Coronavirus
- Part 11 (September
2021)
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?