Drugs to treat COVID-19: how close are we?

Donald Trump has been in disagreement this week with top scientists by claiming that the anti-malarial drug chloroquine should be adopted immediately for treating patients with COVID-19, and even given as a prophylaxis. In this blog I will explore the challenges facing scientists working to develop drugs to treat COVID-19 and discuss recent advances, including chloroquine.

What are the challenges in designing anti-viral drugs? After all, there are a lot of antibiotics out there that work for a whole range of different bacterial infections. Let’s look at the structure of a bacterium, shown below.

Compared with a virus, the structure of a bacterium, shown below, is highly complex. Bacteria carry out a huge number of chemical reactions and process. They release energy through respiration; they make proteins; they replicate their DNA in order to reproduce. And that’s just for starters; there are many, many more processes going on. Viruses, by contrast, can’t do any of these things without infecting a cell and using its organelles.

Structure of a bacterium. There are many different processes which can be targeted by antibiotics.

With bacteria, inhibiting or blocking even one of these reactions or processes can be enough to kill it. All chemical reactions in living organisms are controlled by enzymes, which are a type of protein. Each protein controls one, specific reaction. Disable the enzyme, and you stop the reaction.

For example, penicillin works by disabling the enzyme that bacteria use to maintain and repair their cell walls. The cell wall disintegrates, and the bacterium dies. Baytril, an antibiotic widely used in veterinary medicine, interferes with the replication of DNA, meaning that the bacterium can’t reproduce.

So, why are viruses harder to fight? The answer lies in the fact that viruses are so simple, meaning there are far fewer reactions and processes for drugs to target. One virus that is treated very successfully with drugs is HIV. So, why can’t some of the drugs used to treat HIV be adapted to use against COVID-19? By virus standards, HIV is quite complex. It’s a type of virus called a retrovirus, which has a more complicated reproductive cycle than other viruses. To put it simply, most of the drugs used to treat HIV are blocking or inhibiting processes that just don’t happen in COVID-19. Two HIV drugs, lopinavir and ritonavir, have shown some promise in treating COVID-19.

The structure of a virus is much simpler than that of a bacterium.

One of the most promising potential treatments is a drug called favipiravir. It’s a drug being developed in Japan, specifically to treat RNA viruses, and COVID-19 is an RNA virus. Originally developed as a treatment for influenza, trials have been carried out in China on 340 patients who had tested positive for COVID-19. It was found that the drug significantly shortened the time taken for patients to test negative, and that respiratory symptoms and lung function improved as well.

Why then, is favipiravir not being adopted immediately? The answer is that it has only been licensed to treat influenza. This means that extensive clinical trials must take place before it can be licensed for COVID-19 to ensure that it is safe and effective.

What about chloroquine? Chloroquine is an old drug, it’s been used for over 80 years to treat malaria, which is a disease caused by a parasite carried by mosquitos. It has been known for a while that chloroquine has antiviral activity. It basically prevents viruses from sticking to the membranes of cells, meaning they cannot enter and infect them.

So far, the evidence supporting chloroquine is anecdotal – this means it does not meet the standard to be considered reliable. Some doctors in China and South Korea have given it to patients with COVID-19 and seen improvements; and in France, 24 patients were given a similar drug, hydroxycloroquine, and showed improvements.

Chloroquine shows promise in treating COVID-19, but a lot more research is needed.

These were small scale experiments and not carried out under the controlled conditions of a clinical trial. As a result though, 6 properly designed clinical trials are getting underway around the world to test whether chloroquine or hydroxychloroquine are safe and effective against COVID-19.

If either chloroquine or hydroxychloroquine do turn out to be effective, it would be a major breakthrough. Because both have been used for many years in treating malaria, they are already known to be safe. They are also safe to take during pregnancy; there are concerns that favipiravir may have adverse effects on a developing foetus. Both drugs are cheap, and facilities to manufacture them in large amounts are already up and running.

There are downsides. The side effects of chloroquine or hydroxychloroquine are pretty unpleasant, mainly nausea and diarrhoea. In rare cases chloroquine can cause blindness. An important consideration too is their use in treating malaria. Drug resistance in malaria is a big concern to those involved in treating it.

The risk of malaria developing resistance to chloroquine and hydroxychloroquine must be carefully evaluated.

There are already a number of strains of malaria that are resistant to both chloroquine or hydroxychloroquine. The risk malaria resistance must be evaluated before using them to treat COVID-19 in places where malaria is active. For example, it’s now malaria season in southern Africa and malaria will be active until around the end of April. In India, malaria season begins in May.

In terms of drug development, there is a lot to be optimistic about. It may well be that an effective treatment is developed before a vaccine. Certainly, many scientists are now beginning to talk about a timescale of months, rather than years, for developing an effective treatment. I will keep you all up to date about advances as they occur, meanwhile, stay safe and well!

COVID-19 and pets: facts and fiction

I’m not in full-blown isolation yet but I am practising pretty stringent social distancing. At times like this, the companionship of our pets is more important than ever, particularly for those like me who live alone. I’ve seen a few posts about animals and COVID-19, and as usual, there’s rather more scaremongering than factual information. In this blog, I am going to address four issues. Can domestic pets catch/ spread COVID-19; is it safe to take a pet to the vet; what precautions should pet owners be taking; and is hand-sanitiser toxic to pets.

First, can our pets catch COVID-19? The answer is, no. Coronaviruses are zoonotic, which means they can spread from humans to animals. However, this requires large numbers of humans and animals to be crowded together, as was the case in Wuhan. The current advice from the WHO is that there is no evidence at all that pets can catch COVID-19.

