Viruses are boring! I mean, what’s the point to viruses? All they do is make us sick, right? You just have to look at the past year to know that, and you can’t turn on the TV without seeing some product that “kills all known germs… including the coronavirus… dead!” Shouldn’t we be trying to eliminate all viruses, wouldn’t the World be better if there were no viruses?
 
But some say not all viruses are bad for us!? More importantly, some say there would be no humans if there were no viruses!! How stupid is that?!
 
Well to look at this question, let’s first consider what we are, mammals.

​What is a mammal?
According to the Oxford dictionary a mammal is “any animal that gives birth to live young, not eggs, and feeds its young on milk”. The first important part of the definition is the feeding with milk which is from a mammary gland or breast and hence where the name mammal comes from (“mamma” means breast).
 
Another important part of being a mammal is that the young are born alive and not in eggs. When you think about it this is truly remarkable. Half of the foetal genetics are from the father so as far as the mother’s immune system is concerned this foetus is a foreign object. So why is the foetus allowed to grow inside a mother and thrive? After all, if you took any other organ from a father and implanted it in the mother it would be rejected within a few days! Hence the need for a cocktail of anti-rejection drugs after transplant surgery.
 
Hold on! This is supposed to be a micro-biology blog not a macro-biology blog. Bear with me, I’m getting there.
 
Okay, here we go…
 
The organ that allows the foetus to survive is the placenta [yes, yes we all know this!!!, ECIC]; it’s where the foetus gets oxygen, nutrition and also where waste products are removed. And it exists because of microbiology… or more specifically, virology! WHAT, I hear you cry!!
 
Evolution of the placenta
About 400 million years ago placentas started to appear in fish. Although fish placentas are still relatively uncommon, and most fish still lay eggs, some fish do have a placenta and give birth to live young e.g. blue sharks, rose fish and red banded rockfish (they’re still not mammals though as they don’t feed their young with milk!). Other animals keep their eggs internally until the young hatch e.g. adders, insects and other types of sharks; they do not have a placenta even though they appear to give birth to live young.
 
About 130 million or so years ago mammals developed placentas and started to give birth to live young, but this required a major change in reproductive physiology in order to lead to the formation of the placenta.
 
The placenta evolved due to the action of retroviruses that changed the genetic makeup of cells in early pregnancy back 130 million years ago (and probably ever since!)

Retroviruses
Retroviruses are RNA viruses that convert to DNA inside infected cells which is then incorporated into the cell’s chromosome. If that cell is a germ cell, an early foetal cell giving rise to all of the future baby’s cells, then the retroviral DNA becomes a permanent part of that baby; natural genetic manipulation if you like.
 
The best-known retrovirus is Human Immunodeficiency Virus (HIV) which causes the clinical condition Acquired Immune Deficiency Syndrome (AIDS). But it turns out not all retroviruses are bad.
 
The most important aspect of placental evolution is the ability to produce a protein called “syncytin”. Syncytin is a viral protein that is used by mammals to help form a layer of the placenta called the “syncytiotrophoblast”. The syncytiotrophoblast is the layer of the placenta that invades the uterine wall fixing the placenta in place and allowing the transfer of nutrients and waste across the placental surface. It is also the only part of the placenta that is NOT recognised as abnormal by the mother’s immune system.
 
The gene that now exists in human cells and is responsible for the ability to produce syncytin originated from the envelope gene of Human Endogenous defective RetroVirus known as HERV-W.
 
Over time the placenta has been “improved” by further retroviral “infection” and incorporation of more effective and efficient viral versions, and no doubt it will be further improved in the future. The evidence that the placenta can be improved by further infections does make me wonder if the opposite can happen, and that perhaps infection with a less effective or outright damaging retrovirus could be the reason for some early foetal losses… I’m not sure if anyone has ever looked at that?
 
What about other animals?
Now we all know that lizards are reptiles, right? [Here he goes again with weird facts, ECIC!!] But what about a reptile with a placenta? About 25 million years ago a reptile called the Mabuya lizard, from the Caribbean, evolved a placenta and now gives birth to live young. Wow! I never knew there were so many “non-mammals” which gave birth to live young.
 
Are retroviruses involved in other body organs?
It turns out that retroviruses are involved in the evolution of other body organs as well. In particular the brains of land animals appear to be affected by a retroviral gene known as “Arc” which has led to more effective and efficient neuronal signalling as well as plasticity (where the brain tissue can adapt to change).
 
