Coronavirus - Parts 1,
2, and 3can be accessedhereandhere and here
First, some
elementary biology plus a home truth. Viruses cannot
mutate unless they are replicating and they cannot replicate
unless they can get into cells. Keeping them out by
vaccinating people can shut down that process. That’s
what you want. You want to stay out of the hospital, and
stay out of the morgue.
What a difference a month makes
Consider the data. In Coronavirus – Part 3 (January
2021) I wrote, ‘On 26 January, it was announced that over
100,000 deaths in the UK had been caused by Covid-19. It
is a forbidding milestone. In addition, there has been a
total of almost 4 million UK cases reported since the start of
the pandemic, with currently some 40,000 people hospitalised
and 4,000 on ventilators.’ Now, a month later, at the
end of February 2021, the total UK deaths have slowly risen to
just over 120,000 with barely more than 4 million cases and
with fewer than 15,000 people hospitalised and 2,000 on
ventilators.
The figures are falling steadily, but they are still too
high. The current rate of infection, at about 6,000
cases per day, is still far, far too great. The other
big numerical difference is that in January less than 6
million people had received their first coronavirus
vaccination, whereas by February that figure had reached 20
million.
Are we doing well? Yes and no. UK domestic
hospitalisation and death numbers have undoubtedly
decreased. But, think globally about the 112 million
cases and 2.5 million deaths. And there is one striking
statistic – the UK's current death rate is 1,800 deaths per
million population. We are top of that league table and
therefore the worst in the world. It is far from over.
The vaccination roll-out
This great event began, with appropriate media razzmatazz, on
Tuesday 8 December 2020. It has since made remarkable
progress. It has already been called a ‘game
changer’. Indeed, it has already been linked to a
substantial reduction in hospital admissions.
The UK vaccination plan has set various targets for various
groups. The one-dose target for 15 million people in the
top four priority cohorts was met by mid-February – that was
no small accomplishment. The next goal is to offer a
first dose by 15 April to all those in the Phase 1 priority
groups, namely the 32 million people in the top nine priority
groups, those aged 50 and over and those with underlying
health conditions. And finally, everyone over 18 and
living in the UK will have been offered a coronavirus
vaccination by 31 July.
At the end of February, the Joint Committee on Vaccination and
Immunisation (JCVI) modified the Phase 2 vaccination roll-out
by making it simply age-based, starting with the oldest,
rather than prioritising those in occupational groups, such as
teachers and police officers. The JCVI has stated that
individuals who are at increased risk of severe outcomes from
Covid-19 on account of their occupation, male sex, obesity or
ethnic background are likely to be vaccinated most rapidly by
this revised, operationally straightforward, vaccine
strategy. In other words, since age is the biggest risk
factor, this is considered to be the most effective way to
minimise hospitalisations and deaths.
The road map out of lockdown
On 22 February, the prime minister of the UK, Boris Johnson,
announced his long-awaited road map, the way out of lockdown,
a ‘one-way road to freedom’, at least for England. The
details were set out in a 60-page document. The other
three UK nations have similar plans for monitoring the data
and, when considered appropriate, unlocking activities on
particular target dates. These are wise and cautious
approaches, though they have their detractors – some want
faster progress, some want slower.
The English road map consists of four steps with key
dates. In brief, they are Step 1] 8 March when
schools reopen, and two people are allowed to meet outdoors,
plus 29 March when six people, or two households, will be able
to meet outdoors. Step 2] 12 April when
non-essential retail and outdoor hospitality are due to
open. Step 3] 17 May when six people, or
two households, can meet indoors and indoor hospitality,
cinemas and hotels can open. And finally Step
4] 21 June when all restrictions are due to
end. Health secretary, Matt Hancock, warned that
everybody has to ‘play their part’ if this timetable is to be
achieved.
These dates are not immutable, they are contingent on four
conditions – the vaccination programme going to plan,
decreasing numbers of deaths, no surge in hospitalisations,
and no dangerous emerging variants. The road map’s four
steps include 5-week gaps so that risks can be assessed before
moving onto the next set of lockdown freedoms. This
makes scientific and medical sense. It is reckoned that
each step in the liberalisation of lockdown will take about 4
weeks to show positive effects.
Under the road map, international travel will not return until
17 May at the earliest, but that did not deter people planning
their trips abroad. On the day the road map was
announced, travel bookings leapt. For instance, EasyJet
reported a 337% rush in flight bookings and a 630% jump in
holiday bookings.
