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Covid-19: A Primer On DNA, RNA, and SARS-CoV-2 January 13, 2021

Posted by mwidlake in biology, COVID-19, science.
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<<—- Long term hopeful, short term worried

<<– The new Covid-19 B.1.1.7 variant & threat to the health services

I want to explain a few things about SARS-CoV-2 (the virus that causes Covid-19) and the vaccines that are being rolled out in both the UK and the world. To do so I first need to explain about DNA, RNA, proteins and what is called the central dogma of molecular biology, which is what this post is about. The central dogma is the core – the absolute fundamental key thing of life, of our biology. It is the biological equivalent of what quantum mechanics is to physics.

Thankfully, it is far simpler to understand the basics of the central dogma of molecular biology than the basics of quantum mechanics. It is also a well established concept, I was taught it last century at university and it has not changed much in the 32 years or so, though we better understand so much more of the details and ramifications now (6).

Central Dogma Of Molecular Biology

Basically the Central Dogma is that DNA makes RNA and RNA makes protein – and information does not flow backwards. I’ll try and explain that in steps, but before that I want to give a quick reminder about DNA, which most of you probably remember from school, and protein/polypeptides. Sorry, but it’s necessary. Skip to “The Core Of Biology” if you already know all about these.

DNA and Proteins

DNA molecule – from Yourgenome.org

All living organism contain and are controlled by DNA – Deoxyribonucleic Acid. This is the helical, double-stranded molecule whose structure was worked out by Watson, Crick, and Rosalind Franklin. In all organisms (except bacteria & archaea – together known as prokaryotes) the DNA is held in the nucleus of the cell (1). The whole genome is in every normal cell in an organism (be it a plant, fungus, moss, animal, you. Everything alive that is not bacteria/archaea is a eukaryote – which means the cell has a nucleus). There are some exceptions – such as red blood cells that lack a nucleus, or sex cells that carry one half of the normal amount of DNA for a given species.

The DNA directs all of the biochemistry of an organism (2). Everything. It defines the structure of the proteins we are made of, how the proteins go together, the layers and parts of our organs, the overall plan of our bodies, and the hormones, chemicals, and free-moving cells that go around our bodies like red and white blood cells. We still don’t know how some of this control is done but as DNA changes (mutations) affect all of these things, we know the DNA is basically the instruction book to both make an organism and to keep it functioning.

The DNA of an organism contains (amongst other things) it’s genes. Genes are the instructions for making all of our proteins and we say the genes are “expressed” when the genes are activated and make the proteins. And they do this all the time, at great rates, churning out vast quantities of proteins in each and every cell.

I say proteins but that is not *quite* right. Proteins are made of polypeptides, and polypeptides are made up of amino acids. As an analogy, proteins are paragraphs, polypeptides are sentences, sentences are made of letters which are the amino acids.

In the vast majority of organisms there are 20 different amino acids available to “spell out” all polypeptides. Genes have instructions to make chains of amino acids, called polypeptides. A protein may be a polypeptide, but it might also be made of several polypeptides or polypeptides that have been chemically modified after being initially made. I make this point as below, and in some of the links, polypeptides and amino acids are referenced and general scientific literature can be a bit muddled between polypeptides and proteins. For now, just think of proteins as really complex polypeptides. (3)

DNA consists of four letters as you probably know. Adenine, Cytosine, Guanine, and Thymine. In the double helix the two strands are “inverse mirror images” of each other and the letters pair up – A with T and C with G. So a short strand of DNA might be something like the below and, as indicated, the two halves can be split and, via the pairing of the letters, perfectly copied:

 

Double stranded DNA can be split and (perfectly) duplicated

 

The DNA is unzipped and split (by an enzyme called Helicase) and then DNA Polymerase can come along and add in the missing letters and you end up with two perfect copies. Usually. In my example, to the right, there is a mistake,  – a C has been added in where an A should be. This mistake is an example of a mutation.

However, that is not part of the Central Dogma. Although DNA duplication is vital (after all, every cell needs a full copy of the organism’s genome so the DNA needs to be replicated each time the cell divides). The main function of DNA is to pour out instructions for the creation of polypeptides

Central Dogma by Brownfield 5 on slideshare

The Core of all Biology

All the complexity of what our cells do and how our biochemistry works is via genes being expressed.  I’m not going to even attempt to describe how gene expression is controlled. It’s incredibly complex, it’s an area of understanding that has advanced hugely since I was taught the basics in my degree 32 years ago, and science still does not really understand a lot of it. But it’s the expression of these genes that allow are cells to do what they do, from growing hair, muscles, and making white blood cells to producing the enzymes that digest our food and control our bodies. All cells express thousands of genes all the time, at different levels of expression, and they do this by producing Messenger RNA, known simply as mRNA.

RNA, or Ribonucleic Acid, is (as the name implies) structurally very similar to DNA. It is single stranded, not double stranded like our genomic DNA, and the Thymine is replaced with a very similar chemical called Uracil.

Transcription

When a gene is expressed the relevant piece of DNA is “unzipped” and an enzyme called RNA Polymerase walks along the DNA and creates a complementary (meaning A becomes U, T become A, C becomes G and G becomes C) RNA copy of the DNA, as is shown in the diagram to the right. This is called transcription and it produces something called pre-mRNA. This is itself then processed by by other enzymes which cut out parts of the RNA that represent “Introns” – bits of DNA in the gene that are not to be used. This bit is not shown on the diagram. It is one of the complexities of our DNA that was poorly understood before the Human Genome Project and is still rarely explained. In a complex organism like a mammal or plant or fish, a single gene can produce a range of proteins depending on how this pre-mRNA is processed.

The diagram below shows how the double-stranded DNA is “unzipped” and the RNA polymerase reads one strand of the DNA and produces an RNA strand based on it.

RNA Polymerase, from BC Opentextbooks

The final mRNA consists of three main parts. The first part, at what is called the 5 prime (or 5′) end is a cap that allows the mRNA to be recognised and grabbed by the Ribosomes (see later) and transcribed. Then comes the RNA equivalent of the DNA gene for the protein. At the other end, the 3 prime (or 3′) end, a string of As is added (100-200 of them normally), the poly-A tail. We will see why later.

Pre-mRNA to mRNA from Wikipedia

This mature mRNA is then transported out of the nucleus of the cell and out into the body of the cell, into the cytoplasm. The mRNA may hold markers to say where specifically in the cell it is to go but that’s a detail I won’t go into. This seems to be very important to complex organisms like ourselves, that the DNA sits in the nucleus, mRNA is produced and this is quickly passed out of the nucleus to be processed elsewhere in the cell.

Translation

So we now have an mRNA molecule in the cell ready to be translated, i.e. used to make a polypeptide. In the cell there are thousands and thousands of very complex molecules called “Ribosomes”. A ribosome is actually made of two parts, both of which are themselves made out of RNA, not protein. These ribosomes clamp onto the cap of the mRNA, one part on one side, the other on the opposite side, the mRNA in the middle. The cap is a special starter molecule and the first part of the mRNA, which does not code for a polypeptide but controls how easily the Ribosome attaches to the mRNA. The attached ribosome will then “read” the mRNA, working down the string of letters and creating a polypeptide that is described by the RNA sequence.

Special intermediate molecules are used to translate the RNA to an amino acid. These are the tRNA molecules shown in the diagram below. As a ribosome walks along the mRNA is reads small chunks of the mRNA, finds a tRNA that complements the mRNA and temporarily binds it to the mRNA. At the other end of the tRNA is a specific amino acid and this bonds to the growing polypeptide/protein.

Ribosome translating mRNA – from sites.google.com

Many ribosomes can be walking along a single mRNA molecule  at a time, creating more than one copy of the polypeptide. When a Ribosome gets to the end of the mRNA, to the poly-a tail, it drops off (4) and it will (or at least may) snip off the very end of the poly-a tail. So it shortens the tail. This tail protects the mRNA molecule from being destroyed by the cell so, as it shortens then the mRNA becomes more likely to be destroyed. Why is this important? Well, the cell needs to produce different polypeptides at different concentrations at different times. The poly-a tail is a key part of how the cell controls how long an mRNA molecule last for, creating polypeptides. The longer the tail, the longer the mRNA lasts. The mRNA can’t be allowed to hang about in the cell producing polypeptide for ever. Once it’s tail is gone it is destroyed. Thus for a polypeptide to be constantly produced, the genes in the nucleus need to keep producing the mRNA for it.

As you can appreciate, changes to the 5′ cap can change how quickly (and often) a ribosome latches onto an mRNA molecule, the length of the poly-a tail can control how long the mRNA lasts and so how much polypeptide that one mRNA molecule creates, and the nucleus has overall control over when and how much mRNA is produced. These processes allow constant control and change to how a particular gene is expressed.

I’ve said about the RNA being read and converted into a polypeptide. How does this work? The diagram above and the tRNA give clues to this.

How Codons translate to amino acids

As I said earlier, there are four letters of the RNA alphabet – A,C,G, and U – and a polypeptide is like a sentence. There are 20 types of amino acids that are strung together to make our polypeptides. Our genes are written in sets of 3 letters, called codons. You can think of them as a gene “word”. You can see this with the tRNA molecules in the diagram, at one end they have three RNA letters, and the other end the specific amino acid that those three RNA letters translate to.

A codon, such as UCA, codes for an amino acid called serine (or Ser). GCU codes for alanine (Ala). With 4 letters and a “word” being 3 letters long, there are 64 combinations of A,C,G, & U possible. You can see all 64 of these combinations in the table to the left. So how do the 64 possible codons map to 20 amino acids? Well, some codons have a special meaning.

3 – UAA, UAG, & UGA – are stop codons. They mean “this polypeptide is finished, ribosome stop reading”. One codon is special, AUG. This either means “start reading here” (note, there have to be other sequences in the RNA near it to make it mean this) or amino acid methionine (Met).

As for the others, well several codons mean the same amino acid, as you can see in the table to the left (5). Generally the first two letter in the codon define which amino acid the codon is for (anything starting GU is for valine, Val) but for some the third letter is the deciding factor.

Ribosomes thus start at a special AUG codon on the mRNA and then read three letters at a time and for each one, for each codon, the specific amino acid is added to the growing chain – via the tRNA molecules. The chain can be thousands of amino acids long or just a handful. The chain grows until a stop codon is reached. The longest polypeptide is titin, which is between 27,000-35,000 amino acids long (due to those “introns” I mentioned, sometimes some are cut out, sometimes not) and makes muscle elastic.

That’s it. That is how our DNA, our genes, make all the things that build and control our bodies. Of course, there is an incredible amount of complexity that arises from that central process, like how do the proteins control the inclusion of calcium to make our bones, grab iron and put it in our blood, and stuff all that fat in our cells. But it is all controlled and mediated through polypeptides, through proteins and enzymes.

If you want to see a large version of the Central Dogma diagram you can click here:

->ci350poster-141201170705-conversion-gate02

 

mRNA vaccines.

I won’t go into too many details here, but you may know that a couple of the Covid-19 vaccines are mRNA based. These vaccines are millions of mRNA molecules packaged up into little balls of fat (also called lipid). These mRNA molecules are all the same and are the instructions to produce the spike protein of Covid-19, the bit the virus uses to attach our cells and that the immune system is good at identifying and attacks. This is the Moderna and Pfizer vaccines

The vaccines are ONLY for the spike protein, not the rest of the virus, so the vaccines cannot give you Covid-19. But what the mRNA does do is get into your cells and your cell ribosomes latch on to the mRNA and make the spike protein. The mRNA molecules is not exactly like the one produced by the virus, it is modified to be more stable and last in the cell longer, with for example a longer poly-A tail. The longer it last, the more spike protein is produced. The vaccine mRNA is engineered to produce as much spike protein as possible.

Your body sees this spike protein, it knows it is “foreign” to your body and learns to attack it. Then, if you are infected by the real virus, your body will already know to attack the spike protein and either you do not get ill or you get less ill. Fantastic, isn’t it? I love science and I especially love biology and medicine. Even just 50 years ago this virus would have had to run it’s natural course through us and kill maybe like Spanish ‘flu did, but now we understand so much better what is going on and we can now do something about it. I say “we”, I mean biomedical scientists.

Previous vaccines have relied on getting a modified or damaged version of the whole virus into your body, or modifying another virus that is harmless so that it produces mRNA for exact copies of parts of the dangerous virus. These are hard things to do. The Oxford vaccine is a modified virus (a chimpanzee adenovirus, chosen I believe because it can infect us but does no harm and does not spread in humans).

Advances in handling mRNA, creating it, and understanding how to make it work in our cells, have allowed scientists to create mRNA vaccines which are simpler, more efficient, easy to create or modify , and more targeted than traditional vaccines. Only part of the virus is made and nothing else, so there is no danger whatsoever of the vaccine causing the disease, or a modified version of the disease. Further, if the virus alters (something that is a current worry) then modifying an mRNA vaccine is theoretically very easy and quick. Testing the new version would be necessary and would take months (regulatory bodies allowing – they might let a modified version be fast-tracked, my wife is an expert in pharmacovigilance and she thinks it could be done) , but it means mutations to SARS-CoV-2 can be handled relatively quickly if the need arises. This could be vitally important.

This work has not all been done since Covid-19 appeared about a year ago, it is based on several years of work on MERS, SARS and other viruses. So on the one hand these mRNA vaccines are a new technology, but they are new since 4 or 5 years ago and great advances in how to create them have been made in the last year.

 

Implications of the Central Dogma

Some things follow on from the above that are fundamental to SARS-CoV-2 and vaccines. I’ll touch on them here and expand on them in further posts, as this is a lot in one go.

Mutations and Open Reading Frame

In my previous post on the new variant of SARS-CoV-2 I mention mutations. At the start of this post I mentioned the copying of DNA/RNA and how mistakes can be made, in particular a single letter changing to another. When a single letter of the genome gets changed, this is called a Single Nucleotide Polymorphism or SNP. If that letter is the first one in a codon in a gene, it is almost certainly going to have an impact. It will change the amino acid inserted at that point in the polypeptide. If you look at the codon table earlier it is possible to change the first letter A to C and still get Arginine. Other than that, altering that first letter in the codon alters the polypeptide. Other SNPs can have no effect – changing GUU to GUC still makes valine. Of course, any SNP that creates a stop codon is going to have a potentially massive effect.

SNPs that cause no change to the polypeptide are called synonymous. As they make no difference to the organism, they occur and get passed to the next generation of the organism and all their offspring. We can use these synonymous SNPs to track the lineage of organisms and they are used to track the lineage of SARS-CoV-2. This allows us to, for example, track how the virus has spread geographically. I say us, I mean phylogenetic scientists.

Those SNPs that change the polypeptide sequence are more likely to change something about the biology of the organism. If the change is negative (for example it reduces the efficiency of an enzyme) the organism and it’s descendants will be at a disadvantage and the change will be selected out. If it gives the organism an advantage, it and it’s descendants will do better than those without the change and will take over in the population. This is true of the new variant B.1.1.7 – is better at spreading, it is taking over. Many SNPs that change one amino acid have very little positive or negative effect on the virus. (I don’t know what it is like on modern genetics degree courses but in my day lecturers would almost come to blows over how much effect a single mutation would need to have to be significant, and how much evolution of DNA was just mathematical, accidental drift, and how much was through selection pressure.)

Other, rarer mutations can be deletions and insertions. Extra letters get added or removed. Now, if the number of letters added/removed is 1, 2, 4, 5 or any number that is not divisible by 3, the impact is huge. Why? Well, a gene has something called it’s Open Reading Frame. Codons are always 3 letter long, staring at the ALU that initiates the mRNA being read. That reading frame of 3 letters per word has to be preserved through the whole gene. If you shift all the letters along by anything other than a multiple of 3, everything after that change becomes very different – and usually garbage.

An insertion or deletion of a non-multiple of 3 letters will not be significant if it occurs in DNA/RNA that does not code for something, but if it is in a gene it is 99.9837% (2) of the time a disaster for that gene, destroying the function of that polypeptide it producers. SARS-Cov-2 is an RNA virus and such viruses are almost all functional gene. Thus deletions or insertions that do not preserve the reading frame are rare (but do occur) in SARS-Cov-2 and other viruses.

Variant B.1.1.7 has 3 deletion mutations in it but they all preserve the reading frame. They drop 1,2, or 3 amino acids out of the polypeptides they code for. But the rest of the polypeptide is preserved. One particular deletion, in the spike protein removing amino acids 69 and 70, stops one of the standard PCR tests from detecting RNA fragments of SARS-CoV-2. I’ll revisit this topic in another post, but because it stops one of the standard PCR tests from working, that can be used in many situations for tracking this variant. Don’t worry, PCR tests for SARS-CoV-2 use 2 or 3 RNA sites to identify the virus, so it is still detected. However, the failure of one of the “channels” has turned out to be a boon for tracking this nasty variant.

Single Direction Of Information.

Under the central dogma you will see that information flows from DNA in the cell nucleus, to mRNA that leaves the nucleus and goes into the cell cytoplasm, and this is translated into polypeptides. It does not go the other way.

Nothing I know of in biology can take a polypeptide, let alone a mature protein, and generate RNA from it. Nothing. Humans can make a stab at it, we can look at the amino acid sequence of a protein and design an mRNA strand that might sort-of work but it’s hellishly difficult as organisms like terrestrial plants and vertebrates have complex post-processing of many polypeptides. Biology cannot do it.

There is nothing that takes mRNA and pulls it back into the cell nucleus and shoves it into our DNA. Nothing natural can do this that I am aware of. A couple of people on a social media forum full of biology experts that I mentioned this post on have voiced possibilities, but nothing concrete yet has been forthcoming (and it would be fascinating to learn about if they do, I’m always looking to learn).

