{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:59:38Z","timestamp":1760144378827,"version":"build-2065373602"},"reference-count":26,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,3,31]],"date-time":"2024-03-31T00:00:00Z","timestamp":1711843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Patients treated with hemato-oncological malignancies (HO) or undergoing cellular therapies such as hematopoietic stem cell transplantation (HSCT) or chimeric antigen receptor T cells (CAR-T) were significantly affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite the success of SARS-CoV-2 vaccination, immunocompromised patients remain at increased risk for severe coronavirus disease (COVID-19), rendering this group of population a high priority for additional prevention and treatment options. Tixagevimab and Cilgavimab (TIXA\/CILGA, AZD7442, Evusheld\u00ae) is a combination of two fully human, long-acting monoclonal antibodies. TIXA\/CILGA have been approved as pre-exposure prophylaxis and treatment in patients at risk of severe disease with impaired vaccine response. Our objective was to describe the efficacy and safety among immunocompromised pediatric patients. Methods: This was an observational multicenter cohort study of immunocompromised pediatric patients receiving TIXA\/CILGA conducted at nine Polish centers of Pediatric Oncology, Hematology and Bone Marrow Transplantation. We analyzed patients in two groups; those treated with HO and those undergoing cellular therapies: HSCT or CAR-T cells. In addition, two other cohorts were identified: patients given TIXA\/CILGA as pre-exposure prophylactic and therapeutic intervention. Results: A total of 78 patients were evaluated during the study period: 69 (88.5%) received TIXA\/CILGA as pre-exposure prophylaxis and 9 (11.5%) as a treatment strategy. A total of 52 (66.6%) patients were treated with standard chemotherapy at HO departments; 21 (27%) underwent HSCT, and 5 (6.4%) received CAR-T cell therapy. All children with COVID-19 receiving TIXA\/CILGA presented a mild degree of severity. The most common clinical manifestations were fever, cough and coryza. At least one adverse event (AE) was reported in two (3.8%) patients excluding standard injection site reactions. Reported AEs were mild or moderate in intensity. One child reported mild myalgia and one reported moderate bone pain and weakness. Conclusions: In our observational multicenter cohort study, we explored the use of TIXA\/CILGA as pre-exposure prophylaxis and treatment for COVID-19 among immunocompromised pediatric patients. While our findings suggest a potential benefit in preventing and managing COVID-19 in this vulnerable population, it is important to note the study\u2019s non-comparative design. Our results highlight the need for well-designed clinical trials to confirm these observations and further assess the efficacy and safety of TIXA\/CILGA in immunocompromised children.<\/jats:p>","DOI":"10.3390\/jcm13072029","type":"journal-article","created":{"date-parts":[[2024,3,31]],"date-time":"2024-03-31T13:32:56Z","timestamp":1711891976000},"page":"2029","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pre-Exposure Prophylaxis and Treatment with Tixagevimab\/Cilgavimab for COVID-19 among Immunocompromised Pediatric Patients"],"prefix":"10.3390","volume":"13","author":[{"given":"Jowita","family":"Fr\u0105czkiewicz","sequence":"first","affiliation":[{"name":"Department of Pediatric Stem Cell Transplantation, Hematology and Oncology, Wroclaw Medical University, 50-556 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1212-7629","authenticated-orcid":false,"given":"Katarzyna","family":"Pawi\u0144ska-W\u0105sikowska","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology and Hematology, University Children\u2019s Hospital, Jagiellonian University Medical College, 31-008 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarzyna","family":"Szymbor","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology and Hematology, University Children\u2019s Hospital, Jagiellonian University Medical College, 31-008 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5379-2318","authenticated-orcid":false,"given":"Walentyna","family":"Balwierz","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology and Hematology, University Children\u2019s Hospital, Jagiellonian University Medical College, 31-008 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Szymon","family":"Skocze\u0144","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology and Hematology, University Children\u2019s Hospital, Jagiellonian University Medical College, 31-008 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7704-7518","authenticated-orcid":false,"given":"Krzysztof","family":"Czy\u017cewski","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, Collegium Medicum Nicolaus Copernicus University, 87-100 Torun, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7663-6580","authenticated-orcid":false,"given":"Sylwia","family":"Ko\u0142tan","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, Collegium Medicum Nicolaus Copernicus University, 87-100 Torun, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3158-119X","authenticated-orcid":false,"given":"Jan","family":"Styczy\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, Collegium Medicum Nicolaus Copernicus University, 87-100 Torun, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Ma\u0142ecka","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hematology and Oncology, Medical University of Gdansk, 80-211 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ninela","family":"Irga-Jaworska","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hematology and Oncology, Medical University