Patients with chronic lymphocytic leukemia (CLL) have a high risk of poor outcomes related to coronavirus disease 2019 (COVID-19). This multicenter cohort study evaluated the impact of COVID-19 infection on the population of CLL patients in the Czech Republic. Between March 2020 and May 2021, 341 patients (237 males) with CLL and COVID-19 disease were identified. The median age was 69 years (range 38-91). Out of the 214 (63%) patients with the history of therapy for CLL, 97 (45%) were receiving CLL-directed treatment at diagnosis of COVID-19: 29% Bruton tyrosine kinase inhibitor (BTKi), 16% chemoimmunotherapy (CIT), 11% Bcl-2 inhibitor, and 4% phosphoinositide 3-kinase inhibitor. Regarding the severity of COVID-19, 60% pts required admission to the hospital, 21% pts were admitted to the intensive care unit (ICU), and 12% received invasive mechanical ventilation. The overall case fatality rate was 28%. Major comorbidities, age over 72, male gender, CLL treatment in history, CLL-directed treatment at COVID-19 diagnosis were associated with increased risk of death. Of note, concurrent therapy with BTKi compared to CIT was not associated with better outcome of COVID-19.

1st Department of Medicine Haematology University General Hospital Prague Czech Republic

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

Department of Haematology Oncology University Hospital Olomouc Czech Republic

Department of Hematology and Oncology Medical School and Teaching Hospital in Plzen Charles University Prague Plzen Czech Republic

Department of Hematology and Transfusion Medicine Hospital Pelhrimov Pelhrimov Czech Republic

Department of Hematooncology University Hospital Ostrava Czech Republic

Department of Internal Medicine Haematology and Oncology University Hospital Brno Czech Republic

Department of Internal Medicine Haematology University Hospital Královské Vinohrady Prague Czech Republic

Haematology Tranfusiology Department Silesian Hospital Opava Opava Czech Republic

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Wang C, Horby PW, Hayden FG, Gao GF. A novel coronavirus outbreak of global health concern. Lancet. 2020;395:470–473. doi: 10.1016/S0140-6736(20)30185-9. PubMed DOI PMC

Coronaviridae Study Group of the International Committee on Taxonomy of Viruses The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol. 2020;5:536–44. doi: 10.1038/s41564-020-0695-z. PubMed DOI PMC

Smith A, Howell D, Patmore R, Jack A, Roman E. Incidence of haematological malignancy by sub-type: a report from the Haematological Malignancy Research Network. Br J Cancer. 2011;105:1684–1692. doi: 10.1038/bjc.2011.450. PubMed DOI PMC

Strati P, Parikh SA, Chaffee KG, Kay NE, Call TG, Achenbach SJ, et al. Relationship between co-morbidities at diagnosis, survival and ultimate cause of death in patients with chronic lymphocytic leukaemia (CLL): a prospective cohort study. Br J Haematol. 2017;178:394–402. doi: 10.1111/bjh.14785. PubMed DOI PMC

Roeker LE, Eyre TA, Thompson MC, Lamanna N, Coltoff A, Davids MS et al (2021) COVID-19 in patients with CLL: improved survival outcomes and update on management strategies. Blood: blood.2021011841. 10.1182/blood.2021011841 PubMed PMC

Mato AR, Roeker LE, Lamanna N, Allan JN, Leslie L, Pagel JM, et al. Outcomes of COVID-19 in patients with CLL: a multicenter international experience. Blood. 2020;136:1134–1143. doi: 10.1182/blood.2020006965. PubMed DOI PMC

Chatzikonstantinou T, Kapetanakis A, Scarfò L, Karakatsoulis G, Allsup D, Cabrero AA, et al. COVID-19 severity and mortality in patients with CLL: an update of the international ERIC and Campus CLL study. Leukemia. 2021;35:3444–3454. doi: 10.1038/s41375-021-01450-8. PubMed DOI PMC

Scarfò L, Chatzikonstantinou T, Rigolin GM, Quaresmini G, Motta M, Vitale C, 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;34:2354–2363. doi: 10.1038/s41375-020-0959-x. PubMed DOI PMC

Langerbeins P, Eichhorst B. Immune dysfunction in patients with chronic lymphocytic leukemia and challenges during COVID-19 pandemic. AHA. 2021;144:508–518. doi: 10.1159/000514071. PubMed DOI PMC

Wadhwa PD, Morrison VA. Infectious complications of chronic lymphocytic leukemia. Semin Oncol. 2006;33:240–249. doi: 10.1053/j.seminoncol.2005.12.013. PubMed DOI

