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What’s the problem with looking on the bright side!? - Coming out of lockdown Part 2

30/4/2020

 
So last week we looked at the question of how we generate enough immunity in the population to reduce the reproductive rate of SARS Cov2 to less than 1 and allow us to come out of lockdown. Whoopee!!! Our conclusion was that we need a safe and effective vaccine and that this will take ages to arrive, probably the end of next year at least, booooo!
 
What!? Am I really saying we need to stay locked up in our houses until Christmas 2021?! We’ll all go mad long before then….
 
OK so we can’t stay locked in our houses until then, but how do we come out of lockdown… the answer is carefully… (that reminds me of a joke, “how do hedgehogs have sex? … Carefully!” ha ha!!)… anyway… there is no rule book for this, no one has done it before, there is no manual that says do this, or do that… it’s a case of trying and seeing what happens… and that’s a bit scary. Especially as the media is likely to pick holes in any attempts as they do like a good melodrama.
How to come out of lockdown - Carefully
So how do you come out of lockdown carefully?
Take it slow. If we rush to get out of lockdown we could well cause a second surge in infections which we won’t notice for 3-4 weeks (remember that’s how long it takes for people to get infected, spread it to others and then get sick enough to end up in hospital or die and “affect” the stats, more on that later!).
 
We need to come out of lockdown in controlled phases, with different age groups or occupations coming out over time. Perhaps schools need to go back by age group with older children going first; they would be a “good/better” indicator group being at low risk of severe infection. This group could be monitored to watch for symptoms and show if something is going wrong. However it’s a little controversial to put children first into harm’s way!?! But…
 
After schools, maybe those who have been working from home might be allowed back to their places of work, including the Trades, in order to get the economy moving. Next might be high-street retail, followed by restaurants and entertainment/gyms etc. as these pose the greatest risk of “gathering” and the hardest to maintain social distancing and monitoring. The final group to be “released from lockdown” will be those most at risk of severe infections such as the elderly, co-morbid or immunosuppressed.
 
Whatever order people return to their pre-pandemic life there needs to be sufficient time (3-4 weeks) between each change in order to spot any problems and press the pause button or take a step back towards lockdown. Yep, we need to be prepared to go back in to lockdown if any stage goes wrong. It may also mean travel is restricted so that monitoring is easier e.g. you’ll be restricted to only eating in your local town’s restaurants not travelling to another town’s restaurants etc. If all goes smoothly my 5 phases of returning to “normality” would still take 5-6 months, and that’s assuming only 5 phases, there may need to be more.
 
What do we need to do as we come out of lockdown?
As we slowly come out of lockdown and people start returning to work or school in phases we are still going to have to maintain careful hygiene and social distancing. Remember we have no treatment for Covid-19 and we have insufficient immunity to prevent transmission so we have to prevent transmission in other ways (careful hygiene and social distancing).
 
Whatever happens, until the time when we have sufficient immunity, we will not go back to how things were before this pandemic began. If we do there will be a second surge in infections and we’ll have to go back in to lockdown again.
 
We still need to wash our hands… LOTS!
Hand washing is the best way to protect ourselves from Covid-19, not PPE, masks, visors, aprons or plastic gloves, just good old fashioned hand-washing. But it wasn’t actually so old-fashioned, it’s just no one did it before. Somewhere along the line, washing our hands and covering our mouths when we coughed or sneezed fell out of “fashion”, it was no longer insisted upon by parents or schools so we stopped doing it; a generation or two have grown up not even thinking about it. However Microbiologists and infection control teams bang on about hand hygiene until we are hoarse, it is that important. Many infectious diseases are transmitted via dirty hands and so hand washing is the cornerstone to preventing transmission; Covid-19 is no different. Sure Covid-19 can be spread by someone coughing in your face, but if you don’t get too close and they cough into their hands, elbow or a tissue, that’s not going to happen (especially if they also wash their hands afterwards!!!). So use good cough etiquette and wash your hands.
 
