COVID-19 vaccine challenges: the beginning of the end?
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Vaccines have arrived – ahead of expectations, with high efficacy in clinical trials – and are now beginning mass rollouts, just, at the time of writing, as it would appear a second wave has peaked in many states. They are undoubtably a triumph of science – vaccine development typically takes years – in a time of great trial for humanity. Is this the beginning of the end of the pandemic?
It is too early to start celebrating the end of COVID-19. Vaccines are not a silver bullet. The first challenge is the rollout, not least when the first set of vaccines in the early part of 2021 needed two injections to work fully. Millions have already been immunised; billions need to be. That stretches supply and distribution chains. Some nations are ahead in their programmes and disputes around vaccine nationalism have already come to the fore. Vaccine efficacy appears good in early reports; but we do not know how long immunity will last and what booster regime will we need. Population acceptance also looks good in the early stages of rollout; but opinion polls suggest anti-vaxxers are still out there, possibly in large numbers in some states.
All the while, the virus is moving target. New, more virulent strains have already emerged, fuelling the second wave in many parts of the world. Thus far, although some questions have arisen about the effectiveness of some vaccines against some of the new variants, vaccine rollout continues to accelerate. The concern will be as yet unknown strains emerging, which evade current vaccines. Relatively minor corrections should enable the current vaccines to remain effective against variants; but bring us back to the challenge of retesting and redistributing a new vaccine.
None of this happens in a vacuum. All the while, those countries in lockdown will be planning a way out as the mental exhaustion and economic cost of life in confinement takes its toll. Moreover, viruses do not respect borders. We need international solidarity. If pockets of COVID-19 remain, possibly mutating to new strains, we all remain under threat.
Vaccines were never our only way out of the pandemic. States with pro-active, closed border, zero toleration public health regimes have largely overcome COVID-19. Excess reliance on vaccines is a gamble; one which, fortunately for us, looks like it will pay off with this pandemic.
In our last paper on vaccines, we anticipated that vaccine would be approved and available to be administered by mid-2021 under an accelerated timeframe, but the speed of the vaccine development far exceeded the expectations of the scientific community. In December 2020, first regulatory approvals were given for the Pfizer/BioNTech candidate; subsequent approvals have followed for more than half a dozen vaccines, based on a spectrum of technological approaches. Given that development typically takes many years, the speed at which vaccines have been developed has been truly remarkable.
And yet, in the first quarter of 2021, many countries are mired in a second wave of the virus, and a wave more deadly than the first – particularly in the developed nations. Vaccine development may come to mark the beginning of the end of the pandemic; but there are many hurdles the vaccines still have to overcome:
- They need to be quickly and efficiently distributed, with some vaccines having more challenging storage conditions than others;
- There needs to be sufficient supply;
- They must prove their effectiveness in real-world conditions, not just in trials;
- A major proportion of populations must be willing to accept them;
- They need to stay ahead of viral mutations, or at least be swiftly reengineered;
- They need to be managed in common public health strategy and with recovered COVID-19 patients, all to consider the reopening of public life.
Vaccine Development: Quo Vadis?
As of 19 February, national regulatory authorities have approved ten vaccines for public use in a least one country:
- Two mRNA vaccines, four conventional inactivated vaccines, three viral vector vaccines and one protein subunit vaccine (see figure 1).
- In addition, 76 vaccine candidates are in various stages of clinical research, including 46 in Phase I-II trials and 26 in Phase II–III trials. Furthermore, 223 pre-clinical candidates falling into nine different product categories are under further evaluation for clinical development1.
- In the US, Canada and the EU, the two leading mRNA vaccines – tozinameran from Pfizer/BioNTech and mRNA-1273 from Moderna – received full regulatory approval throughout December 2020 and early January 2021. It is noteworthy that mRNA vaccines had never been approved before for human use.
- In the UK, the Pfizer/BioNTech as well as the adenovirus vector based AZD1222 vaccine from the University of Oxford and AstraZeneca also have been approved in recent weeks. The latter also received full regulatory approval in the EU at the end of January 2021, although countries such as Germany advise that the vaccine should currently only be administered to people under the age of 65.