As a ferret owner myself, I am aware that there is a lot of worry in the ferret community because ferrets can catch flu from humans. Also, the fact that ferrets were initially used in vaccine testing has got people worried. The reasons ferrets were initially thought to be a good choice for vaccine testing were that they are generally quite susceptible to respiratory infections; and they can catch the coronavirus that causes Severe Acute Respiratory Syndrome (SARS).

However, ferrets were very quickly rejected for vaccine testing. It was found that if deliberately infected with the virus, they showed no symptoms. Not only that, but within a few hours, they were testing negative for the virus.

The one thing I would say to ferret owners is that the early symptoms of COVID-19, which ferrets can’t catch, are very similar to those of flu, which they can. With the focus so much on COVID-19 we sometimes forget that all the normal colds and flu that circulate at this time of year are still doing the rounds. So if you get a sore throat, fever and dry cough, it would be prudent to avoid contact with your ferrets until you know what you actually have.

What about dogs? It is known that dogs can be susceptible to coronaviruses. They can catch three specific strains: Type 1 & 2 canine coronavirus, both of which cause diarrhea; and Canine respiratory coronavirus’ that causes kennel cough. There is no evidence that they can catch the COVID-19 strain. A single dog in Hong Kong has tested positive for the virus but did not get any symptoms. Actually, to say that there is no evidence to suggest that dogs can catch COVID-19 isn’t quite correct; it would be more accurate to say and there is plenty of evidence that they CAN’T – there has been extensive testing of dogs in China and Hong Kong.

Cats can also catch one, very specific coronavirus; Feline Infectious Peritonitis. Again, there is absolutely no evidence to suggest that they can catch COVID-19. There is also no evidence to suggest that humans could spread the virus to other pets such as rodents, reptiles and birds.

So to the second question: can pets spread COVID-19? In theory, yes. There is evidence that the virus can survive for short periods outside a host. However, survival is most likely in droplets on smooth, non-porous surfaces. Animal fur does not fit this description. In theory, if you have COVID-19 and cough all over your cat, then someone else puts their face in the cat’s fur, there’s a small risk of transferring viable virus. But if you have COVID-19 self isolation means that should not be happening!

Beenie boys love to get mucky! But that doesn’t mean they are spreading COVID-19.

Another thing to consider is how clean most animals keep themselves. If you cough all over your cat, I guarantee they will gallop off and have a jolly good wash, only pausing now and again to give you their best ‘you humans are absolutely disgusting’ glare. Ferrets are also very clean, with the possible exception of beenie boys but I don’t think poo-surfing is going to spread the virus ;). Dogs aren’t quite as meticulous but again, short of actually coughing on them, they are not going to harbour the virus on their coats.

Basically if you have a pet and are ill, self-isolating or in a vulnerable group, the overwhelming advice is that it’s fine to be around your pet, but practice good hygiene such as regular hand-washing. Also clean food bowls, water bowls, litter trays etc. regularly – which we should all be doing anyway.

So, it it safe to take your pet to the vet? There are two things to consider here: your pet’s safety, and that of yourself and the vet staff. As far as your pet goes, the vet’s surgery is a perfectly safe environment, and if he or she needs treatment, they absolutely MUST be seen by a vet! I’ll talk later about sensible contingency plans for those with pets.

If you are self-isolating, you definitely should not take your pet to the vet yourself, for your own safety and that of the veterinary staff. If you are vulnerable but not in full-blown isolation, it’s not so clear-cut but consider things like how easy it is to practice social isolation in the waiting room or consulting rooms. I do know that in every veterinary practice I’ve ever used, they are absolutely scrupulous about hygiene, and you can bet they will have stepped this up.

You may find in the coming weeks that your vet may cancel or postpone routine, non-urgent procedures. This is to minimise the risk to staff and ensure that if they have staff members going off sick, they still have the capacity to provide care for your pets. You can also be 100% confident before postponing any procedure, your vet will have carried out thorough checks to make sure that doing so will not adversely affect your pet’s health.

Dogs need exercise and it’s important to plan for who will walk them if you can’t

If you have pets, it’s sensible to have a contingency plan for what will happen to them if you become ill or have to self-isolate. This is particularly important for those living alone. I’ve installed a key safe on my property and three good friends have the combination. I have people lined up who would deliver pet supplies, and who would also help out if, for example, I had to go into hospital. Which I have no intention of happening! Dogs will need to be walked no matter what, so dog owners also need to ensure you have someone lined up to walk the dog if you can’t.

So, is it safe for you to take a pet to the vet whose owner is ill or self-isolating? Absolutely yes. Cats, ferrets and small animals will be in carriers. My plan would be that when the person collecting the pet arrives, I would put the pet carrier outside my front door then go back in and shut the door; the person collecting can then come and get the carrier. Wear disposable gloves and wipe the carrier down. On returning the pet, repeat in reverse. With dogs, which are probably on a lead, think about how you could hand the lead over to someone else while maintaining isolation. Planning ahead is the key here!

Finally, what about hand sanitiser? The rumour is that it contains ethylene glycol, which is toxic, and that if your pet licks your hand after you’ve used it, they will be poisoned. Not true. Hand sanitisers contain ethanol, or in some cases propanol. Which is toxic in large doses, but your pet would have to ingest a heck of a lot of it! In the ferret community we’ve used hand sanitiser for years at shows, with no ill effects whatsoever.

