Coronavirus update – Part 11

Dr John Ling continues to provide us with a monthly review of all things Covid. This, his latest offering, was published a few days ago on his personal website, which is well worth a look for many other resources and information. Thank you John!

The Covid-19 numbers

The total number of confirmed Covid-19 cases in the UK, since the pandemic started in November 2019, is now approaching 7.8 million.  It means that more than 10% of the UK’s population have been infected and epidemiologists tell us these figures are underestimates.

Turning to the month of September, the numbers of daily Covid-19 cases in the UK trended ambiguously – somewhat like the men of the grand old Duke of York, they were neither up nor down.  They ranged from a high of 42,076 to a low of 26,227 but mainly loitered around 35,000.  These wretched viruses spent September vacillating here and there, as viruses evidently do.  All this is more motley news – no-one can say the Covid-19 situation is better or worse.

Figures for Covid-19 daily deaths throughout September were similarly wavering.  They ranged from a mere (not le mot juste) 40 to a shocking 209.  The UK total since the pandemic began is now a little over 136,000.  Of course, this is a figure that can trend only upwards, but thankfully, quite slowly.

Another forever upward dataset relates to vaccinations.  In total 48.8 million people in the UK have now had a first dose, and 44.8 million are now double-vaccinated.  So 93.6 million doses have been administered with 72% of the UK population having been single jabbed.  However, the vaccination programme has recently lost momentum, its rate has foundered.  At the end of September, only about 22,000 doses were jabbed each day, whereas in July the average was 100,000 and in mid-March it peaked at 500,000.

Hospitalisations of Covid-19 patients have plateaued mainly because the susceptible elderly have been comprehensibly and safely vaccinated and other vaccinated age groups are now protected from severe Covid-19 and thus the need for hospital admission.  Nevertheless, the current numbers in hospital are approximately 7,000 with 800 on ventilators, similar to the August figures.

Globally, the picture remains grim.  A total of 233 million people have now been plagued by the Covid-19 virus, culminating in 4.8 million deaths.  The USA is still the most infected country (an average of 110,000 new cases per day) with the UK in second place (35,000) followed by India and Turkey.  Top of the total death table is the USA (690,000) followed by Brazil, India and Mexico, with the UK in eighth place (136,000).

After almost two years of Covid-19 might we have hoped that the pandemic would now be under better control?  For sure, enormous scientific advances have been attained, vaccines and other countermeasures employed, public health strategies devised and applied, social and personal sacrifices made.  Yet infection rates continue to rise and almost 10,000 deaths occur worldwide, every day.

This pandemic remains a personal and global calamity.

Plan A and Plan B

On 14 September, in a televised news conference, Boris Johnson announced the UK government’s winter strategy (Plan A with a contingency Plan B) to deal with rising Covid-19 cases plus the annual added threat of winter illnesses menacing and potentially overwhelming the NHS.

Plan A, officially known as the ‘Covid-19 Response: Autumn and Winter Plan’, includes encouraging the unvaccinated (currently 30 million people in the UK) to get jabbed.  It also involves starting Covid-19 third booster jabs for approximately 30 million people, principally among the over 50s and first jabs for 12 to 15 year olds.  In addition, the NHS Test and Trace (NHST&T) service and free PCR tests will be continued.  And free flu vaccinations for oldies and secondary school students will be introduced.  Finally, there will be reminders to open the windows for indoor meetings and wear face coverings in crowded settings, and presumably keep washing hands frequently.

Plan B will be activated ‘as a last resort’ if Plan A proves to be insufficient to prevent ‘unsustainable pressure’ on the NHS.  Among its features, it will involve more face coverings in more settings, more working from home and the introduction of vaccine passports.  Plan B would be launched in response to ‘concerning data’, such as rapid increases of Covid-19 cases and hospitalisations, as well as the general situation within the NHS.  Plan B could be introduced promptly or gradually, nationally or regionally.  Has a Plan C ever been considered?

