Covid16

Counting cases
The UK data used in these Coronavirus updates are derived from the official UK government website, https://coronavirus.data.gov.uk/ which in turn is fed by the UK Health Security Agency (UKHSA). Other statistical sources are available. With so many Covid-19 figures out there in the ether, new numerical milestones are reached every week. For example, in the second week of February there were record totals of 18 million confirmed cases in the UK along with 160,000 deaths.

Now the UK government has announced some different Covid-19 counting rules to track and report the spread of the endemic more accurately. Until recently, only the first episode of a Covid-19 infection was counted in these official daily figures. The government has now started to add in people who have been reinfected, namely, those who have tested positive for a second time at least 90-days apart. This second episode is now counted as a separate infection.

The overall number of reinfections is currently small, only about 4% of the 18 million UK cases. But as the pandemic continues, such reinfections will inevitably become more commonplace for two main reasons. First, because as time passes, more people will experience a first infection and thereby become candidates for a reinfection. Second, because highly-transmissible variants, such as Omicron, will, by their very nature, spread more rapidly to more people either as a first infection or as a reinfection. And if Covid-19 infections persist in a population, there will come a time when the majority, if not all, of new cases will be reinfections.

Other numerical changes have been tweaked. For example, from early February, the official Covid-19 figures have been updated and backdated with nearly 850,000 cases consisting of reinfections and previously unrecorded cases. These additions stretch back to the start of the pandemic.

All Covid-19 case data are questionable. Most Covid-19 case data are underestimates. Is there a better method for case counting? Enter the power of random sampling. This uses a relatively small number of samples to mimic a wider population. A good example is the Office for National Statistics (ONS) Covid-19 Infection Survey. It is the gold standard, beloved of statisticians and epidemiologists. Fortnightly, it randomly tests 180,000 people for Covid-19 from its total pool of 500,000 volunteers. The Survey reckons that LFT and PCR testing spots and reports only around half the true number of daily cases. One obvious weakness in the LFT scheme is its dependence on its users to bother to register their results, whether positive or negative. The ONS volunteers are essentially obligated to comply. Moreover, the sensitivity of the ONS scheme is illustrated by the fact that, based on its own numbers, it has calculated that the risk of reinfection from Omicron is 16 times greater than that for Delta. This highly-regarded ONS data compilation enables surveillance of the virus in order to pinpoint, for example, regional outbreaks and age-related variations. But, in the government’s current Covid-19 cost-cutting proposals, will the ONS Survey be sufficiently funded and scientifically rigorous enough to ensure it remains fit for purpose? These are pertinent questions.

Identifying Covid-19 surges, building mathematical models, formulating governmental policies, and much more, depend upon accurate infection data. As the techies say, ‘garbage in, garbage out’ – the output is only as good as the input. Random sampling works well but it requires sustained effort and adequate funding. It could, even should, play a key role in the future management of this pandemic. In the UK government’s current rush to cancel so many of its previous responses to Covid-19 it should not miss the trick of saving and supporting the Office for National Statistics (ONS) Covid-19 Infection Survey.

Counting Covid-19 cases is a fraught endeavour. Absolute case numbers are unlikely to ever be recorded, or even needed. What is more needful is the scrutiny of trends. For that enterprise, most statistical sources are sufficient, but random sampling is possibly the best.

COVID-19 RESPONSE: LIVING WITH COVID-19
This is the government’s new and radical Covid-19 plan, which was announced by the prime minister, Boris Johnson, on 21 February in the House of Commons, in an evening TV broadcast and in a 63-page document with the above uppercase title. It was expected to be launched at the end of March, but arrived a month earlier, amid rumours of Cabinet disagreements and an inherent lack of scientific rigor. It applies only to England, though the other three devolved UK governments will eventually toe the mark. Indeed, the very next day, on 22 February, Scotland declared that it will end all of its legal Covid-19 restrictions on 21 March.

In the meantime, the new slogan is, ‘living with Covid-19 without restricting our freedoms.’ In brief, the plan effectively scraps all the previous legal restrictions aimed at tackling the pandemic. That is the plan’s legal facet. The medical facet is to cut the vast majority of testing by both LFTs and PCRs. The financial facet will end the £500 Test and Trace Support Payment and statutory sick pay of £96.35 per week for those on low incomes who previously had to self-isolate. In addition, dismantling the testing scheme is reckoned to save about £2 billion a month.

