Blood derivative therapy

There are three main components manufactured from whole blood: red blood cells (RBCs), plasma, and platelets. Plasma contains a multitude of different proteins, peptides, and biologic substances. Approximately 53 million liters of plasma was collected in the United States in 2019. Following collection, plasma is frozen and manufactured into plasma-derived medicinal products (PDMPs). During the manufacture process, several thousand plasma units are pooled for Cohn fractionation, which is based upon cold ethanol precipitation of proteins. The PDMPs are further prepared using ion exchange or affinity chromatography and additional steps to inactivate and remove infectious diseases such as viruses. Almost 20 different therapeutic plasma proteins are purified from plasma via these multi-step manufacturing processes. Interestingly, the demand for pharmaceutical plasma products, particularly intravenous immunoglobulin (IVIG) products, has been increasing. The manufacture and therapeutic role of blood derivatives particularly immunoglobulin therapy, Rh immunoglobulin (RhIG), COVID-19 convalescent plasma (CCP) and hyperimmune globulins, albumin, clotting factors, fibrin sealants, and platelet rich plasma will be described.Copyright © 2022 AME Publishing Company. All Rights Reserved.

SARS-CoV-2 infection in patients with multiple myeloma: survey in 23 centers across Europe and USA

Introduction: Despite several studies, the impact of coronavirus disease 2019 on patients with multiple myeloma remains uncertain. Material(s) and Method(s): We performed a survey that covered the period of the first and second waves of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in 23 centers inseven countries. Out of 352 patients with myeloma and SARS-CoV-2, 23% died. Results/Conclusions: Logistic regression showed a lower risk of death among patients treated with proteasome inhibitor and a higher risk of death for those who had a severe or a very severe course of disease.Copyright © 2023 Sciendo. All rights reserved.

A Descriptive, Retrospective Analysis of Covid-19 Antibody Therapy and Its Effects on Morbidity and Mortality in Patients Receiving B-Lymphocyte Depleting Therapies

Intro: Patients receiving B-cell depleting or inhibiting therapies (BCDT), such as anti-CD20 monoclonal antibodies (CD20-MAB), are at risk for severe COVID-19. BCDT decreases production of neutralizing antibodies, causing delayed viral clearance and prolonged viral shedding. Passive antibody therapy (PAT), including COVID-19 convalescent plasma (CCP) and monoclonal antibodies (MAB), is hypothesized to be an effective Findings: * At the time of treatment, all patients (19/19) receiving CCP were hospitalized compared with10/53 patients treated with MAB. 2/10(20%) hospitalized patients treated with MAB died, compared with 3/19(15%) treated with CCP. **5/43 patients treated outpatient with MAB were hospitalized for COVID following CCP/MAB treatment with no COVID related deaths. Conclusion(s): Our data suggest that patients with COVID-19 who received BCDT within the last year may have improved outcomes after treatment with MAB or CCP. Elderly patients with >3 comorbidities and underlying hematological malignancy who contracted COVID-19 within 30 days of last BCDT had increased morbidity and mortality. To improve clinical outcomes, passive antibody therapy should be administered prior to the development of severe disease requiring hospitalization. Further prospective studies and comparisons to COVID-19 patients that did not receive MAB or CCP are needed to help confirm this association.Copyright © 2023

Hospital Protection Correlates in Outpatient Covid-19 Convalescent Plasma Recipients

