The coronavirus named COVID-19 is a new virus which has struck the world. It shows that infections do 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. This chapter will examine some of the inequalities and causes of them. It has been separated from the chapter COVID-19. What You Need to Know as it was getting too long and unmanageable.
It will contain the following headings:
- Who is at Risk from COVID-19?
- Social Class and COVID-19
- COVID-19 in the Elderly
- Why More Men Die of COVID-19
- Racial Differences in Vulnerability to COVID-19
- Smoking and COVID-19
- Obesity and COVID-19
- Diabetes and COVID-19
- Heart Disease and COVID-19
- Hypertension and COVID-19
- Liver and Kidney Disease with COVID-19
- Rheumatic Disease and COVID-19
- Psychiatric Illness and COVID-19
- COVID-19 in Children
- COVID-19 in Pregnancy
- 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 I try to have the facts correct at the time of writing and to update as necessary but they may rapidly become out of date.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.
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.
Who is at Risk from COVID-19?
Since the start of the pandemic, we have been subjected to a barrage of statistics, some of which help us to understand risk and some of which are designed to cause alarm. Remember that risk is not certainty. Some people from high risk groups may be fine while others from low risk groups may become seriously ill and even die. Certainty can only be known in retrospect.
Some of the figures to come out in the early days but which still seem to be true are that just over half of all deaths were in people aged 80 or over. Just over 90% were in people with pre-existing diseases. People in their 80s or above are unlikely to have no other illnesses. We have seen that the elderly and those with diseases are by no means the only ones to die. All figures for death rates from COVID-19 should be taken with some circumspection. Not all countries are very good at recording such matters, sometimes understating deaths for political reasons.
In the UK, early figures were incomplete compared with later ones. Death rates in residential homes for the elderly are very high. This is unsurprising as all residents must be significantly disabled to be in such a place but they were often missing from early numbers. While 9% had no pre-existing condition recorded on the death certificate, 11% of people had already been suffering from influenza and pneumonia. On average, people dying from coronavirus also had three other health conditions.1One in ten coronavirus deaths have no underlying condition. Whether we say that 90% of deaths occurs in people with pre-existing conditions or 10% occur in people without them amounts to the same. It is just a difference of emphasis.
Statistics are usually based on death certificates but these may give an incomplete picture. COVID-19 may not be named if there was no formal testing. Other diseases may not be included as fully as they should. There may be pressure from the family to exclude dementia from a certificate as it is seen as pejorative. Obesity is very unlikely to be mentioned.
The following list gives an indication of the frequency of co-existing diseases.2Diabetes sufferers account for quarter of hospital coronavirus deaths
- Diabetes 26%
- Dementia 18%
- Chronic pulmonary (lung) disease 15%
- Chronic kidney disease 14%
- Ischaemic (coronary) heart disease 10%
- Asthma 7%
- Received treatment for a mental health condition 5%
- Chronic neurological disorder 3%
- Rheumatological disorder 3%
- Learning disabilities or autism 2%
There is one other group who are at high risk who are most worthy of mention. This is people who work in health or residential care. A paper from Scotland, based on figures from 1st March to 6th June 2020, showed that 1 in 6 of people who were so ill as to be admitted to hospital were health workers or their families.3Risk of hospital admission with coronavirus disease 2019 in healthcare workers and their households: nationwide linkage cohort study
Before returning to the medical risks of death from coronavirus infection, there are some social and other aspects to consider too.
Social Class and Risk of COVID-19 Death
We hold these truths to be self-evident, that all men are created equal.
These words of Thomas Jefferson, incorporated into the American Declaration of Independence, written by Benjamin Franklin are patently untrue. Furthermore, they were written at a time when there was slavery in the USA and many of the Founding Fathers, including George Washington, owned slaves.
The concept of health inequalities, also known as socio-economic gradients, is well established.4Health and Social Class Throughout history, the upper social classes have had a longer as well as better life. In Liverpool in 1842, the average age at death was 35 years for gentry and professionals but just 15 years for labourers, mechanics and servants. There have been enormous improvements but differences between life expectancy of social classes and genders remain. Although the NHS has removed the ability to pay for medical treatment from reasons that poorer classes do worse, health inequalities through the social classes remain.
Those in lower social classes in the UK have a greater risk of dying from COVID-19. The Office for National Statistics (ONS) said that the most deprived areas of England had suffered 55 coronavirus deaths per 100,000 people, compared with 25 in the least deprived.5Coronavirus death rates twice as high in poorer areas, says ONS The Times also reported that 6Men in low-skilled jobs at higher risk of dying from virus. Care home staff and men in low-skilled jobs are twice as likely to die of coronavirus as the general population, but there is no increased risk for doctors and nurses, according to new analysis. The Office for National Statistics looked at registered deaths among the working age population (ages 20 to 64), finding an overall rate of 9.9 deaths per 100,000 men and 5.2 per 100,000 women. Both men and women working in social care had significantly higher death rates, at 23.4 and 9.6 per 100,000 respectively.
