Novel technique for ultrasound-guided needle tracking: An inexpensive reusable phantom model utilising a closed electrical circuit.

Purpose: Purpose:There are a variety of commercially made ultrasound training phantoms available for educational purposes. A new concept in phantoms is presented that utilises a low-cost method to create a reusable phantom. Methods: A closed electric circuit was combined with insulating material to create a novel phantom that can be used to practise needle tracking under ultrasound guidance on repeated occasions. A tricolour light-emitting diode (LED) illuminates when the needle (under ultrasound gudiance) contacts one of three metal objects embedded in the phatom material. Conclusion: This prototype model provides a simple solution for trianing ultrasound needle guidance is particularly geared towards programmes with a high volume of users. This protoype provides a starting point for a new concept in educational phantom trainers.

The National Association of Medical Examiners Position Paper on the Investigation and Certification of Pediatric Deaths From Environmental Neglect.

ABSTRACT: Pediatric deaths that occur because of environmental neglect often involve 4 common scenarios: (1) hyperthermia due to environmental exposure, (2) ingestion of an accessible drug or poison, (3) unwitnessed/unsupervised drownings, and (4) unsafe sleep practices. Given the same fact pattern, the manner of death will vary from accident to homicide to undetermined based on local custom and/or the certifier's training and experience. Medical examiner/coroner death certifications are administrative public health determinations made for vital statistical purposes. Because the manner of death is an opinion, it is understandable that manner determinations may vary among practitioners. No prosecutor, judge, or jury is bound by the opinions expressed on the death certificate. This position paper does not dictate how these deaths should be certified. Rather, it describes the challenges of the investigations and manner determinations in these deaths. It provides specific criteria that may improve consistency of certification. Because pediatric deaths often are of public interest, this paper provides the medical examiner/coroner with a professional overview of such manner determination issues to assist various stakeholders in understanding these challenges and variations.

Microplastic retention in marine vegetation canopies under breaking irregular waves.

The present study provides indications and underlying drivers of wave-induced transport and retention potential of microplastic particles (MP) in marine vegetation canopies having different densities. The anthropogenic occurrence of MP in coastal waters is well documented in the recent literature. It is acknowledged that coastal vegetation can serve as a sink for MP due to its energy dissipating features, which can mimic a novel ecosystem service. While the transport behavior of MP in vegetation has previously been investigated to some extent for stationary flow conditions, fundamental investigations for unsteady surf zone flow conditions under irregular waves are still lacking. Herein, we demonstrate by means of hydraulic model tests that a vegetation's retention potential of MP in waves increases with the vegetation shoot density, the MP settling velocity and decreasing wave energy. It is found that particles migrating by traction (predominantly in contact with the bed) are trapped in the wake regions around a canopy, whereas suspended particles are able to pass vegetated areas more easily. Very dense canopies can also promote the passage of MP with diameters larger than the plant spacing, as the canopies then show characteristics of a solid sill and avoid particle penetration. The particle migration ability through a marine vegetation canopy is quantified, and the key drivers are described by an empirical expression based on the particle settling velocity, the canopy length and density. The findings of this study may contribute to improved prediction and assessment of MP accumulation hotspots in vegetated coastal areas and, thus, may help in tracing MP sinks. Such knowledge can be considered a prerequisite to develope methods or new technologies to recover plastic pollutants and rehabilitate valuable coastal environments.

A Structured Pre- and Post-Operative Voice Therapy Program for Benign Vocal Fold Lesions

Benign vocal fold lesions (BVFLs) are acquired structural anomalies of the vocal folds, and these are primarily a result of vocal abuse or phonotrauma. Phonotraumatic lesions are not generally regarded as recurrent, provided that appropriate behavioral changes are made after resolution or surgical removal. Voice therapy plays a crucial role in this aspect. The aim of this article is to propose a structured pre- and post-operative voice therapy program for patients undergoing surgical intervention for BVFLs. Voice therapy post-surgery has been proven to reduce the rate of recurrence in BVFLs. Having a standard treatment protocol is a useful tool for the therapist, particularly one without extensive voice training.

