Engineering of the current nucleoside-modified mRNA-LNP vaccines against SARS-CoV-2.

Currently, there are over 230 different COVID-19 vaccines under development around the world. At least three decades of scientific development in RNA biology, immunology, structural biology, genetic engineering, chemical modification, and nanoparticle technologies allowed the accelerated development of fully synthetic messenger RNA (mRNA)-based vaccines within less than a year since the first report of a SARS-CoV-2 infection. mRNA-based vaccines have been shown to elicit broadly protective immune responses, with the added advantage of being amenable to rapid and flexible manufacturing processes. This review recapitulates current advances in engineering the first two SARS-CoV-2-spike-encoding nucleoside-modified mRNA vaccines, highlighting the strategies followed to potentiate their effectiveness and safety, thus facilitating an agile response to the current COVID-19 pandemic.

Genotyping of the Major SARS-CoV-2 Clade by Short-Amplicon High-Resolution Melting (SA-HRM) Analysis.

The genome of the SARS-CoV-2 virus, the causal agent of the COVID-19 pandemic, has diverged due to multiple mutations since its emergence as a human pathogen in December 2019. Some mutations have defined several SARS-CoV-2 clades that seem to behave differently in terms of regional distribution and other biological features. Next-generation sequencing (NGS) approaches are used to classify the sequence variants in viruses from individual human patients. However, the cost and relative scarcity of NGS equipment and expertise in developing countries prevent studies aimed to associate specific clades and variants to clinical features and outcomes in such territories. As of March 2021, the GR clade and its derivatives, including the B.1.1.7 and B.1.1.28 variants, predominate worldwide. We implemented the post-PCR small-amplicon high-resolution melting analysis to genotype SARS-CoV-2 viruses isolated from the saliva of individual patients. This procedure was able to clearly distinguish two groups of samples of SARS-CoV-2-positive samples predicted, according to their melting profiles, to contain GR and non-GR viruses. This grouping of the samples was validated by means of amplification-refractory mutation system (ARMS) assay as well as Sanger sequencing.

International heterogeneity in coronavirus disease 2019 pediatric mortality rates.

Background: Severe coronavirus disease 2019 (COVID-19) is infrequent in children and shows a mortality rate of around 0.08%. This study aims to explore international differences in the pediatric mortality rate. Methods: We analyzed several countries with populations over 5 million that report disaggregated data of COVID-19 deaths by quinquennial or decennial age groups. Data were extracted from COVID-19 cases and deaths by age database, National Ministeries of Health, and the World Health Organization. Results: We included 23 countries in the analysis. Pediatric mortality varied from 0 to 12.1 deaths per million children of the corresponding age group, with the highest rate in Peru. In most countries, deaths were more frequent in the 0-4-year-old age group, except for Brazil. The pediatric/general COVID-19 mortality showed a great variation and ranged from 0% (Republic of Korea) to 10.4% (India). Pediatric and pediatric/general COVID mortality correlates strongly with 2018 neonatal mortality (r = 0.77, p < 0.001; and r = 0.88, p < 0.001, respectively), while shows a moderate or no correlation (r = 0.47, p = 0.02; and r = 0.19, p = 0.38, respectively) with COVID-19 mortality in the general population. Conclusions: International heterogeneity in pediatric COVID-19 mortality importantly parallels historical neonatal mortality. Neonatal mortality is a well-known index of the quality of a country's health system, which points to the importance of social determinants of health in pediatric COVID-19 mortality disparities. This issue should be further explored.

Introducción: La COVID-19 grave es poco frecuente en la infancia. El objetivo de este estudio fue explorar las diferencias en la tasa de mortalidad internacional por COVID-19 en la población pediátrica. Método: Se analizaron países con poblaciones superiores a 5 millones de habitantes que reporten muertes por COVID-19 con datos desglosados por grupos de edad quinquenales o decenales. Los datos se extrajeron de la base de datos COVerAge-DBs, de los ministerios nacionales de salud y de la Organización Mundial de la Salud. Resultados: Se incluyeron 23 países. La mortalidad pediátrica varió de 0 a 12.1 muertes por millón de personas del grupo de edad correspondiente, con la tasa más alta en Perú. En la mayoría de los países, las muertes fueron más frecuentes en el grupo de 0 a 4 años, excepto en Brasil. La mortalidad pediátrica/general por COVID-19 mostró una gran variación entre países y osciló entre el 0% (República de Corea) y el 10.4% (India). La mortalidad pediátrica y pediátrica/general por COVID-19 se correlaciona fuertemente con la mortalidad neonatal de 2018, mientras que tiene una moderada o nula correlación con la mortalidad por COVID-19 en la población general. Conclusiones: Existe una importante heterogeneidad internacional en la mortalidad pediátrica por COVID-19, que es paralela a la mortalidad neonatal histórica, la cual es un indicador de la calidad de los sistemas de salud y señala la importancia de los determinantes sociales de la salud en las disparidades de mortalidad pediátrica por COVID-19. Este tema debe explorarse a fondo.