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Reason for optimism?

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 Yanis Nayu 23 Jun 2020

https://www.medrxiv.org/content/10.1101/2020.06.21.20132449v1

What do folks make of this? Would suggest that estimates of numbers of people already infected might be low, owing to the role of T cells in the immune response. 

 jkarran 23 Jun 2020
In reply to Yanis Nayu:

Weird that all the primary infections produced antibodies but none of the secondaries did. Presumably an artefact of the very small study size and perhaps specifically selecting primary cases with developed antibodies.

I'm not sure it's much cause for hope, we know if we go back to normal life we go back to thousands dying daily, as far as I can see all this potentially changes is whether that lasts weeks or months before it slows. 

Jk

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 girlymonkey 23 Jun 2020
In reply to Yanis Nayu:

Interestingly, I was just about to ask whether we think this is a worry!

https://www.bbc.co.uk/news/uk-scotland-highlands-islands-53149046

Were the negatives false negatives or did she catch is again?

So many unknowns still!

 DancingOnRock 23 Jun 2020
In reply to Yanis Nayu:

It was reported in the early days to be seen that the immune system was using a two pronged approach to deal with it. 

 Yanis Nayu 23 Jun 2020
In reply to girlymonkey:

I don’t know if they use PCR for these tests - if so, it can pick up genetic material from the patient after they’re symptomatic and infectious. It’s a PITA investigating food poisonings. 

 Richard Horn 23 Jun 2020
In reply to jkarran:

> I'm not sure it's much cause for hope, we know if we go back to normal life we go back to thousands dying daily

We dont *know* this at all - it is a feasible worst case, and it is very likely there would be a degree of resurgence if all restrictions are lifted but we definitely dont know how bad it would be as you can see the scientists are still highly undecided on the level of exposure people have had...

Post edited at 16:04
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 Offwidth 23 Jun 2020
In reply to Richard Horn:

That's twaddle.. the scientists argue as they don't know how people will behave but they do know enough about the virus that if nearly everyone behaves as 'normal' the virus will spread fast. In reality many are still frightened so they will be keeping distances whatever, so a return to the initial growth rates are unlikely.

ONS estimates safely show around 5% and certainly less than 10% of the UK population have had it so far. Hence a thousand a day is nothing like a feasible worst case. If the virus is allowed to keep growing unchecked until nearly everyone has had it and we could see many thousands of deaths a day. At the last peak death rate many hospitals were at their capacity limits. When capacity is exceeded evidence indicates death rates triple (or worse) and standard hospital use becomes very difficult causing many secondary deaths.

Post edited at 17:22
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 jkarran 23 Jun 2020
In reply to Richard Horn:

We have clear examples of current localised outbreaks infecting the vast majority of those at risk. Take the current German abattoir outbreak, 66% of 1000 tested infected all at once. They weren't quietly immune and while Germany has kept deaths down it has had plenty of cases, I see no cause to think we're in a radically different position.

Jk

1
 DancingOnRock 23 Jun 2020
In reply to jkarran:

Depends what’s happening with the other 34%. Seems to be a chunk of people who are asymptomatic and don’t have antibodies  as per the OP paper. 
 

My friend was tested positive was asymptomatic and sent home. The other 3 people in her household never showed symptoms and to my knowledge haven’t tested positive. 
Another friend tested positive for antibodies having shown symptoms. The rest of the family was tested and 2 showed antibodies and the 4th didn’t. 
I find it very strange that these levels false negatives are showing up. 
It’s a very odd jigsaw to piece together. 

1
 girlymonkey 23 Jun 2020
In reply to DancingOnRock:

It must be a fascinating time to be a virologist! 

Yes, it seems very tricky to pin down what's happening. I would be interested to know if I have anitbodies. I have definitely been exposed. May have had it early Feb but obviously can't be sure (this was before my definite exposure). But even if I did have it, it seems there is no guarantee that I have anitbodies, but I didn't come down with any symptoms of it when I was exposed.

 cb294 23 Jun 2020
In reply to DancingOnRock:

Which do you think are FALSE negatives? PCR and Abs meeasure different things, and have different modes of generating false negatives or false positives.

