SARS-CoV-2 SEROPREVALENCE AMONG UGANDAN BLOOD DONORS: 2019-2022

Background: COVID-19 in Africa was less severe with fewer reported cases, hospitalizations and deaths compared to other continents. However, the lack of adequate surveillance systems in Africa makes estimating the burden of infection challenging. Serosurveillance can aid in determining the frequency of infection within this population. This study is aimed to estimate SARS-CoV-2 seroprevalence, describe the SARS-CoV-2 antibody (Ab) levels, and examine associations of seroreactivity among Ugandan blood donors. Method(s): Samples were obtained from the Mirasol Evaluation of Reduction in Infections Trial (MERIT), a randomized, double blind, controlled clinical trial evaluating transfusion transmitted infections. MERIT blood donor samples (n=3,517) were collected from Kampala, Uganda between October 2019 to April 2022. Additional blood donor samples (n=1,876) were collected from around the country between November-December 2021. Samples were tested for Ab to SARS-CoV-2 nucleocapsid (N) and spike (S) using an electrochemiluminescence immunoassay assay (Meso Scale Diagnostics, Gaithersburg, MD) per manufacturer's protocol. Samples seroreactive to both N and S Ab were considered Ab positive to SARS-CoV-2. Seroprevalence among MERIT donors were estimated within each quarter. Factors associated with seroreactivity from November-December 2021 were assessed by chi-square test. Result(s): SARS-CoV-2 seroprevalence increased from < 2.0% in October 2019- June 2020 to 82.5% in January-April 2022. Three distinct peaks in seroreactivity were seen in October-November 2020, July-August 2021, and January-April 2022 (see Figure). Among seroreactive donors, median N Ab levels increased 9-fold and median S Ab 19-fold over the study period. In November-December 2021, SARS-CoV-2 seroprevalence was higher among donors from Kampala (58.8%) compared to more rural regions of Hoima (47.7%), Jinja (47.9%), and Masaka (54.4%;p=0.007);S seroprevalence was lower among HIV+ donors (58.8% vs. 84.9%;p=0.009). Conclusion(s): Blood donors in Uganda showed high prevalence of Ab to SARSCoV- 2 by March of 2022, indicating that the infection levels were similar to many other regions of the globe. Higher seroprevalence was observed in the capital compared to more rural areas in Uganda. Further, increasingly high antibody levels among seropositive donors may indicate repeat infections. The lower COVID-19 morbidity and mortality was not due to a lack of exposure of the virus, but other factors yet to be determined.

Pathogen reduction of platelets: Experience of a single blood bank

Pathogen reduction technology (PRT) has the potential to prevent pathogen transfusion transmission from blood donor to patient by impeding the replication of bacteria, viruses and parasites in blood components. Additionally, PRT can help to guarantee blood safety in challenging situations for blood supply, as in the Ebola or Chikungunya epidemics, or in a scenario full of uncertainties such as the current SARS-CoV-2 pandemic. The Balearic Islands Blood Bank (BIBB) is one of the few blood establishments worldwide with more than 10 years of experience in the routine use of amotosalen/UVA (Intercept Blood System) and riboflavin/UVA-UVB (Mirasol PRT system) for platelets (PLTs), the use of riboflavin/UVA-UVB for plasma and with research experience in riboflavin/UVA-UVB applied to whole blood. Over the years, we have had the opportunity to evaluate PRT from different perspectives, such as clinical and hemovigilance research in adults and children, in vitro studies on PRT effects on PLTs and assessing the financial impact of PRT implementation. PRT methods offer remarkable benefits but also have certain limitations, which are important to bear in mind during the decision-making process for PRT implementation. The purpose of this study is to review the current knowledge on PRT for PLTs drawing on our experience acquired over the last decade.Copyright © 2021 AME Publishing Company.

Assessment of the impact of pathogen reduction technologies on the neutralizing activity of COVID-19 convalescent plasma.