So, Monday 21 June is now circled in everyone's diary.
From then, hopefully, social distancing will no longer be
legally required, weddings will have no attendance limits and
we can again hug and kiss our families and friends in private
and in public, with their consent, of course!
Vaccine efficacy
No vaccines are 100% effective, but we still want to know how
beneficial they might be. Previous data published by the
manufacturers were obtained under strict clinical-trial
conditions. Now data from so-called ‘real-world’
situations are being published.
At the end of February, early results from three trials were
announced. First, the SIREN (Sarscov2 Immunity and
REinfection EvaluatioN) study focused on healthcare workers
under 65, who, after 21-days post-vaccination with the
Pfizer-BioNTech product, had a more than 70% reduced risk of
catching Covid-19 rising to 86% after the second dose.
This corresponds with data from Israel suggesting that 75%
protection occurs after a single dose of the Pfizer-BioNTech
vaccine in healthcare staff. Second, there were data
from Public Health England (PHE), which showed that in the
over 80 age group there was a 57% decrease in mild or severe
Covid-19 after the primer dose of Pfizer-BioNTech, rising by a
further 30% after the booster. Third, there were results
from the University of Edinburgh, based on 1.14 million
vaccinations, which showed that both the Pfizer-BioNTech and
Oxford-AstraZeneca vaccines were highly effective. By
the fourth week after receiving the initial dose, the risk of
hospitalisation from Covid-19 was reduced by up to 85% and 94%
respectively.
In summary, these preliminary figures show that vaccination
provides a very substantial protection after the first dose
while the second dose provided even greater protection, so it
is important for people to roll up for the booster.
Vaccine hesitancy
It would be too optimistic to expect anti-vaxxers, conspiracy
theorists and maybe even misinformed sceptics to line up for
their jabs. But there are still considerable numbers of
other people who are vaccine hesitant – figures suggest they
account for between 11 to 15% of the adult population.
Top of the numerical list are members of BAME (black, Asian
and minority ethnic) communities.
For example, by 11 February 2021, among those aged over 80
years old, 91% of white people had been vaccinated, compared
with only 58% of black people and 72% of people from South
Asian backgrounds. Similarly among the 70 to 79 year
olds – 66% of white people in this cohort had been vaccinated,
compared with 46% of black people and 62% of people of South
Asian ethnicity. These differences are a concern and
they require attention.
New vaccines and treatments
There are already some 300 Covid-19 vaccines in various stages
of development – 10 are in use or approved and 70 are in
clinical trials. Small biotech businesses, as well as
Big Pharma companies, are busy designing, producing and
testing new Covid-19 vaccines. Other enterprises, such
as those conducted by the Oxford University-based Randomised
Evaluation of Covid-19 Therapy (RECOVERY) trials, are
experimenting with promising Covid-19 treatments. Theirs
are stories of hope, success and failure –
here a few examples.
Antibody therapies are being devised by several companies
including Eli Lilly and Regeneron. For example,
scientists at the University of Pennsylvania and the biotech
firm Regeneron are investigating whether technology developed
for gene therapy can be used to make a nasal spray that will
prevent coronavirus infection. Regeneron’s antibodies
are themselves in clinical testing but have received emergency
approval for patients with mild or moderate Covid-19 who are
at high-risk of getting severe disease. This regimen was
notably used last November to treat President Donald
Trump. Researchers are hoping that the nasal spray could
be squirted into the nostrils, enter nasal epithelial cells
and then hijack their protein-making machinery so that they
generate Regeneron’s antibodies.
Sorrento Therapeutics of San Diego is also working on new
antibody therapeutics. The company has recently
announced a Phase 1 clinical trial to test the safety and
efficacy of COVI-DROPS, nose drops containing the company’s
COVI-AMG neutralising antibody. It is claimed it can
boost immunity against Covid-19 by blocking the infection and
spread of the virus. This intranasal route is attractive
– it is simple, avoiding an injection and a visit to a
vaccination site.
In February, Sanofi and GlaxoSmithKline announced the start of
a new Phase 2 study with 720 volunteers to select the most
appropriate antigen dosage for Phase 3 evaluation of their
adjuvanted recombinant protein Covid-19 vaccine candidate – a
‘refined antigen formulation’. This comes some two
months after they disclosed lower immune responses and higher
levels of adverse events than expected for their first
vaccine. Even if these trials are successful, the
vaccine will not be available until the end of 2021 – a
significant setback of six and more months for a programme
funded by $2.1 billion funding from the US government.