CB

 Yanis Nayu 23 Jun 2020
In reply to Offwidth:

Those estimates are based on antibody testing aren’t they? The whole point of what I posted was that the study suggests antibody testing alone  underestimates the number of people already affected. 

 DancingOnRock 23 Jun 2020
In reply to cb294:

I have no idea. Something isn’t right somewhere. People who are or have been infected aren’t showing up, and with my anecdote there it seems it’s quite a few.
 

I’ve just been speaking to a nurse tonight who works on a Covid ward who has no antibodies. Hasn’t been sick. But cannot understand how she’s not had it. 

 Richard Horn 23 Jun 2020
In reply to Offwidth:

What is twaddle? I was not objecting to what was said merely objecting to the certainty of the assertion that was made. Here we have a scientific paper published by (I assume) scientific experts, then an armchair expert immediately follows up with "we all know its wrong".... If you read the paper you would understand the ONS figure is pretty meaningless. But I am not here to argue the paper is correct, I am not expert myself, merely an interested observer.

In reply to Yanis Nayu:

> Those estimates are based on antibody testing aren’t they? The whole point of what I posted was that the study suggests antibody testing alone  underestimates the number of people already affected. 

It’s been mooted for a while that antibody levels don’t indicate past infection status in a binary way.  Given growing understanding of viral load, this seems to hint at the long running view that mild exposure and weak infection doesn’t produce sufficient antibodies needed to confer protection against a strong infection stemming from exposure to a high viral load.

So it’s promising in terms of things remaining okay so long as the case count and severity decreases; it’s not promising in terms of herd immunity in a situation where case count and severity is increasing.

Post edited at 23:36
In reply to jkarran:

> We have clear examples of current localised outbreaks infecting the vast majority of those at risk. Take the current German abattoir outbreak, 66% of 1000 tested infected all at once. They weren't quietly immune and while Germany has kept deaths down it has had plenty of cases, I see no cause to think we're in a radically different position.

Quite. It’s likely that viral load in this plant is higher than it would be for the same people almost anywhere else.  We have outbreaks in at least one U.K. meat packing plant where many people were infected. 

Neither infection nor immunity are binary statuses; there is a level of exposure one is immune to; it was more than zero but small for most of us before the virus darkened our door; it rises for many people who get infected but it’s never infinite.  How much it rises during an illness depends on ones exposure and myriad other factors.

 jkarran 23 Jun 2020
In reply to Richard Horn:

> What is twaddle? I was not objecting to what was said merely objecting to the certainty of the assertion that was made. Here we have a scientific paper published by (I assume) scientific experts, then an armchair expert immediately follows up with "we all know its wrong".... 

What do you think has changed so dramatically the last three or four weeks? It's still spreading where we give it opportunity, it's still killing. 

The paper is about the detectability of antibodies and at face value the results look very odd, it's clearly small and the primary cases look to have been cherry picked if the findings regarding secondary infections are remotely representative.

Jk

 Offwidth 24 Jun 2020
In reply to Richard Horn:

Twaddle again, the ONS paper is solid science with clear error limits. Your not just an 'interested observer' when you deny scientific mainstream information:. you are playing scientific denial politics.

 Offwidth 24 Jun 2020
In reply to Yanis Nayu:

Yes but so what.... show me any widely agreed scientific paper that says more that 10%  of the UK population have been infected so far. All we have is the likes of the Oxford study that is laughably bad in meeting the rest of the data.

 cb294 24 Jun 2020
In reply to DancingOnRock:

Similar coronaviruses are long known to interfere with antibody mediated immunity (which is important in mucosal infections). This is why you can get coronavirus colds again and again. Fighting the infection therefore relies on T-cell based immunity. If this is efficient, and an infection is cleared quickly (and therefore is asymptomatic or has only very minor symptoms), I can easily imagine that there will not much in ways of antibodies.

