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What is the subsequent risk of mental disorders among individuals with SARS-CoV-2 infection, and are the associations specific for COVID-19?

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In a recent study published in JAMA Psychiatry, researchers estimated psychiatric disorders and psychotropic medication usage risks among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected versus uninfected individuals, those who did not undergo coronavirus disease 2019 (COVID-19) testing, and individuals hospitalized due to non-COVID-19 respiratory tract infections.

Study: COVID-19 and Risk for Mental Disorders Among Adults in Denmark. Image Credit: mapush/Shutterstock.comStudy: COVID-19 and Risk for Mental Disorders Among Adults in Denmark. Image Credit: mapush/Shutterstock.com

Background

COVID-19 has caused unprecedented morbidity and mortality across the globe. Besides the respiratory tract, SARS-CoV-2 may infect various organs, including the brain, as indicated by studies reporting an increased prevalence of persistent neuropsychiatric sequelae of acute COVID-19.

The neuropsychiatric effects may result from indirect immunological mechanisms, and therefore, the impact of SARS-CoV-2 infection on the brain may be comparable to that observed after other conditions of similar severity.

However, national-level studies assessing the neuropsychiatric outcomes of SARS-CoV-2 infections are scarce. Moreover, previous studies included specific cohorts such as United States (US) veterans or individuals from healthcare organizations, limiting the generalizability of the study findings.

The results may also be biased due to potential confounding factors such as socioeconomic status and family history of psychiatric disorders.

About the study

In the present national-level study, researchers investigated psychiatric disorders risks among SARS-CoV-2-positive individuals and whether the associations were specific to SARS-CoV-2 infections.

The study included 4,152,792 adult residents of Denmark registered with the Danish Civil Registration System and alive between 1 January and 1 March 2020, excluding 616,546 individuals with prior history of mental disorders.

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Follow-up assessments were performed until 31 December 2021 until the censoring, outcome, or termination of follow-up. The study exposure was polymerase chain reaction (PCR) results for SARS-CoV-2 infection and associated hospitalization.

The outcomes were the risk of incident mental disorders [according to the International Classification of Diseases, Tenth Revision (ICD-10) codes] and psychotropic medication use [based on the Anatomical Therapeutic Chemical (ATC) codes].

Individuals hospitalized with an infection between 2010 and 1 March 2020 were excluded from the analysis. Survival analysis was performed using Cox proportional hazards regression modeling to calculate the hazard rate ratio (HRR) values.

Data adjustments were made for gender, age, psychiatric disorders among parents, level of education, household income, employment status, and comorbidities assessed using the Charlson Comorbidity Index (CCI).

Data were obtained from Danish national registries linked to the participants using unique personal identification numbers and anonymized for analysis.

The registries included the Danish Psychiatric Central Research Register, the Danish Microbiology Database, the Danish National Hospital Registry, the Danish National Prescription Registry, and the Database for Integrated Labour Market Research.

Results

The sample population included 501,110 individuals who had not undergone PCR testing (mean age of 61 years; 55% males), 526,749 PCR-positive (mean age of 41 years; 50% males), and 3,124,933 PCR-negative (mean age of 49 years; 51% females).

Most (93%) of individuals were followed for two years. In total, the team analyzed 39,528,002 PCR reports.

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Psychiatric disorders risks increased among PCR-positive individuals (HRR 1.2) and PCR-negative individuals (HRR 1.4) in comparison to those who did not undergo PCR testing.

Compared to PCR-negative individuals, incident psychiatric disorders risks were lower among PCR-positive individuals aged between 18 and 29 years (hazard rate ratio 0.8), whereas those aged ≥70.0 years had an elevated risk (hazard rate ratio 1.3).

Similar trends were observed for the use of psychotropic medications, with a lower risk among individuals aged between 18 and 29 years (hazard rate ratio 0.8) and a higher risk for individuals aged ≥70.0 years (HRR 1.6).

Incident psychiatric disorders risks were considerably higher for hospitalized COVID-19 patients than the public (HRR 2.5); however, there were non-significant differences in risk compared to individuals hospitalized for infections not associated with COVID-19 (HRR 1.0).

Conclusions

Overall, the study findings showed that the risk of mental disorders among SARS-CoV-2-infected individuals was comparable to that among uninfected individuals, except for individuals aged ≥70.0 years.

However, individuals with SARS-CoV-2 infection-associated hospitalizations had a considerably higher risk than the public but a similar risk as those with hospitalizations due to other infections. The findings indicated that mental health deterioration after COVID-19-associated hospitalization occurs commonly but is not more frequent than after other equivalently severe infections.

Further research must be conducted with longer follow-ups and immune system-associated biomarkers to improve our understanding of the effects of COVID-19 severity on post-infectious mental health.

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Journal reference:

Honokiol inhibits replication of SARS-CoV-2 in several cell types

A compound called honokiol, which is found in the bark of multiple species of magnolia tree, inhibits replication of SARS-CoV-2 virus in several types of cells, according to a team of researchers in the Netherlands. The research is published in Microbiology Spectrum, a journal of the American Society for Microbiology.

The researchers found that Honokiol inhibits replication of SARS-CoV-2 in several cell types, causing production of infectious SARS-CoV-2 particles in treated cells to fall to around 1,000th of the previous level.

The compound also inhibited replication of other highly pathogenic human coronaviruses, including MERS- and SARS-CoV.

This suggests that it has a broad spectrum of activity and would likely also inhibit novel coronaviruses that might emerge in the future.”

Martijn J. van Hemert, Ph.D., Associate Professor, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands

The motivation for the research was the lack of vaccines and treatments early in the pandemic, and the desire to be prepared for the next new coronavirus. To this end, van Hemert emphasized that his group, as well as others from around the world, responded to COVID-19 by testing many compounds for antiviral effects.

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“If honokiol can be developed into a drug, possibly in combination with other compounds, stockpiling it would help us to increase our preparedness for the emergence of the next coronavirus,” said van Hemert. “Broad-spectrum drugs could then be used to treat early patients and prevent spread, or they could be used prophylactically among healthcare workers, and in high-risk groups, such as among nursing home residents.”

Honokiol also has anti-inflammatory properties, van Hemert noted. That, he said, could be helpful in cases where patients wait until a relatively late stage of the disease to obtain medical treatment-;a frequent occurrence-;by which time the body’s own inflammatory responses to the infection are causing symptoms. “At that point, inhibition of virus replication might no longer be helpful, but honokiol’s anti-inflammatory response might mitigate the illness,” van Hemert explained.

