Coronavirus - Part 18
(April
2022)
[Previous Parts can be accessed by
clicking on the boxes below]
Covid-19 numbers
Somewhat disturbingly, sources of
Covid-19 information have been drying up. Until this month,
most newspapers and media outlets published daily Covid-19 reports
and figures. They have since mostly disappeared. Now
the most consistent and readily-available source of global
information is the Johns Hopkins Coronavirus Resource Center (CRC)
in Baltimore, USA. Indeed, there is concern that the UK
government no longer wants to talk about Covid-19. What has
happened to that no-nonsense, medical double act of Chris Whitty
and Patrick Vallance? Is this a case of ignoring the problem
in the hope it will go away?
So is Covid-19 really on the way out? Currently, the UK key
metrics – cases, hospitalisations and deaths – are mostly trending
downward. In mid-April, the Office for National Statistics
(ONS), perhaps the most reliable data source in the UK, reported
that the number of people who currently had Covid-19 in the UK was
continuing to fall, by about 15% on the previous week. Even
so, in late April, around 3.76 million are still infected – about
one in every 17 people – so the levels of infection are
lingeringly high.
Hospitalisations are decreasing. They currently stand at
about 14,000 admissions with 320 patients on ventilators, whereas
in March the figures were 18,500 and 360. However, related
deaths bucked the data trends and escalated to approximately 330
each day – the equivalent March figure was just 150. In
Easter week it was announced that UK deaths from, or with,
Covid-19 had passed the landmark figure of 170,000. It now
stands at about 174,000.
Globally, the picture remains mixed. Some European countries
are now seeing a slower increase in new cases, or even a
decline. Nevertheless, the region is still reporting over
0.5 million cases every day. Huge infection surges are
occurring elsewhere. For example, China is on the verge of
serious upheaval with cities, such as Shanghai and Beijing,
imposing strict lockdown rules. And by late April, the total
global cases stood at 510 million, total deaths at 6.2 million and
total vaccinations administered at 11.3 billion.
Germany and South Korea have taken over the top spot of the
infection table with a daily average of approximately 170,000
cases, followed by France with 116,000 and Italy with
63,000. The UK has slipped to eighth position with
39,000. The USA still dominates the total death table at
992,000, followed by Brazil (662,000) and India (522,000) with the
UK in seventh place at 174,000.
Is the Covid-19 pandemic outlook appearing a little rosier?
Yes, but no. Yes, cases do seem to be lessening, at least,
in some parts of the world. No, they are definitely
increasing, at least, in other parts of the world. The
refrain is unremitting – this Covid-19 pandemic is not over.
Much of the world is still in its grip.
The UK Covid-19 Inquiry
Consider the response to Covid-19 in the UK – what went right,
what went wrong? These hotly-debated questions began
unofficially long ago in the family hub, the sports club, the
local pub and elsewhere, but the start of the official UK Inquiry
was announced on 12 May 2021. Its chairwoman is The Right
Honourable Baroness Heather Hallett DBE. She is a lawyer,
who rose to become Vice-President of the Court of Appeal Criminal
Division in 2013. In 2019, she retired and was made a
crossbench life peer. She has vast experience in conducting
high-profile inquests, inquiries and reviews, such as acting as
coroner for the July 2005 London bombings.
The Covid-19 Inquiry’s remit is, ‘to examine the UK’s preparedness
and response to the Covid-19 pandemic, and to learn lessons for
the future.’ It started with a four-week public consultation
on its draft Terms of Reference which ended on 7 April 2022.
Currently, over 20,000 responses from people and organisations are
being analysed – a summary is expected to be published in
May. That will shape Baroness Hallett’s recommendations to
the prime minister so that the final Terms of Reference of the
Inquiry can be established and the topics for the Inquiry’s
investigations can be set, probably again in May. In the
meantime, Baroness Hallett and her team have met with over 150
bereaved families and numerous representatives from a wide range
of interested groups, including long Covid survivors, children,
faith leaders, scientists, key workers and many more.
Typically, a public inquiry focusses on three major
questions. First, what happened? Second, why did it
happen and who was responsible? Third, what lessons can be
learned? Once the Terms of Reference are finalised, this
Inquiry will begin its work proper, requesting written evidence
from government and other bodies. Public hearings are
expected to start in 2023. However, the published outcome
from the Inquiry will not appear for several years.
