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Background: At the beginning of the pandemic, COVID-19 convalescent plasma (CCP) containing anti-SARS-CoV-2 antibodies was suggested as a source of therapy. In the last 3 years, many trials have demonstrated the limited usefulness of CCP therapy. This led us to the hypothesis that CCP could contain other elements, along with the desired neutralizing antibodies, which could potentially prevent it from having a therapeutic effect, among them cytokines, chemokines, growth factors, clotting factors, and autoantibodies. Methods: In total, 39 cytokines were analyzed in the plasma of 190 blood donors, and further research focused on the levels of 23 different cytokines in CCP (sCD40L, eotaxin, FGF-2, FLT-3L, ractalkine, GRO-α, IFNα2, IL-1ß, IL-1RA, IL-5, IL-6, IL-8, IL-12, IL-13, IL-15, IL-17E, IP-10, MCP-1, MIP-1b, PDGF-AA, TGFα, TNFα, and TRAIL). Anti-SARS-CoV-2 antibodies and neutralizing antibodies were detected in CCP. Results: We found no significant differences between CCP taken within a maximum of 180 days from the onset of the first COVID-19 symptoms and the controls. We also made a comparison of the cytokine levels between the low neutralizing antibodies (<160) group and the high neutralizing antibodies (≥160) group and found there were no differences between the groups. Our research also showed no correlation either to levels of anti-SARS-CoV-2 IgG Ab or to the levels of neutralizing antibodies. There were also no significant changes in cytokine levels based on the period after the start of COVID-19 symptoms. Conclusions: No elements which could potentially be responsible for preventing CCP from having a therapeutic effect were found.
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At the symposium organized by the International Plasma and Fractionation Association and European Blood Alliance, experts presented their views and experiences showing that the public sector and its blood establishments may strengthen the collection and increase the supply of plasma using the right strategies in plasma donor recruitment, retention and protection, scaling-up collection by increasing the number of donors within improved/new infrastructure, supportive funding, policies and legislation as well as harmonization of clinical guidelines and the collaboration of all stakeholders. Such approaches should contribute to increased plasma collection in Europe to meet patients' needs for plasma-derived medicinal products, notably immunoglobulins and avoid shortages. Overall, presentations and discussions confirmed that European non-profit transfusion institutions are committed to increasing the collection of plasma for fractionation from unpaid donors through dedicated programmes as well as novel strategies and research.
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Transfusión Sanguínea , Plasma , Humanos , Europa (Continente) , Plasma/química , Inmunoglobulinas/análisisRESUMEN
BACKGROUND: Hyperimmune convalescent COVID-19 plasma (CCP) containing anti-SARS-CoV-2 neutralizing antibodies (NAbs) was proposed as a therapeutic option for patients early in the new coronavirus disease pandemic. The efficacy of this therapy depends on the quantity of neutralizing antibodies (NAbs) in the CCP units, with titers ≥ 1:160 being recommended. The standard neutralizing tests (NTs) used for determining appropriate CCP donors are technically demanding and expensive and take several days. We explored whether they could be replaced by high-throughput serology tests and a set of available clinical data. METHODS: Our study included 1302 CCP donors after PCR-confirmed COVID-19 infection. To predict donors with high NAb titers, we built four (4) multiple logistic regression models evaluating the relationships of demographic data, COVID-19 symptoms, results of various serological testing, the period between disease and donation, and COVID-19 vaccination status. RESULTS: The analysis of the four models showed that the chemiluminescent microparticle assay (CMIA) for the quantitative determination of IgG Abs to the RBD of the S1 subunit of the SARS-CoV-2 spike protein was enough to predict the CCP units with a high NAb titer. CCP donors with respective results > 850 BAU/ml SARS-CoV-2 IgG had a high probability of attaining sufficient NAb titers. Including additional variables such as donor demographics, clinical symptoms, or time of donation into a particular predictive model did not significantly increase its sensitivity and specificity. CONCLUSION: A simple quantitative serological determination of anti-SARS-CoV-2 antibodies alone is satisfactory for recruiting CCP donors with high titer NAbs.
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COVID-19 , Humanos , Vacunas contra la COVID-19 , Sueroterapia para COVID-19 , SARS-CoV-2 , Anticuerpos Antivirales , Anticuerpos Neutralizantes , Inmunoglobulina G , Inmunización Pasiva/métodosRESUMEN
BACKGROUND: The association of the ABO blood group with COVID-19 disease has been confirmed by several studies, with the blood group A patients being more susceptible and prone to a more severe clinical course of the disease. Additionally, several authors also addressed the association of ABO-types and the levels of anti-SARS-CoV-2 antibodies in convalescents, mostly supporting a theory that the non-O blood group convalescents present with higher levels of anti-SARS-CoV-2 antibodies. STUDY DESIGN AND METHODS: Since previous findings were based on small convalescent cohorts, we quantified the anti-SARS-CoV-2 antibody levels in a total of 3187 convalescent plasma donors with three commercial serological and one standard neutralizing antibody test. The majority of donors had undergone a mild form of the disease and the median time of sampling was 66 days after diagnosis. RESULTS: None of the antibody quantitation results showed any significant association with the ABO blood group types. The same result was evident in the subgroup of vaccinated individuals (n = 370) and the subgroups when stratified according to post-COVID-19 periods (0-60, 60-120, and 120-180 days). CONCLUSION: In conclusion, we found no evidence to confirm that the ABO blood group types influence the level of SARS-CoV-2 antibody response in COVID-19 convalescent plasma donors.