Jobs requiring low levels of skills or qualifications are called “elementary professions”. Male security guards have the highest risk of death with an age standardised mortality of 74 deaths per 100,000, while men in other elementary professions have an age standardised mortality rate of 39.7 deaths per 100,000. Men and women working in social care were also significantly more at risk with rates of 50.1 deaths per 100,000 for men and 19.1 deaths per 100,000 for women. For men, other occupations with high death rates included taxi drivers and chauffeurs, bus and coach drivers, chefs and sales and retail assistants. The outstanding observation here is that those who deal directly with the public are at high risk.
These figures emphasise the increased susceptibility of men compared with women and this will be examined more closely below. Race will also be discussed.
There are a number of reasons why people in lower social classes may be more susceptible to serious or fatal consequences of the disease. They may live in conditions that make it more difficult to keep apart from others, including being in large households. They are more likely to have a job which cannot be done from home. This may include jobs such as working on public transport or in shops which makes it very difficult to avoid others. People in lower social classes are also more likely to smoke7Changing social gradients in cigarette smoking and cessation and more likely to be obese.8Prevalence of obesity in Great Britain The prevalence of chronic diseases is also higher in lower social classes.
COVID-19 in the Elderly
The elderly are very susceptible to death from the disease compared with younger people. When patients have breathing problems, possibly needing oxygen and even ventilation, there is considerable stress on the body. Older people have less reserve than younger people. They are simply less fit. The elderly are also more likely to have other diseases.
A statistician has calculated that an 80 years old male has 500 times the risk of dying from COVID-19 than a man of 20. However, fitness is also important and a very fit man in his 70s may be at lower risk than a sedentary, obese 40-year-old.
Those with dementia are at very high risk. An observational study found that having a faulty gene linked to dementia doubles the risk of a person developing severe COVID-19 even if they have not developed dementia.9APOE e4 Genotype Predicts Severe COVID-19 in the UK Biobank Community Cohort NHS England data put dementia in second place (18%) after diabetes (26%) in the list of COVID-19 comorbidities. Two faulty copies of the APOE e4 gene are found in 1 in 36 people of European descent. This has been linked to an increased risk of Alzheimer’s disease of nearly 15 times in Caucasian people. The risk of severe COVID-19 disease is more than doubled compared to the more common form of the APOE gene e3e3 at 410 per 100,000 versus 179 per 100,000.
This shows that for the number of deaths, age has a major effect and gender too.
It does not seem that the unduly high death rate in the elderly is a reflection of a high rate of infection. They simply cope with the disease less well.
Why More Men Die of of COVID-19
Around 70% of deaths from COVID-19 are in men. If men and women are working in social care, doing the same job, men are 2½ as likely to die from the disease as women. A population study from the Royal College of General Practitioners found that of 3,802 people tested, there were 587 positive results. This represented 18.4% of men and 13.3% of women.10Risk factors for SARS-CoV-2 among patients in the Oxford Royal College of General Practitioners Research and Surveillance Centre More positive results for men may reflect differences in occupations but the numbers do not account for the difference in deaths between men than women.
It seems that the vulnerability of men lies in their hormones. A fascinating paper from Veneto in Italy found that men with cancer had almost twice the risk of being infected with COVID-19 than men without cancer. However, when they looked at men with prostate cancer who were on androgen deprivation therapy (ADT or hormone suppression treatment), they had a four-fold reduction in the risk of getting the disease compared with men without cancer and a five-fold less risk than men with prostate cancer who were not on hormone suppression. The figures were also very impressive in terms of the severity of the disease. Among 79,661 patients in the Veneto region with cancer other than prostate cancer, 312 developed COVID-19 and 57 (18%) died. This compared to 37,161 men with prostate cancer who were not receiving hormone suppression, among whom 114 men developed the disease and 18 (16%) died. However, only 4 out of 5,273 patients receiving hormone suppression developed the infection and none of these patients died.11Androgen-deprivation therapies for prostate cancer and risk of infection by SARSCoV-2:
The glycoprotein spike (S) is important for the virus to enter the cells.
For those who are interested, the reference gives an insight into the cell biology of how the virus gains access to cells.12Androgens May Explain Male Vulnerability to COVID-19 An important protein is called ACE2. This is an enzyme which is very important in the kidneys for controlling blood pressure. However, it is found in many organs. I do not intent to go into the physiology and biochemistry of the renin-angiotensin system. Coronavirus gains entry into the human cell by binding its viral spike proteins to ACE2 and by S protein priming by a protein called TMPRSS2. These proteins are involved in a number of processes including cancer and viral infections. TMPRSS2 is an androgen-regulated gene that is enhanced in prostate cancer where it supports tumour progression. There is also evidence that the same androgen receptor regulates TMPRSS2 expression in other tissues, including the lung. This explains why androgens increase the risk on COVID-19 and why androgens drive prostate cancer and so androgen deprivation helps in the disease.
