The coronavirus named COVID-19 is a new virus which has struck the world. It does not treat people equally but factors such as gender, social class, race and much more, determine the risk of infection with serious disease or even death. What was initially one chapter has become three to examine some of the clinical features and inequalities, as well as the science behind it and the lessons we must learn from the pandemic.
This chapter will contain the following headings:
- Pandemics Across the Centuries
- Clinical Features and Infectivity of COVID-19
- Face Masks
- Long COVID
- Drugs and Treatments for COVID-19
- A Vaccine for COVID-19
- Following the Science
- The Health of People or the Economy
- Myths and Fake News About COVID-19
- Life After COVID-19
- Further Resources
- Site Index
This is a new disease and much is being learned about it. I try to have the facts correct at the time of writing and to update as necessary but they may rapidly become out of date. If you search for information yourself, be careful to chose reliable sites as there is much nonsense and conspiracy theory out there.
Initially, this was to be just one chapter, but as new things happened and it became progressively longer, the one chapter has become three. The other two related ones are Who is at Risk from COVID-19? which examines the effects of age, gender, race, social class and many diseases on the severity of the disease. There is also What we Must Learn from the COVID-19 Pandemic which looks at the many lessons which must be learned for next time there is a pandemic. Experts agree that the question is not if, but when.
Because it is a coronavirus that was first described in 2019, it is designated COVID-19 (Coronavirus identity 2019). However, it may also be known as SARS-COV-2. They are the same thing. Throughout this article I shall call it COVID-19 but many of the references call it SARS-COV-2.
As with the other chapters on this website, references are given in blue with a number in superscript. If the reference is available online, clicking on the blue will take you to it. There is a list of references by number at the end. On a number of occasions when I am citing current affairs, the reference is to The Times or Sunday Times. I use them because that is what I read online and because The Times is a reliable source and seen as the newspaper of record. However, if you do not have a subscription you may be unable to get access and I apologise. If it is a news story, putting the title into a search engine may give a source that is available without charge.
If this is the first time you have come to this website and you are wondering about randomised controlled trials, meta-analysis, placebos and more, go to the site index at the end and click on the relevant chapter. Randomised Controlled Trials will cover those topics. Other chapters of interest might be Finding Medical Advice and Evidence Based Medicine which includes systematic reviews, How Good is the Evidence? and Fake News and Vaccine Scares.
Pandemics Across the Centuries
Infectious diseases have swept across the world since antiquity. Probably the most dramatic was the Black Death in the 14th century which typically killed a third to half the population where it struck, but sometimes it wiped out entire towns or villages. In Great Yarmouth, the population of 10,000, which was very high for the time, shrank to 3,000. There had been plans to extend the already large church and the foundations had been laid but they remain unbuilt on today.
The Black Death may have killed 20% of the population of the known world
There have been several other epidemics of plague in the UK over the centuries. Other than the Black Death, the worst was the Great Plague of the 1660s. It killed an estimated 100,000 people in London or a quarter of the population and probably killed another 100,000 in the rest of the country. There was a small outbreak in Glasgow in 1900 but it was rapidly contained and the last recorded case in the UK was in Suffolk in 1918.
Viruses are fairly specific to the species that they attack, but sometimes, especially if people live in very close proximity to animals, they can jump species. The Black Death was probably caused by the plague bacterium Yersinia pestis rather than a virus, but it also hopped species. There were three major epidemics of the disease, the first in 541. The biggest epidemic, in the 14th century, is estimated to have killed 75 million people at a time that there were only 360 million people in the known world. There is a interesting review called 111 (sometimes) deadly diseases that hopped across species. Black rats and their fleas are traditionally held to be responsible but more recent research has suggested that human body lice and fleas were the real vector. Diseases passed from animals to humans are called zoonoses. There are more than three dozen that we can catch directly through touch and more than four dozen that result from bites.
The disease that killed the most people in the shortest time was Spanish Flu which struck in 1918 and 1919, killing an estimated 50 million people worldwide; more than were killed in the First World War. Troops returning home at the end of the war helped to spread it fast.
We expect to find that when infectious diseases strike, that the elderly and perhaps the very young with an immature immune system will be the most vulnerable. However, for Spanish Flu, it was young fit adults who had the highest death rate. Their rampant immune system was thought to have produced the inflammation that caused death and so made them more susceptible. One person who died in the epidemic was my maternal grandmother. My father was just 6 years old at the time, so she would have been a young woman. There is also the possibility that older people had acquired some immunity from similar viruses in previous epidemics.
Four terms you may come across to describe infectious disease are:
- Sporadic: When a disease occurs infrequently and irregularly.
- Endemic: When a disease is constantly or usually present in a geographical area.
- Epidemic: When a sudden increase in the number of cases of a disease occurs and this is more than would normally be expected for the population in that area.
- Pandemic: An epidemic that has spread over several countries or continents, affecting a very large number of people.
Many of the outbreaks since the Spanish Flu, have originated in China. There was a major epidemic of Asian Flu in 1957-1958. Severe acute respiratory syndrome (SARS) occurred in 2002-2004. Middle East Respiratory Syndrome (MERS) started in 2012 and was an exception in that it originated in Saudi Arabia rather than the Far East. The problem is thought to be people living in proximity to animals. Ebola and AIDS also started in Africa. AIDS has probably been the most deadly with 32 million deaths.
Both SARS and MERS are due to a coronavirus, so called because its shape resembles a crown. The Coronavirus pandemic that started in 2019 is caused by a virus designated SARS-COV-2 or COVID-19. It is an RNA virus, so it has RNA rather has DNA inside its protein shell.
The COVID-19 virus is a new or novel virus. In the beginning, the world had no idea what to expect. How infectious is it? How it is transmitted? What is the best way to reduce transmission? What is the mortality rate? Who is most susceptible? What treatments will it respond to? Can we get a vaccine? As it was totally novel, I am reluctant to criticise scientists or politicians who had no experience and no evidence to draw on. Hence it is unsurprising that epidemiologists often disagreed. There was the need to prevent too many deaths and to prevent the NHS from being overwhelmed. However, there is the need to protect the economy and this is important for health as as well as wellbeing as will be discussed later.
There are many types of Coronaviruses. Hundreds circulate in mammals including pigs, camels, bats and cats. COVID-19 is the 7th coronavirus believed to have jumped from another animal to a human. There is overwhelming evidence that it originated in bats, but how it transmitted to humans is unknown. There are strong similarities with another corona-like virus found in pangolins. I must admit that I had never heard of them, and neither had my spell-check. The virus may have jumped from a bat to another animal such as a pangolin, where it picked up some extra proteins, before finally jumping to a human. Trafficking in wild animals is common in China. They like to eat exotic animals, especially in south-east China. Furthermore, Chinese Traditional Medicine frequently uses parts from animals, often with cruelty and it is quite common to find endangered species being used. There is much more on Chinese Traditional Medicine in the section of Other Modalities of Complementary and Alternative Medicine.
According to National Geographic, “The pangolin is believed to be the world’s most trafficked non-human mammal. Tens of thousands of pangolins are poached every year, killed for their scales for use in Traditional Chinese Medicine and for their meat which is a delicacy among some ultra-wealthy in China and Vietnam.”2Pangolins
Clinical Features and Infectivity of COVID-19
An early study from Imperial College, London found the COVID-19 infection fatality ratio is about 1.15% of infected people in high-income nations and, surprisingly, 0.23% in low-income nations.3Infection fatality ratio is about 1% The mortality rate is spread very unevenly, being much more lethal as age increases. I wonder if the older age profile of people in high-income countries accounts for the surprising disparity. They found that risk of death doubles for every eight years of aging and ranges from 0.1% for people under 40 to 5% among people over 80 years old. They estimated that around 1 in 260 people aged 50 to 55 years die if infected. Obesity is also be important and may account for some of the vulnerability of developed nations. There are other important risk factors which will also be discussed in the chapter Who is at Risk from COVID-19?
This new disease is much more infectious than the previous SARS. In the old SARS, the virus was mostly deep in the lungs and so it could be spread by coughing. The time of maximum infectivity was about 10 days after infection. For COVID-19, the virus is present in great numbers in the nose and throat from an early stage. Not only coughing and sneezing but even talking can spread it, starting at the beginning of infection, perhaps before symptoms have yet developed.
The incubation period, meaning the time between exposure and showing symptoms, is between 2 and 14 days with an average of about 5 days. Transmission may be airborne via droplets or on surfaces. Coughing or sneezing can spread droplets from 2 metres away although droplet spread from 6 metres is described. A study showed that the virus can survive in droplets for up to 3 hours after a person coughs.4Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1 However, the tests in this study used aerosol machines under laboratory settings rather than human breath. The aerosol from a cough may not stay in the air for as long.
The study also found that the virus survives for longer on surfaces. It can last for up to 24 hours on cardboard and for 72 hours on plastic and stainless steel surfaces. COVID-19 can spread when a person touches the eyes, nose, or mouth after touching a surface or object that the coronavirus has contaminated. A paper from Australia in October 2020, called 5The effect of temperature on persistence of SARS-CoV-2 on common surfaces. suggested that we may have underestimated the lifespan on the virus on some common surfaces. The virus lasts rather longer at 20oC than at 40oC. The coronavirus can remain on some surfaces for 28 days, including phone screens, banknotes and stainless steel. During that time, the concentration of the virus diminishes. After initial uncertainty, it is now thought that the most important source of spread of the disease is droplets, but we should be more careful about our phones, touch-screens and possibly even bank notes too.
People with no symptoms can pass the virus on to others. The estimated number of asymptomatic carriers varies from about 30% to 70%. The true number may be nearer 70%. However, more recent studies have suggested that up to 80% of asymptomatic people (those without symptoms) will develop them later. Hence a better term may be pre-symptomatic.
Reducing droplet spread is the rationale for social distancing, keeping people from different households at least 2 metres apart. Hand washing is important. Antiseptic gels are useful and kill viruses but good old-fashioned soap and water has much to commend it. Physical cleanness is very effective and soap has an antiseptic effect. Infected people spread the virus for several weeks. Simple measures of personal hygiene are important.
The coronavirus is 120 nanometres (nm) in diameter.6Coronavirus A nanometre is 10-9 metre. Hence the virus is 0.12µm or 1.2 of a 1/10,000 of a millimetre, but viruses do not spread alone. They are usually in droplets in the air and these droplets are much larger than the diameter of a virus.
To measure the size of droplets emitted through speech, a group used an intense sheet of laser to visualise bursts of speech droplets produced when subjects said the words “stay healthy.” The method is particularly sensitive in detecting speech droplets with diameters of less than 30 μm, which could remain airborne for longer than the larger droplets that have typically been the subject of research. They estimated that one minute of loud speaking generates at least 1,000 droplets capable of carrying virions which are units of the virus that can cause infection. The droplets remained airborne for 8 to 14 minutes, which is long enough for someone to inhale them and become infected. They say droplet nuclei averaged 12 to 21 μm in diameter when first emitted and 4 μm after drying in the air, and that a 10μm droplet has a 0.37% probability of containing at least one virion.7The airborne lifetime of small speech droplets and their potential importance in SARS-CoV-2 transmission This figure of 0.37% is small but the highly sensitive laser light scattering observations revealed that loud speech can emit thousands of oral fluid droplets per second. It seems very likely that normal speaking causes airborne virus transmission in confined environments. Droplets scatter much quicker outdoors.
A paper published in February 2019,8Aerosol emission and superemission during human speech increase with voice loudness, which was before the coronavirus outbreak, showed that the louder people spoke, the more droplets they emitted. This was true in English, Spanish, Mandarin, and Arabic. A small number of people were “speech superemitters,” consistently releasing many more droplets than others. They also cited a paper from back in 1967 which investigated the role of singing in the spread of tuberculosis and showed that the percentage of airborne droplet nuclei generated by singing is 6 times more than that emitted during normal talking and approximately equivalent to that released by coughing.9Droplet expulsion from the respiratory tract The methodology of the paper from 1967 is rather old but it is a cause for concern.
An opera singer, in full voice, does not make a candle flicker just 15 cm away from his mouth. This would suggest a low risk of spreading droplets. However, this may not apply to untrained singers and as churches re-opened, singing was banned. The problem with choirs is not so much the singing as the social interactions and handling music and chairs. On 28th June 2020, an article in The Sunday Times said that Public Health England were about to launch a trial in Salisbury Cathedral to see how singing spreads droplets. Sir Simon Rattle, the famous conductor, says that as with the opera singer, a candle 15 cm from the bell of a trombone does not flicker. It has been suggested that the flute is a problem because of the way the mouthpiece is blown and it expels the air sideways to the musician on the right.
