Covid-19 numbers
Welcome to the third year of the Covid-19 plague. At
last, there is some cautious optimism about – the virus is
perhaps beginning to become endemic, at least in the
UK. It also looks as though those harsh lockdowns
and other severe restrictions are no longer likely to be
introduced and enforced. Yet just another variant,
or stupid behaviour could trigger a further pandemic.
Meanwhile, Omicron is still whizzing through the
population. That key metric, case numbers, are
reportedly falling, but that is debatable. Are those
apparent falls an artefact of a struggling testing
system? Are fewer people self-testing and are they
now less inclined to report positive results? After
all, on 4 January, the highest ever UK figure of a
whopping 218,724 cases was reported. But that
included a backlog of data from the four home nations
delayed over the New Year holiday period. Cases have
since declined, plateaued and even increased to
approximately 90,000 per day during the second half of
January.
Covid-19 deaths, namely those reported within 28 days of a
positive test, and though erratically relayed at weekends,
they increased in early January and then plateaued at
about 300 each day. Patients in hospital currently
number 17,000 with around 550 on ventilators.
Hospitalisations remain well below the peak of nearly
40,000 in January last year. Since the start of the
pandemic, the UK’s death toll has reached a sad
155,000. The only other European country with a
higher death toll is Russia with a total of 320,000.
Vaccination roll-outs continue but their media campaigns
have started to wind down – they are no longer
particularly newsworthy. However, the total numbers
of first, second and third jabbed people are reported as
52.3, 48.4 and 37.3 million respectively. Overall,
77% of the UK population have received at least one dose,
including 61% of children aged 12 to 15 years. Even
so, there are still some 5 million people in the UK who
remain unvaccinated.
Globally, many countries are resolutely stuck in a
pandemic crisis. Total global cases are approaching
400 million with 6 million deaths. The USA still
tops the daily infection table with an average of 800,000
cases, followed by France with 400,000, India with 300,000
and the UK in eighth place with 90,000. The USA also
still dominates the total death table at 885,000, followed
by Brazil (630,000) and India (500,000) with the UK in
seventh place at 155,000.
What to conclude? Speaking in Geneva on 24 January,
Tedros Adhanom Ghebreyesus, the Director-General of the
World Health Organization (WHO), declared that, ‘The world
must accept that Covid-19 is with us for the foreseeable
future, even if it is possible to end the acute phase of
the pandemic this year.’ He noted that 100 cases
were now reported every three seconds, and someone lost a
life to Covid-19 every 12 seconds. He added, ‘It is
still dangerous to assume that Omicron will be the last
variant, or that we are in the endgame of the
pandemic. On the contrary, globally, the conditions
are ideal for more variants to emerge.’
Nota bene, neither the pandemic nor the endemic is
over – far, far from it.
From Plan
B to Plan A
Reducing the required self-isolation period after a
Covid-19 infection has been a useful indicator of
the government’s strategy and its determination to
press towards a return to some sort of
normality. From 22 December, the isolation
period for infected people was cut from 10 to 7 days
as long as (lateral flow tests (LFTs) were negative
on days 6 and 7. Then from 17 January, the
self-isolation period was cut from 7 to 5 days.
The justifications for these changes have depended
on a combination of scientific facts and computer
modelling. For example, research by the UK
Health Security Agency (UKHSA) had shown that 6.2%
of people would still be infectious after two
negative LFTs by day 7, which was nearly the same as
the 5% of infectious cases if released from
isolation after 10 days with no testing.
However, testing after 5 days of isolation resulted
in 31.4% of people still being infectious. Or
as the health secretary, Sajid Javid, put it more
positively, ‘around two-thirds of positive cases are
no longer infectious by the end of day five.’
In addition, people without Covid-19 symptoms who
have a positive LFT no longer need to take a
confirmatory PCR test.
However, because of the continuing pressure to
alleviate the staffing crisis in the NHS and other
workplaces caused by high numbers self-isolating,
the government reckoned that the risk of viral
spreading after day 5 was proportionate and
responsible. So, from 17 January, people could
leave self-isolation 5 full days after experiencing
symptoms or receiving a positive test result,
whichever was first, provided they had negative
Covid-19 tests on days 5 and 6. Nevertheless,
they should remain cautious around others and avoid
those who are vulnerable.