If you want further information, the PDSA website is fantastic:

https://www.pdsa.org.uk/taking-care-of-your-pet/pet-health-hub/conditions/coronavirus-and-covid-19-in-pets#contents-link-2

It only remains for me to thank those whose photographs appear in this blog: Milo (drooly tabby and white cat); Beezy (ginger ninja cat); Crooks (handsome dark polecat ferret); Wookie (mucky beenie ferret – he’d just been up the chimney! No longer with us but would be very proud to have been chosen as an example of a messy beenie boy); Tess (angora diva ferret whose pic I didn’t need but she insisted); and Ebony (greyhound who’s sadly no longer with us, but who adored the beach!)

COVID-19 and ibuprofen – what are the facts?

Hi everyone, there’s been a bit of scaremongering out there (surely not??) about ibuprofen making the symptoms of COVID-19 worse. In this post, I will give you the facts, and the latest advice from the World Health Organisation (WHO).

It started with a Tweet on 14th March by French health minister Olivier Veran, stating that anti-inflammatories such as ibuprofen could aggravate the symptoms of COVID-19, and that the symptoms of COVID-19 should only be treated with paracetamol.

Ibuprofen is on of a group of drugs known as non-steroidal anti-inflammatory drugs or NSAIDs. Other examples include aspirin and naproxen. M. Veran claimed that ‘serious adverse events’ had been reported in COVID-19 patients being treated with NSAIDs and that their use should be banned. No details were given about these supposed ‘adverse events’ at the time.

On 17th March, the French state-owned news service, Agence France-Presse, stated that this was based on evidence published in the medical journal The Lancet on March 11th. I’ve read the article and trust me, it makes absolutely NO mention of ibuprofen or any other NSAIDs. It’s actually about increased risk of complications from COVID-19 in patients with a combination of diabetes and hypertension (high blood pressure) who are being treated with a specific class of drugs that are not remotely related to ibuprofen or any other NSAIDs.

Following M. Veran’s tweet, the WHO did the sensible thing and advised against the use of ibuprofen to treat COVID-19 until they could clarify the situation. After a full investigation and analysis of all the available evidence, on March 18th both the WHO and the European Medicines Agency (EMA) issued statements saying that there was no evidence of a link between ibuprofen and worsening of COVID-19 symptoms; and that there was no recommendation against taking ibuprofen or other NSAIDs.

So, is there a risk? NSAIDs are known to trigger or worsen the symptoms of asthma in some people. If your asthma is triggered by NSAIDs, you will already know not to take them. I know that for me, the NSAID diclofenac is one of my triggers. Ibuprofen is fine, so are aspirin and naproxen, but to be on the safe side, I try to avoid using them for longer than 2-3 days.

So, there is no reason not to use ibuprofen or any other NSAID to treat symptoms of COVID-19, provided you read all the information and follow the instructions on the pack. Personally, if I am unwell, I prefer to use paracetamol, which relieves pain but is not anti-inflammatory. But that is because inflammation is an important part of how your immune system fights infection so if possible, I prefer to let it do its stuff!

A final note. If you are being prescribed ibuprofen or any other NSAID for a long-term medical condition and you are worried, don’t stop taking it but do consult your doctor for advice. Later today, an update on progress in the search for an anti-viral drug to treat COVID-19. Watch this space!

How scientists study new viruses: crystallography

In the fourth post in my series on how scientists study viruses, I am going to talk about crystallography. Crystallography involves shining a beam of X-rays through a crystal. By looking at how the X-rays pass through the crystal, scientists can actually generate a detailed picture of the structure of a molecule and how the atoms are arranged.

So, how does it work? Think of the waves you see in the ocean. They are straight lines, more or less, like the picture on the left. Now think of what happens when you throw a stone into a pond. The waves spread out in a circle from where the stone hit the water, as in the picture on the right.

Now, let’s look at what happens when a straight wave is forced through a narrow gap. It spreads out in a half-circle. This is called diffraction and is shown in the diagram on the right. What does this have to do with studying viruses? It’s to do with the fact that X-rays behave like waves.

Basically, if you shine X-rays through a crystal, tiny gaps between the atoms act like the narrow gap in the diagram and make the waves spread out into circles. These then meet waves emerging from other gaps, causing an interference pattern. You can see an interference pattern for yourself by dropping two stones into water close together, and watching what happens when the waves meet. By analysing the interference patterns when X-rays pass through a crystal, scientists can work out the arrangements of the atoms.

Dorothy Crowfoot Hodgkin with models of (L-R) penicillin; insulin; vitamin B12. In the frame is the first structure she solved: cholesterol.

One of the most important scientists in the development of X-ray crystallography was Dorothy Crowfoot Hodgkin. She solved the structures of cholesterol and penicillin, and in 1956 she found the structure of vitamin B12, for which she was awarded the Nobel Prize in 1964. However, she is best known for solving the structure of insulin in 1969.

The basic principals of crystallography are no different today to what they were in 1914 when the first crystal structure (table salt) was solved. What has revolutionised crystallography is the development of computers.

To get from measurements of interference patterns to a molecular structure requires some truly horrendous maths – one of the few bits of my chemistry degree that I really didn’t enjoy at all! It took Dorothy Hodgkin 30 years to solve the structure of insulin, and insulin is a comparatively simple molecule. Modern computer processing means that scientists can determine the structures of very complex molecules, like the spike protein on the surface of COVID-19, relatively quickly.

