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

Abstract

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.

Persistent viral shedding of severe acute respiratory syndrome coronavirus 2 after treatment with bendamustine and rituximab: A case report

“…The duration of viral shedding after the onset of COVID-19 is usually 20 days [ 3 ]. However, immunocompromised patients with hematologic malignancies, those undergoing chemotherapy, and especially those treated with BR, have reportedly shed the active virus for longer periods [ [5] , [6] , [7] , [8] ].…”

“…Ref, reference; M, male; F, female; FL, follicular lymphoma; MCL, myeloid cell leukemia; WM/LPL, Waldenström macroglobulinemia/LPL; CLL, chronic lymphocytic leukemia; NA, not available; C, ciclesonide; F, favipiravir; H, hyperimmune plasma infusion; D, dexamethasone; R, remdesivir. Case 1 Case 2 Case 3 Case 4 Case 5 Case 6 age/sex 47 M NA NA 62F 74 M 71 M underlying disease FL MCL WM/LPL FL CLL FL Status CR NA NA CR CR CR last BR therapy before COVID-19 4 months 17 days 8 days NA 5 months 9 months duration of PCR positive for SARS-CoV-2 59 days 42 days 56 days 66 days 111 days above 8 weeks treatment for COVID-19 C, F NA NA H, D, R H, D D, R Outcome cure death cure Cure cure cure References [ 5 ] [ 6 ] [ 6 ] [ 7 ] [ 8 ] This case …”

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

“…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.…”

Treatment of persistent COVID-19 in two B-cell-depleted patients with the monoclonal antibody Sotrovimab

“…In the largest case series to date, Hueso et al treated 17 patients with B-cell depletion and prolonged COVID-19 (median of 56 days since symptom onset) with convalescent plasma, resulting in improvement in symptoms and laboratory parameters in 16 out of 17 patients [12] . Similarly, Zimmerli et al and Jassem et al both successfully treated two patients with B-cell depletion due to hematologic malignancies with convalescent plasma [18] , [19] . More recently, several groups have reported successful treatment of such patients with mAbs [15] , [16] , [17] , [20] .…”