Testing, testing...are you positive?

  • 19 May 2020
  • Reading time 13 mins
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Test

Many people are wondering whether they’ve already had the coronavirus (called SARS-CoV-2) having experienced mild or uncertain symptoms. Some even test antibody positive with no symptoms at all. The purpose of knowing, based on the assumption that once you’ve had it you won't get it again and won’t be able to infect others, would mean you’re ‘in the clear’.

This is the domain of antibody testing, based on testing whether your immune system is producing antibody ‘tags’ that identify the virus (called the ‘antigen’) and move in for the attack much earlier, thus making you more or less immune in the future.

TESTING FOR INFECTION

There is another test for whether or not you have an active viral infection, which looks for viral RNA, much like a detective would look for fingerprints. These are called PCR tests (polymerise chain reaction) and involve swabs in the throat where the virus concentration is highest. This kind of test is further supported by spotting early symptoms including a change in temperature. This kind of test is useful during an epidemic to quickly isolate an individual, and in hospital staff with a high viral exposure, but would need to be done frequently. It’s quite accurate, and generally doesn’t give false positives (ie saying you're infected when you’re not) but has quite a high rate of false negatives ie missing an infection in about 30% of people tested. This is partly to do with taking the sample correctly, and processing it correctly and rapidly.

PCR test accuracy is improving. An example of the usefulness of such a test is South Korea, who set up 633 free testing sites, many being drive-throughs, testing over 20,000 people a day with results texted within 24 hours. Out of over 11,000 people infected with the coronavirus they had only 260 deaths (0.2% mortality), compared to the UK with 230,000 cases and over 33,000 deaths (14.4% mortality). If you look at deaths in relation to population, South Korea being 51.6 million and the UK 66.5million the difference is even more striking with 50 deaths per 100,000 in the UK versus 0.5 deaths per 100,000 in Korea.

The value of such ‘infection’ testing is a) in isolating individuals then testing their contacts and doing the same if found to be infected – in other words ‘intelligent lockdown’; and b) treating early and effectively to prevent deaths. But you have to have effective treatment.

South Koreans take a lot of vitamins, especially vitamin C, with 40 per cent of the population supplementing it every day, many at five times the ‘reference nutrient intake’1. They also used it in hospitals. “In my hospital in Daegu, South Korea, all the patients and staff use oral vitamin C.” said Dr Hyoungjoo Shin. “Some people had light fever, headaches and coughs, and those with symptoms received 30 grams of vitamin C intravenously. Some were better in about 2 days, but with most, the symptoms disappeared after one perfusion.”

In the UK we went, rather late in the day, for a) total lockdown and b) ineffective treatment and couldn’t get infection testing together. Anyway, to a large extent we’ve missed that boat. We still have ineffective treatment, and still don't tell those infected to take large amounts of vitamin C, zinc or vitamin D despite clear evidence that this helps prevent conversion to serious infection. The UK are also struggling to making testing available although this is improving.

ANTIBODY TESTING FOR IMMUNITY

Previous flu epidemics fade away with herd immunity when enough people have had it and thus become naturally immune. That’s also the goal of vaccination – to ‘infect’ enough people via a vaccine to get at least 75 per cent of the population making antibodies to supercharge their immune system against the virus should they become exposed to it. The dream here is that there would be a 100% effective antibody test that tells you if you have natural immunity, which is always better than vaccinated immunity. It would also tell if the vaccination had worked in its goal of generating antibodies.

In a high surveillance, well organised and authoritarian world the existence of such tests might even control one’s ability to travel, insisting on a ‘antibody positive passport’ to restrict the spread of the virus, and a recommended or mandatory vaccination for those not antibody positive. PCR infection testing would also allow clusters of infected people to be isolated thus allowing the majority to get on with life.

Even without these authoritarian approaches knowing you were not antibody positive might make you more cautious, for example in social distancing with those at high risk such as an older person with diabetes, and less concerned with those who had already tested positive. There are lots of behavioural consequences if we all knew if we were or weren’t. These are, however, very much dependent on the scale of the risk if you get infected. Eg if COVID-19 turns out not to be potentially fatal for the majority, especially if properly treated, and easily nipped in the bud, for example with high dose vitamin C, then the need for tight control becomes less relevant. According to a recent risk analysis across Europe, the US and Sweden by Professor John Ioannidis from Stanford University, people under 65 years old without underlying predisposing conditions accounted for only 0.7-2.6% of all COVID-19 deaths which equates to the same risk as being killed in a road traffic accident while driving to work2.

