Virus Exposure Research Articles

Investigation of oxidative stress profile and pathomorphology of lungs in goats sick of pneumonia-enteritis complex

Peste des Petits Ruminants (PPR), which causes pneumonia-enteritis complex, is an acute, highly contagious disease causing immunosuppression and high mortality in sheep and goats. Epidemiology, clinical signs and pathologic findings of the disease have been studied, but information on the oxidative stress profile is scanty. This study investigated the oxidative stress profile and the pulmonary histopathology of PPR infected goats. Twenty male goats were used for this study. The unvaccinated goats were naturally exposed to PPR according to environmental and animal market conditions consistent with routine PPR virus exposure in endemic areas. Following confirmation of PPR in the goats, their blood and serum samples were collected and evaluated for biomarkers of oxidative stress such as superoxide dismutase, malondialdehyde and catalase, while the neutrophil: lymphocyte ratio (NLR) and serum electrolytes were used to assess physiologic stress. Four goats were euthanized before onset of the clinical signs and every three days following clinical manifestations. Severity of histopathology observed in the lungs were scored and used to categorize the goats into four groups as; normal, mild, moderate and severe. Results showed that oxidative stress increased in PPR affected goats from moderate and severe pulmonary lesions as the disease progressed. On the basis of pulmonary histopathology, malondialdehyde was a better indicator of oxidative damage than superoxide dismutase and catalase. The study also indicated that NLR and Ca:P are reliable indicators of generalised physiologic stress in goats naturally affected by PPR

Assessing environmental exposure to viruses in wastewater treatment plant and swine farm scenarios with next-generation sequencing and occupational risk approaches

Occupational exposure to pathogens can pose health risks. This study investigates the viral exposure of workers in a wastewater treatment plant (WWTP) and a swine farm by analyzing aerosol and surfaces samples. Viral contamination was evaluated using quantitative polymerase chain reaction (qPCR) assays, and target enrichment sequencing (TES) was performed to identify the vertebrate viruses to which workers might be exposed. Additionally, Quantitative Microbial Risk Assessment (QMRA) was conducted to estimate the occupational risk associated with viral exposure for WWTP workers, choosing Human Adenovirus (HAdV) as the reference pathogen. In the swine farm, QMRA was performed as an extrapolation, considering a hypothetical zoonotic virus with characteristics similar to Porcine Adenovirus (PAdV). The modelled exposure routes included aerosol inhalation and oral ingestion through contaminated surfaces and hand-to-mouth contact.HAdV and PAdV were widespread viruses in the WWTP and the swine farm, respectively, by qPCR assays. TES identified human and other vertebrate viruses WWTP samples, including viruses from families such as Adenoviridae, Circoviridae, Orthoherpesviridae, Papillomaviridae, and Parvoviridae. In the swine farm, most of the identified vertebrate viruses were porcine viruses belonging to Adenoviridae, Astroviridae, Circoviridae, Herpesviridae, Papillomaviridae, Parvoviridae, Picornaviridae, and Retroviridae.QMRA analysis revealed noteworthy risks of viral infections for WWTP workers if safety measures are not taken. The probability of illness due to HAdV inhalation was higher in summer compared to winter, while the greatest risk from oral ingestion was observed in workspaces during winter. Swine farm QMRA simulation suggested a potential occupational risk in the case of exposure to a hypothetical zoonotic virus.This study provides valuable insights into WWTP and swine farm worker's occupational exposure to human and other vertebrate viruses. QMRA and NGS analyses conducted in this study will assist managers in making evidence-based decisions, facilitating the implementation of protection measures, and risk mitigation practices for workers.