COVID-19 convalescent plasma (CCP) could improve the clinical outcome of COVID-19 patients when high-titer CCP is administered in early stages of disease. However, CCP donors have a risk profile like first-time donors, pathogen reduction treatment (PRT) may mitigate such risk but should not impact CCP quality. The current study aims to assess the impact of PRT-technologies available in Saudi Arabia on the neutralizing activity of CCP. STUDY DESIGN: and Methods: CCP was collected from eligible donors by plasmapheresis. The neutralization titer was determined with an in-house microneutralization assay (MNA) using a local SARS-CoV-2 clinical isolate. Selected units were split and subject to PRT with amotosalen/UVA (AS) or Riboflavin/UVB (RB) (pairwise side-by-side comparison) followed by a second MNA analysis. 51 CCP units were collected, 27 were included in the analysis reaching the minimum MNA titer of 1:40 (4 reached high titer (≥1:250)). 27 CCP units were treated with AS and 14 with RB, the median MNA pre-treatment titer was 1:80 (1:40-640). The impact of AS and RB PRT on CCP neutralizing activity was not significantly different, nor in the total analysis neither in the pairwise comparison (94.6 vs 96.4 % retention, p > 0.05). No correlation of titer and blood group was observed, but a trend for increasing MNA titer with donor age, choosing donors with an age > 45 years would increase the number of high-titer CCP donors. The difference in impact of AS and RB on CCP MNA titer was below the limit of detection of the assay (0.5-fold).

Quality assessment of routine produced mirasol pathogen reduction system treated platelet concentrates

Background: Prevention of transfusion-associated infections remains a challenge in transfusion medicine. The Mirasol Pathogen Reduction Technology (PRT) System uses riboflavin plus UV light to inactivate residual white blood cells and nucleic acid-containing pathogens to reduce the risk of transmission of bacteria, viruses, parasites, novel pathogens e.g SARS-CoV-2. This demonstrates the cumulative quality data of Mirasol-treated PC produced under routine conditions in our institute in the last year Methods: One hundred sixteen whole blood derived PCs, resulting from the pooling of 5 buffy coats with 250ml PAS-E solution were treated with the Mirasol technology. PCs were mixed with 35 ml Riboflavin solution and illuminated with UV-light in accordance to manufacturer's instructions. For quality control (QC) assessment the following parameters were investigated post-production (PP) and at the end of shelf-life (EOS) at days 5, 6 or 7: pH (ABL80 FLEX Blood Gas Analyzer, at 37degreeC), platelet yield (Cell- Dyn Ruby, Abbott) and CD62P-positive cells with and without TRAP-6 (100muM) using the FACS methodology with FITC-labelled CD62P antibody (Cytomics FC 500 Flow Cytometer, Beckman Coulter). Result(s): Mirasol-treated PCs showed a mean pH of 7.3 at PP and ranged 7.1 to 7.0 at EOS1. Platelet yield PP and EOS were consistent with 3.0 to 3.1 x1011 platelets (PLT)/unit. Platelet activation measured with CD62P+ expression w/o TRAP-6 was 27.7% at PP and ranged from 46.9 to 55.8 at EOS1;CD62P+ expression induced by TRAP-6 was 79.3 at PP and ranged from 72.3 to 68.1 at EOS1. Conclusion(s): The QC data on Mirasol-treated PCs produced during the past year showed encouraging results: all pH values remained far above 6.4, platelet yields remained stable suggesting min cell loss, with EOS yields always above the threshold of 2.5x1011 PLT/unit. Rates of CD62P+cells increased with time, an upregulation of CD62P+ with TRAP-6 was still detectable at EOS up to Day 7. The presented results confirm the data of the initial Mirasol validation at our site, showing the robustness of the technology. (Table Presented).

Validation of Viral Inactivation Protocols for Therapeutic Blood Products against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-COV-2).

