14歳の日本の女の子が3回目のワク接種後、他臓器炎を起こして死亡した 医学論文より

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Case Report
A case of fatal multi-organ inflammation following COVID-19 vaccination 

COVID-19ワクチン接種後に致死的な多臓器炎を呈した1例

Hideyuki Nushidaa,*, Asuka Itoa, Hiromitsu Kurataa,b, Hitomi Umemotoa,c, Itsuo Tokunagaa, Hirofumi Iseki a, b, Akiyoshi Nishimura a

a Department of Forensic Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan b Department of Physical Medicine, Nakazu-Yagi Hospital, Tokushima, Japan
c Division of Anatomical Education Support, Tokushima University Graduate School, Tokushima, Japan

 

ARTICLEINFO

Keywords:

Systemic inflammation Myopericarditis COVID-19
Vaccines

Sudden death Autopsy

 

ABSTRACT

A 14-year-old Japanese girl died unexpectedly 2 days after receiving the third dose of the BNT1262b2 mRNA COVID-19 vaccine. Autopsy findings showed congestive edema of the lungs, T-cell lymphocytic and macrophage infiltration in the lungs, pericardium, and myocardium of the left atria and left ventricle, liver, kidneys, stomach, duodenum, bladder, and diaphragm. Since there was no preceding infection, allergy, or drug toxicity exposure, the patient was diagnosed with post-vaccination pneumonia, myopericarditis, hepatitis, nephritis, gastroenter- itis, cystitis, and myositis. Although neither type of inflammation is fatal by itself, arrhythmia is reported to be the most common cause of death in patients with atrial myopericarditis. In the present case, arrhythmia of atrial origin was assumed as the cause of cardiac failure and death. In sudden post-vaccination deaths, aggressive autopsy systemic search and histological examination involving extensive sectioning of the heart, including the atrium, are indispensable. 

14歳の日本人女児が，BNT1262b2 mRNA COVID-19ワクチンの3回目の接種後2日目に突然死した．剖検所見では，肺のうっ血性浮腫，肺，心膜，左心房・左心室の心筋，肝臓，腎臓，胃，十二指腸，膀胱，横隔膜にT細胞リンパ球およびマクロファージ浸潤が認められた．先行する感染症、アレルギー、薬物毒性曝露がなかったため、ワクチン接種後の肺炎、心筋炎、肝炎、腎炎、胃腸炎、膀胱炎、筋炎と診断されました。いずれの炎症もそれ自体では致命的ではないが、心房性心筋炎患者では不整脈が最も多い死因となることが報告されている。本症例では、心房由来の不整脈が心不全と死因として想定された。ワクチン接種後の突然死においては、積極的な剖検全身検索と心房を含む心臓の広範な切開を伴う組織学的検査が不可欠である.

 

1. Introduction

Coronavirus disease 2019 (COVID-19) vaccines are available worldwide. Since their introduction, post-vaccination deaths have been reported, and their association with the vaccine has been forensically examined [1,2]. Post-vaccination myocarditis and pericarditis have been increasingly reported, with male adolescents reported to have a higher incidence of pericarditis with a good prognosis, while middle- aged and older patients are more likely to have severe myocarditis. In this study, we report an autopsy case of a 14-year-old girl who died unexpectedly 2 days after receiving the third dose of BNT1262b2 mRNA COVID-19 vaccine. 

コロナウイルス病2019（COVID-19）ワクチンは世界中で発売されています。導入以来、ワクチン接種後の死亡例が報告され、ワクチンとの関連性が法医学的に検討されている[1,2]。ワクチン接種後の心筋炎や心膜炎の報告も増えており、男性青年では予後良好な心膜炎の発症率が高く、中高年では重症心筋炎の発症率が高いと報告されています。今回，BNT1262b2 mRNA COVID-19ワクチン3回目接種後2日目に突然死した14歳女児の剖検例を報告する．

