Nat Med:余宏杰课题组在新冠病毒Omicron株输入中国所致疾病负担与医疗资源需求领域取得重要进展

2022-05-12 “生命科学前沿”公众号 “生命科学前沿”公众号

近期,复旦大学余宏杰课题组在新冠病毒Omicron变异株输入中国引起潜在流行所致疾病负担与医疗资源需求的研究领域取得重要进展,研究结果以“Modeling transmission of

近期,复旦大学余宏杰课题组在新冠病毒Omicron变异株输入中国引起潜在流行所致疾病负担与医疗资源需求的研究领域取得重要进展,研究结果以“Modeling transmission of SARS-CoV-2 Omicron in China”为题,于5月10日以研究长文(Research Article)加速预览的形式发表在Nature Medicine。

新冠病毒(SARS-CoV-2)奥密克戎变异株(Omicron)最早于2021年11月在南非报告,并很快取代德尔塔变异株(Delta)成为全球优势毒株。相较于Delta株,Omicron株的致病力和毒力减弱,但传染力更强,而且针对既往自然感染和疫苗诱导的中和抗体免疫逃逸能力增强。即使在通过自然感染和疫苗接种已建立高水平人群免疫力的国家(如英国),也经历了较前几波疫情更为严峻的Omicron流行高峰。

我国在面临境外疫情输入和境内反弹的双重压力下,通过综合采取各种非药物干预措施(non-pharmaceutical interventions, NPIs),坚持“动态清零”的防控策略。同时,加速推进新冠疫苗接种以构筑免疫屏障。截至2022年4月18日,3岁以上人群中约91%完成了基础免疫,其中54%的人群完成了加强免疫。然而,当前人群免疫水平仍不足以遏制Omicron株的传播。2022年3月1日至5月9日,我国内地累计报告Omicron本土感染者超73万例。维持NPIs仍是当前应对Omicron暴发、流行的重要手段。此外,我国已批准抗新冠病毒药物(国产BRII-196和BRII-198联合用药、进口Paxlovid)使用,并在近期投入到Omicron疫情的临床救治。

探索可行的新冠肺炎疫情控制策略,如何以最小的疾病负担将我国的防控从大流行遏制阶段过渡到常态阶段,是当前亟待解决的科学问题。为此,余宏杰课题组构建了新冠肺炎的随机易感-潜隐-感染-恢复-易感(SLIRS)传播动力学模型,整合疫苗的基础免疫和加强免疫,及其保护力的衰减过程、疾病进展和使用抗病毒药物等模块,基于上海Omicron疫情数据,校正了Omicron株的传播力和疾病负担等关键参数,模拟了Omicron株输入我国引起流行后半年内所导致的疾病负担及其对医疗资源的需求,探索了可将疾病负担和医疗资源需求控制在特定阈值下的“疫苗免疫+抗病毒药物+NPIs”的干预措施组合。

模型研究的基线情境假设:1)2022年3月1日境外输入20例Omicron株感染者;2)模拟开始时Omicron株的再生数R为3.9,考虑疫苗接种产生的保护效果,再生数R降至3.4,该值与上海Omicron疫情早期实施大规模严格干预措施前(即2022年3月1日至8日)的有效再生数Rt估计值一致;3)使用灭活疫苗同源加强,2022年3月1日后的全国加强免疫接种速度为每日500万剂次;4)已完成2剂次基础免疫至少6个月后的人群,90%会接种加强针;5)疫苗针对不同临床结局的保护效果与我国香港特区Omicron疫情中观察到的灭活疫苗的保护效果一致;6)不使用抗新冠病毒药物。

模型模拟的基线结果显示,在全国尺度上,如不采取大规模严格NPIs,2022年5-7月会出现非常陡峭的流行高峰。在6个月的模拟期间,Omicron流行预计导致508万人次住院,267万人次入住ICU和155万死亡,对应的住院率、ICU入住率和死亡率分别为3.60‰、1.89‰和1.10‰。未接种疫苗的60岁及以上老年人将“贡献”74.7%的死亡(图1),这是由于老年人感染Omicron株后出现重症结局的风险显着高于其他年龄组。而截至2022年3月18日,我国60岁及以上人群疫苗接种率较低(约80%),仍有大约5,200万老年人尚未全程接种疫苗。