Las lesiones benignas de los pliegues vocales (LBPV) son anomalías estructurales adquiridas de los pliegues vocales, y son principalmente el resultado de un abuso vocal o fonotrauma. Las lesiones fonotraumáticas generalmente no se consideran recurrentes, siempre que se realicen cambios apropiados en el comportamiento después de la resolución o la excisión quirúrgica. La terapia vocal juega un papel crucial en este aspecto. El objetivo de este artículo es proponer un programa estructurado de terapia de voz pre y postoperatorio para pacientes que son expuestos a una intervención quirúrgica para LBPV. Se ha demostrado que la terapia de voz después de la cirugía reduce la tasa de recurrencia en LBPV. Tener un protocolo de tratamiento estándar es una herramienta útil para el terapeuta, particularmente uno sin un entrenamiento extenso en patología de la voz.

GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.

OBJECTIVE: Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures. METHODS: This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses. RESULTS: Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors. CONCLUSIONS: This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.

Evidence of autoinflammation as a principal mechanism of myocardial injury in SARS-CoV-2 PCR-positive medical examiner cases.

BACKGROUND: Disease from Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) remains the seventh leading cause of death in the United States. Many patients infected with this virus develop later cardiovascular complications including myocardial infarctions, stroke, arrhythmia, heart failure, and sudden cardiac death (20-28%). The purpose of this study is to understand the primary mechanism of myocardial injury in patients infected with SARS-CoV-2. METHODS: We investigated a consecutive cohort of 48 medical examiner cases who died with PCR-positive SARS-CoV-2 (COVpos) infection in 2020. We compared them to a consecutive cohort of 46 age- and sex-matched controls who were PCR-negative for SARS-CoV-2 (COVneg). Clinical information available at postmortem examination was reviewed on each patient. Formalin-fixed sections were examined using antibodies directed against CD42 (platelets), CD15 (myeloid cells), CD68 (monocytes), C4d, fibrin, CD34 (stem cell antigen), CD56 (natural killer cells), and myeloperoxidase (MPO) (neutrophils and neutrophil extracellular traps(NETs)). We used a Welch 2-sample T-test to determine significance. A cluster analysis of marker distribution was also done. RESULTS: We found a significant difference between COVpos and COVneg samples for CD42, CD15, CD68, C4d, fibrin, and MPO, all of which were significant at p < 0.001. The most prominent features were neutrophils (CD15, MPO) and MPO-positive debris suggestive of NETs. A similar distribution of platelets, monocytes, fibrin and C4d was seen in COVpos cases. Clinical features were similar in COVpos and COVneg cases for age, sex, and body mass index (BMI). CONCLUSION: These findings suggest an autoinflammatory process is likely involved in cardiac damage during SARS-CoV-2 infection. No information about clinical cardiac disease was available.

Whole-genome sequencing analysis of suicide deaths integrating brain-regulatory eQTLs data to identify risk loci and genes.

Recent large-scale genome-wide association studies (GWAS) have started to identify potential genetic risk loci associated with risk of suicide; however, a large portion of suicide-associated genetic factors affecting gene expression remain elusive. Dysregulated gene expression, not assessed by GWAS, may play a significant role in increasing the risk of suicide death. We performed the first comprehensive genomic association analysis prioritizing brain expression quantitative trait loci (eQTLs) within regulatory regions in suicide deaths from the Utah Suicide Genetic Risk Study (USGRS). 440,324 brain-regulatory eQTLs were obtained by integrating brain eQTLs, histone modification ChIP-seq, ATAC-seq, DNase-seq, and Hi-C results from publicly available data. Subsequent genomic analyses were conducted in whole-genome sequencing (WGS) data from 986 suicide deaths of non-Finnish European (NFE) ancestry and 415 ancestrally matched controls. Additional independent USGRS suicide deaths with genotyping array data (n = 4657) and controls from the Genome Aggregation Database were explored for WGS result replication. One significant eQTL locus, rs926308 (p = 3.24e-06), was identified. The rs926308-T is associated with lower expression of RFPL3S, a gene important for neocortex development and implicated in arousal. Gene-based analyses performed using Sherlock Bayesian statistical integrative analysis also detected 20 genes with expression changes that may contribute to suicide risk. From analyzing publicly available transcriptomic data, ten of these genes have previous evidence of differential expression in suicide death or in psychiatric disorders that may be associated with suicide, including schizophrenia and autism (ZNF501, ZNF502, CNN3, IGF1R, KLHL36, NBL1, PDCD6IP, SNX19, BCAP29, and ARSA). Electronic health records (EHR) data was further merged to evaluate if there were clinically relevant subsets of suicide deaths associated with genetic variants. In summary, our study identified one risk locus and ten genes associated with suicide risk via gene expression, providing new insight into possible genetic and molecular mechanisms leading to suicide.

