Categories
Covid-19 Mortality Outcome

Obesity and Covid-19: the challenge is growing

That obesity is a risk factor for doing badly following infection with Covid-19 is well known.  Recent data has given some more precise estimates of the risks and also what the explanations might be. More relevant is the concern that health services should be doing more and, as I will explain at the end of this post, is that health services have not learned the lessons from Hurricane Katrina (and on which I made my first public contribution this week to this debate!)

How is obesity defined?

  • I am sure this is well known to readers of this blog!
  • There are accepted cut offs based on body mass index (BMI) which is calculated from weight (measured in kg) divided by height squared measured (in metres).
  • The following thresholds are used (which I have translated into the nearest stone equivalent) for a women of average height 5ft 3 inches and a man 5 ft 9 inches.
  • From this  a male of this height with a weight over 14 stone is considered obese

Waist hip ratio

  • Apart from BMI, epidemiologists also measure the ratio of waist to hip circumference (WHR)
  • The waist should be smaller than the hips but the cut off for normality varies between the genders-women have smaller waists.  
  • Excess weight around the waist is consider as ‘central obesity’ and is more hazardous for health
  • A report in the British Medical Journal this September reviewed all the major research and found importantly that a central obesity is a predictor of dying prematurely from all causes after allowing for BMI
  • In other words, both body weight and body shape are important   

Obesity and Covid-19: risk of becoming infected

  • The UK Biobank Study published this month data from a large population survey of over 500,000 people who had had different measures of obesity and linked these data to the national laboratory Covid-19 test database
  • The results show a 60% greater risk of catching infection in obese people compared to people of normal weight.
  • They found a similar increase in risk looking at waist circumference 
  • What was even more interesting was that the risk of Covid-19 from obesity was greater in people from black and other ethnic minorities (BME)
    • As an example an obese (BMI>30) person from the BME community will have twice the risk of being CoVid-19 positive than a white person with the same BMI
    • This is not due to the rate of infection in those from  BME groups being higher anyway: the rate of infection in non-obese (BMI<25) was the same in both white and BME groups

Obesity and risk of severe disease

  • On top of an increased risk of getting the infection there are loads of studies showing that people who are obese have a greater chance of being admitted to hospital,  and once admitted ending up in an intensive care unit
  • Below is the up to data information of Covid-19 admissions to all the ICU’s in the UK
  • As shown compared with the background population, more  obese and severe obese patients are admitted to intensive care 
  • Once admitted obese and severe obese patients are at a substantial increased risk of dying. A recent summary of several studies showed that mortality rates approached 70% in the most obese patients admitted to ICU’s
  • Having an unhealthy waist hip ratio, adds to those risks for example leading to a doubling of  the chances of needing hospitalisation

Why does obesity make Covid-19 worse?

There are many theories but these include a mixture of plausible explanations

  • Obese people have a constant low grade of inflammation in their bodies even when they are well, but this gets worse when they have an infection
  • The virus stays longer in the organs such as the lungs as the immune system struggles to get rid of the virus 
  • Obese people make more of a protein called ACE2 which stays on the surface of lung cells and it is that protein which is thought to be what the spikey bit of the Covid-19 virus sticks to
  • Obese people have fewer of the healthy bacteria, we all have, hanging around in their guts and lungs, and this interferes with our natural immunity 
  • Lung capacity is reduced, the more obese people cannot expand their lungs so well 
  • It can be more technically challenging to treat obese people in ICU’s
  • Obese people have greater problems with  diabetes and high blood pressure 

Why am I covering this topic now?

  • The data are overwhelming that obesity, and its disease partners diabetes and high blood pressure, increase the risk of Covid-19, of being admitted to hospital with Covid-19, of ending up in intensive care and of dying
  • We are also faced, as a result of the pressure of managing acute Covid-19,  with a major reduction in routine health care especially in primary care and the putting on hold the preventive health  care that identifies those who have these health issues and actively manages them.
  • Following Hurricane Katrina, general health deteriorated in the population because of diversion of health care to manage the acute problems
  • These recent data from a global survey of health care professionals highlight the great impact of Covid-19 on health care in general, and these easily managed problems in particular
  • The point is that unless there is a return to active prevention programmes, health screening and regular primary care contacts, obesity and its consequences will go unchecked making the outcomes of Covid-19 much worse.
  • I made these points at a workshop I attended this week!
  • Hopefully someone will listen!