This then leads to the fascinating idea that men who are developing severe disease should be treated with hormone blocking agents for a month. This will not have long-term effects but it may help them through the disease. There is also a need to control the cytokine storm and an article in The Times notes 13Drug firms are racing to calm the cytokine storm. Of all the drug trials I have seen, none has involved androgen blockade.
Much is made of the racial differences in susceptibility but the very much greater risk of being a man is usually overlooked. In many ways, men’s health needs far more attention. An article in The Lancet was called 14COVID-19 pandemic highlights need for overdue policy action.
Racial Differences in
Vulnerability to COVID-19
Vulnerability to COVID-19
It has been clear from early days that there are racial differences in the death rates from the infection. However, crude figures need to be viewed with caution as they may hide underlying differences such as social class, occupation and other diseases. There is often a tendency to talk of Black and Minority Ethnic groups abbreviated to BAME. It is wrong to lump all BAME people under the one heading as if they are all the same. The Office of National Statistics (ONS) has produced a paper called 15Coronavirus (COVID-19) related deaths by ethnic group, England and Wales: 2 March 2020 to 10 April 2020. The authors did not just present crude figures but took into account a number of geographic, demographic, socio-economic, living arrangements and health measures from the 2011 Census. These features can obscure any association with ethnicity. It is important to adjust for them to quantify the excess risk associated with ethnicity. It found:
- When taking into account age, black males are 4.2 times more likely to die from a COVID-19-related death and black females are 4.3 times more likely than white ethnicity males and females. People of Bangladeshi and Pakistani, Indian, and mixed ethnicity also had statistically significant raised risk of death involving COVID-19 compared with white people.
- However, after taking account of age and other socio-demographic characteristics and measures of self-reported health and disability at the 2011 Census, the risk of a COVID-19-related death for males and females of black ethnicity reduced to 1.9 times more likely than those of white ethnicity. Males in the Bangladeshi and Pakistani ethnic group were 1.8 times more likely to have a COVID-19-related death than white males after similar correction. Females were 1.6 times more likely to die.
- There was no excess mortality of Chinese people compared with white races although later work has suggested a slight increase in risk for Chinese people.
- These results show that the difference in mortality between ethnic groups is partly a result of socio-economic disadvantage and other circumstances, but a remaining part of the difference has not yet been explained.
These figures look at deaths nationwide but those who work in the NHS or in care homes are more likely to be exposed to infection. A paper from the Health Service Journal 16Exclusive: deaths of NHS staff from covid-19 analysed identified 119 cases but 13 were excluded because of failure to confirm information or because the individual was not an active healthcare worker. Looking at staff employed by the NHS, BAME account for approximately 21% of all staff, 20% of nursing and support staff and 44% of medical staff. They also accounted for 63% of deaths in all staff, 64% of deaths in nursing and support staff and 95% of deaths in medical staff. BAME patients also accounting for 34% of patients admitted to UK intensive care units with COVID-19 but only 17% of the UK population. An advantage of looking at doctors or nurses and midwives or ancillary staff as groups is that there is racial diversity but within the groups, they are of the same social class.
An analysis of 3,370 people admitted to intensive care in the UK with confirmed COVID-19 found that 402 (11·9%) were black, 486 (14·4%) were Asian, and 2,236 (66·4%) were white, compared with respective national figures of 3·3%, 7·5%, and 86·0% of the population. These results did not adjust for potential social or clinical factors such as diabetes, and so may be as exaggerated.
The BAME report was updated in June 2020.17Disparities in the risk and outcomes of COVID-19 The analysis took account of sex, age, deprivation, and region, but not underlying health conditions and obesity which are both very important. It does not make any recommendations. It concluded that people from BAME backgrounds are up to twice as likely to die with COVID-19 than those from a white British background but, overall, age and gender were bigger risk factors than ethnicity. Still it is ethnicity that gets all the media attention.
Death rates from COVID-19 were highest among people of Black and Asian ethnic groups. This is the opposite of what is seen in previous epidemics, when the mortality rates were lower in Asian and Black ethnic groups than White ethnic groups. An analysis of survival among confirmed COVID-19 cases and using more detailed ethnic groups, shows that after accounting for the effect of sex, age, deprivation and region, people of Bangladeshi ethnicity had around twice the risk of death than people of White British ethnicity. People of Chinese, Indian, Pakistani, Other Asian, Caribbean and Other Black ethnicity had between 10% and 50% higher risk of death when compared to White British. These analyses did not account for the effect of occupation, comorbidities or obesity. These are important factors because they are associated with the risk of acquiring COVID-19, the risk of dying, or both. Other evidence has shown that when comorbidities are included, the difference in risk of death among hospitalised patients is greatly reduced.
