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放弃清零死亡 155 万?复旦大学余宏杰论文几点读后感

放弃清零死亡 155 万?复旦大学余宏杰论文几点读后感

科学
最近网上盛传“如果中国放弃清零,会导致 155 万死亡”这一说法,来源是《自然 · 医学》杂志刊登的一篇复旦大学余宏杰教授领衔的一项研究论文。很多人来问我的看法是什么?

通读论文之后,我想说几点读后感:

  1. 这篇论文的标题是《用模型模拟新冠奥密克戎在中国的传播》[1],目前还没有正式发表,还在审稿中,网上刊登的是“预印本”,不排除论文进一步修订的可能性。


  2. 论文内容本身是自洽的,关于模型的局限性,论文作者也明确谈到了三点(见下文引用的“讨论”第四部分)。不过,我还想指出一点:论文中关于病亡总人数的计算,有一个关键性假设,即论文作者提到的“有症状感染者的病死率”,我们可以从结论中反推出作者的假设是 1.38%(1.122 亿有症状感染者,病亡 155 万),这个假设的病亡率似乎与香港和上海的真实世界的数据出入较大。上海目前的有症状感染者(即确诊)的病死率是 0.4% 左右,香港的确诊病死率(即不区分有症状还是无症状感染者)的病死率是 0.7% 左右,而吉林省的有症状感染者的病死率是 0.005%。限于时间和精力,我并没有深究,仅仅是我的第一感受。另外,我没有在论文中找到这个模型估计的总感染人数,即奥密克戎核酸阳性的总人数。虽然理论上,应该可以通过模型估计的“有症状感染者”总数来反推出总感染人数,但问题是,有症状感染者的比例全国各地差别太大,所以缺乏反推的锚点。


  3. 这篇论文讨论了在各种边界条件下的可能后果,其中重点谈到了放弃清零的后果是什么,但更重要的是探讨了中国若要与病毒“共存”,需要具备哪些前提条件。


  4. 155 万死亡是模型的一种假设性结果,其前提是“病毒不受控制地传播”。

论文比较长,我们把论文的「摘要」和「讨论」部分进行了全文翻译,大家可以自己阅读,仁者见仁智者见智,不要断章取义就好。摘要和讨论部分如果读得不过瘾,还可以点击文末附的链接阅读完整原文,里面还藏着更多丰富的信息。因为时间和能力有限,如果翻译有不准确的地方,以英文原文为准。




Modeling transmission of SARS-CoV-2 Omicron in China

《用模型模拟新冠奥密克戎在中国的传播》


Abstract 摘要


Having adopted a dynamic zero-COVID strategy to respond to SARS-CoV-2 variants with higher transmissibility since August 2021, China is now considering whether and for how long this policy can remain in place. The debate has thus shifted towards the identification of mitigation strategies for minimizing disruption to the healthcare system in the case of a nationwide epidemic. To this aim, we developed an age structured stochastic compartmental susceptible-latent-infectious-removed-susceptible (SLIRS) model of SARS-CoV-2 transmission calibrated on the initial growth phase for the 2022 Omicron outbreak in Shanghai, to project COVID-19 burden (i.e., number of cases, patients requiring hospitalization and intensive care, and deaths) under hypothetical mitigation scenarios. The model also considers age-specific vaccine coverage data, vaccine efficacy against different clinical endpoints, waning of immunity, different antiviral therapies, and non-pharmaceutical interventions. We find that the level of immunity induced by the March 2022 vaccination campaign would be insufficient to prevent an Omicron wave that would result in exceeding critical care capacity with a projected intensive care unit peak demand of 15.6-times the existing capacity and causing approximately 1.55 million deaths. However, we also estimate that protecting vulnerable individuals by ensuring accessibility to vaccines and antiviral therapies, and maintaining implementation of non-pharmaceutica interventions could be sufficient to prevent overwhelming the healthcare system, suggesting that these factors should be points of emphasis in future mitigation policies.   