The current thinking of the UK government is to copy what worked in China and South Korea (but without the vitamin C because the UK medical profession have a blind spot regarding it and an uncanny ability to ignore the science), and have a tracking app to do a much more personalised ‘lockdown’ but this is only really going to work once we have an accurate and available antibody test, as well as the ability to test for infection with a PCR test.

But just how accurate are these antibody tests and, even if you are producing antibodies, does that mean you won’t get infected again? Let’s explore the second question first since this is both important for those who prove antibody positive and for those contemplating vaccination.

CAN YOU GET REINFECTED?

Both SARS(2003) and COVID-19 are coronaviruses. Those who tested antibody positive for SARS continued to have antibodies years after the infection. A paper published last week in the Journal of the American Medical Association (JAMA)3 says “To date, no human reinfections have been confirmed… There is also no evidence at present that such persons transmitted SARS-CoV-2 to others after they had clinically recovered.” They also refer to a study on 4 rhesus macaques who were infected with SARS-CoV-2, and following recovery did not become reinfected when rechallenged with the same virus 28 days later.4 They conclude that ‘recovery from COVID-19 might confer immunity from reinfection, at least temporarily.’ How long ‘temporarily’ is will emerge with research but it is likely to be at least several months, if not a year or two.

The answer to this important question depends on having sufficient quantity of reliable antibody test results, as well as being certain someone has had COVID-19 which, in turn, depends on a quantity of reliable PCR tests confirming infection. This will become clearer in the months ahead. Also, it may be that people with stronger immune systems, and antibody positive, may rapidly fight off a potential reinfection, compared to those with weaker immune systems, so it may not be a cut and dried answer. What is emerging is clear evidence that you can be exposed to this virus and develop antibodies with no apparent infection.

A study last week in JAMA tested healthcare workers exposed to the virus, many of whom tested antibody positive but at no point had tested positive for viral infection, nor had symptoms.5 A further study in the same issue tested infants born by caesarean to mothers infected with COVID-19 pneumonia. All infants tested negative for viral infection, but positive for anti-corona antibodies6. My Chinese sources told me – that a small percentage of those testing antibody positive had no symptoms and did not transmit infection to others. This, I suggest, is what happens when one’s immune system is working properly.

CONCERNS ABOUT VACCINATION

Whatever the answer developing natural immunity is always better than vaccination. In the vaccine world ‘live attenuated’ vaccines that introduce the infection, but at a lesser severity, always work better, but have worse adverse effects. With every step away from introducing the actual virus adverse effects may be less but so too is the immune system’s antibody response which is how we learn how to fight back fast. The biggest worry with a coronavirus vaccine is that it might backfire. In some other coronavirus-type vaccines, if someone gets a related coronavirus infection after having had COVID-19, or they then get reinfected with COVID-19, they could get a worse reaction, called a ‘cytopathic’ reaction. That’s why the safest way forward would be to not vaccinate those who are antibody positive.

The only argument against this is cost and logistics but this is a small price to pay to increase safety and efficacy. Anyway, we’ll know soon enough as vaccine trials are underway. The Oxford University trial has given half the ‘covid’ vaccine and half a meningitis vaccine as an ‘enhanced’ placebo. The thinking behind this is that vaccines do produce adverse effects, most of which resolve within a week or so of vaccination. The ‘MenACWY’ meningitis vaccine being used as a placebo won’t provide protection against a coronavirus but will induce similar immediate adverse effects and therefore participants won't be able to ‘guess’ whether they are on the real thing, thus keep them ‘blind’.

While this has merit, the flip side of using this aluminium containing vaccine is that it won’t show how safe the covid vaccine actually is, but how safe it is compared to the mengingitis vaccine. Also, adverse effects have to be monitored for at least a year. It should, however, show to what extent it protects against COVID-19 infection or reinfection.

ANTBODY TESTING – IS IT ACCURATE?

Now lets move on to the critical question, which is the accuracy of antibody testing. Before comparing tests we need to understand the difference between sensitivity (and false positives) and specificity (and false negatives) which are the yin and yang of the testing world. Let’s use pregnancy tests as an example.

