Are we at the beginning of a fifth wave of the COVID-19 pandemic? If yes, is it dangerous and should we be worried about it? Alternatively, is the COVID-19 pandemic over? Has the COVID-19 pandemic evolved towards an endemic illness that is not more dangerous than the seasonal flu? Meanwhile, have we just accepted COVID-19 related death as a fatality, not worth our concern?
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How we “live with the COVID-19”, with different policies according to countries, will vary according to the responses we give to these questions. Success will depend upon the way our answers are adapted to the reality of the COVID-19 pandemic and its evolution in the future.
This article focuses on a global fifth wave of the COVID-19 pandemic. We assess it is likely the fifth wave has just started. We give possible estimates for its length and look at the factors that will shape this wave, namely anti COVID-19 restrictions and travel policies, vaccination and length of immunity, and finally the emergence of variants.
The next article will focus on possible impacts and consequences of this wave.
The dawn of a fifth wave: the emergence of a global periodicity
A couple of indications converge to warn us about the very likely start of a fifth wave of COVID-19, globally.
If we observe the overall statistical trends of the pandemic, using a seven-day average (the yellow line), we see the following graph.
The first wave or a global contamination rise – December 2019 to 9 October 2020
The first wave actually looks like a very large and long wave that did not recede. More than a wave, we can take the analogy of a global sea level rise. It corresponds to the time it took to the virus to spread globally and cover the world with a certain amount of infections and death. It lasted from the start of the pandemic until the beginning of October 2020.
The four months waves
Then, around 10 October 2020 started a second wave with a steep increase of cases (and of deaths) and a summit reached around 14th January 2021. That wave lasted until approximately 18 February, when we reached a dip in infections. At that time, the tides turned and infections started rising again. The second wave thus lasted approximately 4 months.
The next wave started on 18 February 2021, was at its top approximately on 29 April and then decreased until 20 June 2021. Here again, the wave lasted almost exactly 4 months.
The fourth wave started on 20 June 2021, reached a peak on 18 August 2021, and has been decreasing since, until around 20 October 2021. (Nota 3 November 2021: with the statistical updates, to date, infections reached a low on 17 October 2021 at 300.399 and then started rising again).
Even though two, almost three, instances are insufficient to make deductions that are certain, we can nonetheless make the hypothesis that, globally, a pandemic COVID-19 wave lasts four months. Considering the variation found in individual countries, it is amazing to observe such a regular periodicity globally. Once more, as for other phenomena, this pleads towards also adopting a global and systemic perspective on the pandemic, its evolution and its dynamics.
This global periodicity would vary according to simple mechanistic measures against the virus (masks, quarantines, social distancing, lockdown, and hinderance of travels), vaccination and its efficiency – and in the future possibly forthcoming treatments – and strength and length of induced immunity, and virulence and power of infection of variants.
The fifth wave is likely to last from 20 October 2021 to 20 February 2022
If the four months hypothesis is correct, then around 20 October 2021 we should have seen the start of the fifth wave. We are currently at this moment when the number of infections globally are at their lowest but when then nonetheless have started rising again.
Assuming none of the current conditions change, the fifth wave would reach a summit between 20 December 2021 (4th wave shape) and 20 January 2022 (2d wave shape) and then decrease until around 20 February 2022.
The main factors influencing the global shape of the pandemic wave
Let us see now how the various influencing factors are likely to play out
Worldwide relaxation of anti COVID-19 restrictions?
Flexible restrictive measures rather than relaxation
Globally, we are seeing a trend towards relaxing as much as possible various anti COVID-19 measures, called non-pharmaceutical interventions.
Countries try to get rid of masks, promise not to implement lockdown anymore, to stop quarantines and restrictions on travel for vaccinated people.
As examples, we have Australia changing it policy towards less restrictions (Frances Mao, “Why has Australia switched tack on Covid zero?“, BBC News, 3 September 2021).
