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Tywin Manderly

Will We Stand The Corona Test of Time? - Covid #7

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Posted (edited)
4 hours ago, Mudguard said:

Since the virus has been identified and sequenced for a couple months now, it's definitely possible that antibody based tests are close, but they need to be validated.  In this case, we would want the false positive rate, that is the number of people falsely identified as having gotten the virus, to be as low as possible.  For example, if infection with the 2003 SARS-CoV virus doesn't confer immunity to the 2019 SARS-CoV-2 virus, then it will be important for the assay to be able to distinguish between the two coronavirus strains.  That could be tricky.

There are now several Chinese developed covid-19 antibody tests able to sold in the EU. They've been pushed through the approvals process extremely rapidly. I posted about this a couple threads ago.

ETA: Was getting marketing emails trying to sell me these at work yesterday here in Australia.

Edited by Impmk2

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1 hour ago, Tywin Manderly said:

You truly got an employer of horrors. :stunned:

It’s getting even better. I’ve been reassign to oversee wound care. A few years back I was charged with completely redoing the billing process. I did a handful of studies and wrote a lengthy guide as to what is wrong and how it can be fixed. Everything I suggested would be fairly easy to do and it would save the company a ton of money. Shortly after I submitted it I was effectively demoted.

They changed NOTHING!!!!!! It’s still the same broken process.

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In work news - we're now talking about pushing into the SARS-CoV-2 surviellence space. We've got hundreds of human samples sitting in our -80 freezer that have been (and we hope will continue to be) taken over the past 6 months. And how often do you get the opportunity to track a growing pandemic from start until... whenever we're shut down.

Time to start looking at the RT-PCR design.

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More than half a million British citizens - ordinary members of the public - have volunteered to support the NHS. That's pretty amazing, and in the midst of all the bad news is quite positive.

Something that's actually impressive - the sheer scale of the NHS operation is sometimes hard to fathom and I've worked for them several times over the years - is that the NHS is still well under everyday capacity, and in fact its load today is less than under a "normal" winter situation with flu and normal.

That's expected to change rapidly as cases escalate, though. The fatalities today actually dropped significantly, although that appears to be a statistical tic rather than any sign that the UK has stumbled on some golden bullet to avoid the worst.

5 hours ago, Mudguard said:

Since the virus has been identified and sequenced for a couple months now, it's definitely possible that antibody based tests are close, but they need to be validated.  In this case, we would want the false positive rate, that is the number of people falsely identified as having gotten the virus, to be as low as possible.  For example, if infection with the 2003 SARS-CoV virus doesn't confer immunity to the 2019 SARS-CoV-2 virus, then it will be important for the assay to be able to distinguish between the two coronavirus strains.  That could be tricky.

Apparently false positives for C19 are almost unheard of. The virus is so virulent that if the test says you have it, you have it, and I assume even a less sensitive home test will still pick up on that.

False negatives even with the hospital tests are a much bigger concern, as they've been relatively widespread, particularly in low load exposure cases where the virus has been very slow to enter the system and falls below the detection threshold in the first few days. Apparently it's still quite unusual for a false negative once symptoms have presented, but for screening purposes the tests might not be effective in the first day or two of exposure.

Quote

Italian study of the demographics of the deceased patients: 

This massively reinforces the previous position that the elderly are overwhelmingly the most at risk and those younger than ~60 are only at risk of outright fatalities if they have pre-existing health conditions. 3200 is a huge sample size and for exactly 2 deaths under 50 to be unexplained is a tiny number.

We would need more data though, like how many people under 50 were hospitalised or intubed and would have perished without that intervention.

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26 minutes ago, Werthead said:

False negatives even with the hospital tests are a much bigger concern, as they've been relatively widespread, particularly in low load exposure cases where the virus has been very slow to enter the system and falls below the detection threshold in the first few days. Apparently it's still quite unusual for a false negative once symptoms have presented, but for screening purposes the tests might not be effective in the first day or two of exposure.

Been avoiding discussing this, but it's a huge fear here. So many people think that if they get a negative result after they were "exposed" at some point, they're immune. 

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My girlfriend and I seem to have a good chance that we caught that blasted thing. I had some mild symptoms for a couple of days (a very mild sore throat, a little coughing) but she has been dealing with coughing, sore throat, headaches, and shortness of breath for about a week. No fever though.

To my knowledge here in Germany you are only routinely tested when you are confirmed to have had contact with another infected person (not the case for either of us). If things get worse me might know in a couple of days, I guess.

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1 hour ago, Werthead said:

Something that's actually impressive - the sheer scale of the NHS operation is sometimes hard to fathom and I've worked for them several times over the years - is that the NHS is still well under everyday capacity, and in fact its load today is less than under a "normal" winter situation with flu and normal.

