No abstract

In general, the most accurate COVID-19 testing is hands-on and uncomfortable, requiring trained staff and a “brain-tickling” nasopharyngeal swab. Saliva would be much easier on both fronts, since patients could collect it themselves, and it is after all just spit.

BackgroundThe continued need for molecular testing for SARS-CoV-2 and potential for self-collected saliva as an alternative to nasopharyngeal (NP) swabs for sample acquisition led us to compare saliva to NP swabs in an outpatient setting, without restrictions to avoid food, drink, smoking, or tooth-brushing.MethodsA total of 385 pairs of NP and saliva specimens were obtained, the majority from individuals presenting for initial evaluation, and were tested on two high-sensitivity RT-PCR platforms: the Abbott m2000 and Abbott Alinity m (both with limits of detection [LoD] of 100 copies of viral RNA/mL).ResultsConcordance between saliva and NP was excellent overall (Cohen’s κ=0.93), for both initial and followup testing, for both platforms, and for specimens treated with guanidinium transport medium as preservative as well as for untreated saliva (κ=0.88-0.95). Viral loads were on average 16x higher in NP specimens than saliva specimens, suggesting that only the relatively small fraction of outpatients (∼8% in this study) who present with very low viral loads (<1,600 copies/mL from NP swabs) would be missed by testing saliva instead of NP swabs, when using sensitive testing platforms. Special attention was necessary to ensure leak-resistant specimen collection and transport.ConclusionsThe advantages of self-collection of saliva, without behavioral restrictions, will likely outweigh a minor potential decrease in clinical sensitivity in individuals less likely to pose an infectious risk to others for many real-world scenarios, especially for initial testing.Key pointsSaliva has comparable sensitivity and specificity to nasopharyngeal swabs for RT-PCR-based COVID-19 testing (concordance, κ=0.93; n=385 participants), albeit with slightly lower recovery of viral RNA. Treatment with a readily available guanidinium preservative within 24 hours of sample collection improves recovery.

The relationship of SARS-CoV-2 antigen testing results, viral load, and viral culture detection remains to be fully defined. Presumptively, viral culture can provide a surrogate measure for infectivity of sampled individuals, and thereby inform how and where to most appropriately deploy available diagnostic testing modalities. We therefore determined the relationship of antigen testing results from three lateral flow and one microfluidics assay to viral culture performed in parallel in 181 nasopharyngeal swab samples positive for SARS-CoV-2. Sample viral loads, determined by RT-qPCR, were distributed across the range of viral load values observed in our testing population. We found that antigen tests were predictive of viral culture positivity, with the LumiraDx method showing enhanced sensitivity (90%; 95% confidence interval (95% CI) 83-94%) compared with the BD Veritor (74%, 95% CI 65-81%), CareStart (74%, 95% CI 65-81%) and Oscar Corona (74%, 95% CI 65-82%) lateral flow antigen tests. Antigen and viral culture positivity were also highly correlated with sample viral load, with areas under the receiver?operator characteristic curves (ROCs) of 0.94-0.97 and 0.92, respectively. In particular, a viral load threshold of 100,000 copies/mL was 95% sensitive (95% CI, 90-98%) and 72% specific (95% CI, 60-81%) for predicting viral culture positivity. Taken together, the detection of SARS-CoV-2 antigen identified highly infectious individuals, some of whom may harbor 10,000-fold more virus in their samples than those with any detectable infectious virus. As such, our data support use of antigen testing in defining infectivity status at the time of sampling.

Candida auris is an emerging multidrug-resistant fungal pathogen that spreads readily in healthcare settings and has caused numerous hospital outbreaks. Very few treatment options exist for C. auris infections. We evaluated the activity of all two-drug combinations of three antifungal agents (amphotericin B, caspofungin, and voriconazole) and two antibacterial agents (minocycline and rifampin) against a collection of 10 C. auris isolates using an automated, inkjet printer-assisted checkerboard array method. Three antibacterial-antifungal combinations (amphotericin B plus rifampin, amphotericin B plus minocycline, and caspofungin plus minocycline) demonstrated synergistic activity by checkerboard array against ≥90% of strains with fractional inhibitory concentration index (FICI) values of 0.094 to 0.5. The two amphotericin B-containing combinations were also synergistic using the time-kill synergy testing method, with up to a 4.99 log 10 decrease in surviving yeast compared to either agent alone. Our results suggest that combinations of antifungal and antibacterial agents may provide a promising avenue for treatment of this multidrug-resistant pathogen.