Successful recovery from COVID-19 pneumonia after receiving baricitinib, tocilizumab, and remdesivir. A case report: Review of treatments and clinical role of computed tomography analysis

The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic, threatening global public health. In the current paper, we describe our successful treatment of one COVID-19 pneumonia patient case with high mortality risk factors. Our experience underlines the importance of the use of a multidisciplinary therapeutic approach in order to achieve a favorable clinical outcome. Further, enhancing the capability of the COVID-19 diagnosis with the use of the chest imaging modalities is discussed

The management of acute venous thromboembolism in clinical practice - study rationale and protocol of the European PREFER in VTE Registry

Background: Venous thromboembolism (VTE) is a major health problem, with over one million events every year in Europe. However, there is a paucity of data on the current management in real life, including factors influencing treatment pathways, patient satisfaction, quality of life (QoL), and utilization of health care resources and the corresponding costs. The PREFER in VTE registry has been designed to address this and to understand medical care and needs as well as potential gaps for improvement. Methods/design: The PREFER in VTE registry was a prospective, observational, multicenter study conducted in seven European countries including Austria, France Germany, Italy, Spain, Switzerland, and the UK to assess the characteristics and the management of patients with VTE, the use of health care resources, and to provide data to estimate the costs for 12 months treatment following a first-time and/or recurrent VTE diagnosed in hospitals or specialized or primary care centers. In addition, existing anticoagulant treatment patterns, patient pathways, clinical outcomes, treatment satisfaction, and health related QoL were documented. The centers were chosen to reflect the care environment in which patients with VTE are managed in each of the participating countries. Patients were eligible to be enrolled into the registry if they were at least 18 years old, had a symptomatic, objectively confirmed first time or recurrent acute VTE defined as either distal or proximal deep vein thrombosis, pulmonary embolism or both. After the baseline visit at the time of the acute VTE event, further follow-up documentations occurred at 1, 3, 6 and 12 months. Follow-up data was collected by either routinely scheduled visits or by telephone calls. Results: Overall, 381 centers participated, which enrolled 