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Disentangling the Association of Hydroxychloroquine Treatment with Mortality in Covid-19 Hospitalized Patients through Hierarchical Clustering.

Augusto Di CastelnuovoAlessandro GialluisiAndrea AntinoriNausicaa BerselliLorenzo BlandiMarialaura BonaccioRaffaele BrunoRoberto CaudaSimona CostanzoGiovanni GuaraldiLorenzo MenicantiMarco MennuniIlaria MyGiustino ParrutiGiuseppe PattiStefano PerliniFrancesca SantilliCarlo SignorelliGiulio StefaniniAlessandra VergoriWalter AgenoAntonella AgodiPiergiuseppe AgostoniLuca AielloSamir Al MoghaziRosa ArborettiFilippo AucellaGreta BarbieriMartina BarchittaPaolo BonfantiFrancesco CacciatoreLucia CaianoFrancesco CannataLaura CarrozziAntonio CascioGiacomo CastiglioneArturo CicculloAntonella CingolaniFrancesco CipolloneClaudia ColombaCrizia ColomboAnnalisa CrisettiFrancesca CrostaGian Battista DanziDamiano D'ArdesKatleen de Gaetano DonatiFrancesco Di GennaroGiuseppe Di TanoGianpiero D'OffiziFrancesco Maria FuscoCarlo GaudiosiIvan GentileFrancesco GianfagnaGabriele GiulianoEmauele GrazianiGabriella GuarnieriValerio LangellaGiovanni LarizzaArmando LeoneGloria MaccagniFederica MagniStefano MaitanSandro MancarellaRosa ManueleMassimo MapelliRiccardo MaragnaRossella MarcucciGiulio MarescaSilvia MarongiuClaudia MarottaLorenzo MarraFranco MastroianniAlessandro MengozziMarianna MeschiariJovana MilicFilippo MinutoloRoberta MussinelliCristina MussiniMaria MussoAnna OdoneMarco OlivieriAntonella PalimoddeEmanuela PasiRaffaele PesaventoFrancesco PetriCarlo A PivatoVenerino PolettiClaudia RavagliaGiulia RighettiAndrea RognoniMarco RossatoIlaria RossiMarianna RossiAnna SabenaFrancesco SalinaroVincenzo SangiovanniCarlo SanroccoNicola Schiano MorielloLaura ScorzoliniRaffaella SgarigliaPaola Giustina SimeoneMichele SpinicciEnrica TamburriniCarlo TortiEnrico Maria TrecarichiRoberto VettorAndrea VianelloMarco VincetiAgostino VirdisRaffaele De CaterinaLicia Iacoviello
Published in: Journal of healthcare engineering (2021)
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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