Neuropathological lesions in intravenous BCG-stimulated K18-hACE2 mice challenged with SARS-CoV-2.

In the wake of the COVID-19 pandemic caused by SARS-CoV-2, questions emerged about the potential effects of Bacillus Calmette-Guérin (BCG) vaccine on the immune response to SARS-CoV-2 infection, including the neurodegenerative diseases it may contribute to. To explore this, an experimental study was carried out in BCG-stimulated and non-stimulated k18-hACE2 mice challenged with SARS-CoV-2. Viral loads in tissues determined by RT-qPCR, histopathology in brain and lungs, immunohistochemical study in brain (IHC) as well as mortality rates, clinical signs and plasma inflammatory and coagulation biomarkers were assessed. Our results showed BCG-SARS-CoV-2 challenged mice presented higher viral loads in the brain and an increased frequency of neuroinvasion, with the greatest differences observed between groups at 3-4 days post-infection (dpi). Histopathological examination showed a higher severity of brain lesions in BCG-SARS-CoV-2 challenged mice, mainly consisting of neuroinflammation, increased glial cell population and neuronal degeneration, from 5 dpi onwards. This group also presented higher interstitial pneumonia and vascular thrombosis in lungs (3-4 dpi), BCG-SARS-CoV-2 mice showed higher values for TNF-α and D-dimer values, while iNOS values were higher in SARS-CoV-2 mice at 3-4 dpi. Results presented in this study indicate that BCG stimulation could have intensified the inflammatory and neurodegenerative lesions promoting virus neuroinvasion and dissemination in this experimental model. Although k18-hACE2 mice show higher hACE2 expression and neurodissemination, this study suggests that, although the benefits of BCG on enhancing heterologous protection against pathogens and tumour cells have been broadly demonstrated, potential adverse outcomes due to the non-specific effects of BCG should be considered.

SARS-CoV-2 Seroprevalence Studies in Pets, Spain.

SARS-CoV-2 can infect domestic animals such as cats and dogs. The zoonotic origin of the disease requires surveillance on animals. Seroprevalence studies are useful tools for detecting previous exposure because the short period of virus shedding in animals makes detection of the virus difficult. We report on an extensive serosurvey on pets in Spain that covered 23 months. We included animals with exposure to SARS-CoV-2-infected persons, random animals, and stray animals in the study. We also evaluated epidemiologic variables such as human accumulated incidence and spatial location. We detected neutralizing antibodies in 3.59% of animals and showed a correlation between COVID-19 incidence in humans and positivity to antibody detection in pets. This study shows that more pets were infected with SARS-CoV-2 than in previous reports based on molecular research, and the findings highlight the need to establish preventive measures to avoid reverse zoonosis events.

Natural SARS-CoV-2 Infection in Kept Ferrets, Spain.

We found severe acute respiratory syndrome coronavirus 2 RNA in 6 (8.4%) of 71 ferrets in central Spain and isolated and sequenced virus from 1 oral and 1 rectal swab specimen. Natural infection occurs in kept ferrets when virus circulation among humans is high. However, small ferret collections probably cannot maintain virus circulation.

Vitamin B-6 and depressive symptomatology, over time, in older Latino adults.

Background: Low vitamin B-6 status has been linked to depressive symptomatology. We examined the longitudinal association of vitamin B-6 status with depressive symptomatology across 3-time points over ∼5-7 years in a cohort of older Hispanic adults. Methods: We used two-level hierarchical linear regression models for continuous outcomes. Vitamin B-6 status was associated with depressive symptomatology across these time points. Results: Plasma pyridoxyl-5-phosphate (PLP) concentration, a time-varying predictor, was significantly associated with depressive symptomatology. Study participants with PLP deficiency, vs. optimal PLP, had higher baseline depressive symptoms (Center for Epidemiologic Studies-Depression Scale (CES-D) score of 22 ± 14, vs. 20 ± 13); this differential remained constant over time and persisted after controlling for age, sex, education, body mass index, smoking and alcohol use, other relevant nutritional factors, perceived stress, stressful life events, allostatic load, and use of antidepressant medication. However, PLP concentration was not associated with the rate of change in depressive symptomatology over time. Conclusions: Suboptimal plasma PLP is associated with higher depressive symptomatology in older Hispanic of Puerto Rican descent and this appears to persist over time. Our data suggest that identification and treatment of vitamin B-6 deficiency may be a useful preventive approach in this population.