The Microbial Role in Allergy: A Comprehensive Review

Background: The rise in allergic diseases in Western industrial nations has been paralleled by an increased understanding of the intricate relationship between microbial exposure and immune system responses. The hygiene hypothesis suggests a link between reduced exposure to infectious agents and an increase in allergies, emphasizing the need for a deeper investigation into the roles of various microbes in allergic reactions. Objective: This review aims to elucidate the complex mechanisms underlying allergic reactions, specifically focusing on the roles of parasites, bacteria, fungi, and viruses. It seeks to explore the potential of microbial exposure as both a protective and pathogenic factor in the development of allergies, with an eye towards informing future therapeutic strategies. Methods: An extensive literature review was conducted using databases such as Google Scholar, Scopus, PubMed, and Web of Sciences, focusing on studies published up to March 2024. The review synthesized findings on the impact of microbial exposure on allergic diseases, examining the roles of specific microbes, their interaction with the immune system, and the implications for allergic responses. Results: The review highlights the dual nature of microbial exposure in allergies, with some microbes offering protection against allergic diseases through the modulation of immune responses, while others exacerbate allergic conditions. Notably, probiotics and certain parasitic infections demonstrate potential in modulating the immune system to prevent or reduce allergic responses. Conversely, specific bacterial, fungal, and viral exposures are linked to the exacerbation of allergic diseases. Conclusion: Understanding the complex relationship between microbial exposure and allergic diseases is crucial for developing novel therapeutic and preventive strategies. This review underscores the potential of targeted microbial management in modulating immune responses to allergens, suggesting a promising avenue for reducing the global burden of allergic diseases.

The multi-dimensional challenges of controlling respiratory virus transmission in indoor spaces: Insights from the linkage of a microscopic pedestrian simulation and SARS-CoV-2 transmission model.

SARS-CoV-2 transmission in indoor spaces, where most infection events occur, depends on the types and duration of human interactions, among others. Understanding how these human behaviours interface with virus characteristics to drive pathogen transmission and dictate the outcomes of non-pharmaceutical interventions is important for the informed and safe use of indoor spaces. To better understand these complex interactions, we developed the Pedestrian Dynamics-Virus Spread model (PeDViS), an individual-based model that combines pedestrian behaviour models with virus spread models incorporating direct and indirect transmission routes. We explored the relationships between virus exposure and the duration, distance, respiratory behaviour, and environment in which interactions between infected and uninfected individuals took place and compared this to benchmark 'at risk' interactions (1.5 metres for 15 minutes). When considering aerosol transmission, individuals adhering to distancing measures may be at risk due to the buildup of airborne virus in the environment when infected individuals spend prolonged time indoors. In our restaurant case, guests seated at tables near infected individuals were at limited risk of infection but could, particularly in poorly ventilated places, experience risks that surpass that of benchmark interactions. Combining interventions that target different transmission routes can aid in accumulating impact, for instance by combining ventilation with face masks. The impact of such combined interventions depends on the relative importance of transmission routes, which is hard to disentangle and highly context dependent. This uncertainty should be considered when assessing transmission risks upon different types of human interactions in indoor spaces. We illustrated the multi-dimensionality of indoor SARS-CoV-2 transmission that emerges from the interplay of human behaviour and the spread of respiratory viruses. A modelling strategy that incorporates this in risk assessments can help inform policy makers and citizens on the safe use of indoor spaces with varying inter-human interactions.

Individualized Multimodal Immunotherapy (IMI): Scientific Rationale and Clinical Experience from a Single Institution.

Oncolytic viruses and combinatorial immunotherapy for cancer (this Special Issue) are both part of cancer treatment at IOZK. This review focusses on an individual multimodal cancer immunotherapy concept developed by IOZK, Cologne, Germany. The scientific rationale for employing three main components is explained: (i) oncolytic Newcastle disease virus, (ii) modulated electrohyperthermia and (iii) individual tumor antigen and oncolytic virus modified dendritic cell vaccine (IO-VACR). The strategy involves repeated cancer-immunity cycles evoked in cancer patients by systemic oncolytic virus exposure plus hyperthermia pretreatment to induce immunogenic cell death followed by intradermal IO-VACR vaccination. As an example of the experience at IOZK, we present the latest results from combining the immunotherapy with standard treatment of patients suffering from glioblastoma multiforme. The promising clinical results in terms of overall survival benefit of additional individualized multimodal immunotherapy are presented. The cancer-immunity cycle, as introduced 10 years ago, describes key important steps occurring locally at the sites of both tumor and draining lymph nodes. This view is extended here towards systemic events occuring in blood where immunogenic cell death-induced tumor antigens are transported into the bone marrow. For 20 years it has been known that bone marrow is an antigen-responsive organ in which dendritic cells present tumor antigens to T cells leading to immunological synapse formation, tumor antigen-specific T cell activation and memory T cell formation. Bone marrow is known to be the most prominent source of de novo cellular generation in the body and to play an important role for the storage and maintenance of immunological memory. Its systemic activation is recommended to augment cancer-immunity cycles.