Proprotein convertase subtilisin/kexin type 9 targets megalin in the kidney proximal tubule and aggravates proteinuria in nephrotic syndrome.

Proteinuria is a prominent feature of chronic kidney disease. Interventions that reduce proteinuria slow the progression of chronic kidney disease and the associated risk of cardiovascular disease. Here, we propose a mechanistic coupling between proteinuria and proprotein convertase subtilisin/kexin type 9 (PCSK9), a regulator of cholesterol and a therapeutic target in cardiovascular disease. PCSK9 undergoes glomerular filtration and is captured by megalin, the receptor responsible for driving protein reabsorption in the proximal tubule. Accordingly, megalin-deficient mice and patients carrying megalin pathogenic variants (Donnai Barrow syndrome) were characterized by elevated urinary PCSK9 excretion. Interestingly, PCSK9 knockout mice displayed increased kidney megalin while PCSK9 overexpression resulted in its reduction. Furthermore, PCSK9 promoted trafficking of megalin to lysosomes in cultured proximal tubule cells, suggesting that PCSK9 is a negative regulator of megalin. This effect can be accelerated under disease conditions since either genetic destruction of the glomerular filtration barrier in podocin knockout mice or minimal change disease (a common cause of nephrotic syndrome) in patients resulted in enhanced tubular PCSK9 uptake and urinary PCSK9 excretion. Pharmacological PCSK9 inhibition increased kidney megalin while reducing urinary albumin excretion in nephrotic mice. Thus, glomerular damage increases filtration of PCSK9 and concomitantly megalin degradation, resulting in escalated proteinuria.

Shields Diagram and the Incipient Motion of Microplastic Particles.

Incipient motion conditions for 57 regular (spheres, cylinders, disks, square plates, cubes, square prisms, rectangular prisms, tetrahedrons, and fibers) and eight irregular microplastic particle groups, having various sizes and densities, are investigated in a circular flume. The present data set is combined with additional data from the literature and systematically analyzed. A new framework is developed for predicting incipient motion conditions for foreign particles, accounting for variations in static friction, hydraulic roughness, and hiding-exposure effects. Via this framework, incipient motion conditions for microplastic particles lying on a sediment bed are, for the first time, reconciled with the classical Shields diagram.

The EBV Gastric Cancer Resource (EBV-GCR): A Suite of Tools for Investigating EBV-Associated Human Gastric Carcinogenesis.

Epstein-Barr virus (EBV) causes lifelong infection in over 90% of the world's population. EBV infection leads to several types of B cell and epithelial cancers due to the viral reprogramming of host-cell growth and gene expression. EBV is associated with 10% of stomach/gastric adenocarcinomas (EBVaGCs), which have distinct molecular, pathological, and immunological characteristics compared to EBV-negative gastric adenocarcinomas (EBVnGCs). Publicly available datasets, such as The Cancer Genome Atlas (TCGA), contain comprehensive transcriptomic, genomic, and epigenomic data for thousands of primary human cancer samples, including EBVaGCs. Additionally, single-cell RNA-sequencing data are becoming available for EBVaGCs. These resources provide a unique opportunity to explore the role of EBV in human carcinogenesis, as well as differences between EBVaGCs and their EBVnGC counterparts. We have constructed a suite of web-based tools called the EBV Gastric Cancer Resource (EBV-GCR), which utilizes TCGA and single-cell RNA-seq data and can be used for research related to EBVaGCs. These web-based tools allow investigators to gain in-depth biological and clinical insights by exploring the effects of EBV on cellular gene expression, associations with patient outcomes, immune landscape features, and differential gene methylation, featuring both whole-tissue and single-cell analyses.

Settling velocity of microplastic particles having regular and irregular shapes.

