Plague Year Journal V: Science & Sensibility

The Covid-19 pandemic will be the best documented and most analysed in history. Medical scientists around the world are using it as a petri dish to test hypotheses. But the long-term impact will be in terms of changes in behaviour, writes Victor Hill.

Excess Deaths

All deaths are tragic but in medical terms the figure that is getting more attention as the pandemic plays out is the amount of excess deaths – that is to say, the amount by which deaths exceed the normal or average number of expected deaths over a given time period. Total deaths divided by “normal” deaths yields something called a P-score (i.e. excess death rate) which can be used as a comparator between countries and regions within countries. (There is also something called the Z-score which standardises data on excess deaths by scaling them in terms of standard deviations – but let’s not worry too much about that here.)

Figures released by EuroMOMO (which tracks mortality figures across 24 European countries) on 18 May[i] suggest that England’s excess death rate is one of the worst in Europe. Furthermore, England’s excess death rate is not dropping as fast as it is in other countries which have recorded high levels of mortality from the Covid-19 pandemic such as Italy and Spain. These excess deaths include both those who have succumbed to the virus but also include contingent deaths – that is to say, people who missed out on critical treatments which were unavailable due to the pandemic. There is mounting evidence that cancer patients and others who would otherwise have survived are victims of this pandemic. On the other hand, in India road deaths have plummeted relative to normal levels.

In the four weeks to 24 April there were around 79,000 deaths in the UK, compared to an average of 42,000 over the same four weeks in the last five years. Of those 37,000 additional deaths, 27,000 had Covid-19 on their death certificates. The other 10,000 deaths remain “unexplained”. But they could be regarded as the collateral damage of the lockdown.

The UK entered lockdown about three weeks after Italy but will emerge much more than three weeks after Italy’s relaxation. Italy recorded its peak number of 6,557 new Covid-19 cases on 21 March, but since then new cases have fallen steadily to barely a few hundred per day now. The UK hit a peak of 6,199 cases on 05 April: but today (27 May) there were still over 2,000 new cases. The experts do not agree as to why the number of the UK’s new cases remains so stubbornly high. Until it subsides, a partial lockdown will have to continue with disastrous economic consequences.

The genetics of vulnerability

We know that certain groups are more vulnerable to severe symptoms and death from Covid-19 than others. Men fare worse than women; and the elderly, those with diabetes, the obese and those with dementia appear to be more at risk. But why do some young people get very sick while the overwhelming majority do not? And how come an estimated half to three quarters of people infected with the virus remain entirely asymptomatic (but can yet pass it on)?

Children appear to be as likely as adults to contract the virus but the number of children who have died from it is “staggeringly low” (the words of Professor Sir David Spiegelhalter) – just two under-15s have died in England and Wales out of more than ten million. The risk for people over 90 is about 10,000 times as high. But, to put this into perspective, a 90-year old has the same chance of dying from heart disease as from Covid-19 this year.

To work out who gets sick and why, scientists are trying to understand what happens when the virus gets inside us and the role that our genes play in our bodies’ response. The virus that provokes Covid-19 (termed SARS-CoV-2 by clinicians) is a parcel of protein and nucleic acid about 85 nanometres across. Like all viruses it depends on its host to survive and replicate itself. It can only do this by breaking into and “hijacking” healthy cells in the human body.

Children, it is thought, have fewer of the cell surface (ACE2) receptors which the virus needs in order to get inside a cell. Furthermore, young people’s immune systems are less likely to mount an aggressive response that can spiral out of control – a so-called cytokine storm. This is where our own immune system goes haywire and turns against us.

Figures from China suggest that men had a death risk from Covid-19 1.7 times that of women. In New York fatalities amongst men are 60 percent higher than for women. A similar gender imbalance was identified back in 2003 during the SARS epidemic; and MERS, which is still at large in the Middle East, has claimed 3.3 male lives for every female one. SARS and MERS are both coronaviruses. Some scientists have hypothesised that oestrogen (the female hormone) promotes a more vigorous immune response. The downside to that is that women are more at risk of certain autoimmune conditions such as multiple sclerosis.

