Hartigan Devon R, Adelfio Miryam, Shutt Molly E, Jones Stephanie M, Patel Shreya, Marchand Joshua T, McGuinness Pamela D, Buchholz Bryan O, Ghezzi Chiara E
medRxiv. 2021 Nov 24:2021.11.22.21266713. doi: 10.1101/2021.11.22.21266713.
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 ( . . 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 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.
大规模人群检测是减轻呼吸道病原体传播的关键工具，就像当前的新冠疫情一样，在疫情中，拭子被用于在上呼吸道（如鼻咽和中鼻甲鼻腔）采集样本进行诊断。然而，实现大规模人群检测所需的大量耗材给拭子的生产和分发带来了前所未有的挑战，导致全球短缺，严重影响了全球的检测能力，并促使人们开发适合大规模生产的新型拭子。新设计的拭子需要进行严格的临床前和临床验证研究，这些研究成本高昂且耗时（数月至数年）；因此，降低与拭子验证相关的风险对于其快速部署至关重要。为了解决这些短缺问题，我们开发了一种3D打印的组织模型，该模型模拟了鼻咽和中鼻甲鼻腔，并且我们验证了其作为快速测试拭子性能的新工具的用途。除了鼻腔结构外，该组织模型还用丝基海绵衬里模拟了柔软的鼻腔组织，并用具有无症状和有症状粘度的合成粘液模拟了生理性鼻腔液。我们进行了多项试验，比较了标准植绒拭子和注塑拭子。我们对拭子的采集和释放进行了量化，并通过向合成粘液中加入热灭活的SARS-CoV-2病毒来确定病毒载量和粘液粘度对拭子功效的影响。通过分子检测，我们发现注塑拭子与标准植绒拭子相比表现相似或更优，并且我们强调了两种拭子在无症状和有症状粘液之间的循环阈值存在粘度依赖性差异。总之，我们开发了一种鼻腔组织模型，该模型证实了先前临床研究中的拭子性能数据，有可能为研究人员提供一种临床相关、可重复、安全且经济高效的验证工具，用于新设计拭子的快速开发。
