Gosh, deciding what to blog about this week has been hard; ECIC has given me a whole list! I don’t know about you but I’m starting to feel a little overwhelmed with the amount of Covid-19 we are seeing in the UK. I thought it would help me to just sit back and try and take stock of where we are up to and what it all means… maybe it will help you too…. I’ll tackle ECIC’s list another time…

​The new variant
So, many countries are calling this the “UK variant”, and it is often the way that a new pathogen is named after the place it was first detected. Remember back in January when we were calling SARS CoV2 the “Wuhan Virus”? At the moment there isn’t any hard evidence to suggest that the UK variant definitely did originate in the UK but it is possible. What we can say is that the UK has probably the best systems in the World in place to spot this type of problem and identify the cause, especially in terms of genomic analysis. Often those that look for things find things, those that don’t say they haven’t got it!
 
Having warned the rest of the World that this new variant existed, and having everyone shut their doors to us, it turns out that so far 45 other countries already have this new variant. In the US there have been cases in Colorado in people who have not travelled outside of Colorado and who have no contact with any known cases, as well as other cases, all unrelated, in the states of California, Florida, Pennsylvania, New York and Georgia.

​After further work in the UK it appears the new variant was already circulating back in September, but it didn’t take off until December. This new variant is meant to be “more transmissible” but as there is little evidence for these claims I feel there are also other less “great sound bite” factors in play e.g. lack of cooperation with restrictions or environmental factors.
 
I suspect the spread of the new variant probably has more to do with “non-genetic” factors such as it originally arising or being introduced into a population that had inadequate restrictions in place to prevent spread. I think if we hadn’t responded so effectively in the first wave, we might have seen the same potential for “exponential transmission”, but in the first wave we got the R0 down, everyone then was talking about R0. If you remember the “second wave” coincided with  the discovery of the “new variant” which started in the South East which was in Tier 2… and from my experience when we were in Tier 2 the local restrictions were not really being applied, in fact there wasn’t actually much “restricting” at all; the local area was as busy as normal! On top of that we came into winter when viruses transmit more effectively due to indoor crowding and decreased humidity facilitating greater droplet transmission. Think back to the summer when all the experts where saying they were worried about going from autumn into winter… they were right, everything did go wrong, it’s no surprise really!
 
So, case numbers have exploded and we’re now back in a National lockdown.
 
National lockdown and social restrictions
The Government have been talking about having to possibly impose even tighter restrictions on the UK population to get the massive surge of Covid-19 cases under control. It’s hard to see how much tighter they can be? Stay at home, schools closed to all bar essential worker’s children and only essential shops to open! But IS this really what is happening? Do we need tighter restrictions or is better compliance required?
 
I live on a road that should be pretty quiet, it doesn’t really go anywhere except to some open moorlands and woods (lovely I know!) and yet it is just as busy as before anyone had even heard of a coronavirus. There are lots of images from over the weekend of people mixing in parks, playing team sports and generally ignoring the current lockdown rules to “stay at home”.
 
Let’s turn this around and think of this a bit like herd immunity… stick with me! Herd immunity suggests that if enough of a population is immune to a disease then the disease cannot circulate; in the case of a lockdown if enough people stay at home they are not circulating and it therefore stops the virus circulating. If enough of the population do this, then the virus can’t spread from one family or individual to another, providing protection or “herd protection”. We can’t have the situation where everyone stays at home because “keyworkers” have to work (they are key after all), however if enough of the rest of the population do stay at home (and I mean in the home) then viral transmission will be interrupted, and case numbers will go down.
 
At the moment we just don’t have enough people following the stay at home rule and so case numbers are likely to continue to rise.
 
I wonder if this may be because of the over emphasis of the “good news story” vaccine message delivered in December by the Government and media channels. Just look at the holiday booking bonanza announced today, holiday bookings soar from the over 50s… “I’ve had my vaccine, now where’s my passport”, come on guys… really… your priority is a week in Spain!? Those working in the NHS would just like to be able to TAKE any of their annual leave!!! ALL our annual leave is cancelled; we can’t even have a week off to stay at home!!!
 