Honokiol inhibits a later step of the viral replication cycle-;one that takes place after the virus has entered the cell. The investigators suspect that honokiol does so by triggering processes in the host cell that impede replication of the virus. It did so in the case of the original SARS-CoV-2 variants, and also in that of the more recent omicron variants.

At this early stage in the research, “Our study merely provides the basis for further research into potential therapeutic applications,” said van Hemert. “It is important to mention that it is too early to claim that honokiol might be used in SARS-CoV-2 patients. This requires much more research and-;if successful-;properly conducted clinical trials.”

Van Hemert learned about honokiol from Jack Arbiser, M.D., Ph.D., of Emory School of Medicine, during the early stages of the pandemic. Arbiser had been researching honokiol’s anticancer properties, and he told van Hemert he thought that the effects of the compound on the host cell might be beneficial for treatment of COVID-19 patients as well.

Clarisse Salgado-Benvindo, a Ph.D. student in van Hemert’s group, performed most of the experiments, using cultured cells that the researchers infected with SARS-CoV-2, or the highly pathogenic coronaviruses SARS-CoV and MERS-CoV. Experimenters worked inside a BSL-3 lab, which is a special high containment lab, while wearing protective suits with full-face masks to prevent infection.

Source:
Journal reference:

Salgado-Benvindo, C., et al. (2023) Honokiol Inhibits SARS-CoV-2 Replication in Cell Culture at a Post-Entry Step. Microbiology Spectrum. doi.org/10.1128/spectrum.03273-22.

Mouse study offers clues to developing an effective vaccine for Klebsiella bacteria

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A mouse study at Washington University School of Medicine in St. Louis points to data that could be key to developing an effective vaccine for the bacterium Klebsiella pneumoniae. The bug is often resistant to antibiotics, making it difficult to treat in some.

In the U.S., the bacterium Klebsiella pneumoniae is a common cause of urinary tract infection, bloodstream infection and pneumonia. While infections with the bacterium can be easily treated in some, Klebsiella has a dangerous flip side: It also is frequently resistant to antibiotics, making it extraordinarily difficult to treat in others. About half of people infected with a hypervirulent, drug-resistant strain of the bacterium die.

Scientists are working on vaccines for Klebsiella, but the optimal vaccine design is still unknown. However, a new study in mice by scientists at Washington University School of Medicine in St. Louis and Omniose, a St. Louis startup company specializing in vaccine production, provides critical data that could be key to developing an effective vaccine for Klebsiella. The findings, published in PLoS Pathogens, are a step toward taming the superbug.

When you think about the bugs that can be resistant to almost all antibiotics — the scary superbugs in the news — a lot of them are strains of Klebsiella. For a long time, the bacterium wasn’t even a pressing issue. But now it is, due to an explosion in antibiotic-resistant Klebsiella. Our goal is to diminish Klebsiella’s superbug status by developing a vaccine before hypervirulent or resistant strains sicken and kill even more people.”

David A. Rosen, MD, PhD, study’s senior author, assistant professor of pediatrics and of molecular microbiology at Washington University

Hypervirulent Klebsiella strains have spread globally, often causing community-acquired infections.

In the U.S., Klebsiella infections primarily occur in health-care facilities where medically vulnerable patients are immunocompromised, require long courses of antibiotics to treat other conditions, have chronic diseases, or are elderly people or newborns. “But now we’re seeing the emergence of hypervirulent strains dangerous enough to cause serious disease or death among healthy people in the community,” Rosen said.

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Most concerning among scientists are the strains of Klebsiella impervious to carbapenems, a class of broad-spectrum antibiotics used to treat the most severe bacterial infections. For this reason, the World Health Organization and the U.S. Centers for Disease Control and Prevention have identified carbapenem-resistant Klebsiella as an urgent threat to public health.

The rod-shaped bacterium is immobile and, like chocolate-covered candies, encapsulated in sugar coatings. In the new study, researchers created two experimental vaccines based on two different sugars, or polysaccharides, on Klebsiella’s surface: the terminal sugars on lipopolysaccharide, called O-antigen, and a capsular polysaccharide, or K-antigen. Since sugars by themselves tend to produce weak immune responses, the researchers linked each of the sugars to a protein to boost the immune response, creating so-called conjugate vaccines. Sugar-protein conjugate vaccines have proven successful in combating several bacteria including Streptococcus pneumoniae, the most common cause of pneumonia. Historically, this connection between the sugar and protein carrier has been achieved using synthetic chemistry in a test tube; however, the vaccines created for this study are called bioconjugate vaccines, because the researchers connected the sugar to the protein all within an engineered bacteria system.

Once the vaccines were created, the researchers tested the experimental bioconjugate vaccines’ ability to protect mice from disease caused by Klebsiella.

“It turned out that the capsule vaccine was far superior to the O-antigen vaccine,” said the study’s first author, Paeton Wantuch, PhD, a postdoctoral associate in Rosen’s lab. “Mice that received the capsule vaccine were significantly more likely to survive Klebsiella infection in their lungs or their bloodstream than mice that received the O-antigen vaccine.”

Both vaccines elicited high levels of antibodies against their respective targets. But the antibodies against the O-antigen just weren’t as effective as the ones against the capsule. In some strains of Klebsiella, the O-antigen may be obscured by other sugars, so the antibodies that target the O-antigen cannot make contact with their target.

“Our findings suggest that we may also need to include the capsule-based antigens in vaccine formulations developed against Klebsiella,” Rosen said. “This is why it’s so important for us to continue studying antibody-antigen interactions in the different strains, with the goal of identifying the ideal vaccine composition for clinical trials soon. The need has never been more imperative, especially as Klebsiella’s drug-resistant, hypervirulent strains become stronger, bolder and more dangerous to human health.”

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Source:
Journal reference:

Wantuch, P. L., et al. (2023) Area-deprivation, social care spending and the rates of children in care proceedings in local authorities in Engl Capsular polysaccharide inhibits vaccine-induced O-antigen antibody binding and function across both classical and hypervirulent K2:O1 strains of Klebsiella pneumoniae. PLOS Pathogens. doi.org/10.1371/journal.ppat.1011367.