Background: High titer COVID-19 convalescent plasma (CCP) reduces hospitalizations among immunocompetent outpatients. This study evaluated recipient post-transfusion S receptor binding domain (S-RBD) IgG antibody levels and the association of progressing to hospitalization among unvaccinated outpatients with COVID-19 treated with CCP or control plasma. Method(s): This analysis focused on participants from a multicenter doubleblind, randomized, controlled trial comparing treatment of outpatients with COVID-19 convalescent plasma (CCP) or control plasma without SARS-CoV-2 antibodies. Participants with confirmed SARS-CoV-2 infection were transfused within 9-days of symptom onset between June 2020 and October 2021 (n=110 vaccinated control;n=105 vaccinated CCP;n=464 unvaccinated control;n=472 unvaccinated CCP;total n=574 control and n=577 CCP recipients). All subjects had specimens collected the day prior to transfusion (D-1), within 30 minutes after transfusion (D0), 14 (D14), 28 (D28), and 90 (D90) days post-transfusion. Ancestral SARS-CoV-2 S-RBD was measured by an in-house validated ELISA. All 54 COVID-19-related hospitalizations occurred within 2 weeks of transfusion. Result(s): Post-transfusion anti-S-RBD IgG levels on D0 were significantly greater for CCP (median=4 titer,log3) compared to control (median=2 titer,log3;p< 0.001) recipients. Neither sex nor age impacted antibody levels following CCP treatment at D14, D28, and D90. Vaccinated recipients had greater titers than unvaccinated recipients prior to transfusion with little change in titers post-transfusion. Unvaccinated recipients had low antibody titers on D-1 with CCP recipients exhibiting a significant increase in titer from D-1 to D0 compared to controls (mean fold change=1.89;p< 0.001). Among unvaccinated recipients, those who received CCP transfusion late ( >5 days after symptom onset) and had low D0 antibody levels (< 4.24 titer, log3) had the greatest proportion of hospitalizations (5.5%). In contrast, those who received CCP transfusion early (< 5 days after symptom onset) with high D0 antibody levels ( >4.24 titer, log3) had no hospitalizations. Unvaccinated CCP recipient anti-S-RBD IgG antibody levels on D0 correlated with donor anti-S-RBD IgG antibody levels (r=0.30, p< 0.001). Conclusion(s): Among unvaccinated outpatients with COVID-19, CCP recipient antibody dilutional titers after transfusion over 540 titer correlated with protection against hospitalization when transfusion occurred within 5 days of symptom onset. (Figure Presented).

Convalescent plasma therapy for managing infectious diseases: A narrative review

The coronavirus disease 2019 (COVID-19) pandemic in 2020 is one of the worst catastrophic events in human history. A number of therapeutic modalities have been utilized in order to fight the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), although the majority of them failed to demonstrate a beneficial clinical effect. Among the anti-COVID-19 agents being investigated, the convalescent plasma collected from recovered donors has gained a growing interest. Convalescent plasma has been employed for over a hundred years to treat severe acute viral infections when a vaccine or a specific antiviral treatment was not yet available. In this narrative review, we summarize the literature data on the use of convalescent plasma during previous viral outbreaks and pandemics, including influenza viruses, coronaviruses other than SARS-CoV-2 and Ebola virus. A literature search, using the Medline and PubMed electronic database, was performed to retrieve publications on the use of convalescent plasma in previous viral epidemics. In conclusion, the available literature data suggest the safety profile of convalescent plasma and its potential benefit in treating emerging viral infectious diseases. In addition, these data retrieved from previous viral epidemics provide a solid rationale for the employment of plasma from convalescent donors also in COVID-19 patients.Copyright © 2021 AME Publishing Company. All rights reserved.

Cirrhosis and COVID-19: Diffuse venous thrombosis and its clinical implication

A 60-year-old woman with Hepatitis C infection, cirrhosis, recurrent hepatic hydrothorax, and hepatocellular carcinoma was hospitalized with Coronavirus disease-2019 (COVID-19). After her initial discharge, she was re-admitted three weeks later with decompensated liver disease. Imaging revealed extensive thrombosis in the portal vein, superior mesenteric vein, splenic vein and bilateral brachial veins. Given the acute onset and extent of the thrombosis, the patient received therapeutic anticoagulation despite elevated prothrombin time/ international normalized ratio, thrombocytopenia and low fibrinogen. Cirrhotic patients with COVID-19 maybe at high risk of thrombosis, which can present with significant hepatic decompensation.Copyright © 2022 The Author(s)

COVID-19 convalescent plasma: Mechanisms of action and rationale for use: A narrative review

The use of convalescent plasma (CP) transfusions for patients with coronavirus disease 2019 (COVID-19) has gained great interest during the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic. This review aims at summarizing the literature on the potential mechanisms of action of COVID-19 CP (CCP) and the rationale for use. A narrative review of the literature was conducted using PubMed, Google Scholar, and the Cochrane Database through October 2020. The rationale of CCP deployment was based on historical use in other outbreaks and pandemics and the emergent need at the time of lack of proven therapies and vaccines. There are many proposed mechanisms of action including direct neutralization and suppression of viremia, antibody-dependent cellular cytotoxicity, modification of the inflammatory response, restoration of the coagulation factors, immunomodulation of the hypercoagulable state and the potential role of ABO naturally occurring iso-agglutinins. Many donor, product, and patient factors can impact the response to CCP, such as antibody titer in the CCP product, CCP dose, frequency of administration, the severity of underlying illness, and the timing of administration from time of disease onset. Based on current evidence, CCP appears to be safe. However, it remains unknown whether it impacts the improvement of clinical symptoms, time to death, and all-cause mortality. In conclusion, the use of CCP offers quick access as an empirical therapy when specific therapies are not available or under development. Ongoing clinical trials are expected to add to the breadth of knowledge on the safety and efficacy of CCP use in patients with COVID-19.Copyright © 2021 AME Publishing Company.