The vaccines
Whilst I do agree that a successful vaccine is the way out of this Covid-19 mess I do wonder if putting such a positive spin on the story back in December has led to a high degree of complacency in the population. I regularly overhear conversations which go along the lines of “I’m not worried about Covid-19 anymore because we have a vaccine now”. NOOOOOOOOOO…….!
 
Eventually we will have enough people vaccinated to limit the spread of Covid-19 BUT we are nowhere near that level yet. According to the Government nearly 1.5 million people have been vaccinated in the UK, that’s only about 2% of the population. You only have to look at the daily figures for new cases to realise that this has made ABSOLUTELY NO DIFFERENCE to the rate of transmission of SARS CoV2 yet. Remember a previous blog saying that to get immunity you need around 90% of the population vaccinated, that means 60 million people in the UK need to be vaccinated!
 
So, yes we have vaccines, and yes they are being given to people, but nowhere near enough to prevent transmission of SARS CoV2 and nowhere near enough to prevent anyone getting infected. The answer to preventing transmission (whether it is highly transmissible or just transmissible) is to comply with infection control precautions and stay away from other people. I heard a great quote that “the most effective thing to stop transmission is your front door”; basically STAY AT HOME. The other message we hear a lot of is “otherwise the NHS will be overwhelmed”… NEWS FLASH “the NHS is already overwhelmed” but we are not allowed to say this officially because it would cause pandemonium and there would be no toilet rolls on the shelves again! Just look at the USA, they are now triaging patients for “access into A&E” and who they’ll save the oxygen for! This is happening, this is real.
 
Hospital occupancy
The NHS is taking a hammering from Covid-19! Case numbers are a lot more than during the earlier peak in April 2020. The graph shows cases in hospital up until 4th January (the latest figures on the Department of Health website) when they were lower than they are now… now we have 50% more hospitalised patients with Covid-19 than in April 2020.

​It’s not just overall numbers that are the problem. Staff are tired… REALLY tired. Not just physically but mentally as well. Normally people come into hospital and we make them better, sometimes that doesn’t happen but in general we “win”, they come in sick, we look after them and get to know them and then they go home better and we get a box of chocolates (if we are lucky) that gives everyone a feel good factor for the job. Consider now, they come in sick, we look after them and get to know them and then they get worse, and we see their fright and pain, some don’t make it! There is very little “feel good factor” especially as their bed is quickly filled with the same scenario. I do wonder how many of us are going to burnout as a result of the Covid-19 pandemic; I think it will be a lot. There was a study published just recently that found “45% met the threshold for probable clinical significance on at least one of the following measures: severe depression (6%), PTSD (40%), severe anxiety (11%) or problem drinking (7%), and 13% reported frequent thoughts of being better off dead, or of hurting themselves in the past 2 weeks”.  Yet in the same study over half (59%) reported “good well-being”, so surely we are actually just “deceiving” ourselves? Almost half of ITU staff are struggling to cope mentally and physically. I suspect many are holding on whilst the pandemic lasts so they don’t let their friends and colleagues down, but when cases start to drop how many will say “enough is enough”?
 
Whilst it’s hard to say it, I do wonder how many NHS staff feel let down when they see the pictures of people flaunting the lockdown rules whilst they’re working to the limit trying to treat people in hospital? How many in the NHS feel frustrated at yet more restrictions or cancellations of annual leave, bank holidays, and days off, when they see groups of people mixing and enjoying the nice weather in various parks around the country? OK, I’ll say it, I DO; I resent those people’s behaviour!
 