Another important aspect of preventing Covid-19 transmission is distance. Stay 2 metres away from people who might be infected. The large droplets produced by coughing settle out within 2 metres of the person coughing; if you can stay out of that 2 metre range then you won’t get splattered with infected muck. And anyhow they should be coughing into their hands, elbow or tissue and then everyone should wash their hands. Our social attitudes need to regress to old fashioned “catch it in a hankie and apologise” while someone utters “god bless you!”… (NB regardless of your faith)… remember this particular habit came out of the Black Death…
 
This means we are not going to be able to go back to life as it was pre-pandemic. Large mass gatherings, sports venues, concerts, festivals or groups of people in any form will likely be banned for a considerable time. People will still need to wait patiently in the street for people to pass. This kind of distancing is here to stay.
 
In addition to the above another important aspect of controlling Covid-19 is to continue to self-isolate if you have been exposed or if you have symptoms. If you are unlucky enough to get exposed to Covid-19 during the release from lockdown then you will probably still have to self-isolate for 14 days if you don’t develop symptoms, or 7 days if you do. This is so you don’t spread the infection to other people causing more cases. Remember 14 days is the time for you to have developed a minor infection and got better, 7 days is for you to have become non-infectious after developing symptoms.
 
Travel restrictions
I’m not expecting my “dream holiday” hiking in the Drakensberg Mountains to go ahead this autumn. I really hope it does (I’ve been looking forward to it for 20 years!) but in reality we are NOT likely to be back to unrestricted international travel by this time. Even if it is we’re unlikely to be able to find a cat sitter at short notice for our 5 cats! Realistically we may not even be back to widespread national travel.
 
Countries are going to be very careful about not letting SARS Cov2 back within their borders for a long time. It makes sense really; if you manage to eliminate the virus from your population the last thing you will want to do is let it back in again. Rapid international travel is the way Covid-19 spread so quickly in the first place.
 
So that nice summer holiday you had planned, well you might not be going. I really hope I’m wrong about this one but I’m not going to bet on it.
 
How do we know if a second surge is occurring?
Okay, the simple answer to this is that a lot of people will get sick about 2-3 weeks after “something” changes and they got exposed to the virus e.g. restaurants open up and clusters of Covid-19 appear. In reality we need to have a robust surveillance system in place to detect cases as soon as they start to occur, otherwise we’ll get too far down the line before we can establish which “something” caused the problem. This means we need to have the testing capacity to investigate any patient who becomes febrile or develops a cough.
 
So the laboratories can’t relax yet, and in fact labs are going to get busy! We need to make sure we really do have sufficient capacity to test large numbers of slightly unwell people at short notice over a long period. I joked when there was the announcement of the “testing phase” right at the beginning, that using McDonald’s drive-throu’s would be the most effective way of community testing, it seems every community has a drive-throu McD’s… this scale and breadth might actually be needed! (Would you like fries with that?!)
 
But what stats are we using!?
“It’s looking brighter, death rates are falling so we can come out of lockdown!” At the moment the media and Government seem to concentrate on death rates, which is really unhelpful (and alarmist), or the small number of severe infections (approx. 1.5%) that are admitted to hospital (which is a reasonable guess based on recent prevalence studies which suggest lower rates of severe infection than the original 15%). However in order to detect 150 patients with severe infection 10,000 mild cases might be spreading the virus in the community. Guess what? Using these stats for monitoring would pick up on a problem too late and we would all be back in lockdown again. So we are going to need to be more alert for mild cases and not rely on hospital admissions!
 
We actually need to be looking at the number of new cases, not death rates. At the moment we seem to have a fairly steady 4000 newly diagnosed cases a day. This is even with 5 weeks of lockdown. Okay, the number of cases per day isn’t increasing, but we don’t have this under control yet. If the lockdown had brought the reproductive rate (R0) to less than 1 (Imperial College and the Government would have us believe the R0 is 0.7) then the number of new cases should be falling… and it isn’t, in fact the number of reported new cases so far today is 6032, so I don’t think we are there yet, and this might be because the lockdown isn’t actually tight enough.
Covid-19 daily cases
Click for larger image
​Until we see a sustained fall day-by-day in the number of new cases then nothing should change; lockdown needs to continue or in my opinion tighten.
 
