RESUMEN
Large-scale population testing is a key tool to mitigate the spread of respiratory pathogens, as in the current COVID-19 pandemic, where swabs are used to collect samples in the upper airways (e.g. nasopharyngeal and mid-turbinate nasal cavities) for diagnostics. However, the high volume of supplies required to achieve large-scale population testing has posed unprecedented challenges for swab manufacturing and distribution, resulting in a global shortage that has heavily impacted testing capacity world-wide and prompted the development of new swabs suitable for large-scale production. Newly designed swabs require rigorous pre-clinical and clinical validation studies that are costly and time consuming (i.e. months to years long); reducing the risks associated with swab validation is therefore paramount for their rapid deployment. To address these shortages, we developed a 3D-printed tissue model that mimics the nasopharyngeal and mid-turbinate nasal cavities, and we validated its use as a new tool to rapidly test swab performance. In addition to the nasal architecture, the tissue model mimics the soft nasal tissue with a silk-based sponge lining, and the physiological nasal fluid with asymptomatic and symptomatic viscosities of synthetic mucus. We performed several assays comparing standard flocked and injection-molded swabs. We quantified the swab pick-up and release, and determined the effect of viral load and mucus viscosity on swab efficacy by spiking the synthetic mucus with heat-inactivated SARS-CoV-2 virus. By molecular assays, we found that injected molded swabs performed similarly or superiorly in comparison to standard flocked swabs and we underscored a viscosity-dependent difference in cycle threshold values between the asymptomatic and symptomatic mucus for both swabs. To conclude, we developed an in vitro nasal tissue model, that corroborated previous swab performance data from clinical studies, with the potential of providing researchers with a clinically relevant, reproducible, safe, and cost-effective validation tool for the rapid development of newly designed swabs.
RESUMEN
During the COVID-19 public health emergency, many actions have been undertaken to help ensure that patients and health care providers had timely and continued access to high-quality medical devices to respond effectively. The development and validation of new testing supplies and equipment, including collection swab, help expand the availability and capability for various diagnostic, therapeutic, and protective medical devices in high demand during the COVID-19 emergency. Here, we report the validation of a new injection-molded anterior nasal swab, ClearTip, that was experimentally validated in a laboratory setting as well as in independent clinical studies in comparison to gold standard flocked swabs. We have also developed an in vitro anterior nasal tissue model, that offers an efficient and clinically relevant validation tool to replicate with high fidelity the clinical swabbing workflow, while being accessible, safe, reproducible, time and cost effective. ClearTip displayed a greater efficiency of release of inactivated virus in the benchtop model, confirmed by greater ability to report positive samples in a clinical study in comparison to flocked swabs. We also quantified in multi-center pre-clinical and clinical studies the detection of biological materials, as proxy for viral material, that showed a statistically significant difference in one study and a slight reduction in performance in comparison to flocked swabs. Taken together these results underscore the compelling benefits of non-absorbent injected molded anterior nasal swab for COVID-19 detection, comparable to standard flocked swabs. Injection-molded swabs, as ClearTip, could have the potential to support future swab shortage, due to its manufacturing advantages, while offering benefits in comparison to highly absorbent swabs in terms comfort, limited volume collection, and potential multiple usage.