Oh, stop being so negative, we can now treat Covid-19
Well, in fact we still don’t have any particularly good treatments for Covid-19. The only things that really make much of a difference are steroids and possibly Tocilizumab, and then only in those with the severe inflammatory response and who are otherwise fit enough to survive long enough for the medicine to work. Many frail, and some not-so-frail, patients are still dying from this infection even with these “treatments”; there are about 700 Covid-19 related deaths a day in the UK at the moment (that’s the bed count of a large District General Hospital every day!) This is a bit less than during April, but it is still a lot and worrying when you consider the virus “killed off” many of the most vulnerable in the first wave, these deaths are those that might be considered “less vulnerable”. So we have some treatments but they’re not that good; we have a better option it’s called “prevention” and that is still better than cure.
 
So, we’re in a bit of a mess really. Covid-19 is causing havoc within the population and the NHS and there is so far no evidence that things are getting better. We have to start “flattening the curve” again and in my mind the only way this will happen is if people start to respect this infection again and start complying with the restrictions that prevent its spread.
 
And if all that fails, the NHS will have to rely on giving the “gift” of a cuppa coffee to a struggling colleague and eating chocolates; these seem the only sure way to hold up our struggling optimism… now where is my bag of Minstrels?

So, something happened at the end of last year and you will be forgiven for missing it as there were no fanfares, press releases or overly optimistic news stories… no I’m not going to talk about a “Tier 4 lockdown Christmas” or how we didn’t all “crash and burn” (yet) on the stroke of 11 as we “Brexited”. In fact, it is that Pfizer actually published some vaccine data in the New England Journal of Medicine (NEJM) just before Christmas!
 
So, was this an early Christmas present, an opportunity to hide the data in the Christmas furore or did Brexit just swamp our news channels. Let’s have a look and see….

​Okay, it’s all over the news. The UK has pretty much become a Pariah where the rest of the World is concerned with many countries closing their borders to us because of a new variant of SARS CoV2 causing a lot of infections across London, the East and South East. As if that weren’t enough it’s led to the Government effectively banning Christmas… not that I mind too much as I’m working anyway… but I feel sorry for those who were looking forward to a celebration at the end of such a horrible year!
 
So, what is the new variant and what does it mean for us in the UK?
 
Essentially the new variant of SARS CoV2 has acquired a number of mutations (23 in total!) that make it possible for it to spread more efficiently than the original SARS CoV2 virus that was first identified in China a year ago (yes, it really has only been 1 year since this all began). But it’s not surprising to see mutations in RNA viruses, they are pretty rubbish at maintaining stability in their genomes, and we have already seen this happen this year.

Mink-related mutations
Between June and November a number of European countries experienced outbreaks of Covid-19 with new variants of SARS CoV2 associated with mink farms (see the Microbiology Nuts & Bolts Bug Blog for more details). The Netherlands, Denmark and Sweden all had new variants of the virus which occurred after humans working with mink spread the virus to the mink, the virus mutated in the animals and then transferred back to humans.
 
In Denmark there were 214 human cases associated with the mink variant. You may remember the news story where the Denmark Government wanted to cull the 17 million mink in its farms to control the outbreak… we didn’t close our border to them though… just saying (although hospitals were meant to look out for possible mink-related cases… but none have yet been reported). Don’t forget viruses mutate and migrate this is normal; there is also evidence of a new variant that originated in Spain which was introduced into the UK multiple times due to travel from Spain in the summer, and also a new variant originating in Scotland which is now circulating in Europe! “Many thousands of mutations have already arisen in the SARS-CoV2 genome since the virus emerged in late 2019; …the vast majority of mutations have no apparent effect on the virus” (Covid Genomics UK Consortium)
 
In the Denmark mink farm outbreak there were two main variants of SARS CoV2. The first variant had a mutation that increased the affinity of SARS CoV2 for the host cell’s ACE2 receptor which allows the virus to “enter the cell”. As the ACE2 receptor in mink is slightly different to that of human’s, the virus mutated to a new variant that then allowed it to better access into the mink’s cells. It is thought that this mutation lead to increased ability for SARS CoV2 to spread in mink. When this mutated variant transferred back to human’s it was also found to be better able to bind to human ACE2 as well, which potentially made this variant more infectious in humans.
 