Novel computational platform can expand the pool of cancer immunotherapy targets

Researchers at Children’s Hospital of Philadelphia (CHOP) and the University of California, Los Angeles (UCLA) have developed a computational platform capable of discovering tumor antigens derived from alternative RNA splicing, expanding the pool of cancer immunotherapy targets. The tool, called “Isoform peptides from RNA splicing for Immunotherapy target Screening” (IRIS), was described in a paper published today in the Proceedings of the National Academy of Sciences.

Immunotherapy has revolutionized cancer treatment, but for many cancers including pediatric cancers, the repertoire of antigens is incomplete, underscoring a need to expand the inventory of actionable immunotherapy targets. We know that aberrant alternative RNA splicing is widespread in cancer and generates a range of potential immunotherapy targets. In our study, we were able to show that our computational platform was able to identify immunotherapy targets that arise from alternative splicing, introducing a broadly applicable framework for discovering novel cancer immunotherapy targets that arise from this process.”

Yi Xing, PhD, co-senior author, director of the Center for Computational and Genomic Medicine at CHOP

Cancer immunotherapy has ushered in a sea change in the treatment of many hematologic cancers, harnessing the power of a patient’s own immune system to fight the disease. Chimeric antigen receptor T-cell (CAR-T) and T cell receptor-engineered T cell (TCR-T) therapies modify a patient’s own T cells to attack known antigens on the surface of cancer cells and have often led to durable responses for cancers that were once considered incurable. However, the field has encountered challenges in the solid tumor space, in large part due to a lack of known and suitable targets for these cancers, highlighting the need for novel approaches to expand the pool of immunotherapy targets.

Alternative splicing is an essential process that allows for one gene to code for many gene products, based on where the RNA is cut and joined, or spliced, before being translated into proteins. However, the splicing process is dysregulated in cancer cells, which often take advantage of this process to produce proteins that promote growth and survival, allowing them to replicate uncontrollably and metastasize. This happens in many adult and pediatric cancers. Scientists have suggested splicing dysregulation could be a source of novel tumor antigens for immunotherapy, but identifying such antigens has been a challenge.

To address this difficulty, the researchers created IRIS to leverage large-scale tumor and normal RNA sequencing data and incorporate multiple screening approaches to discover tumor antigens that arise due to alternative splicing. Integrating RNA sequencing-based transcriptomics data and mass spectrometry-based proteomics data, the researchers showed that hundreds of IRIS-predicted TCR targets are presented by human leukocyte antigen (HLA) molecules, the part of the human immune system that presents antigens to T cells.

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The researchers then applied IRIS to RNA sequencing data from neuroendocrine prostate cancer (NEPC), a metastatic and highly lethal disease known to involve shifts in RNA splicing, as discovered in a prior study by CHOP and UCLA researchers. From 2,939 alternative splicing events enriched in NEPC, IRIS predicted 1,651 peptides as potential TCR targets. The researchers then applied a more stringent screening test, which prioritized 48 potential targets. Interestingly, the researchers found that these targets were highly enriched for peptides encoded by short sequences of less than 30 nucleotides in length – also known as “microexons” – which may arise from a unique program of splicing dysregulation in this type of cancer.

To validate the immunogenicity of these targets, the researchers isolated T cells reactive to IRIS-predicted targets, and then used single-cell sequencing to identify the TCR sequences. The researchers modified human peripheral blood mononuclear cells with seven TCRs and found they were highly reactive against targets predicted by IRIS to be good immunotherapy candidates. One TCR was particularly efficient at killing tumor cells expressing the target peptide of interest.

“Immunotherapy is a powerful tool that has had a significant impact on the treatment of some cancers, but the benefits have not been fully realized in many lethal cancers that could benefit from this approach,” said Owen N. Witte, MD, University Professor of Microbiology, Immunology, and Molecular Genetics and member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. “The discovery of new antigenic targets that may be shared among different patients – and even different tumor types – could be instrumental in expanding the value of cell-based therapies. Analyzing massive amounts of data on tumor and normal tissues, which requires sophisticated computational tools like those developed by the Xing Lab, provides actionable insights on targets that one day could be tested in the clinic.”

“This proof-of-concept study demonstrates that alternatively spliced RNA transcripts are viable targets for cancer immunotherapy and provides a big data and multiomics-powered computational platform for finding these targets,” Dr. Xing added. “We are applying IRIS for target discovery across a wide range of pediatric and adult cancers. We are also developing a next-generation IRIS platform that harnesses newer transcriptomics technologies, such as long read and single cell analysis.”

This research was supported in part by the Immuno-Oncology Translational Network (IOTN) of the National Cancer Institute’s Cancer Moonshot Initiative, other National Institutes of Health funding, the Parker Institute for Cancer Immunotherapy, the Cancer Research Institute, and the Ressler Family Fund.

Source:
Journal reference:

Pan, Y., et al. (2023) IRIS: Discovery of cancer immunotherapy targets arising from pre-mRNA alternative splicing. PNAS. doi.org/10.1073/pnas.2221116120.

MGI Empowers the Completion of Nearly 60,000 Samples for The Million Microbiome of Humans Project

SHENZHEN, China, 10 May 2023 – MGI Tech Co. Ltd. (MGI), a company committed to building core tools and technology to lead life science, today shared that a total of nearly 60,000 samples have been sequenced among 21 institutes and over 10 participating nations throughout Europe, as part of the Million Microbiome of Humans Project (MMHP) that was officially launched in 2019.

Image Credit: MGI

The project was launched as a joint effort by the Karolinska Institute of Sweden, Shanghai National Clinical Research Center for Metabolic Diseases in China, the University of Copenhagen in Denmark, Technical University of Denmark, MetaGenoPolis at the National Research Institute for Agriculture, Food and Environment (INRAE) in France, and the Latvian Biomedical Research and Study Center. Relying on MGI’s core DNBSEQ™ technology, MMHP aims to sequence and analyze microbial DNA from a million human samples to construct a microbiome map of the human body and build the world’s largest human microbiome database.

“Countless studies have highlighted the importance of the microbiome in human health and disease. Yet, our knowledge of the composition of the microbiome in different parts of the body across countries, ages, sexes, and in relation to human health and disease remains limited,” said Duncan Yu, President of MGI. “Through MMHP, we are pushing forward microbial metagenomic research while empowering researchers within the microbiology community with access to MGI’s innovative sequencing technology. Despite a brief interruption by the COVID-19 pandemic, we are delighted to see such a monumental milestone merely four years into the project.”

