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

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.

A Comparison of High-Dose Cytarabine During Induction Versus Consolidation Therapy in Newly Diagnosed AML.

The proportion of patients with acute myeloid leukemia (AML) cured is increased by administering high-dose cytarabine (HiDAC). It remains uncertain whether to administer HiDAC as induction or consolidation, and whether ≥1 cycle of HiDAC is required. Our retrospective study of 416 adult AML patients, excluding good risk cytogenetics, compared a single cycle of HiDAC-based therapy followed by 2 cycles of standard-dose cytarabine (SDAC) (HiDAC induction cohort) with SDAC-based chemotherapy followed by 2 cycles of HiDAC-based chemotherapy (HiDAC consolidation cohort). Complete remission (CR) rate was greater in the HiDAC induction cohort (90% vs 78%, P < 0.01) which did not lead to an improved overall survival (48% vs 43%, P = 0.18) or disease-free survival (DFS) (39% vs 45%, P = 0.95). We noted that, after censoring for allogeneic hematopoetic stem cell transplant (alloHSCT) in CR1, the cumulative incidence of relapse was lower in the HiDAC consolidation cohort in patients with intermediate risk cytogenetics (68% vs 44%, P = 0.01), which lead to a greater DFS (30% vs 47%, P = 0.095). In the patients with adverse risk cytogenetics, the RR was numerically greater in the HiDAC consolidation cohort (52% vs 80%, P = 0.60) which lead to a lower DFS (27% vs 4%, P = 0.11). Our data show that, although the HiDAC induction cohort (1 cycle of HiDAC) achieved a greater CR rate, there were no overall survival differences between the 2 cohorts, and that the HiDAC consolidation cohort (2 cycles of HiDAC) had a lower RR and greater DFS in those patients with intermediate risk cytogenetics who did not undergo alloHSCT in CR1.