最近網(wǎng)上盛傳“如果中國(guó)放棄清零，會(huì)導(dǎo)致 155 萬死亡”這一說法，來源是《自然 · 醫(yī)學(xué)》雜志刊登的一篇復(fù)旦大學(xué)余宏杰教授領(lǐng)銜的一項(xiàng)研究論文。很多人來問我的看法是什么？
通讀論文之后，我想說幾點(diǎn)讀后感：
一、這篇論文的標(biāo)題是《用模型模擬新冠奧密克戎在中國(guó)的傳播》[1]，目前還沒有正式發(fā)表，還在審稿中，網(wǎng)上刊登的是“預(yù)印本”，不排除論文進(jìn)一步修訂的可能性。
二、論文內(nèi)容本身是自洽的，關(guān)于模型的局限性，論文作者也明確談到了三點(diǎn)（見下文引用的“討論”第四部分）。不過，我還想指出一點(diǎn)：論文中關(guān)于病亡總?cè)藬?shù)的計(jì)算，有一個(gè)關(guān)鍵性假設(shè)，即論文作者提到的“有癥狀感染者的病死率”，我們可以從結(jié)論中反推出作者的假設(shè)是 1.38%（1.122 億有癥狀感染者，病亡 155 萬），這個(gè)假設(shè)的病亡率似乎與香港和上海的真實(shí)世界的數(shù)據(jù)出入較大。上海目前的有癥狀感染者（即確診）的病死率是 0.4% 左右，香港的確診病死率（即不區(qū)分有癥狀還是無癥狀感染者）的病死率是 0.7% 左右，而吉林省的有癥狀感染者的病死率是 0.005%。限于時(shí)間和精力，我并沒有深究，僅僅是我的第一感受。另外，我沒有在論文中找到這個(gè)模型估計(jì)的總感染人數(shù)，即奧密克戎核酸陽性的總?cè)藬?shù)。雖然理論上，應(yīng)該可以通過模型估計(jì)的“有癥狀感染者”總數(shù)來反推出總感染人數(shù)，但問題是，有癥狀感染者的比例全國(guó)各地差別太大，所以缺乏反推的錨點(diǎn)。
三、這篇論文討論了在各種邊界條件下的可能后果，其中重點(diǎn)談到了放棄清零的后果是什么，但更重要的是探討了中國(guó)若要與病毒“共存”，需要具備哪些前提條件。
四、155 萬死亡是模型的一種假設(shè)性結(jié)果，其前提是“病毒不受控制地傳播”。
論文比較長(zhǎng)，我們把論文的「摘要」和「討論」部分進(jìn)行了全文翻譯，大家可以自己閱讀，仁者見仁智者見智，不要斷章取義就好。摘要和討論部分如果讀得不過癮，還可以點(diǎn)擊文末附的鏈接閱讀完整原文，里面還藏著更多豐富的信息。因?yàn)闀r(shí)間和能力有限，如果翻譯有不準(zhǔn)確的地方，以英文原文為準(zhǔn)。
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Modeling transmission of SARS-CoV-2 Omicron in China
《用模型模擬新冠奧密克戎在中國(guó)的傳播》
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 月以來，中國(guó)采取了動(dòng)態(tài)清零的戰(zhàn)略，以應(yīng)對(duì)傳播率較高的新冠病毒變異株。目前，中國(guó)正在考慮這一政策是否能夠維持，以及能夠維持多久。因此，爭(zhēng)議已轉(zhuǎn)向確立更為緩和的戰(zhàn)略，目的是在全國(guó)疫情爆發(fā)的情況下盡量減少對(duì)醫(yī)療系統(tǒng)的破壞。以此為目標(biāo)，我們建了一個(gè)數(shù)學(xué)模型（模型名稱略），并且根據(jù) 2022 年上海奧密克戎疫情的初始增長(zhǎng)階段進(jìn)行了校準(zhǔn)，以預(yù)測(cè)在假設(shè)（政策）緩解的情況下新冠肺炎造成的后果，例如病例數(shù)、住院、重癥、死亡人數(shù)等。該模型還考慮了針對(duì)不同年齡的疫苗覆蓋率數(shù)據(jù)、疫苗針對(duì)不同臨床終點(diǎn)的有效性、免疫力衰退、不同的抗病毒療法以及非藥物干預(yù)等情況。我們發(fā)現(xiàn)，截至 2022 年 3 月所形成的免疫屏障，不足以防止奧密克戎疫情潮，（如果不加以控制）將導(dǎo)致重癥監(jiān)護(hù)病房的容量最高峰時(shí)是現(xiàn)有容量的 15.6 倍，并造成約 155 萬人死亡。然而，我們還預(yù)計(jì)了，通過確保弱勢(shì)的個(gè)體能獲得疫苗和抗病毒療法，以及保持非藥物干預(yù)措施的實(shí)施，可能足以防止醫(yī)療系統(tǒng)的過載。這表明這些因素應(yīng)成為未來政策緩解的重點(diǎn)。
Discussion 討論
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.
我們的研究采用新冠病毒傳播的隨機(jī)動(dòng)態(tài)模型，預(yù)測(cè)了在取消動(dòng)態(tài)清零政策的情況下，中國(guó)大陸輸入奧密克戎病毒造成的新冠（醫(yī)療）負(fù)擔(dān)。在 2022 年 3 月之前采用的疫苗接種戰(zhàn)略的背景下，我們估計(jì)奧密克戎將導(dǎo)致住院、重癥監(jiān)護(hù)室占用和死亡的大幅增加，并將使醫(yī)療系統(tǒng)不堪重負(fù)，其負(fù)擔(dān)估計(jì)是現(xiàn)有重癥監(jiān)護(hù)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.
