table S1), according to the
following formula: 1−odds ratio for Covid-19
hospitalization in the vaccinated population, where
the odds ratio was calculated with the use of logis-
tic regression after adjustment for confounders
of age, sex, previous Covid-19 infection, surveil-
lance week, geographic location, and the number
of CDC risk factors. In this analysis, Covid-19
hospitalization was a dependent variable, and vac-
cination status was included as an independent
variable.
We then performed three sensitivity analyses
on different subsets of data during the omicron
proxy period. First, we performed PCR tests show-
ing S-gene target failure as an indication of omi-
cron infection. Second, we included only PCR re-
sults obtained from patients in Gauteng province,
given the geographic concentration of the omi-
cron variant during the study period. Third, we
limited PCR test results to those obtained from
patients who had been hospitalized (e.g., respi-
ratory medical admissions), with the latter used
as a proxy for identifying tests among a symp-
tomatic population (Table S4).
We analyzed 133,437 PCR test results that had
16 December 2021 Imperial College COVID-19 response team
Report 49: Growth, population distribution and immune escape of
Omicron in England+
Neil Ferguson1
, Azra Ghani, Anne Cori, Alexandra Hogan, Wes Hinsley, Erik Volz on behalf of the
Imperial College COVID-19 response team
WHO Collaborating Centre for Infectious Disease Modelling
MRC Centre for Global Infectious Disease Analysis, Jameel Institute, Imperial College London
1
Correspondence: neil.ferguson@imperial.ac.uk
+.
Updated 20-12-2021 to: (a) correct accidental transposition of S+ and S- columns in Table 3; (b) correct incorrect
total S+ and S- numbers given on page 5; (c) correct the labelling of the 18-20 age band in Table 1; (d) clarify that
VE analysis excluded reinfections; (e) provide separate estimates of the reinfection relative risk for vaccinated
and unvaccinated cases; (f) add a comment on page 5 that the crude ratios of hospitalisations to cases give no
information on severity on their own due to the differences in the age distribution of Omicron and Delta cases.
これらのVEの違いは接種からの期間の違い︖
かもしれない(私⾒)
• オミクロンとは︖変異体は何が問題︖
• オミクロンの診断⽅法
• オミクロンの特徴① 再感染リスク
• オミクロンの特徴② ⼊院・重症化リスク
• オミクロンのワクチン効果(VE)について
• オミクロンに対する今後の予測
[Epub ahead of print, 2021 Dec 30]. JAMA. 2021;10.1001/jama.2021.24868.
Letters
RESEARCH LETTER
Characteristics and Outcomes of Hospitalized
Patients in South Africa During the COVID-19
Omicron Wave Compared With Previous Waves
On November 24, 2021, a SARS-CoV-2 variant of concern,
Omicron (B.1.1.529), was identified in South Africa as respon-
sibleforafourthwaveofCOVID-19.1,2
Thehighnumberofspike
mutations has raised concerns about its ability to evade vac-
cine and spread.3,4
We assessed hospitalized patients with a
positive SARS-CoV-2 test result during the fourth wave com-
pared with previous waves.
Methods | Netcare is a private health care group consisting of
49 acute care hospitals (>10 000 beds) across South Africa.
Analysis wa
(SAS Institut
This stu
provided wr
Results | The
ing the same
4 vs maximu
tients presen
tive COVID-1
3 waves vs 41
ing wave 4 w
59 years in w
males.Signif
mitted in wa
[Epub ahead of print, 2021 Dec 30]. JAMA. 2021;10.1001/jama.2021.24868.
Letters
RESEARCH LETTER
Characteristics and Outcomes of Hospitalized
Patients in South Africa During the COVID-19
Omicron Wave Compared With Previous Waves
On November 24, 2021, a SARS-CoV-2 variant of concern,
Omicron (B.1.1.529), was identified in South Africa as respon-
sibleforafourthwaveofCOVID-19.1,2
Thehighnumberofspike
mutations has raised concerns about its ability to evade vac-
cine and spread.3,4
We assessed hospitalized patients with a
positive SARS-CoV-2 test result during the fourth wave com-
pared with previous waves.
Methods | Netcare is a private health care group consisting of
49 acute care hospitals (>10 000 beds) across South Africa.
Analysis wa
(SAS Institut
This stu
provided wr
Results | The
ing the same
4 vs maximu
tients presen
tive COVID-1
3 waves vs 41
ing wave 4 w
59 years in w
males.Signif
mitted in wa
南アフリカからの報告︓
49の急性期病院(⺠間病院)のデータを公表
[Epub ahead of print, 2021 Dec 30]. JAMA. 2021;10.1001/jama.2021.24868.
確かに重症化率・死亡率は低そうに⾒えるのだが…
(といっても2351⼈の患者のうち、約1%の
27⼈が死亡している)
[Epub ahead of print, 2021 Dec 30]. JAMA. 2021;10.1001/jama.2021.24868.
懸念①
12⽉7⽇までの陽性症例のデータを⽤い
フォローアップ期間は12⽉20⽇まで
→ここから亡くなる⼈が増える可能性もある
[Epub ahead of print, 2021 Dec 30]. JAMA. 2021;10.1001/jama.2021.24868.
懸念②
南アフリカの第4波(11⽉15⽇〜)の患者は
若者が多く基礎疾患も少ない⼈ばかり
→⾼齢者を含めたデータも検討する必要がある
[Epub ahead of print, 2021 Dec 30]. JAMA. 2021;10.1001/jama.2021.24868.
懸念③︓このまま患者数が20倍になったら︖
[Epub ahead of print, 2021 Dec 30]. JAMA. 2021;10.1001/jama.2021.24868.
酸素投与・挿管患者などは結局以前のサージ期と
同じくらいになってしまう可能性…
https://www.imperial.ac.uk/media/imperial-college/medicine/mrc-gida/2021-12-22-COVID19-Report-49.pdf
イングランドでは2⽇で患者が倍になっている…
オミクロンが多くなっている京都府でも5⽇で
患者が倍増している
⼈々の⾏動変容の結果が反映されるのが
15⽇間と仮定すると…
⾏動変容時から8倍の患者が出てもおかしくない
(感染対策次第では16倍の患者が出るかも…)
東京での1⽇の感染者数が2000⼈で「ヤバい」と⼈々が
考え、⾏動変容した場合、、、
しばらく患者は増え続けるので、ピーク時には8倍に当たる
「1⽇の感染者数16000⼈」となるかもしれない
死亡者が少なくとも、保健所機能や医療機能・介護サービス
逼迫の可能性は⾼い
また後遺症がどれくらい残るかも定かでないという問題もある
重症者・死亡者のデータはさらに今後2週間程度でさらに
蓄積していく必要があるが…
早め早めのブレーキをかけて、
来たるべき第6波を⼩さくしましょう︕
医療者は早め早めの準備をしていきましょう︕

