Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial.
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Humanized
/ therapeutic use
Betacoronavirus
/ drug effects
COVID-19
Cohort Studies
Coronavirus Infections
/ drug therapy
Female
Humans
Italy
/ epidemiology
Male
Middle Aged
Mortality
Off-Label Use
Pandemics
Pneumonia, Viral
/ drug therapy
SARS-CoV-2
Treatment Outcome
Validation Studies as Topic
COVID-19
Coronavirus
IL-6
Mortality
Phase 2
Pneumonia
Safety
Tocilizumab
Journal
Journal of translational medicine
ISSN: 1479-5876
Titre abrégé: J Transl Med
Pays: England
ID NLM: 101190741
Informations de publication
Date de publication:
21 10 2020
21 10 2020
Historique:
received:
28
09
2020
accepted:
13
10
2020
entrez:
22
10
2020
pubmed:
23
10
2020
medline:
31
10
2020
Statut:
epublish
Résumé
Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. A 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. In 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. Tocilizumab 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).
Sections du résumé
BACKGROUND
Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients.
METHODS
A 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.
RESULTS
In 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.
CONCLUSIONS
Tocilizumab 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).
Identifiants
pubmed: 33087150
doi: 10.1186/s12967-020-02573-9
pii: 10.1186/s12967-020-02573-9
pmc: PMC7576974
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
tocilizumab
I031V2H011
Banques de données
ClinicalTrials.gov
['NCT04317092']
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
405Investigateurs
Francesco Perrone
(F)
Maria Carmela Piccirillo
(MC)
Clorinda Schettino
(C)
Adriano Gravina
(A)
Piera Gargiulo
(P)
Claudia Cardone
(C)
Laura Arenare
(L)
Paolo Antonio Ascierto
(PA)
Maria Grazia Vitale
(MG)
Claudia Trojaniello
(C)
Marco Palla
(M)
Attilio Antonio Montano Bianchi
(AAM)
Gerardo Botti
(G)
Gianfranco De Feo
(G)
Leonardo Miscio
(L)
Ciro Gallo
(C)
Paolo Chiodini
(P)
Laurenzia Ferraris
(L)
Massimiliano M Marrocco-Trischitta
(MM)
Marco Froldi
(M)
Lorenzo Menicanti
(L)
Maria Teresa Cuppone
(MT)
Giulia Gobbo
(G)
Chiara Baldessari
(C)
Vincenzo Valenti
(V)
Serenella Castelvecchio
(S)
Federica Poli
(F)
Francesca Giacomazzi
(F)
Rosangela Piccinni
(R)
Maria Laura Annnunziata
(ML)
Andrea Biondi
(A)
Cecilia Bussolari
(C)
Manuel Mazzoleni
(M)
Andrea Giachi
(A)
Annalisa Filtz
(A)
Arianna Manini
(A)
Enrico Poletti
(E)
Federico Masserini
(F)
Francesco Conforti
(F)
Gianfranco Gaudiano
(G)
Vittoria Favero
(V)
Alice Moroni
(A)
Tommaso Viva
(T)
Fabiana Fancoli
(F)
Davide Ferrari
(D)
Dario Niro
(D)
Marco Resta
(M)
Andrea Ballotta
(A)
Marco Dei Poli
(MD)
Marco Ranucci
(M)
Diego Ripamonti
(D)
Francesca Binda
(F)
Alessandra Tebaldi
(A)
Giuseppe Gritti
