Growing evidence suggests that ABO blood group may play a role in the immunopathogenesis of SARS‐CoV‐2 infection, with group O individuals less likely to test positive and group A conferring a higher ...susceptibility to infection and propensity to severe disease. The level of evidence supporting an association between ABO type and SARS‐CoV‐2/COVID‐19 ranges from small observational studies, to genome‐wide‐association‐analyses and country‐level meta‐regression analyses. ABO blood group antigens are oligosaccharides expressed on red cells and other tissues (notably endothelium). There are several hypotheses to explain the differences in SARS‐CoV‐2 infection by ABO type. For example, anti‐A and/or anti‐B antibodies (e.g. present in group O individuals) could bind to corresponding antigens on the viral envelope and contribute to viral neutralization, thereby preventing target cell infection. The SARS‐CoV‐2 virus and SARS‐CoV spike (S) proteins may be bound by anti‐A isoagglutinins (e.g. present in group O and group B individuals), which may block interactions between virus and angiotensin‐converting‐enzyme‐2‐receptor, thereby preventing entry into lung epithelial cells. ABO type‐associated variations in angiotensin‐converting enzyme‐1 activity and levels of von Willebrand factor (VWF) and factor VIII could also influence adverse outcomes, notably in group A individuals who express high VWF levels. In conclusion, group O may be associated with a lower risk of SARS‐CoV‐2 infection and group A may be associated with a higher risk of SARS‐CoV‐2 infection along with severe disease. However, prospective and mechanistic studies are needed to verify several of the proposed associations. Based on the strength of available studies, there are insufficient data for guiding policy in this regard.
Studies on severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) suggest a protective effect of anti-A antibodies against viral cell entry that may hold relevance for SARS-CoV-2 infection. ...Therefore, we aimed to determine whether ABO blood groups are associated with different severities of COVID-19. We conducted a multicenter retrospective analysis and nested prospective observational substudy of critically ill patients with COVID-19. We collected data pertaining to age, sex, comorbidities, dates of symptom onset, hospital admission, intensive care unit (ICU) admission, mechanical ventilation, continuous renal replacement therapy (CRRT), standard laboratory parameters, and serum inflammatory cytokines. National (N = 398 671; P = .38) and provincial (n = 62 246; P = .60) ABO blood group distributions did not differ from our cohort (n = 95). A higher proportion of COVID-19 patients with blood group A or AB required mechanical ventilation (P = .02) and CRRT (P = .004) and had a longer ICU stay (P = .03) compared with patients with blood group O or B. Blood group A or AB also had an increased probability of requiring mechanical ventilation and CRRT after adjusting for age, sex, and presence of ≥1 comorbidity. Inflammatory cytokines did not differ between patients with blood group A or AB (n = 11) vs O or B (n = 14; P > .10 for all cytokines). Collectively, our data indicate that critically ill COVID-19 patients with blood group A or AB are at increased risk for requiring mechanical ventilation, CRRT, and prolonged ICU admission compared with patients with blood group O or B. Further work is needed to understand the underlying mechanisms.
•COVID-19 patients with blood group A or AB are at increased risk for requiring mechanical ventilation vs those with blood group O or B.•COVID-19 patients with blood group A or AB appear to exhibit a greater disease severity than patients with blood group O or B.
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BACKGROUND
The development of hemolysis during ex vivo hypothermic storage is multifaceted. Standardization of collection and production processes is used to minimize variability in biologics ...manufacturing and to maximize product quality. However, the influence of various donor characteristics on product quality is often difficult to evaluate and to control. Using a proteomic approach, we aimed to decipher relevant donor characteristics that may predict red blood cell (RBC) quality during storage.
STUDY DESIGN AND METHODS
Ten healthy volunteer donors exhibiting repeated high hemolysis at outdate (>0.8%; RBCHH) and 10 age‐ and sex‐matched control donors (RBCCtrl) were studied. Common quality variables were measured on Days 5, 14, 21, 28, and 42 of storage. Protein profiles of hemoglobin‐depleted membrane fractions from RBCHH and RBCCtrl donors were analyzed using a quantitative proteomics approach based on iTRAQ (isobaric tags for relative and absolute quantitation).
RESULTS
Time‐dependent lesion development was apparent in both donor populations. RBCHH exhibited reduced 2,3‐bisphosphoglycerate levels (p < 0.001) and morphologic score (p < 0.001), but displayed elevated hemolysis level (p < 0.001), RBC‐derived microvesicle formation (p < 0.001), and mean corpuscular fragility (p < 0.001) compared to RBCCtrl, indicating notable differences at the membrane between the two donor populations. Proteomic findings revealed a significant reduction in the level of proteins involved in oxidative response pathways at early time points in RBCHH compared to that of RBCCtrl.
CONCLUSION
The recruitment of these candidate proteins might be part of a response mechanism altered in RBCHH donors and therefore may be useful as a donor screening tool.
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•Storage-related changes were identified in Red Cell Concentrate using SORS.•MuSCA was employed to assess Raman data against parallel bioanalytical measurements.•Spectral markers ...strongly correlated with respective bioassays in RCC were revealed.•Our approach enabled direct quality monitoring of RCC within sealed transfusion bags.