It seems that there is still a racial difference in terms of vulnerability to severe disease from COVID-19 and, as with men, we need to examine why that difference exists. We know that diabetes is a risk factor and that Afro-Caribbean races are twice as likely to develop the disease as white races whilst those from the Indian subcontinent are six-times as susceptible to diabetes. There was also no mention of obesity or hypertension. Black people are also more susceptible to prostate cancer, and considering the relationship to androgen binding, this may be relevant.
A PubMed search for the aetiology of different racial susceptibilities was unproductive except for one article which suggested that the answer may lie along the lines as male susceptibility to prostate cancer and baldness.18Racial Variations in COVID-19 Deaths May Be Due to Androgen Receptor Genetic Variants Associated With Prostate Cancer and Androgenetic Alopecia.
My search of the medical literature was disappointing. An article called 19Is ethnicity linked to incidence or outcomes of covid-19? was also more descriptive than offering an explanation. As with others, it noted social class disparities.
Perhaps it is significant that I have not been able to find any biological explanation for the racial differences. On 21st May 2020, The Times reported 20Covid-19: Being black does not put you at greater risk, researchers say. It said that black and other ethnic-minority Britons are no more likely to die of Covid-19 than white people after taking into account the effects of other illnesses and deprivation. The finding, from research covering almost 24,000 patients admitted to hospital, came from a tranche of study papers released by the Scientific Advisory Group for Emergencies (SAGE), used to inform the government’s decision-making processes. However, the researchers behind the findings cautioned that they were preliminary results, and it was possible they would change when more data came in.
In June 2020, Public Health England issued a report which did confirm that ethnic minorities had worse outcomes from the disease.21Disparities in the risk and outcomes of COVID-19 The analysis took account of sex, age, deprivation, and region, but not underlying health conditions and obesity. It does not make any recommendations. It also noted that age and gender were bigger risk factors than ethnicity.
Another paper used biobank data to analyse the situation.22Ethnic and socioeconomic differences in SARS-CoV-2 infection: prospective cohort study It agreed that much of the ethnic differences in vulnerability to COVID-19 were due to social class and living conditions, but there was some difference which could not be accounted for. I think that there is a difference in racial vulnerability, but nothing like as much as the crude figures would suggest.
Research at the Francis Crick Institute in London has identified dozens of proteins in the blood that appear to predict how a patient is likely to fare. The hope is that these biomarkers could be analysed to identify those at most risk and so prioritise them for treatment. I expect that analysis of this data may show why there are racial differences in susceptibility but we need to wait for the results.
Many people seem eager to make political capital from the racial differences in susceptibility. Instead we must be objective. The fact that more than twice as many men as women die from the disease goes almost unnoticed. If it were the other way round, I am sure it would be a different matter. There have even been suggestions that BAME staff in the NHS should have been exempted from working directly with COVID-19 patients. No one has suggested exempting men or staff who are obese but they are at greater risk.
Smoking and COVID-19
Considering the vulnerability of the lungs in this coronavirus infection, it should come as no surprise that smokers have a poorer outcome. Smoking also increases background inflammation that we have seen is behind the cytokine storm. I am using a single article as my source. It is called 23Prevalence, Severity and Mortality associated with COPD and Smoking in patients with COVID-19: A Rapid Systematic Review and Meta-Analysis. Hence it is quite far-reaching considering that this is a recent disease. Their main conclusions were:
- Compared to former and never smokers, current smokers were at greater risk of severe complications and higher mortality rate.
- Although COPD prevalence in COVID-19 cases was low in current reports, COVID-19 infection was associated with substantial severity and mortality rates in COPD.
- Smoking e-cigarettes or vaping also increases the risk of severe disease, although the exact level of risk does not seem certain yet. The same is probably true of tobacco/waterpipe (shisha) smoking. All forms of smoking have an adverse effect on the lining of the lungs called endothelial function.
The charity Action on Smoking and Health (ASH) says that since the pandemic hit, more than one million people have given up smoking.24Coronavirus: Smokers quit in highest numbers in a decade Of those who had quit in the previous four months, 41% said it was in direct response to coronavirus. About 7 million people in the UK in total were smokers in 2019. On average, 5.9% of surveyed smokers quit per year since 2007. In the year to June 2020, 7.6% of smokers taking part in the survey quit. This is almost a third higher than the average and the highest proportion since the survey began more than a decade ago.