3,545 patients during an observational period of 1 year. Conclusion: The PREFER in VTE registry will provide valuable insights into the characteristics of patients with VTE and their acute and mid-term management, as well as into drug utilization and the use of health care resources in acute first-time and/or recurrent VTE across Europe in clinical practice. Trial registration: Registered in DRKS register, ID number: DRKS0000479

DETERMINANTS OF 6-MONTH MORTALITY IN SURVIVORS OF MYOCARDIAL-INFARCTION AFTER THROMBOLYSIS - RESULTS OF THE GISSI-2 DATA-BASE

none647Background. Current knowledge of risk assessment in survivors of myocardial infarction is largely based on data gathered before the advent of thrombolysis. It must be determined whether and to what extent available information and proposed criteria of prognostication are applicable in the thrombolytic era. Methods and Results. We reassessed risk prediction in the 10 219 survivors of myocardial infarction with follow-up data available (ie, 98% of the total) who had been enrolled in the GISSI-2 trial, relying on a set of prespecified variables. The 3.5% 6-month all-cause mortality rate of these patients compared with the higher value of 4.6% found in the corresponding GISSI-1 cohort, originally allocated to streptokinase therapy, indicates a 24% reduction in postdischarge 6-month mortality. On multivariate analysis (Cox model), the following variables were predictors of 6-month all-cause mortality: ineligibility for exercise test for both cardiac (relative risk [RR], 3.30; 95% confidence interval [CI], 2.36-4.62) and noncardiac reasons (RR, 3.28; 95% CI, 2.23-4.72), early left ventricular failure (RR, 2.41; 95% Cl, 1.87-3.09), echocardiographic evidence of recovery phase left ventricular dysfunction (RR, 2.30; 95% CI, 1.78-2.98), advanced (more than 70 years) age (RR, 1.81; 95% Cl, 1.43 -2.30), electrical instability (ie, frequent and/or complex ventricular arrhythmias) (RR, 1.70; 95% Cl, 1.32-2.19), late left ventricular failure (RR, 1.54; 95% Cl, 1.17-2.03), previous myocardial infarction (RR, 1.47; 95% CI, 1.14-1.89), and a history of treated hypertension (RR, 1.32; 95% Cl, 1.05-1.65). Early post-myocardial infarction angina, a positive exercise test, female sex, history of angina, history of insulin-dependent diabetes, and anterior site of myocardial infarction were not risk predictors. On further multivariate analysis, performed on 8315 patients with the echocardiographic indicator of left ventricular dysfunction available, only previous myocardial infarction was not retained as an independent risk predictor. Conclusions. A