2. Case report

A 14-year-old Japanese girl received a third dose of the BNT1262b2 mRNA COVID-19 vaccine/Pfizer (Comirnaty®) on 10th August 2022. Despite her history of orthostatic dysregulation, she was healthy by nature and was active in her middle school athletic team. The day after vaccination, she developed a fever of 37.9 ◦C, which resolved by the same evening. Her sister, who had slept with her that night, reported that she woke up briefly because she was having difficulty in breathing,

talked with her sister, and went to bed soon after. The following morning, her mother noticed that she was not breathing and had a pale appearance, and she immediately called an ambulance. The patient was in cardiopulmonary arrest when the ambulance crew arrived at their house and attempts to administer advanced life support were unsuc- cessful. She died 45 h after the third vaccination. After the first dose of vaccine on 12th September 2021, she had arm pain without fever. The day after the second dose on 3rd October 2021, she missed school because she had a fever of less than 38 ◦C. All three vaccines were made by Pfizer. An autopsy was performed the following day to evaluate the cause of sudden death. 

14歳の日本人女児が、2022年8月10日にBNT1262b2 mRNA COVID-19ワクチン/ファイザー（Comirnaty®）の3回目の接種を受けた。起立性調節障害の既往があるものの、もともと健康で、中学校の運動部で活躍していた。ワクチン接種の翌日、37.9 ◦Cの発熱があり、同日夕方までに解熱した。その夜、一緒に寝ていた姉から、呼吸困難で一時的に目が覚めたとの報告があった、

彼女は妹と話し、すぐに寝た。翌朝、母親が呼吸がなく、顔色が悪いことに気づき、すぐに救急車を呼んだ。救急隊が自宅に到着したとき、患者は心肺停止状態であり、高度な救命処置を試みたが、うまくいかなかった。3回目のワクチン接種から45時間後に死亡した。2021年9月12日の1回目のワクチン接種後、発熱を伴わない腕の痛みがあった。2回目接種の翌日（2021年10月3日）、38℃以下の発熱のため学校を休んだ。3種類のワクチンはいずれもファイザー社製であった。翌日、突然死の原因を評価するため、解剖が行われた。

2.1. Autopsy findings

The deceased patient was 154 cm tall and weighed 43 kg. The pa- tient’s body showed normal development and nutrition relative to her age. No superficial injuries were observed, except for injection marks from emergency medical treatment. No petechial hemorrhage was observed in the conjunctiva. Her heart weighed 192 g (normal weight, 241.92 ± 42.88 g) [3] and contained dark-red liquid blood (21 g on the left and 110 g on the right side). The heart showed no degeneration or scarring on the grossly superficial surface or cross-sections. 

死亡した患者の身長は154cm、体重は43kgであった。患者の身体は、年齢に比して正常な発育と栄養状態を示していた。救急処置の注射痕を除き、表面的な傷は観察されない。結膜に点状出血は認められませんでした。心臓は192g（正常体重、241.92±42.88g）[3]で、暗赤色の液体血液（左側21g、右側110g）を含んでいた。心臓は肉眼的な表層や断面では変性や瘢痕を認めなかった。

The left lung　weighed 424 g (normal weight, 349.78 ± 143.69 g) [3], 　

while the right lung weighed 471 g (normal weight, 396.28 ± 190.63 g) [3]. In the cross-section, both lungs showed severe pulmonary edema and congestion. 

左の肺は424g（正常値、349.78±143.69g）[3]、

右肺は471g（正常値、396.28±190.63g）[3]である。

断面では、両肺とも重度の肺水腫とうっ血が見られた。

A COVID-19 antigen quantification test performed using a naso- pharyngeal swab taken before autopsy yielded negative results. The serum collected at autopsy tested negative for adenovirus, cytomega- lovirus, influenza virus (A, B), respiratory syncytial virus, Epstein-Barr virus, enterovirus (70, 71), parvovirus, and human immunodeficiency virus. Quantitative testing for the COVID-19 antigen using nasopha- ryngeal swabs yielded negative results. The results of polymerase chain reaction tests performed for COVID-19 using swabs from the lung, heart, liver, kidney, stomach, duodenum, diaphragm, and cerebrum after formalin fixation were also negative. Blood at autopsy was tested for drug toxicity using LC-MS/MS, and the results were negative. 

