Wednesday, 30 September 2020

Getting to know COVID-19 and us.

Summary points:

  • Super-computer analysis of COVID19's genes has worked out the molecular mechanism of how the virus operates.
  • COVID19 targets ACE2 receptors with its spike protein, to gain entry to the cell.
  • It inactivates interferon, our first line of defence against viruses
  • It then induces ACE2 receptors to multiply in lungs and other tissues by 200%.
  • The subsequent excess of ACE2 over ACE interferes with the operation of the Renin Angiotensin system (RAS), important for a number of critical physiological functions including blood pressure.
  • This reduces the breakdown of a regulatory protein called bradykinin leading to low blood pressure, opening of blood vessels, and leakage of fluid into tissues, particularly the lungs.
  • It also interferes with the degradation of hyaluronic acid, a sticky substance which fills the lungs in severe COVID19 leading to the 'gummed up' appearances of the lungs in severe COVID19.
  • Vitamin D has a key role in the regulation of the RAS, and the study offers clues to new treatments for severe COVID19. 
  • Sars-Cov2-19 continues to offer some interesting lessons for humanity

Introduction

This amazing study turns the 'normal' way of looking at disease upside down. 

Instead of learning what happens after the virus infects in terms of the damage it causes and all the resultant clinical information, the researchers have taken a big step back and looked at the expression of COVID19's genes - what it says in the COVID19 "operating manual". In other words, the information that can tell us what proteins it codes for and creates and therefore how it operates as an infective agent.

Sars-Cov2-19 in action

This is a powerful and fascinating way of looking at how a pathogen works. Reading the paper made me reflect on the complexity of our finely balanced physiological systems which allowed me to wake up in the morning able to start the day as a living being. Its mindbogglingly wonderful!

The material they looked at comes from the washings (lavage performed for diagnosis) from the lungs of the first patients with COVID19 in Wuhan compared to those from 40 controls. Analysis of the genetic information in these specimens provides a hypothesis of how COVID19 creates illness with some potentially important hints at treatments and again, highlights the importance of Vitamin D.

One of the first thing this virus does is to produce a protein which counteracts our own inbuilt antiviral called interferon. Rather like a burglar switching off the burglar alarm! 

It then up-regulates ACE2 receptors which affects the balance between ACE and ACE2 activity which leads to low blood pressure and an excess of an important protein, Bradykinin. This explains the widespread and sometimes bizarre symptoms of COVID19.

It also affects the metabolism of an interesting substance called hyaluronic acid which gums up the lungs. Their findings have implications for the race for to find better treatments for COVID19. Lets look at these areas one by one:

ACE and severe COVID19.

The body is a complex array of chemical reactions, with thousands of proteins acting on their receptors on cells like keys entering locks to gain entry to cells and do their precise job. Angiotensin is just one of these, its particular roles are controlling blood pressure, vascular tone and fluid balance and has a central role in what goes wrong in severe COVIDI9 infections.

I'm familiar with ACE receptors from my days as as a GP. I used ACE inhibitors and ACE receptor blockers to treat high blood pressure. Interestingly, both had a predisposition to cause a persistent and unusual dry cough as seen in COVID19 infections.

This picture, taken from the article, offers an overview of the rather neat, but complicated system:

YOUR RENIN ANGIOTENSIN SYSTEM

In other words, it's a beautifully designed complex 
system to maintain our inner physiological balance termed homeostasis.

Early in the pandemic it was realised that COVID19 targets the body's ACE2 receptors. The viruses attach themselves to these proteins on the cell wall like a key inserting into a lock and then invaginate themselves and the receptor into the cell. Once inside, they take over our intracellular protein making machinery to make large number of daughter viruses.

Amazingly, then induce an increase in the number of ACE2 receptors in cells elsewhere, including the lungs, where they are usually uncommon, by 500%. This has the effect of creating more targets for the daughter viruses teeming from infected cells. 

Now, the balance between ACE1 and ACE2 which in the healthy state keeps our blood pressure at normal levels, becomes disrupted by COVID 19. 

This imbalance between ACE and ACE2 leads to overproduction of a key protein called Bradykinin, (from the Latin; "Slow mover") which causes opening up of blood vessels which then leak fluid into the tissues (like the lung) and lowers blood pressure to dangerous levels. 

In essence, its rather like confusing the actions of the accelerator and brakes on your car. 

The resultant 'Bradykinin storm' leads to the widespread and sometimes bizarre symptoms seen in severe COVID19, including increased blood clotting, also commonly seen in COVID19.

Their work accurately describes more or less what seems to happen to people severely affected by COVID9, and offers hints at potential ways of countering some of these effects. 

