Case Report: Stepwise Anti-Inflammatory and Anti-SARS-CoV-2 Effects Following Convalescent Plasma Therapy With Full Clinical Recovery
Authors: Aurelia Zimmerli, Matteo Monti, Craig Fenwick, Isabella Eckerle, Catherine Beigelman-Aubry, Céline Pellaton, Katia Jaton, Dominique Dumas, Gian-Marco Stamm, Laura Infanti, Heidrun Andreu-Ullrich, Daphné Germann, Marie Mean, Peter Vollenweider, Raphael Stadelmann, Maura Prella, Denis Comte, Benoit Guery, David Gachoud, Nathalie Rufer
Journal: Front Immunol (2021)
Keywords: b-cell depletion, chronic sars-cov-2 infection, convalescent plasma therapy, neutralizing antibodies, severe immunosuppression, viral clearance
MeSH terms: Antibodies, Neutralizing / blood, Antibodies, Viral / blood, COVID-19 / immunology, COVID-19 / therapy, COVID-19 Drug Treatment, Case Reports, Research Support, Non-U.S. Gov't, Aged, Antibodies, Neutralizing / administration & dosage, Antibodies, Viral / administration & dosage, Antineoplastic Agents, Alkylating / therapeutic use, Antineoplastic Agents, Immunological / therapeutic use, Bendamustine Hydrochloride / therapeutic use, COVID-19 Serotherapy, Diabetes Mellitus, Type 2 / complications, Humans, Immunization, Passive / methods, Immunoglobulin A / blood, Immunoglobulin G / blood, Immunoglobulin M / blood, Immunosuppression Therapy, Leukemia, Lymphoid / complications, Leukemia, Lymphoid / drug therapy, Male, Rituximab / therapeutic use, SARS-CoV-2 / drug effects, SARS-CoV-2 / immunology, Treatment Outcome, Antibodies, Neutralizing, Antibodies, Viral, Antineoplastic Agents, Alkylating, Antineoplastic Agents, Immunological, Immunoglobulin A, Immunoglobulin G, Immunoglobulin M, Rituximab, Bendamustine Hydrochloride

In these times of COVID-19 pandemic, concern has been raised about the potential effects of SARS-CoV-2 infection on immunocompromised patients, particularly on those receiving B-cell depleting agents and having therefore a severely depressed humoral response. Convalescent plasma can be a therapeutic option for these patients. Understanding the underlying mechanisms of convalescent plasma is crucial to optimize such therapeutic approach. Here, we describe a COVID-19 patient who was deeply immunosuppressed following rituximab (anti-CD20 monoclonal antibody) and concomitant chemotherapy for chronic lymphoid leukemia. His long-term severe T and B cell lymphopenia allowed to evaluate the treatment effects of convalescent plasma. Therapeutic outcome was monitored at the clinical, biological and radiological level. Moreover, anti-SARS-CoV-2 antibody titers (IgM, IgG and IgA) and neutralizing activity were assessed over time before and after plasma transfusions, alongside to SARS-CoV-2 RNA quantification and virus isolation from the upper respiratory tract. Already after the first cycle of plasma transfusion, the patient experienced rapid improvement of pneumonia, inflammation and blood cell counts, which may be related to the immunomodulatory properties of plasma. Subsequently, the cumulative increase in anti-SARS-CoV-2 neutralizing antibodies due to the three additional plasma transfusions was associated with progressive and finally complete viral clearance, resulting in full clinical recovery. In this case-report, administration of convalescent plasma revealed a stepwise effect with an initial and rapid anti-inflammatory activity followed by the progressive SARS-CoV-2 clearance. These data have potential implications for a more extended use of convalescent plasma and future monoclonal antibodies in the treatment of immunosuppressed COVID-19 patients.