Modern X-ray crystallography equipment at the University of Strathclyde

So, how are scientists using crystallography to study COVID-19? They are using it to determine the chemical structures of molecules that make up the virus. The most important of these is possibly the spike protein. This is on the surface of the virus, and the virus uses it to attach itself to the surface of a human cell. An important part of how your immune system fights the virus is by making antibodies which are exactly the right shape to attach to the spike protein.

X-ray crystal structure of the COVID-19 spike protein

Scientists have been able to isolate the spike protein and grow a pure crystal; they have then used crystallography to solve the structure. Knowing the exact structure of the spike protein will help those developing vaccines and anti-viral drugs to combat COVID-19. Also, scientists can monitor how the spike protein changes when the virus mutates; this knowledge will help to make sure that any vaccine will continue to work if there are mutations.

The structures of other important molecules in the virus have also been solved, including an enzyme called protease. Enzymes are substances that control chemical reactions; protease controls the production of the proteins needed to make new viruses. By solving the structure, scientists have identified how it could be stopped from working. As a result, a team in Shanghai are investigating 30 (yes, 30!) molecules that could be used to treat COVID-19. And that’s just one of hundreds of teams around the world.

Structure of COVID-19 protease enzyme. This shows how a potential drug molecule (in green) could bind to the enzyme and stop it working.

I hope this has been interesting/ helpful. As a scientist myself, I am in awe of what has been achieved in such a small time, and how much we now know about the virus. There is actually plenty of good news out there, if you know where to look for it, and you can be sure that I will keep you updated of new discoveries as and when they happen. In fact, I’ve just found out that some drug trials in China are showing real promise, so watch out for a post about that later today.

How scientists study new viruses: microscopy.

Early microscope made by Italian scientist Galileo

Confession time here: microscopes are one of my favourite things, ever! I love investigating things with a microscope and could happily spend hours messing about with one. The strangest experiment I ever did was to get a friend’s cat to lick a microscope slide so we could see what was in her mouth. In this post, I will talk about how scientists use the latest in microscope technology to study viruses.

The use of lenses to make objects look bigger dates back to the 13th century. It’s not certain who actually invented the microscope; but they started to appear in the mid 17th century. Italian scientist Galileo Galilei played an important part, using his knowledge of telescopes to improve on earlier inventions.

Typical optical microscope used in schools and laboratories

If you’ve used a microscope at school, it will have been an optical microscope, also sometimes called a light microscope. If you haven’t used one yet, you will do this in Year 7 and trust me, it’s amazing! Optical microscopes work by shining a light through a sample, and using a combination of lenses to magnify the image. Often, a stain is used – for example, methylene blue to stain animal/ human cells; or iodine for plant cells. Sometimes a combination is used – for example, Wright’s stain, used to examine blood, is a mixture of methylene blue which stains white blood cells, and a different stain for red blood cells.

Human cheek cells, stained with methylene blue and seen under an optical microscope

Optical microscopes have some limitations. The first is magnification. Mitochondria (the organelles of a cell that release energy) are the smallest things that can be seen with a standard optical microscope. Advanced computer processing does allow smaller objects to be observed; but this is very specialised, and still doesn’t produce the magnification needed to see viruses.

The second limitation of an optical microscope is that the images are two-dimensional – in other words, everything appears to be flat. Cells, like the ones seen above, are not flat but are three-dimensional. Being able to study cells, viruses and bacteria in 3-D is very important if we want to properly understand their structure. So, instead of optical microscopes, scientists studying COVID-19 and other viruses will be using electron microscopes.

Optical microscopes work by shining light through a sample. Electron microscopes use a beam of electrons instead of light. This has two advantages. First, you can achieve much greater magnification and resolution (resolution is how detailed and clear an image is); second, an electron microscope can give 3-D images. The disadvantages are that they are expensive; they are not portable; and some samples require very specialised preparation.

Preparing a sample for SEM. This often involves coating the sample with a thin layer of gold or silver.

So, how will scientists be using microscopes to study the virus? There are two types of electron microscopy: scanning electron microscopy (SEM) and transmission electron microscopy (TEM). They can both do different things but broadly speaking, SEM is used to study objects in 3-D and TEM in 2-D.

SEM is particularly useful for scientists studying the structure of the virus, and how the virus attaches to the surfaces of human cells. TEM is very useful for studying how the virus behaves inside infected cells. Some pictures are shown below.

SEM image showing COVID-19 viruses (orange) on the surface of a human cell. The colours are added by computer, to make the image easier to see.

Another SEM image of COVID-19 (in yellow) on the surface of a human cell. Again, colours are added by computer.

TEM image of COVID 19. You can clearly see the spikes that give the virus its name – ‘corona’ means ‘crown’.

TEM showing COVID-19 particles on the surface of, and inside, a human cell.

Another TEM showing COVID-19 particles attaching to and entering human cells.

I hope you have found this interesting! In my next post, I will explain the technique scientists use to study proteins and other molecules on the surface of the virus: crystallography.

Jenner had it easy: the challenges of developing a COVID-19 vaccine

One of the most frequently asked questions at the moment is how long it will take to develop an effective vaccine for coronavirus COVID-19. An effective and safe vaccine would undoubtedly be the best way to halt the spread of the virus. There’s some excellent news on that front – the first human testing of a vaccine began in the US earlier this week. This is an incredible achievement to have got to human testing within such a short time! In this post I’ll explain some of the challenges facing vaccine developers, and some of the amazing leaps forward that have been made in recent weeks.