of Gdansk, 80-211 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1484-4274","authenticated-orcid":false,"given":"Joanna","family":"Treli\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology and Hematology, Medical University of Lodz, 90-549 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2714-5851","authenticated-orcid":false,"given":"Wojciech","family":"M\u0142ynarski","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology and Hematology, Medical University of Lodz, 90-549 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga","family":"Zaj\u0105c-Spycha\u0142a","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Transplantology, Poznan University of Medical Sciences, 61-701 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnieszka","family":"Sobkowiak-Sobierajska","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Transplantology, Poznan University of Medical Sciences, 61-701 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7239-4035","authenticated-orcid":false,"given":"Katarzyna","family":"Derwich","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Transplantology, Poznan University of Medical Sciences, 61-701 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wioletta","family":"Bal","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncohematology, University of Rzeszow, 35-310 Rzeszow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6862-9142","authenticated-orcid":false,"given":"Rados\u0142aw","family":"Chaber","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncohematology, University of Rzeszow, 35-310 Rzeszow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8897-8585","authenticated-orcid":false,"given":"Agnieszka","family":"Ksi\u0105\u017cek","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, Zabrze, Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5336-261X","authenticated-orcid":false,"given":"Tomasz","family":"Szczepa\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, Zabrze, Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7207-156X","authenticated-orcid":false,"given":"Joanna","family":"Zawitkowska","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology, Oncology and Transplantology, Medical University of Lublin, 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarzyna","family":"Drabko","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology, Oncology and Transplantology, Medical University of Lublin, 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnieszka","family":"Choda\u0142a-Grzywacz","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology and Oncology, Children Hospital, 25-734 Kielce, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gra\u017cyna","family":"Karolczyk","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology and Oncology, Children Hospital, 25-734 Kielce, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8023-8585","authenticated-orcid":false,"given":"Christopher","family":"Kobierzycki","sequence":"additional","affiliation":[{"name":"Division of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1174-5799","authenticated-orcid":false,"given":"Krzysztof","family":"Ka\u0142wak","sequence":"additional","affiliation":[{"name":"Department of Pediatric Stem Cell Transplantation, Hematology and Oncology, Wroclaw Medical University, 50-556 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1038\/s41375-022-01578-1","article-title":"Recommendations for the Management of COVID-19 in Patients with Haematological Malignancies or Haematopoietic Cell Transplantation, from the 2021 European Conference on Infections in Leukaemia (ECIL 9)","volume":"36","author":"Cesaro","year":"2022","journal-title":"Leukemia"},{"key":"ref_2","first-page":"1067","article-title":"Effectiveness of Evusheld in Immunocompromised Patients: Propensity Score-Matched Analysis","volume":"76","author":"Gronich","year":"2022","journal-title":"Clin. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"eabl8124","DOI":"10.1126\/scitranslmed.abl8124","article-title":"The SARS-CoV-2 Monoclonal Antibody Combination, AZD7442, Is Protective in Nonhuman Primates and Has an Extended Half-Life in Humans","volume":"14","author":"Loo","year":"2022","journal-title":"Sci. Transl. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"ofac283","DOI":"10.1093\/ofid\/ofac283","article-title":"Characterization of Early-Onset Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Immunocompromised Patients Who Received Tixagevimab-Cilgavimab Prophylaxis","volume":"9","author":"Ordaya","year":"2022","journal-title":"Open Forum Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1080\/22221751.2022.2030200","article-title":"Homologous or Heterologous Booster of Inactivated Vaccine Reduces SARS-CoV-2 Omicron Variant Escape from Neutralizing Antibodies","volume":"11","author":"Wang","year":"2022","journal-title":"Emerg. Microbes Infect."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/S2213-2600(22)00180-1","article-title":"Efficacy and Safety of Intramuscular Administration of Tixagevimab\u2013Cilgavimab for Early Outpatient Treatment of COVID-19 (TACKLE): A Phase 3, Randomised, Double-Blind, Placebo-Controlled Trial","volume":"10","author":"Montgomery","year":"2022","journal-title":"Lancet Respir. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1056\/NEJMoa2107934","article-title":"Early Treatment for COVID-19 with SARS-CoV-2 Neutralizing Antibody Sotrovimab","volume":"385","author":"Gupta","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_8","first-page":"CD014945","article-title":"SARS-CoV-2-neutralising Monoclonal Antibodies to Prevent COVID-19","volume":"2022","author":"Hirsch","year":"2022","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.ijid.2022.06.045","article-title":"Repeat Subcutaneous Administration of REGEN-COV\u00ae in Adults Is Well-Tolerated and Prevents the Occurrence of COVID-19","volume":"122","author":"Isa","year":"2022","journal-title":"Int. J. