Breakthrough COVID-19 in vaccinated patients with hematologic malignancies: results from the EPICOVIDEHA survey

Author:

Pagano Livio12ORCID,Salmanton-García Jon34ORCID,Marchesi Francesco5ORCID,Blennow Ola6ORCID,Gomes da Silva Maria7ORCID,Glenthøj Andreas8ORCID,van Doesum Jaap9ORCID,Bilgin Yavuz M.10ORCID,López-García Alberto11ORCID,Itri Federico12ORCID,Nunes Rodrigues Raquel7ORCID,Weinbergerová Barbora13ORCID,Farina Francesca14ORCID,Dragonetti Giulia1ORCID,Berg Venemyr Caroline8ORCID,van Praet Jens15ORCID,Jaksic Ozren16ORCID,Valković Toni17,Falces-Romero Iker18ORCID,Martín-Pérez Sonia19ORCID,Jiménez Moraima2021ORCID,Dávila-Valls Julio19ORCID,Schönlein Martin22ORCID,Ammatuna Emanuele21ORCID,Meers Stef23ORCID,Delia Mario24ORCID,Stojanoski Zlate25ORCID,Nordlander Anna6,Lahmer Tobias26ORCID,Imre Pinczés László27ORCID,Buquicchio Caterina28ORCID,Piukovics Klára29ORCID,Ormazabal-Vélez Irati30ORCID,Fracchiolla Nicola31ORCID,Samarkos Michail32ORCID,Méndez Gustavo-Adolfo33ORCID,Hernández-Rivas José-Ángel34ORCID,Espigado Ildefonso35ORCID,Cernan Martin36ORCID,Petzer Verena37ORCID,Lamure Sylvain38ORCID,di Blasi Roberta39ORCID,Marques de Almedia Joyce40ORCID,Dargenio Michelina41,Biernat Monika M.42ORCID,Sciumè Mariarita31ORCID,de Ramón Cristina4344ORCID,de Jonge Nick45ORCID,Batinić Josip464748ORCID,Aujayeb Avinash49ORCID,Marchetti Monia50ORCID,Fouquet Guillemette51ORCID,Fernández Noemí52,Zambrotta Giovanni5354ORCID,Sacchi Maria Vittoria50ORCID,Guidetti Anna55ORCID,Demirkan Fatih56ORCID,Prezioso Lucia57ORCID,Ráčil Zdeněk5859ORCID,Nucci Marcio60ORCID,Mladenović Miloš61ORCID,Liévin Raphaël39ORCID,Hanáková Michaela5859,Gräfe Stefanie3462ORCID,Sili Uluhan63ORCID,Machado Marina64ORCID,Cattaneo Chiara65ORCID,Adžić-Vukičević Tatjana61,Verga Luisa5354ORCID,Labrador Jorge66ORCID,Rahimli Laman34,Bonanni Matteo12,Passamonti Francesco67ORCID,Pagliuca Antonio68ORCID,Corradini Paolo69ORCID,Hoenigl Martin707172ORCID,Koehler Philipp3473ORCID,Busca Alessandro74ORCID,Cornely Oliver A.373757677ORCID

Affiliation:

1. 1Hematology Unit, Fondazione Policlinico Universitario Agostino Gemelli - IRCCS, Rome, Italy

2. 2Hematology Unit, Università Cattolica del Sacro Cuore, Rome, Italy

3. 3Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, Excellence Center for Medical Mycology, University of Cologne, Cologne, Germany

4. 4Faculty of Medicine and University Hospital Cologne, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany

5. 5Hematology and Stem Cell Transplant Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy

6. 6Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden

7. 7Portuguese Institute of Oncology, Lisbon, Portugal

8. 8Department of Hematology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

9. 9University Medical Center Groningen, Groningen, the Netherlands

10. 10Admiraal de Ruyter Hospital, Goes, the Netherlands

11. 11Fundación Jimenez Diaz University Hospital, Health Research Institute IIS-FJD, Madrid, Spain

12. 12San Luigi Gonzaga Hospital - Orbassano, Orbassano, Italy

13. 13Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic

14. 14IRCCS Ospedale San Raffaele, Milan, Italy

15. 15Department of Nephrology and Infectious diseases, AZ Sint-Jan Brugge-Oostende AV, Brugge, Belgium

16. 16University Hospital Dubrava, Zagreb, Croatia

17. 17Clinical Hospital Center Rijeka, Rijeka, Croatia

18. 18La Paz University Hospital, Madrid, Spain

19. 19Hospital Nuestra Señora de Sonsoles, Ávila, Spain

20. 20Department of Hematology, Vall d’Hebron Hospital Universitari, Experimental Hematology, Vall d’Hebron Institute of Oncology, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain

21. 21Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain

22. 22Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

23. 23Algemeen Ziekenhuis Klina VZW, Brasschaat, Belgium

24. 24Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari, Bari, Italy

25. 25University Clinic of Hematology, Skopje, North Macedonia

26. 26Medizinische Klinik II, Klinikum rechts der Isar, TU München, Munich, Germany

27. 27Division of Hematology, Department of Internal Medicine, University of Debrecen, Debrecen, Hungary

28. 28Ematologia con Trapianto, Ospedale Dimiccoli Barletta, Barletta, Italy

29. 29Department of Internal Medicine, South Division Faculty of Medicine University of Szeged, Szeged, Hungary