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Categories
Covid-19 Mortality

Vitamin D: it may have helped Donald Trump but what is the evidence?

Amongst the cocktail of old and new drugs pumped into President Trump was vitamin D.  There is no shortage of research with over 200 scientific papers published on the potential role of vitamin D in this disease this year; with much of the evidence emerging in the last few weeks.  In this post I address 2 separate but related questions about this vitamin: (i) does it protect against getting the infection? and (ii) is it useful as a treatment for the infection?  I hope you find the conclusions interesting!

What is vitamin D

  • Vitamin D is a chemical that is found naturally in many foods 
  • By far and away our largest source of vitamin D is our ability to  manufacture it in the body by the action of sunlight
  • Interesting fact is that it is cholesterol that is changed by sunlight to vitamin D, a chemical which is very similar 
  • There are two main forms of vitamin D: D2 and D3 (not sure what happened to D1!)
  • D2 is found in plant oils (and mushrooms)  and D3 is found in animal fats, milk etc.  It is the D3 version that is produced by sunlight
  • Vitamin supplements bought over the counter may contain either D2 or D3
  • Both forms of vitamin D are then converted in the body (in two steps actually: the first in the liver and the second in the kidneys) into the form where it is active  

How much vitamin D do we need?

  • The good news is that vitamin D is stored in the body (in fat tissue) and has a ‘shelf life’ of at least a year, so we don’t need to have vitamin D every day
  • There is a debate as to how easy it is to get all the vitamin D we need from sunlight alone, and of course it depends on how much of the body is exposed and how bright the sun
  • If relying on sunlight, the amount of time needed to get the recommended daily amount of 1000 IU* (stands for international units), varies from 30 minutes to 2 hours
  • You would need to eat 5 cans of tuna to have the same intake!
  • You can have too much vitamin D, very unlikely from diet or sunlight but it is possible if you have an excessive intake of vitamin D supplements

*some have suggested that 400IU is enough

Why do we need vitamin D? 

  • For years the main function of vitamin D was thought to be in giving healthy bones
    • Deficiency in childhood leads to weak bones that fracture, including the disease rickets 
    • Deficiency in adults also affects bones and leads to bone diseases such as osteoporosis
  • We thought that with our knowledge of vitamin D rickets from the Victorian period would have disappeared; it has not!
  • Increasingly it is now known that vitamin D is also needed for the optimum functioning of the immune system and the prevention of inflammation
  • There is some evidence that people who are deficient in vitamin D are at risk of several disorders including heart disease, cancers and some auto-immune diseases
  • Also, well known for years is that vitamin D has a crucial role in the body’s defence against viral infections
  • Prior to the Covid-19 pandemic it had been suggested that vitamin D deficiency could increase the risk of contracting flu in an influenza pandemic, but the data are conflicting 

 

Who is at risk of vitamin D deficiency?

  • The list is fairly obvious from what we know about the key role of sunlight exposure to produce vitamin D
  • Risk groups are those who do not get sufficient exposure to the sun and include 
    • Ethnic and cultural groups, such as South Asian women and ultra-orthodox Jews, who cover themselves 
    • People who live in overcrowded urban conditions
    • Older people who do not go outdoors sufficiently
  • One concern is that with increasing advice to avoid sunlight to protect against skin cancer the pendulum may have swung too far

How is vitamin D deficiency diagnosed?

  • Given the above it is obviously important to know if someone is vitamin D deficient
  • The only way is to do a blood test, which can be done on a finger prick 
  • It is not necessary for people not  in a high risk group to be tested routinely 

How common is vitamin D deficiency?

  • The rates of vitamin D deficiency are startlingly high in UK and North American cities
  • There ae several studies showing high rates of  more than 50% in residents of care homes (relevant given the outbreaks of Covid-19)
  • Similar high rates are found in elderly people living at home 
  • In many studies in the UK up to  50% of BAME (Black, Asian and Minority Ethnic) groups in England are vitamin D deficient

The evidence that vitamin D is important in Covid-19

There are several questions which can be addressed:

  1. Are people who are vitamin D deficient at increased risk of contracting Covid-19 infection?
  2. Will vitamin D supplements protect against catching Covid-19? 
  3. Are people who are vitamin D deficient at increased risk of having a more serious illness if they contract Covid-19 infection?
  4. How useful are vitamin D supplements as a treatment for Covid-19? 

Are people who are vitamin D deficient at increased risk of contracting Covid-19 infection?

