Covid08

The Covid-19 numbers
First of all, a significant newsflash. On Saturday 26 June, we welcomed a new one, a new Secretary of State for Health and Social Care. Out went Matt Hancock, in came Sajid Javid. We wish the incoming newcomer well.

From my side of the keyboard the Covid-19 numbers do not look particularly reassuring. It was all going so well. During most of May, new cases in the UK were down to 2,500 or so each day. Then as May waned there was a worrying upturn to 3,000 a day. By the beginning of June, this has risen to 5,000 cases, though daily deaths remained few, or, on 1 June, even zero. By mid-June daily new cases had hit 7,500 and ended the month at a rather alarming 26,000. Most of these were attributed to the Delta (Indian) variant and geographically in the North-west of England. Will the statistics go horribly exponential? True, the surges have been small, but that is exactly how exponential growth starts. Is this the dawning of a brutal third wave, or just a harmless ripple? Scientists and politicians remain undecided.

Overall the total numbers of Covid-19 cases and deaths in the UK have now reached approximately 4.8 million and 128,000 respectively. However, hospital admissions are beginning to rise again by a little over 200 a day with 1,700 currently hospitalised and 280 on ventilators. Daily death numbers have also risen slightly, but to fewer than 25. This latter datum is additional evidence that the vaccination roll-out has successfully weakened the link between the disease and death – during January 2021, the death figure averaged 1,000 per day.

That notwithstanding, the UK vaccination roll-out has proceeded apace. A total of 77.6 million doses have been administered, consisting of 44.7 million first doses and 32.9 million second doses. Overall, 65% of the UK’s adult population has now been single jabbed.

But this is still perilous territory. As lockdown restrictions are eased, less precautions are followed, more contacts occur, more cases will arise. Nobody wants a full-blown, third UK wave of Covid-19. Remember – this wretched Covid-19 pandemic is not over yet.

The global picture is more assorted. There has now been a total of 180 million Covid-19 cases and 4 million deaths worldwide. Currently, India is the most infected country (46,000 new cases per day) followed by Brazil, Colombia, Russia, Indonesia and the UK (26,000). Countries reporting the most deaths are the USA (a total of 600,000) followed by Brazil, India, Mexico, Peru and the UK (128,000). In terms of deaths per million population, Peru tops the table (5,820) with the UK ranked at number 17 (1,887).

Freedom Day rescheduled
By mid-June, the scientists and politicians were mostly convinced that the Covid-19 figures were going the wrong way. So, on 14 June, the prime minister, Boris Johnson, announced that the easing of lockdown measures, planned for 21 June, would be delayed for up to another four weeks. Freedom Day was reallocated to Monday 19 July. ‘It was’, he maintained, ‘the final stretch.’ And despite the frustrations of many, the move made sound sense. The extra month of lockdown restraint would allow second vaccine doses for the over-50s and first doses for everyone else in the UK. School holidays will have started, so there will be less close personal contact and safer outdoor activities. ‘Caution’ and ‘irreversible’ were the prime minister’s watchwords. But, of course, no political, copper-bottomed guarantees were forthcoming.

It’s all Greek to me
In October 2020, a Covid-19 variant was discovered and named 501Y.V2. Other researchers called it B.1.351, or 20H/501Y.V2, or even GH/501Y.V2. It became commonly known as the ‘South African variant’. Some thought this alias carried a geographical stigma. And that unease was heightened when the so-called ‘Indian variant’ began to infect much of the world.

What to do? How to stop the perceived abusiveness? On 31 May, the World Health Organization (WHO) announced a new, and apparently more courteous, naming scheme. Here are the basics:

New         Scientific      Old
Alpha        B.1.1.7        Kent
Beta         B.1.351    South African
Gamma      P.1           Brazilian
Delta        B.1.617.2    Indian

Let us hope we never get to Epsilon, and especially not 19 variants later, to Omega. Will the new Greek/WHO system catch on? That is really up to you.

