In this article we explore the way the COVID-19 pandemic was born and, hidden, spread globally. Learning from this very early process, we deduce initial key elements and indicators to monitor and control the COVID-19 second wave and recurrent ones.
With this series of articles we are looking for ways to better estimate the likelihood of a COVID-19 second wave and of recurrent ones, as well as the timing and intensity of these waves. These are crucial elements to inform scenario-building, early warning processes, as well as design and steering of policies.
Previously, we looked at epidemiological models, which told us that a second wave, followed by others, was the most likely scenario. Yet, we also found these models did not exactly fit what was happening in East Asia, in terms of timing of the exponential rise of cases and numbers of ICU beds needed. The models also diverged regarding the severity of the second wave.
We thus need to find other factors influencing the possible start of the second wave, its velocity and lethality. We also need a system that will be able to handle recurring waves, if any.
Once we have a better understanding of the way the sanitary situation may evolve, then we may also build larger political and geopolitical foresight. Note that we are concerned with fundamental dynamics of politics and security as we explained in “什么是政治风险“.
Here, we focus on the way the COVID-19 pandemic started and on its very early development throughout the world. Looking at a situation in a forward-looking way, even using hindsight, often brings a new perspective on our understanding of dynamics and underlying processes. We apply this approach here, building upon research in and findings from genomic epidemiology and phylogenetics. We look first at the birth of the virus, its date and at its zoonotic origin and deduce a first indicator to monitor. Then, we turn to the way the virus spread, unnoticed, in the cases of the UK, the U.S., Iceland, Australia, Italy, France, and Spain. Finally, we stress a major lesson that needs to be learned: travels are vectors of choice for the pandemic. We highlight a corresponding indicator. We also underline the very different timeframes for the early spread of the virus.
A new virus is born
Date of birth
When a new virus emerges and causes a disease, as is the case with the SARS-CoV-2 and the COVID-19, it can do so undetected for the very reason that it is new. Being novel, we, human beings, do not look for it. We certainly should set up new warning systems not to be taken by surprise, but this is another topic.
In our case, with hindsight and thanks to the incredibly fast and numerous research done in phylogenetics, we may estimate that the SARS-CoV-2 was born – i.e. it jumped to humans – between 6 October 2019 and 11 December 2019 (Table 1, Lucy van Dorp et al. “Emergence of genomic diversity and recurrent mutations in SARS-CoV-2“, Infection, Genetics and Evolution, 5 May 2020).
Nota: Phylogenetics is the study of evolutionary relationships among biological entities (EMBL-EBI training platform). “A phylogeny, also known as a tree, is an explanation of how sequences evolved, their genealogical relationships, and therefore how they came to be the way they are today” (Ibid.). You can find here other definitions for phylogeny and phylogenetics.
Thus, here we are using research that establishes the genealogy of the SARS-CoV2. Screenshot of the phylogeny of the SARS-CoV-2 at different dates are presented below.
The SARS-CoV-2 belongs to the β‐coronavirus genus of the Coronaviridae family. Most scientists concur to consider the virus is highly likely of a zoonotic origin, i.e. it comes from an animal. However, we do not know yet with certainty which is the zoonotic source, even though a coronavirus hosted in the horseshoe bat shows genetical close identity (ibid.). The SARS-CoV-2 could be “a recombinant virus between bat and pangolin coronaviruses” (Jiao-Mei Huang, et al., “Evidence of the Recombinant Origin and Ongoing Mutations in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)“, bioRxiv 2020.03.16.993816).
The zoonotic origin of the SARS-CoV-2 alerts us to possible further contagion across species, which should be closely monitored. We need to monitor human-to-animal and animal-to-human contagion.
For example, on 19 May 2020, the Dutch government sent a letter to parliament highlighting that a mink-to-human contagion was likely to have taken place in one of the four Dutch infected mink farms (Wageningen University and Research, “COVID-19 detected on four mink farms“, 20 May 2020). Research is ongoing on the topic (e.g. World Organisation for Animal Health).