Meanwhile, the UK government stresses that now the economy comes first. Indeed, according to The Times:
“British finance minister Rishi Sunak said there must be no return to “significant economic restrictions” despite a recent increase in COVID-19 cases in the country.”Reuters, quoting The Times, “UK’s Sunak rules out return to major COVID restrictions -The Times”, 23 October 2021
The UK government indeed reasserts its COVID-19 policy despite demands by scientists to return as quickly as possible to anti-Covid-19 restrictions (e.g. Associated Press, “Scientists urge UK to prep rapid return of COVID measures“, Euronews, 22 October 2021; Skynews, “UK ‘dilly-dallying into lockdown’ – take Plan B action now, warns government adviser“, 23 October 2020).
Likewise, South Korea having vaccinated 70 % of its population aims at removing most constraints apart from face masks by February 2022 (Sangmi Cha, “South Korea plots course to scrapping COVID curbs by early 2022“, Reuters, 26 October 2021).
Travel restrictions are removed or relaxed as much as possible, as in Singapore, Malaysia and Thailand or Canada, that “drops travel advisory” (The Hill, 24 October, 2021; e.g. “Malaysia and Singapore ease international travel restrictions in pivot to living with Covid“, CNN, 11 October 2021; “Singapore launches quarantine-free travel to 10 countries“, Financial Times, 19 October, 2021; Reuters, “Thailand announces reopening rules for tourism reboot“, 22 October 2022), etc.).
Starting 8 November 2021, the U.S. imposes “vaccine requirements for most foreign national air travelers” whilst also “lifting severe travel restrictions on China, India and much of Europe” (David Shepardson, “Biden imposes new international travel vaccine rules, lifts existing restrictions“, Reuters, 26 October 2022)
That said, the trend towards relaxing non-pharmaceutical interventions may, actually, be a subjective feeling generated by a propensity of Western media to focus on changes and novelty.
To assess more objectively the situation, let us look at the Stringency Index, “a composite measure based on nine response indicators” to the COVID-19 developed by “Our World in Data” and based on the Oxford COVID-19 Government Response Tracker.
The video above shows we are still far away from the world as it was before the pandemic. Policies against the COVID-19 are less stringent they may have been, notably during the first semester of 2020 after the start of the pandemic, but they are still operative.
It also emerges that even though countries may try to relax their anti-COVID-19 measures, they reinstate them relatively rapidly when the COVID-19 starts spreading again and hospitalisations and deaths increase. This was the case in Israel when the fourth wave started (Israel to reinstate indoor mask mandate next week as COVID-19 cases keep rising, 24 June 2021; Statement by PM Bennett, 22 July 2020.
This is now the case in Germany, on some travels: “Travel Restrictions Tighten Up for Arrivals From Bulgaria, Croatia, Singapore, Cameroon & Congo” (22 October 2021).
This is also the case in the Netherlands where the government plans new restriction to face an increase in infections and hospitalisations, mainly so far among unvaccinated people (Reuters, “Dutch consider new coronavirus curbs as infections soar“, 25 October 2021).
Current vaccination as a blank cheque: an open door to increasing the global circulation of the virus?
Fundamentally, full vaccination of the most efficient vaccines tends to be seen as the condition, necessary and sufficient, towards a return to normalcy. The new order relative to travel restrictions President Biden signed on 25 October 2021 perfectly exemplifies this belief (White House, “A Proclamation on Advancing the Safe Resumption of Global Travel During the COVID-19 Pandemic“). The vaccines authorised for entry in the U.S. are those the U.S. regulators or the World Health Organization recognise, which means that the Chinese Sinopharm et Sinovac vaccines are accepted, while the Russian Sputnik and other Chinese vaccines are still under review (“Status of COVID-19 Vaccines within WHO EUL/PQ evaluation process“, 20 October 2021). Mixed-dose coronavirus vaccines will also be accepted (Reuters, Ibid.).
