AUTHOR=D’Abramo Alessandra , Vita Serena , Maffongelli Gaetano , Beccacece Alessia , Agrati Chiara , Cimini Eleonora , Colavita Francesca , Giancola Maria Letizia , Cavasio Alessandro , Nicastri Emanuele ,  Spallanzani COVID-19 Case Investigation Team , Corpolongo Angela , Scorzolini Laura , Bartoli Tommaso Ascoli , Palazzolo Claudia , Bevilacqua Nazario , Mariano Andrea , Braccialarghe Neva , Rosati Silvia , Albanese Mattia , Benvenuto Domenico , Matusali Giulia , Francalancia Massimo , Bettini Aurora , Castilletti Concetta , Notari Stefania , Garbuglia Anna Rosa , Meschi Silvia 

TITLE=Clinical Management of Patients With B-Cell Depletion Agents to Treat or Prevent Prolonged and Severe SARS-COV-2 Infection: Defining a Treatment Pathway

JOURNAL=Frontiers in Immunology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.911339

DOI=10.3389/fimmu.2022.911339

ISSN=1664-3224

ABSTRACT=Introduction
Immunocompromised  patients with B-cells depletion agents are at risk for persistence and/or severe SARS-COV-2 infection. We describe a case series  of 21 COVID-19 patients under B cell depletion therapy, mostly treated with a combined therapy based on intravenous remdesevir (RDV) and steroid associated with SARS-CoV-2 monoclonal antibodies against Spike glycoprotein and/or hyper-immune convalescent plasma.
Methods
This is a single-centre longitudinal study. We retrospectively enrolled a total number of 21 B-cell depleted consecutive hospitalized patients with COVID-19 at the Lazzaro Spallanzani National Institute for Infectious Diseases, Rome, Italy, from November 2020 to December 2021. Demographic characteristics, medical history, clinical presentation, treatment, adverse drug reactions, clinical and virological outcome were collected for all patients. In a subgroup, we explore immune T cells activation, T cells specific anti-SARS-COV-2 response and neutralizing antibodies.
Results
Twenty-one inpatients with B-cell depletion and SARS-COV-2 infection were enrolled. A median of 1 B cells/mm3 was detected. Eighteen patients presented hypogammaglobulinemia. All patients presented interstitial pneumonia treated with intravenous RDV and steroids. Sixteen patients were treated with monoclonal antibodies against SARS-CoV-2 Spike protein, four patients were treated with SARS-CoV-2 hyper-immune convalescent plasma infusion, and three patients received both treatments. A variable kinetic of T cell activation returning to normal level at day 30 after immunotherapy infusion was observed. All treated patients recovered.
Conclusion
In COVID-19 immunosuppressed subjects, it is mandatory to establish a prompt, effective and combined multi-target therapy including oxygen, antiviral, steroid and antibody-based therapeutics, tailored to the patient's clinical needs.