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THREAD: ANTIBODY GAME CHANGER TESTS AND DIAGNOSTIC REALITY. Most people don’t understand infectious disease and how ‘tests’ work. Like many things in science they’re not simply black and white things. This thread will explain in simple terms the value of #covid19 tests.
Infectious disease like #COVID19 has four phases: exposure, incubation, disease, resolution. Exposure is when you catch it. With COVID19, it involves coughs, droplets, aerosols and infected surfaces. Incubation is when the virus quietly minds its own business. No symptoms...
... and nothing to detect. Then the virus bursts the banks and floods you with new copies of itself- as many as the stars in the sky. From this point you can start detecting the virus. The most effective way is to look for its genome - a method known as PCR. PCR is best class...
...because it can detect as fe as 3 copies in a sample: 3 pin-sized needles in a barn-sized haystack. If PCR doesn’t see it, nothing will. But PCR doesn’t tell you if the virus is alive: if it can infect. Virus corpses have genomes and you’re looking for genomes.
This means that to test if someone is infectious, you need to be able to grow the virus. This can be quite hit and miss (it’s a bit of an art), it’s dangerous, and takes a lot of time. PCR can be done in minutes - some claim in less than 10 minutes. Cultures take days. PCR...
...can also be done on a smartphone sized device. Cultures cannot, so we go for the next best thing, antibody tests. Many of us recognise them- the pregnancy tests in supermarkets are exactly that. Cheap and cheerful and straightforward. BUT: antibody tests need millions...
...if not billions of copies of virus in a sample to give you a positive result. With PCR you are looking for 3 needles in a barn, with antibody tests you are looking for bales of hay. To put it another way, would you let a shortsighted person drive a supercar without glasses?
No? I didn’t think so either. So between an antibody test and a PCR test trying to detect #covid19, PCR always wins because antibodies will never be as sensitive as PCR. is PCR perfect? Hell no. I’ve tweeted before that nasal swab PCR data for #covid19 show 10-24%...
...false negative according to China data. That’s got to do with how good the sample is. You may find them pins outside the barn if that’s where they are and you look for them in the right place, but toull never find them in the barn unless you step on one by mistake...
...on your way into the barn. You only find what is there in the first place, and you look for it the right way. Moving on; later in the disease your immune response kicks in. Without being too complicated about it, not all of us respond the same way, or as intensely.
But let’s assume we all respond and the antibody test is designed to pick a response up, no matter what (that is doable). Crucially, there is a lag between symptoms and immune response: about a week. So if you are tested in this way during that period there is a risk of a...
...false negative. How bad a risk? Well, compared to PCR (needles vs bales of hay), quite a huge one. The test really works if you’ve gone past the week of symptoms and recovered. THIS IS CRITICAL: China, Korea, Thailand and Singapore put a lid on #COVID19 with PCR tests, ...
...not with Antibody tests for the immune response! The ‘game changer’ claim involves people having recovered and being able to go back to work. Not stopping people from infecting others. Can we say though that an immune response means you are not infectious? NO.
We do not have data proving this to be true for #covid19 with the exception of a study in 4 monkeys who did not get reinfected shortly after clearing the disease. But hang on you say, didn’t the Japanese report patients getting reinfected? No. They reported...
...patients shedding virus- ie producing virus, as measured by PCR. Remember that PCR counts genomes, not live virus, and as far we know genomes do not infect people: live virus does. Washing your hands doesnt destroy the #COVID19 genome, it kills the virus. There is no data...
...yet proving that virus shedding from people recovered from #covid19 is not infectious. Yet the #gamechanger #antibody test claim is supporting the idea of getting people back to work. ON ANOTHER ASSUMPTION. Let’s unpuck the risk here: we know that immune responses to other...
...Coronavirus strains can be forgetful: you can get reinfected, eventually (if you are not a monkey dosed with virus straight after recovery). We also know that many RNA viruses like COVID19 can stealthily hang about making you a risk to others. Cold sores are caused... Herpes virus- not closely related to Coronavirus, but a tricky virus that hides in your nerves and every now and again pops his ugly head up to infect others. You have an immune response to herpes, but it can still infect others, and it hides in your nerves!
Who’s another RNA virus that hides in your nerves? HIV. Again very different to #COVID19 but this stealthiness is what stops current treatments and vaccines for HIV working. Hepatitis C virus hides in your liver - even for decades - but can infect others whilst you happily go...
...about your life (enjoying unprotected sex, or sloppy kisses with a mouth injury, etc.). Hepatitis C is more like Coronavirus than HIV or herpes, it just likes your liver more than your lungs. Do we know all the tissues #COVID19 hides in? NO. Do we know how long it stays...
...around for? NO - Ebola stays in your eyes for months (years?) after you recover. Do we know if #COVID19 will pop out again like herpes or HIV, quietly go about infecting others like hepatitis C, or die away like flu does? NO, NO, NO: yet all the big words and hopes are pegged
...on extrapolations from other viruses like other Coronavirus (4 cause simple colds, MERS and SARS are lethal), like flu (#COVID19 IS. NOT. FLU!!!!) and assumptions on how it will behave. So to close this thread and get back to the business of catching a few Zzz’s befor tomorrow
...PCR will remain best in class so long as virus is there, ie you are infectious, symptomatic, or otherwise recovered and shedding. Antibody tests will never match PCR to #TestTestTest, isolate, contact trace and stop the outbreak, but may have use in letting people back to work
...IF (and we don’t know that yet) it is safe to do so for the rest of the population. THE LATTER IS SPECULATION; THE VALUE OF PCR IN STOPPING #Covid19 TRANSMISSION IS FACT. WE NEED TO FOCUS RESOURCES ON PCR CAPACITY to minimise damage to the economy and then, after we know...
...what recovery means, then help people back to work. I’m not fearmonfering, I’m presenting the gaps in knowledge and the risks inherent to assumptions made at SAGE and Cabinet level that could have long-lasting, crippling effects if not appropriately evaluated.
We can not afford to hope for the best. We can DO our best - and cabinet is now pushing the testing need, finally, but failing to lockdown the country - outdo the rest, and then test those assumptions before making a critical mistake. Now #getonwithit #lockdownuknow
Disclosure: I have no stocks, collaborations, financial interests, direct or indirect, with any diagnostic or research PCR supplier which could benefit me or my research. The breath collector I’m developing works equally well with PCR, antibody tests, cultures. my hypothesis is..
... that #SARSCoV2 is a deep lung pathogen transmitting via aerosols which leave tell tale traces in the nose and that’s why invasive lung samples are more reliable than nasal swabs. If I’m right, my tech is available at cost to LMICs to stop this outbreak, free to all if...
...manufactured under charitable funding. This is no time for money making, its time to save lives. All supporting data will be released directly on twitter over the weekend- since bioRxiv is inundated. Constructive criticism is welcome and sorely needed.
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