The other variant they found in the Denmark mink had 4 mutations. These particular mutations affected the spike protein which helps the virus “bind to host cells”. The new spike protein altered the body’s immune response which may not recognise the new variant as these spike proteins are the main target for both natural and vaccine induced antibodies against SARS CoV2. It was found that in 9 patients who had previously recovered from Covid-19 this variant appeared to make the virus 4 times less susceptible to naturally derived antibodies. There were 12 human cases of this antibody resistant variant identified in people with close contact with mink farming. Fortunately, their disease followed the same course as the original Covid-19 cases, no better no worse.
 
Returning to the UK
The problem in the UK now is that the new variant has acquired a lot of mutations ALL at the same time in the same variant (23 mutations in total). The details are still sketchy but from what I have been able to piece together this is what we have been told so far.
 
It is thought that this new variant may have arisen in someone with impaired immunity who had become chronically infected with SARS CoV2 and who therefore had the virus for a long enough time for multiple mutations to occur before passing it on to someone new.
 
Remember, viruses can only mutate whilst they are reproducing and they can only reproduce inside a host cell not in the environment. In addition, SARS CoV2 mutates very slowly for an RNA virus at about 20 or so mutations per year. So, for SARS CoV2 to mutate 23 times “in one go” it has to have been inside a host cell for a very long time and maybe even up to a year if the normal mutation rate is still correct.
 
The combination of mutations in the new variant is associated with laboratory evidence of:

• Increased affinity for the ACE2 receptor – making it better able to bind to ACE2 which may allow more virus to get into cells to cause an infection and/or may result in needing less virus to cause an infection in the first place as small numbers of virus become more efficient at setting up infections
• Immune evasion – making it less recognisable to pre-existing immune responses such as antibodies and reactive T cells
• False negative laboratory tests – the mutated spike protein is not detected in a few assays that only target the spike protein
• Escape from some monoclonal antibodies – some manufactured monoclonal antibodies that have been trialled in the treatment of Covid-19 do not recognise the new variant spike protein and so do not have any treatment benefit
• Faster growth – the virus appears to replicate faster in cells and therefore could have a shortened incubation period

 
There is increasing evidence that the new variant of SARS CoV2 in the UK does have increased ability to cause infection. A figure of “70% more transmissible” is quoted in the media… but who knows what that really means!? Is it that the infectious dose is 70% less, or does an infected person infect 70% more people or is the incubation period 70% shorter? Added to this, whether the new variant is able to escape the immune response in people who have had the infection before or who have been vaccinated is not yet known. However, reassuringly, most laboratory tests use multiple targets for detecting SARS CoV2, not just the spike protein, so most laboratory tests will still detect the new variant of SARS CoV2 including those used in the Lighthouse Laboratories.
 
At the moment there is a lot we just don’t know about the new variant of SARS CoV2 but there are lot of people looking at what these mutations mean and how they are going to affect the course of the pandemic, clinical disease and the effectiveness of post infection immunity and vaccination. Now I accept that a new mutation may sound alarming, and the media is promoting the story, and France has closed the border (is this a Brexit negotiation strategy?!?!?!) BUT let’s not panic just yet and wait and see where the science takes us… goodness knows we’ve all had enough of “Science by Press Release” this year after all!
 
The most important thing we all need to remember is that the simple things work. It doesn’t matter that the virus has become a bit easier to transmit; we can still stop it transmitting if we do the basics well:

• Strict attention to hand hygiene
• Isolation of patients with suspected or confirmed Covid-19

• Limiting contacts and crowds (no mixing outside of support bubbles)

• Physical (“social”) distancing (2 metres)
• Face masks in indoor spaces

 
Try and have a good Christmas, whatever restrictions you are under, and we’ll see what the New Year brings us….

