Prepared by Professor Alan Whiteside, OBE, Chair of Global Health Policy, BSIA, Waterloo, Canada & Professor Emeritus, University of KwaZulu-Natal – www.alan-whiteside.com
On Wednesday 25th November there were just under 60 million confirmed Covid-19 cases globally. There have been 1.4 million deaths. This pandemic is not under control. Despite the numbers, the last week has brought encouraging news both on medical and political fronts.
In the USA, the process of transition from the Trump presidency to Joe Biden’s has finally begun. The General Services Administrator Emily Murphy felt able to send the letter to Biden on Monday 23rd November saying he could begin the transition and giving him the requisite resources.1 This came as it was clear Trump’s lawsuits challenging the election result were going to fail. What this delay will mean for national security and the Covid-19 morbidity and mortality remains to be seen. The US will sign up to the Paris agreement (again) to address global climate change. They will rejoin the World Health Organisation (WHO), especially welcome as they are the largest bilateral funder.
There are now promising vaccines in Phase Three trials and that is the focus of this communique. I will try to make sense of this and produce a summary table of what is available. The science has leapt forward, and this includes advances in treatments not covered here. As mentioned before, the lens through which I report is most influenced by western news sources and, even narrower, I am most aware of what is going on in the UK and the USA.
I participated in a one-hour debate on BizNews radio2 with South African actuary Nick Hudson. He was one of the movers behind the Great Barrington Declaration (GBD). The moderator suggested that there might be fireworks because, as the publicity noted, I had been uncomplimentary about the GBD. It is a great pity when positions become polarised and I made a mental note to not ‘shoot from the hip’. Nick is a member of Pandemics ~ Data & Analytics (PANDA).3 Disagreement can be healthy, especially in the case of a new disease when there is much to learn. We concurred Covid-19 is a serious new illness, where we part is on how to respond, in particular the value of lockdowns.
My scars are from the Thabo Mbeki years, with the denial of the AIDS epidemic, and unwillingness to roll out treatment. This resulted in hundreds of thousands of premature deaths. With fellow scientists in South Africa, we faced a phalanx of denialists of various categories. Some argued that there was absolutely no such thing as HIV; others, that HIV was a harmless ‘passenger virus’; a third group suggested that whilst HIV existed, the drugs were the real cause of morbidity and mortality, (there was a subtext here of HIV being exploited by the global pharmaceutical industry); finally, in their ranks, were several who were so incoherent we never knew exactly what they stood for.
I write from the UK. We are approaching the end of our third week of our second lockdown, it is supposed to end on 2nd December, in time for Christmas shopping. I am extremely concerned about the impact this will have as millions flock to the streets to buy presents for friends and family. The tier system will be reintroduced and continue to be opaque.
As of 25th November, there have been 55,627,041 cases globally.4 The United States leads with 12.6 million and is extending the gap with the next highest country, India (9.2 million). I urge readers to go to other websites to look at the data that interests them. In many countries data is broken down to localised administrative levels. Please look at the Economist’s excellent data tracker.5
CNN reports that the number of infections in Asia is rising. Japan’s daily caseload is the highest it has been since the pandemic began. In South Korea, daily infections have risen to the highest level since August, about 300 per day. Hong Kong faces a “fourth wave” with multiple isolated clusters. China has seen sporadic cases in multiple cities.6 It should be noted that this is from a very low base, the numbers are miniscule by western standards, and interventions are being rapidly put in place.
In Europe President Macron said the worst of the second wave of the epidemic in France was over, but that restaurants, cafes and bars would stay shut until January 20th 2021 to avoid a third wave. “We must do everything to avoid a third wave, do everything to avoid a third lockdown,” Macron said. There is pressure for this to be eased as individuals and companies face ruin.7 In the UK the government has announced an easing of restrictions for five days over Christmas, to the dismay of many scientists and health care workers. The present lockdown ends on 2nd December. This gives three weeks for numbers to climb before restrictions are further eased. They will then climb further in January. I dip into Biblical knowledge to warn: “they have sown the wind, and they shall reap the whirlwind”.8 This is a dangerous strategy, and the Christmas gift may be increased illness and death.
Early in the pandemic it became apparent that the best, indeed only, way out of the pandemic would be a vaccine.9 This can be seen in the US government’s major initiative, Operation Warp Speed.
“Operation Warp Speed’s goal is to produce and deliver 300 million doses of safe and effective vaccines with the initial doses available by January 2021, as part of a broader strategy to accelerate the development, manufacturing, and distribution of COVID-19 vaccines, therapeutics, and diagnostics (collectively known as countermeasures)”.10
In the UK Boris Johnson’s project was to introduce same day mass testing for Covid-19 in England. This was called Operation Moonshot.11 It was to enable large gatherings of people to take place while controlling the virus. The ‘space theme’ of these initiatives is noted.