The BIG change concerns ending self-isolation. From Thursday 24 February, people in England are no longer legally ‘required’ to self-isolate if they test positive. Until Friday 1 April, those infected will still be ‘advised’ to stay at home and avoid personal contacts. And after that, everyone will be ’encouraged’ to ‘exercise personal responsibility, just as we encourage people who may have flu to be considerate to others.’ So said the prime minister.

The BIG controversy concerns ditching testing. From 1 April, LFTs will no longer be available free of charge on the NHS, but will have to be bought from pharmacies – Boots is already selling packs of four kits for £17 online. A stampede for the last of the free NHS LFTs is predicted - apparently only 1 in 4 people is willing to pay for tests. Could that spark a rebound of infections? In addition, those with Covid-19 symptoms will no longer be entitled to free PCR tests. Students and staff in education will no longer be required to undertake twice weekly asymptomatic testing. Herein lies a fuzziness in the plan. The government will allow ‘a small number of at risk groups’ to continue to be tested, but who and when has yet to be specified. Likewise for healthcare front-line staff.

This whole testing regime is reliant on cash, billions of it. England wants to save some money, but Scotland, Wales and Northern Ireland are free to continue funding their own testing services. But they must pay from current budgets so that means something else must be cut. Waiting lists, hospital builds and social care innovations – they all require urgent attention and they demand billions. Is prioritising governmental fiscal policy over healthcare spending a rash and maybe imprudent exercise?

The prime minister has acknowledged that the end of free symptomatic PCR testing will limit the ability of the UK Health Security Agency (UKHSA) to track new infection spikes and to identify new variants. Johnson’s escape route is his pledge to continue using the Office for National Statistics (ONS) Covid-19 Infection Survey – see the subsection above.

Of course, the UK and the world have to emerge from, or, at least, learn to live with Covid-19. But timing is key. Too soon, and the plague could flare up dangerously, especially if a dearth of testing allows hazardous trends to go unnoticed. Too late, and the general public remains restriction bound, socially deprived with a moribund economy. Yet there are few commentators who are in the ‘too late’ camp. Many more, and with good reason, populate the ‘too soon’ faction. They ask, ‘Is all this derestricting premature? Is it brave or stupid?’ And when Covid-19 is viewed less parochially and more globally, the ‘too soon’ cohort win the argument and the day.

The dominant Omicron variant may be milder but it is still a ghastly virus that injures and kills. How risk averse are you? Is the government’s new Covid-19 plan too fast or too slow, too soon or too late?

The path to global immunity
It is now estimated that 64% of the world’s population has received at least one dose of a Covid-19 vaccine. That equates to 5 billon people receiving 10.5 billion doses. Around 31 million doses are currently being given each day across 184 and more countries. This is the biggest vaccination campaign in history.

Whereas approved vaccines have been shown to be highly effective at preventing severe infections, hospitalisations and deaths, it will take a coordinated campaign to arrest the Covid-19 pandemic worldwide. To approach a return to normality (please, not ‘normalcy’), it is reckoned that between 70% and 85% of the population must present with Covid-19 antibodies. This is the goal for so-called ‘herd immunity’. And it apparently matters not whether these antibodies are generated as a result of Covid-19 natural infections, or from vaccinations, or both. Meanwhile, booster shots may also be required to keep the virus under control.

Globally, this is a daunting prospect. So far, only 77 countries have given at least one jab to 75% of their populations. At this current vaccination rate of 31 million daily doses, it will take another 6 months before 75% of the global population has received at least one dose. Meanwhile, only 10% of people in low-income countries have received even one dose. Halting, or controlling, or even monitoring the pandemic is a challenging task. Nevertheless, the case numbers, in several high-income countries, are beginning to fall. Is it therefore time for them, the UK included, to rebalance the risk-benefit of severe illness at home against their responsibility to care for a watching world far away?

Breakthrough infections
Which is best – jabs then plague, or plague then jabs? Two recent research reports help to answer this question. Breakthrough infections occur in vaccinated people who subsequently become Covid-19 infected. In other words, their Covid-19 antibodies have been triggered by vaccines so they have ‘vaccine immunity’. By contrast, other people get ‘natural immunity’ after having had a Covid-19 infection.

The first report is entitled, ‘Vaccination before or after SARS-CoV-2 infection leads to robust humoral response and antibodies that effectively neutralize variants’ by Timothy Bates et al., and published in Science Immunology (25 January 2022). Initially, it showed that Covid-19 victims, who were subsequently vaccinated, created large numbers of antibodies and those antibodies had neutralising power to destroy an array of Covid-19 variants, though Omicron was not tested.

