In this retrospective international multicenter study, we describe the clinical characteristics and outcomes of patients with chronic lymphocytic leukemia (CLL) and related disorders (small lymphocytic lymphoma and high-count monoclonal B lymphocytosis) infected by SARS-CoV-2, including the development of post-COVID condition. Data from 1540 patients with CLL infected by SARS-CoV-2 from January 2020 to May 2022 were included in the analysis and assigned to four phases based on cases disposition and SARS-CoV-2 variants emergence. Post-COVID condition was defined according to the WHO criteria. Patients infected during the most recent phases of the pandemic, though carrying a higher comorbidity burden, were less often hospitalized, rarely needed intensive care unit admission, or died compared to patients infected during the initial phases. The 4-month overall survival (OS) improved through the phases, from 68% to 83%, p = .0015. Age, comorbidity, CLL-directed treatment, but not vaccination status, emerged as risk factors for mortality. Among survivors, 6.65% patients had a reinfection, usually milder than the initial one, and 16.5% developed post-COVID condition. The latter was characterized by fatigue, dyspnea, lasting cough, and impaired concentration. Infection severity was the only risk factor for developing post-COVID. The median time to resolution of the post-COVID condition was 4.7 months. OS in patients with CLL improved during the different phases of the pandemic, likely due to the improvement of prophylactic and therapeutic measures against SARS-CoV-2 as well as the emergence of milder variants. However, mortality remained relevant and a significant number of patients developed post-COVID conditions, warranting further investigations.

1st Faculty of Medicine 1st Department of Medicine Hematology 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

Belfast City Hospital Belfast Northern Ireland

Centre for Biomedicine Hull York Medical School Hull UK

Consultant Haematologist St James's Hospital Leeds 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 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 Cancer Center Amsterdam Amsterdam University Medical Centers University of Amsterdam Amsterdam the Netherlands

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

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 Leuven Belgium

Department of Hematology University Hospital Dubrava Zagreb Croatia

Department of Hematology Uppsala University Hospital Uppsala Sweden

Department of Hematooncology and Bone Marrow Transplantation Medical University in Lublin Lublin Poland

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 Czech Republic

Department of Internal Medicine Maastricht University Medical Center Maastricht the Netherlands

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

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

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

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

Department of Pharmacy Health and Nutritional Science University of Calabria Rende Italy

Division of Hematology AO S Croce e Carle Cuneo Italy

Division of Hematology Bnai Zion Medical Center Haifa Israel

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

Faculty of Medicine Department of Medical Genetics and Genomics Masaryk University Brno Czech Republic

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

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

Fundaci_on de Investigaci_on del Hospital General Universitario Valencia Spain

Fundaleu Clinical Research Center Buenos Aires Buenos Aires Argentina

Haemato oncology Unit The Royal Marsden Hospital UK

Hematologic Section Department 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 Center after Prof Yeolyan MH RA Yerevan Armenia

Hematology Clinic Azienda Sanitaria Universitaria Friuli Centrale Udine Italy

Hematology Department and HCT Unit G Papanicolaou Hospital Thessaloniki Greece

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

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 Portuguese Institute of Oncology Lisbon Portugal

Hematology Department Ram_on 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 Azienda Ospedaliera Annunziata Cosenza Italy

Hematology Unit Azienda Ospedaliera Universitaria Integrata Verona Verona Italy

Hematology Unit Azienda Unità Sanitaria Locale IRCCS Reggio Emilia Italy

Hematology Unit Cardarelli Hospital Naples Italy

Hematology Unit Department of Translational and Precision Medicine Sapienza University Rome Italy

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

Medical Oncology Unit Faculty of Medicine Oncology Center Mansoura University Mansoura Egypt

Meir Medical Center Kfar Saba Israel

Pathology Service Hospital del Mar Barcelona Spain

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

Spanish Society of Hematology and Hemotherapy Madrid Spain

St Anna University Hospital Ferrara Italy

St James Hospital Trinity College Dublin Dublin Ireland

The Sackler School of Medicine Tel Aviv University Tel Aviv Israel

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

See more in PubMed

Lefrancois T, Malvy D, Atlani-Duault L, et al. After 2 years of the COVID-19 pandemic, translating one health into action is urgent. Lancet. 2023;401(10378):789-794.

