Production and performance assessment of a SARS-CoV-2 biomimetic in a verification program for pandemic readiness

During the early stages of the Covid-19 pandemic in South Africa, one of many challenges included availability of control material proficiency testing programs. Control material utilising live SARS-CoV-2 or RNA extracted from cell culture was either biohazardous and costly, particularly in resource limited settings. Here, we report the development and application of a non-infectious SARS-CoV-2 biomimetic Mycobacterium smegmatis strain that mimics a positive result in the GeneXpert SARS-CoV-2 Xpert Xpress cartridge. Nucleotide sequences located in genes encoding the RNA-dependent RNA polymerase, the nucleocapsid and the envelope proteins were used. The resulting biomimetic was prepared as a Quality Control specimen and distributed to laboratories in South Africa for validation prior to testing of clinical specimens. Between April 2020 and December 2020, a total of 151 instruments were validated to bring Covid-19 mass testing online. These instruments capacitated the country to perform tests in 2532 modules. False negative or false positive findings reflected issues such as workflow/technician error or other related technical issues. This non-infectious, easily scalable control material became available within two months after the start of the pandemic in South Africa and represents a useful approach to consider for other diseases and future pandemics.