The rise of microbial metagenomic sequencing​​​​​​​

Since the first description of human microbiome was published in 2010, the field of human microbiome has moved fast from sampling hundreds of individuals to thousands. Advances in genome sequencing has enabled researchers to better characterize the composition of the microbiome through identification of unculturable microbes. It has also allowed them the opportunity to study how the microbiome influences the development of some cancers and drug responses.

Metagenomics, coupled with high-throughput sequencing technologies, have revolutionized microbial ecology. Today, metagenomic sequencing has become both a powerful and popular tool for identifying and classifying complex microbial communities. It facilitates accelerated discovery of new markers that translate to virulence or antibiotic resistance, as well as de novo discovery and characterization of novel species and assembly of new genomes. Besides human microbiome, it is highly applicable in agricultural microbiome studies, environmental microbiome studies, pathogen surveillance and identification, and monitoring of antimicrobial resistance genes.

Indeed, the global metagenomic sequencing market was estimated to be worth USD 1.86 billion in revenue in 2022 and is poised to reach USD 4.33 billion by 2027, growing at a CAGR of 18.4% during the forecast period. In particular, Europe and Africa account for approximately 29.7% market share from the globe, ranking second after North America at 45.6%. Thanks to continuous technological innovations in high-throughput sequencing platforms, the metagenomic sequencing market within Europe and Africa is projected to grow from USD 551.7 million in 2022 to 1.29 billion by 2027, presenting huge market opportunities and providing local institutions with the impetus to invest and get involved.

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Image Credit: MGI

An optimized workflow with MGI’s cutting-edge technology

Equipped with MGI’s innovative lab systems, the MMHP Consortium guarantees high-throughput processes, extreme precision, and high quality data output. The dedicated, one-stop workflow begins with sample transfer on MGISTP-7000* high-throughput automated sample transfer processing system. It then goes through nucleic acid extraction and library preparation on MGISP-960 high-throughput automated sample preparation system, a flexible and fully automated workstation capable of processing 96 samples per run. MGISP-960’s fully automatic operation design allows DNA extraction of 50,000 samples per year and library preparation of 25,000 samples per year. MGISP-Smart 8, the professional automated pipetting robot, equipped with an independent 8 pipetting channel can be used for the pooling, normalization and DNB making. Lastly, DNBSEQ-T7* ultra-high throughput sequencer and DNBSEQ-G400* versatile benchtop sequencer enables an efficient, productive, and streamlined sequencing experience.

“We are very focused on data quality, cost and time. After contrasting DNBSEQ™ technology by MGI with other sequencing technologies, we are convinced that MGI’s products have met high industry standards and provide a very good user experience,” commented Professor Lars Engstrand, Research Director of Center for Microbial Translational Research (CMTR) at Karolinska Institutet. “MGI’s platforms have enabled our team to upgrade our original microbiological research from 16SrRNA gene amplicon sequencing to shotgun metagenomic sequencing. I look forward to introducing more equipment and super-large projects as human microbiome emerges as a crucial diagnostic and treatment method in precision medicine.”

The next chapter in microbiomics

“Microbiomics will be part of precision medicine in the future, and data from the microbiome biobank that will result from MMHP will be leveraged for therapeutic R&D,” said Professor Stanislav Dusko Ehrlich of University College London, UK. “With 21 public and private institutions and 10+ countries currently involved in MMHP, we are actively looking for more research groups to take part in this landmark international microbiological research partnership and help generate the world’s biggest free-access human microbiome database.”

Since the inception of MMHP, MGI has played an important role in providing the program with state-of-the-art research platforms and technologies. Now entering its second phase towards sequencing and analyzing a final total of one million samples, the project welcomes further exchange and participation from relevant organizations to jointly promote research and applications of cutting-edge translational medicine in the field of microbiome. Those interested can fill the application form on www.mgi-tech.eu/mmhp.

About MGI

MGI Tech Co. Ltd. (MGI), headquartered in Shenzhen, is committed to building core tools and technology to lead life science through intelligent innovation. Based on its proprietary technology, MGI focuses on research & development, production and sales of sequencing instruments, reagents, and related products to support life science research, agriculture, precision medicine and healthcare. MGI is a leading producer of clinical high-throughput gene sequencers*, and its multi-omics platforms include genetic sequencing*, medical imaging, and laboratory automation. MGI’s mission is to develop and promote advanced life science tools for future healthcare. For more information, please visit the MGI website or connect with us on TwitterLinkedIn or YouTube.

*Unless otherwise informed, StandardMPS and CoolMPS sequencing reagents, and sequencers for use with such reagents are not available in Germany, Spain, UK, Sweden, Italy, Czech Republic, Switzerland and Hong Kong (CoolMPS is available in Hong Kong).

*For Research Use Only. Not for use in diagnostic procedures (except as specifically noted).

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How the COVID pandemic has improved genomics

insights from industryDavide CacciharelliMolecular Biology and Genomics ProfessorUniversity of Naples

In this interview, Davide Cacchiarelli, Molecular Biology and Genomics Professor at the University of Naples talks to NewsMed about how the COVID pandemic has highlighted the vital role of genomic surveillance and improved genomics.

Please introduce yourself and what inspired your career in molecular biology and genomics?

My name is Davide Cacchiarelli, and I am a molecular biology and genomics professor at the University of Naples. I was inspired by the fact that genomics is classed as an effective tool to improve human health, dissect the molecular events happening in the cell and nucleus, and better understand how cells and organisms work.

Image Credit: ShutterStock/pinkeyes

In The Telethon Institute of Genetics and Medicine, you combine various disciplines with cell biology, molecular biology, and genomics. Why is having a multidisciplinary approach useful when making discoveries, particularly surrounding infectious diseases such as COVID?

The majority of the time, a single omic, measuring only gene expression by RNA sequencing, measuring only epigenetics, or measuring only phenotype, is insufficient to understand how a cell works.

The best solution is to combine all efforts to understand how these events happen, from the nucleus to the cell’s exterior. COVID, in particular, has been a case where acquiring one single omic or a single view of how the system works is ineffective in understanding how COVID behaviors occur in the population or clinically hospitalized patients.

We, therefore, try to combine the general information and patient outcome to get the best result regarding COVID infection.

Davide Cacciarelli at ICG17 – How the COVID pandemic has improved genomics

On what research areas are you and your team at TIGEM currently focusing?

Our group aims to answer various questions, from basic microbiology to developmental biology. Then we can re-engineer it for real regenerative medicine purposes. We also look at how we can effectively use genomics as a medical instrument that can be used to impact the healthcare of patients in our healthcare system.