Obesity and COVID-19
From an early stage, it became clear that obesity increased the risk of COVID-19 infection. An article from the USA called 25Association of Obesity With Disease Severity Among Patients With COVID-19 showed that severe obesity, defined as a BMI in excess of 35, was associated with an increased risk of admission to intensive care. Obesity with a BMI in excess of 30 along with a history of heart disease, were independently associated with the use of invasive mechanical ventilation. People with a BMI of 30 or above are at significantly increased risk for severe COVID-19, while a BMI of 35 and higher dramatically increases the risk for death.26How important is obesity as a risk factor for respiratory failure, intensive care admission and death in hospitalised COVID-19 patients? Results from a single Italian centre
The previously mentioned article 20Covid-19: Being black does not put you at greater risk, researchers say also noted that among younger people, obesity raises the death rate four-fold, and for those in their fifties it more than doubles it. According to a separate analysis of almost 20,000 patients, the fatality rate among those under 40 who are admitted to hospital is about 3% for people who are not obese, but 12% for those who are. Among those aged 55 to 65, the figures are 16% and 35% respectively. For people are in their seventies, however, their weight appears to be less significant.
We have previously noted the problem of the cytokine storm. People with obesity have a raised level of low-grade chronic systemic inflammation. It is associated with the development of atherosclerosis (hardening of the arteries), type 2 diabetes, and hypertension (high blood pressure). These are well known conditions that adversely affect the outcomes of patients with COVID-19.27COVID-19 and the role of chronic inflammation in patients with obesity
Obesity seems to be a major factor that increases risk in COVID-19 infection. An obese person who is on the back being mechanically ventilated has an enormous amount of fat pushing up on the diaphragm and a heavy chest wall. In addition, there are problems of inflammation that aggravate the disease. As levels of obesity soar, especially but not exclusively in developed countries, an article called 28The Perfect Storm: Coronavirus (Covid-19) Pandemic Meets Overfat Pandemic captures the problem.
Being obese is a problem for the young.29Obesity Can Shift Severe COVID-19 to Younger Age Groups. Obesity is a major factor when young people require hospital admission for the disease. Those with a BMI above 35 have a more than seven-fold increased risk of requiring mechanical ventilation compared to those with a BMI below 25, even after adjusting for age, diabetes, and hypertension.30Obesity Link to Severe COVID-19, Especially in the Under 60s
When Prime Minister Boris Johnson returned from hospital, including some time in intensive care because of coronavirus infection, he declared that there would be much more attention to fighting obesity, both on the personal and the national level.31Boris Johnson to launch war on fat after coronavirus scare. The Times estimated that when he was admitted to hospital, his BMI was 36.
When I see pictures on television of nurses or carers in residential homes or when I visit hospitals, I am appalled at the prevalence of obesity. Doctors do not seem to have the same problem and obesity appears to be much more common among female than male staff. I believe that those involved with healthcare should set an example in terms of lifestyle and healthcare professionals who smoke or who are obese undermine the public health message. Obesity is an enormous problem in the developed world and it has increased vastly in the past 50 years. There is much more in the chapter Exercise, Obesity and Diets for Weight Loss as well as the other chapters in the section on nutrition.
We need to take the problem of obesity seriously. 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.32Highest death rates seen in countries with most overweight populations. This finding is spectacular.
Diabetes and COVID-19
The figure we saw earlier of 26% of deaths occurring in people with diabetes is very high compared with a prevalence of 5% for diabetes in the general population. Since then, a figure of 30% of deaths occurring in diabetics has been quoted. Back in the 1970s, just 1 or 2% of the population had diabetes. This sharp rise to 5% is largely due to the increase in type 2 diabetes associated with obesity but it does not account for all of it and even type 1, which is not associated with obesity, is more common. Diabetes is not spread uniformly throughout all age groups. It gets more common as age advances and it is often associated with overweight or obesity which are also risk factors for death from COVID-19. Most of those admitted to hospital with COVID-19 and diabetes have type 2 diabetes. This is rather more common than type 1 and tends to affect older people and those who are overweight or obese. Interpretation of true risk is much more complex than cursory examination would suggest.33Covid-19: risk factors for severe disease and death
Poor control of blood glucose has been shown to be associated with poor outcomes in this pandemic and in previous ones.34COVID-19 and Diabetes: Knowledge in Progress We know that older patients with chronic diseases, including diabetes, are at higher risk for severe COVID-19 and mortality. The paper discusses that diabetes is a chronic inflammatory condition with multiple metabolic and vascular abnormalities that can affect the response to infection. High glucose and insulin resistance promote increased synthesis of the pro-inflammatory cytokines and oxidative stress. This inflammatory process may be the reason that diabetics have so much worse outcomes.
We have seen the problem of the cytokine storm. Diabetes is generally a major risk factor for the development of severe pneumonia and sepsis due to virus infections, and data from several sources suggest the risk for death from COVID-19 is up to 50% higher in people with diabetes than those without. Infection leads to release of stress hormones and in diabetics this aggravates poor diabetic control. For diabetics, it seems that poor control of blood glucose increases risk35Largest Study to Date Links Glucose Control to COVID-19 Outcomes and close control of blood glucose in those admitted to hospital is mandatory. There is also evidence that the disease may affect the insulin-producing cells of the pancreas.