COVID-19 in a patient with Good's syndrome and in 13 patients with common variable immunodeficiency

Antibody deficiencies constitute the majority of primary immunodeficiencies in adults. These patients have a well-established increased risk of bacterial infections but there is a lack of knowledge regarding the relative risks upon contracting COVID-19. In this monocentric study the disease course of COVID-19 in 1 patient with Good's syndrome and in 13 patients with common variable immunodeficiency (CVID) is described. The severity of disease ranged from very mild to severe. Several patients required hospitalization and immunomodulatory treatment but all survived. Although viral infections are not a typical feature of humoral immunodeficiencies we recommend that vigilance is increased in the management of patients with Good's syndrome and CVID during the COVID-19 pandemic.Copyright © 2021

Immunoserologic and hemotherapy considerations in patients undergoing hematopoietic progenitor cell transplantation

With increasing evidence of the success of hematopoietic progenitor cell (HPC) transplantation in the cure of many benign and malignant diseases, such interventions have been performed at increasing rates for the past several years. Due to myelosuppression caused by the conditioning and graft-versus-host disease (GVHD) prophylaxis regimens, blood component transfusions are almost inevitably needed. During transplantation, patient's hematopoietic lineages reconstitute to the HPC donor's progenitor cell types. Therefore, specific immunoserologic and hemotherapeutic aspects need to be considered for the selection of blood components during different phases of transplantation for successful outcomes. Those considerations include but are not limited to ABO and human leucocyte antigen (HLA) compatibility of the transfused blood components with either or both the patient and the HPC donor according to the particular phase of transplantation, and the special blood component processing to reduce the risk of transfusion associated graft-versus-host disease (TA-GVHD), cytomegalovirus (CMV) transmission in CMV seronegative patients and immune mediated platelets refractoriness. Complications may still arise, particularly in major, minor, or bidirectional ABO mismatched transplantations and/or due to the HLA mismatch and alloimmunization. Here we discuss the indications, immunoserologic considerations and the special component processing of red blood cells (RBCs), platelets, granulocytes, and plasma transfusions, based upon the current evidence and describe the prevention and management of salient, pertinent complications.Copyright © 2022 The authors.

Research progress on clinical application of convalescent plasma from COVID-19 patients.

COVID-19 is an acute respiratory infectious disease caused by 2019-nCoV, which has become a major global public health event and a serious threat to human health. So far, specific antiviral drugs, safe and effective vaccines for 2019-nCoV are still under development, so there is an urgent need to find alternative strategies for the treatment of COVID-19. Convalescent plasma(CP) contains high titer neutralizing antibodies from patients recovering from infectious diseases, which has been used in the treatment of major infectious diseases such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and achieved satisfactory clinical results. Therefore, CP from COVID-19 patient is a meaningful choice for the treatment of severe or life-threatening COVID-19 patients, but its potential risks need to be studied. This review focuses on the clinical mechanism, collection points, clinical application and potential benefits and risks of clinical treatment of CP from COVID-19 patients, which will provide reference for the clinical application of CP from COVID-19 patients.Copyright © 2021 Chinese Medical Association

Clinical efficacy and safety of convalescent plasma therapy for patients with SARS-CoV-2 infection.

Aim: to evaluate the efficacy and safety of convalescent plasma therapy for patients with severe SARS-CoV-2 infection. Material(s) and Method(s): the study included 64 patients with laboratory-confirmed severe new coronavirus infection. The control group consisted of 58 patients who, in addition to standard therapy, received a transfusion of plasma from donors who had recovered from COVID-19. The effectiveness of immune plasma was assessed by the duration of fever, the level of oxygen (SpO2%) in dynamics, the detection of SARSCoV-2 RNA in nasopharyngeal and oropharyngeal swabs using PCR method in dynamics, as well as by the dynamics of blood tests results. Adverse events (any medically adverse events that occurred after immune plasma transfusion) were recorded as safety criteria. Result(s): patients who received convalescent plasma, showed a significantly shorter period of SARS-CoV-2 replication compared with the control group. The use of immune plasma did not have a statistically significant effect on the duration of the fever, as well as the dynamics of blood oxygenation. Also, there were no significant differences compared with the control group when assessing blood tests parameters. Conclusion(s): The use of COVID-19 convalescent plasma to treat severe COVID-19 did not show significant clinical effect but reduced the period of viral replication. It also showed no unexpected or serious adverse events.Copyright © 2022 Interregional public organization Association of infectious disease specialists of Saint-Petersburg and Leningrad region (IPO AIDSSPbR). All rights reserved.