In fact it is now estimated that 8% of the human genome is actually made up of retroviral genes… that means we are at least 8% viral! However, a lot of that genetic material is actually redundant or “fossilised” having no “apparent purpose” anymore, but these fragments may have been important in the past and then been replaced by new improved “features”, who knows?
 
It does make me wonder if apparent jumps in evolution are more than just natural selection? My understanding has been that if a single member of a species has a particular trait that gives it a survival advantage then it is more likely to reproduce and therefore it’s characteristic will be increasingly represented within future generations. This is the basis to Darwin’s work on evolution, but apparently Darwin didn't know about viruses. However, mutations in genes occurring at random are usually small and slow to occur, and therefore would be unlikely to give much of an advantage or “quick change”. A retrovirus incorporating a lot of new genes though could cause a big shift in genetic make up of an organism which in turn could give a more significant “jump” in evolution and a major selective advantage… Wow, that makes my brain hurt!
 
Golly. Time to go and lie down somewhere quiet and let my brain recover… maybe there’s a virus that can help with that….
 
References

• Viruses and the placenta: the essential virus first view
• Identification of an ancient endogenous retrovirus, predating the divergence of placental mammals
• The placenta goes viral: Retroviruses control gene expression in pregnancy

P.S. Who thought of looking for a virus that "created" the placenta anyway, and how do these researchers get funding for that!?!

One thing lockdown has taught me is that being outdoors in whatever weather the UK can throw at me is something to be embraced as much as possible. I’ve been fortunate. By being a healthcare worker, I’ve been able to leave the house and get a change of scenery even if it’s just a hospital building. On top of that the ECIC and I have a nice garden we can use at home to relax in the fresh air (sometimes more fresh than is comfortable!).
 
The ECIC and I are now even more lucky. We have recently been able to buy a bit of land to turn into our own little growing space for fruit and vegetables… okay, this may not be your idea of fun, but we like it…. Whilst we’re busy digging out the brambles and nettles we have been chewing over ideas about how to look after our crops, and one of our problems to solve is water.
 
The land we have has no mains water. We can collect a lot of water from the roof of our shed and greenhouses (planning permission pending!), but if we need more then we’ll have to look somewhere else. One option is the small stream nearby, so we wandered over to have a look at what it’s like… and it’s ORANGE!

The patient was in his 50s and had been previously fit and well, but had become unwell a few months earlier after working in his garden on a hot sunny day. After putting his shirt back on and coming inside his arm had started to itch. This had rapidly spread to his chest and then all over his body. It felt to the patient like he had insects crawling under and over his skin. Nothing helped. He bathed, got changed, took an antihistamine, all to no avail.
 
The following morning, after a terrible night’s sleep, the patient was covered in a scab like rash and the itching continued. He saw his GP who thought this was a probable contact dermatitis and gave advice accordingly.
 
Over the next couple of months things went from bad to worse. The itching continued, he couldn’t sleep, the rash and scabs spread, and he became convinced he was infested with bugs. In fact, the patient was able to squeeze “bug stuff” out of the scabs for his GP to see! The GP took skin samples and sent them off to the microbiology lab, but no parasites were seen and nothing infectious grew.

What is long Covid?
It might surprise you to know that there is still no formal definition of long Covid, even though the term has been used a lot in both the media and scientific literature over the past 6 months or more. Long Covid is the term commonly used to describe the persistence of symptoms in a person who has had Covid-19 infection and “should have got better”, but in whom symptoms persist. However, there is no consensus on what these symptoms are or how long they must be present before they constitute long Covid. Channel 4’s Dispatches, aired on 16th March, reported from Bradford one of the country’s worst hit Covid-19 regions and gave a glimpse into the lives of some people suffering the after effects of Covid-19.  
 
In the National Institute for Health and Care Excellence (NICE) guideline for managing the long-term effects of Covid-19 they refer to long Covid as “the persistence of symptoms or signs of Covid-19 more than 4 weeks after the initial illness”, with the caveat that there isn’t another explanation for the patients symptoms or signs. However other groups, such as the Office for National Statistics (ONS) use 5 weeks as the lower limit of time.
 
Well, we can’t agree on a time scale, surely we can agree what the symptoms are… can’t we?