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Sistema del Grupo Sanguíneo ABO , COVID-19 , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Donantes de Sangre , COVID-19/terapia , Humanos , Inmunización Pasiva , SARS-CoV-2 , Sueroterapia para COVID-19RESUMEN
Pathogen reduction (PR) of selected blood components is a technology that has been adopted in practice in various ways. Although they offer great advantages in improving the safety of the blood supply, these technologies have limitations which hinder their broader use, e.g. increased costs. In this context, the European Centre for Disease Prevention and Control (ECDC), in co-operation with the Italian National Blood Centre, organised an expert consultation meeting to discuss the potential role of pathogen reduction technologies (PRT) as a blood safety intervention during outbreaks of infectious diseases for which (in most cases) laboratory screening of blood donations is not available. The meeting brought together 26 experts and representatives of national competent authorities for blood from thirteen European Union and European Economic Area (EU/EEA) Member States (MS), Switzerland, the World Health Organization, the European Directorate for the Quality of Medicines and Health Care of the Council of Europe, the US Food and Drug Administration, and the ECDC. During the meeting, the current use of PRTs in the EU/EEA MS and Switzerland was verified, with particular reference to emerging infectious diseases (see Appendix). In this article, we also present expert discussions and a common view on the potential use of PRT as a part of both preparedness and response to threats posed to blood safety by outbreaks of infectious disease.
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Transfusión de Componentes Sanguíneos , Seguridad de la Sangre , Control de Enfermedades Transmisibles , Enfermedades Transmisibles , Testimonio de Experto , Reacción a la Transfusión , Enfermedades Transmisibles/sangre , Enfermedades Transmisibles/epidemiología , Europa (Continente) , Unión Europea , Humanos , Reacción a la Transfusión/epidemiología , Reacción a la Transfusión/prevención & controlRESUMEN
Early diagnosis and treatment of giant cell arteritis (GCA) is crucial for preventing ischemic complications. Multiple serological markers have been identified; however, there is a distinct lack of predicting markers for GCA relapse and complications. Our main objective was to identify serological parameters in a large cohort of treatment-naïve GCA patients, which could support clinicians in evaluating the course of the disease. Clinical data was gathered, along with analyte detection using Luminex technology, ELISA, and nephelometry, among others. Unsupervised hierarchical clustering and principal component analysis of analyte profiles were performed to determine delineation of GCA patients and healthy blood donors (HBDs). Highest, significantly elevated analytes in GCA patients were SAA (83-fold > HBDs median values), IL-23 (58-fold), and IL-6 (11-fold). Importantly, we show for the first time significantly changed levels of MARCO, alpha-fetoprotein, protein C, resistin, TNC, TNF RI, M-CSF, IL-18, and IL-31 in GCA versus HBDs. Changes in levels of SAA, CRP, haptoglobin, ESR, MMP-1 and MMP-2, and TNF-alpha were found associated with relapse and visual disturbances. aCL IgG was associated with limb artery involvement, even following adjustment for multiple testing. Principal component analysis revealed clear delineation between HBDs and GCA patients. Our study reveals biomarker clusters in a large cohort of patients with GCA and emphasizes the importance of using groups of serological biomarkers, such as acute phase proteins, MMPs, and cytokines (e.g. TNF-alpha) that could provide crucial insight into GCA complications and progression, leading to a more personalized disease management.
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Biomarcadores/sangre , Arteritis de Células Gigantes/sangre , Anciano , Análisis por Conglomerados , Estudios de Cohortes , Diagnóstico Precoz , Femenino , Arteritis de Células Gigantes/diagnóstico , Humanos , Modelos Logísticos , Masculino , Pronóstico , RecurrenciaRESUMEN
Serum amyloid A (SAA) is a sensitive inflammatory marker rapidly increased in response to infection, injury or trauma during the acute phase. Resolution of the acute phase and SAA reduction are well documented, however the exact mechanism remains elusive. Two inducible SAA proteins, SAA1 and SAA2, with their variants could contribute to systemic inflammation. While unconjugated human variant SAA1α is already commercially available, the variants of SAA2 are not. Antibodies against SAA have been identified in apparently healthy blood donors (HBDs) in smaller, preliminary studies. So, our objective was to detect anti-SAA and anti-SAA1α autoantibodies in the sera of 300 HBDs using ELISA, characterize their specificity and avidity. Additionally, we aimed to determine the presence of anti-SAA and anti-SAA1α autoantibodies in intravenous immunoglobulin (IVIg) preparations and examine their effects on released IL-6 from SAA/SAA1α-treated peripheral blood mononuclear cells (PBMCs). Autoantibodies against SAA and SAA1α had a median (IQR) absorbance OD (A450) of 0.655 (0.262-1.293) and 0.493 (0.284-0.713), respectively. Both anti-SAA and anti-SAA1α exhibited heterogeneous to high avidity and reached peak levels between 41-50 years, then diminished with age in the oldest group (51-67 years). Women consistently exhibited significantly higher levels than men. Good positive correlation was observed between anti-SAA and anti-SAA1α. Both anti-SAA and anti-SAA1α were detected in IVIg, their fractions subsequently isolated, and shown to decrease IL-6 protein levels released from SAA/SAA1α-treated PBMCs. In conclusion, naturally occurring antibodies against SAA and anti-SAA1α could play a physiological role in down-regulating their antigen and proinflammatory cytokines leading to the resolution of the acute phase and could be an important therapeutic option in patients with chronic inflammatory diseases.