One of the most remarkable features of the Respiratory Distress caused by the virus is the unusual sticky substance in the lungs which interferes with gas exchange essential for respiration. They have found out why......

Hyaluronic acid and sticky lungs

I have a personal connection with this amazing substance too. Before I was finally accepted into medical school as a mature student, I worked in the Bone and Joint Unit of the London Hospital looking at how human articular cartilage worked.



Suffice it to say that we were trying to work out how the gristle on the end of each bone could withstand the enormous pressures exerted on it by day to day life. Essentially, cartilage is a tissue containing a complex sugar - hyaluronic acid, held within a scaffold like frame of proteins. The hyaluronic acid can absorb enormous amounts of  water, but is restrained from doing so and expanding by the hard protein scaffold. The resulting stiffness of the tissue gives it its strength and resilience to impact. One sq cm can withstand the weight of an elephant standing on it without giving way.

It is widespread in the body with important functions in the spaces in between cells. It has a role in regulating cell growth and facilitates repair and has been used to treat lung disease. In some ways can be seen as offering a kind of lubricant in between cells as well as having many other important functions. Back to homeostasis again - you want the right amount in the right place. 

Now COVID19 seems causes an increase in the production of hyaluronic acid and reduces the expression of genes responsible for its removal. This results in accumulation of this now sticky stuff (which in this situation is rather like slug slime) in the alveoli of the lungs, the last place you would what too much of it. It then freely absorbs water to form a hydrogel and blocks up of the spaces in the lung needed to exchange gases, leading to the picture found in patients with COVID19 related Adult Respiratory Distress Syndrome on ITU.

The authors describe this in their picture:


Knowledge of these mechanisms could suggest potential ways of treating severe COVID19 which I'll come to later.

Vitamin D

The building block for the whole Renin Angiotensin machinery is Renin. Vitamin D and its receptor (lock and key again) has an important role here too. In essence, low vitamin D levels cause increased production of renin and an injection of Vitamin D reduces it. 

This might explain why patients doing badly with COVID19 are found to have lower levels of Vitamin D and why urgent supplementation has been shown in a small study to reduce admission to ITU for patients admitted to hospital with COVID19.

It might also explain why lower levels of Vitamin D are associated with high blood pressure and thus the increased risk of heart disease and strokes which plague the western world. 

Another retrospective look of 190,000 patients in the US shows that people with lower levels of vitamin D are more likely to test positive for Sars-Cov2-19. 

Vitamin D and COVID19 positive tests


In other words, get out in the sun and take Vitamin D supplements! Why this is not being shouted from the rooftops, as I said in my last post, I have no idea.

Novel treatments.

The information from genetic studies like this can lead to the use of drugs which specifically block the way the virus operates at a number of levels. There are drugs to prevent block bradykinin receptors called Icatebant which is currently prescribed for a certain type of severe allergy called hereditary angio-oedema. It costs about £5,000 a dose, making wider availability a big challenge. 

Another drug interferes with the production of Bradykinin called Ecallantide which is prescribed for the same reason though with more side effects, which might be predictable when trying to manipulate such a fundamental regulatory protein such as bradykinin. 

Hymecromone is an interesting drug which inhibits the production of hyaluronic acid in experimental conditions. It is currently available, interestingly enough, for bilary colic and is inexpensive at just £5 a course. I can't find evidence of any trials with COVID19 as yet. 

Vitamin D is fundamental to this, like so many other physiological processes, is readily available, cheap and without significant side effects. Anyone not taking supplements to counter our indoor, sun blocked life might have to ask themselves why.

Final word:

Viruses in one way (successful replication), are the most enduring, if the most basic, form of life. 

It is argued that they were the first form of life emerging from the primordial soup, that mixture of essential elements 4 billion years ago.
Sometime around then atoms, clumped together to form the first building blocks of life called amino acids, some of which then locked together in chains. 

These short chains of amino acids acted as templates into which other amino acids fitted to form complementary chains.
 
When they unzipped from that symmetry and repeated the process, replication, and the evolution of life on this planet began. It was just one step to genes as we know them, and another to viruses which are essentially genes encapsulated within an envelope. Viruses became the first form of reproducible 'life' on earth.

Here we are, 4 billion years later, with planetary life still dominated by these potent replicators; these amazing catalysts for evolution we are only just beginning to understand. It takes one of the world most potent computers to begin to unravel them.

They are teeming in the soil, there are 10,000 at least in every drop of fresh and sea water, they phage viruses (see pic) are essential to control bacterial populations and indeed release the vital nutrients they manufacture. In other words they are essential to the ecology of the world.