Looking back, the 15th July 2013 was an auspicious date. The Black Lives Matter movement was created in response to the acquittal of George Zimmerman on trial for the murder of Trayvon Martin, Edward Snowden who leaked US Government secrets to the media asked Russia for asylum and China unveiled the World’s largest building which is apparently the size of Monaco. Against this background there was another event which, whilst considerably smaller in World affairs, was far more momentous for Nuts & Bolts… we published our first Bug Blog entitled “The perils of pastimes” which related the tale of someone who developed leptospirosis after jumping in the River Thames!
 
Now, nearly 8 years later we have reached another momentous event in the history of Nuts & Bolts… it’s our 300th Bug Blog! But what do you write about for a 300th blog, I hear you cry? I had the same reaction!

The patient was in her 20s and presented to her GP complaining of vague abdominal pain and weight loss. She had been “surfing the net” and was worried she might have caught Bilharzia when travelling in Africa as a student 6 years before. The Doctors mind flashed back to his own medical student elective in Malawi where he remembered being told something about Bilharzia affecting the bladder of those who, like him, went swimming in the shallows of the lake. He shuffled uncomfortably but tried to reassure her it was unlikely; she was adamant that she ought to be tested.
 
The Doctor phoned the duty Microbiologist to chat things through and the Microbiologist explained that “Bilharzia” not only affects the bladder but some species can cause intestinal infection too, so it was a possibility. They agreed that the Doctor would arrange for a number of stool samples to be sent to the microbiology laboratory as well as a blood test to look for infection. The Doctor wasn’t convinced but the patient was happy for the thoroughness of the investigation.

​What is Bilharzia?
Bilharzia is the common name for schistosomiasis, no not a new dog breed (clearly I’ve been watching too much of the BBC’s series “Pooch Perfect!”), but a parasitic infection caused by flukes that infect blood vessels. Bilharzia is named after Theodor Bilharz, a German doctor who first identified the parasitic cause way back in 1852 but who unfortunately later died, at the age of only 37, from complications of another waterborne-illness, typhoid, caught in Egypt!
 
There are five main species of Schistosome that infect humans in different areas of the World, although the first 3 are the more common:

• Schistosoma haematobium – Africa and the Middle East
• Schistosoma mansoni – Africa and South America
• Schistosoma japonicum – East Asia
• Schistosoma intercalatum – West and Central Africa
• Schistosoma mekongi – Cambodia and Laos

 
Schistosomiasis is more common in rural areas than in urban centres because the life cycle of the parasite requires fresh water snails and these are much less likely to be found in towns and cities. Risk of infection is higher in lakes, rivers and estuaries rather than open water as the snails live on grasses and reads at the banks of the water sources.
 
Schistosomiasis is endemic in many countries but few within these populations have a high enough burden of parasites to be symptomatic or turn into “patients”. In the UK most cases of schistosomiasis are associated with travel to endemic countries, especially Africa.
 
The life cycle of Schistosoma spp.
Each of the Schistosoma spp. has a specific snail species which they require for their life cycle to be completed:

• S. mansoni – Biomphalaria spp.
• S. haematobium and S. intercalatum – Bulinus spp.
• S. japonicum – Oncomelania spp.
• S. mekongi – Tricula spp.

 
The life cycle:
Parasite eggs are excreted into freshwater from the infected faeces of a human (or animal). These eggs hatch and the microscopic larvae penetrate into the freshwater snails where they undergo further maturation before being released back into the water 4-6 weeks later as infectious cercariae; they remain infectious for up to 2 days but they are more infectious when just released. The cercariae then penetrate through the skin, especially if it is waterlogged like “pruned feet in the bath”, of another unsuspecting human (or animal) where it migrates, via the bloodstream, to the liver. Here they mature into adults over the next 2-4 weeks. The adults then swim against the blood flow to reach the blood vessels supplying the intestines or bladder depending on the species of parasite. In the blood vessels male and female worms mate followed by the female producing eggs which penetrate out into the intestine or bladder and the cycle repeats itself. The adult female, is bigger than the male, at around 7-20 mm long… Yep that’s up to 2cm long… its huge… so yes, you would be able to see it without a microscope! Added to this horror, adult worms usually live for 5-7 years but have been known to survive for 30 years or more!

