(Art design: Jean-Dominique Lavoix-Carli
Photo: torstensimon)

The world has started a race for immunisation against the COVID-19. Vaccines are now perceived as the universal panacea, the miracle that will save us all from the pandemic. We shall, finally, be able to find back our old life. Are we right to hope? Or are we likely to discover it was a mirage?

Our objective here is to estimate roughly when, considering current vaccination rates, the countries most advanced in terms of immunisation campaigns could reach herd immunity. In other words, when will our hopes become reality?

First, we highlight that our hopes are grounded in reality because of the success of past vaccination campaigns. However, our perception of the timeframe necessary for vaccination success is likely distorted. Second, we highlight six major uncertainties we still face regarding the vaccination against the COVID-19. We use here a “red team” approach, i.e. we ask all questions, even or rather especially disruptive ones.

Finally, we estimate how long selected countries, from the U.S. to Israel through Russia, China or the U.K., Germany and France, need to reach herd immunity at current daily vaccination rates. Results are very contrasted, and for many countries, the time to herd immunity must be counted in years rather than in months.

This estimate tells us if it is realistic to hope or, on the contrary, if we are facing a mirage. Different strategies and planning will need to be designed accordingly.

A hope grounded in reality

Vaccination successes

Certainly proper vaccines, those to which we are used and stemmed from the research of Jenner, Pasteur and Koch over the 18th and 19th century have done exactly what we hope. They saved humanity from some deadly diseases (Agnes Ullmann, “Louis Pasteur“, Encyclopedia Britannica, 15 Jan. 2021).

Vaccination eradicated smallpox (Edward A. Belongia and Allison L Naleway, “Smallpox vaccine: the good, the bad, and the ugly”, Clinical medicine & research vol. 1,2, 2003). Poliomyelitis is almost also a disease of the past. In 2020, the wild poliovirus type 1 only still affects two countries, Pakistan and Afghanistan, while type 2 and 3 are apparently eradicated (WHO/OMS Poliomyelitis (polio)).

Thus, our hope is grounded in this vision of vaccines and immunisation and their real success.

Eradication campaigns are long processes

Our hope seems also, implicitly, to think that the return to normal will happen tomorrow. At worst, we think we shall move back to our old life within maybe six months.

Yet, as far as eradication is concerned, decades were needed for the mass vaccinations’ campaigns achievements, not months.

The modern vaccine against smallpox was developed in the 1950s and the first global eradication effort started in 1950. In 1966, smallpox still remained endemic in 33 countries (DA Henderson, “The eradication of smallpox“, Sci Am. 1976 Oct; 235(4):25-33). The WHO launched a new global effort in the early 1970s (Belongia and Naleway, Ibid.). The last case of smallpox occurred in 1977 in Somalia (Belongia and Naleway, Ibid.). Thus, it took 27 years to eradicate smallpox.

The vaccine against polio was licensed in 1955, after a massive trial in the U.S. involving 1.3 million children in 1954 (Immunology and Vaccine-Preventable Diseases – Pink Book – Polio – U.S. CDC). In the U.S., immunisation started in 1955 (Ibid.). The last outbreak in America occurred in 1979 (Ibid.). By 1994 polio was eliminated from Western countries (Ibid.). Thus, in this case, and only for Western countries, it took 40 years to eliminate polio.

Mass immunisation and eradication campaigns are not small matters but, on the contrary, complex endeavours (e.g. WHO “Aide Mémoire – To ensure the efficiency and safety of mass immunization campaigns with injectable vaccines“).

Furthermore, up until the COVID-19 pandemic, to develop a new safe vaccine – i.e. also considering as much as possible longer term effects – demanded between 10 and 15 years (The History of Vaccines by The College of Physicians of Philadelphia: “Vaccine Development, Testing, and Regulation“, January 2018).

Now, faced with the COVID-19 pandemic, a threat with completely novel characteristics, we want the disease to disappear very quickly. We want to go back to business as usual. So, we rush and we hope, regardless of reality. And we rush so much that we run the risk of reaching a mirage rather than salvation.

Certainties and uncertainties

Here, we shall consider the various major certainties and uncertainties we face regarding the vaccine. They constitute our framework.

We set aside the critical question regarding the middle and long term safety of the vaccines. This question cannot be answered with certainty. Indeed, humanity does not have the temporal depth necessary to give such an answer. The precautionary principle should certainly have demanded that time be allowed to consider safety. The early twenty-first century globalised, financialized, and libertarian consumerist society chose otherwise.

