Discussion
The present report describes the establishment of a diagnostic workflow for detection of an emerging virus in the absence of physical sources of viral genomic nucleic acid. Effective assay design was enabled by the willingness of scientists from China to share genome information before formal publication, as well as the availability of broad sequence knowledge from ca 15 years of investigation of SARS-related viruses in animal reservoirs. The relative ease with which assays could be designed for this virus, in contrast to SARS-CoV in 2003, proves the huge collective value of descriptive studies of disease ecology and viral genome diversity [8,15-17].
Real-time RT-PCR is widely deployed in diagnostic virology. In the case of a public health emergency, proficient diagnostic laboratories can rely on this robust technology to establish new diagnostic tests within their routine services before pre-formulated assays become available. In addition to information on reagents, oligonucleotides and positive controls, laboratories working under quality control programmes need to rely on documentation of technical qualification of the assay formulation as well as data from external clinical evaluation tests. The provision of control RNA templates has been effectively implemented by the EVAg project that provides virus-related reagents from academic research collections [18]. SARS-CoV RNA was retrievable from EVAg before the present outbreak; specific products such as RNA transcripts for the here-described assays were first retrievable from the EVAg online catalogue on 14 January 2020 (https://www.european-virus-archive.com). Technical qualification data based on cell culture materials and synthetic constructs, as well as results from exclusivity testing on 75 clinical samples, were included in the first version of the diagnostic protocol provided to the WHO on 13 January 2020. Based on efficient collaboration in an informal network of laboratories, these data were augmented within 1 week comprise testing results based on a wide range of respiratory pathogens in clinical samples from natural infections. Comparable evaluation studies during regulatory qualification of in vitro diagnostic assays can take months for organisation, legal implementation and logistics and typically come after the peak of an outbreak has waned. The speed and effectiveness of the present deployment and evaluation effort were enabled by national and European research networks established in response to international health crises in recent years, demonstrating the enormous response capacity that can be released through coordinated action of academic and public laboratories [18-22]. This laboratory capacity not only supports immediate public health interventions but enables sites to enrol patients during rapid clinical research responses.