German Clinical Trials Register

Acronym/abbreviation of the study

PROVID-PROGRESS

URL of the study

https://www.gesundheitsforschung-bmbf.de/de/provid-klinische-molekulare-und-funktionelle-biomarker-fur-prognose-pathomechanismen-und-11690.php

Brief summary in lay language

The pandemic triggered by the new virus SARS-CoV-2 presents the German and international health systems with previously unknown challenges. There are currently no effective specific therapies for the treatment of the lung disease COVID-19 caused by this virus. The effects of infection with SARS-CoV-2 range from symptomless to typical upper respiratory tract infections, which may result in pneumonia, which in turn may result in failure of the lungs and other organs, associated with high mortality. The aim of the joint project PROVID is to contribute to better outcome prediction for COVID-19 patients, to better clinical management, and to the development of new therapies. To this end, we will collect detailed data of on the course of COVID-19 patients and deeply characterize them at the molecular level. We also aim to identify compounds with the potential to improve outcome. Patient recruitment for the PROVID study is supported by three well-established clinical research platforms: CAPNETZ (competence network CAP, since 2002, world's largest database and biobank for CAP), PROGRESS (Pneumonia Research Network on Genetic Resistance and Susceptibility for the Evolution of Severe Sepsis, since 2007) and CAPSyS (Systems Medicine of Community-Acquired Pneumonia, since 2014). Through these platforms, patients will be recruited into three separate patient cohorts (PROVID-CAPNETZ, PROVID-PROGRESS, PROVID-CAPSyS). Data and biomaterials will be jointly analyzed to reach the envisaged aims.

Brief summary in scientific language

Infections with the novel Severe Acute Respiratory Syndrome - Coronavirus-2 (SARS-CoV-2) manifest with a broad spectrum of clinical presentations ranging from asymptomatic infections, upper respiratory tract infections with mild symptoms, and uncomplicated pneumonia to severe pneumonia with lung failure and high mortality. With more close to 40 million documented infections and more than one million deaths (as of October 19, 2020, Johns Hopkins CSSE), there still is a great need to improve the development of therapies and the clinical treatment of COVID-19. We would like to contribute to respective international efforts. Based on current data, COVID-19 associated lower respiratory tract infections and lung damage are not directly comparable to any known types of pneumonia, including viral infections such as influenza or MERS-CoV. Therefore, specific instructions, such as guidelines defined for other forms of pneumonia (CAP), likely have to be adapted for COVID-19. With COVID-19, severe lung damage can be associated with relative well-being. In the course of disease (several days), sudden lung failure may occur. While the lung initially shows a relatively high compliance after intubation, lung function deteriorates rapidly to severe ARDS in most patients. After intubation, patients require mechanical ventilation over a relatively long period of time (17 days on average). To improve the clinical management of COVID-19 and its complications, there is an urgent need for clinical (e.g., scores) and molecular (e.g., biomarkers) predictors of COVID-19 progression and for new therapeutic targets. Advanced age and comorbidities have been identified as risk factors for fatal disease progression. A recent multivariate analysis confirmed that higher age, a higher Sequential Organ Failure Assessment (SOFA) score and a D-dimer concentration > 1 μg/l at hospitalization are associated with higher mortality. However, a severe course of COVID-19 is not excluded in younger and seemingly healthy patients. The course of COVID-19 currently remains unpredictable. Since SARS-CoV-2 is a new virus, host- and virus-dependent mechanisms associated with the clinical appearance of COVID-19 are not yet well understood. Therefore, PROVID aims to identify clinical and molecular predictors of COVID-19 progression and therapeutic targets to improve the clinical management of COVID-19 patients. Specific objectives are: 1) Analysis of established clinical pneumonia and sepsis scores and biomarkers/molecular signatures to predict COVID-19 disease progression, 2) Identification of host factors (RNA, proteins, antibodies) determining the severity and/or course of COVID-19, 3) Analysis of barrier-destabilizing plasma mediators in COVID-19 and evaluation of barrier-stabilizing candidate substances, 4) Comparison of COVID-19 phenotypes, from uncomplicated pneumonia to ARDS, at the clinical and molecular level with CAP caused by other pathogens to improve clinical management, and 5) Analysis of variations of the SARS-CoV-2 genome and their association with specific clinical courses of COVID-19.