Serum concentration of extracellular cold-inducible RNA-binding protein is associated with respiratory failure in COVID-19Show others and affiliations
2022 (English)In: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 13, article id 945603
Article in journal (Refereed) Published
Abstract [en]
Uncontrolled release of damage-associated molecular patterns (DAMPs) is suggested to be a major trigger for the dysregulated host immune response that leads to severe COVID-19. Cold-inducible RNA-binding protein (CIRP), is a newly identified DAMP that aggravates inflammation and tissue injury, and induces respiratory failure in sepsis. Whether CIRP contributes to the pathogenesis of respiratory failure in COVID-19 has not yet been explored.
Aim: To investigate if the concentration of extracellular CIRP (eCIRP) in serum associates with respiratory failure and lung involvement by chest computed tomography (CT) in COVID-19.
Methods: Herein we report a prospective observational study of patients with COVID-19 included at two University Hospitals in Sweden between April 2020 and May 2021. Serum from hospitalized patients in Örebro (N=97) were used to assess the association between eCIRP and the level of respiratory support and its correlation with pulmonary involvement on chest CT and inflammatory biomarkers. A cohort of hospitalized and non-hospitalized patients from Umeå (N=78) was used as an external validation cohort. The severity of disease was defined according to the highest degree of respiratory support; mild disease (no oxygen), non-severe hypoxemia (conventional oxygen or high-flow nasal oxygen, HFNO <50% FiO2), and severe hypoxemia (HFNO ≥50% FiO2, mechanical ventilation). Unadjusted and adjusted linear regression was used to evaluate peak eCIRP day 0-4 in respect to severity, age, sex, Charlson comorbidity score, symptom duration, and BMI.
Results: Peak eCIRP concentrations were higher in patients with severe hypoxemia and were independently associated with the degree of respiratory support in both cohorts (Örebro; p=0.01, Umeå; p<0.01). The degree of pulmonary involvement measured by CT correlated with eCIRP, rs=0.30, p<0.01 (n=97).
Conclusion: High serum levels of eCIRP are associated with acute respiratory failure in COVID-19. Experimental studies are needed to determine if treatments targeting eCIRP reduces the risk of acute respiratory failure in COVID-19.
Place, publisher, year, edition, pages
Frontiers Media S.A., 2022. Vol. 13, article id 945603
Keywords [en]
CIRP, COVID-19, DAMPs, eCIRP, inflammation, severity
National Category
Rheumatology and Autoimmunity
Identifiers
URN: urn:nbn:se:oru:diva-100684DOI: 10.3389/fimmu.2022.945603ISI: 000840651100001PubMedID: 35967397Scopus ID: 2-s2.0-85136034592OAI: oai:DiVA.org:oru-100684DiVA, id: diva2:1687722
Funder
Region Örebro County, OLL-938628 OLL-961416Knut and Alice Wallenberg Foundation, VC-2020-0015Umeå UniversityRegion VästerbottenSwedish Heart Lung FoundationSwedish Research Council, 2020-06235
Note
Funding agency:
Centrum for klinisk forskning (CKF) Region Västmanland
2022-08-162022-08-162024-01-17Bibliographically approved