Even in the case such infections remain few and far between, they may nonetheless start chains of contagion and thus favour future waves. Special attention is warranted, as the WHO explains in “Reducing animal-human transmission of emerging pathogens“. Impacts on biodiversity should also not be neglected. Meanwhile large impacts on actors involved are likely.
The new virus spreads, unnoticed
At the end of the autumn 2019, we thus have a completely new virus that has infected one person, then another and another. We, as human beings of the 21st century, only start thinking that something is amiss when people start being ill, with an illness that does not exactly fit with what we know. If people start dying, then we pay even more attention. The more people are ill or dying, the more we pay attention. However, by the time we reach this stage, the new virus may have spread a lot, or not, according to its characteristics.
Visualising the early spread of the SARS-CoV-2
This is exactly what happened with the SARS-CoV-2. It spread early. In the series of the four screenshots below, you will see the phylogeny of the SARS-CoV-2 up to 23 January 2020 and the corresponding transmission map, then the same up to 26 May 2020 (application Genomic epidemiology of novel coronavirus – Global subsampling, Maintained by the Nextstrain team. Enabled by data from GISAID).
Using genomic epidemiology and phylogeny, research further explored the early spread of the pandemic.
Early spread and multiple entry points in the UK, the U.S., Iceland, Australia
In their study, Lucy van Dorp et al. (Ibid.) found that, apart for China and to a point Italy – so far – each epidemic in the countries considered – the UK, the U.S., Iceland, Australia – had “been seeded by a large number of independent introductions of the virus”. This means that we did not only have one or two “patient(s) zero”, for each of these countries, but many of them. Furthermore, the authors highlight that the spread of the virus took place very early. It would have been useful if authors had detailed further how early was early (see figure S4, in supplementary material 5, not detailed enough for our purpose).
“The genomic diversity of the global SARS-CoV-2 population being recapitulated in multiple countries points to extensive worldwide transmission of COVID-19, likely from extremely early on in the pandemic.”Lucy van Dorp et al. “Emergence of genomic diversity and recurrent mutations in SARS-CoV-2“, Infection, Genetics and Evolution, 5 May 2020
Spain: multiple entry points and possible start of circulation in mid-February
A similar phylogenetic study for Spain reached also the conclusion that the epidemic in Spain resulted from “multiple SARS-CoV-2 introductions” (Francisco Díez-Fuertes et al. “Phylodynamics of SARS-CoV-2 transmission in Spain“, bioRxiv 2020.04.20.050039).
Some of them could be traced to other European countries. Once in Spain, at least “two [SARS-CoV-2 introductions] resulted in the emergence of locally transmitted clusters, with further dissemination of one of them to at least 6 other countries”.
However, in the case of Spain, the virus introductions could have taken place between 14 and 18 February 2020 (Ibid.). This is much later than the timeframe Lucy van Dorp et al. suggested for the countries they studied (Ibid.), which is logical considering the route the virus took.
France: possible start of viral circulation between end of November 2019 and 23 December 2019
In the case of France, a new early COVID-19 case has now been found retrospectively. The patient was admitted in hospital on 27 December 2020 after four days of symptoms (Deslandes et al., “SARS-COV-2 was already spreading in France in late December 2019“, 国际抗菌剂杂志》（International Journal of Antimicrobial Agents, 3 May 2020).
The patient, without a travel history to China, was most probably infected with the SARS-CoV-2 before 23 December 2020, date of symptom onset. If we consider the probable length of incubation, then this patient could have been infected between 26 or 27 November (27 days) and 21 December 2019 (1,8 days) (for the incubation period, Stephen A. Lauer, MS, PhD et al., “The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application“, Annals of Internal Medicine, 5 May 2020). There is a higher likelihood it was infected between 7 December (15.6 days) and 21 December 2019 (1,8 days) (Ibid.).
- 红队分析周刊 - 2022年6月30日
If other cases confirm this study, then the virus could have started circulating in France well before it was officially noticed on 24 January 2020 (Deslandes et al., ibid.), and then exploded exponentially in March 2020. It is however impossible to draw immediate conclusions regarding the dynamics of the epidemic out of this sole case, because, as the cases of Spain, the UK, Iceland, the US and Australia show, France most probably knew multiple points of entry for the virus.