A Chinese child is variolated by nasal insufflation

Edward Jenner is credited with the discovery of vaccination, but in fact, a crude (and highly risky) form of immunisation against smallpox, called variolation, had been in existence for centuries. Variolation dates back to 10th century China, and the earliest form involved taking a powder made of crushed smallpox scabs and then blowing it up children’s noses with a tube – a practice called nasal insufflation. Yes, revolting I know! In Sudan, mothers of babies with smallpox would sell the scabs to other mothers who would rub them on the skin of their children.

By the time Jenner made his discoveries, variolation had been common practice in England for around 80 years and usually involved making a cut or scratch on the arm and introducing pus taken from infected patients. Yes, still revolting! The problem with variolation is that it involved deliberately infecting someone with a dangerous disease. The idea was that variolation gave a much milder illness, and after recovery, the variolated person was immune. The risk was kept to a minimum by ensuring that the material used in variolation was taken only from patients with mild illness; nevertheless, a small but significant proportion of those variolated would get the full-blown disease, leading to disfigurement or even death.

Edward Jenner innoculated 8 year-old James Phipps with cowpox, then deliberately infected him with smallpox

I won’t go into Jenner’s story in detail here, as it is covered in plenty of other places. In short, Jenner discovered that innoculating someone with cowpox, which is a similar virus to smallpox but a very mild illness, gave immunity to smallpox.

Early vaccines were developed basically using trial and error. A major breakthrough was made by Louis Pasteur, who discovered that bacteria and viruses could be artificially weakened, and that the weakened strains induced immunity with either mild symptoms or no symptoms. Pasteur’s arch-rival Robert Koch pioneered the use of dead pathogens (bacteria and viruses) as vaccines; later, the discovery of antibodies enabled better understanding of how vaccines work.

There have been cases where a vaccine has been developed and produced very rapidly. In 1957, a new strain of influenza emerged which had the potential to become a global pandemic. In 9 days, American microbiologist Maurice Hilleman had isolated the new virus, allowing development of a vaccine and saving many thousands of lives.

Maurice Hillman saved many lives by developing a vaccine for the 1957 Hong Kong flu pandemic

This begs the question, why can’t a COVID-19 vaccine be developed that quickly? After all, the virus has been isolated and its genome sequenced. A major difference is that Hilleman was working with a virus that was already well understood – it was simply a new strain. Vaccinations for flu use either dead virus (adults) or live, weakened virus (children). The manufacturing process basically involves growing the required strain in chicken eggs. It’s reliable and can be used for any strain of flu once the virus has been isolated.

A second point is that in 1957, regulatory processes were nothing like as strict as they are now. Hilleman’s Hong Kong flu vaccine did not have to go through the extensive stages of development, testing and approval that a modern vaccine is subjected to before it reaches clinical use. Even so, for a well-understood virus like flu, a vaccine can make it into clinical use relatively quickly. In April 2009, the first cases of a new strain of H1N1 swine flu were reported; by November a vaccine was in clinical use.

So, what are the challenges of developing a vaccine from scratch? Vaccines make use of antigens. These are proteins on the surface of a pathogen that signal the immune system to attack it. As part of the immune response, antibodies will be made to match the antigen. Your immune system then ‘remembers’ how to make those antibodies, so that if you encounter the pathogen again, you can fight it off before symptoms develop.

A major challenge is identifying which type of vaccine will be most effective. Inactivated vaccines use a dead pathogen; the pathogen is killed by heat, radiation or chemical treatment, then introduced into the body to provoke an immune response. Attenuated vaccines use a weakened form of the pathogen. They are highly effective but cannot be given to people with compromised immune systems. Protein sub-unit vaccines use either a protein from the surface of a virus, or the virus envelope with the DNA or RNA removed. DNA or RNA vaccines use part of the virus’ DNA/ RNA; cells in the body take this up and make proteins that mimic those that the virus produces; provoking an immune response.

BCG is an attenuated vaccine – it uses a weaker form of the bacterium that causes TB.

It’s also important to make sure a vaccine is resilient to small mutations of the virus. This is especially important because COVID-19 is an RNA virus and they mutate much more easily and often than DNA viruses – see my post about how viruses change. These mutations are very small, and modern vaccine developers have the tools to create vaccines that will still be effective if the virus undergoes small changes.

A COVID-19 vaccine will need to be 3 things: safe, effective and resilient to minor mutations of the virus. Vaccine development has two stages: pre-clinical and clinical. In the pre-clinical phase, scientists study the virus and its antigens; they test it in test tubes and on animal models; and they develop the manufacturing process. In the clinical phase, there are a series of carefully structured and monitored trials.

So, where are we with COVID-19? A major development is that scientists have determined the structure of the spike protein on the surface of the virus, which acts as an antigen. More about how this was done, and why it’s important, in a separate post.

A computer model of the structure of the COVID-19 spike protein

In brief, studying the structure of the spike protein in detail will help vaccine developers create that mutation resilience I talked about earlier, because they can ensure that a vaccine will still be effective if there are changes to the spike protein. In addition, now the spike protein has been fully characterised, it’s possible to manufacture it artificially and also manufacture artificial antibodies; scientists can use both of these in vaccine research, which is easier and safer than using the actual virus.

Another important tool is genome sequencing, which I explained in an earlier post. Again, in brief, scientists all over the world are sequencing the genome of the virus and entering results into a massive international database. This allows them to track changes in the RNA of the virus, which is also very important in ensuring that a vaccine is resilient to minor changes.