- In China, the state-owned China National Biotec Group, or Sinopharm, has developed two inactivated SARS-CoV-2 virus-based vaccines which received regulatory approval in December 2020 in China, the UAE and Bahrain. Another inactivated virus-based vaccine from the Chinese biotech firm Sinovac has been approved for limited use in China in December 2020. The CanSinos single-dose adenovirus vector-based vaccine candidate was approved for limited use for the Chinese military in June 2020 and is running Phase III trials in a number of countries, including Pakistan, Russia, Mexico and Chile.
- In Russia, the adenovirus-based Sputnik V vaccine from the Gamaleya Research Institute received regulatory approval in August 2020 with expected distribution in Russia and other former Soviet states, India, UAE, Hungary, Saudi Arabia and several countries in Latin America. In addition, EpiVacCorona, a protein subunit vaccine developed by the Russian Vector Institute, has been granted regulatory approval in Russia in October 2020.
- Finally, in India, Bharat Biotech’s inactivated virus based vaccine was approved for emergency use in India in early January 2021 with limited information on detailed trial outcomes2.
Candidate vaccine programmes number over 200; two in particular show promise:
- Johnson & Johnson's single shot adenovirus-based vaccine: In late January 2021, the company announced that in multi-country trials the vaccine had an efficacy of 72% in the United States, 66% in Latin America, and 57% in South Africa, the latter most probably influenced by viral mutations. Against severe disease, efficacy climbed to 85% in all regions. The key advantage of the vaccine is that it is single shot; and that it can be regularly refrigerated for many months.
- Novavax 2-dose recombinant spike protein vaccine: Developed with the Coalition for Epidemic Preparedness, Novavax reported that preliminary results from a UK trial showed a vaccine efficacy of more than 89% against COVID-193. Similarly, the vaccine had reduced efficacy in South Africa.
Challenge one: Immunisation drives
As of the 22 February, 36.8 million people have been vaccinated against COVID-19 across the world as prescribed by the companies' vaccination protocols. Those who have received at least a single vaccination stand at 109 million.
Some states have been more vigorous that others in vaccine rollouts, notably Israel, the UK and the US (see Figure 2); all thanks to faster authorisations, early vaccine purchase agreements and large investments in mass vaccination centres. These three countries also top the 7-day rolling average of vaccines administered per 100 people, while there are some differences in ranking for countries when fully vaccinating with two jabs (33.3% for Israel, 5.3% for the US and 0.9% for the UK as of 22 February). More than 87% of Israelis over 90 have received their first dose and 74% the second; the rate of vaccination is even higher in the 70-79 age band where the percentage of people who received first and second doses is more than 92% and 80%, respectively.
The new US administration announced a target of 100 million vaccines in the first 100 days, a number it is on course to achieve. At the current vaccination speed (1.52 million daily doses on a 7-day average), about 268 million US citizens or about 81% of the population could be vaccinated by year end. The US vaccination plans rely on the Pfizer/BioNTech and Moderna vaccines. Logistics of the rollout depend on individual states, with the Centers for Disease Control and Prevention (CDC) providing recommendations to federal, state and local governments about who to vaccinate first. There are hopes that vaccines will become available to the general population towards mid-summer or early autumn of 2021.
The UK met the government target of around 15 million by mid-February. If the current vaccination speed remains constant (394,000 daily doses on a 7-day average), the UK may be able to vaccinate the entire population by the end of the 2021. The current UK vaccination rollout primarily relies on doses from Oxford/AstraZeneca and Pfizer/BioNTech vaccines. The wide strategy considers age as the greatest priority for vaccination and the plan is to give an initial dose and follow-up with a second dose after a maximum of 12 weeks.
The European Commission President declared that EU aims to have vaccinated 70% of adults in Europe by the end of summer. This will not be achievable at current vaccination speeds and has been the source of some criticism. The EU vaccination strategy is also dependent upon vaccines from Pfizer/BioNTech and Moderna (authorised by European regulators in late December 2020 and early January 2021, respectively). Vaccination commenced in late December 2020 across the EU, as each EU country received the vaccine at the same time, although vaccination rates differ between countries4.