Lower Insulin Sensitivity Through 36 Months of Life With in Utero HIV and Antiretroviral Exposure in Botswana: Results From the Tshilo Dikotla Study.

There are little data on changes in insulin sensitivity during the first few years of life following in utero human immunodeficiency virus (HIV) and antiretroviral (ARV) exposure. The Tshilo Dikotla study enrolled pregnant persons with HIV (PWH) (receiving tenofovir/emtricitabine or lamivudine plus dolutegravir or efavirenz) and pregnant individuals without HIV, as well as their liveborn children. Newborns were randomized to receive either zidovudine (AZT) or nevirapine (NVP) postnatal prophylaxis. Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) was assessed at birth and 1, 18, 24, and 36 months of life. We fit linear mixed-effects models to evaluate the association between in utero HIV/ARV exposure and average HOMA-IR from birth through 36 months of life, adjusting for confounders. A total of 419 children were included (287 with in utero HIV/ARV exposure and uninfected [CHEU] and 132 without in utero HIV/ARV exposure [CHUU]). CHEU were born to older women (29.6 vs 25.3 years of age) with higher gravidity (3 vs 1). HOMA-IR was persistently higher in CHEU versus CHUU in adjusted analyses (mean difference of 0.07 in log10 HOMA-IR, P = .02) from birth through 36 months of life. Among CHEU, no differences in HOMA-IR were observed from birth through 36 months by in utero ARV exposure status or between AZT and NVP infant prophylaxis arms. In utero HIV/ARV exposure was associated with lower insulin sensitivity throughout the first 36 months of life, indicating persistent early life metabolic disturbances which may raise concern for poorer metabolic health later in life.

Identification of miR-29a as a novel biomarker for lumpy skin disease virus exposure in cattle

ABSTRACT Micro RNAs (miRNAs) have been implicated in the regulation of maturation, proliferation, differentiation, and activation of immune cells. In this study, we demonstrated that miR-29a antagonizes IFN-γ production at early times post-LSDV infection in cattle. miR-29a was predicted to target upstream IFN-γ regulators, and its inhibition resulted in enhanced IFN-γ production in sensitized peripheral blood mononuclear cells (PBMCs). Further, stimulation of PBMCs with LSDV antigen exhibited lower levels of miR-29a, concomitant with a potent cell-mediated immune response (CMI), characterized by an increase in LSDV-specific CD8+ T cell counts and enhanced levels of IFN-γ, which eventually facilitated virus clearance. In addition, a few immunocompromised cattle (developed secondary LSDV infection at ~ 6 months) that failed to mount a potent cell-mediated immune response, were shown to maintain higher miR-29a levels. Furthermore, as compared to the sensitized crossbred cattle, PBMCs from sensitized Rathi (a native Indian breed) animals exhibited lower levels of miR-29a along with an increase in CD8+ T cell counts and enhanced levels of IFN-γ. Finally, we analysed that a ≥ 60% decrease in miR-29a expression levels in the PBMCs of sensitized cattle correlated with a potent CMI response. In conclusion, miR-29a expression is involved in antagonizing the IFN-γ response in LSDV-infected cattle and may serve as a novel biomarker for the acute phase of LSDV infection, as well as predicting the functionality of T cells in sensitized cattle. In addition, Rathi cattle mount a more potent CMI response against LSDV than crossbred cattle.

Viral infections in pregnancy and impact on offspring neurodevelopment: mechanisms and lessons learned.

