Emerging Tests: Lab Industry Mobilizes to Develop Coronavirus Detection Test

The global coronavirus (COVID-19) outbreak came without warning and is having a seismic impact on laboratories and the diagnostics business. The imperative for the industry right now is to develop a safe and rapid method of reliably detecting the virus, preferably at the point of care. Here’s a rundown of the progress being made in achieving that objective.

The Central Role of RT-PCR Test Technology

Although much remains to be learned about COVID-19, researchers have noted its similarity to coronaviruses found in bats, including the severe acute respiratory syndrome (SARS) virus. Accordingly, test developers have based tests to detect and confirm the virus on currently existing rapid real-time reverse transcription polymerase chain reaction (RT-PCR) technology. Companies that have previously developed RT-PCR assays for detection of multiple viruses have a head start in bringing a COVID-19 test to market.

RT-PCR is also the technological basis of the lone test currently approved in the U.S. for emergency use to detect COVID-19, the 2019 Real Time RT-PCR Diagnostic Test Panel developed by the U.S. Centers for Disease Control and Prevention (CDC).

Private Sector Initiatives in Asia

Not surprisingly, the most progress has been made in China, Hong Kong, and Southeast Asia where the outbreak began and continues to pose the greatest threat.

The BGI Group Assay

Few private diagnostic companies have played a more direct and active role in COIVD-19 response on the ground in Asia than Chinese genome sequencing company, the BGI Group. BGI and its MGI Tech subsidiary were the first to sequence the 2019-nCoV genome and subsequently developed a real-time fluorescence PCR kit for detecting coronavirus in a few hours. The kit received emergency clearance from China’s National Medical Products Administration (NMPA). In addition to scaling up production of the assay, BGI donated 230,000 kits and opened a medical test laboratory to support COVID-19 response efforts in Wuhan and Hubei Province.

Other private firms that are seeking or have received regulatory approval for COVID-19 detection assays in Asia include:

• Luminex, which is seeking NMPA approval in China for its NxTag Respiratory Pathogen Panel, but only for ruling out COVID-19 infection;
• Kogene Biotech, which received emergency clearance for its 2019 Novel Coronavirus Real-time PCR Kit in Korea; and
• Seegene, which also received emergency clearance in Korea for its Allplex 2019-nCoV Assay.

The Hong Kong Assays

On Jan. 31, the journal Clinical Chemistry published the results of a study by investigators from China and Hong Kong claiming to have developed a pair of assays for rapid identification and confirmation of 2019-nCoV. Using publicly available sequencing information about the virus, the researchers focused on viruses in the sarbecovirus subgroup of betacoronaviruses and developed one-step RT-PCR tests targeting two regions of the viral genome—ORF1b and N. They then evaluated the tests in a panel of negative and positive control samples, including respiratory specimens from patients suspected of having COVID-19 during different stages after the onset of the illness. Each RT-PCR took about an hour and 15 minutes to run.

The researchers found that the assays were sensitive only to sarbecoviruses, with both suspected patients testing positive. They also determined that the N gene assay was 10 times more sensitive than the ORF1b assay in detecting positive samples. Based on these findings, the researchers recommended:

• Using the N gene assay for initial COVID-19 testing;
• Using the ORF1b assay if the patient tests positive to confirm the result; and
• Follow up testing by a World Health Organization (WHO) reference laboratory if the first test is positive and the second test is negative.

The PolyU Multiplex Respiratory Screening Panel

Less than a week after publication of the Clinical Chemistry RT-PCR tests study, scientists from The Hong Kong Polytechnic University (PolyU) announced that they have developed a comprehensive panel capable of detecting 30 to 40 respiratory infectious disease pathogens, including COVID-19, in less than an hour via a single test. Incorporating polymerase chain reaction technology into the diagnostic system allows the device to be fully automated from sample nucleic acid extraction and amplification to signal detection and analysis to achieve point-of-care capability. The system does not require manual interaction across the testing process.

Chips and Apps

Response has also extended to mobile point-of-care test lab-on-chip solutions that can diagnose pathogens via an end user’s cell phone. One of the first applications of this technology to COVID-19 came on Jan. 24 when Singapore biotech firm Veredus Laboratories announced plans for a February 1 commercial launch of a kit capable of detecting the coronavirus with “high specificity and sensitivity.” The VereCoV kit is based on lab-on-chip technology which integrates two molecular biological applications, polymerase chain reaction and microarray. This is the same application that Veredus, which is currently owned by Japanese plastics giant Sekisui Chemicals, has used to create kits for detecting the Mers, Zika, Dengue and H1N1 viruses. The company claims the new kit can detect, differentiate and identify all three coronaviruses in a single test in about two hours.

The Private Sector Response in Europe

Although East and Southeast Asia have been the center of activity, scientists, public health laboratories and commercial test makers in the U.S., Europe and other regions affected by the outbreak are also working furiously to develop and secure expedited emergency regulatory approval for new experimental COVID-19 detection tests.

The first private sector company to gain approval for a COVID-19 to gain test in Europe is Primerdesign, the molecular division of Novacyt. On February 17, just two weeks after launching a research-use-only coronavirus test, Novacyt announced that it had received CE marking for a commercial molecular COVID-19 test. The Paris-based firm is also seeking FDA EUA authorization in the U.S.

On Feb. 24, U.S. firm Co-Diagnostics announced that it has received CE-IVD marking for its Logix Smart Coronavirus COVID-19 test. The reverse-transcriptase quantitative PCR assay uses proprietary Co-Primer technology that the company claims can improve test specificity, reducing the likelihood of a false positive. “We look forward to scaling up production to meet global demand with this regulatory clearance in place, and to obtaining approvals from other bodies that will allow us to further increase the reach of this invaluable diagnostic tool,” noted Dwight Egan, CEO of the Utah-based company, whose stock shout up nearly 30% to $3.93 on the day CE-IVD approval was announced.

Meanwhile, the pioneering BGI Group has teamed with Curetis Group company Ares Genetics to make its COVID-19 molecular tests available in Europe. Under the deal, Ares will launch a next-generation sequencing testing service for the virus using BGI reagents and collaborate in the distribution of NGS and PCR testing kits.

The Private Sector Response in the U.S.

In the U.S., the FDA is following the same playbook it used in responding to previous virus outbreaks like SARS and Zika, by calling on diagnostic test sponsors interested in potential EUA for coronavirus detection tests to contact the agency’s Center for Devices and Radiological Health (CDRH) (CDRH-EUA-Templates@fda.hhs.gov) for information and templates. Several firms have announced plans to seek EUA for new coronavirus tests but, as of February 26, the CDC assay remains the only product approved for COVID-19 detection in the U.S.

Private Sector Companies Working on Coronavirus Detection Tests for FDA Emergency Use Authorization

• Cepheid is developing an automated molecular test for use on its GeneXpert Systems to detect the 2019-nCoV strain in around 30 minutes
• Qiagen is developing an expanded version of its QiaStat-Dx Respiratory Panel to include molecular assays for detecting COVID-19 from nasal swabs of symptomatic patients, which it hopes to submit for FDA approval before the end of February
• Finnish company Mobidiag is working on a Novodiag molecular diagnostic test to identify novel coronavirus and other influenza viruses in 30 minutes via its joint venture with Chinese company Autobio Diagnostics
• Hibergene, a Dublin-based medtech company specializing in developing tests for infectious diseases has fast-tracked a new, rapid test for coronavirus that it hopes will be on the market “in months”