You have recently co-authored a paper, “Improved SARS-CoV-2 sequencing surveillance allows the identification of new variants and signatures in infected patients.” Can you expand on that?

One of the significant issues in Italy regarding SARS-CoV-2 genome sequencing was the cost. Sequencing the COVID genome was also a tedious and elaborate procedure.

Image Credit: ShutterStock/Kateryna Kon

The main objective was first to make this approach economically affordable and create a proof of printing pulled by which this approach could become a cost-effective method for anyone and any country.

Our second approach, therefore, included integrating the genome information and the transcriptomic profiling of the patient airway epithelia. This helps us to understand how the genome evolves and allows us to track its evolution, in addition to seeing the response of the host respiratory epithelium. Finally, we implemented new ways to classify viral variants based on different characteristics using this approach.

What are the advantages of better identifying new cells, or two variants, for healthcare centers and patients?

The European Center for Disease Control has issued several requirements for next year focused on tracking respiratory viruses. One of these is tracking emerging variants as soon as possible, which we have done with COVID-19. We now know that new, specific variants can emerge in a short timeframe, so immediate tracking is crucial to help contain or at least delay the spreading of possible pathogenic variants.

MGI offers a variety of tools and technology surrounding genomics. Can you tell us more about some of the products used during your research and your experience with them?

At MGI, we have typically applied the COVID and whole genome solutions. We also have the freedom to test the stereo-seq they have in production this month. MGI can offer alternative solutions for various genome sequencing needs.

Image Credit: ShutterStock/peterschreiber.media

At present many sequencing genomic companies are coming up with different solutions. At MGI, we understand that the best genomic solution is the one that better fits your needs. With our experience, for example, with COVID, MGI had the right solution at the right moment.

How important is selecting the right sequencing technology for your research? When undertaking new research, what do you look for in a product/sequencer?

When the primary focus is not on identifying genes or mapping gene expression but on identifying or qualifying gene variants, there must be no issues in the sequencing, as the sequencing issue might be an error in the sequencing and misinterpreted data.

The error rate of MGI technology on DNB sequencing is extremely low, which offers significant benefits. Users can confidently rely on the data at the level of leaders in the field, which is what we look for when we start COVID genome sequencing.

You have often collaborated with other researchers throughout your research projects, especially concerning COVID. How vital have these collaborations been in accelerating your research?

Like many scientists who faced the COVID pandemic, I had much to learn. We used our knowledge in medical genetics and variant interpretation, and the crosstalk we had with virologists, MGI scientists, and genomic specialists was a step towards acquiring the best solution and the best effort to try to get those results as soon as possible, which is crucial for COVID sequencing.

Surprisingly, some scientists who had no interest in healthcare possessed knowledge valuable in tackling COVID issues. The circumstances and contingencies around the event forced them to think outside the box.

Do you believe that if we can understand SARS-CoV-2 better, we could better use this knowledge to prepare ourselves for future pandemics better? What advantages would this have for global health?

COVID did not give us any significant advantages for healthcare, but it may have for science. It highlighted how vital advanced genomics is to track diseases which influenced decisions at the governmental level.

Image Credit: ShutterStock/CKA

Today, several diseases require advanced genome sequencing, such as cancer diagnostics and medical genetics. Given that the issues with this problem affect a small population, you do not feel the urgency to improve specific knowledge or tests.

Therefore, the COVID pandemic has highlighted the vital role of genomic surveillance and improved genomics. Today, we have laboratories that, until two years ago, thought they could never afford to set up a genomic workflow; the pandemic forced them to enter the genomics field. Our mission as genomic scientists is to help them implement this solution in their lab because improving genomics in any lab is the best for healthcare in the future.

There is a saying, “omics for all.” As a scientist, what does that mean to you?

‘Omics for all’ has to be understood in two ways. It is critical to give everybody the chance to have access to omics. However, we need to remember that it is still a medical procedure. Thus, the omics flow offers everybody access to high-quality omics profiling of their genome, but under medical supervision.

Finally, what is the future for you in your research?

I will continue my basic research in my lab: studying how pluripotent cells and stem cells can be manipulated and organized for medical purposes. We also want to use the knowledge accumulated in the COVID pandemic to apply fast, cost-effective, and reliable genome sequencing to other types of screening.

Image Credit: ShutterStock/Anusorn Nakdee

With this in mind, we hope to screen for several hereditary cancers, for example, breast cancer inheritance. Therefore, we can effectively use the COVID strategies we set up for COVID sequencing as proof of principle to apply the sequencing to human and human disease-driving genes.

About MGI

MGI Tech Co., Ltd. (referred to as MGI) is committed to building core tools and technology to lead life science through intelligent innovation. MGI focuses on R&D, production, and sales of DNA sequencing instruments, reagents, and related products to support life science research, agriculture, precision medicine, and healthcare. MGI is a leading producer of clinical high-throughput gene sequencers, and its multi-omics platforms include genetic sequencing, mass spectrometry, medical imaging, and laboratory automation.

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Discontinuing oral antibiotics after breast reconstruction does not lead to an increase in infections

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For breast cancer patients undergoing breast reconstruction after mastectomy, avoiding postoperative oral antibiotics does not reduce the risk of infections, reports a study in the May issue of Plastic and Reconstructive Surgery®, the official medical journal of the American Society of Plastic Surgeons (ASPS). The journal is published in the Lippincott portfolio by Wolters Kluwer.

Our experience suggests that discontinuing routine oral antibiotic treatment after implant-based breast reconstruction does not lead to an increase in surgical site infections, and will eliminate a small but significant risk of allergy and other antibiotic-related complications.”

Mark Sisco, MD, ASPS Member Surgeon, NorthShore University HealthSystem, Evanston, Ill

No increase in infections after policy change on preventive antibiotics

A growing number of breast cancer patients are undergoing breast reconstruction after mastectomy, particularly immediate reconstruction using implants. Surgical site infections (SSIs) occur in 10% to 25% of patients undergoing this procedure, leading to increased rates of hospital readmission, repeat surgery, and reconstructive failure.

Historically, plastic surgeons have given extended antibiotic prophylaxis (EAP) to reduce the risk of SSI. The use of postoperative oral antibiotics has continued despite a lack of evidence for its effectiveness, and amid rising concerns about antibiotic resistance. In 2016, the authors’ health system joined the growing trend toward ending routine EAP for post-mastectomy breast reconstruction.

