Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to Coronavirus disease 2019 (COVID-19) due to age, disease, and treatment-related immunosuppression. We aimed to assess risk factors of outcome and elucidate the impact of CLL-directed treatments on the course of COVID-19. We conducted a retrospective, international study, collectively including 941 patients with CLL and confirmed COVID-19. Data from the beginning of the pandemic until March 16, 2021, were collected from 91 centers. The risk factors of case fatality rate (CFR), disease severity, and overall survival (OS) were investigated. OS analysis was restricted to patients with severe COVID-19 (definition: hospitalization with need of oxygen or admission into an intensive care unit). CFR in patients with severe COVID-19 was 38.4%. OS was inferior for patients in all treatment categories compared to untreated (p < 0.001). Untreated patients had a lower risk of death (HR = 0.54, 95% CI:0.41-0.72). The risk of death was higher for older patients and those suffering from cardiac failure (HR = 1.03, 95% CI:1.02-1.04; HR = 1.79, 95% CI:1.04-3.07, respectively). Age, CLL-directed treatment, and cardiac failure were significant risk factors of OS. Untreated patients had a better chance of survival than those on treatment or recently treated.

1st Department of Medicine Hematology 1st Faculty of Medicine Charles University and General Hospital Prague Prague Czech Republic

1st Internal Medicine Department Propaedeutic Hematology Clinical Trial Unit National and Kapodistrian University of Athens Athens Greece

4th Department of Internal Medicine Haematology Faculty of Medicine in Hradec Králové University Hospital and Charles University Prague Hradec Kralove Czech Republic

Belfast City Hospital Belfast Northern Ireland

Carol Davila University of Medicine and Pharmacy Hematology Department from Coltea Clinical Hospital Bucharest Romania

Centre for Atherothrombosis and Metabolic Disease Hull York Medical School Hull UK

Clinical Hematology Unit Oncology Center Faculty of Medicine Mansoura University Mansoura 35516 Egypt

Consultant Haematologist St James's Hospital Leeds LS9 7TF UK

Consultative Hematology Department with a Day Hospital for Intensive High Dose Chemotherapy National Research Center for Hematology Moscow Russia

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

Department and Clinic of Hematology Blood Neoplasms and Bone Marrow Transplantation Wroclaw Medical University Pasteura Street 4 50 367 Wroclaw Poland

Department of Biomedicine and Prevention Hematology University Tor Vergata Rome Italy

Department of Clinical Genetics Uppsala University Hospital Uppsala Sweden

Department of Haematology Athens Medical Center Psychikon Branch Athens Greece

Department of Hematology and Central Hematology Laboratory Inselspital Bern University Hospital University of Bern Bern Switzerland

Department of hematology Gelderse Vallei Ede Ede the Netherlands

Department of Hematology Haga Teaching Hospital The Hague The Netherlands

Department of Hematology Health Research Institute IIS FJD Fundacion Jimenez Diaz University Hospital Madrid Spain

Department of Hematology Hospital del Mar Barcelona Spain

Department of Hematology Hospital General Universitario Valencia Spain

Department of Hematology Odense University Hospital Odense Denmark

Department of Hematology Rigshospitalet Copenhagen University Hospital Copenhagen Denmark

Department of Hematology Santa Chiara Hospital Trento Italy

Department of Hematology Shaare Zedek Medical Center affiliated with the Hebrew University Medical School Jerusalem Israel

Department of Hematology Shamir Medical Center Zerifin Israel

Department of Hematology Tel Aviv Sourasky Medical Center and Sackler School of Medicine Tel Aviv University Tel Aviv Israel

Department of Hematology Universitaire ziekenhuizen Leuven Herestraat 49 3000 Leuven Belgium

Department of Hematology University hospital Dubrava Zagreb Croatia

Department of Hematology Uppsala University Hospital Uppsala Sweden

Department of Immunology Genetics and Pathology Science for Life Laboratory Uppsala University Uppsala Sweden

Department of Internal Medicine Albert Schweitzer hospital Dordrecht the Netherlands

Department of Internal Medicine Hematology and Oncology University Hospital Brno; Department of Medical Genetics and Genomics Faculty of Medicine Masaryk University Brno Czech Republic

Department of Internal Medicine Postgraduate Institute of Medical Education and Research Chandigarh India

Department of Internal Medicine Rijnstate Hospital Arnhem the Netherlands

Department of Mathematics University of Ioannina Ioannina Greece

Department of Medicine and Surgery Institute of Hematology and Center for Hemato Oncological Research University of Perugia Perugia Italy

Department of Medicine Section of Hematology University of Verona Verona Italy

Department of Oncology and Hematology Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII Bergamo Bergamo Italy

Department of Oncology and Hematology University of Milan Milan Italy

Dept Hematooncology and Bone Marrow Transplantation Medical University in Lublin Lublin Poland

Dept Internal Medicine Maastricht University Medical Center Maastricht the Netherlands

Dept of Hematology Cancer Center Amsterdam Amsterdam University Medical Centers University of Amsterdam Amsterdam the Netherlands

