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

Abstract

BACKGROUND: COVID-19 has highlighted deficiencies in the testing capacity of many developed countries during the early stages of pandemics. Here we describe a strategy utilizing pan-family viral assays to improve early accessibility of large-scale nucleic acid testing. METHODS: Coronaviruses and SARS-CoV-2 were used as a case-study for assessing utility of pan-family viral assays during the early stages of a novel pandemic. Specificity of a pan-coronavirus (Pan-CoV) assay for a novel pathogen 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 60 reference coronaviruses, including SARS-CoV-2. 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. RESULTS: Due to common HCoV species, a Pan-CoV assay would return false positives for as few as 1% of asymptomatic adults, but up to 30% of immunocompromised patients with respiratory disease. Half of reported Pan-CoV assays identify SARS-CoV-2 and with small adjustments can accommodate diverse variation observed in animal coronaviruses. The target region of one well established Pan-CoV assay is highly resistant to mutation compared to species-specific SARS-CoV-2 RT-PCR assays. CONCLUSIONS: Despite cross-reactivity with common pathogens, pan-family assays may greatly assist management of emerging pandemics through prioritization of high-resolution testing or isolation measures. Targeting highly conserved genomic regions make pan-family assays robust and resilient to mutation. A strategic stockpile of pan-family assays may improve containment of novel diseases prior to the availability of species-specific assays.