Some of you may have heard of retroviruses such as HIV (the virus that causes AIDS). They can do something that sounds similar – but it is not. They can reverse transcribe their own RNA, i.e. create a DNA copy of their RNA using a reverse transcriptase enzyme, and insert it into the host DNA using an integrase enzyme. The retrovirus has the RNA genes for these two proteins in it’s genome, it brings it’s tools with it. They get into the nucleus of the host cell and use their own tools to insert their own genome into the host, along with control DNA so that the viral DNA can be expressed. What it does NOT do (as far as I know and this is possible where I am wrong) is grab random mRNA from around it and insert it into the DNA of the host. Remember, mRNA is exported out of the nucleus. It’s not there in the nucleus, at least not for long. Also, even if a retrovirus was to insert mRNA into the host’s DNA, it would be doing so without promoter sequences and all the stuff needed to get a gene to be expressed.

I make this point as some people on social media have claimed the mRNA in Covid-19 vaccines could get into your DNA. No, it can’t. It won’t. Anyone claiming this does happen does not understand the central dogma of molecular biology. Either that or they could be in line for a Nobel Prize in biology.

Firstly, the vaccine does not get into the nucleus. Second, there is no biological process native to vertebrates to do the insertion of mRNA into DNA. Third, even if by some chance a virus like HIV was present, and by some miracle some of that mRNA for the vaccine got into the nucleus, HIV is inserting a copy it’s own DNA, not random mRNA hanging around. Finally, even if a miracle on a miracle occurred and the mRNA from the vaccine was inserted into your DNA – there would be nothing to cause it to be expressed. It would just sit there doing absolutely nothing.

What Retroviruses can do is insert into a DNA genome, then when it is expressed it can occasionally pick up DNA from around where it inserted into the genome, which is transcribed and included into the RNA for the virus. If this modified virus then infects another organism and takes that original host DNA (as an RNA copy) with it, it can then insert that picked-up DNA into the new host. It’s very rare, it can happen. But no reverse reading of mRNA was involved.

Basically, the idea of mRNA from a vaccine getting into your genome is damned close to impossible given the current understanding of molecular biology.

Viruses

I’ll finish with some information on viruses.

Viruses are weird. There is an ongoing debate (and has been for over 35 years, as it was a topic of discussion during my degree) whether viruses are alive. Viruses can’t do anything without a cell and it’s machinery to make proteins from DNA/RNA. They can’t move themselves, they get moved about by mechanical processes (in droplets of liquid, floating in water, blown around in the air, transferred via fluids in real living things…). They don’t grow, they do not respond to stimuli (all other life from bacteria up do). They do nothing. A virus consists of just a few things:

  • A string of genetic material, either double stranded DNA similar to what is in us, single stranded DNA or RNA (usually single stranded but occasionally double stranded). SARS-CoV-2 is a single stranded RNA virus.
  • A protein coat, called a capsid, encapsulating the genetic material, keeping it protected and whole. This might be a simple, uniform coat or something more complex made of many proteins. SARS-CoV-2 has a capsid made of several proteins including the famous “spike” protein, which sticks out of the capsid and is what latches onto the ACE2 proteins on our cell walls and allows the virus to get into the host cell.
  • Protein(s) within the capsid, binding to and protecting the genetic material. SARS-CoV-2 has this.
  • A virus may have an outer lipid (fat) layer, usually derived from the lipid layer of the host cell it infected. SARS-CoV-2 does not have this.

I think of viruses as very, very complex poisons and not alive. Others think of it as alive.

If you want to know more about the structure of SARS-CoV-2 this paper on the structure of the virus on the NCBI site is very good but quite technical.

The genetic material for a standard virus (like SARS-Cov-2) codes for a load or mRNAs that usurp the polypeptide making machinery of the host cells. i.e., they use the second half of the central dogma. Once the virus gets into a host cell, the mRNA is released and it hijacks our own cell’s ribosomes. It makes new proteins to make the virus shell and proteins to coat the RNA of the virus. It creates an RNA Polymerase enzyme to replicate it’s own genetic code and, in the case of coronaviruses like SARS-CoV-2 (and other types of virus) it produces a “checking enzyme” to make sure the RNA copies accurately.

This last point is very interesting. All organisms mutate but RNA viruses are the fastest mutating thing we know of. But SARS-CoV-2 mutates slowly for an RNA virus as it has a check enzyme. That’s one thing to be very thankful for. Influenza is an RNA virus that does not have a checking enzyme, which is part of why it changes so quickly and we need a new vaccine for it each year.

All these bits of the virus then self-assemble into thousands of new copies of the virus, burst the host cell and go and infect other cells in the organism. Some are ejected from the host organism in droplets coughed out or similar mechanical processes and infect other hosts.

That’s pretty much all that a virus does.

Notes

1) I said all our DNA is in the nucleus and controls everything. This is not quite true and I am sure some of you know that. We also have DNA in our mitochondria, the organelles in our cells providing us with energy at a biochemical level. Mitochondria look a little like bacterial cells living within our cells and some scientists think this is where they originally came from. It is suggested that a very early Eukaryotic cell absorbed and made a symbiotic relationship with a bacterial cell that was very good at making ATP (the unit of energy in most biology). This was so successful that the organism that did that out-competed all other Eukaryotic life and took over. And, over time the absorbed bacteria became simplified and specialised as the mitochondria. As a result, mitochondria have their own DNA. As do chloroplasts in plants.

2) There is really only one hard, absolute rule in biology. There is an exception to every absolute rule. See 1! Forgive me if I don’t cover all the exceptions in the rest of this post, but what I sat here is true 99.9837% of the time. And treat all percentages in documents with scepticism, many are made up.

3) The distinction between amino acids and peptides has always annoyed me. If “Amino acid” is the term for the building blocks of proteins should not a chain of amino acids be a “polyamino” or something? No, we have peptides/polypeptides.  A peptide has to be 2 or more amino acids as it is named after the bond between the two amino acids. A Peptide bond. Strictly speaking a peptide of between 2 and 20 amino acids is called an oligopeptide, and above that is a polypeptide. It’s just messy.

4) The ribosome may not drop off the mRNA. If the poly-A tail and the mRNA cap are intact, they my bind together to form a loop that allows most of the ribosomes to simply circle around the whole mRNA and make more polypeptide more efficiently. This might help curtail the activity of the mRNA more quickly as, when the poly-A tail or the cap are degraded (as there is some mechanism to degrade the cap too), then the loop is broken and Ribosomes can no longer cycle around. I don’t know the details.

5) The codon to amino acid mapping is very nearly universal. Almost all organism use the same mapping and it is one of the proofs that all life on this planet is related. However, there are some exceptions (as there always are in biology). If you want to nerd out on it look at this Wikipedia page on alternative codon translation tables.

6) The basics of the central dogma of molecular biology has been known for over 50 years. Here’s the start of the chapter on it from my 33 year old  “Genes 3” by Benjamin Lewin. Looking back at this book, which I pretty much knew cover to cover back then, I realise how much knowledge has leaked out my head.

This is the central dogma in my genetics undergraduate text book from 1988

 

Covid-19: The New Variant and the NHS December 29, 2020

Posted by mwidlake in COVID-19, ethics, rant, science.
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<<- Long term hopeful, short term worried

As I said in my blog post a couple of days ago, I’m very concerned about the new variant of SARS-CoV-2 that has been spreading through the UK and is now being found in countries all over the world. My main concern is that this could be what pushes our health services beyond the limit of what they can stretch to and, as a result deaths will jump up – and not just from Covid-19.

New Variant Impact

In my last post I highlighted the new variant of SARS-CoV-2 that is more infections (spreads more easily), but said that there was little evidence that it was any more fatal. Understanding what was going on was hampered at that point as we had hit the festive period and, with the best will in the world, everyone needs a break at some point. New data on hospital admissions, virus sequencing, case numbers were all missing or affected. Scientists studying aspects of Covid-19 were reminding themselves what their partners, kids, and pets looked like after what must have been a heavy year. Now the new information is coming out, as is the analysis by relevant experts.

There is a paper detailing this new variant by Public Health England which was published on 28/12/20. Much of the below is derived from that, but is backed up from many tweets and bits of evidence from the scientific community.

This new variant is know by a few names:

  • VOC 202012/01 – Variant of Concern identified in 2020 month 12, number 1
  • B.1.1.7 – the phylogenetic name of the variant (I think!)
  • 20B/501Y.V1 or simply 501Y.V1 – the identifier given by Nextstrain

B.1.1.7 has many mutations from the original SAR-CoV-2 virus (this STAT article states 17 mutations, the tracking page I mention below lists 17 SNP mutations, this overview by the CDC on VOC 201212/01 lists 20 SNPs and 3 deletions and seems to be the best source of information on this. I’ll explain all the mutations better in a later post) . Mutation is not unusual, viruses change all the time. Each time a virus is copied (and that is how viruses like coronaviruses reproduce, there is no sex, they are identical clones of their only parent) the RNA is copied and occasional mistakes are made and thus changes, mutations, happen. The most common change is a Single Nucleotide Polymorphism, or SNP. One letter of the 30,000 in the viral genome changes.

A single SNP change to the SARS-CoV-2 RNA does not seem to be enough to change the virus into a significantly more infective version (or more lethal, or more likely to infect children, or change it’s behaviour in a way to make it more dangerous). If it did, we would have seen this already – the virus has been so successful in spreading in humans and thus reproducing and so those SNPS occurring, that most individual SNP mutations that are possible will have happened by now (there is evidence for minor change by them though, but that’s for another time). It is going to be a combination of two or more changes I think that has altered the transmissibility.

B.1.1.7 has several changes to the gene that creates the spike protein.

The paper from Public Health England I reference reviews the data that was initially presented to the UK government (on around the 19th December I presume) and resulted in their initial analysis of the 21st, which this paper links to.  This review considers the degree to which the new strain transmits more easily and possible reasons why. It can  be summed up as saying:

  • This new variant is indeed spreading faster.
  • it is becoming the most dominant strain in all the areas it is in.
  • It’s ability to spread to others (secondary attack rate) is increased by about 55%.
  • It is not spreading faster as it is more successful in re-infecting people who have already had Covid-19.
  • There is no evidence it results in more hospital stays or is more fatal.

I’m not sure the evidence is yet firm that this new variant does not also increase the severity of the illness a little as there are too few cases to go on, but it does not like there can be a huge increase. Usual caveat, I’m no epidemiologist.

I’ve also looked at a paper by Nick Davies’ team at the London School of Hygiene and Tropical Medicine.

They considered 4 possible methods by which the new variant (they use the VOC202012/01 name) could be causing the rapid spread of the new variant

  • A) Increased Transmissibility
  • B) avoids current immunity
  • C) Children being more susceptible
  • D) shorter viral generation time

As you can see from the graphs, the model based on (A) Increased Transmissibility fitted the date better than anything else.

You may be aware of the new variant in South Africa that is also more transmissible. This is not the same as B.1.1.7, for example, it does not have the 69/70 deletion mentioned in Public Health England paper that is used as a proxy to identify B.1.1.7 in the UK population (again, more information later on the details of the new mutation). So this deletion either is not key to the increased transmission or else there are two methods by which the transmissibility can be increased (now, that’s a worrying thought).

There has been a lot of other analysis and commentary from the scientific community to back up the hypothesis that B.1.1.7 spreads 50%-55% faster.

Why Is 50% Faster Spread So Significant?

Why is this significant? Wouldn’t 50% more lethal be more of a worry?

No. The reason an epidemic is so scary and has such an impact is down to exponential growth. To use an extreme example such as exists before a new disease is recognised and steps taken to control it, If 1 person infects 2 people who infect 4, 8,16,32… Ten duplications later and you are at 1,024 infected people. If each person infects 3 then it goes 1 person, 3, 9,27, 81…ten tripling’s is 59,049. If you know how many people each infected person will infect (the R number) and how long it takes for an exposed person to themselves become infectious, then you can calculate how quickly the disease will spread and grow. So the transmissibility is key.

Adam Kucharski put it better than I can (if you are on twitter and you are interested in Covid-19 science, if you are not already following Adam then I highly recommend you do, and then follow some of the people he follows). This is how he explained it:

Here in the UK the number of cases and, more importantly, hospital admissions have been shooting up. You cannot compare case from the spring to now as testing now is orders of magnitude improved compared to the shambles back in April. But hospital beds occupied is a very powerful metric and can be compared. Up to a point.

I showed a graph in my last post about how many people are ill in hospital with Covid-19, going up to 24th December. The below is the graph up until the 28th December. We still don’t have data for Wales, Northern Ireland, and Scotland beyond the 22nd December – but England on it’s own ( 20,426) is not far off matching the UK peak of 21,683 back on 12th April. If we optimistically only add on 1,727 for Wales, 1,045 for Scotland, and 451 for Northern Ireland (their figures for the 22nd) we are at 23,649. I’m seeing a lot of stuff on social media and the BBC news about hospitals running out of capacity, cancelling routine work, calling staff in from holiday (and remember, this is staff who have nearly all been pulling extra and double shifts for 9 months already). We suspect are approaching 100% hospital capacity for the NHS.

Patients in hospital with Covid-19 across the UK, 28/12/20

Update, 30/12/20 – we now have the Welsh & Northern Irish data to 28/12, Scotland & England to the 29th . The UK total for the 28/12 is 23,771 (slightly above my optimistic lower threshold of 23,649, as is to be expected. Northern Ireland shows a modest increase that could just be random variation, all three other nations show an increase.

Patients in hospital with Covid-19 across the UK, 29/12/20

 

 

 

100% Hospital Capacity is a Really, Really Bad Thing

I said that hospital beds occupied is a powerful metric up to a point. Why up to a point? At some point that metric stops increasing so fast or even at all – but not because of a lack of patients to treat, but because you are running out of capacity in your hospitals.

I’m sorry, I’m going to go on a bit of a rant here. The below is why I get so vexed at people saying “I need to go on holiday” or “I must have my nails painted” or decide it’s OK if they have a party or that we don’t need a lockdown.

If you get Covid-19 and are badly affected, you may well need supplemental oxygen. You may also need treating for various blood clotting conditions, or to stop your immune system over-reacting, and several other things. That can only be done in hospital. If it is done, most people treated survive (though some of course still sadly die). If you are not treated, you will die. As some of you know, I had personal experience of this late last year when influenza type A and pneumonia landed me in intensive care for a week, on very powerful CPAP ventilators. If I had not had that treatment, I would not be typing this (or anything). So we can (and do) treat and save many people with compromised breathing and the other things that come with Covid-19. Until we run out of trained hospital staff. It’s not beds per se that are the issue, or ventilators, or really any equipment. It is people who have the skills to run that equipment, monitor you, keep you ticking over and otherwise not-dead whilst supporting the broken parts of your body until they heal. Once the capacity of the health service is exceeded, they have to pick who dies. And of course, we do not just have Covid-19, hospitals are dealing with all the other sick patients we always have – car accidents, cancer, influenza, septicaemia, heart attacks…

I’ve seen the stuff by some people about how “only” 377 or so healthy, young people have died of Covid-19. Part of me can’t be bothered explaining to them why they are selfish, clueless idiots right now but what I can say is if we run out of hospital staff capacity, you can be as young and fit and bloody callous as you like but you will die if you need oxygen treatment and do not get it.

I’ve seen some tweets by people who say things like “well, just get more nurses and doctors”. I checked, they are not made in a factory. Training to be a nurse is not like going on a week-long course to learn to use a chainsaw. Doctors and nurses and radiologists and lab staff (and all the others people forget about who are vital to the NHS) are trained for many years. Being an ICU doctor or nurse is particularly technical and needs months or years of training ON TOP of being a standard doctor or nurse.

The UK was desperately short of all NHS clinical staff before Covid-19. One of my closest friends organises the lab rotas for a very large hospital and she never has enough people to fill the rotas. She has to beg and hassle people to do more than their fair share of weekend and night shifts. They constantly have not just one or two but a dozen or more open positions for staff. I’m not getting political here but there was a crisis in care long before the pandemic.

If you see figures saying ICU capacity is at 90% you would probably naturally think “well, they still have 10% spare, it’s fine”. It’s not. One of my first jobs was writing bed management software for hospital systems and teaching hospital staff how to use the software. The software was a god-send for them. A hospital bed is not just a bed. It’s a type of bed, and there are several types in hospitals. Some are for children, most are for adults, some are powered to help move the patient about, some are specialist for ICU (such as being able to pass air around incapacitated patients to reduce bed sores)… And beds move. For my spell in ICU I was initially admitted to A&E and held in a storage room as there was no spare capacity. They brought a suitable bed to me and squeezed it into the storage room. About 12 hours later, 6 or 7 nurses took the bed with me and a shit load of equipment through the hospital to the ward.

You have to know who is in which bed, the consultant & specialty treating them. For very, very good reasons, the specialist or someone in their group needs to approve a lot of what is done to you in a hospital. To administer a drug to a patient you have to find the bed they are in and you have no time to go wandering around the ward as you have 101 other things to do. The same is true of feeding the patient. You have to track when a patient moves (either with their bed or moving from one bed to another) and you need to know where you can move them to, so you need to know what beds are spare or, more likely, probably going to come spare. I worked on another part of the hospital system, “notify patient as dead”. It was horribly complex, lots of stuff has to happen when a patient dies, for example some lab tests get cancelled, others get created. The bed is noted as empty pending a deep clean. Sometimes, heartless though it sounds, the staff need to know when a bed is likely to become available via that route.

The people in charge of beds need to know ASAP when a bed is free so they can try and do all the juggling above that I mentioned. The fewer spare beds they have the harder it gets to make use of the few spare ones you still have and move people around efficiently. Or even inefficiently.