Immune related genes as markers for monitoring health status of honey bee colonies.

BACKGROUND: Honey bee population decline threatens the beekeeping sector, agriculture and global biodiversity. Early detection of colony mortality may facilitate rapid interventions to contain and prevent mortality spread. Among others, deformed wing virus (DWV) is capable of inducing colony losses, especially when combined with Varroa destructor mite. Since the bee immune system plays a crucial role in ensuring that bees are able to face these pathogens, we explored whether expression of immune genes could serve as biomarkers of colony health. RESULTS: Herein, we describe a preliminary immunological marker composed of two immune genes (relish and defensin), which provide insight on honey bee antiviral defense mechanism. Of the tested genes, relish expression correlated with the presence of DWV-Varroa complex, while decreased defensin expression correlated with poor resistance to this complex. CONCLUSIONS: The monitoring of these genes may help us to better understand the complex physiology of honey bees's immune system and to develop new approaches for managing the health impacts of DWV infection and varroa infestation in the field.

Genetic admixture and body composition in Puerto Rican adults from the Boston Puerto Rican Osteoporosis Study.

Population admixture plays a role in the risk of chronic conditions that are related to body composition; however, our understanding of these associations in Puerto Ricans, a population characterized by multiple ancestries, is limited. This study investigated the relationship between genetic admixture and body composition in 652 Puerto Ricans from the Boston Puerto Rican Osteoporosis Study. Genetic ancestry was estimated from 100 ancestry-informative markers. Body composition measures were obtained from dual-energy X-ray absorptiometry. Multivariable linear regression analyses examined associations between bone mineral density (BMD) of the hip and lumbar spine and percent fat mass and lean mass with genetic admixture. In Puerto Ricans living on the US mainland, European ancestry was associated with lower BMD at the trochanter (P = 0.039) and femoral neck (P = 0.01), and Native American ancestry was associated with lower BMD of the trochanter (P = 0.04). African ancestry was associated with a higher BMD at the trochanter (P = 0.004) and femoral neck (P = 0.001). Ancestry was not associated with percent fat mass or lean mass or waist circumference. Our findings are consistent with existing research demonstrating inverse associations between European and Native American ancestries and BMD and positive relationships between African ancestry and BMD. This work contributes to our understanding of the high prevalence of chronic disease experienced by this population and has implications for other ethnic minority groups, particularly those with multiple ancestries. Future research should consider interactions between ancestry and environmental factors, as this may provide individualized approaches for disease prevention.

Lifetime Polyvictimization and Mental Health Outcomes in Women With vs Without Incarceration Histories: A Population-Based Latent Class Analysis.

We use latent class analysis, a life course framework, and information on the type, frequency, and timing of trauma exposure to identify distinct polytrauma groups in a national sample of women (AddHealth). We compare the identified polytrauma groups and their associations with mental health in adulthood in women with and without incarceration histories. A unique group with polyvictimization (neglect, physical, sexual) exposure in childhood by a caregiver in women with incarceration histories was not identified in women without incarceration histories. We find evidence of distinct associations between polytrauma groups and mental health and possibly, criminal justice involvement, in adulthood.

Longitudinal associations between biopsychosocial stress indicators and sleep in older Puerto Rican adults.

