Journal of the Plague Years XIV: Vaccination Year

The overriding priority for 2021 globally will be the roll-out of vaccination programmes to quell and eventually eliminate Covid-19. Some nations will undertake this massive task more successfully than others – with profound consequences, writes Victor Hill.

A gargantuan challenge

Governments across the developed world face the task of vaccinating between 60 and 80 percent of their populations as rapidly as possible in order to quash the coronavirus pandemic. Most vaccines require two shots – though there is some controversy about whether one shot only will suffice (see below). Only then will life be able to return to some semblance of normality with the hospitality sector, sports and the performing arts able to resume activity.

Politicians around the world have spoken about a race between the vaccine and the virus. This analogy is even more pertinent since the more contagious strain of the virus emerged in the South East of England in mid-December. This will be an unparalleled logistical challenge for all countries, many of which returned to stringent national lockdowns in early January.

Let’s take a quick look at how some major countries are faring.

The United Kingdom

The UK was the first country to authorize the Pfizer-BioNTech vaccine (03 December) and the first to give the green light to the Oxford-AstraZeneca vaccine (30 December). By last night, 1.5 million vaccine doses had been administered across the UK.  530,000 doses of the Oxford vaccine were deployed this week out of the 100 million doses on order.

More than 730 vaccination sites have been established across the UK with another 180 GP practices about to become designated vaccination centres. Hundreds more specialist centres are about to open this week which will take the total to over 1,000.  Around 78,000 volunteers have been recruited to give vaccinations. This process was hampered by the requirement for vaccinators to produce certificates for 21 different training courses (including how to combat radicalisation and how to report on female genital mutilation).

The Department of Health has announced steps to remove unnecessary bureaucracy but there is still clearly a problem here. As of last Monday, only 5,000 of the 40,000 retired doctors who applied to return to the front-line to assist with the vaccination programme have been signed up. If the Letters to the Editor page of the Daily Telegraph is an accurate vox pop, most retired doctors regard the NHS as entirely dysfunctional.

All the Chief Medical Officers of the four countries of the UK have endorsed the approach that two doses, up to 12 weeks apart, is appropriate for the Oxford vaccine. This supposedly maximises public immunity in the shortest possible time. The objective is to have offered the first vaccine dose to everyone in the four top priority groups identified by the Joint Committee on Vaccination and Immunisation (JVCI) – that’s about 13.5 million people – by the middle of February.

That means vaccinating all care home residents and their carers, everyone over the age of 70, all front-line health and social care workers, and everyone who is clinically vulnerable. The 25 million most vulnerable people in the country will be vaccinated first. Collectively, these groups represent about 99 percent of preventable mortality.

The military has now been embedded in the NHS for weeks. Members of the 101 Logistics Brigade have desks in the top floor of NHS HQ in Victoria Street. Brigadier Phil Prosser chairs the daily 08:00 hours vaccine meeting.

The Oxford vaccine fluid is being manufactured at three facilities in Oxfordshire (Oxford Biomedica), Staffordshire (Cobra Biologics) and at the Halix plant in the Netherlands. The fluid is then shipped to a plant in Wrexham, North Wales, where it is packaged in glass vials. This site is run by Wockhardt, an Indian biotech specialist. Batches of the vaccine are then systematically tested by the National Institute of Biological Standards (NIBS), predominantly at a laboratory in South Mimms, Hertfordshire.

To order the vaccine, the NHS uses PHE’s ImmForm system, which is run by Movianto, a pharmaceutical logistics company. Unlike the Pfizer vaccine it can be stored in a conventional fridge, making it possible to vaccinate people in care homes, village halls, leisure centres and other hubs. The vaccine arrives in cartons, each of 8-10 vials, which can be refrigerated indefinitely. Once opened, they must be used within six hours.

On Wednesday (06 January) Mr Zahawi, the vaccines minister, confirmed that the UK government’s target was to vaccinate the 13 million over-65s by mid-February. That means the UK must administer between 1.5 and 2 million doses a week, which is achievable though ambitious.

The European Union

Vaccine approval in EU member states is determined by the European Medicines Agency (EMA, once based in London but now in Amsterdam). The EMA finally approved the Pfizer-BioNTech vaccine on 21 December. The founders of BioNTech, Professor Ugur Sahin and Dr Özlem Türeci, have criticised the EMA for the tardiness with which it approved the vaccine and for not ordering enough doses. BioNTech has been in urgent talks with suppliers to ramp up production to meet demand.

The French healthcare system is widely perceived to be amongst the best in the world. And yet the country has made a lacklustre start in the vaccine race with barely 400 people being vaccinated the week after Christmas.