Pregnant individuals with viral illness may experience significant morbidity and have higher rates of pregnancy and neonatal complications. With the growing number of viral infections and new viral pandemics, it is important to examine the effects of infection during pregnancy on both the gestational parent and the offspring. Febrile illness and inflammation during pregnancy are correlated with risk for autism, attention deficit/hyperactivity disorder, and developmental delay in the offspring in human and animal models. Historical viral epidemics had limited follow-up of the offspring of affected pregnancies. Infants exposed to seasonal influenza and the 2009 H1N1 influenza virus experienced increased risks of congenital malformations and neuropsychiatric conditions. Zika virus exposure in utero can lead to a spectrum of abnormalities, ranging from severe microcephaly to neurodevelopmental delays which may appear later in childhood and in the absence of Zika-related birth defects. Vertical infection with severe acute respiratory syndrome coronavirus-2 has occurred rarely, but there appears to be a risk for developmental delays in the infants with antenatal exposure. Determining how illness from infection during pregnancy and specific viral pathogens can affect pregnancy and neurodevelopmental outcomes of offspring can better prepare the community to care for these children as they grow. IMPACT: Viral infections have impacted pregnant people and their offspring throughout history. Antenatal exposure to maternal fever and inflammation may increase risk of developmental and neurobehavioral disorders in infants and children. The recent SARS-CoV-2 pandemic stresses the importance of longitudinal studies to follow pregnancies and offspring neurodevelopment.

Phenotypic and functional characterization of posoleucel, a multivirus-specific T cell therapy for the treatment and prevention of viral infections in immunocompromised patients

BackgroundDeficits in T cell immunity translate into increased risk of severe viral infection in recipients of solid organ and hematopoietic cell transplants. Thus, therapeutic strategies that employ the adoptive transfer of virus-specific T cells are being clinically investigated to treat and prevent viral diseases in these highly immunocompromised patients. Posoleucel is an off-the-shelf multivirus-specific T cell investigational product for the treatment and prevention of infections due to adenovirus, BK virus, cytomegalovirus, Epstein–Barr virus, human herpesvirus 6 or JC virus. MethodsHerein we perform extensive characterization of the phenotype and functional profile of posoleucel to illustrate the cellular properties that may contribute to its in vivo activity. Results and ConclusionsOur results demonstrate that posoleucel is enriched for central and effector memory CD4+ and CD8+ T cells with specificity for posoleucel target viruses and expressing a broad repertoire of T cell receptors. Antigen-driven upregulation of cell-surface molecules and production of cytokine and effector molecules indicative of proliferation, co-stimulation, and cytolytic potential demonstrate the specificity of posoleucel and its potential to mount a broad, polyfunctional, and effective Th1-polarized antiviral response upon viral exposure. We also show the low risk for off-target and nonspecific effects as evidenced by the enrichment of posoleucel in memory T cells, low frequency of naive T cells, and lack of demonstrated alloreactivity in vitro. The efficacy of posoleucel is being explored in four placebo-controlled clinical trials in transplant recipients to treat and prevent viral infections (NCT05179057, NCT05305040, NCT04390113, NCT04605484).

Understanding the multidimensional neurodevelopmental outcomes in children after congenital Zika virus exposure.

Since 2016, international research groups have focused on assessing outcomes of children with in utero Zika virus (ZIKV) exposure. While the more severe outcomes of congenital Zika syndrome (CZS) occur in up to 10% of children with antenatal exposure, early findings among ZIKV-exposed children without CZS ages 0-5 years suggest that they may also have differences in multiple domains of neurodevelopment. Thus, longitudinal follow-up of all children with antenatal ZIKV exposure has been recommended. This review presents a summary of neurodevelopmental phenotypes of infants and children following antenatal ZIKV exposure. We present a multidimensional framework to understand child neurodevelopment from an interdisciplinary and whole-child perspective (International Classification of Functioning, Disability and Health model) and multi-domain ZIKV Outcome Toolboxes. The toolboxes are for clinicians, researchers, child educators, and others to implement longitudinal multi-domain neurodevelopmental assessments between ages 0-12 years. Recent innovations in telehealth and neuroimaging can help evaluate outcomes in ZIKV exposed children. The objective is to describe the multiple facets of neurodevelopmental focused care that can support the health, function, and well-being of children with antenatal ZIKV exposure. The research and clinical follow-up strategies are applicable to ZIKV and other congenital infectious or environmental exposures that can impact child neurodevelopment. IMPACT: International longitudinal cohort studies have revealed a range of differences in neurodevelopment among children with antenatal Zika virus (ZIKV) exposure. A multidimensional and whole-child framework is necessary to understand the neurodevelopment of children with antenatal ZIKV exposure in relation to family life, community participation, and environment. Multi-domain toolboxes that utilize parent questionnaires and child evaluations are presented. These toolboxes can be used internationally alongside telehealth, brain imaging, and other innovations to improve understanding of child outcomes.

