Development and validation of a prediction score for failure to casirivimab/imdevimab in hospitalized patients with COVID-19 pneumonia
IntroductionCasirivimab and imdevimab (CAS/IMV) are two non-competing, high-affinity human IgG1 anti-SARS-CoV-2 monoclonal antibodies, that showed a survival benefit in seronegative hospitalized patients with COVID-19. This study aimed to estimate the day-28 risk of mechanical ventilation (MV) and d...
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2024.1293431/full |
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| author | Alessandro Cozzi-Lepri Vanni Borghi Salvatore Rotundo Bianca Mariani Anna Ferrari Cosmo Del Borgo Francesca Bai Pietro Colletti Piermauro Miraglia Carlo Torti Anna Maria Cattelan Giovanni Cenderello Marco Berruti Carlo Tascini Giustino Parruti Simona Coladonato Andrea Gori Giulia Marchetti Miriam Lichtner Luigi Coppola Chiara Sorace Alessandra D'Abramo Valentina Mazzotta Giovanni Guaraldi Erica Franceschini Marianna Meschiari Loredana Sarmati Andrea Antinori Emanuele Nicastri Cristina Mussini |
| author_facet | Alessandro Cozzi-Lepri Vanni Borghi Salvatore Rotundo Bianca Mariani Anna Ferrari Cosmo Del Borgo Francesca Bai Pietro Colletti Piermauro Miraglia Carlo Torti Anna Maria Cattelan Giovanni Cenderello Marco Berruti Carlo Tascini Giustino Parruti Simona Coladonato Andrea Gori Giulia Marchetti Miriam Lichtner Luigi Coppola Chiara Sorace Alessandra D'Abramo Valentina Mazzotta Giovanni Guaraldi Erica Franceschini Marianna Meschiari Loredana Sarmati Andrea Antinori Emanuele Nicastri Cristina Mussini |
| author_sort | Alessandro Cozzi-Lepri |
| collection | DOAJ |
| description | IntroductionCasirivimab and imdevimab (CAS/IMV) are two non-competing, high-affinity human IgG1 anti-SARS-CoV-2 monoclonal antibodies, that showed a survival benefit in seronegative hospitalized patients with COVID-19. This study aimed to estimate the day-28 risk of mechanical ventilation (MV) and death in individuals hospitalized for severe COVID-19 pneumonia and receiving CAS/IMV. Additionally, it aimed to identify variables measured at the time of hospital admission that could predict these outcomes and derive a prediction algorithm.MethodsThis is a retrospective, observational cohort study conducted in 12 hospitals in Italy. Adult patients who were consecutively hospitalized from November 2021 to February 2022 receiving CAS/IMV were included. A multivariable logistic regression model was used to identify predictors of MV or death by day 28 from treatment initiation, and β-coefficients from the model were used to develop a risk score that was derived by means of leave-one-out internal cross-validation (CV), external CV, and calibration. Secondary outcome was mortality.ResultsA total of 480 hospitalized patients in the training set and 157 patients in the test set were included. By day 28, 36 participants (8%) underwent MV and 28 died (6%) for a total of 58 participants (12%) experiencing the composite primary endpoint. In multivariable analysis, four factors [age, PaO2/FiO2 ratio, lactate dehydrogenase (LDH), and platelets] were independently associated with the risk of MV/death and were used to generate the proposed risk score. The accuracy of the score in the area under the curve (AUC) was 0.80 and 0.77 in internal validation and test for the composite endpoint and 0.87 and 0.86 for death, respectively. The model also appeared to be well calibrated with the raw data.ConclusionThe mortality risk reported in our study was lower than that previously reported. Although CAS/IMV is no longer used, our score might help in identifying which patients are not likely to benefit from monoclonal antibodies and may require alternative interventions. |
| first_indexed | 2024-04-25T01:00:07Z |
| format | Article |