Certainty: Number of injections required

Approved vaccines protect with various efficacy against severe forms of COVID-19, if the tested posology is respected (number of doses and time between two shots). Details on the various vaccines used at the start of 2021 can be found on various official websites, such as the WHO, the European Medicines Agency (EMA).

In the estimate below, we shall not differentiate between vaccines according to efficacy. We shall consider the two doses required in the original posology. Indeed, all COVID-19 vaccines used at the start of 2021 demand two injections: Pfizer and BioNTech, Moderna, AstraZeneca, Russian Sputnik V, Chinese CoronaVac (note that the latter shows mixed results, including a low 50.4% effectiveness, Smriti Mallapaty, “China COVID vaccine reports mixed results — what does that mean for the pandemic?“, Nature, 15 January 2021). Further studies should definitely include variations in terms of efficacy, according to the types of vaccine delivered.

Uncertainties

1/ Delay between required injections

If the delay between the required two injections is increased, we do not know what can happen. We could only make hypotheses and scenarios, each with different likelihoods. Nothing may change regarding efficacy, but efficacy may also be lowered. Other less palatable scenarios can be imagined, according to which people may become more susceptible to other variants, or the delay may favour the occurence of variants.

Here, we shall consider that the time required between two injections, as planned by the laboratory, is not stretched but respected.

2/ It is likely that the vaccines do not stop contamination.

We do not know with certainty if the vaccines stop infection. However, because it does not seem that most vaccines stop asymptomatic types of COVID-19, then it is likely that contamination will continue, even after vaccination (e.g. EMA, “COVID-19 : Le vaccin rend asymptomatique mais rend-il moins infectieux ?” Santélog, 4 January 2021).

A study from Israel, which is massively vaccinating its population, gives us further indications, for the Pfizer-BioNTech vaccine (Clalit study: decreased infection in the corona due to the vaccine. 13 January 2021; Elisabeth Mahase, “Covid-19: Reports from Israel suggest one dose of Pfizer vaccine could be less effective than expected“, BMJ 2021;372:n217). People over 60 who received one dose remained as susceptible to infections for 13 days. Then the likelihood to become infected dropped by 33% between day 14 and day 17. In other words, after one vaccine shot and after 13 days, the likelihood to become positive to the COVID-19 is 67% of what it was without vaccination. Thus, after one dose, the potential for contagion remains unchanged for almost two weeks, then remains very high compared with no vaccination.

We do not have further indication about what happens after the second dose.

Vaccines may reduce infection but, fundamentally, we do not yet know.

Thus, for the time being, people who will have been vaccinated will need to go on wearing masks, and using protective social distanciation, at least until the famous herd immunity is reached.

As a result, if your main interest is to go back to the global world we knew before the COVID-19 pandemic, you need to wonder when all countries in the world will reach herd immunity thanks to developed vaccines. Because, for the time being and considering current vaccines, before then there will be no return to “normal”.

You may be more modest – as well as cynical – and only hope to see some countries, yours and these countries that are your major partners – to reach herd immunity. You would then start creating this international COVID-19 world with COVID-19 safe bubbles that we see possibly emerging (Helene Lavoix, “The emergence of a COVID-19 international order“, 15 June 2021). You may even change partners according to their sanitary situation, of course to a point, the point to which you need specific countries for various reasons.

3/ Immunity

We know more on immunity than we knew at the start of the pandemic in January 2020. According to a large study the British NHS carried out, people who have had the COVID-19 have a 83% lower risk of infection for at least 5 months and a 94% lower odds of symptomatic infection (Public Health England, Press release, “Past COVID-19 infection provides some immunity but people may still carry and transmit virus“, 14 January 2021; V Hall, et al., “… Large multi-centre prospective cohort study (the SIREN study), England: June to November 2020“, medRxiv 2021.01.13; Heidi Ledford, “COVID reinfections are unusual — but could still help the virus to spread“, Nature, 14 January 2021).

However, the next stage of the study also shows that it is likely that the reinfected individuals can also continue infecting others.

Unfortunately, we do not know if the immunity obtained with one variant of the virus protects from another variant, and if this varies according to variants.

We may hope that the immunity induced by vaccines is better than natural immunity, but again this is an unknown.

Thus, considering this still imperfect knowledge, if we want to stop or, more humbly, control the pandemic with certainty, we would need to obtain a herd immunity in 5 months. If a longer lasting immunity can be obtained, then the time to reach herd immunity can be lengthened.

