在这篇文章中，我们首先解释说 我们有工具 即使考虑到完全不确定的情况，也要适当和建设性地提前计划。我们决不能让同样在冲击我们的无准备灾难继续下去。因缺乏预期而导致的无准备状态也必须停止。
最后，我们开始构建一个结构，用于 我们的一套方案 这将勾勒出可能的未来。我们强调，有两个因素是至关重要的，将决定我们的未来：疫苗和抗病毒预防和治疗。在这里，我们重点讨论这个因素中的第一个。 疫苗.我们不仅关注发现合适的COVID-19疫苗，还关注免疫接种过程的各个阶段。因此，我们得到了一个初步估计，大规模的疫苗接种运动最早可能在以下时间开始 2022-2023年冬季 (所有候选疫苗）。该 下一篇文章 重点是抗病毒的预防和治疗。
- 红队分析周刊 - 2022年6月30日
- 乌克兰的核战场--人类世的战争 (2)
例如，正如安德森等人所表明的，如果我们遇到一个新的问题，并且没有很多相关的信息，我们的大脑就会创建一个第一个非常近似的模型。这个模型使我们拥有的任何数据都有意义（Craig A. Anderson, Mark R. Lepper, and Lee Ross, 社会理论的持久性。解释在信誉不佳的信息持续存在中的作用, 《人格与社会心理学杂志》1980年，第39卷，第6期，1037-1049）。
那么，一旦这种模式被创造出来，要改变它就变得非常困难。要做到这一点，必须付出努力。换句话说，大多数人，会坚持他们最初的模式，即使出现新的事实和证据。这并不是说他们撒谎或表现出不良意愿，尽管这当然也可能发生。而是这些人首先要在信息不充分的情况下对一个新问题做出解释。当他们收到新的信息时，他们的模型已经变得不充分，但它仍然过滤了他们的理解（Craig A. Anderson等人，同上）。
因此，我们又意识到了生存作为首要动机的重要性。我们正活在政治真正的本质中：人类在社会中的组织是为了生存，而政治当局的基本使命是确保他们的生存和安全（如 什么是政治风险？ 和相关书目）。大多数人已经忘记了这些基本要素，但这场大流行病有力地、无情地提醒了我们这些基本要素。
如果你仔细想想，我们都在经历的事情绝对是超乎寻常的。一个又一个国家，在几天内，根据案例，我们从一个照常的状态（对于那些不关注世界的人来说）变成了完全的禁锢，经济优势的结束，封闭的边界，自由的结束，"乐趣 "的结束。而 168个国家 在几个月内，一个接一个地面临同样的磨难。而我们看到它，并跨越遥远的距离进行交流。这也是完全新的。
The reconstruction, in turn, will depend upon what “part” of the pre-COVID-19 world as a socio-ideological and political system has been destroyed and how this destruction was carried out. It will be determined by the amount of damages and sheer destructions the pandemic directly caused. The state of the various actors at the end of the pandemic, i.e strength, capabilities, intentions, trauma etc., will also, and as strongly, influence reconstruction.
The case of face mask shortages
For example, what the populations and their ruling authorities live, the intractable hurdles and fear they face, will remain as a burning mark in their memories. Those will certainly strongly shape their future decisions and actions.
For instance, the whole of Europe and the U.S. face an incredible shortage of face masks (e.g. Yanqiu Rachel Zhou, “The global effort to tackle the coronavirus face mask shortage“, The Conversation, 17 March 2020; Keith Bradsher 和 Liz Alderman, “The World Needs Masks. China Makes Them — But Has Been Hoarding Them“, 13 March 2020, updated 16 March, 纽约时报).
This results from past mismanagement and from intense outsourcing of face mask manufacturing capabilities, notably to China that produces half of them (Ibid.; Fabien Magnenou, “Coronavirus : pourquoi la France manque-t-elle de masques de protection respiratoire ?“, 法国信息, 19 March 2020).
Consequently, the non-producers must wait on others’, and notably China, good will and benevolence and gifts. They must wait until exports become available again.
Thus, new production capabilities must be recreated from scratch, in a hurry, thanks to imagination, courage and good will, while the know-how must be reinvented. Adequate materials may lack. At the beginning, the resulting products may not be as safe as needed (e.g. Juliette Garnier, “Coronavirus : mobilisation générale pour fabriquer des masques en tissu“, Le Monde, 17 March 2020).
In the meantime, the contagion spreads and people die. On the bright side, innovation and new ways to produce will emerge from this struggle for face masks.