Okay, so I could be accused of doing a lot of vaccine bashing over the past few weeks. I have been very open with my concerns about how quickly we are rolling out vaccination programs across the World with vaccines that haven’t finished clinical trials and for which there is no published data (I’m looking at you Pfizer!).
 
So, what about vaccines where there is published data? Well so far there is only one vaccine that I am aware of where data has been published in a peer review journal, and that is the Oxford vaccine made by AstraZeneca (based in Cambridge!) in collaboration with Oxford University in the UK (don’t Oxford and Cambridge normally compete in boats against each other?). 

Before I start I’d like to state that I am pro-vaccination and have nothing personal against any drug companies or the Department of Health; but I am deeply concerned about how fast the new Covid-19 vaccination program is being rolled out. I realise there may be some people who will think I'm being irresponsible questioning the vaccination program for Covid-19 but I really am concerned about it. If you want the Covid-19 vaccine or have had it already then that’s okay, please don’t let me cause you to second guess yourselves. This is just my opinion and not that of any organisation I’m otherwise affiliated to, but I have been asked my own opinion many times so here it is.

I actually wrote this blog back on the 7th April 2020 when the Covid-19 pandemic was just starting to hot up but didn’t get around to publishing it as there were other more pressing “All-Things-Covid” to blog about. However, as we come to the end of the year, I thought I’d reflect and have another look at this blog to see if my fears materialised or not…. I’ve kept the original text and added “December 2020 notes” after as to what I think now.

Earlier this year we all went into lockdown… remember? Not like the current lockdown where most people seem to be carrying on regardless, I mean when the streets were eerily quiet, and our capital cities looked like a set from a post-apocalyptic movie.
 
During this time, I remember seeing news stories about the positive impact of the Covid-19 pandemic on the environment as everyone moved indoors, cars stayed off the roads and heavy industry shut down. There were striking pictures of Nitric Oxide levels over China showing a massive reduction in the production of greenhouse gases. It seemed that something good may come out of the pandemic, almost as if the Earth was pressing the reset button and taking back control.

They look so cute and cuddly! I’m not talking about the Giant Microbes SARS CoV2 toys (gosh they do make great bugs, don’t they?!). No, I’m talking about mink! Well I like them…But personally, I think mink coats look better on mink!
 
Maybe Covid-19 is going to finally put an end to the production of fur coats… I can but hope. What am I talking about? This is a microbiology blog, not a rant against animal fur in fashion… or is it?
 
So last week, before all the vaccine shenanigans (Congrats to Oxford; at least their vaccine interim results are published in the Lancet not just the BBC!), I was going to write a blog about Covid-19 and mink. So, what was this all about?
 
Last week it was reported that there was a new strain of SARS CoV2 which had transferred from mink into humans, and that there was no protection even if you had had Covid-19. The way it was reported would have us all believing that another new pandemic was about to start….

“Today is a great day for science and humanity. The first set of results from our Phase 3 COVID-19 vaccine trial provides the initial evidence of our vaccine’s ability to prevent COVID-19,” said Dr. Albert Bourla, Pfizer Chairman and CEO on 09/11/2020. “We are reaching this critical milestone in our vaccine development program at a time when the world needs it most with infection rates setting new records, hospitals nearing over-capacity and economies struggling to reopen. With today’s news, we are a significant step closer to providing people around the world with a much-needed breakthrough to help bring an end to this global health crisis.”
 
Or perhaps in other words “the end of the pandemic is nigh!”

We’re all waiting for a vaccine against SARS Cov2, right? Once we have a vaccine, we can all get back to normal and 2020 will be a period of time that we look back on as a bad time in our lives. Well this is what I hear a lot of people saying… SPOILER ALERT! I think we need a reality check; the new normal is NOT going to look like the old normal.