Earlier this week, a vaccine in the USA entered what is known as Phase I clinical trials – this is when the vaccine is tested on a small number of carefully selected, healthy volunteers to assess safety and immune response. If those are successful, Phase II trials will begin; these involve a larger group of volunteers who will be vaccinated and then deliberately infected with the vaccine. Phase III would be a large scale trial involving hundreds of volunteers in multiple locations to test whether the vaccine is safe and effective across the population as a whole. If that is successful, the manufacturers can apply for a license and the vaccine can be adopted for clinical use.

I will stress here, only a small proportion of Phase I trials progress to Phase II. However, to have a vaccine in Phase 1 trials this quickly (within about 3 months of the virus appearing) is amazing progress. I’m keeping a very close eye on vaccine development and will keep you all updated, so watch this space!

How do scientists study new viruses? Genome sequencing

In the second in a series of posts explaining how scientists study new viruses, I will talk about genome sequencing. Thanks again to 9-year-old Chloe for asking about how new viruses are studied.

If you’ve read my post ‘What is a virus?’, you may remember that a virus consists of a protective envelope, and inside that envelope is a strand of either DNA or RNA. DNA and RNA are molecules that store information in the form of a code. This code contains all the instructions that the virus needs for reproducing, and is called the genome. All living organisms also have a genome, including each of us.

Believe it or not, the code that makes up the genome only has four letters. In DNA these letters are C, G, A and T; in RNA they are C, G, A and U. Each letter represents a chemical called a base: A is adenine; T is thymine; G is guanine; C is cytosine and U is uracil. In the genome, the letters are arranged in groups of 3, called triplets. I won’t go into the maths, but there are 64 possible triplets.

Part of a DNA molecule. It forms a spiral called the double-helix, joined across the middle by bases. Here, purple represents thymine (T), orange is adenine (A), yellow is guanine (G) and green is cytosine (C)

RNA is a single strand. It’s shorter and less stable than DNA, and thymine (T) has been replaced by uracil (U) which is coloured red.

DNA and RNA contain the instructions for making proteins. Proteins are long molecules made up of chemicals called amino acids. There are 20 amino acids, and DNA and RNA have the instructions for which amino acids to join in which order to make a specific protein – this works because each amino acid is matched to a specific triplet. There are 64 possible triplets and only 20 amino acids. Several amino acids match more than one triplet. There are a few unused triplets which do not match any amino acid – these are called non-coding triplets and they are used to create spaces between instructions for different proteins.

Genomes are unique. When a new virus appears, its genome will be different to anything else, because it’s alterations to the genome that have made the virus change. Genome sequencing basically involves reading a genome and finding out the combinations of letters making up the code. This isn’t easy. The first full genome to be sequenced was a bacterium,and it had over 1,800,000 bases. Sequencing the human genome took 13 years!

Viruses are a lot simpler than bacteria with fewer bases – COVID-19 has around 30,000. That’s still a lot, but improvements in technology mean that when a new virus appears, it’s genome can be sequenced fairly rapidly. Within weeks of the first cases appearing, Chinese scientists had sequenced the virus’ genome using samples taken from patients.

Why is genome sequencing important? Although the genome of COVID-19 is unique, it has similarities to other strains of coronavirus. By comparing the genome of COVID-19 to other strains, scientists can get important information about where the virus came from and how it has changed to affect humans. In the case of COVID-19, they found that the virus is most likely to have come from bats or snakes; epidemiologists (see an earlier post) were able to use this information to confirm their theory that the virus originated in a livestock market in Wuhan, China.

The study of COVID-19’s genome is a world-wide project. In every country where cases appear, scientists are sequencing the genome and adding their findings to a massive international computer database. As recently as 13th March, scientists from the University of Sheffield published the genome sequence of the virus from the first patients in the UK. Collecting and analysing this information from across the world means that scientists can monitor how the virus is changing as it spreads, and it provides vital information for those working on vaccines and treatments. Monitoring minute changes in the genome also provides important information which epidemiologists can use in studying how the virus is spreading.

Something to be reassured about with COVID-19 is that scientists are making discoveries about the virus at an incredible rate. I’d hazard a guess that if this virus had appeared even 10-15 years ago, it would have taken scientists several years to discover what has been discovered in a few months. As a scientist myself I am literally in awe of what has been achieved in such a short time. I hope you found that interesting. My next post in this series will look at how microscopes are being used to study the virus.

Why gargling with vinegar will NOT cure you of coronavirus!

Hot on the heels of panic buying, we are starting to see people posting about supposed ‘cures’ for COVID-19 that some mysterious ‘they’ are not telling us about for ‘their’ own sinister reasons. Folks, this is reality, not the X-Files (I know, showing my age). Seriously, I’ve seen the image below posted on Facebook by several people in the last 24 hours (minus the red X – that’s my addition!). In this post I am going to explain why it’s incorrect, and why anyone who shares or follows it is NOT saving someone, but is putting themselves and others at risk.

The reason this is incorrect lies in the way viruses reproduce. As explained in my earlier post, ‘What is a virus?’, viruses consist of a strand of genetic material (RNA in the case of COVID-19) inside a protective envelope. In order to reproduce, they have to get inside a cell, hijack its organelles, then destroy the cell membrane to release the new virus particles. The image below shows this. It’s for an influenza virus, but all viruses work the same way.

When you have a sore throat from COVID-19 (or any other virus), it’s because the virus is invading the epithelial cells that line the throat, and using them to reproduce. A combination of damage to the lining of the throat, and inflammation from your immune response, is what gives you a sore throat.

