Disentangling the Association of Hydroxychloroquine Treatment with Mortality in Covid-19 Hospitalized Patients through Hierarchical Clustering
Augusto Di Castelnuovo, Alessandro Gialluisi, Andrea Antinori, Nausicaa Berselli, Lorenzo Blandi, Marialaura Bonaccio, Raffaele Bruno, Roberto Cauda, Simona Costanzo, Giovanni Guaraldi, Lorenzo Menicanti, Marco Mennuni, Ilaria My, Giustino Parruti, Giuseppe Patti, Stefano Perlini, Francesca Santilli, Carlo Signorelli, Giulio Stefanini, Alessandra Vergori, Walter Ageno, Antonella Agodi, Piergiuseppe Agostoni, Luca Aiello, Samir Al Moghazi, Rosa Arboretti, Filippo Aucella, Greta Barbieri, Martina Barchitta, Paolo Bonfanti, Francesco Cacciatore, Lucia Caiano, Francesco Cannata, Laura Carrozzi, Antonio Cascio, Giacomo Castiglione, Arturo Ciccullo, Antonella Cingolani, Francesco Cipollone, Claudia Colomba, Crizia Colombo, Annalisa Crisetti, Francesca Crosta, Gian Battista Danzi, Damiano D'ardes, Katleen De Gaetano Donati, Francesco Di Gennaro, Giuseppe Di Tano, Gianpiero D'offizi, Francesco Maria Fusco, Carlo Gaudiosi, Ivan Gentile, Francesco Gianfagna1, Gabriele Giuliano, Emauele Graziani, Gabriella Guarnieri, Valerio Langella, Giovanni Larizza, Armando Leone, Gloria Maccagni, Federica Magni, Stefano Maitan, Sandro Mancarella, Rosa Manuele, Massimo Mapelli, Riccardo Maragna, Rossella Marcucci, Giulio Maresca, Silvia Marongiu, Claudia Marotta, Lorenzo Marra, Franco Mastroianni, Alessandro Mengozzi, Marianna Meschiari, Jovana Milic, Filippo Minutolo, Roberta Mussinelli, Cristina Mussini, Maria Musso, Anna Odone, Marco Olivieri, Antonella Palimodde, Emanuela Pasi, Raffaele Pesavento, Francesco Petri, Carlo A Pivato, Venerino Poletti, Claudia Ravaglia, Giulia Righetti, Andrea Rognoni, Marco Rossato, Ilaria Rossi, Marianna Rossi, Anna Sabena, Francesco Salinaro, Vincenzo Sangiovanni, Carlo Sanrocco, Nicola Schiano Moriello, Laura Scorzolini, Raffaella Sgariglia, Paola Giustina Simeone, Michele Spinicci, Enrica Tamburrini, Carlo Torti, Enrico Maria Trecarichi, Roberto Vettor, Andrea Vianello, Marco Vinceti, Agostino Virdis, Raffaele De Caterina, Licia Iacoviello
Journal of Healthcare Engineering, doi:10.1155/2021/5556207
e efficacy of hydroxychloroquine (HCQ) in treating SARS-CoV-2 infection is harshly debated, with observational and experimental studies reporting contrasting results. To clarify the role of HCQ in Covid-19 patients, we carried out a retrospective observational study of 4,396 unselected patients hospitalized for Covid-19 in Italy (February-May 2020). Patients' characteristics were collected at entry, including age, sex, obesity, smoking status, blood parameters, history of diabetes, cancer, cardiovascular and chronic pulmonary diseases, and medications in use. ese were used to identify subtypes of patients with similar characteristics through hierarchical clustering based on Gower distance. Using multivariable Cox regressions, these clusters were then tested for association with mortality and modification of effect by treatment with HCQ. We identified two clusters, one of 3,913 younger patients with lower circulating inflammation levels and better renal function, and one of 483 generally older and more comorbid subjects, more prevalently men and smokers. e latter group was at increased death risk adjusted by HCQ (HR [CI95%] � 3.80[3.08-4.67]), while HCQ showed an independent inverse association (0.51[0.43-0.61]), as well as a significant influence of cluster * HCQ interaction (p < 0.001). is was driven by a differential association of HCQ with mortality between the high (0.89[0.65-1.22]) and the low risk cluster (0.46[0.39-0.54]). ese effects survived adjustments for additional medications in use and were concordant with associations with disease severity and outcome. ese findings suggest a particularly beneficial effect of HCQ within low risk Covid-19 patients and may contribute to clarifying the current controversy on HCQ efficacy in Covid-19 treatment.