Yet, our understanding of contagion and transmission in vaccinated people is still imperfect and inconclusive, as detailed in the US CDC “Infections in fully vaccinated persons: clinical implications and transmission” in Science Brief: COVID-19 Vaccines and Vaccination – update 15 September 2021. Notably, even if the strength of the contagion potential among vaccinated people remains unclear, studies show that transmission and contagion continue (Ibid.). The efficiency of the vaccines is especially assessed for severe form of COVID-19 – with the aim to prevent hospitals being overwhelmed – and deaths. Data are rarer and show less efficiency of vaccines against “symptomatic disease” in general or “infection” (e.g. Qatar study: 80% of effectiveness of COVID-19 vaccination against asymptomatic SARS-CoV-2 infection, Delta variant, for Moderna, but 36% for Pfizer-BioNTech, Ibid.).
As a result, to consider vaccination as a blank cheque, if no other measure is applied, actually favours the global circulation of the virus rather than restricts it.
Vaccination and its efficiency
The case of Israel
Let us look now at the pattern of the pandemic waves in Israel, as a case study. Having reached a high level of immunization in its population early, Israel is in advance on other countries and provides us with advanced warning of what could happen elsewhere.
On the graph above, we see that, in Israel, vaccination lengthened the time during which infections were at a low level. Rather than having a dip of a few days between the third and the fourth wave, we have a very low level plateau lasting between 9 April and 2 July – i.e. 3 months.
This low level plateau results from the meeting and dynamics of various forces: vaccination and length of the induced immunity, relaxation of non-medical measures and, on the other hand, the dynamic of the virus.
Before the end of the fourth wave Israel started an aggressive campaign of vaccination for a third dose (“Over 1 million Israelis who haven’t had 3rd dose to lose Green Pass on Sunday“, Times of Israel, 28 September 2021). Plans are made to reopen borders only according to relatively stringent conditions, notably a full vaccination scheme (two doses or one accordingly) that is less than six months old, or full vaccination with a third dose (“Hoteliers doubt eased tourist rules will make a difference“, Times of Israel, 24 October 2021).
During the fourth wave, deaths were lowered compared with the previous waves, but only approximately by half. Between 20 June and 25 October 2021, cumulative deaths went from 6427 to 8049, i.e. 1622 people died during the fourth wave.
The start of the fourth wave in Israel stems from two major factors related to vaccination. First, vaccination induced immunity starts to falter after 4 months for milder forms of the disease even so efficiency remains strong for most severe form of the illness for most probably six months (e.g. Matthew Loh and Hilary Brueck, “Pfizer’s COVID-19 protection against infection may wane in months, but it still prevents hospitalization and death for at least 6, new studies suggest“, Insider, 8 October 2021). After six months, data from an Israeli study shows that immunity is “substantially” lowered (Ibid.). Meanwhile, vaccination does not stop contagion, but only reduces it, as seen. Together, these factors mean that as soon as immunity wanes, then as the virus is present and circulates, we have a new peak in contagions, with new peak hospitalisations and deaths, true enough at a lower level than without vaccination.
Global vaccination: insufficient for an impact on the COVID-19 pandemic wave pattern
Knowing that at world level, 3,758 bn people have received one dose of vaccine, that 2,825 bn people are fully vaccinated (WHO COVID-19 dashboard), and that we are approximately 7.9 billion, then it means that only 47,56% of the world population has received at least one dose, and 35,76% is fully vaccinated.
As a result, as one dose of vaccine is quite inefficient against the virus, especially against the Delta variant – or a worse strain – and that the immunity of the fully vaccinated population has started waning, as shown in the case of Israel, it is hard to see vaccination right now having a very strong effect on the shape and pattern of the pandemic waves.
A major global effort, as many times highlighted by the WHO, must be made globally if we want to hope reducing or more boldly mastering the COVID-19 (e.g. AFP/Reuters, ‘Pandemic will end when world chooses to end it’ – WHO chief, RTE, 25 October 2021).
For the time being, if we consider the impact of the anti-COVID measures taken notably related to travel, and the relaxation endeavoured focusing on vaccination, then we can expect that the virus has started circulating more on the planet and that its circulation will increase in the coming weeks or months (actually as long as the current approach continues). As a result, first unvaccinated people will be more at risks. Then, as immunity related to vaccination wanes, as in Israel, we shall see a resurgence and probably rapid increase in cases (we shall look at prospects on lethality on the next article).