Antic D, Milic N, Chatzikonstantinou T, et al. Thrombotic and bleeding complications in patients with chronic lymphocytic leukemia and severe COVID-19: a study of ERIC, the European Research Initiative on CLL. J Hematol Oncol. 2022;15(1):116.

Vijenthira A, Gong IY, Fox TA, et al. Outcomes of patients with hematologic malignancies and COVID-19: a systematic review and meta-analysis of 3377 patients. Blood. 2020;136(25):2881-2892.

Sharafeldin N, Bates B, Song Q, et al. Outcomes of COVID-19 in patients with cancer: report from the National COVID Cohort Collaborative (N3C). J Clin Oncol. 2021;39(20):2232-2246.

Chatzikonstantinou T, Kapetanakis A, Scarfo L, et al. COVID-19 severity and mortality in patients with CLL: an update of the international ERIC and campus CLL study. Leukemia. 2021;35(12):3444-3454.

Roeker LE, Eyre TA, Thompson MC, et al. COVID-19 in patients with CLL: improved survival outcomes and update on management strategies. Blood. 2021;138(18):1768-1773.

Scarfo L, Chatzikonstantinou T, Rigolin GM, et al. COVID-19 severity and mortality in patients with chronic lymphocytic leukemia: a joint study by ERIC, the European Research Initiative on CLL, and CLL Campus. Leukemia. 2020;34(9):2354-2363.

Niemann CU, da Cunha-Bang C, Helleberg M, Ostrowski SR, Brieghel C. Patients with CLL have a lower risk of death from COVID-19 in the omicron era. Blood. 2022;140(5):445-450.

Bronstein Y, Gat R, Levi S, et al. COVID-19 in patients with lymphoproliferative diseases during the omicron variant surge. Cancer Cell. 2022;40(6):578-580.

Mauro FR, Visentin A, Giannarelli D, et al. Pre-exposure prophylaxis with tixagevimab/cilgavimab in patients with chronic lymphocytic leukaemia treated with targeted agents. Br J Haematol. 2023;201(3):564-567.

Mauro FR, Giannarelli D, Galluzzo CM, et al. Antibody response to the SARS-CoV-2 vaccine and COVID-19 vulnerability during the omicron pandemic in patients with CLL: two-year follow-up of a multicenter study. Cancer. 2023;15(11):2993.

Angotzi F, Petrella M, Berno T, et al. Tixagevimab/cilgavimab as pre-exposure prophylaxis against SARS-CoV-2 in patients with hematological malignancies. Frontiers in Oncology. 2023;13:1212752.

Davis HE, McCorkell L, Vogel JM, Topol EJ. Long COVID: major findings, mechanisms and recommendations. Nat Rev Microbiol. 2023;21(3):133-146.

Soriano JB, Murthy S, Marshall JC, Relan P, Diaz JV, WHO Clinical Case Definition Working Group on Post-COVID-19 Condition. A clinical case definition of post-COVID-19 condition by a Delphi consensus. Lancet Infect Dis. 2022;22(4):e102-e107.

Pinato DJ, Tabernero J, Bower M, et al. Prevalence and impact of COVID-19 sequelae on treatment and survival of patients with cancer who recovered from SARS-CoV-2 infection: evidence from the OnCovid retrospective, multicentre registry study. Lancet Oncol. 2021;22(12):1669-1680.

Thompson EJ, Williams DM, Walker AJ, et al. Long COVID burden and risk factors in 10 UK longitudinal studies and electronic health records. Nat Commun. 2022;13(1):3528.

Subramanian A, Nirantharakumar K, Hughes S, et al. Symptoms and risk factors for long COVID in non-hospitalized adults. Nat Med. 2022;28(8):1706-1714.

Parikh SA, Achenbach SJ, Rabe KG, et al. The risk of coronavirus disease 2019 (COVID-19) among individuals with monoclonal B cell lymphocytosis. Blood Cancer J. 2022;12(11):159.

