key: cord-0926643-6e54dkpp authors: Garraud, O.; Burnouf, T. title: Convalescent Covid-19 plasma: Back-to-basics and ethics, and next steps date: 2021-08-03 journal: Transfus Clin Biol DOI: 10.1016/j.tracli.2021.07.005 sha: a86107a4215c2540bca63228c6271030b9313ec4 doc_id: 926643 cord_uid: 6e54dkpp nan The SARS-CoV-2 infection is worldwide; the virus mutates fast, speeding the spreading of the infection and subsequent disease due to numerous consecutive emerging variants, each more infectious than the previous one. Efficient vaccines have been made available against the first viral strains within an amazingly short period of time [1] . Despite this tremendous achievement, too few people can get full vaccination schedule to successfully stop the virus progression, and many places in the world are currently struggling to fight both the virus transmission and the disease especially in the most vulnerable populations [2] . Vaccination is recognized as the sole protective measure that can be set in place readily to limit the pandemics and to eventually allow coming back to normal life. Convalescent plasma therapy has swiftly been tested for its safety and efficacy to limit Covid-19 pathology in the sickest [3, 4] , as has been the case when several past viral infections have threatened public health during the last century [5] . A year back, points to consider and questions were raised about applicability [6, 7] , logistic issue, impact, safety and usefulness of plasma passive immunotherapy in Covid-19 patients [8, 9] ; other issues dealing with ethics of plasma collection and allocation [10] [11] [12] [13] , and best protocol scaling have been addressed, and some of these questions have been resolved. Large cohorts of treated patients versus controls have been scrutinized and results on efficacy were not as straightforward as initially expected [14] [15] [16] [17] [18] . An innumerable number of studies have been proposed for publication in journals of different specialties; as could have been anticipated, studies coming from almost unknown teams experienced difficulties to be published, contrary to the ones led by key opinion leaders. Transfusion Clinique et Biologique made a considerable effort to emphasize experiences from countries reporting struggles to raise sustainable plasma therapy while facing organizational, financial, and networking difficulties [19] [20] [21] [22] [23] [24] [25] [26] [27] ; the Journal's goal has been to assist teams from countries facing similar situations and to disseminate valuable experiences. As the vaccine programs develop-especially in high-income countries-reports on convalescent plasma therapy decrease reciprocally. For the time being, good evidence exists that antibodies raised post natural infection and/or using vaccines licensed by recognized regulatory agencies (i.e. the U.S. Food and Drug Administration and the European Medicines Agency) efficiently block the virus variant entry into people's respiratory cells. One may however question whether stepping back from convalescent plasma therapy programs is justified and wise. Several reasons argue against such a position. 1) Several clinical studies suggest that early passive immunotherapy using high-titre plasma can save patients if administered within three days of disease onset and prior to active seroconversion [28, 29] ; 2) Convalescent plasma therapy has been demonstrated beneficial in treatment of Covid-19 patients with various causes of immunodeficiency [30] ; 3) Convalescent plasma may thus well still be a justified therapeutic option, if used wisely, in certain countries that cannot afford expensive biologicals (such as monoclonal antibodies) to limit pathological hyper-inflammation; 4) Novel SARS-CoV-2 variants may eventually be loosely targeted by the immunity procured by current vaccines (at least until vaccine production is adapted and the ad hoc shots given to exposed populations) [31] ; 5) If interrupted, it would take time, effort and considerable organization to re-initiate plasma collection and therapy, when needed (as may be the case if no other suitable therapeutic option is available for any reason, or if supply of vaccines or monoclonal antibodies is interrupted). It must be kept in mind that an efficient plasma therapy program relies primarily on voluntary blood donors who must not be demotivated. For example, the experience acquired from the recent Ebola virus infection, where convalescent plasma collection was initiated and then discontinued when the epidemics resolved, has not been maintained, forcing many teams to rescale convalescent plasma collection, quality control and transfusion procedures, thereby delaying the implementation of Covid-19 convalescent plasma therapy. Some may claim that it is unethical to collect therapeutic plasma not immediately intended for direct clinical use. Still, as the SARS-CoV-2 progression goes on, international assistance programs could be put in place -i.e. with a special derogation from e.g. the European regulatory authorities-to supply safe pathogen-reduced therapeutic plasma to resource-constrained countries facing slow vaccine programs and a lack of intensive care facilities. Effort has been made to elaborate safety and quality programs designed for low and medium-income countries regarding plasma collection, pro-cessing, and use [32] [33] [34] [35] . Thus, we urge public health authorities at global level, including in low-and middle-income countries, to consider maintaining the expertise and infrastructure for convalescent plasma collection. Besides, an ad hoc continuous influx and availability of therapeutic Covid-19 plasma as a safeguard and contingency for possibly urgent clinical use under the optimized therapeutic conditions known to-date (i.e. high titre and early clinical use) should be ensured. This would avoid the risk of becoming the hostage of an unethical plasma collection system put in place in case of an emergency situation [36] . The authors declare that they have no competing interest. The opinions expressed by the authors in this editorial do not necessarily reflect those for employers and chaired organizations. 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OG is the Chairman of the European and Mediterranean Initiative in Transfusion Medicine (EMITm). TB is the Secretary of the Working Party on Global Blood Safety and a member of the working group on COVID-19 convalescent plasma of the International Society of Blood Transfusion.