decline in 6-month mortality of myocardial infarction survivors, seen within 6 hours of symptom onset, has been observed in recent years. Ineligibility for exercise test, early left ventricular failure, and recovery-phase left ventricular dysfunction are the most powerful (RR, >2) predictors of 6-month mortality among patients recovering from myocardial infarction after thrombolysis. Qualitative variables reflecting residual myocardial ischemia do not appear to be risk predictors. The lack of an independent adverse influence of early post-myocardial infarction angina on 6-month survival represents a major difference between this study and those of the prethrombolytic era.noneVOLPI A; DEVITA C; FRANZOSI MG; GERACI E; MAGGIONI AP; MAURI F; NEGRI E; SANTORO E; TAVAZZI L; TOGNONI G; FERUGLIO GA; LOTTO A; ROVELLI F; SOLINAS P; TAVAZZI L; TOGNONI G; BRUNO M; CAPPELLO T; COPPINI A; FINCATI F; MANTOVANI G; PANGRAZZI J; POGNA M; TURAZZA FM; ANSELMI M; BARBONAGLIA L; BIGI R; CAVALLI A; FRIGERIO M; GIORDANO A; GUALTIEROTTI C; TORTA D; CAROLA R; GIORDANO F; BARLOTTI R; LOPARCO G; VIGLINO GL; RUGGERI G; GIAMUNDO L; DANESI A; PACIARONI E; GAMBINI C; URBANO G; PURCARO A; FRANCESCONI M; FIGLIOLIA S; CANNONE M; ANTOLINI R; DEVOTI G; CRISTALLINI P; PORCIELLO PI; TEONI P; BURALI A; ZUCCONELLI V; DEMATTEIS C; IERVOGLINI A; SCATASTA M; AMABILI S; CARATTI CA; ZOLA G; FERRAGUTO P; SALICI G; CENTARO A; ROTIROTI D; GENOVESE M; GINEVRINO P; DAMATO N; ALTAMURA CM; COLONNA L; CASTELLANETA G; BOVENZI F; MESSINA D; GALANTINO A; CAMPOREALE N; CUCCHINI F; CAMPOSTELLA L; MALACRIDA R; GENONI M; PELLEGRINI P; BRIDDA A; RIGGI L; ACONE L; MOSCATIELLO G; BRUNO A; INVERNIZZI G; TESPILI M; GUAGLIUMI G; CASARI A; ALBANO T; TOMASSINI B; TORTA D; DIBIASE G; SCARAMUZZINO G; RUGGERO S; BRACCHETTI D; DECASTRO U; FULVI M; BRAITO E; ERLICHER A; OBERLECHNER W; GAGLIARDI RS; BIGHIGNOLI L; BONIZZATO G; RIZZI GM; SCAZZINA L; PERRINI A; STRANEO G; STRANEO U; SCIRE A; VERRIENTI A; GUADALUPI M; STORELLI A; ZUCCA L; DABUSTI M; ALBONICO B; DEPETRA V; TABACCHI GC; SCERVINO R; MEREU D; MAXIA P; BIANCO A; CRABU E; MANGIAMELI S; CENTAMORE G; MALFITANO D; AMICO C; VANCHERI F; SANTOPUOLI G; BALDINI F; PANTALEONI A; CONTESSOTTO F; TERLIZZI R; MERIGHI A; TURCHI E; TEGLIO V; PIGNATTI F; PEZZANA A; GOZZOLINO G; GIGLIO M; PETTINATI G; IEVA M; CIRICUGNO S; CORREALE E; ROMANO S; DIFUCCIA A; CASTELLANO B; NATALE A; CERNETTI C; CELEGON L; CANDELPERGHER G; ARIENZO F; RUSSO F; DEVIVO L; MAY L; ACHILLI G; BLASI A; SORRENTINO F; DATO A; GALLONE P; PALUMBO C; DELLAMONICA R; PAGANO L; ALBERTI A; ORSELLI L; DEPONTI C; PARMIGIANI ML; FERRARI M; ACITO