Conflicts of Interest e authors declare that they have no conflicts of interest.
Authors' Contributions e raw data analyzed in the present work may be made available under approval by each local center involved in the study, in a way which does not affect patients' privacy. ADiC, RDC, and LI conceived the CORIST study. AG, ADiC, and LI conceptualized the present work. AG performed statistical analyses and wrote the first draft of the manuscript, under the supervision of ADiC and LI. All the co-authors contributed to collection, curation, and elaboration of the analyzed data, and/or to a critical review and editing of the manuscript. Di Castelnuovo and Gialluisi contributed equally to this manuscript.
Supplementary Materials Figure S1 . Cross-patient dissimilarity matrix based on Gower distance. Figure S2 . Optimal number of clusters (k) to apply in the hierarchical clustering analysis. Figure S3 . Check for basic assumptions of Cox PH models. Table S1
References
Arshad, Kilgore, Chaudhry, Treatment with hydroxychloroquine, azithromycin, and combination in patients hospitalized with COVID-19, International Journal of Infectious Diseases
Ayerbe, Risco-Risco, Ayis, e association of treatment with hydroxychloroquine and hospital mortality in COVID-19 patients, Internal and Emergency Medicine
Barchitta, Maugeri, Favara, A machine learning approach to predict healthcare-associated infections at intensive care unit admission: findings from the SPIN-UTI project, Journal of Hospital Infection
Barchitta, Maugeri, Favara, Cluster analysis identifies patients at risk of catheter-associated urinary tract infections in intensive care units: findings from the SPIN-UTI Network, e Journal of Hospital Infection
Barchitta, Maugeri, Favara, Early prediction of seven-day mortality in intensive care unit using a machine learning model: results from the SPIN-uti project, Journal of Clinical Medicine
Biot, Daher, Chavain, Design and synthesis of hydroxyferroquine derivatives with antimalarial and antiviral activities, Journal of Medicinal Chemistry
Burdick, Lam, Mataraso, Is machine learning a better way to identify COVID-19 patients who might benefit from hydroxychloroquine treatment?-the IDENTIFY trial, Journal of Clinical Medicine
Cassone, Iacoviello, Cauda, Chloroquine/ hydroxycloroquine and COVID-19: need to know more about, Future Microbiology
Catteau, Dauby, Montourcy, Low-dose hydroxychloroquine therapy and mortality in hospitalised patients with COVID-19: a nationwide observational study of 8075 participants, International Journal of Antimicrobial Agents
Cavalcanti, Zampieri, Rosa, Hydroxychloroquine with or without azithromycin in mildto-moderate covid-19, New England Journal of Medicine
Collaborative, Effect of hydroxychloroquine in hospitalized patients with covid-19, e New England Journal of Medicine
Core, R: A Language and Environment for Statistical Computing
Di Castelnuovo, Bonaccio, Costanzo, Common cardiovascular risk factors and in-hospital mortality in 3,894 patients with COVID-19: survival analysis and machine learning-based findings from the multicentre Italian CORIST Study, Nutrition, Metabolism and Cardiovascular Diseases
Di Castelnuovo, Costanzo, Antinori, RAAS inhibitors are not associated with mortality in COVID-19 patients: findings from an observational multicenter study in Italy and a meta-analysis of 19 studies, Vascul Pharmacol
Di Castelnuovo, Costanzo, Antinori, Use of hydroxychloroquine in hospitalised COVID-19 patients is associated with reduced mortality: findings from the observational multicentre Italian CORIST study, European Journal of Internal Medicine
Di Castelnuovo, Costanzo, Cassone, Low Dose Hydroxychloroquine Is Associated with Lower Mortality in COVID-19 a Meta
Emani, Goswami, Nandanoor, Emani, Reddy et al., Randomised controlled trials for COVID-19: evaluation of optimal randomisation methodologies-need for data validation of the completed trials and to improve ongoing and future randomised trial designs, International Journal of Antimicrobial Agents
Gower, A general coefficient of similarity and some of its properties, Biometrics
Grambsch, Modeling Survival Data : Extending the Cox Model
Horby, Emberson, Hydroxychloroquine for COVID-19: balancing contrasting claims, European Journal of Internal Medicine
Khan, Alotaibi, Applications of artificial intelligence and big data analytics in m-health: a healthcare system perspective, Journal of Healthcare Engineering
Kowarik, Templ, Imputation with the R package VIM, Journal of Statistical Software
Li, Wang, Agostinis, Is hydroxychloroquine beneficial for COVID-19 patients?, Cell Death & Disease