List of symptoms expanded
When the Covid-19 infections started some two years ago, a short
list of symptoms was issued. There were just three – a high
temperature or fever; a new persistent cough; and a loss of sense
of smell or taste. As the pandemic developed, more symptoms
became commonly observed and several groups began lobbying for an
expansion to that list.
On 1 April 2022, the UK Health Security Agency published a revised
list of ten extras. The full catalogue is now, a continuous
cough; high temperature, fever or chills; loss of, or change in,
your normal sense of taste or smell; shortness of breath;
unexplained tiredness, lack of energy; muscle aches or pains that
are not due to exercise; not wanting to eat or not feeling hungry;
headache that is unusual or longer lasting than usual; sore
throat, stuffy or runny nose; diarrhoea, feeling sick or being
sick. Oh dear, who isn’t suffering from a few of these
lurgies right now?
These criteria are not particularly diagnostic of Covid-19 and
other respiratory infections, such as colds and flu, can exhibit
very similar symptoms. Meanwhile, the official advice is, if
you feel unwell with a few of these symptoms, you should rest,
keep hydrated and maybe take analgesics, such as paracetamol.
These symptoms vary among patients, but a recent study has found
that symptoms also vary according to which variant has been the
infecting culprit. These observations were derived from a
large cohort study entitled, ‘Symptom prevalence, duration, and
risk of hospital admission in individuals infected with SARS-CoV-2
during periods of omicron and delta variant dominance: a
prospective observational study from the ZOE COVID Study.’
It was undertaken by Cristina Menni et al., and published
in The Lancet (23 April, 2022, 399: 1618-1624).
Among the findings, involving 63,003 participants, were that
vaccinated people infected with the Omicron variant had symptoms
for 6.87 days on average, compared with 8.89 days for those with
the Delta variant. Moreover, patients infected with Omicron
reported a loss of smell less frequently and were more likely to
have a sore throat and a hoarse voice than those infected with the
Delta variant. And those infected during the Omicron wave
were around half (47%) as likely to display at least one of the
three ‘classic’ Covid-19 symptoms compared with people infected
with Delta. And patients infected during the Omicron wave
were 25% less likely to be admitted to hospital (1.9%) than
patients infected during the period of high Delta prevalence
(2.6%). These data suggest that infection with the Omicron
variant is notably less severe than with the previous dominant
variants.
Though the incidence of Covid-19 seems to be in retreat, at least
in the UK, this new list of symptoms is more embracing, and
although these were never intended to be diagnostic, they may
encourage people to think that they may be infected with
Covid-19. Counter to this, is the governmental-driven
withdrawal of free lateral flow tests (LFTs) and their more
accurate detection of infection. So, are you
Covid-19-positive? Do you guess or test? For many, it
is an unsatisfactory dilemma.
Moderna updated
As the Covid-19 pandemic has unfolded so have offensive
vaccines. But their efficacies are always less than total
and always subject to waning. Come on manufacturers, we want
better and longer-lasting vaccines. The US-based company
Moderna has responded with the announcement in mid-April of its
updated Covid-19 vaccine, known as mRNA-1273.211.
This Moderna upgrade was designed as a booster against two
variants, the original Wuhan strain of the virus and the Beta
strain, first identified in late 2020 in South Africa. Now
it appears to provide better protection against Omicron and other
variants.
The initial Moderna product was an mRNA vaccine based on the Wuhan
spike. This latest version is a bivalent vaccine because it
includes two varieties of mRNA, derived from the spike proteins of
the Wuhan and the Beta variants. In trials, volunteers
inoculated with the new booster produced about twice the number of
antibodies against the Beta, Delta and Omicron variants one month
after their jab, compared with people who received the original
Moderna vaccine. After six months, the new booster remained
more effective against Beta and Omicron. These results were
published as a preprint entitled, ‘Safety, Immunogenicity and
Antibody Persistence of a Bivalent Beta-Containing Booster
Vaccine’ by Spyros Chalkias et al., in Research Square
on 15 April 2022.
