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We report a case series of adult patients with B cell malignancies and\/or undergoing B cell targeting therapies with persisting SARS\u2010CoV\u20102 infection and treated with a combination antiviral therapy of remdesivir and nirmatrelvir\/ritonavir, in three Italian tertiary academic hospitals. A total of 14 patients with impaired adaptive humoral immunity and prolonged SARS\u2010CoV\u20102 infection were treated with the dual antiviral therapy. The median age was 60 (IQR 56\u201368) years, and 11 were male. Twelve patients had B cell lymphoma, one patient had chronic lymphocytic leukemia and one patient had multiple sclerosis. Thirteen out of 14 patients had received prior B cell\u2010targeting therapies, consisting of anti\u2010CD20 monoclonal antibodies in 11 patients, and chimeric antigen receptor T therapy in 2 patients. The median time between diagnosis and therapy start was 42.0 (IQR 35\u201346) days. Seven patients had mild, 6 moderate and one severe disease. Nine patients had signs of interstitial pneumonitis on chest computed tomography scans before treatment. The median duration of nirmatrelvir\/ritonavir and remdesivir combination therapy was 10\u00a0days. All patients showed resolution of COVID\u201019\u2010related symptoms after a median of 6 (IQR 4\u201311) days and viral clearance after 9 (IQR 5\u201311) days. Combination therapy with remdesivir and nirmatrelvir\/ritonavir is a promising treatment option for persistent COVID\u201019 in immunocompromized patients with humoral immunity impairment, worthy of prospective comparative trials.<\/jats:p>","DOI":"10.1002\/hon.3206","type":"journal-article","created":{"date-parts":[[2023,7,15]],"date-time":"2023-07-15T07:36:25Z","timestamp":1689406585000},"page":"904-911","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Dual combined antiviral treatment with remdesivir and nirmatrelvir\/ritonavir in patients with impaired humoral immunity and persistent SARS\u2010CoV\u20102 infection"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5581-9887","authenticated-orcid":false,"given":"Zeno","family":"Pasquini","sequence":"first","affiliation":[{"name":"Infectious Diseases Unit IRCCS Azienda Ospedaliero\u2010Universitaria di Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Toschi","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit IRCCS Azienda Ospedaliero\u2010Universitaria di Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Casadei","sequence":"additional","affiliation":[{"name":"Institute of Hematology \"L. e A. 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