Evaluation of a Screening Program for SARS-CoV-2 Infection in the General Population Based on the Use of New Detection Approaches or for Diagnostic Orientation on Saliva

COVID-19 Clinical Trial

— SALICOV  

Official title:

Evaluation of a Screening Program for SARS-CoV-2 Infection in the General Population Based on the Use of New Detection Approaches or for Diagnostic Orientation on Saliva (COVID-19)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04578509
• Other study ID #: APHP200960
• Secondary ID: 2020-A02431-38
• Status: Completed
• Start date: October 19, 2020
• Est. completion date: June 9, 2021

Study information

• Verified date: October 2022
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The investigators hypothesize that detection of SARS-CoV2 on saliva samples will increase the performance of the screening program compared to the reference strategy (RT-PCR on a nasopharyngeal swab).

Description:

Containment of the COVID19 pandemic relies on mass screening to allow rapid identification and isolation of cases to break transmission chains. The reference diagnostic method is based on detection of viral genomes by PCR on a nasopharyngeal swab sample (NPS).

However, the pandemic has generated a very high demand causing a shortage of specific swabs and difficulties in the supply of reagents and consumables. Nasopharyngeal sampling requires skilled personnel, and is sometimes poorly accepted by patients. These issues can reduce the quality of sampling and therefore the sensitivity of the test. This strategy also requires sending samples to specialized laboratories, generating a delay in providing results.

New diagnostic approaches on saliva samples are being developed allowing 1) an easier sampling procedure and 2) a diagnostic technique that can be performed in point-of-care.

Previous evaluations suggest that these approaches have a lower sensitivity than the reference strategy (PCR on NPS), around 50 to 90% depending on the technique used.

Despite lower sensitivity compared to the reference strategy, the investigators hypothesize that detection of SARS-CoV2 on saliva samples will improve the performance of the screening program by considerably increasing the number of individuals tested in shorter times.

The main objective of the study is to evaluate, for the detection of SARS-CoV-2 infection, the performance of various alternative virological diagnostic strategies on saliva samples, in comparison with the reference technique (RT-PCR on NPS).

The primary endpoint of the study is positivity of the standard technique (RT-PCR on NPS) for the SARS-CoV-2 virus. The result of the alternative strategies on a saliva sample will be considered as positive or negative according to criteria specific to each of them and compared to the result of the reference technique to estimate their respective sensitivity.

The secondary objectives are to compare the diagnostic performances of RT-PCR on saliva versus RT-PCR on NPS, the diagnostic performances of alternative techniques on saliva versus RT-PCR on saliva, to evaluate the acceptability of the saliva self-sampling and the cost-effectiveness of new diagnostic strategies compared to the reference technique.

The study will include adults and children in whom a NPS is performed for SARS-CoV-2 screening. After informed consent, participants will be asked to provide a saliva sample before nasopharyngeal sampling. Both samples will be analyzed in parallel. The analytical performance of each technique will be assessed, centrally or delocalised, depending on the feasibility of the techniques and according to the advice of the scientific board. The analyzes will be carried out by a team of technicians specifically recruited for the study. All samples collected will be stored in a centralized in a biobank.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5197
• Est. completion date: June 9, 2021
• Est. primary completion date: June 9, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Adult or child subject able to receive nasopharyngeal swab, regardless of age

• Subject in whom nasopharyngeal swab is performed for detection of SARS-CoV-2 as part of the screening system managed by APHP

• Subject or parent not opposed to saliva sampling and data collection as part of this research

Exclusion Criteria:

• None

Related Conditions & MeSH terms

• Communicable Diseases
• COVID-19
• Infections
• SARS-CoV-2 Infection

Intervention

Diagnostic Test:
• Nasopharyngeal swab
Research of SARS-CoV-2 infection in nasopharyngeal swab by RT-PCR and by antigenic test
• Saliva sample
Research of SARS-CoV-2 infection in saliva samples by RT-PCR and by new detection approach
• axillary sweat sample
Research of volatile olfactory compounds of SARS-CoV-2 infection by canine detection on axillary sweat.

Other:
• Data collection
Demographics, symptoms, medical history, acceptability of specimen, consumption in precedents hours are collected

Locations

Country	Name	City	State
France	SARS-CoV-2 screening device of Assistance Publique des Hôpitaux de Paris (AP-HP)	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

References & Publications (17)

Angle C, Waggoner LP, Ferrando A, Haney P, Passler T. Canine Detection of the Volatilome: A Review of Implications for Pathogen and Disease Detection. Front Vet Sci. 2016 Jun 24;3:47. doi: 10.3389/fvets.2016.00047. eCollection 2016. — View Citation