A French friend tells me that the vaccine roll-out is mired in bureaucracy. Even the most vulnerable are required to fill out a ten-page form. If they fill out this correctly, they are then offered a four-day cooling off period during which they can withdraw consent. Only then can the first jab be administered. By Wednesday this week, there was uproar with a number of mayors criticising the Ministry of Health. President Macron went on air to declare that France would catch up with its neighbours “within days”.

The French would no doubt prefer the Sanofi vaccine – but that is, apparently, still far away from approval. One problem is anti-vaxxer sentiment. In a 15-country poll carried out by Ipsos Global, just 40 percent of French respondents said that they would be willing to have the vaccine – as compared with 77 percent in the UK.

There has been some consternation in Germany about the slowness of the roll-out of a vaccination programme. Chancellor Merkel’s government was criticised for failing to secure enough doses of a vaccine which was largely developed in Germany. When Berlin ordered an additional 30 million doses, it came under fire from Italy for breaking an agreement that the EU would buy vaccine doses as a bloc, and not country by country.

Last week in Germany four care home workers ended up in hospital after mistakenly being given four times the standard dose of the Pfizer vaccine. In Switzerland, a 91-year-old died after vaccination. About 100,000 Italians had been vaccinated by the beginning of this week.

The EMA approved the Moderna vaccine on Wednesday (06 January). Moderna announced that deliveries to Europe would begin next week.

Israel

Israelis have endured one of the toughest lockdown regimes in the world over the last ten months. But since 20 December the country’s vaccination drive has been relentless, assisted by Israel’s conscript army. About 1.2 million Israelis had received their first jab by the middle of this week out of a total population of about 9.3 million, making Israel the world leader in the vaccination race.

Vaccine clinics are run by four Health Maintenance Organisations (HMOs) whose clinicians have been working from 08:00 hours to 22:00 hours every day to administer the Pfizer vaccine. Israelis are legally required to sign up with an HMO, with which they have an online account, but can switch between providers, making for an element of competition in healthcare. Currently, the priority for vaccination is the over-60s, front-line workers and all those with chronic conditions. Israel is committed to the recommended two-jab approach.

Benyamin Netanyahu, the prime minister, has said that the aim is to have vaccinated over two million Israelis by the end of January, by which time, he hopes, the Moderna vaccine will be available. Israel has ordered 6 million doses from Moderna, but, according to Israel’s Channel 12, they are not likely to arrive before April.

The USA

Thus far the Food and Drug Administration (FDA) has approved the Pfizer vaccine (11 December) and the Moderna vaccine, both of which are messenger RNA (mRNA) technologies. The US vaccination programme began on 14 December but had only vaccinated 3.5 million people by the New Year.

India

India is the second most populous nation on Earth with about 1.3 billion inhabitants. The country approved the Oxford vaccine on New Year’s Day for emergency use and a vaccination programme will start by mid-month. The country has the third highest death toll from Covid-19 after the United States and Brazil with over 150,000 fatalities. However, given its huge population the deaths per million figure is comparatively low at 109 (as compared to well over 1,000 for the USA, UK and France). With over 10.4 million confirmed cases of the virus India stands second only to the USA.

India is thought to have 50 million doses of the Oxford vaccine, known as Covishield there, already in stock – far more than the UK. These have been manufactured by the Serum Institute of India (SII) in Mumbai under licence from AstraZeneca. The government in New Delhi plans to vaccinate 300 million people (about one quarter of the entire population) by August this year. This figure includes 10 million healthcare workers, 20 million front-line workers and 270 million people who are either over-50 or under-50 with chronic conditions.

Some of these shots will be paid for by the Gavi Alliance, an agency of the World Health Organisation dedicated to the equitable distribution of vaccines to 92 low and middle-income countries. Last year, the Bill & Melinda Gates Foundation and the Gavi Alliance announced a $150 million donation to SII.

India will start a dry run immediately in which patients receive a placebo. Apparently, this is intended to test the logistics. SII and AstraZeneca have plans to manufacture 3.2 billion doses of coronavirus vaccine in Maharashtra. These will require a WHO pre-qualification for export to third countries. 100 million doses will shortly be heading from Mumbai to South Africa.

One jab or two?

Just before Christmas the former prime minister, Mr Blair, writing in The Independent, called for an overhaul of the government’s vaccine strategy. He argued that in order to spread immunity more widely, those who had already been given their first jab should forego the second so that someone else might get their first.

From the moment this was proposed there was controversy. Once again, while politicians talk about following the science, the scientists are often at variance with one another. Professor Peter Openshaw of Imperial College, London said that Mr Blair’s proposal “made good sense”. But Professor Wendy Barclay, also of Imperial College, told MPs on the Science and Technology Committee that changing dosing would be “too risky”. Dr Simon Clarke of the University of Reading branded the proposal as “ridiculous”. The BMA expressed its opposition to one jab.

