Breakthrough COVID-19 in vaccinated patients with hematologic malignancies: results from EPICOVIDEHA survey
Livio Pagano
(1)
,
Jon Salmanton-García
(2)
,
Francesco Marchesi
(1)
,
Ola Blennow
(3)
,
Maria Gomes da Silva
(4)
,
Andreas Glenthøj
(5)
,
Jaap van Doesum
(6)
,
Yavuz Bilgin
(6)
,
Alberto Lopez-Garcia
(7)
,
Federico Itri
(8)
,
Raquel Nunes Rodrigues
(4)
,
Barbora Weinbergerová
(9)
,
Francesca Farina
(8)
,
Giulia Dragonetti
(10)
,
Caroline Berg Venemyr
(5)
,
Jens van Praet
(11)
,
Ozren Jaksic
(12)
,
Toni Valkovic
(13)
,
Iker Falces-Romero
(14)
,
Sonia Martin-Perez
(15)
,
Moraima Jiménez
(16)
,
Julio Davila-Valls
(15)
,
Martin Schonlein
(17)
,
Emanuele Ammatuna
(16)
,
Stef Meers
(18)
,
Mario Delia
(19)
,
Zlate Stojanoski
(20)
,
Anna Nordlander
(3)
,
Tobias Lahmer
(21)
,
László Imre Pinczés
(22)
,
Caterina Buquicchio
(23)
,
Klára Piukovics
(24)
,
Irati Ormazabal-Velez
(25)
,
Nicola Stefano Fracchiolla
(26)
,
Michail Samarkos
(27)
,
Gustavo-Adolfo Mendez
(28)
,
José-Ángel Hernández-Rivas
(29)
,
Ildefonso Espigado
(30)
,
Martin Cernan
(31)
,
Verena Petzer
(32)
,
Sylvain Lamure
(33, 34)
,
Roberta Di Blasi
(35)
,
Joyce Marques de Almeida
(36)
,
Michelina Dargenio
(37)
,
Monika Maria Biernat
(36)
,
Mariarita Sciumè
(38)
,
Cristina de Ramón
(39)
,
Nick Alexander de Jonge
(40)
,
Josip Batinic
(12)
,
Avinash Aujayeb
(41)
,
Monia Marchetti
(42)
,
Guillemette Fouquet
(43)
,
Noemi Fernández Escalada
(44)
,
Giovanni Paolo Maria Zambrotta
(45)
,
Maria Vittoria Sacchi
(42)
,
Anna Guidetti
(46)
,
Fatih Demirken
(47)
,
Lucia Prezioso
(48)
,
Zdenek Racil
(49)
,
Marcio Nucci
(50)
,
Miloš Mladenovic
(51)
,
Raphaël Lievin
(35)
,
Michaela Hanakova
(49)
,
Stefanie Grafe
(17)
,
Uluhan Sili
(52)
,
Marina Machado
(29)
,
Chiara Cattaneo
(53)
,
Tatjana Adzic-Vukicevic
(51)
,
Luisa Verga
(45)
,
Jorge Labrador
(54)
,
Laman Rahimli
(2)
,
Matteo Bonanni
(55)
,
Francesco Passamonti
(56)
,
Antonio Pagliuca
(57)
,
Paolo Corradini
(58)
,
Martin Hoenigl
(59)
,
Philipp Koehler
(60)
,
Alessandro Busca
(61)
,
Oliver Cornely
(2)
1
Unicatt -
Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma]
2 University Hospital of Cologne [Cologne]
3 Karolinska University Hospital [Stockholm]
4 IPO Porto - Instituto Português de Oncologia do Porto / Portuguese Oncology Institute of Porto
5 Copenhagen University Hospital
6 UMCG - University Medical Center Groningen [Groningen]
7 Hospital Universitario HM Sanchinarro [Madrid, Spain]
8 IRCCS Ospedale San Raffaele [Milan, Italy]
9 University Hospital Brno
10 Fondazione Policlinico Universitario Agostino Gemelli IRCCS
11 Openbare Bibliotheek Brugge
12 University of Zagreb
13 University of Rijeka
14 La Paz University Hospital
15 UNICA - Universidad de Ciego de Avila
16 UAB - Universitat Autònoma de Barcelona = Autonomous University of Barcelona = Universidad Autónoma de Barcelona
17 UKE - Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg]
18 VIB [Belgium]
19 Polytechnic University of Bari / Politecnico di Bari
20 Institute of Public Health of Republic of North Macedonia [Skopje]
21 University-Hospital Munich-Großhadern [München]
22 University of Debrecen
23 ICB - Istituto di chimica biomolecolare [Padova, Italy]
24 University of Szeged [Szeged]
25 UNAV - Universidad de Navarra [Pamplona]
26 Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan]
27 University of Athens Medical School [Athens]
28 UCA - Pontificia Universidad Católica Argentina
29 Hospital General Universitario "Gregorio Marañón" [Madrid]
30 Universidad de Sevilla = University of Seville
31 Univerzita Palackého [Olomouci]
32 IMU - Innsbruck Medical University = Medizinische Universität Innsbruck
33 CHU Montpellier
34 IGMM - Institut de Génétique Moléculaire de Montpellier
35 AP-HP - Hopital Saint-Louis [AP-HP]
36 Wrocław Medical University
37 University of Salento [Lecce]
38 Unit of Melanoma Medical Oncology [Fondazione IRCCS Istituto Nazionale Tumori, Milan]
39 Universidad de Salamanca
40 Amsterdam UMC - Amsterdam University Medical Center
41 Newcastle University [Newcastle]
42 DISIT - Dipartimento di Scienze e Innovazione Tecnologica [Alessandria]
43 AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP)
