We need reliable serological tests to track coronavirus flare-ups. Are they finally here?

After flattening the curve, Australia is now attempting to kick-start the new normal amid persistent low levels of the SARS-CoV-2 coronavirus.
 
To do that, we need to be able to track any emerging clusters. Contact tracing – whether by humans or through the COVIDSafe app – is one tool. 
 
But, until now, we have lacked another puzzle piece – a reliable antibody test.
 
That wait could potentially be over, with encouraging results from new tests developed by major biotech companies.
 
The ability to accurately test people for SARS-CoV-2 antibodies opens up the possibility of detecting hidden clusters and gaining a sense of the true prevalence of the virus – as well as enabling better targeting of control measures. 
 
In a Lancet Infectious Diseases comment, two Johns Hopkins University epidemiologists note that serological analysis ‘can be useful for contact tracing in urban environments and linking clusters of cases retrospectively to delineate transmission chains and ascertain how long transmission has been ongoing or to estimate the proportion of asymptomatic individuals in the population’.
 
These tests have been controversial to date, with Doherty Institute experts cautioning in a recent post-market review that antibody tests are not suitable for diagnosis of acute COVID-19 and have limited clinical utility.
 
Early antibody tests bought in bulk by the Australian Government have been significantly less reliable than claimed in independent testing, according to reports in Nine Newspapers, while the UK Government purchased millions of tests that did not work.
 
Dozens of different antibody tests have been produced since the beginning of the pandemic, but their quality and reliability varies widely, leading GP Dr Wendy Burton to suggest two weeks ago that the chances of a false positive are ‘unacceptably high’.
 
The Therapeutic Goods Administration (TGA) moved to ban serology tests aimed at home use after warnings in March by the Public Health Laboratory Network that the ‘quality and clinical utility of these emerging tests, in the majority of cases, is uncertain’.
 
The TGA is now reviewing all serology-based point-of-care tests for SARS-CoV-2 to ‘verify their ability to detect antibodies to COVID-19’.
 
Newer tests are showing more promise, however, with experts suggesting the new Roche test now approved for use in the UK and the cPass test developed in Singapore may have overcome these issues.
 
The TGA this week approved the use of the Roche test for medical use in Australia, while the cPass test is understood to be undergoing testing at the Doherty Institute.
 
Immunology professor Ian Frazer told newsGP the Roche test has been put through ‘rigorous quality control’ with 99.5% sensitivity and 100% specificity for SARS-CoV-2 antibodies, and has been approved for emergency use by the US Food and Drug Administration.
 
University of Queensland virologist Associate Professor Ian Mackay told newsGP the Roche test is much more reliable than some other lateral flow tests at detecting the presence of the immunoglobulin G antibody.
 
‘[However], it doesn’t seem to specifically determine whether those antibodies are neutralising,’ he said.
 
‘In the early days, knowing this information is important. Later, we may better understand how often neutralising antibodies are produced in a recovering patient.’
 
Associate Professor Mackay said the new cPass test developed by Duke-NUS in Singapore is ‘exciting’ given it is a rapid kit-based test that can specifically identify neutralising antibodies in patients who have been infected with SARS-CoV-2, with results available within one hour.
 
He said the cPass test would be a ‘fantastic addition to the diagnostic armamentarium’.
 
‘Being able to identify these antibodies without reliance on traditional culture-based methods makes for faster, safer testing,’ he said.
 
‘The test identified whether a patient is likely producing not just any old antibodies, but those that can protect them from future disease by binding to and disabling the virus, should the person ever be reinfected.’


Two Johns Hopkins University epidemiologists have noted that serological analysis ‘can be useful for contact tracing in urban environments and linking clusters of cases retrospectively to delineate transmission chains’.

Professor Frazer stressed that even accurate antibody tests are not a standalone response.
 
‘The problem with these tests is that while they might be pretty accurate at telling whether a person has been infected with the SARS-CoV-2 virus in the past, they don’t accurately reflect current infection, [as] the test is negative for the first few days of infection and infectiousness. And they don’t, to our knowledge, predict future immunity against further exposure to the same virus,’ he said.
 
However, the tests may improve the ability to detect hidden clusters of the virus, in combination with testing of sewage and genomic analysis.
 
Researchers from the Doherty Institute and Victorian Infectious Diseases Reference Laboratory this week announced they had used genomic analysis to detect 76 distinct genomic clusters in Victoria, representing 75% of the cases.
 
These include large clusters ‘associated with social venues, healthcare facilities and cruise ships,’ the researchers note in their preprint paper.
 
In a press conference, director of the Microbiological Diagnostic Unit Public Health Laboratory at the Doherty Institute, Professor Ben Howden, said genomic analysis could resolve unknown cases and link them to known clusters.
 
The ability to detect hidden clusters is gaining importance as more evidence comes in suggesting that the SARS-CoV-2 virus relies on super-spreaders for the bulk of its transmission, while many carriers do not transmit the virus at all.
 
Microbiologist and science writer Kai Kupferschmidt notes in Science that SARS-CoV-2 ‘seems especially prone to attacking groups of tightly connected people while sparing others’ – similar to the related coronaviruses that cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS).
 
‘[W]e are certainly seeing a lot of concentrated clusters where a small proportion of people are responsible for a large proportion of infections,’ University of Hong Kong modeller Gabriel Leung told Science.
 
That seems to accord with emerging patterns in Australia, where clusters have popped up in meatworks and aged care facilities even as the virus has been broadly contained.
 
Associate Professor Mark Morgan, Chair of the RACGP Expert Committee – Quality Care (REC–QC), has previously told newsGP a reliable antibody test could be crucial. 
 
‘If GPs were able to identify patients who have protective immunity – either from infection or from future immunisation – this would be game-changing,’ he said.
 
‘Identifying those patients who are at risk of deterioration would be very helpful for GPs who could then proactively follow up at-risk patients more closely. Rural and remote GPs could also have advanced notice of which patients might need emergency transfer.’
 
A TGA spokesperson told newsGP the Doherty Institute is undertaking validation testing of all COVID-19 tests ‘to inform their best use’.
 
‘The TGA is unable to comment on applications currently being considered by the TGA as this information is considered to be commercial-in-confidence,’ the spokesperson said.
 
A Department of Health spokesperson told newsGP choices about which COVID-19 tests to use are made by pathologists and medical laboratory scientists ‘based on workflow and suitability in their medical testing laboratories’.
 
‘The Australian Government is aware of the Singaporean manufactured cPass test as well as the Roche serological test, plus others.’
 
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