First jabs for children

The experts have disagreed.  After months of debating and dithering, the scientists were finally pitted against the medics during September.  The scientists, represented by the 15-member Joint Committee on Vaccination and Immunisation (JCVI), decided on 3 September not to recommend the mass vaccination of healthy children.  It concluded that although the health benefits of vaccinating children slightly outweighed the risk of adverse side-effects, the margin was too small given that most children suffer only mild Covid-19 symptoms.  The JCVI then handed over its decision to the chief medical officers (CMOs) of the four home nations.

On 13 September, the medics, represented by Professor Chris Whitty, the CMO for England, and speaking on behalf of the other nations’ CMOs, recommended that all over-12s should be offered the vaccine after concluding that it would help avoid further disruption to their education and social lives, tipping the balance in favour of routine teenage immunisation.  Whitty estimated that about half of children in this age group have already been infected, with transmission in those aged 10 to 19 now higher than in any other age group.

Also on 13 September, Sajid Javid, the Health and Social Care Secretary, stated, ‘I have accepted the recommendation from the Chief Medical Officers to expand vaccination to those aged 12 to 15 – protecting young people from catching COVID-19, reducing transmission in schools and keeping pupils in the classroom.’

The upshot is that 3 million healthy 12 to 15 year olds in the UK will now be offered just one dose of the Pfizer-BioNTech Covid-19 vaccine.  The parents of such children will be asked to decide if their youngsters can be vaccinated.  A decision on a second jab will be postponed until next term.  The first of these jabs were administered by school nurses and their teams from 20 September.

This teenage jabbing has raised at least two major issues.  The first is informed consent.  Who decides?  The government considers it to be a joint affair between parent and child, but conflicts can be foreseen.  Here the principle of ‘Gillick competency’ can be used to determine if a person under 16 can opt for treatment without the need for parental consent.  The term originated after the long-running legal battle of Gillick vs. West Norfolk and Wisbech Area Health Authority.  It was brought by Victoria Gillick and concluded with a 1985 decision by the House of Lords in a case concerning contraception advice given by an NHS doctor.  The ruling holds that the authority of parents to make decisions for their underage children is not absolute, but diminishes with the child’s evolving maturity.  In other words, decision-making shifts from the parent when the child achieves sufficient understanding and intelligence to comprehend fully what is proposed.  How this might be adjudicated in possibly thousands of family conflicts over Covid-19 vaccinations is unclear.

The second major issue concerns the very rare cases of vaccine-induced inflammation seen in children’s hearts.  About 10 per million children suffer some form of cardiac disease after taking the vaccine.  Two conditions occasionally arise.  In pericarditis, the membranes around the heart are inflamed, whereas in myocarditis the heart muscles are affected.  Symptoms in both diseases include chest pain and breathlessness.  When unrelated to vaccination, pericarditis is the less serious disease and usually resolves itself with time, whereas myocarditis can be associated with long-term problems and lead to life-threatening arrhythmias or cardiac arrest.

Moreover, post-vaccination, myocarditis would probably still appear infrequently.  The JCVI reckons that 3 to 17 cases of myocarditis would occur per million children vaccinated.  Before the pandemic, that is, in non-vaccine induced myocarditis, between 20 and 130 cases in children would be seen in UK hospital settings each year.  Although recovery is common, it is the long-term effects upon heart and general health that remain largely unknown and of concern.

So, because of their relative novelty, namely, less than 2 years of the pandemic, these incidents and outcomes of vaccine-induced pericarditis and myocarditis have been neither fully investigated nor fully understood.  Therefore some children and their parents may consider it prudent to wait for more detailed information before opting into this teenage vaccination programme.  After all, it is not generally regarded as an immediately essential prophylaxis because the childhood benefits only narrowly outweigh the potential risks – wholly unlike the situation with the vaccination programme for adults.

On the other hand, several countries, such as the USA, France and Israel have been offering jabs to teenagers for months.  Furthermore, recent research from the USA has shown that such cardiac complications were six times more likely after a Covid-19 infection than after a Covid-19 vaccine in 12 to 15-year-old boys.

None should consider these matters trivial.  For many, there is genuine uncertainty about the ethics and facts, as well as the benefits and risks, surrounding these issues.  The way forward will require honesty and transparency.  And time.