Yet, the stress and the fatalities and the fear will certainly not be forgotten in our lifetime and maybe for generations. As a result, it is very likely that major outsourcing to China or elsewhere is over, especially for goods that could be of critical importance.
To come back to our main question, we are thus faced with a twin task. We must foresee the near future to be able to survive while, in the same time, identifying various scenarios of destruction and nascent reconstruction. Then, building from and upon this first layer, we must foresee possible ways to reconstruct.
Looking for a first structure for our set of scenarios
On the importance of time
As a preamble, we need to stress a supplementary challenge we face when building the architecture of our set of scenarios for the COVID-19 pandemic.
We need to introduce a relatively precise timeframe. Indeed, the length of time during which the pandemic will last, as well as the timing and duration of measures taken does matter. This is obvious when looking at epidemiological studies, which will be one of the main materials upon which we shall build (e.g. Imperial College COVID-19 Response Team, Ibid.; Joseph T Wu et al. 预测和预报源自中国武汉的2019年nCoV疫情的潜在国内和国际传播：一个模型研究, 柳叶刀》杂志，2020年1月31日）。
Key critical factors: vaccine and antiviral prophylaxis and treatment
The first factor that determines all the others is the existence – or rather in our case the non-existence – of vaccine and/or antiviral prophylaxis and treatment. Once either vaccine or treatment or both are viable, then a second key question is their availability in sufficient quantity where they are needed. Finally, we have the operationalisation of mass vaccination and/or treatment. These elements are absolutely critical.*
Indeed, once a vaccine will have become widely available and will have immunised the population, then the pandemic will end. In the case of treatments, we shall have potentially more variations and shades, but, fundamentally, the way the factor operates will likely be similar. We shall refine this statement after analysis.
The scientific effort to identify possible vaccines candidates and antiviral prophylaxis and treatment is considerable. This could take place thanks notably to very early Chinese efforts to “sequence the genetic material of Sars-CoV-2” and willingness to share it as quickly as possible (e.g. Wu, F., Zhao, S., Yu, B. 等人。 A new coronavirus associated with human respiratory disease in China. 自然界 579, 265–269 (2020), 3 February 2020; updated GenBank “SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) Sequences“; Laura Spinney, “When will a coronavirus vaccine be ready?“, 卫报, 13 March 2020).
We should, however, note – for the next pandemic – that time has been lost those last years and notably since the SARS 2003 epidemic. Indeed, “medication against coronaviruses” were not included in the progress made over the last 25 years in antiviral medication (interview of Matthias Götte, a biochemist and viral researcher from Hamburg in Kerstin Kullmann und Veronika Hackenbroch, “The Urgent Search for a Cure for COVID-19“, Der Spiegel, 13 March 2020).
Various companies, universities and research laboratories would currently be exploring between 15 (Pang et al., Feb 2020, see table on vaccines) and 35 vaccine candidates of various types (Laura Spinney, Ibid.). They are all in the early stages of the overall process (Ibid.; John Hodgson, “The pandemic pipeline“, 自然界, 20 March 2020). By 15 April, more than 70 vaccine candidates would be explored, five being at the preliminary trials’ stage (Christine Soares, “The lifeline pipeline“, 路透社, 13 April 2020).
For example, human trials have already started for U.S. Moderna Therapeutics’ candidate vaccine (Michelle Roberts, “Coronavirus: US volunteers test first vaccine“, BBC, 17 March 2020). In that case the animal trials have even been skipped (Ibid.). Other human trials will start in April 2020 (Spinney, Ibid.). French Sanofi is also working on a candidate vaccine (see below).
Hodgson states that another candidate vaccine, developed by Singapore, would be at the manufacturing stage (Hodgson, Ibid.). This is probably an editing mistake, because after verification, the vaccine, developed with the Company Arcturus has not yet entered clinical trials. They expect to start phase 1 of clinical trials “in the third quarter of the year” and to complete it at the end of 2020 or beginning of 2021 (Joyce Teo, “Countries, including Singapore, in race to develop vaccine“, Straits Times, 25 March 2020). Thus, Singapore and Arcturus are nowhere near the manufacturing stage. However, Arcturus suggests that their manufacturing process will be quicker than for other vaccines (Arcturus website ibid.).
Chinese CanSino Biologics Inc. has also started conducting first phase clinical trial, which should last until December 2020 (China embarks on clinical trial for virus vaccine, The Star, 22 March 2020).