(G)
Luisa Pasulo
(L)
Leonardo Gaglio
(L)
Roberto Del Fabbro
(R)
Leonardo Alborghetti
(L)
Paolo Bonfanti
(P)
Nicola Squillace
(N)
Giulia Giustinetti
(G)
Paola Columpsi
(P)
Marina Cazzaniga
(M)
Serena Capici
(S)
Luca Sala
(L)
Riccardo Di Sciacca
(R)
Giacomo Mosca
(G)
Maria Rosa Pirozzi
(MR)
Francesco Castelli
(F)
Maria Lorenza Muiesan
(ML)
Franco Franceschini
(F)
Aldo Roccaro
(A)
Massimo Salvetti
(M)
Anna Paini
(A)
Luciano Corda
(L)
Chiara Ricci
(C)
Lina Tomasoni
(L)
Paola Nasta
(P)
Silvia Lorenzotti
(S)
Silvia Odolini
(S)
Emanuele Focà
(E)
Eugenia Quiros Roldan
(EQ)
Marco Metra
(M)
Stefano Magrini
(S)
Paolo Borghetti
(P)
Nicola Latronico
(N)
Simone Piva
(S)
Matteo Filippini
(M)
Francesco Zuccalà
(F)
Sergio Cattaneo
(S)
Francesco Scolari
(F)
Nicola Bossini
(N)
Mario Gaggiotti
(M)
Martina Properzi
(M)
Miriam Lichtner
(M)
Cosmo Del Borgo
(C)
Raffaella Marocco
(R)
Valeria Belvisi
(V)
Tiziana Tieghi
(T)
Margherita De Masi
(M)
Paola Zuccalà
(P)
Paolo Fabietti
(P)
Angelo Vetica
(A)
Vito Sante Mercurio
(VS)
Anna Carraro
(A)
Laura Fondaco
(L)
Blerta Kertusha
(B)
Ambrogio Curtolo
(A)
Emanuela Del Giudice
(E)
Riccardo Lubrano
(R)
Maria Gioconda Zotti
(MG)
Antonella Puorto
(A)
Marcello Ciuffreda
(M)
Antonella Sarni
(A)
Gabriella Monteforte
(G)
Domenico Romeo
(D)
Emanuela Viola
(E)
Carla Damiani
(C)
Antonietta Barone
(A)
Barbara Mantovani
(B)
Daniela Di Sanzo
(D)
Vincenzo Gentili
(V)
Massimo Carletti
(M)
Massimo Aiuti
(M)
Andrea Gallo
(A)
Piero Giuseppe Meliante
(PG)
Salvatore Martellucci
(S)
Oliviero Riggio
(O)
Vincenzo Cardinale
(V)
Lorenzo Ridola
(L)
Maria Consiglia Bragazzi
(MC)
Stefania Gioia
(S)
Emiliano Valenzi
(E)
Camilla Graziosi
(C)
Niccolò Bina
(N)
Martina Fasolo
(M)
Silvano Ricci
(S)
Maria Teresa Gioacchini
(MT)
Antonella Lucci
(A)
Luisella Corso
(L)
Daniela Tornese
(D)
Parni Nijhawan
(P)
Francesco Equitani
(F)
Carmine Cosentino
(C)
Marcello Palladino
(M)
Frida Leonetti
(F)
Gaetano Leto
(G)
Camillo Gnessi
(C)
Giuseppe Campagna
(G)
Roberto Cesareo
(R)
Francesca Marrocco
(F)
Giuseppe Straface
(G)
Alessandra Mecozzi
(A)
Lidia Cerbo
(L)
Valentina Isgrò
(V)
Sergio Parrocchia
(S)
Giuseppe Visconti
(G)
Giorgio Casati
(G)
Carlo Calzetti
(C)
Alarico Ariani
(A)
Lorenzo Donghi
(L)
Nicola Duccio Salerno
(ND)
Evelina Tacconelli
(E)
Marco Bertoldi
(M)
Paolo Cattaneo
(P)
Lorenza Lambertenghi
(L)
Leonardo Motta
(L)
Luca Omega
(L)
Giovanni Albano
(G)
Roberto Parrella
(R)
Fiorentino Fraganza
(F)
Luigi Atripaldi
(L)
Vincenzo Montesarchio
(V)
Francesco Scarano
(F)
Annunziata De Rosa
(A)
Amalia Buglione
(A)
Sabrina Lavoretano
(S)
Gianfranco Gaglione
(G)
Mario De Marco
(M)
Vincenzo Sangiovanni
(V)
Francesco Maria Fusco
(FM)
Rosaria Viglietti
(R)
Elio Manzillo
(E)
Carolina Rescigno
(C)
Raffaella Pisapia
(R)
Giulia Plamieri
(G)
Alberto Maraolo
(A)
Giosuè Calabria
(G)
Mario Catalano
(M)