Italy: entry of virus between the second half of January and early February 2020 from Germany
In Italy, a study focusing on three patients from the early outbreak in Lombardy, a cluster of 16 cases reported on 21 February 2020, estimates that the “SARS‐CoV‐2 virus entered northern Italy between the second half of January and early February 2020” (Zehender G, Lai A, Bergna A, et al. “Genomic characterization and phylogenetic analysis of SARS‐COV‐2 in Italy“, J Med Virol, 29 March 2020).
The cases are all related to the 24 January 2020 asymptomatic contagion in Germany in a business meeting (Ibid.), as also found by Stefanelli et al. (“Whole genome and phylogenetic analysis of two SARS-CoV-2 strains isolated in Italy …“. Euro Surveill. 2020;25(13)). Genetically, Stefanelli et al. show that the viral clade in Lombardy is not directly related to the viral cluster of the Chinese tourists diagnosed in Rome on 29 January 2020 (Ibid.).
Lessons Learned and Indicators
The phylogenetic country studies we sampled here highlight crucial points in our quest for indicators regarding COVID-19 waves. Some of this points may be obvious or common sense, however, in the light of policy-decisions taken, it is worthwhile stressing them again.
Travels matter for the spread of a pandemic
Unsurprisingly, human travels, whatever the motivation, are the way through which the virus spreads. Actually, the virus spread internationally, thanks to our way of life, very early in the pandemic. Indeed, apart from Spain and Italy, the virus could have spread before China identified it faced a new coronavirus on 7 January 2020 (WHO first situation report), and before the WHO published its first situation report on 21 January 2020 (Ibid.).
On 27 January, the WHO advised “against the application of any restrictions of international traffic based on the information currently available on this event” With hindsight, had the WHO, on the contrary, advised against travels and been followed by all countries, then probably some countries, but not all, would have averted the pandemic.
Considering, however the ideological and economic emphasis on trade and travels, it was near-impossible for political authorities, be they international or national to decide to close all borders that early.
Because of the multiplication of virus entry points throughout countries so early in the pandemic process, then the travel restrictions’ measures that were initially solely directed against China – the country of visible outbreak – were insufficient. They probably contributed nonetheless to lower the number of infections. Hence, the timing of the exponential rise of COVID-19 cases was possibly delayed.
Yet, what should have been done is to apply pandemic-types measures, such as quarantines, to all travels immediately. Of course, because at the time we had no idea about the SARS-CoV-2 and the COVID-19, that was impossible. The only alternative would thus have been to completely close all borders.
As a result, considering the possible multiplication of new diseases in the future, because of climate change and loss of biodiversity, we may imagine that free intensive international travels as we have known will increasingly be something of the past. Assuming this is possible, and beyond the framework of the COVID-19 pandemic, a completely new system integrating both travels and more frequent and intense new diseases needs to be created.
COVID-19 social distancing exit strategies and travels: a second wave indicator
In Europe and the Middle East notably, we are facing multiple decisions across countries to reopen borders, in a way or another, in May, June and July 2020. Meanwhile, some travels will be authorised as exit strategy are implemented (e.g. Michelle Baran, “When Will We Be Able to Travel to Europe?“, AFAR, 14 May 2020; “Coronavirus: Emirates announces limited passenger flights for May“, Khaleej Times, 30 April 2020; “Press conference of the Croatian Minister of the Interior Davor Božinović: Croatia wants to open borders for business travellers for urgent personal and economic reasons after the COVID-19 pandemic caused by SARS-CoV-2 as of 11 May”, Seahelp, 9 May 2020, etc.).
In the light of the initial spread of the pandemic, these decisions to reopen borders and to re-authorise travels appear highly dangerous if we are not certain that very strict anti-COVID-19 measures, considering all parameters, are implemented. In the next article we identify these parameters: see 传染的动力和COVID-19的第二波行情 – last part, the case of quarantine for arrivals on a territory.