This novel vaccine strategy, more tailored towards particular
variants and maybe more than one at a time, may signal a new
generation of vaccines and a better way of tackling
Covid-19. After all, annual influenza jabs typically
generate immunity against up to three different influenza strains
in one vaccine dose. As the Moderna researchers conclude,
‘These results indicate that bivalent booster vaccines can induce
potent and durable antibody responses providing a new tool in
response to emerging variants.’ Indeed, better and
longer-lasting vaccines may be on the horizon.
Valneva approved
In mid-April, the Valneva vaccine (technically known as VLA2001)
became the sixth Covid-19 jab to be approved by the Medicines and
Healthcare products Regulatory Agency (MRHA) for use in the UK as
long as its recipients are aged 18 to 50 years, with their first
and second doses taken at least 28 days apart. Back in 2020,
the Pfizer-BioNTech jab was the first to be approved and this was
followed by the Moderna, Oxford-AstraZeneca, Janssen and Novavax
vaccines, although the latter two are not currently available in
the UK. Nor, somewhat strangely, is this approved Valneva
vaccine – in September, the UK government cancelled its contract
to buy some 140 million doses over allegations of agreement
breaches.
Valneva is manufactured by the French pharmaceutical company of
the same name. Unlike the other five UK-approved Covid-19
vaccines, Valneva is an inactivated whole-virus vaccine, which
means that the live Covid-19 virus is grown in a laboratory,
inactivated so as to be incapable of infecting human cells,
combined with two adjuvants, alum and CpG 1018, to induce higher
antibody levels and then administered to patients to trigger their
immune responses. There is evidence to suggest that such
vaccines, based on this more traditional technology of inactivated
whole viruses, and with long-term usage in vaccines against polio,
hepatitis A and influenza, may result in broader immune responses
than those that involve only the spike protein, and that they may
also be more effective against new Covid-19 variants.
Furthermore, Valneva can be stored in a standard refrigerator.
Herein, is this rather weird, even gloomy, saga. Yes,
Valneva is a safe and effective vaccine, but No, you cannot have a
jab of it because of some bureaucratic quarrel. Perhaps in
some ways, none of this matters. The UK’s population is
already fairly well vaccinated, especially among its elderly and
vulnerable. And there are other suitable vaccines currently
readily available. On the other hand, Valneva and its
traditional manufacturing procedure may appeal to the vaccine
hesitant. And Valneva may yet find a major role in
low-income countries because of its ease of transport and storage.
Yes to monoclonals, no to ivermectin
‘The earlier, the better’ is a catchphrase that applies to much of
human life, especially to medical treatments. And so it does
to monoclonal antibodies in relation to Covid-19 remedies. A
recent analysis of data from 37 relevant clinical trials, looking
at timing and dosage, produced this clear message – the earlier
people get this type of treatment, the better they fare. The
work entitled, ‘Determinants of passive antibody effectiveness in
SARS-CoV-2 infection’ was carried out by Eva Stadler and her
colleagues mostly from the Kirby Institute, New South Wales,
Australia, and was published as a preprint in medRxiv on
22 March. They concluded, ‘However, we find that
effectiveness of passive antibody therapy in preventing clinical
progression is significantly reduced with administration at later
clinical stages.’ In other words, the earlier, the better.
Monoclonal antibodies are very effective at keeping people with
Covid-19 out of hospital. Early treatment can reduce the
risk of hospitalisation by around 70%. Stadler and
co-workers also reported that such synthetic antibody therapies
might function at doses lower than currently recommended.
Doses up to 1,000 times lower than typically administered can
still achieve high, around 90%, efficacy. Given the
exorbitant costs of monoclonal antibodies, this could be good news
since it should allow a more widespread usage at a lower cost.
The bad news is that of the six monoclonal antibodies the
researchers studied, only two were likely to be effective against
the BA.2 version of Omicron. They predicted that imdevimab
and sotrovimab were only 60% and less than 20% effective
against hospitalisation caused by BA.2.
In a different context, the anti-parasitic drug ivermectin
has repeatedly been controversially recommended as an effective
therapy for Covid-19. Several of the contentious issues have
already been documented in Coronavirus - Part 12 (October
2021), yet some people, mostly vaccine opponents, still consider
it to be a Covid-19 ‘miracle’ drug.