剖検前に採取した鼻咽頭ぬぐい液を用いて行ったCOVID-19抗原定量検査では、陰性であった。剖検時に採取した血清は、アデノウイルス、サイトメガロウイルス、インフルエンザウイルス（A、B）、呼吸器合胞体ウイルス、Epstein-Barrウイルス、エンテロウイルス（70、71）、パルボウイルスおよびヒト免疫不全ウイルスに対して陰性であった。鼻・喉頭ぬぐい液によるCOVID-19抗原の定量検査では陰性であった。肺、心臓、肝臓、腎臓、胃、十二指腸、横隔膜、大脳の綿棒をホルマリン固定し、COVID-19のポリメラーゼ連鎖反応検査を行った結果も陰性であった。剖検時の血液をLC-MS/MSで薬物毒性検査を行ったが、結果は陰性であった。

2.2. Histological findings　組織学的初見

The autopsied organs were examined histologically, focusing particularly on the resected heart, anterior and posterior walls of the left and right atria and ventricles, atrial septum, ventricular septum, sinus node, and atrioventricular node. Tissue samples were fixed in phosphate-buffered formalin and embedded in paraffin. Paraffin sec- tions of 5 μm thickness were then stained with hematoxylin and eosin. Lymphocyte cellular infiltrates, including eosinophils, were observed in the lungs, pericardium of both atria and adjacent myocardium, liver, kidneys, stomach, duodenum, and diaphragm (Fig. 1), and mild cellular infiltration was also observed in the pericardium of the right ventricle. The brain showed congestion. In the hippocampus a slight lymphocytic infiltration was observed. Immunostaining with an anti-CD3 antibody (Dako 1:200) (Fig. 1) and anti-CD68 antibody (Dako 1:200) (Fig. 1) revealed that most of the infiltrating cells were T cells and macrophages. 

解剖された臓器は、特に切除された心臓、左右の心房と心室の前壁と後壁、心房中隔、心室中隔、洞結節、房室結節に焦点を当てて組織学的に検査された。組織サンプルは、リン酸緩衝ホルマリンで固定し、パラフィンに包埋した。厚さ5μmのパラフィン切片をヘマトキシリンとエオジンで染色した。肺、両心房の心膜と隣接する心筋、肝臓、腎臓、胃、十二指腸、横隔膜に好酸球を含むリンパ球の細胞浸潤が認められ（図1）、右心室の心膜にも軽度の細胞浸潤が観察された。脳にはうっ血が見られた。海馬ではわずかなリンパ球の浸潤が観察された。抗CD3抗体（Dako 1:200）（図1）および抗CD68抗体（Dako 1:200）（図1）による免疫染色では、浸潤細胞のほとんどがT細胞およびマクロファージであった。

2.3. Biochemical analysis　生化学的所見

Laboratory studies revealed elevated SARS-CoV-2 antibody (43600 U/mL, normal less than 0.80), elevated IL-6 (226 pg/mL, normal ≦4.0), slightly elevated C-reactive protein (0.910 mg/mL). IgE (30.8 IU/mL, normal ≦170) and C3 (126 mg/dL, normal 86–160) were within the normal range. The biochemical analysis was performed by SRL, Inc. (Tokyo, Japan). 

臨床検査では、SARS-CoV-2抗体の上昇（43600U/mL、正常値0.80未満）、IL-6の上昇（226pg/mL、正常値≦4.0）、CRP（0.910mg/mL）の微上昇が認められた。IgE（30.8IU/mL、正常値≦170）、C3（126mg/dL、正常値86～160）は正常範囲内でした。生化学的分析は、株式会社エスアールエル（東京、日本）により実施された。 

橋本評：当院ではSARS-CoV-2抗体（抗コロナ抗体）をアボット法で測っている。この方法で測るとこれを７倍したものとなる。ゆえに、アボット法では28万という値となるであろう（アボット法では正常値は50以下）

2.4. Diagnosis　診断

A diagnosis of vaccine-related multiple-organ inflammation was made based on the absence of bacterial or viral infection, lack of a past medical history suggestive of autoimmune disease, no allergic reaction, and no drug exposure other than the vaccine. Myopericarditis is a form of multiple-organ inflammation. Although pneumonia is involved, pneumonia alone is rarely a cause of sudden death, and the presence of erythrocyte-laden macrophages as well as congestive edema of the lungs on histology suggested signs of heart failure from the previous day. Although the extent of inflammation was relatively narrow, the presence of foci centered on the atria and breathlessness are the findings that raise the suspicion of heart failure several hours before death. This led to the diagnosis that the cause of death was vaccine-related myopericarditis, which led to severe arrhythmias and progressive heart failure. 

