Utility of Pan-Family Assays for Rapid Viral Screening: Reducing Delays in Public Health Responses During Pandemics

ABSTRACT

BackgroundThe SARS-CoV-2 pandemic has highlighted deficiencies in the testing capacity of many developed countries during the early stages of emerging pandemics. Here we describe the potential for pan-family viral assays to improve early accessibility of large-scale nucleic acid testing. MethodsCoronaviruses and SARS-CoV-2 were used as a case-study for investigating the utility of pan-family viral assays during the early stages of a novel pandemic. Specificity of a pan-coronavirus (Pan-CoV) assay for viral detection was assessed using the frequency of common human coronavirus (HCoV) species in key populations. A reported Pan-CoV assay was assessed to determine sensitivity to SARS-CoV-2 and 59 other coronavirus species. The resilience of the primer target regions of this assay to mutation was assessed in 8893 high quality SARS-CoV-2 genomes to predict ongoing utility during pandemic progression. FindingsDue to infection with common HCoV species, a Pan-CoV assay would return a false positive for as few as 1% of asymptomatic adults, but up to 30% of immunocompromised patients displaying symptoms of respiratory disease. Two of the four reported pan-coronavirus assays would have identified SARS-CoV-2 and we demonstrate that with small adjustments to the primers, these assays can accommodate novel variation observed in animal coronaviruses. The assay target region of one well established Pan-CoV assay is highly resistant to mutation compared to regions targeted by other widely applied SARS-CoV-2 RT-PCR assays. InterpretationPan-family assays have the potential to greatly assist management of emerging public health emergencies through prioritization of high-resolution testing or isolation measures, despite limitations in test specificity due to cross-reactivity with common pathogens. Targeting highly conserved genomic regions make pan-family assays robust and resilient to mutation of a given virus. This approach may be applicable to other viral families and has utility as part of a strategic stockpile of tests maintained to better contain spread of novel diseases prior to the widespread availability of specific assays.