P; BUSI F; DELLAVITTORIA G; BELLET C; BORTOLINI F; ROSSI A; CORONA C; BONDI S; NICCOLINI D; GAMBERI G; ARCURI G; MAIOLINO P; CARROZZA A; DELIO U; CAPRETTI G; MARINONI C; GUASCONI C; SONNINO S; PAGLIEI M; FERRARI G; LOMBARDI R; AGNELLI D; DERINALDIS G; CALCAGNILE A; SIGNORELLI S; BENDINELLI S; LUSETTI L; MOLLAIOLI M; COSMI F; PLASTINA F; VENNERI N; FERACO E; CATELLI P; POLUZZI C; DISTANTE S; BIANCHI C; COPPETTI S; ZAMPAGLIONE G; GATTO C; ZURLO R; USLENGHI E; MARGARIA F; MILANESE U; LOMANTO B; ZIACCHI V; RIVA D; BERTOCCHI P; TIRELLA G; DAULERIO M; SAURO G; BINI A; MAZZONI V; POGGI P; MARESTA A; JACOPI F; PATRONCINI A; PUPITA F; GAGGI S; FRAUSINI G; ANTONIOLI GE; MALACARNE C; CODECA L; CAPPATO R; ANDREOLI L; VARACCA S; BUIO E; FAZZINI PF; PUCCI P; SARRO F; VERGASSOLA R; BARCHIELLI M; DEMATTEIS D; CARRONE M; BRUNOZZI LT; MENICONI L; LIBERATI R; RADOGNA M; TALLONE M; CONTE R; IERI A; ZIPOLI A; SANSONI M; CANZIANI R; GUIDALI P; CRISTALLO E; MARIELLO F; MUZIO L; BENVENUTO MR; BALDINI MR; VECCHIO C; CHIARELLA F; FALCIDIENO M; CECCHI A; GIULIANO G; SEU V; PERUGINI P; TOSELLI A; BASSO F; CORTI E; ROSSI P; DELFINO R; CAPONNETTO S; GNECCO G; GHIGLIOTTI G; PENNESI A; LOMBARDI G; RUGGIERI A; BERTOLO L; SLOMP L; LANZETTA T; MAZZARONE L; CRESTI A; BELLODI G; ZUARINI AM; VENERI L; PARCHI C; GIOVANELLI N; NEGRONI S; DETHOMATIS M; BARGHINI A; MARINO E; RICCI D; LEMME P; DIGIACOMO U; AQUARO G; RONZANI G; OTTELLO B; VONTI V; MORETTI S; PALERMO R; MARSILI P; SIDERI F; RAGAZZINI G; GRAMENZI S; BATTISTINI S; DIODATO T; VALERIO A; TUCCI C; DEPASQUALE B; GELFO PG; BERTULLA A; BOLLINI R; DEMARCHI E; BACCA F; DEGIORGI V; LOCATELLI V; SAVOIA MT; FERRACINI C; BARBARESI F; COTOGNI A; FRANCO G; ROMANO S; PASSONI F; DURBANO M; MORETTI G; PEROTTI S; CAPRETTI M; DELBENE P; CASCONE M; BALDINI U; ORLANDI M; ODDONE A; CAIZZI V; MASINI G; LAZZARI M; BALLERINI B; BOZZI L; MOCETTI T; BERTOLINI A; PASOTTI E; SANGUINETTI M; MANTOVANI R; TOGNOLI T; MAGGI A; TUSA M; CAMERONI E; GUERRA GP; REGGIANI A; REDAELLI S; GIUSTI S; TANTALO L; RIZZI A; DIGIOVANNI N; GUZZO V; GABRIELE M; COLOMBO G; ALBERZONI A; SALVIOLI G; GALFETTI F; DOVICO E; BELLUZZI F; GOLA E; CASELLATO F; LECCHI G; CONSOLO F; SACCA CB; CONSOLO A; PICCOLO E; GASPARINI G; DEVITA C; ALBERTI A; MASSA D; BELLI C; DOSSENA MG; CORSINI C; SANNA GP; AZZOLLINI M; TRUAZZA F; LOTTO A; NADOR F; DEMARTINI M; BOZZI G; SEREGNI R; PASTINE I; MORPURGO M; CASAZZA F; REGALIA F; MAGGIOLINI S; RIGO R; PANCALDI S; POZZETTI D; PASCOTTO P; FRANCESCHI L; DAINESE F; MELINI L; CAPPELLI C; BERNARDI C; PALMIERI M; BORGIONI L; ZILIO G; SANDRI R; ALITTO F; MASARO G; VALAGUSSA F; SCHIAVINA R; RAVESI