New month, new Covid update

Dr John Ling has been keeping us updated each month about all things Covid. Here he is again with another forthright, clearly-expressed summary of the facts, figures and events we need to know about. Read on…

Coronavirus – Part 10 (August 2021)

The Covid-19 numbers

A month ago, at the start of August, daily Covid-19 cases in the UK were falling.  It looked as though the Freedom Day on 19 July, when nearly all restrictions were lifted, had been a shrewd move.

Whoa!  Not so fast.  This wretched virus has not been defeated.  True, the exponential growth of previous months has disappeared.  But throughout August new cases have been consistently rising, albeit only slowly.  They started the month at about 25,000 each day, and ended it at about 35,000.  The month’s highest number was 38,281 and its lowest was 21,691.  This is not a wanted trend.  It is motley news – it could be better, but it could be worse.

And these rising new cases are not the only unwelcome parameters.  Covid-19 hospitalisations and deaths have also been rising.  They started August at 6,000 and 20 respectively, and ended the month at 7,000 and 120.  These figures are not the marks of a land recovering from a pandemic.

Across the UK there have now been totals approaching 6,800,000 cases with 133,000 deaths.  Currently, there are approximately 7,000 Covid-19 patients hospitalised with 950 on ventilators.

There is some consolation – the vaccination figures are always going up.  At the end of August, 48 million UK citizens had had their first vaccine dose – that is equivalent to 71% of the population, while 43 million had had a second jab.  Has the vaccination programme been worth it?  Public Health England (PHE) estimates that it has now prevented about 24 million Covid-19 infections and more than 105,000 deaths.  Quarrel with that you anti-vaxxers, QAnon conspiracy theorists, Bill Gates obsessives, 5G wingnuts and Covid-19 contrarians.

Globally, the picture remains grim.  A total of 216 million people have now been infected by Covid-19, culminating in 4.5 million deaths.  The USA is still the most infected country (150,000 new cases per day) followed by India and Iran with the UK in fourth place (35,000).  Top of the total death table is the USA (638,000) followed by Brazil, India, Mexico, Peru, Russia, and in seventh place, the UK (133,000).

There is only one appropriate conclusion from all these data – the Covid-19 pandemic is not over yet, far from it.

That Delta variant

August has been the showcase month for the B.1.617.2 variant, once called the Indian mutation, but nowadays known as the Delta variant.  It now accounts for almost all Covid-19 cases in the UK.  And it is ultra-hazardous.  A report in The Lancet at the end of August found that UK residents who contract this Delta variant are twice as likely to need hospital care compared with those who are infected by the Alpha variant, originally known as B.1.1.7 or the Kent variant, which until recently was the dominant Covid-19 virus in the UK.

And Delta is now causing the most Covid-19 trouble the world over.  For example, it is because of Delta infections that Sydney in Australia has been experiencing its highest daily Covid-19 outbreaks since the pandemic began, leading to a city-wide lockdown lasting until the end of September.  Similarly, the Japanese health ministry’s advisory board has recently urged people to stay at home as the Delta variant was confirmed to account for more than 90% of the surge of new cases in Japan.  The health authorities in Israel have accelerated their schedule of third booster vaccines as cases of the Delta variant continued to soar there.  Also, as a result of the worldwide spread of Delta, the US Department of Defense has insisted on mandatory vaccinations for members of the US military.  Right now, Delta is leading the global pandemic.

Delta is at least 40% more transmissible than the Alpha variant.  But what makes the Delta variant spread like wildfire?  It seems that a simple amino acid mutation in the virus’s spike protein, that key molecule for recognising and invading human cells, could be the cause.  The change is called P681R and it transmutes a proline residue into an arginine – this simple modification seemingly creates such a huge effect.  In turn, that mutation makes the Delta variant more efficient at cutting the spike protein at the so-called furin cleavage site, a process that is the precursor to gaining access into human cells.  Hence, probably, the cause of Delta’s high infectivity and transmissibility.

Unravelling the complexities of the biology of Delta and the other Covid-19 variants is a complex and time-consuming process.  But be comforted, some of the best biologists’ brains in the world are working at it.

A UK fourth wave?

The UK is currently in its third, albeit somewhat indistinct, wave of Covid-19 infections.  A fourth may be imminent.  There are now ominous signs from around the world of its advent.  For example, the USA appears to be on the cusp of its dreaded fourth wave.  Israel, one of the world’s most-vaccinated nations, is already experiencing a surprise fourth wave of infections and hospitalisations.  The country is rushing to provide booster vaccinations.  Germany has also recently declared a fourth spate.  We should take note.

