Laboratories, IVD vendors get to work on novel coronavirus

Updated Jan 29, 2020
2020 01 27 21 38 4451 Lab 2019 Coronavirus Test 400

The novel 2019 coronavirus originating in the Hubei province in China and spreading to several nations worldwide has put the tools of IVD vendors to work, particularly reverse transcription polymerase chain reaction (RT-PCR) systems and sequencers.

Bruce Carlson of Kalorama Information.Bruce Carlson of Kalorama Information.

The first known cases emerged in December 2019 and were traced to an animal market in Wuhan, China, from patients who are believed to have come in contact with live animals that were infected. Wuhan is a large hub city with a population of 11 million, located 500 miles from Shanghai. At the time of writing, 81 people had died from the virus and 2,700 were infected, with reports changing rapidly. The spread of the disease to other nations including the U.S. is a top story in the news media and, of course, a concern to laboratorians.

The emergence of novel viruses undermines any notion of a known quantity of infectious disease threats and the idea that today's lab menus will remain adequate to test for them. Kalorama Information projects the microbiology lab-based testing market to be worth more than $9 billion, with revenue in the high single digits, which is greater than the 4% of normal testing markets. Swine flu, Ebola, and the Zika virus were reminders that laboratories need to be vigilant and that the IVD test makers must constantly update menus.

RT-PCR the logical test

The new virus -- dubbed 2019-nCoV -- has already been sequenced, and Chinese health authorities have posted the full genome via the Global Initiative on Sharing All Influenza Data (GISAID) portal, which collects information on respiratory diseases. This allowed other researchers to quickly detect the RNA mechanisms of the virus and develop novel detection methods. Using this information, the U.S. Centers for Disease Control and Prevention (CDC) has developed its own RT-PCR test.

Study of the genetic code revealed that the novel betacoronavirus is in the same virus family as SARS-CoV (severe acute respiratory syndrome) and MERS-CoV (Middle East respiratory syndrome); in those diseases, bats were the source. The name coronavirus comes from the virus' crown-shaped appearance when viewed in electron microscopy, and indeed the shape appears to be a significant detail. It is believed that the heavily glycosylated "spike" protein helps it fuse with host cell membranes, which assists the virus in spreading to host cells.

Other enveloping mechanisms help it trick immune defenses. Fortunately, these same mechanisms are also the key for laboratories in finding the virus. The CDC's test and those in development can track these telltale RNA markers to identify a 2019-nCoV case. RT-PCR is the logical test for that purpose due to its speed, sensitivity, and reproducibility and the reduced risk of contamination.

CDC shares testing protocols

At the time of writing, the CDC laboratory in Atlanta was the only U.S. lab indicated to complete viral isolation and perform RT-PCR to diagnose 2019-nCoV; however, the agency has distributed test protocols and plans to make reagents available. For cases of suspected coronavirus in patients having recently traveled to affected regions, the CDC procedures call for the collection of three key specimen types:

  • Lower respiratory, such as sputum
  • Upper respiratory, such as nasopharyngeal swabs
  • Blood

Stool and urine samples should be collected but will merely be stored in case the CDC needs them in the future.

In addition to sending the sample to the central CDC lab to test for coronavirus, government, reference, and hospital labs are still recommended to test for common respiratory pathogens, such as influenza. Labs are to report additional test results to the CDC -- these additional tests may be used to confirm or rule out coronavirus.

Currently, no testing kits specifically for 2019-nCoV are commercially available. On January 23, Altona Diagnostics announced it was in the process of developing a molecular diagnostic assay for detecting 2019-nCoV, in close cooperation with major reference institutes for emerging diseases. Altona Diagnostics was one of the first companies to make reliable molecular diagnostic kits commercially available during outbreaks of SARS-CoV, MERS-CoV, and the Ebola and Zika viruses, among others.

Also, molecular diagnostics maker Co-Diagnostics announced several days ago that it has completed design work for a PCR screening test for the new virus.

Learning from Ebola and Zika

If experiences with the Ebola and Zika viruses are any indication, IVD vendors will be at work modifying test technologies and developing tests for emergency approval.

Roche and Chembio were among vendors to produce emergency use authorization (EUA) tests for Ebola. A number of coronavirus MERS tests are on the market -- including Siemens Fast Track, Seegene Anyplex, Roche LightMix, and Bio-Rad CFX96 -- and the manufacturers are in a good position to adapt their technology for related novel viruses. Abbott Laboratories indicated that it is actively monitoring the 2019-nCoV outbreak in a recent podcast.

Globally, World Health Organization (WHO) guidelines call for PCR testing for broad coronavirus targets and for samples to be sent away and/or sequenced for positive results.

Vendors have been present in the research phase of the identification and characterization of this novel virus. Illumina MiSeq sequencers have been referenced in studies of the virus. RNA extraction kits that could be used to generate highly purified RNA include BioMérieux NucliSens systems, Qiagen's QIAamp viral RNA minikit, and Roche's MagNA instruments. Bio-Rad's Bio-Plex 200 has been used in studies to characterize the effect of coronavirus on the production of cytokines or chemokines in the acute phase of the illness.

HIV treatment regimen deployed

Currently, there is no treatment for 2019-nCoV infection. Pharmaceutical company AbbVie is working on clinical trials to study the effects of its marketed HIV combination regimen of protease inhibitors lopinavir and ritonavir (Aluvia/Kaletra) for a new indication. The combination treatment is designed to stave off viral replication. Vaccines are also in development: Moderna Therapeutics and Inovio Pharmaceuticals are among the companies turning their focus to the emerging virus.

The origin of the virus is still under debate, though a study just published in the Journal of Medical Virology made the case that its protein codes are similar to those of snakes who had eaten infected bats. Snakes were sold in the local seafood market in Wuhan, raising the possibility that this virus may have "jumped" species from bats to snakes. However, how such a transmission would occur has not been confirmed, and further study will be required to interpret these findings.

There is some debate as to whether the danger posed by the virus is overhyped as a result of the media attention, or whether worldwide health authorities are simply introducing the requisite caution for a deadly disease. On one hand, there has been a rapid geographic spread of cases. Also, the viral structure with an unusually long viral RNA genome and suspected homologous recombination mechanism echo severe diseases such as dengue virus or hepatitis C.

On the other hand, the world has seen well-publicized coronavirus incidents before that were ultimately controlled. SARS-CoV, for instance, was first reported in Asia in February 2003. The illness spread to more than two dozen countries in North America, South America, Europe, and Asia and killed 774 people. But it was contained, and since 2004, there have been no known cases of SARS reported anywhere in the world. MERS-CoV continues to be seen due to continued transmission, but it is limited to cases where the disease travels from camels to people and some person-to-person transmission. It's possible that despite all the attention given to it, the new threat could become like these cases.

Testing and laboratory pathology and IVD technologies play a role not only in diagnosing patients and determining treatment but also in answering questions as to the resource allocation of healthcare systems or the proper concern of government policy. The more testing that occurs, the better the true scope of the threat can be assessed.

Bruce Carlson is the publisher of Kalorama Information, part of Science and Medicine Group.

Disclosure: is a sister company of Kalorama Information