One side effect of the social distancing might be that the amount of flu going around reduces as well, which would hopefully reduce some of the normal demands on the NHS.

1 hour ago, Lord Varys said:

My girlfriend and I seem to have a good chance that we caught that blasted thing. I had some mild symptoms for a couple of days (a very mild sore throat, a little coughing) but she has been dealing with coughing, sore throat, headaches, and shortness of breath for about a week. No fever though.

If you do have it, I hope it remains a mild case.

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2 hours ago, Werthead said:

Apparently false positives for C19 are almost unheard of. The virus is so virulent that if the test says you have it, you have it, and I assume even a less sensitive home test will still pick up on that.

False negatives even with the hospital tests are a much bigger concern, as they've been relatively widespread, particularly in low load exposure cases where the virus has been very slow to enter the system and falls below the detection threshold in the first few days. Apparently it's still quite unusual for a false negative once symptoms have presented, but for screening purposes the tests might not be effective in the first day or two of exposure.

 

You are mixing up the false positive/false negatives issues for the PCR based assay, which is used for diagnosis, and future antibody based assays, which are generally only used to gather data on the general population (i.e., for surveillance purposes).  

The antibody based assay would never be used for diagnosis, since it takes time for the antibodies to be generated by the body after infection.  It generally performs best about two weeks post infection.  The virulence of the virus really has little to no effect on the false positive rate for the virus in an antibody based assay. 

One common way for the antibody based assay to be constructed is to produce in a lab one or more proteins of the virus that are likely to be important in a patient's immune response.  For COVID-19, the spike protein in the outer membrane of the virus that is used to bind to your cells is one good target.  This protein is immobilized onto a substrate.  The test subject's blood is then flowed over the immobilized protein.  If you were infected, you should have antibodies in your blood that will bind to the immobilized protein, which we can detect.  The problem is that other coronaviruses also have a spike protein that may be very similar to COVID-19's spike protein.  It's possible that if you've gotten a cold in the past cause by another coronavirus, you will have antibodies that bind to the immobilized COVID-19 spike protein, even if you've never been exposed to COVID-19.  This lack of specificity (a term of art in the diagnostic field) is generally what causes false positives.  It's why it generally takes more time to develop a good antibody based assay than a PCR based assay.  People try different target proteins, and can tweak the native protein to improve the specificity.  But this takes time and you need to really validate the test against many different viruses and many different patients to be able to get a good idea on the false positive rate.  

For the antibody based assay that could be used to tell a person that they've already gotten and recovered from COVID-19, false positives are a bigger concern because if you wrongly tell a person that they are immune because of past infection, that person is less likely to observe social distancing measures and could inadvertently get infected later and spread the disease all over the place before finding out that, actually, they hadn't been infected in the past.  In contrast, a false negative means that the person should continue to observe all social distancing measures, which is the most important thing right now for controlling the spread of the disease. 

Note that the PCR based assay cannot detect whether a person has been infected in the past; it's only good when the patient is actively shedding viruses.  There is however a period of time where you have both antibodies and are actively shedding virus and are still infectious, so a positive antibody test needs to be combined with a PCR based assay to determine whether you are completely cleared of infection. 

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My throat is killing me. It has gotten so much worse in the last hour. If I feel like this in the morning I'm going to whatever employee health looks like now.

 

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5 hours ago, Filippa Eilhart said:

Italian study of the demographics of the deceased patients: 

https://www.epicentro.iss.it/coronavirus/bollettino/Report-COVID-2019_20_marzo_eng.pdf

Looks really bad for older men.  Til you get to 90+ where I’m sure the fact that women tend to be more likely to live to that long in the first place kicks in.  
 

It’s so hard to keep my mind from turning over these statistics constantly.  Like, my wife should be safe because she’s a younger woman, I should be safe because I’m type O, my parents should be safe because they aren’t quite into the most at risk range yet!  Blah.  Ready for it to be over already.

This situation sucks.  I don’t want anyone to have to deal with this.  I just hope it’s a wake up call for all of us.  Not just in emergency preparedness on a national and personal level, but in that we are all starting to get a little stir crazy and I hope we can realize that it isn’t material surroundings that make life worth living, but community with others.  It’s only been less than a month of hunkering down and I’m already excited to just sit at any restaurant and have a good meal and a couple of drinks with my wife, but also with other people in the community in the background.  I’m pretty damn comfortable with hermit life compared to most people, but even I appreciate the vibe a person gets just being around a group of people, even if we don’t personally interact.