Outcome of COVID-19 in children: results of a 12-month follow-up.

At present, there are isolated data on the clinical outcomes of COVID-19 in children, especially those who have experienced asymptomatic and mild forms of infection. Purpose(s): to analyze the nature and frequency of post-COVID symptoms in children during 12 months. after recovery. Materials and methods. The influence of demographic indicators, premorbid background, severity of infection and therapy in the acute period of the disease on the nature and frequency of symptoms in 1079 children who underwent laboratory-confirmed COVID-19 was studied. The results are presented with proportions (%) and calculation of 95% confidence interval according to Klopper-Pearson. Differences between groups were assessed using Pearson's chi-square test. Differences in the groups were considered statistically significant at p < 0,05. Results. Health disorders in the post-COVID period were observed in 8,5% of children, more often in schoolchildren aged 7-17 years (68.4%). Concomitant conditions were found in 38,0%. In most cases, the consequences were noted after a mild form of COVID-19 (77.2%), however, 13,0% of patients experienced an asymptomatic form of infection. Among convalescents, changes in the emotional sphere (2,1%), headache (1,8%), symptoms of asthenia (1,6%), cardiovascular (1,5%), dyspeptic (1,3%) were more often observed, cognitive (1,3%) disorders, neurotic disorders (1,0%), less often respiratory (0.8%), endocrine (0,4%) and visual (0,4%) systems, musculoskeletal system were involved (0.2%). Girls were significantly more likely to have vegetative disorders, while boys were significantly more likely to suffer from cognitive functions. Various antiviral therapy options (interferon-alpha, an oral antiviral drug, or a combination thereof) in the acute period of COVID-19 did not affect the possibility of post-COVID disorders, but there was a tendency to increase the frequency in children who did not receive etiotropic treatment (control group). In 14.1% of cases, post-COVID symptoms appeared late - after 5-10 months. after recovery. The course of rehabilitation therapy, including drug treatment and non-drug methods, made it possible to quickly restore the state of health of the observed children. Conclusion. In most cases, the violations were of a functional nature, due to a disorder of autonomic regulation. Rehabilitation and dispensary observation programs will allow timely restoration of the quality of life of children who have had COVID-19, including in a mild and asymptomatic form.Copyright © 2022 Authors. All rights reserved.

Early Short-Term Use of Different Doses of Corticosteroid in Hospitalized Pediatric Patients with Coronavirus Disease 2019 Pneumonia

Objective Encouraged by reports of favorable outcomes following the use of corticosteroids in patients with moderate-to-severe coronavirus 2019 (COVID-19) pneumonia, we aimed to present our experience with early short-term corticosteroid use at our center in pediatric patients with COVID-19 pneumonia. Methods One hundred and twenty-nine pediatric patients were included in the study. Patients were divided into four groups according to the type and dose of corticosteroids given: Group 1 (those receiving dexamethasone 0.15 mg/kg/d);Group 2 (those receiving methylprednisolone 1 mg/kg/d);Group 3 (those receiving methylprednisolone 2 mg/kg/d);and Group 4 (those receiving pulse methylprednisolone 10-30 mg/kg/d). Results Of 129 patients, 19 (14.7%) patients were assigned to Group 1, 30 (23.3%) patients to Group 2, 30 (23.3%) patients to Group 3, and 50 (38.8%) patients to Group 4. Thirty-two (24.8%) patients were followed in the pediatric intensive care unit (PICU), of whom 13 (10%) required mechanical ventilation, and 7 (%5.4) died. In Group 4, the hospitalization length was significantly longer than in other groups (p < 0.001, p < 0.001). No significant difference was found among the groups in terms of mortality (p = 0.15). The most common comorbidity was obesity (33%). A significant association was found between the presence of comorbidity and mortality (p < 0.001). All patients who died had an underlying disease. Cerebral palsy was the most common underlying disease among the patients who died. Worsening of lymphopenia was significant in patients with severe COVID-19 pneumonia at the time of transfer to the PICU (p = 0.011). Conclusion Although children usually have a milder course of COVID-19 than adults, underlying diseases and obesity increase the severity of disease manifestations also in children. Further studies are needed to define the exact role of corticosteroids in COVID-19 patients. © 2022. Thieme. All rights reserved.