This was a pragmatic move, which has been largely
welcomed, as long as more workers can safely return
and it does not significantly add to the risk of
viral transmission. Governments sometimes
resort to such pragmatism and to knee-jerk
policies. An example of the latter occurred in
early January. At that time, there were
apparently serious LFT kit shortages. They
were simply unavailable via the NHS website or from
many chemists or other regular outlets. On 9
January, The Sunday Times ran a feature
suggesting that free LFTs would soon no longer be
available. Up went the maroon. Talk
about hyped journalism!
It was all something and nothing. Yet the
government felt under pressure to act
decisively. So early in January, it announced
a new initiative affecting some 100,000 critical
workers to include those employed in the national
infrastructure, national security, transport, food
distribution and processing. Police and fire
and rescue services’ control rooms, electricity
generation, test kit warehouses and test surge
laboratories were also included. These
employees would start to receive free, daily LFTs in
an effort to reduce the spread of Covid-19 within
this essential workforce. Supply and delivery
of LFTs had suffered a major, albeit temporary,
glitch over the Christmas and New Year holidays and
so this knee-jerk initiative was more style over
substance. Supplies were soon
restored.
Indeed, it truly was something and nothing.
However, on 26 January, something far more weighty
was announced, namely, that the restrictions of Plan
B had expired and those of Plan A were to be
restored, at least in England. The four home
nations have different Covid-19 rules, but these are
gradually aligning. The move to Plan A
involved lifting some principal curbs, such as
working from home, wearing masks for indoor settings
and the need for vaccine passports at large
events. Other restrictions were also
relaxed. For example, from 31 January, care
home residents have been able to receive unlimited
visitors rather than the three-person limit brought
in under Plan B.
As well as
pragmatism and knee-jerk initiatives, governments
sometimes resort to policy U-turns. In
December, it was announced that front-line NHS
workers in England must be fully vaccinated by 1
April, meaning they would need a first jab by 3
February. On 31 January, the health
secretary, Sajid Javid, announced in the Commons
that the mandatory vaccination strategy for NHS
and social care workers was to be reconsidered
with a view to axing it. The anticipated
exodus from among the 77,000 or so unvaccinated
NHS workforce would apparently create a major
staffing shortage crisis. And he added that
because Covid-19 immunity was rising and Omicron
was intrinsically less severe, the mandatory
policy was no longer proportionate. This
U-turn shift will be subject to a
consultation.
Herein lies the hope of
the government, industry and the public
for a return to something ‘much closer to
normality’. But
are these radical moves too slow or too
fast? Or are they basically a
shambles? Surprise, surprise, opinions
differ. Time will tell. For the
moment, it certainly seems as though the dreaded
Plan C has been ditched.
From pandemic to endemic?
The Covid-19 question of January has been, ‘Are we
there yet?’ No, not that children’s chorus
from the back seat of the car, but the genuine
request from a world weary of Covid-19. The
straightforward answer, if you mean, ‘Are we now
virus free?’ is, ‘No.’ Overall, the world is
still in pandemic mode, and for some, the worst is
definitely yet to come. For others, the future
looks somewhat brighter, that is, ‘It could be ...
very soon.’ In fact, a rather different
question in now beginning to be asked, namely, ‘How
are we to live with Covid-19 in 2022 and
beyond?’ At least in the UK, there are growing
calls for an alternative future approach to
Covid-19, one that stresses living with it rather
than constantly fighting it. Indeed, Michael
Gove, the levelling-up secretary, declared on 10
January that ‘the UK had to learn to live with
Covid-19.’
But there will be no overnight viral vanishing like
a morning mist. Instead we will move slowly
from pandemic to endemic. In other words,
Covid-19 is here to stay, but its influence will be
less malicious, more benign. Endemic means
that the virus will constantly continue to circulate
in a region, but with a relatively low spread of
infection among the population so that social
isolation, illness and death will continue, but at
much reduced, and at a mostly static, rates.
Infection case numbers will be more consistent and
predictable. Communication care is
needed. Misuse of the word endemic in relation
to Covid-19 may encourage a misplaced
complacency. Endemic does not necessarily mean
local and mild. Endemic diseases can be both
widespread and deadly. For example, malaria is
an endemic disease that killed more than 600,000
people worldwide during 2020. Policymakers,
scientists, citizens take note. We need to
continually tackle this virus head-on, effectively
and globally.
The two big unknowns are first, how immunity,
derived from either infection or vaccination or
both, will play out, and second, how the virus will
evolve into other variants. Influenza is a
useful template – immunity and vaccines keep it
largely endemic with no official requirement for
masks, social distancing or lockdowns.
