Perspectives from the Frontlines of COVID-19 testing: Post-event write-up

Written by:  Shainan Hora

COVID-19 has made an unprecedented impact on the lives of millions worldwide and put to test healthcare systems and biotech resources across many developed countries. Biotech Connection Singapore (BCS) hosted its first webinar on 12^thMay 2020 and had the pleasure to speak with A/Prof Timothy Barkham, Senior Consultant and Clinical Microbiologist from the Department of Laboratory Medicine at Tan Tock Seng Hospital (TTSH). The event, moderated by Dr Natasha Ng, President of BCS, included an hour-long candid conversation about Dr. Barkham’s experience working at the frontlines in the laboratory during the COVID-19 pandemic, and insights on how the healthcare sector can learn from the current outbreak.

The webinar started with Dr. Barkham highlighting the challenges he and his team were facing being on the frontlines from day one. He shared the importance of collaborative work, addressing the right questions and having an experienced team working round-the-clock to deliver the results. He highlighted the ongoing efforts at getting the regulatory approvals when procuring new reagents or instruments for timely detection of COVID-19 infections. “Given the nature of the work in these extraordinary times, a real effort at regulatory harmonization and convergence should be undertaken to avoid delays and to quickly adapt to the process”, advised Dr. Barkham.

Compared to the SARS outbreak of 2003, where ~300 samples per day were tested, his team today is better adept at ramping up due to their maintenance of high standards, decreased test error rate and better preparedness. He proudly credited his team’s readiness with high technical and ethical standards and being effective at getting the task-in-hand done. “The only way you can push things forward is by getting people to use their abilities to help you reach that goal”, said Dr. Barkham. Although the COVID-19 PCR tests are essentially the same across all labs in the world, managing test results can be challenging due to the natural variation in the limit of detection of different assays, as well as the need for careful interpretation of what qualifies as positive and negative. “We don’t want to miss any cases; our approach has prepared us to detect samples with high specificity and sensitivity”, said the expert.

In collaboration with A*STAR’s Dr. Masafumi Inoue and Dr. Sebastian Maurer-Stroh with support from the Diagnostics Development (DxD) Hub, the team developed the Fortitude 2.0 kit that detects the presence of SARS-CoV-2, the virus that causes COVID-19, in patient samples by amplifying unique regions of the viral genome. The primers are designed and modified consequently to detect more than one target site (for extra robustness) as well as to consider mutations on the continuously evolving virus. Dr. Barkham’s team helped optimise the test parameters, created positive control material, and evaluated the kit on clinical samples. “A swab sample received by our lab undergoes a virus-inactivation step at 70 °C, followed by RNA extraction and RT-PCR, with a turn-around time of 6-8 hrs, depending on the work load”, Dr. Barkham shared.

A key aspect of diagnostic testing is to able to address clinically relevant questions. In this outbreak testing is not just confined to people with symptoms. As an infection control measure, all COVID-19 cases are being looked at to help with contact tracing and to complete the epidemiological picture. However, the emphasis on sensitivity or specificity can be different, depending on the use of the results; e.g. “If a test is negative, our current guidelines require a repeat of COVID-19 test after few days if an epidemiological feature connecting the patient to other known cases is established, but if it doesn’t, the test is not repeated. If suspicion of COVID-19 is high in a symptomatic patient, we may test additional samples from different bodily areas, such as stool. However, we must be careful not to be blinded/biased by the outbreak, and to consider other diagnoses/diseases”, said Dr. Barkham. The team is integrating influenza tests with COVID-19 tests, as it seems sensible to test them both if they are circulating. “Since we tend to import influenza cases during the Australian winter season, it will be really interesting to see if our usual influenza peak in June/July happens this year; it may be muted due to social distancing and travel restrictions”.

The event generated a lot of interest and questions amongst almost 150 attendees. Due to time constraint, BCS conducted a special follow-up session with Dr. Barkham to address the remaining questions that was later shared with the attendees. He continued to share his insights and discussed how researchers could help in this hour of need. According to him, developing a direct PCR kit that doesn’t require an RNA extraction step would assist in eliminating a laborious and time-consuming process. Another way would be to find creative ways to evaluate the true COVID-19 disease burden by considering the surveillance and containment measures (or the lack of) in different countries and mining diverse data sets for a comprehensive picture.