A Journal of the Plague Year – Part the First

Daniel Defoe (of Robinson Crusoe fame) published his Journal of the Plague Year in 1722 – an eye-witness account of the Great Plague in London of 1665. How plagues play out can teach us lessons today. Victor Hill has begun to keep such a journal.

Salus populi suprema lex esto

So said Boris on arriving back in Downing Street last Monday (27 April), quoting the Roman poet, Cicero. But whatever Cicero said, most leaders have not put the health of the people first historically. In September 1665, when 7,000 people were dying every week, the court of King Charles II decamped from London to Salisbury, leaving plague-stricken homes in London boarded up. Quarantine, then as now, was the principal defence against pestilence.

The science writer Matt (Lord) Ridley wrote recently that medical science at present has no therapy against viruses to compare with the antibiotics which treat bacterial infections. The reason is that viruses do not have their own biochemistry with which we can interfere; instead they interfere with ours. Viruses are just a bunch of genes – just 15 in the case of Covid-19. These highjack our own metabolisms to replicate themselves.

Anti-viral economics

Viruses differ greatly from one another; so treatments that work for one (such as HIV-1, which causes of AIDS) seldom work for another. Anti-viral medications which attack more than one kind of virus, such as Ribavirin, can be toxic to patients since they attack the metabolism as well.

Anti-viral drugs aimed at eliminating a specific pathogen require extensive clinical trials – which are expensive. But once cured, a patient with a virus does not need to come back for repeat prescriptions – so the pharmaceutical companies do not generate a sufficient return on investment. AIDS and herpes were exceptions because they are long-lasting, sexually transmitted diseases. But by the time drugs developed to treat Ebola in the epidemic of 2014-15 in West Africa were ready, the epidemic was over. That said the experience of developing treatments for AIDS and Ebola has taught medical scientists where to look for chemicals that inhibit viruses.

The long search for a cure for AIDS was won thanks to the development of a class of drugs called protease inhibitors. These work by preventing protein molecules from breaking open to admit a virus. There is one protease inhibitor already approved for use in Japan as a treatment for pancreatitis. It is called camostat mesylate, and it is manufactured by Japan’s Ono Pharmaceutical (TYO:4528). This was found to work against SARS in 2012.

Remdesivir, developed by Gilead Sciences (NASDAQ:GILD) to combat Ebola, works by preventing a virus’s genes from replicating themselves if they are made up of RNA (a variant of DNA). In 2015 Remdesivir worked against Ebola in monkeys – but it failed to help Ebola patients in Congo in 2018. Recently, it was found to have cured cats of a coronavirus infection. Lord Ridley thinks that Remdesivir works best if administered early, through an intravenous drip – though it has severe side effects.

On Wednesday (29 April) the NASDAQ surged by 3.5 percent after White House health advisor Dr Anthony Fauci announced that a Remdesivir drug trial, which involved about 800 patients, showed quite good news. Speaking at a White House press conference, Dr Fauci said that data from the trial showed a “clear-cut positive effect in diminishing time to recover”[i].

One of the few anti-virals which is showing promise against multiple viruses is Favipiravir, branded as Avigan and manufactured by Fujifilm (TYO:4901). This drug has been cleared for use against coronavirus in Japan. It is taken in pill form.

Ritonavir and Lopinavir were first combined to treat HIV. The combination has been trialled against Covid-19 in China – but the jury is still out. Tamiflu, manufactured by Roche (SWX:RO), was stockpiled for the 2005 swine flu scare. It is unlikely to work against coronavirus as it targets an enzyme only found in influenza viruses.

US biotech firm Regeneron Pharmaceuticals (NASDAQ:REGN) is working on a cocktail of monoclonal antibodies for use against Covid-19. It hopes to start clinical trials in the early summer. Anti-inflammatories have been widely used to combat pain and swelling. Severely sick patients with Covid-19 can experience extreme inflammation as a result of a cytokine storm (a severe and acute inflammatory response) as their bodies try to arrest the infection. In China, if a patient’s level of the signalling molecule interleukin-6 is high, doctors administer monoclonal antibodies – but this needs to be done early.

Vaccinology frustrated

The Oxford Vaccine Group has now recruited 800 people in the UK from 18 to 55 years old to trial a vaccine for Covid-19. Half will be given the vaccine, and half a placebo (meningitis vaccine). Then they will return to “normal” life. Except that life is not normal at the moment since we live under a lockdown: so the guinea pigs are much less likely to be exposed to the virus than would otherwise be the case. As a result, scientists would prefer to recruit front-line health workers who are more likely to come into contact with coronavirus. The Oxford team is even working with scientists in Kenya on a possible vaccine trial there.