30. 30Complejo Hospitalario de Navarra, Iruña-Pamplona, Spain

31. 31Hematology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy

32. 32Laikon Hospital, Athens, Greece

33. 33Hospital Escuela de Agudos Dr. Ramón Madariaga, Posadas, Argentina

34. 34Hospital Universitario Infanta Leonor, Madrid, Spain

35. 35Department of Hematology, University Hospital Virgen Macarena - University Hospital Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS/CSIC), Universidad de Sevilla (Departamento de Medicina), Seville, Spain

36. 36University Hospital Olomouc, Olomouc, Czech Republic

37. 37Department of Hematology and Oncology, Medical University of Innsbruck, Innsbruck, Austria

38. 38CHU Montpellier, Montpellier, France

39. 39Hopital Saint Louis, Paris, France

40. 40Istituto Oncologico della Svizzera Italiana, Bellinzona, Switzerland

41. 41Ospedale Vito Fazzi, Lecce, Italy

42. 42Department of Haematology, Blood Neoplasms, and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw, Poland

43. 43Hematology Department, Hospital Universitario de Salamanca, Salamanca, Spain

44. 44Instituto de Investigación Biomédica de Salamanca, Centro de Investigación del Cáncer-IBMCC (USAL-CSIC), Salamanca, Spain

45. 45Amsterdam UMC, location VUmc, Amsterdam, the Netherlands

46. 46University Hospital Centre Zagreb, Zagreb, Croatia

47. 47Croatian Cooperative Group for Hematological Diseases (CROHEM), Croatia

48. 48Faculty of Medicine University of Zagreb, Zagreb, Croatia

49. 49Northumbria Healthcare, Newcastle, United Kingdom

50. 50Azienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare Arrigo, Alessandria, Italy

51. 51Cochin Hospital, Assistance Publique – Hôpitaux de Paris, Paris, France

52. 52Hospital Universitario Marqués de Valdecilla, Santander, Spain

53. 53Azienda Ospedaliera San Gerardo - Monza, Monza, Italy

54. 54Università Milano-Bicocca, Milan, Italy

55. 55Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

56. 56Dokuz Eylul University, Division of Hematology, Izmir, Turkey

57. 57Hospital University of Parma - Hematology and Bone Marrow Unit, Parma, Italy

58. 58Institute of Hematology and Blood Transfusion, Prague, Czech Republic

59. 59Department of Physiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic

60. 60Department of Internal Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

61. 61COVID hospital “Batajnica,” Belgrade, Serbia

62. 62Universitätsklinikum Hamburg Eppendorf, Hamburg, Germany

63. 63Marmara University, Istanbul, Turkey

64. 64Clinical Microbiology and Infectious Diseases Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain

65. 65Hematology Unit, ASST-Spedali Civili, Brescia, Italy

66. 66Department of Hematology, Hospital Universitario de Burgos, Burgos, Spain

67. 67Department of Medicine and Surgery, University of Insubria and ASST Sette Laghi, Ospedale di Circolo of Varese, Varese, Italy

68. 68Department of Hematological Medicine, King’s College Hospital NHS Foundation Trust, Kings College London & Anthony Nolan, London, United Kingdom

69. 69University of Milan and Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

70. 70Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, San Diego, CA

71. 71Clinical and Translational Fungal-Working Group, University of California San Diego, La Jolla, CA

72. 72Division of Infectious Diseases, Department of Internal Medicine, Medical University of Graz, Graz, Austria

73. 73Faculty of Medicine and University Hospital Cologne, Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany

74. 74Stem Cell Transplant Center, AOU Citta’ della Salute e della Scienza, Turin, Italy

75. 75Faculty of Medicine and University Hospital Cologne, Chair Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany

76. 76Faculty of Medicine and University Hospital Cologne, Clinical Trials Centre Cologne (ZKS Köln), University of Cologne, Cologne, Germany

77. 77German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany

Abstract

Abstract Limited data are available on breakthrough COVID-19 in patients with hematologic malignancy (HM) after anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Adult patients with HM, ≥1 dose of anti-SARS-CoV-2 vaccine, and breakthrough COVID-19 between January 2021 and March 2022 were analyzed. A total of 1548 cases were included, mainly lymphoid malignancies (1181 cases, 76%). After viral sequencing in 753 cases (49%), the Omicron variant was prevalent (517, 68.7%). Most of the patients received ≤2 vaccine doses before COVID-19 (1419, 91%), mostly mRNA-based (1377, 89%). Overall, 906 patients (59%) received COVID-19-specific treatment. After 30-day follow-up from COVID-19 diagnosis, 143 patients (9%) died. The mortality rate in patients with the Omicron variant was 7.9%, comparable to other variants, with a significantly lower 30-day mortality rate than in the prevaccine era (31%). In the univariable analysis, older age (P < .001), active HM (P < .001), and severe and critical COVID-19 (P = .007 and P < .001, respectively) were associated with mortality. Conversely, patients receiving monoclonal antibodies, even for severe or critical COVID-19, had a lower mortality rate (P < .001). In the multivariable model, older age, active disease, critical COVID-19, and 2-3 comorbidities were correlated with a higher mortality, whereas monoclonal antibody administration, alone (P < .001) or combined with antivirals (P = .009), was protective. Although mortality is significantly lower than in the prevaccination 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.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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