BACKGROUND: The COVID-19 pandemic heightened risks for individuals with hematological malignancies due to compromised immune systems, leading to more severe outcomes and increased mortality. While interventions like vaccines, targeted antivirals, and monoclonal antibodies have been effective for the general population, their benefits for these patients may not be as pronounced. METHODS: The EPICOVIDEHA registry (National Clinical Trials Identifier, NCT04733729) gathers COVID-19 data from hematological malignancy patients since the pandemic's start worldwide. It spans various global locations, allowing comprehensive analysis over the first three years (2020-2022). FINDINGS: The EPICOVIDEHA registry collected data from January 2020 to December 2022, involving 8767 COVID-19 cases in hematological malignancy patients from 152 centers across 41 countries, with 42% being female. Over this period, there was a significant reduction in critical infections and an overall decrease in mortality from 29% to 4%. However, hospitalization, particularly in the ICU, remained associated with higher mortality rates. Factors contributing to increased mortality included age, multiple comorbidities, active malignancy at COVID-19 onset, pulmonary symptoms, and hospitalization. On the positive side, vaccination with one to two doses or three or more doses, as well as encountering COVID-19 in 2022, were associated with improved survival. INTERPRETATION: Patients with hematological malignancies still face elevated risks, despite reductions in critical infections and overall mortality rates over time. Hospitalization, especially in ICUs, remains a significant concern. The study underscores the importance of vaccination and the timing of COVID-19 exposure in 2022 for enhanced survival in this patient group. Ongoing monitoring and targeted interventions are essential to support this vulnerable population, emphasizing the critical role of timely diagnosis and prompt treatment in preventing severe COVID-19 cases. FUNDING: Not applicable.

Aga Khan University Karachi Pakistan

Amsterdam UMC Location VUmc Amsterdam Netherlands

Ankara University Ankara Turkey

AOU Policlinico Rodolico San Marco Catania Italy

Aseer Central Hospital Abha Saudi Arabia

ASST Grande Ospedale Metropolitano Niguarda Milan Italy

AZ KLINA Brasschaat Belgium

Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello Palermo Italy

Azienda Ospedaliera San Gerardo Monza Monza Italy

Azienda Ospedaliera Sant'Anna e San Sebastiano Caserta Italy

Azienda Sanitaria Universitaria del Friuli Centrale Udine Italy

BioTechMed Graz Austria

Center for Radiology University Clinical Center of Serbia Belgrade Serbia

Centre Hospitalier de Versailles Le Chesnay France

Centro Hospitalar e Universitário São João Porto Portugal

CIBERINFEC Instituto de Salud Carlos 3 Madrid Spain

Cipto Mangunkusumo General Hospital Jakarta Indonesia

Clinical Hematology Department ICO Hospital Germans Trias i Pujol Josep Carreras Research Institute Badalona Spain

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

Clinical Microbiology Laboratory Medical School Attikon University General Hospital National and Kapodistrian University of Athens Athens Greece

Comenius University and National Cancer Institute Bratislava Slovakia

COVID Hospital Batajnica Belgrade Serbia

CRA from CRC Centre Hospitalier Victor DUPOUY Argenteuil France

Croatian Cooperative Group for Hematological Diseases Croatia

Department of Clinical Hematology Montpellier University Hospital IGMM UMR5535 CNRS University of Montpellier Montpellier France

Department of Hematological Medicine King's College Hospital NHS Foundation Trust London United Kingdom

Department of Hematology and Oncology Comprehensive Cancer Center Innsbruck Innsbruck Austria

Department of Hematology CH Sud Francilien Corbeil Essonnes France

Department of Hematology Copenhagen University Hospital Rigshospitalet Copenhagen Denmark

Department of Hematology Hospital Universitario de Burgos Burgos Spain

Department of Hematology Research Unit Hospital Universitario de Burgos Burgos Spain

Department of Hematology University Hospital Virgen Macarena University Hospital Virgen del Rocío Instituto de Biomedicina de Sevilla Seville Spain