D; DANIELLO L; PIANTADOSI FR; BARRA P; ROMEO D; MININNI N; SEVERINO S; MOSTACCI M; CASTELLARI M; BANDA D; ROLANDI R; VILLA WD; CARBONE V; ALLEGRI M; FASCIOLO L; PITTALIS M; MUREDDU V; SORO F; DELEDDA MG; MARRAS E; MARCHI SM; DELUCA C; MANETTA M; VOLTA SD; SPERANDEO V; DONZELLI M; VITRANO MG; GERACI E; PITROLO F; LAMONICA S; BELLANCA G; MESSINA G; MIRTO U; RAINERI A; TRAINA M; DIBENEDETTO A; RIBAUDO E; DIFRANCESCO M; RONCHITELLI R; CARONE M; DIGREGORIO D; DIPAOLO G; PASQUALE M; COREA L; COCCHIERI M; ALUNNI G; PAPI L; CHIRIATTI G; LUPETTI M; GAZZOLA U; ARRUZZOLI S; VILLANI GQ; MELLINI M; MADRUZZA L; PIAZZA R; MICHELI G; FRANCHINI C; BECHI S; MARTINES C; MARCHESE D; GABBIA G; BIGALLI A; CIUTI M; CABANI E; DELCITERNA F; ALFIERI A; CHITI M; LONGHINI J; CODELUPPI P; NEGRELLI M; ZANUTTINI D; NICOLOSI GL; MARTIN G; PETRELLA A; BARDAZZI L; BIANCO GA; CELLAMARE G; GIANNELLI F; LICITRA G; LICITRA R; LETTICA GV; TUMIOTTO G; BELLANTI G; BOSI S; CASALI G; MONDUCCI I; BARONE A; PARENTI F; HEYMAN J; COZZI E; BALDACCI G; BACCOS D; BRIGHI F; DESANCTIS A; BOCK R; PALMIERI M; ROSSI F; AMATI P; SEMPRINI P; NARDELLI A; BOTTERO G; VARTOLO C; MILAZZOTTO F; DICROCE G; DIMARIO F; ANGRISANI G; AZZOLINI P; NEJA CP; MANZOLI U; ROSSI E; TRANI C; MASINI V; SEBASTIANI F; TOPAI M; BORGIA MC; LUCIANI C; FERRI F; DEPAOLA D; CAPURSO S; TUGNOLI F; VETTA C; ALTIERI T; BORZI M; VISCOMI A; STRIANO U; SALITURI S; ZONZIN P; FIORENCIS R; BADIN A; RAVERA B; BALDI C; SILVESTRI F; ALLEMANO P; REYNAUD S; SANSON A; MILANI L; DESIMONE MV; RUSSO A; VILLELLA A; GRAZINI M; AMIDEI S; ANSELMI L; PICCANICOLINO R; MASCELLI G; TAGLIAMONTE A; MESSINA V; TEDESCHI C; BOSSI M; BISIOLI M; TACCHI G; PAGNI G; VIVALDI F; IBBA GV; SANNIA L; PEDRAZZINI F; BAGNI E; FABII S; ALVINO A; ANTONIELLI E; DORONZO B; MARTINENGO E; BECCHI G; SALMOIRAGHI A; DIGIOVANNA F; CARAMANNO G; CAPORICCI D; BRUN M; GIANI P; FERRARIO G; PECI P; RONCONI G; SKOUSE D; BIANCHI C; GIUSTINIANI S; CUCCHI GF; TAVASCI E; SILVERII A; MARCELLINI G; SPECA G; STANISCIA D; CIMINO A; SERAFINI N; DEBONIS P; CERRUTI P; BAZZUCCHI M; DALPRA F; SPEROTTO C; MOLE GD; BARBANO G; POMARI F; GASCHINO G; PARIGI A; GANDOLFO N; RONDONI F; BRUSCA A; DILEO M; GOLZIO PG; ABRATE M; SCLAVO MG; ROCCI R; POGGIO G; GIANI S; CUZZUCREA D; BRASCHI GB; SCIACCA R; SAMMARTANO A; FURLANELLO F; BRAITO G; CUZZATO V; TOTIS O; FAURETTO F; LEO F; GALATI A; PALMA P; CAMERINI F; MORGERA T; BARBIERI L; FERUGLIO GA; SLAVICK GA; FRESCO C; CUDA A; SARNICOLA P; ARZILLO P; BINAGHI G; MACCHI G; CALVERI G; DIMARCO G; LEVANTESI G; PANERAI C; CATURELLI G; FACCHIN L; SARTORE G; ZARDINI P; MARINO P; CARBONIERI E; NAVA S; MAZZINI