Globally, it is thus very likely (between 70% and 85%) that the coming wave will be as serious if not more so than previous waves.
We must also take into account that the second, third and fourth wave took place as borders were more closed and international travels more retrained than what may happen considering new policies. Thus, we should also envision that it is possible to see a new wave looking like the first “wave”, i.e. that would actually not be a wave but a new “global contamination rise”. In that case, the minimal global contamination reached between waves could be much higher than what we have known, and summits could be higher too. In other words, if we imagine the mass of contamination and shape of the pandemic as an iceberg, the height of the iceberg mass could be much higher with peaks over the main mass.
Furthermore, global circulation and contagion favours the emergence and then spread of variants.
The emergence and rise of variants of concern
Our main source for this part is GISAID, which maintains a global database of the genetic sequences of the pandemic coronavirus, EpiCoV, and “employs tools to assign phylogenetic clades and lineages to” these genetic sequences (website). Note that data for Russia, at the date of writing, were last updated on 1 October 2021 and thus do not account for the October 2021 rise in cases.
The variants of the first rise of the COVID-19 pandemic
The first period of “pandemic level rise” corresponded to the spread of the original virus, of its European types variants as well as other variants of concern (VoC) according to continents and countries.
The phylogeny of the SARS-CoV-2 variants is shown in the figure below as created by GISAID (access interactive image on GISAID by clicking on the picture below). We chose to use the now out dated GISAID clades to be able to see the diversity of past variants. The original “Wuhan strain” is the orange dot at the bottom left of the tree.
The second wave of the COVID-19 pandemic and its variants
The second wave corresponded to the continuous spread of the VoCs of the previous period, to which we now had to add the Alpha, Beta (South Africa) and Gamma (South America/Brasil) variants. The Alpha variant had appeared probably on 1st September 2020 in the UK and notably drove the second wave in Europe. The Beta variant appeared probably on 30 September 2020 and the Gamma variant on 10 November 2020.
The third and fourth wave of the COVID-19 pandemic and the Delta variant
The third wave corresponded to the rise and spread of the Delta variant. The Delta variant appeared probably on 5 October 2020 in India. It strongly drove the third wave and became preeminent.
The fourth wave is also coterminous with the Delta variant that has achieved predominance. The next image shows the global share of the SARS-CoV-2 variants in the world on 22 October 2021.
Variants for the fifth wave?
So far, many variants are observed and surveilled but none has emerged as capable to replace the Delta variant (see, for example, ECDC VoC dashboard).
Delta AY.4.2 aka “Delta plus”
The UK has reported a rise in a new mutation of the Delta variant, AY.4.2 or VUI-21OCT-01, dubbed “Delta Plus” (included within the Delta variant section of GISAID and without a more specific name at the time of writing).
The UK government, produced on 22 October 2021 an extra briefing “to provide information on the new Variant Under Investigation VUI-21OCT-01, AY.4.2” (Technical briefing 26 – Official French analysis using mainly the British technical briefing: “Analyse de risque sur les variants émergents du SARS-CoV-2 réalisée conjointement par Santé publique France et le CNR des virus des infections respiratoires Analyse partielle du 21/10/2021 concernant le sous-lignage AY.4.2” – 21 October 2021).
According to the most recent and complete set of data, “VUI-21OCT-01 accounts for 3.8%, 5.2%, and 5.9% of Delta cases in England in the weeks beginning 19 September, 26 September, and 3 October 2021 respectively (Ibid.).
AY.4.2/VUI-21OCT-01 would also be present in Russia that faces record infections and deaths, and a few cases were observed in Denmark and in the U.S. (Reuters, Russia puts onus on regional leaders to step up COVID fight, 27 October 2021; “Covid-19: New mutation of Delta variant under close watch in UK“, BBC News, 19 October 2021). It was also detected in India and would be present to date in around thirty countries (Malathy Iyer, “Classification of AY.4.2 forces Indian scientists into a huddle …, Times of India, 27 October 2021).
To anticipate on the next article, it is too early to worry about this variant, yet the AY.4.2/VUI-21OCT-01 is closely monitored. Change in severity and lethality cannot yet be assessed (Technical briefing 26). The new variant would appear as maybe slightly more contagious that the original Delta variant but differences do not appear so far to be considerably significant (Ibid.). Assessment will evolve with time.