| id | doaj.art-0b97388ee1594886bbcecb9b15b4c631 |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-04-25T01:00:07Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Medicine |
| spelling | doaj.art-0b97388ee1594886bbcecb9b15b4c6312024-03-11T05:04:23ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2024-03-011110.3389/fmed.2024.12934311293431Development and validation of a prediction score for failure to casirivimab/imdevimab in hospitalized patients with COVID-19 pneumoniaAlessandro Cozzi-Lepri0Vanni Borghi1Salvatore Rotundo2Bianca Mariani3Anna Ferrari4Cosmo Del Borgo5Francesca Bai6Pietro Colletti7Piermauro Miraglia8Carlo Torti9Anna Maria Cattelan10Giovanni Cenderello11Marco Berruti12Carlo Tascini13Giustino Parruti14Simona Coladonato15Andrea Gori16Giulia Marchetti17Miriam Lichtner18Luigi Coppola19Chiara Sorace20Alessandra D'Abramo21Valentina Mazzotta22Giovanni Guaraldi23Erica Franceschini24Marianna Meschiari25Loredana Sarmati26Andrea Antinori27Emanuele Nicastri28Cristina Mussini29Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, University College London, London, United KingdomClinic of Infectious Diseases, Azienda Ospedaliero-Universitaria Policlinico, Modena, ItalyUnit of Infectious and Tropical Diseases, University Magna Græcia, Catanzaro, ItalyUnità Organizzativa Complessa Malattie Infettive, Fondazione Istituto di Ricovero e Cura a Caratetre Scientifico, Cà Granda Ospedale Maggiore Policlinico, Milan, ItalyUnità Organizzativa Complessa Malattie Infettive, Azienda Ospedale Università, Padova, ItalyUnità Organizzativa Complessa Malattie Infettive, Ospedale SM Goretti, Latina, ItalyClinica delle Malattie Infettive, Dipartimento di Scienze della Salute, ASST Santi Paolo e Carlo, University of Milano, Milan, ItalyUnit of Infectious Diseases, Paolo Borsellino Hospital, ASP Trapani, Trapani, ItalyUnit of Infectious Diseases, Paolo Borsellino Hospital, ASP Trapani, Trapani, ItalyUnit of Infectious and Tropical Diseases, University Magna Græcia, Catanzaro, ItalyUnità Organizzativa Complessa Malattie Infettive, Azienda Ospedale Università, Padova, ItalySC Malattie Infettive Asl1 Imperiese, Imperia, ItalySC Malattie Infettive Asl1 Imperiese, Imperia, Italy0Clinic of Infectious Diseases, University of Udine, Udine, Italy1Unit of Infectious Diseases, Hospital of Pescara, Pescara, Italy1Unit of Infectious Diseases, Hospital of Pescara, Pescara, Italy2Infectious Disease Unit, Ospedale L. Sacco, University of Milano, Milan, ItalyClinica delle Malattie Infettive, Dipartimento di Scienze della Salute, ASST Santi Paolo e Carlo, University of Milano, Milan, ItalyUnità Organizzativa Complessa Malattie Infettive, Ospedale SM Goretti, Latina, Italy3Clinical Infectious Diseases, Tor Vergata University, Rome, Italy3Clinical Infectious Diseases, Tor Vergata University, Rome, Italy4Istituto Nazionale Malattie Infettive L. Spallanzani, Rome, Italy4Istituto Nazionale Malattie Infettive L. Spallanzani, Rome, Italy5Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Emilia-Romagna, Italy5Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Emilia-Romagna, Italy5Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Emilia-Romagna, Italy3Clinical Infectious Diseases, Tor Vergata University, Rome, Italy4Istituto Nazionale Malattie Infettive L. Spallanzani, Rome, Italy4Istituto Nazionale Malattie Infettive L. Spallanzani, Rome, Italy5Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Emilia-Romagna, ItalyIntroductionCasirivimab and imdevimab (CAS/IMV) are two non-competing, high-affinity human IgG1 anti-SARS-CoV-2 monoclonal antibodies, that showed a survival benefit in seronegative hospitalized patients with COVID-19. This study aimed to estimate the day-28 risk of mechanical ventilation (MV) and death in individuals hospitalized for severe