And looking ahead, the team behind the original
Oxford-AstraZeneca vaccine has been devising a new product
that could be effective against all Covid-19 variants.
Instead of targeting the spike protein, as all current
vaccines do, it would target the core of the virus. It
could be ready for use in as little as a year.
In addition, several non-antiviral agents are being
studied. The World Health Organization (WHO) already
strongly recommends that corticosteroids, such as
dexamethasone, hydrocortisone and prednisone, be given orally
or intravenously for the treatment of patients with severe and
critical COVID-19.
And there is, tocilizumab, a monoclonal antibody, commonly
used as an anti-inflammatory drug in the treatment of
rheumatoid arthritis. Preliminary results from the
Randomised Evaluation of COVid-19 thERapY (RECOVERY) trial
conducted by Oxford University showed that tocilizumab
significantly reduced deaths in patients hospitalised with
Covid-19 – for every 25 patients treated with tocilizumab, one
additional life can be saved. And for Covid-19 patients
who were not on invasive mechanical ventilation, tocilizumab
also significantly reduced the likelihood of their progression
to either invasive mechanical ventilation or death by 38% and
33% respectively.
And there is azithromycin, an antibiotic medication.
However, when almost 8,000 patients were enrolled in a
RECOVERY trial to assess its effects in patients admitted to
hospital with Covid-19, it did not improve survival or other
pre-specified clinical outcomes. In other words,
azithromycin had no meaningful clinical benefit for patients
hospitalised with severe forms of the disease.
The first Covid-19 challenge study
The first of its kind, a Covid-19 human challenge study, has
begun in the UK by recruiting up to 90 healthy volunteers,
aged between 18 and 30. They will be deliberately
exposed to the Covid-19 virus in a safe and controlled
environment, closely monitored by doctors and
scientists. Later, a test vaccine will be given to see
if it is successful in preventing the coronavirus infection,
as well as identifying any adverse side effects.
According to Clive Dix, of the Vaccines Taskforce, ‘We expect
these studies to offer unique insights into how the virus
works and help us understand which promising vaccines offer
the best chance of preventing the infection.’
However, such challenge studies are controversial and not
without risks to the volunteers, who will in this particular
investigation, be compensated up to the tune of £4,500.
Professor Julian Savulescu, the provocative bioethicist from
Oxford University, has stated (The Lancet, 2020, 30
December), ‘Despite their ethical justifiability, it is quite
possible that the backlash against a death of a healthy
volunteer might shut down or significantly retard the use of
challenge studies, and perhaps vaccines in general.’
Nevertheless, he added that in this worldwide pandemic
emergency, time lost means lives lost, and thus there is a
moral imperative to develop a safe and effective vaccine as
soon as possible. He continued, ‘The chance of someone
aged 20 to 30 years dying of Covid-19 is about the same as the
annual risk of dying in a car accident. That is a
reasonable risk to take, especially to save hundreds of
thousands of lives. It is surprising challenge studies
were not done sooner. Given the stakes, it is unethical
not to do challenge studies.’ The results from this
particular study will be eagerly awaited.
Vaccination passports or immunity
certificates
These are prickly topics surrounded by complex legal, ethical
and logistical paraphernalia. Should a government make
it a legal requirement to prove that a person has been
vaccinated, whether for employment, or travel, or
whatever? Is ‘no jab, no job, no journey’ the best way
forward? For instance, should such a passport be
compulsory for healthcare workers in hospitals or care
homes? What about those attending schools or football
matches? The ideological shift has already begun.
For example, from 2021, the Australian airline Qantas will
demand passengers provide proof that they have had a Covid-19
vaccination if they want to fly into or out of that country.
Again, Julian Savulescu comments that, ‘Smallpox was
eradicated by 1979 through vaccination, which was mandatory in
many countries (parents were fined in the UK if they did not
vaccinate their baby in time). In the face of that kind
of emergency, research and control are moral imperatives, even
involving compulsory vaccination. There is a moral
imperative to prevent and treat any disease that causes
suffering and death.’
UK governments have long been opposed to issuing
identification cards. And so it was with this current
administration. After all, who wrote in 2004, ‘Ask to
see my ID card and I'll eat it’? Boris Johnson, of
course. Nevertheless, the UK appears, in line with many
other countries, to be capitulating. Michael Gove,
Chancellor of the Duchy of Lancaster, who in December 2020
announced there were no plans to introduce such passports, has
recently been appointed to lead a review into the need and
style of such documentation. It will not be easy.