Phage viruses keeping bacterial populations 
under control


Im sure we will become ever more aware of their fundamental role in evolution as well as our own internal world. Watch out for knowledge of our "virome" transforming our understanding of human physiology.  

Understanding COVID19, as I have mentioned elsewhere, involves understanding ourselves as a species, but also the world we inhabit. Not only in terms of our own evolution, but in terms of our collective human behaviour.

Deadly spillover of pathogens from ever shrinking ecosystems; unsustainable regional and international travel, our pathological food production system, the hideous manifestations of excess wealth and poverty, and the consequent generation of billions of people vulnerable to COVID19 have all been signposted in big red letters which we do not need supercomputers to decode.

Understanding our relationship with this and other viruses would lead to a better world with better prospects than now. Time is short.

In the meantime, for those of us lucky enough to have choices, think about ending self-poisoning with sugar and smoke, stay as fit as you can, eat good food produced by good farming, and make sure you have enough Vitamin D on board. More on this soon. This is the essence of reducing your risk of experiencing the sort of problems this study highlights.

While we haphazardly grapple with the unfolding story of this virus, take good care of yourself and those around you. 















Wednesday, 23 September 2020

Second Wave time?

SUMMARY

  • Summer testing and tracing has not prevented COVID19 from spreading.
  • COVID19 positive tests has been accelerated by the new school and university terms with the usual associated epidemic of respiratory symptoms
  • There is a real danger that the ability of hospitals to care for patients and schools to function is being compromised by the over-promising and under-provision of testing 
  • This is is not a second wave as the first wave was defined by hospital admissions, this spike by increased positive tests.
  • A second wave is likely, but there are reasons why is will not be as bad
  • Threats of a national lockdown are not helpful. Last time our reaction was too little too late, now it might well be too much too early.

Introduction

Well, all matters pandemic are moving along quickly and we have barely entered Autumn. I'm sure for many the coronavirus news is very depressing. After such a difficult year, are six more months of restrictions going to solve more problems than they create?

Increase measures have been announced by Boris Johnson and in Scotland you are not even allowed to visit friends in another house. The air is full of threats of worse and the measures are applied across all areas despite the local nature of outbreaks. Worse, the changes have been applied without proper parliamentary scrutiny, and for six months. 

Fears are increased by the fact that the virus seems to be spreading rapidly. This means our  summer scheme of testing and tracing, isolation and local lockdowns have not done what they aspired to do. The virus is behaving like the seasonal virus it is. It seems we have been out-thought by a virus that cannot think. Its simple task, to replicate and spread has seemingly overcome our high tech, scientifically advanced, complex, collective ability to respond. All those sacrifices in the summer have come to nothing.

It might also be the case that the technology available has outstripped our ability to use it sensibly and our Victorian political processes have been found wanting. There seems to be cycles of problems and promises, problems and promises....

However this is a novel situation and far less predictable than we might think. Mass testing, despite its lack of effect, has changed everything in terms of perception. 

Imagine for a moment if this testing technology was not available - COVID19 would be, right now, on the inside pages of the newspapers, and way down the list of threats to humanity. 

There are of course genuine concerns about increasing cases attending hospital, (134 today), nonetheless cases and thankfully deaths remain low (sadly, 37 today). Of course this might change, the virus is highly evolved to infect and spread, and right now, it seems to be on top.

So what is happening?

The return of youngsters to school (particularly large schools and universities) is an epidemiological phenomenon which heralds the rapid spreading of colds and flu, coughs and sneezes. I remember it clearly heralding the end of the quiet phase (if such a thing exists) in general practice. It is as predictable as Christmas. 

Atchoo!
The wave of respiratory symptoms combined with the rules for testing have created chaos for schools, families, employers and, the functioning of the NHS.

Children with symptoms need to be tested to get back to school, so the testing and tracing system has been swamped by affected children, their families and contacts trying to get their lives back on line with what is, in 98% of tests a negative result. The more testing you do, the more tracing is needed, so the system is grinding to a halt, meaning more blunderbuss measures released from the grouse shooters running Westminster.

Whole school years are being sent home for a fortnight after a single positive test affecting a child with minor symptoms. Millions of children will have their education fragmented and this will affect those who need it the most. 

Remember too that the PCR tests are very sensitive and can pick up the genetic signal from a single virus. The larger the number of tests done, the more the false positives which can have huge consequences for families as well as the running of education and hospitals.

Similarly the NHS is struggling due to similar absentee staff waiting at home for a negative test to allow them to get back to the work of trying to clear the backlog of work accumulated since spring as well as new cases of COVID19.

Our over-centralised, privatised system of testing, operated by poorly performing private companies and their many sub-contractors are staffed with people with no clinical skills following online algorithms. This result is bizarre advice including driving for hours to get a tested in infection hot spots. Answer - operation Moonshot - more on this later.

