Journal of the Plague Year XIII – The Vials of Destiny

The mass global vaccination programme against Covid-19 began in the UK on Tuesday (08 December) when a 91-year-old grandmother wearing a Christmas duck T-shirt was inoculated in Coventry. Is this the beginning of the end? Victor Hill inquires.

The fate of mankind in pizza boxes

First up, some practical facts about how the Pfizer-BioNTech mRNA-based vaccine will be transported and administered.

The UK’s MHRA was the first medical regulatory agency to approve the vaccine on Wednesday last week (02 December). Shipments of the vaccine began to arrive from their place of manufacture in Puurs, in the Antwerp Province of Belgium, almost immediately – by truck through Dover and by air. The vaccine, which must be maintained at a temperature of around minus 70 Celsius (much colder than a regular freezer), comes in glass vials about the size of a little finger. Each vial contains five doses.

The vials are packed into what clinicians have dubbed pizza boxes – white flat trays – each of which contains about 175 vials. Five of these pizza boxes are loaded into a special refrigerated suitcase which is packed with dry ice (deep-frozen carbon dioxide). Thus, each suitcase contains 975 vials or 4,875 doses and can be stored for up to ten days. After that the pizza boxes can be transferred either to a super-freezer for further storage or to a conventional fridge and stored at 2-5 Celsius for up to five days – after which time they will become unusable as they cannot be re-frozen.

Presumably, it will take about a day for the vaccines to thaw from minus 70 to plus 3 Celsius – they could not be injected while still frozen. The content of each vial is then diluted with sterile saline solution before injection into the patient’s shoulder. Patients will be requested to wait for a short time after their jabs to check that there are no immediate serious side-effects.

50 hospitals in England which have the necessary super-freezers have been designated vaccination hubs. In addition, numerous GP surgeries will carry out vaccinations for which they will be paid £12.58 per jab (that’s 25 percent more than for the flu jab). And there will be so-called mass vaccination centres located in sporting venues and conference centres. (Perhaps the Nightingale hospitals could be re-modelled for that purpose). In the first phase the hospital hubs will take the strain.

It is still not clear what is the storage capacity of these hospitals. There is also talk about a possible shortage of glass vials and indeed of dry ice. Not to mention needles, alcohol wipes and protective equipment for clinicians. And then there is staffing capacity: will enough trained healthcare professionals be available where they are needed? What is clear is that the roll-out of the vaccination programme will require a high degree of logistical planning. There is much that could go wrong.

The UK government has ordered 40 million doses of the Pfizer-BioNTech vaccine – enough to vaccinate 20 million people, given that each person will require two shots 21 days apart. However, when the order was placed, Pfizer had a production schedule of 100 million doses before the end of this year. That has now been cut to half that number. So, it is not clear how long it will take for delivery of the full order. That makes the roll-out more problematic as the government must coordinate vaccination slots in accordance with when the vaccine is available.

The first batch of deliveries was for 800,000 jabs; but a second shipment before the end of the year will supply millionsmore – though that has been questioned. Pfizer has said it plans to manufacture 1.3 billion doses of the vaccine in 2021. Morgan Stanley reckons that the vaccine could earn Pfizer and BioNTech $10 billion in revenue next year.

Uncertainty about availability is especially challenging since, in Week 4 of the vaccination roll-out, the number of doses will have to double as a result of the second shots. Let’s assume that the roll-out succeeds in vaccinating 500,000 people a week (optimistic, in my view) over Weeks 1-3. In Week 4 that rises to one million vaccinations as the Week 1 people come back for their second shot – and so on thereafter. It’s not clear to me whether, in the event that there is a shortage of vaccine, the second-shot people would be prioritised over the new first-shot people. The administrators need to know, as far as possible, exactly how many doses are coming into the country and on precisely which days, and indeed where they have gone.

The MHRA’s license for the vaccine is not just a green light – it specifies exactly where and when, and under what conditions, the vaccine can be administered. Vaccinations will not be administered in care homes because of the cold storage issue. Though, there seems to be some dissent on this in Scotland where the SNP government has said it has found a way to split a suitcase in two. That could be challenged by the regulator.