Department of Hematology Vall d'Hebron Hospital Universitari Experimental Hematology Vall d'Hebron Institute of Oncology Vall d'Hebron Barcelona Hospital Campus Barcelona Spain

Department of Infectious Diseases and Clinical Microbiology Faculty of Medicine Eskisehir Osmangazi University Eskisehir Turkey

Department of Infectious Diseases and Clinical Microbiology School of Medicine Marmara University Istanbul Turkey

Department of Infectious Diseases Hospital Clinic de Barcelona University of Barcelona IDIBAPS Barcelona Spain

Department of Infectious Diseases Karolinska University Hospital Stockholm Sweden

Department of Internal Medicine ADRZ Goes Netherlands

Department of Internal Medicine Federal University of Rio de Janeiro and Grupo Oncoclinicas Rio de Janeiro Brazil

Department of Internal Medicine South Division Faculty of Medicine University of Szeged Szeged Hungary

Department of Medicine A for Hematology Oncology and Pneumology University Hospital Münster Münster Germany

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

Department of Mental Health and Public Medicine University of Campania Naples Italy

Department of Nephrology and Infectious diseases AZ Sint Jan Brugge Oostende AV Brugge Belgium

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

Department of Physiology Faculty of Medicine Masaryk University Brno Czech Republic

Division of Hematology Department of Internal Medicine University of Debrecen Debrecen Hungary

Division of Infectious Diseases ECMM Excellence Center for Clinical Mycology Department of Internal Medicine Medical University of Graz Austria

Dokuz Eylul University Division of Hematology Izmir Turkey

Ematologia con Trapianto Ospedale Dimiccoli Barletta Barletta Italy

Faculty of Medicine and Faculty of Health Studies of University of Rijeka Rijeka Croatia

Faculty of Medicine University of Chile Infectious Diseases Unity Salvador Hospital of Santiago Santiago de Chile Chile

Faculty of Medicine University of Zagreb Zagreb Croatia

Fundación Jimenez Diaz University Hospital Health Research Institute IIS FJD Madrid Spain

General Hospital of Thessaloniki George Papanikolaou Thessaloniki Greece

German Centre for Infection Research Partner Site Bonn Cologne Cologne Germany

Gomel State Medical University Gomel Belarus

Hamad Medical Corporation Doha Qatar

Head ICU and CRC Centre Hospitalier Victor DUPOUY Argenteuil France

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

Hematology and Stem Cell Transplant Unit Osperadiela University Pisana Company Pisa Italy

Hematology and Stem Cell Transplantation Unit AOUC Policlinico Bari Italy

Hematology and Transplant Unit Azienda Ospedaliera SS Antonio e Biagio e Cesare Arrigo Alessandria Italy

Hematology Department of Biomedicine and Prevention University of Rome Tor Vergata Rome Italy

Hematology Unit ASST Spedali Civili Brescia Italy

Hematology Unit Center for Translational Medicine Azienda USL Toscana NordOvest Livorno Italy

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

Hematology Unit Fondazione Policlinico Universitario Agostino Gemelli IRCCS Rome Italy

Hematology Unit Università Cattolica del Sacro Cuore Rome Italy

Hopital Saint Louis Paris France

Hospital Escuela de Agudos Dr Ramón Madariaga Posadas Argentina

Hospital Nuestra Señora de Sonsoles Ávila Spain

Hospital Rey Juan Carlos Móstoles Spain

Hospital Universitario 12 de Octubre Madrid Spain

Hospital Universitario de Cabueñes Gijón Spain

Hospital Universitario de Navarra Iruña Pamplona Spain

Hospital Universitario de Salamanca Salamanca Spain

Hospital Universitario Infanta Leonor Madrid Spain

Hospital Universitario Lucus Augusti Lugo Spain

Hospital Universitario Marqués de Valdecilla Santander Spain

Hospital Universitario Puerta de Hierro Majadahonda Spain

Hospital Universitario Virgen del Puerto Plasencia Spain

Hospital University of Parma Hematology and Bone Marrow Unit Parma Italy

ICANS Strasbourg France

Institute of Hematology and Blood Transfusion Prague Czech Republic

Instituto Nacional do Cancer Rio de Janeiro Brazil

IRCCS Ospedale San Raffaele Milan Italy

Istituto Oncologico della Svizzera Italiana Bellinzona Switzerland

King Abdullah Medical City Makkah Saudi Arabia

KU Leuven Leuven Belgium

Laikon Hospital Medical School National and Kapodistrian University of Athens Athens Greece

