Coronavirus - worldwide spread and control

[Simon M]

They were talking specifically about what is known about coronaviruses, and the suggestion was that immunity wanes after about a month. Given that there is also recent evidence that SARS-nCoV2 clobbers memory T cells, that would sort of make sense.

Could you say which episode of The Week in Virology this is from? There have been a lot of episodes this week…

 

[Sly Saint]

Harley Street clinic has sold 2k coronavirus home test kits at £375 to celebs

The rich and famous appear to be bypassing Government rules by paying hundreds of pounds for private coronavirus tests.

After being refused NHS testing, more than 2,000 stars, as well as members of the nobility and Britain's business elite have splashed out on £375 home kits to check if they have the potentially deadly disease.

Around 60 firms have ordered the tests made by a Harley Street clinic for all employees, according to the Daily Telegraph.

Public Health England confirmed this week that only those with symptoms so severe they would need immediate hospital treatment would receive a free test on the NHS.

https://www.mirror.co.uk/news/uk-news/coronavirus-harley-street-clinic-sold-21711100

 

[Simon M]

This is a very important thread, in my view, putting forward the idea that suppression can be better sustained if we move to a programme of massive testing (though not testing everyone).



The author calls this "the Apollo challenge of our time".



Basically, a massive if expansion of testing and contact tracing (presumably after a massive short term lockdown to be clear on who isn't infected). And also massive antibody testing to establish who has already been infected and so can get back to work to keep the economy and society moving.



Possibly also a huge expansion of contact tracing, including using anonymous mobile phone GPS data to alert people who might of being exposed, so they can get quarantined and organise a test.



The author is proposing this — it can't be done yet, but might be a better long term solution than the current plan. Worth considering, anyway.

 

[Lucibee]

Could you say which episode of The Week in Virology this is from? There have been a lot of episodes this week…

I think it was the one with Ralph Baric: http://www.microbe.tv/twiv/twiv-591/
but it's a long one.

I'll edit this post when I get a timestamp.

edit 1: OK. At 47mins, Baric discusses history of coronaviruses, immunity, cross-immunity - suggests that immunity acquired in childhood *is* protective. But we just don't know yet.

The CD4 data I saw was from severe cases, so may indicate that those who recover from severe disease are less protected against reinfection?


Still trying to track down the bit about immunity waning after a month... it might just be in severe cases.

edit 2: OK. It's at 15 mins in. I'll try to do a transcript so that those whose immunology is better than mine can tell me where I have misunderstood it!

 

[lunarainbows]

Harley Street clinic has sold 2k coronavirus home test kits at £375 to celebs

https://www.mirror.co.uk/news/uk-news/coronavirus-harley-street-clinic-sold-21711100

People have been questioning why celebrities are getting access to coronavirus tests when even frontline healthcare workers aren’t.

Then there’s also the fact that MPs also got tested (even under the old rules - which meant you had to have had contact with a confirmed case, or had returned from an “infected region” within 14 days), when they didn’t fulfil either criteria to get tested.

 

[lunarainbows]

This is a very important thread, in my view, putting forward the idea that suppression can be better sustained if we move to a programme of massive testing (though not testing everyone).



The author calls this "the Apollo challenge of our time".



Basically, a massive if expansion of testing and contact tracing (presumably after a massive short term lockdown to be clear on who isn't infected). And also massive antibody testing to establish who has already been infected and so can get back to work to keep the economy and society moving.



Possibly also a huge expansion of contact tracing, including using anonymous mobile phone GPS data to alert people who might of being exposed, so they can get quarantined and organise a test.



The author is proposing this — this can't be done yet, but might be a better long term solution than the current plan. Worth considering, anyway.

Do we even know what the current plan is? I am unclear on it. Sometimes I feel we are still in herd immunity. (And some twitter commentators like Devi Sridhar and the times journalist I posted above seem to agree). Sometimes I think we are under suppression. Sometimes I think we are under mitigation.

 

[ME/CFS Skeptic]

That has been done in Austria and the data is probably already out of date but showed 1% had the virus.

1% seems very high. Do you happen to have a link for this?

Don't know if this article has been discussed yet, I think it's quite interesting: "Coronavirus: Why it’s so deadly in Italy" - Andreas Backhaus, 13 march 2020.

It argues that the death rate in Italy is soo high because a lot of the confirmed cases are old people. That could be because the outbreak in Italy has mainly spread among older segments of the population or because testing is restricted so that younger persons who tend to have milder complications are not picked up.

The interesting part of the article is when the author presents data from South-Korea, another country that has been greatly affected but that tested much wider than Italy. In contrast to the situation in Italy, the age-distribution of confirmed cases in Korea is quite similar to the general population. So their case fatality rate (around 1%) is probably a more accurate estimate of what would happen if the virus were to spread among the general population in a more controlled manner.

Although, even in South-Korea, I think there will be a significant selection bias where those infected with the virus and develop significant symptoms are much more likely to be picked up than those who don't. So I wouldn't be surprised if the CFR (EDIT: I meant the infection fatality rate (IFR) here) for a modern healthcare system that is not overloaded as is currently the case in Italy, would be significantly lower than 1%, probably somewhere between 0.1% and 1%. Any thoughts on this?

