The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Um perfil UML para o Paradigma Orientado a Notificações (PON)

Este artigo apresenta uma proposta de perfil UML para a modelagem de software utilizando o Paradigma Orientado a Notificações (PON). A UML possui mecanismos de extensão que permitem a adição de novas sintaxe e semântica aos seus elementos visando a modelagem de domínios particulares de aplicação. Um conjunto desses mecanismos de extensão agrupados dentro de um pacote UML é denominado Perfil UML. Por sua vez, o PON se apresenta como uma alternativa aos Paradigmas de Programação Imperativa (PI), incluindo o Paradigma Orientado a Objetos (POO), e aos Paradigmas de Programação Declarativa (PD), propondo-se a eliminar deficiências destes nos aspectos de redundâncias e acoplamento de avaliações causais que impactam no desempenho e paralelismo/distribuição de aplicações. Este novo paradigma tem sido materializado em termos de programação, mas não possuía ainda um método formalizado para orientar os desenvolvedores na elaboração de projetos de software. Portanto, o perfil proposto define um primeiro passo na criação deste método: formalizar os principais conceitos do PON por meio da utilização de mecanismos de extensão - como estereótipos, valores etiquetados e restrições – que melhor adéquam a sua modelagem em UML. A aplicação do perfil UML é ilustrada com exemplos envolvendo a modelagem de um Simulador de Portão Eletrônico. Os resultados demonstram que o perfil criado possui grande valia na definição de programas em PON e visa sua aplicação em processos de projetos de software que utilizam este paradigma de programação

Integration between Requirements Modeling and Software Development in the Notification Oriented Paradigm: A Security System Case Study

This paper presents the integration between the requirementsmodeling approach named Notification Oriented Requirements (NOR) and theSoftware Development method known as Notification Oriented Development(NOD). This integration is demonstrated by means of the case study of asimulated access control security system implemented in the NotificationOriented Paradigm (NOP). Results show that the integration between NORmodel and NOD method is possible and facilitates the development of NOPsoftware, since NOR clarifies the necessary elements to perform the softwarestructural modeling (class model) and the behavioral modeling (high levelstates model and component model)

Notification Oriented Paradigm for Distributed Systems

Notification Oriented Paradigm (NOP) has been proposed as a newway to design software that is more efficient, decoupled, and with better performance than other paradigms. NOP is built based on a well-defined set of entities that interact by means of notifications. The way those entities are designedenables a declarative and rule-based programming model that is suitable fordistributed systems. This paper introduces a method to write distributed NOPprograms that maintains the same characteristics of performance and cohesionthat its local counterpart has. The method is presented with two case studiesthat have their design and performance compared to equivalent programs writtenwith traditional models and paradigms. The results show that distributedNOP programs behave correctly and, beyond the distribution, present similarbenefits as their single instance counterparts