Masaryk University and University Hospital Brno Department of Internal Medicine Hematology and Oncology Brno Czech Republic

Medical University of Graz Graz Austria

Medizinische Klinik 2 Klinikum Rechts der Isar TU München Munich Germany

Microbiology and Parasitology Department University Hospital La Paz Madrid Spain

National Cancer Institute Fondazione 'G Pascale' IRCCS Hematology Oncology and Stem Cell Transplantation Unit Naples Italy

Necker Enfants Malades Hospitals Paris France

North Western State Medical University Named after Iliá Ilich Méchnikov Saint Petersburg Russia

Northumbria Healthcare Newcastle United Kingdom

Oncology Center Mansoura University Mansoura Egypt

Ospedale Policlinico San Martino Genoa Italy

Ospedale Vito Fazzi Lecce Italy

Oxford University Hospitals Oxford United Kingdom

Policlinico Borgo Roma Verona Verona Italy

Portuguese Institute of Oncology Lisbon Portugal

San Bortolo Hospital Vicenza Italy

San Luigi Gonzaga Hospital Orbassano Orbassano Italy

Sapienza University of Rome Rome Italy

Service d'Hématologie Clinique et de Thérapie Cellulaire Hôpital Saint Antoine Assistance Publique Hôpitaux de Paris Sorbonne Université Inserm UMRs 938 Paris France

Shaukat Khanum Memorial Cancer Hospital and Research Centre Lahore Pakistan

Stem Cell Transplant Center AOU Citta' della Salute e della Scienza Turin Italy

Sultan Qaboos University Hospital Muscat Oman

Università Milano Bicocca Milan Italy

Universitätsklinikum Frankfurt am Main Frankfurt am Main Germany

Université Paris Saclay UVSQ Inserm Équipe Exposome et Hérédité CESP Villejuif France

University Clinic of Hematology Skopje North Macedonia

University Clinical Center of Serbia Belgrade Serbia

University Clinical Center Serbia Belgrade Serbia

University Hospital Centre Rijeka Rijeka Croatia

University Hospital Centre Zagreb Zagreb Croatia

University Hospital Dubrava Zagreb Croatia

University Hospital Hradec Králové Hradec Králové Czech Republic

University Hospital of Basel Basel Switzerland

University Hospital of Královské Vinohrady Prague Czech Republic

University Hospital Olomouc Olomouc Czech Republic

University Hospital Ostrava Ostrava Czech Republic

University Hospital Pilsen Pilsen Czech Republic

University Medical Center Groningen Groningen Netherlands

University Medical Center Hamburg Eppendorf Hamburg Germany

University of Cologne Faculty of Medicine and University Hospital Cologne Clinical Trials Centre Cologne Cologne Germany

University of Cologne Faculty of Medicine and University Hospital Cologne Institute of Translational Research Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases Cologne Germany

University of Cologne Faculty of Medicine University Hospital Cologne Department 1 of Internal Medicine Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf Cologne Germany

University of Kansas Medical Center Kansas City United States

University of Milan and Fondazione IRCCS Istituto Nazionale Dei Tumori Milan Italy

UOC Hematology AORN Cardarelli Naples Italy

Weill Cornell Medicine New York United States

Wroclaw Medical University Wroclaw Poland

Zealand University Hospital Roskilde Denmark

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Respiratory Viruses in Patients With Hematological Malignancy in Boreal Autumn/Winter 2023-2024: EPICOVIDEHA-EPIFLUEHA Report