When I moved out of ICU it was a rush job. Someone needed one of the very most critical ICU beds (yes, there are tiers to what we non-medics think of as ICU), they felt able to move another person into my intermediate dependency bed as they were improving – IF they could get me out of it and into the Respiratory Medicine ward. Which they did, at about midnight. The sticking point was I needed to be isolated to I could not give someone with COPD influenza and finish them off. Another complication. It being night there were fewer staff so only 2 people could be spared to move me. Admittedly, less equipment came with me but half of it (including a heavy oxygen cylinder) was on the bed with me, I had hold of something on wheels, the 2 nurses somehow corralled the bed and other equipment.

The point I am making is that the closer a hospital gets to 100% capacity, the harder all that juggling becomes, and you actually end up having to move patients to other hospitals – and moving a sick patient to a different hospital is generally not in the best interest of the moved patient – or discharge patients who could really benefit from being there longer (but don’t need it as much as the person who is dying that they can’t find a bed for).

I’ve only ranted about beds. I have no idea how they keep track of other equipment, plan who is allocated to do what, how to cover for say a member of staff going ill, a major road traffic accident when all ICU is full…

If we do not see some sort of miraculous downturn in hospital admissions (and all indicators are against this happening) I’m expecting the UK to be in full national lockdown in a week, kids returning to schools cancelled. If we hit 100% hospital capacity and are not in a strict lockdown, then our government will have failed us in this crisis once more.

Even more distressingly, we may see avoidable deaths.

 

 

Communicating on Covid-19 Again December 27, 2020

Posted by mwidlake in COVID-19.
Tags: ,
4 comments

New Variant & impact on NHS->>

<<- Start of Original Post beginning in March 

After quite a break, I’ve decided to return to converting my notes & thoughts on Covid-19 and SARS-CoV-2 into blog posts again, but I’m going to do so in a slightly different format. Why am I returning to blogging on the topic? Well, people do still keep asking me what is going on and I’ve mostly been answering on Twitter or Facebook (or in person on the rare occasions I meet people!), but I don’t feel Twitter and Facebook are particularly good forums for explaining things. And writing it down in a way I feel someone with a little bit of scientific understanding can understand helps me understand and, more importantly, makes me check the scientific output to try and make sure I am right.

As for the different format, I’m going to do shorter, less comprehensive posts. This is because when I did this last spring/early summer I would spend a week doing a post that I thought would take a day and, by the end of the week, some things were changing and the post was just too loooooong.  If you feel something is missing from my future posts or you have any question a post prompts, please ask. If I can I will try and answer, or at least point you in the direction of a scientist or similar expert saying something about it.

On the subject of expertise, as anyone who has followed my blog knows I am a computer person (I specialise in the performance of Oracle databases). As ever I am going to stress that I am not an epidemiologist, not a virologist, and I have no medical qualifications. I have never been a working scientist (closest I got was I did a summer as a volunteer in a genetics lab before my final year at university, I mutated moss). What I do do is look at the output of scientists who communicate on Covid-19. I only listen to scientific and medical output. I do look at what the UK government says but I don’t see their briefings as a reliable source. This is not due to conspiracy theory, it’s more that (a) the UK government does not have a good back history of actually ‘Following The Science’ as they keep claiming (b) their job is not to explain stuff, it’s to get the population to do what they want them to do and yet remain as popular as they can (c) when a minister or one of the experts on the public briefings do explain something, they have to keep it simple and short.   

Given I am not an expert, why do I think I can explain to you what is going on? Well, I have an ancient degree in genetics & zoology and I’ve maintained an interest in science all my adult life. I’ve worked (developing computer systems) in or alongside the UK NHS for 7 years, in biological academia (mostly ‘the human genome project’) for 7 years, so I have a lot of experience in communicating with medics and scientists. For the last 15 years I have presented at conferences (and I get good speaker scores), written articles, done the odd webinar, and produced this blog. So I have experience of communicating what I do know to an audience.

If you want a refresher on Covid-19 (what it is, what it does to you) there are endless resources out there, but This summary I wrote back in March is still mostly relevant and it is interesting to see the predictions I made and which were right and wrong. Spoiler, I’m pretty good at saying how things will go for a few weeks (as are millions of others), I’m not so good beyond that, so I’m leaving that to the epidemiologists!

I’m hoping to put out my first real posts on the current situation on Covid-19 in the UK over the next couple of days, but I wanted to mention what is really concerning me and what helped prompt me to dig back into the scientific details again.

Long term – I’m really hopeful.

One thing I was wrong about was how long it would take to create a vaccine that was safe and gave good protection. I’ve never been happier to be wrong!

It’s a testament to the long hours and days of work of thousands of scientists, the worldwide sharing of information between scientific groups, the funding made available to them by governments & charitable bodies, and the efforts of the regulators & pharmacovigilance experts working to ensure Due Diligence in compressed timescales – i.e. that the vaccines are proven safe.

We have three vaccines in the West that are approved or close to being approved over a growing number of countries – 

  • BioNTech/Pfizer and Moderna/NIAID that use the new mRNA-based methodology. They need to be kept very cold (minus 70C and minus 20C respectively) but are approximately 95% effective,
  • The Oxford University/AstraZeneca vaccine which is a more traditional vaccine that uses a modified, harmless adenovirus and is less effective (work still being done on how effective: 60-90%?) but does not need to be frozen and so is much, much easier to transport.

Many more vaccines are still in development. Having a set of vaccines will be a real boon as, for example, the Oxford/AZ one will be a lot easier to administer in warm countries lacking in ultracold-chain facilities, but where such infrastructure is present, we can use the more effective vaccines.

Gary Myers corrected  my information on how cold the two mRNA vaccines need to be kept and pointed me to this article by NPR

Nine months ago I would have been overjoyed for a single vaccine that was 75% effective by the summer of 2021, so to have three by the end of the year and more on the way is fantastic.

But it is a massive logistical effort to roll these vaccines out and the impact on the spread of Covid-19 and our lives will evolve over the next 12 months. For the whole globe we are looking at 2 years probably and I am sure there will be bumps along the way, such as one of the vaccines proving to be not very long lasting so re-vaccination is needed for some.

One thing I want to point out is that there have been over 1/2 a million 5 million people inoculated (wow, that’s shot up so quickly) to date with very, very few contraindications (things going wrong) reported. I am not aware of any life-threatening reactions to the vaccines to date but they protect the vast majority of people from a life-threatening disease.

You can track world numbers for vaccinations at this “ourworldindata” site. I have not looked at it much myself yet but it certainly seems to give you the key information.  

Short term – I am very worried

I was already concerned that world figures for cases & deaths continue to rise, the figures in the UK are constantly going up, and yet more and more people seem to be wanting to believe there is no problem. And now we have new variants of Covid-19 that spread more easily, both in the  UK and across the globe.

In summary, as some of you will be aware, we have a new, more contagious, variant of SARS-CoV-2 in the UK, which is most prevalent in the South of England. It appears to spread a lot more efficiently than other versions and it has worried the scientific community. For once, the UK government actually responded very quickly to this change and they “cancelled Christmas”, put the South East and London effectively into lockdown and soon after announced many other areas would go into the new Tier 4 the day after Christmas. (To be clear, many scientists had already called for the proposed relaxation of social distancing for 5 days over Christmas to be abandoned and replaced with tighter controls, based only on the growing case figures – which Boris Johnson and his cabinet seemed set to ignore).

With the new information about the new, more virulent variant of SARS-CoV-2, many countries have stopped flights to/from the UK or brought in stricter checks and/or rules on isolating people arriving from the UK. France closed their border with the UK preventing (amongst other things) any lorry freight (as people drive the lorries). This island became pretty much isolated (and people started worrying about getting fresh salad, which tells you a lot about some people’s priorities).

Cases of C-19 in UK Regions since August

It seems some people think these national and international restrictions were brought in simply because the number of cases of Covid-19 in the UK were escalating quickly, but it was this new variant that has mostly worried other countries.

The graph is from an excellent twitter thread by Christina Pagel, based on official UK government figures. It shows how the last UK lockdown had the intended effect of suppressing Covid-19 in most areas, reducing the number of people affected by the disease (unlike the regional tier approach which had struggled to really reduce transmission). However, look at the black East of England, orange London and green South East lines. The lockdown had less effect there and by the end of lockdown cases were rising in these areas. Why? It could have been more testing being done (so you see more cases) or people ignoring the rules, or something else. It turns out it was something else, this new variant. Correlation is not causation, but the percentage of people with the new variant of SARS-CoV-2 is much, much higher in these areas. Lap tests have shown the new variant latches onto ACE2 proteins, it’s door into our cells, more efficiently.

At the moment there is no evidence that this new variant is any more deadly or makes people sicker, or that it means the vaccines that are currently being rolled out will not work against it, but time and more study will tell.

C-19 patients in English hospital 14/12. It will increase.

So why is this new variant a worry? Because if this new variant is spreading more easily (and the figure quoted by the media is “70% faster” but I’ll dig into that in a later post) it means the number of people who are ill will double much more quickly – and we are in real danger of flooding the NHS with ill people. All along, since this new disease reared its head, the overwhelming of healthcare systems has been the main worry, much more than the actual raw number of people it will kill and harm. That is what all that talk about flattening the curve was about in March & April, spread the people getting sick over a longer period so at no point do you run out of hospital capacity. The more infectious version of Covid-19 is pushing up the curve, and threatens to do so very significantly.

The graph to the left is for hospital beds occupied by Covid-19 patients as of Christmas Eve – the latest day we have figures for as I type. They are only just below the April high. In Wales, for which we only have figures up to the 22nd December, bed occupancy greatly exceeds the spring high. I am sure that if we have not already exceeded the previous national high for hospital bed occupancy UK-wide then we will in a very few days and it will get worse, as people catching the disease over the last week or two get admitted. Cases precede hospital admissions precede number of deaths.

The new variant is most common in the South East, East and London areas of the UK, but it is present across the whole of the UK. (In Wales there appears to be slightly different more-contagious version of SARS-CoV-2 but again for a later post.)

Here in the UK we are in for a rough ride and the government is going to have to bring in more restrictions to try and keep this new variant under control. 

New Variant across the world

What about across the world? Well this new variant is already present in many countries. It might have originated in the UK, it might not, this is still being investigated. The reason we do not know for sure is that the UK sequences a lot more SARS-CoV-2 samples than other countries, so they might not have spotted what we did. Again, I plan to expand on this in a later post.

The new varient, B.1.1.7, has been seen now in France, Netherlands, Singapore, Italy, Israel, Denmark, Australia. The list will grow daily.

I’m afraid the genie is out the bottle and, much as we saw with the original spread of Covid-19, with international travel and it having got out before we could close borders on it, it is probably inevitable that this new variant will take over in all countries where SAR-CoV-2 is spreading.

In South Africa there is yet another more virulent strain, with some of the same mutations the new UK strain has, which seems to have arisen independently. I have no idea why more than one highly virulent strain has occurred in relatively close temporal proximity (same time) in different locations, it is probably just bad luck. Genetic mutation is random and directionless (well, with a few odd exceptions that as far as I know do not apply here). This other new strain is known as B.1.351

Both variants can be tracked at this site, which is where the image to the left is from. Updates are a little slow at the moment due to the time of year but, even with it being Chistmas, the people behind the site have added more information. Scientists, nothing stops them for long.

I think we are at a crucial point:

  • Vaccines are on their way and that is brilliant.
  • World wide we were already struggling to keep the Covid-19 situation from getting worse.
  • The new variant(s) are increasing the spread rate, possibly significantly.

Despite my reputation for it this year, I don’t like being all doom & gloom, but I feel right now like I did at the end of February/start of March. Very anxious about how this is going to play out for so many people, especially those who (for whatever reason) have decided Covid-19 is being blown out of all proportion or is not going to impact them.

I cancelled Christmas before the government did, it was not wise to go see my mother and brother, even though we all keep ourselves fairly isolated and take all the proper precautions. I think no matter what, for the next 6 months until the vaccines are making more of a difference (and by this I mean reducing the stress on the NHS by protecting those most likely to get critically ill, as opposed to herd immunity), I’m going to be a hermit, read books, sort out the garden, and keep watching what the scientists say.

I think Christina Pagel summed it up perfectly:

COVID-19: The Current Situation in the UK and June. May 30, 2020

Posted by mwidlake in COVID-19, Perceptions, Private Life, rant, science.
Tags: , , , ,
7 comments

I’ve not said anything about Covid-19 for much longer than I expected, but really it has been a case of watching the coming peak come and go, pretty much following the pattern of Italy, Spain, Belgium and France. I plan to do a post soon which pulls together the current scientific position, but for now I wanted to record where we are and where my gut feeling (based as ever on reliable scientific sources and not so much on what the daily government updates would like us to think) says we will be in a month or so.

The number of UK recorded deaths where C-19 was present, and detected cases

We’ve not done very well in the UK. If you are based in the UK you may not be aware of the fact that most of Europe think we have,as a nation, been idiots – failing to learn from other countries, late to lock-down, lock-down was not strict enough, too early to open up, our PPE fiasco… I can’t say I can disagree with them. We have one of the highest deaths-per-million-population rates in Europe, exceeded only by Spain and Belgium. But it could have been worse. A lot worse.

I’m truly relieved my predictions in my last post were (for once) too pessimistic. I misjudged when the peak in deaths would be by over a week – it was 9 days earlier than I thought, happening around the 11th April. As a result of coming sooner, the peak was lower than my little model predicted. Even allowing for that, the increase in number of deaths did not mirror the increase in cases (I used the cases pattern as my template for deaths). I think this is because the UK finally started ramping up it’s testing rate. The more testing you do, the more of the real cases you detect, so some of the increase in cases was simply better testing and not continuing spreading. That’s what happens when the source of your metrics changes, your model loses accuracy.

Deaths are directly related to real case numbers, it does not actually matter how many cases you detect. This is part of why case numbers are a much poorer metric for epidemics, whereas deaths are better. The best metric is a random, large sample for those who have had the disease – but we still do not have reliable, large-scale antibody or similar tests to tell us this.

If you look at the actual figures and compare to what I predicted for the peak of deaths, I seem to have been pretty accurate. I said 1,200 to 1,500 around the 20th April and the peak was 1,172 in the 21st April. But I was predicting hospital deaths only. Up until 29th April this was the number reported each day but since then the daily number of deaths reported included community (mostly care home) deaths. The previous figures were altered to reflect this and the graphs to the right are based on these updated figures. Hospital deaths seem to have peaked at 980 on the 11th April, so I was wrong.

I think it is crucial in science and technology (and actually, just in general) that you be honest when you are wrong – even if (like in this case) I could made a fallacious claim to have hit the nail on the head.

The bottom line is, we are well past the first peak and it did not overwhelm the NHS. It got really close and our issues with personal protective equipment was a scandal and must have resulted in more illness and some avoidable deaths to our front-line NHS staff. But, apparently, saying so is Political.

All in all we followed the pattern of European counties that were impacted by Covid-19 before us and implemented similar country-wide lock-downs.

One difference between us and other European countries that have been hit hard is our tail of cases is thicker and longer. We have not been as rigorous in our lock-down as those other countries (e.g we did not have to have written permission to leave or enter an area and children were not utterly forbidden from leaving home, which are just two examples how our lock-down was softer). I know it might not feel like it, but we were not.

What really concerns me is that we are easing lock-down measures so soon in the UK. Our daily new case rate and number of deaths are both still really quite high. The figures always drop over the weekend, especially Sunday and Monday (due to the numbers reported being for the day before). Over the last 3 days (Wed to Fri) we averaged 1998 new cases and 371 deaths per day. If you think Covid-19 has gone away, every single day there are 371 families who sadly know different.

I understand that the economy is important, that unless things are being manufactured, services provided, money earned and spent, that a large part of our society is not functioning. Maybe I don’t really appreciate how important it is as economics has always looked more like a dark art based on greed than anything logical, but some people feel getting back to normal business is critical and the long-term impact of not doing so is potentially as serious as Covid-19.

I also know that not being able to go to places, eat out, have a drink in the pub, meet up with friends in a building or in more than small numbers is frustrating. For many, not seeing your family and loved ones who are not in your home is very upsetting.

I’m sure that parents are desperate for kids to go back to school (partly for education and partly as it turns out kids are a lot of work), couples need a bit of time apart, people are missing their jobs. Nearly all of us have never had to spend so much time with a very small number of other people.

But I’m also sure that what we don’t want is in 4-8 weeks to have to go into the same level of lock-down as we spent most of this spring in. And the next lock-down may be even more draconian as there is a difference now to where we were at the second week of March when we should have locked down first.

SARS-Cov-2 is now endemic and prevalent across the UK. It is everywhere.

At the start of an epidemic the disease is growing in a small number of places, so usually (such as was the case with MERS and SARS) you can contain it by strong isolation and tracking efforts in those areas it occurs, as most of the population are not exposed. This is why you cannot contain seasonal ‘flu epidemics by isolating people, it does not work if it is wide-spread enough. ‘Flu simply flows through the population and it does in some years kill a lot of people.

With Covid-19 right now, If our R(e) – the effective reproduction number – goes above 1 anywhere across the UK, Covid-19 cases will rapidly increase in that area. And with restrictions being lifted across the whole UK and in England especially, I am privately convinced the disease will burst fourth again in many, many places and it is going to go very wrong again. I think the government is being utterly disingenuous about the impact of opening up schools and my friends who are teachers and medics have no doubt this is a significantly more dangerous step than it is being sold as. It might be the right move, but lying about it’s potential impact is not helpful long-term.