​How does schistosomiasis present?
S. haematobium primarily infects blood vessels supplying the bladder whereas the other Schistosoma spp. infect blood vessels supplying the bowel. Symptoms are therefore related to where the infection is happening in the body. Most infections are asymptomatic, especially in people from endemic countries who have developed immunity to the parasite and therefore do not get the hypersensitivity reactions which are characteristic of this infection.
 
The initial infection in schistosomiasis is known as “swimmer’s itch” because when the parasite penetrates through the swimmers skin it can cause a dermatitis reaction; this localised immune reaction only occurs with repeat exposure as it requires priming however you can still develop the later signs of infection without having had “swimmers itch”.
 
Katayama fever is the name given to the later acute hypersensitivity reaction to schistosomiasis occurring 3-8 weeks after the initial infection. It is caused by an immune response to the parasites within the blood stream. The symptoms of Katayama fever include sudden onset of fever, urticaria and angioedema, chills, myalgias, arthralgia, cough, diarrhoea, abdominal pain, and headache.
 
The most significant consequences of schistosomiasis are from chronic infections and are worse with high numbers of locally trapped eggs, longer duration of symptoms and a strong immune response:

• Intestinal – weight loss, iron deficiency anaemia, colonic ulceration, polyps and dysplasia (early cancer) and occasionally strictures and bowel obstruction
• Hepatosplenic – occlusion of portal veins causes portal hypertension and splenomegaly followed by the development of gastrointestinal varices and the possibility of variceal bleeding
• Pulmonary – occurs especially with hepatosplenic chronic infection where eggs bypass the liver to embolise the lungs causing pulmonary hypertension and cor pulmonale (heart failure due to pulmonary hypertension)
• Genitourinary – bladder fibrosis and calcification leading to urethral strictures, obstruction and renal failure as well as bladder cancer
• Neurological – worms can occasionally enter blood vessels to the spinal cord and brain causing nerve damage, cerebral lesions and encephalopathy

 
How is schistosomiasis diagnosed?
A clinical history suggesting possible exposure is the key to diagnosis in non-endemic countries like the UK. Patients with bladder schistosomiasis may have terminal haematuria (bleeding at the end of passing urine… this is not life-threatening bleeding as its name might suggest!)
 
The two main methods for diagnosing schistosomiasis are serology and microscopy.
 
Serology tests detect either antibodies or antigens. The antibody test is useful in returned travellers and becomes positive 6-12 weeks after infection however it doesn’t distinguish between past or current infection and so is of little use in patients from endemic countries. The antigen tests are of more use in that they detect active infection and can be additionally helpful as they become negative again 5-10 days after successful treatment. 
 
Microscopy can be performed on urine or stool depending on the species of interest. Each type of Schistosome spp. has a characteristic appearance, usually dependent on size, shape and the location of the operculum (the little pointy bit that sticks out from the egg and makes it look like a “speech bubble”).

​In the UK a combination of microscopy, antibody and antigen tests are recommended:

​Patients with schistosomiasis often also have a raised eosinophil count in peripheral blood and patchy shadowing on a chest x-ray - if they have respiratory symptoms. These should both resolve following correct treatment.
 
How is schistosomiasis treated?
The mainstay of treatment of schistosomiasis is the drug Praziquantel. Praziquantel works by damaging the surface of the worm as well as causing it to become paralysed. Praziquantel is not active against larvae so the infection has to have been present for at least 4-6 weeks before it will be effective. NB The damage to the surface of the worm can cause more antigens to leak out and worsen the hypersensitivity reaction so in acute infection it is essential to give steroids prior to Praziquantel to first dampen down this reaction.
 
Chronic schistosomiasis is treated with Praziquantel without steroids. The dose is dependent on the species:

​Patients should have follow up microscopy and antigen tests to look for cure as well as repeat blood eosinophil counts.
 
Attempts to prevent schistosomiasis are undertaken in endemic countries by trying to ensure clean water supplies, safe disposal of faeces and regular mass treatment of the population to reduce the amount of environmental contamination.
 