The so-called Freedom Day on 19 July, when almost all UK restrictions, in England at least, were loosened, went off without either an explosion of new cases or an overwhelming of the NHS.  Is all therefore OK?  Have we reached herd immunity?  Should we even be bothered?

No, no and yes.  We should care.  And here is why.  Throughout the UK, the numbers of new cases, hospitalisations and deaths are creeping up.  And at the start of September, most schools return – last year, this event triggered the start of the UK’s second wave.  At that time, 1,000 new cases were recorded each day – now the figure is 35,000.

Why?  There are several reasons.  For instance, UK tourism, belated, though latterly high, has started.  Popular resorts have proved to be popular Covid-19 hotspots too.  Large gatherings, such as festivals, like the Boardmasters mix of surf and music, aimed principally at 50,000 young people over several days in Cornwall during August, suddenly increase risky close social contacts between mostly unvaccinated people.  And although such outdoor attractions limit the likelihood of catching Covid-19, the UK weather is not always sunny and is often more conducive to indoor, and more contagious, entertainment events.

And there is a chastening lesson from Scotland.  Most restrictions were loosened there in early August.  Children returned to school there in mid-August.  And then, a few days later, new Covid-19 cases soared to 3,367, twice the number of the previous week.  Could the rest of the UK see a similar surge when its schools return early in September?  Could such a limited surge turn into a boundless wave?

Are the efficacies of vaccines waning?

The immunity provided by some vaccines, such as those for measles, can be life-long.  However, the effectiveness of most vaccines typically wanes with time, maybe over a few years.  But after just a few months, are the current Covid-19 vaccines sufficiently effective?  There are now doubts.  Though the present-day vaccines remain highly protective against the worst consequences of Covid-19 infections, namely hospitalisations and deaths, they may not be sufficient to stop the spread of variants, particularly that Delta variant.

There is significant evidence from two recent studies.  First, there are the results of a massive study, involving over half a million individual participants, from the Office for National Statistics and the Oxford Vaccine Group.  These data were first published on 24 August as an online preprint at medRxiv, entitled ‘Impact of Delta on viral burden and vaccine effectiveness against SARS-CoV-2 infections in the UK’ by Koen B. Pouwels and colleagues.

This research demonstrated that the effectiveness of both the Pfizer-BioNTech and the Oxford-AstraZeneca Covid-19 vaccines apparently wanes with time.  The Pfizer-BioNTech vaccine was 92% effective 14 days after the second dose, but its protection fell to 90%, 85% and 78% after 30, 60 and 90 days, respectively.  Similarly, the Oxford-AstraZeneca vaccine was 69% effective 14 days after the second dose, but this decreased to 61% after 90 days.

Second, there are the results from the so-called ‘real-world’ Zoe Covid Study, led by Tim Spector and released on 25 August.  It too demonstrated that vaccine protection provided by two doses of either the Pfizer-BioNTech or the Oxford-AstraZeneca Covid-19 vaccines is evidently waning among those first vaccinated several months previously.  Protection from the Pfizer-BioNTech vaccine decreased from 88% after one month to 74% after about six months.  Protection from the Oxford-AstraZeneca vaccine decreased from 77% after one month to 67% after about five months.

Both studies have their critics and weaknesses of experimental design, but both agree that waning of immunity is apparent.  In other words, though Pfizer-BioNTech and Oxford-AstraZeneca Covid-19 vaccines are remarkably safe and effective, the protection they provide do not make people invulnerable for evermore.  This phenomenon is of considerable concern.  Indeed, Tim Spector has estimated that protection against infection could drop to 50% by this winter.  Not all agree.  But these studies have spooked calls for third doses of booster vaccines.

To boost or not to boost?

A riddle for our times.  Do you want a booster, a third Covid-19 vaccination?  ‘Yes, please.’  Do you need one?  ‘Probably not.’

In early August, the World Health Organization (WHO) called on wealthier nations to establish a moratorium on Covid-19 booster shots until the end of September so that more vaccines could be sent to poorer nations.  Some four billion vaccine doses have already been administered globally, but more than 80% of them have gone to high and upper-middle income countries, which make up less than half the world’s population.  In Africa, for example, only 2% of its 1.3 billion people are fully vaccinated, and many healthcare workers and elderly people remain totally unprotected.  Would the decent, moral approach be to hold back on ‘luxury’ boosters to enable the poor world to catch up?