And the future?
Our understanding of variants, considering the fact that it is the first time in history that a virus can circulate so far and so quickly, is still insufficient to be able to make any valid projections.
What we know is that the more a virus replicates, the higher the odds to see a variant emerging that would also be more efficient, from the virus point of view (e.g. S.A. Rella et al., “Rates of SARS-CoV-2 transmission and vaccination impact the fate of vaccine-resistant strains“, Sci Rep 11, 15729, 2021; Sarah P. Otto, et al., “The origins and potential future of SARS-CoV-2 variants of concern in the evolving COVID-19 pandemic“, Current Biology, Volume 31, Issue 14, 2021; Jessica A Plante et al. “The variant gambit: COVID-19’s next move.” Cell host & microbe vol. 29,4 2021; Vaughn Cooper and Lee Harrison, “Massive numbers of new COVID–19 infections, not vaccines, are the main driver of new coronavirus variants“, The Conversation, 9 September 2021).
Thus, a first primary factor that we must consider is contagion (Ibid.). The length during which the virus stays within an individual also matters (e.g. S.A. Rella et al., “Rates of SARS-CoV-2 transmission, …).
There are also various perspectives, currently, on the dangers an imperfectly vaccinated population constitute regarding the emergence of variants that would escape the immunity induced by vaccines (e.g. S.A. Rella et al., “Rates of SARS-CoV-2 transmission and Cooper and Harrison, “Massive numbers of new COVID–19 infections).
Some scientists stress that, currently, considering the low rate of global vaccination, new variants of concern are more likely to emerge among the non-vaccinated population (Cooper and Harrison, “Massive numbers of new COVID–19 infections). As a result, the vaccinated population is not that much at risk, and the new variants may or not be capable of evading vaccines (Ibid.).
However, an interesting model also highlights that:
“The counterintuitive result of our analysis is that the highest risk of resistant strain establishment occurs when a large fraction of the population has already been vaccinated but the transmission is not controlled.”Rella, S.A., Kulikova, Y.A., Dermitzakis, E.T. et al. Rates of SARS-CoV-2 transmission and vaccination impact the fate of vaccine-resistant strains. Sci Rep 11, 15729 (2021). https://doi.org/10.1038/s41598-021-95025-3
Assuming this result obtained through modelisation is correct and valid in reality, then it means that abandoning non-pharmaceutical interventions in largely vaccinated people, as is currently done, is a bad idea. It could indeed favour the emergence of VoCs evading current vaccines.
Thus, to this date, our knowledge is too imperfect for anticipation regarding the emergence of variants of concern. As a result, we can only monitor the through sequencing the evolution of these variants.
Meanwhile, we must also act preventatively by trying to mitigate contagion and length of infection and thus the development of variants, especially those that could escape induced immunity.
Unfortunately, this does not seem to be the direction current policies take.
As a result, it is likely we shall see other variants of concern emerging. The worst case scenario would be to see the emergence of one or many variants evading current vaccines. The capability to “rapidly” create new vaccines using technologies such as Messenger RNA (mRNA) would only partially help handling the threat, considering factors such as testing for safety, manufacturing, delivery of vaccines and then vaccination campaign.
Taken together these factors suggest that we are certainly, globally, at the start of a new wave of the COVID-19 pandemic. The exact start of the wave and its shape will vary according to country.
If measures regarding traveling continue to be relaxed and centred mainly around a simplistic understanding of vaccination, without care for related immunity and continuous spread of infection among and by vaccinated people, and if simple measures such as quarantine, notably at arrival in countries, and efficient face-masks are abandoned, then the coming wave could be worse than the previous one. In such a configuration, the odds to see new worrying variant of concerns would appear to also increase.
The flexibility various governments show to rapidly reinstate stronger and more adapted measures could let us hope that the fifth wave will be controlled.
A global planned approach must imperatively be designed and implemented if we want to move towards a future that we could truly call “post-COVID-19”.