Fundamentally, many with infections have not been tested, either failing tor report symptoms, or because they have none. ONS results suggest that for everyone coming forward for testing, 5 people with infections are not. So contacts have not been properly traced, and the system has failed. The solution to this is operation Moonshot, an attempt to fly before we can walk.

What I think of when I
imagine Operation
Moonshot!


We now paying the price for the lack of integration of new services with tried and tested NHS public health teams and primary care. 

This is what chaos looks like, but it is likely to get worse as the weather cools, people spend more time indoors, and the air dries. Viruses like all that. 

What they also like is modern society -  busy airports and lots of travel, large schools with big catchment areas, teeming cities with polluted air and town sized hospitals. Many people come into contact with many people in so many different ways, the virus spreads and this leads to what is increasingly being called the second wave.

The "Second Wave"

The upshot of this testing is what is commonly termed a "second wave" and the graph show this clearly.  

 POSITIVE TESTS - A SECOND WAVE?

However the first wave on the left comprised hospital cases and the current peak on the right  total positive tests only. So its chalk and cheese, as I have blogged before, a confusion of what comprises a "case".  This particular graph means little.

In terms of hospital admissions, (or deaths) there really is no second wave at all as yet.

 ADMISSIONS - NO SECOND WAVE!

It may be that there will be a lag between viral spread and subsequent illness. We might be in for a bigger caseload as we are are barely into autumn as opposed to the first wave which started at the end of winter. I just wonder how this graph will look in a few months? I'm afraid there is lots of time to go. 

In France, there are now 750 COVID19 cases on ITU compared to a maximum of 7000 in the Spring and a low of 370 two months ago. Cases there have been steadily increasing and might be the start of a genuine second wave, but this is not certain.

In Spain, a closer look at the regions suggest that the wave in many of the regions is past its peak, suggesting that what is happening is comprised of many local outbreaks which need local management and are in decline.

In Sweden, whose initial management did not feature the use of face masks and shutting down of the hospitality sector, there has been little happening in terms of COVID 19. Cases and deaths remain low. 

Here, it's so far so bad. The testing and tracing performed over the summer may well have been pretty much a frustrating waste of time, as clinical problems from COVID19 were few in the warm season, just like any other seasonal virus and now it is spreading with seeming impunity. So its all bad news then? No, read on.........

Is a second wave just a matter of time?

Extrapolating the present trend to the future is tempting, but we have to remember the terrible predictions made in the Spring - 500,000 deaths were predicted, and this was out by a factor of 10. The Government, usually so reluctant to manage public health risks, from our dreadful food, polluted air and climate change, now seem to have become entirely risk-averse. The worst case scenario proved simply wrong last time, but is again driving policy.

There are many reasons why things might be different this time:

A different Influenza season. Interestingly we seem to have seems to have more or less abolished the flu season in the overwintering nations of the south. This is despite some very different approaches to restrictions.  This would be really helpful if it applies to the north this winter. Deaths in Australia have plummeted from an average of 130 to just one, and cases from the usual 86,000 to just 627. That is pretty amazing! With flu killing 300-650,000 people a year globally, this is a welcome respite.

Given that flu causes an average of 11,000 deaths a year in the UK, such reductions would certainly offset the overall number of winter deaths from COVID19.

Changes in behaviour.  The significant effect on flu suggests that behaviour makes a big difference to viral spread. Is it the more widespread wearing a masks in public places, or the fear of COVID19 causing isolation of anyone with any respiratory symptoms, or more simple measures of less hugging kissing and more distancing?  However, the reduction in flu rates in so many southern countries with so many different approaches suggests that government action may not be the key factor. 

Better Herd immunity -  herd immunity has increased, not only through the production of antibodies but also T cells and other 'front line' defences, doing and remembering their work. They only reason they feature so little in our decision making is that they are difficult to measure. This important aspect of innate immunity is why so many people with infections have so few symptoms and means that many people are immune to the virus and are less  spread it to family members. 

Vitamin D levels are currently higher than the were in the spring, and the glorious September till now will have helped - a little. However our levels will be now be dipping as the sun lowers in the sky and UV levels drop. More on this later, but the best evidence shows Vitamin D can reduce your risk of severe COVID19 significantly. Not to be taking 4-5000iu daily is missing a big opportunity to reduce your risk from COVID19 despite the governments startling silence. 

Better preparedness. Last year the first wave arrived at our hospitals with no public preparation and short warning for the health sector. The respiratory distress caused by the virus was novel and there was much learning to be done. Hospitals and care homes are now well equipped and experienced. Any significant outbreaks in care homes are simply inexcusable. 