Convalescent Plasma Therapy in the Management of a Pediatric Patient with COVID-19 Infection

Introduction: In 2020, coronavirus rapidly became a global pandemic leading to high mortality rates. Extensive studies done have yet to provide consistent and successful treatment options to improve disease progression and mortality. Convalescent plasma is being studied in adults with very minimal studies in the pediatric population. Here we report a case of a 16 year old with COVID-19 infection resulting in ARDS who showed drastic improvement after convalescent plasma therapy. Case Description: A 16 year old female with morbid obesity, presented to our pediatric emergency department (ED) for a 5 day history of fever, cough, congestion and respiratory distress, along with vomiting, diarrhea and diffuse abdominal pain. Patient arrived on 3 LPM (or litres/min) of oxygen, vitals stable and in no acute respiratory distress, with bilateral coarse breath sounds and diffuse abdominal pain. She tested positive on PCR test for SARSCoV-2 done via nasopharyngeal swab, otherwise unremarkable blood count and comprehensive metabolic panel. Imaging showed chest x-ray with multifocal pneumonia and an electrocardiogram was normal. She was admitted and treated Remdesivir and IV immunoglobulin (IVIG) due to the concern for multi system inflammatory syndrome in children (MIS-C). She was started on a 5 day course of low dose steroids. However, by the third day of hospitalisation, patient's respiratory status rapidly declined, eventually requiring intubation and mechanical ventilation. She was placed on Synchronised Intermittent Mandatory Ventilation (SIMV) mode, volume control with autoflow, tidal volume 550ml, requiring up to FiO2 of 80-90% and peak inspiratory pressure was ranging from 36-45. Following Mayo clinic protocol and attaining emergent FDA approval, she received Covid-19 convalescent plasma, following which she showed significant improvement in peak inspiratory pressure (ranging 20-30), within 24-36 hours of plasma therapy. Through the course of the next few days, the patient tolerated successful weaning of respiratory support and was extubated and gradually weaned to room air. She showed tremendous recovery and was discharged home. Discussion: COVID-19 infection continues to show high mortality rates. Studies show that obesity is a risk factor for severe illness as seen in case. The use of convalescent plasma along with significantly improved this patient's clinical status which is also seen on imaging. Convalescent plasma has previously been used successfully for the treatment of other viral infections including SARS-CoV, Middle East respiratory syndrome, influenza A (H1N1), and Ebola. Data from these infections also suggest that convalescent plasma is most effective when given early in the disease process. Conclusion: COVID-19 is a serious infection leading to multifocal pneumonia, ARDS and death, even in children. This case report shows the beneficial use of convalescent plasma therapy in a pediatric patient. There continues to be a need for further studies on pediatric patients on management, of which convalescent plasma is a considerable option.

FLASH in the Clinic Track (Oral Presentations) RAPID CONVALESCENT PLASMA STERILIZATION USING HIGH DOSE RATE ELECTRON RADIATION

Background and Aims: Passive antibody administration through convalescent plasma has shown benefit in treating COVID-19 in the early stages of the disease in patients >65 years old, and in other viral outbreaks. A practical, rapid method to sterilize convalescent plasma while also maintaining antibody function would be valuable for safe treatment in future viral pandemics. Plasma sterilization by irradiation requires kGy of dose to deactivate bacteria and viruses of concern. Conventional lab-based irradiators would require days to reach such doses, while ultra-high dose rate irradiation (FLASH) would require minutes. We present a proof-of-concept on sterilizing plasma with 25 kGy in approximately 3 minutes without damaging the antibodies in the plasma. Methods: A Varian Trilogy LINAC was configured for 16 MeV FLASH electron irradiation. Frozen aliquots of convalescent plasma from patients with COVID-19 were placed in a 3D printed holder submerged in liquid aiming to preserve sample temperature (RT, 4°C or –20°C). The number of pulses was estimated with EBT-XD film. Samples were irradiated with a dose of 25 kGy in ~33,330 pulses over 185 seconds. Antibody binding against the receptor-binding domain (RBD) of the S1 region of SARS-CoV-2 was measured by ELISA pre- and post-irradiation. Results: Frozen plasma aliquots from 10 COVID-19 convalescent plasma donors were irradiated in frozen state to 25 kGy dose. IgG antibody binding against SARS-CoV-2 RBD after irradiation remained at 90.8% of non-irradiated samples (Fig. 1;OD 1.25 vs. 1.36, p<0.0003). (Figure Presented) Fig. 1 ( O034). Plasma aliquots from 10 convalescent plasma samples were irradiated at sterilizing 25-kGy doses. IgG binding to SARS-CoV-2 RBD antigen by ELISA is 90.8% compared to unirradiated. Conclusions: FLASH irradiation allows for rapid sterilization of blood plasma from potential pathogens while largely preserving antibody binding function and specificity.