Moreover, this move from pandemic to endemic will
not occur all at once across the globe, but rather
nationally or regionally – inequity of vaccine
distribution will make sure of that.
Incidentally, in epidemiological parlance there is
an in-between state known as an epidemic, whereby a
sudden increase in cases spreads through a large
population. It is a term rarely used. In
truth, the world will probably never be
Covid-19-free, there will always be the distinct
possibility of sudden increases or local
outbreaks. That is not necessarily scary – we
already live with a host of endemic diseases such
as, common colds, measles, malaria, tuberculosis,
and expectantly around the corner, Covid-19.
Listen to some experts. Professor Julian
Hiscox, Chair in Infection and Global Health at the
University of Liverpool, said in mid-December 2021,
‘I think life in 2022 will be almost back to before
the pandemic.’ And Professor David Heymann of
the London School of Hygiene and Tropical Medicine,
who again stated in mid-December that, ‘the UK is
the closest to any country in being out of the
pandemic if it isn’t already out of the pandemic and
having the disease as endemic.’ Such boffins
could, of course, be entirely mistaken. But
the optimists’ ace card is immunity – it will be THE
game-changer. Just two years ago an unknown
virus flew out of Wuhan and zipped around the
world. None of humankind’s 7 billion
individual immune systems had ever seen anything
like it. And there were no Covid-19 vaccines
or drugs in our armamentaria. We were
vulnerable. Now in 2022, we have effective
ways and means of making us all immune, so now we
are far less vulnerable. The major obstacle
would be a new variant that could outcompete others,
in particular Omicron, and cause significantly more
severe disease, hospitalisations and deaths.
So what about the UK – are we there yet? We
have already paid a terrible price with severe
illness and over 155,000 Covid-19 deaths, though all
such numbers are likely to be significant
underestimates. Yet paradoxically, these
infections and associated vaccinations have left a
legacy of high immunity. But that immunity
will wane. So, with Omicron as the principal
transmissible variant, we are still likely to catch
endemic Covid-19, though as a less severe
disease. Nevertheless, deaths will still
occur, especially among the old and
vulnerable. Fewer deaths could occur if harsh
lockdowns were again enforced. But society
will probably not stand for a return to such
restrictions. Thus a balance has to be
struck. How many deaths are tolerable?
During a bad winter flu season some 200 to 300
people die each day. Is that where the line
should be drawn? Will lockdowns, restrictions
on large gatherings and mass testing disappear this
year? And the compulsory wearing of face masks
too? Many think so, though even more hope
so. More certain is the use of booster
vaccines, especially among the vulnerable, in order
to maximise those antibodies before winter 2022 sets
in. Autumn 2022 is going to be a time of
double jabbing for Covid-19 plus influenza.
Maybe autumn 2022 will look more like autumn 2019.
Those are some predictions for an endemic UK.
What about the rest of the world? According to
the World Health Organization (WHO), a different
long-term policy is needed. Giving repeated
booster doses of existing Covid-19 vaccines, as
already happening in some rich, developed countries,
is not a sustainable global strategy for tackling
the pandemic. Instead, the WHO argues that the
focus should shift towards producing new vaccines
that work better against transmission of emerging
variants.
Make no mistake, the poor and undeveloped world is
still in a pandemic, far, far from an endemic.
These countries are also vaccine poor. For
many, including the vulnerable and front-line
healthcare workers, have yet even to see a vaccine
syringe. For countries that have locked down
and closed their borders and successfully minimised
deaths now have less immunity across their
populations as they seek to re-join the rest of the
infected world. The WHO has concluded that the
world is a long way off describing Covid-19 as an
endemic. Without doubt it is still in a
pandemic and an acute medical emergency. Some
even predict that the darkest days are yet to
come. May they be proved wrong.
LFT and PCR testing
Millions upon millions of us have been through the
rigours, discomfort and inconvenience of Covid-19
testing using LFTs (lateral flow tests). We
have dutifully stuffed little sticks down our
throats and up our noses for a good reason, or so we
thought. Fewer of us have been through a PCR
(polymerase chain reaction) test, yet again we
thought it must be a useful exercise. But do
we know how they work? An excellent
question! Are we sure we know what they tell
us? Another excellent question! And
beyond the how and what of testing there is THE
fundamental rationale of testing. It is not
how well Covid-19 molecular fragments can be
detected in a single sample, but how effectively
infections can be detected in a population by the
repeated use of such tests as part of an overall
testing strategy – ultimately it is about the
sensitivity of the entire testing and subsequent
treatment regime that counts.