Singing is important to many people and this work would impinge on choirs, religious services, musical performances and much more, not just in the UK but throughout the world. I am astounded that the only research I could find dates back to 1967 and methodology has improved much since then.
In August 2020, the preliminary results from the trial were reported.10Comparing the Respirable Aerosol Concentrations and Particle Size Distributions Generated by Singing, Speaking and Breathing (preliminary report) There were 25 professional performers breathing, speaking, coughing, and then singing and speaking ‘Happy Birthday’ at 50-60, 70-80, and 90-100 dB. The last is incredibly loud. Although aerosol mass increased by a factor of 20 to 30 times as speaking and singing became louder, singing did not produce significantly more aerosol than speaking at a similar volume. No differences were found between different musical styles, including choral, musicals, opera, gospel, rock, and pop. It was recommended that performances may restart but areas should be well ventilated.
A paper from Australia, using similar methodology, was published in August 2020.11Droplets and Aerosols Generated by Singing and the Risk of Coronavirus Disease 2019 for Choirs Its results were similar.
The main features of the disease are a high temperature and a persistent cough. Another important feature is loss of taste and smell which affects about half of all sufferers.12About Half of COVID-19 Patients Have Altered Sense of Taste Lack of smell, called anosmia, was added to the official symptom list on 18th May 2020. People with the disease usually have at least two of the following:
- repeated shaking with chills
- muscle pain
- a headache
- sore throat
- new loss of taste or smell
In addition, the World Health Organization (WHO) states that less common symptoms include diarrhoea, a skin rash, and discoloration of the fingers or toes. Something rather like chilblains has been described.
In most cases, diagnosis can be based on clinical findings but, to be sure, laboratory tests are required. Testing and tracing will be discussed later.
Most people will recover from the disease without serious illness, but a small number get much more severe symptoms which can require admission to hospital, treatment with oxygen, even ventilation and they can result in death. The problem seems to be an excessive response from the immune system. The immune system kills invading organisms but it can produce inflammation that causes more harm than good.
A group of chemicals that are involved are called cytokines. An excessive reaction called a 13cytokine storm is the problem. It most obviously affects the lungs but it can affect many other organs too. There may be multiple organ failure. The inflammation makes the blood capillaries more permeable and fluid leaks out. Fluid in the lungs impairs the exchange of oxygen and carbon dioxide and causes extreme respiratory distress. I do not intend to delve deeply into the problems of the inflammatory process but this does emphasise that the immune system has to be finely balanced between failing to deal with threats and causing more trouble than it solves.
The cytokine storm can affect far more than just the lungs. The heart, kidneys, liver, brain and other organs may be affected. With breathing problems, multiple organ failure and possibly the need for ventilation, patients are often in intensive care for 3 or 4 weeks but many are there for several weeks.
There is an interesting organisation called UK Coronovirus Immunology Consortium that has examined five aspects of the disease. Its website at https://www.uk-cic.org/research It discusses:
- Primary immunity: Why are some people’s immune systems better able to fight off the virus?
- Protective immunity: What parts of the immune system are involved in generating a protective response against COVID-19 and how long does this immunity last?
- Immunopathology: How does the immune system respond to COVID-19 on a molecular and cellular level and what happens when the immune system overreacts?
- Cross-reactive coronavirus immunity: Does immunity to previous infection with seasonal coronaviruses (which cause the common cold) alter a person’s outcome with COVID-19?
- Immune evasion: How does COVID-19 “hide from” the immune system and how can this be tackled?
As we shall see rather later, the antibody response after infection can be very short-lived, especially if the infection was mild. However, it is not so much antibodies as the T-cells or thymus dependent lymphocytes that are important in viral infections. They may be activated for six months and we may hope for a longer response after vaccination but the latter is too early to be sure.
The value of face masks for the general population was dubious at first but the World Health Organisation (WHO) has become more convinced as time has passed. For those in high-risk clinical areas, the benefit is clear. For years, face masks have been worn in public by many people in the Far East. I have heard that they are more to keep the sun off their faces than to protect against airborne infection or pollution. If a person coughs or sneezes while wearing a mask, it will reduce the distance of spread. In the clinical situation, visors are often worn too as they give full cover to the face and the virus can even be absorbed through the eyes.
Some work from the Mater Hospital in Ireland, that was unpublished at the time of writing, suggested that if an uninfected person wears a mask and one who is infected does not, the risk of transmission is 70%. If it is the other way round, and the infected person wears a mask but the uninfected person does not, the risk of infection falls to 5%. If they both wear a mask, it is down to 1.5%. Hence it seems that wearing a mask is more important to protect others than to protect oneself.
Once put on, masks should be left alone. If they get damp, they should be changed. A howling error that is common in medical dramas, is when surgeons are scrubbed up, wearing gowns and gloves and then they touch their masks. The gowns and gloves are sterile. The masks are not and by touching them, they have just contaminated themselves. This applies to sterile areas such as operating theatres, not the social wearing of masks for COVID-19 protection.
The WHO became more impressed by masks and advice about wearing them is now well established. This applies to public transport and shops where social distancing is more difficult.
The best type of face masks, and the ones that are used in clinical conditions of high risk, are designated N95. It is a particulate-filtering facepiece respirator that filters at least 95% of airborne particles. They should not be used for more than two days, but discarded after that time as they deteriorate. They may become less close fitting and the filtration may be impaired. They are also said to have a shelf life of 5 years, which may seem surprising as there seems little to deteriorate in storage but the elastic ear straps can become brittle and they may snap and put the wearer at risk at an unfortunate time. The filter is made from interlaced layers of polypropylene fibres. Small particles have to wind through a rather tortuous path.
Droplet spread is probably rather more important than touch. The virus has also been detected in semen but spread by sexual contact is unlikely to happen without the risk of spread by touch and droplets too. Very small droplets stay in the air longer than larger droplets. This may indicate the value of good ventilation in buildings and the relative safety of being outdoors where droplets disperse fast. However, air conditioning may recycle the virus. It has been suggested that air-conditioning should be turned off in hospitals where there are COVID-19 patients.
With so much attention to the acute disease in the early stages of the pandemic, the chronic form was neglected. The terms acute and chronic have nothing to do with severity and lay people often misuse them. Acute means of brief duration, usually less than six weeks. Chronic, from the Greek word kronos meaning time, means of long duration, usually more than 3 months. Between six weeks and three months may be called sub-acute. Long COVID is defined as the perseverance of symptoms for at least 12 weeks following infection with COVID-19.
In the middle of October 2020, the National Institute for Health Research published a report called 14Living with Covid19. An excellent summary of its findings is freely available on the BBC website.15Coronavirus: ‘Long Covid could be four different syndromes’
This report was produced fairly swiftly and with limited data, but it is an important landmark in identifying this highly significant aspect of the disease. No doubt, a more studied report, using far more research data will be produced in the future when this disease is better understood. Much of the report was based on interviews with 14 of the members of the support group on Facebook. This resource has been invaluable to some.
The National Institute for Health and Care Excellence (NICE), the Scottish Intercollegiate Guidelines Network (SIGN) and the Royal College of GPs (RCGP) have defined post-COVID syndrome as: “Signs and symptoms that develop during or following an infection consistent with COVID-19, continue for more than 12 weeks and are not explained by an alternative diagnosis. It usually presents with clusters of symptoms, often overlapping, which can fluctuate and change over time and can affect any system in the body.” Some estimates suggest that 10% of COVID patients may still be experiencing symptoms more than three weeks after infection, and perhaps 60,000 people could be suffering from long COVID symptoms after more than three months.” It also says, “It is now clear that long COVID can have a major impact on the lives of a significant minority of patients weeks or months after they have contracted the virus.
One of the findings of the report, which surprised even the authors, is that there seems to be no correlation between the severity of the disease and the risk of developing long COVID. The disease also shows much more equality in terms of the age and even young adults may be affected. It is also more likely to affect certain groups, such as black or Asian people as well as those with existing mental illness or learning difficulties.
Symptoms may fall into four groups:
- permanent organ damage to the lungs and heart
- post-intensive-care syndrome
- post-viral fatigue syndrome
- continuing Covid-19 symptoms
We have seen that the virus affects not only the lungs, but there may be inflammation in many organs of the body, including the heart and brain and in long COVID, this continues long after the body has eliminated the virus. Continued inflammation of the heart leads to runs of fast heart rate (tachycardia), palpitations and shortness of breath on exertion. There may be chest pain. Continued inflammation of the brain can cause fatigue, “brain fog” and other psychiatric problems. Psychiatric problems affect about 25%. Muscle wasting is common but much of this may be due to disuse, especially if the person was seriously ill for a long period.
When people need ventilation, this requires intensive care in the real sense of the term. They have to be sedated to prevent them from fighting the machine and trying to breathe against it. They may be in an induced coma for this for several weeks. They will need intravenous feeding to maintain energy and nutrition whilst the fight against the disease goes on. They may need other support if organs fail, including the kidneys and liver. At the end, they do not wake up and walk out of hospital. They will be very weak after weeks of this. Muscles will be wasted with strength and coordination impaired. Standing up will drop blood pressure until a normal response develops again. Intense rehabilitation is required to get the patient fit to leave hospital.
A study from King’s College, London that has not been published at the time of writing, found that long COVID can affect anyone but some features increase the risk.16Long Covid: Who is more likely to get it? A person with cough, fatigue, headache, diarrhoea, and loss of smell is at greater risk than a person with cough alone. Increasing age, especially being over 50, also increases the risk. However, in contrast to the risk of severe and even fatal disease, women are at greater risk than men. No previous medical conditions were linked to long COVID except asthma and lung disease.
The study found that:
- One in seven people is ill for at least four weeks
- One in 20 people is ill for at least eight weeks
- One in 45 people is ill for at least 12 weeks
As time has gone by and there is more experience, some other figures emerge. The risk of serious acute disease is low in the young but there is much less of an age gradient in terms of who gets long COVID. About 1 in 10 will develop long COVID and 40% of them will still have symptoms a year later.
I do not wish to go into the management of long COVID as it depends upon the type and knowledge of this new disease is changing fast. However, one matter that is rarely mentioned is the effect of the COVID-19 vaccine on the disease. Initially people were wary as it may increase the inflammation and make matters worse. However, it seems that it often, but not always, improves the condition. 17Some With Long COVID See Relief After VaccinationBased on polls on social media, it seems that 3% to 5% of people do deteriorate after the vaccine. Why is unclear. However, between 30% and 50% of patients find that symptoms improve after they receive the mRNA vaccines. I think there is inadequate data with the adenovirus vaccines. People say that their brain fog improves, their fatigue is gone, the fevers that persisted resolve have now gone. The observation has launched several studies. There are several theories about how the vaccines might be affecting long COVID.
Nowadays there are far too many people complaining about their mental health when they do not have mental illness but a normal reaction to the stresses of life. If a person is on short time at work, fears for his job in a poor job market and fears for his ability to pay the bills if he loses his job and he is anxious, that is not a mental health issue. It is a normal reaction to circumstances. If a person is bereaved or a relationship has ended and that person is sad, that is a normal feeling. Calling normal responses mental health issues trivialises real mental health problems which can lead to the tragedy of suicide. Many people will need help with the problems of long COVID and to have so many others claiming to have mental health issues, detracts from their real problems.
The difficulties faced by people who have been immobilised in a hospital bed for many weeks are obvious and have been mentioned. Post viral fatigue is well recognised from other illnesses including glandular fever and flu. The chapter Chronic Fatigue Syndrome (CFS) or Myalgic Encephalitis (ME) discusses this recognised illness.
At this stage, it is difficult to be sure of the scale of the problem. It is too soon even to say how long the condition will last. As many as 60,000 may be affected with more to come and they will be a burden to the NHS for some time yet. With so many people suffering from long COVID, the demands on the NHS are considerable. At the time of writing, there are 60 clinics dedicated to patients with long COVID in the UK. Patients will have to be referred by a GP or another health professional and doctors will be expected to rule out other underlying illnesses, such as lung cancer, before making referrals.
The aetiology of the disease is uncertain. There may be persistence of the virus. There is thought to be damage to mitochondria, which are the power source of cells. There may be an autoimmune element with the body attacking its own tissues. There may be permanent organ damage. There may be a mixture of all three.