Vaccines in Context
Covid-19 is too infectious for normal human life and activity to continue in its presence. Tomas Pueyo sets out the four layers of defence for keeping the virus under control.12
- Stop as many infections as possible from coming into a country or area. This is through closing borders, quarantining people who enter, and testing. There may be concessions such as allowing people with negative tests to enter and requiring self-isolation.
- For those who cross the borders, minimize the number of people they meet. This includes quarantine, lockdowns of various degrees, social bubbles, bans on gatherings or limits on the numbers meeting, and curfews.
- When people meet others, minimize the likelihood that they will infect somebody else. This is done through social distancing, hand washing and masks.
- When infections occur, identify that infection quickly and neutralize it. This is the test, trace and isolate that was such a spectacular failure in the UK.
I have taken this from Pueyo’s ‘Coronavirus: The Swiss Cheese Strategy’. As he says ‘How Any Country Can Learn to Dance and Stop the Coronavirus’. I strongly urge you to read it.
The early stages
Development of vaccines began as soon as the genome of the virus had been identified. There have been hundreds of groups working on this. A number of vaccines are close to being available. However, the vaccine world is complex. This week I want to try to give a sense of where we are. It must be remembered that this is a political and economic issue, not just one of health. Who develops the successful vaccine, who owns it, who gets it, what does it cost, and so on?
Normally vaccine development takes years. Indeed, we are nowhere close to having a vaccine against the HIV and we are nearly 40 years into that epidemic. Nonetheless the research done in the HIV world provided a good base for the science needed to develop a Coronavirus vaccine. There have been well over 100 vaccines put forward. At the moment there are three vaccines close to being made available in the West. There may be others in China, India and Russia.
The process is to develop a concept for a vaccine. It is tested on cells and animals to see if it will produce an immune response. Currently there are three broad types of vaccine.
- Genetic vaccines that deliver genes from the coronavirus into human cells to provoke an immune response.
- Viral vector vaccines are protein-based, made from weakened or dead viruses (inactivated or attenuated).
- Repurposed vaccines are ones used for other diseases that may protect against coronavirus.
There are various websites tracking the development of these vaccines. The ones I used were the New York Times and Johns Hopkins,13 there are many others. Given the complexity of the vaccines I have developed a table of the ones that are the most advanced in their development. It is probable that other companies will report soon and there may well be other successful candidates.
On 25th November there were three advanced vaccines in development in the west. First to report was US-based pharmaceutical Pfizer Inc. and BioNTech SE, a German biotechnology company. This was reported to be 95% effective, but must be stored at -70°. Moderna, based in Cambridge, Massachusetts, says it has a vaccine that is 94.5% effective in a preliminary analysis. It must be frozen but to as low a temperature as Pfizer’s. AstraZeneca and Oxford University were the last (to date) to announce an effective vaccine. It should be noted, to some extent, this is science by press release.
We would be naïve not to recognise the financial, political and personal benefits that will accrue to the successful vaccines. It was evidenced by Johnson’s apparent glee in announcing the British advance with AstraZeneca. The recent claim that this vaccine would not win approval from US regulators lead to shares in AstraZeneca closing down almost 4% on 23rd November.14 as investors were left disappointed by an update on its coronavirus vaccine trial and one analyst claimed the vaccine would not win approval from US regulators. NOTE ANY VACCINE NEEDS APPROVAL FROM THE REGULATORS BEFORE IT CAN BE ROLLED OUT.
|Name||Pfizer with BioNTech||Moderna with NIH||AstraZeneca & Oxford University|
|Country||US, Germany||US||UK, Sweden|
|Government / other support||Not clear||$1B US govt.||US$1.2B16|
|Announcement||9 November||16 November||19 November|
|Effectiveness||95% (94% in older people)||94.5%||90%|
|Location of trial||USA, Brazil, Argentina, Germany||USA||UK, India, Brazil, South Africa, USA|
|Number in trial||30,000, then 43,000||30,000||560 older people|
|Application for use||20 November||Not yet||See text|
|Dosage||2 doses three weeks apart||2 doses several weeks apart||2 doses trial.
A: half dose then full.
B: two full doses.