Gargling with warm water and salt/ vinegar may destroy some of the free virus particles, or wash them away. What it won’t do is affect cells infected with the virus. Any viruses that are already inside cells will be completely unaffected because they are protected by the cell membrane; they will be busy reproducing away like crazy. As soon as you stop gargling, viruses leaving infected cells will once again go on to affect other cells.

So why might gargling and drinking plenty of water make a sore throat feel better or even disappear? If the lining of the throat becomes dry, it makes the soreness worse, so drinking plenty of water will prevent drying out. Gargling warm salt water to soothe a sore throat is nothing new, it’s a tried and tested remedy. I can remember my granny making me do this during childhood bouts of tonsillitis and it really does help. You can also use bicarbonate of soda. So, hydration and gargling will soothe a sore throat, as will throat lozenges, or in fact any boiled sweet because they generate production of saliva.

Please though, take it from me, the advice in the picture at the top of the post will NOT cure you of COVID-19 infection. Posts like this are extremely dangerous for two reasons. First, they may make people think they are cured, so they are unprepared when more serious symptoms appear. But the biggest danger is someone might believe they are cured and go out and about, potentially spreading the virus.

The take-home message from this post is, if you want information about how to treat COVID-19, PLEASE get it from a reputable source. In the UK, your first port of call should be the NHS; there is plenty of advice available online. If you have a health condition, charities and support organisations have specific, up to date advice – personally, I check Asthma UK daily for updates. Whatever you do, DON’T follow advice from random, unaccredited sources on social media. And if you see something like the post I’ve been talking about here, please, PLEASE do not re-post or share it! If you’ve found this post useful though, please do share.

A footnote. Vinegar or salt water may not kill cells infected with the virus, but your immune system will. There are two types of white blood cell that do just that. Natural killer cells (NKCs) and killer T-cells. So alongside good hygiene, the best thing you can do to protect yourself is make sure that you are fit and well, so that your immune system is as strong as possible. Good diet, enough sleep and plenty of exercise are important in maintaining a strong immune system. Looking after your mental health is also vital, as there is a strong link between mental health and your immune system. In the list below there is a link to advice from Mind on taking care of your mental health which I can’t recommend enough, it has some fantastic advice 😀

Some good sources of reliable information:

https://www.nhs.uk/conditions/coronavirus-covid-19/

https://www.mind.org.uk/information-support/coronavirus-and-your-wellbeing/ – This is a brilliant resource for anyone who has mental health issues; and excellent advice for taking care of your mental health generally.

https://www.diabetes.org.uk/about_us/news/coronavirus – Epecific advice for those with diabetes.

https://www.macmillan.org.uk/cancer-information-and-support/get-help/physical-help/cancer-and-coronavirus – A FAQ developed by a number of cancer charities for those living with cancer.

https://www.mariecurie.org.uk/help/support/coronavirus – Excellent advice from Marie Curie for those dealing with a terminal illness.

https://www.asthma.org.uk/advice/triggers/coronavirus-covid-19/ – Great advice for those with asthma.

https://www.ageuk.org.uk/information-advice/health-wellbeing/conditions-illnesses/coronavirus/ – Advice aimed at older people.

Herd Immunity

Herd immunity has been talked about a lot in recent days, particularly here in the UK. I’ve been asked by a few people to explain what herd immunity is, and how it protects vulnerable members of a population. I won’t comment on the strategies being employed by any particular country or politician with regard to herd immunity to COVID-19. But I am going to try and explain what it is and how it works, so here goes.

Antibodies are Y-shaped proteins involved in fighting off disease

When you are exposed to a pathogen (a micro-organism that causes disease), your immune system responds to fight it. Important weapons in the immune system’s arsenal are chemicals called antibodies. I won’t go into how they work – if folks are interested, I’ll do a separate post. Antibodies are specific – each antibody will only fight the particular pathogen it was designed for. When you are first exposed to a pathogen, it takes several days for your immune system to start making antibodies.

After you recover, white blood cells called memory B-cells remain in your bloodstream. They do exactly what the name implies – they ‘remember’ how to make antibodies to that pathogen. This means that if you are exposed to that particular pathogen again, your immune system will start making antibodies straight away, and will defeat the infection before you develop any symptoms. This is called immunity.

Immunity can be developed in two ways – naturally, through catching and recovering from an infection; and artificially, through vaccination. I’m going to talk about vaccination in another post, because a few people have asked about it in regard to COVID-19, so I won’t go into the details here. Basically, vaccination is away of provoking your immune system into making antibodies, and memory B-cells, without you having to get the illness; it usually uses a dead or weakened form of the pathogen.

So, how does herd immunity work? The diagram below will help explain:

The diagram shows the number of people in a population that are immune from a disease. On the left, we can see that the majority of the population are immune to the disease. The probability of those who are not immune coming into contact with the infection is low, and so is the probability that they will infect each other.

Now look at the population on the right, where there is a high proportion of individuals who are not immune. If just one of those individuals contracts the disease, the probability of them coming into contact with someone else who is not immune is high, and the disease will be able to spread through the non-immune members of the population.

How is herd immunity developed? In the case of common and mild infections, it occurs naturally. For example, there is significant natural herd immunity to some strains of flu that only cause mild illness. For more serious infections, herd immunity is developed artificially through mass vaccination programs.

In any population, there will be people who cannot be vaccinated or do not have immunity to a disease. Some vaccines can’t be given to people with compromised immune systems, such as those undergoing chemotherapy. Others may be allergic to one of the vaccine’s ingredients; for example, the flu vaccine can’t be given to people who are allergic to chicken eggs. There will also be people who have had the vaccine but do not have immunity. It takes time to build up immunity following a vaccine, so those who have only had the vaccine recently may not yet be immune. In addition, those who have been vaccinated but whose immune system is compromised may be vulnerable to the disease.

