{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T07:55:05Z","timestamp":1771660505010,"version":"3.50.1"},"reference-count":32,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T00:00:00Z","timestamp":1660176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Bergen and the Medical faculty","award":["TMS2020TMT05"],"award-info":[{"award-number":["TMS2020TMT05"]}]},{"name":"University of Bergen and the Medical faculty","award":["F12626"],"award-info":[{"award-number":["F12626"]}]},{"DOI":"10.13039\/100016190","name":"Trond Mohn Stiftelse","doi-asserted-by":"publisher","award":["TMS2020TMT05"],"award-info":[{"award-number":["TMS2020TMT05"]}],"id":[{"id":"10.13039\/100016190","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016190","name":"Trond Mohn Stiftelse","doi-asserted-by":"publisher","award":["F12626"],"award-info":[{"award-number":["F12626"]}],"id":[{"id":"10.13039\/100016190","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Helsevest Research","award":["TMS2020TMT05"],"award-info":[{"award-number":["TMS2020TMT05"]}]},{"name":"Helsevest Research","award":["F12626"],"award-info":[{"award-number":["F12626"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Background: Persistent fever after SARS-CoV-2 infection in rituximab-treated patients has been reported. Due to reduced sensitivity in conventional sampling methods and unspecific symptoms in these patients, distinguishing between low-grade viral replication or hyperinflammation is challenging. Antiviral treatment is recommended as prophylactic or early treatment in the at-risk population; however, no defined treatment approaches for protracted SARS-CoV-2 infection exist. Results: We present a case of 96 days of persistent fever and SARS-CoV-2 infection in a patient receiving B cell depletion therapy for multiple sclerosis. Migratory lung infiltrates and positive PCR tests from serum (day-58 post infection) and lower airways (day-90 post infection) confirmed continuous viral replication. The dominant symptoms were continuous high fever, dyspnea and mild to moderate hypoxemia, which never developed into severe respiratory failure. The patient was hospitalized three times, with transient improvement after late antiviral treatment and full recovery 6 months post-rituximab infusion. Conclusions: A strategy for securing samples from lower airways and serum should be a prioritization to strengthen diagnostic certainty in immunocompromised patients. B-cell-deprived patients could benefit from late treatment with SARS-CoV-2-specific monoclonal antibodies and antivirals. Importantly, increased intervals between immunosuppressive therapy should be considered where feasible.<\/jats:p>","DOI":"10.3390\/v14081757","type":"journal-article","created":{"date-parts":[[2022,8,12]],"date-time":"2022-08-12T01:51:11Z","timestamp":1660269071000},"page":"1757","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Persistent Fever and Positive PCR 90 Days Post-SARS-CoV-2 Infection in a Rituximab-Treated Patient: A Case of Late Antiviral Treatment"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5243-9101","authenticated-orcid":false,"given":"Nina Urke","family":"Ertesv\u00e5g","sequence":"first","affiliation":[{"name":"Influenza Centre, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway"},{"name":"Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sunniva Todnem","family":"Sakkestad","sequence":"additional","affiliation":[{"name":"Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway"},{"name":"Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, 5021 Bergen, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9918-3422","authenticated-orcid":false,"given":"Fan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Influenza Centre, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingrid","family":"Hoff","sequence":"additional","affiliation":[{"name":"Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Trygve","family":"Kristiansen","sequence":"additional","affiliation":[{"name":"Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5955-9544","authenticated-orcid":false,"given":"Trygve M\u00fcller","family":"Jonassen","sequence":"additional","affiliation":[{"name":"Department of Thoracic Medicine, Haukeland University Hospital, 5021 Bergen, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabeth","family":"Folles\u00f8","sequence":"additional","affiliation":[{"name":"Radiology Department, Haukeland University Hospital, 5021 Bergen, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0593-2731","authenticated-orcid":false,"given":"Karl Albert","family":"Brokstad","sequence":"additional","affiliation":[{"name":"Influenza Centre, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway"},{"name":"Department of Safety, Chemistry and Biomedical Laboratory Sciences, Western Norway University of Applied Sciences, 5063 Bergen, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruben","family":"Dyrhovden","sequence":"additional","affiliation":[{"name":"Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway"},{"name":"Department of Microbiology, Haukeland University Hospital, 5021 Bergen, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3249-1719","authenticated-orcid":false,"given":"Kristin G.-I.","family":"Mohn","sequence":"additional","affiliation":[{"name":"Influenza Centre, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway"},{"name":"Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e603","DOI":"10.1097\/HS9.0000000000000603","article-title":"COVID-19 in Patients Receiving CD20-depleting Immunochemotherapy for B-cell Lymphoma","volume":"5","author":"Gaitzsch","year":"2021","journal-title":"Hemasphere"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1093\/cid\/ciab380","article-title":"Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Sequence Characteristics of Coronavirus Disease 2019 (COVID-19) Persistence and Reinfection","volume":"74","author":"Choudhary","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","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":"ref_4","doi-asserted-by":"crossref","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":"ref_5","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1053\/j.seminhematol.2010.01.011","article-title":"Rituximab: Mechanism of action","volume":"47","author":"Weiner","year":"2010","journal-title":"Semin. Hematol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/s00415-020-10362-z","article-title":"Rituximab for the treatment of multiple sclerosis: A review","volume":"269","author":"Chisari","year":"2022","journal-title":"J. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"103371","DOI":"10.1016\/j.msard.2021.103371","article-title":"COVID-19 outcomes in persons with multiple sclerosis treated with rituximab","volume":"57","author":"Iyer","year":"2022","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/s41590-021-01122-w","article-title":"The T cell immune response against SARS-CoV-2","volume":"23","author":"Moss","year":"2022","journal-title":"Nat. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e243469","DOI":"10.1136\/bcr-2021-243469","article-title":"Effective use of monoclonal antibodies for treatment of persistent COVID-19 infection in a patient on rituximab","volume":"14","author":"Rabascall","year":"2021","journal-title":"BMJ Case Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"763412","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":"Furlan","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/cei.13495","article-title":"COVID-19 vaccine-readiness for anti-CD20-depleting therapy in autoimmune diseases","volume":"202","author":"Baker","year":"2020","journal-title":"Clin. Exp. Immunol."},{"key":"ref_12","first-page":"8712424","article-title":"Progression of COVID-19 in a Patient on Anti-CD20 Antibody Treatment: Case Report and Literature Review","volume":"2022","author":"Burgener","year":"2022","journal-title":"Case Rep. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.3389\/fonc.2020.01578","article-title":"Prolonged Course of COVID-19-Associated Pneumonia in a B-Cell Depleted Patient After Rituximab","volume":"10","author":"Kos","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1177\/0091270005277075","article-title":"Population pharmacokinetics of rituximab (anti-CD20 monoclonal antibody) in rheumatoid arthritis patients during a phase II clinical trial","volume":"45","author":"Ng","year":"2005","journal-title":"J. Clin. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/s00467-018-4052-x","article-title":"Effect of different rituximab regimens on B cell depletion and time to relapse in children with steroid-dependent nephrotic syndrome","volume":"34","author":"Hogan","year":"2019","journal-title":"Pediatr. Nephrol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1093\/cid\/ciaa863","article-title":"COVID-19 in Immunocompromised Hosts: What We Know So Far","volume":"72","author":"Fung","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Wang, Y., Jin, C., Wu, C.C., Zhao, H., Liang, T., Liu, Z., Jian, Z., Li, R., Wang, Z., and Li, F. (2020). Organizing pneumonia of COVID-19: Time-dependent evolution and outcome in CT findings. PLoS ONE, 15.","DOI":"10.1101\/2020.05.22.20109934"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"101541","DOI":"10.1016\/j.bjid.2021.101541","article-title":"Organizing pneumonia: A late phase complication of COVID-19 responding dramatically to corticosteroids","volume":"25","author":"Vieceli","year":"2021","journal-title":"Braz. J. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.jinf.2020.10.017","article-title":"C(t) values from SARS-CoV-2 diagnostic PCR assays should not be used as direct estimates of viral load","volume":"82","author":"Dahdouh","year":"2021","journal-title":"J. Infect."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1080\/21645515.2018.1462639","article-title":"H3N2 influenza viruses in humans: Viral mechanisms, evolution, and evaluation","volume":"14","author":"Allen","year":"2018","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s12985-022-01802-5","article-title":"Replication kinetics and infectivity of SARS-CoV-2 variants of concern in common cell culture models","volume":"19","author":"Mautner","year":"2022","journal-title":"Virol. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e13","DOI":"10.1016\/S2666-5247(20)30172-5","article-title":"SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: A systematic review and meta-analysis","volume":"2","author":"Cevik","year":"2021","journal-title":"Lancet Microbe."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"115595","DOI":"10.1016\/j.diagmicrobio.2021.115595","article-title":"Duration of SARS-CoV-2 viremia and its correlation to mortality and inflammatory parameters in patients hospitalized for COVID-19: A cohort study","volume":"102","author":"Hagman","year":"2022","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"m1443","DOI":"10.1136\/bmj.m1443","article-title":"Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: Retrospective cohort study","volume":"369","author":"Zheng","year":"2020","journal-title":"BMJ"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e2898","DOI":"10.1093\/cid\/ciaa1316","article-title":"Detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) RNA in Blood of Patients With Coronavirus Disease 2019 (COVID-19): What Does It Mean?","volume":"73","author":"Jacobs","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1186\/s13054-020-03398-0","article-title":"Viral RNA load in plasma is associated with critical illness and a dysregulated host response in COVID-19","volume":"24","author":"Almansa","year":"2020","journal-title":"Crit. Care"},{"key":"ref_27","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_28","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/S1473-3099(21)00751-9","article-title":"Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): A randomised controlled trial","volume":"22","author":"Self","year":"2022","journal-title":"Lancet Infect. Dis."},{"key":"ref_29","unstructured":"The National Institutes of Health (2022, June 06). Therapeutic Management of Hospitalized Adults with COVID-19, Available online: https:\/\/www.covid19treatmentguidelines.nih.gov\/management\/clinical-management\/hospitalized-adults--therapeutic-management\/."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1056\/NEJMoa2116044","article-title":"Molnupiravir for Oral Treatment of COVID-19 in Nonhospitalized Patients","volume":"386","author":"Musungaie","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"102329","DOI":"10.1016\/j.dsx.2021.102329","article-title":"Molnupiravir in COVID-19: A systematic review of literature","volume":"15","author":"Singh","year":"2021","journal-title":"Diabetes Metab. Syndr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1016\/S1473-3099(22)00422-4","article-title":"Augmented neutralisation resistance of emerging omicron subvariants BA.2.12.1, BA.4, and BA.5","volume":"22","author":"Arora","year":"2022","journal-title":"Lancet Infect. Dis."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/8\/1757\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:07:26Z","timestamp":1760141246000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/8\/1757"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,11]]},"references-count":32,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["v14081757"],"URL":"https:\/\/doi.org\/10.3390\/v14081757","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,11]]}}}