(A more effective)
|Buyers||USA, Japan, EU||USA, Canada, Japan, Qatar||USA, EU|
|Special requirements||Frozen to -70°C||Frozen||Refrigeration|
|Side effects||Mild to moderate||Mild to mderate||None reported yet|
|Type||Messenger RNA||Messenger RNA||Viral vector|
|Price||Not known||Not known||$3-$4 made widely available|
In addition to these vaccines Johnson & Johnson have a candidate in Phase 3 trials which started in September with 60,000 participants. Maryland-based Novavax launched trials for a Covid-19 vaccine in May, and has received funding from the Coalition for Epidemic Preparedness Innovations, $384 million and the U.S. government, $1.6 billion. In Canada Medicago, which is partly funded by the cigarette maker Philip Morris, is attempting to grow vaccines in a plant, Nicotiana benthamiana, a wild species related to tobacco.17 A Phase 2/3 trial of the vaccine has begun. In Australia The Murdoch Children’s Research Institute is looking at the Bacillus Calmette-Guerin vaccine, developed in the early 1900s against tuberculosis, to see if it can partly protect against coronavirus.
There are a number of Phase 3 candidates from China. The company CanSino Biologics has a vaccine in development based on an adenovirus called Ad5. This is in partnership with the Institute of Biology of the Academy of Military Medical Sciences. The Chinese military approved the vaccine on 25th June for a year, as a “specially needed drug.” In August CanSino began running Phase 3 trials in other countries, including Saudi Arabia, Pakistan and Russia. The Chinese company Anhui Zhifei Longcom and the Chinese Academy of Medical Sciences partnered to make a candidate vaccine. On 20th November it was reported a Phase 3 trial had started. The plan is to recruit 29,000 volunteers and then expand to Ecuador, Indonesia, Pakistan, and Uzbekistan.
The Wuhan Institute of Biological Products has developed an inactivated virus vaccine, put into clinical tests by state-owned company Sinopharm. Phase 3 trials have been run in the United Arab Emirates, Morocco and Peru. The Chinese government gave the company approval to inject the Wuhan vaccine as well as a second candidate from the Beijing Institute of Biological Products into government officials, health care workers, and other select groups. In September the UAE gave approval for the vaccine to be used on health care workers and government officials, others were also receiving it. Sinopharm is testing an inactivated virus vaccine developed by the Beijing Institute of Biological Products. There have been/are Phase 3 trials in China, the UAE and Argentina.
The Gamaleya Research Institute, part of Russia’s Ministry of Health, has a vaccine based on two adenoviruses. Their preliminary results announced in November suggested the vaccine has a high efficacy rate in Phase 3 trials. In August President Putin announced a Russian health care regulator had approved the vaccine, Sputnik V, even before Phase 3 trials had begun. This was revised to say the approval was a “conditional registration certificate.” The trials will involve 40,000 Russian volunteers as well as volunteers from Belarus, the UAE, Venezuela and India.
Key questions to be answered are:
- How much is being spent on vaccine development and by whom (government, private sector, foundations, charities), is anyone doing economic analysis?
- How many doses are being promised by the manufacturers?
- Governments are seeking to pre-purchase, how many doses have they committed to? Do they still pay if the vaccine does not work?
- What happens to the many unsuccessful companies?
- How much will the vaccine cost?
- How will it reach developing countries? WHO Director-General Tedros argues the goal should be to ‘vaccinate some people in all countries, not all people in some countries’.
It is always difficult to know how to finish this weekly note. Hopefully, the recent vaccine developments will lift some of the dark clouds that have settled over everyone. However, it is important to note we do not have a vaccine yet. This means extra caution over the holiday period. It is sadly possible the outcome of Thanksgiving in the USA tomorrow will be a harbinger of what an uncontrolled relaxation in the UK could bring. I hope the government is looking at this. The pilgrimage to Mecca this year saw fewer than 20,000 pilgrims. Normally there would be two million.
Let us hope the UK will be sensible. I do not have a high opinion of the UK leadership. Boris has, however, made sense in the last few days. “Think carefully before getting together”, “the virus does not know it is Christmas” and “it is the season to be jolly and be jolly careful”. Covid-19 is a disease that thrives on social contact so it is critical to take note of this. If anyone wants some sobering reading take a look at the UK Government’s Covid-19 Winter Plan.18
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- A process known as ascertainment. https://edition.cnn.com/2020/11/24/politics/gsa-2020-election-decision/index.html
- Available at https://iono.fm/e/960822
- Johns Hopkins University – https://coronavirus.jhu.edu/map.html
- The Book of Hosea Chapter 8 Verse 7
- Fact Sheet: Explaining Operation Warp Speed http://www.hhs.gov/coronavirus/explaining-operation-warp-speed/index.html
- https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html and https://coronavirus.jhu.edu/vaccines
- Based on the New York Times unless otherwise indicated
- No comment other than ‘really, talk about repurposing.