Third jabs for adults

For several weeks, the arguments for and against third booster jabs for adults have been presented, discussed and disputed.  For example, Professor Dame Sarah Gilbert, the brains behind the Oxford-AstraZeneca vaccine, reasoned against such third jabs.  She maintained that booster vaccinations for everyone were unnecessary, except for those in vulnerable groups.  After all, she claimed, immunity, though waning, was still high.  Instead, she called for spare doses of vaccines to be sent to more needy countries.

Despite such persuasive perspectives, the government decided otherwise.  On 14 September it announced that all UK oldies (over 50s), care workers and younger adults with certain chronic health conditions, will be offered a third booster jab of either a full dose of the Pfizer-BioNTech or half a dose of the Moderna vaccine irrespective of the first two brands previously administered, and at least six months after their second dose.  From 15 September, the scheme began with the vaccination of frontline healthcare workers.

Note – Mrs Gilbert’s Oxford-AstraZeneca vaccine did not make the cut and therefore it will not form a routine part of the UK’s booster programme.  Apparently the reasons are that, despite a billion doses distributed worldwide, fears of those rare, but sometimes life-threatening, clotting events have limited its use, and ‘mix and match’ trial results have favoured the two mRNA vaccines rather than the adenovirus-based one.

Breakthrough cases and deaths

Vaccine breakthrough cases are to be expected, though seldom.  Most people who develop Covid-19 are unvaccinated.  However, since vaccines are not 100% effective at preventing infection, some people who are fully vaccinated will get Covid-19, become ill, be hospitalised and may even die.  Such illnesses in fully vaccinated people are referred to as ‘vaccine breakthrough infections’.

Fully vaccinated people, who suffer from a vaccine breakthrough infection, tend to exhibit certain features.  For instance, they are less likely to develop serious symptoms compared with those who are unvaccinated and who contract Covid-19.  This means they are much less likely to be hospitalised or die compared with people who have received only one shot or no such vaccinations.  However, people who suffer vaccine breakthrough infections can still be Covid-19 spreaders.

According to the Office for National Statistics (ONS), out of the tens of thousands of Covid-19 deaths recorded in England since the pandemic began, during the sixth-month period, from 2 January to 2 July 2021, there were a total of 51,281 Covid-19 deaths, of which only 256 were in fully vaccinated people.  Moreover, among this latter cohort, they had been double jabbed and first had a positive PCR test more than two weeks after their second jab, and they were mainly people who were over 84, who were immunosuppressed, and more often men (61%) rather than women (39%).

Breakthrough cases are rare – vaccinations do protect.  In addition, using the so-called ‘non-pharmaceutical interventions’ can further limit breakthrough infections.  They consist of that simple three-step routine – wear a face covering, maintain social distancing and wash hands frequently.

Autoantibodies

Covid-19 has challenged many of our ideas about the aetiology and progress of such a disease.  For example, why do Covid-19 patients display such a spectrum of symptoms ranging from mild snuffles to death?  And what causes long Covid and its often months of trouble from minor aches and pains to multiple organ failure?  Several studies suggest that the answer could be autoimmunity.

This phenomenon is caused by the presence of autoantibodies.  These are antibodies, typically regarded as rogue antibodies, produced by a person’s own immune system, that fail to recognise foreign substances and instead turn against and attack a person’s own tissues and organs.

At the beginning of the pandemic, researchers suggested that some infected people had overactive immune responses to Covid-19 infections.  Components of the immune system known as cytokines can surge and trigger ‘cytokine storms’ which in turn can damage the body’s own cells.  However, as the pandemic has progressed, the additional role of autoantibodies has become more evident.  In contrast to ‘cytokine storms’, which tend to cause systemic, short-duration problems, autoantibodies are thought to result in targeted, long-term damage.  Studies have reported that as many as 10% of individuals with Covid-19 possess autoantibodies that can attack and block type-I interferons – these are blood-borne components that have a vital role in fighting viral infections.  Moreover, autoantibodies have been detected in 18% of people who have died from Covid-19.

