Molecular pathology of acute respiratory distress syndrome, mechanical ventilation and abnormal coagulation in severe COVID-19

Abstract

Systemic inflammation in critically ill patients can lead to serious consequences such as acute respiratory distress syndrome (ARDS), a condition characterized by the presence of lung inflammation, edema, and impaired gas exchange, associated with poor survival. Understanding molecular pathobiology is essential to improve critical care of these patients. To this end, we use multimodal profiles of SARS-CoV-2 infected hospitalized participants to the Biobanque Québécoise de la COVID-19 (BQC-19) to characterize endophenotypes associated with different degrees of disease severity. Proteomic, metabolomic, and genomic characterization supported a role for neutrophil-associated procoagulant activity in severe COVID-19 ARDS that is inversely correlated with sphinghosine-1 phosphate plasma levels. Fibroblast Growth Factor Receptor (FGFR) and SH2-containing transforming protein 4 (SHC4) signaling were identified as molecular features associated with endophenotype 6 (EP6). Mechanical ventilation in EP6 was associated with alterations in lipoprotein metabolism. These findings help define the molecular mechanisms related to specific severe outcomes, that can be used to identify early unfavorable clinical trajectories and treatable traits to improve the survival of critically ill patients.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This work was made possible through open sharing of data and samples from the Biobanque Québécoise de la COVID-19, funded by the Fonds de recherche du Québec - Santé, Génome Québec, the Public Health Agency of Canada and, as of March 2022, the Ministère de la Santé et des Services Sociaux du Québec. We thank all participants to BQC19 for their contribution. This study was supported by the Fonds de recherche du Québec - Santé (FRQS)- Cardiometabolic Health, Diabetes and Obesity Research Network (CMDO)- Initiative. This work was also supported by Natural Sciences and Engineering Research Council of Canada (NSERC) grant RGPIN-2019-04460 (AE).

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study was approved by the Institutional Ethics Review Board of the Centre intégré universitaire de santé et de services sociaux du Saguenay-Lac-Saint-Jean (CIUSSS-SLSJ) affiliated to Université de Sherbrooke [protocol #2021-369, 2021-014 CMDO - COVID19].

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data Availability

Input data corresponding to the cohort can be obtained form BQC19 (www.quebeccovidbiobank.ca). The data generated as a result of the analyses are provided as tables and supplementary tables.

https://www.quebeccovidbiobank.ca

留言 (0)

沒有登入
gif