To evaluate the impact of this practice change, Dr. Sisco and colleagues compared outcomes in two groups of patients: 654 women (1,004 breasts) receiving EAP and 423 women (683 breasts) not receiving postoperative oral antibiotics. Both groups received a single dose of intravenous antibiotic before surgery.

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After surgery, the overall infection rate was similar between groups: 7.9% with EAP and 9.1% without EAP. After adjustment for differences in patient characteristics, the risk of SSIs was not significantly different between groups. This was even though patients in the non-EAP were more likely to receive some newer techniques – including nipple-sparing mastectomy and pre-pectoral (“above the muscle”) implant placement – thought to carry an increased risk of complications.

‘Thousands of women nationwide’ may have adverse reactions to EAP

Meanwhile, patients receiving EAP had some “infrequent but not insignificant” adverse events, including a two percent rate of moderate to severe allergic reactions. At least four women in the EAP group developed infection with antibiotic-resistant Clostridium difficile (“C-diff”) bacteria. Neither of these complications occurred in patients who did not receive extended antibiotics.

There was also evidence that EAP affected the types of bacteria isolated from patients who developed infections, including a higher rate of gram-negative bacteria. Extended antibiotic use was associated with a “broader range of pathogens” and more frequent need for second-line intravenous antibiotics.

“Although the use of EAP does not appear to worsen clinical outcomes, marked differences in the microbiology of associated infections may make them more difficult to treat,” Dr. Sisco and coauthors write. Especially at a time when breast reconstruction rates are rapidly increasing, “Our findings suggest that thousands of women are having adverse reactions to EAP nationwide, and some of these are likely to be serious,” the researchers add.

While acknowledging some important limitations of their study, the authors note that a definitive randomized trial of ending routine EAP is unlikely to be performed. Dr. Sisco and colleagues conclude, “We hope that our experience will give surgeons additional evidence and courage to change their practice.”

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Source:
Journal reference:

Sisco, M., et al. (2022). Oral antibiotics do not prevent infection or implant loss after immediate prosthetic breast reconstruction: Evidence from 683 consecutive reconstructions without prophylaxis. Plastic & Reconstructive Surgery. doi.org/10.1097/prs.0000000000010073

What are the trends in severe outcomes among patients hospitalized with COVID-19 during the first 2 years of the COVID-19 pandemic?

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In a recent study published in the JAMA Network Open, researchers performed a cohort study for prospective surveillance across a network of 155 acute care hospitals in Canada between March 15, 2020, and May 28, 2022, i.e., during the first two years of the coronavirus disease 2019 (COVID-19) pandemic.

Study: Trends in Severe Outcomes Among Adult and Pediatric Patients Hospitalized With COVID-19 in the Canadian Nosocomial Infection Surveillance Program, March 2020 to May 2022. Image Credit: angellodeco/Shutterstock.comStudy: Trends in Severe Outcomes Among Adult and Pediatric Patients Hospitalized With COVID-19 in the Canadian Nosocomial Infection Surveillance Program, March 2020 to May 2022. Image Credit: angellodeco/Shutterstock.com

Introduction

The study summarized trends in severe outcomes among adult and pediatric patients, aged ≥18 years and zero to 17 years, respectively, hospitalized with reverse transcription-polymerase chain reaction (RT-PCR)-confirmed COVID-19 at any of the Canadian Nosocomial Infection Surveillance Program (CNISP)–participating hospitals.

Background

Any changes to the clinical manifestations of COVID-19, especially its severe or critical cases, have significant implications for the healthcare system.

However, data summarizing the trend of severe illness outcomes for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients is limited in Canada. Data from a network of Canadian hospitals, such as CNISP, could help inform public health measures in the future.

CNISP, an alliance between Canada’s Public Health Agency, sentinel hospitals, and the Association of Medical Microbiology and Infectious Disease, began collating weekly data on COVID-19 patients, stratified by age, source, and vaccination status, from March 2020 onwards.

About the study

In the present study, trained infection control professionals reviewed patient medical records from 155 acute care hospitals in 10 Canadian provinces and one territory.

They identified patients with the first COVID-19-positive RT-PCR test result within 14 days before they sought hospital admission or while in the hospital. The study population comprised adults and pediatric patients.

For study analysis, they considered several severe outcomes in patients testing positive for COVID-19, as follows:

i) hospitalization;

ii) those admitted to an intensive care unit (ICU);

iii) those receiving mechanical ventilation;

iv) those receiving mechanical ventilation (MV);

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v) those receiving extracorporeal membrane oxygenation (ECMO); and

vi) all-cause in-hospital mortality

The team identified healthcare–related COVID-19 cases based on three prespecified criteria, the onset of symptoms or a positive RT-PCR test at least seven days after hospital admission, rehospitalization with a positive RT-PCR test within seven days after discharge, or a case with an epidemiological link to another COVID-19 case among staff members.

Further, the team identified six waves (periods) for the study with different SARS-CoV-2 variant predominance based on the weeks they detected increased COVID-19-related hospitalizations in the CNISP network.

For instance, the wild-type variant was dominant during waves one and two, while Alpha, Beta, and Gamma variants were predominant during wave three. During wave four, only Alpha was predominant, while the Omicron variant remained dominant during waves five and six.

The week-on-week proportion of severe disease outcomes indicated COVID-19–positivity per 1,000 hospital admissions. For this assessment, the researchers estimated weekly patient admissions by dividing quarterly hospital admissions during 2020-2021 by weeks in a quarter.

The main comparison parameter was severe outcome trends during waves five and six compared to earlier waves. For all severe outcomes, the team pooled patient data from waves one to four and waves five to six. Conversely, they pooled all wave (1-6) data for adult patients for all-cause in-hospital mortalities.

The team computed odd ratios (OR) and 95% confidence intervals (CIs) (unadjusted) to compare the severe outcomes between pooled data of all pandemic waves. They compared proportional variations using the χ2 test, where two-tailed P≤ 0.05 held statistical significance.

Finally, the team computed cumulative incidence rates (IRs) by COVID-19 vaccination status and age-stratified incidence rate ratios (IRRs) to compare these rates between these groups.

Results

Between March 15, 2020, and May 28, 2022, there were 1,513,065 admissions in 155 CNISP hospitals, where 51,679 and 4,035 were adult and pediatric patients, respectively. Of these, 8,683 adults and 498 children sought ICU admission.