The Delta variant
Delta, also known as B.1.617.2, belongs to a viral lineage first identified in India during a ferocious wave of infections there in April and May. The virus grew rapidly in some parts of the country, and showed signs of resistance to vaccines. But determining its properties was especially challenging because of confounding factors, such as new cases in excess of 400,000 per day and the continuation of mass political rallies and public meetings.

Two months later, we are better informed. Delta seems to be around 60% more transmissible than the already highly infectious Alpha variant as identified in the UK in late 2020. Severely Delta-infected people are about twice as likely to end up in hospital as those infected with Alpha. Delta is moderately resistant to vaccines, particularly in people who have received just a single dose. Of course, those at greatest risk are people who have no access to Covid-19 vaccines, particularly for instance, those in Africa, where most nations have vaccinated less than 5% of their populations. Now detected in at least 85 countries, Delta’s rise could yet be devastating.

The Delta variant continues making headway throughout the UK. Already it may have precipitated a third UK wave and that possibility has forced the government to postpone Freedom Day until 19 July. And Delta has been associated with disappointingly poor vaccine data. For example, a second dose of the Oxford-AstraZeneca vaccine boosted protection against Delta to only 60% (compared to 66% against Alpha), although two doses of the Pfizer-BioNTech jab were 88% effective (compared to 93% against Alpha).

By the end of June, cases of the Delta variant in the UK were doubling roughly every 11 days. But even people with one vaccine dose are still 75% less likely to be hospitalised, compared with unvaccinated individuals, and those who are double-dosed are 94% less likely to be hospitalised.

But make no mistake, Delta is set to flourish globally, and not just in poor nations, as in Africa where it has already been detected in Malawi, Uganda and South Africa. Rich countries are also under threat. For instance, virologists expect Delta to become the dominant strain in the USA, where regional vaccination rates are vastly disparate. Vigilance and vaccines are the order of the day to fight and defeat Delta and any of its emergent allies. This is a hazardous contest.

New vaccine news
The Novavax vaccine, which uses a constituent protein subunit of the Coronavirus, a different technology from the other Covid-19 vaccines authorised in the West so far, is back in the news. And it is good news from a 30,000 person trial conducted in the USA and Mexico. The Novavax vaccine was 90.4% effective against symptomatic Covid-19 infections and 100% protective against the moderate and severe disease. Against eight viral variants of interest and concern, its efficacy was 93.2%. And the vaccine appeared safe and well-tolerated with only mild side effects.

And there has been good preliminary news of a much-awaited nasal spray vaccine against Covid-19 – no needles, no syringes, no jabs, no squeals, little waste. Scientists in America have reported that a nasal spritz of a therapy based on engineered immunoglobulin M (IgM) neutralising antibodies is effective against the Alpha, Beta and Gamma variants. Squirts of the IgMs six hours before or six hours after infection, sharply reduced the amount of virus in the lungs two days after infection. Sadly, this work was murine-based, that is carried out in mice, not men. But …. it is a start.

Now some bad news. Already two messenger RNA (mRNA) vaccines (from Pfizer-BioNTech and Moderna), have proved to be spectacularly effective at overcoming Covid-19. However, another mRNA vaccine has recently crashed. In the last edition of Coronavirus – Part 7 (May 2021), successful results from the Phase 2b/3 trial of the mRNA vaccine, known as CVnCoV from CureVac, were anticipated. Furthermore, regulatory approval from the European Medicines Agency (EMA) was expected in early June. But the trial failed. On 16 June, researchers from the German company, CureVac, based in Tübingen, announced the results of its 40,000-person, Phase 2b/3 clinical trial. They reported that its two-dose vaccine demonstrated an interim efficacy of only 47% against Covid-19. In total, 134 cases of Covid-19 were detected among the participants, albeit in the environment of at least 13 variants. This was hugely disappointing. However, the trial will continue as its volunteers are being monitored for additional cases of Covid-19, with a final assessment expected in July.

