Serum concentration of extracellular cold-inducible RNA-binding protein is associated with respiratory failure in COVID-19.

Abstract

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.

• Authors: Felix Schagatay, Klara Diamant, Mats Lidén, Alicia Edin, Simon Athlin, Olof Hultgren, Clas Ahlm, Mattias N E Forsell, Johanna Savilampi, Johan Normark, Anna Lange, Sara Cajander
• Journal: Frontiers in immunology (Front Immunol) Vol. 13 Pg. 945603 ( 2022) ISSN: 1664-3224 [Electronic] Switzerland
• PMID: 35967397 (Publication Type: Journal Article, Observational Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Schagatay, Diamant, Lidén, Edin, Athlin, Hultgren, Ahlm, Forsell, Savilampi, Normark, Lange and Cajander.

Chemical References

• Alarmins
• RNA-Binding Proteins
• Oxygen

Topics

• Alarmins
• COVID-19
• Humans
• Hypoxia (complications)
• Oxygen
• RNA-Binding Proteins
• Respiratory Distress Syndrome
• Respiratory Insufficiency (etiology)