Therapeutic blood products including convalescent plasma/serum and immunoglobulins concentrated from convalescent plasma, such as intravenous immunoglobulins or hyperimmune globulins, and monoclonal antibodies are passive immunotherapy options for novel coronavirus disease 2019 (COVID-19). They have been shown to improve the clinical status and biological and radiological parameters in some groups of COVID-19 patients. However, blood products are still potential sources of virus transmission in recipients. The use of pathogen reduction technology (PRT) should increase the safety of the products. The purpose of this study was to determine the impact of solvent/detergents (S/D) procedures on SARS-COV-2 infectivity elimination in the plasma of donors but also on COVID-19 convalescent serum (CCS) capacity to neutralize SARS-COV-2 infectivity. In this investigation, S/D treatment for all experiments was performed at a shortened process time (30 min). We first evaluated the impact of S/D treatments (1% TnBP/1% TritonX-45 and 1% TnBP/1% TritonX-100) on the inactivation of SARS-COV-2 pseudoparticles (SARS-COV-2pp)-spiked human plasma followed by S/D agent removal using a Sep-Pak Plus C18 cartridge. Both treatments were able to completely inactivate SARS-COV-2pp infectivity to an undetectable level. Moreover, the neutralizing activity of CCS against SARS-COV-2pp was preserved after S/D treatments. Our data suggested that viral inactivation methods using such S/D treatments could be useful in the implementation of viral inactivation/elimination processes of therapeutic blood products against SARS-COV-2.

Characterization of pathogen-inactivated COVID-19 convalescent plasma and responses in transfused patients.

BACKGROUND: Efficacy of donated COVID-19 convalescent plasma (dCCP) is uncertain and may depend on antibody titers, neutralizing capacity, timing of administration, and patient characteristics. STUDY DESIGN AND METHODS: In a single-center hypothesis-generating prospective case-control study with 1:2 matched dCCP recipients to controls according to disease severity at day 1, hospitalized adults with COVID-19 pneumonia received 2 × 200 ml pathogen-reduced treated dCCP from 2 different donors. We evaluated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in COVID-19 convalescent plasma donors and recipients using multiple antibody assays including a Coronavirus antigen microarray (COVAM), and binding and neutralizing antibody assays. Outcomes were dCCP characteristics, antibody responses, 28-day mortality, and dCCP -related adverse events in recipients. RESULTS: Eleven of 13 dCCPs (85%) contained neutralizing antibodies (nAb). PRT did not affect dCCP antibody activity. Fifteen CCP recipients and 30 controls (median age 64 and 65 years, respectively) were enrolled. dCCP recipients received 2 dCCPs from 2 different donors after a median of one hospital day and 11 days after symptom onset. One dCCP recipient (6.7%) and 6 controls (20%) died (p = 0.233). We observed no dCCP-related adverse events. Transfusion of unselected dCCP led to heterogeneous SARS CoV-2 antibody responses. COVAM clustered dCCPs in 4 distinct groups and showed endogenous immune responses to SARS-CoV-2 antigens over 14-21 days post dCCP in all except 4 immunosuppressed recipients. DISCUSSION: PRT did not impact dCCP anti-virus neutralizing activity. Transfusion of unselected dCCP did not impact survival and had no adverse effects. Variable dCCP antibodies and post-transfusion antibody responses indicate the need for controlled trials using well-characterized dCCP with informative assays.

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. .

Inactivation of SARS-CoV-2 in All Blood Components Using Amotosalen/Ultraviolet A Light and Amustaline/Glutathione Pathogen Reduction Technologies.

No cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transfusion-transmitted infections (TTI) have been reported. The detection of viral RNA in peripheral blood from infected patients and blood components from infected asymptomatic blood donors is, however, concerning. This study investigated the efficacy of the amotosalen/UVA light (A/UVA) and amustaline (S-303)/glutathione (GSH) pathogen reduction technologies (PRT) to inactivate SARS-CoV-2 in plasma and platelet concentrates (PC), or red blood cells (RBC), respectively. Plasma, PC prepared in platelet additive solution (PC-PAS) or 100% plasma (PC-100), and RBC prepared in AS-1 additive solution were spiked with SARS-CoV-2 and PR treated. Infectious viral titers were determined by plaque assay and log reduction factors (LRF) were determined by comparing titers before and after treatment. PR treatment of SARS-CoV-2-contaminated blood components resulted in inactivation of the infectious virus to the limit of detection with A/UVA LRF of >3.3 for plasma, >3.2 for PC-PAS-plasma, and >3.5 for PC-plasma and S-303/GSH LRF > 4.2 for RBC. These data confirm the susceptibility of coronaviruses, including SARS-CoV-2 to A/UVA treatment. This study demonstrates the effectiveness of the S-303/GSH treatment to inactivate SARS-CoV-2, and that PRT can reduce the risk of SARS-CoV-2 TTI in all blood components.

Pathogen Reduction for Platelets-A Review of Recent Implementation Strategies.

The development of pathogen reduction technologies (PRT) for labile blood components is a long-pursued goal in transfusion medicine. While PRT for red blood cells and whole blood are still in an early phase of development, different PRT platforms for plasma and platelets are commercially available and routinely used in several countries. This review describes complementary strategies recommended by the US FDA to mitigate the risk of septic reactions in platelet recipients, including PRT and large-volume delayed sampling, and summarizes the main findings of recent reports discussing economical and organizational issues of platelet PRT implementation. Sophisticated mathematical analytical models are available to determine the impact of PRT on platelet costs, shortages and outdates in different settings. PRT implementation requires careful planning to ensure the availability of sufficient economical, technological and human resources. A phased approach was used in most PRT implementation programs, starting with adult and pediatric immunocompromised patients at higher risk of developing septic platelet transfusion reactions. Overall, the reviewed studies show that significant progress has been made in this area, although additional efforts will be necessary to reduce the storage lesion of PRT platelets and to expand the sustainable applicability of PRT to all labile blood components.

SARS-CoV-2 variants inactivation of plasma units using a riboflavin and ultraviolet light-based photochemical treatment.

BACKGROUND: Test the ability of Mirasol Pathogen Reduction Technology (PRT, Terumo BCT, Lakewood Co, USA) treatment with riboflavin and ultraviolet light (R + UV) in reducing SARS-CoV-2 infectivity while maintaining blood product quality. MATERIAL AND METHODS: SARS-CoV-2 strains were isolated and titrated to prepare cell free virus for plasma units infection. The units were then under treatment with Mirasol PRT. The infectious titers were determined before and after treatment with an in house microtitration assay on Vero E6 cells. Thirty-six plasma pool bags underwent PRT treatment. RESULTS: In all the experiments, the measured titer following riboflavin and UV treatment was below the limit of detection of microtitration assay for all the different SARS-CoV-2 strains. Despite the high copies number detected by RT-PCR for each viral strain after treatment, viruses were completely inactivated and not able to infect VERO E6 cells. CONCLUSION: Riboflavin and UV light treatment effectively reduced the virus titers of human plasma to the limit of detection in tissue culture, regardless of the strain. These data suggest that pathogen reduction in blood products highlight the safety of CP therapy procedures for critically ill COVID-19 patients, while maintaining blood product quality.

Impact of different pathogen reduction technologies on the biochemistry, function, and clinical effectiveness of platelet concentrates: An updated view during a pandemic.