Compared to Omicron-dominant waves five and six, for waves one through four combined, the proportion of COVID-19 hospitalizations among adult and pediatric patients per 1,000 hospital admissions were much lower. (24.7 vs. 77.3).

During wave five, hospitalized cases peaked for adult and pediatric patients at 146.8 and 96.3, respectively, and outpaced all previous and following waves.

During the January 16, 2022 week (wave five), the highest proportion of adult and pediatric ICU COVID-19 admissions were 18.3 and 15.6 per 1,000 hospital admissions, respectively.

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Among 51,496 adult patients hospitalized during the study, 7,012 acquired COVID-19 while in the hospital. This number was higher for waves five and six combined than for waves two through two (16.9% vs. 10.8%).

Likewise, the proportion of adult patients who needed ICU admission during waves five and six was lower than in waves two through four (8.7% vs. 21.8%).

The proportion of adult patients in the ICU who received MV during waves five and six was markedly lower than for waves two through four (47.6% vs. 67.2%).

Likewise, those who received extracorporeal membrane oxygenation (ECMO) were markedly lesser during waves five and six (1.3 vs. 4.6%). The cases of all-cause in-hospital mortality also declined from waves one and two to waves five and six (16% vs. 7%).

Among pediatric patients, the proportion of hospitalized patients needing an ICU was significantly lesser in waves five and six (9.4% vs. 18.1%) than in waves one through four. However, those who received MV during waves five and six were comparable to observed numbers for waves one through four [25.8% vs. 26.8%].

Only one pediatric patient received ECMO, 31 died, and even all-cause in-hospital deaths in a total of 1,359 pediatric cases were comparable across all pandemic waves, 0.9% for waves one through four and 0.7% for waves five & six combined, though this finding was statistically insignificant (p=0.60).

Strikingly, the age-standardized IR for ICU admission in unvaccinated vs. fully vaccinated patients during waves five and six was much higher. However, the same for all-cause in-hospital mortality was lower in unvaccinated vs. fully vaccinated patients (3.9 vs. 15.1).

Conclusions

Although COVID-19-related hospitalizations peaked in wave five, a markedly reduced proportion of adult and pediatric patients sought ICU admission. Even lesser adult COVID-19 patients received MV or ECMO during later than earlier waves, though numbers were significantly higher among unvaccinated patients.

However, during waves five and six, although Canadian hospitals experienced a surge in COVID-19-related hospitalizations and nosocomial transmission, severe disease outcomes declined substantially.

Yet, the COVID-19 burden on the Canadian healthcare system remained substantial even during waves five & six. Multiple factors likely resulted in the observed reductions, such as greater COVID-19 vaccine uptake & coverage by the time Omicron became predominant, which was inherently less virulent.

During later pandemic waves, people also developed natural immunity, and even COVID-19 management at hospitals improved over time.

Together, the study data highlighted the significance of COVID-19 vaccination in reducing the burden of COVID-19 and its severe outcomes on the Canadian healthcare system.

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Journal reference:

University Hospital Bonn coordinates eWHORM project to combat worm infections in sub-Saharan Africa

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African and European partners join forces to enable the World Health Organisation’s (WHO) “Road Map for Neglected Tropical Diseases” (NTDs) and reduce the burden of disease associated with worm infections.

Worm infections (helminthiases) affect around 1.5 billion people worldwide, making them one of the most prevalent infections in humans. Parasitic worms (helminths) are often transmitted through insect bites or contaminated soil in areas with limited access to clean water, sanitation, and healthcare. These infections can cause chronic and debilitating health problems, such as lymphatic filariasis, onchocerciasis (river blindness), loiasis (African eye worm), mansonellosis, and trichuriasis (whipworm infection).

To combat various soil-transmitted helminths (STH) and filarial worms, a new multidisciplinary consortium of research institutes, universities and not-for-profit organisations in sub-Saharan Africa (SSA) and Europe, coordinated by the University Hospital Bonn (UKB) in Germany, will work together to establish a new adaptive clinical trial platform and improve the clinical research infrastructure in several SSA countries. While each partner will bring unique know-how and complementary experience to achieve the project’s objectives, strong representation from the Global South will drive eWHORM activities. eWHORM will be funded with EUR 7.9 million from the European Union’s European and Developing Countries Clinical Trials Partnership (EDCTP3) programme and additional EUR 3.4 million from the Swiss Government over the next five years.

Achieving the ambitious WHO Road Map goals

Despite significant progress in preventing and controlling helminthiases, many existing drugs have proven problematic in terms of efficacy, treatment duration, and safety. In addition, the chronic underinvestment in healthcare in developing countries has led to poor infrastructure and inadequately trained technical staff.

The eWHORM project aims to address these issues by further developing and testing more efficacious and safe treatment options that act across different helminth species. The project will also train healthcare professionals to enable the diagnosis of multiple diseases in four endemic countries: the Democratic Republic of the Congo, the Gabonese Republic, the Republic of Cameroon, and the United Republic of Tanzania.

This major leap will help to achieve two pressing WHO objectives: (1) eliminating filarial and STH infections and (2) building capacity in endemic countries.

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Responding to persisting and future health challenges

Establishing a robust and equitable clinical research infrastructure is crucial to sustaining the progress that will be brought about by eWHORM. To this end, project partners will promote research network building, knowledge exchange, skill sharing, and gender equality awareness. Early career scientists in SSA will be supported through a Master’s and PhD programme, mentorship programme, and dedicated webinars on all aspects of clinical trial conduct and research. This will, in turn, increase effectiveness and preparedness for both current and future health crises and ensure equitable access to treatment, care, and support for all patients.

Cutting-edge clinical trial to end multiple neglected tropical diseases

The broad-spectrum helminth-killing (pan-nematode anthelmintic) drug oxfendazole (OXF) is used since several decades in the veterinary field to treat multiple species of helminths safely and effectively. In the recent drug development initiative “Helminth Elimination Platform” (HELP), a field-applicable formulation of the cost-effective and easy-to-manufacture drug OXF was developed and a bioavailability study was performed in humans. Several partners, who worked towards a superior, pan-nematode anthelmintic in HELP, are now continuing their ground-breaking research in eWHORM.

Our mission in eWHORM is to assess the efficacy of OXF for simultaneous evaluation against onchocerciasis, loiasis, mansonellosis, and trichuriasis. To do this, we plan to set up a state-ofthe-art adaptive basket trial that can test OXF against multiple diseases at once. This will help us to quickly find out if OXF works and get it to patients faster.”