Vaccination strategies – the carrot
We all respond to rewards, be they carrots, cash, or guns! It is the basis of operant conditioning. And nowhere has adopted this psychological trickery to the level of the USA in order to boost Covid-19 vaccination rates.

For example, to encourage residents of West Virginia to get jabbed, the state is offering the chance to win deadly weaponry (what?!) as part of a prize-winning vaccination lottery. For receiving a first jab, ‘lucky’ winners will receive one of five custom-made hunting rifles, or one of five bespoke shotguns. Other prizes include two customised pick-up trucks, five life-time hunting and fishing licences and 25 weekend getaways to West Virginia state parks. There are also mundane cash incentives of weekly $1 million payments.

Several other US states have also started vaccine lotteries. Perhaps the most bizarre scheme is that from Washington State – it allows adults, over the age of 21, to claim a free, pre-rolled marijuana joint when they receive either a primary or booster Covid-19 vaccination shot. The scheme is known as ‘Joints for Jabs’.

Will these strategies encourage the vaccine-reluctant to come forward and bare the deltoid? Probably. But beware of that stoned guy carrying that hunting rifle. And I thought California was ‘the land of fruit and nuts’!

And not to be outdone by the decadent West, the Russians have also adopted vaccine incentive schemes. For example, the mayor of Moscow announced in mid-June that, in an effort to speed up its sluggish Covid-19 vaccination rate, residents who get a Sputnik V shot will be entered into a lottery draw with cars as prizes. Apparently five cars, each worth 1 million roubles (about £10,000), will be given away every week.

Has the UK even discussed such niceties? Perhaps we should. Perhaps I should have delayed.

Vaccination strategies – the stick
At the other end of the scale of enticements are forced vaccinations driven by a proverbial stick. These are hugely divisive. Just thinking about the complexities of their legalities, ethics and logistics brings on brain-ache. Could it yet be a case of ‘no jab, no job’? For months, some UK hospitals and other businesses have been pushing for mandatory jabs.

Is this example from the USA a possible blueprint for others? Johns Hopkins Medicine, the colossal healthcare facility in Baltimore, Maryland, is requiring clinical and non-clinical personnel to be fully vaccinated against Covid-19 by 1 September 2021. The edict applies to all faculty, staff, temporary staff, students, postdoctoral fellows, house staff, providers, volunteers and vendors.

The organisation insists this move is essential to protect the health of patients, staff and the surrounding community. Requests for exemption, on religious or medical grounds, are allowed. Personnel who remain unvaccinated after 1 September will be asked to submit to a Covid-19 test every week. In addition, Johns Hopkins Medicine will continue to require clinical staff to wear appropriate personal protective equipment, and patients must continue to wear face coverings inside Johns Hopkins Medicine buildings. Patients are currently not required to be vaccinated.

A similar move is afoot among US universities. From late March, a few US colleges and universities began issuing requirements for students to be fully vaccinated against Covid-19 if they want to return to campus this autumn. Some policies include academic and other staff. The practice has blossomed – what began as a handful of institutions rapidly turned into dozens by mid-April and soon after to 350 and more.

Vaccination strategies – the stick in the UK
Are these the sort of protocols that will inevitably be enforced, sooner or later, in the UK? They will be resisted by many citizens, politicians, lawyers, trade unions and other groupings. Yet already the UK government has dipped its toe into the icy waters of confrontation. According to advice provided to the government by the Scientific Advisory Group for Emergencies (SAGE) social care working group, 80% of staff and 90% of residents in each care homes must receive at least one dose of a Covid-19 vaccine in order to provide a minimum level of protection against outbreaks. However, only 65% of care homes in England are currently meeting this target, falling to 44% of care homes in London.

Back in April, a five-week government consultation entitled, ‘Making vaccination a condition of deployment in older adult care homes’ was launched. The deadline was extended to 26 May. The consultation outcome was published on 15 June and then updated on 16 June.