 

[lunarainbows]

Our chief scientific adviser / chief medical officer, Whitty & Vallance on Sky news just now, after being asked about the lack of PPE and tests on NHS:

“Only science-y questions please, not on the NHS and things like that”

@Jonathan Edwards

So who is responsible for this then, if it is not them? They are the ones advising the govt.

 

[Mij]

Top doctors here are now saying to keep stores closed and self isolate for 3+ weeks.

 

[Leila]

Data on comorbidities in the deceased from Italy retrieved from this news article.

From what I understand around 99% had pre-existing conditions like heart disease, diabetes and high blood pressure, often 2 or three (see table 1).

Seems similiar to the data from China before.

 

[Roy S]

There are other stories of getting ventilators from outpatient and veterinary clinics as well as military and "obsolete" stockpiles.

 

[Jonathan Edwards]

So who is responsible for this then, if it is not them? They are the ones advising the govt.

Mr Johnson is responsible at present. Previously Mr Hunt, Mr Hancock, Mr Lansley... also Mr Milburn in his way. The NHS has been restructured such that nobody is responsible because nobody has enough resources.

This lunchtime Whitty is still talking of flattening a peak. Either this is a deliberate obfuscation strategy to make it look as if the policy has been right all along on the basis that now is not the right moment to admit that it was four legs bad, not two (referring to Animal Farm), or they really are that dim that they do not realise what they have to try to achieve.

The BBC seem to be sticking to government message as much as possible yet at the same time are undermining the plan by constant clips of people having trouble working at home saying they cannot cope and wondering whether we will be able to survive lockdown with 'no escape route'. The reality of course is that this is a war situation and it is up to people to bite the bullet, unless they are happy for people to die like flies from all the conditions that won't get treated, as well as the virus.

 

[FMMM1]

1% seems very high. Do you happen to have a link for this?

Although, even in South-Korea, I think there will be a significant selection bias where those infected with the virus and develop significant symptoms are much more likely to be picked up than those who don't. So I wouldn't be surprised if the CFR for a modern healthcare system that is not overloaded as is currently the case in Italy, would be significantly lower than 1%, probably somewhere between 0.1% and 1%. Any thoughts on this?

I think the South Korean data is probably as good as it gets i.e. they did mass testing including those without symptoms, who had been in contact with someone with coronavirus, (I think!). I take your point i.e. we don't know the true fatality rate and I assume will not - unless we had a statistically significant sample of people tested for antibodies (establishing total number exposed and recovered).

 

[Jonathan Edwards]

The author is proposing this — this can't be done yet, but might be a better long term solution than the current plan. Worth considering, anyway.

I don't quite see why it cannot be done yet. Or at least for everything to be done to get it started - i.e. stringent lockdown and as much testing as feasible. At least it should be possible to test people known to have been in close contact with positive cases and people with cough and fever.

 

[Lucibee]

edit 2: OK. It's at 15 mins in. I'll try to do a transcript so that those whose immunology is better than mine can tell me where I have misunderstood it!

OK. I've done a quick transcript [apols for any errors - I haven't gone through it thoroughly] - from 15 mins 32 secs in:

Brianne Barker: Given the large number of people who may be infected, can we expect some of those people to have immunity? To maybe be protected against this virus in the future?

Ralph Baric: Almost certainly. And I saw some very interesting data from Stan Perlman the other day, who’s been looking at serum neutralisation titres of MERS patients from the middle east Kingdom of Saudi Arabia, and it’s quite interesting that people peak fairly quickly with high neutralisation titres, but then they wane over the next year or two to almost background levels or just slightly above background levels by the second year. And with MERS, there have been several reports of people who seroconverted – they were RT-PCR positive and then their serum neutralising titres, even the lyser titres, went almost zero within a few months. It has not been well studied. But it should be studied. And this is the contemporary human coronaviruses.

Nobody knows how they maintain themselves in human populations. They don’t undergo rapid antigenic variation like influenza. There’s not 115 common cold or coronavirus type genotypes, or whatever they’re called, serotypes. Sorry, Vincent, I just butchered picornaviruses! [laughter] So one hypothesis is that they cause a transient immune response, protective immune response, that wanes quickly and then it can reinfect and cause mild upper respiratory tract infections and that’s how they maintain themselves. So it is quite possible, and there’s been a number of reported cases in China of SARS-2 infections where people were documented to be infected, and recovered, they were RT-PCR-negative, went home, and then they became reinfected a month later or so. It’s an interesting question that you ask. In this case, the United States has sufficient cases that we can actually track the serological responses in the individuals, and their general immune B and T cell responses to infection, and we can get a handle on the long-term immunity that may be illicited after infection.

Speaker 3: And that’s a factor in what’s going on in China now, at least from reports I’ve seen, is that they seem to have seen a tapering off in cases , and of course the Chinese government is interpreting this as the draconian measures they implemented must have worked. Another interpretation might be that everybody who was susceptible got infected, and either immune or dead, and now the virus has burned out. But presumably that’s one of the reasons you’re not going to do serology tests. But hopefully other countries will be monitoring as this develops, right?

