Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease , has spurred a global health crisis. To date, there are no proven options for prophylaxis for those who have been exposed to SARS-CoV-2, nor therapy for those who develop COVID-19. Immune (i.e. "convalescent") plasma refers to plasma that is collected from individuals, following resolution of infection and development of antibodies. Passive antibody administration through transfusion of convalescent plasma may offer the only short-term strategy to confer immediate immunity to susceptible individuals. There are numerous examples, where convalescent plasma has been used successfully as post-exposure prophylaxis and/or treatment of infectious diseases, including other outbreaks of coronaviruses (e.g. SARS-1, Middle East Respiratory Syndrome [MERS]). Convalescent plasma has also been used in the COVID-19 pandemic; limited data from China suggest clinical benefit, including radiological resolution, reduction in viral loads and improved survival. Globally, blood centers have robust infrastructure to undertake collections and construct inventories of convalescent plasma to meet the growing demand. Nonetheless, there are nuanced challenges, both regulatory and logistical, spanning donor eligibility, donor recruitment, collections and transfusion itself. Data from rigorously controlled clinical trials of convalescent plasma are also few, underscoring the need to evaluate its use objectively for a range of indications (e.g. prevention vs treatment) and patient populations (e.g. age, comorbid disease). We provide an overview of convalescent plasma, from evidence of benefit, regulatory considerations, logistical work flow and proposed clinical trials, as scale up is brought underway to mobilize this critical resource.
The proximate cause of autoantibodies characteristic of systemic autoimmune diseases has been controversial. One hypothesis is that autoantibodies are the result of polyclonal nonspecific B cell activation. Alternatively, autoantibodies could be the result of antigen-driven B cell activation, as observed in secondary immune responses. We have approached this question by studying monoclonal anti-DNA autoantibodies derived from unmanipulated spleen cells of the autoimmune MRL/lpr mouse strain. This analysis shows that anti-DNAs, like rheumatoid factors (19), are the result of specific antigen-driven stimulation. In addition, correlation of sequences with fine specificity shows that: (a) somatic mutations can cause specificity for dsDNA and that such mutations are selected for; (b) arginine residues play an important role in determining specificity; and (c) anti-idiotypes that recognize the majority of anti-DNA are probably not specific for any one family of V regions.
Recruitment of low-risk blood donors in developing countries is challenging. We studied the attitudes towards blood donation in several populations in a city in Western China. A survey of knowledge, attitude and practice was performed including 1280 individuals from eight distinct populations in Urumqi, Xinjiang Uyghur Autonomous Region, China. Included were Han Chinese and Uyghur populations of blood donors, non-donors, injection drug users, students and factory workers. Knowledge about blood donation varied between the groups. Factors motivating blood donation included social pressure, desire to know screening results and altruism. Inhibiting factors included fear of contracting an infection and other adverse health effects, including loss of vitality. Misconceptions about the effects of blood donation are widespread, even among educated persons in Urumqi. Fear of acquiring a serious infection may have been increased by the reports of HIV acquisition during plasma donations in China.
Background
The Recipient Epidemiology and Donor Evaluation Study -III (REDS-III) is a 7-year multicenter transfusion safety research initiative launched in 2011 by the National Heart, Lung, and Blood Institute.
Study design
The domestic component involves 4 blood centers, 12 hospitals, a data coordinating center, and a central laboratory. The international component consists of distinct programs in Brazil, China, and South Africa which involve US and in-country investigators.
Results
REDS-III is using two major methods to address key research priorities in blood banking/transfusion medicine. First, there will be numerous analyses of large “core” databases; the international programs have each constructed a donor/donation database while the domestic program has established a detailed research database that links data from blood donors and their donations, the components made from these donations, and data extracts from the electronic medical records of the recipients of these components. Secondly, there are more than 25 focused research protocols involving transfusion recipients, blood donors, or both that are either in progress or scheduled to begin within the next 3 years. Areas of study include transfusion epidemiology and blood utilization; transfusion outcomes; non-infectious transfusion risks; HIV-related safety issues (particularly in the international programs); emerging infectious agents; blood component quality; donor health and safety; and other donor issues.
Conclusions
It is intended that REDS-III serve as an impetus for more widespread recipient and linked donor-recipient research in the US as well as to help assure a safe and available blood supply in the US and in international locations.
To recruit voluntary donors effectively in China and other countries with traditional cultures, efforts need to counteract traditional beliefs and perceptions of risk that discourage donation by emphasizing the benefits, safety mechanisms, physiology, and epidemiology of blood donation. In China, there is a rich opportunity to convert prior employer-organized donors into volunteer donors, and the institution of a confidential predonation screening system may help to facilitate truthful risk factor disclosure.
Qualified donations after routine blood donor screening still carry potential risk for transmitting HEV. HEV antigen screening could be one measure to reduce the risk of HEV transmission by blood transfusion.
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