图1.基线情境下(即不实施大规模严格NPIs和不使用抗新冠病毒药物),模拟Omicron变异株在我国流行半年所致疾病负担。最左列为每日新增住院、入住ICU和死亡发生率;中间两列分别为半年模拟期间累计住院人次、入住ICU人次和死亡人数的状态来源和年龄构成;最右列为分年龄和状态来源的住院率、ICU入住率和死亡率。

考虑到疫苗接种率、人口年龄结构、人群接触模式以及医疗资源等方面的地区差异,研究还以上海、山东和山西三个省市为代表,进行了模拟分析。Omicron变异株在不同省市流行半年所致疾病负担差异显着,例如,基线情境下(即不实施大规模严格NPIs和不使用抗新冠病毒药物),上海(截至2022年4月15日,60岁及以上老年人基础免疫全程接种率62%,加强免疫接种率38%)和山东(截至2022年3月21日,60岁及以上老年人基础免疫全程接种率89%,加强免疫接种率72%)的死亡率分别为1.79‰和0.84‰。

在基线情境模拟的基础上,研究首先探究了采取单一类别干预措施(即疫苗接种,包括异源加强接种和提高60岁及以上老年人的疫苗接种率;使用抗新冠病毒药物;NPIs)对缓解我国Omicron流行所致疾病负担的影响,并估计了相应的医院床位需求。如图2所示,提高60岁以上老年人的疫苗接种率、广泛使用抗新冠病毒药物,以及实施严格的NPIs(Rt: 2.0)可显着降低住院、ICU和死亡。然而,上述单一类别干预措施情境均不能将Omicron流行所致死亡人数降至接近我国季节性流感流行平均每年所致超额呼吸系统疾病的死亡人数(88,100)。

图2.模拟采取单一干预措施对Omicron株在我国流行半年所致疾病负担的影响。干预措施包括疫苗接种、使用抗新冠病毒药物和NPIs等三类。纵轴所列干预措施含义依次如下:基线;采用智飞重组蛋白亚单位疫苗进行异源加强;对截至2022年3月18日大约5200万仍未完成全程接种的60岁及以上老年人接种疫苗;50%的12岁以上有症状病例及时使用具有80%治疗效果的国产抗新冠病毒药物(BRII-196和BRII-198联合用药);100%的12岁以上有症状病例及时服用具有89%治疗效果的辉瑞抗新冠病毒药物(Paxlovid);在基线情境基础上采取只关闭学校、同时关闭学校和工作场所的NPIs;采取不同程度的NPIs将有效再生数Rt从基线情境的3.9分别降低到3.0、2.5和2.0。

从医院床位需求来看,在基线情境和采取单一类别干预措施的情境下,疫情高峰时的非ICU床位需求都低于我国现有呼吸系统感染相关的床位总数(310万,来源为2021年中国卫生健康统计年鉴,包括传染科、内科、儿科和重症医学科床位数)(图2a);而ICU床位需求峰值均超过我国现有ICU床位总数(64,000,来源为2021年中国卫生健康统计年鉴),是我国ICU床位总数的1.7-15.6倍,流行期可导致19-48天的ICU床位短缺(图2b)。这是由于我国人均ICU床位数存在严重不足(我国ICU床位:3.6张/10万人,远低于美国34.7张/10万人)。

图3.模拟采取单一干预措施时,Omicron株在我国流行半年所致医院床位需求。a,每日非ICU住院床位需求;b,每日ICU床位需求,绿色虚线表示我国ICU床位总数(64,000),插入的子图表示与之比较,不同程度ICU床位数缺乏的天数。

如上所述,采取任何单一类别的干预措施既不足以将死亡人数降低至季节性流感水平,也不足以防止疫情对医疗资源的冲击,尤其是重症救治的需求。因此,研究又进一步评估了综合采取疫苗接种(同源/异源加强方案与提高60岁以上老年人接种率)、抗病毒药物(不同的使用比例与治疗效果)和NPIs三类干预措施对医院床位需求和死亡的影响,从而确定可行的综合干预策略。

如图4所示,所有三类干预措施的组合可使非ICU床位需求峰值低于我国呼吸系统感染相关的床位总数,但避免ICU床位超负荷以及将死亡人数降至与季节性流感相当的水平,则需要综合采取不同类别干预措施。协同干预策略的关键在于提高老年人的疫苗接种率,并广泛使用抗病毒药物。否则,就需要采取严格的NPIs将有效再生数Rt降低2或者更低,才能避免医疗资源超负荷。