Better management and treatment. If you do get infected, and develop the disease, then there is good news too. We now know so much more about the virus and how it operates. Its management and treatment are far better and ITU admissions and ventilation will be reduced by better understanding of what the virus actually does when we are infected, so the least invasive most effective treatments will be given. Steroids are helpful here and novel drugs are still being investigated, more on this soon. 

Vaccines are irrelevant at this point in time. By the time they are available we will be coming out of the winter and know far more that we do now. They might well stamp on the tail of the pandemic later. 

It would be wonderful to have a crystal ball. We might be in for something far worse than last winter, or it the inevitable second wave might be much smaller, it is just so hard to say. Much is drive by what you want to believe and how we see things more generally. 

My hope is for a smaller wave for the reasons I have laid out. There are some who think we have arrived at herd immunity already. I think we are further down the road than Government seems to think. In any case, severely restricting life right now seems to be just a little early to me.  We shall soon find out.

We clearly need more powerful local authorities to manage local situations and we need a healthier population. 

We shall soon find out. Whatever happens over the next decisive month, are you ready for the worst case scenario as possible? 

Are you ready?

Despite the chaos and recurrent fiascos in the UK in particular, and the uncertainties, we have to think of our own state of readiness should the pandemic take hold. 

I shall post on this shortly, but now is the time to stop smoking, improve the quality of the diet, lose weight, increase activity and exercise and ensure you have enough Vitamin D on board. For those with medical conditions, is your management as good as it can be? For those at particular risk, have you a pulse oximeter? 

Now is the time for whatever fine-tuning we can put in place.

Final word

That we have been laid low by what might be seen as the 'lowest' form of life is humbling. We need to be humble. The tragedy of the modern world is not COVID19 unleashes, but the reasons behind its arrival. 

I personally felt unable to watch Attenborough's look at the extinction of wildlife, but Im aware that he laid out clearly that our treatment of the planet in which we live has caused immense and ongoing suffering for wildlife and has led to COVID19.

As the remnants of the natural world are further compressed into what is left of their environments, ecologies break down and we come into contact with new pathogens. With all due respect to the suffering and loss it has caused, with COVID19 we have been lucky. The mortality rate could have been far higher if we had no immunity to it at all. 

There are many other pathogens waiting, mutating, jumping hosts, and further spillover is inevitable. This is not withstanding the pathological farming methods themselves destroying the environment and providing the conditions in teeming chicken and pig factories for mutation and spillover of new strains of influenza, many of which will be deadly.

The relatively comfortable post war era in which I have led my life is over. 






Monday, 14 September 2020

Vitamin D - some good news

SUMMARY

  • There are causes for concern in the recent upturn in positive tests and hospital admissions with COVID19.
  • In a pilot trial of 76 people with COVID19 admitted to hospital in Spain, treatment with Vitamin D reduced the need for admission to ITU from 50% to 2%
  • Supplementation with Vitamin D has never made more sense.

In terms of COVID19 the winter might be coming early..... 

I clearly remember the increase in workload in general practice as the summer ended and school term started, particularly with universities competing for students from all over the country and indeed world; a phenomenon which gives viruses a free ride.  I would know when the summer was well and truly over by the suddenly busier clinics and the preponderance of respiratory infections.

So a consistent increase in positive COVID19 tests and cases is to be expected as schools and universities get back into action. Unsurprisingly, positive tests seems to be mainly in the younger age group but there is a slight increase in the number of hospital admissions which is now a cause for concern. On the 9th of September there were 192 admissions for COVID19 in the UK, while this is a small number compared to the spring, this is about double the number the previous week. 

Thankfully deaths remain low; 6 on the 11th September, but there is always a lag between infection, diagnosis, hospital admission and death. This is mirrored in France where 80 people died on the 11th September after a summer with daily deaths in the twenties or lower. What happens in the next few weeks will be critical is predicting what the next few months will bring.

Vitamin D levels over 2002-4

As well as the migration of young people to universities, return to schools and new jobs (when they can get it!) the most significant physiological feature of this time of the year is falling Vitamin D levels. 

This would usually be happening from September onwards, but levels may well have be falling earlier after one of the dullest Augusts I can remember. Although the weather is a little better in September, sunny days have been scarce, UV levels dropping, and the indoor life continues to dominate, particularly for those shielding or during restrictions. 

The graph above shows the pattern in vitamin D levels in 2002-4, and if you take the normal level of 70nmol/l it shows that very few people have levels of vitamin D which are needed for immune health. As we head for the winter, this is becoming more important.

Now, an important study from Spain highlights the benefits of Vitamin D during this pandemic.