OBJECTIVES: To examine the association of biopsychosocial stress indicators (perceived stress, perceived discrimination, stressful life events, and allostatic load) with sleep outcomes (sleep duration and insomnia symptoms) and to examine sex and age interactions for associations between stress and sleep in older Puerto Rican adults. METHODS: Secondary analyses were performed with 830 participants (72% female) from wave 2 (2006-2011) of the Boston Puerto Rican Health Study (BPRHS), a prospective population-based cohort study (45-75years at baseline) and Boston Puerto Rican Osteoporosis Study (BPROS) (2007-2012), an ancillary study of the BPRHS. Recruitment occurred in randomly selected census blocks using door-to-door and community-based activities. In-home data collection visits included a baseline assessment and follow-up interviews. Questionnaires assessed perceived stress, discrimination, stressful life events, and sleep. Allostatic load indicators were measured objectively. Regression models controlled for sociodemographic, behavioral, and health factors, with interaction analyses, followed by sex- and sex-by-age-stratified analyses. RESULTS: In the prior 2years, participants with chronic stress had 50% greater odds of reporting nonoptimal sleep duration (<7 or >9 hours). Life events trajectories were significantly related to insomnia symptoms. Men ≥65years who experienced chronic stress had greater insomnia symptoms than women, or than men with low stress or acute stress. CONCLUSIONS: Stressful life events may affect sleep duration and insomnia symptoms among older Puerto Rican adults, particularly men 65 years and older who experienced chronic stress. Given the differences in sleep patterns experienced by older adults and their relationships with health outcomes, identifying methods to support sleep health among those with chronic stress is important.

Challenging boundaries: is cross-protection evaluation necessary for African swine fever vaccine development? A case of oral vaccination in wild boar.

African swine fever (ASF) poses a significant threat to domestic pigs and wild boar (Sus scrofa) populations, with the current epidemiological situation more critical than ever. The disease has spread across five continents, causing devastating losses in the swine industry. Although extensive research efforts are ongoing to develop an effective and safe vaccine, this goal remains difficult to achieve. Among the potential vaccine candidates, live attenuated viruses (LAVs) have emerged as the most promising option due to their ability to provide strong protection against experimental challenges. However, ASF virus (ASFV) is highly diverse, with genetic and phenotypic variations across different isolates, which differ in virulence. This study highlights the limitations of a natural LAV strain (Lv17/WB/Rie1), which showed partial efficacy against a highly virulent and partially heterologous isolate (Arm07; genotype II). However, the LAV's effectiveness was incomplete when tested against a more phylogenetically distant virus (Ken06.Bus; genotype IX). These findings raise concerns about the feasibility of developing a universal vaccine for ASFV in the near future, emphasizing the urgent need to assess the protective scope of LAV candidates across different ASFV isolates to better define their limitations.

Comparative SARS-CoV-2 Omicron BA.5 variant and D614G-Wuhan strain infections in ferrets: insights into attenuation and disease progression during subclinical to mild COVID-19.

Introduction: As the SARS-CoV-2 virus continues to evolve and new variants emerge, it becomes crucial to understand the comparative pathological and immunological responses elicited by different strains. This study focuses on the original Wuhan strain and the Omicron variant, which have demonstrated significant differences in clinical outcomes and immune responses. Methods: We employed ferrets as an experimental model to assess the D614G variant (a derivative of the Wuhan strain) and the Omicron BA.5 variant. Each variant was inoculated into separate groups of ferrets to compare disease severity, viral dissemination, and immune responses. Results: The D614G variant induced more severe disease and greater viral spread than the Omicron variant. Notably, ferrets infected with the D614G variant exhibited a robust neutralizing antibody response, whereas those infected with the Omicron variant failed to produce a detectable neutralizing antibody response. Despite the clearance of the virus from nearly all tissues by 7 days post-infection, an increase in pathological lesions was observed from 14 to 21 days, particularly in those infected with the D614G variant, suggesting a sustained immune response even after viral clearance. Discussion: These findings underscore the adaptability of SARS-CoV-2 and illuminate how susceptibility and clinical manifestations vary across different strains and species. The results emphasize the necessity of considering both the direct effects of viral infection and the indirect, often prolonged, impacts of the immune response in evaluating the outcomes of SARS-CoV-2 infections.

Determinants of self-rated health and the role of acculturation: implications for health inequalities.

