Guiding equitable prioritisation of COVID-19 vaccine distribution and strategic deployment in South Africa to enhance effectiveness and access to vulnerable communities and prevent waste.

BACKGROUND: In South Africa (SA), >2.4 million cases of COVID­19 and >72 000 deaths were recorded between March 2020 and 1 August 2021, affecting the country's 52 districts to various extents. SA has committed to a COVID­19 vaccine roll-out in three phases, prioritising frontline workers, the elderly, people with comorbidities and essential workers. However, additional actions will be necessary to support efficient allocation and equitable access for vulnerable, access-constrained communities. OBJECTIVES: To explore various determinants of disease severity, resurgence risk and accessibility in order to aid an equitable, effective vaccine roll-out for SA that would maximise COVID­19 epidemic control by reducing the number of COVID­19 transmissions and resultant deaths, while at the same time reducing the risk of vaccine wastage. METHODS: For the 52 districts of SA, 26 COVID­19 indicators such as hospital admissions, deaths in hospital and mobility were ranked and hierarchically clustered with cases to identify which indicators can be used as indicators for severity or resurgence risk. Districts were then ranked using the estimated COVID­19 severity and resurgence risk to assist with prioritisation of vaccine roll-out. Urban and rural accessibility were also explored as factors that could limit vaccine roll-out in hard-to-reach communities. RESULTS: Highly populated urban districts showed the most cases. Districts such as Buffalo City, City of Cape Town and Nelson Mandela Bay experienced very severe first and second waves of the pandemic. Districts with high mobility, population size and density were found to be at highest risk of resurgence. In terms of accessibility, we found that 47.2% of the population are within 5 km of a hospital with ≥50 beds, and this percentage ranged from 87.0% in City of Cape Town to 0% in Namakwa district. CONCLUSIONS: The end goal is to provide equal distribution of vaccines proportional to district populations, which will provide fair protection. Districts with a high risk of resurgence and severity should be prioritised for vaccine roll-out, particularly the major metropolitan areas. We provide recommendations for allocations of different vaccine types for each district that consider levels of access, numbers of doses and cold-chain storage capability.

Synthesis and preliminary characterisation of charged derivatives and hydrogels from scleroglucan.

The synthesis of negatively and positively charged polyelectrolytes from scleroglucan is described. Polycarboxylates were synthesised through nucleophilic substitution with chloroacetic acid or through a selective 2,2,6,6-tetramethyl-l-piperidinyloxy (TEMPO)-mediated oxidation of the primary alcohol groups. Amine groups were introduced through nucleophilic substitution with 2-chloroethylamine or 3-chloropropylamine. Reaction conditions were varied to obtain insight into the influence of variables on the degree of substitution. The conformational behaviour of the obtained polyelectrolytes was studied as a function of pH, temperature and solvent. For the products with a low degree of modification, evidence of an ordered conformation was found, whereas the polymers with a higher degree of modification behaved as random coils in solution. The negatively charged polymers were reticulated using the Ugi four-component condensation, obtaining negatively charged hydrogels. The positively charged polymers were reticulated using diethyl squarate (3,4-diethoxy-3-cyclobutene-1,2-dion, DES) to obtain positively charged hydrogels.

Ionic polysaccharide hydrogels via the Passerini and Ugi multicomponent condensations: synthesis, behavior and solid-state NMR characterization.

Original data are provided demonstrating that the title condensations are simple and versatile methods for the synthesis of hydrogels based on a variety of carboxylated polysaccharides. In this work, the biopolymers considered are sodium hyaluronate and sodium alginate. Nonnatural carboxylated polysaccharides were commercial (carboxymethyl)cellulose or were obtained by carboxymethylation or selective oxidation of primary alcohol groups of scleroglucan and dextran. Hydrogels prepared via the Passerini reaction were transparent, alkali labile materials whereas the transparency of the Ugi gels depended on the polysaccharide, the cross-linker, and the degree of cross-linking. The Ugi gels were stable for several months at a pH ranging from 1.3 to 11 and up to temperatures over 90 degrees C. The structure of the networks was studied by means of 13C CP-MAS and 15N CP-MAS NMR spectroscopy. A quantitative NMR analysis and elemental analysis of the dry gels allowed us to estimate the efficiency of the reactions, i.e., the actual degree of cross-linking, which appeared to be about 80% of theoretical. The influence of added salt and pH on the swelling of several Ugi gels with different degrees of cross-linking was studied in a qualitative manner.

Epimerization of nonnatural uronans with mannuronan C-5-epimerases to obtain alginatelike polysaccharides.

Different polysaccharides containing D-mannose residues have been C-6-oxidized by a selective TEMPO-mediated hypohalite oxidation to obtain the corresponding uronans. These have been treated with various recombinant mannuronan C-5-epimerases and the resulting products were analyzed by 1H NMR spectroscopy. Oxidized konjac mannan could be epimerized to obtain a uronan with a content of about 12% alpha-L-gulopyranuronate (G) residues. On prolonged epimerization, beta-elimination was observed. The oxidized galactomannan locust bean gum could only be scarcely epimerized, probably due to steric effects exerted by its 26% alpha-D-galacturopyranosyl side groups. Oxidized, galactose-depleted guar gum with a alpha-D-galactosyl content of 11% could be epimerized to a G content of about 15%. With oxidized cellulose as a substrate, mainly beta-elimination was observed. It thus seems that the mannuronan C-5-epimerases employed recognize glucuronate residues and abstract proton-5 but are unable to perform the second epimerization step and instead yield beta-eliminated products.