Date: 10th April 2020
The ability to carry out serological/antibody testing is considered critical in getting the spread of the coronavirus under control and will allow the world to start relaxing lockdown rules – an absolutely necessity for economic recovery. With the first generation of tests starting to hit the market will these tests deliver?
A serological test, detects the presence (or absence) of antibodies in blood and it can indicate whether a person has been infected by SARS-CoV-2. It offers the advantage that asymptomatic, or mildly-affected people, as well as those who have developed full symptoms, can be tested to discover if they are potentially immune to the virus and therefore less likely to be re-infected. Armed with this information it may allow those with immunity to more safely go back into society and the workplace.
However, an inherent challenge in novel diseases is that early in the emergence of a pathogen, researchers are often unable to obtain blood samples from infected patients. As such the advent of antibody tests often lags behind that of PCR-based diagnostic tests, which we have seen in current COVID-19 pandemic.
With the first wave of serological tests now becoming available for use, they will only make a strategic difference if they are accurate, and fit-for-cause. Herein lies the problem and, with such a rapidly evolving yet embryonic market, many are only just being independently evaluated for the first time. Indeed, whilst many tests look accurate in the confines of small data sets that are typically done in-house, once applied to large data sets accuracy levels can alter.
An additional key to their success will be test availability and having sufficient tests on the market to test such a large volume of the world’s population.
In the US, over 70 test developers have notified the FDA that they have serology tests available for use but have not yet applied for authorisation, so a large part of the market remains unapproved.
However, last week the FDA granted its first emergency use authorisation (EUA) for a rapid antibody blood test for COVID-19, where a lateral flow immunoassay can deliver a reading from blood in 15 minutes. The test, developed by Cellex Inc, US, qualitatively detects IgM and IgG antibodies against SARSCoV-2 in serum, plasma, or venipuncture whole blood from individuals suspected of COVID-19 and it is the first test of its kind to be authorised.
Whilst the expectations for Cellex’s test are high, the route to widespread launch should be met with caution. The FDA has specified that this test should not be used as the sole basis to diagnose or exclude SARS-CoV-2 infection and should be used in conjunction with clinical presentation and the results of other laboratory tests.
However, with so many other tests waiting in the wings in the US, and with more available around the world (there are over 60 CE-marked rapid SARS-CoV-2 antibody tests), it won’t be long before the market becomes flooded and implementing stringent external validations will be crucial.
So with availability now looking promising, the key to success will be accuracy and assessing this is the next big step in the process.
In the UK, the government has stressed that the roll-out of antibody tests, in particular home test kits, will only occur if the tests have been validated and shown to be fit-for-purpose.
The UK government is reportedly working with 9 companies that have coronavirus serological tests. With initial orders of 3.5 million tests, and further provisional orders of 17.5 million tests, a team from Oxford University has been given the task of determining which, if any, are suitable.
The team led by John Bell, have used multiple tests, with a range of convalescent sera, to determine whether they are able to correctly identify both low and high levels of antibodies. Unfortunately so far, however, the team has seen many false negatives (tests where no antibody is detected despite the fact we know it is there) and also false positives. None of the tests they have tried to validate so far have been able to meet the criteria for a good test as agreed with the MHRA (Medicines and Healthcare Products Regulatory Agency).
This is a massive blow to the UK government, and this news is likely to delay the implementation of antibody testing programmes by at least a month. With similar reports of Spanish and German tests also failing, this is becoming a real problem for suppliers, governments and for us.
With the stakes so high for serological tests, it is crucial we validate and confirm accuracy before we rush into their wide-spread use. Whilst, the validation results in the UK are challenging, they are hopefully not indicative of the state of the tests as a whole. The results do however, highlight the importance of relevant due diligence prior to use. With so many available tests to choose from, clinical validation should unearth those that perform well in the not so distant future.
What is clear, is that scientists and companies will continue to work tirelessly to solve these early issues. It is hoped that by working with suppliers both old and new that these first-generation tests can be optimised and improved to deliver fast, accurate results. However, the question still remains as to whether this first wave of tests is meeting needs, only time will tell. With many pinning their hopes for an economic recovery on these tests the pressure is on!