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Background: Since the beginning of 2024, several European countries reported unusually high numbers of Human parvovirus B19 (B19V) infections. An increase in B19V incidence rate might have implications for blood products for direct transfusion, however, large data sets for analysis of this outbreak are missing., Study Design and Methods: B19V nucleic acid testing (NAT) of plasma donations collected between June 2018 and May 2024 from mainly Central European countries (n = 9.6 million) and the United States (n = 70.7 million) was done to the individual donation level., Results: In Central Europe, there was a marked increase in B19V incidence from November 2023 onwards, which peaked in April 2024 with a 33-fold higher than average B19V incidence versus before the COVID-19 pandemic. In the United States, a similar trend was seen, with a yet still 6-fold lower increase than in Europe at the same time. The largest increase in B19V positivity was seen in the youngest plasma donor cohort., Discussion: A B19V infection gap during the COVID-19 pandemic is likely the basis for the rebound outbreak in 2023/2024, particularly in Europe. B19V NAT of millions of plasma donations provides for large scale numbers to solidify available epidemiology insight, and to support adequate risk assessments. Based on the situation it may be prudent to consider B19V NAT for blood components specifically directed towards transfusion to higher risk recipients, or alternatively, preselecting B19V seropositive individuals or advanced age donors at higher likelihood of seropositivity and thus lower risk of virus transmission., (© 2024 The Author(s). Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Background: Human Circovirus 1 and 2 were recently described in a French hepatitis case and in two Chinese drug users. Because of its small size and presumable high resistance to both inactivation and removal by nanofilters, such viruses-if determined to be even pathogenic-should be considered with respect to the safety of plasma derivatives. We, therefore, investigated the prevalence and titer of these viruses in plasma pools before fractionation., Methods and Materials: We tested for the presence of Human Circovirus 1 and 2 by qPCR in 48 plasma pools derived from healthy donors from Europe, USA, and Japan, corresponding to more than 200,000 plasma donations., Results: We did not detect the presence of Human Circovirus 1 and 2 in any of the plasma pools, with a limit of detection of 300-600 genome copies per mL of plasma., Conclusions: These results indicate that high levels of circovirus are not widely prevalent in such donations., (© 2023 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

After >2 years of the coronavirus disease 2019 (COVID-19) pandemic, immunoglobulins (IGs) contain highly potent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibodies, based on the large proportion of United States (US) plasma donors who have gone through COVID-19 or vaccination against the virus. Neutralization of Omicron SARS-CoV-2 by antibodies generated after non-Omicron infection or vaccination has been lower though, raising concerns about the potency of IG against this new virus variant. Also, as plasma collected in the US remains the main source of IG, the neutralization of SARS-CoV-2 for plasma collected elsewhere has been less well studied. Here, we confirm Omicron neutralization by US as well as European Union plasma-derived IG lots., Competing Interests: Potential conflicts of interest. The authors are employees of Takeda Manufacturing Austria AG, Vienna, Austria. M. R. F., M. K., and T. R. K. have Takeda stock interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

The 2020 SARS-CoV-2 pandemic is caused by a zoonotic coronavirus transmitted to humans, similar to earlier events. Whether the other, seasonally circulating coronaviruses induce cross-reactive, potentially even cross-neutralizing, antibodies to the new species in humans is unclear. The question is particularly relevant for people with immune deficiencies, as their health depends on treatment with immunoglobulin preparations that need to contain neutralizing antibodies against the pathogens in their environment. Testing 54 intravenous immunoglobulin preparations, produced from plasma collected in Europe and the United States, confirmed highly potent neutralization of a seasonal coronavirus; however, no cross-neutralization of the new SARS-CoV-2 was seen., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Vaccination against measles has reduced disease, although measles virus antibody (MVAb) levels are lower after vaccination than natural infection. Immunoglobulin (IG) preparations thus contain decreasing MVAb titers. US IG lot release requires a minimum titer of MVAb, yet equivalent information is not available for other geographies. Using a measles virus neutralization assay, IG fractionated from US or EU plasma is shown to contain similar levels of MVAb always above US regulatory requirements, supportive of equivalent protection against MV infection. Thus, the dosage for post-exposure prophylaxis in the EU could be aligned with the US FDA's treatment recommendations., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Cytomegalovirus (CMV) remains one of the most important pathogens after transplantation, potentially leading to CMV disease, allograft dysfunction, acute, and chronic rejection and opportunistic infections. Immunoglobulin G (IgG) preparations with high antibody titers against CMV are a valuable adjunctive prevention and treatment option for clinicians and apart from standard intravenous immunoglobulin (IVIG), CMV hyperimmune preparations are available. The CMV antibody titer of these preparations is typically determined by Enzyme-linked immunosorbent assay (ELISA), also used for the selection of high titer plasma donors for the production of the CMV Hyperimmune product. However, CMV ELISA titers do not necessarily correlate with CMV antibody function which is determined by virus neutralization tests., Methods: CMV antibody titers were determined by both ELISA and virus neutralization assay and the IgG subclass distribution was compared between a CMV hyperimmune licensed in Europe and standard IVIG preparations., Results: Although the expected high CMV IgG ELISA antibody titers were confirmed for three lots of a CMV hyperimmune preparation, the functionally more relevant CMV neutralizing antibody titers were significantly higher for 31 lots of standard IVIG preparations. Moreover, considerably lower IgG3 levels were found for the CMV hyperimmune preparation compared with standard IVIG preparations., Conclusions: The higher functional CMV neutralization titers of standard IVIG preparations and the better availability of these preparations, suggest that these products could be a valuable alternative to the CMV hyperimmune preparation.

