Stepwise anti-inflammatory and anti-SARS-CoV-2 effects following convalescent plasma therapy with full clinical recovery

Zimmerli, Aurelia; Monti, Matteo; Fenwick, Craig; Eckerle, Isabella; Pellaton, Céline; Jaton, Katia; Dumas, Dominique; Stamm, Gian-Marco; Infanti, Laura; Andreu-Ullrich, Heidrun; Germann, Daphné; Méan, Marie; Vollenweider, Péter; Stadelmann, Raphael; Prella, Maura; Comte, Denis; Guery, Benoît; Gachoud, David; Rufer, Nathalie

doi:10.21203/rs.3.rs-76799/v1

Cited by 2 publications

(2 citation statements)

References 23 publications

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“…Convalescent plasma was collected from 32 male donors (CP), who had fully recovered for at least 28 days after COVID-19 onset and presented an anti-S protein-specific IgG response, ranging from 29.4-135.6 ratio, with an average ratio of 79 using an in-house developed Luminex assay (42), correlating to neutralizing titers (43,44). Due to the difficulties to obtain high-titer plasma from convalescent donors, we collected from March, 1 st , 2021 onwards, plasma from 24 non-COVID-19 male donors (VP), who had received their second dose of an mRNA-based vaccine (Moderna or Pfizer) and exhibited an anti-S protein IgG response ranging from 73.3-143.7.6 ratio, with an average ratio of 118 by Luminex.…”

Section: Plasma Collection and Preparationmentioning

confidence: 99%

Antibody response and intra-host viral evolution after plasma therapy in COVID-19 patients pre-exposed or not to B-cell depleting agents

Gachoud

Pillonel

Tsilimidos

et al. 2022

Preprint

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BackgroundAdministration of plasma therapy may contribute to viral control and survival of COVID-19 patients receiving B-cell depleting agents that hinder the endogenous humoral response. However, little is known on the impact of anti-CD20 pre-exposition and the use of different sources of plasma (convalescent versus vaccinated) on the kinetics of SARS-CoV-2-specific antibodies and viral evolution after plasma therapy.MethodsEligible COVID-19 patients (n = 36), half of them after anti-CD20 targeted therapy, were treated with therapeutic plasma from convalescent (n = 17) or mRNA-vaccinated (n = 19) donors. Each plasma-transfused patient was thoroughly monitored over time by anti-S IgG quantification and whole-genome SARS-CoV-2 sequencing.ResultsThe majority of anti-CD20 pre-exposed patients (15/18) showed progressive declines of anti-S protein IgG titers following plasma therapy, indicating that they mostly relied on the passive transfer of anti-SARS-CoV-2 antibodies. Such antibody kinetics correlated with prolonged infection before virus clearance, contrasting with the endogenous humoral response predominantly present in patients who had not received B-cell depleting agents (15/18). No relevant differences were observed between patients treated with plasma from convalescent and/or vaccinated donors. Finally, 4/30 genotyped patients showed increased intra-host viral evolution and 3/30 included 1 to 4 spike mutations, potentially associated to immune escape.ConclusionsConvalescent and/or vaccinated plasma therapy may provide anti-SARS-CoV-2 antibodies and clinical benefit to B-cell depleted COVID-19 patients. Only a limited number of patients acquired viral mutations prior to clinical recovery, yet our study further emphasizes the need for long-term surveillance for intra-host variant evolution, to guide best therapeutic strategies.

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Section: Plasma Collection and Preparationmentioning

confidence: 99%

Antibody response and intra-host viral evolution after plasma therapy in COVID-19 patients pre-exposed or not to B-cell depleting agents

Gachoud

Pillonel

Tsilimidos

et al. 2022

Preprint

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“…This manuscript has been released as a pre-print at Research Square, (Zimmerli et al 29 ). We are grateful to patient A.P.…”

Section: Acknowledgmentsmentioning

confidence: 99%

Case Report: Stepwise Anti-Inflammatory and Anti-SARS-CoV-2 Effects Following Convalescent Plasma Therapy With Full Clinical Recovery

et al. 2021

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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.

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Stepwise anti-inflammatory and anti-SARS-CoV-2 effects following convalescent plasma therapy with full clinical recovery

Cited by 2 publications

References 23 publications

Antibody response and intra-host viral evolution after plasma therapy in COVID-19 patients pre-exposed or not to B-cell depleting agents

Antibody response and intra-host viral evolution after plasma therapy in COVID-19 patients pre-exposed or not to B-cell depleting agents

Case Report: Stepwise Anti-Inflammatory and Anti-SARS-CoV-2 Effects Following Convalescent Plasma Therapy With Full Clinical Recovery

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