The total adult GP-registered population of the UK is about 50 million, and each adult will require two shots – so 100 million in total. If the target roll-out is for one million a week then the entire programme will take nearly two years. To vaccinate the over-60s alone (13.5 million people) will take over three months. 

NHS guidelines prevent the vaccination programme from operating at full capacity in the first phase, as doctors are required personally to supervise every vaccination. As a result, the 50 hospital hubs in England will only be able to carry out 300 vaccinations per day. That means that the network of hospital hubs will only undertake 105,000 vaccinations in the first week. But one senior clinician has written that administering a vaccine can be taught safely to laypeople in 15 minutes. Members of the armed forces are trained to administer vaccines as are non-medic in travel clinics. 

And so long as Covid-19 vaccination is prioritised, other serious health conditions, cancer included, will remain untreated.

The doctor will see you now…

The prevailing message from the NHS across the UK is: Don’t call us – we’ll call you. UK residents who are registered with a GP will be invited to attend a vaccination centre at a certain time and date as time goes by in order of their priority. Up until at least the end of this year, the focus will be on the over-80s, care home residents and carers. Most of the people getting the jab on Tuesday were nonagenarians. Consider that about one third of the UK’s Covid death toll of 63,000 people were care home residents (that includes people who were normally in residential care but died in hospital). On that basis, going forward, vaccinating less than one percent of the population might obviate one third of all mortality, which represents a good return on investment for health economists. Another nearly one third of UK deaths occurred amongst over-80s who were not care home residents, and they are second in line.

Just to complicate the picture further, the Moderna (NASDAQ:MRNA) and Oxford-AstraZeneca (LON:AZN)vaccines might also be approved soon – possibly even before Christmas. The UK government has pre-ordered seven million doses of the Moderna vaccine and 100 million of the Oxford one. These will be subject to different logistical issues and will thus carry different licenses. It is not clear whether the same vaccination hub might administer more than one type of vaccine. As I told the (virtual) Master Investor Show last week, it would be nice if citizens could be offered a choice of vaccine – but I much doubt they will be. We’ll get what we’re given.

In any case, the Moderna vaccine might be in short supply. The vaccine claims a 94.5 percent success rate – even in the elderly – and can be stored at just minus 20 Celsius; though it is more costly as each dosage is 100 micrograms – three times that of the Pfizer-BioNTech vaccine. Even if approved this month, the jab will not be available in the UK before the spring because the USA has been given priority. Additional orders have been placed for pipeline vaccines developed by Novavax (NASDAQ:NVAX), Janssen (owned by Johnson & Johnson (NYSE:JNJ), GSK-Sanofi Pasteur (LON:GPA/EPA:SAN) and Valneva (EPA:VLA).

The UK government (whose writ only runs, so it seems, in England) has said that it does not envisage any step towards making vaccination compulsory. However, Nadim Zahawi MP, recently appointed the minister for vaccines, has indicated that daily life would become difficult for vaccine refuseniks since many activities will require evidence of vaccination. Qantas (ASX:QAN) has already announced that when it resumes normal service all passengers will be required to provide vaccination certificates in order to board an aircraft. Even restaurants and theatres might require vaccination certificates in time.

Some commentators are already thinking about the additional challenges that will arise when vaccination programmes are rolled out in developing countries – particularly tropical ones. By the end of 2021, the vaccine haves and the vaccine have-nots will stand in stark contrast. We can expect Dr Ugur Sahin and Dr Ozlem Türeci, the co-founders of BioNTech who have spoken about their humanitarian concerns, to act on this. And there will be a debate about how much of our foreign aid budget to divert in this direction. Until this coronavirus is eradicated in the developing world too, and if there is a relaxation of the vaccination programme here, there will remain the risk that it might return to the first world with a vengeance.

A word of caution. Although there is strong evidence that the Pfizer-BioNTech vaccine will confer immunity, we still don’t know if it can stop transmission of the virus from the vaccinated to the non-vaccinated. Nasal vaccines which are administered directly into the respiratory tract might be more effective at reducing transmission than those injected into the arm.