細菌感染やウイルス感染がないこと、自己免疫疾患を示唆する過去の病歴がないこと、アレルギー反応がないこと、ワクチン以外の薬物曝露がないことを根拠に、ワクチン関連多臓器炎と診断されました。心筋炎は多臓器炎の一種である。肺炎も関与しているが、肺炎だけで突然死の原因となることは少なく、組織学的に赤血球を含むマクロファージの存在や肺のうっ血性浮腫から、前日からの心不全の徴候が考えられた。炎症の範囲は比較的狭かったが、心房を中心とした病巣の存在と息苦しさは、死の数時間前に心不全を疑わせる所見である。このため、死因はワクチンに関連した心筋炎であり、重症の不整脈と心不全が進行したものと診断されました。

3. Discussion

3.1. Death after COVID-19 vaccination:

Vaccine development and its widespread application are key ele- ments in the fight against the COVID-19 pandemic. The COVID-19 vaccine is now used worldwide and has contributed to the contain- ment of the pandemic. However, adverse events caused by vaccines have

been a problem. A forensic examination for the evaluation of the asso- ciation between vaccination and death was conducted in cases of post- vaccination deaths [1,2,4]. The majority of these cases were nega- tively associated with vaccination; however, anaphylaxis, vaccine- induced immunothrombotic thrombocytopenia, myocarditis, and peri- carditis have all been listed as having a suspected association with vaccination and vaccination-related death [2,4]. Murata et al. also re- ported four cases of death after vaccination, in which the only autopsy findings were organ congestion with no evidence of myocarditis. RNA analysis of the blood showed that neutrophil degranulation and cytokine signaling were upregulated in the control group, which led them to conclude that the deaths were due to cytokine storm [5]. 

ワクチンの開発とその普及は、COVID-19パンデミックとの闘いにおける重要な要素である。COVID-19ワクチンは現在世界中で使用されており、パンデミックの抑制に貢献している。しかし、ワクチンによって引き起こされる有害事象が問題となった。ワクチン接種後の死亡例について、ワクチン接種と死亡との関連性を評価するための法医学的検査が行われた[1,2,4]。これらの症例の多くはワクチン接種との関連が否定的であったが、アナフィラキシー、ワクチン誘発性免疫血栓性血小板減少症、心筋炎、心周囲炎はいずれもワクチン接種やワクチン関連死との関連が疑われるものとして挙げられている［2，4］。村田らもワクチン接種後に死亡した4例を再掲載しているが、剖検所見は臓器うっ血のみで、心筋炎の所見はなかった。血液中のRNA解析から、好中球の脱顆粒とサイトカインシグナルが対照群で上昇していることがわかり、死亡の原因はサイトカインストームであると結論づけた[5]。

3.2. Myocarditis and pericarditis after COVID-19 vaccination 

3.2. COVID-19ワクチン接種後の心筋炎・心膜炎について

Reports of myocarditis and pericarditis after COVID-19 vaccination have increased since the report by Albert et al. [6]. The frequency of occurrence of myocarditis and pericarditis has been reported in a US military survey including 23 cases of myocarditis/2,800,000 persons with a mean age of 25 years, all males, and no deaths [7]. A total of 40 U. S. hospitals reported 20 cases/2,000,287 with myocarditis and 37 cases/ 2,000,287 with pericarditis; both groups showed male predilection, mean age of onset of 36 years for myocarditis and 59 years for peri- carditis, and no deaths in either group [8]. The Nordic cohort study reported that myocarditis occurred in 1,077/23,122,522 patients and pericarditis in 1,149/23,122,522 patients; both were more common in young men aged 16–24 years and most commonly occurred after the second vaccination [9]. Thus, post-vaccination myocarditis and peri- carditis had incidence rates of 0.0008–0.0047% and 0.0019–0.0050%, respectively. Although usually mild, these conditions can occur; how- ever, severe cases resulting in death are rare. As of September 2022, the number of COVID-19 vaccine recipients in Japan was approximately 103 million for the second dose and 82 million for the third dose [10]. Based on the above report, at least 800 cases of myocarditis and approximately 1,500 cases of pericarditis occurred after vaccination in Japan. Since the incidence of myocarditis and pericarditis is reported to be higher with second dose of the vaccine than with first dose [11], third dose of the vaccine are likely to further increase the frequency of occurrence of the disease. 

