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The burden and influence of health-care associated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is unknown. We aimed to examine the use of rapid SARS-CoV-2 sequencing combined with detailed epidemiological analysis to investigate health-care associated SARS-CoV-2 infections and inform infection control measures. In this prospective surveillance study, we set up rapid SARS-CoV-2 nanopore sequencing from PCR-positive diagnostic samples collected from our hospital (Cambridge, UK) and a random selection from hospitals in the East of England, enabling sample-to-sequence in less than 24 h. We established a weekly review and reporting system with integration of genomic and epidemiological data to investigate suspected health-care associated COVID-19 cases. Between March 13 and April 24, 2020, we collected clinical data and samples from 5613 patients with COVID-19 from across the East of England. We sequenced 1000 samples producing 747 high-quality genomes. We combined epidemiological and genomic analysis of the 299 patients from our hospital and identified 35 clusters of identical viruses involving 159 patients. 92 (58%) of 159 patients had strong epidemiological links and 32 (20%) patients had plausible epidemiological links. These results were fed back to clinical, infection control, and hospital management teams, leading to infection-control interventions and informing patient safety reporting. We established real-time genomic surveillance of SARS-CoV-2 in a UK hospital and showed the benefit of combined genomic and epidemiological analysis for the investigation of health-care associated COVID-19. This approach enabled us to detect cryptic transmission events and identify opportunities to target infection-control interventions to further reduce health-care associated infections. Our findings have important implications for national public health policy as they enable rapid tracking and investigation of infections in hospital and community settings. COVID-19 Genomics UK (supported by UK Research and Innovation, the National Institute of Health Research, the Wellcome Sanger Institute), the Wellcome Trust, the Academy of Medical Sciences and the Health Foundation, and the National Institute for Health Research Cambridge Biomedical Research Centre.

Despite more than fifty years since its discovery in the 1970s, Serum Amyloid A (SAA)’s true biological functions remain enigmatic. The research so far has primarily associated SAA with chronic inflammatory conditions such as cardiovascular disease, obesity, and type 2 diabetes; its role in acute inflammation is less understood. Unlike the modest elevations observed in chronic conditions, SAA levels surge dramatically during acute inflammatory responses. Notably, approximately 2.5% of hepatic protein synthesis is devoted to SAA production during acute inflammation—despite the high energy demands required for synthesizing pro-inflammatory cytokines and immune cell activation—leaving its precise necessity unclear. Elucidating SAA’s physiological role in acute inflammation is crucial to determine the therapeutic potential of SAA inhibition for chronic inflammatory diseases, such as atherosclerosis and abdominal aortic aneurysms. The evidence suggests that SAA may play a protective role in acute inflammation, positioning it as a “double-edged sword”: detrimental in chronic inflammation, yet potentially beneficial in acute settings. This review explores the divergent roles of SAA in chronic versus acute inflammation, proposing that while SAA inhibition could offer therapeutic benefits for chronic conditions, it might pose risks during acute inflammation. As the primary transporter of SAA in circulation, high-density lipoprotein (HDL) has been shown to become dysfunctional in chronic inflammation, at least partly due to SAA’s effects. However, we propose that SAA may confer functional properties to HDL during acute inflammatory states, such as sepsis, thereby highlighting the context-dependent nature of its impact.

A recent outbreak of Zika virus in Brazil has led to a simultaneous increase in reports of neonatal microcephaly. Zika targets cerebral neural precursors, a cell population essential for cortical development, but the cause of this neurotropism remains obscure. Here we report that the neural RNA-binding protein Musashi-1 (MSI1) interacts with the Zika genome and enables viral replication. Zika infection disrupts the binding of MSI1 to its endogenous targets, thereby deregulating expression of factors implicated in neural stem cell function.We further show that MSI1 is highly expressed in neural progenitors of the human embryonic brain and is mutated in individuals with autosomal recessive primary microcephaly. Selective MSI1 expression in neural precursors could therefore explain the exceptional vulnerability of these cells to Zika infection.

We report on an Ebola virus disease (EVD) survivor who showed Ebola virus in seminal fluid 531 days after onset of disease. The persisting virus was sexually transmitted in February 2016, about 470 days after onset of symptoms, and caused a new cluster of EVD in Guinea and Liberia.

The Eastern Mediterranean Region (EMR) faces ongoing challenges in its public health system due to limited resources, logistical issues, and political disruptions. The COVID‐19 pandemic accelerated the need for stronger laboratory capacities to handle the increased demand for testing. In a phased response, EMR countries utilized the National Influenza Centers to rapidly establish and scale molecular testing for SARS‐CoV‐2, the causative agent of COVID‐19. The expansion of capacity included strong collaborations between public health bodies and private and academic sectors to decentralize and expand testing to the subnational level. To ensure that the quality of testing was not impacted by rapid expansion, national and subnational laboratories were enrolled in external quality assurance programs for the duration of the response. Implementation of genomic surveillance was prioritized for variant tracking, leading to the establishment of regional sequencing reference laboratories and the distribution of MinION sequencing platforms to complex emergency countries who previously had limited experience with pathogen sequencing. Challenges included a lack of technical expertise, including in implementing novel diagnostic assays and sequencing, a lack of bioinformatics expertise in the region, and significant logistical and procurement challenges. The collaborative approach, coordinated through the WHO Eastern Mediterranean Regional Office, enabled all 22 countries to achieve SARS‐CoV‐2 diagnostic capabilities, highlighting the pivotal role of laboratories in global health security.