So our patient’s blood tests confirmed that she did indeed have active schistosomiasis and the laboratory where able to identify S. mansoni. She was treated with Praziquantel and her symptoms settled over the next few weeks. Her repeat tests all showed successful treatment and everyone was pleased; the patient was better, the Microbiologist had a good story for his next teaching session and the Doctor, although he had considered doing an antigen test on himself too, decided he’d just jot it down as a great case for his CPD portfolio… 

A couple of weeks ago the news was full of another game-changer treatment for Covid-19, a drug with the almost unpronounceable name of Tocilizumab. But then we heard very little about it, but was this because nobody could say its name or was it perhaps not as exciting as first appeared!?

Last night I got told off for grumbling at the TV; I think this was a little unfair as I thought I had good reason to grumble. The news was all about coming out of lockdown… again! So why was I grumbling? Surely, I’m as fed up as everyone for not being able to go out and do the things I normally do? The lockdown has worked, case numbers are falling. So, what is my problem with coming out of lockdown?

This week marks one year since the World woke up to the fact that we were on the brink of a global pandemic due to a novel coronavirus coming out of China. The media were full of questions, where did it come from, how does it spread, is everyone going to get sick and die? All very good questions to which we now know a lot of the answers; probably bats, large droplets, some of those with risk factors e.g. old age, obesity, hypertension etc. and yes it is a global disaster with 99.8 million cases and 2.14 million deaths worldwide; the USA being hardest hit, 25.3 million cases and 421,000 deaths, over 6 times the number of cases and 4 times as many deaths compared to the UK 3.67 million cases and 98,530 deaths… UK deaths are over 100,000 now (how quickly my blogs date!)

​The scientific press had other questions as well, and one of the most important was “will this virus cause repeat infections?” They were looking at this from the perspective of immunity. Experience from previous novel coronavirus infections such as the original SARS and MERS suggested that antibody levels waned over time, and it was known that at least 4 species of coronavirus regularly circulated within the human population causing “the common cold”. So, the worry is that people can get coronaviruses more than once… a scary prospect.
 
A recent report from Public Health England’s SARS-CoV2 Immunity and Reinfection Evaluation (SIREN) Study has shown that a small number of people have already had Covid-19 twice (44 out of 6,614 people), and their conclusion has been that immunity following infection only provides up to 5 months protection in 83% of people; but that it is not known how long this protection will last after this. They also noted that past infection doesn’t prevent carriage of the virus and therefore further spread of SARS CoV2 is possible.
 
This is disappointing but it does prove two things:

• You must continue to follow infection control precautions even if you have previously been infected; to protect yourself and others
• Natural infection will not provide sufficient herd immunity to protect the population

 
WHOA!!! What about the vaccine? Well that “should be different” and hopefully this will give sustained immunity, but there is no long-term data to back this up… REMEMBER Pfizer were first with a vaccine and their next data point in their “ongoing clinical trial” is February 2021.
 
So why is this happening? Why do people get the infection twice? What might this mean for both natural and vaccine induced immunity and the future of the pandemic? Is there another possible explanation for this phenomenon other than waning immunity? Wouldn’t it be concerning if coronaviruses can evolve to overcome immunity?!? NO! STOP IT!!!
 
We know that all RNA viruses mutate over time, in fact it is the basis of Darwin’s natural selection whereby new traits that provide a “selective advantage” will continue in a population. Some viruses like Influenza Virus do this all the time in a process called “antigenic drift” where they slowly evolve over time to escape immunity; this is why we need new flu vaccines every year. On the other hand, some viruses don’t evolve much at all e.g. Measles Virus, where any mutation that affects immunity tends to be terminal for the Measles Virus itself; this is the reason the measles vaccine is very effective at giving long-term immunity.
 
But what about SARS CoV2? Mutation does occur but fortunately it appears to happen slowly, much slower than for most RNA viruses, because SARS CoV2 has an effective RNA polymerase that corrects errors. As a result, it is thought that the SARS CoV2 genome of 30,000 bases only changes by about 20 bases a year…
 
But we know it does change because we are seeing new variants in the UK, South Africa and Brazil, which have changed “enough” to start causing concerns about spread and immunity. How likely are these new variants to matter? That’s the question a group from Seattle, USA, have been investigating… and the answer is a bit scary!
 
A scary research paper from Seattle
I think this study from Seattle published at the end of last year is one of the best and most important pieces of research about coronaviruses I have read; and the results have implications for the current Covid-19 pandemic. When you think about it even the title sounds scary – a human coronavirus evolves antigenically to escape antibody immunity. Aren’t they cheery souls!
 
