FOUND - Ancillary Study to Smile Protocol NCT03654105

Summary

During the current pandemic, in Italy the majority of asymptomatic or pauci-symptomatic COVID-19 cases were not identified nor diagnosed and this fact caused a decrease in the effectiveness of the various containment measures implemented. Therefore, in a future scenario where a new viral swarm is expected, the early identification of all infected cases becomes essential to plan and activate a containment strategy for the spread of the virus, given the current absence of vaccines.

The typical radiological finding of COVID-19 is an interstitial pneumonia, which can be responsible, in a significant portion of patients, of an acute respiratory distress syndrome (ARDS).

Low-dose chest CT and simple blood tests could identify sub-solid pulmonary nodules (SSNs) indicative of COVID-19 infection in asymptomatic subjects.

Objectives of this observational study are the early detection of COVID-19 markers indicative of prior exposure or persisting viral infection in asymptomatic subjects and the assessment of the frequency and outcome of COVID-19-related SSNs in asymptomatic subjects by time, domicile, and other individual risk factors.

SMILE lung CT screening program cohort has been considered, based on 960 subjects at high lung cancer risk for tobacco smoking (≥20 pack/year) and age (50-75 years), together with inflammatory and respiratory profile. SMILE utilizes a top technology dual-source CT scanner (Somatom Force) with the lowest radiation dose ever applied to lung screening. All chest CT images from screening subjects will be re-evaluated by two additional CAD programs, specifically designed for the analysis of SSNs and quantification of the total volume of lung parenchyma showing an increased density. This re-evaluation will improve the sensitivity and specificity of radiomic assessment.

This study cohort, enriched by the already established longitudinal biobank of frozen plasma samples, represent an ideal opportunity to assess the frequency of SSNs in asymptomatic subjects, due to the effect of COVID-19, particularly among subjects living in areas at high risk of viral exposure. It will also be possible to evaluate if COVID-19-related SSNs are associated with chronic co-morbidity, other individual risk factors, inflammatory (CRP) / immunomodulatory (25(OH)D) blood profile, and/or can be traced by immune markers such as IgM/IgG and other cytokines.

Clinical data will be integrated with an analysis of the IgG-IgM profile specific for covid-19, on the plasma samples taken at the time of the CT scan, or subsequently, in collaboration with University of Milan, Luigi Devoto Work Clinic.

The lasting collaboration with the Radiological Science Department of the University of Parma in lung screening also offers the opportunity to validate the results obtained in this cohort on chest CT performed at the University Parma Hospital during the last two months in symptomatic subjects for suspected covid-19 pneumonia.

In collaboration with University of Milano Bicocca, Machine Learning (ML) tools will be applied to predict the clinical relevance, severity and ultimate outcome of SSNs, based on radiomic CT features, epidemiologic risk, co-morbidity and inflammatory/immune blood biomarkers. ML analysis will generate a predictive algorithm for clinical outcome of SSNs, and specifically the risk of COV-I9 infection and unfavorable disease prognosis.

Conditions

• COVID 19
• Inflammatory Status

Sponsors & Collaborators

• University of Parma

  collaborator OTHER

• University of Milan

  collaborator OTHER

• University of Milano Bicocca

  collaborator OTHER

• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

  lead OTHER

Principal Investigators

• Ugo Pastorino, MD · Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

Eligibility

Min Age

50 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2019-07-23

Primary Completion

2024-12-31

Completion

2024-12-31

Countries

• Italy

Study Locations