Good news

A randomised double blind trial of the effect of Vitamin D on COVID19 outcomes of 76 patients  looked at the effect of taking Vitamin D when admitted to hospital with proven COVID19. This was a small study but with big findings. They wanted to know if treatment with Vitamin D affected admission to ITU or death. This is what they found:

Only one of the 50 patients (2%) who were given the fast acting version of Vitamin D was admitted to Intensive Care, against 13 (50%) of the 26 patients in the placebo group. There were no deaths in the treatment arm, and two in the non-treated group. 

The authors conclude:

"Our pilot study demonstrated that administration of a high dose of Calcifediol or 25-hydroxyvitamin D, a main metabolite of vitamin D endocrine system, significantly reduced the need for ICU treatment of patients requiring hospitalisation due to proven COVID-19."

They are proceeding to a larger study which I hope will attract the necessary funding but these results are incredibly encouraging, suggesting a far greater positive effect than dexamethasone, remdesivir, or indeed any treatment to date.

They used a a fast acting form of Vitamin D called Calcifediol as levels of D3, the usual supplement, build up over the space of a few weeks and would not help in the acute situation.

They summarise the potential benefits of Vitamin D with COVID19:

  • Decreasing the cytokine storm - the over-reaction of the immune system which causes chills, aching and fever, and can spiral out of control in severe cases.
  • Regulating the Renin Angiotensin system which controls blood pressure.
  • Modulating neutrophil activity to prevent damage to lung tissues
  • Maintain the integrity of the pulmonary epithelial barrier. (the lining of the lungs)
  • Stimulate epithelial repair - repair damage to the lining of the lungs.
  • Taper down the increased blood clotting seen in severe COVID19.

This is against the background of studies which have showed the clear associations between vitamin D levels and the incidence and mortality from COVID19. 

Further information has emerged from a computer analysis of how COVID19 does its damage. Despite not being 'alive' in the conventional sense, the virus plays havoc with the metabolism of a couple of molecules called bradykinin and hyaluronic acid. Bradykinin plays an important part in epithelial damage and blood clotting seen in COVID19 and Vitamin D plays an important role in its regulation.

Hyaluronic acid is responsible for filling the lungs with a sticky substance (think slug slime) the presence of which in the lungs of COVID19 patients mystified doctors earlier in the year.

More on this later, but this provides more evidence that Vitamin D is a big part of this story and is another good reason for making sure you have the levels of Vitamin D which up to recently, have been the norm.

Why is this not standard advice?

This study arrived come after NICE and SACN failed to recommend Vitamin D in this setting, a review criticised in the British Medical Journal and by the Royal Society. The reluctance of the medial advisors to recommend Vitamin D is depressing. 

In the middle of a pandemic, the sound physiological reasoning behind the use of Vitamin D, our current low levels of Vitamin D in the population, clear associations between Vitamin D levels and outcomes and now this study does not seem to generate the headlines it should. It was briefly reported in the Daily Mail albeit with emphasis on the imperfections of the trial rather than the hopeful message it contains.

The other main problem is what we call the inverse care rule. In our inequal society, those who need it most - the obese, those eating a poor diet, living in a polluted area, smokers, those with other illnesses, and the deprived, are the ones least likely to take vitamin D, or even be aware of its benefits, so sing it from the rooftops please.

Supplementation is particularly important for those in the BAME community who have been hit hardest by COVID19.

Suffice it to say that in the middle of a pandemic the evidence that Vitamin D is useful is good enough to recommend its widespread use as we face the winter. 4-5000iu daily will usually bring levels up to what can be considered normal. Like many people with MS, I have been taking this dose for the last 8 years since my diagnosis and without any problem.

In full sunlight, the body can make about 15,000iu of Vitamin D daily, so this dose will not do any harm, so get whatever sun you can while you have a chance and while this autumnal mini heatwave lasts.

As I write, I look out of the window and see squirrels busily harvesting nuts and burying them in the garden. They are preparing for the winter. We should too. 









Monday, 7 September 2020

August Pandemic update

The days are shortening and the cool damp Autumn seems here rather prematurely as we leave behind another climate change altered damp squib of an August. Despite the resultant diminished harvest, COVID19 remains the headline story in every paper and every news bulletin just about daily. 

We are entering a crucial phase of the pandemic, but will this next phase be a gigantic new terrifying wave, or just a demonstration that the pandemic is over?

What's the score with COVID19?

"Cases" are rising everywhere and there is anticipation in the air. Schools are heading back next week in England and are already back in Scotland, this annual exodus is usually accompanied by a flurry of viral infections and a sigal that winter will be here soon and with it the threat of a second wave, though perhaps not; no one really knows for certain. 