I have no proof that this is indeed the case, but IMO it fits much better than a 30% false negative rate for AB tests (one of the most proven diagnostic techniques, so robust that you can buy such tests for home use over the counter, e.g. for pregnancy or HIV tests).

PCR tests are more tricky. Actually, the tests themselves are automated and robust, the problem lies in the much harder sample collection.

CB

 Richard Horn 24 Jun 2020
In reply to jkarran:

Nothing has changed, but we do not fully understand what has happened so far. 

What seems odd to me - the virus has spread to pretty much every corner of the UK in a short period of time, yet antibodies only show up in ~7% of random population studies. If we made the assertion that only people with antibodies have been exposed - how can something be super-contagious on a national level but pretty un-contagious on a local level? This pattern of spread sounds a little implausible without a degree of asymptomatic / undetected transmission. On this basis the papers argument that there is an underestimation of exposure based simply on antibody testing to me at least sounds realistic.

Obviously the degree of asymptomatic infection is pretty key as it determines how lethal the virus is. The number of people who have died would mandate a cautious approach in any case.

 Richard Horn 24 Jun 2020
In reply to Offwidth:

I was not saying the ONS study was wrong, but it was a study on antibody infection, not a study on overall exposure. 

What exactly have I denied?

In reply to Richard Horn:

> What seems odd to me - the virus has spread to pretty much every corner of the UK in a short period of time, yet antibodies only show up in ~7% of random population studies. If we made the assertion that only people with antibodies have been exposed - how can something be super-contagious on a national level but pretty un-contagious on a local level? 

Two points:

1.  The virus is only ever contagious on a local level.  It moves on a larger spatial scale because people move on larger scales.  In the UK some people move about a lot.  The key part of the virus that exploits this is the transmission by people who have not presented symptoms.  

2. A recent paper showed that the virus had been independently imported into the UK at least 1,400 times; it came in distributed all over the place so it started “everywhere” at a level of 0.002% and worked outwards from there.  The visualisation I have for this is a hundred fireballs from MIRVs spreading out from their impact sites and merging across the nation, think the iconic scene from War Games.  https://m.youtube.com/watch?v=ir5bTic17k4

That being said, the anti body tests only tell you who has anti bodies not who has had the virus.  But it’s likely the antibody levels are the key factor - not past infection status - for a “herd immunity” situation (which some have argued for as a basis for dropping lockdowns ~2 months ago) where infection levels and critically viral loads would spike massively.

Post edited at 09:56
 DancingOnRock 24 Jun 2020
In reply to wintertree:

I would think there’s enough data now on who is typically dying, who ends up on a ventilator and who ends up seriously ill, to mean that anti-bodies are really a pointless indicator of anything other than of passing interest. 
 

The important thing now is to identify and isolate any flare-ups quickly because it’s not possible to shield those people above. Something that wasn’t really possible to do before lockdown for various reasons. 
 

Seems like no one was notified about the Anglesey factory outbreak until it was too late. It didn’t actually spread like wildfire through the factory, it progressed as expected. 

 jkarran 24 Jun 2020
In reply to DancingOnRock:

> Depends what’s happening with the other 34%. Seems to be a chunk of people who are asymptomatic and don’t have antibodies  as per the OP paper. 

That's a reasonable question.

Some will be false negatives, we know swab testing even done well isn't totally reliable. I'm not sure what the current rate is believed to be.

Some will have not been exposed by luck and or their position in the plant/rota/workforce.

Some may have had it and recovered, unless we're saying R is 660 this has rippled through the workforce, very roughly you'd need an R of ~10 given an incubation period of 5 days to get all 660 infected in 2 weeks so the first and the last infected could simultaneously test positive. Possible for sure but I've seen R being reported as high 2's for Germany, a figure largely dominated as I understand it by this big outbreak. With people isolating at home with relatives (right?) R in the wider community is unlikely to be very far below 1 as residual infections ripple through households.

