A year has now passed since the word arrived of a new viral illness in Wuhan, accompanied by the alarming rumour that it seemed to pass from person to person even before symptoms had developed. If this is true, I thought, it could be a big one, one I had long warned medical students about but hoped never to see. Since then, I have watched it closely and recorded my observations for readers of Scottish Review. It was soon recognised to be a pandemic, and we are still learning more about its behaviour and our reaction to it; it is too early to come to final conclusions, but something has evidently gone seriously wrong in our response, and there are some hard lessons to learn.
The Great Plague, 1665
In 1722, a similar episode was threatening Europe and the journalist and author Daniel Defoe decided as a warning to write an historical but fictional journal of the Great London Plague of 1665, an event that occurred in his early childhood but had been recorded in some detail, including in Bills of Mortality and the diaries of Samuel Pepys.
This was at a time when such events were considered acts of God as a punishment for sin, mediated by miasma, but it was recognised that the plague was transferred internationally through seaports and passed from person to person. Isolation and hygiene measures, including attempts to detoxify the air with fumigants, were the preventive measures. Quack doctors and quack remedies made money for some, and wild rumour circulated as to who and what were to blame. It was recognised that infection could be spread by contact with clothing and bedding and such items were burned after the patient died. Those who could afford it fled the city, leaving the poor to bear the brunt of the disease.
Infected families (infection was a general term for such diseases, long before bacteria were discovered) were locked in their houses and charitable folk took food for them until they died. As now, the least well-off provided the services that the majority relied on, suffering as a consequence. Most doctors fled the city and those who remained only had opium, blood-letting and purging to offer. Burial services were overwhelmed, and bodies were thrown into large pits. Defoe's book is not a comfortable read.
The plague spread to other cities where it attracted less attention than in London, but it ended rather abruptly as the cold of winter arrived. We now know the cause was a bacterium injected by a flea bite, the fleas usually being rat parasites that had found human blood to their taste. Bacteria were first proposed as a cause of infection by Louis Pasteur in the 1880s and one of his pupils, Alexandre Yersin, discovered the causative bacterium during a plague epidemic in Hong Kong in 1894. Hygiene measures have proved successful in preventing the disease and it is curable by antibiotics, but still occurs in poor parts of the world and in situations where hygiene breaks down. In London in 1665, it is estimated that 68,590 citizens died, a rate of almost 15% of the population of the city.
The concept of viruses, too small to be seen even by powerful light microscopes also goes back to the work of Pasteur who was initially studying plant infections. Their presence was induced from experimental observations of infection transferred by fluid that had passed through a bacterial filter, but it only become possible to see them after the invention of the electron microscope by the German physicist, Ernst Ruske, in the 1930s. He shared the Nobel prize for this somewhat belatedly in 1986, at the age of 80.
The coronavirus was first seen by a Glaswegian, June Almeida, working in the Medical Research Council Common Cold Unit near Salisbury in 1965 with its director, David Tyrell. One famous experiment done there was devised by James Lovelock, best known for his concept of Gaia and books on climate change. A fluorescent dye was trickled into the nose of a staff member and after a game of cards the light was turned off and a fluorescent lamp showed the dye to have diffused throughout the room. This demonstration of the transfer of small particles is central to all I have written this past year about the way COVID-19 is passed from person to person.
Tyrell's unit demonstrated that coronaviruses are an important cause of the common cold but also showed that their propensity to mutate made finding a vaccine all but impossible at that time. This observation is being repeated with COVID-19 and its effect on vaccine efficacy is likely to prove a challenge.
The COVID-19 pandemic
By mid-January 2021, it had been reported that over two million of the world's population of 7.6 billion had died from COVID-19. This number will inevitably increase but, to give a perspective, two curable and preventable diseases, tuberculosis and malaria, still currently kill around 1.5 million and 500,000 respectively every year, many of their victims being children and young people. They attract less attention and altruistic support as they are not perceived to be a threat to the rich world.
As with the Great Plague, COVID-19 kills the poor and disadvantaged selectively but is also strikingly more fatal in the elderly and barely affects children at all. It is not known why. As with all toxic agents, its effect seems to be related to dose in that those most heavily exposed are most likely to fall seriously ill, but individual susceptibility to its effects on immune response is an important determinant, again not yet understood but upon which some partially effective treatments have been based. A striking risk factor for death is obesity, something that is very obvious to doctors on the front line. The presence of diabetes also seems to increase risks.
It is not yet clear why there is a strong negative association with educational/social status nor why BAME individuals are at greater risk; these may in large part relate to increased likelihood of high exposures owing to the need to go out to work, mixing in large families and a higher prevalence of chronic illness.
What is very apparent is the difference in mortality between different nations. Even when one takes account of differences in methods of registration, as I have discussed previously (30 May 2020
), these are striking. In the Far East, mortality is universally low – China 0.34 per 100,000, Taiwan 0.03, Malaysia 1.6, S Korea 1.9. Japan 2.85. Experience in dealing with earlier epidemic threats is likely to explain a large part of this in populations which know how to behave. India 11, Philippines 8.7, Indonesia 8.6, Pakistan 4.9 and Bangladesh 4.8 are a little higher. African countries, with the exceptions of South Africa 51.9 and Libya 23.0, have shown extraordinarily low mortalities ranging from Namibia at 8.9 to Cote d'Ivoire 0.5, Nigeria 0.7 and Uganda 0.6.