Should holes in the surveillance net exist, then the virus will spread again. Thus, assessing travel reopening’s decisions and related measures in the light of what we know on the virus and the illness it causes will be an excellent indicator to estimate the possibility and intensity of the second wave. We shall need to assess and monitor this indicator not only nationally, but also possibly at company level, according to types of travels and routes.
A still elusive timing
As far as timing is concerned, the early start of the pandemic could suggest a longer timeframe for the period from the start of contagion to outbreak, i.e. cases starting to rise exponentially that are difficult or impossible to control.
If some identifiable trend emerged, then we could use it to crudely assess the start of a second wave and recurrent ones. Indeed, we could make an analogy between the very start of the COVID-19 and the situation post-social distancing exit, because most of the time, in the post-first wave framework, we do not know exactly how many people are infected and even less who is infected. The assessment would be crude, however, because, two differences between the start of the first wave and the post-first wave world operate in opposite directions. First, the number of infected people is much higher than at the very start of the pandemic, so the timeframe we would obtain would have to be shortened. On the other hand, we now have knowledge that did not exist and use measures that could not implemented at the very beginning of the pandemic. This should lengthen the time to a new possible outbreak, and even possibly make such an outbreak impossible.
To estimate the time it took between early infection and “start of outbreak proper”, we use the findings we collected earlier, and create the following table. We use the threshold of 50 identified cases of COVID-19 for the “start” of each national outbreak.
|Estimated date for early infections||Start of “outbreak”||Time to “outbreak”|
|中国||between 6 October 2020 and 1st December 2020||95 cases on 23 January||between 54 and 109 days|
|意大利||between the second half of January and early February 2020||93 cases on 23 February||between 23 and 38 days|
|法国||between 26 or 27 November (27 days) and 21 December 2019||61 cases on 2 March||between 71 and 96 days|
|西班牙||between 14 and 18 February 2020||57 cases on 4 March||between 10 and 14 days|
Unfortunately, we obtain wide differences between countries, which is not very helpful for our purpose. Furthermore, we are not sure that all early cases have been identified and accounted for in each country, apart from China. We thus have to look for other approaches and factors if we want to find a useful way to improve our assessment of the timing of a second wave.
This is what we shall do with the next article, while continuing to identify useful indicators regarding the second wave and possible other waves.
Detailed Bibliographical References
Deslandes, A., V Berti, Y Tandjaoui-Lambotte MD, Chakib Alloui MD, E Carbonnelle MD, PhD, JR Zahar MD, PhD, S Brichler MD, PhD, Yves Cohen MD, PhD, “SARS-COV-2 was already spreading in France in late December 2019“, International Journal of AntimicrobialAgents, 3 May 2020, doi: https://doi.org/10.1016/j.ijantimicag.2020.106006
Díez-Fuertes, Francisco, María Iglesias Caballero, Sara Monzón, Pilar Jiménez, Sarai Varona, Isabel Cuesta, Ángel Zaballos, Michael M Thomson, Mercedes Jiménez, Javier García Pérez, Francisco Pozo, Mayte Pérez-Olmeda, José Alcamí, Inmaculada Casas, “Phylodynamics of SARS-CoV-2 transmission in Spain“, bioRxiv 2020.04.20.050039; doi: https://doi.org/10.1101/2020.04.20.050039.
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Lauer, Stephen A., MS, PhD; Kyra H. Grantz, BA; Qifang Bi, MHS; Forrest K. Jones, MPH; Qulu Zheng, MHS; Hannah R. Meredith, PhD; Andrew S. Azman, PhD; Nicholas G. Reich, PhD; and Justin Lessler, PhD, “The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application“, Annals of Internal Medicine, Vol. 172 No. 9, 5 May 2020, https://doi.org/10.7326/M20-0504.
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Featured image: Mexican free-tailed bats exiting Bracken Bat Cave – Nota: these bats are not those considered so far for the SARS-CoV-2 – The picture was chosen from an art and aesthetic point of view – photo credit: USFWS/Ann Froschauer / [Public Domain]