The settling velocities of 66 microplastic particle groups, having both regular (58) and irregular (eight) shapes, are measured experimentally. Regular shapes considered include: spheres, cylinders, disks, square plates, cubes, other cuboids (square and rectangular prisms), tetrahedrons, and fibers. The experiments generally consider Reynolds numbers greater than 102, extending the predominant range covered by previous studies. The present data is combined with an extensive data set from the literature, and the settling velocities are systematically analyzed on a shape-by-shape basis. Novel parameterizations and predictive drag coefficient formulations are developed for both regular and irregular particle shapes, properly accounting for preferential settling orientation. These are shown to be more accurate than the best existing predictive formulation from the literature. The developed method for predicting the settling velocity of irregularly-shaped microplastic particles is demonstrated to be equally well suited for natural sediments in the Appendix.

Mortality and Sequential Organ Failure Assessment Score in Patients With Suspected Sepsis: The Impact of Acute and Preexisting Organ Failures and Infection Likelihood.

The Sequential Organ Failure Assessment (SOFA) was chosen in the definition of sepsis due to superior validity in predicting mortality. However, few studies have assessed the contributions of acute versus chronic organ failures to SOFA for mortality prediction. OBJECTIVES: The main objective in this study was to assess the relative importance of chronic and acute organ failures in mortality prediction in patients with suspected sepsis at hospital admission. We also evaluated how the presence of infection influenced the ability of SOFA to predict 30-day mortality. DESIGN SETTING AND PARTICIPANTS: Single-center prospective cohort study including 1,313 adult patients with suspected sepsis in rapid response teams in the emergency department. MAIN OUTCOMES AND MEASURES: The main outcome was 30-day mortality. We measured the maximum total SOFA score during admission (SOFATotal), whereas preexisting chronic organ failure SOFA (SOFAChronic) score was assessed by chart review, allowing calculation of the corresponding acute SOFA (SOFAAcute) score. Likelihood of infection was determined post hoc as "No infection" or "Infection." RESULTS: SOFAAcute and SOFAChronic were both associated with 30-day mortality, adjusted for age and sex (adjusted odds ratios [AORs], 1.3; 95% CI, 1.3-14 and 1.3; 1.2-1.7), respectively. Presence of infection was associated with lower 30-day mortality (AOR, 0.4; 95% CI, 0.2-0.6), even when corrected for SOFA. In "No infection" patients, SOFAAcute was not associated with mortality (AOR, 1.1; 95% CI, 1.0-1.2), and in this subgroup, neither SOFAAcute greater than or equal to 2 (relative risk [RR], 1.1; 95% CI, 0.6-1.8) nor SOFATotal greater than or equal to 2 (RR, 3.6; 95% CI, 0.9-14.1) was associated with higher mortality. CONCLUSIONS AND RELEVANCE: Chronic and acute organ failures were equally associated with 30-day mortality in suspected sepsis. A substantial part of the total SOFA score was due to chronic organ failure, calling for caution when using total SOFA in defining sepsis and as an outcome in intervention studies. SOFA's mortality prediction ability was highly dependent on actual presence of infection.

Altered transcriptomes, cell type proportions, and dendritic spine morphology in hippocampus of suicide deaths.

Suicide is a condition resulting from complex environmental and genetic risks that affect millions of people globally. Both structural and functional studies identified the hippocampus as one of the vulnerable brain regions contributing to suicide risk. Here, we have identified the hippocampal transcriptomes, gene ontology, cell type proportions, dendritic spine morphology, and transcriptomic signature in iPSC-derived neuronal precursor cells (NPCs) and neurons in postmortem brain tissue from suicide deaths. The hippocampal tissue transcriptomic data revealed that NPAS4 gene expression was downregulated while ALDH1A2, NAAA, and MLXIPL gene expressions were upregulated in tissue from suicide deaths. The gene ontology identified 29 significant pathways including NPAS4-associated gene ontology terms "excitatory post-synaptic potential", "regulation of postsynaptic membrane potential" and "long-term memory" indicating alteration of glutamatergic synapses in the hippocampus of suicide deaths. The cell type deconvolution identified decreased excitatory neuron proportion and an increased inhibitory neuron proportion providing evidence of excitation/inhibition imbalance in the hippocampus of suicide deaths. In addition, suicide deaths had increased dendric spine density, due to an increase of thin (relatively unstable) dendritic spines, compared to controls. The transcriptomes of iPSC-derived hippocampal-like NPCs and neurons revealed 31 and 33 differentially expressed genes in NPC and neurons, respectively, of suicide deaths. The suicide-associated differentially expressed genes in NPCs were RELN, CRH, EMX2, OXTR, PARM1 and IFITM2 which overlapped with previously published results. The previously-known suicide-associated differentially expressed genes in differentiated neurons were COL1A1, THBS1, IFITM2, AQP1, and NLRP2. Together, these findings would help better understand the hippocampal neurobiology of suicide for identifying therapeutic targets to prevent suicide.