Despite such entreaties, the UK is forging ahead with plans for an autumn booster campaign.  General practitioners and hospitals have been told to implement the programme between 6 September and 17 December.  Questions arise.  Who will be vaccinated?  The over 50s and vulnerable groups?  With what will they be vaccinated?  The same brand of vaccine as their jabs one and two, or will there be a mix and match scheme?  What time gap will be allowed between the second and third doses?  Twelve weeks, six months?  Will this campaign be carried out in conjunction with the annual influenza vaccination programme – a contemporaneous jab in each arm?  The UK’s Joint Committee on Vaccination and Immunisation (JCVI) is currently analysing research results to answer these and other questions.  The truth is that data on the effectiveness of a third dose, and therefore the evidence to recommend such a strategy, are meagre.

While the UK is deliberating, others are pressing ahead.  For example, Israel has already started offering third injections to its population aged over 50.  Yet others are also somewhat unsure.  In early August, the US Centers for Disease Control and Prevention confirmed that most Americans did not need Covid-19 booster jabs.  However, a few days later, US health officials recommended that booster jabs should be given to all adults from 20 September.  Similarly, France and Germany are expected to offer booster vaccinations to their vulnerable people from September.

To boost or not to boost?  Anna Durbin, an infectious disease expert at Johns Hopkins Bloomberg School of Public Health, put it well, ‘Giving a booster to vaccinated people is not going to control Delta.  What’s going to control Delta is vaccinating unvaccinated people.  That is the bottom line.’

Jabs for twentysomethings and schoolchildren

The years of early adulthood are archetypically challenging.  For most, that period between childhood and adulthood is a time of rebellion, or at least, some negativity.  It is often called growing up.  So why would the young not reject the adult world of vaccination?  And they have.  Vaccination rates among young UK people are the lowest of all age groups – just 64% of those between 18 and 24 years old have been jabbed along with only 62% of the 25 to 29 year olds.  For comparison, the uptake across all cohorts of the over 60s is greater than 90%.

The UK authorities have responded.  All 18 to 29 year olds have, since June, been eligible for Covid-19 vaccinations.  In addition, an official video, starring hospitalised and long Covid sufferers, has recently been released and linked to various social media platforms and service companies.  It recounts stories of several previously healthy, young people who suddenly contracted Covid-19 and became bedbound, exhausted and fearful of the future.  All the participants have two things in common – they are young and unvaccinated.  The take-home message – get a jab, get a life.

This is serious.  The twentysomethings are Covid-19 prone.  The highest rate of Covid-19 cases is currently among this age group at 670 cases per 100,000 people.  And those aged between 18 to 34 account for 20% of those currently hospitalised with Covid-19.

Schoolchildren are also a problematic group.  Because healthy children and young people are generally at a lower risk of catching a serious Covid-19 illness, there has been considerable debate about the wisdom, or even the necessity, of vaccinating them.  Benefit-risk balances are not always easy to weigh up.  At present, the Pfizer-BioNTech vaccine is the only jab authorised for younger children and is being offered to them only if they have adverse health conditions or live with someone who is clinically vulnerable.

From 4 August, the UK’s National Health Service (NHS) extended its vaccination programme to include 16 and 17-year-olds.  Then on 23 August, the government achieved its target of inviting all 16 and 17-year-olds to have a Covid-19 vaccine.  Over a million NHS letters were sent out urging them to get vaccinated before returning to college or sixth-form in September.

The NHS has since made plans to vaccinate schoolchildren from the first week of September, after most schools return from their summer holidays.  Hospital trusts in England have been told to prepare for a roll-out for healthy 12 to 15-year-olds from 6 September.

In addition, schools and colleges have been instructed to strive to return to normality, again using facemasks and testing rather than being allowed to close or send pupils home – schools will be told not to be ‘overzealous’ if Covid-19 outbreaks occur.  Testing is expected to occur twice on site, three to five days apart.  It will not be straightforward.  It is anticipated that this mandated transformation of schools from educational establishments to coronavirus-testing centres, serviced by redeployed teachers, will be a considerable logistical challenge from early September.