In short, the government has announced that everyone working in a care home in England must be vaccinated. The new legislation means that from October – assuming Parliamentary approval and a subsequent 16-week grace period to get jabbed – all care home staff must have had two doses of a Covid-19 vaccine, unless they have a medical exemption. The requirement will apply to full-time and part-time staff, those employed by an agency, volunteers and others, such as tradespeople, hairdressers and beauticians deployed in the care home.

As far back as 30 May, the UK government's vaccine minister, Nadhim Zahawi, revealed that officials were considering requiring NHS workers to be vaccinated against Covid-19. He stated, ‘It’s absolutely the right thing and would be incumbent on any responsible government to have the debate, to do the thinking as to how we go about protecting the most vulnerable by making sure that those who look after them are vaccinated.’ And Zahawi continued, ‘There is precedent for this. Obviously, surgeons get vaccinated for hepatitis B, so it is something that we are absolutely thinking about.’

And so it has come to pass. Ministers are now considering extending the vaccination requirement to all NHS staff. On 17 June, the government opened a public consultation on requiring vaccination as a condition of employment for NHS workers in an attempt to reduce transmission in hospitals and to save lives. OK, here come the questions. What about other so-called front-line workers, such as teachers, police officers, ambulance and court staff? And shop staff? And what about an employment law to allow employers to sack employees who refuse to be vaccinated without a valid medical reason. And what constitutes ‘a valid medical reason’? And will the government be sued under European human rights legislation for breaching personal freedoms? And will the plans backfire so that staff resign rather than get vaccinated? As the British Medical Association has warned, ‘compulsion is a blunt instrument that carries its own risks.’

This is a prickly topic that will not solve itself. If the world has to live with Covid-19 for the foreseeable future – and it does – then some guidelines, directives, regulations and laws for wearing face coverings, social distancing and the like, plus compulsory vaccinations would seem to be unavoidable.

China’s vaccination achievements
For more than a week in mid-June, an average of about 20 million people were vaccinated against Covid-19 every day in China. What logistics! At that rate the entire UK adult population could be single jabbed in just two days.

Chinese citizens have been given – probably with no choice – one of two vaccines approved by the WHO for worldwide use. One is CoronaVac manufactured by Sinovac, a Beijing company. In clinical trials it has shown an efficacy of 65% against symptomatic Covid-19 and 86% protection against the severe disease and death. It has already been approved for use in 29 countries. The other vaccine is a product from the state-owned firm Sinopharm and has a demonstrated efficacy of 79% against both the symptomatic disease and hospitalisation.

Both of these approved Chinese vaccines are two-dose vaccines to be administered between two to four weeks apart. Both are easier to store in domestic fridges than other approved vaccines – a considerable advantage in resource-poor settings. Both use well-established technology based on an inactivated virus. Both offer less, but judged to be sufficient, protection against the disease than do the novel mRNA vaccines with their 95% efficacies.

Meeting the global need
These vaccines from China, with that country’s enormous potential for manufacturing, could become central players in curbing the global pandemic. The grand project is to vaccinate 70% of the world’s population with 11 billion doses in order to achieve the estimated threshold for herd immunity. And these Chinese vaccines could become key suppliers to COVAX, (Covid-19 Vaccines Global Access), the worldwide initiative for supplying vaccines to low-income countries. Certainly, their ease of storage and transport will bring big advantages to those nations.

But such nations need cash as well as vaccines. A recent pitch from the International Monetary Fund (IMF) entitled, ‘A Proposal to End the COVID-19 Pandemic’, promoted a rational action plan with targets, schedules and costs. It builds on the current work of the WHO and partners, such as COVAX, the World Bank Group and the World Trade Organization. It states, ‘The proposal targets: (1) vaccinating at least 40 percent of the population in all countries by the end of 2021 and at least 60 percent by the first half of 2022, (2) tracking and insuring against downside risks, and (3) ensuring widespread testing and tracing, maintaining adequate stocks of therapeutics, and enforcing public health measures in places where vaccine coverage is low.’