COVID-19ワクチン接種後の心筋炎・心膜炎の報告は、Albertらの報告[6]以降、増加しています。心筋炎および心膜炎の発生頻度は、米軍の調査で心筋炎23例/2,800,000人、平均年齢25歳、全員男性、死亡者なしと報告されている[7]。米国の40の病院では、心筋炎20例/2,000,287人、心膜炎37例/2,000,287人、両群とも男性優位、平均発症年齢は心筋炎36歳、心膜炎59歳、両群とも死亡はなかったと報告されています [8]。北欧のコホート研究では、心筋炎は1,077/23,122,522人、心膜炎は1,149/23,122,522人に発症し、いずれも16～24歳の若い男性に多く、2回目の接種後に最もよく発症したと報告されました［9］。したがって、ワクチン接種後の心筋炎と心膜炎の発生率は、それぞれ0.0008～0.0047％、0.0019～0.0050％となりました。通常、これらの症状は軽度ですが、死亡に至る重症例はまれです。2022年9月現在、日本におけるCOVID-19ワクチンの接種者数は、2回目が約1億300万人、3回目が約8200万人である[10]。上記の報告から、日本ではワクチン接種後に少なくとも800例の心筋炎、約1,500例の心膜炎が発生したことになります。心筋炎や心膜炎の発生率は、1回目の接種よりも2回目の接種で高くなることが報告されているため[11]、3回目の接種でさらに発生頻度が高くなる可能性があります。 

橋本評：なるほど。心筋炎の発症率は3回目の接種でさらに高くなるのですね

The mechanism by which the COVID-19 vaccine causes myocarditis and pericarditis is unclear; however, several hypotheses have been proposed. The mRNA vaccine results in modifications to the nucleoside to reduce its antigenicity. In some individuals, mRNA is recognized as an antigen, resulting in the activation of the inflammatory cascades and immune pathways; in such cases, myocarditis occurs as part of a sys- temic inflammatory response [12,13]. Some researchers have also hy- pothesized that in some patients, the spike protein of the COVID-19 virus and an unknown protein in the myocardium are molecular mimics and that the vaccine elicits antibodies that damage the myocardium [14,15]. Others have hypothesized that the angiotensin-converting enzyme 2 receptor of myocytes binds to the glycoprotein of mRNA vaccines and causes hypersensitivity to myocytes [16]. 

COVID-19ワクチンが心筋炎や心膜炎を引き起こすメカニズムは不明であるが、いくつかの仮説が提唱されている。mRNAワクチンでは、ヌクレオシドが修飾され、抗原性が低下する。個体によっては、mRNAが抗原として認識され、炎症カスケードや免疫経路が活性化される。このような場合、心筋炎はシステム的な炎症反応の一部として起こる [12,13] 。また、一部の研究者は、一部の患者では、COVID-19ウイルスのスパイク蛋白と心筋の未知の蛋白が分子模倣され、ワクチンが心筋を損傷する抗体を誘発するとハイポッシブルしている[14,15]。また、筋細胞のアンジオテンシン変換酵素2受容体がmRNAワクチンの糖タンパク質に結合し、筋細胞への過敏症を引き起こすという仮説もある[16]。

Many histological features of myocarditis after COVID-19 vaccina- tion have been reported, such as the infiltration of inflammatory cells, mostly including T cells and macrophages, mixed with the presence of eosinophils [2,16–21]. Neutrophilic infiltration [17,19], the appearance of mast cells [2], myocyte necrosis [18], and the coexistence of contraction bands [17,19] have also been observed. These findings are consistent with our findings of T cell- and macrophage-dominated cellular infiltrates mixed with eosinophilic cells but are not character- istic of post-vaccination myocarditis. Eosinophilic cells are said to appear in myocarditis following hypersensitivity reactions to drugs or other substances [22], and other histological features are also influenced by cardiac diseases such as myocardial ischemia and mitral valve regurgitation before vaccination as well as the course of the disease leading to death [2,21]. In the present case, the patient showed a similar 