Right now there is lots of concern about the increasing number of positive tests, but what we do know is that people with COVID19 are not turning up at hospitals in any significant number and the number of deaths remains low.

UK COVID19 Deaths
The graph on the left shows deaths from COVID19 in the UK. Despite the increase in what are incorrectly called 'cases' there is no upturn in the number of people arriving in hospital or dying. 

So things right now are very different from spring. Those huge summer bank holiday day beach parties and other  social gatherings have not led to any problems for the NHS or any demonstrable health problems to outweigh the health benefits of the fun had by participants.

Around Europe the picture is repeated with no increase in mortality anywhere. so far. There has nonetheless been lots of worry in the news, local lockdowns, quarantines and ever more testing of people with and without symptoms. Matt "Handsfree" Hancock has even been talking up saliva tests which would enable us all to be tested every week and yet another app to trace our every move and contact. The project, appropriately enough, is called "Operation Moonshot".

Just 3,999,999 to go then! (From Open Democracy)

Once again most of the work is to be outsources to private sector chums Deloitte (revenue $43bn) in what has been called the biggest single act of privatisation ever. No change there. 

Handsfree's rhetoric is as usual way ahead of the technology available and seems designed to make a "world beating" headline rather than advance public health. It is also a gigantic shift in resources from the public purse to the private sector as well as missing the opportunity to get the NHS ready for the winter by building on locally based services already in place. 

Yet, the plans are already being scaled back by the real world. They now plan to test 4 million people a day with a longer timeframe. The upshot of this is that more tests will come back as positive. There will be more infections detected, and they will be called "cases". Confusion reigns! 

Infections or cases - there's a big difference

There is a fundamental problem going on with simple out-dated terminology which is having some major implications. This refers to the rather anodyne "case fatality" and "infection fatality" rates. 

In past pandemics, such terminology made little difference. Historically, people with infections became ill and sought help. The case fatality rate (CFR) was simple to calculate; divide the number of deaths by the number of people turning up with infections (cases) and then multiply times 100. In March the CFR in the UK from COVID19 was 14% and has been falling fast ever since. 

"Infection fatality rates" count anyone at all with the infection, including those with few or no symptoms. You may have to do more looking to count the people who had milder illnesses and didn't seek help to know how bad the overall infection is. This will be of course, be lower than the case fatality rate. In COVID19, 10 times lower. 

This is the first pandemic where we have been able to go out and test widely for infection among the general population and so the difference between the two measures are widening all the time. Infections appear to be rising everywhere, causing panic, yet clinical cases remain thankfully uncommon. Panic is entirely inappropriate. It is chalk and cheese.

In March, we were only testing people who were admitted to hospital, severe clinical cases, and the case fatality rate was 14%. Now we are testing 180,000 people a day and yet treating the resultant number of often clinically positives with the same sense of anxiety.

What we have really found is that the virus has continued its spread through the summer and is widespread in the community. This is no surprise at all as the young become active and the economy grinds back to normal, including 100 million state subsidised meals (how many of them will be adding to the obesity problem I wonder?).

So far, I am rather reassured by the apparent lack of impact of the virus in the summer despite the ongoing number of cases. ONS estimate that in the last week, there have been 27,000 people infected with COVID19 in the UK and there has been a total of 40 deaths. An infection fatality rate of 0.15%, that is 1 in 6,75. 

Good news?

In this sense a higher level of infection coupled with a low case load is good news. It might mean that the virus is, or has become less virulent, that more people have developed immunity, that higher Vitamin D levels have had a positive effect, and that vulnerable and older people are continuing to shield. 

It may also be that many people are getting infected with a lower viral load. That is, coming being infected with a small number of viruses by passing someone in the street or in a cafe and inhaling a small number of viruses, as opposed to trying to manage an unwell household member who is expelling millions of viruses with each cough. 

Or a bit of all of this. 

Or, that it is highly seasonal and we have not yet entered the difficult winter phase to come. We shall see, but such a high number of infections without much clinical impact has to be reassuring at this point in time. 

If people infected develop immunity to the virus, either through the development of antibodies or memory T cells, they will also be contributing to herd immunity and will be protecting, in that sense, family members and others they are in contact with through the winter. 

So let's have another think about the logic behind this mammoth testing project? 

What is testing and tracing for?

The test itself look for fragments of viral RNA and are able to pick up a single strand from a single virus, and so will tell you that you have had the infection, but will not necessarily tell you if you are infected, or infectious. It's rather like a bank statement that just tells you that you have, or don't have money in your account, not how much. All a bit blunderbuss really.

It means that if people with positive tests are traced and isolated, it will slow down the spread of the virus. This makes sense, but it is working?