Marc Hübner, project coordinator, professor of translational microbiology at the Institute for Medical Microbiology, Immunology and Parasitology (IMMIP) at the University Hospital Bonn

“The Drugs for Neglected Diseases initiative (DNDi) and Dr. Sabine Specht, Head of Filarial Disease at DNDi, have a long-standing track record in developing and enabling access to more effective and affordable drugs for Neglected Tropical Diseases,” adds Hübner. “Together with some of the most eminent research and development partners and national stakeholders worldwide, we are looking forward to contributing to what can generate a profound change in the treatment and elimination of helminth diseases.”

Next to the University of Buea, the Centre de Recherches Médicales de Lambaréné, and the Institut National de Recherche Biomédicale, the consortium includes experts from the Bernhard-Nocht-Institute for Tropical Medicine, the Medical University of Vienna, the Erasmus University Medical Center, the Swiss Tropical and Public Health Institute and Eurice – European Research and Project Office GmbH.

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HIV diagnoses increases more than three-fold after implementing targeted testing in EDs

Targeted testing for HIV in emergency departments has great potential for increasing diagnoses, this year’s European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) in Copenhagen, Denmark, (15-18 April), will hear.

An analysis of data from 34 emergency departments (ED) in Spain found that the number of HIV diagnoses more than trebled after targeted testing was implemented.

Researcher Dr Juan González del Castillo, head of the Infectious Disease Group of Spanish Emergency Medicine Society (SEMES), says: “Early diagnosis is key to avoiding the spread of HIV infection and improving patients’ prognosis but rates of undiagnosed and late-diagnosed infections are still high.

“An estimated 20% of infected people globally do not know they are living with HIV and late diagnosis rates are close to 50% in the developed world. In Spain, the figure is 48%.

“Screening for HIV in hospital emergency departments could increase the number of diagnoses, as well as allow more cases to be detected earlier.”

Guidance released by SEMES in 2021 recommends the promotion of HIV testing and referral to appropriate specialists for follow-up in individuals attending emergency departments (ED) for treatment related to one of six conditions or behaviours: sexually transmitted infections (STI), mononucleosic syndrome (MN), herpes zoster virus (HZ), community-acquired pneumonia (CAP), practice of chemsex (CS) and HIV post-exposure prophylaxis (PEP). These are common in people with HIV and are also frequently seen in ED.

In this longitudinal study, Dr González del Castillo, head of the emergency department at Hospital Clínico San Carlos, Madrid, Spain, and colleagues used administrative data and medical charts from 34 Spanish EDs (13% of the national network) participating in the Dejatuhuella (Leave your mark) programme to evaluate levels of HIV testing before (July-Dec 2019) and after (Jan to June 2022) the SEMES guidance was implemented.

The number of HIV tests ordered in ED increased from 7,080 to 13,436. This represents an increase of 75%, when differences in the number of people attending ED are taken into account.

The number of HIV diagnoses increased more than three-fold, from 65 to 224. This represents an increase of 220%, when ED attendance figures are factored in.

The positive test rate increased from 0.92% to 1.67%. This was expected, as previous studies had shown a high positive rate in the six conditions and behaviors covered by the SEMES recommendations.

There was a significant increase in HIV testing in all of the recommended areas, apart from practice of chemsex. STI (36% of patients tested for HIV before implementation vs. 67% after implementation), MS (27% vs. 51%), CAP (7% vs. 21%), HZ (6% vs. 29%), PEP (68% vs 83%). The rate of HIV in CS remained unchanged at 78%.

The demographic and health characteristics of the individuals diagnosed in both periods were similar.

There was a significant reduction in the time between ED attendance and the first appointment with an HIV specialist (median of 30 days vs. 7 days), as well as the initiation of antiviral treatment (median of 24 days vs.14 days).

The study’s authors conclude that the implementation of targeted testing for HIV in emergency departments led to a significant increase in HIV diagnoses.

To date, a total of 103 EDs have implemented the recommendations. Data from SEMES shows that in 2021 and 2022, 113,030 tests were performed, with 287 HIV diagnoses in 2021 and 601 in 2022 –888 new diagnoses in these two years.3 (It isn’t possible to make comparison with earlier years.)

If it is assumed that one diagnosis prevents another two to four cases, the new diagnoses in these two years will have led to 1,756 to 3,512 new cases being avoided.

Dr González del Castillo says: “We really hope that the Dejatuhuella programme will reverse the downward trend in HIV diagnoses in Spain and reduce the spread of HIV and the high rates of late diagnosis.

“EDs could play a crucial role in HIV diagnosis. We know from previous research that one in three missed opportunities to diagnose HIV occurs in ED and we also know that for many people, their ED is their only point of contact with the healthcare system.

“Increasing the rates of diagnosis and early diagnosis doesn’t just have huge implications for individuals’ health and public health, it would also be cost-effective.

“A recent economic assessment of the SEMES strategy calculated that it would prevent 13,615 new infections and have potential savings for the healthcare system of €4,411 million in two decades, with an economic return of €224 per euro invested.”

Targeted screening is one of the two main methods of HIV screening in ED; the other is opt-out screening.

A project in the England is using opt-out HIV testing in A&Es in areas with the highest prevalence of HIV. All adults who are having blood tests while in A&E are tested for HIV unless they opt out. In many areas, hepatitis B and hepatitis C are also tested for.

Data from the 28 A&Es participating in the first 100 days of the project (April to July 2022) shows that more than 250,000 HIV tests were carried out. There were 128 HIV diagnoses, 325 hepatitis B diagnoses and 153 hepatitis C diagnoses.

“It would be difficult to implement a universal testing strategy like this in Spain, where explicit consent for HIV testing is required,” says Dr González del Castillo. “In addition, some ED physicians may be reluctant to order tests that will not help them diagnose and treat the condition that patient has presented with.

“Targeted HIV screening in the ED, as we are doing in Spain, can be impactful, more cost-effective, and better accepted by both patients and physicians than universal testing.

“On the other hand, we are working on recommendations for hepatitis B and C testing and many EDs have already started doing it at the same time as HIV, with 63 new hepatitis C diagnosis in 2021 and 2022.”

He concludes: “The role that ED can play in HIV detection is pivotal and must be recognised and promoted, whatever the strategy and wherever people are in the world.”