As the COVID-19 epidemic rises towards its peak, memories of an earlier time come crowding back. As the Second World War drew to a close, parents dreaded the recurrent epidemics of measles, diphtheria, poliomyelitis and smallpox. Death of young people, especially among the poorer in society was a constant fear, along with the death of young men in warfare. We read the public health messages on trams and buses: ‘Coughs and sneezes spread diseases’ and ‘No spitting’, recognising the constant fear of spread of tuberculosis from airborne distribution of the bacillus.
The recognition by Liberal and Labour politicians of the need to protect the public from Beveridge’s five Great Evils – Want, Disease, Ignorance, Squalor and Idleness – led to the Welfare State. Many will smile wryly at its caricature as the ‘Nanny State’ by people who are wealthy enough to have had nannies themselves but deplore the State providing such altruistic services for others. And think again of those five evils in the light of the current pandemic.
The Welfare State brought in an NHS which ensured that the newly developed vaccines against common infections and curative antibiotics (first M&B tablets and penicillin injections) could be available to all citizens. We could all access good quality healthcare from our GPs and hospitals, a uniform and unified system across the whole population. It was transformative for those who lived through that period; we have never underestimated it. Attlee and Bevan remain our heroes, but few young people will have even heard of them.
We do not wish to dwell on why this epidemic has hit us so hard; that is for another time. Rather, here we shall address some questions that need answering in relation to management of the current pandemic. They all relate to public health issues: protective equipment, immunity, and antibiotic usage. All are currently widely discussed and to some extent misunderstood.
Personal protective equipment (PPE)
This term includes every piece of clothing or equipment used to protect a worker from external hazard. While it includes steel-toed boots and earplugs, in the present context of an airborne hazard the important issue is protection of the respiratory tract (from nose and mouth to the deep lung) by devices ranging from simple masks to whole-body suits.
An important principle is that PPE is the last form of defence after all other protective measures have been taken; this is widely misunderstood by many people who believe that a mask is the only method of protection and, following from this, that other methods may not be necessary. These other methods include stopping exposure to the source of hazard, reducing exposure to a safe level, and enclosing the source so the hazard is confined. It is easy to understand this in terms of say the work of a miner. To prevent dust diseases, the primary objective is to reduce dust levels and limit time of exposure, not to make him wear an uncomfortable mask all shift. It puts the responsibility on both employer and worker.
You will already be familiar with this with respect to the current epidemic; the primary action would have been to try to stop it gaining hold in the UK by identifying infected individuals early with tests, isolating them and tracing their contacts, who then also are isolated. We know now that this was unsuccessful and led to the next stage, which was to reduce the risks to everyone, especially those most susceptible, by restricting movement and simple but crucial hygiene measures, hand-washing, coughing/sneezing etiquette, and avoiding physical contact.
Ultimately, as such measures have also proved insufficient, it has been necessary to impose much more restrictive measures and to rely on medical services to treat the casualties, services which have been forewarned by the experience of other countries. We are now waiting to see how well they work. And as we wait, we are wondering how on earth we are going to get out of this economically and socially disastrous situation. Could PPE be an aid to this?
With COVID-19 we are dealing with a very small particle (a few thousand millionths of a metre in diameter) that is carried in millionth of a metre (micron)-sized drops of moisture over several metres and can survive when it lands on surfaces for up to several days. Thus, it can be breathed in if you are close to a person who coughs, sneezes or even talks loudly, and you can pick it up in smaller doses simply by handling contaminated surfaces and passing it to your face.
There is a great deal of good hard science behind the use of respiratory protection, science that does not rely on matters such as modelling probabilities. Some things are obvious. A leaky mask over the face will keep very little out of your lungs but will catch some of the wet matter that comes out when you cough or sneeze, so will give a small measure of protection from you to others in speaking range. Viruses being very small, only very specially designed face masks (respirators) that fit tightly on your face will protect against them. Facial hair will cause it to leak. If you wear a mask, you will have to take it off, and in doing so you will probably touch your face unless you have been shown how to do it properly.
Moreover, many people wearing a mask rely on it and forget to carry out the hand-washing that is so necessary to interrupt the passage of virus from one person to another. This explains why widespread use of masks holds potential risks to the wearer even if it reduces spread to others. In other words, general use of face masks is only likely to be helpful in controlling an epidemic if almost everyone wears one.
There is a compelling reason to take every possible precaution in protecting health and social service workers. No worker should be compelled to hazard their life; think of how asbestos is handled, for example. Workers removing it wear full-body protection and the whole area is closed off to unprotected people. This for a hazard to life that is not immediate but decades in the future. Health workers are rightly expected to be protected in a way that prevents them inhaling the virus and becoming contaminated by it, including the use of a special respirator; hygiene measures are rigorous. Yet many still contract the disease and sadly sometimes give their lives.
No measures ever guarantee 100% protection, particularly against the unexpected high exposure which can occur during medical procedures. This is especially the case when pressure on staff is greatest, people are tired, and mistakes occur. The preparation for an epidemic must include measures to relieve such pressures.