I think there will be a somewhat celebratory period after this passes over us but I do hope that those of us who will live through this will remember, for the rest of our lives, the things that make life worth living and stop being dickheads to each other all the time.

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A demographic study of the victims at this stage is useless. Like 100% useless. 
I give you another empirical fact: once intubated duration of procedure 3-4 weeks (median). Average is „only“ 8 days. But average is useless statistic. A 70 year old with Asthma will be dead after 3 days of intubation, a 30 year old with Asthma will fight for 3 weeks. And then die. 
The case explosion in Italy started two weeks ago. Let’s make the same studies end of April. 
 

Anyway, different countries, different risk factors. 
USA: obesity (will be killer no 1)

UK: a bit of obesity and heavy alcohol consumption (which quite negatively effects the immune systems). 
 

Germany: a bit of the above but to a lesser degree, smoking is more prevalent here (like myself jay ;) )

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47 minutes ago, Tywin et al. said:

My throat is killing me. It has gotten so much worse in the last hour. If I feel like this in the morning I'm going to whatever employee health looks like now.

 

All due respect, dude, this is a serious Boy Who Cried Wolf situation.  

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2 minutes ago, Triskele said:

All due respect, dude, this is a serious Boy Who Cried Wolf situation.  

How so? I was the person warning people, and now I can't stop coughing and my throat hurts like hell; I'm going to watch some Tiger King as I sleep, and have a roomie who also works in the medical profession wake me up. The next six hours are mine to rest.

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5 minutes ago, Tywin et al. said:

How so? I was the person warning people, and now I can't stop coughing and my throat hurts like hell; I'm going to watch some Tiger King as I sleep, and have a roomie who also works in the medical profession wake me up. The next six hours are mine to rest.

You're seriosly claiming Tiger King?  Fuck, man.  Not cool to go there.  I'm allowed a response....

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5 hours ago, Lord Varys said:

My girlfriend and I seem to have a good chance that we caught that blasted thing. I had some mild symptoms for a couple of days (a very mild sore throat, a little coughing) but she has been dealing with coughing, sore throat, headaches, and shortness of breath for about a week. No fever though.

To my knowledge here in Germany you are only routinely tested when you are confirmed to have had contact with another infected person (not the case for either of us). If things get worse me might know in a couple of days, I guess.

Uff. Take care! Both of you. We still have twow to discuss! 

In my case I've been feeling dizzy every evening for a while. I blame stress. I got a bad flu mid February and I still haven't fully recovered. 

Btw. What is the treatment for mild cases at home? Same with the flu? Drink lots of liquids, stay warm, paracetamol? Something else?

It would be good to have some guide of things that help to confront the disease and favor better outcomes

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18 hours ago, Arakan said:

Russia acted silently but decisively. The borders to China were closed in January. Screening of visitors from the West early on. Mandatory self-isolation for suspected cases under the threat of severe punishment if self-isolation is broken (5 years prison in Sibiria). Borders to Belorussia closed. IIRC self-quarantine for arrivals from other countries. Of course they do underreport figures. To be expected but they acted swiftly, silently and hard. I expected nothing less to be honest. The Russian authorities esp. MVD is quite paranoid. In this case, it helped. Furthermore the MVD has quite good contact tracing capabilities and it is said (whether true I don’t know) they early on started systematic mass testing (something up to 150k as of beginning of March). This will be regarded as the biggest single failing of all major Western countries. Systematic mass testing early on. Particularly the Italians and Spaniards blew it here. I mean significant testing didn’t start in both countries until the people were already dying in the hundreds. 
 

And mass testing is NOT a primary question of money but preparation. No one in the West was sufficiently prepared. 
 

Germany for example. 
base testing capacity February: 12k/day

testing:

09.-15.03 5k/day 

16.03- 22.03 15k/day 

since 23.03 25k/day. 
 

Now it’s ok but we blew it in the first two March weeks. No excuses possible. Simple underestimating of the transmissibility of the virus. 

Well, the total number of cases case in Russia is still small but increasing fast. Doesn't really look like they have the virus contained. Apparently they are going into lockdown mode, too.

https://www.bbc.com/news/world-europe-52038814

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40 minutes ago, Loge said:

Well, the total number of cases case in Russia is still small but increasing fast. Doesn't really look like they have the virus contained. Apparently they are going into lockdown mode, too.

https://www.bbc.com/news/world-europe-52038814

They react swiftly. And they will succeed. And be it just because no one wants to get in trouble with Russian Police or MVD security. 

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Swiftly and swiftly. The mayor in Moscow was talking about it being much worse than anyone else was willing to admit. Authoritarian governments like Russia and China tend to have this problem.

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