ABSTRACT
Background: In modern transfusion therapy, whole blood is used only in certain limited circumstances and trust is placed in the use of specific blood components (BCs). BC must be processed using appropriate validated procedures, including measures to avoid contamination and microbial growth in the initial and final prepared BCs (Directive 2005/62/EC, Annex 6.42). Consequently, methods of centrifugation of whole blood, filtration of leukocytes, washing and irradiation must be specified. Aim(s): We analyse national data on non-haemolytic pyrexial and allergic reactions related to blood transfusion reported to the Coordinating Haemovigilance Centre and Surveillance of Transfusion (SKAEM) of the Hellenic National Public Health Organization (EODY) by hospital Transfusion Departments in 2010-2020, in relation to the processing procedures applied using conventional blood bank methodologies. The results of an automated blood processing system employed in two hospital blood banks are also discussed in view of the national policy for stepwise implementation of a centralized automated processing procedure aiming to improve the quality and safety of blood transfusion. Method/Study: Annual haemovigilance data for all adverse reactions associated with BCs transfusion are reported to SKAEM using standardized questionnaires. Protocols are in line with International Haemovigilance Network guidelines and ISBT definitions of the types of adverse reactions associated with blood transfusion. The processing procedures used are: buffy coat removal, leukocyte depletion after storage, pre-storage leukodepletion, red cell washing in additive solution, and irradiation. The Reveos Automated Blood System (Terumo BCT) was also used, processing 4 units of whole blood to two components (plasma and red cells) or three main components (plasma, concentrated red cells and interim platelet unit) according to the manufacturer's instructions. Both protocols collect a Leukopak unit containing the main leukocyte fraction which is discarded. The resulting RCC is further leukoreduced by gravity using the Reveos in-line filter. Consistent leukoreduction of plasma is done through the simultaneous centrifugation/ extraction step of this method. Result(s): 13005 adverse reactions (AR) associated with the transfusion of 7 894 054 blood components were reported. Febrile nonhaemolytic transfusion reactions were 43.7% and allergic 37%. The distribution of febrile reactions in relation to processing procedure was: in RBCs with buffy coat 61.7%, without buffy coat 10.9%, leukodepletion after storage 16.5%, leukodepletion pre-storage 6.7%, washing 4.1% and irradiation 0.1%. Results from the use of the Reveos Automated Processing System (Terumo BCT) by the National Blood Centre for processing the blood collected and used by two large HBBs over a two-year period showed a statistically significant reduction of pyrexial reactions (p = 0.044 in one hospital and 0.002 in the other) in comparison with the relevant data before the use of this system. The corresponding difference in the allergic reactions was not statistically significant. Conclusion(s): This study demonstrates high incidence of pyrexial nonhaemolytic and allergic reactions associated with the use of blood components processed without leukodepletion, particularly during the COVID-19 pandemic when blood transfusion services were shortstaffed owing to re-assignment to other duties. Compliance with Good Practice Guidelines and improvement of blood processing and safety by automation should be a national priority.
ABSTRACT
Background: The speed of development of COVID-19 vaccines, and the need to balance their effectiveness versus possible complications, raised doubts over vaccine acceptance in the first period of the national vaccination campaign aiming at herd immunity against SARSCoV- 2. In the field of transfusion medicine, timely vaccination of the blood donor population represents a powerful measure in the general strategy to sustain blood collection and optimize the blood supply. Aims: To explore perceptions and attitudes of blood donors towards SARS-CoV-2 vaccination, in comparison to the general population. Methods: Donors in 20 blood collection services throughout Greece in May-October 2021 answered voluntarily and confidentially a structured questionnaire, covering: donor demographics;date and type of blood donation;frequency of donation;history of COVID-19;SARSCoV- 2 vaccination including type and doses;reasons for getting vaccinated or not;satisfaction with the vaccination procedure;side effects;feelings after vaccination;certainty about return to normality;and recommending vaccination to others. Hesitancy and beliefs leading to not getting vaccinated, worries over future side effects, and not recommending vaccination to others were also investigated. Results: Completed questionnaires were received from 3361 blood donors (61% response rate) aged 18-65 years during blood sessions at mobile sites and within hospitals. Respondents were mainly males (72%). A very high proportion (92%) of responders had completed high school of higher education and the majority resided in large cities. Almost half were regular donors. A small proportion (5.4%) had undergone a mild COVID19 infection and 17.3% mentioned COVID-19 in a relative. 52% had already been vaccinated. The proportion vaccinated increased steadily throughout the study. Vaccine acceptance was highest in males 45-54 years old and in females 18-24 and 50-59 years old. All four EMA approved vaccines (Pfizer, Moderna, Astra Zeneca and Johnson) were used. Mild complications were reported by 21% of vaccinated donors after the first dose and 19% after the second. Thirty-five donors reported fever and local pain at the vaccination site after both doses. The vast majority (79%) of vaccinated donors were very satisfied with the vaccination procedure and only 10 complained. After vaccination, 20% of donors felt safe and protected against COVID-19 and 55% intended to continue all recommended personal protective measures in their families and felt satisfaction for doing the right thing. Among unvaccinated respondents, 48% were awaiting their appointment, 19% were undecided, 16% were afraid of complications, a few said that they were waiting for more information about the beneficial effect of the vaccines, or that COVID-19 is not a severe disease, and 10% did not specify their reasons. In the general population of Greece surveyed in May 2021 in the Flash Eurobarometer study, COVID-19 vaccination acceptance was 59%. The proportion of those with negative perception and attitude towards vaccination was 12%. Key reasons for getting vaccinated or not were similar to those found in blood donors. Summary/Conclusions: The benefits of vaccination and the need to continue all personal protection measures were highly recognized by blood donors, whether already vaccinated or awaiting vaccination. The perceptions and attitudes towards vaccination against COVID-19, especially of regular donors, are compatible with their high social, altruistic and humanitarian behaviour.