But widespread screening will cure Covid-19, the WHO says so!
Lots of people are talking about how South Korea controlled their outbreak. This does appear to have worked but would you accept how they did it:
  • Screen everyone for Covid-19
  • Use the populations credit card activity, mobile phone and laptop GPS, etc. to track where everyone is or has been
  • Identify who has been in contact with people who tested positive (using the data above)
  • “Encourage” (new laws passed) all contacts of infected people to self-isolate at home for 14 days
  • Repeat…
 
I wonder how we would accept such a control of our liberty… it’s the Law in South Korea and they just accepted that was what was required, remember the Chinese media images of people being forcibly locked up and how we all balked at the idea!?
 
The sceptic in me thinks the government’s widespread testing (green) just allows us to have a nice looking statistic called “rate” (yellow), but remember if you test more (especially asymptomatic “patients” who don’t have signs of Covid-19) the no. of positives will remain the same the actual “rate” will decrease, which obviously looks nice and make us all feel better; it’s the number of confirmed cases that is worrying (red) they are still chugging along at the same rate of around 4000 per day!
Covid-19 testing
Click for larger image
​ARGH!!! Plan for the worst… let’s hope for the best
So as part of the strategy for coming out of lockdown there needs to be a clear plan of what will be done at what stage? When can we move forward with plans, what indicates we should pause, and when should we step back? The Government needs to be robust and take hard and possibly unpopular decisions if necessary.
 
I’m usually pretty unforgiving of politicians but in this case I have a huge amount of sympathy. If they are perceived to be too slow, everyone is going to complain. If they get it wrong, everyone is going to complain. If we get a second surge, everyone is going to complain. If they get it right, no one will say anything! In some respects it’s a bit of a no-win situation…
 
Remember: there is no rule book for how to come out of a nationwide lockdown where we have no vaccine and no treatment. Currently, in my opinion, based on no. of cases and seeing the no. of people out and about, we actually need to tighten the lockdown! We need to be patient and maintain our infection control aspects such as hand washing, social distancing and self-isolation. We need to continue to follow the instructions from Government and if we have to take a step back we need to do it with good grace and without reluctance; trying not to complain or break the rules. It’s going to be a tough year but we don’t really have much of a choice.
 
The slower and more carefully we do this the faster it will all be over.
 
Now where did I leave my Drakensberg guidebook… well I can hope…
GP
4/5/2020 08:16:31 am

Thanks for writing this blog, I follow it carefully and find it extremely informative. Please keep it up, it's appreciated.

David
13/5/2020 10:50:20 am

Hi, I'm so glad you enjoy the blog, it makes it so worthwhile. I do this in my own time (and Jenny ECIC, aka my wife, edits them) so it really helps to know that people like you value what we do.
Thank you, David

David
20/5/2020 06:37:35 pm

I second this comment - your blogs are fantastic, the writing style fun, humorous and engaging. I learn so much from the material and often recommend 'Micro Nuts and Bolts blog' to other trainees. Thanks so much to you and your wife. From David, Kent ACCS Trainee and future ED Intensivist (fingers crossed!)

Peter M B English link
5/5/2020 12:40:27 pm

Hi, David! (I'm one of the CsCDC in Surrey and Sussex - we have met!)

I keep being surprised at some of the things that I think we don't know. (Some of them might be known, just not by me!) I was hoping you might be able to help clarify some of them!

One of them relates to distinguishing "live", potentially infectious virus, from left-over RNA from "dead" viruses. Woelfel et al - only found viable, infectious virus up to day 7 or 8; and I think I saw another study that did viral culture and only found viable, culturable (potentially infectious) virus up until day 5 (from onset of symptoms in both cases).

I imagine that hospital patients would have throat/nose swabs or broncheo-alveolar lavage samples tested regularly for virus and for secondary bacterial infections.

I know that it's very easy (given the kit and the primers) to do RT-PCR testing for RNA - but surely other people have been looking for live virus?

The significance is obvious.