OBJECTIVES: Self-rated health (SRH) is an important indicator of overall health, predicting morbidity and mortality. This paper investigates what individuals incorporate into their self-assessments of health and how acculturation plays a part in this assessment. The relationship of acculturation to SRH and whether it moderates the association between indicators of health and SRH is also examined. DESIGN: The paper is based on data from adults in the Boston Puerto Rican Health Study, living in the greater Boston area (n=1357) mean age 57.2 (SD = 7.6). We used multiple regression analysis and testing for moderation effects. RESULTS: The strongest predictors of poor SRH were the number of existing medical conditions, functional problems, allostatic load and depressive symptoms. Poor SRH was also associated with being female, fewer years of education, heavy alcohol use, smoking, poverty, and low emotional support. More acculturated Puerto Rican adults rated their health more positively, which corresponded to better indicators of physical and psychological health. Additionally, acculturation moderated the association between some indicators of morbidity (functional status and depressive symptoms) and SRH.Self-assessments of overall health integrate diverse indicators, including psychological symptoms, functional status and objective health indicators such as chronic conditions and allostatic load. However, adults' assessments of overall health differed by acculturation, which moderated the association between health indicators and SRH. The data suggest that when in poor health, those less acculturated may understate the severity of their health problems when rating their overall health, thus SRH might thus conceal disparities. Using SRH can have implications for assessing health disparities in this population.

Caregiving for Foreign-Born Older Adults With Dementia.

OBJECTIVES: This study examines how nativity, dementia classification, and age of migration (AOM) of older foreign-born (FB) adults are associated with caregiver psychological well-being and care burden. METHODS: We used linked data from Round 1 and Round 5 of the National Health and Aging Trends Study and Round 5 of the National Study of Caregiving for a sample of nondementia caregivers (n = 941), dementia caregivers (n = 533), and matched care recipients. Ordinary least squares regression models were estimated, adjusting for caregiver characteristics. RESULTS: Relative to nondementia caregivers, dementia caregivers were more likely to provide care for an older FB adult (8.69% vs. 26.70%), reported more assistance with caregiving activities, worse quality of relationship with care recipients, and higher care burden than nondementia caregivers. In adjusted models, interactions of nativity status × dementia and AOM × dementia revealed that overall, caregivers of older FB adults with dementia who migrated in late life (50+) reported lower psychological well-being than those caring for older FB older adults who migrated at (20-49 years) and (0-19 years). Moderating effects of AOM on the link between dementia caregiving and care burden were not observed. DISCUSSION: Age of migration of older FB adults with probable dementia may have unique effects on the caregiver's psychological well-being. Our results underscore the importance of considering sociocultural factors of FB adults beyond nativity and the need for research to develop culturally appropriate interventions to enhance psychological well-being and reduce the care burden among dementia caregivers.

Longitudinal Associations Between Sleep and Cognitive Function in a Cohort of Older Puerto Rican Adults: Sex and Age Interactions.

BACKGROUND: Evidence on sleep duration or quality and cognitive function in diverse older adults is limited. We examined prospective associations between subjective sleep measures and cognitive function, with modifying effects of sex and age (<65 vs ≥65 years). METHODS: Data are from the longitudinal Boston Puerto Rican Health Study, Waves 2 (n = 943) and 4 (n = 444), with mean follow-up of 10.5 years (range 7.2-12.8). Subjective measures of sleep duration (short <7, ref. 7, or long ≥8 hours) and insomnia symptoms (sum of difficulty falling asleep, waking up at night, and early morning awakening), were assessed at Wave 2. Linear regression models were used to assess changes in global cognition, executive function, memory, and Mini-Mental State Examination, and tested for modifying roles of sex and age. RESULTS: Significant 3-way interaction (sex × age × cognition) in fully adjusted models showed greater decline in global cognitive function in older men with short (ß [95% confidence interval]: -0.67 [-1.24, -0.10]) or long sleep duration (-0.92 [-1.55, -0.30]), compared to women, younger men, and older men with 7 hours of sleep. Insomnia symptoms were associated with a greater decline in memory (-0.54, [-0.85, -0.22]) among older men, compared to women and younger men. CONCLUSION: Sleep duration showed a U-shaped association with cognitive decline, and insomnia symptoms were associated with memory decline in fully adjusted models. Older men, versus women and younger men, were at relatively greater risk for cognitive decline associated with sleep factors. These findings are important for personalizing sleep interventions to support cognitive health.

