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Can we improve coronavirus testing? – Expert Q&A

Nearly a million Kiwis have been tested for COVID-19 since January.

While nasal swabs and PCR analysis are currently the standard practice for testing in New Zealand, scientists continue to investigate new types of tests and testing strategies.

The SMC asked experts to comment on the latest COVID-19 testing developments. 

John Mackay, Technical Director at dnature diagnostics & research Ltd, comments:

What new tests are in development?

“New testing procedures are in development – both here in NZ and overseas. Much of the testing development is in faster, decentralised testing methods – that is, tests that can be done outside the clinical laboratory (after appropriate performance is verified). These tests are still detecting the viral RNA but doing it in a smaller format or a single temperature (isothermal) technology.

“Other test developments are using saliva, using a rapid lysis method that greatly speeds up testing. The recent paper from Yale University suggests that this method is as sensitive as the nasopharyngeal swabs but via less invasive methods (and potentially collected by the patient themselves.) Other testing in development is community monitoring via testing wastewater (sewage) for the presence of the COVID virus. ESR has been performing this type of viral work for many years now, testing for norovirus and other easily transmitted viruses. And of course, ‘genomic sequencing’ to help rapidly determine cluster linkages is in everyone’s lexicon these days!”

How is NZ’s testing strategy evolving?

“New Zealand’s testing shows we still have significant untapped capacity, should it be required. Currently we are averaging just over 5,000 tests per day but in mid-August testing was over 20,000 samples per day. The use of pooling (combining several samples into one test, thereby increasing throughput) is a standard method for molecular diagnostics where there is a low disease prevalence and not many positives are expected. If a pooled sample tests negative, then all samples in that pool are considered negative. In the case of a positive results, then the pool must be split apart and the original samples making up that pool are tested to find the positive case. In addition, there is still unused PCR testing capacity that could be used if required.

“The danger in our testing is that as we drop Alert Levels, we drop our alertness – we become complacent. Comparing the daily testing after the latest Auckland Level 3 with testing rates following national lockdown indicates that current testing remains higher than previously, to help ensure there are no unknown cases in the community.”

What is the state of the supply chain for testing resources in NZ?

“Testing reagents for the PCR testing remain in good supply. The strategy of using multiple different testing kits and methods, as well as various testing platforms, helps to mitigate the risk of any one supplier having a stock issue and unable to supply.”

Conflict of interest statement: Mackay is the technical director of dnature, a company that has developed a laboratory kit for COVID diagnostics and received HRC funding to develop rapid decentralised diagnostics.

Dr Joshua Freeman, Clinical Director Microbiology and Virology and Acting Clinical Director Infection Prevention and Control, Canterbury District Health Board, comments:

How is NZ’s testing strategy evolving?

“High volume testing is a cornerstone of the pandemic response. To make it possible, laboratory scientists have been the silent heroes behind the scenes.

“Within just a few weeks, laboratory scientists in NZ not only set up and validated entirely new tests, but somehow found ways to reliably perform those tests thousands of times per day. This is a remarkable achievement but it’s unfortunately been poorly understood and appreciated by the public and politicians. For many months now, laboratory scientists have been working long hours under sustained political pressure and close public scrutiny. The work is gruelling.

“Contrary to popular belief, COVID testing is not fully automated. There are a number of manual steps that have to be repeated up to thousands of times per day. The risks of occupational overuse and burnout among laboratory scientists is very real. This threatens the sustainability of our public health response. For this reason, labs are putting a lot of ongoing work into eliminating manual steps from processing and testing COVID specimens.

What new tests are in development?

“It’s against this background that some of the enthusiasm for saliva testing ought to be examined. From the point of view of those being tested, saliva may certainly have appeal as an alternative to nasopharyngeal swabs, but from a laboratory standpoint, testing of saliva at high volumes isn’t currently viable. Saliva specimens require additional manual steps to homogenise and liquefy the sample. Once homogenised there remains big unanswered questions about whether high volumes of specimens can be reliably processed on the available automated instruments.

“So when comparing the merits of saliva over nasopharyngeal swabs, consideration needs to be given to the implications for our laboratory scientist workforce and realism about what’s practically achievable in the laboratory setting. Saliva may certainly have a niche role as an alternative to nasopharyngeal swabs, but a lot more work’s required before we know whether high volume saliva testing is a realistic option.”

No conflict of interest.

Professor David Murdoch, Clinical Microbiologist and Infectious Diseases Physician, Dean and Head of Campus, University of Otago, Christchurch, Co-Director, One Health Aotearoa, comments:

What new tests are in development?

“An initiative to make available affordable COVID-19 rapid antigen tests to low and middle-income countries was announced by the World Health Organization this week. These tests detect specific proteins (antigens) on the surface of the virus that causes COVID-19. They are attractive because they are easy to use, may not need to be performed in a laboratory, and provide results quickly, e.g. in 15-30 minutes. In comparison, the standard test for COVID-19 (PCR) requires technical expertise, needs to be performed in a laboratory, and provides results with 24 hours.

How is NZ’s testing strategy evolving?

“We first heard about rapid antigen tests for COVID-19 several months ago, so why have we not seen them more widely deployed, including in New Zealand? A major reason has been concern about the accuracy of these tests and, until recently, there were little data on their performance. We now know rapid antigen tests are less sensitive than PCR at detecting cases of COVID-19, and may fail to detect >20% of cases. In other words, they can produce a relatively high proportion of false-negative results. So, in deciding whether to use rapid antigen tests we need to weigh up the benefits of ease of use and rapid turnaround times with knowledge that more cases will be missed than when using PCR.

“There is a valid argument that people who have a positive rapid antigen test are most likely to have high levels of the virus and are more likely to be infectious to others. However, it is still unclear just how confident we can be that a person with a negative rapid antigen test is not infectious.

“In New Zealand, we are still relying on PCR, which is the most accurate COVID-19 test, and are able to do so because we currently have the capacity. However, it would be useful to model potential roles of rapid antigen tests as part of our border security system.”

No conflict of interest.

Dr Joep de Ligt, Lead Bioinformatics & Genomics, ESR, comments:

What are the latest developments in genomic sequencing?

“Many of the cases in managed isolation had very low viral loads, so there is often little RNA for us to work with, and it might be broken up in small pieces. Currently, we are working on a more sensitive assay for these low viral loads (as mentioned by Dr Ashley Bloomfield last week) to more thoroughly investigate cases where we were previously unable to generate a genome. Now that we know what mutations we are looking for (based on the genomes from the community cases), we have designed a more sensitive assay that can work on lower concentrations and shorter pieces of RNA to be used for these situations.”

No conflict of interest.