To further determine the permutation for the best production of antibodies, the team from the Oregon Health & Science University, Portland, tested the blood serum of participants who had had breakthrough infections (vaccinated then infected), others who were infected before vaccination (hybrid immunity), and vaccinated people who had no history of infection (naïve vaccinated). Blood serum samples from both the previously infected groups had more antibodies that possessed similarly enhanced neutralising abilities against the Covid-19 spike protein than did serum samples from those protected only by vaccines.

In other words, according to the researchers, ‘The additional antigen exposure from natural infection substantially boosts the quantity, quality, and breadth of humoral immune response regardless of whether it occurs before or after vaccination.’ And, ‘Infection before or after vaccination gives a significantly larger boost to the neutralizing antibody response compared to two doses of vaccine alone.’ And they concluded, ‘Because vaccination protects against severe disease and death, it is safer for individuals to be vaccinated before rather than after natural infection.’

The second study is entitled, ‘SARS-CoV-2 breakthrough infections elicit potent, broad, and durable neutralizing antibody responses’ by Alexandra Walls et al., in Cell (19 January 2022). These researchers, from the University of Washington and elsewhere, examined three groups of Covid-19 infected people – those who subsequently had two jabs, those double-vaccinated people who then had breakthrough infections, and those who had three jabs but no infection. Serum levels of antibodies that neutralised Covid-19 variants, including Omicron, were higher and persisted for longer in all three infected groups compared with people who had two doses of vaccine but had never been infected.

In other words, people with breakthrough cases, or those infected then vaccinated (hybrid immunity), ‘are endowed with a greater potency, breadth, and durability of serum-neutralizing activity relative to individuals who received 2 doses of COVID-19 vaccine.’ So, three-dose vaccinations are good. Breakthrough infections are better. Multiple exposure to infections plus vaccinations are best.

Vaccinating children
In mid-February, Wales became the first of the four UK nations to offer all healthy 5 to 11-year-old children Covid-19 vaccinations – the other home countries quickly followed suit. Medically-vulnerable children have been entitled to vaccinations since January 2022.

The Joint Committee on Vaccination and Immunisation (JCVI) had concluded that vaccinations should go ahead to protect a ‘very small number of children from serious illness and hospitalisation’ in any future waves of Covid-19. And because only a very small number of children become severely ill with Covid-19, the health secretary, Sajid Javid, said the roll-out, to begin this coming April, would be ‘non-urgent’ with an emphasis on parental choice.

And the scientific basis of this new government policy? The JCVI guidance, published on 16 February and entitled, ‘JCVI statement on vaccination of children aged 5 to 11 years old’ stated that fewer than two out of one million children vaccinated would develop inflamed heart muscle (myocarditis). However, vaccinating one million children would prevent 98 hospitalisations if the next wave was more severe than previous variants and 17 hospitalisations if the next wave was less severe or relatively mild, like Omicron. Moreover, because more than 85% of children have had prior Covid-19 infections, they will already have some natural immunity. Here is the crucial question, would that alone, namely without vaccinations, be enough?

The approved paediatric treatment will consist of two 10 microgram doses of the Pfizer-BioNTech vaccine, with at least 12 weeks between each dose. This is just a third of the adult prescription, but, because children’s immune systems respond more robustly, this lower dose is regarded as sufficient. Similar protocols for the over-5s are already being used widely in other European countries. In the USA, over 8 million children in this age group have already been vaccinated. In total, about 6 million children in the UK will be offered these jabs.

Human-challenge trials
This is a controversial topic that was first mentioned here in Coronavirus – Part 4 (February 2021) at http://www.johnling.co.uk/Covid04.html There is an on-going human-challenge trial conducted by Oxford University that is deliberately infecting healthy, young volunteers between 18 and 29-years-old with Covid-19. The aim of this project is to study immune responses so that improved Covid-19 vaccines can be produced and refined and administered to obtain optimal levels of therapeutic antibody and T cell responses. Or as Clive Dix, of the Vaccines Taskforce has said, ‘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.’

The phase 1 of the trial, which began in April 2021, aimed to define the lowest viral dose, of the original Wuhan strain, that would trigger Covid-19 infections in approximately 50% of the 34 volunteers. There were no serious adverse events reported. The preliminary results have now been published as a preprint entitled, ‘Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge’ by Ben Killingley et al., at Research Square (1 February 2022). It raised important questions. For example, why were roughly half of the participants not infected though exposed to the virus? What was different about their immune systems? Why did symptoms vary among those infected? Why did long Covid-19 persist in only some?