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1001\/jama.2021.8828","article-title":"Effect of Bamlanivimab vs Placebo on Incidence of COVID-19 Among Residents and Staff of Skilled Nursing and Assisted Living Facilities: A Randomized Clinical Trial","volume":"326","author":"Cohen","year":"2021","journal-title":"JAMA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2188","DOI":"10.1056\/NEJMoa2116620","article-title":"Intramuscular AZD7442 (Tixagevimab-Cilgavimab) for Prevention of COVID-19","volume":"386","author":"Levin","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Bakkes, J., Cheatle, M., M\u017eavanadze, N., Pint\u00e9r, L., and Witt, R.G. (2022). Keeping the World\u2019s Environment under Review: An Intellectual History of the Global Environment Outlook, Central European University Press.","DOI":"10.7829\/j.ctv209xmzx"},{"key":"ref_13","unstructured":"Food and Drug Administration (2024, February 17). FACT SHEET FOR HEALTHCARE PROVIDERS: EMERGENCY USE AUTHORIZATION FOR EVUSHELDTM (Tixagevimab Co-Packaged with Cilgavimab) HIGHLIGHTS OF EMERGENCY USE AUTHORIZATION (EUA) These Highlights of the EUA Do Not Include All the Information Needed to Use EVUSHELDTM, Available online: https:\/\/www.fda.gov\/media\/154701\/download."},{"key":"ref_14","unstructured":"De Filippo, M., Magri, P., Bossi, G., Brambilla, I., Castagnoli, R., Mascolo, A., Votto, M., Licari, A., and Marseglia, G.L. (2022). Clinical and Epidemiological Features of Pediatric Patients with COVID-19 in a Tertiary Pediatric Hospital. Acta Biomed., 93."},{"key":"ref_15","unstructured":"(2024, February 17). NIH Clinical Spectrum | COVID-19 Treatment Guidelines, Available online: https:\/\/www.covid19treatmentguidelines.nih.gov\/."},{"key":"ref_16","unstructured":"National Institutes of Health Treatment Guidelines Panel (2021). Coronavirus Disease 2019 (COVID-19), NIH."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1186\/s13045-022-01387-0","article-title":"Pre-Exposure Prophylaxis with Tixagevimab\/ Cilgavimab (AZD7442) Prevents Severe SARS-CoV-2 Infection in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation during the Omicron Wave: A Multicentric Retrospective Study of SFGM-TC","volume":"15","author":"Jondreville","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"ref_18","first-page":"2021","article-title":"Safety and Antibody Response after 1 and 2 Doses of BNT162b2 MRNA Vaccine in Recipients of Allogeneic Hematopoietic Stem Cell Transplant","volume":"44","author":"Guillaume","year":"2021","journal-title":"JAMA Netw. Open"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1002\/ajh.26385","article-title":"SARS-CoV-2-Reactive Antibody Detection after SARS-CoV-2 Vaccination in Hematopoietic Stem Cell Transplant Recipients: Prospective Survey from the Spanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group","volume":"97","author":"Martino","year":"2022","journal-title":"Am. J. Hematol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Alhumaid, S., Al Mutair, A., Alali, J., Al Dossary, N., Albattat, S.H., Al HajjiMohammed, S.M., Almuaiweed, F.S., AlZaid, M.R., Alomran, M.J., and Alqurini, Z.S. (2022). Efficacy and Safety of Tixagevimab\/Cilgavimab to Prevent COVID-19 (Pre-Exposure Prophylaxis): A Systematic Review and Meta-Analysis. Disease, 10.","DOI":"10.3390\/diseases10040118"},{"key":"ref_21","unstructured":"(2023, November 23). Our World in Data. Available online: https:\/\/www.google.com\/search?q=our+world+in+data&oq=&aqs=chrome.0.35i39i362l6j46i39i175i199i362i654j46i39i362.852170j0j7&sourceid=chrome&ie=UTF-8."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Zabidi, N.Z., Liew, H.L., Farouk, I.A., Puniyamurti, A., Yip, A.J.W., Wijesinghe, V.N., Low, Z.Y., Tang, J.W., Chow, V.T.K., and Lal, S.K. (2023). Evolution of SARS-CoV-2 Variants: Implications on Immune Escape, Vaccination, Therapeutic and Diagnostic Strategies. Viruses, 15.","DOI":"10.3390\/v15040944"},{"key":"ref_23","unstructured":"(2024, February 17). Map Tracked of Varian Occurrence. Available online: https:\/\/gisaid.org\/hcov19-variants\/."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"69","DOI":"10.5603\/OCP.2022.0035","article-title":"Recommendations for Prevention of SARS-CoV-2 Infection in Immunocompromised Patients","volume":"19","author":"Tomasiewicz","year":"2023","journal-title":"Oncol. Clin. Pract."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1229655","DOI":"10.3389\/fonc.2023.1229655","article-title":"SARS-CoV-2 Infection in High-Risk Children Following Tixagevimab-Cilgavimab (Evusheld) Pre-Exposure Prophylaxis: A Single-Center Observational Study","volume":"13","author":"Hijano","year":"2023","journal-title":"Front. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"892","DOI":"10.7326\/M22-1026","article-title":"Belt and Suspenders: Vaccines and Tixagevimab\/Cilgavimab for Prevention of COVID-19 in Immunocompromised Patients","volume":"175","author":"Kotton","year":"2022","journal-title":"Ann. Intern. Med."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/7\/2029\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:21:42Z","timestamp":1760106102000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/7\/2029"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,31]]},"references-count":26,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["jcm13072029"],"URL":"https:\/\/doi.org\/10.3390\/jcm13072029","relation":{},"ISSN":["2077-0383"],"issn-type":[{"type":"electronic","value":"2077-0383"}],"subject":[],"published":{"date-parts":[[2024,3,31]]}}}