Not only are we relaxing social distancing steps too early, but I feel the government has utterly bolloxed up (technical term meaning “done a jolly poor job of”) the messaging. As examples:

  • The very clear “Stay at Home” became the vacuous “Stay Alert”, which no one seems to be able to clearly define and every one seems to have a different interpretation of.
  • We were given contradicting and non-nonsensical rules such as you could see one family member from outside your household in the park, but you could have people come and view your house. So if you want to see your mum & dad at the same time, put your house up for sale and have them view it.
  • Parts of the UK (Wales, Northern Ireland, Scotland) have said they were not consulted on changes, they do not agree with them, and they are doing their own thing. That’s not confusing to people is it?
  • The whole Cummings affair. Dominic Cummings did break the rules, he acted like a selfish idiot, he lied about what he did, he had pathetically stupid excuses (“I drove my child around in a car to test my eyesight” which shows he either does not care at all for other people’s safety or has too low an IQ to be allowed out on his own). The issue is not that one arrogant, self-important person decided the rules do not apply to him. It is that the government fail to understand that not sanctioning him is being interpreted by many to mean they can make up their own minds about which rules apply to them and which they can ignore. Continuing to say “look, get over it” is simply coming across as telling us all to bugger off.

To help steer us through this crisis, we really needed a government with both the mandate to introduce new rules and also the acceptance by most of the population of those rules, and at least acquiescence from the majority to put up with limitations placed upon us. What we have now is a not just the hard-core “we won’t be told what to do” people that would always be a negative factor in limiting the spread of a disease, but a large number of angry, confused, worried people across the country. Almost everyone I personally know in the UK feel angry, confused, worried, and mostly with a progressively declining respect for the government and their advice.

I know I’m not very good at understanding people, it does not come naturally to me. If someone does not think like I do, I can have a devil of a job working out why. But I’m pretty sure that here in the UK a lot of people are going to start saying “to hell with the lock-down rules, everyone else is ignoring them and I’ve not seen anyone die in front of me…”

I went to see my Mum this week. I had to drive 100+ miles to do it. Unlike in Dominic’s case, it’s allowed now and I have no Covid-19 symptoms. I took a mask, I took my own food, we sat in her garden (I got sunburn, so Covid-19 might not get me but skin cancer might). I assured myself she was OK and that her tech will keep working so we can stay in touch. And I felt a little naughty doing it.

But I made a conscious decision to do it now – as I think SARS-CoV-2 is about at it’s lowest prevalence in our population right now (end of May 2020) than it is going to be for months. Admissions and deaths are going down and I expect at least deaths to continue to do so for another week or two. Personally I am deeply worried that in 4 weeks time new cases, hospital admissions, and deaths will be going up again. I don’t want them to be but I’ll be (very happily) surprised if they don’t go up  – what we see in cases & deaths at any point in time is based on the level of spread one or two weeks ago respectively. I suspect that as I type our R(e) number is going up and will exceed 1 this week.

If you don’t agree with me, just keep an eye on what the scientists are saying. Some are already making noises of anxiety as an article on the BBC is already saying today. Scientists tend to make cautious statements such as “we do not think this is wise” or “we feel there is a danger in this choice of action”. It’s a normal person’s equivalent of screaming “Are you bloody idiots?!?”.  Once again, the experts are saying we should do one thing and the government are doing another. It’s not gone too well to ignore the scientists so far.

There is a T-shirt you can get at the moment, which I really must order a dozen of.

“All disaster movies start with someone ignoring a scientist”.

 

 

COVID-19: The Coming Peak in the UK & Beyond. April 9, 2020

Posted by mwidlake in biology, COVID-19, off-topic, science.
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<<<<<<Introduction to Covid-19
<<<< Why we had to go into lock-down
<< What we could do to help ease social distancing

The UK government is now talking more in it’s daily briefings about what will come “next”, that is after we have seen the number of diagnosed cases & deaths continue to grow, plateau, and then fall. It will plateau & fall, so long as we all keep staying at home and limiting our social interactions. If we do not, we risk the virus spreading out of control again.

When Will the Peak Be?

My estimates so Do Not Trust At All

First of all, there will be two peaks. First the number of new cases a day will peak and then, about 8 days later, the number of deaths per day will peak. This is because of the average gap between being diagnosed in hospital and succumbing, for those unfortunate enough to do so.

The number of deaths a day looks to me like it will peak around April 20th, at somewhere between 1,200 and 1,500 a day (see below why I think tracking deaths is more reliable than case numbers and why case numbers are a poor metric). We will know that peak is coming as, if the lock-down measures have worked as intend, their effect will result in a plateauing and then drop in new cases during next week ( April 12th-18th). We might be seeing that plateauing already. Deaths will plateau (stay steady) for maybe a longer period than cases due to the fact that the gap between diagnosis and recovery or death is variable. That period will be something like April; 20-27th

If we follow the same “curve” as Italy and Spain,  the number of new cases will slowly start dropping but not as sharply as early models indicated. Deaths will also drop, about 8-10 days later. What happens then I have no idea really, it depends on how well the current social distancing measures work and if people continue to stick to them as spring progresses and people want to escape confinement.

A disproportionate number of deaths in this peak will be from our health services and critical works – people working in shops, bus drivers, refuse collectors, GP’s, teachers – because they are the most exposed. The care industry workers and lower paid people in our society will be hardest hit, which seems monumentally unfair.

The plan of pretty much all national governments so far is the same:

  • Isolation of all people who are non-key workers
  • Slow the spread
  • Expand the respiratory Intensive Care capabilities of the health services as much as possible
  • Look after as many of the wave of people already infected & becoming ill as possible

As I’ve covered in prior blogs, if the government’s measures work we are then we are left “sleeping with the tiger”. The virus is in our population, it will be slowly spreading still, and when social isolation measures relax there is a real risk of the illness and deaths exploding again because most of us are not immune. This is know by all epidemiologists studying this, it is a situation that China, Italy, Spain, and most other countries will face.

The big question is – what comes after the peak?

I’m going to cover three four things:

  1. Why we cannot go on “Cases” the number most often graphed and discussed. We have to go on deaths, and even then there are some confusing factors.
  2. Why the Infection Fatality Rate is key – and we do not know that yet
  3. A “test” or “vaccine” is not a black and white thing, it’s grey, and especially for a Vaccine, it is not coming soon.
  4. How we might manage the period between either a reliable vaccine or herd immunity. Both currently look like at least 18-24 months away.

Why Case Numbers Cannot Be Relied On.

Case Numbers do not tell you as much as you may think

Case numbers (the number of people who have been confirmed as having Covid-19) are the most commonly reported figures, many of us track if things are getting better or worse by them. But they are a very poor indicator really and they certainly cannot be used to compare between countries.

First of all, how are the diagnoses being made? Most countries are using the WHO-approved test or a very similar one, called a PCR test. I won’t go into the details here, I’ll put them in the section of the post on testing, but the test is accurate if done in a laboratory. Why in a lab? because any cross-contamination can give a false positive and if the sample or test chemicals are not kept/handled correctly, can give a false negative.

Not all countries are using just PCR tests. China made some diagnoses based only on symptoms. I’m not sure if other countries are making diagnoses from symptoms only and including them in official figures.

More significantly is who is being tested. In the UK the test was originally only being done on seriously ill patients in hospital. It is now being done on a few NHS staff and certain key people (like Boris Johnson!). In South Korea and Germany, many, many more people were tested, so there will be more cases identified. Add on to that the number of tests a country can do.

In the UK are testing rates have been very poor

In the UK we were limited to a pitifully small number of tests per day, less than 6,000 until March 17th and we only reached 10,000 test a day at the start of April. You cannot detect cases in people you have not tested.

Case numbers will also vary from country to country based on the country’s population! The UK is going to have a lot more cases than Denmark as we have over 10 times as many people.

The final confusion is that even in a single country, what counts as a day for reporting can vary and it can take time for information to be recorded. The UK sees a drop of cases against the prevailing trend on Sunday and Monday. As the cases are for the prior day and it seems like the data is not being as well processed at weekend.

Estimations of how many people really have Covid-19 at any time, as opposed to validated Case numbers, vary wildly. In the UK I doubt we are detecting even 1/3 of cases.

So, all in all, Case Rates are pretty poor as an indicator of how many people are really ill.

Infection Fatality Rate and Tracking Deaths Not Cases.

As I mentioned in my previous post last week, what we really need to know is the Infection Fatality Rate (IFR). This is the percentage of infected people who die. It is not the same as the Case Fatality Rate (CFR), which is the percentage of known cases that die. As the number of known cases is such an unreliable number (see above!) then of course the CFR is going to be rubbish. This is a large part of why the CFR varies so wildly from country to country. France has a CFR of 8.7%, almost as bad as the UK at 10.4%. The US has a CFR of 2.9% (but they will catch up).

As I also covered last week, we cannot calculate the IFR until we know the number of people who have been infected. For that we need a reliable antibody test and one does not exist yet. Yes, they are being sold, but the reliability is poor. Last I knew the UK NHS had reviewed several candidates and none were reliable enough to use.

Scientist have suggested many Infection Fatality rates. I feel 0.5% is a fair estimate. It is vital we know this number with some accuracy as if we have an Infection Fatality Rate we can flip the coin and calculate the number of people who have been infected from the number of people who have died.

IFR * deaths =  number immune

You can go from a graph like the example one I show (either from a model or, after the peak, from real figures) and as you have the number who died (say 20,000 to keep it simple) and the IFR of 0.5% you know that 4 million people (minus the 20,000 who died) had the disease and are now immune.

Of course, once we have a reliable antibody test we can verify the exact value for Infection Fatality Rate and the percentage of the population now immune.  But we only need that information from one country and it can be used, with minor modifications for population age and capacity of the health services, to estimate how many people are immune and thus how many are still at risk from Covid-19. In my example, about 62.5 million people in the UK would still be susceptible to Covid-19. Which is why this will be far from over after this initial peak.

There is one huge caveat in respect of the IFR. If in the UK the NHS is over-run, we will have extra deaths. People who would have survived with treatment die as too many people needed treatment at the same time. This is the whole “flattening the curve” argument, we have to protect the NHS from being over-run to limit this extra, avoidable deaths. In effect the IFR is elevated due to the limitations of the health system.

Countries which do have a poor health service or other aspects of their society that block them from the health service (cultural bias, fear of crippling debt) or more likely to have an elevated IFR, as are countries that allow Covid-19 to run unchecked through their population.

There is another aspect to the IFR and measuring progress of Covid-19 via the death rate. The number of deaths is a more reliable measure. I know that sounds callous, but as we have seen, the Case Number is totally reliant on how you do your testing and there needs to be a huge testing capacity to keep up. Deaths are simpler:

  • There are fewer deaths so fewer tests are needed (to confirm SARS-CoV-2 was present in the deceased, if not already tested).
  • Deaths have to be recorded in a timely manner.
  • Deaths are noticed. There are going to be people who are seriously ill and would be tested if they went to hospital but don’t, they get better and it is not recorded. They are “invisible”. Dead people invariably get noticed.
  • A country that wants to hide the active level of Covid-19 can do so by not testing, under-testing, or not reporting honestly on the tests. It’s not impossible, but it’s hard to cover up a significant increase in the number of deaths.

I stress that is is not a perfect indicator though. There is no clear distinction made as to whether the patient dies of some other illness but SARS-CoV-2 was present; whether the patient was likely to die “soon” anyway – again due to other illnesses; patients who die outside hospitals are not counted in the UK daily figures yet. (If you follow me on Twitter you will have possibly seen me querying the figures last Monday – and people pointing out the reason!)

Reported deaths will also suffer from spikes and dips due to how the reporting is done. The UK and some other countries I checked (France, Italy, Spain) show a dip in all figures, against trend, on Sunday or Monday (or both).

There is a really nice article on all of this this by New Scientist which is itself partly based on this paper by the lancet that gives an IFR of 0.66%

There is also a whole plethora of graphs and information on ourworldindata.org/coronavirus , as well as text explaining in more detail what I have said here. It is well worth a look and you can change which countries appear on the graphs.

 

Test are Not Black And White

There has been a lot of talk in the UK and elsewhere (including the USA), about not doing enough testing. On the other hand their is a constant stream of media reports about quick home tests, both for if you have Covid-19 or have antibodies to SARS-CoV-2 and so are immune. So what is the reality?

A test is only any good if it is reliable as used. For something like a deadly pandemic, it needs to be really reliable. Let me explain why.

Let’s say a company is selling an antibody test and someone uses it, it says they are immune,  and they stop self-isolating. But the test is 75% accurate. 75% sounds good, yes? No. it means 1 in 4 people who take that test and it says they are immune are not –  and they have now gone out, spread the disease to their aunt Mary and she dies. Plus infecting a large number of people and keeping the whole sorry mess going.

{Update – as a friend reminded me, when you are testing for an “unlikely” event, which being immune to C-19 is right now, even a 95% accurate test will give far more false positives than real positives across the whole population – I’ll try and do another blog to explain why}.

And that is if they take the test properly – companies are most likely to give you the best, under-ideal-conditions accuracy rate as they want to sell more kits than Sproggins Pharma selling a similar kit which they claim is 73% accurate.

If you are reading this, you are probably the sort of person who will read the instructions, follow them carefully, not put the swab down on a table,  not let the dog chew it.  And you note the bit on reliability. Most won’t. They will do the test quickly, it says they are immune and they will believe it, especially if the quoted reliability rate is high.

Any home test that can be used by the public has to be both very reliable (less then 5% false positives) and utterly idiot-proof. I’m really concerned that countries that put money first will allow companies to sell tests that do not meet these criteria and it will make the situation a lot, lot worse. It might even result in the pandemic running out of control.

Test For Being Infected – PCR test

PCR stands for Polymerase Chain Reaction. The WHO-approved test for Covid-19 is a PCR test and has been fully described since the end of January. You can even download the details of the test and methods from the WHO page I link to.

A PCR test is a genetic test. A primer is added to the sample to be tested and that primer latches on to a very specific DNA or RNA sequence. A biochemical reaction is then used, called a Polymerase Chain Reaction, to make copies of that DNA/RNA, doubling the number in the sample. These steps are repeated 30 to 40 times to make millions of copies of DNA/RNA. With an old-style PCR test you would then need to run the processed sample through a second process to detect it, like a Southern Blot – you get a square of gel with black lines on it. The PCR test for COVID-19 should be a real-time PCR test. With this the new copies made are attached to a florescent dye so that it can be easily detected as soon as there are enough copies in the sample, say after 30 iterations not the full 40, saving time.

If the original sample contains even just a few pieces of the DNA/RNA you are testing for, you will detect it. The process takes a few hours.

The RNA of the SARS-CoV-2 virus was sequenced (read) back in January and the WHO identified sequences that were unique to the virus, and these are used to make the primers. As I understand it most countries use the WHO identified primers but the USA had some “discussions” between commercial companies over which primers they thought should be used. I won’t suggest there was an element of these commercial companies looking to make a fortune from this, i’m sure it was all about identifying an even more unique RNA sequence to target.

The test has to be done in laboratory conditions. Because the test is so sensitive any cross contamination can give a false positive. e.g the sample taken from a patient was done by someone with COVID-19 themselves or there was SARS-Cov-2 virus in the air from another nearby patient. If a swab is used to get a sample from the back of the throat, it has to be put into a sealed tube as soon as it is used.

If the sample to be tested has not been looked after properly (kept cool, not kept for too long etc) or the chemicals for running the test are similarly not kept in a laboratory environment, you may fail to detect the RNA – a false negative.

Finally, the virus RNA has to be there to be detected. A patient early in their illness may not be shedding virus at a high enough level for the swab to pick up some of it. Once a patient’s own immune system has wiped out the virus (or almost wiped it out) again the swap may not have any or enough virus in it to be detected.

Done right a PCR test is a powerful, incredibly reliable (over 99%) diagnostic tool and is used for detecting many viral diseases, including HIV, Influenza, and MERS.

How a simple yes/no infected test might work

You can probably now understand why creating a PCR test for Covid-19 that can be used at home or in the ward and gives a result in minutes is a bit of a challenge.

Some companies are trying to create a different sort of test. These depend on creating a chemical that will bind to the virus itself, probably one of the viral surface proteins. That chemical or part of it will then react with something else, a marker chemical, to give a visible change, much like a pregnancy test. You put the sample in a well or spot where the detecting chemical is. Fluid is then dragged along the strip carrying the thing to be detected (the virus in this case) and the detecting chemical. Any detecting chemical that did not bind will be left behind. When the fluid goes past the marker chemical, if there is enough detecting chemical, it will change colour. Neat!

Best I know at time of writing, no one has come up with such a test that was reliable. I’m pretty sure someone will, in a few weeks or months. It should be accurate but no where near as sensitive as a PCR test. I must stress, to actually be of use in handling Covid-19 as a nation, the rate of false positive would need to be very low. False negative, though not good for the individual, is nothing like as big a problem in containing the pandemic).

Antibody Test

An Antibody test will show if you have had Covid-19. It will not show if you currently have it, or at least not until the very late stages. This is because it is testing for the natural ability for your immune system, via antibodies, to recognise and attack the SARS-Cov-2 virus.

We desperately need an antibody test as it will allow us to identify people who have had the disease and are now immune. This is vital for 2 reasons:

  1. Someone who is immune does not need to be restricted by social distancing. See my prior post on why this is vital and how we might identify such people.
  2. We can find out how many people have had the disease and compare it to the number of people who have died of the disease and get that very useful Infection Fatality Rate.

Unfortunately, making an antibody test is not easy. Some are in trials and I think the UK government have tried some –  and none have proven trustworthy.

An antibody test is simply not simple. What you need to do is design something that an antibody reacts against, so let me just describe something about antibodies. Before I go any further, I must make it very, very, very clear that of all the biological things I have touched on so far, antibody technology is something my academic background hardly touched on and most of what I know comes from popular science magazines and a few discussions with real experts last year when my work life touched that area.

Your body creates antibodies when it detects something to fight, an invader in our tissues. This is usually a viral or bacterial infection. It also includes cells that “are not our own”, which is why we reject organ transplants unless they are both “matched” to us and we take drugs to dial down our immune response. Our antibodies recognise bits of the invader, in the case of viruses that is (usually) proteins that are in the coat, the outer layer, of viruses. Usually it’s the key proteins, the ones that give them access to our cells. Our immune cells learn to recognise these proteins and attack anything with them on it.