  • The circumstantial evidence is compelling given for example the high rates of transmission and infection in groups known to be at high risk of vitamin D deficiency 
    • Care homes
    • Groups in Western countries living in overcrowded conditions
    • South Asian groups in the Northwest of England
    • Slum areas in India
  • There are some direct data suggesting that this link might be real: a  recent study from Chicago showed that the rate of Covid-19 was twice as high in people who were vitamin D deficient as in those who had normal levels 
  • By contrast a very large population study from the UK (Biobank) did not show a relation between vitamin D levels in the blood and being tested positive for Covid-19.  
  • That study has been criticised on the basis that that the vitamin D was measured in blood samples that were 15 years old

Will vitamin D supplements protect against catching Covid-19?

  • The short answer is ‘we don’t know’!
  • To examine this, we would need very large clinical trials of thousands or tens of thousands either:
    • who had been tested and then, if deficient, randomised to take vitamin D supplements or not.  This is almost certainly unethical
    • general population sample randomised to be given a vitamin D supplement or not, independent of whether they were deficient (ie a similar trial design to testing the value of a vaccine)
  • with then both groups being followed up to ascertain their chances of catching Covid-19.  The logistics of undertaking such studies are formidable 

Are people who are vitamin D deficient at increased risk of having a more serious illness if they contract Covid-19 infection?

  • Again, there is a large amount of circumstantial evidence.  Groups whom we might expect to be vitamin D deficient have much higher mortality risks from Covid-19 including:
    • Elderly people
    • Care home residents
    • Those South Asian and other communities that have less sunlight exposure
  • The ‘cytokine storm’, the body’s over-reaction of its entire immune system to infection which has been considered responsible for a high proportion of Covid-19  deaths, may be related to vitamin D deficiency 
  • A study in Italy showed that the chances of having a bad respiratory illness if admitted with Covid-19 was increased in those with vitamin D deficiency 
  • Similarly, a study last week from the UK found a threefold increase in the risk of being admitted to ICU if the patient was vitamin D deficient

How useful are vitamin D supplements as a treatment for Covid-19?

  • In a Lancet medical journal article in August, the case was put forward for undertaking clinical trials of  using vitamin D as a treatment.  Such clinical trials are now underway
  • The first trial has now been reported from Spain.  It was not the greatest clinical trial in terms of its quality and more information is needed but:
    • Of the 50 patients randomised to receive vitamin D only 1 needed admission to ICU
    • Whereas of the 26 patients randomised to receive placebo, 13 needed admission to ICU
    • It is not known if these patients were deficient in vitamin D before they became infected
  • And then of course there is Donald!

Conclusions

  • From a public health perspective, even before the Covid-19 pandemic, there is overwhelming evidence that there are unacceptably high levels of vitamin D deficiency in some population groups
  • These groups are the same as those who have more Covid-19, and more serious outcomes if they catch the disease
  • There is no evidence, nor does it seem likely, that for people who are not deficient taking extra vitamin D would protect against catching Covid-19
  • More clinical trials are needed to see if vitamin D is useful as a treatment both in the general population and more usefully in those who are deficient 
  • At the very least those who are diagnosed with Covid-19 infection should have their vitamin D levels measured

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Categories
Mortality Outcome transmission

Is there any evidence to suggest that Covid-19 is becoming less severe ?

Although in the USA and many other countries deaths from Covid-19 are not showing any major decline, deaths in Europe including the UK have been falling steadily since the peak of the epidemic in April.  In contrast to this positive news about falling death rates, there is no sustained slowing in the number of new cases detected.  This raises the question that possibly the infection may be becoming less serious as time passes.  In this post, I take a detailed look into the available data, and consider whether there is any support for such a possibility.

How large is the decline in deaths? 

The graph below shows the decline in total reported deaths from Covid-19 in Europe, which has occurred  since the peak in late March/early April (the blip in June was probably due to changes in recording deaths)

 
Source: https://www.statista.com/statistics/1102288/coronavirus-deaths-development-europe/

How does the  decline in deaths compare with the rates of infection?

  • The decline in number of deaths could, of course,  be explained by a similar drop in the numbers who are infected.
  • I have used the official UK data to show the patterns of  decline in both deaths and number of cases. 
  • To make the comparison easier, the figures in the graph below are the percent of deaths and cases  at each of the 4-week periods relative to the peak (which I called 100%).  Thus a figure of 50% percent for any 4-week period means that the number was half that of the peak
  • The graph shows that relative to the peak, deaths are falling at a greater rate than the fall in the number of cases.
  • However before concluding that the virus is becoming less severe, there are a number of other explanations that should be considered first.

