Antibody testing key to assessing spread of Covid-19 in population

There are two critical phases to global efforts against Covid-19; flattening the curve as cases ratchet up, and then re-emerging from lockdown gradually once an infection peak has been negotiated.

The differing strategies in each scenario are informed by two separate tests: the first is a basic test to find presence of the virus; the second is to detect antibodies in the immune system indicating infection has passed. The former requires lab capacity; the latter is simple and quick.

As the current pandemic unfolds, antibody tests assume greater importance amid the considerable risk the coronavirus might return with vengeance in the absence of a vaccine.

Scientists need to determine as quickly as possible where and when new cases are emerging. Equally important is to pinpoint individuals who have already been infected, in some cases without realising it. Both cohorts are critical to understanding the virus’s behaviour – especially its spread over time.

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To locate the first cohort, the newly infected, a polymerase chain reaction (PCR) swab test is used . To identify the second, a blood test for antibodies generated in response to infection is used; ideally those tested should at that point be immune.

As the virus continues its spread, rolling out an effective antibody test would create more certainty about where we stand and further measures that need to be taken to limit spread. But that option is not across the line yet.

In the UK, prime minister Boris Johnson hailed antibody test kits as "a game changer" as his government bought 17.5 million of them. He has since been forced into admitting none of them work well enough to be used.

His ministers had high hopes they would give a much clearer picture about how many people had been infected, paving the way for easing of restrictions.

They wanted to send out finger-prick testing kits for use at home, though the medical community had reservations.

Many Covid-19 antibody tests on the market claim high accuracy, yet they were developed in a matter of months, with accuracy rates based on only a few hundred samples.

The hard reality is that neither virus nor antibody tests are totally reliable and an inaccurate test would be worse than no test at all.

So health worker protection is really difficult. With a viral swab, it could be a “false negative”, when you cannot be certain they don’t have the infection brewing.

False positives

Meanwhile, if a person had an antibody test which tests as a “false positive” – meaning the test is picking up antibodies to other viruses – they cannot be certain they are immune. People will go to work with false confidence.

Most immunity tests may not come on stream because their “specificity” for Covid-19 is probably not good enough, though UK company Mologic predicts its 10-minute test will clear validation by June.

More than 60 antibody test kits have been developed globally, "but to my knowledge none have been properly tested," says Dr Derek Doherty of TCD School of Medicine. There is a risk, for example, they cross-react with other harmless coronaviruses out there and generate false positives.

That said, he has no doubt Ireland has the capacity and expertise to test kits and lead in getting a validated test over the line. TCD is proposing to test many kits "to come up with the one with the best results" and to make their own kit in a project subject to funding. He estimates this will be starting within the month.

Lockdown is not going to affect this, while TCD has the patients and blood samples to work quickly. Antibody testing will be a critical part of the next phase, but not the only one, he believes. This is because of the possibility that antibodies might not provide protection, or that it dissipates over time. In that case “T cells” activated to fight an invading pathogen might come into the picture.

Dr Doherty believes some form of “immunity passport” will be needed as lockdown is eased. He concedes it would be a logistical nightmare but necessary to ensure lifting of restrictions in a systemic way – who can go where and when, based on reliable test results.

The alternative is saying everybody is free to go with inevitable risk they will be exposed to the virus.

Testing people for antibodies will be "massively important" over the coming weeks and months, according to immunologist Prof Paul Moynagh of Maynooth University. "The antibody test can tell whether you have ever been infected with this virus. This means that even if you have cleared the virus, we can still tell if you once had it."

For such testing to be effective, it will need to be carried out at scale and at speed, says Prof Moynagh, with a test that can specifically determine whether someone has been exposed to the virus known medically as SARS-CoV-2.

“It is possible to carry out antibody testing at scale in labs, because many hospital labs have the requisite equipment, and large numbers of blood samples can often be put through quickly,” he said.

“But we need to ensure that any tests we use are specific for antibodies against this particular virus. Many of us will have antibodies against, for example, other coronaviruses that cause the common cold. So it is important that the tests we use are well validated for being specific for SARS-CoV-2.”

Having robust information about the levels of antibodies in the population would help to predict the path of the pandemic, and could also help to identify who is at lower or higher risk of infection.

A clear picture of the level of immunity in the population will be essential to formulating an exit strategy out of the current lockdown, Prof Moynagh said. “If someone has made antibodies against this virus in their blood, we can’t say for sure that they won’t be infected again, but the evidence so far suggests the antibodies that our bodies make to this virus can neutralise it, so the likelihood is that if you have antibodies you have some immunity to it.”

The Health Service Executive said antibody testing is not currently a priority, though “the evidence for such technologies are continuously under review”.

“The antibody response is often not detectable at onset of symptoms and may take up to 10 days after onset of symptoms to be detectable in some patients. Thus antibody testing has significant limitations for early detection of Covid-19,” it said.