Giuseppe Fiorentino
(G)
Anna Annunziata
(A)
Giorgio Polistina
(G)
Pasquale Imitazione
(P)
Mariano Mollica
(M)
Vincenzo Esposito
(V)
Maurizio D'Abraccio
(M)
Rodolfo Punzi
(R)
Vincenzo Bianco
(V)
Costanza Sbreglia
(C)
Rosa Fontana Del Vecchio
(RF)
Alessandro Bordonali
(A)
Antonina Franco
(A)
Carlo Salvarani
(C)
Marco Massari
(M)
Giovanni Dolci
(G)
Pierpaolo Salsi
(P)
Giuseppe Virzì
(G)
Calderone Ornella
(C)
Alfredo Molteni
(A)
Silvia Gennarini
(S)
Umberto Gnudi
(U)
Maria Anastasia Ricci
(MA)
Giancarlo Titolo
(G)
Giulio Mensi
(G)
Pietro Vuotto
(P)
Beatrice Gasperini
(B)
Mauro Mancini
(M)
Zeno Pasquini
(Z)
Paolo Spanu
(P)
Stefano Clementi
(S)
Simona Pierini
(S)
Daniela Bokor
(D)
Daniela Gori
(D)
Morena Ciofetti
(M)
Marina Caimi
(M)
Laura Bettazzi
(L)
Elisabetta Allevi
(E)
Silvia Furiani
(S)
Chiara Capitanio
(C)
Bernardino Mastropasqua
(B)
Claudio Fara
(C)
Grazia Pulitanò
(G)
Jun Sebastian Matsuno
(JS)
Francesca Della Porta
(FD)
Viola Dolfini
(V)
Nebiat Balei Beyene
(NB)
Michela Bezzi
(M)
Mauro Novali
(M)
Pierluigi Viale
(P)
Sara Tedeschi
(S)
Renato Pascale
(R)
Raffaele Bruno
(R)
Alessandro Di Filippo
(A)
Michele Sachs
(M)
Tiberio Oggionni
(T)
Michele Di Stefano
(M)
Caterina Mengoli
(C)
Cesarina Facchini
(C)
De Nardo Daniele
(N)
Gabriele Frausini
(G)
Luciano Mucci
(L)
Silvia Tedesco
(S)
Rita Girolimetti
(R)
Elena Manfredini
(E)
Anna Maria Di Carlo
(AM)
Emma Espinosa
(E)
Donatella Dennetta
(D)
Andrea Ticinesi
(A)
Tiziana Meschi
(T)
Antonio Nouvenne
(A)
Norbiato Claudio
(N)
Francesco Vitale
(F)
Marta Saracco
(M)
Mauro Codeluppi
(M)
Elisa Fronti
(E)
Patrizia Ferrante
(P)
Giorgio Amadio Nespola
(GA)
Daniela Francisci
(D)
Andrea Tosti
(A)
Cristiano Matteo Carbonelli
(CM)
Antonio Greco
(A)
Maria Giulia Tinti
(MG)
Roberto Stellini
(R)
Camilla Appiani
(C)
Piera Reghenzi
(P)
Venerino Poletti
(V)
Claudia Ravaglia
(C)
Danilo Tacconi
(D)
Costanza Malcontenti
(C)
Pier Paolo Sainaghi
(PP)
Raffaella Landi
(R)
Veronica Vassia
(V)
Eleonora Rizzi
(E)
Mattia Bellan
(M)
Antonella Rossati
(A)
Luigi Castello
(L)
Claudio Maria Mastroianni
(CM)
Gianluca Russo
(G)
Toffoletto Fabio
(T)
Francesco Saverio Serino
(FS)
Lucio Brollo
(L)
Elena Momesso
(E)
Maria Luisa Turati
(ML)
Antonella D'arminio Monforte
(AD)
Giulia Marchetti
(G)
Fabrizio Boni
(F)
Elisabetta Teopompi
(E)
Chiara Trenti
(C)
Luca Boracchia
(L)
Enrica Minelli
(E)
Matteo Fontana
(M)
Giulia Ghidoni
(G)
Anaflorina Matei
(A)
Andrea Caruso
(A)
Giuseppe Arcoleo
(G)
Gaetana Camarda
(G)
Filippo Catalano
(F)
Mario Spatafora
(M)
Donato Bettega
(D)
Massimo Andreoni
(M)
Elisabetta Teti
(E)
Loredana Sarmati
(L)
Andrea Di Lorenzo
(A)
Mariagrazia Celeste
(M)
Fabio Baratto
(F)
Jacopo Monticelli
(J)
Pietro Criveller
(P)
Antonini Andrea
(A)
None Anselmo
None Riccio
Maurizio Castellano
(M)
Carlo Cappelli
(C)
Federica Corvini
(F)
Barbara Zanini
(B)