LRP2 contributes to planar cell polarity-dependent coordination of motile cilia function.

Motile cilia are protruding organelles on specialized epithelia that beat in a synchronous fashion to propel extracellular fluids. Coordination and orientation of cilia beating on individual cells and across tissues is a complex process dependent on planar cell polarity (PCP) signaling. Asymmetric sorting of PCP pathway components, essential to establish planar polarity, involves trafficking along the endocytic path, but the underlying regulatory processes remain incompletely understood. Here, we identified the endocytic receptor LRP2 as regulator of PCP component trafficking in ependyma, a multi-ciliated cell type that is involved in facilitating flow of the cerebrospinal fluid in the brain ventricular system. Lack of receptor expression in gene-targeted mice results in a failure to sort PCP core proteins to the anterior or posterior cell side and, consequently, in the inability to coordinate cilia arrangement and to aligned beating (loss of rotational and translational polarity). LRP2 deficiency coincides with a failure to sort NHERF1, a cytoplasmic LRP2 adaptor to the anterior cell side. As NHERF1 is essential to translocate PCP core protein Vangl2 to the plasma membrane, these data suggest a molecular mechanism whereby LRP2 interacts with PCP components through NHERF1 to control their asymmetric sorting along the endocytic path. Taken together, our findings identified the endocytic receptor LRP2 as a novel regulator of endosomal trafficking of PCP proteins, ensuring their asymmetric partition and establishment of translational and rotational planar cell polarity in the ependyma.

Experimental investigation on the nearshore transport of buoyant microplastic particles.

This paper presents experimental measurements of beaching times for buoyant microplastic particles released, both in the pre-breaking region and within the surf zone. The beaching times are used to quantify cross-shore Lagrangian transport velocities of the microplastics. Prior to breaking the particles travel onshore with a velocity close to the Lagrangian fluid particle velocity, regardless of particle characteristics. In the surf zone the Lagrangian velocities of the microplastics increase and become closer to the wave celerity. Furthermore, it is demonstrated that particles having low Dean numbers (dimensionless fall velocity) are transported at higher mean velocities, as they have a larger tendency to be at the free-surface relative to particles with higher Dean numbers. An empirical relation is formulated for predicting the cross-shore Lagrangian transport velocities of buoyant microplastic particles, valid for both non-breaking and breaking irregular waves. The expression matches the present experiments well, in addition to two prior studies.

Evaluation of single-cell RNAseq labelling algorithms using cancer datasets.

Single-cell RNA sequencing (scRNA-seq) clustering and labelling methods are used to determine precise cellular composition of tissue samples. Automated labelling methods rely on either unsupervised, cluster-based approaches or supervised, cell-based approaches to identify cell types. The high complexity of cancer poses a unique challenge, as tumor microenvironments are often composed of diverse cell subpopulations with unique functional effects that may lead to disease progression, metastasis and treatment resistance. Here, we assess 17 cell-based and 9 cluster-based scRNA-seq labelling algorithms using 8 cancer datasets, providing a comprehensive large-scale assessment of such methods in a cancer-specific context. Using several performance metrics, we show that cell-based methods generally achieved higher performance and were faster compared to cluster-based methods. Cluster-based methods more successfully labelled non-malignant cell types, likely because of a lack of gene signatures for relevant malignant cell subpopulations. Larger cell numbers present in some cell types in training data positively impacted prediction scores for cell-based methods. Finally, we examined which methods performed favorably when trained and tested on separate patient cohorts in scenarios similar to clinical applications, and which were able to accurately label particularly small or under-represented cell populations in the given datasets. We conclude that scPred and SVM show the best overall performances with cancer-specific data and provide further suggestions for algorithm selection. Our analysis pipeline for assessing the performance of cell type labelling algorithms is available in https://github.com/shooshtarilab/scRNAseq-Automated-Cell-Type-Labelling.