图4.模拟综合采取疫苗接种、使用抗病毒药物和非药物干预三类措施,Omicron株在我国流行半年所致医院床位需求和死亡人数。a,非ICU住院床位需求峰值,红色数字表示非ICU住院需求峰值低于我国呼吸系统感染相关的床位总数(310万);b,ICU床位需求峰值,红色数字表示ICU床位需求峰值低于我国ICU床位总数(64,000);c,累计死亡数。每个子图的中间罗盘由内至外表示不同干预措施的组合,包括不同加强免疫方案(灭活疫苗同源加强vs.重组蛋白亚单位疫苗异源加强、是否对截至2022年3月18日大约5200万仍未完成全程接种的60岁及以上老年人接种疫苗、不同治疗效果的抗新冠病毒药物、不同比例的有症状病例使用抗新冠病毒药物,以及不同强度的NPIs。Rt=3.9指不采取严格NPIs。

综上,考虑到Omicron株更高的传染力和增强的免疫逃逸能力,尽管截至2022年3月我国人群新冠疫苗的接种率超过90%,且其中≥40%的人群完成了加强免疫,但在不采取严格NPIs和不使用抗新冠病毒药物的情况下,Omicron株一旦在我国流行,仍将造成非常严重的疾病负担和医院资源挤兑,尤其是ICU床位短缺。其中,近5,200万尚未完成疫苗全程接种的60岁及以上老年人将“贡献”74.7%的死亡。

研究结果建议,应综合采用疫苗接种、抗新冠病毒药物和NPIs三类干预措施,尤其是尽快提高60岁及以上人群的疫苗接种率,并且储备充足的抗新冠病毒药物以保护脆弱人群;否则,就需要维持相当强度的NPIs。加强重症病例医疗救治服务体系的建设,研发保护效果更好(例如针对预防感染的结局)、保护持久性更长的广谱新冠疫苗是未来防控的优先事项。

本研究基于我国的最新参数,包括香港特区Omicron株的临床严重性和灭活疫苗针对Omicron株感染不同临床终点的真实世界保护效果,同时利用上海Omicron疫情早期数据校正了Omicron株的传播力和疾病负担等关键参数,使模拟的情境更接近我国的真实世界。此外,本研究针对疫苗接种、抗新冠病毒药物和NPIs三类干预措施的不同组合开展了全面的干预情境分析,定量评估了Omicron株在我国流行所致疾病负担和医疗资源需求,为我国新冠肺炎疫情防控策略的制定提供了坚实的科学证据。

复旦大学公卫学院博士后蔡俊、2020级博士生邓晓伟和复旦大学公卫学院杨娟副教授是共同第一作者,复旦大学公卫学院教授、上海市重大传染病和生物安全研究院、复旦大学附属华山医院感染病科双聘PI余宏杰为通讯作者。本研究得到国家自然科学基金重点项目(82130093)的资助。

原始出处:

Cai, J., Deng, X., Yang, J. et al. Modeling transmission of SARS-CoV-2 Omicron in China. Nat Med (2022). https://doi.org/10.1038/s41591-022-01855-7.