Monitoring and Characteristics of Mpox Contacts, Virginia, USA, May-November 2022.

During 2022, a global outbreak of mpox resulted primarily from human-to-human contact. The Virginia Department of Health (Richmond, VA, USA) implemented a contact tracing and symptom monitoring system for residents exposed to monkeypox virus, assessed their risk for infection, and offered interventions as needed. Among 991 contacts identified during May 1-November 1, 2022, import records were complete for 943 (95.2%), but 99 (10.0%) were not available for follow-up during symptom monitoring. Mpox developed in 28 (2.8%) persons; none were healthcare workers exposed at work (n = 275). Exposure risk category and likelihood of developing mpox were strongly associated. A total of 333 persons received >1 dose of JYENNOS (Bavarian Nordic, https://www.bavarian-nordic.com) vaccine, most (n = 295) administered after virus exposure. Median time from exposure to vaccination was 8 days. Those data tools provided crucial real-time information for public health responses and can be used as a framework for other emerging diseases.

Coronavirus Anxiety, COVID Anxiety Syndrome and Mental Health: A Test Among Six Countries During March 2021.

The negative impact of the COVID-19 pandemic on mental health outcomes is widely documented. Specifically, individuals experiencing greater degrees of severity in coronavirus anxiety have demonstrated higher levels of generalized anxiety, depression and psychological distress. Yet the pathways in which coronavirus anxiety confers vulnerability are not well known. The present investigation sought to address this gap in the scientific literature by testing the indirect effect of the COVID-19 anxiety syndrome, which centres on the function of detecting and managing the environmental threat of virus exposure and its sequalae. Data were collected during the height of the pandemic (March 2021) and included 5297 adults across six countries. Structural equation modelling techniques revealed that the COVID-19 anxiety syndrome evidenced a statistically significant indirect effect between coronavirus anxiety and generalized anxiety, depression and work/social adjustment. Overall, results suggest there could be public health merit to targeting anxiety related to virus exposure to improve behavioural health for those who are struggling with excessive fear and worry.

Heterologous DNA Prime/Protein Boost Immunization Targeting Nef-Tat Fusion Antigen Induces Potent T-cell Activity and in vitro Anti-SCR HIV-1 Effects.

Heterologous combinations in vaccine design are an effective approach to promote T cell activity and antiviral effects. The goal of this study was to compare the homologous and heterologous regimens targeting the Nef-Tat fusion antigen to develop a human immunodeficiency virus-1 (HIV-1) therapeutic vaccine candidate. At first, the DNA and protein constructs harboring HIV-1 Nef and the first exon of Tat as linked form (pcDNA-nef-tat and Nef-Tat protein) were prepared in large scale and high purity. The generation of the Nef-Tat protein was performed in the E. coli expression system using an IPTG inducer. Then, we evaluated and compared immune responses of homologous DNA prime/ DNA boost, homologous protein prime/ protein boost, and heterologous DNA prime/protein boost regimens in BALB/c mice. Finally, the ability of mice splenocytes to secret cytokines after exposure to single-cycle replicable (SCR) HIV-1 was compared between immunized and control groups in vitro. The nef-tat gene was successfully subcloned in eukaryotic pcDNA3.1 (-) and prokaryotic pET-24a (+) expression vectors. The recombinant Nef-Tat protein was generated in the E. coli Rosetta strain under optimized conditions as a clear band of ~ 35 kDa detected on SDS-PAGE. Moreover, transfection of pcDNA-nef-tat into HEK-293T cells was successfully performed using Lipofectamine 2000, as confirmed by western blotting. The immunization studies showed that heterologous DNA prime/protein boost regimen could significantly elicit the highest levels of Ig- G2a, IFN-γ, and Granzyme B in mice as compared to homologous DNA/DNA and protein/protein regimens. Moreover, the secretion of IFN-γ was higher in DNA/protein regimens than in DNA/DNA and protein/protein regimens after exposure of mice splenocytes to SCR HIV-1 in vitro. The chimeric HIV-1 Nef-Tat antigen was highly immunogenic, especially when applied in a heterologous prime/ boost regimen. This regimen could direct immune response toward cellular immunity (Th1 and CTL activity) and increase IFN-γ secretion after virus exposure.