Under-reporting and the very much younger and slimmer demographic may well be part of the explanation, but other protective factors must be at play; traditional efficient public health responses and inherent immunity from exposure to other infections may be relevant. But what stands out most clearly is the high mortality in Europe and the Americas.
The UK so far has a mortality of 124 per 100,000. Scotland as I write has recorded over 7,700 deaths among about 145,000 cases, an overall mortality so far of 141 per 100,000 of the population. Compare this rate with other small countries: New Zealand 0.5, Uruguay 6.1, Denmark 11.7, Norway 8.18, Finland 10.2, Costa Rica 44.6, Ireland 46.1. Only Sweden among small counties has a similar record to ours at 147. Our popular holiday destinations have fared little better: France 99.5, Spain 110, Italy 128, USA 111, Switzerland 96.2. But Germany 47.4, Greece 48.5 and Netherlands 71 have achieved some control.
Where now? Prevention and treatment
I discussed the vaccines in my last article. Our future now depends critically on protection of the public by their rapid distribution and administration. Once again, the UK has responded to the news of the new variant poorly initially, leading to overload of the NHS with COVID-19 patients. In particular, the Christmas relaxation of rules on congregation that I warned against in December has led to an upsurge. There are now many sad tales of grandparents who ate their last Christmas dinner with the families from whom they had previously been shielded.
Viruses do not obey man's laws; their spread is subject to the laws of physics. The spread of infection owing to the new variant and the repeated failure of the expensive and almost useless privatised test and trace system have once again led to so many cases of illness that it is no longer feasible to trace contacts and we have to rely on extreme measures of isolation of the whole population; only vaccination now holds hope of preventing disaster.
In addition to hoping that our governments can get the vaccine out quickly, we need to remember one simple thing that I pointed to when the pandemic first hit us in the UK. The virus is spread largely by inhaling the breath of others, especially indoors. If you want to avoid falling ill, assume you and everyone you meet are carrying the virus and avoid talking to others save at a distance. Confined spaces such as rooms in houses and public transport are dangerous in relation to the numbers of people in them. Wear a mask that covers nose and mouth whenever you are in contact with others. Physical contact is also a risk, and hand/face hygiene remain important. It is almost certain that the countries which have avoided the worst of COVID-19 are those which have applied public health measures and contact tracing/isolation rigorously. I fear we have not.
Treatment of COVID-19 has improved dramatically over the past year. Better ways of providing oxygen have been found, dexamethasone has been shown to prevent a significant proportion of fatalities, and two more expensive drugs used in rheumatoid disease have also been shown to have a more modest ability to prevent a proportion of the most serious consequence of infection and save one life for every 12 seriously ill patients treated. Thanks to all this, more patients are surviving but many occupy hospital beds longer and go on to have prolonged disabling symptoms.
All this comes at a cost; doctors and nurses continue to fall ill and some die, tragedies adding to the stresses on those who remain at work. The management of these ill patients requires many experienced hands that are in short supply, and specialist nurses are hopelessly overburdened. Small wonder that my profession is outraged at the careless behaviour of those who regard COVID-19 as trivial.
A note on nanoscience
Seventeen years ago, I sat on a Royal Society working party in London commissioned to advise the government on risks and benefits of nanotechnology. We described possible hazards and advised on their prevention, but also recognised the enormous possibilities in the many potential technologies. However, I don't think that any of us conceived that within two decades the understanding of nature at the level of billionths of a meter (nanometers) would be central to both the deaths and the survival of so many people.
The virus SARS-CoV-2 is a very small particle, about 100 nanometers across. All airborne particles fall under the influence of gravity according to their density and diameter but viruses are so small they remain suspended almost indefinitely unless in a larger particle. When they are exhaled, they are enclosed in fluid and the larger ones fall to contaminate anything around them, but water evaporates quickly so many viral particles remain airborne for hours. Thus, being two metres from an infected person in a room does not protect you. Your risk depends on how many viruses are being breathed into the room, how well ventilated it is, and how long you stay there.
Unfortunately, the masks that we are rightly urged to wear are only weakly protective of the wearer but they do reduce the numbers of viruses the wearer exposes others to, so if you go into a place where everyone is wearing a mask properly you are less likely to catch the virus than if one or more of them are not wearing masks. This makes the wearing of face covering a moral imperative in such circumstances.
Coincidentally, one of the amazing tricks used by two of the vaccine makers, Pfizer/BioNTech and Moderna, has been to encapsulate the viral mRNA in a lipid nanoparticle to stabilise it and present it to the body's defences in a form suitable to be taken up by cells. After injection, this particle is taken into defensive cells and stimulates them to produce viral antigen which in turn stimulates an antibody response which seems likely to be effective in preventing death and serious illness. Thus, we are not only under attack by nanoparticles but also man-made nanoparticles may turn out to the be our most effective defence.
As I used to tell my students when I warned them about future plagues, the only advantage we have over micro-organisms is the ingenuity of mankind, especially in vaccine development. I wonder if our ministers have now revised their well-publicised views on the value of experts.
Anthony Seaton is Emeritus Professor of Environmental and Occupational Medicine at Aberdeen University and Senior Consultant to the Edinburgh Institute of Occupational Medicine. The views expressed are his own