COVID-19ワクチン接種後の心筋炎の組織学的特徴として、T細胞やマクロファージを中心とした炎症細胞の浸潤に好酸球の存在が混在することなどが多く報告されています[2,16-21]。また、好中球の浸潤 [17,19] 、肥満細胞の出現 [2] 、筋細胞の壊死 [18] 、収縮帯の併存 [17,19] も観察される。これらの所見は、好酸球が混在するT細胞やマクロファージ主体の細胞浸潤という我々の所見と一致するが、ワクチン接種後の心筋炎の特徴とは言えない。好酸球は薬剤などの過敏反応後の心筋炎で出現すると言われており[22]、その他の組織像もワクチン接種前の心筋虚血や僧帽弁閉鎖不全症などの心疾患や死に至る経過に影響される[2,21]。本症例では、同様の

 

Fig. 1. Histopathology of the heart (left atrium), lung, liver, kidney, diaphragm, stomach, duodenum, and bladder. All images are × 200 magnification. HE: He- matoxylin and eosin staining showing lymphocytic infiltration. CD3: Immunohistochemical staining for CD3 showing inflammatory cells including CD3-positive T- cells. CD68: Immunohistochemical staining for CD68 shows the infiltrating cells include macrophages. 

図1. 心臓（左心房）、肺、肝臓、腎臓、横隔膜、胃、十二指腸、膀胱の病理組織像。画像はすべて倍率200倍。HE: リンパ球の浸潤を示すHe- matoxylin and eosin staining。CD3：CD3陽性T細胞を含む炎症性細胞を示すCD3の免疫組織化学染色。CD68： CD68の免疫組織化学染色により、マクロファージを含む浸潤細胞を示す。 

 

https://www.nicovideo.jp/watch/sm42084553

ここは大事なところなので動画で見ていただこう（橋本）

 

inflammatory cell infiltrate in the myopericardium as well as in the lungs, liver, kidney, stomach, duodenum, diaphragm, and brain, thus indicating systemic inflammation. Reports of neutrophil degranulation and upregulation of cytokine signaling in the RNA sequences of post- vaccination deaths have also suggested that post-vaccination cytokine upregulation triggers systemic inflammation [3]. This is consistent with the increase in lymphocytes due to the degranulation of neutrophils and an increase in cytokines. These factors may also explain the fever, malaise, and arthralgia, which are common adverse reactions after vaccination. 

心筋だけでなく、肺、肝臓、腎臓、胃、十二指腸、横隔膜、脳にも炎症性細胞の浸潤が認められ、全身性の炎症であることがわかる。ワクチン接種後の死亡者のRNA配列における好中球の脱顆粒とサイトカインシグナルのアップレギュレーションの報告も、ワクチン接種後のサイトカインアップレギュレーションが全身的な炎症を誘発することを示唆している[3]。これは、好中球の脱顆粒によるリンパ球の増加やサイトカインの増加と一致する。また、ワクチン接種後の一般的な副反応である発熱、倦怠感、関節痛も、これらの要因で説明できると思われる。

橋本評：なるほど、外来で倦怠感、関節痛を呈する人が多いがこれは  炎症反応なのですね。

3.3. Death due to atrial myocarditis and pericarditis 

3.3. 心房性心筋炎・心膜炎による死亡例

In our case, inflammation of the heart was primarily found in the bilateral atria. Deaths due to myopericarditis are often caused by heart failure resulting from extensive damage to the myocardium, including the ventricles [20]. In the past, three deaths due to myocarditis in the atria alone have been reported, all of which were considered deaths due to arrhythmias caused by the extension of inflammation into the stim- ulatory conduction system, resulting in heart failure [17,23,24]. In a routine autopsy, the atria are rarely excised for histological examination of the heart, and often, only the ventricles are examined. However, when investigating the cause of death in cases of sudden death, such as the present case, it has been pointed out that if there are no gross changes, histological examination of the ventricles alone may increase the risk of missing lesions confined to the atria [19,23,24]. Complete histological examination of the heart, including the atria, is important in the absence of an obvious gross cause of death at autopsy. 