Source: Our World In Data
Challenge two: Supply chains and distribution
The race is on: Individual countries have been keen to acquire vaccine stocks as quickly as possible (see Figure 3). Vaccine acquisitions have already seen a number of high-profile disputes. An additional complication for all currently approved vaccines: the vaccinations approved at the start of 2021 require two doses for full efficacity.
Source: Launch and scale faster
Given the nature of large-scale global vaccination efforts in a time-efficient manner, many governments have been considering or are enacting options of modifying vaccination plans, to partially immunize a greater portion of the population at a faster speed. This may include reducing the number of doses, longer waiting periods between two doses, or even combining doses from different vaccines. Studies of the AstraZeneca/Oxford vaccine given at an extended interval showed vaccine efficacy is higher with longer intervals, and that a single dose of the vaccine is 76% effective from 22 to up to 90 days post vaccination5. New analysis on the Pfizer/BioNTech vaccine showed the first dose being already 92.6% effective beginning from two weeks after the first dose, a finding similar to the first-dose efficacy of 92.1% reported for the Moderna vaccine, and rising to an overall 95% efficacy after the second dose6.The FDA continues to recommend the Pfizer and Moderna vaccines be given at the 3 to 4 week intervals used in trials7.
New clinical trials to ‘mix and match’ COVID-19 vaccines are currently underway with the hope that they may boost immune responses and provide a greater degree of global flexibility to vaccine rollouts and dwindling supplies. The US FDA meanwhile emphasizes the importance of following initial plans, based on available evidence and data from existing clinical trials, and warned of putting public health at risk and undermining the overall efforts to reach protection and immunisation at a population level.
Storage and logistics
Vaccine distribution is not easy. All vaccines are sensitive to temperature changes, and they can become ineffective or unsafe if not stored under the right conditions8. mRNA vaccines are a particular challenge to manage, requiring extremely cold storage temperatures.
Challenge three: Vaccine efficacy
The good news: positive trial data has largely been replicated during the initial weeks of the vaccine rollout. Early starter Israel, which has committed to regular data updates on vaccine efficacy, confirmed an efficacy rate of 92% for Pfizer/BioNTech. This is the first large-scale, controlled data outside clinical trials, and the small difference in reported efficacy in clinical trials versus the wider population in Israel is insignificant, according to Israeli health officials 11.
In clinical trials, the Moderna mRNA vaccine also showed a very high 94% efficacy against symptomatic disease. The Oxford/AstraZeneca vaccine has demonstrated an overall efficacy against disease of 70%, ranging from 62% to 90% with different dosing regimens, but unlike the mRNA vaccines, the Oxford/AstraZeneca vaccine was tested against asymptomatic infection, which likely lowered the efficacy. All three vaccines showed 100% efficacy against severe disease or death (though data is limited by the size of the trials). Vaccines from Russia and China, such as Sputnik V, Vector, Sinopharm and Sinovac, have varied clinical trial data, ranging between 50-92%, delaying approvals in some countries12.
Still unclear is the duration of immunity from any vaccine but it is assumed that it may persists at least for several months, if not years. A recent study showed that COVID-19 patients who recovered from the disease still have robust immunity from the coronavirus eight months after infection. This suggests that reinfection should only be a problem for a very small percentage of people who have developed immunity – whether through an initial infection or by vaccination. Experience with previous SARS and MERS coronavirus epidemics suggests that immunity can last up to three years or more and with low risk of reinfection for recovered patients13, 14.
Preliminary information towards vaccine effectiveness in limiting transmission is thus far limited. A small study from Israel, current leader in COVID-19 vaccination rates, suggests that the Pfizer/BioNTech vaccine could reduce transmission. Researchers found that among 102 medical workers who received the vaccine, most developed an immune response significantly stronger than COVID-19 survivors. This may also prevent COVID-19 transmission.
This is largely backed up by a larger study from Israel, including 200,000 people older than 60 years who received the Pfizer/BioNTech vaccine, compared with a matched group of 200,000 who did not. Researchers found that the chances of testing positive for the virus were 33% lower two weeks after the first injection15.
Separate figures recorded by Israeli health provider Maccabi showed that in over 400,000 vaccinated people the vaccine caused a 60% drop in infectivity 14 days after taking the first shot11. This data is a positive; although more proof is needed to demonstrate that mass vaccination might indeed affect infectability or transmissibility.