In phase 2, all the participants will receive, via nasal drops, this standardised dose of the virus that was established in phase 1. The volunteers will be isolated and monitored in a specially-designed hospital suite for a minimum of 17 days. They will undergo a batch of medical tests including CT scans of the lungs and MRI scans of the heart. Any participants who develop Covid-19 symptoms will be prescribed Regeneron’s monoclonal antibody treatment, Ronapreve. Follow-up appointments will be conducted for the next 12 months.

Oxford University is currently recruiting participants for this phase 2 of the trial. They will be paid at least £4,995 as compensation for time, inconvenience and travel expenses. See, https://trials.ovg.ox.ac.uk/trials/sites/default/files/trials_attachments/COV-CHIM01PISv8.0_25.11.2021_Clean.pdf for details.

The above is the relatively simple, factual description of this research. The ethical bit about human-challenge trials is more complex. True, human-challenge trials have been used for decades to research diseases, such as influenza and malaria. But this is the first Covid-19 human-challenge trial. True, it can provide unique opportunities to study Covid-19 viral infections in a controlled environment by monitoring the full course of the infection, from the moment a person first encounters the virus until it is apparently eliminated. And true, such information should help improve vaccines, antivirals and diagnostics. But human-challenge trials can pose risks, known and unknown, to the participants – after all, Covid-19 can be a long-term, dangerous and even lethal disease.

Consider some pertinent ethical questions. First, is it right to deliberately infect healthy people with a deadly disease for which there are few effective treatments and currently no cures? The history of medical experimentation is littered with atrocious examples of human exploitation – for a start, think Mengele and Auschwitz. Second, have the experimenters provided all reasonable care to minimise harm? ‘Reasonable care’ maybe, but probably not ‘all-inclusive care’. Third, has proper consent – high-quality, fully informed and continuous – been obtained? That is subjectively impossible to confirm. Is payment for participation justified? Maybe, but could it be inappropriately attractive to impecunious students and others? After all, medical procedures, such as donations of blood or transplant organs, are generally given freely. Will the insights gained from this trial be sufficiently valuable to justify these and other risks? Could such information not be obtained using other, more traditional, experimental protocols?

May this potentially-risky Oxford human-challenge trial deliver its objectives and may the participants be protected from all ills.

Moderna mimicked in South Africa
Two of the chief stumbling blocks impeding worldwide vaccination are the availability and cost of most Covid-19 vaccines. Part of the answer is for Big Biotech to lessen their profits, share their vaccine patents and allow localised production in low-income countries. This commercial revolution has just begun in South Africa, the original source of the Omicron variant. And in the near future, other countries, such as Egypt, Kenya, Nigeria, Senegal and Tunisia, are also set to receive the necessary technologies to produce game-changing mRNA vaccines.

Afrigen Biologics and Vaccines, a pharmaceutical company based in Cape Town, has begun using the publicly-available sequence of Moderna’s Covid-19 mRNA vaccine to make its own version. It is part of an initiative launched by the World Health Organization (WHO) to create vaccine technology hubs in low- and middle-income countries. The WHO initially asked Moderna, Pfizer and BioNTech to share their vaccine production methods, but none of them responded.

So, in early February, with the help of sympathetic scientists from around the world, the South African company forged ahead and announced that it had nearly managed to mimic the Moderna vaccine. It is expected to be tested in human clinical trials before the end of this year to be followed soon after by production and distribution across the African continent and beyond. That is, if Moderna holds off any lawsuits over vaccine patents. Yet Afrigen’s managing director, Petro Terblanche, is adamant, ‘But this is not Moderna’s vaccine, it is the Afrigen mRNA hub vaccine.’

Novavax approved
It has been a rocky road, but at last, on 3 February, Novavax vaccine, also known as Nuvaxovid or NVX-CoV2373, was approved for use by the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) for first and second doses in people aged 18 and over. Some of those impeding rocks have been detailed in Coronavirus 14 (December 2021).

In late February, the companies announced that they are planning to submit their trial results to the US Food and Drug Administration (FDA) for regulatory authorisation. Can the world have too many effective vaccines against Covid-19?