Both people with type 1 and type 2 diabetes are at risk. They do not seem to be more susceptible to catching the virus, but if they do, there is an approximately two-to-threefold higher risk of mortality from the infection. The highest risk is in type 1 diabetes, even after adjustment for factors such as sex, ethnicity, deprivation, and pre-existing diseases. However, the number of people with all types of diabetes dying in hospital from coronavirus under the age of 40 is very small, suggesting the risk for younger people is considerably lower. Those with poor control of their diabetes were at greater risk. Underweight is also a problem. Those with both types of diabetes who were underweight with a BMI below 20, had approximately double the risk of death from COVID-19 compared to those with a BMI of 25 to 30. Severe obesity with a BMI above 40 increased the risk by 2.15 for type 1 and 1.46 for type 2 diabetes, compared with those with a BMI of 25 to 30.36Deep Dive Quantifies Risk of COVID-19 Death in Both Diabetes Types
Heart Disease and COVID-19
Severe illness and death is more common when patients with heart disease get COVID-19 infection. About 10% of patients with cardiovascular disease who contract COVID-19 will die, compared with only 1% of patients who are otherwise healthy. This is illustrated by an article from Harvard.37How does cardiovascular disease increase the risk of severe illness and death from COVID-19? Again, it seems to be a problem of inflammation. Some patients appear to be having a heart attack but are really suffering from marked inflammation of the heart muscle, called myocarditis. The electrocardiogram (ECG) in these patients shows changes suggestive of a major heart attack, and blood tests reveal elevated enzymes that are released when heart muscle is damaged. The heart muscle becomes weak, and dangerous heart rhythms may develop.
The myocarditis may be due to a direct effect of the virus on the heart muscle, or to an overactive immune response to the virus.38Potential Effects of Coronaviruses on the Cardiovascular System: A Review Increased risk has also been seen in people with high blood pressure (hypertension) and coronary artery disease (CAD), though it is not clear why. Certain medications for blood pressure and heart failure, called angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) will be discussed later.
Another article confirmed that not only may heart disease be a risk factor for more severe COVID-19, but having the infection may increase the risk of a heart attack. Some of the enzymes that are raised in a heart attack are also raised in the disease and so it is may be necessary to ignore these results if there are no ECG findings suggestive of heart disease.39Covid-19 and cardiovascular disease It is an area fraught with danger.
Hypertension and COVID-19
A number of reviews have said that hypertension (raised blood pressure) is associated with an increased risk for severe disease and death in COVID-19 infection. A paper examining data from various sources concluded that “This pooled analysis of the current literature would suggest that hypertension may be associated with an up to 2.5 fold higher risk of severe or fatal infection, especially in older individuals”.40Hypertension in patients with coronavirus disease 2019 (COVID-19): a pooled analysis In the discussion at the end, they note that this is only apparent in patients over 60 years old.
A systematic review, meta-analysis and meta-regression came to a similar conclusion.41Hypertension Is Associated With Increased Mortality and Severity of Disease in COVID-19 Pneumonia.
There are still questions to be answered about the true risk of hypertension with this infection. Many people have hypertension as an isolated disease. Many more have other conditions such as diabetes or obesity, or both. Are they all equally at risk?
The other important question is if it is the diagnosis of hypertension that makes the difference or the level of high blood pressure. Most people with hypertension are on drug treatment and the blood pressure is reduced to a normal level. Are they still at risk? Prolonged and uncontrolled hypertension will cause damage to the heart and circulation. It seems plausible that this is the mechanism of vulnerability. If this is so, then a person with a diagnosis of hypertension who has well controlled blood pressure and no cardiovascular damage, should not be at risk.
The answer seems unclear, but I think that it is the raised blood pressure that is the problem. A paper from China confirms that raised blood pressure is a risk factor and people must not stop their treatment for their blood pressure. ACE inhibitor and ARB class of drugs that will be discussed later, probably give protection.42 Association of hypertension and antihypertensive treatment with COVID-19 mortality All experts say, “Keep taking the tablets”.
Liver and Kidney Disease with COVID-19
Considering what has come before, it will come as no surprise that liver and kidney disease also increase the risk of the infection. An early systematic review and meta-analysis found that disease of these organs increased the risk of serious disease and death considerably. Numbers in this review were rather small but the increased risk was large.43Prognosis of COVID-19 in Patients With Liver and Kidney Diseases
In a study, patients with liver disease had 2.8 times the mortality of those without liver disease. For patients with cirrhosis, the relative risk of mortality compared with those without liver disease was 4.6. Liver patients also had substantially more other diseases, and a large proportion had hypertension (68%) and diabetes (48%).44Clinical Characteristics and Outcomes of COVID-19 Among Patients With Pre-Existing Liver Disease in United States
An article looking at patients with chronic kidney disease found even more striking results. The pneumonia-related mortality rate in such patients seems to be 14 to 16 times higher than in the general population.45Chronic kidney disease is associated with severe coronavirus disease 2019 (COVID-19) infection
Rheumatic Disease with COVID-19
We have seen that the diseases that put patients at high risk if they should develop COVID-19 infection, are also diseases with chronic inflammation. The rheumatic diseases often have quite marked inflammation. The classic example is rheumatoid arthritis. This, along with many other rheumatic diseases, is classified as autoimmune as the body’s overactive immune system is responsible for the damage. Osteoarthritis does not come into this category. The autoimmune diseases are often treated with drugs that dampen down the immune system. The question is if this makes the individuals more susceptible to infection or if it helps to reduce the cytokine storm.