The majority of reported side effects are mild and involve known reactions from the clinical trials such as injection site pain, tiredness, headache, muscle pain, chills and fever. In very rare cases, the vaccine has caused a severe allergic reaction. While all vaccines are likely to lead to minor symptoms, there is a suggestion that mRNA vaccines (Moderna and Pfizer/BioNTech) could be experiencing more side effects. In Israel, figures released by the Health Ministry showed that that out of almost two million vaccinated people, only 1,127 people reported suffering side effects, the large majority of which were minor16.
Challenge four: Population acceptance
Does everyone want to take the vaccine? A systematic review of peer-reviewed COVID-19 papers highlighted that global vaccine hesitancy appeared to be greatest in several Middle Eastern and European countries, and the USA. While some are still hesitant to get vaccinated, a YouGov poll found that few felt so because they identified as 'anti-vaxxers'17.
This was similar to research carried out by Swiss Re. Research into the behavioural science impact of vaccinations showed a wider range of vaccine acceptance, with older groups (more likely to be impacted by COVID-19) more willing to be vaccinated. Additionally, they suggested that the insured population is more likely to agree to be vaccinated than the general population.
Source: YouGov as of 15 January 2021
Challenge five: Viral mutations
At the time of writing, the world is contending with three known significant variants of the SARS-CoV-2 virus, originating from the UK, South Africa (SA) and Brazil. Viral mutations pose new challenges in the ever-changing COVID-19 landscape. As promising vaccines are being deployed around the world at accelerated pace, mutations stand to potentially delay inoculation plans by threatening vaccine efficacy.
The UK initially reported a mutation in December 2020, with the first known infected cases approximated to have emerged in early autumn18. Public Health England (PHE) classified the strain, B.1.1.7 lineage, as a 'Variant of Concern' with multiple mutations of immunological significance. Preliminary studies have highlighted substantially elevated transmission associated with the mutation on the spike protein and increased infectivity in animal studies19.
The mutation alters the spike protein which in turn enhances binding with the human ACE2 receptor – the last line of defence before a virus enters and infects a host cell20. Studies have suggested that the transmissibility of that variant is 30-50% greater than other variants, with higher viral loads in infected individuals21. Whilst data is sparse, preliminary reports from The UK New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG) suggest that this variant may be associated with an increased risk of death, however, more research is needed on this.
In January 2021, the CDC reported cases of the UK variant in 30 countries and multiple states in the USA, with the modelled trajectory predicting rapid growth through community transmission, leading to the strain becoming the predominant variant in the US by March22.
South African authorities announced a new variant, in the B.1.351 lineage, in December 2020, which emerged independently of the UK variant. Early studies suggest that this variant is also associated with a higher viral load and potential for increased transmissibility23. While the SA variant has three main mutations, including multiple alterations to the spike protein, one mutation appears to reduce antibody recognition. It is possible that this mutation would enable it to bypass prior immune protection (achieved by infection or vaccination), conferring resistance to neutralising antibodies. Rapid spread has resulted in the SA variant becoming the dominant strain in the country.
This is of concern given the worldwide rollout of vaccines with the now added pressure of vaccinating people before they potentially come into contact with this variant. However, due to increased transmission, the likelihood of knock-on effects of elevated infection rates, hospitalisations and mortality counts have been classed as ‘high’, particularly so in vulnerable populations due to age and pre-existing co-morbidities24.
As countries scrambled to contend with the two known variants of concern, in January 2021, the Japanese National Institute of Infectious Disease (NIID) detected a new variant in four people with a recent travel history to Brazil25. Less is known about the Brazilian P.1 variant (descendent of the B.1.1.28 lineage), which likely emerged last summer and was detected by Brazilian authorities around Rio de Janeiro in late October 2020. This variant has a host of new mutations, including the three previously identified ones in the SA mutant26. More recently, a newer variant found in the UK is itself a variant of the "main" UK variant. Interestingly, the new UK variant and the South African variant both contain a specific mutation which may cause the virus to escape the vaccine. AstraZeneca has already committed to releasing a new version of its vaccine to counter this mutation, which is due towards the end of 202127.