Anyone infected with SARS-Cov-2 who survives (which is, thankfully, most of us) now have antibodies that recognise the virus. There is no guarantee that what Dave’s immune system recognises SATS-CoV-2 by is what Shanti’s immune system does. It will be a bit of the virus, but not necessarily the same bit!

So an antibody test has to include proteins or fragments of proteins that most human immune systems that recognise SARS-Cov-2 will recognise. And as that will potentially vary from person to person…. Oh dear. Thus a good antibody test probably needs to have several proteins or protein fragments in it to work. This is why it is complex.

Again, the tests will come but the first ones will almost certainly not be specific/reliable enough to really trust.

 

Vaccine

The bad news? Despite all the media hype and suggestions in government announcements of creating a vaccination in 18 months (maybe sooner), it is very unlikely. Sorry. It is very, very unlikely. Don’t get me wrong, I would love us to have one right now, or in a month, or even in 6 months. But unless there is a medical miracle, we won’t and by suggesting to everyone that we might, I think the powers that be are storing up a lot of anger, frustration and other issues

A vaccine needs to do something similar to the Antibody test. It needs to contain something that either is part of the virus or looks like part of it. This is usually:

  • An inactivated version of the virus
  • a fragment of the virus
  • One of the key proteins on the virus
  • Rarely, a related virus that is much less harmful (for example cowpox for smallpox vaccine).

The vaccine is administered and the person creates antibodies to it. Now, when the person is exposed to the real virus, the immune system is ready to attack it. Neat!

Influenza Vaccine is often less than 50% effective

Creating vaccines is a long process. You need to come up with something that is safe to administer, prompts our immune systems to create the antibodies, and the antibody reliably attack the virus the vaccine is for – and nothing else! (Occasionally a new vaccine is found to prompt some people’s immune system to attack other things – like the healthy, useful protein the virus actually attacks). And you have to produce a LOT of that thing if you are going to administer it to a large number of people, such as most of the UK population.

The vaccine has to work on most people as you need 60-70% of people to be immune to SAR-CoV-2 get herd immunity from Covid-19 – the higher the better. The influenza vaccine is often much less effective than 50%, especially in older people.

You are giving the vaccine to healthy people and to lots and lots of them. It has to be really, really, really safe. If it seriously harms 1 in a thousand people (which might sound reasonable at first glance, for treating something as bad as Covid-19) – well, that is almost as bad as Covid-19 itself. You would be harming hundreds of thousands of people.

With a drug you use to treat the ill, you can afford for it to be less safe – as you are only giving it to people who are ill (so a smaller number) and they have more to lose. The risk/reward balance is more likely to be positive for a drug. Even if a drug for a life-threatening illness harms 5% of people but cures 50%, it is worth (with informed consent) using it.

We have never, ever created a vaccine in 18 months before. I’m struggling to get a scientific reference as searches are swamped with talk pieces (like this one!) on why it will take a long time. However, this video by an American doctor  Zubin Damnia who does social media about medical matters explains better than I can and this history of vaccines makes it clear at the top it often takes 10 years.

The bottom line is, much though I want to be wrong, the often stated aim of having a suitable vaccine in 18 months or less will need a medical miracle and a huge amount of work.

After The Peak And With No Vaccine – How Do We Cope?

After the peak, most people are still at risk from Covid-19. As I said earlier, if the Infection Fatality Rate is 0.5% then for each person who died there will be 200 people who are now immune, so if there are 20,000 deaths that is 4 million people immune. 6

If there is no vaccine then we have, I think, four options:

  1. Continue social isolation measures as they are to keep the virus from spreading.
  2. Relax isolation a little and let cases creep up but held as steady rate, but within the capacity of the NHS.
  3. Relax isolation quite a bit, monitor number of admissions to ICU (or something similar) and re-impose strict social isolation at  the current level if things start getting worse.
  4. Relax isolation a lot and massively increase testing and case tracking – copying the South Korea/Singapore approach.

Option 1 to hold us all in isolation is, I think, untenable. People will stop doing it and the impact on our economy must be massive. The impact on our society will also be massive, especially if this continues into the next academic year.

I don’t think we can manage option 4 in the UK yet.

So I think we will see an attempt at option 2, relaxing some social isolation rules (such as allowing restaurants to open and small gatherings) but then option 3, tightening social isolation if numbers of new cases start to build.

Option 4 could become a reality in a few months, especially if we can get people to use mobile phone apps to track movements and aid identifying the contacts of people who become ill,  but not everyone has a mobile phone and I think a good percentage of people will not agree to be tracked.

At present, without a vaccine, we will be living with some sort of social until we reach herd immunity, with at the very least 60% of us immune. How long will that take? 60% of the UK population is 40.5 million people. That equates to 202,500 deaths from Covid-19 to get there (remember, see the bit on IFR above).

This current peak of Covid-19 will last about 3 months, from the start of March to the end of May. It remains to be seen if we exceed the NHS expanded capacity. If we allow 20,000 deaths a peak with 4 million people becoming immune each peak, that’s 10 peaks, so 2.5 years.

A better option could well be to aim for a steady rate of new cases and deaths from Covid-19, say 1000 a week. At that rate herd immunity will take just over 200 weeks, 4 years. If we allow 4000 deaths a week than we could be there in a year, but our NHS would have to be handling the many, many thousands of ill patients that would entail.

Of course, in reality, our treatment of Covid-19 patients will get better over time, so fewer people will die from it, but it will still be a horrible thing to go through. And, if we DO get a vaccine sooner rather than later, many of those people will have died needlessly.

So, as you can see, we are in this for a long while.

The expanded health services, better knowledge of what social movement restrictions work, improved testing (including home testing), even my idea of cards for those immune, would all make life easier, it is not all doom and gloom. But I just wish all of what I have put here was being discussed and shared with people (preferably in a shorter form than this blog!) in a clear and constant message. I think if more people understood where we are and what is likely to to happen (or not), we will save ourselves a lot of issues weeks/months/even years down the line.

I honestly don’t know what the answer is – I don’t think anyone does. Which is why all of this talk about an “exit strategy” results in lots of hand waving and no clear plan.

As ever, if you think I’ve got something wrong, you know of a good academic source covering this, or you simply have a comment – let me know.

Friday Philosophy – Concentrating and Keeping Calm. April 3, 2020

Posted by mwidlake in biology, COVID-19, Friday Philosophy, Perceptions, Private Life, science.
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I was talking with a friend this week (via a webcam of course) about how he had been looking & looking at some misbehaving code for days. His team mates had looked too. It was not working and logically it should work. None of them could work it out. The problem turned out to be a small but obvious mistake.

My guesses for UK cases & deaths. Do Not Trust

This of course happens to us all occasionally, but we both agreed that, at the moment, we have the attention spans of a goldfish and are as easily distracted as a dog in squirrel country. I asked around a few other friends and it seems pretty much universal. All of us are making cups of tea and then taking the milk into the lounge & putting the cup of tea in the fridge. Or walking into the kitchen and asking who got the bread out to make lunch. It was you. The cat is wondering why I open the pouch of cat food and then leave it on the worktop and go do my email for 20 minutes. She’s getting annoyed.

Why are we all failing to function? Because we are all worried. This is one of the things anxiety does to us.

The whole COVID-19 thing is stressful – the feeling of being trapped inside, concern for friends and family, the ever growing numbers of infected & dying. I actually think if you are not at all worried then you are either:

  • Not understanding the situation
  • In denial
  • A total sociopath
  • Someone who should not be allowed out alone
  • Have reached a level of Zen calm usually only attainable by old oriental masters/mistresses

I’m by my nature often in camp 3 above, but even I am worried about this and I know it is making me tetchy and less able to focus. I’m struggling to keep my mind on things. Except on COVID-19. I tend to handle things I find unnerving by studying them and I probably spend about 3 or 4 hours a day looking at the latest information and scientific output on COVID-19. However, I note more things to “look at later” than I actually look at, as I am trying to manage my stress.

After an hour I make myself get up, go trim some roses, play a computer game, read a book. Anything to distract me. I’ve even started talking to the other person in the house and my wife is finding that particularly annoying. Sue seems easily annoyed and quite distracted at the moment. I wonder why?

Another way I cope is I talk with people about topics that are causing me stress. If I can’t talk, I write. Thus I wrote this Friday Philosophy – think of yourself as my counsellor.

I’ve seen a lot of social media “memes” about how long ago the 1st of March feels like, when we first started worrying about this. It seems like months ago, yes? To me it seems like a year. I started worrying about this a good while before the 1st March. I think the worry started about early/mid-February. Why? Because I’m a genius of course. {Note, this is called British self-deprecating sarcasm – I’m not a genius!}. No, the reason I picked up on all of this early was that chance primed me to.

I have a background in biology and some of the job roles I have held over my career have been in healthcare and the biological sciences. One role last year was working with a small biotech company working on immunology. So I take an interest in this sort of thing, it’s “my bag”. I was also pretty ill in December with Influenza (and yes, it WAS influenza, type A – I am not “the first case of COVID-19 in the UK”). So I was convalescing at home and took a specific interest in a new illness spreading through China that was influenza-like… And was worrying the hell out of the Chinese authorities who were coming down on it in a way we have not seen before, even with SARS and MERS.

My play spreadsheet.  I should leave this to the experts really

I have to confess, I initially suspected (wrongly, I hasten to add) that this new disease had escaped from a lab. The way it spread, that it seemed to be ‘flu-like, the rapid response by the authorities. I don’t doubt research into modifying diseases goes on – by the UK, China, USA, the Vatican, by every country with a biotech industry. I know we have the tools to directly mess with genomes, I did it myself, crudely, 30 years ago and I know people now who do it now, with considerable accuracy, for medical and other altruistic reasons. However, genetically engineering an organism leaves traces and when COVID-19 was sequenced there was no sign of this and it could be tracked to similar, previously known samples. I might even know some of the people who sequenced it and checked. But, anyway, that suspicion also made me watch.

The rate of spread in Wuhan was as shocking as the authority’s response and then through February the scientific analyses started appearing. The R(0) number (infection rate) and the high case fatality rate were both high. I’m not an epidemiologist but I had been taught the basics of it and I knew what was coming. No, that’s not right, I suspected what was coming, and I was worried. It was when the number of countries with cases started to increase that I felt I knew what was coming. By the end of February I was sure that unless something huge happened to change it, 2-3% of people, everywhere, would be killed. This was going to be like Spanish ‘flu only quicker (as we all travel so much). I became “The Voice Of Doom”.

On 2nd March I recommended to our CEO that UKOUG cancelled our Ireland event (people & organisations were pulling out so it was making it financially untenable anyway, but my major concern was that this was going to explode in the population). Thankfully the rest of the board agreed. I created my tracking spreadsheet about the 5th March. So far it’s been depressingly good at predicting where we are about a week in advance, and not bad for 10 days. I leave it to the experts for anything beyond that. All so depressing so far.

But Something Huge has happened. Governments did take it seriously. Well, most of them. And those who took it seriously soonest and hardest have fared best. The social lock-downs and preparation work that is going on in the UK is going to reduce the impact down dramatically and, more importantly, give us time to try and find solutions. But it still worries me. And I think they could have done it sooner. But most of the world is taking this very seriously – as it is very serious.

Part of me wants to keep watching how COVID-19 develops, and maybe writing more articles on it. I’ve had some really nice feedback on the first two and I want to do a post on where we might go in the coming months and why. But part of me wants to stop as it is making me very anxious and I’m sick of losing my cups of tea, or being stared at hard by the cat, and the wife asking me what the hell am I doing with the spanner and tin of peas.

I can’t easily listen to the government announcements each day as it is obvious, if you look at the scientific data and what medical professionals are saying, that they are simply not being candid. It’s all “we can beat this in the next few weeks” and “we will get you testing kits this month that are utterly reliable” despite the fact that’s going to need a scientific miracle to do that, let alone develop a reliable vaccine. I understand we need to keep positive but I think bullshitting the population now is only going to make telling them anything they will believe in 2 months even harder. In 6 months time when there is still no reliable vaccine and so many people have been wrongly diagnosed and the first few countries have had this rip through them almost uncontrolled, the lack of candid honesty will come back to roost. I worry about that a lot.

So I’m worried and I’m worried I’m going to be worried for months and months and months.

But for now I’m going to go for my daily (local) walk along a path I know will be almost empty of people and relax.

 

* Note, the graph and the spreadsheet are just “decoration”. They are my wild guesses on what may happen and have no reliability at all. Just saying

 

 

 

COVID-19: What Can We Do to Reduce Social Distancing March 27, 2020

Posted by mwidlake in biology, COVID-19, off-topic, science.
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<<<< COVID-19 Basics: What it is & what it does to us
<<…. COVID-19 Outlook for the Month(s) Ahead
The Coming UK Peak and Beyond >>

Summary

The impact of COVID-19 on our society and our economy is going to be long and hard. I hope I am not the first to come up with this idea, but just in case…

Having everyone on lock-down on and off for months will be hard to maintain. But not everyone will need to be in lock-down. You do not need to be locked down if you are immune.

I think we need to look at having a “COVID-19 Immunity Card” – you get the card to prove that you are probably immune to COVID-19 and that you are no longer a danger to others and are not in danger yourself.

Once you have a card you no longer have to abide by social distancing measures in the same way as those not immune. You are also a known “safe” person who can interact with those who are not. This would be particularly reassuring in the “caring” industries.

The number of people with cards will grow over time due to:

  • People being diagnosed with the disease and recovering – not many yet.
  • People being tested and found to have had the disease (possibly without knowing and have recovered) – coming soon?
  • People who have been vaccinated against it – future group.

There are potentially serous drawbacks to this idea. Such a card would be a source of division for as long as we have them and they would be a huge target for criminal activity, but it could help us “sleep with the tiger” of COVID-19.

It could/would allow our economy, health services, and society function more effectively whilst we are living with COVID-19.

Background – Once we “stop” COVID-19 this time, we have a problem…

The UK, like a growing number of countries, is now in a strong, country-wide, social shut-down. The aim is to suppress COVID-19 (see COVID-19: What’s Going To Happen Now ) i.e. drop the levels of person-to-person transmission (The “R” number) below 1. If each person with COVID_19 infects fewer than 1 other person on average, the spread stops. Quickly. It will take another 2-3 weeks for those already infected or sick (as of the date I am writing this, 27/3/20) to develop the symptoms and possibly need hospital treatment, so between now and mid-April we will see cases continuing to rise rapidly, followed by the number of deaths.

Then, something like Mid-April onwards, new cases will drop and, less slowly, the number of deaths.

COVID-19 will have been stopped. However, it will not have gone away, it will still be in the population. If we relax the social isolation we are currently living under, it will start spreading again and we will have another outbreak. Why? As only a small percentage of the population will be immune to the SARS-COV-2 virus. Governments are giving the impression that we will have “beaten COVID-19!” at this point, when the first peak of cases has come and gone, but the scientific consensus is clear that it will return if we all start living normally again. There are several studies going on at present to model what we can do and how. For example, China is relaxing restrictions and the world-wide epidemiological community is watching. For example, this Imperial College Paper on how China is coming out of strict social distancing is interesting.

I think of this as sleeping with a tiger that we don’t want to wake up.

The Imperial/WHO/MRC paper does cover all of this and suggests a way of relaxing social isolation steps and re-introducing them, over a 2 year period. The chances are, this is all going to go on far longer than most people realise and way longer than any of us want!

Reasoning on why COVID-19 will be with us “until something changes”.

The rest of this post is me being an “Armchair Epidemiologist” – proposing untested ideas with only a tenuous grasp of the true facts. But I thought I would put this out there. Note, there will be a lack of links to any solid references from this point. When you see this in articles discussing scientific ideas, it usually indicates it is a thought experiment.

There is general scientific consensus that, if we had better testing, the Case Fatality Rate would be about 1-2%. Case Fatality Rate (CFR) is the percentage of diagnosed cases that die. What we actually need is the Infection Fatality Rate (IFR) of COVID-19:- Taking into account all people who get the disease (whether they show symptoms or not or were tested or not) what is the percentage of people who die. See the Wikipedia entry on CFR for more details of CFR and IFR.

IFR is being argued about by the scientific community as you have to test a large, random set of people to see how common the disease is and testing by most countries is limited to suspected cases. Thus estimates are being made. The really good news is that the estimates of IFR are a lot lower than CFR. numbers seem to vary from 0.2% to 0.6%. See this pre-print of an article on CFR/IFR  and this paper by Nuffield Primary Care Health Sciences  at Oxford University. I’ll be pessimistic and take 0.5%

I am assuming the  Infection Fatality Rate is 0.5%

The reason we need the Infection Fatality Rate is that we can then calculate the number of infected people from the number of people who died – ONCE number of infection and deaths have reduced to low numbers again. You can’t do this (well, I can’t) when the number of new cases or deaths is increasing.

If 10,000 people die in the peak of cases we are currently enduring, if it is killing 0.5% of people and ICU limits are NOT exceeded, that means 2 million people will be immune once the peak has passed (as 99.5% of that 2 million have it and survive).

However, 64 Million will not be immune.

As has been described, we could now relax social distancing and let businesses and the economy start up to some degree again – but then tighten up social distancing again when cases or ICU admissions rise. We have a series of mini-outbreaks.

We have a population of 66 million. At 2 Million becoming immune in each “Outbreak”, we would need 20 outbreaks to get to a level of people who have had the disease where herd immunity is stopping the disease spreading – 60% or 44 or so million people (but we would still have 22 million susceptible to the disease).