Novel protocol for selection of SARS-CoV-2 convalescent plasma donors

Background/Aim. Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) 2019 infection represents a global problem. At this moment, in October 2020, there is no vaccine or efficient treatment for infected patients. Treatment with blood plasma rich with anti-SARS-CoV-2 specific antibodies might be a safe, and effective therapy for COVID-19 patients. Methods. A total of 768 patients were analyzed in this study, whose samples were collected in a time interval from May 1, 2020, till August 15, 2020. Patients were enrolled in the study from COVID-19 hospitals and out-clinics. In-house ELISA tests were developed to measure the concentration of anti-S1S2 spike and anti-nucleoprotein (np) (IgG, IgA, IgM) SARS-CoV-2 antibodies. Blood convalescent plasma was selectively collected from recovered patients according to specific antibodies concentration. Results. The highest concentrations of anti-S1S2 spike or anti-np specific IgG antibodies were detected in patients with the moderate/heavy clinical form of the infection. An extremely high concentration of anti-S1S2 spike IgG and anti-np IgG was demonstrated in 3% and 6% of patients who recovered from severe COVID-19, respectively. Of tested hospitalized patients, 63% and 51% had modest levels of anti-S1S2 spike and anti-np, respectively. After 60 days, in our selected donors, concentrations of antiS1S2 spike IgG and anti-np IgG antibodies increased in 67% and 58% of donors, respectively. Conclusion. In-house developed ELISA tests enable a novel protocol for selecting convalescent blood plasma donors recovered from SARS-CoV-2 infection.

The impact of different pathogen reduction technologies on total IgG and subclass profiles of COVID-19 convalescent plasma

Background: COVID-19 convalescent plasma (CCP) was shown to reduce disease progression if high-titre CCP is administered in early infection. CCP donors have a risk profile like first time donors, especially with respect to window-period viral transmissions. Pathogen reduction (PR) could mitigate that risk, but may have impact on quality and quantity of plasma proteins, including neutralizing antibodies. It has been shown that different IgG subclasses contribute differently to CCP neutralizing activity, raising the question of a potential impact of PR on different IgG subclasses. Aims: Side-by-side comparison of the impact of 3 commercially available PR technologies on total IgG and subclasses quantity and subclass distribution in CCP. Methods: 36 apheresis CCP donations collected with a MCS+ 9000 plasmapheresis device (Haemonetics S.A., Switzerland), or DigiPla 80 (Sichuan Nigale Biomed, China) plasmapheresis device (650-750 ml) were allocated to 3 study groups with 12 units respectively. The impact of amotosalen/UVA (AS)-treatment (INTERCEPT Blood System, Cerus) against Riboflavin UVB (RB) (Mirasol Pathogen Reduction System, Terumo BCT), AS against Methylene Blue (MB) (Theraflex MB, Macopharma) and RB against MB on the quantity and distribution of IgG and subclasses was assessed in a side-by-side comparison study with a nephelometric analyser (BN II System, Siemens Healthcare). PRtreatment was conducted immediately post collection. All samples for analysis were frozen within 6 h post collection and stored at -75°C until testing. All samples were analysed simultaneously with the same device, the same lot of reagents and the same operator. Results: IgG subclass distributions were not significantly changed post PR-treatment with all 3 technologies (p > 0.05). There was also no significant difference in the median loss of concentration for IgG1 and IgG2 between the three technologies (p > 0.05). The median loss (%) of IgG3 (2.1 and 2.6-fold compared to AS and MBtreatment respectively, p < 0.01) and IgG4 (1.6 and 5.9-fold compared to AS and MB-treatment respectively, p < 0.01) post RBtreatment was significantly higher. The median loss (%) of IgG4 post AS-treatment was significantly higher compared to MB-treatment (3.5-fold, p < 0.01). Summary/Conclusions: The 3 commercially available PR systems do not significantly change the IgG subclass distribution, but impact differently IgG3 and IgG4 post-treatment loss. It was reported that IgG1 and IgG3 play an important role in neutralization, which should be considered when planning PR-treatment for CCP. .