These two tests obviously measure different
parameters. LFTs are rapid antigen diagnostic
tests that use immunoassay technologies to produce
results, in a similar way to pregnancy tests.
The LFTs contain antibodies designed to recognise
and bind to the Covid-19 antigens produced on the
outer surface of the virus. As the sample
moves along the nitrocellulose strip by capillary
action, it encounters coloured nanoparticles and it
reacts with other reagents. If a coloured band
appears, the person being tested has been infected
by Covid-19. And these LFTs have been
ingeniously developed so testing can be done in the
kitchen, at the bedside, or in the field. In
other words, they do not need sophisticated
laboratory settings to conduct them. They are
not as accurate as PCR testing, but they are a
simple and fast way to test people who do not have
symptoms of Covid-19, but who may still be spreading
the virus. As such, they are an important tool
in the control of the Covid-19 pandemic.
By contrast, PCR testing screens directly for the
presence of viral RNA, which is detectable before
antibodies form or symptoms of the disease are
present. PCRs can tell whether or not someone
has the virus very early on in their illness.
The tests are quite sophisticated and therefore need
to be carried out in a laboratory, hence the delay
and typical turnaround time of several days.
Even if you have been triple-jabbed, a positive LFT
means you are infectious because viral protein is
present in your throat or nose – the virus is still
multiplying inside your body. By contrast, a
PCR test can be positive for days or weeks after an
infection because it detects small amounts of the
viral RNA that are not necessarily infectious.
Here is a typical comparative timeline. Start
with the time (day 1) when our patient, Scott Dive,
an anagrammatical imaginary friend, is exposed to
the Covid-19 virus. His viral load, the amount
of virus in his body, begins to increase on that
day. And the higher the viral load the more
infectious he is likely to be. A PCR test is
able to detect that upsurge of antibodies by day 2,
before Mr Dive becomes infectious. It is only
by day 3 that the LFT would be positive. Mr
Dive is infectious from day 3 to day 8. LFTs
would return test positives throughout this 5-day
phase. By contrast, PCR tests would be
positive from day 2 through to day 13, that is, not
only one day before, but also five days after Scott
is no longer infectious.
T cells
This is not the place for a tutorial on this
wonderful, but complex, piece of bodily equipment we
all carry around – the human immune system.
First, a general observation. With respect to
Covid-19, antibodies have been regarded as our main
line of defence against its upper respiratory tract
symptoms. Antibodies have stolen the
limelight. But the immune system has numerous
other components including T cells.
T cells, also called T lymphocytes, are a type of
white blood cell and an essential constituent of the
human immune system. T cells originate in bone
marrow and migrate and mature in the thymus – hence
they are called thymus-dependent (T) lymphocytes, or
T cells. They then multiply and differentiate
into various types of T cells, such as helper,
regulatory, or cytotoxic T cells, until required by
the immune system. Fascinating and complex.
However, during the Covid-19 pandemic T cells have
been the poor cousins of neutralising antibodies,
the unsung members of the immune system. T
cells are now making a comeback. It is
well-known that neutralising antibodies can bind to
sites on the Covid-19 spike protein – these features
have been used as templates for several Covid-19
vaccines. But if those sites mutate then
antibody protection can wane. Yet T cells are
more resilient. Among their immune functions,
they can act as cytotoxic, or ‘killer’, T cells that
seek out and destroy virus-infected cells. So,
by annihilating infected cells, T cells can limit
the spread of infection and potentially reduce the
possibility of serious illness.
Moreover, T-cell levels tend not to decline as
quickly as antibodies do after either infection or
vaccination. And because T cells can recognise
more sites along the spike protein than antibodies
can, they should be better able to recognise mutated
variants.
And that is the case with Covid-19. Recently,
it has become clear that T cells can recognise
Covid-19 variants, including Omicron, even when
antibodies cannot. So here is a fundamental
question. Have those researchers, who have
been assessing the efficacy of Covid-19 vaccines,
mistakenly concentrated on measuring antibody
responses while ignoring important T-cell
responses? True, antibodies are easier to
study, making them simple parameters to measure in
those large, international, Phase 3-type clinical
trials. But Covid-19 variants remain highly
susceptible to T-cell attacks. Surely they too
should be assessed. Moreover, while antibody
efficacy can fade, that of T cells can last for
years providing long-term immunity.
