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.

Disentangling the association of hydroxychloroquine treatment with mortality in covid-19 hospitalized patients through hierarchical clustering / A. Di Castelnuovo, A. Gialluisi, A. Antinori, N. Berselli, L. Blandi, M. Bonaccio, R. Bruno, R. Cauda, S. Costanzo, G. Guaraldi, L. Menicanti, M. Mennuni, I. My, G. Parruti, G. Patti, S. Perlini, F. Santilli, C. Signorelli, G. Stefanini, A. Vergori, W. Ageno, A. Agodi, P. Agostoni, L. Aiello, S.A. Moghazi, R. Arboretti, F. Aucella, G. Barbieri, M. Barchitta, P. Bonfanti, F. Cacciatore, L. Caiano, F. Cannata, L. Carrozzi, A. Cascio, G. Castiglione, A. Cicullo, A. Cingolani, F. Cipollone, C. Colomba, C. Colombo, A. Crisetti, F. Crosta, G.B. Danzi, D. D'Ardes, K. de Gaetano Donati, F. Di Gennaro, G. Di Tano, G. D'Offizi, F.M. Fusco, C. Gaudiosi, I. Gentile, F. Gianfagna, G. Giuliano, E. Graziani, G. Guarnieri, V. Langella, G. Larizza, A. Leone, G. Maccagni, F. Magni, S. Maitan, S. Mancarella, R. Manuele, M. Mapelli, R. Maragna, R. Marcucci, G. Maresca, S. Marongiu, C. Marotta, L. Marra, F. Mastroianni, A. Mengozzi, M. Meschiari, J. Milic, F. Minutolo, R. Mussinelli, C. Mussini, M. Musso, A. Odone, M. Olivieri, A. Palimodde, E. Pasi, R. Pesavento, F. Petri, C.A. Pivato, V. Poletti, C. Ravaglia, G. Righetti, A. Rognoni, M. Rossato, I. Rossi, M. Rossi, A. Sabena, F. Salinaro, V. Sangiovanni, C. Sanrocco, N.S. Moriello, L. Scorzolini, R. Sgariglia, P.G. Simeone, M. Spinicci, E. Tamburrini, C. Torti, E.M. Trecarichi, R. Vettor, A. Vianello, M. Vinceti, A. Virdis, R. de Caterina, L. Iacoviello. - In: JOURNAL OF HEALTHCARE ENGINEERING. - ISSN 2040-2295. - 2021:(2021 Jun 25), pp. 5556207.1-5556207.10. [10.1155/2021/5556207]

Disentangling the association of hydroxychloroquine treatment with mortality in covid-19 hospitalized patients through hierarchical clustering

M. Mennuni;P. Agostoni;M. Mapelli;R. Maragna;F. Petri;
2021

Abstract

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.
Settore MED/11 - Malattie dell'Apparato Cardiovascolare
25-giu-2021
Article (author)
File in questo prodotto:
File Dimensione Formato  
5556207.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 1.45 MB
Formato Adobe PDF
1.45 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/861242
Citazioni
  • ???jsp.display-item.citation.pmc??? 1
  • Scopus 1
  • ???jsp.display-item.citation.isi??? 0
social impact