In this work we employ Spatially Offset Raman Spectroscopy (SORS) to non-invasively identify storage-related changes in red blood cell concentrate (RCC) in-situ within standard plastic transfusion bags. To validate the measurements, we set up a parallel study comparing both bioanalytical data (obtained by blood-gas analysis, hematology analysis and spectrophotometric assays), and Raman spectrometry data from the same blood samples. We then employ Multisource Correlation Analysis (MuSCA) to correlate the different types of data in RCC. Our analysis confirmed a strong correlation of glucose, methemoglobin and oxyhemoglobin with their respective bioassay values in RCC units. Finally, by combining MuSCA with k-means clustering, we assessed changes in all Raman wavenumbers during cold storage in both RCC Raman data from the current study and parallel RCC supernatant Raman data previously acquired from the same units. Direct RCC quality monitoring during storage, would help to establish a basis for improved inventory management of blood products in blood banks and hospitals based on analytical data.
Background
Randomized clinical trial data show that early plasma transfusion may save lives among trauma patients. Supplying plasma in remote environments is logistically challenging. Freeze‐dried ...plasma (FDP) offers a possible solution.
Study Design and Methods
A Terumo BCT plasma freeze‐drying system was evaluated. We compared pooled frozen plasma (FP) units with derived Terumo BCT FDP (TFDP) units and pooled COVID‐19 convalescent apheresis fresh‐frozen plasma (CC‐AFFP) with derived CC‐TFDP units. Parameters measured were: coagulation factors (F) II; V; VII; VIII; IX; XI; XIII; fibrinogen; Proteins C (PC) and S (PS); antithrombin (AT); α2‐antiplasmin (α2AP); ADAMTS13; von Willebrand Factor (vWF); thrombin–antithrombin (TAT); D‐dimer; activated complement factors 3 (C3a) and 5 (C5a); pH; osmolality; prothrombin time (PT); and activated partial thromboplastin time (aPTT). Antibodies to SARS‐CoV‐2 in CC‐AFFP and CC‐TFDP units were compared by plaque reduction assays and viral protein immunoassays.
Results
Most parameters were unchanged in TFDP versus FP or differed ≤15%. Mean aPTT, PT, C3a, and pH were elevated 5.9%, 6.9%, 64%, and 0.28 units, respectively, versus FP. CC‐TFDP showed no loss of SARS‐CoV‐2 neutralization titer versus CC‐AFFP and no mean signal loss in most pools by viral protein immunoassays.
Conclusion
Changes in protein activities or clotting times arising from freeze‐drying were <15%. Although C3a levels in TFDP were elevated, they were less than literature values for transfusable plasma. SARS‐CoV‐2‐neutralizing antibody titers and viral protein binding levels were largely unaffected by freeze‐drying. In vitro characteristics of TFDP or CC‐TFDP were comparable to their originating plasma, making future clinical studies appropriate.
See editorial on page 257–260, in this issue
Background
Equitable allocation of scarce blood products needed for a randomized controlled trial (RCT) is a complex decision‐making process within the blood supply chain. Strategies to improve ...resource allocation in this setting are lacking.
Methods
We designed a custom‐made, computerized system to manage the inventory and allocation of COVID‐19 convalescent plasma (CCP) in a multi‐site RCT, CONCOR‐1. A hub‐and‐spoke distribution model enabled real‐time inventory monitoring and assignment for randomization. A live CCP inventory system using REDCap was programmed for spoke sites to reserve, assign, and order CCP from hospital hubs. A data‐driven mixed‐integer programming model with supply and demand forecasting was developed to guide the equitable allocation of CCP at hubs across Canada (excluding Québec).
Results
18/38 hospital study sites were hubs with a median of 2 spoke sites per hub. A total of 394.5 500‐ml doses of CCP were distributed; 349.5 (88.6%) doses were transfused; 9.5 (2.4%) were wasted due to mechanical damage sustained to the blood bags; 35.5 (9.0%) were unused at the end of the trial. Due to supply shortages, 53/394.5 (13.4%) doses were imported from Héma‐Québec to Canadian Blood Services (CBS), and 125 (31.7%) were transferred between CBS regional distribution centers to meet demand. 137/349.5 (39.2%) and 212.5 (60.8%) doses were transfused at hubs and spoke sites, respectively. The mean percentages of total unmet demand were similar across the hubs, indicating equitable allocation, using our model.
Conclusion
Computerized tools can provide efficient and immediate solutions for equitable allocation decisions of scarce blood products in RCTs.
Background
Convalescent plasma products are a potential passive immunotherapy for Coronavirus disease 2019 (COVID‐19) disease. Various approaches have been utilized to determine the concentration of ...Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2)‐neutralizing antibodies in plasma products. The Canadian Blood Services used Plaque Reduction Neutralization Test 50 (PRNT50)‐generated values to qualify convalescent plasma donations supporting clinical trials in Canada. This manuscript describes changes in PRNT50 titers of repeat male plasma donations collected approximately 1–4 months after onset of COVID‐19 signs and symptoms in donors.