What information do we need?

  • What is really needed is the ‘case fatality’ rate.  This is the proportion of people who develop the disease who then die.
  • Thus, a case fatality rate of 50% means that half of the people who develop Covid-19 are dying from the disease 
  • In order to calculate the case fatality rate, we need accurate data on the number of new cases. I have discussed this in my last post*. On one estimate, only about 1 in 10 cases in England are actually diagnosed and recorded
  • The impact of the under-reporting on the case fatality rate is large. For example, in the UK today (6th August) there have been 308134 cases and 46413 deaths.  At face value this suggests a case fatality rate of 15%.  That is ludicrously high.  We do not know what the true figure is, with the best available data being from China suggesting a rate of under 1%

*https://makingsenseofcovid19withs.com/2020/08/03/recent-peak-of-cases-in-manchester-neither-new-nor-unexpected/

Could the trends still be accurate?

  • The trends might be accurate even if the absolute numbers of cases are not
  • However, there is a problem given that at the beginning of the epidemic fewer people got tested, so more cases would have been missed 

What about other approaches to measuring severity?

  • Of course, death is not the only marker of how bad the infection is.  How many are admitted to intensive care is also a useful measure. 
  • That number though depends on how many intensive care beds are available and the threshold for admitting a person
  • Data from the UK indeed show a steady decline in the number of admissions to ICUs

Source: https://www.cebm.net/covid-19/covid-19-declining-admissions-to-intensive-care-units/

If the decline in deaths and ICU admissions is real, what are the explanations?

There are a number of possible explanations for the decline in the severity profile and deaths.  These are:

  • Relatively fewer older people, and relatively more younger people, are getting the infection, probably because of greater protective behaviours in the older age groups
  • Similarly, those with underlying health problems will also be avoiding risk more than those without
  • The treatment for those most seriously affected is improving.  This is indeed the case.  At the beginning of the epidemic only around 50% of cases admitted to ICUs survived in the UK.  By the end of May this had increased to 70% and is probably higher today.

Is there any possibility that the virus itself is becoming less deadly?

  • All of the above explanations are reassuring; in part suggesting our preventive measures and improvements in health care are working 
  • What would be really exciting would be if the virus itself was changing to become less severe!
  • As they spread in the population, viruses can change their genetic structure, or ‘mutate’.  This particular virus seems to be mutating approximately twice a month 
  • Indeed, one of the early changes was to generate a form of virus that would more easily transmit to humans.
  • Covid-19 is not mutating as much, though, as  is seen with many other viruses.  This is good news insofar as it might mean that those working to develop a vaccine would not need to worry about entirely new strains 
  • It can be argued that for the virus to survive, it would not do itself any favours if it killed everyone: the argument being that the milder the disease, the more likely that the virus gets passed on.  This is a possibility, but there is no evidence yet that this is happening with Covid-19 
  • Interestingly, the SARS epidemic in 2002 died out after about 8 months, for reasons that are not totally clear 

Conclusions

  • There are no definitive data that show the virus is causing less severe infections 
  • We are probably succeeding in reducing the spread in those most at risk and in the treatment of those with the most severe forms
  • It is not impossible that over time the virus itself may change to become less severe 
Categories
Covid-19 Mortality

Mortality from CoVid amongst Jews

[First circulated 29th June 2020]

Widely reported in both the Jewish and non-Jewish press was the high mortality from Covid amongst Jews in England and Wales.  This brief paper summarises the data, what is known and what is not known.

The study data : 

The Office for National Statistics in England and Wales linked the names on the death certificates that mentioned CoVid occurring between 2nd March and 15th May to those individuals’ self-reported religion on the 2011 census

The denominator was the total who self-reported one of the nine different religious groupings (including no religion) in that census

For each person who died the research also extracted from the census data:

  • Age
  • Gender
  • Self-reported ethnicity-ie white/non-white (not relevant for Jews but is important in comparing with data from Muslims 
  • Various indices of socio-economic deprivation
  • Self-reported health 

Comment: The number of Jews from the 2011 census amounts to 0.5% of the population.  Obviously like any estimate it is subject to errors. 

 Analysis

The research calculated the numbers of deaths per 100,000 in each religious group, separately by gender, overall and divided into those above and below 65.

