{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T23:08:08Z","timestamp":1768691288057,"version":"3.49.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T00:00:00Z","timestamp":1673222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>COVID-19 in immunocompromised patients is difficult to treat. SARS-CoV-2 interaction with the host immune system and the role of therapy still remains only partly understood. There are no data regarding the use of monoclonal antibodies and the combination of two antivirals in fighting viral replication and disease progression. We report the cases of two patients, both treated with rituximab for non-Hodgkin lymphoma and granulomatosis with polyangiitis, respectively, and both hospitalized for COVID-19 with positive SARS-CoV-2 RNAemia, who were successfully treated with a salvage combination therapy with sotrovimab, remdesivir and nirmatrelvir\/ritonavir.<\/jats:p>","DOI":"10.3389\/fmed.2022.1062450","type":"journal-article","created":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T09:00:51Z","timestamp":1673254851000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":27,"title":["Case report: Sotrovimab, remdesivir and nirmatrelvir\/ritonavir combination as salvage treatment option in two immunocompromised patients hospitalized for COVID-19"],"prefix":"10.3389","volume":"9","author":[{"given":"Federico","family":"Baldi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Dentone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malgorzata","family":"Mikulska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Fenoglio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Mirabella","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Magn\u00e8","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Portunato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiziana","family":"Altosole","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Sepulcri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniele Roberto","family":"Giacobbe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Uras","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graziana","family":"Scavone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia","family":"Taramasso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Orsi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Cittadini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gilberto","family":"Filaci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo","family":"Bassetti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1813","DOI":"10.1056\/NEJMoa2007764","article-title":"Remdesivir for the treatment of COVID-19 \u2014 final report.","volume":"383","author":"Beigel","year":"2020","journal-title":"N Engl J Med."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2108163","article-title":"REGEN-COV antibody combination and outcomes in outpatients with COVID-19.","volume":"385","author":"Weinreich","year":"2021","journal-title":"N Engl J Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1016\/S0140-6736(22)00163-5","article-title":"Casirivimab and imdevimab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.","volume":"399","year":"2022","journal-title":"Lancet."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1382","DOI":"10.1056\/NEJMoa2102685","article-title":"Bamlanivimab plus etesevimab in mild or moderate COVID-19.","volume":"385","author":"Dougan","year":"2021","journal-title":"N Engl J Med."},{"key":"B5","doi-asserted-by":"publisher","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":"B6","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1056\/NEJMoa2116044","article-title":"Molnupiravir for oral treatment of COVID-19 in nonhospitalized patients.","volume":"386","author":"Jayk Bernal","year":"2022","journal-title":"N Engl J Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1397","DOI":"10.1056\/NEJMoa2118542","article-title":"Oral nirmatrelvir for high-risk, nonhospitalized adults with COVID-19.","volume":"386","author":"Hammond","year":"2022","journal-title":"N Engl J Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1056\/NEJMoa2116846","article-title":"Early remdesivir to prevent progression to severe COVID-19 in outpatients.","volume":"386","author":"Gottlieb","year":"2022","journal-title":"N Engl J Med."},{"key":"B9","year":"2021","journal-title":"A randomized, double-blind, placebo-controlled, phase 2 study to evaluate the efficacy and safety of mono and combination therapy with monoclonal antibodies in participants with mild to moderate COVID-19 illness (BLAZE-4)."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofab466.1646","article-title":"PROVENT: phase 3 study of efficacy and safety of AZD7442 (tixagevimab\/ cilgavimab) for pre-exposure prophylaxis of COVID-19 in adults.","author":"Levin","year":"2021","journal-title":"Open Forum Infect Dis."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1637","DOI":"10.1016\/S0140-6736(21)00676-0","article-title":"Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.","volume":"397","year":"2021","journal-title":"Lancet."