It continues, ‘The benefits of such measures at about $9 trillion far outweigh the costs which are estimated to be around $50 billion – of which $35 billion should be paid by grants from donors and the residual by national governments potentially with the support of concessional financing from bilateral and multilateral agencies.’

Will this Proposal work? Will it bring the pandemic to an end faster in the developing world? Will it reduce infections and loss of lives? Will it accelerate the economic recovery? Will it benefit people’s health and lives? Who can say? What alternative plans are available? Surely it must be worth a punt.

Covid-19 has undeniably created a global rich versus poor conflict. The pandemic was on the agenda of that mid-June meeting of the world’s richest G7 leaders at Carbis Bay in Cornwall. Ask some pertinent questions. Were there any signs of a cobelligerent unity in fighting the virus? Will the poor be helped? Apparently, yes and yes. At the end of the summit, the host, Boris Johnson, judged that countries were now rejecting ‘selfish, nationalistic approaches’ to the pandemic. And the G7 leaders pledged one billion Covid-19 vaccine doses to poor countries. ‘It was’, said Boris Johnson, ‘a big step towards vaccinating the world.’ In addition, the prime minister promised to donate at least 100 million surplus Covid-19 vaccine doses within the next year, including 5 million beginning in the coming weeks, either directly or through the COVAX scheme.

Jabs for adolescents
On 4 June, the UK vaccine regulator approved the use of the Pfizer-BioNTech vaccine in children aged 12 to 15. The Medicines and Healthcare products Regulatory Agency (MHRA) said, after conducting a ‘rigorous review’, that this vaccine is safe and effective in this age group and the benefits outweigh any risks.

The Pfizer-BioNTech vaccine has already been approved for use in people aged 16 and over. The UK’s Joint Committee on Vaccination and Immunisation (JCVI) will now decide whether children, those under 12, should be vaccinated. In addition to approval, the JCVI must advise the government whether these cohorts should be included in the UK’s vaccination roll-out.

The Tokyo 2020 Olympic Games
Friday 23 July is the scheduled opening ceremony for the Games of the XXXII Olympiad, better known as Tokyo 2020. Will it ever start? It has already been postponed from last year. Will it ever get to the closing ceremony on Sunday 8 August 2021? Will all of the 339 events in 33 sports have been completed?

Long Covid
Long Covid is variously described as the long-term adverse sequelae after a SARS-CoV-2 infection, or as a poorly-defined syndrome that exhibits at least one lingering symptom after a Covid-19 infection.

Because the number of Covid-19 cases in the world has now exceeded 180 million, it is time to ask some pointed questions. What are the long Covid figures? A US review of several studies published in March reported that between 33% and 87% of post-hospitalised patients reported at least one symptom persisting after several months. Those are among the severely ill Covid-19 patients. What about the non-hospitalised Covid-19 patients? A general study by the Office of National Statistics (ONS), published in April 2021, estimated that 1.1 million UK people who had suffered from Covid-19, still reported adverse symptoms. When a cohort of 20,000 Covid-positive people were tracked, the ONS found that 13.7% reported symptoms after at least 12 weeks. A June study from Imperial College London estimated that almost 6% of adults in England have suffered from long Covid. And remember, all such numbers are generally regarded as underestimates.

Although our understanding and treatment of this lingering illness have increased, many mysteries remain. While most people with Covid-19 recover and return to normal health, some patients have symptoms that can last for weeks, or months, maybe even years. In other words, for some people Covid-19 is more than an acute disease, it develops into long Covid.

These long-term symptoms typically include fatigue, shortness of breath, cough, joint and chest pain. In addition, there are reports of smell and taste problems, sleep issues, difficulty with concentration, memory troubles, depression and anxiety. One UK study found that after six months, the most common symptoms were fatigue, post-exertional malaise and cognitive dysfunction. And these symptoms fluctuate with patients often going through phases of improved health followed by periods of relapse.