Selfish people, mostly young people, who have flouted the rules of the pandemic, may think that they are invulnerable but they are wrong. If they are not killing themselves and their friends, they may be killing their grandparents. They and their friends may develop long COVID. As we shall see later, the pandemic has had a disastrous effect on the economy, and the young suffer most.
Drugs and Treatments for COVID-19
As with any virus infection, when the patients feels unwell with a high temperature and aches and pains, good old-fashioned paracetamol is the first line. Many people like to take non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or diclofenac. Aspirin also falls into that class. There was a warning from France that this class of drugs can aggravate the condition and make the illness worse. However, other counties in Europe and elsewhere were not of the same opinion and the European Medicines Agency declared that there is no evidence that NSAIDs can worsen the disease.18Are Warnings Against NSAIDs in COVID-19 Warranted?
A paper found that in patients with heart failure, plasma concentrations of ACE2 were higher in men than in women, but neither an ACE inhibitor nor an ARB was associated with higher plasma ACE2 concentrations. This might help to explain the higher incidence and fatality rate of COVID-19 in men, but it does not support previous reports suggesting that ACE inhibitors or ARBs increase the vulnerability for COVID-19 through increased plasma ACE2 concentrations.19Circulating plasma concentrations of angiotensin-converting enzyme 2 in men and women with heart failure and effects of renin–angiotensin–aldosterone inhibitors
Researchers in London examined records of people on these drugs who had influenza between 1998 and 2016. They found that the use of ACE inhibitors and ARBs was associated with either no effect on the incidence of influenza or a lower incidence. These associations regarding observed susceptibility to influenza may reflect mechanisms that are shared with coronaviruses, including COVID-19.20Association between Angiotensin Blockade and Incidence of Influenza in the United Kingdom Expert opinion is that these drugs do not have an adverse or protective effect in COVID-19 infection and they should not be stopped.
A meta-analysis of four published studies has shown that treatment with statins was associated with a reduced risk of a severe or fatal course of COVID-19 by 30%.21Meta-analysis of Effectiveness of Statins in Patients with Severe COVID-19. Statins are very commonly used to reduce blood cholesterol and to reduce the risk of coronary heart disease. However, their effect seems to be in excess of the effect n cholesterol and they are thought to stabilise the formation of thrombi which lead to occlusion of the coronary arteries. Hence, an anti-inflammatory effect may be behind their apparent benefit.
One group of drugs that may increase the risks in this infection is the proton pump inhibitors.22Increased Risk of COVID-19 Among Users of Proton Pump Inhibitors. They are potent drugs to suppress stomach acid and include lansoprazole, omeprazole and others with a similar -azole ending. Why they should have this effect seems unclear. The H2 antagonist group of drugs which are less potent acid suppressors, do not seem to have the same problem.
Antibiotics are of no use against viruses but there are some anti-viral drugs and they are worth considering for treatment. A double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults in hospital with Covid-19 with evidence of lower respiratory tract involvement showed that remdesivir was superior to placebo in shortening the time to recovery.23Remdesivir for the Treatment of Covid-19 — Preliminary Report The authors claim that this is the first positive report for a drug to treat the disease. Remdesivir was originally developed as an Ebola treatment and is described as a broad-spectrum antiviral drug. However, the British researchers warned in June 2020 that their study, the RECOVERY trial, suggested few benefits. In October 2020, an Oxford-based study, involving more than 5,000 patients found the drug made no significant different to survival rates.
In the USA, in April 2020, the FDA gave emergency approval, saying: “While there is limited information known about the safety and effectiveness of using remdesivir to treat people in the hospital with COVID-19, the investigational drug was shown in a clinical trial to shorten the time to recovery in some patients.” However, a WHO-sponsored study said that remdesivir did not work. They said, “The unpromising overall findings from the regimens tested suffice to refute early hopes, based on smaller or non-randomized studies, that any will substantially reduce inpatient mortality, initiation of ventilation or hospitalisation duration.”24Repurposed antiviral drugs for COVID-19 –interim WHO SOLIDARITY trial results
Remdesivir is produced by an American company and the USA has bought most of the world’s supply.
A combination of interferon, a well-established anti-viral agent, with lopinavir and ritonavir seems to shorten the duration of illness.25Triple combination of interferon beta-1b, lopinavir–ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial Lopiavar and ritonavir are a combination that is used in treating HIV/AIDS. However, later results suggested that the antiretroviral drugs did not benefit patients with COVID-19.At the time of the research 23% of patients receiving the drug died as did 22% of those in a control group.26Lopinavir–ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
A combination that has been promoted by Donald Trump, without any evidence, is hydroxychloroquine with azithromycin. Azithromycin is an antibiotic and so we would not expect an anti-viral effect. Hydroxychloroquine is an anti-malarial drug but it is also of value in rheumatoid arthritis and other auto-immune diseases where is damps down the destructive inflammatory process. The combination has now been tested. The conclusion was that there was no benefit. Survival in hospital was reduced and ventricular arrhythmias (abnormal heart rhythms) were seen.27Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis In other words, not only is it ineffective but it increases risk and reduces survival. It is worse than useless. However, this trial has since been retracted. Nevertheless, other trials have found that it is useless.
A randomised, double-blind, placebo controlled trial using the drug for prophylaxis (prevention) recruited 821 subjects who had no symptoms at the time. The drug made no significant difference in preventing illness but side effects were more common with hydroxychloroquine than with placebo but they were not serious.28 A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19.
Hydroxychloroquine is not an innocent drug. It can have an adverse effect on the heart causing delays in the conducting system that coordinates the heart beat. Chloroquine and hydroxychloroquine may be associated with serious psychiatric side effects, even in patients with no family or personal history of psychiatric disorders.29Psychiatric side effects of chloroquine
The Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial, is led by the University of Oxford. It is the world’s largest randomised clinical trial of potential COVID-19 treatments. The drugs being assessed are:
- Lopinavir-ritonavir (commonly used to treat HIV/AIDS)
- Low-dose dexamethasone, a potent steroid to dampen the risk of a cytokine storm
- Hydroxychloroquine already mentioned. Originally for malaria but also for auto-immune diseases
- Azithromycin, an antibiotic
Over April and May 2020, it has recruited more than 10,000 in-patients in 176 hospitals with suspected or confirmed COVID-19. In mid-June 2020, the first results came through. The drug that did best was dexamethasone. It is not new or expensive but costs about £5 for a course. A total of 2,104 patients were randomised to receive dexamethasone 6mg once per day by mouth or by intravenous injection for 10 days and were compared with 4,321 patients randomised to usual care alone. Of those who required ventilation, dexamethasone reduced deaths by one-third and in other patients receiving oxygen it reduced it by by one fifth. There was no benefit among those patients who did not require respiratory support. This treatment will save the life of 1 in 8 needing ventilation and 1 in 25 needing oxygen without mechanical ventilation. This is called the NNT or number needed to treat. Numbers needed to treat (NNT) and numbers needed to harm (NNH) are discussed on Basic Maths in Medical Research and Decision Making. Needing to treat 8 or even 25 patients to get one important result may seem a high number, but compared with many treatments, it is rather good. If it is necessary to treat 25 patients to save one life at a cost of £5 per course, this comes to £125 per life saved. For those on ventilators, with a NNT of 8, this is £40 per life saved. These are a remarkably low figures.
The trial continues. A hydroxychloroquine arm of the study was halted because of lack of efficacy. RECOVERY is also examining the anti-viral combination lopinavir-ritonavir, the antibiotic azithromycin, convalescent plasma and the anti-inflammatory tocilizumab.
Vitamin D is also worthy of mention. Deficiency can lead to inadequacy in the immune system. Much of it is synthesised in the skin in a reaction with sunlight. Especially in winter, it is possible that there may be deficiency. The Royal College of Physicians, British Dietetic Association and Society for Endocrinology have concluded that there is no evidence for recommending high doses of vitamin D for the general population. This does not exclude the possible value of lower dose vitamin D where there may be some deficiency. At the end of June 2020, a NICE rapid evidence review was unable to support vitamin D supplements to reduce the risk or severity of COVID-19.30COVID-19 rapid evidence summary: vitamin D for COVID-19 BAME groups are already advised to take 10 micrograms of vitamin D daily throughout the year for musculoskeletal health because sunlight alone is insufficient in the UK’s climate. No clinical trial evidence was available but five observational studies on vitamin D and COVID-19 published on or before 18th June 2020 were included. NICE said that there was high risk of bias due to the low quality of evidence. However, a systematic review and controlled trials on vitamin D and COVID-19 are underway and new evidence will be considered as it becomes available.
When discussing COVID-19 in men, I mentioned the possibility of androgen blockade as a possible treatment. I have found articles that discuss its potential but I have found no results of trials in this field. I have found a registered trial in the USA that uses an oestrogen patch to achieve this effect.
There are also some trials of modulators of the immune system to dampen down the cytokine storm.
There is much more about Randomised Controlled Trials in the chapter. Click on the blue if you wish to go there.
Another drug that has been touted as an effective treatment for COVID-19 is ivermectin. It is used to treat parasite infestations in humans, including head lice, scabies, strongyloidiasis, ascariasis, lymphatic filariasis and several others. It is also used in veterinary medicine. However, reviews of the evidence have not been complementary. An article from the BBC shows that critical analysis of the papers show that many results are negative and of the positive results there is a mixture of bad science and overt fraud. The more spectacular the results, the more serious were the flaws involved.31Ivermectin: How false science created a Covid miracle drug Problems include evidence that selection of patients for allocation to groups was not random. For example, in one study, those in the control group had rather lower blood oxygen levels than the test group and so they had a worse prognosis. Statisticians found that some of the numbers given were unlikely to occur naturally and so were selected. There were several papers where the same patient data was used for supposedly different people. Sometimes there were basic errors in calculating percentages.
These are very serious problems with the research. The drug has not been approved for COVID-19 in the UK, the USA or the EU. Interestingly, it is championed by opponents of vaccines.
A Vaccine for COVID-19
By the middle of August 2020, it was estimated that about 6% of the population of the UK had been infected with the virus. That is well below the number needed to achieve herd immunity. Even in Sweden, that had decided against a lock-down policy to permit herd immunity, the figure was only 15%. The only reasonable way to get herd immunity and to get life back to normal, is a mass vaccination programme.
Creating a vaccine is a major step. It has to provide a high level of immunity and there has to be a high level of uptake. This also requires a low level of adverse effects. Vaccines are discussed much more in the chapter Fake News and Vaccine Scares.
Normally, it takes about 10 years to develop a vaccine. There has been unprecedented cooperation between pharmaceutical companies and countries. Furthermore, the technology, which had not been available even 5 years previously, made it possible to produce vaccines in 9 months. Previously the fastest time from start to approval for a vaccine was 5 years. Vaccines were produced ready for distribution before the results of testing were in but not distributed before approval. The risk is financial rather than the risk of unidentified problems.
Experts say that even if acquiring the disease may induce comparatively limited immunity, a vaccine can induce a stronger and longer lasting immunity than the real disease.
Influenza vaccine has to change each year to try to catch the current strain. There is also considerable variation between individuals as to how much immunity they develop after infection.32Coronavirus is evolving. Knowing how could help us stop the pandemic It seems that we may require annual boosters that cover the new variants of concern that may be less susceptible to the original vaccines.
Several different types of vaccine have been developed simultaneously. The world cannot wait. Some are based on the protein coat of the vaccine and contain no RNA, so it is impossible to mutate and infect instead. This virus has RNA rather than DNA surrounded by a protein coat. One is based on messenger RNA (m-RNA) to prime the immune system to produce antibodies and a cell-mediated response.
Another approach which is taken by the Oxford group is called an adenovirus vaccine. Traditionally, a vaccine works by giving the body an inactivated coat of the virus so that the immune system learns to recognise and reject the real thing, producing antibodies that lock on to the surface of the virus. Adenovirus vaccines are more sophisticated. Adenoviruses can easily be tweaked so that they can still infect cells, but they do not replicate themselves inside. The vaccine containing the adenovirus infects the cells but instead of copying itself, it makes the cells copy the coronavirus spike. In this way the body learns to identify the spike without the dangerous coronavirus attached.
In both the Russian and the Oxford vaccine, the adenoviruses used have been shown in other vaccines to be safe. The Russians started with an adenovirus that infects humans. In contrast the Oxford team started with an adenovirus that infects chimpanzees. A virus that humans are not generally exposed to is less likely to stimulate our immune systems. We do not want our immune systems to attack the vaccine that produces the immunity.