Healthy people can generate autoantibodies, but they are usually in low concentrations.  However, some Covid-19 patients seem to be genetically predisposed to producing autoantibodies in high concentrations.  Or it may be that the infection itself may initiate their production.  A better understanding these possibilities could help devise additional, effective Covid-19 treatments.

Nanobodies

Somewhat unexpectedly, llamas and camels have recently been recruited in the cause of developing Covid-19 therapies.  These camelids naturally produce nanobodies in response to infections.  These are small, simpler versions of antibodies.  And they have ‘potent therapeutic efficacy’ against Covid-19 infections, at least in rodents, such as the cute Syrian golden hamster, and they ‘prevented disease progression’ and enabled full recovery after six days of treatment.  What is more, they can be delivered as a nasal spray as well as by injection.

This ground-breaking work has been recently reported as, ‘A potent SARS-CoV-2 neutralising nanobody shows therapeutic efficacy in the Syrian golden hamster model of COVID-19’ by J Huo et al., in Nature Communications (22 September 2021).

These researchers used Fifi, the llama belonging to the Rosalind Franklin Institute in Oxfordshire.  By vaccinating her with a piece of the Covid-19 viral spike protein, they stimulated her immune system to synthesise nanobodies.  Those nanobodies most able to bind with the Covid-19 virus were selected and cultured.  These, known as C5, H3, C1 and F2, were shown to neutralise several Covid-19 variants.

Public Health England has said that these nanobodies were among the ‘most effective SARS-CoV-2 neutralising agents’ it had ever tested.  Of course, more data on efficacy and safety are needed before human trials can begin.  Nevertheless, nanobody treatments for Covid-19 look to be exciting additions to vaccines in the therapeutic armoury – they are cheaper to produce than antibodies and easier to administer.

Johnson & Johnson vaccine update

Besides storage in a domestic refrigerator, one of the other major advantages of the US-produced Johnson & Johnson, so-called Janssen, vaccine is that it requires only a single dose.  Its one-shot overall efficacy in preventing Covid-19 was reported to be 67% and 85% effective in preventing severe disease or hospitalisation.  But now comes data from further studies in the US showing that giving a second shot generates an even greater protection against moderate to severe Covid-19.symptomatic infection, namely, up to 94%.  That is comparable with the two-shot regimen of the widely used vaccines from Pfizer-BioNTech and Moderna.

Moreover, another of the US studies showed that withholding a booster shot for 6 months or longer, rather than the regular 2 months, gave a 12-fold increase in antibodies rather than the regular 4-fold increase.  In other words, protection is stronger if people get boosters later.

Back in May, the Medicines and Healthcare products Regulatory Agency (MHRA) approved the Janssen vaccine for use in the UK and the government secured 20 million doses.  These are expected to be available for use later this year.

ZyCoV-D a new vaccine for Covid-19

A whole new class of so-called DNA vaccines has been developed and trialled for use in people against various diseases.  ZyCoV-D is one such vaccine that has now been approved by Indian authorities in the fight against Covid-19.

ZyCoV-D was developed by the Indian biotech company Zydus Cadila.  The efficacy figure of 67% came from trials involving more than 28,000 participants, which recorded 21 symptomatic cases of Covid-19 in the vaccinated group and 60 among people who received a placebo.  In late August, India’s drug regulator authorised ZyCoV-D for people aged 12 and over.  The first doses were administered in September with plans to produce up to 50 million doses by early 2022.

ZyCoV-D contains circular strands of DNA known as plasmids.  These encode the spike protein of the SARS-CoV-2 virus, together with a promoter sequence for turning the gene on.  These plasmids must first enter the nuclei of cells, where they are converted into mRNA, which is translated into the spike protein in the cells’ cytoplasm.  The body’s immune system then responds against the spike protein and produces immune cells that can attack future infections.  Although plasmids typically degrade within weeks to months, their immunity remains.