Importance of genomic surveillance of SARS-CoV-2 in cats during reverse zoonosis events: potential viral evolution may occur.

The apparition of new variants of severe acute respiratory syndrome coronavirus 2 and lineages is constantly happening because of the high viral mutation rate. Since numerous reverse zoonosis events have been reported so far, genomic surveillance should be conducted in susceptible species to evaluate potential adaptations that may trigger the apparition of new variants. Here, we evaluate the evolution of the infection in a cat naturally infected in parallel with its owner, performing a comparative phylogenetic analysis. Sequencing analysis showed that both were infected with the Omicron BA.5/BF.1 lineage and revealed the presence of nucleotide substitution in the viral genome recovered from the cat with respect to the viral genome from the human sample. This nucleotide substitution (C11897A) produced the amino acid change Orf1a: Q3878K. Therefore, genomic surveillance in the case of reverse zoonosis events is still necessary in order to control possible adaptations of the virus to other susceptible species. IMPORTANCE Genomic surveillance of pets for severe acute respiratory syndrome coronavirus 2 is important to monitor the emergence of new variants of the virus associated with these animals. Pets can serve as a potential reservoir for the virus, and their close contact with humans increases the risk of transmission. By conducting genomic surveillance in pets, it is possible to detect and track new variants early on, allowing for more effective control measures to be put in place. This can help prevent the spread of these variants to human populations and potentially mitigate the impact of the pandemic. Furthermore, it may also provide insight into the evolution and spread of the virus within the animal population.

A retrospective study of SARS-CoV-2 seroprevalence in dogs and cats in the Community of Madrid, Spain.

To date, susceptibility to SARS-CoV-2 infection in domestic animals including cats and dogs has been described. However, it is important to carry out passive surveillance of these animals to be aware of any changes in the outcomes of the disease in these species that may occur. In this study, we have performed a retrospective study in which we analyzed sera (n = 1,640) from random animals: dogs (n = 1,381) and cats (n = 259) belonging to both homes (n = 1,533) and animal protection centers (n = 107) in the Community of Madrid, Spain. Neutralizing antibodies were evaluated between November 2021 and May 2022 using a surrogate ELISA kit to determine the seroprevalence. Based on the results obtained, a few animals (both cats and dogs) presented neutralizing antibodies to SARS-CoV-2 (2.3%), all of them from private owners. However, the seroprevalence in cats (4.6%) resulted to be almost twice as much as in dogs (1.9%) which reinforces that cats' susceptibility to the infection seems higher than in the case of dogs, maybe due to the lower ACE2 expression of the dogs in the respiratory tract. These findings also confirm that the probability of infection is considerably higher in domestic animals in close contact with infected owners, compared to animals living in animal shelters whose contact with humans is markedly lower.

A useful tool for the safe diagnosis and control of the two main pandemics of the XXI century: COVID-19 and African Swine Fever disease.

The COVID-19 pandemic and the disease triggered by the African Swine Fever virus are currently two of the main problems regarding public and animal health, respectively. Although vaccination seems to be the ideal tool for controlling these diseases, it has several limitations. Therefore, early detection of the pathogen is critical in order to apply preventive and control measures. Real-time PCR is the main technique used for the detection of both viruses, which requires previous processing of the infectious material. If the potentially infected sample is inactivated at the time of sampling, the diagnosis will be accelerated, impacting positively on the diagnosis and control of the disease. Here, we evaluated the inactivation and preservation properties of a new surfactant liquid for non-invasive and environmental sampling of both viruses. Our results demonstrated that the surfactant liquid effectively inactivates SARS-CoV-2 and African Swine Fever virus in only five minutes, and allows for the preservation of the genetic material for long periods even at high temperatures such as 37°C. Hence, this methodology is a safe and useful tool for recovering SARS-CoV-2 and African Swine Fever virus RNA/DNA from different surfaces and skins, which has significant applied relevance in the surveillance of both diseases.

