Preclinical and clinical validation of a novel injected molded swab for molecular assay detection of SARS-CoV-2 virus

Ghezzi, Chiara E.; Hartigan, Devon R; Hardick, Justin; Gore, Rebecca; Adelfio, Miryam; Diaz, Anyelo R; McGuiness, Pamela D; Robinson, Matthew L.; Buchholz, Bryan; Manabe, Yukari C.

doi:10.1101/2021.10.19.21265200

Cited by 1 publication

(4 citation statements)

References 17 publications

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“…Thus, the tissue model would be a great tool to support initial research and development explorations with clinical relevancy for swab design and optimization. Data from clinical trials showed that IM swabs perform similarly to SF swabs and those results are comparable with our findings [3][4][5] . In fact, the IM2 IM swabs had an agreement of 96% with the FLOQ standard flocked swab during their clinical trials 3 , as also supported by our findings with the in vitro tissue model.…”

Section: Discussionsupporting

confidence: 91%

“…Our initial anterior nasal passage model consisted of a silicone tubing lined with a cellulose sponge 5 , with sizes compatible with the human nostril 19,21 . This model was subsequently modified with the proposed 3D-printed tissue model, to replicate the entire structure of the midturbinate and nasopharyngeal walls of the nasal cavity.…”

Section: Discussionmentioning

confidence: 99%

“…Validation for swab prototypes typically requires preclinical testing before transitioning to clinical studies, which can take months to years. To streamline this initial pre-clinical validation process, there is compelling need for the development of an in vitro experimental model that recapitulates physical and structural features of the human nasal cavities to bridge bench-top and clinical studies [5][6][7][8][9][10] . An in vitro nasal model can be efficiently and safely used by stakeholders to perform preclinical evaluations, anticipating device design modifications, before confidently moving to design-lock stage during clinical studies.…”

Section: Text Introductionmentioning

confidence: 99%

“…By solely relying on clinical studies even for pre-clinical validation, the swabs meet a great deal of variability, thus needing to expand participant enrollment, with a significant increase in associated time and costs. Therefore, we hypothesize that the initial validation of swab prototypes on a simplified, reliable, and physiologically relevant nasal tissue model would provide more consistent and reproducible results, allowing investigators to assess swab performance in a time and cost-efficient manner 5,12 .…”

Section: Text Introductionmentioning

confidence: 99%

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In VitroNasal Tissue Model for the Validation of Nasopharyngeal and Mid-turbinate Swabs for SARS-CoV-2 Testing

Hartigan

Adelfio

Shutt

et al. 2021

Preprint

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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.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%