自 2021 年 8 月以来,中国采取了动态清零的战略,以应对传播率较高的新冠病毒变异株。目前,中国正在考虑这一政策是否能够维持,以及能够维持多久。因此,争议已转向确立更为缓和的战略,目的是在全国疫情爆发的情况下尽量减少对医疗系统的破坏。以此为目标,我们建了一个数学模型(模型名称略),并且根据 2022 年上海奥密克戎疫情的初始增长阶段进行了校准,以预测在假设(政策)缓解的情况下新冠肺炎造成的后果,例如病例数、住院、重症、死亡人数等。该模型还考虑了针对不同年龄的疫苗覆盖率数据、疫苗针对不同临床终点的有效性、免疫力衰退、不同的抗病毒疗法以及非药物干预等情况。我们发现,截至 2022 年 3 月所形成的免疫屏障,不足以防止奥密克戎疫情潮,(如果不加以控制)将导致重症监护病房的容量最高峰时是现有容量的 15.6 倍,并造成约 155 万人死亡。然而,我们还预计了,通过确保弱势的个体能获得疫苗和抗病毒疗法,以及保持非药物干预措施的实施,可能足以防止医疗系统的过载。这表明这些因素应成为未来政策缓解的重点。


Discussion 讨论


Using a stochastic dynamic model of SARS-CoV-2 transmission, our study projects the COVID-19 burden caused by the importation of Omicron infections in mainland China, should the dynamic zero-COVID policy be lifted. In the context of the vaccination strategy adopted until March 2022, we estimated that the introduction of  the Omicron variant would cause substantial surges in hospitalizations, ICU admissions, and deaths, and would overwhelm the healthcare system with an estimated burden of 15.6 times the available ICU capacity. 


我们的研究采用新冠病毒传播的随机动态模型,预测了在取消动态清零政策的情况下,中国大陆输入奥密克戎病毒造成的新冠(医疗)负担。在 2022 年 3 月之前采用的疫苗接种战略的背景下,我们估计奥密克戎将导致住院、重症监护室占用和死亡的大幅增加,并将使医疗系统不堪重负,其负担估计是现有重症监护室容量的 15.6 倍。


Should an Omicron variant epidemic be allowed to spread uncontrolled in mainland China, we project 1.10 deaths per 1,000 inhabitants over a 6-month period. By comparison, 187,372 deaths have been reported in the USA38 261 (i.e., 0.57 deaths per 1,000 inhabitants) over the period from December 15, 2021 to April 15, 2022, roughly corresponding to the Omicron wave. We estimate that around 77% of the death toll in China would occur in unvaccinated individuals, with most deaths occurring among unvaccinated individuals aged 60 years or more (52 million people). A similar trend has been observed in the Omicron-driven fifth COVID-19 wave in Hong Kong Special Administrative Region (SAR) of China, which began in early 202239 267 . Our findings highlight the key role of increasing vaccine uptake rate among the elderly to limit COVID-19 burden and to prevent overwhelming the healthcare system. A second key factor to reach these goals is represented by the widespread and timely distribution of a highly efficacious antiviral therapy. When both vaccine uptake in the elderly is substantially increased (97%) and 50% or more of symptomatic infections are treated with antiviral therapies, the peak occupancy of ICUs may not exceed the national capacity and the death toll may be comparable to that of seasonal influenza. In the absence of these two conditions, the most optimistic strategy to prevent overwhelming the healthcare system appears to be the reliance of strict NPIs.


如果允许奥密克戎变异株疫情在中国大陆不受控制地传播,我们预计在 6 个月内每 1000 名居民中有 1.1 人死亡。作为对比,从 2021 年 12 月 15 日到 2022 年 4 月 15 日,美国报告的死亡人数为 187,372 人(即每 1000 名居民死亡 0.57 人),这大致对应了奥密克戎的疫情期。我们估计,中国 77% 的死亡人数将发生在未接种疫苗的人群中,其中大多数死亡发生在 5200 万 60 岁或以上的未接种人群中。在中国香港特别行政区开始于 2022 年初的奥密克戎驱动的第五波新冠疫情中,也观察到了类似的趋势。我们的研究结果突出了提高老年人疫苗接种率在限制新冠负担和防止医疗系统不堪重负方面的关键作用。实现这些目标的第二个关键因素是广泛和及时地进行高效的抗病毒治疗。当老年人接种疫苗率大幅提高到 97%,且 50% 或以上有症状感染者接受抗病毒治疗时,高峰期时全国 ICU 的占用可能不会超出现有能力,死亡人数可能与季节性流感相当。但在未满足这两种条件的情况下,防止医疗系统崩溃的最佳策略似乎是依赖严格的非药物介入措施(NPI)。


China is a highly diverse country with urban megalopolises on the eastern seaboard and rural areas in the northwest. Such diversity is also reflected by heterogeneous vaccination coverage, demographic structure of the population, mixing patterns, and capacity of the healthcare system. When accounting for these heterogeneities, our simulations show considerable differences in the projected COVID-19 burden for different areas of China. According to our projections, the population of Shanghai would experience a higher COVID-19 burden than other areas such as Shandong and Shanxi. This increased burden would be led by a much larger incidence of severe infections in the population aged 60 years or older, which is associated with a lower vaccination coverage in this segment of the population. This result confirms the importance of filling the vaccination gap among the elderly and the need to tailor  interventions on the specific immunological landscape of the population.