Immunity, antigens and antibodies
In earlier articles ( 4 March and 18 March ) we discussed the general course of an epidemic and why herd immunity seemed unlikely to influence the current one in the short term. Immunity is an important way in which the body protects itself against other organisms; in essence, it recognises proteins from those organisms (foreign antigens) and produces neutralising proteins (antibodies) that render them harmless. It also usually remembers the stranger so that if it makes its appearance again, the antibodies are produced quickly to prevent harm. Thus, immunity may be life-long but more usually lasts a few years. This is the basis of vaccination/immunisation; we are given a harmless dose of antigen and, when the germs come round, we don’t fall ill.
Many people, not least our politicians, are confused by talk of ‘testing’. You can test with a throat swab, for example, for the presence of the invading organism, in this case the virus SARSCoV-2. This test detects the antigens from the virus and tells you whether infection is present. If we look back to our first article, we said that on the cruise ship 19% of passengers were infected. This suggests that around 81% either had some natural immunity or did not encounter the virus. The explanation for this is not known but would be of considerable interest – could it be genetic, for example?
Looking at why some people appear resistant is a crucial issue for research. Those people who have been infected and recover, the large majority, are assumed to develop the relevant antibodies and these proteins can be detected in the blood. At present, scientists are working to find a reliable means of measuring these antibodies and when this is successful it will be possible to test anyone to find if they have been infected. It normally takes several weeks for the body to make antibodies to a new infective organism in measurable amounts, so antibody tests are carried out some time after the infection took place.
The development of antibodies implies some future immunity to that infection. This may be very strong and last decades (smallpox, yellow fever and polio, for example) or quite short-lived and relatively unreliable. It is also specific to the organism, so that if it mutates frequently like influenza, the vaccine needs to be changed annually. To date, the antibody response to COVID-19 is not fully understood – another crucial area of research. Ultimately, human immunity is key to overcoming the viral threat and is most likely to be achieved by widespread vaccination. At present, at least five candidate vaccines are being investigated in early trials and others are in the pipeline.
Treatment
Antivirals
We previously discussed how scientists have concentrated research towards better understanding COVID-19 disease, its prevention and its treatment. The last few weeks have seen important advances in our understanding on how best to care for patients with COVID-19 in hospitals and clinical trials are now well underway investigating at least five different treatment approaches to the infection including drugs with activity directly against the virus (anti-viral) or against the body’s reaction to the virus (anti-inflammatory).
All drugs have adverse effects and the balance of benefit and risk needs to be assessed in these trials. An example is the emerging story of chloroquine/hydroxychloroquine and COVID-19. Long used in the prevention and treatment of malaria and in rheumatic conditions, these drugs have been lauded and promoted by President Trump on flimsy scientific evidence, and this has led to controversy and criticism from the International Society of Antimicrobial Chemotherapy. Their benefits and toxicity in COVID-19 remain entirely unknown and they are not approved for use by the USA and European/UK regulatory bodies.
Despite this, hydroxychloroquine is already widely used in the United States in the treatment of COVID-19. Its use in the UK to date has been appropriately restricted to ongoing well-designed clinical trials. Evaluation in these large-scale trials is sure to yield a clear answer as to whether it has a place in treatment of COVID-19. But, importantly, the global demand for these unproven therapies has threatened the already fragile supply chain for those patients with rheumatic disease where they have proven benefit.
Antibiotics
Alexander Fleming, the Ayrshire-born microbiologist and scientist, discovered the antibacterial effect of the fungus, Penicillium, in 1928 in his laboratory in St Mary’s Hospital, London. Penicillin was subsequently developed in its therapeutic form, mass produced and successfully deployed in the treatment of infected wounds, pneumonia and other infections in the later part of the Second World War. Fleming was awarded the Nobel Prize for physiology or medicine with collaborators Florey and Chain at the conclusion of the war in 1945. In Fleming’s Nobel lecture he warned:
The time may come when penicillin can be bought by anyone in the shops. Then there is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug make them resistant.
This forewarned us of antibiotic resistance or ‘drug resistant infections’, driven primarily by uncontrolled antibiotic availability and indiscriminate prescribing (particularly in viral infections) but made considerably worse by poor sanitation and hygiene. Drug resistant infections are now a global phenomenon and, like COVID-19, currently disproportionately affecting those with the poorest economies and weakest health systems, although this is rarely discussed on daily news bulletins.
Penicillin had not been discovered at the time of the last great pandemic of 1918/19, when it undoubtedly would have been of immense benefit in treating the bacterial pneumonia which so frequently and fatally complicated influenza. In the absence of approved anti-viral treatments, a key question for doctors currently is to decide when the addition of an antibiotic would be of benefit when COVID-19 is suspected.
In contrast to the influenza pandemic a century ago, bacterial co-infection appears to be unusual with COVID-19. However, many of the clinical features of the severe form of the viral infection are almost indistinguishable from pneumonia. In the absence of proven COVID-19 therapies, there is a tendency to prescribe antibiotics ‘just in case’. Whilst this is absolutely justified for patients with the severest forms of the infection, the additional prescribing of antibiotics over this pandemic period for hundreds of thousands of people globally will have undoubted longer-term consequences for drug resistant infections in the future.
