SARS-CoV2 (COVID-19) Diagnosis in Human Saliva by MALDI-TOF MS Profiling (CoviDiagMS)

Since March 2020, SARS-CoV2 virus (nCoV19; COVID-19) is considered pandemic. Its high rate of spread and infection in the human population and the lack of effective and validated treatment have led the authorities of several countries to confine their populations to slow the spread of COVID-19. As part of the management of this health crisis, the screening of individuals is essential in order to isolate "infected cases". These screening tests are currently performed on nasopharyngeal swabs using RT-PCR for the detection of viral RNA. Although sensitive and specific, these tests remain relatively long (2-5 hours), expensive and the strong international demand for nucleic extraction kits and enzymes are factors limiting the implementation of widespread screening (problem of supply of swabs, molecular biology consumables).

In order to prevent the risks of a shortage of screening means, we propose to develop an innovative alternative strategy, PCR-free, based on the detection of specific protein signatures in human saliva by MALDI-TOF MS profiling. MALDI-TOF MS profiling is a method used in routine diagnostics by microbiology laboratories for the identification of microorganisms. MALDI-TOF MS profiling has been successfully used to classify individuals according to their infectious status (oral pathologies) based on the analysis of their saliva, but also as a tool for the identification of respiratory viruses from cell culture supernatants. In addition, we have expertise and skills in the field of MALDI-TOF MS profiling and have implemented new strategies to improve the quality of profiles and their analysis, particularly in the context of entomological and vector identification projects. Finally, recent Chinese studies have reported that COVID-19 was detectable in saliva by RT-PCR.

The main objective of this study is to develop a test based on the MALDI-TOF profiling method to detect individuals infected with SARS-CoV2 from saliva sample.

Study Overview

• Status: Completed
• Conditions: SARS-CoV 2
• Intervention / Treatment: Biological: Saliva collection; Other: Clinical assessment

• Study Type: Observational
• Enrollment (Actual): 779

Contacts and Locations

• Study Contact: Name: Lionel ALMERAS, PhD; Email: almeras.lionel@gmail.com
• Study Contact Backup: Name: Emilie JAVELLE, MD; Phone Number: +33 491617459; Email: emilie.javelle@intradef.gouv.fr

Study Locations

• France
  • Marseille, France, 13013
    • Hôpital d'Instruction des Armées Laveran

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The study population consists of patients and caregivers infected and uninfected with CoV2-SARS.

Description

Inclusion Criteria:

• 18 years of age;
• screened for SARS-CoV2 by RT-PCR from a nasopharyngeal swab within 96 hours prior to inclusion.

Exclusion Criteria:

• Patient admitted to intensive care;
• Pregnant woman.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Covid+ hospitalization group; Patients hospitalized with SARS-CoV2 infection	Biological: Saliva collection; Saliva samples are regularly collected over a period of up to 30 consecutive days.; Other: Clinical assessment; The participant's clinical data will be collected regularly over a period of up to 30 consecutive days.
Covid+ outpatient group; Patients or caregivers followed on an outpatient basis for an SARS-CoV2 infection	Biological: Saliva collection; Saliva samples are regularly collected over a period of up to 30 consecutive days.; Other: Clinical assessment; The participant's clinical data will be collected regularly over a period of up to 30 consecutive days.
Covid- group; Caregivers not infected with an SARS-CoV2	Biological: Saliva collection; Saliva samples are regularly collected over a period of up to 30 consecutive days.; Other: Clinical assessment; The participant's clinical data will be collected regularly over a period of up to 30 consecutive days.
Non-SARS pathology group; Individuals not infected with SARS-CoV2 but with another acute and/or infectious non-SARS pathology	Biological: Saliva collection; Saliva samples are regularly collected over a period of up to 30 consecutive days.; Other: Clinical assessment; The participant's clinical data will be collected regularly over a period of up to 30 consecutive days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Development of a test based on the MALDI-TOF profiling method to detect individuals infected with SARS-CoV2 from saliva sample.	The development of this test is based on machine learning techniques, which involve "training" a mathematical model, in which the results of the mass spectrometry analysis of saliva samples and clinical data will be used to determine the information needed to distinguish a saliva sample from a SARS-CoV2-infected participant from a healthy saliva sample.	Day 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of correct classification by the test (MALDI-TOF MS profiling) from saliva sample	For each saliva sample, the status ("correct" or "incorrect") of the classification of the sample ("infected" or "not infected") by the test (MALDI-TOF MS profiling) will be determined. Then the rate of correct classification will be calculated. The test will be considered efficient when it has reached a correct classification rate of more than 95%.	Day 30
Rate of correct classification by RT-PCR from saliva sample	For each saliva sample, the status ("correct" or "incorrect") of the classification of the sample ("infected" or "not infected") by RT-PCR will be determined. Then the rate of correct classification by RT-PCR will be calculated.	Day 30
Identification of proteins specific to the SARS-CoV2 infection	On each saliva sample, the expression of proteins will be determined using mass spectrometry. By comparison between SARS-CoV2 infected saliva samples and non-infected saliva samples, the presence of proteins that are specifically expressed in SARS-CoV2 infected saliva samples will be determined.	Day 30
Presence of a positive anti-SARS-CoV2 antibody response by RT-PCR	On each SARS-CoV2 infected saliva sample, the presence of anti-SARS-CoV2 antibodies, by RT-PCR, will be determined.	Day 30
Correlation between the identified protein markers and the clinical course of the participants.	In SARS-CoV2 infected participants (Covid+ hospitalization group and Covid+ outpatient group), the presence of a correlation between the presence of proteins specific to the SARS-CoV2 infection and the clinical evolution of patients will be determined.	Day 30

Collaborators and Investigators

• Sponsor: Direction Centrale du Service de Santé des Armées

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2020
• Primary Completion (Actual): August 13, 2021
• Study Completion (Actual): August 13, 2021

Study Registration Dates

• First Submitted: July 6, 2020
• First Submitted That Met QC Criteria: July 6, 2020
• First Posted (Actual): July 7, 2020

Study Record Updates

• Last Update Posted (Actual): September 6, 2023
• Last Update Submitted That Met QC Criteria: September 4, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: MALDI-TOF MS
• Other Study ID Numbers: 2020-COVID19-15; 2020-A01249-30 (Other Identifier: IDRCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No