"A Most Equitable Drug": How the Clinical Studies of Convalescent Plasma as a Treatment for SARS-CoV-2 Might Usefully Inform Post-Pandemic Public Sector Approaches to Drug Development.

Interventional clinical studies of convalescent plasma to treat COVID-19 were predominantly funded and led by public sector actors, including blood services operators. We aimed to analyze the processes of clinical studies of convalescent plasma to understand alternatives to pharmaceutical industry biopharmaceutical research and development, particularly where public sector actors play a dominant role. We conducted a qualitative, critical case study of purposively sampled prominent and impactful clinical studies of convalescent plasma during 2020-2021.

A critical contribution in a time of crisis: Examining motivations and deterrents to COVID-19 convalescent plasma donation and future donation intentions among prospective Canadian donors.

OBJECTIVES: To understand motivations and deterrents to donate COVID-19 convalescent plasma for a clinical trial and determine whether they predict intention to donate source plasma. BACKGROUND: During the COVID-19 pandemic, Canadian Blood Services was involved in three nationally coordinated convalescent plasma clinical trials, requiring the recruitment of several thousand prospective convalescent plasma donors. Understanding the motivations and deterrents of donors in the unique context of a clinical trial and ongoing pandemic can inform recruitment for source plasma donation beyond a clinical trial. METHODS AND MATERIALS: We invited 2785 Canadians who had registered interest in donating COVID-19 convalescent plasma to participate in an online survey containing a 42-item scale on motivators of and deterrents to donation. Between April 26th and May 19th, 2021, 979 responded (35.1%). We included a final sample of 820 participants with sufficient data across all scales. Exploratory and confirmatory factor analysis determined the factor structure of the scale. Regression analysis assessed the extent to which the factors predicted intention to donate. RESULTS: Four factors were identified: 'helping relationally', 'deterrents to donation', 'social facilitators', and 'access to the donation centre', each with good internal consistency (α = 0.78-95). Higher scores on the helping relationally scale were associated with higher odds of intention to donate, whereas higher scores on the deterrents scale were associated with lower odds of intention to donate. CONCLUSION: Participants were motivated by an interest in helping people who are ill and contributing to research committed to finding treatments in a time of crisis. Outside the crisis context, blood service operators seeking to recruit source plasma donors should emphasise its lifesaving potential and the impact of donation on the community.

Genome-based taxonomic framework for the class Negativicutes: division of the class Negativicutes into the orders Selenomonadales emend., Acidaminococcales ord. nov. and Veillonellales ord. nov.

The class Negativicutes is currently divided into one order and two families on the basis of 16S rRNA gene sequence phylogenies. We report here comprehensive comparative genomic analyses of the sequenced members of the class Negativicutes to demarcate its different evolutionary groups in molecular terms, independently of phylogenetic trees. Our comparative genomic analyses have identified 14 conserved signature indels (CSIs) and 48 conserved signature proteins (CSPs) that either are specific for the entire class or differentiate four main groups within the class. Two CSIs and nine CSPs are shared uniquely by all or most members of the class Negativicutes, distinguishing this class from all other sequenced members of the phylum Firmicutes. Four other CSIs and six CSPs were specific characteristics of the family Acidaminococcaceae, two CSIs and four CSPs were uniquely present in the family Veillonellaceae, six CSIs and eight CSPs were found only in Selenomonas and related genera, and 17 CSPs were identified uniquely in Sporomusa and related genera. Four additional CSPs support a pairing of the groups containing the genera Selenomonas and Sporomusa. We also report detailed phylogenetic analyses for the Negativicutes based on core protein sequences and 16S rRNA gene sequences, which strongly support the four main groups identified by CSIs and by CSPs. Based on the results from different lines of investigation, we propose a division of the class Negativicutes into an emended order Selenomonadales containing the new families Selenomonadaceae fam. nov. and Sporomusaceae fam. nov. and two new orders, Acidaminococcales ord. nov. and Veillonellales ord. nov., respectively containing the families Acidaminococcaceae and Veillonellaceae.

Comparative proteome analysis of Acidaminococcus intestini supports a relationship between outer membrane biogenesis in Negativicutes and Proteobacteria.

The presence of bona fide outer membranes in members of the class Negativicutes is anomalous as phylogenetic analyses place this class within the phylum Firmicutes. To explore the relationships of a representative member of Negativicutes, we have performed a whole proteome BLAST analysis of Acidaminococcus intestini, which indicates that a substantial proportion (7 %) of the A. intestini proteome is closely related to sequences from members of the phylum Proteobacteria. In addition, we have identified key proteins involved in outer membrane biogenesis in A. intestini. This work highlights the need for further studies to define the relationships and evolutionary history of the Negativicutes.