An Engineer's take on testing for Covid-19

[sophiecentaur]

Some governments seem to think that testing for the virus is not central to controlling its effect on the population. So far, nearly all I read about the statistics are based on people who actually present with the symptoms. If you are not a 'key worker' then tests in the UK are not available until you have 'obvious' symptoms. So what sort of magic is possible with such a limited data set that can yield a conclusion about people's risk of having the virus, having it badly, dying of it, or what long terms effects they can expect?

If an Engineer is presented with a malfunctioning system then the universally accepted way of dealing with it is to MEASURE as much about it as possible and then use those measurements to point to a way of mending it. There are millions of people, by now, who could provide data points for analysis and the future of our economy hangs on a compromise between health risk and loss of GDP. The only weapon we have (if and until there are drugs and vaccines available) is statistics. Each data point must be worth the sort of the (not for profit) cost of a few tens of GBP - a few hours' wages.

The UK government (and others) behave as if they are doing the population a favour by offering tests when it's actually the other way round - if they want to be elected next time round.

 

[BillTre]

I completely agree with your outlook on this.
Testing is critical to a long term solution.

I used to run a research zebrafish facility (~80,000 fish in about 3,000 tanks, on a recirculating water system (once through a tank then through a disinfection treatment (UV))) and helped establish a stock center.
By the time I was in charge of the facility and could do something about it (sound familar?), the fish were widely infected with two different pathogens, a fish mycobacterium (related to but different from tuberculosis) and an intracellular pathogen (Pseudoloma neurophilia).
Fish infected with either of these pathogens can show no symptoms (at least for a while, sound familar?) but still are able to spread pathogens.
In addition, these pathogens are on the high end of UV sensitivity.
There is no useful treatment for infected fish (sound familar?), typically they are just destroyed (euthanized, we don't do that with people).
These infections are are now largely controlled or getting close to elimination in well run facilities, largely due to careful testing of all the fish (in the family groups they are born in) using PCR tests (run in the research labs) for parts of their genome sequences.
Otherwise, even in the very controlled environment of a high tech research facility, this infection would still be out of control as it had been for 20 or 30 years before we get effective testing down.

Zebrafish facilities have long used an extreme form of quarantining:
new fish are brought into a separate room with a separate water system
the fish are bred and eggs quickly collected and bleached (kills everything on the outside of the egg, (this would kill adults Mr. Trump, but the eggs/embryos don't have gills, so they can survive))
Bleached eggs are transferred to either the main fish facility to grow up (untested entry, not so good) or they are transferred to another separate room for another generation of de-pathgenating quantining (until they test as pathogen free).
The second more stringent version of this also depends upon testing and has worked well when utilized to keep pathogens out.

 

[berkeman]

If an Engineer is presented with a malfunctioning system then the universally accepted way of dealing with it is to MEASURE as much about it as possible and then use those measurements to point to a way of mending it.

And for the Medics, Docs and Nurses involved in all of this, (quality) knowledge is power. Incorrect information is the Devil, and can hurt our patients (Pts).

I was in an EMS briefing Friday where the topic was the various testing modalities currently available and the advantages/disadvantages and false positives/negatives that we are dealing with. The quality of the test is super important at this point, with many (most?) of the tests coming from China not trustworthy at this point.

We discussed the different kinds of tests (Direct, Indirect, PCR [various versions], Lateral Flow Immunoassays and Antigen/Antibody indicators over time [IgM, IgG], various Serological tests, etc.). Wow, this is a very fluid and rapidly evolving bunch of science, and it should keep improving at an increasing pace.

It's good to push for more testing, but it's also good to educate yourself about the various kids of tests, and what they are best used for. It's also good to understand the potential throughput rates for the various tests, to help understand why our triage protocols right now are the way they are.

The good news is that there are improvements on all fronts, with better quality tests and more quantity of tests becoming available, and more and more scientific results coming out to help us understand how best to use the testing.

https://www.goodrx.com/blog/coronavirus-covid-19-testing-updates-methods-cost-availability/

https://en.wikipedia.org/wiki/COVID-19_testing

https://www.cdc.gov/coronavirus/2019-ncov/lab/testing-laboratories.html

 

[hutchphd]

The good news is that there are improvements on all fronts, with better quality tests and more quantity of tests becoming available, and more and more scientific results coming out to help us understand how best to use the testing.

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Having designed and developed several point of care instruments (like glucose meters) I am interested in knowing whether POC instruments are in the mix.
I have designed optical, electrochemical, and lateral flow meters to measure glucose, coagulation, pregnancy, drugs of abuse, and a host of other things. Typically a single-analyte meter can be manufactured for <~$30 provided an appropriate disposable cartridge can exist. They require minimal training and produce consistent and verifiable (certifiable if necessary) results.

Would certainly reduce the trained manpower requirements. Need a good saliva or fingerstick blood test. Anybody doing this actively?

 

[berkeman]

Having designed and developed several point of care instruments (like glucose meters) I am interested in knowing whether POC instruments are in the mix.

Yes, the briefing addressed POC PCR testing, with the main limitation being throughput and test quality.

Would certainly reduce the trained manpower requirements. Need a good saliva or fingerstick blood test. Anybody doing this actively?

Yes, finger sticks are used to acquire the blood sample for the lateral flow ImmunoAssay tests. The main limitations there right now appear to be the quality of the cartridges that are used for the testing, with sub-standard capillary action substrates being a big problem for imported cartridges currently.