C; NAVA R; SERRA N; SASSARA M; NICROSINI F; GANDOLFI P; BERGOGNONI G; BALLESTRA AM; VIOLO CVOLPI A; DEVITA C; FRANZOSI MG; GERACI E; MAGGIONI AP; MAURI F; NEGRI E; SANTORO E; TAVAZZI L; TOGNONI G; FERUGLIO GA; LOTTO A; ROVELLI F; SOLINAS P; TAVAZZI L; TOGNONI G; BRUNO M; CAPPELLO T; COPPINI A; FINCATI F; MANTOVANI G; PANGRAZZI J; POGNA M; TURAZZA FM; ANSELMI M; BARBONAGLIA L; BIGI R; CAVALLI A; FRIGERIO M; GIORDANO A; GUALTIEROTTI C; TORTA D; CAROLA R; GIORDANO F; BARLOTTI R; LOPARCO G; VIGLINO GL; RUGGERI G; GIAMUNDO L; DANESI A; PACIARONI E; GAMBINI C; URBANO G; PURCARO A; FRANCESCONI M; FIGLIOLIA S; CANNONE M; ANTOLINI R; DEVOTI G; CRISTALLINI P; PORCIELLO PI; TEONI P; BURALI A; ZUCCONELLI V; DEMATTEIS C; IERVOGLINI A; SCATASTA M; AMABILI S; CARATTI CA; ZOLA G; FERRAGUTO P; SALICI G; CENTARO A; ROTIROTI D; GENOVESE M; GINEVRINO P; DAMATO N; ALTAMURA CM; COLONNA L; CASTELLANETA G; BOVENZI F; MESSINA D; GALANTINO A; CAMPOREALE N; CUCCHINI F; CAMPOSTELLA L; MALACRIDA R; GENONI M; PELLEGRINI P; BRIDDA A; RIGGI L; ACONE L; MOSCATIELLO G; BRUNO A; INVERNIZZI G; TESPILI M; GUAGLIUMI G; CASARI A; ALBANO T; TOMASSINI B; TORTA D; DIBIASE G; SCARAMUZZINO G; RUGGERO S; BRACCHETTI D; DECASTRO U; FULVI M; BRAITO E; ERLICHER A; OBERLECHNER W; GAGLIARDI RS; BIGHIGNOLI L; BONIZZATO G; RIZZI GM; SCAZZINA L; PERRINI A; STRANEO G; STRANEO U; SCIRE A; VERRIENTI A; GUADALUPI M; STORELLI A; ZUCCA L; DABUSTI M; ALBONICO B; DEPETRA V; TABACCHI GC; SCERVINO R; MEREU D; MAXIA P; BIANCO A; CRABU E; MANGIAMELI S; CENTAMORE G; MALFITANO D; AMICO C; VANCHERI F; SANTOPUOLI G; BALDINI F; PANTALEONI A; CONTESSOTTO F; TERLIZZI R; MERIGHI A; TURCHI E; TEGLIO V; PIGNATTI F; PEZZANA A; GOZZOLINO G; GIGLIO M; PETTINATI G; IEVA M; CIRICUGNO S; CORREALE E; ROMANO S; DIFUCCIA A; CASTELLANO B; NATALE A; CERNETTI C; CELEGON L; CANDELPERGHER G; ARIENZO F; RUSSO F; DEVIVO L; MAY L; ACHILLI G; BLASI A; SORRENTINO F; DATO A; GALLONE P; PALUMBO C; DELLAMONICA R; PAGANO L; ALBERTI A; ORSELLI L; DEPONTI C; PARMIGIANI ML; FERRARI M; ACITO P; BUSI F; DELLAVITTORIA G; BELLET C; BORTOLINI F; ROSSI A; CORONA C; BONDI S; NICCOLINI D; GAMBERI G; ARCURI G; MAIOLINO P; CARROZZA A; DELIO U; CAPRETTI G; MARINONI C; GUASCONI C; SONNINO S; PAGLIEI M; FERRARI G; LOMBARDI R; AGNELLI D; DERINALDIS G; CALCAGNILE A; SIGNORELLI S; BENDINELLI S; LUSETTI L; MOLLAIOLI M; COSMI F; PLASTINA F; VENNERI N; FERACO E; CATELLI P; POLUZZI C; DISTANTE S; BIANCHI C; COPPETTI S; ZAMPAGLIONE G; GATTO C; ZURLO R; USLENGHI E; MARGARIA F; MILANESE U; LOMANTO B; ZIACCHI V; RIVA D; BERTOCCHI P; TIRELLA G; DAULERIO M; SAURO G; BINI A; MAZZONI V; POGGI P; MARESTA