With a peak every 2 months (so no single one exceeds the expanded capabilities of our NHS) getting to 60% immunity would take… several years. This is why all those discussions about getting herd immunity in weeks or months is, frankly, naive. We could only have that happen if we did not control the outbreak.

It might be that we can work out a level of social distancing that allows the economy to keep some semblance of normality and the COVID-19 cases at a level the NHS can keep up with, but that is a very, very fine tightrope to walk.

In any case, if we do not simply let COVID-19 rip through our society (killing more people than it would if controlled, as it vastly overwhelms the health services) we have to sleep with the tiger until we we have another option. But I think there is a way to make sleeping with the tiger more comfortable.

People will become immune to SARS-COV-2

A reliable, widely available test for seeing if someone has had COVID-19 and is now resistant to the  SARS-COV-2 is desperately needed and, I think, will become available soon – in a couple of months, long before a vaccine arrives.

We will then have 2 ways of knowing someone is immune:

  • Those who were tested positive for COVID and survived. They are immune.
  • Those that pass an antibody test. They are probably immune – depending on the reliability of the test. There could be several tests that have different levels of reliability.

These people can be given an “I am immune” card and they will not be limited (at least not so much) in lock downs.

Initially there will only be a hundred thousand people who can have the card, as they have been identified by testing to have had COVID_19,  have got better, and are now immune . But, crucially, a disproportionately high percentage of them will be NHS and first responder workers. This is because those groups are suffering very high exposure to COVID-19, by the very nature of what they do. The ranks of these groups are (and will continue to be) literally decimated by COVID-19. Lots and lots and lots of nurses, doctors, lab staff, cleaners, police, paramedics, GPs are going to be in the first wave getting ill.

Once we have the cheap, reliable antibody test , we can look for the rest of the 2 million.

As you can see, the more testing we do, both for having COVID-19 or for having antibodies against SARS-COV-2, the more people we can give an immunity card.

Over time, especially if we have further outbreaks, the number of people who are immune and are found via the above will increase.

Later, when vaccines are developed, there will be a third group of people we can count as immune:

  • Those who are vaccinated
  • Better still, those who are vaccinated and are latter tested for (and pass) an antibody test.

The first vaccines are likely to not be very effective – think the low end of the level of protection the annul ‘flu vaccines achieve, 20-40%. The antibody tests to confirm you have immune to SARS-COV-2 might also vary. But the details on the card will give which tests and vaccines you have had.

The card will hold details of why the person is immune, what test(s) were used to identify they had the disease, what vaccine(s) they had had, and when these events occurred. Minimal details would be held on the card itself.

A central database would hold the details of vaccination & test efficacy, corroborative information about the person etc.

If the reliability of historical tests or vaccinations change, then the immunity status of the individual may change.

The database of information would of course need to be well secured, kept in more than one place (so that a single IT disaster does not destroy all this key information) and protected. These are technical problems that can be solved.

Drawbacks off the COVID-19 Immunity Card

The cards will need to be very reliable, trusted, and protected from abuse.

Both the data they hold (or link to) and the information about the person the card is for needs to be highly dependable. The data needs to specify which sort of immunity this person has, when they were ill (if they have been) or tested, when any vaccine(s) were administered and when. It may turn out that immunity to SARS-COV-2 will reduce over time (that is, our immune systems “forget” about the disease) and the virus may mutate over time such that it avoids our immune response (whether natural or via vaccine).

The link to the person will need to be reliable, so no one can use a stolen or fake card. Obviously pictures, basic information, etc need to be on the card for a quick check, and information on the card links to a data source that can be used to further check identity and give more detailed information about immunity, such as may be needed if the person is in a medical situation.

It strikes me that this is a perfect use for blockchain. Each card, the data associated with it, when & how it is updates, can be accurately tracked in a way that is very, very hard to fake.

The data and the card should link to nothing else. There would be a temptation to be able cross reference the medical data with socioeconomic data, geographic information, even information about shopping habits to see if there are any correlations between between these factors and how people respond to COVID-19. This would be a nightmare as it introduces questions of consent, privacy, abuse of the data, fear of being spied upon.  Ensuring this card is for one purpose alone, with no link to anything else, would reduce the next drawback.

ID cards by the back door.

This will effectively be introducing ID cards, which some people object to strongly on moral or philosophical grounds. I’m not going to do more than note that this is an issue and observe that many societies have ID cards already. If these cards are kept to this one purpose, it would help make them more acceptable.

Criminality

Of course, as soon as such a valuable thing as a card that allows you to avoid social limitations is available, some people will want one, even though they know they are not immune. Criminals will want to create and sell them, so we need something, probably several things, (again, like a blockchain identifier on the card) to help guard against this. I would also suggest we would want to see strong punishment of individuals who try to use a fake card or get one by deceit. After all, these are probably the same selfish gits who bought all the toilet paper. As for criminals trying to make and sell fake cards, the punishments would be draconian – they would be putting a lot of people at risk.

Two-Tier Society

The cards would by their nature split society. Those who have a card would have more freedom. Those who do not would not.

Some people would never be able to get a card as they are immunocompromised  or similarly unable to be vaccinated.

Human nature says some people would discriminate or persecute people who are not immune if there was a way to identify this. I actually see this as the main reason to not have such a card.

Laws would be required to back up a repeated and strong message about why such discrimination is utterly wrong.

SARS-COV-2 Could Change

We do not yet know how the virus underlying COVID-19 will change over time. It is mutating – but ALL life mutates. We use the mutation to track how SARS-COV-2 has spread across the globe and the mutations, so far, are not known to alter it’s infection rate or how it impacts people (though I think I have seen some suggestions about this on social media that are more trustworthy than general scuttle).

However if it turns out that C-19 becomes C-23 and C-28 etc like Influenzela A, the card scheme still works but you are now stuck with identity cards and potential discrimination against those who are not immune etc.

End Life of the cards

I would want to see an agreed termination point for the cards stated when they are brought in. They or the data they link to will be deleted utterly in 3 years time. This can only be changed by a cross-political-party agreement.

 

That’s my idea. If you have any comments – for, against, highlight things I have wrong – I would love to hear.

COVID-19: What’s Going To Happen Now March 24, 2020

Posted by mwidlake in biology, COVID-19, off-topic, Perceptions, Private Life, science.
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I thought I’d record what the scientific evidence and epidemiological modelling is saying about what is going to happen in respect of COVID-19 in the UK (and, to some extent, elsewhere) over the next weeks and months. As with my intro to COVID-19 this post is mostly “for me”. I’m sharing it but please, please, treat all of this post (not the science I link to!) with some scepticism.

The figures are shocking so I want to spell out right at the start that, if our governments does what it needs to do and does it right (and over the last 2 or 3 weeks the UK government has fallen a tad short on this, but it’s improving) in the end over 99% of us will be OK. If they get it wrong, it’s more like 97% of us will come through this.

And, I feel it is important to say:

90% of even high risk people will also be OK.

I strongly feel that the message is constantly that it is the at-risk people who are dying and not that most people at risk will be OK. Yes, COVID-19 is more of a danger to those over 70 and those with underlying medical conditions, but with the media and government constantly saying “the people who died are old” etc it makes it sound like COVID-19 is a death sentence to them – and it is not.

Yes, I’m quite angry about that that poor messaging.

Source of Epidemiological information

ICU beds needed per 100,000 people

My main source is This paper by Imperial College in collaboration with the World Health Organisation and British Medical Research Council. If you can, please read this paper. It spells out how COVID-19 will spread and what happens when the NHS intensive care unit (ICU) beds are all full. It’s a hard read in two ways.  It is technically dense; and it says things people are still refusing to believe:

  • If we had done nothing and had an infinite number of critical care beds, it would burn through the population of the UK (and all other countries) in 3 months, infecting 81% of people. At that point herd immunity stops it.
  • In the UK 510,000 people would die (COVID-19 kills about 1% of people even with ICU treatment). 2.2M would die in the USA.
  • At the time of publication of the report, the “mitigation” plans by the UK government would have failed to stop even more deaths (more than 1%) as the NHS would have been overwhelmed by the 2nd week of April.
  • At the peak we would have needed 30 times the number of ICU beds we have.
  • The paper does not fully spell this out, but if you need an ICU bed and there is not one, you will almost certainly die. Thus the death rate would be more like 2.3% {Note, that is my figure, I have not spotted it in the report. It is based on 4.4% of the population needing hospitalisation and 30% of them needing critical care, figures that are in the report}. I’ll let you work that out based on the UK population of 66.5 million. OK, it’s about 1.17 million.

These figures are truly scary. They won’t happen now as it shocked our government enough to ramp up the social isolation. If anyone questions why we need the social isolation, give them the figures. If they refuse to believe them,  tell them to read the paper and various articles based on it and point out where they are significantly wrong. If they won’t, thank them for their baseless “opinion”.

The calculation of 510,000 deaths in the UK did not factor in self-isolating naturally, as we all saw people fall ill and die. That would slow down the disease.

However, if the hospital is full to absolute bursting capacity with COVID-19 patients, any person who needs ICU care for other illnesses (cancer, cardiovascular disease, stroke) or accident. How do you fit them in? Deaths for other reasons will increase.

One thing I am not sure of is that in the paper critical care is stated as “invasive mechanical ventilation or ECMO”. If you need just a ventilator and one is not available, I’m pretty sure you would also be likely to die or suffer brain and other organ damage from oxygen deprivation.

As I understand it, this report is what made the UK and other governments take COVID-19 a lot more seriously and really understand the need to implement strict social isolation.

I’d like to say why I put so much trust in this source:

  1. The three organisations behind it are all highly respected (WHO, MRC, and Imperial College)
  2. They state clearly at the top their assumptions – the R number, incubation period, types of social isolation, the percentage of people who will comply with each one.
  3. They created a model that was then verified by running the numbers and seeing if it predicted what had happened in reality to that point.
  4. The subject matter experts I follow have all endorsed this piece of work.

Mitigation or Suppression

The Imperial College report spells out the distinction between Mitigation and Suppression:

Mitigation is where you reduce the R number (the number of people each infected person in turn infects) down from the natural number of around 2.4 but it is still above 1. At this rate the disease continues to spread and the number of cases per day continues to increase, but more slowly. The idea seems to be that it would lead to herd immunity. This was the UK governments aim until Monday 16th March.

Suppression is where you reduce the R number below 1. Within a few weeks the disease is no longer spreading. But it is still there in the population. This is what Wuhan did and Italy is making progress on.

To achieve mitigation the government isolated people infected, asked those who had had contact with them to self isolate, and asked us all to wash our hands and keep a distance and think about working from home. The impact on daily life, business, the economy is minimal. Further steps would be introduced later, like closing universities and schools.

The Imperial college report demonstrated that mitigation was a terrible idea as the number of cases would still explode, but just be delayed a little, and the NHS would be absolutely overwhelmed.

The graph at the top of this article shows the mitigation steps being considered and how it only shifted the curve and did not lower to anywhere like the NHS ICU capacity. It was simply not enough.

Isolation involves the sort of steps most of us would have previously thought only an authoritarian regime like China or North Korea could manage. Schools, universities and non-critical business shut, everyone not doing a critical job made to stay at home except to buy food etc. Basically, Wuhan. And now Italy is doing very similar. As of the 23rd March the UK is following suit.

Most western countries are now implementing many of the steps needed for isolation levels that will suppress COVID-19, but not all the steps needed.

The graph to the right shows the impact of two implementations of Isolation, both implementing several measures but the orange line does not include closing schools and universities. The green line does. The green line keeps the number of cases within the NHS ICU capactiy, the orange does not. That is why schools and universities were closed.

The graph also makes the point about the main problem with Isolation. It is only stopping the virus spreading, it is NOT getting rid of it. Remember, no one is immune unless they have had COVID-19. When the steps to enforce isolation are relaxed, COVID-19 will burst back.

This is potentially the position that China is in. They have locked down Wuhan province tightly and it worked. The number of cases there rocketed even after the lock-down but have since reduced, almost as fast as they increased. China as a whole now have very few new cases. The lock-down is being relaxed as I prepare this post. Epidemiologists expect the number of cases in China to increase again.

The degree to which either mitigation or suppression is enforced obviously impacts society and commerce. The Imperial College report makes the point that they are not addressing those concerns, they are simply saying what social isolation changes will have what effect on COVID_19 spread, deaths, and the ability of the NHS to cope.

Delayed impact.

UK daily cases to March 20th, Italy deaths to March 20.

This next point is being made widely, by both non-scientific observers and the scientific community, but I want to re-iterate it as it is so far being played down by government (which could be changing at the very moment I am typing).

There is no way to avoid the huge increase in COVID-19 cases and deaths that are going to happen in the UK over the next 2-3 weeks. Expect our levels to be the same levels as Italy. In fact, expect them to be 20, 30% higher. This is because the UK government were too slow to lock down and did it in stages when, based on the epidemiology, we should have shut down totally on Monday 16th when the paper I reference was published, or within 2 days to allow for planning.

Up until now COVID-19 has been spreading exponentially (1 person has it, passes it to 2-3 people. They pass it to 4 people who pass it to 8…16…. 32… 64… 128… 256… 512… 1024). This has been seen in the way the number of case had double every 3-4 days, deaths are now following the same pattern.

The two graphs to the right show the number of cases in the UK to the 20th March above, and the number of deaths in Italy to the 20th. They look like the same graph as they sort of are. This is how something grows exponentially when the growth rate is the same – the same as both cases and deaths are caused by the same thing.

(these graphs are from Worldometers – I use this site as I think the John Hopkins site has more incorrect information on it).

Covid-19 takes on average 5.1 days to show symptoms from when you catch it (this can be up to 2 weeks – with all these averages there will be some cases which are two or three times as long). It takes less time, 4.6 days on average, from when you catch it to when you spread it. So you can spread the disease before you get ill. And some people do not get ill (or only very mildly) and spread it. Like “Typhoid Mary”. If you are going to be ill enough to need hospitalisation it takes 5 days from first symptoms for you to deteriorate to that point.. At this point you will be admitted to hospital, tested, and will join the number of confirmed cases. If you are going to die (I know, this sounds really callous) that is another few days. The report does not spell it out but going on the figures they use for time spent in intensive care in the model, about a week.

Add it all together and someone who dies of COVID-19 today caught it 15-20 days ago on average, so the spike will be delayed that much.

Yesterday, 23rd March, almost total lock-down in the UK was announced. Cases and deaths will rise for 20 more days in the UK. Exponentially. To Italy levels, maybe 20-30% higher. Then they will plateau for a few days and drop quickly, depending on how well people respect the social distancing or are forced to. I am expecting over 9,000 will die in this first spike, with a peak number of deaths between 750 and 900 in one day. Sadly my predictions so far have all been correct or a little too optimistic.

That is the reality and that is why we are seeing the actions of our government that have never been seen outside World Wars before.

Three choices – or is it four?

To summarise the above, there were 3 choices available to the UK (and all other countries):

  1. Let COVID-19 burn through the population in 3 months. It would kill 2-3% of the population as the NHS collapsed and also anyone who needed medical treatment during that time would probably not get it. During the 3 months lots of people would have “bad ‘flu”. 80%  of survivors would be resistant to COVID-19 for now.
  2. Mitigate the impact by the measures implemented in stages during mid-March, reduce the impact a little and stretch the curve a little, and have 1.5-2.5% of the population die over 4 months. 70% of survivors {my guess!} would be resistant to COVID-19 for now.
  3. Suppress COVID-19, 10,000 dead and everyone in lock-down until “something changes”, which could be 18 months or more.  A tiny percent, maybe 5% {my guess} resistant to COVID-19.

The UK government chose option 3, after considering 2 for a while (and thus increasing the death count by, hmmm, 3,000 in that first spike).

The “something changes” in option 3 is that scientist create a vaccine for SARS-COV-2, the underlying organism to COVID-19, or we have a quick and reliable immunity test for it that allows those who have survived the disease to move about unrestricted. See further down in this post. Most of us stay in lock-down until “something changes”

But this Imperial College paper has a solution 4:

Turning social isolation up and down

  1. sorry, 4. I can’t get the layout to work. solution 4 is to
    1. suppress.
    2. Let the known bubble of cases come and deal with it.
    3. Once it has passed, relax (not remove!) the Suppression rules to let business and normal life start up again.
    4. Monitor the number of COVID-19 cases coming into ICU.
    5. When it hits a threshold, back to total lockdown and deal with the next bubble.
    6. Repeat.

It is a clever idea. No one wants to stay at home until a vaccine is created in 18 months. Economically, total lock-down until we have a vaccine would be a disaster. So varying the lock-down based on NHS demand indicators would allow some relief from the restrictions. But not back to normal.

Option 4 comes at a cost. More people will die reach time you relax the lock-down, depending on what is allowed. Much of the rest of the paper details this plan and, based on the figures they state at the top of the report in respect of how many people will abide by the rules, what different isolation strategies and key triggers (how many new COVID-19 ICU cases in a week) to increase isolation levels, gives death rates varying from 8,700 to 120,000. This also takes into account a range of R values (how easy it spreads naturally) as there is still some uncertainty about this.

The paper makes one thing clear – we would need to maintain the isolation levels for suppression for 2 years – their cautious estimate of how long it will be until we have a widely available vaccine.

The best case is deaths creep up (after the initial surge we can no longer avoid) with very strong lockdown only relaxed at very low levels of ICU cases and deaths. I personally doubt very strongly that enough people will abide by the rules for long and, as people start ignoring them, others will feel “why should I play by the rules when they don’t”.

I do not have anything like the understanding of human nature needed to predict how people are going to react so I won’t. But the figures being bandied around a few days of keeping UK deaths to 8,000 or less seem utter fantasy to me.

