Case Report: Effects of Anti-SARS-CoV-2 Convalescent Antibodies Obtained With Double Filtration Plasmapheresis

Passive antibody therapy has been used to treat outbreaks of viral disease, including the ongoing pandemic of severe respiratory acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) or COVID-19. However, the real benefits of the procedure are unclear. We infused a concentrated solution of neutralizing anti-SARS-CoV-2 antibodies obtained from a convalescent donor with a single session of double filtration plasmapheresis (DFPP) into a 56-year-old woman with long history of unremitting, severe COVID-19. She was unable to establish an adequate antiviral immune response because of previous chemotherapy, including the infusion of the anti-CD20 monoclonal antibody rituximab, administered to treat a diffuse large B-cell lymphoma. The disease promptly recovered despite evidence of no endogenous anti-SARS-CoV-2 antibody production. The observation that passive antibody therapy might prove particularly effective in immunodepressed COVID-19 patients requires evaluation in prospective randomized controlled trial.

MO661COMPARISON OF CLINICAL EFFICACY OF CENTRIFUGAL-MEMBRANOUS DOUBLE FILTRATION PLASMAPHERESIS AND MEMBRANOUS DOUBLE FILTRATION PLASMAPHERESIS ON SEVERE LUPUS NEPHRITIS

Background and Aims The Study delves into the clinical efficacy and advantages of centrifugal double filtration plasmapheresis on severe lupus nephritis (LN) by comparing it with membranous double filtration plasmapheresis (DFPP). Method A retrospective analysis was performed on 56 patients who were diagnosed with severe LN and had received DFPP treatment from May 2016 and January 2020. Of them, 38 were given centrifugal DFPP and had their plasma centrifuged in a blood cell separator, and 18 were given membranous DFPP and had their plasma centrifuged in an MPS07 plasma separator. An EC20W plasma component separator was used as the secondary filter to reprocess the separated plasma of all of them. The two DFPPs were compared for differences in clinical efficacy, vascular access, dosage of anticoagulant, treatment cost and adverse events in patients with severe LN. Results Of the 56 severe LN patients (including 43 females and 13 males), the median of age of onset was 29 years old, the SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) was 18.6±6.0 points and the serum creatinine was 402(294,553) umol/L, and all patients had acute kidney injury and 51 of them (91.1%) required renal replacement therapy (RRT). A total of 142 DFPPs were performed, including 97 centrifugal DFPPs and 45 membranous DFPPs. After treatment and at Month 3 of follow-up visit, patients in both the centrifugal DFPP group and the membranous DFPP group had ANA, AdsDNA titer, quantitative urinary protein, urinary red blood cell count and serum creatinine significantly dropped and hemoglobin significantly increased over those before treatment, the differences in which between the two groups, however, were not statistically significant. The centrifugal DFPP group had a more significant drop in complements C3 and C4 after treatment. Comparison of the data before and after a single DFPP treatment showed that the membranous DFPP group had a more significantly longer prothrombin time, but there were no differences in partial prothrombin time, fibrinogen and platelet change between the two groups. At Month 3 of follow-up visit, 31 of the 51 RRT patients (60.8%) (including 34 given centrifugal DFPP and 17 given membranous DFPP) were released from dialysis, including 23 given centrifugal DFPP and 8 given membranous DFPP. In the membranous DFPP group, all patients had the vascular access built via the central venous catheter, while in the centrifugal DFPP group, 6 patients (15.8%) had the vascular access built by puncturing into the artery or vein. The dosage of the anticoagulant, the low molecular weight heparin, to the centrifugal DFPP group was significantly lower than that to the membranous DFPP group (1174±243 vs 4106±399IU, P<0.001), and in the centrifugal DFPP group, 29 patients (76.3%) were given 4% citric acid alone for anti-coagulation. No blood coagulation occurred. In terms of treatment consumables, the membranous DFPP group had a significantly higher cost than the centrifugal DFPP group (RMB4340.2±237.0 vs 5677.0±0.0, P<0.001). Two patients (4.4%) in the membranous DFPP group developed skin ectasis, epistaxis or aggravated alveolar hemorrhage after treatment, and four patients (4.1%) in the centrifugal DFPP group developed perioral numbness, numbness in distal extremities or tetany during treatment, which was alleviated after calcium supplementation. Conclusion Centrifugal DFPP differed little from membranous DFPP in clinical efficacy in severe LN patients, but had lower anti-coagulation requirements, cost less on treatment consumables, and caused no severe adverse events, so it can be used as an important means to treat severe LN.

Apheresis Efficacy and Tolerance in the Setting of HLA-Incompatible Kidney Transplantation

Nearly 18% of patients on a waiting list for kidney transplantation (KT) are highly sensitized, which make access to KT more difficult. We assessed the efficacy and tolerance of different techniques (plasma exchanges [PE], double-filtration plasmapheresis [DFPP], and immunoadsorption [IA]) to remove donor specific antibodies (DSA) in the setting of HLA-incompatible (HLAi) KT. All patients that underwent apheresis for HLAi KT within a single center were included. Intra-session and inter-session Mean Fluorescence Intensity (MFI) decrease in DSA, clinical and biological tolerances were assessed. A total of 881 sessions were performed for 45 patients: 107 DFPP, 54 PE, 720 IA. The procedures led to HLAi KT in 39 patients (87%) after 29 (15–51) days. A higher volume of treated plasma was associated with a greater decrease of inter-session class I and II DSA (p = 0.04, p = 0.02). IA, PE, and a lower maximal DSA MFI were associated with a greater decrease in intra-session class II DSA (p < 0.01). Safety was good: severe adverse events occurred in 17 sessions (1.9%), more frequently with DFPP (6.5%) p < 0.01. Hypotension occurred in 154 sessions (17.5%), more frequently with DFPP (p < 0.01). Apheresis is well tolerated (IA and PE > DFPP) and effective at removing HLA antibodies and allows HLAi KT for sensitized patients.

Successful treatment of positive-sense RNA virus coinfection with autoimmune hepatitis using double filtration plasmapheresis

Double filtration plasmapheresis (DFPP) is an apheretic technique that selectively removes high molecular weight substances using a plasma component filter. DFPP has been used to treat positive-sense RNA virus infections, mainly chronic hepatitis C virus (HCV) infection, because of its ability to directly eliminate viral particles from blood plasma from 2008 to about 2015, before direct-acting antiviral agents was marketed. This effect has been termed virus removal and eradication by DFPP. HCV is a positive-sense RNA virus similar to West Nile virus, dengue virus and the SARS and Middle East respiratory syndrome coronaviruses. SARS-CoV-2 is classified same viral species. These viruses are all classified in Family Flaviviridae which are family of single-stranded plus-stranded RNA viruses. Viral particles are 40–60 nm in diameter, enveloped and spherical in shape. We present a rare case of HCV removal where an RNA virus infection that copresented with virus-associated autoimmune hepatitis was eliminated using DFPP. Our results indicate that DFPP may facilitate prompt viraemia reduction and may have novel treatment applications for SARS-CoV-2, that is, use of therapeutic plasma exchange for fulminant COVID-19.