Pandemic SARS-CoV-2 (COVID-19) respiratory infection is responsible for more than 4,000 deaths, mainly (67%) secondary to acute respiratory distress syndromes (ARDS). ARDS is usually associated with a mortality of around 40%, but this rate reaches 61% in patients infected with SARS-CoV-2. Two endotypes have been described in patients with ARDS: one, hyper-inflammatory, associated with very high mortality (51%); the second, slightly inflammatory (immunoparalysis), associated with much lower mortality (19%). In COVID-19 patients, distinct immune response profiles have also been observed. Some patients present deep lymphopenia and/or prolonged viral excretions associated with more frequent occurrence of co-infections (+ 29% of virus, + 23% of bacteria, + 10% of fungi). The latter group may be at higher risk in terms of mortality. The intensity of the inflammatory response and/or microbial coinfections therefore appear as risk factors for severity and mortality in patients infected with SARS-CoV-2 which determine the course of the disease. To adapt early optimal therapeutic management to each forms of the disease, it is essential to be able to characterize these profiles on the microbiological and inflammatory level. With a committed network of 6 intensive-care units across eastern and northern Ile-de-France, 180 patients with ARDS and infected with SARS-CoV-2 are being enrolled. For these patients, a nasopharyngeal swab is collected at inclusion; followed by a new nasopharyngeal swab and a deep respiratory sample once a week, until D28, for an exploration of co-infections and for monitoring the viral load of SARS-CoV-2. The rest of each of these samples are collected for the study. In parallel, the clinical data usually collected in the context of intensive care will be collected on a CRF. They will allow to calculate risk scores such as SOFA.
Clinical metagenomics is a technique that has the ability to explore the host's inflammatory
response by transcriptomics and the co-infection(s) of all microorganisms. For this, an
accredited method according to standard 15189 and used in diagnostic routine for the
exploration of complex infections will be used. In practice, the samples will be
pre-extracted (chemical, enzymatic and mechanical lysis) then extracted using QiaSymphony
(Qiagen). The library will be prepared jointly by Nextera XT kit for DNA and Stranded TruSeq
Total RNA (Illumina) then sequenced by NovaSeq (Illumina). The metagenomic and transcriptomic
analysis will be performed by our MetaMIC software, supplemented with a specific module
recently added for the analysis of SARS-CoV-2 genetic variability and its dynamics over time.
Finally, an unsupervised data-mining analysis will be carried out to establish the presence
of the "hyperinflammatory" and "immunoparalysis" groups, then allow the analysis of the
determinants guiding their clustering. Each group will be analyzed according to its clinical,
biological and virological data to determine specific prognostic markers.
The proposed project will therefore comprehensively assess the dynamics of SARS-CoV-2
infection, the inflammatory profile and the microbiological documentation of COVID-19
patients in ARDS by metagenomics / transcriptomics with the aim of detecting profiles of
patients at higher risk, to understand the mechanisms of severe forms of the disease and to
allow a more precise and earlier evaluation of the prognosis, as well as an adaptation of the
management.
Other: retrospective metagenomics on clinical samples collected during hospitalization
Massive sequencing of respiratory samples (restrospective)
Inclusion Criteria:
- Patient admitted to intensive care for ARDS (Berlin definition) documented at
SARS-CoV-2
- Major patient (age ≥ 18 years)
- Collection of the non-opposition of the patient or his support person, family member
or close friend (newsletter)
Exclusion Criteria:
- Minor patient
- Refusal to participate in the study
- Patient protected by law
- Prisoner
CHU Henri Mondor
Créteil, France
Christophe Rodriguez, PharmD, PhD, Principal Investigator
Assistance Publique - Hôpitaux de Paris