A; JACOPI F; PATRONCINI A; PUPITA F; GAGGI S; FRAUSINI G; ANTONIOLI GE; MALACARNE C; CODECA L; CAPPATO R; ANDREOLI L; VARACCA S; BUIO E; FAZZINI PF; PUCCI P; SARRO F; VERGASSOLA R; BARCHIELLI M; DEMATTEIS D; CARRONE M; BRUNOZZI LT; MENICONI L; LIBERATI R; RADOGNA M; TALLONE M; CONTE R; IERI A; ZIPOLI A; SANSONI M; CANZIANI R; GUIDALI P; CRISTALLO E; MARIELLO F; MUZIO L; BENVENUTO MR; BALDINI MR; VECCHIO C; CHIARELLA F; FALCIDIENO M; CECCHI A; GIULIANO G; SEU V; PERUGINI P; TOSELLI A; BASSO F; CORTI E; ROSSI P; DELFINO R; CAPONNETTO S; GNECCO G; GHIGLIOTTI G; PENNESI A; LOMBARDI G; RUGGIERI A; BERTOLO L; SLOMP L; LANZETTA T; MAZZARONE L; CRESTI A; BELLODI G; ZUARINI AM; VENERI L; PARCHI C; GIOVANELLI N; NEGRONI S; DETHOMATIS M; BARGHINI A; MARINO E; RICCI D; LEMME P; DIGIACOMO U; AQUARO G; RONZANI G; OTTELLO B; VONTI V; MORETTI S; PALERMO R; MARSILI P; SIDERI F; RAGAZZINI G; GRAMENZI S; BATTISTINI S; DIODATO T; VALERIO A; TUCCI C; DEPASQUALE B; GELFO PG; BERTULLA A; BOLLINI R; DEMARCHI E; BACCA F; DEGIORGI V; LOCATELLI V; SAVOIA MT; FERRACINI C; BARBARESI F; COTOGNI A; FRANCO G; ROMANO S; PASSONI F; DURBANO M; MORETTI G; PEROTTI S; CAPRETTI M; DELBENE P; CASCONE M; BALDINI U; ORLANDI M; ODDONE A; CAIZZI V; MASINI G; LAZZARI M; BALLERINI B; BOZZI L; MOCETTI T; BERTOLINI A; PASOTTI E; SANGUINETTI M; MANTOVANI R; TOGNOLI T; MAGGI A; TUSA M; CAMERONI E; GUERRA GP; REGGIANI A; REDAELLI S; GIUSTI S; TANTALO L; RIZZI A; DIGIOVANNI N; GUZZO V; GABRIELE M; COLOMBO G; ALBERZONI A; SALVIOLI G; GALFETTI F; DOVICO E; BELLUZZI F; GOLA E; CASELLATO F; LECCHI G; CONSOLO F; SACCA CB; CONSOLO A; PICCOLO E; GASPARINI G; DEVITA C; ALBERTI A; MASSA D; BELLI C; DOSSENA MG; CORSINI C; SANNA GP; AZZOLLINI M; TRUAZZA F; LOTTO A; NADOR F; DEMARTINI M; BOZZI G; SEREGNI R; PASTINE I; MORPURGO M; CASAZZA F; REGALIA F; MAGGIOLINI S; RIGO R; PANCALDI S; POZZETTI D; PASCOTTO P; FRANCESCHI L; DAINESE F; MELINI L; CAPPELLI C; BERNARDI C; PALMIERI M; BORGIONI L; ZILIO G; SANDRI R; ALITTO F; MASARO G; VALAGUSSA F; SCHIAVINA R; RAVESI D; DANIELLO L; PIANTADOSI FR; BARRA P; ROMEO D; MININNI N; SEVERINO S; MOSTACCI M; CASTELLARI M; BANDA D; ROLANDI R; VILLA WD; CARBONE V; ALLEGRI M; FASCIOLO L; PITTALIS M; MUREDDU V; SORO F; DELEDDA MG; MARRAS E; MARCHI SM; DELUCA C; MANETTA M; VOLTA SD; SPERANDEO V; DONZELLI M; VITRANO MG; GERACI E; PITROLO F; LAMONICA S; BELLANCA G; MESSINA G; MIRTO U; RAINERI A; TRAINA M; DIBENEDETTO A; RIBAUDO E; DIFRANCESCO M; RONCHITELLI R; CARONE M; DIGREGORIO D; DIPAOLO G; PASQUALE M; COREA L; COCCHIERI M; ALUNNI G; PAPI L; CHIRIATTI G; LUPETTI M; GAZZOLA U; ARRUZZOLI S; VILLANI GQ; MELLINI