Manufacturing vaccin doses matters too
In general, scientific studies estimate that we are at best between 10 and 18 months away from a vaccine (e.g. interviews in Spinney, Ibid.; Helen Stillwell, “SARS-CoV-2 – The vaccine landscape“, Virology Blog; 11 March 2020; Roy M Anderson et al., “How will country-based mitigation measures influence the course of the COVID-19 epidemic?" - 柳叶刀》杂志 – Published online March 09, 2020). These studies however rarely mention which phase of the vaccination process is included in these 10 to 18 months.
The director of the U.S. National Institute of Allergy and Infectious Diseases (N.I.A.I.D.) assesses that “the earliest it [a vaccine] would be deployable is in a year to a year and a half,” which would tend to imply that it has been manufactured by then (Carolyn Kormann, “How Long Will It Take to Develop a Coronavirus Vaccine?“, The New Yorker, 8 March 2020).
For its part, the global head of vaccine research and development of Sanofi estimates that, at best “a vaccine could be fully ready for licensure in a year and a half.” (Ibid.) In that case, this means that the time to manufacture doses is not included in the year and a half. This may sound logical as without the composition of the vaccine, it may be hard to assess the time needed to produce it and in which quantities.
As far as estimates of manufactured doses are concerned, the firm Inovio, for example has as target 1 million doses by the end of 2020 (Tarryn Mento, “Inovio Pharamaceuticals Fast-Tracking Human Trials, Working On 1 Million Doses Of Coronavirus Vaccine“, KPBS, 20 March 2020). This is only a target as its production capability by end of January 2020 was 100.000 doses a year (Jon Cohen, “Scientists are moving at record speed to create new coronavirus vaccines—but they may come too late“, 科学, Jan. 27, 2020).
Moderna could produce at best 100 million doses a year, but would use all its production capability for it (Cohen, ibid.). For another candidate vaccine, “the Queensland team says it could make 200,000 doses in 6 months” (Cohen, Ibid,).
Sanofi, for the U.S., “has the established capacity and infrastructure to make up to 600 million doses in two existing facilities based in New York and Pennsylvania, without compromising the supply of vaccines for other illnesses, including influenza” (Sanofi, “Sanofi Mobilizes to Develop a Vaccine against COVID-19“, 23 march 2020). Meanwhile, on 23 March 2020, Sanofi confirmed its timeline: “We estimate that we will have a vaccine candidate available for in vitro testing within six months and potentially enter clinical trials within a year and a half” (Sanofi, “Sanofi’s Response in the Fight against COVID-19“, 23 march 2020).
In he meantime, the 2017 created Coalition for Epidemic Preparedness Innovation (CEPI) is building up its capacity to produce “multiple millions of doses available within 12–18 months” (Hodgson, Ibid.).
China vaccines manufacturers also now have massive capabilities to produce vaccines. In 2018, Yaming Zheng et al. estimated that China produced annually 700 million vaccine doses (The landscape of vaccines in China: history, classification, supply, and price. BMC Infect Dis).
Global estimates of future production of vaccine doses remain quite elusive and will need to be handled through scenarios, waiting for further research.
How long could the emergency or survival period last? A first estimate
This first open source brief review gives us the guidelines to conduct further in-depth study and to define the monitoring that will need to take place. Indeed, we now have the material to identify at least a first batch of indicators to monitor to follow the situation on the ground.
Meanwhile, each uncertainty related to the “vaccine factor” will create a sub-branch in our scenario tree. In other words, in the following paragraphs, each time I’ll make an assumption and use a word such as “imagine” or “if”, this means that we are dealing with sub-branches and sub-scenarios.
Waiting for a finalised architecture for our scenario tree, we can already roughly outline a very optimistic scenario. This is a scenario where at least one current candidate vaccine goes successfully through all the trials, in 12 months. This brings us, for the start of the manufacturing process to March 2021.
Here, we must remember that Singapore and those using a technology similar to Arcturus could produce more quickly the vaccines. However, the clinical trials must be successful first.
Now, a 2018 presentation by the chair of RA WG at Vaccines Europe (a specialised vaccines group within the European Federation of Pharmaceutical Industries and Associations (EFPIA), the professional association of the pharmaceutical industry in Europe) gives 24 months for the overall vaccine manufacturing process, up to distribution (slide 6 – see below).
