Journal of the Plague Years XV – Mutation Anxiety

There are now at least three sequenced mutations of the SARS-CoV-2 virus which causes Covid-19. There is evidence that they are more contagious than the original virus and could be deadlier. But the vaccine developers are on the case, writes Victor Hill.

Good news, bad news

The good news is that here in the UK plus in certain other countries (Israel, the UAE, Bahrain) the roll-out of the vaccination programme is on track. As of Thursday (28 January), 7.45 million British people had been vaccinated with their first shot, and 467,000 with their second shot. That means the UK government is on course to meet its target of vaccinating the 13.5 million over-70s by mid-February (though many of those will still be awaiting the second round). There is a good chance that all over-50s will be vaccinated (or at least offered a vaccination) by Easter – despite the current vaccine spat between AstraZeneca and the EU.

We can therefore be reasonably confident that the number of hospitalisations and consequently fatalities will begin to fall quite soon. Indeed, despite record levels of Covid sufferers in hospital, we have probably already passed the peak of the second wave. Though, on Tuesday (26 January), the UK passed the grim milestone of 100,000 deaths.

The bad news is that there are at least three known mutations of the original virus which are most likely more contagious and possibly deadlier. The available vaccines may have to be re-engineered in order to combat them. Right now, there is a great deal of uncertainty about just how worried we should be.

What we know and what we don’t know about coronavirus mutations

The first mutation emerged, it seems, in Kent in December and quickly spread through London. Mr Hancock, the Health Secretary for England announced the existence of the Kent strain to the House of Commons on 22 December – in response to which the French promptly closed their border, causing traffic mayhem across the county. The New York Times hysterically dubbed Britain plague island. In contrast, the Frankfurter Allgemeine pointed out that it was Britain’s scientific excellence that had enabled the country to identify the new strain:

It has only come to light now because the UK – unlike most other countries, including Germany – has established an effective network for the genetic collection of Sars-CoV-2 isolates from patient samples…

This is correct. The UK has been undertaking genetic sequencing of the virus continuously since the beginning of the pandemic, so was able to spot a new strain early on. The Covid-19 Genomics UK Consortium, harnessing the research expertise of 16 British universities, was established last March with a £20 million government grant.

We cannot be sure that this mutation (known as B1.1.7) did originate in Kent since it could have been brought into the country from elsewhere – not least from mainland Europe given that Kent is the home of Britain’s busiest ferry port, Dover. But we were already aware of the high concentration of cases of Covid-19 in parts of Kent in mid-December. In particular, the district of Swale (the municipal centre of which is the town of Sittingbourne) stood out as a red zone.

My conjecture is that this Kent mutation might have originated in the high security Swaleside Prison located on the Isle of Sheppey. This overcrowded prison has about 1,200 inmates many of whom are lifers and foreign nationals. We know that Swaleside had reported a high incidence of Covid previously. (There is a debate currently underway in the UK about whether murderers should be vaccinated – but let’s not get into that here.) Professor John Edmunds of the London School of Hygiene and Tropical Medicine (also a member of the SAGE Committee) has stated that the virus tends to mutate in areas where many people have it (such as a prison).

One scientific paper produced by the New and Emerging Respiratory Virus Threats Group (NERVTAG) – itself a review of three existing academic papers – has suggested that the Kent variant may be 30 percent more lethal than the original virus. The paper by the University of Exeter even suggested that the strain could be up to 90 percent more deadly. But the NERVTAG findings have been disputed. The sample sizes in question are too small – only eight percent of fatalities are known to have had the Kent strain. And it seems there was no increase in mortality when only hospitalised patients were considered. Moreover, figures may have been skewed by the fact that cold snaps (and it has been a cold January in the UK) can increase mortality.

The second variant has come from South Africa. The two variants are entirely unconnected but appear to be more transmissible (i.e. contagious). They carry higher viral loads, and the South African variant appears to spread more readily amongst young adults with no previous co-morbidities. Many countries, including Britain, have restricted travel with South Africa as a result. The danger is that in future countries will be reluctant to own up to new strains of the virus for fear that neighbours will close their borders.

The South African strain – dubbed B.1.351 or 501.B2 – has mutations on its spike protein which make it more difficult for the immune system to recognise it. That could possibly make it resistant to vaccines. This strain was first identified at the University of Kwa-Zulu Natal in Durban as early as 01 December^[i]. This strain is thought to be responsible for South Africa’s second wave which has torn through Eastern and Western Cape Provinces. However, Moderna (NASDAQ:MRNA) announced on Monday (25 January)  that its vaccine is still effective against the South African strain though it confers less immunity. The company added that it is launching trials of a new booster jab. The UK government has pre-ordered 17 million doses of the Moderna vaccine, but they are not expected to arrive until the spring.

It also seems that immunity acquired against the original virus protects people against the new strain. The developers behind the Pfizer-BioNTech vaccine believe that their jab will still be effective. Even if it ceases to be so, they say they could modify the mRNA technology within about six weeks. Dr Uğur Şahin, CEO of BioNTech, said that their vaccine had already been found to work on 20 mutations.

A third mutant strain has emerged in Brazil (dubbed P1), prompting the UK government and others to ban all flights coming from South America (plus Portugal, because of its close links to Brazil). This was first identified in the Amazonian city of Manaus – where, significantly, there were already high levels of immunity to the original strain. An article in New Scientist this week argues that despite the high rate of coronavirus infections in Amazonas during the first wave of the virus, the second wave of the variant strain has still wrought havoc. This suggests that herd immunity may be harder to achieve than previously thought.

This morning Novavax (NASDAQ:NVAX) announced that its coronavirus vaccine was 89.3 percent effective in large-scale UK trials and 60 percent effective in its South African trials. The vaccine will be manufactured in Stockton-on-Tees but is still awaiting regulatory approval.