Let’s look again at the population on the left of the diagram. From the previous paragraph, you have no doubt realised that if this represents a population where mass vaccination is in place, the majority of people who have no immunity are also those who are most vulnerable to serious illness and life-threatening complications. Herd immunity protects them by minimising the risk of them coming into contact with the disease. On the right, however, there is no such protection.

Take the example of measles. Measles is a serious viral infection that can result in life-changing or even fatal complications. There is, however, a safe and effective vaccine, and where mass vaccination programs are in place, herd immunity protects the vulnerable. If uptake of the vaccine is poor, then this protection is no longer there and vulnerable individuals are at a high risk of catching the disease.

Serhiy Butenko died from complications of measles, despite being vaccinated, because his immune system was compromised.

You’ve probably never heard of Serhiy Butenko, but his case illustrates this perfectly. Ukraine has a serious measles problem due to poor uptake of the vaccine; in 2018, there were approximately 54,000 cases. Serhiy Butenko was an 18-year-old medical student in Ukraine who had been vaccinated against measles as a child. In early 2018, he was recovering from a bad bout of mononucleosis (glandular fever) that had severely depleted his immune system. He was exposed to measles, and because his immune system was suppressed, he became ill despite having been vaccinated. He developed pneumonia, which is a common complication of measles, and in February 2018 he died after several days in intensive care. Serhiy is a good example of someone who would be protected by herd immunity.

So what about COVID-19? At the moment, there is no vaccine, so the only way to develop herd immunity is for the majority of the population to catch it and recover. Which is fine if you are one of the vast majority who would only experience mild illness, but not ideal if you are one of those who is at high risk of more serious illness. I said I wouldn’t comment on the strategy of any specific government with regard to herd immunity, but speaking as one of those at-risk individuals (I have asthma), I am not entirely convinced by this thinking. Still, I will wait to pass judgement until the scientific evidence supporting this strategy has been released, and I can evaluate it for myself.

How do scientists study new viruses? Epidemiology

If there is anything to be thankful for about the COVID-19 outbreak, it’s that it is happening at a time when scientists have more tools than ever available to study new diseases. Doctors and scientists studying the virus have already made discoveries that even as recently as 15 – 20 years ago would probably have taken several years. Chloe, who is 9, has asked me to explain how scientists study new viruses. Four of the most important methods are epidemiology, genome sequencing, microscopy and crystallography, and in this post I will explain about epidemiology.

Victorian cartoon showing the conditions in big cities that allowed cholera to spread.

Epidemiology is the science of how a disease spreads. It may not sound that interesting but it’s one of the oldest methods of studying disease. The science of epidemiology started in 1854, and was the result of an outbreak of cholera. Cholera is an infection of the intestines that is caused by bacteria. It causes severe diarhea and vomiting, and left untreated it frequently results in death. Cholera bacteria are spread when faeces (as in poo) from infected people get into a water supply, and other people drink the water.

John Snow, the doctor who investigated how cholera spreads.

In the 1850s, cholera was a major problem in big cities because of overcrowding and poor living conditions. Poor people were crowded together in slums and did not have clean water or proper sewage systems – ideal conditions for cholera to spread. In 1854 there was a large outbreak of cholera in London, and it was centred on Broad Street in Soho, and the surrounding areas. A doctor named John Snow used a map to mark where cases were located, and noticed that they were all occurring in houses that used the same water pump, located in Broad Street. John Snow realised that cholera was being spread by water from the pump, and had the handle removed.

Dr John Snow’s map of the 1854 cholera outbreak. Houses were there was cholera are shown in black, and the Broad Street pump is circled in red.

The Broad Street pump, with the handle removed. It’s actually a replica.

Snow’s investigations did not stop there. He started looking at cholera cases for the whole of London, and realised that the majority were occuring in areas supplied by two water companies, both taking their water from the River Thames and supplying it to households without any attempt to clean it. Parts of London that were supplied by companies that got their water from clean sources, and filtered it before supplying it to households, had far fewer cases of cholera.

In 1858, engineer Joseph Bazalgette began work on a system of sewers and pumping stations to prevent sewage from running through the streets or being dumped in cesspools underneath houses. As a result, cholera was completely eliminated from London’s water system. The spread of other diseases such as thyphus and thyphoid decreased dramatically.

So, how will will scientists be using epidemiology to study COVID-19? In the first few days and weeks after the virus appeared, scientists in China used epidemiology to investigate whether the victims had anything in common. Just as John Snow was able to link the 1854 cholera outbreak to the Broad Street pump, Chinese epidemiologists were able to link COVID-19 to a livestock market in Wuhan. This led them to realise that the virus had originated in animals sold at the market, which is really important information for other scientists studying it.

Map showing cases of COVID-19 in China and surrounding countries on January 23rd 2020

Once the virus started spreading more widely, epidemiologists will be looking at where the virus appears and how quickly it spreads. Epidemiologists working for organisations like the World Health Organisation (WHO) are constantly monitoring the spread of the virus. This provides important information about how the virus is spreading. It also allows scientists to evaluate how well measures to prevent or slow down the spread are working; they can then use this information to advise governments on what they should do to try and slow down the spread of the virus in their own country.

I hope this has been useful. If you want to see the latest map from the WHO, you can find it by following this link:

https://bit.ly/2TMWEn4