An amazing aspect of the new technology for both m-RNA and adenovirus vaccines is that it does not require the virus that is the target to produce the vaccine. In the past, vaccine contained dead, inactivated or attenuated micro-organisms. Now, what is required is the genome sequence of the virus.
Enormous efforts have been made to create vaccines. Safety has not being compromised. An article in the Sunday Times was called 33For a coronavirus vaccine to work, first inoculate against lies. When we have so much trouble getting well-established childhood vaccines widely accepted, can we get adequate uptake of a new and rapidly developed vaccine?
There was also an amazing article on the BBC website called 34Coronavirus: False and misleading claims about vaccines debunked Quite astounding stories are told that some people believe, and not just the usual conspiracy theorists.
The article looked at the anti-vax movement and the lies it tells and noted that a YouGov poll in the USA found that only 55% of adults said they would take a coronavirus vaccine if one became available, 26% said they were not sure and 19% that they would refuse a vaccine. An earlier survey in the UK found that 15% of adults were unsure whether they would accept a vaccine, with 4% saying they would refuse.
One of the fake claims that struck me was the suggestion that the vaccine may cause infertility. This is the same as the false claim made about polio vaccine by the Taliban. At the time, it was far to early to asses is it may cause infertility. Most of those who had been vaccinated were over 60 and of the vaccinated over 60s, not a single one got pregnant. Back in August 2021, the MHRA did review the evidence and concluded that the vaccine does not cause infertility, nor does it cause menstrual irregularities. It is also safe in pregnancy.
This picture from the Sunday Times article shows a protest against lock-down in London
An article in the BMJ was called 35Even covid-19 can’t kill the anti-vaccination movement. However, it found that opposition to a vaccine was declining. It did not help when Donald Trump said that vaccines are being developed “at warp speed”. It makes rational people wary about safety.
Research by King’s College London and Ipsos Mori in August 2020 found that one in six respondents to a survey said they would definitely not or would be unlikely to have a vaccine. A poll published in the USA found that only 70% were willing to be vaccinated and about half wanted to wait until they were sure the vaccine was safe. Both these figures provide too poor coverage for herd immunity. There is more about attempts to undermine the uptake of vaccine in the section Myths and Fake News About COVID-19
An ethical dilemma is whether or not to test the vaccine by giving a challenge dose of the disease to normal, healthy people who have received the vaccine to assess its effectiveness. This is a disease with a 2% mortality rate and effectiveness in young healthy people does not assure effectiveness for all ages. Edward Jenner was the pioneer of vaccination. After giving his gardener’s son cowpox to produce immunity, Edward Jenner gave the boy smallpox to prove that he was immune. Fortunately, it worked but ethics were rather different in those days. There will be tests of challenging people who have been vaccinated with the disease to see how they respond, but it may be an attenuated or weakened strain that is used.
On 11th August 2020, Russia announced that it has approved the world’s first coronavirus vaccine for use. President Putin said that it had “passed all the checks” and been administered to one of his daughters.36Russia claims victory as it approves ‘Sputnik’ Covid vaccine. He had not tried it himself. There were six other vaccines in phase 3 trials at the time, which means that they were really ahead of the Russians who had not even done phase 3 trials. The name of the vaccine, Sputink-5, shows that it is seen as part of Russian kudos. It was greeted with widespread condemnation as it had not had the phase 3 trial in which thousands of people participate. Mass vaccination with an improperly tested vaccine is unethical. Any problem with the Russian vaccination campaign would set back the acceptance of vaccines in the population.
The BMJ suggested that there had not even been phase 2 trials and this had been released on the basis of an unpublished phase 1 trial of 38 subjects. The Times says the Sputnik vaccine was approved after being tested on 76 people, in a study that has been criticised for statistical irregularities. I suspect that the difference between “38 subjects” and “76 people” is that the trial contained 76 people of whom 38 were given the vaccine and 38 received placebo. Not only do the team behind it not know if it is safe, they do not even know if it works.
The order of priority for the vaccine is those in residential care and their carers, healthcare workers, the over 75s, then the over 70s and those with chronic diseases.
Immunology, is a vast and complex subject. An important type of white blood cell is the lymphocyte. There are two main types called thymus dependent or T-cells and there are B-cells. At the most simple, B-cells produce antibodies but T-cells are the killer cells that attack invading cells or infected cells. When they have been primed, they spring into action in the event of another infection much faster than if they had not been activated. Researchers in Singapore compared patients who have recovered from COVID-19 with those recovered from SARS 17 years ago. They found that patients who had recovered from SARS retained virus specific memory T-cells and also enjoyed some protection against the new virus.37SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls Since as far back as 1970, I have felt that the role of T-cells rather than antibodies in viral infections needs more attention to determine immunity. Priming T-cells may be more important for a vaccine than inducing antibodies. There can be cooperation between T and B-cells and they can help a more rapid antibody response. Lack of circulating antibodies does not necessarily mean lack of immunity.
October 2020 saw phase 3 trials for several vaccines in a number of countries and they looked positive. They require two injections. The first priority was those who work in health care and residential care and then the elderly and vulnerable. Those under 50 will be regarded as low priority unless the have underlying risks. There is also the problem of inadequate coverage due to refusals for spurious reasons.
Those who are obese may respond poorly to the vaccine, with twice the risk of failure to achieve an immunological response. This is based on other studies that have shown that those who are obese respond poorly to vaccines.38The weight of obesity on the human immune response to vaccination. This applies to influenza vaccine, pneumococcus (a common cause of pneumonia) vaccine and hepatitis B vaccine. It also seems to apply to obese children when they receive their childhood vaccines. There may be a poor response to COVID-19 vaccines too. Amidst the many complications of obesity must be added increased susceptibility to a number of infections and a decreased response to vaccines.
In November 2020, Pfizer announced that their m-RNA vaccine had completed a successful phase 3 assessment and it would soon be ready to distribute. The success rate was said to be 90% and this was widely hailed as a great success. This means that 10% of those who have been vaccinated will not achieve immunity. It requires a second injection three weeks after the first. It must be stored at -70o but can be brought down to normal fridge temperature for 24 hours before use. This is a logistical problem as general practice, which is the basis for giving the vaccines, would not have facilities for storage at such a very low temperature. Domestic deep freezers operate at -18 to -21o.
With both the Pfizer and Moderna vaccines boasting effectiveness of 90 to 95%, it might come as a disappointment that the Oxford adenovirus vaccine was showing just 70% effectiveness. More than 20,000 volunteers were involved, half in the UK, half in Brazil. There were 30 cases of COVID-19 in people who had two doses of the vaccine and 101 cases in people who received a placebo or dummy injection. This is around 70% protection.39Covid-19: Oxford University vaccine shows 70% protection It may seem that the Pfizer vaccine is rather more effective than the AstraZeneca one but as the vaccines were assessed in different ways, it is unfair to reach that conclusion. Experts say that they both work. The latter received approval around Christmas 2020.
A very interesting finding is that when volunteers were given two full doses, the protection was 62%, but this rose to 90% when people were given a half dose followed by a full one. This came as a surprise and we may wonder why it was tested. It was a mistake. However, later analysis suggested that the better result with the lower dose was due to a longer interval between doses. This is part of the justification of prolonging the time between injections from 3 or 4 to 12 weeks.40Single-dose Oxford–AstraZeneca COVID-19 vaccine followed by a 12-week booster.
There were also lower levels of asymptomatic infection in the low followed by high dose group which is important for halting the spread of the virus. There was also lower rates of asymptomatic infection in all vaccinated groups. This would make it the first trial to provide an answer to the key question of whether the vaccine stops transmission as well as illness. No one who received the Oxford vaccine became seriously ill.
Headline numbers for vaccine efficacy can be misleading. Do not take these figures as referring to any particular vaccines. They are to make a point. Suppose that vaccine A reduces infections by 90% and vaccine B reduces infections by 70%. Which would you prefer? However, suppose that the 10% who get infected after vaccine A suffer the disease as severely as the unvaccinated but of the 30% who still get the disease after vaccine B, it is much milder, hospital admissions are rare and none has died. Which would you prefer now? They both do a very good job but I would go for vaccine B as the better overall.
As the trials of the vaccines had been based on 3 or 4 weeks between doses, it was at first surprising that the Government decided to change the routine from 4 weeks between doses to 12 weeks. The rationale was to get as many people as possible given the first dose as quickly as possible. If one dose confers around 90% immunity while two doses confers 97% immunity, this makes sense. Furthermore, a longer period between the first and second vaccine seems to improve immunity. Later research has shown that the longer gap between the two injections, does improve the effectiveness of the Oxford vaccine.41Single-dose Oxford–AstraZeneca COVID-19 vaccine followed by a 12-week booster. This is in keeping with experience with other vaccines.
The Oxford, vaccine has two important advantages over the m-RNA vaccines. It does not need refrigeration at -70o and can be kept at normal domestic refrigerator temperatures. This will be much more suitable for distribution through general practice. It is also much cheaper.
An article in the BMJ at the end of November 2020 summarised some important points about the three front runners.
- The Pfizer and BioNTech vaccine has a problem with logistics as it must be stored at -70oand it is estimated to cost around £15 per dose.
- The Moderna and US National Institutes of Health vaccine can be stored in a household fridge for 30 days, at room temperature for up to 12 hours, and at −20o for up to six months. It costs approximately £25 per dose.
- University of Oxford and AstraZeneca vaccine can be stored at fridge temperature of 2 to 8o and it costs around £3 per dose.
The Oxford vaccine is much cheaper and easier to distribute, even if efficacy may be slightly lower than the rivals and that is uncertain. Distribution is much easier in developing countries and the cost is much better for all countries. However, there have been some problems of complications related to the clotting system that seem to affect the adenovirus vaccines rather than the m-RNA vaccines and they will be discussed below. Therefore, the m-RNA vaccines should be used in preference for younger people who are also less susceptible to serious complications of the disease.
In late 2020, the Pfizer vaccine was the first to be given approval. This was followed, a little later by the AstraZeneca or Oxford vaccine and in January 2021, the Moderna vaccine was approved for the UK. This just left the enormous logistical problem of manufacture and delivery of the vaccines to the people.
In early 2021, two new variants of concern were found. One appears to have originated in Kent, the other in South Africa. A third has originated in Brazil. There has been some concern that the vaccines may be less effective against them. This may be true to some extent for the South African and Brazilian variants but probably not the Kent one. There is also a new Indian or delta variant that is much more infectious. The great causes for concern are the much greater infectivity and possibly a tendency to cause severe disease in younger people.
In March 2021, a number of EU countries halted use of the AstraZeneca vaccine because of fears of association with thrombosis. The European Medical Agency stated that there was no evidence of increased risk and no reason to stop the rollout. The UK and the producers agreed. The vaccine rollout in the EU is substantially slower than in the UK. Stopping it, even temporarily and feeding vaccine hesitancy have been a bad thing. It seems to have be led by politicians rather than scientists and it has been an “own goal”.
The situation is complex. A possible explanation for the rare clots reported among some people who received the vaccine is similar to heparin-induced thrombocytopenia (HIT), in which heparin triggers the immune system to produce antibodies that activate platelets. Other drugs can cause clotting disorders that strongly resemble HIT and the AstraZeneca vaccine may be another such trigger. Four previously healthy people who had the vaccine and developed life-threatening clots had the same kind of antibodies that activate platelets and initiate clotting in HIT. Twenty who received the vaccine but did not develop clots did not have these antibodies.
In April 2021, the MHRA had received 22 reports of cerebral venous sinus thrombosis (CVST) and eight reports of other thrombosis events with low platelets from 18.1 million doses of the AstraZeneca vaccine administered. This total in the UK 30 cases from 18.1 million doses of the vaccine, is a rate of about one per 600,000. Seven people have died. In Germany the rate is higher at 31 cases of CVST and 9 deaths from 2.7 million people vaccinated there. The EU medical regulator has estimated that the risk of CVST in people under the age of 60 who have been given the Oxford vaccine is about one in 100,000. The normal background rate of these clots in the general population is uncertain. Some groups estimate that it is about 2 cases per million people in a normal year but others say 16. It is important to remember that these complications are very rare. They failed to show in the phase 3 trials of tens of thousands of patients and they must be balanced against the risk of the disease,
These thromboses seem to be associated with the AstraZeneca vaccine but not the Pfizer one. Hence it seems to be a feature of DNA rather than m-RNA vaccines. Some European countries that have been wary of the AstraZeneca vaccine have ordered the Russian Sputnik vaccine instead. This is also a DNA vaccine and so may show the same rare problems when it is properly assessed.