COVID-19 pneumonia and receiving CAS/IMV. Additionally, it aimed to identify variables measured at the time of hospital admission that could predict these outcomes and derive a prediction algorithm.MethodsThis is a retrospective, observational cohort study conducted in 12 hospitals in Italy. Adult patients who were consecutively hospitalized from November 2021 to February 2022 receiving CAS/IMV were included. A multivariable logistic regression model was used to identify predictors of MV or death by day 28 from treatment initiation, and β-coefficients from the model were used to develop a risk score that was derived by means of leave-one-out internal cross-validation (CV), external CV, and calibration. Secondary outcome was mortality.ResultsA total of 480 hospitalized patients in the training set and 157 patients in the test set were included. By day 28, 36 participants (8%) underwent MV and 28 died (6%) for a total of 58 participants (12%) experiencing the composite primary endpoint. In multivariable analysis, four factors [age, PaO2/FiO2 ratio, lactate dehydrogenase (LDH), and platelets] were independently associated with the risk of MV/death and were used to generate the proposed risk score. The accuracy of the score in the area under the curve (AUC) was 0.80 and 0.77 in internal validation and test for the composite endpoint and 0.87 and 0.86 for death, respectively. The model also appeared to be well calibrated with the raw data.ConclusionThe mortality risk reported in our study was lower than that previously reported. Although CAS/IMV is no longer used, our score might help in identifying which patients are not likely to benefit from monoclonal antibodies and may require alternative interventions.https://www.frontiersin.org/articles/10.3389/fmed.2024.1293431/fullcasirivimab/imdevimabCOVID-19mechanical ventilationmortalityprediction scoreSARS-CoV-2 |
| spellingShingle | Alessandro Cozzi-Lepri Vanni Borghi Salvatore Rotundo Bianca Mariani Anna Ferrari Cosmo Del Borgo Francesca Bai Pietro Colletti Piermauro Miraglia Carlo Torti Anna Maria Cattelan Giovanni Cenderello Marco Berruti Carlo Tascini Giustino Parruti Simona Coladonato Andrea Gori Giulia Marchetti Miriam Lichtner Luigi Coppola Chiara Sorace Alessandra D'Abramo Valentina Mazzotta Giovanni Guaraldi Erica Franceschini Marianna Meschiari Loredana Sarmati Andrea Antinori Emanuele Nicastri Cristina Mussini Development and validation of a prediction score for failure to casirivimab/imdevimab in hospitalized patients with COVID-19 pneumonia Frontiers in Medicine casirivimab/imdevimab COVID-19 mechanical ventilation mortality prediction score SARS-CoV-2 |
| title | Development and validation of a prediction score for failure to casirivimab/imdevimab in hospitalized patients with COVID-19 pneumonia |
| title_full | Development and validation of a prediction score for failure to casirivimab/imdevimab in hospitalized patients with COVID-19 pneumonia |
| title_fullStr | Development and validation of a prediction score for failure to casirivimab/imdevimab in hospitalized patients with COVID-19 pneumonia |
| title_full_unstemmed | Development and validation of a prediction score for failure to casirivimab/imdevimab in hospitalized patients with COVID-19 pneumonia |
| title_short | Development and validation of a prediction score for failure to casirivimab/imdevimab in hospitalized patients with COVID-19 pneumonia |
| title_sort | development and validation of a prediction score for failure to casirivimab imdevimab in hospitalized patients with covid 19 pneumonia |
| topic | casirivimab/imdevimab COVID-19 mechanical ventilation mortality prediction score SARS-CoV-2 |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2024.1293431/full |
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