Standard platelet concentrates (PCs) stored at 22°C have a limited shelf life of 5 days. Because of the storage temperature, bacterial contamination of PCs can result in life-threatening infections in transfused patients. The potential of blood components to cause infections through contaminating pathogens or transmitting blood-borne diseases has always been a concern. The current safety practice to prevent pathogen transmission through blood transfusion starts with a stringent screening of donors and regulated testing of blood samples to ensure that known infections cannot reach transfusion products. Pathogen reduction technologies (PRTs), initially implemented to ensure the safety of plasma products, have been adapted to treat platelet products. In addition to reducing bacterial contamination, PRT applied to PCs can extend their shelf life up to 7 days, alleviating the impact of their shortage, while providing an additional safety layer against emerging blood-borne infectious diseases. While a deleterious action of PRTs in quantitative and qualitative aspects of plasma is accepted, the impact of PRTs on the quality, function, and clinical efficacy of PCs has been under constant examination. The potential of PRTs to prevent the possibility of new emerging diseases to reach cellular blood components has been considered more hypothetical than real. In 2019, a coronavirus-related disease (COVID-19) became a pandemic. This episode should help when reconsidering the possibility of future blood transmissible threats. The following text intends to evaluate the impact of different PRTs on the quality, function, and clinical effectiveness of platelets within the perspective of a developing pandemic.

The 4-Year Experience with Implementation and Routine Use of Pathogen Reduction in a Brazilian Hospital.

(1) Background: We reviewed the logistics of the implementation of pathogen reduction (PR) using the INTERCEPT Blood System™ for platelets and the experience with routine use and clinical outcomes in the patient population at the Sírio-Libanês Hospital of São Paulo, Brazil. (2) Methods: Platelet concentrate (PC), including pathogen reduced (PR-PC) production, inventory management, discard rates, blood utilization, and clinical outcomes were analyzed over the 40 months before and after PR implementation. Age distribution and wastage rates were compared over the 10 months before and after approval for PR-PC to be stored for up to seven days. (3) Results: A 100% PR-PC inventory was achieved by increasing double apheresis collections and production of double doses using pools of two single apheresis units. Discard rates decreased from 6% to 3% after PR implementation and further decreased to 1.2% after seven-day storage extension for PR-PCs. The blood utilization remained stable, with no increase in component utilization. A significant decrease in adverse transfusion events was observed after the PR implementation. (4) Conclusion: Our experience demonstrates the feasibility for Brazilian blood centers to achieve a 100% PR-PC inventory. All patients at our hospital received PR-PC and showed no increase in blood component utilization and decreased rates of adverse transfusion reactions.

Molecular validation of pathogen-reduction technologies using rolling-circle amplification coupled with real-time PCR for torquetenovirus DNA quantification.

BACKGROUND: Pathogen reduction technologies (PRT) based on nucleic-acid damaging chemicals and/or irradiation are increasingly being used to increase safety of blood components against emerging pathogens, such as convalescent plasma in the ongoing COVID-19 pandemic. Current methods for PRT validation are limited by the resources available to the blood component manufacturer, and quality control rely over pathogen spiking and hence invariably require sacrifice of the tested blood units: quantitative real-time PCR is the current pathogen detection method but, due to the high likelihood of detecting nonviable fragments, requires downstream pathogen culture. We propose here a new molecular validation of PRT based on the highly prevalent human symbiont torquetenovirus (TTV) and rolling circle amplification (RCA). MATERIALS AND METHODS: Serial apheresis plasma donations were tested for TTV before and after inactivation with Intercept® PRT using real-time quantitative PCR (conventional validation), RCA followed by real-time PCR (our validation), and reverse PCR (for cross-validation). RESULTS: While only 20% of inactivated units showed significant decrease in TTV viral load using real-time qPCR, all donations tested with RCA followed by real-time PCR showed TTV reductions. As further validation, 2 units were additionally tested with reverse PCR, which confirmed absence of entire circular genomes. DISCUSSION: We have described and validated a conservative and easy-to-setup protocol for molecular validation of PRT based on RCA and real-time PCR for TTV.

Efficient inactivation of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in human apheresis platelet concentrates with amotosalen and ultraviolet A light.