Covid-19 natural history typically follows one of three paths:

1) No or mild symptoms (but still infectious - this is why the R value was so high at first; people didn't realise they were ill and carried on their busy lives).

2) An unpleasant flu-like illness with cough and fever, that lasts about a week, after which you recover gradually.

3) For a small (but rising with age) proportion of the population, as in 2, but on about day 7 or 8 of symptoms you develop an interstitial pneumonia and/or other complications, your oxygen saturation levels drop, and you need more intensive therapy (complementary oxygen, CPAP, mechanical ventilation...)

Now if Woelfel et al's findings are correct, and apply to all patients, by the time people's condition deteriorates and they need admission to hospital on day 7 or 8, they are at the very end of their infectious period. By the time they make it into the ICU, they probably aren't infectious.

So... Are people who develop these complications different in the way they clear the virus?

How, indeed, do you distinguish "dead" RNA from "live", potentially infectious viruses? (Woelfel et al appear to have used a different technique, not viral culture; I wish I could remember which paper I read that used culture - ISTR they could only culture the virus from samples taken up to day 5 after symptom onset...)

Indeed, what - for the benefit of a public health doctor who hasn't worked on a hospital ward for decades - causes the deterioration?

Does it depend on continuing viral replication? I gather it has to do with an excessive immune response overstimulating an inflammatory response (a "cytokine storm") in lung and other tissues... but does the virus have to continue to replicate for this to happen?

Why have there not been further studies looking at ongoing infectiousness?

When we've sorted all of that out, perhaps we can start thinking about how the 2m guidance. I gather it is based on indoor data. Some have suggested 1m is sufficient outdoors - which fits with what we know about other diseases, like TB...

In fact, I posted a number of questions that I, at least, don't know the answer to (and I gather Chris Whitty has added some more that I didn't include): https://peterenglish.blogspot.com/2020/04/more-questions-about-science-what-do-we.html


Woelfel R, Corman VM, Guggemos W, Seilmaier M, Zange S, Mueller MA, et al. Clinical presentation and virological assessment of hospitalized cases of coronavirus disease 2019 in a travel-associated transmission cluster. medRxiv 2020:2020.03.05.20030502, DOI: 10.1101/2020.03.05.20030502 (https://www.medrxiv.org/content/10.1101/2020.03.05.20030502v1 or https://www.medrxiv.org/content/medrxiv/early/2020/03/08/2020.03.05.20030502.full.pdf).

David
6/5/2020 04:59:46 pm

Hello Peter

Good to hear from you.

To try and answer the questions as simply as possible:

Doing cell culture to study live virus is difficult. You have to have types of cells that will reliably culture the virus. You have to have the expertise to keep this cell line alive whilst the virus is trying to kill the cells, which involves regularly changing the cells and keeping them free from contamination. On top of that the laboratory doing the studying has to have at least Biological Safety Level 3 classification and accreditation (the same we use for TB) and my understanding is that not many research labs have this kind of facility. The studies are definitely needed though so I hope people out there are doing them.

In terms of what is happening when someone gets sick this is tricky. the severe clinical illness does appear to be more immune mediated and microvascular in nature rather than direct viral damage. By the time patients present to hospital in the second week of illness the virus is on it's way out. RNA detection by PCR though can remain positive for a long time after the virus is no longer able to cause further infections. The problem is that we're not sure how long the seriously ill patients remain infectious. I'm not aware of any study looking at this as you need to be able to get samples from patients who aren't well enough to be sampled and are not able to consent to take part in research.

It's all a bit of a minefield but all of your questions are good ones... we just don't yet have all the answers...

Watch this space. If I find out anything more I'll let you know.

David

Peter M B English
5/5/2020 12:57:04 pm

Just checking the "notify me of new comments" checkbox...

David Jones
20/5/2020 06:31:23 pm

Hi there, Could we have a blog on COVID-19 testing? Many Trust are insisting on 2 negative swabs before stepdown from a COVID area to a non-COVID area. Is this logical? Does Gambler's fallacy not apply here? Your views would be very much appreciated.


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    David Garner
    Consultant Microbiologist
    Surrey, UK

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