Frank DA, Mahajan S, Ritz J. Fludarabine-induced immunosuppression is associated with inhibition of STAT1 signaling. Nat Med. 1999;5:444–447. doi: 10.1038/7445. PubMed DOI

Reinwald M, Silva JT, Mueller NJ, Fortún J, Garzoni C, de Fijter JW, et al. ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Intracellular signaling pathways: tyrosine kinase and mTOR inhibitors) Clin Microbiol Infect. 2018;24(Suppl 2):S53–70. doi: 10.1016/j.cmi.2018.02.009. PubMed DOI

Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner H, et al. iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood. 2018;131:2745–2760. doi: 10.1182/blood-2017-09-806398. PubMed DOI

Salvi F, Miller MD, Grilli A, Giorgi R, Towers AL, Morichi V, et al. A manual of guidelines to score the modified cumulative illness rating scale and its validation in acute hospitalized elderly patients. J Am Geriatr Soc. 2008;56:1926–1931. doi: 10.1111/j.1532-5415.2008.01935.x. PubMed DOI

Shuster JJ. Median follow-up in clinical trials. J Clin Oncol. 1991;9:191–192. doi: 10.1200/JCO.1991.9.1.191. PubMed DOI

Garg S, Patel K, Pham H, Whitaker M, O’Halloran A, Milucky J, et al. Clinical trends among U.S. adults hospitalized with COVID-19, March to December 2020: A cross-sectional study. Ann Intern Med. 2021;174:1409–19. doi: 10.7326/M21-1991. PubMed DOI PMC

Levin AT, Hanage WP, Owusu-Boaitey N, Cochran KB, Walsh SP, Meyerowitz-Katz G. Assessing the age specificity of infection fatality rates for COVID-19: systematic review, meta-analysis, and public policy implications. Eur J Epidemiol. 2020;35:1123–1138. doi: 10.1007/s10654-020-00698-1. PubMed DOI PMC

Wu Z, McGoogan JM. Characteristics of and important lessons from the Coronavirus Disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese center for disease control and prevention. JAMA. 2020;323:1239–1242. doi: 10.1001/jama.2020.2648. PubMed DOI

Williamson EJ, Walker AJ, Bhaskaran K, Bacon S, Bates C, Morton CE, et al. Factors associated with COVID-19-related death using OpenSAFELY. Nature. 2020;584:430–436. doi: 10.1038/s41586-020-2521-4. PubMed DOI PMC

Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054–1062. doi: 10.1016/S0140-6736(20)30566-3. PubMed DOI PMC

Smith CIE, Zain R, Österborg A, Palma M, Buggert M, Bergman P, et al. Do reduced numbers of plasmacytoid dendritic cells contribute to the aggressive clinical course of COVID-19 in chronic lymphocytic leukaemia? Scand J Immunol. 2022;95:e13153. doi: 10.1111/sji.13153. PubMed DOI PMC

Malinowski KP, Kawalec P, Trąbka W, Czech M, Petrova G, Manova M, et al. Reimbursement legislations and decision making for orphan drugs in central and eastern European countries. Front Pharmacol. 2019;10:487. doi: 10.3389/fphar.2019.00487. PubMed DOI PMC

Skoupá J. Drug policy in the Czech Republic. Value Health Reg Issues. 2017;13:55–58. doi: 10.1016/j.vhri.2017.08.002. PubMed DOI

Smolej L, Špaček M, Pospíšilová Š, Jarošová M, Papajík T, Urbanová R, et al. Recommendations for chronic lymphocytic leukaemia diagnosis and therapy 2021. Transfuze a Hematologie Dnes. 2021;27:91–106. doi: 10.48095/cctahd202191. DOI

Wagner C, Griesel M, Mikolajewska A, Mueller A, Nothacker M, Kley K, et al. Systemic corticosteroids for the treatment of COVID-19. Cochrane Database Syst Rev. 2021;8:CD014963. doi: 10.1002/14651858.CD014963. PubMed DOI PMC

WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group. Sterne JAC, Murthy S, Diaz JV, Slutsky AS, Villar J, et al. Association between administration of systemic corticosteroids and mortality among critically Ill patients with COVID-19: A meta-analysis. JAMA. 2020;324:1330–41. doi: 10.1001/jama.2020.17023. PubMed DOI PMC

Fauci AS, Dale DC, Balow JE. Glucocorticosteroid therapy: mechanisms of action and clinical considerations. Ann Intern Med. 1976;84:304–315. doi: 10.7326/0003-4819-84-3-304. PubMed DOI