Efficacy

On Wednesday (09 December) it was reported that two healthcare workers who had been vaccinated on Tuesday had reported severe anaphylactoid reactions. The MHRA warned NHS trusts that people with significant allergies may not be suitable candidates for this vaccine. Significant allergies means susceptible people who carry adrenaline auto-injectors (Epi-pens) at all times. This will only confirm the prejudices of the anti-vaxxers. It will be interesting to see how they influence the take-up as time unfolds.

Unfortunately, precisely because the vaccine has been first administered to the most vulnerable, there are likely to be more reports of adverse reactions. Care home residents suffer from all kinds of naturally occurring medical conditions almost daily and some may result after vaccination – though not due to it. Dr Helen Talbot, associate professor of medicine at Vanderbilt University stated last week in a congressional hearing that there is no data yet to show that the Pfizer-BioNTech vaccine works in the old and frail.

The four UK chief medical officers warned the NHS last week that any vaccine roll-out would only have a marginal impact on case numbers and hospital admissions over the next three months. Some fear that the four-nation agreement to ease restrictions over five days at Christmas will provoke a third wave of new infections thereafter.

Influenza – flu – cannot be entirely eradicated because there are dozens of flu strains, each of which is in rapid evolution such that scientists must develop a new flu vaccine every year. The Covid-19 coronavirus, on the other hand, evolves far more slowly, so it seems at present. The quicker we eradicate it, the more chance we have to stop it evolving into something really deadly like smallpox or Ebola.

Stock market euphoria and economic woe

The stock markets, particularly in the USA, seem to think that we are in the Roaring Twenties which followed the Spanish flu – and you remember how they ended in 1929. The assumption is that the vaccination programme will restore normality by mid-2021. In that notion they are encouraged by President-elect Biden’s target to vaccinate 100 million Americans within his first 100 days.

According to the OBR, UK output will not get back to 2019 levels until late 2022 with GDP three percent lower than it might otherwise have been. More worrying is the outlook on the employment front. Retail jobs are in precipitous decline – especially further to the demise of Debenhams and Arcadia which jointly account for about 25,000 jobs. That is important because, for many people such as students and those engaged in seasonal professions, retail and hospitality offer a perennial source of part-time work. Think of fashion models moonlighting in Topshop and resting actors working as waiters in Covent Garden restaurants. The demise of these businesses is bad news for public finances but also for the flexible labour market which has given the UK an economic edge.

In terms of pharma stock prices, Pfizer (NYSE:PFE) is up from $37 on the day that the vaccine was declared viable (09 November) to around $41 as I write; but Moderna (NASDAQ:MRNA) has more than doubled from $76 to $156. In contrast, the AstraZeneca (LON:AZN) price has fallen from £8.30 to £8.10. Clearly the markets are not impressed by the latter’s efficacy statistics. But will the regulator have similar reservations?

Leading by example

Dr Sahin has suggested that HM The Queen and Sir David Attenborough might get vaccinated on live TV pour encourager les autres. Queen Charlotte, the wife of George III (Mad King George who lost America) was keen on Jenner’s smallpox vaccination programme, having lost two sons to the disease. Similarly, Queen Victoria popularised the use of chloroform.

The UK government is already mooting celebrity endorsement – and that is sure to be the case in Mr Biden’s America too. We are in for months of Gwyneth Paltrow, George Clooney, Sir Ian McKellen, Hugh Grant, Dames Judy and Maggie puckering on screen and then wittering: If I did it, you can too.

***

Earlier this week we drove across a frozen Norfolk to the prize-winning Winbirri Vineyard, located just outside the Doomsday village of Surlingham. When we arrived (masked, of course) the pruned-back vines were flecked with frost – it was minus two, although the winter sun came out to greet us. Lee, owner-manager and son of the founder, a life-long local, took me through the list unfussily. Then he repaired to the hangar-like wine store, emerged with a loaded trolley and transferred my purchases into the hatchback himself.

A goodly portion of those bottles will be Christmas presents – partly my campaign to convince friends that the output from English vineyards, even at this latitude, is more than half decent; and partly out of my increasing conviction that we should think globally but eat (and drink) locally. (Localism versus globalism.) No doubt the imminent imposition of tariffs on wine imports will make the price differential less discouraging.

This year has changed us all – in some small ways for the better. And some not.