Vaccines, fertility and pregnancy

During the early, and therefore relatively uninformed, days of Covid-19 and vaccines, there was a natural uncertainty about all possible adverse effects, including those relating to reproductive health – the general advice was for pregnant women to avoid the jab.  Now, after numerous clinical trials and billions of vaccinations there is informed support for the general safety of these vaccines.  Even so, misinformation, myths and rumours still abound.  Some say vaccines will damage you, your fertility and your baby.  They are wrong.

First, there is a fundamental distinction to be clearly understood – though the vaccines have not been specifically associated with adverse effects upon reproduction and sexual functioning, Covid-19, the disease, certainly has.

In early August, the US Centers for Disease Control and Prevention declared, ‘COVID-19 vaccination is recommended for all people aged 12 years and older, including people who are pregnant, breastfeeding, trying to get pregnant now, or might become pregnant in the future.  Pregnant and recently pregnant people are more likely to get severely ill with COVID-19 compared with non-pregnant people.’

Similarly, in mid-August, the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) stated, ‘There is no pattern from the [Yellow Card adverse reaction] reports to suggest that any of the COVID-19 vaccines used in the UK, or any reactions to these vaccines, increase the risk of miscarriage or stillbirth.  There is no pattern from the reports to suggest that any of the COVID-19 vaccines used in the UK increase the risk of congenital anomalies or birth complications.  Pregnant women have reported similar suspected reactions to the vaccines as people who are not pregnant.’

The corollary is this, pregnant women, who are vaccinated, are at no increased risk from the vaccines, whereas pregnant women, who become infected with Covid-19, are at increased risk of severe complications from the disease.  Scientists from Oxford University recently reported that more than 99% of expectant mothers who were admitted to hospital suffering with Covid-19 were unvaccinated.

Some women have reported menstrual cycle problems after vaccination against Covid-19.  In early August, the European Medicines Agency (EMA) reported, ‘No causal association between COVID-19 vaccines and menstrual disorders has been established so far.’  Again, in mid-August, the MHRA reported, ‘The rigorous evaluation completed to date does not support a link between changes to menstrual periods and related symptoms and COVID-19 vaccines.’

On the other hand, there is some evidence that women who have been infected with Covid-19 do experience menstrual disruption, including less bleeding and longer cycles.  Of course, the onset of any disease is likely to cause stress and stress is a notorious driver of disrupted menstrual cycles.

Both the Joint Committee for Vaccination and Immunisation (JCVI) and the World Health Organization (WHO) state that vaccines can be safely administered while breastfeeding – Covid-19 cannot be passed on through breast milk.  For breastfeeding mothers, who are healthy and under 40, it is preferable to have the Pfizer-BioNTech or Moderna vaccines, otherwise any of the vaccines are suitable for the over 40s.

In the case of men, no detrimental changes in sperm counts or other fertility measures have been reported after vaccination.  However, there is limited evidence that Covid-19 can affect sperm quality and erectile performance.

In summary, contrary to the many fertility falsehoods regarding proposed adverse effects of vaccines, there is no supporting evidence.  However, the clear medical and scientific consensus is that to protect against the adverse reproductive and sexual effects of the Covid-19 disease, get vaccinated.

New vaccines – Sputnik V and GSK-CureVac

Covid-19 vaccines are currently hot commodities in terms of health, prestige and finance.  Around the globe, throughout societies, and across cultures, Covid-19 scientists are busy during long nights and relentless days researching and developing.  For instance, Russian researchers have recently reported that they have developed a modified version of their Sputnik V vaccine, also known as Gam-COVID-Vac.  It is now claimed to protect against that contagious Delta variant.  The Russian health minister, Mikhail Murashko, has stated it is 83% effective at preventing hospitalisation.  A new report by a group of St Petersburg scientists led by Anton Barchuk and heralded as the first real-world study of the vaccine, was published as an online preprint at medRxiv on 23 August.  It was entitled, ‘Vaccine Effectiveness against Referral to Hospital and Severe Lung Injury Associated with COVID-19: A Population-based Case-control Study in St. Petersburg, Russia.’  It recorded a vaccine effectiveness against referral to hospital of 81%.  Close enough.  The hope is that such a statistic will boost Russia’s flagging vaccination campaign where only 24% of its citizens are full vaccinated.