RB: I think those are certainly excellent points. A potential point is that the Chinese are primarily reporting cases in quarantine zones, which involve 100 million people and that the Chinese in rural communities are not being picked up by their surveillance systems.

Vincent: So, there must be memory, so maybe the second infections are mild?

RB: Absolutely. In the case of the contemporary human coronaviruses, the data supports the idea that they are much more mild.

VR: So that would still encourage us to make vaccines, because even then you would have a milder second infection, right?

RB: The advantage of a vaccine may well be that you include an adjuvant as a boost of immunity that circumvents whatever anti [immunity] viral gene sets present that are attenuating the long-term protective immune response.

VC: So Brianne, do you think this is a problem with memory? Or is it something else?

BB: Um. It could be a problem with memory. I think I would have to look a little more closely at things like the specific cytokines, and some of the T-cell data that we can see from some of the patients. But given the short-term persistence of the virus and the lack… err… the short-term persistence of the *immunity* and the lack of antigenic drift that Ralph mentioned, I could certain imagine this being a problem with memory and you are of course making me want to run to the lab and start playing around and looking at this right now!

RB: I would say that the global expert on that would be Stan Perlman – he would be a wonderful person to have on the show. And another possibility is that the virus just confines itself to the upper respiratory tract and nose, and so we’re suddenly having to deal with the pre-existing mucosal immune response that is present – maybe – which may allow for a much more transient infection before memory gets boosted.

They then continued to talk about herd immunity as if none of the above had been said. So I'm confused!

 

[Andy]

To Beat COVID-19, Social Distancing is a Must - https://directorsblog.nih.gov/2020/03/19/to-beat-covid-19-social-distancing-is-a-must/

There are three key conclusions we can draw from the health statistics. Firstly, we can conclude from Hubei and Italy that not acting quickly and limiting activities to simply diagnosing and managing cases is potentially disastrous. Secondly, we can conclude from South Korea that even quite large outbreaks with community transmission can be brought under control. Thirdly, when we look at the various different measures employed by Asian countries who have been successful, there is one common intervention that stands out - it is called Rapid Case Contact Management. This is simply rapid early diagnosis of as many cases as possible and rapid early isolation of all their contacts. It doesn’t even need to be 100% perfect.

Opinion: The common factor to Asia's success against Covid-19 - https://www.odt.co.nz/opinion/opinion-common-factor-asias-success-against-covid-19

 

[Cheshire]

 

[Jonathan Edwards]

OK. I've done a quick transcript [apols for any errors - I haven't gone through it thoroughly] - from 15 mins 32 secs in:

Thanks for that @Lucibee, very useful.
It seems that there is some evidence for antibody titres dropping rather early with coronaviruses. I am not sure that it is easy to interpret that. Humoral immune memory is complex and we don't have a model that really explains what we find. Tests may be predominantly picking up antibodies from short-lived scenic plasma cells that are not actually critical to protection, and not so sensitive to critical antibodies from bone marrow based plasma cells or something like that. There may also be enough high affinity memory B cells capable of generating plasma cells rapidly during a re-infection.

What sounds rather plausible is that this may belong to a group of viruses that stimulates adequate immunity but at a level that allows low grade replication after re-infection and recurrent grumbling symptoms. That of course is OK if everyone has had the virus but not so good if the idea is to keep vulnerable people free of virus because the virus may go on circulating at a subclinical level indefinitely. That is an important caveat, although it seems likely that second time round bouts of the virus are very unlikely to be life-threatening. That might not be true for people severely immunocompromised but then they are at risk of things they have seen before anyway.

Edit: I thought the answer to the comment that maybe numbers dropped in Wuhan because everyone was infected seemed a bit flabby - although I know how easy it is to try to sound in agreement for politeness. My understanding is that even now no more than one person in a thousand or so in Wuhan has been ill. Maybe 999 out of a thousand are asymptomatic but that does not seem to be what we are hearing from elsewhere.

 

[Roy S]

 

[ahimsa]

Is there any data from Asia on virus mutating?

I don't know anything about that. But it reminded me of news reports from a few weeks ago saying that the virus found in Washington state had been circulating for about six weeks.

Article dated March 2nd:
https://www.theverge.com/2020/3/2/2...ath-life-care-washington-testing-surveillance

The virus may have been circulating in Washington for six weeks, according to a genetic analysis. Researchers compared two samples of the virus, one from a person who traveled to Snohomish County from China in January, and one from a recently diagnosed high school student with no obvious cause. The genetic sequences were nearly identical, according to Trevor Bedford, a computational biologist at Fred Hutchinson Cancer Research Center in Seattle. Although the work is early, Bedford believes there isn’t another good explanation for the similarity because of an unusual variant on one of the genes.

The website https://nextstrain.org/ncov is way beyond my abilities but I'm sure some folks on here can understand it. Or perhaps understand the twitter thread (second link in the quote above).