中国是一个高度多元化的国家,东部沿海地区有大城市,西北部有农村地区。这种多样性还体现在疫苗接种覆盖率、人口结构、人群混合模式和卫生系统能力的差异性。考虑到这些差异性,我们的模拟显示,中国不同地区预计的新冠负担大相径庭。根据我们的预测,上海的人口将比山东、山西等其他地区承受更高的新冠负担。导致这一负担增加的原因是 60 岁及以上人口严重感染的发生率大大增加,这与这部分人口的疫苗接种覆盖率较低有关。这一结果证实了填补老年人疫苗接种缺口的重要性,以及根据人口的特点量身定制干预措施的必要性。


Our study has several limitations. First, we assumed that the mortality rate remains constant over the projection period; however, studies have suggested that the mortality rate may increase during periods of high strain on hospital services. Second, although we conducted a comprehensive literature search, the epidemiological characteristics of Omicron, clinical severity, VEs of primary and booster vaccination and its persistence against different clinical endpoints, as well as the effectiveness of antiviral therapies are not fully understood. For this reason, we have conducted extensive sensitivity analyses to explore the impact of the uncertainty of model parameters. Third, data on antiviral therapy availability by region is unknown and thus not included in our analysis. Possible regional differences in stockpiles of antiviral therapies could widen the already large differences in COVID-19 burden that we have estimated among the study locations. 


我们的研究有几个局限性。首先,我们假设新冠病死率在预测期内保持不变;然而研究表明,在医疗服务高度紧张的时期,病死率可能会增加。第二,虽然我们进行了全面的文献检索,但对奥密克戎的流行病学特征、临床严重程度、初、加强接种的疫苗有效性及其对不同临床终点的持久保护性,以及抗病毒治疗的有效性尚不完全了解。为此,我们进行了广泛的敏感性分析,探讨模型参数不确定性的影响。第三,按地区划分的抗病毒治疗可用性数据是未知的,因此不包括在我们的分析中。我们估计,不同研究地点之间的抗病毒治疗药物的库存可能存在地区差异,这可能会使已经很大的的新冠负担差异进一步扩大。


In conclusion, should the Omicron outbreak continue unabated, despite a primary vaccination coverage of ≥90% and homologous booster vaccination coverage of ≥40% as of March 2022, we project that the Chinese healthcare system will be overwhelmed with a considerable shortage of ICUs. The contemporary increasing of vaccine uptake in the elderly and widespread distribution of antiviral therapies or the implementation of strict NPIs would be needed to prevent overwhelming the healthcare system and reduce the death toll of an epidemic wave to a level comparable with that of an influenza season. Protecting vulnerable individuals by ensuring access to vaccination and antiviral therapies, as well as maintaining implementation of NPIs (e.g., mask-wearing, enhanced testing, social distancing, and reducing mass gatherings), should be emphasized together with tailoring region-specific interventions. In the long term, improving ventilation, strengthening critical care capacity, and the development of new highly efficacious vaccines with long-term immune persistence would be key priorities.   

综上所述,如果奥密克戎疫情持续不减,尽管截至 2022 年 3 月,基础免疫疫苗接种率≥90%,同源加强疫苗接种率≥40%,但我们预计中国医疗系统将面临重症监护室的严重短缺。目前我们仍需要不断增加老年人接种疫苗的人数,广泛推广抗病毒疗法,或实施严格的非药物介入的措施。上述措施是为了防止医疗系统承受过大压力,并将这股疫情潮的死亡人数降低到与流感季节相当的水平。应强调通过确保获得疫苗接种和抗病毒治疗来保护弱势个体,并保持实施非药物介入措施(如佩戴口罩、加强检测、保持社交距离和减少大规模集会),同时针对不同区域采取精准的干预措施。从长期来看,改善通风、加强重症监护能力和开发具有长期免疫持久性的新型高效疫苗,将是关键的优先事项。



信源


[1]https://www.nature.com/articles/s41591-022-01855-7_reference.pdf?origin=ppub 


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