Replacement therapy using intravenous immunoglobulin (IVIG) preparations in people with antibody deficiencies is effective in preventing the majority of common bacterial and viral infections, yet echovirus break-through infections have occurred. Currently, only limited information on neutralization capacity variability of individual IVIG lots against the different echovirus serotypes is available. Infectivity assays were established for the most prevalent echovirus serotypes (E 9, E 11, E 13, and E 30) circulating in the United States (US) and the European Union (EU). The echovirus serotype-specific neutralization titers of 41 IVIG lots manufactured from either whole blood (Recovered) or collected by apheresis (Source) and from either the US or EU, were determined. Significantly higher (P < 0.0001) neutralization titers against E 11 and E 30 were found in IVIG lots manufactured from US Source plasma compared to US Recovered plasma. Geographically, IVIG lots made from US plasma contained significantly (P < 0.0001) higher neutralization titers against E 9 and E 11 than lots manufactured from EU plasma, whereas lots made from EU plasma showed significantly higher neutralization of E 30. To conclude, IVIG lots differ in their neutralizing antibody content against different echovirus serotypes, depending on plasma collection practices and geographic origin. Based on these results, an informed choice in selecting IVIG lots with the highest available neutralization titer against the specific echovirus serotype would seem to be beneficial during treatment of break-through infections., (2010 Wiley-Liss, Inc.)

Background: Persons with primary immune deficiency receive intravenous immunoglobulin (IVIG) as antibody replacement therapy. These patients depend on the presence of protective antibody levels against circulating pathogens in IVIG., Objectives: The incidence of hepatitis A virus (HAV) infections has been decreasing globally. We investigated whether this decrease in HAV incidence is reflected in human plasma pools and evaluated whether HAV antibody titers in IVIG preparations are still adequate for antibody replacement., Methods: By using ELISA, the HAV antibody titer of 3,953 plasma pools sourced from March 2003 through September 2008 in the European Union (EU) or United States (US) and of 169 IVIG lots manufactured from 2005 through 2007 was determined. The functionality of the HAV antibodies contained in IVIG was assessed by using a microneutralization assay., Results: The results confirm a decrease in HAV antibody titers in EU (-28%) and US (-41%) plasma. Furthermore, the mean HAV antibody content in EU (1.70 +/- 0.12 IU/mL) and US (0.82 +/- 0.09 IU/mL [mean +/- SEM]) plasma was significantly different (P = .0001). A significant difference (P < .0001) was also evident in the IVIG preparations KIOVIG (22.91 +/- 0.68 IU/mL) and Gammagard Liquid (14.60 +/- 0.48 IU/mL), respectively, made from EU or US plasma. In accordance with the ELISA results, there was a significant difference (P < .0001) in HAV neutralization titer 50% (NT(50)) values between IVIG produced from EU-sourced (2,477 +/- 265 NT(50) [1:X]) or US-sourced (844 +/- 82 NT(50) [1:X]) plasma., Conclusion: Although HAV antibody seroprevalence continues to decrease in Europe and the US, HAV antibody titers in IVIG lots appear to remain adequate for antibody replacement therapy., (Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)