Nearer home, the Covid-19 vaccines currently authorised for emergency use in the UK are those from Moderna, Oxford-AstraZeneca, Pfizer-BioNTech and, available later this year, the one-dose Janssen.  Dozens more are waiting in the developmental wings worldwide, though most are unlikely to seek UK licencing permission, but some, including the British drug manufacturer GlaxoSmithKline (GSK), might.

Indeed, in June, GSK announced that the first version of its Covid-19 vaccine, developed with the German company CureVac, achieved only 47% immunity in large-scale Phase 3 human trials.  It was something of a biotechnical and reputational calamity.  GSK has now reported that its revised, second-generation vaccine has produced good results in initial laboratory Phase 1 trials with monkeys.

These latest trials were conducted in collaboration with Harvard Medical School and involved macaque monkeys being vaccinated with either the original vaccine or the new version, known as CV2CoV.  The new version was shown to stimulate more robust immune responses, with higher levels of antibodies and stronger activation of the immune system components known as ‘memory B’ and ‘T’ cells.

The vaccine is based on the same type of mRNA technology that is found at the heart of the Pfizer-BioNTech and Moderna jabs.  GSK and CureVac maintain that their mRNA technology could be used to create a so-called multivalent vaccine, which could protect against several viral variants.  Human clinical trials are expected to begin later this year and the UK government has already said it could purchasqe 50 million doses – there is perhaps an ulterior motive for such an order.  It could lead to the UK developing the ability to manufacture its own mRNA vaccines.  At present, Britain is relying on mRNA vaccines produced overseas – chiefly by Pfizer-BioNTech in Belgium to vaccinate people under 40.

New treatments – Ronapreve and AZD7442

In mid-August, the Medicines and Healthcare products Regulatory Agency (MHRA), the UK’s drugs regulator, approved the first drug of its kind, an artificial antibody treatment developed specifically to treat Covid-19.  It is known as Ronapreve and is a drug linked to several twofolds – it was developed by two companies, Regeneron and Roche.  It is administered as either a subcutaneous injection or an intravenous infusion.  And it is a two-antibody cocktail, a combination of two types of laboratory-made antibodies (casirivimab and imdevimab) that mimic the body’s natural defence against Covid-19.  Its use has therefore been described as a ‘belt and braces’ approach.  In effect, it binds with two different sites on the Covid-19 spike protein and halts the virus’s ability to infect human respiratory cells.  Unlike other Covid-19 treatments, such as the steroid dexamethasone, which palliates the body’s overactive immune system, Ronapreve attacks the virus.

Japan was the first country to licence Ronapreve in July 2021, but it gained world notoriety in October 2020 when it was used to treat President Trump after he contracted Covid-19.  It has been available in the US since last November after trials showed it to speed recovery from Covid-19, reduce hospital admission, death and catching the virus after contact with an infected person by about 70% compared with a placebo.  It reduced the duration of symptoms from 14 to 10, namely, by four days.

The NHS is now assessing how to roll-out this intravenous (IV) treatment to which particular patients.  However, since it is estimated to cost between £1,000 and £2,000 per person, its use is likely to be limited to vulnerable patients whose immune systems are seriously compromised.

Similarly, AstraZeneca has recently reported results with its monoclonal antibody drug, called AZD7442, which is a combination of two long-acting antibodies (LAABs), tixagevimab (AZD8895) and cilgavimab (AZD1061).  It performed well in the Phase 3 human trial by reducing the risk of developing symptomatic Covid-19 infection by 77%.

The trial included 5,197 participants, two thirds of whom were given AZD7442.  There were no cases of severe Covid-19 or related deaths in those treated with the drug, but among participants in the placebo section of the trial, there were three cases of severe Covid-19, which resulted in two deaths.  It could become a useful alternative to other intramuscular (IM) vaccines for some people.  AstraZeneca has already proclaimed it to be the ‘first long-acting antibody combination to prevent COVID-19.’

Antibody testing

There are already two familiar Covid-19 tests – the lateral flow (LF) test and the polymerase chain reaction (PCR) test.  They reveal if a person has the virus at the time of testing.  Antibody tests are different.  They report if the patient’s immune system has previously responded to fight off the disease as a result of either infection or vaccination.

From 24 August, a new UK-wide programme began testing people’s concentrations of Covid-19 antibodies.  Up to 8,000 participants per day, who have presented with a positive PCR test, will be given the option of joining this antibody surveillance testing scheme.

