AUTHOR=D’Abramo Alessandra , Vita Serena , Beccacece Alessia , Navarra Assunta , Pisapia Raffaella , Fusco Francesco Maria , Matusali Giulia , Girardi Enrico , Maggi Fabrizio , Goletti Delia , Nicastri Emanuele , ImmunoCOVID team , Bartoli Tommaso Ascoli , Bevilacqua Nazario , Corpolongo Angela , De Marco Patrizia , Giancola Maria Letizia , Maffongelli Gaetano , Mariano Andrea , Scorzolini Laura , Palazzolo Claudia , Rosati Silvia , Tomassi Virginia , Faraglia Francesca , Fabeni Lavinia , Rueca Martina , Meschi Silvia , Maria Gruber Cesare Ernesto TITLE=B-cell-depleted patients with persistent SARS-CoV-2 infection: combination therapy or monotherapy? A real-world experience JOURNAL=Frontiers in Medicine VOLUME=Volume 11 - 2024 YEAR=2024 URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2024.1344267 DOI=10.3389/fmed.2024.1344267 ISSN=2296-858X ABSTRACT=Abstract Objectives The aim of the study was to describe a cohort of B cell-depleted immunocompromised (IC) patients with prolonged or relapsing COVID-19 treated with mono- or combined-therapy. Methods This is a multicentre observational retrospective study conducted on IC patients consecutively hospitalized with prolonged or relapsing SARS-CoV-2 infection from November 2020 to January 2023. IC COVID-19 subjects were stratified according to the mono or combination anti-SARS-CoV-2 therapy received. Results Eighty-eight patients were enrolled, 19 under monotherapy and 69 under combined therapy. All study population had a history of immunosuppression (median of 2 B cells/mm3, IQR 1-24 cells) and residual hypogammaglobulinemia was observed in 55 patients. A reduced length of hospitalization and time to negative SARS-CoV-2 molecular nasopharyngeal swab in combined versus monotherapy group was observed. On univariable and multivariable analysis, the percentage change in the rate of days to nasopharyngeal swab negativity showed a significant reduction in patients receiving combination therapy compared to those receiving monotherapy Conclusions In IC persistent COVID-19 patients it is essential to explore new therapeutic strategies such as combined multi-targets therapy (antiviral or double antiviral plus antibody-based therapies) to avoid persistent viral shedding and/or severe SARS-CoV-2 infection.