Study Design and Methods
Men were eligible to donate if they: met standard criteria, were < 67 years of age, reported a previous SARS‐CoV‐2‐positive nucleic acid test, and recovered and were symptom free for at least 28 days prior to donation. Repeat donation analysis required at least one original and one repeat donation where a PRNT50 was performed.
Results
From April 29, 2020 to July 25, 2020, 156 donors donated once, with 78 (50%) of the donated plasma having PRNT50 titers of ≥1:160. Thirty‐seven (23.7%) of the donated plasma had a titer of 1:40 or 1:80 (individuals donating this plasma were asked to donate a second time only). A total of 30 donors (19.2%) had repeat donations. Of the repeat donors, 15 (50%) had at least an eightfold change from peak to trough PRNT50 titers within greater than 90 days after onset of COVID‐19 symptoms.
Conclusions
Blood operators cannot infer that SARS‐CoV‐2 PRNT50 will remain high in repeat plasma donors 3–4 months after onset of COVID‐19 symptoms.
Polyglycidols are flexible hydrophilic polyethers that are potentially biocompatible polymers based on their similarities to the well-studied poly(ethyleneglycol). Polyglycidols can be prepared as ...branched or linear polymers by suitable synthetic methods. Biocompatibility testing of these polymers conducted in vitro as well as in vivo are reported here. The in vitro studies included hemocompatibility testing for effects on coagulation (PT and APTT), complement activation, red blood cell aggregation, and whole blood viscosity measurements. In vitro cytotoxicity experiments were also conducted. The results were compared with some of the common biocompatible polymers already in human use. Results from these studies show that polyglycidols are highly biocompatible. Hyperbranched polyglycidols were found to be well tolerated by mice even when injected in high doses.
Coronavirus disease 2019 convalescent plasma (CCP) has emerged as a potential treatment of COVID-19. However, meta-analysis data and recommendations are limited. The Association for the Advancement ...of Blood and Biotherapies (AABB) developed clinical practice guidelines for the appropriate use of CCP.
These guidelines are based on 2 living systematic reviews of randomized controlled trials (RCTs) evaluating CCP from 1 January 2019 to 26 January 2022. There were 33 RCTs assessing 21 916 participants. The results were summarized using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method. An expert panel reviewed the data using the GRADE framework to formulate recommendations.
The AABB suggests CCP transfusion in addition to the usual standard of care for outpatients with COVID-19 who are at high risk for disease progression (weak recommendation, moderate-certainty evidence).
The AABB recommends against CCP transfusion for unselected hospitalized persons with moderate or severe disease (strong recommendation, high-certainty evidence). This recommendation does not apply to immunosuppressed patients or those who lack antibodies against SARS-CoV-2.
The AABB suggests CCP transfusion in addition to the usual standard of care for hospitalized patients with COVID-19 who do not have SARS-CoV-2 antibodies detected at admission (weak recommendation, low-certainty evidence).
The AABB suggests CCP transfusion in addition to the usual standard of care for hospitalized patients with COVID-19 and preexisting immunosuppression (weak recommendation, low-certainty evidence).
The AABB suggests against prophylactic CCP transfusion for uninfected persons with close contact exposure to a person with COVID-19 (weak recommendation, low-certainty evidence).
CCP is most effective when transfused with high neutralizing titers to infected patients early after symptom onset.
Abstract Pathogen inactivation (PI) of platelet concentrates (PCs) reduces the proliferation/replication of a large range of bacteria, viruses, and parasites as well as residual leucocytes. ...Pathogen-inactivated PCs were evaluated in various clinical trials showing their efficacy and safety. Today, there is some debate over the hemostatic activity of treated PCs as the overall survival of PI platelets seems to be somewhat reduced, and in vitro measurements have identified some alterations in platelet function. Although the specific lesions resulting from PI of PCs are still not fully understood, proteomic studies have revealed potential damages at the protein level. This review merges the key findings of the proteomic analyses of PCs treated by the Mirasol Pathogen Reduction Technology, the Intercept Blood System, and the Theraflex UV-C system, respectively, and discusses the potential impact on the biological functions of platelets. The complementarities of the applied proteomic approaches allow the coverage of a wide range of proteins and provide a comprehensive overview of PI-mediated protein damage. It emerges that there is a relatively weak impact of PI on the overall proteome of platelets. However, some data show that the different PI treatments lead to an acceleration of platelet storage lesions, which is in agreement with the current model of platelet storage lesion in pathogen-inactivated PCs. Overall, the impact of the PI treatment on the proteome appears to be different among the PI systems. Mirasol impacts adhesion and platelet shape change, whereas Intercept seems to impact proteins of intracellular platelet activation pathways. Theraflex influences platelet shape change and aggregation, but the data reported to date are limited. This information provides the basis to understand the impact of different PI on the molecular mechanisms of platelet function. Moreover, these data may serve as basis for future developments of PI technologies for PCs. Further studies should address the impact of both the PI and the storage duration on platelets in PCs because PI may enable the extension of the shelf life of PCs by reducing the bacterial contamination risk.
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