key: cord-0809040-4u11lswg authors: Alemany, Andrea; Millat-Martinez, Pere; Ouchi, Dan; Corbacho-Monné, Marc; Bordoy, Antoni E.; Esteban, Cristina; Hernández, Águeda; Casañ, Cristina; Gonzalez, Victoria; Costes, Gèlia; Capdevila-Jáuregui, Mar; Torrano-Soler, Pamela; José, Alba San; Ara, Jordi; Prat, Núria; Clotet, Bonaventura; Bassat, Quique; Gimenez, Montserrat; Blanco, Ignacio; Baro, Bàrbara; Mitjà, Oriol title: Self-collected mid-nasal swabs and saliva specimens, compared with nasopharyngeal swabs, for SARS-CoV-2 detection in mild COVID-19 patients date: 2021-09-16 journal: J Infect DOI: 10.1016/j.jinf.2021.09.012 sha: 1b6a36ee4eabc3336c7c2549d793723d5b0aea20 doc_id: 809040 cord_uid: 4u11lswg nan The use of self-collected specimens for the screening of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has gained interest as they may facilitate massive screening campaigns. Various authors have reported that mid-nasal swabs 1, 2 and saliva [3] [4] [5] [6] are reliable specimens, alternative to nasopharyngeal swabs, to detect SARS-CoV-2 infections by RT-qPCR, irrespective of the age group tested. 7 Despite drawing consistent conclusions, studies reported heterogeneous results regarding the performance of each type of sample, particularly sensitivity, which strongly depends on the viral load distribution of the investigated population and sample collection protocols. In the case of saliva, discrepancies regarding sensitivity might be even higher due to optimized protocols for RNA extraction adapted to the rheological properties of saliva. 6, 8 Therefore, there is a need for better characterizing-also from a quantitative perspective-the performance of self-collected specimens before using them as an alternative to nasopharyngeal swabs for SARS-CoV-2 screening. In the context of a randomized clinical trial targeting mild COVID-19 patients (NCT04621123), we enrolled 130 adults in a sub-study to directly compare selfcollected mid-nasal swabs and saliva specimens for SARS-CoV-2 detection by RT-qPCR, using nasopharyngeal swabs collected by the study nurses as a reference. Included patients had a mean age of 59 (SD 8.5) and a median of 4 days (95% IC [3] [4] [5] from symptoms onset; 43.2% were females. Patients received written instructions to self-collect a mid-nasal swab from both nostrils by introducing the swab 2-3 cm and rotating during 5 sec, and 1 mL of saliva by spitting inside the funnel of a collection device (DANASALIVA™ sample collection kit). Participants were advised to avoid eating, drinking, smoking, and brushing their teeth within 30 minutes prior to sample collection. Self-collection was done in the presence of a study nurse, although they did not intervene during the collection process. Next, the study nurse collected a nasopharyngeal swab from both nostrils. Swab specimens were placed into sterile tubes containing viral transport media (DeltaSwab Virus). Saliva was mixed with 1 mL of saliva preservation solution in the collection device, following manufacturer's instructions. No additional pre-treatment step potentially increasing saliva sensitivity 6, 8 was used before RNA extraction. All three specimens were transported to the Figure 1B) . As expected, the mean viral load was lower at day 7 than at baseline (p < 0.001). Compared to nasopharyngeal swabs, self-collected mid-nasal swabs and saliva specimens showed a sensitivity of 72.8% (67/92) and 42.4% (39/92), respectively, suggesting poorer performance at low viral loads. Of note, most negative self-collected samples with a positive paired nasopharyngeal swab yielded Ct values above 30 (92% and 52% of the nasal and saliva specimens, respectively). The viral load correlation with nasopharyngeal swab was poor for saliva specimens (R=0.3; p = 0.003) and moderate for mid-nasal swabs (R=0.67; p < 0.001) ( Figure 2B ). In summary, our findings show that self-collected mid-nasal swabs have better performance than saliva for detecting SARS-CoV-2 when compared with the goldstandard nasopharyngeal swabs. Of note, the sensitivity of saliva was remarkably high in samples with higher viral load, despite not using any of the RNA extraction protocols adapted to the rheological properties of this sample. Considering that respiratory specimens with Ct above 33-34 are unlikely to be contagious, 9 our finding indicates that saliva would be sensitive enough to identify individuals at risk of transmission. Furthermore, the enhanced sensitivity achieved with adapted protocols for RNA extraction from saliva suggests that this might be the sample of choice for systematic screenings in settings in which a specific laboratory pathway can be implemented (e.g., Comparison of Unsupervised Home Self-collected Midnasal Swabs with Clinician-Collected Nasopharyngeal Swabs for Detection of SARS-CoV-2 Infection Self-Collected Oral Fluid and Nasal Swabs Demonstrate Comparable Sensitivity to Clinician Collected Nasopharyngeal Swabs for Coronavirus Disease Detection Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19 . The COVID-19 resource centre is hosted on Elsevier Connect , the company ' s public news and information Viral dynamics of SARS-CoV-2 in saliva from infected patients Comparison of saliva and nasopharyngeal swab SARS-CoV-2 RT-qPCR testing in a community setting Saliva or nasopharyngeal swab specimens for detection of SARS-CoV-2 Validation and implementation of a direct RT-qPCR method for rapid screening of SARS-CoV-2 infection by using non-invasive saliva samples Turbinate Nasal Swabs and Saliva for Detection of SARS-CoV-2 RNA Viral RNA load as determined by cell culture as a management tool for discharge of SARS-CoV-2 patients from infectious disease wards We thank Gerard Carot-Sans for providing medical writing support with manuscript preparation and Roser Escrig for her support in the study design and medical writing assistance with the study documentation. We also thank Laia Bertran, Mireia Clua, Jordi The study was conducted according to the Helsinki Declaration of the World Medical Association. The study protocol was approved by the Ethics Committee at Hospital Germans Trias i Pujol (number PI 20-313) and the institutional review boards of participating centers. All patients provided written informed consent before enrolling the study, which was supervised by an independent data and safety monitoring board.