Let us imagine – but further sub-scenarios will be necessary here actually – that efforts will be made and succeed at speeding up this process and reduce it to 20 months. This brings us to November 2022. And then a mass vaccination campaign must start. We shall leave this part aside for now, but it is nonetheless important to underline that a mass immunization campaign is not a small endeavour (e.g. WHO “Aide Mémoire – To ensure the efficiency and safety of mass immunization campaigns with injectable vaccines“)
Here, we must wonder about the number of doses that need to be injected for immunization. We must wonder about the length of the immunization. If ever the SARS-CoV-2 mutates and changes every year, as with the flu, or if it does not, we have different scenarios in front of us.
In the best of case, we can imagine that only one dose needs to be injected, and that immunization will last for years. We may also assume that herd immunity can be reached with only 70% of the population receiving the vaccine (a crude estimate of what is considered as necessary for the influenza, see, Kenneth A.McLean, Shoshanna Goldin, Claudia Nannei, Erin Sparrow, Guido Torelli, “The 2015 global production capacity of seasonal and pandemic influenza vaccine“,Vaccine, Volume 34, Issue 45, 26 October 2016, pp. 5410-5413; “Community Protection“, table in Paul E.M. Fine, … W. John Edmunds, in Plotkin’s Vaccines (Seventh Edition), 2018).
In these conditions, as a crude approximation, we may need a production of 70% x 7,7 billion = 5,39 billion doses to immunize the world against the SARS-CoV-2.
Various scenarios of collaboration and possible international tensions related to this production may thus also need to be built.
In any case the evolution of the vaccine process must be closely anticipated and monitored for action as no nation and no government will be there able to afford a situation looking like what happened with face masks.
As a conclusion, a first crude estimate of a best case scenario for the vaccine suggests that we shall have to wait until winter 2022-2023. This assessment includes many unknowns that we must handle through scenarios, monitoring and ongoing revision. Furthermore, completely unpredictable events, can also occur, such as a mutation of the virus towards less lethality for example, to be optimistic.
We have progressed into building the overall structure of our scenario tree. We also have a timeframe. Meanwhile, this timeframe also tells us that we cannot sit and wait for a vaccine. At this very early stage of our work, the years ahead for the surviving system or surviving stage, will likely need to include a vast array of imaginative solutions, mixing isolation and lock down, new ways of organisation and production, improved personal protection, new technological capabilities such as artificial intelligence, and, critically, antiviral prophylaxis and treatment.
We shall look next at main potential antiviral treatment including the chloroquine that generates so much hope (e.g. Zhonghua Jie He He Hu Xi Za Zhi. 2020 Mar 12;43(3):185-188. doi: 10.3760/cma.j.issn.1001-0939.2020.03.009 “Expert consensus on chloroquine phosphate for the treatment of novel coronavirus pneumonia”; Jianjun Gao, Zhenxue Tian, Xu Yang, “Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies“, BioScience Trends, 2020, Volume 14, Issue 1, Pages 72-73, Released March 16, 2020, [Advance publication] Released February 19, 2020).
*For vaccines, the 2017 created Coalition for Epidemic Preparedness Innovation (CEPI) identifies five steps: Discovery, Development /licensure, Manufacture, Delivery/stockpiling, Last mile.
Further detailed bibliography
Anderson, Roy M, Hans Heesterbeek, Don Klinkenberg, T Déirdre Hollingsworth, “How will country-based mitigation measures influence the course of the COVID-19 epidemic?" - 柳叶刀》杂志 – Published online March 09, 2020
Pang J, Wang MX, Ang IYH, Tan, SHX, Lewis RF, Chen, JI, Gutierrez RA, Gwee SXW, Chua PEY, Yan Q, Ng XY, Yap RKS, Tan HY, Teo YY, Tan CC, Cook AR, Yap JCH, Hsu LY, “Potential Rapid Diagnostics, Vaccine Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review,” J. Clin. Med. (2020) 9(3), doi: 10.3390/jcm9030623 (received 13 February 2020 ).
Wu, F., Zhao, S., Yu, B. 等人。 A new coronavirus associated with human respiratory disease in China. 自然界 579, 265–269 (2020), 3 February 2020. https://doi.org/10.1038/s41586-020-2008-3.
Thevarajan, I., Nguyen, T.H.O., Koutsakos, M. 等人。 患者康复前的伴随性免疫反应的广度：非严重COVID-19的案例报告. 医学 (2020). https://doi.org/10.1038/s41591-020-0819-2
Zheng, Y., Rodewald, L., Yang, J. 等人。 The landscape of vaccines in China: history, classification, supply, and price. BMC Infect Dis18, 502 (2018). https://doi.org/10.1186/s12879-018-3422-0