The results of a large clinical trial from Brazil should now dash
all hopes that ivermectin has any benefit as a treatment for
Covid-19. The trial was a gold-standard, double-blind,
randomised, placebo-controlled trial with 1,358
participants. They were infected with Covid-19 and given
either ivermectin (for 3 days at a dose of 400 μg per kilogram per
day), or a placebo. The work was published as, ‘Effect of
Early Treatment with Ivermectin among Patients with Covid-19’ by
Gilmar Reis et al., in The New England Journal of
Medicine on 30 March 2022.
The researchers concluded, ‘Treatment with ivermectin did not
result in a lower incidence of medical admission to a hospital due
to progression of Covid-19 or of prolonged emergency department
observation among outpatients with an early diagnosis of
Covid-19.’ In other words, ivermectin had no significant
effect on Covid-19 patients, specifically, it did not reduce a
Covid-19 patient’s risk of ending up in hospital.
Will these results end the arguments over the effectiveness of
ivermectin? Probably not. Numerous small-scale trials
are still currently being carried out around the world. We
await their data. Nevertheless, ivermectin has its champions
no matter what.
Nasal Covid-19 vaccines
Talk about Covid-19 vaccines has focused almost entirely on the
syringe-and-needle delivery method. There have been random
references to nasal delivery, more in jest than reality. But
since the wretched virus mostly enters the victim’s body up a
human nose, perhaps a nasal-sprayed vaccine deserves more
attention. After all, the virus has the spectacular ability
to jump from one nose to another. Indeed, the next leap in
coronavirus vaccine strategy could be nasal sprays.
Some have already taken up the challenge seriously. It is
reckoned that there are a half-dozen Covid-19 nasal sprays
currently in clinical trials across the world. For example,
in early April, the Russian Health Ministry registered a version
of its Sputnik-V vaccine as the world's first nasal vaccine
against Covid-19. It is expected to be available to ordinary
Russians within the next three to four months.
The original Sputnik-V vaccine was developed by researchers at the
Gamaleya National Research Centre for Epidemiology and
Microbiology in Moscow. According to Alexander Gintsburg,
the director of the Gamaleya Centre, ‘Laboratory tests show the
Sputnik V protects against the Omicron in its ordinary injection
form, and it will certainly be efficient in the nasal form.’
Maybe. Some hard experimental data will be more convincing.
Back to the UK. The following is a somewhat uncanny news
story. Did you know that you can now buy a Covid-19 nasal
spray from your local high-street chemist? For example,
LloydsPharmacy has just begun selling its Viralize anti-viral
nasal spray, online and in-store, for £15. It claims to
irreversibly inactivate nearly 100% of multiple strains of the
Covid-19 virus within one minute. Its active ingredient is
sodium astodrimer, known primarily as a non-antibiotic treatment
for bacterial vaginosis, but now with proven in vitro
activity against the Covid-19 virus, though its mode of action is
currently unclear and no in vivo data are available.
Its efficacy, publicity and sales may therefore be regarded as
premature.
And here is another. BHM anti-viral nasal spray is a joint
product of Birmingham Biotech and the University of
Birmingham. It is designed to help prevent the inhalation of
infectious viruses, such as Covid-19. Its two main active
ingredients are carrageenan and gellan gum – the former is a
natural anti-viral derived from red seaweed and the latter is a
polysaccharide gel. The product, a patented blend of natural
ingredients named Norizite, appears to merely physically trap
viral particles rather than exert any destructive neutralising
action. Presumably inhaled viruses are removed with a
sneeze.
The manufacturers have a rather flashy website laden with
clichés. They are currently seeking Norizite distribution
partners. But will customers actually pay for this nasal
spray? It has no serious pharmaceutical activity and no
human clinical trial data.
Omicron variants BA.4 and BA.5
Backtrack and recap. The global persistence of Covid-19 has
been largely driven by the appearance of new variants of the
original virus that was first reported in January 2020 at Wuhan,
and technically identified as SARS-CoV-2. Like all viruses
it is prone to mutate and variants, such as Alpha, Beta, Gamma and
Delta, have circled and infected much of the world.