Intelligent digital tools for screening of brain connectivity and dementia risk estimation in people affected by mild cognitive impairment: the AI-Mind clinical study protocol.

More than 10 million Europeans show signs of mild cognitive impairment (MCI), a transitional stage between normal brain aging and dementia stage memory disorder. The path MCI takes can be divergent; while some maintain stability or even revert to cognitive norms, alarmingly, up to half of the cases progress to dementia within 5 years. Current diagnostic practice lacks the necessary screening tools to identify those at risk of progression. The European patient experience often involves a long journey from the initial signs of MCI to the eventual diagnosis of dementia. The trajectory is far from ideal. Here, we introduce the AI-Mind project, a pioneering initiative with an innovative approach to early risk assessment through the implementation of advanced artificial intelligence (AI) on multimodal data. The cutting-edge AI-based tools developed in the project aim not only to accelerate the diagnostic process but also to deliver highly accurate predictions regarding an individual's risk of developing dementia when prevention and intervention may still be possible. AI-Mind is a European Research and Innovation Action (RIA H2020-SC1-BHC-06-2020, No. 964220) financed between 2021 and 2026. First, the AI-Mind Connector identifies dysfunctional brain networks based on high-density magneto- and electroencephalography (M/EEG) recordings. Second, the AI-Mind Predictor predicts dementia risk using data from the Connector, enriched with computerized cognitive tests, genetic and protein biomarkers, as well as sociodemographic and clinical variables. AI-Mind is integrated within a network of major European initiatives, including The Virtual Brain, The Virtual Epileptic Patient, and EBRAINS AISBL service for sensitive data, HealthDataCloud, where big patient data are generated for advancing digital and virtual twin technology development. AI-Mind's innovation lies not only in its early prediction of dementia risk, but it also enables a virtual laboratory scenario for hypothesis-driven personalized intervention research. This article introduces the background of the AI-Mind project and its clinical study protocol, setting the stage for future scientific contributions.

DNA Repair Mechanisms are Activated in Circulating Lymphocytes of Hospitalized Covid-19 Patients.

Purpose: Reactive oxygen species (ROS) are an important part of the inflammatory response during infection but can also promote DNA damage. Due to the sustained inflammation in severe Covid-19, we hypothesized that hospitalized Covid-19 patients would be characterized by increased levels of oxidative DNA damage and dysregulation of the DNA repair machinery. Patients and Methods: Levels of the oxidative DNA lesion 8-oxoG and levels of base excision repair (BER) proteins were measured in peripheral blood mononuclear cells (PBMC) from patients (8-oxoG, n = 22; BER, n = 17) and healthy controls (n = 10) (Cohort 1). Gene expression related to DNA repair was investigated in two independent cohorts of hospitalized Covid-19 patients (Cohort 1; 15 patents and 5 controls, Cohort 2; 15 patients and 6 controls), and by publicly available datasets. Results: Patients and healthy controls showed comparable amounts of oxidative DNA damage as assessed by 8-oxoG while levels of several BER proteins were increased in Covid-19 patients, indicating enhanced DNA repair in acute Covid-19 disease. Furthermore, gene expression analysis demonstrated regulation of genes involved in BER and double strand break repair (DSBR) in PBMC of Covid-19 patients and expression level of several DSBR genes correlated with the degree of respiratory failure. Finally, by re-analyzing publicly available data, we found that the pathway Hallmark DNA repair was significantly more regulated in circulating immune cells during Covid-19 compared to influenza virus infection, bacterial pneumonia or acute respiratory infection due to seasonal coronavirus. Conclusion: Although beneficial by protecting against DNA damage, long-term activation of the DNA repair machinery could also contribute to persistent inflammation, potentially through mechanisms such as the induction of cellular senescence. However, further studies that also include measurements of additional markers of DNA damage are required to determine the role and precise molecular mechanisms for DNA repair in SARS-CoV-2 infection.