Variants and existing vaccines
There have been established concerns that excessive targeting of the spike protein without enough focus on other structural elements of the virus may lead to any vaccine being ineffective if alterations in the protein were to occur. While all coronaviruses tend towards lower genetic diversity compared to other RNA viruses, this is particularly true with this virus, initially suggesting that a single vaccine may suit current variants in circulation.
Global vaccination efforts commenced on the assumption of immunity against current variants, at which point the effectiveness and duration of immunity was uncertain, as they were untested for in the initial clinical trials. Both Pfizer/BioNTech and Moderna have announced that their vaccines are effective against the UK variant with some limited protection against SA variants28. Booster jabs are in the process of being developed by Pfizer/BioNTech, Moderna and AstraZeneca, to combat subsequent variants. Early trials, however, have shown minimal protection offered by the Oxford/AstraZeneca formulation against the SA variant, in mild to moderate disease states, but good protection against the UK variant. Similar reports have emerged from the Johnson & Johnson and Novavax trials, which have both proven to be less effective against the SA variant. Currently, there is insufficient research to conclude how the Brazilian variant responds to existing vaccines.
As we traverse unchartered territory, novel mutations to the SARS-CoV-2 virus will continue to emerge, potentially disrupting vaccine plans. It is here that mRNA vaccines come to the fore; the technology behind them lends itself to easier modifications of the genetic code and reprogramming the synthesis of a new strand of RNA. Should the need arise, vaccines offerings from Pfizer/BioNTech and Moderna will be the likely candidates for initial tweaks.
At this critical stage mRNA vaccines have attracted considerable interest as the potential modality for COVID-19 vaccines. mRNA vaccines are not new, and researchers have been studying and working with them for decades. Initially aimed at developing cancer vaccines, the approach has matured at just the right time for a viral infection as well.
A key advantage of an mRNA vaccine is that it is very easy to synthesise once the sequence of the spike protein is known. mRNA vaccines work on segments of the spike protein, allowing the virus to invade a host cell, and those mRNA sequences are much easier to generate in the lab than the spike protein itself. This allows accelerated speed of production compared to other vaccine platforms, and allows scientists to rework the vaccine quickly if any highly resistant mutations arise. It has been suggested that a modified RNA vaccine could be designed and manufactured for clinical testing within six weeks, however, it may take approximately five months for the initial trial data to be submitted to the relevant regulatory bodies29.
Below, we can see the information on the main three variants currently in circulation as collected by the CDC22:
Challenge six: Opening up
All the while, the pressure is on national governments to end the purgatory of lockdown, the costs to economic well-being, educational attainment and mental health. Winning the vaccine race currently is Israel; Prime Minister Benjamin Netanyahu described the vaccine programme as 'Operation Getting Back to Life'30. The problem for Israel: despite a world leading programme, it has been blindsided by the arrival of new COVID-19 variants, hitting particularly the 50-60 demographic – with older populations already being vaccinated. Despite handling the initial waves well, Israel is having significant challenges with this most recent outbreak.
As with other populist governments, the Israeli regime became too relaxed in the wake of the first wave. People were encouraged to mingle and socialise. Lessons have been taken on board. Another state with an advanced vaccine programme, the UK – which had previously promised a five-day holiday 'amnesty' over Christmas – has been notable in managing expectations downwards in exiting the second wave. Realism has also been injected into US politics; there will be hesitancy in sounding the claxon to mark the end of the pandemic, even with vaccines.
However, tensions will continue in returning to normality, whether it involves keeping schools open or staging the Olympics. Vaccine programmes are being executed in a complex and evolving sphere of public health.
Challenge seven: Global equity
While the first challenge of a vaccination is always developing the vaccines themselves, attention soon turns to more practical considerations of buying and distributing them. Countries hardest hit, such as the US and UK, have sought to acquire and distribute large quantities of vaccines. The EU, on the other hand, despite also suffering badly in places, is currently facing severe shortages due to logistical challenges. And yet, the virus will not respect the boundaries of these intwined entities in a world as interconnected as ours. It is a microcosm of a problem confronting the whole world. Nation states can rush to vaccination programmes; but borders in a globalised planet cannot again be opened while COVID-19 continues to ravage other countries.