The “The hammer and the dance” paper…

Some of you may have come across “The hammer and the dance”, which is based on a paper by Tomas Pueyo on “Medium”, a home for science papers that have not been verified by anyone. I would not normally look at things here very much but several people have mentioned the paper or even linked to it. If you recognise the term, you will probably recognise the “dance” part as choice 4 above.

Context is paramount

Lots of numbers are being thrown about, but to understand the true impact of COVID-19 those numbers need to be interpreted in light of some general background.

Let’s start with the base rate of mortality. In the UK there were 541,589 deaths in 2018. That give 9.3 deaths per 1,000 residents. See the office for national statistics article for this figure. Over the year that is 1,483 deaths a day, from all causes. People keep on insisting on comparing COVID-19 to influenza. I’ve struggled to get a definitive number of deaths due to Influenza in the UK but it seems to be between 8,000 and 17,000 a year. Let’s take 17,000 as a top estimate, that is 46 a day.

(you may wonder why it is hard to say how many people die of influenza. Well, influenza kills people who are already seriously ill and likely to die anyway, and I believe not every death attributed to influenza is tested for sure to be influenza.

Our key figures are 1,482 deaths by any means a day and 46 a day from influenza, in the UK.

On the 21st March 56 people in the UK died of COVID-19. More than Influenza, about 4% of the daily mortality rate. Bad, but nothing that significant. In Italy, 793 people died of COVID-19 on 21st March (and it looks like that might be the peak). Our figures in the UK for known diagnoses and deaths are following the Italy pattern very closely (for very good scientific reasons) just 2 weeks behind – 15 days to be more precise. In 15 days the death rate for COVID_19 is likely to be very similar to Italy so, despite my hunch the UK peak will be higher, let’s use Italy’s peak number:

  • 50% of the total death rate for everything in the UK.
  • And 17 times the death rate by ‘flu.

So COVID-19 is incredibly serious,  but it could have been worse. It looks like for a period at least, for each country, it will increase the daily death rate by 50% and maybe more. But it is not killing a large percentages of the population.

I’ve seen some scare stories about this disease sending us back to the dark ages as it kills half the population of the world. Rubbish. It might stop the world population growing for a year.

Why will social distancing last 18 months?

No one is naturally immune to COVID-19 until they have had it. Let’s assume that once you have had it you are immune for several years, as you are with many other viral diseases (Influenza A is a special case as changes so fast and in a way that reduces the effectiveness of both vaccines and immunity via exposure).

We could let COVID-19 spread naturally or at least in a contained way – but it will overwhelm our health services as discussed, and 1-3% of us would die.

The other way is to create a vaccine, which gives immunity or partial immunity without having the disease (or maybe a very mild version of it). Vaccination works, it rid us of smallpox totally and, until the loony anti-vaxxer movement got going, it was vastly reducing measles, rubella and many other diseases.

But creating a vaccine that works is hard. Lots of biomedical scientists are working on it and we might get lucky and someone comes up with a very effective vaccine that can be created in bulk, but by lucky we are still talking months. (There is at least one early trial running – but that absolutely does not mean it will be available next month!)

Any vaccine has to be tested, proven effective, and shown not to itself harm.

All of this is why specialist in the field all say “18 months”. It’s a guess based on science and experience. It could take longer, it could be only 12 months, it might be that an initial vaccine is only as effective as the yearly flu vaccine (the flu vaccine generally protects 40-60% of people – see  this oxford university paper).

We can test for if people currently have COVID-19, the test is accurate and relatively cheap. It checks for the RNA of the virus, an established diagnostic practice. Production of the test is being massively increased and improved and we need that so we can better track the disease and accurately identify who has the disease and put them in isolation. In the short term, wider testing will help a lot and those countries that have gone in for huge testing efforts (South Korea and Singapore are examples) have done well in containing COVID-19.

The other tool we really need is a test for immunity, which is usually for the antibodies to a disease. Again, these tests take time to devise. If we could identify those who have had the disease (but were not tested) and are now immune. They would not need to be isolating themselves. A small and growing part of our population could return to normal. But we have no idea when such a tool will be ready, how accurate it is, how cheap it is to do etc.

Finally, scientists need to work out if immunity to COVID-19 is long-lasting, for how long, and if the immunity is strong or weak. We just do not know yet.

Until we have a vaccine (ideally), or the immunity test (it would really help) we have to suppress COVID-19 via social distancing etc.

Basically we are sleeping with a tiger. Best not wake her.

Disclaimer

All of what I put here is based on what is said by experts, scientists, epidemiologists. I’m just pulling some of it together. As I said in the previous blog, I am not an expert in any of this. I’ll make it clear when something is my opinion. I also want to highlight that I only look at sources that I feel are backed by good science. The only information I take from the government is official statistics on cases & deaths. I’m heartened that our government is now taking the spread and impact of COVID-19 more seriously but I remain angry that the experts told them what was coming weeks ago and they were slow to act, putting business concerns before lives.

Any mistakes in this blog post are mine. There are bound to be a couple.

I would love to hear about sources of information you feel are good. I had several excellent sources pointed out to me after my last post, including being corrected on a couple of counts – which I am very happy about.

However, I will probably ignore anything based on rumour or anecdote. Ginger & Garlic are not going to boost your immune system and protect you, quinine is almost certainly not a magic protector. If you have a peer reviewed article in a reputable journal or the support of a respected epidemiologist to back those opinions, then let me know.

 

COVID-19: Information And Outlook March 13, 2020

Posted by mwidlake in biology, COVID-19, off-topic, Private Life, science, Uncategorized.
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Outlook for the months ahead >>
Reducing the need for social distancing by knowing who is immune>>>>
The coming UK Peak and Beyond >>>>>>

I decided to put together some information on COVID-19 purely for my own interest – but then decided I might as well put it on a blog post. I’m only going to link to what I feel are reputable sources, nothing from tabloid papers or people promoting conspiracy theories.

If you know of a good site I should include or there is an area I have not touched on that you would like more information on, please feel free to let me know.

Update. At long last, as of the evening of Monday 16th March, the UK government listened to the WHO and other epidemiologists and accepted that draconian measures to suppress COVID-19 (reduce the R rate, the number of people each infected person in turn infects to below 1) rather than mitigate it (reduce the natural R value of 2.4 towards 1 but above 1) will save thousands of lives.

This paper by the Imperial College London in conjunction with the Medical Reaserch Council & WHO is being cited as the root of this change in opinion. It’s a hard read as it is a scientific paper, but it is excellent. It helps make clear many things such as the local spread rate, infection rate, how it transmits between countries. the likely number of real cases as opposed to tested and verified cases. And the simulations match what we have seen to date.

In summary, suppression, such has been managed in South Korea and China, virtually stops the disease for a while. It does not end it. When the measures to suppress it (very strong social control) it will burst out again. There is always a chance it will escaped to areas it is not suppressed and blow up again. But it buys time to work on a vaccine and develop better treatment regimes.

Mitigation slows the spread down. But it continues to spread. An argument was put forward that this will develop “herd immunity” by letting most people get the disease. It means it would be over sooner – but at the cost of hundreds of thousands of lives, just in the UK. The NHS would be utterly swamped during this time.

I’ll move this down into the body of this post later.

{Update 15/4 – I obviously did not move this down as I feel that change of direction was so key}.

 

Firstly, for anyone who does not know me or just stumbles over this page via “Google”, I am not an expert in any of this – I am not a medic, I am not a scientist, and I am certainly not an epidemiologist (someone who studies the transmission of disease). I’m a computer professional with a really old degree in genetics & zoology who has at times worked on systems for the UK National Health Service (NHS), the Human Genome project, and some other scientific organisations.

Secondly, although this is a very serious disease and it is going to continue to have a huge impact,  most people who get it will not be seriously ill. We are not all going to die!

Most people with underlying medical conditions or who are elderly are also going to be fine

The press, at least in the UK, keeps making a huge point that anyone who dies had “Underlying medical conditions” and it is affecting “the old” more. This is true, but the message that comes across is that if you are old or have an underlying medical condition you will die. This is not true.

Even if you are 79 with diabetes and are diagnosed with COVID-19, you have over an 85% chance of being OK, even if you develop the symptoms.

However, the fact that this disease is eventually going to kill tens, hundreds of thousands of people {Update 15/3: 127,000 worldwide so far and that will be an under-estimate , so hundreds of thousands. I’m sure it will hit the million by June. UK it is 13,000 including care homes} is why saying “I’m stronger than this” or “I’m not letting it impact ME!” is, in my opinion, a highly arrogant or stupid approach. Just as wrong is making it the focus of your life. Most of us, around 90-95%, will be mildly ill at most, or not noticeably ill at all. {Caveat – by mildly ill, you may well feel terrible and spend a few days in bed, but that’s like a normal dose of ‘flu.  Take it from someone who has spent a week on ventilators recently, a few days in bed is nothing 🙂 }

Thirdly, though COVID-19 is going to kill quite a few people, the main impact is probably going to be what it does to our health services. It is almost certainly going to over-whelm the health services of most countries, as it has in Italy. Preventative actions, 99% of what we can do, is aimed to spread the load on the health services so that as many people can be treated as best as possible. It is absolutely key that we slow down the rate of cases by not getting together as groups and taking the simple precautions of washing hands well with soap, catching coughs in tissues, things like that. {update 15/4 – THe NHS did an amazing job of preparation. The field hospitals built are not being used very much yet, but the NHS has been sorely tested. Any treatment for other conditions that can be delayed seems to have been deleyed}

This article by The Lancet explains in some detail (maybe too much for general consumption) why social distancing and hand washing are vital to “flattening the hump” and helping the health services cope.

As ever, the best approach is a balance. Personally, I am concerned and I am going to avoid mixing with large numbers of people I do not know. I am actually in an “at risk” category as I was ill with influenza & pneumonia in December, in intensive care getting the sort of treatment bad cases of COVID-19 are getting now. But I am not self-isolating. If I get symptoms, I will self-isolate.

Basics

Names and terms

COVID-19 is the name of the disease. It was first reported in Wuhan in China on the 17th November 2019 but came to general prominence in early 2020 as it spread and infected more people, who then started dying in numbers. The World Health Organisation was informed (WHO).

 

The disease is caused by a virus called SARS-CoV-2. SARS stands for “Severe Acute Respiratory Syndrome” which describes what it does to people. It can cause a serious and sudden problem with breathing, which is when it can be fatal. CoV stands for Coronavirus, which is the type of virus.

It is commonly referred to in the media as “Coronavirus”, which is not a very accurate name. It would be a bit like going to a restaurant and ordering “mammal” (beef, lamb, pork, cat). But the name has stuck and is understood to mean the disease COVID-19 that is worrying everyone at the moment.

This wikipedia article describes the COVID-19 epidemic and this wiipedia article describes the disease itself

What COVID-19 does to you

The virus infects your lungs. It attacks the lining of the alveoli, the little “bags” in the lungs which absorb oxygen and release carbon dioxide. That’s why in mild cases you cough and in serious cases you get short of breath while at rest. If you are sitting quietly but finding you are having to breath hard (as if you have just exercised but you have not), contact the health services immediately. And if you pass out due to not being able to breath, call an ambulance (when you wake up, obviously…).

When the alveoli are infected by the virus they fill with fluid and their linings are damaged. This stops them from absorbing oxygen. All the cells in your body need oxygen, delivered by your blood. In a serious case of COVID-19 you have to breath harder and harder to get that oxygen until you reach a point where you simply cannot breath in and out hard enough.

The treatment is simple. Normal air holds about 20% oxygen, so the medical staff give patients air with extra oxygen in it, or even 100% oxygen, via a mask. If this is not enough a ventilator is used, which is basically a pump or fan that blows the oxygen out under pressure and pushes it into the patient’s lungs. It reduces the effort of breathing also. Ventilators come in increasing powers.

If this is still not enough, the patient is anaesthetised to make them unconscious and a tube is put down the throat (this is called intubation) which is used to push oxygen directly into the lungs. Making patients unconscious also reduces their need for oxygen. If even this is not enough the only final step is to use an artificial lung such as is used in major heart surgery. Hospitals won’t have many (or any!) of those.

In these extreme cases where more and more powerful ventilation is needed then the patient is possibly suffering from something called a Cytokine storm. Basically, the immune system over-reacts and causes damage to other organs like the kidneys.

Normal influenza tends to attack higher in the lungs, so is less dangerous. This is part of the reason COVID-19 is worse than influenza.

This article on how it impacts your lungs is quite technical but very good. The article then goes on to explain how the impact on our health services is a massive concern.

 

What we need to do to slow the spread

COVID-19 can no longer be stopped. To be frank,  it could not be stopped 3 weeks ago. Once enough people were infected with the disease, it became impossible to track them all down by contacting all the people who someone diagnosed with the disease had interacted with. What we could have done is taken the advice of the WHO and the example/evidence of what was coming set by other European countries and locked down earlier. {Update 15/4 – I strongly feel that the government had clear evidence to take each step it took at least a week earlier and it would have saved thousands of lives}.

Two main factors control how quickly a disease spreads:

  • How easily it is passed from one person to another
  • How many people an infected person is in contact with

That second point is not just the people the infected person is physically in a room with. It is, for example, if they cough on a door handle or touch it after coughing into their hand, the live virus will be on the handle. The people who then touch the door handle can be infected.

Washing yours hands with soap and not touching your face is reducing how easily it is passed.

Banning large gatherings reduces how many people are in contact.

Self-isolating will greatly reduce how many people you can infect (or can infect you).

This video describes how exponential growth works  and why reducing gatherings and simply hygiene will slow down the spread of the disease, with COVID-19 as the example.

It also explains how you can tell if things are getting worse or could be getting better. It is to do with the “inflection point”, when the number of new cases starts to drop. Until that happens, it’s going to get worse. This is a significant part on what epidemiologists look at in respect of how a current illness is spreading. In the UK, Spain, US, pretty much all countries where you cannot control the population, the rate of spread is staying high and the numbers of new cases and deaths is growing exponentially. This is what makes COVID-19 such a problem and why scientists worried back in January. It spreads really well and sometimes before symptoms show, which is why we all need to wash our hands, keep away from large gatherings, cover our coughs. You might feel fine, you could be spreading this.

Why washing with soap is the best protection

A virus is piece of RNA (very similar to DNA) covered in a coat of fat – called a lipid layer. Soap dissolves fat. That is why soap is so good at destroying viruses like COVID-19. Alcohol can do the same but it needs to be strong alcohol (70% or more) and works best if it also contains a soap or detergent.

The antibacterial chemicals in antibacterial cleaner do nothing to viruses. Bacteria are totally different to viruses, Bacteria are much more complex.

This twitter thread explains in some detail how soap destroys viruses

 

Monitoring (probably what most people are staring at)

The below are links to pages with info that is updated regularly.

****

Update, 19/3. The data on number of cases coming out for the UK has become less unreliable. The official Public Health England page is not being update until later and later in the day – and it is for figures for the previous day. Worldometers figures do not match the Public Health England figures for most of the last 2 weeks now, except the last 3 days. I think the official figures get corrected but worldometers is not picking up those corrections.

I still check both but I use the official public health England figures for my own trending.

Some days, most annoyingly for me the 16th March, have a figure for new cases that is not at all in line with those before and after. In fact, I think unbelievably different.

****

I tend to go to this worldometers  site as it is updated quicker than the official UK one.  On Friday 13th in the evening it showed an increase in the day’s total and the 11th death before the official UK site did. However, it does not seem to be corrected in retrospect like the official UK one is (I am not sure if that is good or bad)

This is the UK government page that tracks UK COVID-19 cases . It is designed for PC. For mobile phones go to this entry point and pick the option Note that it is a day behind. Information is gathered as-of 9am in the morning and is usually published at around 2pm. {this is now more like 6pm in the evening)

{update 24/3 I removed the link to John Hopkins as their figures consistently fail to match the UK government figures in any way, or the worldometers numbers – which are more consistent between them. Also, a JH person was tweeting how it was THE BEST source and did not reply to two response pointing out it is flawed. It might look nice but it is a poor source of data.}

Lots of people have shared the John Hopkins institute site, but I find information drops off it or the list of countries on the left do not match what is highlighted on the map, so I don’t it.

This page is a global view.  I have to confess, I have not looked at it in a couple of days, but it has lots of interesting information

 

Why certain diseases make things worse

As has been widely shared, a lot of people dying “have underlying medical conditions” or are old. I want to stress that people who are old or have these conditions (and even both)  will most likely recover. But it is true that if you have cardiovascular disease, diabetes, high blood pressure and several other conditions, you are at higher risk. The advice is to maintain your treatment and to keep as fit and healthy as you can. If you can exercise, do so!

If you are generally in poor health or have a debilitating condition, all disease are going to impact you more. Especially anything that reduces your lung function or blood supply as the virus makes you ill by reducing how much oxygen is absorbed by your lungs and taken to e.g. your brain and liver by the blood. Maybe now is a good time to stop smoking if you do!

I could not understand the increased diabetes risk. A suggested answer is very technical, but it might be to do with the levels of ACE & ACE2 proteins you have. COVID-19 seems to enter cells by using our own ACE2 proteins, but it is unknown if this is a genuine link or not.

This “The Lancet” article describes  suggests why diabetes and hypertension make you more susceptible to COVID 19. It’s short but quite technical. To balance that, the European Society of Cardiology claim there is no link (thank you David Harper for that).

This does highlight that COVID-19 is a new disease, most focus is on understanding and treating it and details like this will become clearer over time.

I should stress, never stop taking medicine based on social media guff – including this page! Even *IF* there is a link between drug X and COVID-19 susceptibility, you are taking drug X for a good reason and that reason has not disappeared. If the potential impact is large, it will be obvious to medics who will highlight it as an issue.

What facilities do the UK have to treat COVID-19?

According to announcements by the government on how well prepared we are in the UK for the “peak” of cases (which we are no where near yet):

Apparently in the UK we have 4,000 intensive care beds and “more are being made available” but there seems to be no detail on that.