Participants will be sent two finger-prick kits to collect blood samples at home (not as simple as you may suppose) and return them to a designated laboratory.  The first sample must be taken as soon as possible after the positive PCR result, that is, before the body has had time to generate a detectable antibody response.  The second test should be taken 28 days later and will measure the antibodies generated in response to the infection.  By measuring the two levels of Covid-19 antibodies, originating from both infection and vaccination, estimates of patient protection will be made.  By comparing the two results, scientists from the UK Health Security Agency will calculate how much immunity is boosted by infection in vaccinated people, and how that might vary with different variants.

Furthermore, the tests are expected to provide insights into which groups of people do not develop satisfactory immune responses.  This is key information that should help assess the merits of an autumn booster vaccination programme.  The fundamental idea behind the programme is that rather than give a booster jab to everyone in a specific age group, or workplace, irrespective of their health, testing a person’s antibody status will identify those at particular risk – so, low antibodies, get a booster.

Lessons from New Zealand

The five million Kiwis had gone for six months without a single case of Covid-19.  Indeed, the country had been praised for its rapid and stringent lockdowns in recent months which had squashed earlier outbreaks and stopped the virus at its borders.

Then in mid-August, BAM!  One unvaccinated 58-year-old man in Auckland tested positive for the Delta variant.  An instant lockdown was declared in the city.  Schools, offices and businesses were affected, while people 400 miles away in Wellington and elsewhere were also infected.  Within days there were a hundred and more cases.  By the end of August there were over 600.  The Auckland lockdown was initially for a week but will likely remain for an unspecified time.  Genetic analyses have shown the outbreak was linked to that in Sydney, Australia, though the viral route remains unclear.

New Zealand was doing so well.  It had seen only 3,000 cases and 26 deaths throughout the entire pandemic.  It had a policy of ‘go hard, go early.’  What went wrong this time?  By late-August not even a million residents had been double vaccinated and only 1.7 million had received a single jab.  In other words, hardly 20% of its residents were fully protected.  Therefore this current crisis has been mainly attributed to the slow speed and limited extent of the roll-out of New Zealand’s vaccination programme – one of the lowest among the developed countries.  That is not an effective strategy against the Delta variant.  Will it be stoppable?  New Zealand is looking very vulnerable.

Cashing in on Covid-19

Covid-19 vaccines cost money and drug companies charge different prices to different countries.  For example, earlier this year, South Africa purchased doses of the Oxford-AstraZeneca vaccine for $5.25, more than twice the $2.15 paid by the European Union (EU).  The EU pays considerably more for the Pfizer-BioNTech product at $14.70 whereas the Moderna vaccine costs an even higher $18.

In the UK, both Moderna and Pfizer-BioNTech have been criticised for charging, respectively, £26 and £15 for each dose of the required two shots.  These are expensive compared with the Oxford-AstraZeneca vaccine, which costs about £3 per dose, and which the company, along with Johnson & Johnson and its Janssen product, when it becomes available, have committed to selling on a not-for-profit basis while the pandemic lasts.  Moderna and Pfizer-BioNTech have made no such pledge.

Now prices have risen as countries race to order booster vaccines and to build stockpiles against possible waves of infection next year.  Noubar Afeyan, Moderna’s founder and chairman, has been unapologetic about the price of its Covid-19 vaccine.  He has said, ‘This mRNA [technology] was not some academic science that suddenly we found ourselves using to make a vaccine.  There were ten years, over $2 billion of investment and hundreds of scientists working for many years to make all this possible.’

Moderna has agreed to supply 17 million doses to the UK and is now said to be charging European countries $25.50 (£18.40) a dose, up from $22.50 (£16.20). Similarly, Pfizer-BioNTech is said to be charging the UK £22 a dose for booster jabs, compared with £18 previously.

Covid-19 vaccines are big business.  Consider Pfizer-BioNTech.  It has so far delivered more than one billion doses of its vaccine with about another 2.2 billion doses on order.  The company now expects it will generate annual sales of €15.9 billion, having previously forecast trading of €12.4 billion.

Biotech companies are not charities and they need to make profits for their shareholders and for funding their own future research and development projects.  A ‘bullseye’ (£50) for a rich country can hardly be regarded as an excessive price for Pfizer-BioNTech’s life-saving treatment.  By comparison, a ‘Lady Godiva’ (£5) for the required two Oxford-AstraZeneca doses may be considered to be a basement bargain.