Hallek M, Cheson BD, Catovsky D, et al. iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood. 2018;131(25):2745-2760.

Agathangelidis A, Chatzidimitriou A, Gemenetzi K, et al. Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL. Blood. 2021;137(10):1365-1376.

Baliakas P, Jeromin S, Iskas M, et al. Cytogenetic complexity in chronic lymphocytic leukemia: definitions, associations, and clinical impact. Blood. 2019;133(11):1205-1216.

Malcikova J, Tausch E, Rossi D, et al. ERIC recommendations for TP53 mutation analysis in chronic lymphocytic leukemia-update on methodological approaches and results interpretation. Leukemia. 2018;32(5):1070-1080.

Visentin A, Facco M, Gurrieri C, et al. Prognostic and predictive effect of IGHV mutational status and load in chronic lymphocytic leukemia: focus on FCR and BR treatments. Clin Lymphoma Myeloma Leuk. 2019;19(10):678.e4-685.e4.

Visentin A, Bonaldi L, Rigolin GM, et al. The complex karyotype landscape in chronic lymphocytic leukemia allows the refinement of the risk of Richter syndrome transformation. Haematologica. 2022;107(4):868-876.

Barouch DH. Covid-19 vaccines-immunity, variants, Boosters. N Engl J Med. 2022;387(11):1011-1020.

Munblit D, O'Hara ME, Akrami A, Perego E, Olliaro P, Needham DM. Long COVID: aiming for a consensus. Lancet Respir Med. 2022;10(7):632-634.

Forconi F, Moss P. Perturbation of the normal immune system in patients with CLL. Blood. 2015;126(5):573-581.

Mauro FR, Giannarelli D, Galluzzo CM, et al. Response to the conjugate pneumococcal vaccine (PCV13) in patients with chronic lymphocytic leukemia (CLL). Leukemia. 2020;35(3):737-746.

Shadman M, Liu C, Eakle K, et al. COVID-19 vaccination response and its practical application in patients with chronic lymphocytic leukemia. Hemasphere. 2023;7(1):e811.

Herishanu Y, Rahav G, Levi S, et al. Efficacy of a third BNT162b2 mRNA COVID-19 vaccine dose in patients with CLL who failed standard 2-dose vaccination. Blood. 2022;139(5):678-685.

Agius R, Brieghel C, Andersen MA, et al. Machine learning can identify newly diagnosed patients with CLL at high risk of infection. Nat Commun. 2020;11(1):363.

Visentin A, Imbergamo S, Gurrieri C, et al. Major infections, secondary cancers and autoimmune diseases occur in different clinical subsets of chronic lymphocytic leukaemia patients. Eur J Cancer. 2017;72:103-111.

Visentin A, Compagno N, Cinetto F, et al. Clinical profile associated with infections in patients with chronic lymphocytic leukemia. Protective role of immunoglobulin replacement therapy. Haematologica. 2015;100(12):e515-e518.

Visentin A, Gurrieri C, Imbergamo S, et al. Epidemiology and risk factors of invasive fungal infections in a large cohort of patients with chronic lymphocytic leukemia. Hematol Oncol. 2017;35(4):925-928.

Ujjani CS, Gooley TA, Spurgeon SE, et al. Diminished humoral and cellular responses to SARS-CoV-2 vaccines in patients with chronic lymphocytic leukemia. Blood Adv. 2022;7:4728-4737.

Tadmor T, Alapi H, Rokach L. Effectiveness of nirmatrelvir plus ritonavir treatment for patients with chronic lymphocytic leukemia during the omicron surge. Blood. 2023;141(18):2239-2244.

Kuodi P, Gorelik Y, Zayyad H, et al. Association between BNT162b2 vaccination and reported incidence of post-COVID-19 symptoms: cross-sectional study 2020-21, Israel. NPJ Vaccines. 2022;7(1):101.

Realizing precision medicine in chronic lymphocytic leukemia: Remaining challenges and potential opportunities