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Lancet子刊:迄今大规模新冠尸检研究揭示新冠感染者真正的死因

2022-03-22 Swagpp MedSci原创

柳叶刀子刊:来自德国全国的1095份尸检报告显示,在86%的病例中,COVID-19是导致死亡的根本原因;而在剩下的14%中,COVID-19仅是一种伴随疾病。

3月以来,吉林省疫情形势严峻,累计感染者破万。18日,吉林通报新增2例本土死亡病例,引起社会广泛关注。
 
次日,国家卫健委医政医管局局长焦雅辉在新闻发布会上介绍,吉林新增的2例死亡病例,其中1位是高龄,另外1位年纪也超过60岁,都合并严重的基础疾病;其中1位没有接种过新冠肺炎疫苗。
 
焦雅辉强调,两人新冠肺炎的病情本身不重,是轻型,直接的死亡原因是由基础疾病导致。这两例而言,新冠病毒只是压倒患者最后一根稻草,并不是主因!
 
图片
2例死亡病例的具体情况
图注:从上图可以看出,病例1的死亡原因为:高钾血症、严重代谢性酸中毒、低血糖、急性非ST段抬高性心肌梗死;病例2的死亡原因为:急性大面积肺栓塞
 
一石激起千层浪。该事件一出,诱发了一波对于“新冠与死亡”的讨论热潮。
 
怎么样的情况能被定义为“新冠死亡”?在感染者中,直接死于新冠病毒的比例有多大?由于国内数据太少,我们无法从现有案例得到回答。
 
事实上,纵观全球,各国对于新冠死亡的定义不尽相同。根据WHO的规定,在疑似或确诊的新冠病例中,由临床相关的疾病导致的死亡,即可被定义为“新冠死亡”,除非有明确的与新冠无关的替代死因(比如创伤等)。在患病和死亡之间,COVID-19不应有完全康复的时期。
 
图片
全球新冠死亡数据(图源:WHO)
 
为深入了解新冠的病理生物学和患者的死亡原因,来自德国RWTH Aachen医学院的研究团队,开展了迄今为止规模最大的新冠尸检病例研究。
 
研究分析了来自德国全国的1095份尸检报告发现,在86%的病例中,COVID-19是导致死亡的根本原因;而在剩下的14%中,COVID-19仅是一种伴随疾病。该研究论文发表在THE LANCET Regional Health-Europe上。
 
图片
https://doi.org/10.1016/j.lanepe.2022.100330
本研究中,死因数据源自组织检查后的最终尸检报告,依照官方文件,进行集中审查和整理后得到。
 
文件包括:《国际疾病分类和相关健康问题国际统计分类第10版 第2次修订》、《死亡率和发病率编码规则和准则》、《COVID-19作为死亡原因的认证和分类(编码)国际准则》。
 
图片
图注:1a指直接死亡原因,包括最后的疾病、伤害、或直接导致死亡的并发症;1b或1c指潜在死亡原因,包括引发一系列直接导致死亡的疾病事件的最初疾病或损伤,表格中b、c的行数取决于患者潜在疾病的情况。2记录了其他导致死亡的重要疾病,如冠状动脉性心脏疾病、糖尿病、肥胖等。
 
研究纳入了2020年4月-2021年10月之间,来自德国全境的1095例COVID-19尸检病例(包括临床前、临床或验尸时,由鼻拭子抗原或核酸检测确定为SARS-CoV-2阳性)。该时期内,德国尚未出现奥密克戎变异株。
 
按照德国新冠流行的时间段,研究者将尸检病例分为三组。第一波为2020年第10周至第31周,;第二波为2020年第32周至2021年第11周,第三波为2021年第12周至第38周。约在第二波疫情期间,德国为老年人口开放了疫苗接种。
 
梅斯查阅了Our world in data官网上的数据发现,第一波疫情中,德国的新冠病毒以原始毒株为主;在第二波疫情中,2021年开始Alpha毒株占比不断增加,增至与原始株约1:1的水平;第三波疫情,Alpha逐步成为主流株,直到Delta变异株的出现,并迅速“占领”德国。
 
图片
三波疫情期间,死亡与尸检情况
 
总样本中,男女比例为1.8 : 1。根据年龄和性别分布,发现男性死者的死亡年龄多集中在65-69岁和80-84岁,而女性的死亡高峰年龄在85岁及以上。该数据提示,高龄老年人的新冠病毒所致死亡风险更大。
 
观察尸检报告中的死亡原因,研究者发现,在86.2%的病例中,COVID-19是导致死亡的根本原因。其中,最常见的直接死因为弥漫性肺泡损伤(DAD)和急性呼吸窘迫综合征(ARDS),占全部病例的52.5%;位列第二的为多器官衰竭,占18%;其他有关COVID-19的直接死亡原因,包括5.7%的细菌重复感染,4.0%的肺栓塞等。
 
而剩下的13.8%病例中 ,COVID-19被判定为一种伴随疾病。7.4%的病例死于循环性疾病,如缺血性心脏病、心肌梗死;0.9%死于呼吸性疾病,如吸入性肺炎等。
 