We have 5,000 ventilators. The government is asking other companies to make them.

Update 19/3 the UK government is talking to companies about the details of making more ventilators and I know of at least one company that is offering to make many more. The issues is that there are stringent tests for suppliers of medical equipment and of the equipment itself. Any equipment used for medical purposes has to be built in a clean environment.

5 hospitals are stated as having ECMO equipment (Extra-corporeal Membrane Oxygenation machines) available for treating COVID-19 patients. These can re-oxygenate blood in the the same way the lungs do. They are massive and complex and they won’t be able to build extra ones for months – and of course every country will want them.

These figures are oddly “round” which suggests they are estimates or guesses. As the only real treatment for COVID-19 is extra oxygen and ventilating patients, then treatment will again be limited by the equipment we have or can be made. I’m no expert on equipment manufacture, I’ve seen no information on how easy it would be to ramp up production but I do know that when our Prime Minister asked companies that don’t make them to swap production to them the answer was “give us a full specification and a set of patterns and we *might* be able to). Medical equipment has to work, no company is going to want to “give it a go” and, if the machines don’t work or break down or harm the patient, face being sued into bankruptcy once this is over.

 

There is no vaccine and there is no known drug treatment that has anything but sketchy “it seems it might help” evidence.

Vaccines take years to develop normally. This can be fast-tracked by reducing the level of testing and precautions, but that means risking creating an ineffective vaccine at best or even killing more people. On the plus side, scientists already have targets for creating a vaccine – the RNA of COVID-19 has been sequenced (read), we know some of the proteins involved, it looks like the main target to infect cells is known (ACE2). The trick is to develop something that looks like one of those elements and that prompts the human immune system to develop antibodies against it (without harming the human) that then attacks the COVID-19 virus (without attacking anything else in the human) and that can be created in huge amounts (there are a huge number of humans).

There is no existing drug that seems to work very well. Existing antiviral treatments are being tested. Anything with any hope at all are being tested. If they worked well, we’d probably know already and the international medical community would be making it known. ANYthing you see on the internet about a miracle cure or “In India they have discovered that vitamin C, Ibuprofen and Tamiflu taken in large quantities together cures 76% of cases” is utter bullshit. Spreading this bullshit on social media is extremely not-helpful as some people will believe it and start demanding a treatment that does not work.

Medics and scientists will continue to work and they will get something eventually, but almost certainly not in the next few months. Sorry.

There appears to be no natural immunity

Like most viruses that attack us, the only way to be immune to it is to either catch the disease and get better, or be given a vaccine (which, in effect, is the same to the body as getting the disease but without most of the illness).  This means that, given how well COVID-19 spreads, we will all get this eventually until herd immunity slows it right down. At that point, everyone who has not had it will still be at risk of getting COVID-19 if they meet someone with the disease.

Bottom line, until a vaccine is created and everyone takes it, COVID-19 will continue to spread until most people have had it. The key thing is to try to slow it down so that our medical services can cope with the number of people it makes seriously ill.

 

Predictions

Before reading any of this, remember – I am not an expert! I’m a computer programmer with a smattering of some relevant experience.

However, about 3 weeks ago I felt I knew what was coming and I’ve spent the last 2 weeks being “the voice of doom”. Sadly I think I have been mostly right. So I thought I’d put somewhere how I think some things are going to play out.

I’m not trying to scare people. Well, sort of I am. I want people to be aware that it is going to be bad for a while, that as nations and individuals we need to take the right, simple actions. And that governments will lie to you about some of this stuff. Look for scientific/medical information.

(predictions made on 13th March 2020)

  • In the UK we will have about 250-350 new cases on Monday 16th March.
  • By the weekend of the 21st/22nd we will see 1000 new cases a day in the UK.
  • Numbers of deaths will “take off” around the 18th March and will double about every 3 days for at least 2 weeks.
  • Deaths as a percentage of known cases in the UK will be between 0.8% and 1.8% by the end of the month and will escalate.
  • The rate of new cases will stop growing so fast, but the rate of deaths will continue to grow as a faster rate. This is due to 2 factors – (1) the delay from getting ill to dying is on average a week or so (2) the UK is no longer testing everyone, buggering up the figures.

****

Update 19/3 – how did I do prediction-wise. Well, on the 16th March there were officially 152 new cases. But on the 15th there were 330, and 407 on the 17th. So I was wrong in both directions! On the actual date, I overestimated. But for the 3 days around the 15th and going on the trend, I had underestimated. I was not pessimistic enough.

The deaths did take of in the middle of this week – 16,33, and 41 for the 17th, 18, &19th March.

And we are well on track to hit 1,000 new cases by the weekend, but given the ever changing information on who is being tested, I’m not sure that confirmed cases is very accurate. I think the percentage death rate will have to be increased to take into account the lack of testing.

So, sadly, I seem to be still predicting quite well what is happening. BTW I base my predictions by stealing the work of proper, real scientists and mostly ignoring the UK government. I’m not doing anything more “clever” than choosing my sources and a simple spreadsheet.

Update 21/3. We hit over 1,000 cases – 1,035 today. So “my” prediction (really I just use a simple calculation based on the work of the real epidemiologist) is sadly spot on.

Deaths reported, 56. It’s taken off but not doubling every 3 days. It will.

Update 15/4 – Death rates did indeed double every three days – actually 3.3.

23/3       54
26/3       115
29/3       209
1/4        563!
4/4        708

Thankfully, the various distancing measures started to slow the rate in the first week of April, as self isolating and then pub etc closures kicked in

As predicated,  the slowdown of new cases predicates the slow down of deaths, but the UK’s poor testing numbers make this connection weaker and weaker

*****

19/3/20

  • Daily deaths in the UK due to COVID-19 will exceed a thousand in the first week of April.

Update 15/4 – thankfully I was wrong, but we hit 980 on the 8/4. If we include the 10% of care home deaths missing from the figures, we did hit 1,000

  • I’m not so sure about this one – I think we will have a slowdown of new UK cases in about a month and than after a gap of about a month  it will take off again.

 

  • COVID-19 will reach every country by April

Update 15/4 – pretty much true

  • China will have a second wave of infections in a month or two.

I think this because although they managed to control the first outbreak (by taking measures most western countries would not entertain), the virus has not spread through the rest of the population and it will get re-introduced from another location.

Update 15/4 – I’m not sure on this. Their figures are really good at them moment. They have shut down and quarantined another area but there has not been a second large outbreak we know of.

  • This is going to hit the USA very hard indeed.

This is because:

They initially had little capacity for testing (it is still poor despite political promises – and they have been having a damned argument about which commercial company gets to set up a new, Invented In America test to make a few people very rich indeed)

Their health service is far more about making a profit than treating people, so ill people will not get treated (or tested!);

The percentage death rate is going to look terrible, maybe 3 or 4%, as the number of cases actually tested will be low (if they “guess” at the infected numbers this might not happen);

Ill people will not self isolate as most US employees have little or no sickness pay.

Update 15/4 – The US has been really badly hit and when it took off, it took off large. I think a large part of this is because President Trump was a bloody moron and spent weeks downplaying this. As he likes to say “it’s all on tape” – he claimed this would be finished by Easter, was not as bad as ‘flu etc. The only thing he can claim to have done (and has done so repeatedly) was to stop flights from China. But he was advised then it was not going to have any impact as it had spread. And was already in the US.

I think it will continue to hit the US really hard, not just for the reasons I cited before, but because the president seems determined to do exactly the wrong things to contain this, such  as “opening for business” very soon and sacking anyone who disagrees with him.

I was wrong on the % death rate as they have massively increased testing, which was an amazing achievement.

 

 

Postponing Ireland Conference – & Maybe Myself? March 5, 2020

Posted by mwidlake in conference, Presenting, Private Life, science, UKOUG, User Groups.
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As I tweeted a couple of days ago, I never thought I would write something announcing cancelling an event due to a worldwide pandemic. And yet that was what I was asked to do earlier this week (first week of March 2020). It will be interesting to look back at this in the future and judge if it was a wise decision or an over-reaction. At present, I am 100% for Wise Decision.

This week UKOUG decided that, in light of the impacts & concerns around the COVID-19 coronavirus, to postpone this year’s annual Irish conference we hold in Dublin. I thought it would be interesting to some of you to know a little of how we came to that decision.

Firstly, this was a joint decision made by the event committee, the UKOUG board, and the UKOUG senior management. Discussions around the topic of COVID-19 and  had taken place between some of us over the prior 24 hours and the event committee had decided that, in their opinion, there was a strong case to not hold the event at this time. They discussed this with the UKOUG senior management and our CEO decided this deserved an emergency board call. This board call would not just consider the event in Ireland but also our future events, our staff, and our members. (In this post I’m only talking about the Irish event, but enough to say that we are taking steps to protect our staff and consider future events and how they might impact our members & the public, plus how we may replace physical events with remote ones).

Secondly, as you can see above, this was a considered decision and not a knee-jerk reaction.  We had people who live in Ireland involved, we considered feedback we had received from partners/sponsors and also delegates. We talked with the venue. We looked at factual information about COVID-19, it’s communicability & mortality rate (how easily you can be infected and how likely you are to die respectively). In the end the decision was easy as we were all in agreement, we needed to postpone the event.

Thirdly, there were several factors behind the decision to postpone OUG Ireland.

Public Concern

We had several presenters pull out from the event. For most their employing company had banned non-essential (or even all) travel, and some had decided that they personally did not want to risk exposure. A couple of sponsors were in the same situation of being told they could not attend. Further, we had concerned delegates contacting us asking if the event was still on or what steps we were taking. Some cancelled coming, again a mixture of diktat from employer or a personal decision not to attend.

Interestingly, we were getting as many new delegates signing up for the event as dropping out, so obviously some people felt COVID-19 was not an issue.

We knew we had enough speakers in reserve that we could call on to fill agenda holes but we also could see that more and more events were being cancelled across Europe and more companies were announcing travel limitations, so the cancellations were likely to escalate on the run-up to the event. What happens months ahead, no one knows, but for now the public concern is very, very high.

I considered titling this section as FUD – Fear, Uncertainty, & Doubt. But FUD is usually a derogatory term indicating a baseless over-reaction. I think there is a lot of FUD going on in the general public, but people in IT tend to be smarter than average and more balanced. I think it is very reasonable to be concerned to some degree and, as you will see at the end of this piece, the concern will vary depending on your personal circumstances. For some people (e.g those with Asthma or similar decreased lung capacity) there is a significant increased personal risk from this specific illness, it is not always a case of a simple “I’m worried about a pandemic”.

Financial Considerations

With the best will in the world, user groups needs money to put on events. There is a commercial aspect to this. Putting on an event that fails and loses money is a danger. We at UKOUG do insure our major events against Force Majeure, basically events beyond our control, but we are like all user groups in that we walk a tightrope of finance.

Cancelling an event does not always save any money as it has already been paid out. But if a sponsor gets a poor experience in return for their sponsorship £/€/$ they are not happy (and neither are we as the organisers). If delegates come and the event feels like an empty room or the agenda is not what they want, they may not come again. As you can see, it is complex

I have to say that for Ireland we benefit from an excellent relationship with our venue, we have held the event at the Gresham in Dublin for several years and our committee & office know them well. They reduced the potential financial impact on us by offering us flexibility in re-arranging this event.

I make this point as some user groups (and of course, other companies) putting on public events in the near future may find that they have no such flexibility. For them cancelling a conference could actually kill the user group financially or result in individuals losing a lot of money. Did you know that sometimes it is individuals or a very small company that is bank-rolling your usergroup events?

For some user groups the financial consideration will be far more acute than it is for UKOUG.

Public Health

This is not the same as public concern. Public concern is about the actions people take in response to a danger or threat. Public Health is about the actual, real threat.

At present you (yes, you reading this) are almost certainly in more danger of being murdered, killed in a road accident, or dying of normal ‘flu than of dying from COVID-19. And have been all year. And yet none of you stopped living your normal life because of those threats. Most people who will think they have COVID-19 over the next month will actually have either a standard cold or normal influenza. And in fact 90% or so of those who catch COVID-19 will not be that ill. Medical testing is the only sure way of knowing which disease you have had.

But COVID-19 spreads relatively easily via fluid contact – droplets in the air through coughs & sneezes but, more commonly, similar dampness on hard surfaces by people touching their mucous membranes (think eyes, nose, and mouth) and then door handles, surfaces, smart devices. You then touch these surfaces and then your face and you have transmitted the disease to yourself.  Prevention methods are all about constant washing of hands and avoiding touching things. Face masks do diddly squit except if you are in the situation where people might cough in your direction (so medical staff) or to help prevent you coughing the virus out and infecting others. I find it somewhat ironic that in some places so many people have rushed to wear face masks to protect themselves from others but actually it will be doing more to protect others from them.

COVID-19 also has a higher degree or mortality than ‘flu. It stands at about 3.4% at present, compared to 0.1% for standard influenza. I’ve seen arguments that “the real rate is lower as it kills mostly old people or those with underlying conditions”. Well, of COURSE it kills those groups more, that is true for all other diseases. Influenza mostly kills the old, the very young, and the at-risk. That 0.1% is measuring a similar spread of deadliness as the 3.4%. If you get COVID-19 you are something like 30-40 times more likely to die of it than if you get typical influenza. An oddity of COVID-19 is that it does not seem to affect babies and toddlers as much as influenza does. So this new disease is overall more dangerous to adults, especially older adults, than flu than the basic figures indicate…

The mortality rate has increased from around 2% to 3.4% over the last month. Why? Mostly as people are now aware of COVID-19 and deaths will be correctly attributed to it rather than wrongly to other, similar things (like ‘flu). It’s almost certainly not getting more potent. In fact, we might expect the mortality rate to drop as people with a mild version of the disease were probably not being recorded or were being wrongly diagnosed, so the total number of cases would be a lot higher. I expect this figure to drop below 2% for countries with a good health service and no unusually high elderly population.

So what are the chances of holding a user group event and someone infected with the disease coming to the event? Very, very low. The number of known cases outside China are, as a percentage of the population, sod all. But if someone infectious does come to the event? Catching COVID-19 (and in fact a lot of people catching it and it becoming a new source or widespread infection) is quite high.

For those of use who look at project risks it is a very low likelihood/very high impact risk. Something like a hard disk overheating and setting fire to the server. I’ve had that, by the way.

So far the steps taken to keep this disease from spreading are proving effective at slowing it down. But it is spreading. I personally think it is going to get worse before it gets better. Maybe a lot worse, and I am pretty cynical about most “we are doomed” news stories.

Large Oracle user group events are more of a risk than say a big party. Why? A lot of speakers and exhibitors come from geographically distant places, so you are bringing people together from a large area. These people travel a lot and meet a lot of people. It increases the risk. At a party everyone is probably local and if there is no one local with the disease, you are safe. Safer.

This is partly why I was very much in favour of postponing the Irish conference, it had an enhanced risk associated with it as we had an international contingent coming.

What makes me feel qualified to think this? I am not a medic and I am certainly not an epidemiologist (someone who studies disease spread), but I have the advantage of a degree in genetics & zoology and many years of working with the National Health Service and biological academia (some of it on disease and immunology). I am not an expert, but by accident of my history I am better informed than most.

These factors made Ireland too much of a risk, even if the likelihood of something bad happening was actually very low.

Smaller events are less risky and, at present, will go ahead. But all will be reviewed.

 

People want the event

The final factor is that people want the event. Either they do not think the risk is real or they feel that they will be OK anyway as they are young(ish) and healthy or “fate” or whatever. So they will come to the event anyway and cancelling it is “giving in”. Lots of large sporting events are now being cancelled (such as come 5 nations rugby matches) and I am sure a lot of fans are not happy about this. But these are exactly the mass gatherings of disparate people that will really help to spread COVID-19 and create a true epidemic.

In some ways, cancelling a large event could be seen as protecting the ignorant 🙂

 

Maybe Myself?

In the title I mentioned I might need to postpone myself. Why?

At the moment I am an At Risk person. 3 months ago I was in intensive care attached to the most powerful ventilator the NHS uses which does not need the patient to be knocked unconscious and a tube put down into the lungs. In fact, shortly after I was admitted and I was deteriorating, it was expected that I would probably be put into a medical coma and mechanically ventilated. I’m generally fine now – but my lungs are still damaged and recovering. I had influenza & pneumonia. I’ve been asked by a couple of people if I could have actually been a very early COVID-19 case? No. It was not known outside China at the time and lab tests identified the exact strain of influenza I had. If I had been diagnosed with an unknown strain I’d expect the sample would have been re-tested, but this is not the case.

I’m no more likely to catch COVID-19 than any of you, but if I do catch it I am more likely to be at the 3.4% end of things due to the slowly healing lung damage. This is another reason I have paid extra attention to the science behind COVID-19.

I probably should have cancelled my trip to Ireland before the event was postponed, but I was in that last area of consideration. I was not thinking it would effect me and I wanted to go to the event. In the last few days I’ve been advised by people who are clinically qualified that airports & public transport are not a good idea for me. My wife has expressed a desire for me to not give the whole intensive-care-kept-going-by-machines thing a second go as it stressed her. And the cat.

Smaller events I will probably still go to as the risk is lower. And events where everyone is local and there is no signs of the disease there. I really want to go to a meeting in Poland where this will be the case. But to get there I have to go through airports. Full of people from all over the globe. Hmmm.

Personally I am expecting more events, both user groups and generally, to be cancelled. Part of me thinks they should be, the very small risk of a very bad impact is not worth learning a bit more about some software – and you all know how passionate I am about learning.

I think I should be more mindful of the risks myself, but then am I over-reacting?

And I think COVID-19 is going to spread more and kill more people before prevention steps and, eventually, treatment is developed to keep it in check. But I really hope I am wrong on that.