44 Hospital Universitario Marqués de Valdecilla [Santander]
45 UNIMIB - Università degli Studi di Milano-Bicocca = University of Milano-Bicocca
46 Human Tumor Immunobiology Unit [Fondazione IRCCS Istituto Nazionale dei Tumori, Milan]
47 DEÜ - Dokuz Eylül Üniversitesi = Dokuz Eylül University [Izmir]
48 UNIPR - Università degli studi di Parma = University of Parma
49 IPP PRAGUE - Institute of Plasma Physics, Association EURATOM
50 UFRJ - Universidade Federal do Rio de Janeiro [Brasil] = Federal University of Rio de Janeiro [Brazil] = Université fédérale de Rio de Janeiro [Brésil]
51 University of Belgrade [Belgrade]
52 Marmara University [Kadıköy - İstanbul]
53 UniBs - Università degli Studi di Brescia = University of Brescia
54 Universidad de Burgos
55 Unicatt - Università cattolica del Sacro Cuore [Milano]
56 Uninsubria - Universitá degli Studi dell’Insubria = University of Insubria [Varese]
57 King‘s College London
58 UNIMI - Università degli Studi di Milano = University of Milan
59 UC San Diego - University of California [San Diego]
60 University of Cologne
61 Clinique Turin
2 University Hospital of Cologne [Cologne]
3 Karolinska University Hospital [Stockholm]
4 IPO Porto - Instituto Português de Oncologia do Porto / Portuguese Oncology Institute of Porto
5 Copenhagen University Hospital
6 UMCG - University Medical Center Groningen [Groningen]
7 Hospital Universitario HM Sanchinarro [Madrid, Spain]
8 IRCCS Ospedale San Raffaele [Milan, Italy]
9 University Hospital Brno
10 Fondazione Policlinico Universitario Agostino Gemelli IRCCS
11 Openbare Bibliotheek Brugge
12 University of Zagreb
13 University of Rijeka
14 La Paz University Hospital
15 UNICA - Universidad de Ciego de Avila
16 UAB - Universitat Autònoma de Barcelona = Autonomous University of Barcelona = Universidad Autónoma de Barcelona
17 UKE - Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg]
18 VIB [Belgium]
19 Polytechnic University of Bari / Politecnico di Bari
20 Institute of Public Health of Republic of North Macedonia [Skopje]
21 University-Hospital Munich-Großhadern [München]
22 University of Debrecen
23 ICB - Istituto di chimica biomolecolare [Padova, Italy]
24 University of Szeged [Szeged]
25 UNAV - Universidad de Navarra [Pamplona]
26 Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan]
27 University of Athens Medical School [Athens]
28 UCA - Pontificia Universidad Católica Argentina
29 Hospital General Universitario "Gregorio Marañón" [Madrid]
30 Universidad de Sevilla = University of Seville
31 Univerzita Palackého [Olomouci]
32 IMU - Innsbruck Medical University = Medizinische Universität Innsbruck
33 CHU Montpellier
34 IGMM - Institut de Génétique Moléculaire de Montpellier
35 AP-HP - Hopital Saint-Louis [AP-HP]
36 Wrocław Medical University
37 University of Salento [Lecce]
38 Unit of Melanoma Medical Oncology [Fondazione IRCCS Istituto Nazionale Tumori, Milan]
39 Universidad de Salamanca
40 Amsterdam UMC - Amsterdam University Medical Center
41 Newcastle University [Newcastle]
42 DISIT - Dipartimento di Scienze e Innovazione Tecnologica [Alessandria]
43 AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP)
44 Hospital Universitario Marqués de Valdecilla [Santander]
45 UNIMIB - Università degli Studi di Milano-Bicocca = University of Milano-Bicocca
46 Human Tumor Immunobiology Unit [Fondazione IRCCS Istituto Nazionale dei Tumori, Milan]
47 DEÜ - Dokuz Eylül Üniversitesi = Dokuz Eylül University [Izmir]
48 UNIPR - Università degli studi di Parma = University of Parma
49 IPP PRAGUE - Institute of Plasma Physics, Association EURATOM
50 UFRJ - Universidade Federal do Rio de Janeiro [Brasil] = Federal University of Rio de Janeiro [Brazil] = Université fédérale de Rio de Janeiro [Brésil]
51 University of Belgrade [Belgrade]
52 Marmara University [Kadıköy - İstanbul]
53 UniBs - Università degli Studi di Brescia = University of Brescia
54 Universidad de Burgos
55 Unicatt - Università cattolica del Sacro Cuore [Milano]
56 Uninsubria - Universitá degli Studi dell’Insubria = University of Insubria [Varese]
57 King‘s College London
58 UNIMI - Università degli Studi di Milano = University of Milan