Mathur, Ding, Riddell, Vanderweele, Web site and R package for computing E-values, Epidemiology
Maugeri, Barchitta, Agodi, A clustering approach to classify Italian regions and provinces based on prevalence and trend of sars-cov-2 cases, International Journal of Environmental Research and Public Health
Mikami, Miyashita, Yamada, Risk factors for mortality in patients with COVID-19 in New York city, Journal of General Internal Medicine
Noor, Islam, Prevalence and associated risk factors of mortality among COVID-19 patients: a metaanalysis, Journal of Community Health
Novales, Ramírez-Olivencia, Estébanez, Early Hydroxychloroquine Is Associated with an Increase of Survival in COVID-19 Patients: An Observational Study
Panr, Peto, Repurposed antiviral drugs for covid-19 -interim WHO solidarity trial results WHO Solidarity Trial Consortium
Rousseeuw, Silhouettes: a graphical aid to the interpretation and validation of cluster analysis, Journal of Computational and Applied Mathematics
Roux, A comparative study of divisive and agglomerative hierarchical clustering algorithms, Journal of Classification
Sharma, López, Tsunoda, Divisive hierarchical maximum likelihood clustering, BMC Bioinformatics
Skipper, Pastick, Engen, Hydroxychloroquine in nonhospitalized adults with early COVID-19, Annals of Internal Medicine
Sulaiman, Mohana, Alawdah, e Effect of Early Hydroxychloroquine-Based erapy in COVID-19 Patients in Ambulatory Care Settings: A Nationwide Prospective Cohort Study
Vanderweele, Ding, Sensitivity analysis in observational research: introducing the E-Value, Annals of Internal Medicine
Wynants, Van Calster, Collins, Prediction models for diagnosis and prognosis of covid-19: systematic review and critical appraisal, BMJ
Yao, Ye, Zhang, In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Clinical Infectious Diseases
Ye, Lu, Tang, Identification of COVID-19 clinical phenotypes by principal component analysis-based cluster Analysis, Frontiers in Medicine
Yu, Li, Chen, Low dose of hydroxychloroquine reduces fatality of critically ill patients with COVID-19, Science China Life Sciences
Zhang, Navarese, Zheng, Analytics with artificial intelligence to advance the treatment of acute respiratory distress syndrome, Journal of Evidence-Based Medicine
DOI record:
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"abstract": "<jats:p>The efficacy of hydroxychloroquine (HCQ) in treating SARS-CoV-2 infection is harshly debated, with observational and experimental studies reporting contrasting results. To clarify the role of HCQ in Covid-19 patients, we carried out a retrospective observational study of 4,396 unselected patients hospitalized for Covid-19 in Italy (February–May 2020). Patients’ characteristics were collected at entry, including age, sex, obesity, smoking status, blood parameters, history of diabetes, cancer, cardiovascular and chronic pulmonary diseases, and medications in use. These were used to identify subtypes of patients with similar characteristics through hierarchical clustering based on Gower distance. Using multivariable Cox regressions, these clusters were then tested for association with mortality and modification of effect by treatment with HCQ. We identified two clusters, one of 3,913 younger patients with lower circulating inflammation levels and better renal function, and one of 483 generally older and more comorbid subjects, more prevalently men and smokers. The latter group was at increased death risk adjusted by HCQ (HR[CI95%] = 3.80[3.08-4.67]), while HCQ showed an independent inverse association (0.51[0.43-0.61]), as well as a significant influence of cluster∗HCQ interaction (<jats:inline-formula>\n <math xmlns=\"http://www.w3.org/1998/Math/MathML\" id=\"M1\">\n <mi>p</mi>\n <mo><</mo>\n <mn>0.001</mn>\n </math>\n </jats:inline-formula>). This was driven by a differential association of HCQ with mortality between the high (0.89[0.65-1.22]) and the low risk cluster (0.46[0.39-0.54]). These effects survived adjustments for additional medications in use and were concordant with associations with disease severity and outcome. These findings suggest a particularly beneficial effect of HCQ within low risk Covid-19 patients and may contribute to clarifying the current controversy on HCQ efficacy in Covid-19 treatment.</jats:p>",
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"title": "Disentangling the Association of Hydroxychloroquine Treatment with Mortality in Covid-19 Hospitalized Patients through Hierarchical Clustering",
"type": "journal-article",
"volume": "2021"
}
