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

TROPHERYMA WHIPPLEI, AGENT DE LA MALADIE DE WHIPPLE

Maladie de Whipple et Tropheryma whipplei sont de bonsexemples de l’impact des technologies modernes sur la connaissance médicale. La maladie de Whipple est une maladie chroniquedécrite il y a un siècle (plus précisément en 1907) par le pathologisteaméricain George Hoyt Whipple (Whipple, 1907). À cette époque,un trouble du métabolisme des graisses a été considéré commeresponsable de la maladie, qui fût alors nommée « lipodystrophieintestinale ». Quant à Tropheryma whipplei, la bactérie responsablede la maladie de Whip</jats:p

COVID-19 Management at IHU Méditerranée Infection: A One-Year Experience

Background: The Hospital-University Institute (IHU) Méditerranée Infection features a 27,000 square meter building hosting 700 employees and 75 hospitalized patients in the center of Marseille, France. Method: Previous preparedness in contagious disease management allowed the IHU to manage the COVID-19 outbreak by continuing adaptation for optimal diagnosis, care and outcome. We report here the output of this management. Results: From 5 March 2020, and 26 April 2021, 608,313 PCR tests were provided for 424,919 patients and 44,089 returned positive. A total of 23,390 patients with COVID-19 were followed at IHU with an overall case fatality ratio of 1.7%. Of them 20,270 were followed as outpatients with an overall CFR of 0.17%. We performed 24,807 EKG, 5759 low dose CT Scanner, and 18,344 serology. Of the 7643 nasopharyngeal samples inoculated in cell cultures 3317 (43.3%) yielded SARS-Cov-2 isolates. Finally, 7370 SARS-Cov-2 genomes were analyzed, allowing description of the first genetic variants and their implication in the epidemiologic curves. Continuous clinical care quality evaluation provided the opportunity for 155 publications allowing a better understanding of the disease and improvement of care and 132 videos posted on the IHU Facebook network, totaling 60 million views and 390,000 followers, and dealing with COVID-19, outbreaks, epistemology, and ethics in medicine. Conclusions: During this epidemic, IHU Méditerranée Infection played the role for which it has been created; useful clinical research to guarantee a high-quality diagnostic and care for patient and a recognized expertise.</jats:p

Screen-and-treat program by point-of-care of Atopobium vaginae and ă Gardnerella vaginalis in preventing preterm birth (AuTop trial): study ă protocol for a randomized controlled trial (vol 16, 470, 2015)

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The Impact of Human Immunodeficiency Virus Infection on Gut Microbiota α-Diversity: An Individual-level Meta-analysis

AbstractBackgroundWhether human immunodeficiency virus (HIV) infection impacts gut microbial α-diversity is controversial. We reanalyzed raw 16S ribosomal RNA (rRNA) gene sequences and metadata from published studies to examine α-diversity measures between HIV-uninfected (HIV–) and HIV-infected (HIV+) individuals.MethodsWe conducted a systematic review and individual level meta-analysis by searching Embase, Medline, and Scopus for original research studies (inception to 31 December 2017). Included studies reported 16S rRNA gene sequences of fecal samples from HIV+ patients. Raw sequence reads and metadata were obtained from public databases or from study authors. Raw reads were processed through standardized pipelines with use of a high-resolution taxonomic classifier. The χ2 test, paired t tests, and generalized linear mixed models were used to relate α-diversity measures and clinical metadata.ResultsTwenty-two studies were identified with 17 datasets available for analysis, yielding 1032 samples (311 HIV–, 721 HIV+). HIV status was associated with a decrease in measures of α-diversity (P &amp;lt; .001). However, in stratified analysis, HIV status was associated with decreased α-diversity only in women and in men who have sex with women (MSW) but not in men who have sex with men (MSM). In analyses limited to women and MSW, controlling for HIV status, women displayed increased α-diversity compared with MSW.ConclusionsOur study suggests that HIV status, sexual risk category, and gender impact gut microbial community α-diversity. Future studies should consider MSM status in gut microbiome analyses.</jats:sec

Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths

Autoantibodies neutralizing type I IFNs increase in prevalence over 60 years of age and underlie about 20% of all fatal COVID-19 cases.</jats:p

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

Significance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population.</jats:p

Inborn errors of type I IFN immunity in patients with life-threatening COVID-19

The genetics underlying severe COVID-19 The immune system is complex and involves many genes, including those that encode cytokines known as interferons (IFNs). Individuals that lack specific IFNs can be more susceptible to infectious diseases. Furthermore, the autoantibody system dampens IFN response to prevent damage from pathogen-induced inflammation. Two studies now examine the likelihood that genetics affects the risk of severe coronavirus disease 2019 (COVID-19) through components of this system (see the Perspective by Beck and Aksentijevich). Q. Zhang et al. used a candidate gene approach and identified patients with severe COVID-19 who have mutations in genes involved in the regulation of type I and III IFN immunity. They found enrichment of these genes in patients and conclude that genetics may determine the clinical course of the infection. Bastard et al. identified individuals with high titers of neutralizing autoantibodies against type I IFN-α2 and IFN-ω in about 10% of patients with severe COVID-19 pneumonia. These autoantibodies were not found either in infected people who were asymptomatic or had milder phenotype or in healthy individuals. Together, these studies identify a means by which individuals at highest risk of life-threatening COVID-19 can be identified. Science , this issue p. eabd4570 , p. eabd4585 ; see also p. 404 </jats:p