The researchers looked at one of the common cold coronaviruses known as 229E (isn’t that a new Star Wars droid, like R2D2?)… 229E is like the SARS CoV2 virus. It is known to circulate all the time within the human population. So they decided to extrapolate their “known” results to the current pandemic. So, what did they do?
 
They started by collecting 229E spike protein sequences from genetic databases and then genetically modified lentiviruses which they could study in a lab to express the spike proteins… rather than making a “new coronavirus” which has the potential to cause another pandemic!!! (Don’t get me started on the China bashing laboratory released conspiracy theorists! Just phooey). This would then allow them to test whether antibodies could neutralise the new lentiviruses by the antibody’s ability to bind to the artificially created spike protein. They chose spike protein sequences and created artificial viruses that represented 229E when it was circulating in 1984, 1992, 2001, 2008 and 2016.
 
Next the researchers collected serum samples from a “serum bank” and screened them for antibodies against the spike protein that occurred most recently BEFORE the serum was collected. For example, a serum from 1985 would be tested against the virus from 1984, serum from 1998 would be tested against the virus from 1992, etc. They also collected sera from children born after 2016.
 
The clever bit of the study is when they tested all of the sera they had collected against all of the viruses from the different years. The idea was to see if old sera contained antibodies capable of neutralising FUTURE viruses that hadn’t evolved yet. If sera from the past were capable of neutralising virus from the future then the virus wasn’t evolving it’s spike protein to escape the immunity; if sera from the past couldn’t neutralise the virus from the future then the virus had evolved it’s spike protein to escape immunity… simple and brilliant!
 
What did they find?
This is the scary bit. The results of the study were clear; antibody in serum was capable of neutralising ALL of the viruses that had come before but most could NOT neutralise those that came after the serum had been collected. Think of it as your Microsoft Word doc; you can open “.doc” files on the old word 97 software but not the new 2007 XML-based file format “.docx”, but new versions of the software can open both file types. They found that their “229E coronavirus” mutates its spike protein over time in a way that overcomes previous immunity. In other words, the virus is capable of evolving itself to cause repeat infections. This may be why the same 4 types of coronavirus continue to cause common colds.
 
This is scary because the implication is that SARS CoV2 can do the same; it can evolve to escape immune recognition by antibodies against the spike protein making long-term immunity less effective whether it is naturally acquired, or vaccine induced. This would mean that whatever we do SARS CoV2 isn’t going to go away! ARGH!!
 
BUT before you run off screaming there are 2 really important factors that mean this may not be as bad as it first appears!
 
Firstly, the study didn’t account for the evolution of the immune response over time, just the evolution of the virus. It is very likely that continued and repeat exposure to “229E coronavirus” every year will ALSO cause the immune system to evolve in response to small mutations in the spike protein over the same time. Even though the antibodies against the spike protein may not be perfect, they are likely to be “good enough” to prevent severe disease. This would explain why 229E just causes the “common cold” rather than debilitating us all with a severe respiratory infection. It is expected that the same will eventually happen with SARS CoV2 once enough of us have been infected or vaccinated. The continued adaptation of our immune systems after the initial insult will protect us from getting really sick in the future.

Secondly, even if our immune systems don’t adapt fast enough to the changing spike protein, the new ways of producing vaccines make them adaptable and as they have already been “approved in principle” it is easier to modify current vaccines against future variants of SARS CoV2 and this could be produced at very short notice e.g. Pfizer say they can change their Covid-19 vaccine within 6 weeks!
 
So, there it is. It turns out that other coronaviruses do show “antigenic drift” and evolve to escape immunity over time, much like influenza viruses, and this is probably likely to occur in SARS CoV2. BUT what always accompanies “antigenic drift” in all good microbiology textbooks? “Antigenic shift”!!! Influenza Virus uses both shift and drift; antigenic shift is the way that it genetically recombines to create new viruses and why we have always been worried about flu pandemics occurring. I suspect this is one of the main reasons that the WHO are in China looking for the source of SARS CoV2; they want to be sure it hasn’t “antigenically shifted” e.g. a bat coronavirus and a different pig coronavirus have recombined to create a novel coronavirus, neither bat nor pig but human! Just targeted at us!
 
So far there is no evidence that coronaviruses are able to “antigenically shift” and produce an entirely new virus… at least so far… don’t have nightmares…!