M; MADRUZZA L; PIAZZA R; MICHELI G; FRANCHINI C; BECHI S; MARTINES C; MARCHESE D; GABBIA G; BIGALLI A; CIUTI M; CABANI E; DELCITERNA F; ALFIERI A; CHITI M; LONGHINI J; CODELUPPI P; NEGRELLI M; ZANUTTINI D; NICOLOSI GL; MARTIN G; PETRELLA A; BARDAZZI L; BIANCO GA; CELLAMARE G; GIANNELLI F; LICITRA G; LICITRA R; LETTICA GV; TUMIOTTO G; BELLANTI G; BOSI S; CASALI G; MONDUCCI I; BARONE A; PARENTI F; HEYMAN J; COZZI E; BALDACCI G; BACCOS D; BRIGHI F; DESANCTIS A; BOCK R; PALMIERI M; ROSSI F; AMATI P; SEMPRINI P; NARDELLI A; BOTTERO G; VARTOLO C; MILAZZOTTO F; DICROCE G; DIMARIO F; ANGRISANI G; AZZOLINI P; NEJA CP; MANZOLI U; ROSSI E; TRANI C; MASINI V; SEBASTIANI F; TOPAI M; BORGIA MC; LUCIANI C; FERRI F; DEPAOLA D; CAPURSO S; TUGNOLI F; VETTA C; ALTIERI T; BORZI M; VISCOMI A; STRIANO U; SALITURI S; ZONZIN P; FIORENCIS R; BADIN A; RAVERA B; BALDI C; SILVESTRI F; ALLEMANO P; REYNAUD S; SANSON A; MILANI L; DESIMONE MV; RUSSO A; VILLELLA A; GRAZINI M; AMIDEI S; ANSELMI L; PICCANICOLINO R; MASCELLI G; TAGLIAMONTE A; MESSINA V; TEDESCHI C; BOSSI M; BISIOLI M; TACCHI G; PAGNI G; VIVALDI F; IBBA GV; SANNIA L; PEDRAZZINI F; BAGNI E; FABII S; ALVINO A; ANTONIELLI E; DORONZO B; MARTINENGO E; BECCHI G; SALMOIRAGHI A; DIGIOVANNA F; CARAMANNO G; CAPORICCI D; BRUN M; GIANI P; FERRARIO G; PECI P; RONCONI G; SKOUSE D; BIANCHI C; GIUSTINIANI S; CUCCHI GF; TAVASCI E; SILVERII A; MARCELLINI G; SPECA G; STANISCIA D; CIMINO A; SERAFINI N; DEBONIS P; CERRUTI P; BAZZUCCHI M; DALPRA F; SPEROTTO C; MOLE GD; BARBANO G; POMARI F; GASCHINO G; PARIGI A; GANDOLFO N; RONDONI F; BRUSCA A; DILEO M; GOLZIO PG; ABRATE M; SCLAVO MG; ROCCI R; POGGIO G; GIANI S; CUZZUCREA D; BRASCHI GB; SCIACCA R; SAMMARTANO A; FURLANELLO F; BRAITO G; CUZZATO V; TOTIS O; FAURETTO F; LEO F; GALATI A; PALMA P; CAMERINI F; MORGERA T; BARBIERI L; FERUGLIO GA; SLAVICK GA; FRESCO C; CUDA A; SARNICOLA P; ARZILLO P; BINAGHI G; MACCHI G; CALVERI G; DIMARCO G; LEVANTESI G; PANERAI C; CATURELLI G; FACCHIN L; SARTORE G; ZARDINI P; MARINO P; CARBONIERI E; NAVA S; MAZZINI C; NAVA R; SERRA N; SASSARA M; NICROSINI F; GANDOLFI P; BERGOGNONI G; BALLESTRA AM; VIOLO

Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial

BackgroundTocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients.MethodsA multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival.ResultsIn the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6-24.0, P=0.52) and 22.4% (97.5% CI: 17.2-28.3, P<0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline.ConclusionsTocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline.Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092)