 

[hutchphd]

If the lateral flow are dosed with whole blood I think the cells tend to get in the way. Saliva is easier. There are some clever ways to build the blood strips though. I never did the wet stuff much...mostly electro-optics and calibration.
Glad to hear it is in the mix seems to me nearly a requirement to make it work at required scale.

 

[berkeman]

If the lateral flow are dosed with whole blood I think the cells tend to get in the way. Saliva is easier. There are some clever ways to build the blood strips though. I never did the wet stuff much...mostly electro-optics and calibration.
Glad to hear it is in the mix seems to me nearly a requirement to make it work at required scale.

Are the IgM and IgG markers present in saliva for the secondary immunoassay testing? I was under the impression that they were mainly present in serological samples, but I could be wrong. For primary PCR testing for the virus, NP swabs work well of course.

 

[hutchphd]

I was speaking generically about the instrumental reading details. i am painfully ignorant as to the details of the underlying assay and have no idea about immunoglobulin. You are very likely correct.

 

[sophiecentaur]

I only wish that the decision makers who choose a suitable level of testing were as informed about the business as some of the contributors to this thread. How many politicians have a clue about Bayesian Statistics? The risk of false positives and false negatives weighs very heavy and so does limited high profile anecdotal evidence. They "follow the Science" until there's a hint of a possibility of egg on face; then it goes out of the window.

I heard (yet again) on the radio today that there is no testing or even thermal screening for air passengers arriving at London Heathrow. Where does the decision come from to have a more stringent régime when entering a supermarket than when entering the country from any random Covid hotspot?

Very early on, Boris Johnson went on record to warn people (the Nation) that family members will die. No one seems to have dared to repeat that statement but it seems to be the reality. We need to be looking at a (fairly low) percentage of all the population dying from Covid and that needs to get into our culture. A bit of a change from the complacent idea of endlessly increasing expectation of life but humans have managed to accept that over the rest of our history.

It comes down to The Economy vs just one specific aspect of Our Health. That's a false dichotomy because of all the other aspects of Our Health.

 

[Ygggdrasil]

Having designed and developed several point of care instruments (like glucose meters) I am interested in knowing whether POC instruments are in the mix.
I have designed optical, electrochemical, and lateral flow meters to measure glucose, coagulation, pregnancy, drugs of abuse, and a host of other things. Typically a single-analyte meter can be manufactured for <~$30 provided an appropriate disposable cartridge can exist. They require minimal training and produce consistent and verifiable (certifiable if necessary) results.

Would certainly reduce the trained manpower requirements. Need a good saliva or fingerstick blood test. Anybody doing this actively?

A test for viral RNA is very different for a test for blood glucose. Glucose is present in the blood around 4-7 mM. The CDC RT-qPCR test is capable of detecting viral RNA at a limit of detection of ~1 molecule/µL (~1.7e-18 M), about 15 orders of magnitude lower concentration than blood glucose. Even with that sensitivity, there are claims that the CDC test may have a false negative rate ~30%.

Because the virus mainly infects the respiratory pathway, it is unlikely the blood would be a good place to test for viral RNA to catch early signs of infection. However, recent research suggests that testing saliva could be more sensitive than testing nasopharyngeal swabs (the current standard). Blood tests would be appropriate for detecting antibodies against the virus, but because it takes time for the body to develop antibodies against the virus, these types of tests may not be the best for early detection of infection.

Rapid PCR tests (e.g. the Abbott machine), serological tests, or https://www.scientificamerican.com/article/https://www.physicsforums.com/insights/dont-fear-crispr-new-gene-editing-technologies-wont-lead-designer-babies/-gene-editing-may-help-scale-up-coronavirus-testing/ may be best for fast diagnosis of severe symptomatic individuals in emergency rooms, whereas for screening the general population, the RT-qPCR tests may be better suited.

 

[berkeman]

Here is a good summary of considerations for Immunoassay testing for COVID-19 antibodies:

https://www.ucsf.edu/news/2020/04/4...xBDFa2fj0-S3GZfFAWnBS0oOvAqjj6zHGnDONrGH2GAbc

The Promise and Uncertainties of Antibody Testing for Coronavirus

 

[bob012345]

Testing for antibodies is virtually no better than testing if an electron spin is up or down.

 

[DarkMattrHole]

So the first at home Covid test is available. Awesome. I think it should be made available to everyone.

Could a small, inexpensive Covid 'test kit' be created that detects pre-symptomatic Covid in spit? That way more people could add 'spitting' to their morning routine, and they could report when they contract Covid long before they get symptoms. If an early detection spit test could be made as inexpensive as toothpaste i would use it every day. If everyone could use something like that, this virus and future virus' can be spotted upon arrival, and overtaken, not chased around but never caught.

 

[Fervent Freyja]

So the first at home Covid test is available. Awesome. I think it should be made available to everyone.

Could a small, inexpensive Covid 'test kit' be created that detects pre-symptomatic Covid in spit? That way more people could add 'spitting' to their morning routine, and they could report when they contract Covid long before they get symptoms. If an early detection spit test could be made as inexpensive as toothpaste i would use it every day. If everyone could use something like that, this virus and future virus' can be spotted upon arrival, and overtaken, not chased around but never caught.

The issue with using sputum as a source is that many with COVID don’t have a productive cough. It is a better source than the current gold-standard using NP sources.

There are some at-home PCR tests being approved, but those still have to be shipped off to a lab for testing.