Postpandemic Evaluation of the Eco-Efficiency of Personal Protective Equipment Against COVID-19 in Emergency Departments: Proposal for a Mixed Methods Study.

BACKGROUND: The COVID-19 pandemic has had a profound impact on emergency department (ED) care in Canada and around the world. To prevent transmission of COVID-19, personal protective equipment (PPE) was required for all ED care providers in contact with suspected cases. With mass vaccination and improvements in several infection prevention components, our hypothesis is that the risks of transmission of COVID-19 will be significantly reduced and that current PPE use will have economic and ecological consequences that exceed its anticipated benefits. Evidence is needed to evaluate PPE use so that recommendations can ensure the clinical, economic, and environmental efficiency (ie, eco-efficiency) of its use. OBJECTIVE: To support the development of recommendations for the eco-efficient use of PPE, our research objectives are to (1) estimate the clinical effectiveness (reduced transmission, hospitalizations, mortality, and work absenteeism) of PPE against COVID-19 for health care workers; (2) estimate the financial cost of using PPE in the ED for the management of suspected or confirmed COVID-19 patients; and (3) estimate the ecological footprint of PPE use against COVID-19 in the ED. METHODS: We will conduct a mixed method study to evaluate the eco-efficiency of PPE use in the 5 EDs of the CHU de Québec-Université Laval (Québec, Canada). To achieve our goals, the project will include four phases: systematic review of the literature to assess the clinical effectiveness of PPE (objective 1; phase 1); cost estimation of PPE use in the ED using a time-driven activity-based costing method (objective 2; phase 2); ecological footprint estimation of PPE use using a life cycle assessment approach (objective 3; phase 3); and cost-consequence analysis and focus groups (integration of objectives 1 to 3; phase 4). RESULTS: The first 3 phases have started. The results of these phases will be available in 2023. Phase 4 will begin in 2023 and results will be available in 2024. CONCLUSIONS: While the benefits of PPE use are likely to diminish as health care workers' immunity increases, it is important to assess its economic and ecological impacts to develop recommendations to guide its eco-efficient use. TRIAL REGISTRATION: PROSPERO CRD42022302598; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=302598. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50682.

Plasmodium infection is associated with cross-reactive antibodies to carbohydrate epitopes on the SARS-CoV-2 Spike protein.

Sero-surveillance can monitor and project disease burden and risk. However, SARS-CoV-2 antibody test results can produce false positive results, limiting their efficacy as a sero-surveillance tool. False positive SARS-CoV-2 antibody results are associated with malaria exposure, and understanding this association is essential to interpret sero-surveillance results from malaria-endemic countries. Here, pre-pandemic samples from eight malaria endemic and non-endemic countries and four continents were tested by ELISA to measure SARS-CoV-2 Spike S1 subunit reactivity. Individuals with acute malaria infection generated substantial SARS-CoV-2 reactivity. Cross-reactivity was not associated with reactivity to other human coronaviruses or other SARS-CoV-2 proteins, as measured by peptide and protein arrays. ELISAs with deglycosylated and desialated Spike S1 subunits revealed that cross-reactive antibodies target sialic acid on N-linked glycans of the Spike protein. The functional activity of cross-reactive antibodies measured by neutralization assays showed that cross-reactive antibodies did not neutralize SARS-CoV-2 in vitro. Since routine use of glycosylated or sialated assays could result in false positive SARS-CoV-2 antibody results in malaria endemic regions, which could overestimate exposure and population-level immunity, we explored methods to increase specificity by reducing cross-reactivity. Overestimating population-level exposure to SARS-CoV-2 could lead to underestimates of risk of continued COVID-19 transmission in sub-Saharan Africa.

Structure-guided insights into potential function of novel genetic variants in the malaria vaccine candidate PfRh5.

The recent stall in the global reduction of malaria deaths has made the development of a highly effective vaccine essential. A major challenge to developing an efficacious vaccine is the extensive diversity of Plasmodium falciparum antigens. While genetic diversity plays a major role in immune evasion and is a barrier to the development of both natural and vaccine-induced protective immunity, it has been under-prioritized in the evaluation of malaria vaccine candidates. This study uses genomic approaches to evaluate genetic diversity in next generation malaria vaccine candidate PfRh5. We used targeted deep amplicon sequencing to identify non-synonymous Single Nucleotide Polymorphisms (SNPs) in PfRh5 (Reticulocyte-Binding Protein Homologue 5) in 189 P. falciparum positive samples from Southern Senegal and identified 74 novel SNPs. We evaluated the population prevalence of these SNPs as well as the frequency in individual samples and found that only a single SNP, C203Y, was present at every site. Many SNPs were unique to the individual sampled, with over 90% of SNPs being found in just one infected individual. In addition to population prevalence, we assessed individual level SNP frequencies which revealed that some SNPs were dominant (frequency of greater than 25% in a polygenomic sample) whereas most were rare, present at 2% or less of total reads mapped to the reference at the given position. Structural modeling uncovered 3 novel SNPs occurring under epitopes bound by inhibitory monoclonal antibodies, potentially impacting immune evasion, while other SNPs were predicted to impact PfRh5 structure or interactions with the receptor or binding partners. Our data demonstrate that PfRh5 exhibits greater genetic diversity than previously described, with the caveat that most of the uncovered SNPs are at a low overall frequency in the individual and prevalence in the population. The structural studies reveal that novel SNPs could have functional implications on PfRh5 receptor binding, complex formation, or immune evasion, supporting continued efforts to validate PfRh5 as an effective malaria vaccine target and development of a PfRh5 vaccine.

Leveraging genome editing to functionally evaluate Plasmodium diversity.

The ambitious goal of malaria elimination requires an in-depth understanding of the parasite's biology to counter the growing threat of antimalarial resistance and immune evasion. Timely assessment of the functional impact of antigenic diversity in the early stages of vaccine development will be critical for achieving the goal of malaria control, elimination, and ultimately eradication. Recent advances in targeted genome editing enabled the functional validation of resistance-associated markers in Plasmodium falciparum, the deadliest malaria-causing pathogen and strain-specific immune neutralization. This review explores recent advances made in leveraging genome editing to aid the functional evaluation of Plasmodium diversity and highlights how these techniques can assist in prioritizing both therapeutic and vaccine candidates.

Plasmodium infection induces cross-reactive antibodies to carbohydrate epitopes on the SARS-CoV-2 Spike protein.

Individuals with acute malaria infection generated high levels of antibodies that cross-react with the SARS-CoV-2 Spike protein. Cross-reactive antibodies specifically recognized the sialic acid moiety on N-linked glycans of the Spike protein and do not neutralize in vitro SARS-CoV-2. Sero-surveillance is critical for monitoring and projecting disease burden and risk during the pandemic; however, routine use of Spike protein-based assays may overestimate SARS-CoV-2 exposure and population-level immunity in malaria-endemic countries.

Assessing the functional impact of PfRh5 genetic diversity on ex vivo erythrocyte invasion inhibition.

The PfRh5-Basigin ligand-receptor interaction is an essential step in the merozoite invasion process and represents an attractive vaccine target. To reveal genotype-phenotype associations between naturally occurring allelic variants of PfRh5 and invasion inhibition, we performed ex vivo invasion inhibition assays with monoclonal antibodies targeting basigin coupled with PfRh5 next-generation amplicon sequencing. We found dose-dependent inhibition of invasion across all isolates tested, and no statistically significant difference in invasion inhibition for any single nucleotide polymorphisms. This study demonstrates that PfRh5 remains highly conserved and functionally essential, even in a highly endemic setting, supporting continued development as a strain-transcendent malaria vaccine target.