Azzi L, Baj A, Alberio T, Lualdi M, Veronesi G, Carcano G, Ageno W, Gambarini C, Maffioli L, Saverio SD, Gasperina DD, Genoni AP, Premi E, Donati S, Azzolini C, Grandi AM, Dentali F, Tangianu F, Sessa F, Maurino V, Tettamanti L, Siracusa C, Vigezzi A, Monti E, Iori V, Iovino D, Ietto G; ASST dei Sette Laghi Rapid Salivary Test Nurse staff Research Group, Grossi PA, Tagliabue A, Fasano M. Rapid Salivary Test suitable for a mass screening program to detect SARS-CoV-2: A diagnostic accuracy study. J Infect. 2020 Sep;81(3):e75-e78. doi: 10.1016/j.jinf.2020.06.042. Epub 2020 Jun 21. — View Citation

Chen JH, Yip CC, Poon RW, Chan KH, Cheng VC, Hung IF, Chan JF, Yuen KY, To KK. Evaluating the use of posterior oropharyngeal saliva in a point-of-care assay for the detection of SARS-CoV-2. Emerg Microbes Infect. 2020 Dec;9(1):1356-1359. doi: 10.1080/22221751.2020.1775133. — View Citation

Grandjean D, Sarkis R, Lecoq-Julien C, Benard A, Roger V, Levesque E, Bernes-Luciani E, Maestracci B, Morvan P, Gully E, Berceau-Falancourt D, Haufstater P, Herin G, Cabrera J, Muzzin Q, Gallet C, Bacqué H, Broc JM, Thomas L, Lichaa A, Moujaes G, Saliba M, Kuhn A, Galey M, Berthail B, Lapeyre L, Capelli A, Renault S, Bachir K, Kovinger A, Comas E, Stainmesse A, Etienne E, Voeltzel S, Mansouri S, Berceau-Falancourt M, Dami A, Charlet L, Ruau E, Issa M, Grenet C, Billy C, Tourtier JP, Desquilbet L. Can the detection dog alert on COVID-19 positive persons by sniffing axillary sweat samples? A proof-of-concept study. PLoS One. 2020 Dec 10;15(12):e0243122. doi: 10.1371/journal.pone.0243122. eCollection 2020. — View Citation

Jamal AJ, Mozafarihashjin M, Coomes E, Powis J, Li AX, Paterson A, Anceva-Sami S, Barati S, Crowl G, Faheem A, Farooqi L, Khan S, Prost K, Poutanen S, Taylor M, Yip L, Zhong XZ, McGeer AJ, Mubareka S; Toronto Invasive Bacterial Diseases Network COVID-19 Investigators. Sensitivity of Nasopharyngeal Swabs and Saliva for the Detection of Severe Acute Respiratory Syndrome Coronavirus 2. Clin Infect Dis. 2021 Mar 15;72(6):1064-1066. doi: 10.1093/cid/ciaa848. — View Citation

Jendrny P, Schulz C, Twele F, Meller S, von Köckritz-Blickwede M, Osterhaus ADME, Ebbers J, Pilchová V, Pink I, Welte T, Manns MP, Fathi A, Ernst C, Addo MM, Schalke E, Volk HA. Scent dog identification of samples from COVID-19 patients - a pilot study. BMC Infect Dis. 2020 Jul 23;20(1):536. doi: 10.1186/s12879-020-05281-3. — View Citation

Kernéis S, Elie C, Fourgeaud J, Choupeaux L, Delarue SM, Alby ML, Quentin P, Pavie J, Brazille P, Néré ML, Minier M, Gabassi A, Gibaud A, Gauthier S, Leroy C, Voirin-Mathieu E, Poyart C, Vidaud M, Parfait B, Delaugerre C, Tréluyer JM, LeGoff J. Accuracy o — View Citation

Lai CKC, Chen Z, Lui G, Ling L, Li T, Wong MCS, Ng RWY, Tso EYK, Ho T, Fung KSC, Ng ST, Wong BKC, Boon SS, Hui DSC, Chan PKS. Prospective Study Comparing Deep Throat Saliva With Other Respiratory Tract Specimens in the Diagnosis of Novel Coronavirus Disease 2019. J Infect Dis. 2020 Oct 13;222(10):1612-1619. doi: 10.1093/infdis/jiaa487. — View Citation

Lambert-Niclot S, Cuffel A, Le Pape S, Vauloup-Fellous C, Morand-Joubert L, Roque-Afonso AM, Le Goff J, Delaugerre C. Evaluation of a Rapid Diagnostic Assay for Detection of SARS-CoV-2 Antigen in Nasopharyngeal Swabs. J Clin Microbiol. 2020 Jul 23;58(8). pii: e00977-20. doi: 10.1128/JCM.00977-20. Print 2020 Jul 23. — View Citation

Landry ML, Criscuolo J, Peaper DR. Challenges in use of saliva for detection of SARS CoV-2 RNA in symptomatic outpatients. J Clin Virol. 2020 Sep;130:104567. doi: 10.1016/j.jcv.2020.104567. Epub 2020 Jul 31. — View Citation