OBJECTIVES: The detection of SARS-CoV-2 RNA in blood and platelet concentrates from asymptomatic donors, and the detection of viral particles on the surface and inside platelets during in vitro experiments, raised concerns over the potential risk for transfusion-transmitted-infection (TTI). The objective of this study was to assess the efficacy of the amotosalen/UVA pathogen reduction technology for SARS-CoV-2 in human platelet concentrates to mitigate such potential risk. MATERIAL AND METHODS: Five apheresis platelet units in 100% plasma were spiked with a clinical SARS-CoV-2 isolate followed by treatment with amotosalen/UVA (INTERCEPT Blood System), pre- and posttreatment samples were collected as well as untreated positive and negative controls. The infectious viral titer was assessed by plaque assay and the genomic titer by quantitative RT-PCR. To exclude the presence of infectious particles post-pathogen reduction treatment below the limit of detection, three consecutive rounds of passaging on permissive cell lines were conducted. RESULTS: SARS-CoV-2 in platelet concentrates was inactivated with amotosalen/UVA below the limit of detection with a mean log reduction of>3.31±0.23. During three consecutive rounds of passaging, no viral replication was detected. Pathogen reduction treatment also inhibited nucleic acid detection with a log reduction of>4.46±0.51 PFU equivalents. CONCLUSION: SARS-CoV-2 was efficiently inactivated in platelet concentrates by amotosalen/UVA treatment. These results are in line with previous inactivation data for SARS-CoV-2 in plasma as well as MERS-CoV and SARS-CoV-1 in platelets and plasma, demonstrating efficient inactivation of human coronaviruses.

Impact of pathogen reduction methods on immunological properties of the COVID-19 convalescent plasma.

BACKGROUND AND OBJECTIVES: COVID-19 convalescent plasma is an experimental treatment against SARS-CoV-2. The aim of this study is to assess the impact of different pathogen reduction methods on the levels and virus neutralizing activity of the specific antibodies against SARS-CoV2 in convalescent plasma. MATERIALS AND METHODS: A total of 140 plasma doses collected by plasmapheresis from COVID-19 convalescent donors were subjected to pathogen reduction by three methods: methylene blue (M)/visible light, riboflavin (R)/UVB and amotosalen (A)/UVA. To conduct a paired comparison, individual plasma doses were divided into 2 samples that were subjected to one of these methods. The titres of SARS-CoV2 neutralizing antibodies (NtAbs) and levels of specific immunoglobulins to RBD, S- and N-proteins of SARS-CoV-2 were measured before and after pathogen reduction. RESULTS: The methods reduced NtAbs titres differently: among units with the initial titre 80 or above, 81% of units remained unchanged and 19% decreased by one step after methylene blue; 60% were unchanged and 40% decreased by one step after amotosalen; after riboflavin 43% were unchanged and 50% (7%, respectively) had a one-step (two-step, respectively) decrease. Paired two-sample comparisons (M vs. A, M vs. R and A vs. R) revealed that the largest statistically significant decrease in quantity and activity of the specific antibodies resulted from the riboflavin treatment. CONCLUSION: Pathogen reduction with methylene blue or with amotosalen provides the greater likelihood of preserving the immunological properties of the COVID-19 convalescent plasma compared to riboflavin.

Impact of pathogen-reduction technologies on COVID-19 convalescent plasma potency.

Pathogen reduction technologies (PRT) have been recommended by many regulatory authorities to minimize the residual risk of transfusion-transmitted infections associated with COVID19 convalescent plasma. While its impact on safety and its cost-effectiveness are nowadays well proven, there is theoretical concern that PRT could impact efficacy of convalescent plasma by altering concentration and/or function of the neutralizing antibodies (nAb). We review here the evidence supporting a lack of significant detrimental effect from PRTs on nAbs.

Maintaining plasma quality and safety in the state of ongoing epidemic - The role of pathogen reduction.