What are the environmental factors that affect respiratory viral pathogen transmission and outcomes? A scoping review of the published literature

IntroductionRespiratory viral pathogens are a major cause of morbidity and mortality, and there is a need to understand how to prevent their transmission.MethodsWe performed a scoping review to assess the amount and scope of published research literature on environmental factors, including meteorological factors and pollution, that affect the transmission of respiratory viral pathogens. We used Joanna Briggs Institute methodology for conducting a scoping review. We searched the electronic databases: MEDLINE, Register of Controlled Trials (Cochrane CENTRAL), TRIP database, WHO Covid-19 Database, Global Index Medicus, LitCovid, medRxiv, and Google Scholar. We included studies on environmental exposures and transmission of respiratory viruses (including but not restricted to: influenza, respiratory syncytial virus (RSV), human coronaviruses, viral pneumonia).ResultsThe searches identified 880 studies for screening; after screening we included 481 studies, including 395 primary studies and 86 reviews. Data were extracted by one reviewer (ES) and independently checked by a second reviewer for accuracy (AP). All primary studies were observational, mostly using an ecological design; 2/395 primary studies were prospective cohorts. Among the primary studies, 241/395 were on SARS-CoV-2/COVID-19; 95 focussed on influenza; the remaining 59 reported on RSV, other coronaviruses, and other respiratory viruses. Exposures were most commonly temperature (306 primary studies) and humidity (201 primary studies); other commonly reported exposures were air pollution, wind speed, precipitation, season, and UV radiation. It was frequently reported, but not consistently, that temperature, humidity and air pollution were positively correlated with COVID-19 cases/deaths; for influenza, season/seasonality was commonly reported to be associated with cases/deaths.DiscussionThe majority of studies reported on SARS-CoV-2/COVID-19 and were of ecological design. Few prospective cohort studies have been done for any respiratory virus and environmental exposures. Understanding the role of environmental factors on transmission is limited by the lack of prospective cohort studies to inform decision making.Systematic Review Registrationhttps://osf.io/ntdjx/, identifier: 10.17605/OSF.IO/NTDJX.

Rubella: from etiology to prevention, a comprehensive overview with a focus on congenital rubella syndrome

This review article aims to explore rubella, highlighting its historical evolution, clinical manifestations, and contemporary challenges in global health. The emphasis is on Congenital Rubella Syndrome (CRS), addressing its complexity, manifestations, and preventive strategies. Rubella, recognized as a viral entity in 1962, remains a global challenge despite vaccination efforts. The Global Vaccine Action Plan 2011-2020 seeks to eliminate rubella in five of the six WHO regions by 2020. Although there has been a reduction in cases, underreporting underscores the need for enhanced surveillance. CRS, resulting from infection during pregnancy, presents clinical complexities ranging from permanent physical defects to transient manifestations such as thrombocytopenia. Vaccination, notably with the measles, mumps, and rubella (MMR) vaccine, plays a crucial role in preventing rubella and CRS. Despite progress, challenges persist, including the lack of adequate global vaccine coverage. Early diagnosis of rubella during pregnancy is crucial, with serological and molecular methods playing a central role. Preventive strategies during pregnancy are essential due to the severity of CRS complications. Brazil, like other regions, adopts preventive measures, emphasizing the importance of pre-pregnancy vaccination and clinical surveillance in cases of virus exposure. Current symptomatic treatment does not eliminate the infection, emphasizing the ongoing need for research into specific antiviral therapies. An interdisciplinary approach and coordinated efforts are imperative to address the challenges of rubella and CRS on a global scale.