In this war against Covid-19, T cells have perhaps
come of age. Maybe. Whatever, don’t diss
T cells!
R numbers
The R, or reproduction, number is a way of
estimating how a viral disease is spreading within a
population. The government has said that R
numbers for Covid-19 are one of the most important
factors in its policy-making decisions to control
the pandemic.
In statistical theory, R numbers are estimated by
independent computer modelling groups based in UK
universities and the UK Health Security Agency
(UKHSA). They typically use a variety of data
sources. For example, some groups will use
epidemiological figures, such as testing data,
hospital admissions, ICU admissions and
deaths. This is a backward-looking approach
that typically takes up to 3 weeks to assess changes
because of the time delays between initial
infections and the need for hospital care.
Other groups use data from contact pattern surveys
that gather information from participants.
These can be rapid, but because these rely on
self-reporting, they are susceptible to bias.
And there are household infection surveys where swab
testing is performed by individuals and reported for
collation. They are direct, but again
dependent on patient collaboration.
Whatever the method used all these sources have
inherent uncertainties, so estimates can vary
between the different models. Moreover,
estimates of R values are usually shown as a range
because of statistical unevenness across a region
caused, for example, by local outbreaks. A
single value would not necessarily reflect the
variations of infection rates within that particular
area.
In statistical practice, the R value represents the
average number of people a Covid-19-infected person
will pass the disease onto. If R is below 1,
then the number of people contracting the disease
will fall and the pandemic will be shrinking.
If R is above 1, the number of infected people will
be growing. So, an R value between 1.2 and 1.5
means that, on average, every 10 people infected
will infect between 12 and 15 other people.
In the early days of the Covid-19 pandemic, the
government would regularly publish R numbers for the
whole of the UK. However, nowadays, because of
the increasingly-localised approach to managing the
pandemic, values are published for each of the four
home nations. The latest R values (released on
27 January) for England were between 0.8 and 1.1,
for Scotland they were 0.7 to 1.1 and for Wales they
were 1.1 to 1.5 and for Northern Ireland they were
0.7 to 0.9.
R values cannot be measured directly. However,
they are useful estimates of the spread and
intensity of Covid-19, but they have their
limitations. For instance, they convey little
about geographical differences – the smaller the
subsection sampled, the greater the potential
variation and the less reliable they become.
And they say nothing about different viral
variants. Nevertheless, despite such
shortcomings R numbers are valuable guides to the
general developmental trends of Covid-19. In
summary, with respect to R numbers, less is best.
mRNA vaccines
The Pfizer-BioNTech and Moderna vaccines are
messenger RNA vaccines, also known as mRNA
vaccines. These were among the first Covid-19
vaccines authorised and approved for use in the
United States and elsewhere. mRNA vaccines
prompt the human body to make a protein that is part
of the pathogen, triggering an immune response.
The development, approval and use of mRNA vaccines
have been staggeringly successful. According
to a recent Commonwealth Fund study, in the absence
of such vaccines there would have been approximately
1.1 million additional Covid-19 deaths in the US and
10.3 million more hospitalisations by November
2021. In other words, mRNA vaccines have saved
lives and prevented severe disease with
comparatively few adverse events.
Yet mRNA vaccines have suffered a
bad press, especially among a vociferous
minority. Anti-vaxx individuals and groups
have persistently referred to mRNA vaccines as
‘experimental gene therapies’. These people
are gravely mistaken. Vaccines that use mRNA
technology do not alter a person’s genes, therefore
their use cannot be considered as gene
therapy. Nor are mRNA vaccines particularly
novel, or ’experimental’. It was in 1961 that
mRNA was discovered and so for decades, well before
Covid-19 appeared, hundreds of scientists have
rigorously studied and worked on mRNA
vaccines. Its first human clinical trial as a
vaccine was against rabies in 2013.
Pfizer-BioNTech and Moderna mRNA vaccines contain
the genetic code for cells to produce the spike
protein that the Covid-19 virus uses to enter cells,
to elicit an immune response in recipients.
More precisely, the Pfizer-BioNTech and Moderna
vaccines use mRNA that has been chemically modified
to replace the uridine nucleotide with
pseudouridine. This change is thought to stop
the immune system reacting to the introduced mRNA.