On 7th April 2021, it was announced that the vaccine would no longer be used on those younger than 30 in the UK. This is a sensible compromise as this age group is less vulnerable to serious adverse effects or death from the disease but they are susceptible to scare stories, however poorly founded.
A study from Oxford found that people who have the infection are 8 to 10 times more likely to get thrombotic syndromes than those who have received the AstraZeneca vaccine. Young women seem vulnerable with 30% of cases occurring in those under 30. Women on oral contraceptives have a risk of thrombotic syndromes about 250 times greater than those who have the vaccine.
Pregnancy is a time of high risk for the disease but it is easy to understand why women may be reluctant to have a vaccine during pregnancy. However, for pregnant women, some figures are important to note:
- In the three months to August 2021, 171 pregnant women were admitted to hospitals in England with COVID-19
- Of theses 171, three had received only one vaccine, none had received both and the other 168 were all unvaccinated
- 1 in 3 pregnant women admitted to hospital develop pneumonia
- 1 in 7 pregnant women admitted to hospital need intensive care
- 1 in 5 pregnant women admitted to hospital will deliver prematurely
- Well over 100,000 pregnant women in the USA and many thousands more in the UK have received the vaccine without evidence of significant adverse effects
Expert opinion is that the virus will be with us for several years to come and that it will require annual vaccination, like flu. If it mutates significantly, the vaccine will need to be tweaked. However, the spike protein which is the target of all the vaccines is very large. It is presumably mutated in the variants that are more infectious, but it would take a very great change for the vaccines to be ineffective against the variants. A booster campaign, along with flu vaccines, from September 2021 aims at those over 70, those with health problems that put them at risk and then everyone over 50 years old.
Initially, there was no plan to vaccinate teenagers but as time progressed, various countries, including the USA did so and considerable data suggests that it is safe and effective. In the UK in the second half of 2021, there are plans to vaccinate the 12 to 15 age group but with only one dose. A study that at the time of writing, has not yet been published, suggests that giving two does to that age-group in England could prevent thousands of cases of long COVID.42Vaccinating adolescents against SARS-CoV-2 in England: a risk-benefit analysis
Following the Science
When I was practising medicine, politicians often told us that doctors should practise evidence-based medicine. They were right, but my response was always that I would like to see them practising evidence-based politics. Therefore, when politicians say that they are following the science in dealing with the COVID-19 pandemic, I am delighted.
However, that is not the full story. They have scientific advisers, as we have seen in the innumerable briefings, but there is a major problem. This is a new disease and there was not very much science to guide advice. Scientists and engineers use models to predict things. It may be a scaled down model of a car or aircraft in a wind tunnel or, as discussed in the chapter Global Warming and Climate Change, models can be used to predict climate or weather. Models can also be used to predict the spread of disease. However, there is not much knowledge on which to base a model for this new disease that does not necessarily behave like others. I have seen an authority suggest that the epidemiology models are about 20% science and 80% intuition.
Some of the modelling is really quite remarkable. CCTV pictures have been analysed to show how people move in crowds. Even mobile phone data has been used to see how people behave. If a Government wanted everyone to carry a personal tracking device there would be a great outcry but the majority of us choose to carry such a device. We call it our smartphone.
An important figure that the models seek to predict is the R value, also known as the effective reproductive number or reinfection ratio. This means how many new people each infected person will infect on average. If that figure is above 1, the number of new cases will increase. If it is below 1, they will decrease.41What is the ‘R’ value and why is it so important for the easing of the coronavirus lockdown?
Sir Adrian Smith, a statistician and president-elect of the Royal Society, said that the “extraordinary amounts of uncertainty” with new viruses had been played down in a political environment where ministers felt they needed to appear decisive.43Coronavirus: Stop passing the buck, top scientist tells politicians He fears that scientists may get blamed for failings when advisers advise and politicians make decisions. There really is little evidence to draw on. Many other scientists have expressed similar views.
A major aim of lockdown is to delay transmission so that the health service can cope
When looking at figures for new cases or deaths, it is important to look at trends rather than individual days. There can be marked blips on odd days. By autumn 2020 the trend was far more gloomy. Cases rose markedly, even above first wave levels, but better testing would accentuate this. Deaths lag at least 3 weeks behind cases and they also rose but not as markedly. Comparing deaths and hospital admission, it is clear that doctors were better at treating disease and so there are fewer deaths, but deaths were rising too. Trends were going the wrong way and death rates were at record levels.
It is very easy to miss cases, especially where there is not widespread testing and even deaths due to COVID-19 may by mislabelled. Some countries are poor at counting the numbers. Some omit deaths in residential homes. A way round this is to compare the average death rate for that month over the past five years. If it is very much higher, this suggests many deaths from the virus. If it is not much different from normal, this suggests a low rate. A brief video on the BBC website explains this.44BBC Reality Check explains what “excess deaths” reveal about Covid-19
Sweden took the unusual decision not to implement lockdown but kept most schools, restaurants, bars and businesses open. The idea was to permit herd immunity. There were different levels of immunity in different parts of the population, ranging from 4 to 5% in some to 20 to 25% in others. Overall, only around 6.1% of Swedes had developed antibodies and this is well below levels deemed adequate to achieve even partial herd immunity. In the middle of August 2020, it was estimated that 6% of the population of the UK and 15% of the population of Sweden had been infected. Sweden’s death rate is lower than some countries that opted for strict lockdowns, such as Britain, Spain and Italy but it is many times higher per capita than its Nordic neighbours. This must be the relevant comparison and their open policy has be widely deemed a failure.
There have been calls from some sections to abandon the attempts to control spread and build herd immunity. A letter in the Lancet from 80 specialists, including doctors in public health and infectious disease, says it is necessary to continue restrictions and that uncontrolled transmission among young people would inevitably have an impact on older generations. They say that the probable result of letting the virus run loose would be successive waves of epidemics.45Scientific consensus on the COVID-19 pandemic: we need to act now
An important decision to make was when to re-open schools. The evidence for the safety of children is high, for the susceptibility of children is medium and for the infectiousness of children is low. Children appear less likely than adults to bring the infection into the household. It is usually the adults who do this. Data from families of 39 children younger than 16 years showed that in 31 (79%), at least one adult family member had a suspected or confirmed infection before the onset of symptoms in the child.46COVID-19 in Children and the Dynamics of Infection in Families These findings support data from previous studies in China, Australia and France. In only 3 of 39 (8%) households was the child the first to develop symptoms. This is reassuring for schools. Where children live in a household with a vulnerable person, it is reassuring to know that they are unlikely to bring the disease home.
The Government has been blamed for delays in initiating lock-down at the beginning of the outbreak. In the early days it was hoped that herd immunity would soon make the country safe but it became clear that this would require about 60% of the population to have been infected, and with an overall mortality rate of about 2%, this was an unacceptable policy. A headline in The Sunday Times saying 4722 days of dither and delay on coronavirus that cost thousands of British lives I think is unfair. It said that cases were doubling in as little as three days, but no one was to know if this would continue or plateau.
There are political considerations too. It only worked because of trust and good faith. The economic consequences are also enormous. Young people seem to have ignored the rules from the outset, still gathering in groups and ignoring social distancing. They are at low personal risk but they could still spread the disease and kill their grandparents. Low risk is not no risk and young people have a sense of their own invulnerability. This is said to change around 25 years old when the prefrontal area of the brain becomes fully myelinated.
A reason that was put forward for why we were slow to have lockdown is that if it were implemented too soon, there would be behavioural fatigue and people would slip back to their former ways. Behavioural science is important but research is poor and often neglected. It may be that the concept of behavioural fatigue is flawed.48Behavioural fatigue: a flawed idea central to a flawed pandemic response.
However, I am not convinced that the concept of behavioural fatigue is flawed. A study of more than 90,000 people, done at University College London, found that in the week ending 25th May 2020, “complete” compliance declined from an average of 70% of adults to just over 50%. For young adults, compliance levels were even lower, with only 40% reporting completely following lock-down rules. Since then, we have seen some very irresponsible behaviour with much, but by no means all, coming from young adults. As time went by, people were less compliant with lock-down rules. I think they were just fatigued and as the weather improved vast numbers appeared on the beaches or in the countryside and social distancing was impossible. In some places, local people said that there were more crowds than they had ever seen in the days before restrictions. The lock-down was being eased slightly but people were impatient. Some claimed that the rules were unclear but I think only for those who wanted them to be unclear.
There is no doubt that mistakes have been made and this is unsurprising in such an unprecedented situation. When it is finished we need experts to look at what went right and what went wrong in a non-judgmental way, looking at what lessons we can learn for the future. This would be a learning exercise, not a blame-game. It would be most unwise to think that it will be another 100 years before we see another such pandemic. This is so important that I have added an extra chapter called What we Must Learn from the COVID-19 Pandemic.
I am sure that we need to stockpile personal protective equipment (PPE) for the future and to have exercises in dealing with such events. The counties of the Far East learned lessons from SARS and MERS and they were far better prepared for COVID-19 than the west. South Korea had systems in place at an early stage, including track and trace, and its death rate was far lower than western counties. They also avoided the catastrophic economic effects of lockdown.
Testing and tracing people who have the disease is important. Testing is essential, especially to find the asymptomatic carriers. This requires plenty of testing kits. I am concerned at our reliance on sources from abroad for both PPE and testing kits. We have a manufacturing base that was shut down and not properly utilised to manufacture PPE. We have a world-class biotechnology sector which should have been able to meet our demands. An effective track and trace system probably helped Germany to cope better than most countries.49The first wave: How Germany’s coronavirus contact tracers helped to ease its lockdown
Early days of test and track threw up some surprises. Of the first batch tested, 70% of those who tested positive had no symptoms. This was possibly not a random sample but it makes contact tracing less effective if only about a third of people who have the virus present for testing with symptoms. However, some experts cautioned that many of the test results could be false positives, caused by the inherent difficulties of checking people at random for a disease that affects fewer than 1 in 400 people at present. The results also show that only 1 in 15 people had antibodies, indicating that they had recovered from corona–virus, dealing another blow to hopes that herd immunity would end the epidemic without the need for a vaccine or treatments. If antibody response to infection is poor, we may expect a poor result from vaccination too but vaccination can produce a better immune response than the disease.50Seven in ten testing positive for virus show no symptoms
There are two main types of testing for the virus. PCR (polymerase chain reaction) is more sensitive than lateral flow tests but PCR takes 24 hours to get a result whereas lateral flow tests can yield results inside an hour. With both types of test, false positives do not seem to be a problem, only false negatives. To compare the two, the following graph shows the rate of shedding of virus on the ordinate (Y-axis) and time since infection on the abscissa (X-axis).
The x-axis shows days since infection. Y-axis shows viral shedding. The curve is the level of virus shedding. The green line is the threshold for lateral flow test. Red line is for PCR
There are a number of points that can be made from this graph:
- Both fail to be positive in the very early stages but PCR becomes positive before lateral flow tests.
- PCR stays positive longer than lateral flow tests
- A positive test means positive but a negative test may not be so reliable, especially for lateral flow tests. To be sure, they may need repeating in a couple of days.
Antibody testing is useful to discover who has had the disease, but according to a Cochrane review, it is important not to test too soon. The review of 54 studies found that antibody tests carried one week after a patient first developed symptoms detected only 30% of people who had covid-19. Accuracy increased to 72% at two weeks and to 94% in the third week.51What is the diagnostic accuracy of antibody tests for the detection of infection with the COVID-19 virus?
On a world scale, it is good to have an organisation that can coordinate action and collate the science and best practice. This is where the World Health Organisation (WHO) comes in. Therefore, it is unfortunate that Donald Trump decided to pull the USA out of the organisation and to withdraw funding.52Coronavirus: Backlash after Trump signals US exit from WHO The true reason for this, with an election looming and his populist stance was transparent. He needed to find someone else to blame for the serious shortcomings of the American response. Donald Trump was elected on a slogan of “Make America Great Again.” His re-election slogan was “Keep America Great.” He has probably done more to abdicate America’s role in world leadership than any other president. Other western leaders have insisted that they are following the science. Donald Trump is anti-science. He prefers his unsubstantiated assertions.
The Prime Minister was naturally very reluctant to initiate the second lockdown considering the cost to The Treasury, the economy and jobs but eventually he really had no option but to follow other European countries. Again, it was necessary to prevent the NHS from being overwhelmed.
