A diagnostic study comparing different tests for the diagnosis of COVID-19

ISRCTN	ISRCTN13990999
DOI	https://doi.org/10.1186/ISRCTN13990999
ClinicalTrials.gov (NCT)	Nil known
Clinical Trials Information System (CTIS)	Nil known
Protocol serial number	Nil known
Sponsor	IRCCS Sacro Cuore Don Calabria hospital
Funder	Ministero della Salute

Submission date: 23/06/2020
Registration date: 24/06/2020
Last edited: 17/03/2021

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Respiratory

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
COVID-19 is a condition caused by the coronavirus (called SARS-CoV-2) that was first identified in late 2019. This virus can infect the respiratory (breathing) system. Some people do not have symptoms but can carry the virus and pass it on to others. People who have developed the condition may develop a fever and/or a continuous cough among other symptoms. This can develop into pneumonia. Pneumonia is a chest infection where the small air pockets of the lungs, called alveoli, fill with liquid and make it more difficult to breathe.

Italy has been one of the most affected countries in Europe. The virus has posed an extremely difficult challenge for health units and health workers. Reliable and fast tests for diagnosis at the Emergency room level are of the highest importance. The aim of this study is to assess the performance of different tests for the diagnosis of COVID-19

Who can participate?
Adult patients with symptoms of COVID-19 who provide consent to participate in the study and to the donation of biological samples.

What does the study involve?
All patients presenting to the Emergency Room (ER) of the participating hospital with suspected COVID-19 will be given information about the study and asked for consent to participate. Participants who agree to participate will undergo several diagnostic tests for COVID-19 which involve blood withdrawal and a nose and throat swab.

What are the possible benefits and risks of participating?
Participants will receive standard care guided by the results of the validated test (PCR) used for the diagnosis of COVID-19. There are no additional direct benefits or risks. Adverse events are not expected.

Where is the study run from?
IRCCS Sacro Cuore Don Calabria hospital (Italy)

When is the study starting and how long is it expected to run for?
From March 2020 to May 2020

Who is funding the study?
Partially funded by the Italian Ministry of Health (Italy)

Who is the main contact?
Prof Zeno Bisoffi
zeno.bisoffi@sacrocuore.it

Contact information

Prof Zeno Bisoffi
Scientific

IRCCS Sacro Cuore don Calabria hospital
Via Sempreboni 5
Negrar
37024
Italy

ORCID ID	0000-0001-9530-8742
Phone	+39 (0)456013326
Email	zeno.bisoffi@sacrocuore.it

Study information

Primary study design	Observational
Study design	Single-centre observational prospective diagnostic study
Secondary study design	Longitudinal study
Study type	Participant information sheet
Scientific title	Sensitivity, specificity and predictive values of molecular and serological tests for COVID-19: a longitudinal study in the emergency room
Study objectives	To assess sensitivity, specificity and predictive values of different test methods for the diagnosis of SARS-CoV-2 infection used at the hospital emergency room: five IgG-IgM rapid diagnostic tests (RDT), an ELISA IgA-IgG test, and three Reverse Transcriptase-real-time PCR (RT-PCR) tests, with different gene targets, validated and widely used for diagnosis.
Ethics approval(s)	Approved 02/04/2020, amendment approved 16/06/2020, Ethics Committee for the Clinical Trials (CESC) of Verona and Rovigo Provinces (AOUI di Verona, Servizio di Farmacia dell'Ospedale, Borgo Trento, P.le Stefani, 1, Verona 37126, Italy; +39 (0)45 8123236; comitatoetico.veronarovigo@aovr.veneto.it; comitatoetico.aovr@pecveneto.it), ref: 19408, amendment ref: 33102
Health condition(s) or problem(s) studied	COVID-19 (SARS-CoV-2 infection)
Intervention	Current interventions as of 25/06/2020: Patients will be recruited at the participating centre emergency room. They will have nasopharyngeal swabs for PCR and blood taken for serological tests. The assessment will be carried out using the standard, RT-PCR used within the department as the gold standard and compared using the statistical technique of Latent Class Analysis. An exploratory analysis will also be carried out using a Composite Reference Standard (CRS). Participants will then be managed according to the results of the validated PCR (a few hours to have the results). All assessment will occur within the same emergency room visit. There will be no follow up, except for cases of uncertain classification, and for the final outcome that will be recorded for all patients admitted to hospital. Previous interventions: Patients will be recruited at the participating centre emergency room. They will have nasopharyngeal swabs for PCR and blood taken for serological tests. The assessment will be carried out using the standard, RT-PCR used within the department as the gold standard and compared using the statistical technique of Latent Class Analysis. An exploratory analysis will also be carried out using a Composite Reference Standard (CRS). Participants will then be managed according to the results of the validated PCR (a few hours to have the results). All assessment will occur within the same emergency room visit. There will be no follow up.
Intervention type	Procedure/Surgery
Primary outcome measure(s)	Current primary outcome measure as of 25/06/2020: Test accuracy for the diagnosis of SARS-CoV-2 infection assessed through comparison against a patient classification made using all the molecular tests and selected clinical variables, using the statistical technique of Latent Class Analysis (LCA) and with clinical reassessment of uncertain cases; the standard molecular test is performed at baseline (upon patient recruitment), while the six serological and two additional molecular (Rt-PCR) tests will be performed on cryopreserved swabs (Rt PCR) and serum specimens (serological tests), after completion of patient recruitment. Previous primary outcome measure: Test accuracy for the diagnosis of SARS-CoV-2 infection assessed through comparison against a patient classification using the standard molecular test, performed at baseline (upon patient recruitment) and with clinical reassessment of uncertain cases; and the six serological and three molecular (Rt-PCR) tests, performed on cryopreserved swabs (Rt PCR) and serum specimens (serological tests), after completion of patient recruitment (within 1 h)
Key secondary outcome measure(s)	Current secondary outcome measures as of 25/06/2020: Test accuracy of the six serological tests in the subset of patients reporting symptom duration ≥7 days assessed using the standard molecular test, performed at baseline (upon patient recruitment). Previous secondary outcome measures: Test accuracy in the subset of patients reporting symptom duration ≥7 days assessed using the standard molecular test, performed at baseline (upon patient recruitment); and the six serological and three molecular (Rt-PCR) tests, performed on cryopreserved swabs (Rt PCR) and serum specimens (serological tests), after completion of patient recruitment (within 1 h)
Completion date	25/05/2020

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	400
Total final enrolment	346
Key inclusion criteria	1. Aged ≥18 years 2. Clinical suspicion of COVID-19 3. Consent to participate in the study and to the donation of biological samples given
Key exclusion criteria	1. Missing or invalid samples
Date of first enrolment	03/04/2020
Date of final enrolment	09/05/2020

Locations

Countries of recruitment

Italy

Study participating centre

IRCCS Sacro Cuore Don Calabria hospital

Via Sempreboni 5
Negrar
37024
Italy

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Stored in repository
IPD sharing plan	The datasets generated during and/or analysed during the current study will be stored in a publically available repository (Mendeley Data)

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	03/09/2020	17/03/2021	Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

17/03/2021: The following changes have been made:
1. Publication reference added.
2. The final enrolment number has been added from the reference.
25/06/2020: The following changes were made to the trial record:
1. The interventions were changed.
2. The primary outcome measure was changed.
3. The secondary outcome measures were changed.
24/06/2020: Trial’s existence confirmed by Ethics Committee for the Clinical Trials (CESC) of Verona and Rovigo Provinces.