Combination of WFDC2, CHI3L1, and KRT19 in Plasma Defines a Clinically Useful Molecular Phenotype Associated with Prognosis in Critically Ill COVID-19 Patients.

Abstract

BACKGROUND:

COVID-19 is now a common disease, but its pathogenesis remains unknown. Blood circulating proteins reflect host defenses against COVID-19. We investigated whether evaluation of longitudinal blood proteomics for COVID-19 and merging with clinical information would allow elucidation of its pathogenesis and develop a useful clinical phenotype.

METHODS:

To achieve the first goal (determining key proteins), we derived plasma proteins related to disease severity by using a first discovery cohort. We then assessed the association of the derived proteins with clinical outcome in a second discovery cohort. Finally, the candidates were validated by enzyme-linked immunosorbent assay in a validation cohort to determine key proteins. For the second goal (understanding the associations of the clinical phenotypes with 28-day mortality and clinical outcome), we assessed the associations between clinical phenotypes derived by latent cluster analysis with the key proteins and 28-day mortality and clinical outcome.

RESULTS:

We identified four key proteins (WFDC2, GDF15, CHI3L1, and KRT19) involved in critical pathogenesis from the three different cohorts. These key proteins were related to the function of cell adhesion and not immune response. Considering the multicollinearity, three clinical phenotypes based on WFDC2, CHI3L1, and KRT19 were identified that were associated with mortality and clinical outcome.

CONCLUSION:

The use of these easily measured key proteins offered new insight into the pathogenesis of COVID-19 and could be useful in a potential clinical application.

• Authors: Takeshi Ebihara, Tsunehiro Matsubara, Yuki Togami, Hisatake Matsumoto, Jotaro Tachino, Hiroshi Matsuura, Takashi Kojima, Fuminori Sugihara, Shigeto Seno, Daisuke Okuzaki, Haruhiko Hirata, Hiroshi Ogura
• Journal: Journal of clinical immunology (J Clin Immunol) Vol. 43 Issue 2 Pg. 286-298 (02 2023) ISSN: 1573-2592 [Electronic] Netherlands
• PMID: 36331721 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s).

Chemical References

• Blood Proteins
• CHI3L1 protein, human
• Chitinase-3-Like Protein 1

Topics

• Humans
• COVID-19
• Critical Illness
• Prognosis
• Phenotype
• Blood Proteins
• Chitinase-3-Like Protein 1