If you had a test that had 100% specificity that means that if it says you are not pregnant, you aren’t. If it had 90% specificity it means that one in ten told they aren’t pregnant, are actually pregnant (a false negative). On the other hand if the test had 80% sensitivity that means that two in ten people would be told they were pregnant (false positive) when in fact they weren’t. So, using this example of a pregnancy test with 90% specificity and 80% sensitivity, one in ten would be told they weren’t pregnant when they were and two in ten would be told they were pregnant when they weren’t.

Of course, what we want in relation to the coronavirus, and pregnancy, is 100% specificity and sensitivity so there’s no doubt. Most important is specificity eg if it tells you you don't have positive antibodies to the virus you don’t. Then you can choose, for example, whether to be vaccinated or not, if/when a safe and efficacious vaccine comes along.

DIFFERENT KINDS OF TESTS

Without going through all the different kinds of tests most fall into two camps: those, much like a pregnancy test, called an LFIA device (lateral flow immune-assay) and the other, much like a food intolerance test, requires a blood sample that has to be sent to the lab who then perform what’s called a quantitative ELISA IgG analysis. You might have heard of this before because it’s exactly the process that’s used to measure food intolerances by laboratories such as Yorktest.

‘ELISA’ is a well established testing method; ‘quantitative’ means it quantifies the strength of the reaction from low to high – for example, on a food intolerance test you get a red, orange, yellow or green reaction with green meaning no IgG antibodies to that food; ‘IgG’ means Immunoglobulin type-G. This is a kind of antibody your immune system produces, in this case against the SARS-Cov2 virus.

We produce another kind of antibody, IgM, immediately on or after an infection, the amount of which fades away quite rapidly once the infection is over. Think of the ‘M’ as Mop Up. That’s what IgM antibodies do. They mop up everything after an infection, then IgM levels fall away. They are not very specific, much like a cleaner who cleans up mess, but not specifically one kind of mess, in this case the coronavirus. Think of the G in IgG as Gotcha, spotting and attacking SARS-Cov2.

Then our immune systems start producing an increasing amount of IgG antibodies, specific to the virus. About 7 to 14 days after the onset of an infection specific coronavirus IgG antibodies can be detected, and remain detectable for several months.

WHICH IgG TESTS ARE BEST?

Many labs are now working hard to produce commercially available tests with some success. Big companies such as Abbott laboratories in the US, Siemens in Germany, Roche in Switzerland and DiaSorin in Italy are leading the way. The Abbott test has just published a trial showing 100% specificity (eg no false negative results) and 99% sensitivity (eg one in a hundred might be told their antibody positive but not be).7 Roche's antibody test has specificity of 99.8% and sensitivity of 100%, when used on samples taken 14 days after the confirmation of infection. Siemens are also claiming over 99% sensitivity and specificity and DiaSorin 97.6% and 99% respectively. A trial at Oxford University compared the LFIA tests, which ranged from 66 to 88% sensitive so lots of false positives, to ELISA IgG testing which produced 100% sensitivity, so no false positives.8 So the holy grail of testing is moving ever closer. The UK government hasn’t yet decided whose test to use but have approved both the Roche and Abbott test.

Meanwhile, the issue of making all tests standardised and comparable is well under way. The National Institute for Biological Standards and Control (NIBSC) are establishing ‘standards’ that is samples that should produce a negative antibody result, and a low, medium or high antibody positive result to allow all labs to calibrate their tests to.

What hasn’t happened yet, but most likely will do soon, is to adapt these technologies to create fingerprick tests, such as Yorktest use for food intolerance using the same Abbott technology, so one can buy a kit and self test. I’ll let you know as soon as one becomes available, hopefully soon. Meanwhile, if any clinics you use are offering IgG tests using the above technologies, they have high accuracy.

References

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5793278/

Ironically, this use of high dose vitamin C is reported as a dangerous activity!

2. https://www.medrxiv.org/content/10.1101/2020.04.05.20054361v2

3. https://jamanetwork.com/journals/jama/fullarticle/2766097

4. https://www.biorxiv.org/content/10.1101/2020.03.13.990226v2.full

5. https://jamanetwork.com/journals/jama/fullarticle/2766215

6. https://jamanetwork.com/journals/jama/fullarticle/2763854

7. https://jcm.asm.org/content/early/2020/05/07/JCM.00941-20

8. https://www.medrxiv.org/content/10.1101/2020.04.15.20066407v2

FURTHER INFORMATION

Visit Flufighters.net to find out more on Vitamin C and Immunity as lockdown measures relax.

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