TY - JOUR
T1 - Disentangling the association of hydroxychloroquine treatment with mortality in covid-19 hospitalized patients through hierarchical clustering
AU - Di Castelnuovo, Augusto
AU - Gialluisi, Alessandro
AU - Antinori, Andrea
AU - Berselli, Nausicaa
AU - Blandi, Lorenzo
AU - Bonaccio, Marialaura
AU - Bruno, Raffaele
AU - Cauda, Roberto
AU - Costanzo, Simona
AU - Guaraldi, Giovanni
AU - Menicanti, Lorenzo
AU - Mennuni, Marco
AU - My, Ilaria
AU - Parruti, Giustino
AU - Patti, Giuseppe
AU - Perlini, Stefano
AU - Santilli, Francesca
AU - Signorelli, Carlo
AU - Stefanini, Giulio
AU - Vergori, Alessandra
AU - Ageno, Walter
AU - Agodi, Antonella
AU - Agostoni, Piergiuseppe
AU - Aiello, Luca
AU - Moghazi, Samir Al
AU - Arboretti, Rosa
AU - Aucella, Filippo
AU - Barbieri, Greta
AU - Barchitta, Martina
AU - Bonfanti, Paolo
AU - Cacciatore, Francesco
AU - Caiano, Lucia
AU - Cannata, Francesco
AU - Carrozzi, Laura
AU - Cascio, Antonio
AU - Castiglione, Giacomo
AU - Cingolani, Antonella
AU - Fusco, Francesco Maria
AU - Gaudiosi, Carlo
AU - Gianfagna, Francesco
AU - Mapelli, Massimo
AU - Mussinelli, Roberta
AU - Musso, Maria
AU - Odone, Anna
AU - Olivieri, Marco
AU - Rossato, Marco
AU - Rossi, Marianna
AU - Sabena, Anna
AU - Scorzolini, Laura
AU - Iacoviello, Licia
N1 - Publisher Copyright:
Copyright © 2021 Augusto Di Castelnuovo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
PY - 2021
Y1 - 2021
N2 - 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 (p < 0.001). 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.
AB - 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 (p < 0.001). 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.
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U2 - 10.1155/2021/5556207
DO - 10.1155/2021/5556207
M3 - Article
AN - SCOPUS:85110514370
VL - 2021
JO - Journal of Healthcare Engineering
JF - Journal of Healthcare Engineering
SN - 2040-2295
M1 - 5556207
ER -