A number of mutations of the virus have been found in animals, in particular mink in Denmark proved highly susceptible. Zoetis Inc. (NYSE:ZCS), a large US veterinary pharmaceutical company and a smaller biotech outfit called Medgene Labs have both been working on coronavirus vaccines for animals.

Viral evolution

Viruses evolve as do all organisms – but, because they are essentially autonomous strings of amino acids (proteins) with very few genes, they can evolve extremely rapidly. They exist solely in order to replicate themselves; therefore, successful viruses tend not to kill – if they killed all their hosts then they would be unable to spread and would thus die out. Normally, then, viruses become less fatal but more contagious over time. There are many such viruses in circulation that cause the common cold – and we generally manage to live with them.

There could be many more strains of the SARS-CoV-2 virus out there which have not yet been identified. Some may be more tractable than others. Coronaviruses were previously considered stable – meaning they do not mutate very much. But if there are three mutations in circulation already, there could be many more to come – especially for a country like Britain which has been so slow to impose quarantine requirements on foreign visitors. Professor Andrew Pollard of the Oxford Vaccines Group has predicted that many more coronavirus mutations will be identified this year.

Britain’s Vaccines Manufacturing and Innovation Centre (VMIC) is currently under construction at Harwell in rural Oxfordshire. It will be capable of producing both conventional vaccines and mRNA-type vaccines at scale by the beginning of next year. A spokesperson for AstraZeneca said that they “are starting the processes needed for rapid development of adjusted Covid-19 vaccines” there.

It may be that in due course we all receive annual vaccinations for new strains of coronavirus, just as many people in the first world receive an annual flu jab. That suggests that we shall become more dependent on big pharma over time.

Israel’s Pfizer data

Part of the deal between Pfizer and Israel was that the Israelis, who have unrivalled digital healthcare records, would share data so as to estimate the efficacy of the vaccine more accurately. Preliminary data from Israel on the immunity response of 200,000 vaccinated patients suggest that the efficacy of the first jab does not confer as much immunity as per the original trials. On the plus side, the Israeli data shows a 25 percent fall in serious illness and mortality in the over-60s two weeks after vaccinating 20 percent of that demographic.

This is important for the UK where the government has determined that the delay between administering the first and second jabs should be extended to 12 weeks (from the recommended three). The reasoning behind this is to vaccinate as many people as possible in the shortest available time, given limited supply of vaccine. This is essentially an optimisation strategy which has proven highly controversial. If the first dose is less effective than once thought, then a 12-week delay might lead to a new strain becoming vaccine-resistant.

Is the second wave deadlier than the first?

On 20 January 1,820 people were recorded as having died from Covid-19 in the UK. That was the highest daily figure since the virus first arrived in the country around late February last year – although it may have been inflated by the deaths going unrecorded on previous days. There are about 50 percent more people in hospital with Covid-19 than at the peak of the first wave in April – 36,931 on Tuesday. It has been widely reported that the second wave (late September to the present) has killed more people than the first (March to late June 2020). However, when we look at the excess death statistics, we get a somewhat different picture.

According to the Continuous Mortality Investigation (CMI) set up by the Institute and Faculty of Actuaries, there were 72,900 excess deaths from the start of the pandemic in March to the end of December 2020. Surprisingly, 60,800 of these occurred in the first wave but just 12,000 in the second. That suggests that a large number of people who died from Covid-19 in the second wave would have been expected to die of other causes anyway.

Whereas back in April the number of deaths soared above the five-year average it is now running just a little above the trend line, especially when we consider that the population has grown over the last five years. On some days towards the end of December we were below the trend line. Last month’s Monthly Mortality Analysis from the ONS stated that “Although mortality rates due to Covid-19 increased between October and December 2020, these remain significantly lower than in April 2020”. All this suggests that we have to drill down into the data when dealing with a disease that disproportionately affects the elderly and the chronically ill.

This is not to be complacent. A study by the University of Leicester suggested that almost one third of recovered Covid hospital patients will end up back in hospital within five months and one in eight will die. Many of the hospital admissions during the second wave will have been of people who got sick in the first wave. The toll of Covid-19 will continue long after the pandemic is declared over.

Yes, we should be worried.

***

At present, as I know from personal experience, if you test positive for coronavirus in the UK, you are not told which strain of the virus you have contracted. And those of us who had cold and flu symptoms and who tested positive for coronavirus may have had flu viruses sitting on top of the asymptomatic coronavirus infection – we shall never know.

The NHS is recommending people – especially over-60s, like me – to get the flu jab even before we are called upon to get the vaccine for SARS-CoV-2. I even got a letter last week reminding me that it was not too late get a flu jab. (No, thank you.) I wonder if that is the best use of resources at a moment when, we are told, the NHS is at breaking point, and the reported incidence of flu this year is below average for winter. (No doubt that is partly due to social distancing and better hygiene, which I predict will persist long after Covid-19 is a nasty memory.)

And, by the way, do people who have tested positive for coronavirus, and who are asymptomatic, benefit from the vaccine, assuming they already have immunity? A study by Public Health England suggested that people who have had coronavirus carry 83-99 percent immunity for at least five months, maybe longer. Ideally, people should have an antibody test before vaccination to avoid wasting vaccine stocks.

There is something else in play which is momentous. I am averse to conspiracy theories, but I sense that a growing body of serious academic opinion is tilting towards the view that this virus did not originate in a bat cave – but in a laboratory. I’ll have more to say about that soon.

^[i] See: https://www.wired.com/story/worrisome-new-coronavirus-strains-are-emerging-why-now/?xtor=ES-208-[41633_NEWS_NLB_ACT_WK04_Thur_28_Jan]-20210128-[Wired]