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1752","DOI":"10.1038\/s41591-021-01499-z","article-title":"Early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels: a double-blind, randomized controlled phase 3 trial.","volume":"27","author":"Kyriazopoulou","year":"2021","journal-title":"Nat Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1407","DOI":"10.1016\/S2213-2600(21)00331-3","article-title":"Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial.","volume":"9","author":"Marconi","year":"2021","journal-title":"Lancet Respir Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"e737","DOI":"10.1016\/S2352-3026(20)30251-9","article-title":"Clinical characteristics and risk factors associated with COVID-19 severity in patients with haematological malignancies in Italy: a retrospective, multicentre, cohort study.","volume":"7","author":"Passamonti","year":"2020","journal-title":"Lancet Haematol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"2881","DOI":"10.1182\/blood.2020008824","article-title":"Outcomes of patients with hematologic malignancies and COVID-19: a systematic review and meta-analysis of 3377 patients.","volume":"136","author":"Vijenthira","year":"2020","journal-title":"Blood."},{"key":"B16","doi-asserted-by":"publisher","first-page":"2885","DOI":"10.1038\/s41375-021-01302-5","article-title":"COVID-19 and stem cell transplantation; results from an EBMT and GETH multicenter prospective survey.","volume":"35","author":"Ljungman","year":"2021","journal-title":"Leukemia."},{"key":"B17","doi-asserted-by":"publisher","first-page":"3585","DOI":"10.1038\/s41375-021-01466-0","article-title":"Poor outcome of patients with COVID-19 after CAR T-cell therapy for B-cell malignancies: results of a multicenter study on behalf of the European society for blood and marrow transplantation (EBMT) infectious diseases working party and the European hematology association (EHA) lymphoma group.","volume":"35","author":"Spanjaart","year":"2021","journal-title":"Leukemia."},{"key":"B18","doi-asserted-by":"publisher","first-page":"2071","DOI":"10.1038\/s41409-020-0919-0","article-title":"The challenge of COVID-19 and hematopoietic cell transplantation; EBMT recommendations for management of hematopoietic cell transplant recipients, their donors, and patients undergoing CAR T-cell therapy.","volume":"55","author":"Ljungman","year":"2020","journal-title":"Bone Marrow Transplant."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofab217","article-title":"The longest persistence of viable SARS-CoV-2 with recurrence of viremia and relapsing symptomatic COVID-19 in an immunocompromised patient\u2014a case study.","volume":"8","author":"Sepulcri","year":"2021","journal-title":"Open Forum Infect Dis."},{"key":"B20","doi-asserted-by":"publisher","first-page":"2586","DOI":"10.1056\/NEJMc2031670","article-title":"Shedding of viable SARS-CoV-2 after immunosuppressive therapy for cancer.","volume":"383","author":"Aydillo","year":"2020","journal-title":"N Engl J Med."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1901","DOI":"10.1016\/j.cell.2020.10.049","article-title":"Case study: prolonged infectious SARS-CoV-2 shedding from an asymptomatic immunocompromised individual with cancer.","volume":"183","author":"Avanzato","year":"2020","journal-title":"Cell."},{"key":"B22","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1093\/infdis\/jiaa666","article-title":"Prolonged severe acute respiratory syndrome coronavirus 2 replication in an immunocompromised patient.","volume":"223","author":"Baang","year":"2021","journal-title":"J Infect Dis."},{"key":"B23","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/j.jiac.2020.12.001","article-title":"Prolonged viral shedding of SARS-CoV-2 in an immunocompromised patient.","volume":"27","author":"Nakajima","year":"2021","journal-title":"J Infect Chemother."},{"key":"B24","doi-asserted-by":"publisher","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":"B25","doi-asserted-by":"publisher","first-page":"2291","DOI":"10.1056\/NEJMc2031364","article-title":"Persistence and evolution of SARS-CoV-2 in an immunocompromised host.","volume":"383","author":"Choi","year":"2020","journal-title":"N Engl J Med."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1093\/infdis\/jiaa446","article-title":"Persistent COVID-19 in an immunocompromised patient temporarily responsive to two courses of remdesivir therapy.","volume":"222","author":"Helleberg","year":"2020","journal-title":"J Infect Dis."},{"key":"B27","doi-asserted-by":"publisher","first-page":"e51","DOI":"10.1111\/bjh.17212","article-title":"SARS-CoV-2 persistence and non-protective immunity in infected haematological patients.","volume":"192","author":"Akinosoglou","year":"2020","journal-title":"Br J Haematol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1016\/S0140-6736(20)30628-0","article-title":"COVID-19: consider cytokine storm syndromes and immunosuppression.","volume":"395","author":"Mehta","year":"2020","journal-title":"Lancet."},{"key":"B29","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1016\/j.healun.2020.03.012","article-title":"COVID-19 illness in native and immunosuppressed states: a clinical\u2013therapeutic staging proposal.","volume":"39","author":"Siddiqi","year":"2020","journal-title":"J Heart Lung Transplant."