Massimo Crippa
(M)
Maurizio Ronconi
(M)
Raffaella Costa
(R)
Silvia Casella
(S)
Loretta Brentana
(L)
Livio Bernardi
(L)
Andrea Frascati
(A)
Sandro Panese
(S)
Fabio Presotto
(F)
Lucio Michieletto
(L)
Cristina Bernardi
(C)
Maurizio Fusar
(M)
Vanni Agnoletti
(V)
Martina Farina
(M)
None Russo
Federico Lavorini
(F)
Roberta Ginanni
(R)
Fabrizio Palmieri
(F)
Silvia Mosti
(S)
Angelo Amaglio
(A)
Alessandra Cattaneo
(A)
Silvia Cirri
(S)
Andrea Montisci
(A)
Chiara Gallazzi
(C)
Daniele Cosseta
(D)
Barabara Baronio
(B)
Lorenzo Rampa
(L)
Paolo Maggi
(P)
Vincenzo Messina
(V)
Emanuele Alberto Negri
(EA)
Maria Cecilia Sabatti
(MC)
Michele Palumbo
(M)
Antonino Mazzone
(A)
Paola Faggioli
(P)
Linda Bussini
(L)
Giacomo Fornaro
(G)
Francesca Volpato
(F)
Daniele Imperiale
(D)
Emilpaolo Manno
(E)
Enrico Ferreri
(E)
Domenico Martelli
(D)
Andrea Verhovez
(A)
Silvia Giorgis
(S)
Luciana Faccio
(L)
Rachele Delli Quadri
(RD)
Cristina Negro
(C)
Marcella Converso
(M)
Francesca Bosco
(F)
Paolo Prandini
(P)
Silvia Cocchi
(S)
Vinicio Manfrin
(V)
Veronica Del Punta
(V)
Giovanni Mazzola
(G)
Giuseppe Sportato
(G)
Micaela Romagnoli
(M)
Francesco Cristini
(F)
Francesca Facondini
(F)
Tiziana Perin
(T)
Andrea Boschi
(A)
Cristina Mussini
(C)
Marianna Meschiari
(M)
Giovanni Guaraldi
(G)
Sara Modica
(S)
Sara Moneta
(S)
Daniela Boccalatte
(D)
Clara Ricci
(C)
Valentina Marchetti
(V)
Silvia Amadasi
(S)
Gabriele Ebbreo
(G)
Michael Dalè
(M)
Paolo Tura
(P)
Damiano Rizzoni
(D)
Gianluca Edoardo Mario Boari
(GEM)
Silvia Bonetti
(S)
Enrico Marini
(E)
Italiani Daniele
(I)
Paolo Antonio Grossi
(PA)
Nichola Walter Delfrate
(NW)
Othmar Bernhart
(O)
Gilbert Spizzo
(G)
Klaus Mahlknecht
(K)
Thomas Volkl
(T)
Massimo Antonio Di Pietro
(MA)
Michele Trezzi
(M)
Cecilia Monacci
(C)
Adriano Peris
(A)
Manuela Bonizzoli
(M)
Luigi Cavanna
(L)
Carlo Moroni
(C)
Elisa Maria Stroppa
(EM)
Alessandra Manini
(A)
Maria Cristina Savio
(MC)
Francesca Gatti
(F)
Clara Bartolaminelli
(C)
Nicola Petrosillo
(N)
Davide R Donno
(DR)
Fabrizio Taglietti
(F)
Simone Topino
(S)
Pierangelo Chinello
(P)
Vincenzo Galati
(V)
Gianpiero D'offizi
(G)
Chiara Taibi
(C)
Barbara Cimolato
(B)
Federico Moroni
(F)
Nicolas Palagano
(N)
Lorenzo Pelagatti
(L)
Seravalle Cristiana
(S)
Giancarlo Landini
(G)
Maria Amitrano
(M)
Mariangela Raimondo
(M)
Sara Mangiacapra
(S)
Annamaria Romano
(A)
Mariangela Atteno
(M)
Katia Casinelli
(K)
Ilaria Uccella
(I)
Sergio Harari
(S)
Antonella Caminati
(A)
Filippo Lipani
(F)
Giovanni Di Perri
(G)
Andrea Calcagno
(A)
Guido Calleri
(G)
Chiara Montrucchio
(C)
Anna Maria Caputo
(AM)
Susanna Cozzio
(S)
Livia Delle Donne
(LD)
Matteo Bassetti
(M)
Mikulska Malgorzata
(M)
Laura Ambra Nicolini
(LA)
Chiara Russo
(C)
Chiara Sepulcri
(C)
Sabrina Beltramini
(S)
Federica Mina
(F)
Massimo Puoti
(M)
Anna Gandino
(A)
Thomas Langer
(T)
Federico D'amico
(F)
