Respiratory rate-oxygenation index on the 3<sup>rd</sup> day is the best predictor of treatment failure in COVID-19 patients

Federico Raimondi; Stefano Centanni; Fabrizio Luppi; Stefano Aliberti; Francesco Blasi; Paola Rogliani; Claudio Micheletto; Marco Contoli; Alessandro Sanduzzi Zamparelli; Marialuisa Bocchino; Paolo Busatto; Luca Novelli; Simone Pappacena; Luca Malandrino; Giorgio Lorini; Greta Cairoli; Fabiano Di Marco

doi:10.4081/monaldi.2024.3033

Authors

Federico Raimondi

Respiratory Medicine Unit, ASST Papa Giovanni XXIII, Bergamo, Italy.

Stefano Centanni

Respiratory Medicine Unit, ASST Santi Paolo e Carlo, Milan; University of Milan, Italy.

Fabrizio Luppi

https://orcid.org/0000-0001-5775-5947

Department of Medicine and Surgery, University of Milan Bicocca, Milan; Respiratory Disease Unit, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy.

Stefano Aliberti

Department of Biomedical Sciences, Humanitas University, Pieve Emanuele; Respiratory Unit, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.

Francesco Blasi

https://orcid.org/0000-0002-2285-9970

University of Milan; Respiratory Unit and Adult Cystic Fibrosis Center, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy.

Paola Rogliani

https://orcid.org/0000-0001-7801-5040

“Tor Vergata” University, Rome; Unit of Respiratory Medicine, “Tor Vergata” Hospital Foundation, Rome, Italy.

Claudio Micheletto

https://orcid.org/0000-0002-1138-3882

Respiratory Medicine Unit, University Hospital of Verona, Italy.

Marco Contoli

Department of Translational Medicine, University of Ferrara, Italy.

Alessandro Sanduzzi Zamparelli

https://orcid.org/0000-0002-0977-2643

Department of Clinical Medicine and Surgery, Section of Respiratory Diseases, University Federico II, Azienda Ospedaliera dei Colli-Monaldi Hospital, Naples, Italy.

Marialuisa Bocchino

https://orcid.org/0000-0001-5477-072X

Department of Clinical Medicine and Surgery, Section of Respiratory Diseases, University Federico II, Azienda Ospedaliera dei Colli-Monaldi Hospital, Naples, Italy.

Paolo Busatto

https://orcid.org/0000-0002-3546-9947

Pneumology, Ospedale di Lucca, Azienda USL Toscana Nord Ovest, Lucca, Italy.

Luca Novelli

lnovelli@asst-pg23.it

https://orcid.org/0000-0002-2705-248X

Respiratory Medicine Unit, ASST Papa Giovanni XXIII, Bergamo, Italy.

Simone Pappacena

https://orcid.org/0000-0003-2495-7512

Respiratory Medicine Unit, ASST Papa Giovanni XXIII, Bergamo; University of Milan, Italy.

Luca Malandrino

Respiratory Medicine Unit, ASST Papa Giovanni XXIII, Bergamo; University of Milan, Italy.

Giorgio Lorini

https://orcid.org/0000-0002-5735-7647

Respiratory Medicine Unit, ASST Papa Giovanni XXIII, Bergamo, Italy.

Greta Cairoli

https://orcid.org/0000-0002-7012-707X

FROM Research Foundation, Papa Giovanni XXIII Hospital, Bergamo, Italy.

Fabiano Di Marco

Respiratory Medicine Unit, ASST Papa Giovanni XXIII, Bergamo; University of Milan, Italy.

Predictors of outcomes are essential to identifying severe COVID-19 cases and optimizing treatment and care settings. The respiratory rate-oxygenation (ROX) index, originally introduced for predicting the failure of non-invasive support in acute hypoxemic respiratory failure (AHRF), has not been extensively studied over time during hospitalization. This multicenter prospective observational study analyzed COVID-19-related AHRF patients admitted to eight Italian hospitals during the second pandemic wave. The study assessed the ROX index using receiver operator characteristic curves and areas under the curve with 95% confidence intervals to predict treatment failure, defined as endotracheal intubation (ETI) or death. A total of 227 patients (69.2% males) were enrolled, with a median arterial partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio at admission of 248 (interquartile range: 170-295). Nearly one-third (29.5%) required ETI or died during hospitalization. Those who experienced treatment failure were older (median age 70 versus 61 years, p<0.001), more likely to be current or former smokers (8.5% versus 6.4% and 42.4% versus 25.5%, p=0.039), had a higher prevalence of cardiovascular diseases (74.6% versus 46.3%, p<0.001), and had a lower PaO2/FiO2 ratio at presentation (median 229 versus 254, p=0.014). Gender, body mass index, and other comorbidities showed no significant differences. In patients who failed treatment, the ROX index was higher at presentation and worsened sharply by days 3 and 4. Conversely, in patients who survived without requiring ETI, the ROX index remained stable and reduced after 5-6 days. The ROX index's predictive ability improved notably by the third day of hospitalization, with the best cut-off value identified at 8.53 (sensitivity 75%, specificity 68%). Kaplan-Meier curves indicated that a ROX index of 8.53 or lower on days 1, 2, or 3 was associated with a higher risk of treatment failure. Thus, a single ROX index assessment on day 3 is more informative than its variability over time, with values of 8.53 or lower predicting non-invasive respiratory support failure in hospitalized COVID-19 patients.

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Citations

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Ethics Approval

This study was approved by the respective ethics committees involved (Comitato etico di Bergamo - n.308-20, 05/02/2021; Comitato etico della Brianza - EC approval on 02/04/2021; Comitato etico di Ferrara - n.373/2021/Oss/AOUFe, 22/04/2021; Comitato etico Ospedale Sacco Milano - n.2021/ST/091, 19/04/2021; Comitato etico di Palermo - n.3/2021, 31/03/2021; Comitato etico Policlinico Milano - n.433/2021, 23/04/2021; Comitato etico San Paolo Milano - n.965, 21/04/2021; Comitato etico di Verona - n.3171CESC, 11/03/2021).

How to Cite

Raimondi, Federico, Stefano Centanni, Fabrizio Luppi, Stefano Aliberti, Francesco Blasi, Paola Rogliani, Claudio Micheletto, et al. 2024. “Respiratory Rate-Oxygenation Index on the 3<sup>rd< sup> Day Is the Best Predictor of Treatment Failure in COVID-19 Patients”. Monaldi Archives for Chest Disease, October. https://doi.org/10.4081/monaldi.2024.3033.

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Respiratory rate-oxygenation index on the 3^rd day is the best predictor of treatment failure in COVID-19 patients