Introduction The COVID‐19 pandemic placed unprecedented stress on laboratories in the Eastern Mediterranean Region. Building on existing capacity for influenza diagnostics, countries introduced COVID‐19 diagnostic support to ~100% regional coverage. A key challenge during the expansion was maintaining quality testing in laboratories, ensuring that correct results were shared with medical facilities. Methods WHO organized two rounds of independently monitored severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) external quality assurance programs (EQAP). The Public Health Laboratory (PHL) division of WHO supplied external quality assurance (EQA) panels, from the Royal College of Pathologists of Australasia Quality Assurance Programme (RCPAQAP) Australia to laboratories not enrolled in recurring Global Influenza Surveillance and Response System (GISRS) quality assurance programs, in which national influenza centers routinely participate. Results Fifteen and 14 countries participated in PHL/EQAP for SARS‐CoV‐2 between 2020 and 2022. Concordance was consistent between rounds, reaching 96.4% and 89.9%. A separate assessment of GISRS/EQAP to national‐level laboratories identified high levels of response and concordance for SARS‐CoV‐2 (100% response, 93% concordance), which was reduced for influenza (50% response rate, 80% concordance), reflecting the challenge of prioritizing pathogens during outbreaks. Conclusion The proliferation of laboratories in response to COVID‐19 was a success story from the pandemic. However, monitoring the quality of laboratories was challenging via existing EQAP. The addition of PHL/EQAP provided a mechanism to monitor performance of laboratories that were not designated as national influenza centers. While a high proportion of laboratories attained good results, continual emphasis on quality and enrollment in EQAP is key to ensuring sustainability of laboratory testing in future.

Zika virus (ZIKV), an emerging mosquito-borne flavivirus, is associated with congenital neurological complications. Here, we investigate potential pathological correlates of virus gene expression in representative ZIKV strains through RNA sequencing and ribosome profiling. In addition to the single long polyprotein found in all flaviviruses, we identify the translation of unrecognised upstream open reading frames (uORFs) in the genomic 5′ region. In Asian/American strains, ribosomes translate uORF1 and uORF2, whereas in African strains, the two uORFs are fused into one (African uORF). We use reverse genetics to examine the impact on ZIKV fitness of different uORFs mutant viruses. We find that expression of the African uORF and the Asian/American uORF1 modulates virus growth and tropism in human cortical neurons and cerebral organoids, suggesting a potential role in neurotropism. Although the uORFs are expressed in mosquito cells, we do not see a measurable effect on transmission by the mosquito vector in vivo. The discovery of ZIKV uORFs sheds new light on the infection of the human brain cells by this virus and raises the question of their existence in other neurotropic flaviviruses. Here the authors identify upstream open reading frames (uORFs), uORF1 and uORF2 in the Asian/American lineage and African uORF in the African lineage of Zika viruses, and show that uORF1 affects vimentin filaments and that the identified uORFs affect virus replication in neural cells.

The COVID‐19 pandemic highlighted the critical role of pathogen sequencing in making informed public health decisions. Initially, the Eastern Mediterranean Region faced limitations in sequencing capacity. However, with robust WHO and stakeholder support, the situation significantly improved. By 2022, COVID‐19 sequencing was underway in 22 out of 23 regional countries, with varying throughput and capacity. Notably, three genomic hubs were established in Oman, UAE, and Morocco, playing a key role in providing expanded genomics training and support across the region. While primarily for COVID‐19 surveillance, this sequencing capacity offers an opportunity to integrate genomic surveillance into existing networks. This integration can enable early detection and response to high‐threat pathogens with pandemic potential. To advance this, WHO/EMRO collaborated with stakeholders to formulate the Eastern Mediterranean Regional Genomic Surveillance Strategy for Emerging Pathogens of Pandemic Concern. Consultative meetings with regional and international genomic surveillance experts identified strategy focal points, key partners, priority pathogens, and implementation steps. As the strategy awaits member states' ratification in Q4 2023, this manuscript outlines pivotal facets defined by member states and the strategic document's key deliverables and opportunities. These efforts aim to yield a substantial positive impact within the region.

The use of real-time genomic epidemiology has enabled the tracking of the global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), informing evidence-based public health decision making. Ukraine has experienced four waves of the Coronavirus Disease 2019 (COVID-19) between spring 2020 and spring 2022. However, insufficient capacity for local genetic sequencing limited the potential application of SARS-CoV-2 genomic surveillance for public health response in the country. Herein, we report local sequencing of 103 SARS-CoV-2 genomes from patient samples collected in Kyiv in July-December 2021 using Oxford Nanopore technology. Together with other published Ukrainian SARS-CoV-2 genomes, our data suggest that the third wave of the epidemic in Ukraine (June-December 2021) was dominated by the Delta Variant of Concern (VOC). Our phylogeographic analysis revealed that in summer 2021 Delta VOC was introduced into Ukraine from multiple locations worldwide, with most introductions coming from Central and Eastern European countries. The wide geographic range of Delta introductions coincides with increased volume of travel to Ukraine particularly from locations outside of Europe in summer 2021. This study highlights the need to urgently integrate affordable and easily scaled pathogen sequencing technologies in locations with less developed genomic infrastructure, in order to support local public health decision making.