This problem is fortunately recognised. The COVAX programme aims to have 2 billion vaccine doses available to member countries, regardless of income, by the end of 2021, a figure that should cover the high risk population and frontline health workers31. Working with other disease monitoring and managing initiatives, frequently in parts of the world with more recent histories of serious infectious conditions, COVAX seeks a more equitable distribution of vaccine resources.
Nonetheless, vaccine demand will outstrip supply for the foreseeable future. If national hoarding does occur – and initial signs are not good – there are not only issues of international equity. If pockets of COVID-19 remain in the world – most likely in poorer states with lesser developed infrastructures – the potential for future mutations increases, potentially mutations that escape current vaccine regimes. The only defence will be quarantines; or restarting vaccine development and distribution. We will be reading much more about global vaccine distribution over the coming year.
Outlook and what it means for insurers
The development of several functional COVID-19 vaccines within a year was exceptional and driven by extraordinary global collaboration and cooperation. Benefitting from previous research on related viruses, faster ways of manufacturing vaccines and enormous funding, allowed developers to run multiple trials in parallel resulting in several approvals by regulators who moved more quickly than normal.
The efficacy of leading vaccines in clinical trials is very high – in the 90% ranges – and seems to be confirmed in countries with accelerated vaccine administration, such as Israel, allowing an optimistic outlook about 2021.
However, challenges remain. Vaccination production and distribution did not always go as planned and vaccine administration is behind schedule in many markets. For emerging markets, the situation is even more challenging as almost no country has enough vaccines on order to vaccinate its entire population. In addition, poor infrastructure and difficult environmental conditions, such as tropical temperatures, will make vaccine distribution even more difficult. New emerging variants have developed that could lead to a resurgence in infection and fatality rates. Manufacturers are already working to create new vaccines to counter variants.
Insurers will need to continue to stay cautious in their outlook while the vaccination programmes are being implemented. It is likely that lockdowns and other social control measures will continue in countries across the world. This could further strain mental health, as reported by multiple European studies during the initial quarantine period in spring last year. Globally, the mutated virus threatens to increase the case count in the coming months. Higher case counts lead to more hospitalisations, increased mortality rates, and a bigger proportion of people impacted by long-COVID. Governments are likely to continue with cycles of lockdowns and opening to encourage economic activity while ensuring the pandemic stays controlled during the long road to herd immunity through the inoculation programmes. This means that insurers' business plans may continue to be affected through 2021. Our Medical Officers and Underwriters continue to review the latest science/data and update our guidance in Life Guide.
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- Covid-19: Indian health officials defend approval of vaccine. BMJ. 2021;372:n52.
- Callaway E, Mallapaty S. Novavax offers first evidence that COVID vaccines protect people against variants. Nature. 2021;590(7844):17.
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- Voysey M, Clemens SAC, Madhi SA, Weckx LY, Folegatti PM, Aley PK, et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet. 2021;397(10269):99-111.
- Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. New England Journal of Medicine. 2020;383(27):2603-15.
- US Food and Drink Administration. FDA Statement on Following the Authorized Dosing Schedules for COVID-19 Vaccines. 2021.
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- Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, et al. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. New England Journal of Medicine. 2020.
- Knoll MD, Wonodi C. Oxford-AstraZeneca COVID-19 vaccine efficacy. Lancet. 2021;397(10269):72-4.
- The Times of Israel. Vaccine found 92% effective in Israel, in first controlled result outside trials 2021 [Available from: https://www.timesofisrael.com/vaccine-found-92-effective-in-israel-in-first-controlled-result-outside-trials/.
- Logunov DY, Dolzhikova IV, Shcheblyakov DV, Tukhvatulin AI, Zubkova OV, Dzharullaeva AS, et al. Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia. The Lancet. 2021.
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- Anderson RM, Vegvari C, Truscott J, Collyer BS. Challenges in creating herd immunity to SARS-CoV-2 infection by mass vaccination. The Lancet. 2020;396(10263):1614-6.
- Mallapaty S. Are COVID vaccination programmes working? Scientists seek first clues. Nature. 2021;589(7843):504-5.
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- Public Health England. COVID-19 (SARS-CoV-2): information about the new virus variant 2020 [Available from: https://www.gov.uk/government/news/covid-19-sars-cov-2-information-about-the-new-virus-variant.
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