In reality the virus continues to spreading very well despite the measures. This is hardly surprising given that it is very infections and most infections will come from household members, particularly in multi generational households and deprived areas which are taking the brunt of the resultant restrictions.

Testing will only work is the tracing is effective and people are financially supported to isolate for a fortnight. The recent £13/day uplift will not be enough if you need income on a day by day or week by week basis. You can apply for Universal credit as well as SSP - Im sure the form filling for all that will take up the whole two weeks!

Yes, even in poorer areas, with their increased rate of infections there is still no increase in cases, for now at least.

So might restrictions be following the wrong numbers? PCR tests should be the driver of the tracing strategy, wider restrictions decided on local impact on health.

To add to the problems, care homes continue to complain of ongoing delays to results for tests which will compromise the safety of some very vulnerable people. Add this to the list of problems not sorted out over the summer. 

Lockdowns

Local lockdowns might be better designed to react to outbreaks of illness,  when clinical disease is counted by calls to GP's (still uncounted) or call centres, or hospital admissions. But they are being put in place simply according to the number of positive tests irrespective of why this has happened. 

It's reasonable to expect this will, as usual, impact on the most densely populated, more polluted and poorer communities which have already been hit hardest by the virus and its economic consequences. Insisting a member of a busy household stays at home for two weeks is a pretty good way to spread the infection to other household members and then to their contacts. 

In these areas with high levels of zero hour and low paid workers unable to afford sick leave, it is hardly surprising they are more infected. The poorer are hit harder in every epidemic you might think of from Cholera to TB and Influenza, and in this country we have high and increasing levels of inequality

Perhaps "lockdown" might be better applied household by household, but the support is not there to allow this to happen and advice from distant tracers is easy to ignore.

It's as if the politicians assume that we all have facilities like spare rooms and en-suite toilets and bathrooms to isolate at home. "I'm off to the East Wing for a fortnight darling - tell the butlers to leave the dinner by my door." 

Certainly if there is one situation where masks are useful, it is sharing a house with someone  who is infectious. 

So what is going to happen now?

Viruses are very unpredictable. Remember the impact of the terrible Zika virus in South America? Those infected mothers whose babies had small brains (microcephaly) - thankfully, and for poorly understood reasons, the virus changed its behaviour and no longer carries this threat. COVID19 might change too.

The case of a young man from Hong Kong with a second COVID19 infection made the news, and showed that his immune system had successfully kept the virus from causing any symptoms. There had been some changes in the proteins of the capsule signifying that this virus is capable of mutating too. The evolutionary pressure will be for illness to become milder as milder viruses spread more widely. Fingers crossed. 

So there are reasons to be hopeful that we wont see a repeat of the spring. Yet, hospitals continue to have little spare capacity after a decade of cuts and our low level of provision of hospital beds, but have more experience with the illness and how to manage it. 

With schools and soon universities back in business, an increase in infections is not just likely, but certain; yet how this translates into people who need help is uncertain. Perhaps there will be a middle way as an outcome for all these uncertainties. A smaller more manageable winter wave which will not swamp the NHS and so allow life to carry on till the next modern crisis.

As I write there has been an increase in positive tests to 3,000 or so a day for the last two days. If this rise is sustained as activity increases then the next few weeks will be telling. The positive tests are mainly in the young who deal with the infection well, but there are concerns it will spread to older, more vulnerable groups and then hospital admissions will rise, I have hopes this will not happen, we shall now see. 

The alternative to allowing this to happen is to lockdown again, and there is a general agreement that this is not affordable or even possible, and indeed that it may not ever work. The lack of a locally based public health test and trace operation will be a big disadvantage as well as the lack of the financial support needed to ensure people testing positive are able to stay at home and isolate where they can, though this is not straightforward either.

I shall be wearing a mask in shops and following the rules, but now is the time to focus on health again. I shall post on Vitamin D shortly as more evidence has emerged regarding its usefulness and all those other measures to improve immunity.

Meanwhile...

I can't but help reflect on the causes of the pandemic; agribusiness and destruction of

ecosystems where the planets remaining wildlife largely resides. Bad farming is behind this problem, and is continuing to foment the next spillover pandemic. Our forthcoming trade bills are unlikely to address this and more likely to make matters worse.

Brexit too is emerging from behind the scenes, being pushed on all the time by a prime minister whose competence is clearly lacking and is likely to be put out to grass before the brown stuff hits the fan. This is despite the pandemic clearly demonstrating  the need for international co-operation and unity.

I sigh in frustration that this gigantic financial and administrative effort would be so more effectively targeted at the transformations needed in our society to adapt to climate change which as we speak is far, far more dangerous than COVID19.