4/ Herd immunity and the SARS-CoV-2

If we use the WHO definition,

“‘Herd immunity’, also known as ‘population immunity’, is the indirect protection from an infectious disease that happens when a population is immune either through vaccination or immunity developed through previous infection.

…Vaccines train our immune systems to create proteins that fight disease, known as ‘antibodies’, just as would happen when we are exposed to a disease but – crucially – vaccines work without making us sick. Vaccinated people are protected from getting the disease in question and passing on the pathogen, breaking any chains of transmission.”

WHO, “Coronavirus disease (COVID-19): Herd immunity, lockdowns and COVID-19“, 31 December 2021

Thus here, a critical unknown appears considering what we saw on immunity and contamination after vaccination. It would indeed appear that, for the COVID-19, neither natural immunity nor vaccines fully break the chain of transmission. The efficacy of the way the chain of transmission is stopped seems to be varying and complex.

In other words, considering contamination is not stopped or imperfectly stopped by the vaccine, do we need to rephrase statement of the WHO according to which “We think it needs at least 60 to 70% of the population to have immunity to really break the chain of transmission”? Indeed, in the case of the SARS-CoV-2 the chain of transmission is not broken or imperfectly broken by the vaccines.

If we contrast, for example with the vaccine against polio, here is what we read from the WHO website, contrasting between two types of vaccines, IPV and OPV:

“Inactivated polio vaccine (IPV) … prevents infection, but it does not stop transmission of the virus….The oral polio vaccine (OPV)… After three doses of OPV, a person becomes immune for life and can no longer transmit the virus to others if exposed again. Thanks to this “gut immunity”, OPV is the only effective weapon to stop transmission of the poliovirus when an outbreak is detected. “

WHO Europe, “Poliomyelitis (polio) and the vaccines used to eradicate it – questions and answers“, 8 April 2016

IPV is increasingly used only in countries where eradication of polio has taken place (Ibid.).

To come back to the COVID-19, the vaccines we develop are similar, everything being equal to the IPV. And thus not that good for outbreaks…

Hence, is the way herd immunity is planned to be applied still valid? Can we apply the same objectives as thought?

We shall still use the current approach to herd immunity in our rough assessment below but it is critical to think that a different approach may be sought.

5/ Manufacturing and delivery

Manufacturing and delivery problems, as well as logistical difficulties are a major uncertainty. This is all the more so that competing interests exist. For example, we may wonder if the American policy promoted by new President Biden, with first his pledge to administer 100 million shots in his first 100 days then his willingness to boost further vaccination in the U.S., did not have and will not have direct consequences on European delivery problems (e.g. Josh Wingrove and Mario Parker, “Biden Team to Buy 200 Million More Doses, Speed Up Vaccinations“, Bloomberg, 26 January 2021; Raf Casert, “EU demands that vaccine makers honor their commitments“, AP, 25 January 2021).

Manufacturing and delivery challenges are partly included in the current daily rates of vaccination we use below. Further detailed research would, of course, be needed to improve estimates, to finely identify specific chokepoints and thus to design efficient strategies and vaccination campaigns.

6/ Vaccines and SARS-CoV-2 variants

Variants and Vaccines efficacy

Some of the vaccines currently injected may not be efficient or as efficient as expected against some variants.

It would seem that the UK variant – known as 20B/501Y.V1, VOC 202012/01, or B.1.1.7 lineage (CDC) does not question the current vaccines, to the least those by Pfizer and BioNTech, Moderna, and AstraZeneca. However these tests have been carried out mainly in vitro.

Things look less good for the South African variant – 20C/501Y.V2 or B.1.351 lineage (CDC). For example, Moderna, after in vitro tests, found that “The samples’ neutralizing antibodies were … only about one-fifth to one-tenth as effective at neutralizing 501YV.2” (Nature News, “COVID research updates: Moderna vaccine vanquishes viral variants“, 26 January 2021 update).

We do not know for the Brazilian variants – one, known as P.1 (CDC), while another variant could exist too.

Another study, carried out by the Rockefeller University and not by vaccines manufacturers, looking at main vaccines and various possible mutations found that “Some of these neutralizing antibodies [produced after injections] … were only one-third as effective at blocking the mutated variants” (Ibid., 21 January 2021 update).