Dept of Hematology Lymmcare Cancer Center Amsterdam Amsterdam University Medical Centers University of Amsterdam Amsterdam the Netherlands

Dept of Medical Sciences Section of Hematology University of Modena and Reggio E Modena Italy

Dipartimento di Diagnostica per Immagini Radioterapia Oncologica ed Ematologia Fondazione Policlinico Universitario Agostino Gemelli IRCCS Rome Italy

Division of Hematology A O U Città della Salute e della Scienza di Torino and Department of Molecular Biotechnology and Health Sciences University of Turin Turin Italy

Division of Hematology AO S Croce e Carle Cuneo Italy

Division of Hematology Department of Translational Medicine Università del Piemonte Orientale Amedeo Avogadro Azienda Ospedaliero Universitaria Maggiore della Carità Novara Novara Italy

Division of Hematology Fondazione IRCCS Policlinico San Matteo Pavia Italy

Experimental Hematooncology Department Medical University of Lublin Lublin Poland

Faculty of Medicine Clinical Centre of Vojvodina University of Novi Sad Novi Sad Serbia

Federal State Budgetary Educational Institution of Higher Education Academician 1 P Pavlov 1st St Petersburg State Medical University of the Ministry of Healthcare of Russian Federation St Petersburg Russia

Fundación de Investigación del Hospital General Universitario Valencia Spain

FUNDALEU Clinical research center Buenos Aires Buenos Aires Argentina

Hematologic Section Dept of Internal Medicine Hospital Union West Herning Denmark

Hematology and Clinical Immunology Unit Department of Medicine University of Padova Padova Italy

Hematology and Stem Cell Transplant Center Marche Nord Hospital Pesaro Italy

Hematology and Stem Cell Transplantation Unit Ospedale Oncologico A Businco ARNAS G Brotzu Cagliari Italy

Hematology Bnai Zion Medical Center Haifa Israel

Hematology Center after Prof Yeolyan MH RA Yerevan Armenia

Hematology Clinic ASUFC Udine Italy

Hematology Department and HCT Unit G Papanicolaou Hospital Thessaloniki Greece

Hematology Department Hospital Universitario 12 de Octubre Madrid Spain

Hematology Department Hospital Universitario de La Princesa Madrid Spain

Hematology Department Hospital Universitario Puerta de Hierro Majadahonda Madrid Spain

Hematology Department Infanta Leonor University Hospital Madrid Spain

Hematology Department of Translational and Precision Medicine Sapienza University Rome Italy

Hematology Department Portuguese Institute of Oncology Lisbon Portugal

Hematology Department Ramón y Cajal University Hospital Madrid Spain

Hematology Department St John's Cancer Center Lublin Poland

Hematology Department Unit Research Complejo Asistencial Universitario de Burgos Burgos Spain

Hematology Department University Hospital and Research Institute of Marqués de Valdecilla Santander Spain

Hematology Fondazione IRCCS Istituto Nazionale Tumori Milan Italy

Hematology Section Department of Medical Oncology National Center for Cancer Care and Research Doha Qatar

Hematology Unit 1st Dept of Internal Medicine AUTH AHEPA Hospital Thessaloniki Greece

Hematology Unit and BM Transplant Center AO SS Antonio e Biagio e Cesare Arrigo Alessandria Italy

Hematology Unit AO Cosenza Cosenza Italy

Hematology Unit Azienda Unità Sanitaria Locale IRCCS Reggio Emilia Italy

Hematology Unit Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico of Milan Milan Italy

Hematology Unit Nepal Cancer Hospital and Research Centre Lalitpur Nepal

Hematology Unit Terrassa Hospital Terrasa Spain

HematologyDepartment Colentina Clinical Hospital Bucharest Romania

Hospital Clínic of Barcelona Barcelona Spain

Hospital Clinico Universitario de Salamanca Salamanca Spain

Hospital Italiano La Plata Buenos Aires Argentina

Inst J Bordet Brussels Belgium

Institute of Applied Biosciences Centre for Research and Technology Hellas Thessaloniki Greece

IRCSS Ospedale San Raffaele Milan Italy

Laboratory for Leukemia Diagnostics Department of Medicine 3 University Hospital LMU Munich Munich Germany

Pathology Service Hospital del Mar Barcelona Spain

Rabin Medical Center Petah Tikva and the Sackler School of Medicine Tel Aviv University Tel Aviv Israel

S C Ematologia ASST Spedali Civili Brescia Brescia Italy

S C Ematologia Città della Salute e della Scienza di Torino Turin Italy

Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel

School of Medicine University of Belgrade Belgrade Serbia

Sezione di Ematologia Dipartimento di Scienze Radiologiche ed Ematologiche Università Cattolica del Sacro Cuore Rome Italy

Spanish Society of Haematology and hemotherapy Madrid Spain

St Anna University Hospital Ferrara Italy

Università Vita Salute San Raffaele and IRCC Ospedale San Raffaele Milan Italy

University Clinical Center of Serbia Belgrade Serbia

UOC Ematologia PO Vito Fazzi Lecce Lecce Italy

Zuyderland Medical Center Sittard the Netherlands

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