Low transmission risk of African swine fever virus between wild boar infected by an attenuated isolate and susceptible domestic pigs.

African swine fever (ASF) is a lethal infectious disease that affects domestic and wild pigs. This complex virus has already affected five continents and more than 70 countries and is considered to be the main threat to the global swine industry. The disease can potentially be transmitted directly through contact with infectious animals, or indirectly by means of contaminated feed or environments. Nevertheless, the knowledge regarding the transmission patterns of different ASF virus isolates at the wildlife-livestock interface is still limited. We have, therefore, assessed the potential transmission of an attenuated ASF virus isolate between infectious wild boar and directly exposed domestic pig. We registered 3,369 interspecific interactions between animals, which were brief and mostly initiated by wild boar. The major patterns observed during the study were head-to-head contact owing to sniffing, thus suggesting a high probability of pathogen transmission. However, only one of the five domestic pigs had a short period of viremia and became serologically positive for ASF virus antibodies. It was additionally discovered that the wild boar did not transmit the virulent virus isolate to the domestic pigs, which suggests that the presence of attenuated ASF virus isolates in affected areas may control the spreading of other more virulent isolates. These outcomes may help make decisions related to large-scale targeted management actions against ASF in field conditions.

New insights into the pathogenesis and transmission of Brucella pinnipedialis: systemic infection in two bottlenose dolphins (Tursiops truncatus).

IMPORTANCE: Brucella spp. are zoonotic pathogens that can affect both terrestrial and marine mammals. Brucella ceti has been identified in various cetacean species, but only one sequence type (ST27) has been reported in humans. However, it is important to conduct surveillance studies to better understand the impact of marine Brucella species on marine mammals, a typically understudied host group. Here, we describe a systemic infection by two related strains of Brucella pinnipedialis (ST25) in a couple of live-stranded bottlenose dolphins, with more severe lesions in the younger animal. Furthermore, B. pinnipedialis was first detected in milk from a female cetacean that stranded with its offspring. Our study reveals novel insights into the epidemiology and pathological consequences of B. pinnipedialis infections in cetaceans, emphasizing the crucial importance of ongoing surveillance and accurate diagnosis to understand the impact of this pathogen on marine mammal populations.

The Omicron (B.1.1.529) SARS-CoV-2 variant of concern also affects companion animals.

The emergence of the Omicron variant (B.1. 1.529) has brought with it an increase in the incidence of SARS-CoV-2 disease. However, there is hardly any data on its incidence in companion animals. We have detected the presence of this new variant in domestic animals (dogs and cats) living with infected owners in Spain. None of the RT-qPCR positive animals (10.13%) presented any clinical signs and the viral loads detected were low. In addition, the shedding of viral RNA lasted a short period of time in the positive animals. Infection with this variant of concern (VOC) was confirmed by RT-qPCR and sequencing. These outcomes suggest a lower virulence of this variant in infected cats and dogs. They also demonstrate the transmission from infected humans to domestic animals and highlight the importance of active surveillance as well as genomic research to detect the presence of VOCs or mutations associated with animal hosts.

First Detection of SARS-CoV-2 B.1.617.2 (Delta) Variant of Concern in a Symptomatic Cat in Spain.

Natural and experimental SARS-CoV-2 infection in pets has been widely evidenced since the beginning of the COVID-19 pandemic. Among the numerous affected animals, cats are one of the most susceptible species. However, little is known about viral pathogenicity and transmissibility in the case of variants of concern (VOCs) in animal hosts, such as the B.1.617.2 (Delta) variant first detected in India. Here, we have identified the B.1.617.2 (Delta) VOC in a cat living with a COVID-19 positive owner. The animal presented mild symptoms (sneezing) and a high viral load was detected in the oropharyngeal swab, suggesting that an active infection was occurring in the upper respiratory tract of the cat. Transmission from the owner to the cat occurred despite the human being fully vaccinated against SARS-CoV-2. This study documents the first detection of B.1.165.2 VOC in a cat in Spain and emphasizes the importance of performing active surveillance and genomic investigation on infected animals.