ABSTRACT
Background: Elucidating the characteristics of human immune response against SARS-CoV-2 is of high priority for determining vaccine strategies. The duration of the persistence of anti-SARS-CoV-2 antibodies in individuals who suffered from COVID-19 is not clearly defined yet. Aims: The aim of this study was to assess the kinetics of anti-SARS-CoV-2 antibodies and neutralizing antibodies among convalescent plasma donors during an 8-month period from their first symptoms of COVID-19. Methods: Participants were enrolled in a phase 2 study of plasma donors (NCT04408209) for the use of convalescent plasma for the treatment of COVID-19 in Greece. For the detection of anti-SARS-CoV-2 antibodies, we used four in-house ELISA assays measuring antibodies to (i) trimeric Spike (S), (ii) Spike Receptor Binding Domain (Spike-RBD), (iii) Nucleocapsid, and (ii) Nucleocapsid RNA Binding Domain (N-RBD). For the Neutralizing Antibody (NAb) assay using SARS-CoV-2 pseudotyped virus, serial dilutions of heat-inactivated sera were incubated with an equal volume of the pseudotyped virions (pHIVNLEnv-Nanoluc) and the virion-Ab mixture was used to transduce HEK293T/ACE2wt cells. Two days later, the luciferase levels were measured in the cell extracts and the ID50 (50% Inhibitory Dose) was calculated using GraphPad Prism version 8.0 for MacOS X (GraphPad Software, Inc, La Jolla, CA) with nonlinear regression curve fit using inhibitor vs responses variable slope (four parameters). Results: In total, 148 convalescent plasma donors (median age: 50 years, range: 18-65) with a median follow-up of 8.3 (range 6.8-10.5) months post their first disease symptoms were included in this analysis. Ninetyone patients did not need hospitalization and 57 were hospitalized due to COVID-19. At the initial screen, all patients showed positive antibody responses recognizing trimeric Spike, Spike-RBD, Nucleocapsid and N-RBD. At the 6-month follow-up, we continue to detect positive responses to Spike, Spike-RBD, Nucleocapsid and N-RBD in all plasma donors but at lower levels compared to screening (p<0.001). At the 8-month follow-up, no significant reduction was observed compared to 6-month values. A piecewise, random-effects, generalized least squares multivariate regression analysis showed a two-phase pattern of antibody responses, with more pronounced decrease during the first 6 months and a plateau phase after the 6th month post-symptoms onset. Spike antibodies showed better persistence than Nucleocapsid antibodies, whereas antibodies recognizing only the Spike-RBD or N-RBD persisted less than the mixture of antibodies recognizing the respective complete proteins. Neutralization ability contracted faster, since neutralizing antibodies persisted in 76% of patients at the last time point. In the multivariate analysis, older age and hospitalization were independently associated with higher antibody Spike, Spike-RBD, Nucleocapsid, N-RBD and NAb levels. Summary/Conclusion: We found persistence of anti-SARS-CoV-2 antibodies, especially against Spike and Spike-RBD, up to 8 months post-symptoms onset. However, a loss of neutralizing antibodies became evident in 24% of convalescent donors at 8 months from initial symptoms of COVID-19. A prolonged follow-up of the donors is necessary to further characterize the kinetics of anti-SARS-CoV-2 B-cell mediated immunity over time and to establish a link between the presence of antibodies and the level of protection against re-infection. Such data should help to optimize vaccination strategies and public health decisions.
ABSTRACT
COVID-19 is a global pandemic associated with increased morbidity and mortality. Convalescent plasma (CP) infusion is a strategy of potential therapeutic benefit. We conducted a multicenter phase II study to evaluate the efficacy and safety of CP in patients with COVID-19, grade 4 or higher. To evaluate the efficacy of CP, a matched propensity score analysis was used comparing the intervention (n = 59) to a control group (n = 59). Sixty patients received CP within a median time of 7 days from symptom onset. During a median follow-up of 28.5 days, 56/60 patients fully recovered and 1 patient remained in the ICU. The death rate in the CP group was 3.4% vs. 13.6% in the control group. By multivariate analysis, CP recipients demonstrated a significantly reduced risk of death [HR: 0.04 (95% CI: 0.004-0.36), p: 0.005], significantly better overall survival by Kaplan-Meir analysis (p < 0.001), and increased probability of extubation [OR: 30.3 (95% CI: 2.64-348.9), p: 0.006]. Higher levels of antibodies in the CP were independently associated with significantly reduced risk of death. CP infusion was safe with only one grade 3 adverse event (AE), which easily resolved. CP used early may be a safe and effective treatment for patients with severe COVID-19 (trial number NCT04408209).