Identification of Predictors for the Evolution of COVID-19 Related Pneumonia by Transcriptomic and Seroproteomic

Active, not recruiting

• Conditions: Covid19; Interstitial Pneumonia

• Registration Number: NCT04441502
• Lead Sponsor: IRCCS Policlinico S. Donato

Brief Summary

The investigating group aims at performing an observational, prospective study that involves the evaluation of circulating biomarkers predictive of clinical evolution in patients suffering from COVID-19 disease.

In particular, the aim will be to verify whether there are transcripts or cytokines / chemokines in peripheral blood, modulated differently in patients with COVID-19, distinguished on the basis of the evolution towards more severe clinical pictures that require patient intubation or that show signs of cardiovascular damage.

The study will be based on the transcriptional analysis of the entire genome and serum protein to evaluate the expression of a broad spectrum of cytokines and chemokines. Genome analysis will allow the genotype to be correlated to the identified gene expression profiles.

Detailed Description

Study design This observational, prospective, monocentric study will make use of the recruitment of consecutive patients with COVID-19. Enrollment will last 6 months or, considering the desirable drop in infections in the next few weeks, until exhaustion of enrolled patients. Enrollment will be followed by 18 months dedicated to transcriptomics and seroproteomics investigations, for a total duration of the study of 24 months.

All patients will receive optimal medical therapy, and will undergo laboratory or instrumental examinations (chest x-ray, CT, echocardiography) as needed.

Blood samples will be taken at the entrance and then twice a week for the duration of the hospitalization (generally 2-3 weeks).

Anamnesis will be noted for all patients. In addition, at all times, patients will undergo clinical evaluation and the following laboratory tests, which include:

* blood count

* biochemistry

* standard coagulation and thrombin generation, fibrin generation and fibrinolysis (INR, PTT, D-dimer, Tissue Plasminogen Activator TPA, Plasminogen Activator Inhibitor PAI-2, Plasmin-AntiPlasmin complex PAP, Thrombin activated Fibrinolysis Inhibitor TAFI, Thrombin-AntiThrombin complex TAT, Prothrombin Fragment PF 1+2, Fibrinopeptide A)

* inflammation/infection (IL-6, procalcitonin, ferritin, PCR, sCD14, TLR3 and 4, RANTES, CCR3 and 4

* other (troponin I, NT-pro-BNP, Hb1Ac). A subgroup of patients will undergo a microcirculation analysis with SDF (Sidestream Dark Field imaging).

Study Timeline

• Study Start: 2020-03-30
• Study First Submitted: 2020-06-12
• Study First Submitted QC: 2020-06-19
• Study First Posted: 2020-06-22
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-16
• Last Update Posted: 2023-11-18
• Primary Completion: 2024-12-31
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 204

Inclusion Criteria

1. Age 18 years or older
2. Positivity to the test for SARS-Cov-2
3. Informed consent to enrollment in the study.
4. For Intensive Care patients: entry into the intensive unit and / or endotracheal intubation for no more than 4 days.
5. For patients in the COVID19 wards: home hospitalization or emergency room for no more than 4 days.

Exclusion Criteria

1. Age less than 18 years
2. Pregnant women
3. Patients with malignant neoplasm, autoimmune diseases.
4. Hospitalization as transfer from another hospital or other similar facility.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Circulating markers for COVID-19 signature	From ICU/ward admission for 8 weeks follow/up	Identify circulating transcripts (coding and non-coding for proteins) or cytokines and chemokines which, alone or in combination (COVID19_signature), are predictive of adverse events (death, endotracheal intubation) and the prognostic capacity of COVID19_signature in the prediction of adverse events in additional to the use of standard clinical parameters

Secondary Outcome Measures

Name	Time	Method
COVID-19 signature and adverse cardiovascular events	From ICU/ward admission for 8 weeks follow/up	Evaluate the association of COVID19_signature with adverse cardiovascular events. Adverse cardiovascular events are defined: death from cardiovascular causes, acute coronary syndrome, troponin T levels greater than the ninety-ninth percentile of the upper reference limit, stroke, cardiac arrhythmias, development of heart failure, venous thromboembolism
COVID-19 related coagulation pattern	From ICU/ward admission for 8 weeks follow/up	Evaluate, in a subset of 20 patients, the characteristics of the coagulation pattern with specific tests for thrombin generation and fibrinolysis.

Trial Locations

Locations (1)

IRCCS Policlinico San Donato; 🇮🇹 San Donato Milanese, MI, Italy