Moreover, long Covid seems to be more common in women than in men. It is most common in middle-aged people, those between 35 and 49 years old. And it is least common in younger and older people. However, the ONS estimates that about 10% of children aged 2 to 11, who have had Covid-19, will suffer prolonged symptoms.

Long Covid has now become recognised as a serious public health problem. Since January 2021, the WHO has recommended that all Covid-19 patients should have access to follow-up care to minimise long Covid. Since February 2021, the US National Institutes of Health (NIH) announced that it would spend $1.15 billion over four years to research long Covid, quaintly renamed as ‘post-acute sequelae of Covid-19’ (PASC). Again, since February, the UK’s National Institute for Health Research (NIHR) has invested £18.5 million to fund four studies of long Covid. And in March 2021, it unveiled additional funding worth £20 million.

So, what causes long Covid? It is unlikely to be the virus itself. Infected people are clear of the virus after a few weeks. What about viral fragments? These are known to persist for months. Or is it caused by the immune system going haywire? Is it therefore an autoimmune disease? On that hypothesis, the jury is currently out. Yet studies have found unusual concentrations of cytokines, chemicals that help to regulate immune responses, in the blood of people who have had Covid-19, which suggest that their immune systems are skewed.

Some current studies are examining blood and saliva samples of Covid-19 patients at 4-monthly intervals for factors, such as inflammation, cardiovascular problems and other significant changes. Additional studies are taking a different approach by researching physical impairments, mental health difficulties and cognitive impairments. These are scattergun approaches because the biology of long Covid remains largely a mystery. So far, it seems unlikely that there is one simple underlying cause and so there is unlikely to be one simple treatment for long Covid. Causes and effects are so far entirely elusive.

Here is a fascinating question – is long Covid similar to other illnesses that linger after viral infections? A possible link might be to myalgic encephalomyelitis, also known as chronic fatigue syndrome (ME/CFS). People with this debilitating illness typically become exhausted after even mild activity and exhibit other symptoms common to long Covid. After all, ME/CFS is also a post-viral illness. Yet differences are evident. For example, long Covid sufferers are more likely to report shortness of breath than are those with ME/CFS.

What treatments are available for long Covid patients? Not many. By May, the NHS had provided £24 million for a network of 80 and more clinics to start assessing and helping people with the condition. Yet no evidence-based treatments currently exist. The real need is for multidisciplinary teams because long Covid affects so many parts of the sufferer’s body and mind. Perhaps the immediate need is for rest, maybe for several weeks or even months. And learning from the quarrelsome history of ME/CFS, long-Covid needs to be recognised as a genuine disability by healthcare professionals. The number of people with long Covid implies the need for more care and support.

Not all is downbeat – a few putative medicines are already being tested. For example, PureTech Health, a biotechnology company in Boston, Massachusetts, has started a clinical trial of deupirfenidone, its own anti-fibrotic and anti-inflammatory agent. Preliminary results are expected in the second half of 2021. And intensive-care specialist, Charlotte Summers and her colleagues at the University of Cambridge, have launched a study called HEAL-COVID, which aims to prevent long Covid ever taking hold. Participants, who have been previously hospitalised with Covid-19, are given one of two drugs after being discharged. They are apixaban, an anticoagulant that might reduce the risk of dangerous blood clots, and atorvastatin, an anti-inflammatory agent. Results are awaited.

And there is the seemingly rhetorical question, could Covid-19 vaccines prevent long Covid? A UK survey of over 800 people with long Covid, reported in March that after a first vaccine dose, 57% of participants saw an overall improvement in their symptoms, 24% no change and 19% a deterioration.

Long Covid is proving to be a huge medical challenge. It is beset by hitches and glitches. Since its aetiology currently remains a mystery, it is like fighting with an unknown adversary – and that is never an easy way to win a battle.

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