Until further evidence emerges, it may be cautiously recommended to continue steroids and other disease-modifying agents (DMARDs) in patients receiving these therapies.46Rheumatologists’ perspective on coronavirus disease 19 (COVID-19) and potential therapeutic targets
Psychiatric Illness and COVID-19
I have called this section psychiatric illness rather than mental health because too often people talk about mental health when they really mean anxiety or sadness that is a normal response to the issues in life. If a person’s job is a risk and he fears for his ability to pay the bills and he is anxious, this is a normal response. If someone is bereaved or a relationship is over and that person is sad, that is normal. Calling such responses mental health belittles the severe psychiatric problems that may even result in suicide.
We have seen that those with dementia have a high mortality from COVID-19. In addition, it seems that those with a psychiatric illness of almost any kind are more likely to develop the disease but also that after the disease, people are at risk of developing true psychiatric illness. 47 Bidirectional associations between COVID-19 and psychiatric disorder: This is not simply the lethargy and “brain fog” that may accompany long-Covid. The paper says that 1 in 5 COVID-19 patients are diagnosed with a psychiatric disorder such as anxiety or depression within 3 months of testing positive for the virus. The study also showed that having a psychiatric disorder independently increases the risk of getting COVID-19. The psychiatric conditions of pathological anxiety and depression should not be confused with normal worry and sadness.
Between 14 and 90 days after being diagnosed with COVID-19, 5.8% of patients received a first diagnosis of psychiatric illness. Among patients with health problems other than COVID, 2.5% to 3.4% of patients received a psychiatric diagnosis. The risk was greatest for anxiety disorders, depression, and insomnia.
Older COVID-19 patients had a two- to threefold increased risk for a first diagnosis of dementia. Individuals with a psychiatric diagnosis were about 65% more likely to be diagnosed with COVID-19 in comparison with their counterparts who did not have such illness.
Disorders That Were Followed 14 – 90 Days Later by a First Psychiatric Diagnosis
|Other Respiratory Infections||3.4%|
|Stones in Urinary Tract||2.5%|
COVID-19 in Children
We may expect to find that children are very vulnerable to the infection, especially the very young with an immature immune system. However, the opposite is true. Children represent about 2% of known cases.48COVID-19 in children: analysis of the first pandemic peak in England. The number of children who have died of the disease is in single figures.
At first, figures seemed to suggest that children are no more likely to become infected than adults, despite the difficulties in getting them to take the necessary precautions. It now seems that they may be less contagious than adults too. Perhaps as few as 20% with infection show symptoms and this may give a high risk of them spreading the disease to others with no one knowing that they are contagious.49Children With COVID-19 May Be Less Contagious Than Adults, Two UK Epidemiologists Say Fears that children should not return to school in case they catch the disease which has killed so many are unfounded unless the child has serious underlying problems such as being immunosuppressed after a kidney transplant or recent therapy for leukaemia.
A case control study from Italy found that children are not more likely to be asymptomatic carriers of the disease.50Frequency of Children vs Adults Carrying Severe Acute Respiratory Syndrome Coronavirus 2 Asymptomatically The researchers studied 83 children and 131 adults admitted to the paediatric and adult emergency departments at a hospital in Milan for non-infectious conditions and with no symptoms or signs of COVID-19. Only one child (1.2%) tested positive for COVID-19, compared with 12 adults (9.2%), yielding an odds ratio of 0.12 compared with adults. These numbers are small but reassuring.
Unsurprisingly, older children are more like young adults than younger children in terms of their ability to spread the disease. Their hormones are like adults. Therefore, they need to be more diligent in adhering to the rules that apply to adults. If it is possible to get young children to do as they are told, it should be possible for teenagers too.
There is a rare complication that seems specific to children. They can present with an inflammatory shock syndrome that is similar to Kawasaki syndrome, a rare condition that can cause inflammation of arteries. In London, eight children with hyperinflammatory shock, showing features similar to atypical Kawasaki disease, presented within 10 days to the Evelina London Children’s Hospital. Seven of the children needed mechanical ventilation to stabilise the circulation, although most of them had no significant respiratory involvement.51Novel Inflammatory Syndrome in Children Possibly Linked to COVID-19 Most children responded well to treatment but one died when the arterial problem caused a massive stroke. This remains a rare occurrence and must be kept in perspective.