ZyCoV-D has distinct advantages.  For example, it is administered, with a special needle-free applicator, just below the skin surface where the DNA is more efficiently captured than in muscle – so needleless administration, so less fear and less pain.  Yet, as stated above, in clinical trials ZyCoV-D was only 67% protective against symptomatic Covid-19.  While that figure is comparatively low, it demonstrates a proof of principle for this new class of DNA vaccines.  They are also relatively easy to manufacture – around the world 20 or so such DNA vaccines are in various developmental stages and clinical trials.  And they are more stable than mRNA vaccines, so storage is less demanding.  This new class of DNA vaccines look therapeutically promising.

Covid-19 overtakes Spanish flu

The Spanish flu pandemic of 1918 was reckoned to have been the deadliest disease the world had ever known.  It was caused by the H1N1 influenza A virus.  The first outbreak was recorded in February 1918 in Kansas and then it zipped around the world in waves from the USA to France, Germany, the UK, China and elsewhere until April 1920.  There were an estimated 500 million cases globally, accounting for about one-third of the world’s population, and it caused 25 to 50 million deaths.

Now the Covid-19 pandemic has seemingly surpassed the Spanish flu figures, at least in the USA.  According to its Centers for Disease Control and Prevention (CDCP), an estimated 675,000 Americans died during the 1918 pandemic.  But on 22 September 2021, Covid-19 deaths in the USA were reported to have reached 676,076.  It may, of course, be argued that because the US population in 1918 was a third of today’s number, the Spanish flu was more deadly.  Comparisons have been made with that other great US lethal crisis, the American Civil War, which amassed a death toll of only 620,000, though the population in the 1860s was even less than those of 1918 or 2021.  Moreover, the victims of the Civil War and the Spanish flu did not have access to the therapeutic wonders of twenty-first century medicine.  Then again, the current numbers of Covid-19 deaths in the US and elsewhere are still climbing.

Regardless of such historical assessments, America is today about the worst affected nation of all those categorised as rich with an ageing population.  Indeed, US deaths make up 14% of the 4.7 million worldwide Covid-19 fatalities, and yet the US represents only about 4.2% of the global population.  Why so bad?  Most commentators point to the country’s inadequate response when the pandemic first struck.

New Zealand revisited

In Coronavirus – Part 10 (August 2021) the story of New Zealand’s radical fight against Covid-19 was outlined.  The country had seen only 3,000 cases and 26 deaths since the pandemic began.  It had a policy of ‘go hard, go early’ with stringent lockdowns that had created a nation of zero Covid-19 cases.  Then in mid-August, one man brought in the Delta virus to the country’s largest city, Auckland.  It ripped across the islands developing into hundreds of cases.  And with hardly 20% of residents having been double jabbed, New Zealand was looking very vulnerable.  The country’s response had moved from praiseworthy to blameworthy.

Now, in late September, Auckland still remains in lockdown.  Despite the prime minister, Jacinda Ardern, pledging to eliminate the virus, the health director-general, Dr Ashley Bloomfield, has warned that the nation may not be able to return to zero Covid-19 cases.  His somewhat belated plea has again emphasised the need to trace, test and isolate in order to break the spread of the virus, as well as the fundamental importance of increasing the vaccination rate.  Currently 40% of adult New Zealanders have been double jabbed with 75% single jabbed.

Arden has recently declared a revised strategy in which vaccinations will replace lockdowns.  She has announced a target of 90% fully vaccinated.  But even if that were achieved, new modelling data suggest that there would still be 171,000 infections, 6,000 hospital admissions and just over 600 deaths within the next 12 months.  The slow speed and limited extent of the roll-out of New Zealand’s vaccination programme – one of the lowest among the developed countries – is bearing its bad fruit.  The previous target of elimination of the virus and zero cases now looks forlorn.

But at the end of September, the vaccination figures have fallen off the cliff.  For example, on Monday 27 September, just 12,641 New Zealanders got a first dose – the lowest weekday total since mid-July.  Alas, this is a trend, not a blip.  During mid-September, the average daily rate dropped to about 20,000 – less than half the lockdown-driven rate of 55,000 earlier in September.  New Zealanders have come late to the vaccination party.  Too late?