In the field of transfusion medicine, many pathogen reduction techniques (PRTs) are currently available, including those based on photochemical (PI) and photodynamic inactivation (PDI). This is particularly important in the face of emerging viral pathogens that may pose a threat to blood recipients, as in the case of the COVID-19 pandemic. However, PRTs have some limitations, primarily related to their adverse effects on coagulation factors, which should be considered before their intended use. A comprehensive search of PubMed, Wiley Online Library and Science Direct databases was conducted to identify original papers. As a result, ten studies evaluating fresh plasma and frozen-thawed plasma treated with different PI/ PDI methods and evaluating concentrations of coagulation factors and natural anticoagulants both before and after photochemical treatment were included in the review. The use of PI and PDI is associated with a significant decrease in the activity of all analysed coagulation factors, while the recovery of natural anticoagulants remains at a satisfactory level, variable for individual inactivation methods. In addition, the published evidence reviewed above does not unequivocally favour the implementation of PI/PDI either before freezing or after thawing as plasma products obtained with these two approaches seem to satisfy the existing quality criteria. Based on current evidence, if implemented responsibly and in accordance with the current guidelines, both PI and PDI can ensure satisfactory plasma quality and improve its safety.

Treatment for emerging viruses: Convalescent plasma and COVID-19.

Use of convalescent plasma transfusions could be of great value in the current pandemic of coronavirus disease (COVID-19), given the lack of specific preventative and therapeutic options. This convalescent plasma therapy is of particular interest when a vaccine or specific therapy is not yet available for emerging viruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19. This report summarizes existing literature around convalescent plasma as a therapeutic option for COVID-19. It also includes recommendations for establishing a convalescent plasma program, enhancement considerations for convalescent plasma, and considerations around pathogen reduction treatment of convalescent plasma. Time is of the essence to set up protocols for collection, preparation, and administration of apheresis-collected convalescent plasma in response to the current pandemic. The immediate use of convalescent plasma provides prompt availability of a promising treatment while specific vaccines and treatments are evaluated and brought to scale. Further development of improved convalescent plasma, vaccines and other therapeutics depends on quick generation of additional data on pathogenesis and immune response. Additionally, given the lack of information around the natural history of this disease, PRT should be considered to add a layer of safety to protect recipients of convalescent plasma.

Inactivation of severe acute respiratory syndrome coronavirus 2 in plasma and platelet products using a riboflavin and ultraviolet light-based photochemical treatment.

BACKGROUND AND OBJECTIVE: Severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is a member of the coronavirus family. Coronavirus infections in humans are typically associated with respiratory illnesses; however, viral RNA has been isolated in serum from infected patients. Coronaviruses have been identified as a potential low-risk threat to blood safety. The Mirasol Pathogen Reduction Technology (PRT) System utilizes riboflavin and ultraviolet (UV) light to render blood-borne pathogens noninfectious, while maintaining blood product quality. Here, we report on the efficacy of riboflavin and UV light against the pandemic virus SARS-CoV-2 when tested in both plasma and platelets units. MATERIALS AND METHODS: Stock SARS-CoV-2 was grown in Vero cells and inoculated into either plasma or platelet units. Those units were then treated with riboflavin and UV light. The infectious titres of SARS-CoV-2 were determined by plaque assay using Vero cells. A total of five (n = 5) plasma and three (n = 3) platelet products were evaluated in this study. RESULTS: In both experiments, the measured titre of SARS-CoV-2 was below the limit of detection following treatment with riboflavin and UV light. The mean log reductions in the viral titres were ≥3·40 and ≥4·53 for the plasma units and platelet units, respectively. CONCLUSION: Riboflavin and UV light effectively reduced the titre of SARS-CoV-2 in both plasma and platelet products to below the limit of detection in tissue culture. The data suggest that the process would be effective in reducing the theoretical risk of transfusion transmitted SARS-CoV-2.