According to a medical website, Professor Russell Viner, president of the Royal College of Paediatrics and Child Health, said: “Children are around half as susceptible to COVID-19 as adults and very rarely get symptoms and almost never get severely ill. The evidence from many countries around the world is that transmission in schools is very low. Most children catch COVID-19 from adults in their household. Individual children can pass the virus on and we will inevitably see occasional outbreaks in schools, especially if there is a rise in infection rates in the general population. Reactive school closures have a place in stamping out local spikes in this pandemic, but this must be evidence-based. The risks to children of keeping schools closed are high, and schools should be reopened again as soon as possible.” This has happened and the Government is keen to keep places of education open.
At the end of August 2020, Professor Chris Whitty, Chief Medical Officer, cited a study that looked at 260 hospitals in England, Wales and Scotland.52All children who died of Covid-19 were already seriously ill. Of the 69,500 patients admitted with proven COVID-19 in the first six months of the year, there were 651 or 0.9% who were under 19 years of age. He said that six deaths of minors were recorded, of which three were new-born babies with other severe health problems. The other three were aged 15 to 18 years old and also had “profound health issues”. The term “profound co-morbidities” does not include asthma or even cystic fibrosis, but serious life-shortening illnesses.
This should be very reassuring for those who were worried about sending their children back to school. It seems that teachers are more likely to spread the disease than the children.
COVID-19 in Pregnancy
Illness in pregnancy is always worrying and this is new and uncharted territory. We know that a number of viruses can have serious consequences in pregnancy. They include German measles (rubella) and chicken pox (varicella). The disease may also be more severe if contracted in pregnancy. However, so far it seems from observations in China and elsewhere, that COVID-19 infection in pregnancy does not cause serious problems for either the mother or baby.53Pregnancy Doesn’t Pose Higher Risk for Severe COVID-19 Nevertheless, to be safe, the Royal College of Obstetricians and Gynaecologists has issued guidance about it.54Coronavirus (COVID-19) infection and pregnancy
Low risk is not no risk as shown by a prospective cohort study using the UK Obstetric Surveillance System.55Characteristics and outcomes of pregnant women admitted to hospital with confirmed SARS-CoV-2 infection in UK Of the 427 patients admitted to hospital, 41 (10%) needed respiratory support in a critical care unit, and 5 (1%) women died. Of the 5 deaths, 3 were as a direct result of complications of COVID-19 and 2 were from other causes. Almost all were in the second half of pregnancy and most in the last trimester (3 months). Only 12 (5%) of the babies born tested positive for COVID-19, 6 of them within the first 12 hours after birth. The authors said that most women do not have severe illness and that transmission of COVID-19 to infants is uncommon. They also support guidance for continued social distancing measures in later pregnancy. No mention is made of complications on the babies.
Black and minority ethnic (BAME) women were over-represented with 25% being Asian and 22% black. This was the part of the paper which caught the headlines. The Royal College of Midwives noted that even before the pandemic, women from black, Asian or ethnic minority backgrounds were more likely to die in and around their pregnancy or to have serious complications. Another statistic of note is that 40% of those patients were aged 35 or over and one third had existing health conditions. What particularly struck me was that 70% were overweight or obese. We know from previous reports that 40% of complications in pregnancy occur in women who are overweight or obese. We know that obesity is a risk factor for COVID-19 as is diabetes. Even fairly young women who are obese may have type 2 diabetes and it is also a risk factor for gestational diabetes which is diabetes of pregnancy. This has all the risks of diabetes for mother and baby but it usually disappears after delivery. However, anyone who has had gestational diabetes is at risk of developing type 2 diabetes later. Once again, obesity is an important and avoidable risk factor.
An analysis conducted by the Royal College of Midwives and the Royal College of Obstetricians and Gynaecologists56Maternal, Newborn and Infant Programme: Learning from SARS-CoV-2-related and associated maternal deaths in the UK found that at least eight women died during or shortly after pregnancy from COVID-19 infection. They were mostly from ethnic minorities. The women represented half the maternal deaths during March, April and May. Another two women had the virus at the time of death although death was recorded as being from other causes. There were four maternal deaths from suicide and two from domestic violence during the period. The chief executive of the Royal College of Midwives said, “Isolation during the pandemic has been very difficult for some women during their pregnancy and after birth. That is why we must ensure that they are able to access appropriate community-based care from midwives, health visitors and perinatal mental health teams. While we welcome the greater use of technology to support pregnant women, it is not a wholesale substitute for face-to-face support. This is particularly true for picking up on safeguarding issues, including women at risk of domestic abuse.”
In view of all this, COVID-19 infection in pregnancy is regarded as a reason for concern. Unless the evidence changes, when we have a vaccine, pregnant women will be offered it and some of the subjects in phase 3 trials have been pregnant.
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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.
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For those who are keen on the science. Some may get lost in the technical terms and concepts. Not available in full without charge
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Public Health England examines the evidence about weight and COVID-19 risk
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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.