The Covid-19 pandemic has allowed Pfizer and
BioNTech to develop a strong partnership, with
Pfizer providing its antigen research and BioNTech
providing its proprietary mRNA platform
technology. Such has been the success of their
mRNA Covid-19 vaccine that the two have agreed to
develop an mRNA-based vaccine for another viral
infection, shingles. This is a widespread and
painful condition triggered by the same virus that
causes chickenpox. Clinical trials are
expected to start in the second half of 2022.
This will be the third collaborative project for the
two companies – in 2018 for influenza, 2020 for
Covid-19 and now 2022 for shingles. Pfizer is
making an equity investment worth $150 million for
this latest deal and BioNTech will receive $225m
upfront. BioNTech is also currently developing
an mRNA vaccine targeting malaria. And in late
January, Pfizer and BioNTech announced they have
begun enrolment for a clinical trial to evaluate
their novel, Omicron-specific vaccine for
Covid-19. A day later, rival Moderna did the
same.
These mRNA vaccines – big business using startling
technologies with life-enhancing and life-saving
possibilities.
One new vaccine
Pfizer-BioNTech and Moderna are not the only duo in
the Covid-19 vaccine trade. Recently, two
other companies, the manufacturer, Bharat Biotech
and Ocugen, the distributor, based in India and the
US respectively, have applied for regulatory
approval of their Covaxin vaccine by the US
Food and Drug Administration (FDA).
Covaxin appears to have at least four
advantages. First, it has already, on 3
November 2021, received authorisation for emergency
use from the World Health Organization (WHO).
Second, Covaxin has been shown to possess high
antibody neutralising activity, similar to the mRNA
vaccines, against both Delta and Omicron.
Third, for those who are cautious about the newish
technology of mRNA vaccines, Covaxin is an
old-school, inactivated virus vaccine. Fourth,
while some other vaccines have a remote link to
abortion via testing on foetal cell lines, Covaxin
has no such connection in production, development,
or testing.
Dr Krishna Ella, the chairman and managing director
of Bharat Biotech, declared in an upbeat statement
that, ‘Our goals of developing a global vaccine
against Covid-19 have been achieved with the use of
Covaxin as a universal vaccine for adults and
children.’
However, controversy has arisen. According to
Bharat Biotech, the vaccine was more than 90%
effective in a late-stage, Phase 3, US-based
clinical trial, but this was even before the Indian
regulators had approved its use. The company
has since published data suggesting 78% efficacy
against Covid-19 of any severity. And a
real-world study, published in The Lancet
(23 November 2021), gave Covaxin an even lower
effectiveness against symptomatic Covid-19 at 50%.
Not all vaccine trials are the same – treatments,
dosages, patients, variants and other variables make
testing and comparing vaccines a thorny
problem. Manufacturers and regulators would do
well to confer and to increase transparency and to
assist with the proper interpretation of their data.
One new Omicron variant
On 21 January, the UK Health and Security Agency
(UKHSA) announced that it was investigating a
sub-lineage of the Omicron coronavirus that it had
formally designated as a ‘Variant Under
Investigation’ (VUI). It is known as Omicron
BA.2 and nicknamed by some scientists
as ‘stealth Omicron’.
The UKHSA has reported that, ‘Early analyses suggest
an increased growth rate compared to BA.1 [the
original Omicron variant], however, growth rates
have a low level of certainty early in the emergence
of a variant and further analysis is needed.’
However, BA.2 appears to be outpacing other forms of
the variant around the world and is raising fears of
an even more transmissible strain of the
virus. By 21 January, some 426 cases of BA.2
had been detected in the UK, with the earliest
dating back to 6 December. According to Dr
Meera Chand, Covid-19 Incident Director at UKHSA,
‘So far, there is insufficient evidence to determine
whether BA.2 causes more severe illness than Omicron
BA.1, but data are limited and UKHSA continues to
investigate.’
Meanwhile, according to scientists in Denmark, where
BA.2 is dominant, it appears to be more contagious
but not more severe than the more common BA.1
sub-lineage. Moreover, the UKHSA has recently
reported that BA. 2 has now been identified in 40
countries.
Three new doubtful variants
With the possible exception of BA.2, so far in 2022,
there have been no reports of new variants, or at
least the potentially dangerous variants of concern
(VOC). However, there have been three
interesting and seemingly false alarms of such
variants nicknamed ‘Deltacron, ‘Flurona’ and ‘IHU’.