Some probably have been exposed and shrugged it off, it seems to be possible but it clearly isn't the majority response by any stretch.

> It’s a very odd jigsaw to piece together. 

Extremely. In part that's because there is lots of muddled reporting of statistics and amplification of small, flawed or misunderstood studies by motivated actors. In part it just seems like a rather odd illness.

jk

Post edited at 12:01
 DancingOnRock 24 Jun 2020
In reply to jkarran:

A large proportion of the workforce were living together in houses of multiple occupancy and travelling in and out together - possibly in minibuses.

 jkarran 24 Jun 2020
In reply to DancingOnRock:

> A large proportion of the workforce were living together in houses of multiple occupancy and travelling in and out together - possibly in minibuses.

Does that alter what I said? It seems to me to support the idea that those not in that position will have been exposed to less risk, they could make up a fair chunk of the uninfected third.

jk

 DancingOnRock 24 Jun 2020
In reply to jkarran:

Why does everything written on this forum get taken as an argument? I made a statement to further inform. 

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In reply to DancingOnRock:

> Why does everything written on this forum get taken as an argument? I made a statement to further inform. 

To which you got a perfectly reasonable response.

 jkarran 24 Jun 2020
In reply to DancingOnRock:

> Why does everything written on this forum get taken as an argument? I made a statement to further inform. 

I just wasn't sure if you agreed with my take or saw something in the information you added that I didn't. I could have ignored it but we're here to interact, right. Perhaps I got the tone wrong, I've never been much of a diplomat.

jk

 DancingOnRock 24 Jun 2020
In reply to jkarran:

It could be that the majority of the transmission wasn’t happening in the factory. The factory was just the common factor. I’m getting an image in my head, possibly unfairly, of a community of people who may have been ignoring other distancing rules. 

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 Cobra_Head 24 Jun 2020
In reply to Richard Horn:

> We dont *know* this at all - it is a feasible worst case, and it is very likely there would be a degree of resurgence if all restrictions are lifted but we definitely dont know how bad it would be as you can see the scientists are still highly undecided on the level of exposure people have had...


It would be a very novel virus, if this wasn't true. Increased cases in Germany, another outbreak in China, Miami,  now removing deaths from the registers to dis-prove a massive rise in cases!!

You are right we don't know lots about this virus, but judging by what's happening in places where they've lifted restrictions early, you'd need blinkers to think it's not going to happen here.

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In reply to DancingOnRock:

> I would think there’s enough data now on who is typically dying, who ends up on a ventilator and who ends up seriously ill, to mean that anti-bodies are really a pointless indicator of anything other than of passing interest. 

I disagree, because all those people had no antibodies when they became exposed and infected – this is a reasonable assumption. Now, 14% of people in London have antibodies approximately.  Perhaps that 14% are now at lower risk of reinfection.  By studying such people we will learn if herd immunity can eventually develop, or not.  That has a massive impact on policy decisions in the longer term. 

Also, the anti body studies tell us a minimum bound for the number of people who have had the virus which is a useful data point for putting a maximum bound on the fatality rate.  

It is data with many uses but it never has told us how many people have had the virus, only a minimum bound for that.

 DancingOnRock 24 Jun 2020
In reply to wintertree:

If the fatality rate is 3% then by the time 13m in London have had it we’d have close on 400k deaths. Even at 1% it’s 130k deaths. 
 

I guess it depends how many you think you need for herd immunity but it’s going to leave a lot of people dead unless the antibody test gets very reliable and start showing huge numbers of asymptomatic people with antibodies. Couple this with people who don’t seem to develop antibodies and you really don’t have a lot of useful data, even if the anti bodies don’t stay around or do stay around, do offer protection, or don’t offer protection. 
 

Which is why I say the data from people who have died is the most important and autopsies on what they actually died of, not just whether fighting the COViD infection over stressed a struggling system. 
 

The next few months will show what happens with the numbers of ‘normal’ deaths. Preliminary figures for last week show below average weekly figures. 


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