Why Are Antibody Tests Failing?

published on July 9, 2020

A few weeks ago I came down with a fever andstarted to feel really achy, kind of flowyI'm feeling a lot better, but I still havethis cough that hasn't totally cleared upOkayDid I have COVID-19?I didn't get tested so I don't know, but ifI did, it might mean that I'm immune, whichmeans I could go to a yoga class, go to thosethree comedy shows that I had tickets to lastmonth or go to the national Arboretum withYuca

She misses it thereAnd not worry about risking my health or thehealth of other peopleIf we could all find out if we fought offCOVID-19 it could mean getting back to normallifeHere's where an antibody test would come inWhat these antibody tests are trying to dois trying to determine if your immune system

Has somehow reacted to the virusThey willThey will show that you were exposed to thevirus long after the viral particles havedisappeared long after your body has clearedthe viral particlesSo what we're essentially trying to do withthese antibody tests is open up a historybook to see whether you've been exposed tothe virus at some time in the past

Here's the thing, although there are now sometests that are showing a lot of promise, ittook us a while to get to this point and thereare still a lot of tests out there that don'tseem to work wellThey're like the reactions teams, animatorsduring quarantineThey make a lot of big claims about what theycan do, but then they don't really delivermuch of anything

So what's the holdup?Why has it been so hard to get a test?That's goodLet's first look at how they're supposed toworkAntibody tests look for antibodies againstSARS-CoV-2, usually in your bloodAntibodies are proteins that your immune systemcreates when you've been exposed to a virus

Or some other foreign invader and then theyhelp your body fight off that invader if youever see it againThe antibodies that most SARS-CoV-2 antibodytests are trying to detect are immunoglobulinM and immunoglobulin G IgM is the first typeof antibody your immune system makes whenyou're fighting a new infectionIgG arrives later when you've cleared or almostcleared an infection and it sticks around

A lot longerYou start the test by adding a few drops ofyour blood to the test stripYour blood starts to move down the strip whereit comes across SARS-CoV-2 antigensAntigens are parts of the virus that yourimmune system might recognize like a pieceof the spike proteinIf you have IgM and IgG antibodies that arespecific to SARS-CoV-2 antigens, they'll bind

To those antigens through hydrogen bonding,London dispersion forces and other chemicalinteractions in the antibody testThe antigens are attached to golden nanoparticles,which will be important in a secondSo the antibody antigen and that gold nanoparticlecontinue to move down the strip until theyreached the M lineThere are actually antibodies on that linethat will bind to any of the IgM in your blood

Sample, but you'll only see IgM specific toSARS-CoV-2 because they have those gold nanoparticlesbound to themAs the gold nanoparticles accumulate, a linewill formA little further down the test strip the samething happens with IgGThere's another antibody that we didn't mentionthat binds at the control line

It shows that your blood sample made it allthe way down the testYou should always get a line thereLet's say this test is 100% accurateYou might see a combo of thingsA line at M and C would mean that you're maybestill fighting off SARS-CoV-2 or you foughtit off more recently

A line at G and C would mean you are at theend of that fight or maybe even fought itoff quite a while agoAnd a line at M, G and C would mean you'resomewhere in betweenJust a line at C would mean that you don'thave any antibodies specific to SARS-CoV-2so you probably weren't exposed to itIt seems straightforward

IshAntibody tests are not some crazy new idea,so why are there so many out there that arenot reliable?That comes down to issues with sensitivityand specificitySome of the tests on the market right noware still only 95% sensitiveThat sounds really good, but it means thatfor 5% of people who do have antibodies, this

Test will tell them that they don't becauseit's not sensitive enough to detect low levelsof antibody that is called a false negativeSo that 5% of people can't go back to visitingfriends or family or getting a haircut assoon as they actually couldFalse negatives, huge bummer, but they'renot putting you or anyone else in dangerFalse positives on the other hand are dangerous

Those come from issues with test specificitySo the SARS-CoV-2 antigens and the test arenot specific enough to only bind to SARS-CoV-2antibodiesThey're binding to other antibodies, yourimmune system made against entirely differentpathogensSo you go out, you meet up with friends thinking,I can't get COVID, I already had it, but in

Actuality you absolutely can get sick andyou can give it to other peopleRight now there are still a bunch of testsfloating around that have a specificity of96% or less96% might sound really good, but let's thinkabout what that meansIf you gave it to a hundred thousand people,4,000 of them would get a false positive andreenter the world

That's 4,000 people who could still get sickand spread it to othersAnd since this virus is incredibly contagious,we might very quickly have a second surgeryof infections on our handsSo yeah, I test with 96% specificity is actuallyreally badAnd to get back to normal life safely, weactually need to testThat's really, really close to a hundred percentspecific and a hundred percent sensitive

Very recently there've been a few tests thathave almost met that requirement, which isgreat newsSo things are headed in the right direction,but even if we got a test that was 100% specificand 100% sensitive tomorrow, there are a coupleother potential problemsFirst, we haven't actually confirmed thathaving these antibodies will prevent you fromgetting sick again, that's a huge questionto tackle and deserves its own separate video

Second problem, even if they do, we don'tknow how long they'll stick around in yourbloodstreamAntibodies against some strains of influenzacan go away after just a few monthsWhereas antibodies against say measles canactually stick around and protect you fordecadesSo the question is where does SARS-CoV-2 fall?

In other words, could I be immune today butthen no longer immune six months from now?The question of how long the antibodies remainin your system is probably going to be oneof the most important mysteries for us tosolve in the in the coming weeks and comingmonths and some information that we do havefrom the previous SARS illnessThe one that struck China and Canada in 2002in 2003 tells us that the antibody responsewe generate is not very strong and not verylong lived

People who fought off the original SARS acouple decades ago showed immunity for aboutthree yearsWill that be the case with this virus?We don't knowSo even if you are immune right now, thatimmunity might not last long to make surewe're all fully safe and protected

We need a vaccine and that's something thatpeople are working onThere is still a bunch of unanswered questionsand scientists are trying to answer them asquickly as possibleNo, there's no amazing test that's just outon store shelves and you can go buy it rightnowDr Kroll says that we should keep an eyeout for tests that had been reviewed and authorized

By the FDAIf you're feeling frustrated, being stuckat home, we totally feel youBut I'm trying to remind myself that thereare so many people out there who are workingtirelessly to try and get us back out in theworld as quickly and as safely as possible

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