This means that it will take longer to develop a vaccine. On Wednesday (29 April) New Scientist reported that the idea of completing human trials by August was “unrealistic”[ii]. Even if everything were to go according to plan in the first phase of trials, researchers will need time to determine how well the vaccine protects people from Covid-19 – and whether it provokes any side-effects when a vaccinated person is subsequently exposed to the virus. Historically, the average time to develop a vaccine is 10.7 years.

This week Oxford’s Jenner Institute announced a not-for-profit tie-up with AstraZeneca (LON:AZN). AstraZeneca clearly wants to get onto this pitch. The vaccine giants are: GSK (LON:GSK), Pfizer (NYSE:PFE), Merck (NYSE:MRK) and Sanofi (EPA:SAN). In early April the US government committed $1 billion to a project with Johnson & Johnson (NYSE:JNJ), co-financing research through the Biomedical Advanced Research and Development Authority (BARDA).

Charterhouse Square in central London is now the campus for St. Bartholomew’s Hospital and the London School of Medicine and Dentistry’s (part of St. Mary’s College, London) new project to investigate the mysteries surrounding Covid-19’s microbiology under the leadership of Professor Sir Mark Caulfield. Why do some people contract nothing more than a sniffle, while others succumb to rapid respiratory collapse? Why do men suffer more than women, and the old more than the young? Why are black people in the USA and the UK disproportionately affected?

The task is to decrypt the biomarkers in human blood samples in order to understand the way in which Covid-19 invades the body. One study released by King’s College London (KCL) suggests that a person’s genetic make-up may influence their chances of catching the virus in the first place. The findings arise from data generated by the Covid-19 Symptom Tracker app that has been downloaded 2.7 million times since it was launched on 24 March.

There is no guarantee that the coronavirus is amenable to a vaccine. We don’t yet know how our immune systems respond to the virus, and whether it is possible to induce long-lasting immunity. Therefore, we might have to live with multiple waves of the virus over years to come.

Hydroxychloroquine update

Last week the French medicines agency ANSM warned doctors against using hydroxychloroquine – the anti-malarial drug developed in WWII, which Mr Trump described as a game-changer in the fight against Covid-19. ANSM reported that 80 percent of all cases where the drug had been administered had developed serious, and sometimes fatal, side-effects – especially cardiac damage. The drug had been touted as a possible cure if used in tandem with the antibiotic azithromycin.

Hydroxychloroquine is used against rheumatoid arthritis and the autoimmune disease lupus. It is sometimes used with zinc which has been shown to be a remedy for colds. Many people, especially in developing countries, are deficient in zinc; and the metal has become a popular sports supplement in the developed world. Strangely, too much zinc can kill your sense of taste – which is often a symptom of Covid-19.

Why is Asia doing so much better than Europe and America?

Britain (population 67 million) has now had 27,000 fatalities (including those in care homes), while South Korea (population 51.7 million) has had 246.

On 20 January this year the authorities in South Korea invited 20 South Korean pharmaceutical companies to develop a test for Covid-19 which they promised would be rushed through the regulatory process. Within weeks, South Korean people were being tested in large numbers. Those who were found to be positive had all their recent contacts traced – and these people were isolated too. Thus South Korea was able to contain the virus without a wholescale lockdown. In contrast, UK Health Secretary Matt Hancock said last week: “We have the best scientific labs in the world but we did not have the scale [to develop mass testing]”.

All the leading Asian nations had pandemic plans which envisaged that a future pandemic could be contained and eliminated through a sequence of inter-related initiatives. First, there would be large-scale testing capacity in order to identify clusters of infection rapidly. Second, contact-tracing technologies using smartphones (which all carry GPS technology these days) would identify carriers of the pathogen – and they would then be isolated rigorously. Third, all businesses and households in Singapore and South Korea had been advised to maintain a 3-6 month stockpile of facemasks, gloves and hand sanitizers. Fourth, border guards were issued with detailed protocols to screen all new arrivals – and, in many cases, borders were sealed at an early stage. (In contrast, the UK welcomed 80,000 Romanian fruit pickers to our shores last week and didn’t even check their temperatures). Fifth, these measures were not to beadvisory or proportionate – but enforced with military discipline.

Hardly any countries with nationalised, state-run healthcare sectors have done well. Germany has a compulsory social insurance-based system with about 100 competing health insurers and dozens of competing hospital groups, most of which are privately owned. Similarly, in Asia, the state pays for healthcare but buys services from a range of competing providers.