By the middle of December 2020, numbers were still rising despite efforts at local and national government levels. There was a mutation in the virus, found in Kent, which made it more infectious 50 to 70% more infectious. This is very significant. There is another variant of concern from South Africa and another from Brazil. Such mutations of viruses are common, especially in coronavirus. It may be striking at younger people, giving serious illness. The mortality rate from the new variants is higher. Sir Patrick Vallance, the chief scientific officer, said that with the old one, if 1,000 men aged 60 were to contract the disease, we would expect to see 10 deaths. With the new variant, that figure would be 13 or 14 deaths. Whether the vaccine will be less effective against it is uncertain but it is unlikely that they will be ineffective.
In early 2021, the number of cases was falling fast and, as the graph shows, falling rather faster than in the first wave. This was probably due to augmentation by the vaccine. It reduces cases, it reduces spread and it reduces the number of serious cases that will result in hospital admission and death.
The second wave reached a much higher peak than the first but is falling away much quicker
Results from a flight into Ireland in the summer of 2020 changed the way that we must think about transmission.53A large national outbreak of COVID-19 linked to air travel, Ireland, summer 2020. The flight brought 49 passengers into Ireland, of whom 13 tested positive. However, testing and tracing showed that only 5 of that 13 people infected others. It seems that some people are spreaders and some are not.
This means that we must think differently about how the disease is spread. A figure called the K number indicates how variable people are in terms of their ability to spread. A high K represents low variability. For COVID-19, it seems that 90% of disease is spread by 10% of infected people. This is said to emphasise the need not just to test and trace forward to see who a person may have infected, but to trace backwards to find who is the spreader. This was done well in the early stages of the pandemic in south-east Asia and it accounts for much of their success.
Another very important question to answer is how many people need to be vaccinated to produce adequate herd immunity. This will depend on such factors as the effectiveness of the vaccine and the rate of spread of the vaccine when there are no restrictions in place. The latter is called R0. The R0 for COVID-19 is thought to be around 3 but for the new variants of concern that may be more infectious, it could be 4 or even 4.5.
The formula that is used is:
H = (1-1/R0) / E
H is the number of people that need to be vaccinated to achieve herd immunity. It is expressed as a decimal so that 90% is 0.9. R0 has been explained. E is the efficacy of the vaccine, again as a decimal, not per cent.
To put a few numbers in there for the sake of illustration:
H = (1-1/3)/ 0.8 if the vaccine is 80% effective. That is (2/3 / 0.8) = 20/24 x 10/8 = 5/6 or 83% of the population. Herd immunity requires 83% of the population to be immune. It is clear that a high vaccine efficacy decreases that number but a high R0 increases it. If R is 4, this increases H to 94%. Herd immunity requires 94% of the population to be immune. However, the Indian variant, now known as the delta variant, may have a R of 5. However, not only is it more infectious but, contrary to initial fears, it seems to be more susceptible to the vaccines that may have an efficacy of 90% or more. If we put in R = 5 and E = 0.9, we get 89%. However, when the Prime Minister announced the continuation of restriction for another 4 weeks on 14th June 2021, he also said that we may have to learn to live with the disease for many more years.
The Health of People or the Economy
It is very easy to take the moral high ground and to state that the health and lives of people must take precedence over the economy. The truth is far more complex.
The lock-down has had a disastrous effect on the economy and politicians need to make the call about how to lift it. This must be done in stages, monitoring the effect as a secondary spike in cases and deaths may result. Indeed, the question is really how big a spike is acceptable? It is unrealistic to say, “We must protect lives over making money.” The economy has a marked effect on people’s health. Sir Michael Marmot said that England had experienced continuous improvements in life expectancy since the beginning of the 20th century but that from 2011, “these improvements slowed dramatically, almost grinding to a halt”. Life expectancy actually fell in the most deprived communities outside London for women and in some regions for men. For men and women everywhere the time spent in poor health is increasing.54Health Equity in England Although he was eager to attribute the negative trends in health to the necessary austerity of the 20-teen years, when I questioned him, he had to admit that much may have been due to ever-increasing levels of obesity. Countries that experienced less austerity still had a similar trend.
It is well recognised that a bad economy is bad for health. Job insecurity or unemployment puts strains on people’s lives. The cost of the NHS is enormous and only in a thriving economy is it possible to get anywhere near the demands of the system. If you want to vote for the party that will be best for the NHS, vote for whom you think will deliver the best economy. The economy must be re-opened. It is a perilous call to decide the line between avoidable deaths and the serious adverse effects on health from a badly damaged economy.
By the end of May 2020, a headline in the BMJ said:55UK’s response has so far cost “unprecedented” £124.3bn The budget for the Department of Health and Social Care in England for 2019-20, is £140.4billion and this figure of more than £120billion was for rather less than a full year. £120 billion represents £2,000 for every man, woman and child in the UK. The National Audit Office (NAO) says the money covers the main actions taken by the UK government in England in funding to devolved administrations up to 4 May 2020, and subsequent large funding commitments. Around £82.2billion was for schemes for businesses, such as job retention and loans, while £19.5billion went towards benefits, sick pay, and support for vulnerable people. Spending on health and social care measures for equipment, testing services, and vaccine development, among other things, amounted to £6.6billion. This figure does not include £13.4billion of NHS debt written off from 1 April 2020. There will also be pressure to get the NHS to catch up on the considerable backlog of work that was not done when all attention was on ascertaining that it would not be overwhelmed.
The Department of Health is by far the largest spending government department, and so to find that the cost of the pandemic will be rather more than a whole year of funding for that department is an enormous blow to the economy. However, there is another side to the problem. As well as increased expenditure, HMRC will have reduced receipts from income tax, VAT, corporation tax and capital gains tax. It will take a very long time for the economy to recover from such a blow. The economy and health are intimately related.
Myths and Fake News About COVID-19
This situation is sure to attract myths, fake news, conspiracy theories and peddlers of fake cures. When you read a story and you wonder if it is true, there are several questions to ask. Where did you see it? Was it the website of a reputable newspaper, the BBC or the Gov.uk website or was it something less reliable such as a re-tweet or a website that you had not heard of? How is it presented? Fake news if often emotive as it is designed to make you angry. Can you find the story elsewhere and that does not include a re-tweet? Pictures can be taken out of context. An example was a picture of Italian troops who were said to be facing COVID riots but in reality they were returning from a routine exercise. Put the claim in a search engine with “hoax” and see what comes up. You can also use the British website https://fullfact.org/.
In the early stages of the pandemic, The Times had an article called 56Don’t let fake news infect the war on Covid-19 This is an interesting article which includes Donald Trump’s tweet, “HYDROXYCHLOROQUINE and AZITHROMYCIN, taken together, have a real chance to be one of the biggest game changers in the history of medicine. Hopefully they will BOTH be put in use IMMEDIATELY. PEOPLE ARE DYING, MOVE FAST, and GOD BLESS EVERYONE.” (His block capitals, not mine. They are the Twitter equivalent of shouting). We have seen above just how unwise, unfounded and untrue that was.
Fake new can spread at a phenomenal speed. Suppose that a group of 20 on Whatsapp gets a false story and relay it to another 20 people who all do the same. If this happens 5 times, it reaches more than 3.2 million people.
In the early days the BBC also had an article on its website called 57Coronavirus: The fake health advice you should ignore. This looked at six silly stories. The most notable were:
- Garlic has been advised. We have seen in the chapter Herbal Remedies that garlic does not prevent or cure the cold. It does not work for this either.
- Then came the “miracle mineral supplement”, called MMS which contains the bleach chlorine dioxide. Youtube have censored videos that promoted it. The proponents blame “Big Pharma” as they “want people ignorant”. This MMS is also mentioned in the chapter Introduction to Alternative Healthcare in the section on regulation, lamenting the appalling rubbish that is peddled, including this bleach as a cure for autism, malaria and much more. These people are dangerous.
- There was home-made hand sanitiser that might be effective on surfaces but it was far too caustic for the skin
- The use of colloidal silver was promoted on US televangelist Jim Bakker’s show. Colloidal silver is tiny particles of the metal suspended in liquid. A guest on the show claimed the solution kills some strains of coronavirus within 12 hours (while admitting it hadn’t yet been tested on Covid-19). It can cause serious side effects including kidney damage, seizures and argyria which is a condition that makes the skin turn blue.
The BBC had another amazing article in May 2020, looking at serious illness as a result of fake stories around the world.58Coronavirus: The human cost of virus misinformation Most came from the USA, but the stories were widespread and some were from the UK too. The article makes worrying reading. People can be so stupid.
A Russian disinformation campaign aims to undermine the Oxford University coronavirus vaccine and to spread fear. Pictures, memes and video clips portraying the British vaccine as dangerous have been devised in Russia and middlemen are now “seeding” the images on social media around the world. The crude theme is that the vaccine could turn people into monkeys because it uses a chimpanzee virus. This is as absurd as James Gilray’s cartoon of cows spurting from the bodies of people who had received smallpox vaccination but this was in 1802. The campaign is aimed at countries where Russia aims to sell its own Sputnik V vaccine, as well as the west. It has the potential to damage not just the Oxford programme but the whole wider global effort to protect against the virus by encouraging conspiracy theorists and the anti-vaccination movement.
There is evidence that some Russian officials were involved in its organisation and dissemination and it is thought unlikely that in a system as centralised as Russia, that it could have happened without a nod from the top. Reports featuring some of the images appeared on the Vesti News programme in Moscow, described as the equivalent of BBC’s Newsnight.
The messages of the campaign echo statements from high-level Kremlin officials describing a “monkey vaccine” and contrasting it with the Russian vaccine derived from a human adenovirus. In fact, the British “monkey vaccine” is inherently safer. The Oxford labs have been hit by cyberattacks from Russia and intelligence officials are concerned that the dark arts of disinformation would be used.
In the UK in July 2020, it was reported that a survey, conducted on behalf of the research group Centre for Countering Digital Hate (CCDH), found that 6% would definitely not get vaccinated, 10% would “probably not” get vaccinated, while 15% said they did not know. Only 38% said they would “definitely” get vaccinated, and 31% said they “probably” would. According to The Times, CCDH said that the results come amid a sharp rise in the presence of social media channels promoting anti-vaccine content. “Our hope for a return to normal life rests with scientists developing a successful vaccine for coronavirus. But social media companies’ irresponsible decision to continue to publish anti-vaccine propaganda means a vaccine may not be effective in containing the virus.” In a way, I welcome the absurdity of the monkey vaccine misinformation as it shows the utterly idiotic stand of the fake news and anti-vax campaigners.
When it comes to promoting fake news about the vaccine, at least the AstraZeneca vaccine, Emmanuel Macron and Angela Merkel must both shoulder some blame. They have both sought to undermine the Oxford vaccine for political reasons. The Germans would prefer the Pfizer vaccine which is produced in Germany and Belgium while the French wanted to delay the rollout of vaccine in the EU so that the French vaccine would have a chance to compete. Both must take some blame for the lack of faith in the Oxford vaccine. They made disparaging remarks about it as the European Medicine Agency was approving it for use in all adults, including the elderly. Now they have even arranged to buy the Russian Sputnik-5 vaccine despite it having its phase 3 trial after it was released.
During lockdown, the Marsh family have amused many of us with their YouTube collections. The father, Ben Marsh, writes the lyrics. I would especially recommend the one about the vaccine called Get the new Jab. Click on the title in blue to see it.
When it comes to promoting fake news or bad advice, we have to return to Donald Trump yet again. At a press conference he seemed to be suggesting that because disinfectants and ultraviolet light kill the virus, that swallowing or injecting disinfectant was a possible remedy or shining light inside the body. He said that he was just thinking aloud but the fact that he even thinks such things shows how pitifully uneducated he is. Disinfectants work by killing the cells of bacteria or viruses. They also kill the cells of the body. The “magic bullet” of antibiotics is something that can kill the infection without harming the host. He later said that he was being sarcastic but it sounded like someone just back-pedalling. It is frightening to think that the most powerful man in the world has so little knowledge and such crass contempt for the truth.
Researchers at Cornell University in New York analysed 38 million articles about the virus in English-language media and found that references to Mr Trump comprised almost 38% of the “misinformation conversation”.59Trump ‘worst offender’ for spreading fake health news The study searched for 11 kinds of misinformation, such as a conspiracy theory claiming that the pandemic had been manufactured by the Democratic Party to coincide with the president’s impeachment trial at the start of the year, and supposed miracle cures. The president of the United States was the single biggest driver of misinformation. On 24th April, the day after Mr Trump suggested at a White House press conference that disinfectants and ultraviolet light could treat the virus, there was a surge in misinformation about miracle cures.