Home or office?
Covid-19 has undeniably ripped up much of the world of healthcare – pandemic, endemic, vaccinations, infections, deaths and so forth have all taken their toll. Medicine will never be the same again, but nor will many other aspects of modern daily life. Take for instance, the world of work.

Will the traditional working week, from Monday to Friday, sitting deskbound, from 9 to 5, in a mind-numbing office, ever again be the norm for millions? Before Covid-19, working from home, or WFH, was uncommon and typically eyed by management as a bit of a skive. Then came the Covid-19 lockdown and the governmental diktat, ‘Work from home if possible.’ The streets and motorways grew eerily quiet, trains and buses were mostly empty, cafes, sandwich shops and gyms became hushed if not bankrupt. Meanwhile, that new breed of sedentary home workers, including a mostly first-time cohort of men, sat staring at their computer screens, while in their pyjamas and slippers, next to their fridges, intermittently eating and drinking and continually gaining weight, together with their ‘lockdown’ dogs. It has been said that we will leave the pandemic either as a chunk, a hunk, a drunk or a skunk.

Will these quasi-office workers return to the office? By mid-February, office occupancy in the UK had reached about 30%, well below the pre-pandemic level of 60%. For many the post-pandemic pattern will be hybrid working – part home, part office. Unsurprisingly, Mondays and Fridays are the favourite days to work from home. Already more than 80% of firms, including major companies, especially those in the banking, accountancy and legal sectors, have begun making the switch to hybrid. And it is largely popular. One recent poll of global businesses reported that 68% of workers prefer the hybrid working model, while almost everyone (95%) favours working flexibility. And with less staff arriving each day, are those high-rise city office blocks really necessary? For some, hot desking is in vogue with its lower costs and apparently higher productivity. Mass commuting, that dreadful, early morning rush of workers from the suburbs to the cities and its evening reversal, may yet become an historic phenomenon.

What a mini revolution! Spending more time at home than in the office is a significant social transformation. Both living and working at home have become more attractive, cheaper and healthier, especially when home is at the bucolic fringes of ‘this sceptered isle’. And there have been other unexpected perks, such as spending more time with family and walking that ‘lockdown’ dog and using the erstwhile three hours of commuting more gainfully, including tackling Wordle. Most workers like this post-lockdown pattern. And several employers are now allowing staff to work permanently from the kitchen table. Will there ever be a return to pre-pandemic patterns of work? Probably not. But for some the novelty has already begun to wear off. WFH staff evidently miss the fun, the buzz, the office bonding and banter, the gossipy chats by the water cooler and the sense of shared mission. For them, sitting in front of a computer screen in the kitchen or spare bedroom is just not the same. The sociable and gregarious are finding it tough. Yet, for many, the world of work has moved on. Of course, Covid-19 has changed our world, mostly for the worse, yet with some surprising and constructive benefits. Thank you internet, Zoom, Slack, Teams et al.

Of course, most of the above has little relevance to millions and millions of non-office workers, the self-employed, the unemployed, home-makers and pensioners and countless others. Nevertheless, this home-office hodgepodge is a new and Covid-19 driven reality. Fascinating.

Pets at home
Do you have pets at home? Are they rodents? Do you have any adorable hamsters? If so, then read on. In January, a scientific report entitled, ‘Transmission of SARS-CoV-2 (Variant Delta) from Pet Hamsters to Humans and Onward Human Propagation of the Adapted Strain: A Case Study’ by Hui-Ling Yen et al., was published online as a preprint in The Lancet (28 January, 2022).

In early February, following genomic analysis of viral samples from pet hamsters, came confirmation that these little members of the subfamily Cricetinae were the carriers of the Delta variant of Covid-19 that sparked a human Covid-19 outbreak affecting about 50 people in Hong Kong. A pet shop was identified as the source after a 23-year-old worker at the store tested positive for Delta on 15 January. Covid-19 antibodies against the virus were subsequently found in 15 of 28 Syrian hamsters (Mesocricetus auratus). As a result some 2,000 pet hamsters from across the city were culled.

Hamsters are only the second animal known to be able to infect people with Covid-19. In late 2020, mink caused minor outbreaks of Covid-19 in people in Denmark and the Netherlands. Mass culling followed.

How can pets as endearing as hamsters spread such a dangerous disease as Covid-19? Come on, don’t be duped by their cuteness!

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Coronavirus - Part 13 (November 2021)	Coronavirus - Part 14 (December 2021)	Coronavirus - Part 15 (January 2022)