59 UC San Diego - University of California [San Diego]
60 University of Cologne
61 Clinique Turin
Livio Pagano
- Fonction : Auteur
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Jon Salmanton-García
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Ola Blennow
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Federico Itri
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Jens van Praet
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Emanuele Ammatuna
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Mario Delia
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Zlate Stojanoski
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László Imre Pinczés
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Caterina Buquicchio
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Roberta Di Blasi
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Joyce Marques de Almeida
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Monika Maria Biernat
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Nick Alexander de Jonge
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Avinash Aujayeb
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Monia Marchetti
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Miloš Mladenovic
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Raphaël Lievin
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Stefanie Grafe
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Uluhan Sili
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Marina Machado
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Chiara Cattaneo
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Francesco Passamonti
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Antonio Pagliuca
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Paolo Corradini
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Martin Hoenigl
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Oliver Cornely
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Résumé
Limited data have been published on the epidemiology and outcomes of breakthrough COVID-19 in patients with hematological malignancy (HM) after anti-SARS-CoV-2 vaccination. Adult HM who received at least one dose of anti-SARS-CoV-2 vaccine and diagnosed with breakthrough COVID-19 between January 2021 and March 2022 and registered in EPICOVIDEHA were included in this analysis. A total of 1548 cases were included, mainly with lymphoid malignancies (1181 cases, 76%). After viral genome sequencing in 753 cases (49%), Omicron variant was prevalent (517, 68.7%). Most of the patients received at least two vaccine doses before COVID-19 (1419, 91%), mostly mRNA-based (1377, 89%). Overall, 906 patients (59%) received specific treatment for COVID-19. After 30-days follow-up from COVID-19 diagnosis, 143 patients (9%) died. The mortality rate in patients with Omicron variant was of 7.9%, comparable to that reported for the other variants. The 30-day mortality rate was significantly lower than in the pre-vaccine era (31%). In the univariable analysis, older age (p<0.001), active HM (p<0.001), severe and critical COVID-19 (p=0.007 and p<0.001, respectively) were associated with mortality. Conversely, patients receiving monoclonal antibodies, even for severe or critical COVID-19, had a lower mortality rate (p<0.001). In the multivariable model, older age, active disease, critical COVID-19 and at least 2-3 comorbidities were correlated with a higher mortality, whereas the administration of monoclonal antibodies, alone (p<0.001) or combined with antivirals (p=0.009), was observed protective. While mortality is significantly lower than in the pre-vaccination era, breakthrough COVID-19 in HM is still associated with considerable mortality. Death rate was lower in patients who received monoclonal antibodies, alone or in combination with antivirals. EPICOVIDEHA (www.clinicaltrials.gov; National Clinical Trials identifier NCT04733729) is an international open web-based registry for patients with HMs infected with SARS-CoV-2.
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