During the first week of January, a team of
scientists from Cyprus reported the existence of
‘Deltacron’, this novel Covid-19 variant that
combines characteristics of Delta and Omicron.
However, the claim has been widely dismissed as
being a result of contaminated laboratory samples or
laboratory processing errors, though some suggest
that it could be due to a genuine mutation caused by
a recombination of the two viruses.
According to Leonidos Kostrikis, professor of
biological sciences at the University of Cyprus, he
and his colleagues identified 25 cases of the
so-called ‘Deltacron’ variant, which had resulted in
the hospitalisation of 11 patients and 14 with less
severe Covid-19. On 7 January, the scientists
submitted their data to the GISAID global
surveillance database which tracks changes in
viruses – a further development is awaited.
Meanwhile in Israel, a 31-year-old pregnant woman
contracted Covid-19 and seasonal influenza at the
same time. It has been reported as the world's
first case of ‘Flurona’, a neologism of flu and
coronavirus. The patient, who was only mildly
ill, was not vaccinated against either Covid-19 or
influenza. She was discharged without
complications. However, this incident has led
to fears of a possible ‘twindemic’, but in truth, it
seems like a false media story that should worry
no-one.
‘Flurona’ is neither a new, nor a single, viral
variant. It is two viruses acting in
tandem. It is a two-viruses-at-once
condition. Indeed, such infections with two or
more disease-causing organisms at the same time,
correctly called a co-infection, are not
uncommon. Specifically, cases of flu and
Covid-19 appeared together in the USA during the
spring of 2020. And in the same year, a
Chinese study reported that 7 out of 257 Covid-19
patients also tested positive for influenza.
If viral co-infections occur, the best advice is,
get both treated, get both vaccinated.
The third suspected Covid-19 variant was first
detected in October 2021 and was thought to have
been introduced into France by a traveller returning
from the Cameroons. The World Health
Organization (WHO) classified it as B.1.640.2 and on
22 November 2021 designated it as a variant under
monitoring (VUM), meaning its spread and severity
would be repeatedly scrutinised and assessed.
By December 2021, it was reported to have infected
12 patients in France. It was temporarily
dubbed the ‘variant IHU’ because a team from the
Méditerranée Infection University Hospital Institute
(IHU) in Marseilles, France were the first to report
the variant in a pre-print paper entitled,
‘Emergence in Southern France of a new SARS-CoV-2
variant of probably Cameroonian origin harbouring
both substitutions N501Y and E484K in the spike
protein’ by Philippe Colson et al., in MedRxiv
on 29 December 2021. Variant ‘IHU’ apparently
has 46 mutations and 37 deletions in its genetic
code, many of which affect the
biologically-significant spike protein, including
the familiar N501Y and E484K. Further testing
to assess the virological, epidemiological or
clinical features of this ‘IHU’ variant are
ongoing. The French researchers, rather
disrespectfully, did not submit their data to
GISAID, the global surveillance database.
Both ‘Deltacron’ and ‘Flurona’ are less about
serious aspects of Covid-19 and influenza than about
the power of social media to create hyped stories
based on meagre evidence. The WHO has
subsequently reported that ‘IHU’ or B.1.640.2 has
been spreading more slowly than Omicron and so it
was of relatively little concern, so far. This
is not unusual. There are scores of new
Covid-19 variants frequently being discovered, but
the vast majority are of no or little consequence
with respect to human health.
Whatever the eventual outcome of these three reports
about ‘Deltacron’, ‘Flurona’ and ‘IHU’ so-called
'variants', they can all be largely avoided by
getting both Covid-19 and influenza jabs – ask your
doctor for details!
And another antiviral
In mid-January, Molecular Partners, a small Swiss
biotech company, agreed with Novartis, the giant
Swiss drug maker, to in-licence its Covid-19
antiviral drug known as Ensovibep for 150
million Swiss francs (£120 million). It is
being promoted as the first antiviral to attack the
coronavirus’s spike protein not in just one, but in
multiple ways. This multipronged attack
suggests that it might work well against future
highly-mutated variants.
In mid-December, Novartis had released some
preliminary Phase 2 results that showed Covid-19
patients who took the therapy achieved a
statistically significant reduction in their viral
load over an eight-day study period and also had a
78% lower risk of being hospitalised or dying.
Novartis had already reported that its Phase 1
laboratory studies indicated that Ensovibep could
neutralise variants of concern including Alpha,
Beta, Gamma, Delta and Omicron.