Neurodevelopmental Outcomes of Normocephalic Colombian Children with Antenatal Zika Virus Exposure at School Entry.

The long-term neurodevelopmental effects of antenatal Zika virus (ZIKV) exposure in children without congenital Zika syndrome (CZS) remain unclear, as few children have been examined to the age of school entry level. A total of 51 Colombian children with antenatal ZIKV exposure without CZS and 70 unexposed controls were evaluated at 4-5 years of age using the Behavior Rating Inventory of Executive Function (BRIEF), the Pediatric Evaluation of Disability Inventory (PEDI-CAT), the Bracken School Readiness Assessment (BSRA), and the Movement Assessment Battery for Children (MABC). The mean ages at evaluation were 5.3 and 5.2 years for cases and controls, respectively. Elevated BRIEF scores in Shift and Emotional Control may suggest lower emotional regulation in cases. A greater number of cases were reported by parents to have behavior and mood problems. BSRA and PEDI-CAT activity scores were unexpectedly higher in cases, most likely related to the COVID-19 pandemic and a delayed school entry among the controls. Although PEDI-CAT mobility scores were lower in cases, there were no differences in motor scores on the MABC. Of 40 cases with neonatal neuroimaging, neurodevelopment in 17 with mild non-specific findings was no different from 23 cases with normal neuroimaging. Normocephalic children with ZIKV exposure have positive developmental trajectories at 4-5 years of age but differ from controls in measures of emotional regulation and adaptive mobility, necessitating continued follow-up.

SARS-CoV-2 Infection Alters the Phenotype and Gene Expression of Adipocytes.

Epidemiological evidence emphasizes that excess fat mass is associated with an increased risk of severe COVID-19 disease. Nevertheless, the intricate interplay between SARS-CoV-2 and adipocytes remains poorly understood. It is crucial to decipher the progression of COVID-19 both in the acute phase and on long-term outcomes. In this study, an in vitro model using the human SGBS cell line (Simpson-Golabi-Behmel syndrome) was developed to investigate the infectivity of SARS-CoV-2 in adipocytes, and the effects of virus exposure on adipocyte function. Our results show that SGBS adipocytes expressing ACE2 are susceptible to SARS-CoV-2 infection, as evidenced by the release of the viral genome into the medium, detection of the nucleocapsid in cell lysates, and positive immunostaining for the spike protein. Infected adipocytes show remarkable changes compared to uninfected controls: increased surface area of lipid droplets, upregulated expression of genes of inflammation (Haptoglobin, MCP-1, IL-6, PAI-1), increased oxidative stress (MnSOD), and a concomitant reduction of transcripts related to adipocyte function (leptin, fatty acid synthase, perilipin). Moreover, exogenous expression of spike protein in SGBS adipocytes also led to an increase in lipid droplet size. In conclusion using the human SGBS cell line, we detected SARS-CoV-2 infectivity in adipocytes, revealing substantial morphological and functional changes in infected cells.

Assessing the Association Between Head and Neck Cancer and Granulomatosis with Polyangiitis.

Objective: To determine the odds of head and neck cancer (HNC) in patients with a concurrent or prior diagnosis of granulomatosis with polyangiitis (GPA). Methods and Materials: The TriNetX Analytics Network, a federated research platform that aggregates de-identified electronic health record data of over 130 million patients worldwide, was queried for patients with at least one ICD-10 encounter diagnosis of GPA. Patients within this group with an encounter diagnosis of cancer of the sinonasal, oral cavity, oropharynx, nasopharynx, and larynx concurrent or after the initial encounter diagnosis of GPA were recorded and compared to a standardized control population to determine odds ratios with a 95% confidence interval (CI). Relevant confounding variables, including human papillomavirus, Epstein Barr virus, tobacco, and alcohol exposure, were balanced between cohorts by 1:1 propensity matching. Results: Of the patients in the GPA cohort, 126 (0.48%) had an ICD-10 diagnosis of HNC. When stratifying by head and neck subsites, 20 (0.08%), 18 (0.07%), 23 (0.09%), 70 (0.27%), and 22 (0.084%) GPA patients had an ICD-10 encounter diagnosis of cancer involving the sinonasal, nasopharynx, larynx, oral cavity, and oropharynx. When comparing the experimental GPA group with the standardized control population after matching, patients in the GPA group had 1.3 times (95% CI: 1.03-1.175) greater odds of HNC when including cases diagnosed after or concurrently with the diagnosis of the vasculitis. There was no statistical difference in the odds of cancer at each anatomical subsite between the GPA and control cohort after matching. Conclusion: Our study identifies a statistically significant increase in the odds of HNC encounter diagnoses in patients with GPA.