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  2. [GetPortalCommentsPageByObjectIdResponse(id=2060699, encodeId=3b922060699cb, content=<a href='/topic/show?id=4a6d26e30b8' target=_blank style='color:#2F92EE;'>#余宏杰#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=26730, encryptionId=4a6d26e30b8, topicName=余宏杰)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8409354, createdName=闆锋旦, createdTime=Wed Jun 08 22:59:10 CST 2022, time=2022-06-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2026409, encodeId=5db6202640924, content=<a href='/topic/show?id=4c02960e649' target=_blank style='color:#2F92EE;'>#重要进展#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=96076, encryptionId=4c02960e649, topicName=重要进展)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=cc52251, createdName=yhy100200, createdTime=Thu Feb 23 01:59:10 CST 2023, time=2023-02-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1885765, encodeId=4c1d1885e65d1, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=778d36, createdName=柳叶一刀, createdTime=Sun Oct 09 02:59:10 CST 2022, time=2022-10-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1858045, encodeId=57901858045f3, content=<a href='/topic/show?id=3f48525849' target=_blank style='color:#2F92EE;'>#CRO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5258, encryptionId=3f48525849, topicName=CRO)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c30265, createdName=jiafufeng@yaho, createdTime=Wed Nov 02 09:59:10 CST 2022, time=2022-11-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2084733, encodeId=39282084e33bd, content=<a href='/topic/show?id=61f411e013b' target=_blank style='color:#2F92EE;'>#Micro#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11701, encryptionId=61f411e013b, topicName=Micro)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d59291, createdName=xjy02, createdTime=Sat Dec 24 20:59:10 CST 2022, time=2022-12-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1333637, encodeId=2d05133363e64, content=<a href='/topic/show?id=1a1de07305e' target=_blank style='color:#2F92EE;'>#疾病负担#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=70730, encryptionId=1a1de07305e, topicName=疾病负担)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/1103841572/B389FA68ECBF51BE2FE14093CF61F6AE/100, createdBy=eb8e2500096, createdName=夏天与十三菇凉, createdTime=Sat May 14 00:59:10 CST 2022, time=2022-05-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1346945, encodeId=34ff1346945e8, content=<a href='/topic/show?id=a252351803c' target=_blank style='color:#2F92EE;'>#医疗资源#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=35180, encryptionId=a252351803c, topicName=医疗资源)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=93e223, createdName=bluefate121, createdTime=Sat May 14 00:59:10 CST 2022, time=2022-05-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1611580, encodeId=67de1611580a0, content=<a href='/topic/show?id=eb6b1145939' target=_blank style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11459, encryptionId=eb6b1145939, topicName=Med)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=552a19396740, createdName=ms3994565386320060, createdTime=Sat May 14 00:59:10 CST 2022, time=2022-05-14, status=1, ipAttribution=)]
  3. [GetPortalCommentsPageByObjectIdResponse(id=2060699, encodeId=3b922060699cb, content=<a href='/topic/show?id=4a6d26e30b8' target=_blank style='color:#2F92EE;'>#余宏杰#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=26730, encryptionId=4a6d26e30b8, topicName=余宏杰)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8409354, createdName=闆锋旦, createdTime=Wed Jun 08 22:59:10 CST 2022, time=2022-06-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2026409, encodeId=5db6202640924, content=<a href='/topic/show?id=4c02960e649' target=_blank style='color:#2F92EE;'>#重要进展#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=96076, encryptionId=4c02960e649, topicName=重要进展)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=cc52251, createdName=yhy100200, createdTime=Thu Feb 23 01:59:10 CST 2023, time=2023-02-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1885765, encodeId=4c1d1885e65d1, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=778d36, createdName=柳叶一刀, createdTime=Sun Oct 09 02:59:10 CST 2022, time=2022-10-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1858045, encodeId=57901858045f3, content=<a href='/topic/show?id=3f48525849' target=_blank style='color:#2F92EE;'>#CRO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5258, encryptionId=3f48525849, topicName=CRO)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c30265, createdName=jiafufeng@yaho, createdTime=Wed Nov 02 09:59:10 CST 2022, time=2022-11-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2084733, encodeId=39282084e33bd, content=<a href='/topic/show?id=61f411e013b' target=_blank style='color:#2F92EE;'>#Micro#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11701, encryptionId=61f411e013b, topicName=Micro)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d59291, createdName=xjy02, createdTime=Sat Dec 24 20:59:10 CST 2022, time=2022-12-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1333637, encodeId=2d05133363e64, content=<a href='/topic/show?id=1a1de07305e' target=_blank style='color:#2F92EE;'>#疾病负担#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=70730, encryptionId=1a1de07305e, topicName=疾病负担)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/1103841572/B389FA68ECBF51BE2FE14093CF61F6AE/100, createdBy=eb8e2500096, createdName=夏天与十三菇凉, createdTime=Sat May 14 00:59:10 CST 2022, time=2022-05-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1346945, encodeId=34ff1346945e8, content=<a href='/topic/show?id=a252351803c' target=_blank style='color:#2F92EE;'>#医疗资源#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=35180, encryptionId=a252351803c, topicName=医疗资源)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=93e223, createdName=bluefate121, createdTime=Sat May 14 00:59:10 CST 2022, time=2022-05-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1611580, encodeId=67de1611580a0, content=<a href='/topic/show?id=eb6b1145939' target=_blank style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11459, encryptionId=eb6b1145939, topicName=Med)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=552a19396740, createdName=ms3994565386320060, createdTime=Sat May 14 00:59:10 CST 2022, time=2022-05-14, status=1, ipAttribution=)]
    2022-10-09 柳叶一刀
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    2022-12-24 xjy02
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