如果允許奧密克戎變異株疫情在中國(guó)大陸不受控制地傳播，我們預(yù)計(jì)在 6 個(gè)月內(nèi)每 1000 名居民中有 1.1 人死亡。作為對(duì)比，從 2021 年 12 月 15 日到 2022 年 4 月 15 日，美國(guó)報(bào)告的死亡人數(shù)為 187,372 人（即每 1000 名居民死亡 0.57 人)，這大致對(duì)應(yīng)了奧密克戎的疫情期。我們估計(jì)，中國(guó) 77% 的死亡人數(shù)將發(fā)生在未接種疫苗的人群中，其中大多數(shù)死亡發(fā)生在 5200 萬 60 歲或以上的未接種人群中。在中國(guó)香港特別行政區(qū)開始于 2022 年初的奧密克戎驅(qū)動(dòng)的第五波新冠疫情中，也觀察到了類似的趨勢(shì)。我們的研究結(jié)果突出了提高老年人疫苗接種率在限制新冠負(fù)擔(dān)和防止醫(yī)療系統(tǒng)不堪重負(fù)方面的關(guān)鍵作用。實(shí)現(xiàn)這些目標(biāo)的第二個(gè)關(guān)鍵因素是廣泛和及時(shí)地進(jìn)行高效的抗病毒治療。當(dāng)老年人接種疫苗率大幅提高到 97%，且 50% 或以上有癥狀感染者接受抗病毒治療時(shí)，高峰期時(shí)全國(guó) ICU 的占用可能不會(huì)超出現(xiàn)有能力，死亡人數(shù)可能與季節(jié)性流感相當(dāng)。但在未滿足這兩種條件的情況下，防止醫(yī)療系統(tǒng)崩潰的最佳策略似乎是依賴嚴(yán)格的非藥物介入措施（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.
中國(guó)是一個(gè)高度多元化的國(guó)家，東部沿海地區(qū)有大城市，西北部有農(nóng)村地區(qū)。這種多樣性還體現(xiàn)在疫苗接種覆蓋率、人口結(jié)構(gòu)、人群混合模式和衛(wèi)生系統(tǒng)能力的差異性?？紤]到這些差異性，我們的模擬顯示，中國(guó)不同地區(qū)預(yù)計(jì)的新冠負(fù)擔(dān)大相徑庭。根據(jù)我們的預(yù)測(cè)，上海的人口將比山東、山西等其他地區(qū)承受更高的新冠負(fù)擔(dān)。導(dǎo)致這一負(fù)擔(dān)增加的原因是 60 歲及以上人口嚴(yán)重感染的發(fā)生率大大增加，這與這部分人口的疫苗接種覆蓋率較低有關(guān)。這一結(jié)果證實(shí)了填補(bǔ)老年人疫苗接種缺口的重要性，以及根據(jù)人口的特點(diǎn)量身定制干預(yù)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.
我們的研究有幾個(gè)局限性。首先，我們假設(shè)新冠病死率在預(yù)測(cè)期內(nèi)保持不變；然而研究表明，在醫(yī)療服務(wù)高度緊張的時(shí)期，病死率可能會(huì)增加。第二，雖然我們進(jìn)行了全面的文獻(xiàn)檢索，但對(duì)奧密克戎的流行病學(xué)特征、臨床嚴(yán)重程度、初、加強(qiáng)接種的疫苗有效性及其對(duì)不同臨床終點(diǎn)的持久保護(hù)性，以及抗病毒治療的有效性尚不完全了解。為此，我們進(jìn)行了廣泛的敏感性分析，探討模型參數(shù)不確定性的影響。第三，按地區(qū)劃分的抗病毒治療可用性數(shù)據(jù)是未知的，因此不包括在我們的分析中。我們估計(jì)，不同研究地點(diǎn)之間的抗病毒治療藥物的庫存可能存在地區(qū)差異，這可能會(huì)使已經(jīng)很大的的新冠負(fù)擔(dān)差異進(jìn)一步擴(kuò)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.
綜上所述，如果奧密克戎疫情持續(xù)不減，盡管截至 2022 年 3 月，基礎(chǔ)免疫疫苗接種率≥90%，同源加強(qiáng)疫苗接種率≥40%，但我們預(yù)計(jì)中國(guó)醫(yī)療系統(tǒng)將面臨重癥監(jiān)護(hù)室的嚴(yán)重短缺。目前我們?nèi)孕枰粩嘣黾永夏耆私臃N疫苗的人數(shù)，廣泛推廣抗病毒療法，或?qū)嵤﹪?yán)格的非藥物介入的措施。上述措施是為了防止醫(yī)療系統(tǒng)承受過大壓力，并將這股疫情潮的死亡人數(shù)降低到與流感季節(jié)相當(dāng)?shù)乃?。?yīng)強(qiáng)調(diào)通過確保獲得疫苗接種和抗病毒治療來保護(hù)弱勢(shì)個(gè)體，并保持實(shí)施非藥物介入措施（如佩戴口罩、加強(qiáng)檢測(cè)、保持社交距離和減少大規(guī)模集會(huì)），同時(shí)針對(duì)不同區(qū)域采取精準(zhǔn)的干預(yù)措施。從長(zhǎng)期來看，改善通風(fēng)、加強(qiáng)重癥監(jiān)護(hù)能力和開發(fā)具有長(zhǎng)期免疫持久性的新型高效疫苗，將是關(guān)鍵的優(yōu)先事項(xiàng)。
信源
[1]https://www.nature.com/articles/s41591-022-01855-7_reference.pdf?origin=ppub
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