图片
尸检报告中,病例的死亡原因
 
对比不同大流行波之间、由COVID-19直接导致死亡的尸检病例,可以发现从第一波到第三波疫情,DAD/ARDS、肺部细菌重复感染、肺栓塞所致死亡的病例有所下降,但多器官衰竭的占比增加。
 
图片
不同流行波次间,直接死亡原因的区别
 
除此之外,研究者还调查了病例从感染新冠到死亡的病程时间。大多数情况下,从首次出现新冠感染症状或检测呈阳性到死亡的持续时间不足2周(三波占比分别为49%,52%,41%)。超过1/3的病程在2-5周之间,超过1/10的死于5周后。
 
图片
从第一次出现症状或检测为阳性到死亡的病程
 
对比不同死因的病程发现,死于DAD/ARDS的病例,多于感染新冠后的2周内死亡,反之,由多器官衰竭直接导致死亡的相对感染疾病时间更长,多死于5周后。可见,由新冠导致的DAD/ARDS发病更急,致死率更高。
 
图片
不同病程之间,直接死亡原因的区别
 
综上所述,在全部纳入分析的1095例尸检病例中,男性病例大多死于65-69岁和80-84岁时,而女性病例的死亡高峰时间≥85岁。在所有病例中,COVID-19是86%病例死亡的根本原因,其中最常见的直接死亡原因是弥漫性肺泡损伤和急性呼吸窘迫综合征,其次是多器官衰竭。
值得注意的是,作者提到,COVID-19是一种血管中心(angiocentric)的疾病,可能会导致心血管或神经血管疾病的恶化。然而本研究并未将此类疾病纳入新冠致死的范畴,不然研究中新冠死亡的比例将达到90%以上。
 
本次大规模的尸检报告,有助于研究者更深入地了解新冠病毒的病理生物学,为疾病的治疗提供理论基础。虽然此次研究并未纳入奥密克戎变异株的死亡情况,但结果仍具有一定参考意义,为未来的研究指明了方向。

参考资料

[1]https://www.thelancet.com/journals/lanepe/article/PIIS2666-7762(22)00023-0/fulltext#%20 

[2]https://ourworldindata.org/covid-cases

[3]https://covid19.who.int/

[4]https://www.who.int/classifications/icd/Guidelines_Cause_of_Death_COVID-19.pdf

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    2022-07-21 howi
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    2022-05-19 ylz8403
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    2022-03-24 zhouqu_8
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createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=医者仁者, createdTime=Tue Mar 22 20:28:51 CST 2022, time=2022-03-22, status=1, ipAttribution=)]
    2022-03-24 ms8000001377634725

    希望尽早揭开新冠病毒的神秘面纱,早日找到有效的治疗方法!让人们不在恐惧它。

    0

  5. 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createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=医者仁者, createdTime=Tue Mar 22 20:28:51 CST 2022, time=2022-03-22, status=1, ipAttribution=)]
    2022-03-23 ms52577694926948

    拜读

    0

  6. 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createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=医者仁者, createdTime=Tue Mar 22 20:28:51 CST 2022, time=2022-03-22, status=1, ipAttribution=)]
    2022-03-23 ms7000001100972409

    这篇文章比较切合实际!

    0

  7. 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    2022-03-23 無為

    COVID-19是一种血管中心(angiocentric)的疾病,可能会导致心血管或神经血管疾病的恶化,这也可能是致死因素之一

    0

  8. 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createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=医者仁者, createdTime=Tue Mar 22 20:28:51 CST 2022, time=2022-03-22, status=1, ipAttribution=)]
    2022-03-23 12346c4dm64暂无昵称

    新冠轻症多

    0

  9. 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topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b2b82397018, createdName=12346c4dm64暂无昵称, createdTime=Wed Mar 23 08:13:00 CST 2022, time=2022-03-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1205103, encodeId=2a481205103a4, content=学习一下, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b7a31928393, createdName=学医无涯, createdTime=Wed Mar 23 07:08:07 CST 2022, time=2022-03-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1205021, encodeId=28b41205021a9, content=COVID-19是一种血管中心(angiocentric)的疾病,可能会导致心血管或神经血管疾病的恶化,这也可能是致死因素之一, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=医者仁者, createdTime=Tue Mar 22 20:28:51 CST 2022, time=2022-03-22, status=1, ipAttribution=)]
    2022-03-23 学医无涯

    学习一下

    0

  10. 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topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b2b82397018, createdName=12346c4dm64暂无昵称, createdTime=Wed Mar 23 08:13:00 CST 2022, time=2022-03-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1205103, encodeId=2a481205103a4, content=学习一下, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b7a31928393, createdName=学医无涯, createdTime=Wed Mar 23 07:08:07 CST 2022, time=2022-03-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1205021, encodeId=28b41205021a9, content=COVID-19是一种血管中心(angiocentric)的疾病,可能会导致心血管或神经血管疾病的恶化,这也可能是致死因素之一, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, 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    2022-03-22 医者仁者

    COVID-19是一种血管中心(angiocentric)的疾病,可能会导致心血管或神经血管疾病的恶化,这也可能是致死因素之一

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