Reports from China, a country already disproportionately affected by drug-resistant infections, has shown that almost all of those with the COVID-19 infection received antibiotics despite little evidence of associated bacterial infection in the majority. It is important, as our understanding of COVID-19 grows, for the indications for antibiotics to be clearly defined and for doctors to take great care to prescribe only to those with the clearest evidence of secondary bacterial infection. The impact of COVID-19 on future drug-resistant infections runs parallel to the economic impact of the pandemic. Resilience and forethought today are required to minimise the longer-term consequences.
Although there is genuine concern regarding the longer-term consequences of over-prescribing of antibiotics in the context of the COVID-19 pandemic there is a flip side. Efforts to reduce unnecessary GP assessment and hospital admission of patients with suspected mild symptoms (e.g. fever for less than one week) may inadvertently delay treatment for those with other serious bacterial infections. This is particularly important in children and in young adults where other illnesses such as sepsis and meningitis must be diagnosed and treated urgently. This requires further careful thought and Government health messaging.
Prevention is always better than cure; the two most vital things we now require are an effective vaccine and a reliable antibody test. However, for frontline healthcare workers, affected patients and their families there remains an urgent need for effective, safe, evidence-based and affordable treatments.
Coming out of the epidemic
All epidemics wane. Some do so as dramatically as they appeared, others more slowly, some persist as an endemic disease, prone to sporadic outbursts, and some return on an annual basis. This pattern is a part of the unending battle by the two organisms, animals and microbes, for survival. Microbes have the advantage from their ability to reproduce and mutate rapidly, but we have the unique advantage of ingenuity, expressed through our scientists. Politicians may state in simplistic terms their determination to win the battle while scientists recognise the problems and work out ways to overcome them. And this viral pandemic is a completely new experience for most scientists, so we must above all be patient and compliant with the advice we receive.
The economy
The difficult issue for politicians is that there are two related threats, to health and to the economy, and the responses to them must be balanced. No nation can survive long without a productive economy nor without a healthy workforce, so both must be protected. At present, our workforce has been pared down to what is essential – health and social care, the military, police and other services, governance, food production and medical supplies and their distribution, waste disposal and so on. Politicians need to consider what else is needed to get productivity growing and to put people back to work in those industries essential to that purpose.
A good start might be physical work on infrastructure and engineering projects, drug and chemical manufacture, education, bioscience, and catering facilities for the workers. Widespread re-distribution of employment opportunities is likely to be necessary while work and education from home is likely to increase considerably. Inevitably, the costs must initially be borne by borrowing, to be paid back, as was the UK’s war debt, over many decades.
The workforce
The vital issue is the healthy workforce. We now inadvertently have a huge population of healthy people out of work. There is little choice for politicians; we must be put back to work as quickly as possible in such a way as to prevent a further outbreak that overcomes the NHS resource. This implies an element of risk, in the knowledge that complete safety is impossible to achieve; some people will continue to die with or from COVID-19. We know who are at greatest risk; the elderly, people with particular chronic illnesses and disabilities. If they go back into the community quickly, they will over-fill the hospitals, so should remain longest in isolation.
Least at risk are the under-50s and those who have had the infection; they are the first who should be able to return to work. Unfortunately, we do not know how to identify more than a small proportion of those who have recovered, so here development of an antibody test is crucial. A great deal of judgement will be necessary to decide who can return to an active life and when, but a graduated age-related approach seems likely to be advisable, probably with locally determined differences.
Subsequent outbreaks
As the hospitalisations and deaths reduce, control of local outbreaks will become increasingly important. It is here that the original control strategy needs to be reintroduced, with testing for the viral antigen in the population, tracing of contacts and testing them. We need to be prepared now for the supply of appropriate testing material and facilities to prevent resurgence.
Whatever return policy is adopted, life will necessarily be different. We shall need to continue all the personal hygiene measures and social distancing for many months, if not years. It may be that we shall get into the habit of wearing masks when we have respiratory symptoms. The NHS and social services will need to continue with careful measures to protect staff, and the public will have to tolerate long waiting times for non-urgent conditions as the backlog is slowly overcome.
We should expect post-war levels of taxation and austerity. Never again should we try to impose a supermarket model of business on the NHS or to open it up to competition from the discredited US system. We shall wait patiently for a vaccine to be found, trialled and then administered to the whole population. When, and if, that happens, we can look forward to giving immunity to the human herd and a return to something resembling normality. But we may hope that we shall all learn to live simpler lives, less demanding of the planet’s resources and more sustainable, remembering that we are all dependent on each other.
Anthony Seaton is Emeritus Professor of Environmental Medicine at Aberdeen University
Andrew Seaton is Consultant Physician in Infectious Diseases in NHS Greater Glasgow and Clyde and an Honorary Associate Clinical Professor at the University of Glasgow (@raseaton66 on Twitter)
The views expressed here are those of the authors and do not represent the views of their affiliated organisations or employers
By Anthony Seaton | 15 April 2020