Auditory Neural Responses and Communicative Functioning in Children With Microcephaly Related to Congenital Zika Syndrome.

Children with microcephaly exhibit neurodevelopmental delays and compromised communicative functioning, yielding challenges for clinical assessment and informed intervention. This study characterized auditory neural function and communication abilities in children with microcephaly due to congenital Zika syndrome (CZS). Click-evoked auditory brainstem responses (ABR) at fast and slow stimulation rates and natural speech-evoked cortical auditory evoked potentials (CAEP) were recorded in 25 Brazilian children with microcephaly related to CZS ( M age: 5.93 ± 0.62 years) and a comparison group of 25 healthy children ( M age: 5.59 ± 0.80 years) matched on age, sex, ethnicity, and socioeconomic status. Communication abilities in daily life were evaluated using caregiver reports on Vineland Adaptive Behavior Scales-3. Caregivers of children with microcephaly reported significantly lower than typical adaptive functioning in the communication and socialization domains. ABR wave I latency did not differ significantly between the groups, suggesting comparable peripheral auditory function. ABR wave V absolute latency and waves I-V interwave latency were significantly shorter in the microcephaly group for both ears and rates. CAEP analyses identified reduced N2 amplitudes in children with microcephaly as well as limited evidence of speech sound differentiation, evidenced mainly by the N2 response latency. Conversely, in the comparison group, speech sound differences were observed for both the P1 and N2 latencies. Exploratory analyses in the microcephaly group indicated that more adaptive communication was associated with greater speech sound differences in the P1 and N2 amplitudes. The trimester of virus exposure did not have an effect on the ABRs or CAEPs. Microcephaly related to CZS is associated with alterations in subcortical and cortical auditory neural function. Reduced ABR latencies differ from previous reports, possibly due to the older age of this cohort and careful assessment of peripheral auditory function. Cortical speech sound detection and differentiation are present but reduced in children with microcephaly. Associations between communication performance in daily life and CAEPs highlight the value of auditory evoked potentials in assessing clinical populations with significant neurodevelopmental disabilities.

Chimeric oncolytic adenovirus evades neutralizing antibodies from human patients and exhibits enhanced anti-glioma efficacy in immunized mice

Oncolytic viruses are a promising treatment for patients with high-grade gliomas, but neutralizing antibodies can limit their efficacy in patients with prior virus exposure or upon repeated virus injections. Data from a previous clinical trial using the oncolytic adenovirus Delta-24-RGD showed that generation of anti-viral neutralizing antibodies may affect the long-term survival of glioma patients. Past studies have examined the effects of neutralizing antibodies during systemic virus injections, but largely overlooked their impact during local virus injections into the brain. We found that immunoglobulins colocalized with viral proteins upon local oncolytic virotherapy of brain tumors, warranting a strategy to prevent virus neutralization and maximize oncolysis. Thus, we generated a chimeric virus, Delta-24-RGD-H43m, by replacing the capsid protein HVRs from the serotype 5-based Delta-24-RGD with those from the rare serotype 43. Delta-24-RGD-H43m evaded neutralizing anti-Ad5 antibodies and conferred a higher rate of long-term survival than Delta-24-RGD in glioma-bearing mice. Importantly, Delta-24-RGD-H43m activity was significantly more resistant to neutralizing antibodies present in sera of glioma patients treated with Delta-24-RGD during a phase 1 clinical trial. These findings provide a framework for a novel treatment of glioma patients that have developed immunity against Delta-24-RGD.