Hundreds of thousands of patients have now been informed that their second jabs are either cancelled or postponed indefinitely. There are medical precedents for this. The human papillomavirus vaccine which prevents cervical cancer was initially administered in three doses but was found to be so effective that it is now restricted to two.

Two doses of the Pfizer vaccine induce 95 percent immunity; the efficacy falls substantially with one dose. For the Oxford-AstraZeneca vaccine, the efficacy is 62 percent for two full doses but rises to 90 percent for those who are given a first half-dose and a second full dose.

The current consensus in the UK is that the two doses of the Oxford-AstraZeneca vaccine will now be administered between four and 12 weeks apart; but the Pfizer vaccine could be given as a single dose initially – despite the fact that it was authorised by the MHRA as a two-dose vaccine. According to a paper released by the MHRA this week, a longer gap between the first and second dose will confer a “stronger immune response”.

The Janssen (the Belgian subsidiary of Johnson & Johnson (NYSE:JNJ)) vaccine will be a single-shot vaccine which uses adenovirus and mRNA technology. It could be approved in the UK, Europe and the USA as early as next month. Watch this space.

Bottlenecks

Glass vials are in critically short supply across the globe. Last weekend, AstraZeneca had 15 million doses on hand waiting to be put into vials. Pascal Soriot, AstraZeneca’s CEO said the company could supply a million doses per week but that will rise to two million by mid-January. The Oxford vaccine needs to spend 20 days in a sterilisation process after manufacture before it can be used. Then each batch has to be checked by the NIBS.

As well as the 100 million doses of the Oxford vaccine ordered by the UK, the USA has ordered 300 million, the EU 400 million and Japan 120 million. Another 170 million have been earmarked for the Gavi alliance. At the current level of production, it will take years to deliver these orders.

Objectives

The objectives of a vaccination programme are two-fold. The first is to cut the number of hospitalisations and thus subsequently deaths; the second is to generate herd or population immunity at which point the R-rate falls to increasingly lower levels and the virus ceases to circulate.

Modelling suggests that at least 60 percent of the population would need to be vaccinated in order to achieve herd immunity, according to Danny Altman of Imperial College, London. On the other hand, given the rapid spread of the second strain of the virus (dubbed B117) and the possibility of further mutations, the threshold to achieve herd immunity may be as high as 80 percent. On that basis, at a rate of one million vaccinations a week, herd immunity might be achievable in the UK by November this year.

But we still don’t know the extent to which the various vaccines prevent transmission, so it is difficult to predict the future R-rate, even given a successful vaccination programme. That said, we can reasonably assume that the level of hospitalisations and mortality will be drastically reduced even if the virus continues to circulate. Speaking just before Christmas, Bill Gates told CNN that lockdowns may have to continue until 2022. Normality may not be restored this year. Professor Whitty said much the same on Tuesday.

We should assume that 2021 will continue to be a year of economic disruption as was 2020. Indeed, we might well spend more time in lockdown this year than last. Realistically, as I suggested last year, normality will not return until around Q2 2022.

Unless, that is, governments adopt a less risk-averse approach and begin to regard a certain (low) level of mortality as part of the cost of allowing the economy to remain open. We know that seasonal flu kills 7,000 people in a good year and 20,000 in a bad one – but we have never shut down the economy because of flu in the past. As Professor Robert Dingwall has said, we shall never get to zero-Covid risk.

Pandemic update – darkest before dawn

Since just before Christmas the data coming out of the UK has been sobering. More than 50,000 new cases have been recorded almost every day in the UK – 60,100 on Tuesday. There were an estimated 2.8 million people infected in across the UK on Wednesday (06 January). At more than 30,000, there are now 40 percent more people in hospital suffering from Covid-19 than there were at the height of the first wave around 08 April last year. The NHS is said to be at breaking point. On 03 January, 3,351 people suffering with Covid-19 were admitted to UK hospitals – the highest daily figure yet.

The UK Covid death toll this morning stood at 78,508 – well above the best-case scenario of 60,000 which the Imperial College team envisaged last March. We shall be lucky to get away with a final death toll of double that – even if the vaccination programme is carried out successfully. Let’s remind ourselves, however, that is overwhelmingly an affliction of the most vulnerable. Healthy under-60s account for less than one percent of Covid deaths.

In the USA, the total death toll now stands at 375,000. Much of Europe is heading back into full lockdown. It’s not alarmist to say that the pandemic is now as intense and disruptive as it ever has been – and we are nearly one-year in. The great hope is that the vaccination programme will turn the tide.

We should remain sanguine, but realistic.

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I see that the UK government now requires that all passengers boarding flights to Britain from abroad show proof that they have tested negative for the virus within 72 hours of departure. That’s something I advocated in these pages eleven months ago.

Nice work, Ms Patel. Shame it took so long.