The fifth and latest variant of concern, known as B.1.1.529 or
Omicron, emerged from South Africa in late November 2021. It
has since mutated into an Omicron family of sub-lineages starting
with BA.1 and BA.2. These are caused by small genetic
changes, yet exhibit different properties, such as resistance to
antibodies, and thus differences in Covid-19 severity and
transmissibility. So, BA.2 is less severe but more
transmissible than BA.1. BA.3 has been detected but has
never posed a threat to human health.
Will there be a BA.4, BA.5 and BA.ad nauseam until a Sigma variant
appears? An excellent question. And how will we
know? Fewer case numbers and deaths do not necessarily mean
good news of ‘lower risk’. Someone should be on watch and
looking out for dangerous mutations. In the UK this task is
handled by the COVID-19 Genomics UK Consortium (COG-UK).
This is ‘a group of public health agencies and academic
institutions in the United Kingdom created in April 2020 to
collect, sequence and analyse genomes of SARS-CoV-2 [the infecting
virus of Covid-19] as part of COVID-19 pandemic response.’
Another such lookout post is based at the Centre for Epidemic
Response and Innovation (CERI) at Stellenbosch University in South
Africa. There it runs one of the world’s strongest genomic
surveillance programmes for Covid-19 mutations. It has
recently recorded the appearance of the Omicron sub-variants
called BA.4 and BA.5. During the last month, these have
spread rapidly in South Africa and have been detected in at least
nine other countries, including the UK and France. Should we
be worried? Not really. Covid-19 cases and
hospitalisations in South Africa have remained numerically stable,
indicating that BA.4 and BA.5 pose no overwhelming threat to
public health. But, of course, they could mutate and begin
to evade human immunity and become a serious medical
problem. For now, they are under the watch of bodies, such
as the COG-UK, the CERI and the World Health Organization
(WHO). As Tulio de Oliveira, head of CERI, says, ‘It’s just
time to work carefully and diligently, but calmly.’
And that is how these particular mutations have been
tracked. During the first week of March, the abnormal genome
sequences of BA.4 and BA.5 that encode the virus’s spike proteins
comprised around 5% of the 500 or so genomes sequenced in South
Africa. By the first week of April, that proportion had
risen to 50%. These sequences were documented as separate
sub-lineages on the Omicron family tree and assigned their drab
identities. A significant feature of both BA.4 and BA.5 is
an amino acid mutation they share called F486V. This occurs
on the spike protein in a location that operates like a door to
infection – this is where antibodies from vaccines and prior
infections can neutralise the virus by attachment at this
location.
Such genomic sequencing information derived from novel Covid-19
variants needs to be handled carefully. The general public
can be easily alarmed. Misleading news of new variants can
leak out, cause shock and result in some health organisations
adopting largely futile policies, such as travel bans that can
cause more harm than good. ‘Watch out’ and ‘keep calm’ are
the appropriate watchwords for genomic scientists and
epidemiologists (and the general public).
Covid, iPhones and cars
Covid-19 has caused disrupting, even devastating, illness as well
as death. Such events must not be belittled. However,
not all of Covid-19’s trail of destruction has been so up-front
and personal. Take two auxiliary problems that have, perhaps
as yet, not been fully appreciated.
First, the Covid-19 crackdown has raised fears for the supply of
iPhones. Oh no! The root of the problem is a global
shortage of semiconductor parts – it’s a chip crisis. And
the principal cause? As China battles its worst outbreaks of
Covid-19 amid record numbers of deaths, strict rules have been
imposed on the Chinese factories that account for about 50% of
global smartphone production. The output of computers and
other electronic gizmos have been similarly affected.
Second, are you looking to buy a car, either new or
second-hand? Look away and think again. There is a
pent-up, post-pandemic demand for most cars. And the cause
is largely due to Covid-19. There is a huge supply-demand
mismatch. Dealers have full order books but the pandemic has
disrupted the manufacturer’s supply chains, primarily because of
illness and absenteeism among workers. Prices of both new
and used cars have increased by as much as 25% over pre-pandemic
prices.
Do you really need all this new technology? Are you
sure? Covid-19 may have indirectly helped you safeguard
yourself from it.