However, while these results look encouraging, there
is a lack of information on safety data and
protocols for use, such as dosage and timings of
administration. But perhaps the biggest
downside of Ensovibep is that the therapy needs to
be given via an intravenous infusion, hence only in
a medical environment. Whereas the Merck and
Pfizer antivirals, molnupiravir and Paxlovid, as
more convenient pills, can be administered anywhere.
On the plus side, Ensovibep belongs to a new class
of drugs called DARPins (Designed Ankyrin Repeat
Proteins), which can be manufactured relatively
simply, cheaply and in bulk. Novartis is
therefore emphasising the potential of Ensovibep for
large volumes at lower cost, for equitable access
across Africa, Asia and Latin America.
Novartis is now preparing for a 1,700-patient
clinical trial of Ensovibep around the world.
And there are plans to apply for emergency use
authorisation in the US and for talks with European
agencies too.
And another antibody
Covid-19 treatments as alternatives to vaccines are
big business. Think of the potential numbers
of patients. The hunt is up and running.
Antibodies seem like sensible candidates since they
are dominant components of the remedial immune
system.
David Veesler thought so too. He and his
colleagues at the University of Washington, Seattle,
have taken a pragmatic approach to finding a
suitable monoclonal antibody. They searched
the blood of an infected person, the so-called
convalescent plasma approach, for antibodies that
bind to the Covid-19 spike protein, the gateway
which lets the virus enter human cells. They
found one particularly potent antibody, called
S2K146, which protected cells from infection
by the original strain of Covid-19 as well as the
Alpha, Beta, Delta and Kappa variants and more
recently, in a separate study, the Omicron variant
too.
This is very preliminary work. However,
administering S2K146 to hamsters infected with
Covid-19 greatly reduced or eliminated replication
of the virus. In addition, the team found that
mutations that prevented S2K146 from binding to
spike protein also rendered Covid-19 much less
effective at infecting cells. Maybe variants
will be less likely to mutate in order to escape the
effects of S2K146.
This research has been reported as
‘Antibody-mediated broad sarbecovirus neutralization
through ACE2 molecular mimicry’ by Young-Jun Park et
al., published in Science, 6 January
2022.
So, here is S2K146, another monoclonal antibody
treatment, maybe, along with GlaxoSmithKline’s
Sotrovimab and AstraZeneca’s Evusheld, and numerous
others already in early trials. S2K146 may yet
prove to be effective in treating and preventing
Covid-19. Time and money and commitment and
enthusiasm are required to bring it to fruition, but
S2K146 does appear to be an ideal candidate for
clinical development.
The nocebo effect
Nobody likes having a vaccination jab. And
vaccinations often come with adverse effects.
Common reactions to Covid-19 jabs are headaches,
short-term fatigue and arm pain. Now American
scientists have reported that more than two-thirds
of these side effects can be attributed to a
negative version of the placebo effect rather than
the vaccine itself. They call it the nocebo
effect.
The scientists examined data from 12 clinical trials
of Covid-19 vaccines and found that the nocebo
effect accounted for about 76% of all common adverse
reactions after the first dose and nearly 52% after
the second dose. These reactions were
evidently caused not by the vaccine per se, but by
other factors including anxiety, expectation and
wrongly attributing various ailments to having had
the jab.
This work has been reported as, ‘Frequency of
Adverse Events in the Placebo Arms of COVID-19
Vaccine Trials: A Systematic Review and
Meta-analysis’ by Julia Haas et al., in JAMA
Open Network (18 January 2022).
The researchers think that better public information
about nocebo responses may improve Covid-19 vaccine
uptake by reducing the concerns that make some
people hesitant. ‘But’, they say, ‘we need
more research.’
Five Covid-19 jokes
It is said that humour is an essential coping tool
for surviving tough times. On the basis that
shared laughter can apparently give strength in
adversity, here are five Covid-19-related
jokes. Sincere apologies to those who may find
them gratuitous – they are included with only good
intentions.
1] I would make a Covid-19 joke, but it would
be tasteless.
2] Has Covid-19 forced you to wear glasses and
a mask at the same time? You may be entitled
to condensation.
3] Why did the chicken cross the road?
Because the chicken behind it didn’t know how to
socially distance properly.
4] What’s the difference between Covid-19 and
Romeo and Juliet? One is the coronavirus and
the other is a Verona crisis.
5] Day 7 isolating at home and the dog is
looking at me like, ‘See? This is why I chew
the furniture!’