Back in the UK, having hugely increased ICU capacity by rolling out five NHS Nightingale hospitals, these now stand largely empty. Meanwhile, deaths in care homes outstrip those in hospitals. Yet care home employees have been left at the back of the queue for protective equipment. Carl Heneghan, Professor of Evidence-based Medicine in Oxford said this week: We should shift our resources from Nightingale Hospitals to care homes.

By the way, the Asian Tigers have relatively low levels of healthcare spending. Singapore spends 4.5 percent of GDP on healthcare; Taiwan 6.1 percent; Hong Kong 6.2 percent; and South Korea 7.3 percent. In contrast, the UK spends 9.8 percent of GDP on healthcare and the USA a staggering 17.7 percent.

It is not all good news in Asia. Singapore was heralded as a role model for testing, tracing and treating in March with a 6,000-strong team of disease detectives. Schools, restaurants and businesses remained open. But on Monday last week (20 April) new daily infections spiked to record levels. It turned out that silent clusters had been developing in the migrant community (mostly from poor Asian countries such as Bangladesh) who often live in cramped dormitories. Now, some 300,000 foreign workers must remain confined – though they get fed by the government. And even in South Korea some patients who apparently recovered have now relapsed.

The irony is that Europeans and Americans think that Asians are fatalistic; and Asians think that Westerners are pragmatic. But when the history of this pandemic is written, it will be clear that the British were guided by a fatalistic scientific elite; while the South Koreas were guided by pragmatists. The Europeans – the British and the Spanish – didn’t even count their dead; while the Asians kept tally in meticulous detail.

Women on top

History might judge that the nations with the most efficacious management of the pandemic were all led by women. I wrote last week that New Zealand, under Jacinda Ardern, has been a case study in pandemic management. The country has got through the emergency with just 19 fatalities. Germany, under Frau Merkel, has a mortality rate of around five percent – less than half that of Italy, France and the UK. Denmark under Mette Frederiksen was one of the first European countries to impose a comprehensive lockdown in early March. The country has recorded just 443 fatalities. Iceland, where Katrin Jakobsdottir is in charge, has had just ten.

Why have women leaders been so effective? One view is that a female management style has proven more conducive to swift, decisive action. Another is that women have to be exceptional to get to the top at all.

I wrote recently that President Trump would come through the crisis with his authority intact – but I doubt that now. I’m sorry to say that his lack of emotional intelligence and weak grasp of detail has contributed to the severity of the pandemic in America. More Americans have died of Covid-19 (62,000+) than were killed by the Vietcong. If he weren’t facing such a weak Democratic presidential contender he would now be in trouble.

By early summer there will be a league table, not of football scores, but of how well nations did in minimising fatalities from the pandemic. As things stand, the UK will be placed well down that league, with a final death toll of possibly 60,000 by the end of the year (not including contingent deaths – for example cancer patients whose treatments were interrupted).

The UK may well have the highest mortality rate in Europe – and there will be political consequences. I now think a resurgence of the Labour Party under Sir Keir Starmer is quite possible, if not probable. But there will certainly be no debate about how healthcare is delivered in the UK: the NHS has now been deified; and it will soon be illegal not to genuflect before those three letters. The momentum for a National Care Service is probably unstoppable – an impending disaster that I shall consider soon.

Anyway, I’m now predicting that most nations of the world will have women leaders by 2030. Not Russia or China, though – and probably not America either.

In search of Robinson Crusoe…

Daniel Defoe came upon his eponymous shipwreck hero in the churchyard of St. Nicholas Church in King’s Lynn, Norfolk. There are still memorials to a local man of that name there today (though his dates are imprecise). Defoe may have written part of the Journal in that fair Hanseatic city. The 1665 plague reached King’s Lynn from London – but that was the last incidence. There were numerous outbreaks of cholera there in the 1840s-50s. But nobody wanted to read about that.

[i] See: https://www.cnbc.com/2020/04/29/dr-anthony-fauci-says-data-from-remdesivir-coronavirus-drug-trial-shows-quite-good-news.html

[ii] See: https://www.newscientist.com/article/mg24632804-000-why-itll-still-be-a-long-time-before-we-get-a-coronavirus-vaccine/?utm_source=NSDAY&utm_campaign=35ccfae8af-NSDAY_300420&utm_medium=email&utm_term=0_1254aaab7a-35ccfae8af-373843547 {Paywall}