我々の症例では、心臓の炎症は主に両側の心房に見られた。心筋炎による死亡は、心室を含む心筋の広範囲な損傷による心不全が原因であることが多い[20]。過去に心房だけの心筋炎による死亡例が3例報告されているが、いずれも炎症が刺激伝導系に及ぶことで不整脈を起こし、心不全になったことによる死亡と考えられる[17,23,24]。通常の剖検では、心臓の組織検査のために心房が切除されることはほとんどなく、心室のみが検査されることが多い。しかし、本症例のような突然死の死因を調べる場合、肉眼的な変化がない場合、心室の組織検査だけでは心房に限局した病変を見逃す危険性が高まることが指摘されている[19,23,24]。剖検時に明らかな肉眼的死因がない場合には、心房を含む心臓の完全な組織学的検査が重要である。

Declaration of Competing Interest　競合する利害関係の宣言

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. 

著者らは、本論文で報告された研究に影響を及ぼすと思われる既知の競合する金銭的利益または個人的関係がないことを宣言する。

 

References

1. [1]  C. Edler, A. Klein, A.S. Schro ̈der, J.P. Sperhake, B. Ondruschka, Deaths associated with newly launched SARS-CoV-2 vaccination (Comirnaty®), Legal Med 51 (2021), 101895.

2. [2]  J. Schneider, L. Sottmann, A. Greinacher, M. Hagen, H.U. Kasper, C. Kuhnen, S. Schlepper, S. Schmidt, R. Schulz, T. Thiele, C. Thomas, A. Schmeling, Postmortem investigation of fatalities following vaccination with COVID-19 vaccines, Int J Legal Med 135 (2021) 2335–2345.

3. [3]  A. Yeo, B. Kuek, M. Lau, S.R. Tan, S. Chan, Post COVID-19 vaccine deaths – Singapore’s early experience, Forensic Sci Int 332 (2022) 11199.

4. [4]  Planning and Investigation Committee of the Japanese Society of Legal Medicine. Weights and sizes of internal organs measured in forensic autopsy cases from 2009 to 2013 in Japan. (in Japanese). Questionnaire research performed by the Japanese society of legal medicine. 2015, URL:http://www.jslm.jp/problem/zouki.pdf.

5. [5]  Murata K, Nakao N, Ishiuchi N, Fukui T, Katsuya N, Fukumoto W, Oka H, Yoshikawa N, Nagao T, Namera A, Kakimoto N, Oue N, Awai K, Yoshimoto K, Nagao M. Four cases of cytokine storm after COVID-19 vaccination: Case report. Front Immunol 13:967226. doi:10.3389/fimmu.2022.967226. 

    

6. [6]  E. Albert, G. Aurigemma, J. Saucedo, D.S. Gerson, Myocarditis following COVID-19 vaccination, Radiol Case Report 16 (2021) 2142–2145.

7. [7]  J. Montgomery, M. Ryan, R. Engler, D. Hoffman, B. McClenathan, L. Collins,
   D. Loran, D. Hrncir, K. Herring, M. Platzer, N. Adams, A. Sanou, L.T. Cooper, Myocarditis following immunization with mRNA COVID-19 vaccines in members of the US military, JAMA Cardiol 6 (10) (2021) 1202–1206.

8. [8]  G.A. Diaz, G.T. Parsons, S.K. Gering, A.R. Meier, I.V. Huchinson, A. Robicsek, Myocarditis and pericarditis after vaccination for COVID-19, JAMA 326 (12) (2021) 1210–1212.

9. [9]  O. Karlstad, P. Hovi, A. Husby, T. Ha ̈rka ̈nen, R.M. Selmer, N. Pihlstro ̈m, J.
   V. Hansen, H. Nohynek, N. Gunnes, A. Sundstro ̈m, J. Wohlfahrt, T.A. Nieminen, M. Grünewald, H.L. Gulseth, A. Hviid, R. Ljung, SARS-CoV-2 vaccination and myocarditis in a Nordic cohort study of 23 million residents, JAMA Cardiol 7 (6) (2022) 600–612.

10. [10]  COVID-19 Vaccines. Ongoing topics. Prime minister of Japan and his cabinet. https://japan.kantei.go.jp/ongoingtopics/vaccine.html/ (accessed 2022-9-9).

11. [11]  B. Bozkurt, I. Kamat, J. Hotez, Myocarditis with COVID-19 mRNA vaccines,

    Circulation 144 (6) (2021) 471–484.