They then calculated a full age-adjusted analysis to  compare these rates with the rate in Christians and other religions (including those who declared no religion).

Comment: The analysis was a standard epidemiological analysis.  One concern might be that using Christian as the comparator might be based on a very selective part of  the population.  In fact, 60% of the England and Wales population declared themselves as Christian in 2011 compared to just 7% who did not state their religion

The results 

There were a total of 453 deaths in people who were identified as Jewish on the 2011 census, 23 were aged 64 and under  and 430 above that age.  268 were males and 185 were female.  

The headline rates of deaths per 100,000, after adjusting for the age distribution of the population were  as below:

 Males: Females: 
Jews187.798.2
Muslims198.994.3
Hindus154.893.3
Christians92.654.6

* Note that the death rates for those with no religion or not prepared to say were similar  to the Christian population

  • Restricting the data to just the population aged over 64, this was the ranked order of deaths, taking account of the age structure, by religion
Ordered by highest death rateMales: Females: 
1stJewsJews
2ndMuslimMuslim
3rdHinduHindu
4thSikhSikh
  • Restricting the data to just the population aged 64 and under this was the ranked order, taking account of the age structure of deaths by religion
Ordered by highest death rateMales: Females: 
1stMuslimMuslim
2ndHinduHindu
3rdSikhSikh
4thJewishChristian

 * Note that the number of female deaths under the age of 65 was too small for some religions (including Jewish women and thus age-adjusted rates were not calculated  

  • After allowing for socio-economic and other indices of deprivation and self-reported ill health at the 2011 census this was the ranked order:
Ordered by highest death rate Males: Females: 
1stMuslimMuslim
2ndJewishHindu
3rdHinduJewish
4thSikhSikh

Comment: There is no doubt that Jews have a much higher death rate from CoVid than the background Christian population and indeed were similar to, or higher than, other religious groups This analysis takes into account that some of the differences in death rates may reflect differences in factors such as poverty and overcrowding.    Indeed, the death rate in Jewish males was still approximately twice that in Christians.  Although British Jews as a group may be better off economically, there are those in the growing Charedi community who are poorer and more overcrowded.  This analysis takes account of these differences 

The above analysis was repeated after allowing for self-reported ethnicity ie white/non-white.  This was the result:

Ordered by highest death rate Males: Females: 
1stJewishHindu
2ndMuslimJewish
3rdHinduMuslim
4thSikhChristian

Comment: This in some ways is the most interesting result.  Whilst Jews virtually always describe themselves as being of  ‘white ethnicity’ this is not true for Muslims.  (Detailed figures are available). After allowing for the ethnicity question, the effect of Muslim religion is much diminished.  The interpretation is that it is not the Muslim religion that is associated with the higher death rates but the ethnic aspect (ie white Muslims are not at risk of higher death rates)

How should the results be interpreted?

These are death rates and reflect the combination both  of how common CoVid is (the ‘incidence’ rate’)  in the different religions and how likely sufferers will die (the ‘case fatality’) in those who contract the virus. 

Is the higher death rate in Jews due to a higher incidence, a higher case fatality (or a mixture of both)?

Of these two possibilities the second is the less likely.  It is known that in the UK, Jewish males have death rates about 40% lower from all causes than the background population with females about 20-30% lower. Thus, British  Jews live longer with, for example, approximately twice as many being over 85 as the background population.  Also, though  not comparing like with like, Israel has one of the highest life expectancies in the world- being similar to Switzerland and Singapore

Thus, the more likely conclusion must be that there is (or was) a higher incidence of CoVid in Jews, rather than a higher case fatality 

It could be debated as to whether this was due to (i) being more likely to be exposed to the virus because of increased likelihood of social contact with an infected individual, and/or (ii) once exposed being more likely to get an actual infection with the same level of contacts.  Theoretically the latter is possible: ie  that Jews are less likely to remain asymptomatic for example are less likely to have pre-existing immunity. There are no data on this.

But one intriguing unanswered question!

In all the analyses on deaths, Jewish males have twice the age adjusted death rate as Jewish females.  That there is an excess death rate from CoVid in UK males  is well described and publicised but the data on Jews are different.  Indeed, Jewish males have around 2.2 times the death rate  of Christian males, whereas Jewish females have only about 1.5 times the death rate of Christian females.  Is it as simple as Jewish men spending more time mixing with each other??