A day or two after this article appeared, it was announced that Donald Trump had contracted COVID-19, as had his wife and several of his aids. He was admitted to hospital and even the bulletins from the doctors seemed contradictory and economical with the truth at times. The story gave an opportunity for a cartoon in The Times from Peter Brookes which said what so many of us must have been thinking.
Another very silly story concerned 5G, the latest technology for mobile phones. It has been the victim of conspiracy theories before the pandemic with allegations that it impairs the immune system.60Coronavirus: False Claims About 5G, Inhaling Steam and Skin Colour There have even been claims that the virus is spread via the network, which is a ridiculous and implausible idea. Telecoms engineers have been threatened. 5G masts have been attacked.61Twitter bans incitement to attack 5G towers If you are still unsure, try 625G is not accelerating the spread of the new coronavirus. Fullfact Ofcom says that theories linking Covid-19 and 5G theories are the most common misinformation
The BBC also examined 63The seven types of people who start and spread viral misinformation They included conspiracy theorists, politicians and celebrities.
The Charity Commission has widened an inquiry into a “church” in South London that was selling a fake “plague protection kit” which it claimed would protect users against COVID-19. The Commission said it now wanted to investigate the finances of The Kingdom Church GB. The kits contain cedar wood, hyssop, and scarlet yarn to wrap around the wrist as “an invisible barrier to the powers of darkness”. They were on sale for £91.64Charity regulator launches inquiry into church found promoting fake Covid-19 protection kits I have had a look online at various other products that they sell. They include Divine Cleansing Oil, Scarlet Yarn to tie around the wrist and a Special Divine Protection Miracle Prayer Card all for £50. No Weapon Stop Them Anointing Oil sells for £10. They make claims about “curing” homosexuality. The shop is called “Prophet Climate Megastore” but I could not see if they make any claims about climate change or if it is just related to prophecy. Every person that I saw in every picture on their website was of Afro-Caribbean race.
Tanzania is a country with a problem as its president, John Magufuli, denied that COVID-19 ws a problem. He denigrated masks as protection against the disease and rejected the vaccine.65Coronavirus in Tanzania: The country that’s rejecting the vaccine He said, “If the white man was able to come up with vaccinations, he should have found a vaccination for Aids, cancer and TB by now.” He was both an idiot and a racist. The following month it was reported that he had died at the age of 61 from heart failure. This was probably really a complication of COVID-19.66Covid: Does Tanzania have a hidden epidemic? There was a similar problem in South Africa when President Mbeke denied that the HIV virus caused AIDS.67Mbeki Aids denial ’caused 300,000 deaths’
Finally, we have to turn to that man again. Donald Trump says that the virus was engineered in a Chinese lab and released by accident. His own experts say that there is no evidence that it was engineered and it occurred naturally.68Trump says he’s seen evidence coronavirus came from Chinese lab. US intelligence agencies say it was not man-made As we shall see below, I think that the virus came from a Chinese laboratory, but it was being stored, not synthesised. The genetic code of the virus suggests that it was not synthesised.69No, COVID-19 Coronavirus Was Not Bioengineered. Here’s The Research That Debunks That Idea The British Intelligence Services also believe that the virus originated in a wet market in Wuhan.
At last, Twitter has started to flag up some of Donald Trump’s tweets as fake news. Like any petulant despot, he has threatened to close them down.70Trump threatens to shut Twitter for censuring him He should have just boycotted them instead. Alternatively, they could ban him for repeated violations.
In March 2021, an article in The Independent was called 71CDC removes false Trump-era Covid recommendations that purported to come from scientists. This is a matter for enormous concern as the American Centers for Disease Control (CDC) is respected around the world for its scientific credentials. The idea that a politician could hijack it to promote fake news undermines its credibility and questions must be answered.
Life After COVID19
We shall not wake up one morning and find that COVID-19 is gone. There will be a slow return to normality, with blips. The virus will fade away over many years. The speed of change will depend on many factors that are currently unclear. This includes if an effective vaccine can be produced that will give good, long term immunity. We do not know how much immunity previous infection will give. At present it seems that this may be quite variable between individuals. We do no know how much it may mutate, making it more difficult to eradicate.
We have lived our lives differently with far more working from home and conference calls instead of meetings. I wonder if much of that may continue. A great deal of time is spent in travel to and from work each day as well as the cost of travel. It is good to see people face-to-face but time spent travelling to meetings, especially if far away or even abroad, is very costly. If conference calls are effective, they are a much better use of resources. I even wonder if the ill-fated HS2 rail network may give poor returns for a great deal of money compared with establishing a super-fast national broadband system.
Consultations in hospital and in general practice have made heavy use of telephone or video consultations. They should reduce when we return to normal but they will become far more part of normal than before. In general practice the number of face-to-face consultations fell from 80%, which I regard as rather low, to 15% which I regard as unacceptable and dangerous. It is impossible to examine patients who are not physically present, although it is possible to look at them on video. There are personal interactions that are more difficult in tele-consultations. Patients will tell doctors things face-to-face that they will not say by video or telephone. We shall see more remote consultations, especially where examination is not required but it would be dangerous to take it as far as during the emergency.
Attendance at accident and emergency departments has fallen and perhaps some of this is people who did not need to be there. However, it also seems that people have been failing to present with serious conditions such as heart attacks and strokes and this increases mortality. Attendances were down from 2.17 million in May 2019 to 1.26 million in May 2000. There have also been significantly fewer referrals for possible cancer as people have stayed away. GP referrals were down 60% on the previous year. The price will be paid later as people present with more advanced malignancies. Modelling has suggested that late presentation and delated treatment of cancer may lead to an additional 7,000 deaths. If you have seen the figure of 35,000 deaths, which is not far short of all the deaths from COVID-19 infection, this is the most extreme scenario and not the median or “expected”.
Much of the NHS reduced or stopped activity because of the crisis and this has created a considerable backlog which will take time and money to catch up.
Many sections of the economy have been severely damaged and many firms may not survive. Economists are warning that there will not be a rapid bounce back to the economy of before the pandemic. The world may take 10 years to recover. Restaurants, pubs and the hospitality industry have problems. Airlines will not return to previous passenger loads, probably for around three years. How will the holiday industry cope? What is the future for cruise lines? Cunard is due to receive a fourth ship in 2022. Will they have passengers and routes for it? Many cruise lines have mostly older passengers. How long will they stay away?
During lockdown I often saw people congregating together and ignoring social distancing or playing football or basketball with contact. They were almost all young people. They probably thought that the pandemic did not affect them as the death rate in the young is very low. However, it is the young who will pay the biggest price for the effect of the pandemic on the economy. If their actions helped to spread the disease, they are now paying the price.
Many people are looking at their occupations and wondering if a career change may give them better job stability. People from the hospitality industry are considering going into caring. No one expects it to be another 100 years before another such pandemic strikes. Governments throughout the world have gone into debt to protect their people and their economies. How deep and how prolonged a recession can we expect to see? What will this do to politics? When nations borrow money, the source of often China, the country where this all started. Will it make them even stronger in the world? The are already showing more military aggression and are taking a more aggressive line with Hong Kong and Taiwan. How reliant should we be an Chinese technology and manufacturing?
Air quality has been better with fewer cars on the roads and wildlife has thrived as humans kept to their homes. This will not last but perhaps more home working will lead to less traffic and there may be an incentive to improve air quality. Some people may work three days a week in the office and two days a week from home. However, with a struggling economy and much public debt, there will not be much money for new initiatives. Many people have taken to cycling rather than using public transport or even their own cars. This is fine in good weather. When it is cold and wet with a strong wind, cycling becomes far less attractive.
We need to take the problem of obesity seriously. It is an avoidable cause of disease. The perfect storm of an obesity epidemic and a COVID-19 epidemic have met.72The Perfect Storm: Coronavirus (Covid-19) Pandemic Meets Overfat Pandemic COVID-19 death rates are 10 times higher in countries where more than half of the adult population is classified as overweight or obese than in other countries. Taking data from over 160 countries, there is a linear correlations between a country’s Covid-19 mortality and the proportion of adults that are overweight. There is not a single example of a country with less than 40% of the population overweight that has a death rate over 10 per 100,000. No country with a death rate over 100 per 100,000 had less than 50% of their population overweight.73Highest death rates seen in countries with most overweight populations. This finding is spectacular.
One good thing that I think has come from all this is that during lock-down, there were many people who were caring and kind and who looked about for the more vulnerable in their communities. Community spirit has been good. I would like to think that Neighbourhood Watch could become a way of looking out for each other rather than a paranoia about crime, especially in neighbourhoods where most of the crime is online. If we could become more caring for each other, something good will have come out of it.
We need an inquiry into what went well and what went badly. This is not a blame game but an honest attempt to learn from mistakes and to be better prepared for when it happens next. This is why I have added the chapter What we Must Learn from the COVID-19 Pandemic. As this was unprecedented, it is unsurprising that there were mistakes and it is very easy to be wise with the benefit of hindsight. It would be foolish to assume that it will be another 100 years before we see such a pandemic again.
A long and interesting article in The Sunday Times was called 74Revealed: Seven year coronavirus trail from mine deaths to a Wuhan lab. I have given the reference but you are unlikely to be able to access it without a subscription. They say that the virus came from a high bio-security laboratory in Wuhan, but there is no suggestion that it was developed as a biological weapon. The closest known relative to the COVID-19 virus was found in 2013 by Chinese scientists in an abandoned copper mine in the hills south of the town of Tongguan in the Mojiang region. This is in south-east China, about 1,000 miles from Wuhan. It was linked to deaths caused by a coronavirus-type respiratory illness. Six researchers performed a year long study and sent hundreds of samples back to their home city of Wuhan. They were trying to identify the source of the SARS (severe acute respiratory syndrome) pandemic from 10 years earlier. The problem came with workers who had been exposed to bat droppings. They had been given the task of clearing out piles of bat faeces in an abandoned copper mine. Workers became unwell. Some had worked for two weeks before falling ill, and others just a few days. It would seem that several years later, the virus had been unintentionally released by a lapse in biosecurity at the lab in Wuhan.
A Panorama programme suggested that China had been far from open about the disease in the early days. There was about three weeks between finding that the new virus could spread from human to human and not just from animals and informing the world. Although the Chinese Communist Party has had an iron grip on the country since 1949, the programme said that they are still very scared of panic as it may result in social unrest and threaten their control. Hence, when Dr Li Wen tried to warn colleagues about what was unfolding, he was detained by police in Wuhan for “spreading false rumours”. He was forced to sign a police document to admit he had breached the law and had “seriously disrupted social order.” In February 2020, he died of COVID-19 in his own hospital in Wuhan.75‘Hero who told the truth’: Chinese rage over coronavirus death of whistleblower doctor
We must take China to task over the origin of this and other pandemics. It must be handled tactfully but firmly, or they will take umbridge and nothing will be achieved. Nowadays many are reluctant to confront China and they are becoming more powerful and more assertive in the world. They are now a much more affluent country and can afford to give up ancient ways of keeping animals. We need strong regulation on an international level, probably via the UN. It requires global cooperation and goodwill. At present China is still in a state of denial about the scale of the emergency there and many who have tried to warn others have faced the wrath of the state. Indeed, China now insists that the virus did not start in China. They do not know where it did start, but they are adamant that it was not China.
Both the level of denial from the Chinese Communist Party and their power is illustrated by a story from Germany. A book for children to explain about the pandemic included the statement that the disease originated in China. That is absolutely true. However, the Chinese Government objected and the book was pulped.76Covid kids’ book pulped after China complains.
China is rather proud of Traditional Chinese Medicine (TCM) which it regards as part of its culture although it is totally useless, is often cruel to animals and commonly involves endangered and protected species. TCM and the quest for exotic species for food includes the hunting of elephants, rhinos, tigers, pangolins, endangered species of sea horses and much more. They must join the 21st century. In the chapter Other Modalities of Complementary and Alternative Medicine there is a section on Traditional Chinese Medicine
A report in a microbiology journal said, “The presence of a large reservoir of SARS-CoV-like viruses in horseshoe bats, together with the culture of eating exotic animals in southern China, is a time bomb.”77Severe acute respiratory syndrome coronavirus as an agent of emerging and re-emerging infection. This was published in October 2007. Twelve years later is became true.
