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Serum concentration of extracellular cold-inducible RNA-binding protein is associated with respiratory failure in COVID-19
Department of Infectious Diseases, CKF Region Västmanland, Västerås Hospital, Västerås, Sweden.
School of Medical Sciences, Örebro University, Örebro, Sweden.
Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Radiology.ORCID iD: 0000-0002-1346-1450
Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden.
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2022 (English)In: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 13, article id 945603Article 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

Available from: 2022-08-16 Created: 2022-08-16 Last updated: 2024-01-17Bibliographically approved

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Lidén, MatsAthlin, SimonHultgren, OlofSavilampi, JohannaLange, AnnaCajander, Sara

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