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. 2025 Jul 16;15(1):25696.
doi: 10.1038/s41598-025-09229-y.

FeNO as a biomarker of interstitial and fibrotic pulmonary sequelae in patients admitted for severe SARS-CoV-2 pneumonia

Diego Ferrer-Pargada  1   2 , Carlos A Amado  3   4   5 , Beatriz Abascal-Bolado  6 , Sandra Tello Mena  6 , Pilar Alonso Lecue  7 , Carlos Armiñanzas  7   8   9 , Francisco Arnaiz de Las Revillas  10   7   8   9 , Miguel Santibáñez  10   7 , Juan Agüero  6 , Víctor Fernández Lobo  11 , J Gonzalo Ocejo-Vinyals  7   12 , José Manuel Cifrian  6   10   7
Affiliations

FeNO as a biomarker of interstitial and fibrotic pulmonary sequelae in patients admitted for severe SARS-CoV-2 pneumonia

Diego Ferrer-Pargada et al. Sci Rep. .

Abstract

Pulmonary fibrosis after severe SARS-CoV-2 pneumonia is a major sequela in surviving patients which requires evaluation. Fractional exhaled nitric oxide (FeNO) is a marker of airway inflammation, easy to obtain and available in most functional testing laboratories of pulmonology services. Our objective was to evaluate the capacity of FeNO as a biomarker of interstitial and fibrotic pulmonary sequelae in patients admitted for severe SARS-CoV-2 pneumonia. We recruited 335 patients admitted for severe pneumonia secondary to SARS-CoV-2 who were being followed up at the Diffuse Interstitial Lung Disease unit at Hospital Universitario Marqués de Valdecilla. FeNO levels were higher in patients with fibrotic interstitial sequelae: mean 24.3 vs. 19.8 ppbs, p = 0.002, with an area under the curve (AUC) of 0.63; 95% confidence interval (CI) 0.57-0.69 and an optimal cut-off point of 11 ppb maximizing the weighted combination of Sensitivity and specificity. FeNO ranked 6th among the 18 variables studied using various methods (forward selection, backward elimination, and stepwise regression) in evaluating the predictive ability for fibrotic interstitial sequelae, and it was the 5 th most predictive variable after using the cut-off point of 11 ppb. The joint predictive ability of the overall model with the 6 more predictive variables was higher than 0.8: AUC (Use of systemic corticosteroids + peak C-reactive Protein at admission + Age + Endotracheal intubation + Diffusing Capacity for CO (DLCO) + FeNO as quantitative continuous) = 0.81; 95%CI (0.77-0.86). AUC of the same model with FeNO as dichotomous (11 ppb cut-off point) = 0.82; 95%CI (0.78-0.87). Our study shows an increase in FeNO in patients who, after admission for severe SARS-CoV-2 pneumonia, present fibrotic interstitial sequelae at the three-month follow-up, as one of the different predictive variables related to the presence of these sequelae.

Keywords: COVID-19; FeNO; ILD; Pulmonary fibrosis; SARS-CoV-2; Sequeale.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests. Ethical declarations: This study complies with internationally accepted standards for research practice and reporting. The Ethics Committee of our Institution approved the study (2018.276). All patients gave informed written consent to take part in this study.

Figures

Fig. 1
Fig. 1
Flow-chart of patients included in the study.
Fig. 2
Fig. 2
FeNO levels according to the presence of fibrotic interstitial sequelae in the HRCT at three months.
Fig. 3
Fig. 3
ROC curves for the most predictive quantitative variables in relation to existence of fibrotic interstitial sequelae on HRCT at three months.
See this image and copyright information in PMC

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