Lifestyle and behavioural factors could also go some way to explaining this particular gender gap. Supposedly, men tend to be less fastidious about handwashing – and hygiene generally. Though, I haven’t seen any studies that confirm that with hard evidence and we must be careful not to fall into stereotyping. Men do smoke more than women – especially in China – and that makes them more susceptible to forms of chronic pulmonary disease.

Chronic conditions, including diabetes, high blood pressure and cancer, put people at higher risk of developing severe complications with Covid-19 because they can compromise the immune system. As at the end of March, according to the US Centers for Disease Control and Prevention (CDC), 89 percent of people hospitalised with Covid-19 had at least one underlying chronic condition.

Some medical scientists have suggested that the key factor may not necessarily be the chronic condition itself but the medication prescribed to treat it. For example, many people with hypertension (high blood pressure) take ACE inhibitors which target an enzyme that works alongside ACE2 receptors to regulate blood pressure. That might make it easier for coronaviruses to penetrate cell linings – we still don’t know for sure.

One worrying trend is that in many western countries ethnic minorities appear to suffer from a disproportionate level of mortality. Numerous hypotheses have been proposed to explain this. Many ethnic minorities – particularly illegal immigrants of which there are an estimated 11 million in the USA – have limited access to healthcare and live in poverty which always leads to poorer health outcomes. So the explanation is unlikely to be genetic: indeed many African countries, though lower-income, have suffered a remarkably low incidence of Covid-19. In fact, Africa, which accounts for 13.7 percent of the global population, only accounts for 0.43 percent of deaths from Covid-19. This might be explained by the fact that Africans are young: the median age in Africa is 19.4, as compared with 45.4 in Italy.

Genetic factors are nevertheless critical. Back in 1996 scientists in New York and Boston worked out that people who carried a mutation in a gene called CCR5 were immune to HIV/AIDS. The CCR5 protein wedges itself into the outer membrane of T-cells – these being the key players in our immune systems. Similarly, some genetic mutations make people less susceptible to HVC – the virus that causes hepatitis C. This has prompted a joint programme between Stanford University in California and the University of Helsinki called the Covid-19 Host Genetics Initiative which has inspired over 150 studies involving 500 scientists around the world.

The genomes of 300 Covid-19 patients are also being analysed by the University of Glasgow in collaboration with biotech start-up Oxford BioDynamics. The trial will also assess which antiviral drugs – such as Remdesivir (manufactured by Gilead Sciences (NASSAQ:GILD)) – assist recovery or decrease severity.

People with blood type group A have a significantly higher risk of developing Covid-19 compared with non-A blood groups, according to a study conducted by the Southern University of Science and Technology in China[ii]. This study, corroborated by work done in New York, suggests that people with blood type O seemed to carry a higher degree of immunity to Covid-19 than people with other blood groups (principally, A, B and AB). This, if true, would be good news for people of Celtic heritage; but the sample size of this study is thought to be too small to be statistically meaningful.

Studies suggest that while pregnant women don’t seem to be at greater risk of developing severe symptoms from the virus, Covid-19 is linked to a higher rate of caesarean deliveries and premature births – in fact 25 percent of births to Covid-19-infected women are pre-term. It seems that the virus might be able to cross the placenta – which normally acts as a shield against infection – to the foetus. In contrast, SARS killed about a quarter of the pregnant women who contracted it in the pandemic of 2002-04. The good news now is that most new-born babies who carry the virus have recovered well so far.

Fat chance

An audit of 28,000 hospitalised cases in the UK released by SAGE shows that obese patients are 43 percent more likely to die from the virus than the non-obese. I understand that “obese” means someone with a body mass index (BMI) of more than 30 – which is unscientific because it doesn’t consider body composition. That means that many bodybuilders down the gym are considered to be “obese”. I find it extraordinary that such a sloppy metric has become the standard.