Weitere ähnliche Inhalte

Mehr von mimonism

Zaitaku covid 19_0316_2
Zaitaku covid 19_0316_2Zaitaku covid 19_0316_2
Zaitaku covid 19_0316_2mimonism
 
在宅診療におけるCOVID-19診療について
在宅診療におけるCOVID-19診療について在宅診療におけるCOVID-19診療について
在宅診療におけるCOVID-19診療についてmimonism
 
在宅診療におけるCOVID-19対応【2月26日修正アップロード済】
在宅診療におけるCOVID-19対応【2月26日修正アップロード済】在宅診療におけるCOVID-19対応【2月26日修正アップロード済】
在宅診療におけるCOVID-19対応【2月26日修正アップロード済】mimonism
 
在宅診療におけるCOVID-19対応
在宅診療におけるCOVID-19対応在宅診療におけるCOVID-19対応
在宅診療におけるCOVID-19対応mimonism
 
2019_Stmariana
2019_Stmariana2019_Stmariana
2019_Stmarianamimonism
 
Stmariana2
Stmariana2Stmariana2
Stmariana2mimonism
 
2019 ekisaikai
2019 ekisaikai2019 ekisaikai
2019 ekisaikaimimonism
 
2019 iiduka
2019 iiduka2019 iiduka
2019 iidukamimonism
 
2019 hachinohe
2019 hachinohe2019 hachinohe
2019 hachinohemimonism
 
2019 maebashiredcross
2019 maebashiredcross2019 maebashiredcross
2019 maebashiredcrossmimonism
 
2019 kawasakimunicipal
2019 kawasakimunicipal2019 kawasakimunicipal
2019 kawasakimunicipalmimonism
 
2019 stmariana
2019 stmariana2019 stmariana
2019 stmarianamimonism
 
2019 kokuritsukokusai
2019 kokuritsukokusai2019 kokuritsukokusai
2019 kokuritsukokusaimimonism
 
2019yokohamarousai
2019yokohamarousai2019yokohamarousai
2019yokohamarousaimimonism
 
Nichidaiitahashi
NichidaiitahashiNichidaiitahashi
Nichidaiitahashimimonism
 

Mehr von mimonism (20)

Zaitaku covid 19_0316_2
Zaitaku covid 19_0316_2Zaitaku covid 19_0316_2
Zaitaku covid 19_0316_2
 
在宅診療におけるCOVID-19診療について
在宅診療におけるCOVID-19診療について在宅診療におけるCOVID-19診療について
在宅診療におけるCOVID-19診療について
 
在宅診療におけるCOVID-19対応【2月26日修正アップロード済】
在宅診療におけるCOVID-19対応【2月26日修正アップロード済】在宅診療におけるCOVID-19対応【2月26日修正アップロード済】
在宅診療におけるCOVID-19対応【2月26日修正アップロード済】
 
在宅診療におけるCOVID-19対応
在宅診療におけるCOVID-19対応在宅診療におけるCOVID-19対応
在宅診療におけるCOVID-19対応
 
2019_Stmariana
2019_Stmariana2019_Stmariana
2019_Stmariana
 
Stmariana2
Stmariana2Stmariana2
Stmariana2
 
Stmariana
StmarianaStmariana
Stmariana
 
2019 hmu
2019 hmu2019 hmu
2019 hmu
 
2019 ekisaikai
2019 ekisaikai2019 ekisaikai
2019 ekisaikai
 
2019 iiduka
2019 iiduka2019 iiduka
2019 iiduka
 
2019 hachinohe
2019 hachinohe2019 hachinohe
2019 hachinohe
 
2019 maebashiredcross
2019 maebashiredcross2019 maebashiredcross
2019 maebashiredcross
 
2019 kawasakimunicipal
2019 kawasakimunicipal2019 kawasakimunicipal
2019 kawasakimunicipal
 
2019 stmariana
2019 stmariana2019 stmariana
2019 stmariana
 
2019 kokuritsukokusai
2019 kokuritsukokusai2019 kokuritsukokusai
2019 kokuritsukokusai
 
2019yokohamarousai
2019yokohamarousai2019yokohamarousai
2019yokohamarousai
 
Teikyou
TeikyouTeikyou
Teikyou
 
Kyourin
KyourinKyourin
Kyourin
 
Yonemori
YonemoriYonemori
Yonemori
 
Nichidaiitahashi
NichidaiitahashiNichidaiitahashi
Nichidaiitahashi
 

Omicron・第6波に備える 〜何が分かっていて何が分かっていないか〜