},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2119893119","article-title":"COVID-19 therapeutics: challenges and directions for the future.","volume":"119","author":"Robinson","year":"2022","journal-title":"Proc Natl Acad Sci USA."},{"key":"B31","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1158\/2159-8290.CD-21-1033","article-title":"Prolonged SARS-CoV-2 infection in patients with lymphoid malignancies.","volume":"12","author":"Lee","year":"2022","journal-title":"Cancer Discov."},{"key":"B32","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/j.ccell.2020.09.007","article-title":"SARS-CoV-2 viral load predicts mortality in patients with and without cancer who are hospitalized with COVID-19.","volume":"38","author":"Westblade","year":"2020","journal-title":"Cancer Cell."},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2022.10.007","article-title":"The unique presentation of SARS-CoV-2 Infection in patients with B-cell depletion: definition of \u201cpersistent inflammatory sero-negative COVID\u201d.","author":"Belkin","year":"2022","journal-title":"Clin Microbiol Infect."},{"key":"B34","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1016\/j.jaci.2021.10.031","article-title":"Treatment of chronic or relapsing COVID-19 in immunodeficiency.","volume":"149","author":"Brown","year":"2022","journal-title":"J Allergy Clin Immunol."},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.947174","article-title":"Real-life data on monoclonal antibodies and antiviral drugs in Italian inborn errors of immunity patients during COVID-19 pandemic.","volume":"13","author":"Garzi","year":"2022","journal-title":"Front Immunol."},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.935952","article-title":"Editorial: current status of oral antiviral drug treatments for SARS-CoV-2 infection in non-hospitalized patients.","volume":"28","author":"Parums","year":"2022","journal-title":"Med Sci Monit."},{"key":"B37","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1056\/NEJMc2119407","article-title":"\u00abEfficacy of antibodies and antiviral drugs against COVID-19 omicron variant\u00bb.","volume":"386","author":"Takashita","year":"2022","journal-title":"N Engl J Med."},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3390\/v14061334","article-title":"\u00abResistance of SARS-CoV-2 omicron BA.1 and BA.2 variants to vaccine-elicited sera and therapeutic monoclonal antibodies\u00bb.","volume":"14","author":"Zhou","year":"2022","journal-title":"Viruses."},{"key":"B39","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1111\/bjh.16896","article-title":"Persisting SARS-CoV-2 viraemia after rituximab therapy: two cases with fatal outcome and a review of the literature.","volume":"190","author":"Tepasse","year":"2020","journal-title":"Br J Haematol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1038\/s41422-022-00618-w","article-title":"SARS-CoV-2 Omicron variant is highly sensitive to molnupiravir, nirmatrelvir, and the combination.","volume":"32","author":"Li","year":"2022","journal-title":"Cell Res."},{"key":"B41","doi-asserted-by":"publisher","first-page":"2337","DOI":"10.1007\/s00277-022-04924-6","article-title":"Early administration of remdesivir plus convalescent plasma therapy is effective to treat COVID-19 pneumonia in B-cell depleted patients with hematological malignancies.","volume":"101","author":"Magyari","year":"2022","journal-title":"Ann Hematol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1111\/imm.13262","article-title":"T-cell responses and therapies against SARS-CoV-2 infection.","volume":"162","author":"Toor","year":"2021","journal-title":"Immunology."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1122","DOI":"10.1126\/science.abm8108","article-title":"The immunology and immunopathology of COVID-19.","volume":"375","author":"Merad","year":"2022","journal-title":"Science."},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00109-21","article-title":"SARS-CoV-2 antiviral therapy.","volume":"34","author":"Tao","year":"2021","journal-title":"Clin Microbiol Rev."},{"key":"B45","doi-asserted-by":"publisher","first-page":"3384","DOI":"10.1111\/ene.14690","article-title":"COVID-19 in multiple sclerosis patients: susceptibility, severity risk factors and serological response.","volume":"28","author":"Zabalza","year":"2021","journal-title":"Eur J Neurol."},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.763412","article-title":"COVID-19 in B cell-depleted patients after rituximab: a diagnostic and therapeutic challenge.","volume":"12","author":"Forner","year":"2021","journal-title":"Front Immunol."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.1062450\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T09:00:55Z","timestamp":1673254855000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.1062450\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,9]]},"references-count":46,"alternative-id":["10.3389\/fmed.2022.1062450"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2022.1062450","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,9]]},"article-number":"1062450"}}