The real point is that type-2 diabetes is generally driven by obesity (as in the common sense understanding of being fat). The British (29 percent) are not materially much more obese than the Germans (24 percent) and are much less obese than our American friends (nearly 40 percent). So the correlation between obesity rates and deaths per million is fragile.

Was the lockdown worth it?

This is the question that will rage for years to come, given the economic damage of lockdown and the spike in excess deaths discussed above. Professor Michael Levitt of Stanford University, a British-American-Israeli scientist who won the Nobel Prize for chemistry in 2013, has developed a model (another one) which suggests that the lockdown of itself saved no lives at all. The same outcomes would have been achieved by rigorous social-distancing and by wearing masks.

Someday, someone will attempt to quantify the economic cost of the social damage – domestic abuse, increased divorce, increased alcoholism, loss of fitness (no gym sessions), stroke weight gain, loneliness, cancelled funerals – plus the damage to millions of children’s education. And what is the cost of the suspended elections and curtailment of democratic institutions? Not to mention all the postponed investment decisions. We may never know for sure.

On the other hand, modelling by British climate scientist James Annan, suggests that if Britain had imposed a lockdown seven days earlier than 23 March our mortality figures would have been closer to Germany’s than Italy’s. (They are now actually worse than Italy’s.) One thing that might come out of this, going forward, is that those climate models, of the kind that Mr Annan develops, might come under increased scrutiny too – especially since their predictive value has been negligible.

Changes ahead

Until the 1970s Britain used to have more than 600 small fever and isolation hospitals. If there were clusters of cholera, typhoid, smallpox or tuberculosis, sufferers were packed off to isolation hospital such as the Joyce Green Hospital on the Dartford marshes which was surrounded by walls to prevent airborne infections from spreading. The Centre for Evidence-Based Medicine at Oxford University recently called for the return of isolation hospitals for infectious diseases. Such a programme, combined with tracing technology, might obviate the need for future wide-scale lockdowns.

Many infectious diseases are subject to the 80/20 rule in so far as 80 percent of new infections are spread by 20 percent of activities. Analysis by the London School of Hygiene and Tropical Medicine and the Alan Turing Institute suggests that transmission of the virus between individuals varies widely. I explained two weeks ago why “R” is suspect. The focus, instead, should be on super-spreading events. We already knew that there are super-spreading venues, including hospitals, care homes, dormitories (that means crew accommodation on cruise ships, by the way), food processing plants and football matches.

I’m sorry to say that now we have to add indoor gyms and exercise classes to this list. When the gyms re-open (04 July?) we are likely to find that gym etiquette has changed. We shall need to book a slot in advance via an app; use of changing rooms will be discouraged; and there may even be Perspex partitions between exercise stations. Gym chains that get this right will be able to prosper – I hear that PureGym (private) is working on this. The cost of gym subscriptions will inevitably rise.

As for the 14-day quarantine period on new arrivals in the UK (which as I write is still planned to begin on 09 June) even Tory MPs are saying that such a measure should have been imposed at the beginning of the crisis rather than at the end.

***

I wrote last week that I could not bring myself to blame Mr Johnson for the myriad of things that have gone wrong. But it now seems to me – and the brouhaha around Mr Cummings is telling, though I don’t want to swim in that particular mire – that Mr Johnson’s political capital is diminishing at a critical moment.

Everything pivots on the outcome of the Brexit talks – and the month of June is when we shall find out if any kind of deal is possible. Thus, next week, I shall abandon my plague year journal and return to the Badlands of Brexit. A vampire will only die once a stake is plunged through its heart…But this vampire’s creatures are circling in the night…The rumour in Tory circles is that while both Mr Johnson and Mr Cummings were laid low with coronavirus the Deep State signalled to Brussels that an extension to the transition period was inevitable…And any extension would entail that Britain be tied into the EU’s next seven-year budget cycle…No wonder Mr Cummings felt the need to return to London in haste.

[i] See: https://voxeu.org/article/excess-mortality-england-european-outlier-covid-19-pandemic

[ii] See: https://www.pharmacytimes.com/news/study-suggests-blood-type-a-associated-with-higher-risk-of-covid-19