LeGoff J, Kernéis S, Elie C, Mercier-Delarue S, Gastli N, Choupeaux L, Fourgeaud J, Alby ML, Quentin P, Pavie J, Brazille P, Néré ML, Minier M, Gabassi A, Leroy C, Parfait B, Tréluyer JM, Delaugerre C. Evaluation of a saliva molecular point of care for th — View Citation

McCormick-Baw C, Morgan K, Gaffney D, Cazares Y, Jaworski K, Byrd A, Molberg K, Cavuoti D. Saliva as an Alternate Specimen Source for Detection of SARS-CoV-2 in Symptomatic Patients Using Cepheid Xpert Xpress SARS-CoV-2. J Clin Microbiol. 2020 Jul 23;58(8). pii: e01109-20. doi: 10.1128/JCM.01109-20. Print 2020 Jul 23. — View Citation

Migueres M, Mengelle C, Dimeglio C, Didier A, Alvarez M, Delobel P, Mansuy JM, Izopet J. Saliva sampling for diagnosing SARS-CoV-2 infections in symptomatic patients and asymptomatic carriers. J Clin Virol. 2020 Sep;130:104580. doi: 10.1016/j.jcv.2020.104580. Epub 2020 Aug 5. — View Citation

Rao M, Rashid FA, Sabri FSAH, Jamil NN, Zain R, Hashim R, Amran F, Kok HT, Samad MAA, Ahmad N. Comparing Nasopharyngeal Swab and Early Morning Saliva for the Identification of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2021 May 4;72(9):e352-e356. doi: 10.1093/cid/ciaa1156. — View Citation

To KK, Tsang OT, Leung WS, Tam AR, Wu TC, Lung DC, Yip CC, Cai JP, Chan JM, Chik TS, Lau DP, Choi CY, Chen LL, Chan WM, Chan KH, Ip JD, Ng AC, Poon RW, Luo CT, Cheng VC, Chan JF, Hung IF, Chen Z, Chen H, Yuen KY. Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study. Lancet Infect Dis. 2020 May;20(5):565-574. doi: 10.1016/S1473-3099(20)30196-1. Epub 2020 Mar 23. — View Citation

To KK, Tsang OT, Yip CC, Chan KH, Wu TC, Chan JM, Leung WS, Chik TS, Choi CY, Kandamby DH, Lung DC, Tam AR, Poon RW, Fung AY, Hung IF, Cheng VC, Chan JF, Yuen KY. Consistent Detection of 2019 Novel Coronavirus in Saliva. Clin Infect Dis. 2020 Jul 28;71(15):841-843. doi: 10.1093/cid/ciaa149. — View Citation

Williams E, Bond K, Zhang B, Putland M, Williamson DA. Saliva as a Noninvasive Specimen for Detection of SARS-CoV-2. J Clin Microbiol. 2020 Jul 23;58(8). pii: e00776-20. doi: 10.1128/JCM.00776-20. Print 2020 Jul 23. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Positivity of RT-PCR on nasopharyngeal swab for the SARS-CoV-2 virus	RT-PCR on nasopharyngeal is considered as gold standard	At diagnosis
Secondary	Positivity of RT-PCR on saliva sample for the SARS-CoV-2 virus		At diagnosis
Secondary	Positivity of new detection approach on saliva sample for the SARS-CoV-2 virus		At diagnosis
Secondary	Positivity of antigenic test on nasopharyngeal swab for the SARS-CoV-2 virus		At diagnosis
Secondary	Practicability to samples	Number of samples tested in a day for each test	At diagnosis
Secondary	Practicability to premises	Quantity of premises required for each test	At diagnosis
Secondary	Practicability to interpretation	Feasibly Reading and interpretation For each test	At diagnosis
Secondary	Practicability to render time	Render times for each test	At diagnosis
Secondary	IgG Antibody detection in saliva	Research of IgG by ELISA and RDT	At diagnosis
Secondary	IgM Antibody detection in saliva	Research of IgM by ELISA and RDT	At diagnosis
Secondary	IgA Antibody detection in saliva	Research of IgA by ELISA and RDT	At diagnosis
Secondary	Positivity of canine olfactory detection of SARS-CoV-2		At diagnosis
Secondary	Patient tolerance of the salivary self-sampling	Evaluation by questionnaire of the patient tolerance of the salivary self-sampling compared to the nasopharyngeal swab (questions are about pain, discomfort, speed of performance)	At diagnosis
Secondary	Operator tolerance of the salivary self-sampling	Evaluation by questionnaire of the operator tolerance of the salivary self-sampling compared to the nasopharyngeal swab (questions is about pain, discomfort, speed of performance)	At diagnosis
Secondary	Cost of each approach	Including sampling, transport, technique (consumables, reagents, machine), human resources	At diagnosis