There have been jokes, pictures and videos exchanged to keep up morale. When we have nothing else, laughter is still the best medicine
- The Government website that gives updates on coronavirus in a comprehensible manner and the content is reliable.
Reliable information from the NHS. Many topics covered.
- The Anatomy of a Pandemic. What Have Scientists Discovered Six Months On? By Claire Press. BBC 7 June 2020.
An excellent article about the origins of the virus and how genomics is used to track it and to help produce a vaccine
- Disparities in the risk and outcomes of COVID-19. Public Health England June 2020.
A summary from Public Health England of the many factors that affect risk and outcome in this disease including age, gender, ethnicity, occupation, geography and much more.
- The BMJ Interview: Tim Spector on how data can arm us against covid-19. BMJ 2020;371:m3921 (Published 14 October 2020).
Professor Tim Spector discusses how we could better use data to fight the pandemic
- Liu PP, Blet A, Smyth D, Li H. The Science Underlying COVID-19: Implications for the Cardiovascular System. Circulation. 2020 Apr 15. doi: 10.1161/CIRCULATIONAHA.120.047549.
For those who are keen on the science. Some may get lost in the technical terms and concepts. Not available in full without charge
- Coronavirus: ‘Baffling’ observations from the front line. BBC 24 May 2020
A good article from the BBC about the many challenges that this new disease has brought.
- ‘Hundreds dead’ because of Covid-19 misinformation. BBC News 13 August
Another article from the BBC about the devastating effect of false information
- Coronavirus: False and misleading claims about vaccines debunked. By Jack Goodman and Flora Carmichael BBC Reality Check
It shows how even normally sensible people can be taken in by wild and untrue assertions.
- Excess Weight and COVID-19. Insights from new evidence. Public Health England July 2020.
Public Health England examines the evidence about weight and COVID-19 risk
- 11 (sometimes) deadly diseases that hopped across species. Live Science, March 2020
- Pangolins. National Geographic.
- van Elsland SL. COVID-19 deaths: Infection fatality ratio is about 1% says new report. Imperial College London.
- van Doremalen N, Bushmaker T, Morris DH, Holbrook MG, Gamble A, Williamson BA et al. Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1. N Engl J Med 2020; 382:1564-1567 [full text]
- Riddell S, Goldie S, Hill A, Eagles D, Drew TW. The effect of temperature on persistence of SARS-CoV-2 on common surfaces. Virology Journal volume 17, Article number: 145 (2020). [full text]
- Coronavirus. Encyclopaedia Britannica.
- Stadnytskyi V, Bax CE, Bax A, Anfinrud P. The airborne lifetime of small speech droplets and their potential importance in SARS-CoV-2 transmission. PNAS first published May 13, 2020 [full text]
- Asadi S, Wexler AS, Cappa CD, Barreda S, Bouvier NM, Ristenpart WD. Aerosol emission and superemission during human speech increase with voice loudness. Sci Rep 2019 Feb 20;9(1):2348. [full text]
- Loudon, R. G. & Roberts, R. M. Droplet expulsion from the respiratory tract. Am Rev Respir Dis. 1967 Mar;95(3):435-42
- Preprint submitted on 19.08.2020, 10:54 and posted on 20.08.2020, 16:27 by Gregson Watson Orton Haddrell McCarthy Finnie Nick Gent Donaldson Shah Calder Bzdek Costello Jonathan Reid. Comparing the Respirable Aerosol Concentrations and Particle Size Distributions Generated by Singing, Speaking and Breathing.
- Bahl P, de Silva C, Bhattacharjee S, Stone H, Doolan C, Ahmad A, et al. i Droplets and Aerosols Generated by Singing and the Risk of Coronavirus Disease 2019 for Choirs Clinical Infectious Diseases, ciaa1241, https://doi.org/10.1093/cid/ciaa1241 27 August 2020
- About Half of COVID-19 Patients Have Altered Sense of Taste. Medscape 13 May 2020.
- Cytokine Storm. New Scientist.
- National Institute for Health Research. Living with Covid19. NIHR. 15 October 2020.
- Coronavirus: ‘Long Covid could be four different syndromes’. BBC 15 October 2020
- Long Covid: Who is more likely to get it? BBC 21 October 2020
- Some With Long COVID See Relief After Vaccination. Medscape 17 March 2021
- Are Warnings Against NSAIDs in COVID-19 Warranted?. Medscape 17 March 2020.
- Sama IE, Ravera A, Santema BT, van Goor H, ter Maaten JM, Cleland JGF, et al. Circulating plasma concentrations of angiotensin-converting enzyme 2 in men and women with heart failure and effects of renin–angiotensin–aldosterone inhibitors. European Heart Journal, Volume 41, Issue 19, 14 May 2020, Pages 1810–1817 [full text]
- Chung SC, Providencia R, Sofat R. Association between Angiotensin Blockade and Incidence of Influenza in the United Kingdom. N Engl J Med
. 2020 May 8;NEJMc2005396.
- Know CS, Hassan SS. Meta-analysis of Effectiveness of Statins in Patients with Severe COVID-19. Am J Cardiol. Published online August 11, 2020 [full text]
- Almario CV, MD, Chey, Spiegel BMR. Increased Risk of COVID-19 Among Users of Proton Pump Inhibitors.
- Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, et al. Remdesivir for the Treatment of Covid-19 — Preliminary Report. DOI: 10.1056/NEJMoa2007764
- WHO Solidarity trial consortium. Repurposed antiviral drugs for COVID-19 –interim WHO SOLIDARITY trial results. 15 October 2020. Pre-publication report not yet peer reviewed
- The RECOVERY Collaborative Group. Lopinavir–ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.The Lancet 5 October 2020. Online publication [full text]
- Triple combination of interferon beta-1b, lopinavir–ritonavir,and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. Multiple authors. Lancet online 20 May 2020.
- Mehra MR, Desai SS, Ruschitzka F, Patel AN. Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis. Lancet online 22 May 2020. [full text]
- Boulware DR, Pullen MF, Bangdiwala AS, Pastick KA, Lofgren SM, Okafor EC, et al. A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19. N Engl J Med. 2020 Jun 3. doi: 10.1056/NEJMoa2016638. [full text]
- Gressier F, Verstuyft C, Becquemont L, et al. Psychiatric side effects of chloroquine. J Clin Psychiatry. 2020;81(5):20l13476.
- COVID-19 rapid evidence summary: vitamin D for COVID-19. Evidence summary [ES28]Published date: 29 June 2020
- Ivermectin: How false science created a Covid miracle drug. BBC News 7 October 2021
- Coronavirus is evolving. Knowing how could help us stop the pandemic. New Scientist 20 May 2020 (Only a short part available without subscription)
- For a coronavirus vaccine to work, first inoculate against lies. James Ball, Sunday Times 31 May 2020.
- Coronavirus: False and misleading claims about vaccines debunked. By Jack Goodman and Flora Carmichael BBC Reality Check
- Megget K. Even covid-19 can’t kill the anti-vaccination movement. BMJ 2020;369:m2184 [full text]
- Russia claims victory as it approves ‘Sputnik’ Covid vaccine. The Times 12 August 2020
- Le Bert, N., Tan, A.T., Kunasegaran, K. et al. SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls. Nature (2020).
- Tagliabue C, Principi N , Giavoli SE, Obesity: impact of infections and response to vaccines. Eur J Clin Microbiol Infect Dis. 2016 Mar;35(3):325-31
- Covid-19: Oxford University vaccine shows 70% protection. BBC News 23 November 2020
- Hung IFN, Poland GA. Single-dose Oxford–AstraZeneca COVID-19 vaccine followed by a 12-week booster. The Lancet Volume 397, Issue 10277, P854-855, March 06, 2021
- Vaccinating adolescents against SARS-CoV-2 in England: a risk-benefit analysis. Journal of the Royal Society of Medicine. unpublished.
- What is the ‘R’ value and why is it so important for the easing of the coronavirus lockdown? Daily Telegraph. 18 May 2020.
- Coronavirus: Stop passing the buck, top scientist tells politicians. The Times 19 May 2020.
- BBC Reality Check explains what “excess deaths” reveal about Covid-19. BBC News 18 June 2020
- Scientific consensus on the COVID-19 pandemic: we need to act now. Alwan NA, Burgess RA, Ashworth S, Beale R, Bhadelia N, Bogaert D, et al. Published:October 15, 2020DOI:https://doi.org/10.1016/S0140-6736(20)32153-X.
- Posfay-Barbe KM, Wagner N, Gauthey M, Moussaoui D, Loevy N, Diana A, L’Huillier AG. COVID-19 in Children and the Dynamics of Infection in Families. Pediatrics July 2020, e20201576 [full text]
- 22 days of dither and delay on coronavirus that cost thousands of British lives. The Sunday Times 24 May 2020
- Abassi K. Editor’s Choice. Behavioural fatigue: a flawed idea central to a flawed pandemic response BMJ 2020; 370
- The first wave: How Germany’s coronavirus contact tracers helped to ease its lockdown. The Times 26 May 2020.
- Seven in ten testing positive for virus show no symptoms. The Times 29 May 2020.
- What is the diagnostic accuracy of antibody tests for the detection of infection with the COVID-19 virus? Cochrane Review 25 June 2020.
- Coronavirus: Backlash after Trump signals US exit from WHO. BBC News 30 May 2020.
- Murphy N, Boland M, Bambury N, Fitzgerald M, Comerford L, Dever N et al. , A large national outbreak of COVID-19 linked to air travel, Ireland, summer 2020. Euro Surveill. 2020 Oct;25(42):2001624. [full text]
- Health Equity in England. The Marmot Review 10 years on.
- Griffin S. Covid-19: UK’s response has so far cost “unprecedented” £124.3bn. BMJ 2020;369:m2057.
- Don’t let fake news infect the war on Covid-19. The Times 8 April 2020
- Coronavirus: The fake health advice you should ignore. BBC News 8 March 2020
- Coronavirus: The human cost of virus misinformation. BBC News 27 May 2020
- Trump ‘worst offender’ for spreading fake health news. The Times 2 October 2020
- The News Explained. Coronavirus: False Claims About 5G, Inhaling Steam and Skin Colour. Reality Check’s Chris Morris tackles the latest false claims. BBC 3 minute video.
- Coronavirus: Twitter bans incitement to attack 5G towers. BBC News 23 April 2020
- 5G is not accelerating the spread of the new coronavirus. Fullfact 31 March 2020.
- Coronavirus: The seven types of people who start and spread viral misinformation. BBC Trending 4 May 2020
- Charity regulator launches inquiry into church found promoting fake Covid-19 protection kits. The Charity Commission. 26 August 2020.
- Coronavirus in Tanzania: The country that’s rejecting the vaccine. BBC News 6 February 2021
- Covid: Does Tanzania have a hidden epidemic? BBC News 11 March 2021
- Mbeki Aids denial ’caused 300,000 deaths’ The Guardian 26 November 2008
- Trump says he’s seen evidence coronavirus came from Chinese lab. US intelligence agencies say it was not man-made. USA Today 4 May 2020.
- No, COVID-19 Coronavirus Was Not Bioengineered. Here’s The Research That Debunks That Idea. Bruce Lee. Forbes Magazine 17 March 2020.
- Trump threatens to shut Twitter for censuring him. The Times 27 May 2020
- CDC removes false Trump-era Covid recommendations that purported to come from scientists. The Independent 17 March 2021
- Maffetone PB, Laursen PB. The Perfect Storm: Coronavirus (Covid-19) Pandemic Meets Overfat Pandemic. Front Public Health. 2020; 8: 135.
- Wise J. Covid-19: Highest death rates seen in countries with most overweight populations. BMJ 2021;372:n623
- Revealed: Seven year coronavirus trail from mine deaths to a Wuhan lab. The Sunday Times 5 July 2020
- ‘Hero who told the truth’: Chinese rage over coronavirus death of whistleblower doctor. The Guardian. 7 February 2020.
- Covid kids’ book pulped after China complains. The Spectator March 2021
- Cheng VC, Lau SK, Woo PC, Yuen KY. Severe acute respiratory syndrome coronavirus as an agent of emerging and reemerging infection. Clin Microbiol Rev. 2007 Oct;20(4):660-94. doi: 10.1128/CMR.00023-07. [full text]
This website is now completed, although I shall continue to do updates. The following list shows the sections or chapters. Just click on the topic in blue to go to that part of the site.