In the middle of these uncertainties, what we know is that if three identified and challenging variants could emerge, then others will too. We must thus include these emergence in the way we plan ahead. For example, the speed with which variants appear and become prevalent would be a key data to obtain for immunisation campaigns. According to the ECDC, the UK and South African variants needed between 1 and 4 months to spread and become prevalent (Risk related to the spread of new SARS-CoV-2 variants of concern in the EU/EEA – first update, 21 January 2021). But how often will how many variants appear per year and where?

Furthermore, we may wonder if the way and the speed with which the current vaccines will be injected within the population could possibly favour new variations of the SARS-CoV2. We are here in the classical action-reaction dynamic.

Multiple vaccines injections?

If new versions of the vaccines are necessary against new variants, we do not know what could happen to the immune system of people having received the “old” vaccines. Can they receive the new vaccine? Will it be dangerous? Will it be efficient? What could be the long term side-effect? How many different injections and how often can be safely handled by people’s systems?

Increased manufacturing challenges

Companies developing ARN messenger vaccines may assert that they can change their formula rapidly to adapt to the new variants if need be. Nonetheless, this means throwing away doses already produced and starting manufacturing everything from the start. The manufacturing challenges are thus heightened.

Manufacturing boosters, as Moderna suggested may be a way forward, but only if this is a sufficiently efficient approach (Nature, 26 January, Ibid).

How long to obtain herd immunity?

Now we have all these uncertainties in mind, let us look at the time needed to vaccinate the population of various countries to obtain herd immunity.

Using “Our world in data: Coronavirus (COVID-19) Vaccinations“, we obtained the number of months that would be needed to reach herd immunity, considering cumulated vaccinations and current daily rates of vaccination. We look at three hypotheses for herd immunity: 70%, 75% and 80%, to consider potential changes stemming from variants.

Incidentally, as is obvious from the chart above, the sheer size of population matters. The countries faring the best are also those with a small or smaller population, apart from the U.K. and the U.S.. The price the world must possibly pay to see the U.S. being able to vaccinate its population relatively rapidly needs however to be pondered.

Nonetheless, at current rates, i.e. assuming there is no supply problems, and considering all the uncertainties above, only Israel and the U.A.E. can reach herd immunity within 6 months. The U.K. will have to wait between 8 an 10 months, while the U.S. will need between 13 and 16 months to reach herd immunity. This is easier to see on the following figure enlarged to focus on 24 months only.

If ever immunity were to drop after 6 months, or if a new variant defeating current vaccines were to appear within 6 months from the start of the vaccination campaign, then, at current vaccination rates, all countries apart from Israel and the U.A.E. would see their efforts reduced to naught. They most probably would have to restart everything without have time for respite. Those countries that would have reached immunity would have had some time with a normal life, until they too had to start vaccinating everyone.

Furthermore, it is likely that to see variants stop emerging, then we would need to stop contagion globally and see herd immunity taking place worldwide. We are obviously even further away from this goal. Thus, most probably, new variants will go on emerging. We are thus in a vicious circle where inability to stop contagion increases the likelihood to see variants appearing, which, in turn lowers our ability to stop contagion.

If disrupting variants were to appear every six months, then daily vaccination rates would have to be greatly increased to reach herd immunity for one variant.

If we do not find vaccines that stop contagion, and if new variants appear every six months, then we may find ourselves in the case shown in the figure below. We may have to vaccinate a staggering amount of people daily forever, or rather until a better solution is found.

The cost to societies, just in terms of vaccines, would be considerable. The logistics and organisation needed may also involve deep changes.

It would thus seem that, with the current approach, considering the SARS-CoV2 variants, the specificities of the vaccines available, and all the known uncertainties, we may not be close to find our old life back.

If we do not want our hopes dissolving into a mirage, we need to further innovate strategically and supplement vaccination with other measures, waiting for better and more efficient vaccines to be found.

Further detailed reference

V Hall, S Foulkes, A Charlett, A Atti, EJM Monk, R Simmons, E Wellington, MJ Cole, A Saei, B Oguti, K Munro, S Wallace, PD Kirwan, M Shrotri, A Vusirikala, S Rokadiya, M Kall, M Zambon, M Ramsay, T Brooks, SIREN Study Group, CS Brown, MA Chand, S Hopkins, “Do antibody positive healthcare workers have lower SARS-CoV-2 infection rates than antibody negative healthcare workers? Large multi-centre prospective cohort study (the SIREN study), England: June to November 2020“, medRxiv 2021.01.13.21249642; doi: https://doi.org/10.1101/2021.01.13.21249642

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Featured image: Design by Jean-Dominique Lavoix-Carli – Photo by torstensimon, Pixabay – Public Domain.

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