12. [12]  K. Kariko ́, M. Buckstein, H. Ni, D. Weissman, Suppression of RNA recognition by

    Toll-like receptors: the impact of nucleoside modification and the evolutionary

    origin of RNA, Immunity 23 (2) (2005) 165–175.

13. [13]  F. Caso, L. Costa, P. Ruscitti, L. Navarini, A.D. Puente, R. Giacomelli, R. Scarpa,

    Could Sars-coronavirus-2 trigger autoimmune and/or autoinflammatory mechanisms in genetically predisposed subjects? Autoimmun Rev 19 (5) (2020), 102524.

14. [14]  Y. Segal, Y. Shoenfeld, Vaccine-induced autoimmunity: the role of molecular mimicry and immune crossreaction, Cell Mol Immunol 15 (2018) 586–594.

15. [15]  K. Larsen, E. Ammirati, L.T. Cooper, K.N. Hong, G. Saponara, D. Couri, A. Cereda, A. Procopio, C. Cavalotti, F. Oliva, T. Sanna, V.A. Ciconte, G. Onyango, D.
    R. Holmes, D.D. Borgeson, Myocarditis after BNT162b2 and mRNA-1273 vaccination, Circulation 144 (2021) 506–508.

16. [16]  S. Choi, S. Lee, J.W. Seo, M.J. Kim, Y.H. Jeon, J.H. Park, J.K. Lee, N.S. Yeo, Myocarditis-induced sudden death after BNT162b2 mRNA COVID-19 vaccination in Korea: Case report focusing on histopathological findings, J Korean Med Sci 36 (40) (2021) e286.

17. [17]  K.A. Verma, K.J. Lavine, C.Y. Lin, Myocarditis after Covid-19 mRNA vaccination, N Engl J Med 385 (2021) 1332–1334.

18. [18]  R.Ameratunga,S.T.Woon,M.N.Sheppard,J.Garland,B.Ondruschka,C.X.Wong, R.A.H. Stewart, M. Tatley, S.R. Stables, R.D. Tse, First identified case of fatal fulminant necrotizing eosinophilic myocarditis following the initial dose of the Pfizer-BioNTech mRNA COVID-19 vaccine (BNT162b2, Comirnaty): an extremely rare idiosyncratic hypersensitivity reaction, J Clin Immunol 42 (2022) 441–447.

19. [19]  J.R. Gill, R. Tashjian, E. Duncanson, Autopsy histopathologic cardiac findings in 2 adolescents following the second COVID-19 vaccine dose, Arch Pathol Lab Med 146 (8) (2022) 925–929.

20. [20]  S. Kazama, T. Okumura, Y. Kimura, R. Ito, T. Araki, T. Mizutani, H. Oishi,
    T. Kuwayama, H. Hiraiwa, T. Kondo, R. Morimoto, T. Saeki, T. Murohara, Biopsy- proven fulminant myocarditis requiring mechanical circulatory support following COVID-19 mRNA vaccination, CJC Open 4 (2022) 501–505.

21. [21]  N.Hoshino,M.Yanase,T.Ichiyasu,K.Kuwahara,H.Kawai,T.Muramatsu,H.Ishii, T. Tsukamoto, S. Morimoto, H. Izawa, An autopsy case report of fulminant myocarditis: Following mRNA COVID-19 vaccination, J Cardiol Cases 26 (6) (2022) 391–394, https://doi.org/10.1016/j.jccase.2022.06.006.

22. [22]  A.M.A. Ali, L.P. Straatman, M.F. Allard, A.P. Ignaszewski, Eosinophilic myocarditis: Case series and review of literature, Can J Cardiol 22 (14) (2006) 1233–1237.

23. [23]  R. Tse, J. Garland, K. Kesha, Y. Triggs, L. Modahl, D. Milne, Z. Yap, S. Stables,
    A rare case of isolated atrial myocarditis causing death with no postmortem computed tomography scan correlation, Am J Forensic Med Pathol 39 (2) (2018) 123–125.

24. [24]  M. Duffy, K. O’Connor, D. Milne, B. Ondruschka, R. Tse, J. Garland, Isolated atrial neutrophilic myocarditis: A rare cause of death and potential “blind spot” for postmortem computed tomography and postmortem examination, Am J Forensic Med Pathol 43 (1) (2022) 73–75.