Marialma Berlendis
(M)
Chiara Rocchetti
(C)
Francesca Cettolo
(F)
Frausini Gabriele
(F)
Pietro Bocchi
(P)
Giorgio Cioni
(G)
Cinzia Cappi
(C)
Silvia Corcione
(S)
Francesco Giuseppe De Rosa
(FG)
Silvia Scabini
(S)
Francesca Canta
(F)
Simone Mornese Pinna
(SM)
Anna Pensa
(A)
Pierluigi Blanc
(P)
Lorenzo Roberto Suardi
(LR)
Carlo Pallotto
(C)
Monica Rocco
(M)
Maria Teresa Cirasa
(MT)
Michele Spinicci
(M)
Jessica Mencarini
(J)
Lorenzo Zammarchi
(L)
Cenderello Giovanni
(C)
Katiuscia Sciolè
(K)
Flavio Bassi
(F)
Michele Bianchi
(M)
Sillia Frigerio
(S)
Sandra Spaziani
(S)
Antonia Nucera
(A)
Giuliano Rizzardini
(G)
Maria Vittoria Cossu
(MV)
Marco Antivalle
(M)
Giuseppe Carpinteri
(G)
Sebastiano Macheda
(S)
Demetrio Labate
(D)
Maurizio Bottiroli
(M)
Anacleto Romano
(A)
Elke Maria Erne
(EM)
Zocchetti Cristina
(Z)
Valeria Di Biase
(V)
Fabio Malberti
(F)
Giovanni Montani
(G)
Paolo Poisa
(P)
Daniela Bettini
(D)
Roberto Cauda
(R)
Arturo Ciccullo
(A)
Niccolò Riccardi
(N)
Andrea Angheben
(A)
Mauro Turrini
(M)
Raffaella Clerici
(R)
Angelo Gardellini
(A)
Luigi Liparulo
(L)
Tizana Rossini
(T)
Claudio Ucciferri
(C)
Francesco Cipollone
(F)
Jacopo Vecchiet
(J)
Andrea Nico
(A)
Lorenzo Marra
(L)
Armando Leone
(A)
Antonia Sdanganelli
(A)
Giuseppe Antonio Palmiotti
(GA)
Giancarlo D'Alagni
(G)
Teresa Antonia Santantonio
(TA)
Sergio Lo Caputo
(S)
Irene Bottalico
(I)
Antonio Ponticiello
(A)
Felicia Di Perna
(F)
Enrico Bernardi
(E)
Angela Beltrame
(A)
Stefania Bravi
(S)
Marco David
(M)
Paola Bernardi
(P)
Dario Galante
(D)
Maria Cristina Uccelli
(MC)
Katiela Prestini
(K)
Monica Drera
(M)
Enea Zini
(E)
Alessio Peregrinelli
(A)
Laura Blanzuoli
(L)
Valentina Benedetti
(V)
Rovberta Calvi
(R)
Nadia Scaglione
(N)
Gabriella Nallino
(G)
Maurizio Bonazzi
(M)
Tiziano Crespi
(T)
Tiziana Masolin
(T)
Angelo Regazzetti
(A)
Maria Chiara Cerri
(MC)
Elena Maffezzini
(E)
Manuela Piazza
(M)
Claudia Papetti
(C)
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(C)
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Giovanna D'Andrea
(G)
Filippo Amoroso
(F)
Antonio Arcidiacono
(A)
Anna Maria Bella
(AM)
Agata Belsito
(A)
Ylenia Berté
(Y)
Giulia Carubia
(G)
Maria Grazia Caruso
(MG)
Orazio Casella
(O)
Francesco Chiereleson
(F)
Chiara Costa
(C)
Daniela De Franco
(D)
Giuseppe Germanà
(G)
Antonio Messina
(A)
Diana Musumeci
(D)
Concetta Noto
(C)
Marco Valenti
(M)
Carlo Sorrentino
(C)
Rosanna Panico
(R)
Giuseppe Schettino
(G)
Jolanda Piccoli
(J)
Antonio Pepe
(A)
Francesco De Rosa
(F)
Mario Ottaviano
(M)
Gerarda Marrazzo
(G)
Gianna Raponi
(G)
Stefania Diberardino
(S)
Simona Bausi
(S)
Alessandro Ferrari
(A)
Sara Francesca Marini
(SF)
Elena Giubellino
(E)
Giorgio Innocenti
(G)
Gaspare Gugliemi
(G)
Daniela Maccari
(D)
Izabela Baciu
(I)
Commentaires et corrections
Type : ErratumIn
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