In February, the SET-C (Science in Emergencies Tasking –
COVID) responded to a government request by proposing 12
criteria that should be satisfied by a Covid-19 vaccination
passport. They are, a passport should 1] meet benchmarks
for Covid-19 immunity, 2] accommodate differences between
vaccines in their efficacy, and changes in vaccine efficacy
against emerging SARS CoV-2 variants. It should be 3]
internationally standardised with 4] verifiable credentials
for 5] defined uses, and based on 6] a platform of
interoperable technologies, 7] secure for personal data, 8]
portable and 9] affordable for individuals and
governments. It should meet 10] legal and 11] ethical
(equity and non-discrimination) standards, and 12] the
conditions of use should be understood and accepted by
passport holders. Complex, eh?
Fertility and vaccinations
The internet has been buzzing with vaccination misinformation
including that Covid-19 jabs can adversely affect fertility,
so making some men and women vaccine hesitant. The
Association of Reproductive and Clinical Scientists and the
British Fertility Society have recently published a 2-page
joint-document entitled, ‘Covid-19 vaccines and fertility’.
In answer to the key question, ‘Can any of the Covid-19
vaccines affect fertility?’ it states, ‘No. There is
absolutely no evidence, and no theoretical reason, that any of
the vaccines can affect the fertility of women or men.’
Pregnancy and vaccinations
Are pregnant women at risk of severe complications from
Covid-19? Uncertain healthcare professionals have often
advised them to get vaccinated even though vaccine trials have
not included pregnant women.
In mid-February, Pfizer-BioNTech started a clinical trial with
pregnant women to evaluate the safety, tolerability and immune
response of its vaccine. The company is recruiting 4,000
women, over 18 years old, who are between 24 and 34 weeks into
their pregnancies. After her baby is born, if the mother
was given the placebo, she will be offered the vaccine.
In addition, the babies will be monitored for six months to
see if they have protective antibodies, transferred from their
mothers. That is all well and good, but vaccines also
need to be tested with women much earlier in their pregnancies
to determine risks of birth defects and miscarriage.
Children and vaccinations
The University of Oxford has launched the first study to
assess the safety and immune responses in children and young
adults of its Oxford-AstraZeneca vaccine. When given to
adults this vaccine has proven to be safe and effective in
producing strong immune responses with a high efficacy.
The new trial will assess if children and young adults, aged 6
to 17 years, respond similarly.
From February, this single-blind, randomised Phase 2 trial,
will enrol 300 volunteers, with up to 240 of these volunteers
receiving the vaccine and the remainder given a safe
meningitis vaccine as an active control. Though most
children are relatively unaffected by coronavirus, it is
important to establish the vaccine’s safety and immune
response as some children may benefit from inclusion in
vaccination programmes in the near future.
Employment and Covid-19
Besides the devastating medical outcomes of Covid-19
infections, the subsequent lockdowns have created a battered
UK economy, with many enterprises in the hospitality, retail
and entertainment industries forced to close their
doors. Owners of such businesses are still required to
pay rent, rates and so on, but with no hope of any trading
income. Theirs are dire situations.
So far, unemployment has been somewhat protected with about
six million people currently on furlough schemes, but job
losses are expected to rise during 2021. According to
the Office for National Statistics (ONS), the UK unemployment
rate from October to December 2020 was 5.1% – the highest for
five years and disproportionately affecting the under 25 year
olds. And according to the Bank of England’s latest
forecast unemployment will peak at 7.75% by mid-2021,
especially if job support schemes are not extended. On
the other hand, the vaccine roll-out and the easing of
lockdown restrictions may help to keep job losses down.
It is proving to be a turbulent time for both employers and
employees.
And what of the future?
In January, the journal Nature surveyed more than 100
immunologists, infectious disease researchers and virologists
asking their views on the future of the Covid-19
pandemic. The results of the survey have been published
as, ‘The coronavirus is here to stay – here’s what that means’
by Phillips N., in Nature (2021, 590:
382-384).
Almost 90% of respondents expected that the coronavirus will
not be eradicated, but will become endemic, continuing to
circulate in pockets of the global population for years to
come and causing outbreaks in regions where it had been
previously eliminated. Nevertheless, the future impact
of the virus on the world, in terms of deaths, illness and the
need for social isolation, will probably lessen as more of the
population acquires some immunity to it through either
exposure to the virus or from vaccination. That’s quite
heartening. Roll on the roll-out!