Seroprevalence of Severe Acute Respiratory Syndrome Coronavirus 2 Among Skilled Nursing Facility Residents and Staff Members-Los Angeles County, August-September 2020.

BACKGROUND: The prevalence of current or past coronavirus disease 2019 in skilled nursing facility (SNF) residents is unknown because of asymptomatic infection and constrained testing capacity early in the pandemic. We conducted a seroprevalence survey to determine a more comprehensive prevalence of past coronavirus disease 2019 in Los Angeles County SNF residents and staff members. METHODS: We recruited participants from 24 facilities; participants were requested to submit a nasopharyngeal swab sample for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) testing and a serum sample for detection of SARS-CoV-2 antibodies. All participants were cross-referenced with our surveillance database to identify persons with prior positive SARS-CoV-2 results. RESULTS: From 18 August to 24 September 2020, we enrolled 3305 participants (1340 residents and 1965 staff members). Among 856 residents providing serum samples, 362 (42%) had current or past SARS-CoV-2 infection. Of the 346 serology-positive residents, 199 (58%) did not have a documented prior positive SARS-CoV-2 PCR result. Among 1806 staff members providing serum, 454 (25%) had current or past SARS-CoV-2 infection. Of the 447 serology-positive staff members, 353 (79%) did not have a documented prior positive SARS-CoV-2 PCR result. CONCLUSIONS: Past testing practices and policies missed a substantial number of SARS-CoV-2 infections in SNF residents and staff members.

Analysis of Domestic Violence Related Homicides in Los Angeles County: Media Portrayals, Demographics, and Precipitating Circumstances.

Intimate partner violence (IPV) remains a pressing public health issue. Nationally, 1 in 5 women and 1 in 10 men have sustained severe physical violence from an intimate partner. Intimate partner homicides (IPH) are the most serious IPV outcome. This study examined documented IPH in Los Angeles County during 2017, analyzing if precipitating circumstances, victim demographics, victim/suspect relationship, and weapon type were related to how often a homicide was reported in online media stories. Cases were identified from the National Violent Death Reporting System (NVDRS), and standardized internet searches identified media articles associated with each case. Victim demographics from NVDRS and media articles were compared using Chi Square tests. Media report frequency, within different categorical predictor values, were examined using ANOVA models. 44 incidents were identified; averaging 5.2 articles per decedent. Univariate analyses showed significant difference in media reporting by poverty level (low versus high socioeconomic status) and presence of preceding argument. Multivariate analyses found significantly more media reports (p = 0.002) for incidents in which a preceding argument is reported, the victim was 30-39 years old and from a low socioeconomic status zip code. From our results certain characteristics of IPH are associated with greater media reporting. Promotion of consistent and responsible IPH media reporting guidelines is an opportunity to reinforce public health messaging and dispel myths. In turn, this will encourage the development of future policies and funding streams across the spectrum of preventing and stopping IPV.

Early Social Stress Promotes Inflammation and Disease Risk in Rhesus Monkeys.

Early social stress has potent lifelong health effects. We examined the association of early stress in the attachment relationship (low maternal sensitivity, low MS), lower maternal social hierarchy rank, and greater frequency of group-level social conflict, with biomarkers of inflammatory stress response in plasma (IL-8, MCP-1 and CRP collected two hours after temporary separation from mothers and social groups) and risk for developing a common macaques disease outcome (infectious colitis) in 170 socially-housed rhesus monkeys. We controlled for gene-environment correlations by comparing cross-fostered subjects with infants reared by their biological mothers. Low MS predicted higher levels of pro-inflammatory cytokines and proteins at 3-4 months of age (F(3, 162) = 3.508, p = 0.002, partial eta2 = 0.061) and higher lifetime risk for developing colitis for up to twelve years of age (chi square = 5.919, p = 0.026). Lower maternal social rank (F (3, 162) = 3.789, p = 0.012, partial eta2 = 0.06) and higher rates of social conflict (F (3, 162) = 4.264, p = 0.006, partial eta2 = 0.074) each also predicted greater inflammation in infancy, but not lifetime colitis risk (both p > 0.05). The effects of low MS, lower social rank, and higher social conflict were significant in infants reared by biological mothers and cross-fostered infants, suggesting that our results did not arise from gene-environment correlations, but environmental stressors alone. We conclude that several types of early social stress confer risk for inflammation in infancy, but that stress in the mother-infant relationship may confer the longest-term risk for adverse health outcomes.

Arginine vasopressin in cerebrospinal fluid is a marker of sociality in nonhuman primates.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by core social impairments. ASD remains poorly understood because of the difficulty in studying disease biology directly in patients and the reliance on mouse models that lack clinically relevant, complex social cognition abilities. We use ethological observations in rhesus macaques to identify male monkeys with naturally occurring low sociality. These monkeys showed differences in specific neuropeptide and kinase signaling pathways compared to socially competent male monkeys. Using a discovery and replication design, we identified arginine vasopressin (AVP) in cerebrospinal fluid (CSF) as a key marker of group differences in monkey sociality; we replicated these findings in an independent monkey cohort. We also confirmed in an additional monkey cohort that AVP concentration in CSF is a stable trait-like measure. Next, we showed in a small pediatric cohort that CSF AVP concentrations were lower in male children with ASD compared to age-matched male children without ASD (but with other medical conditions). We demonstrated that CSF AVP concentration was sufficient to accurately distinguish ASD cases from medical controls. These data suggest that AVP and its signaling pathway warrant consideration in future research studies investigating new targets for diagnostics and drug development in ASD.

Intermittent pair-housing, pair relationship qualities, and HPA activity in adult female rhesus macaques.

Laboratory rhesus macaques are often housed in pairs and may be temporarily or permanently separated for research, health, or management reasons. While both long-term social separations and introductions can stimulate a stress response that impacts inflammation and immune function, the effects of short-term overnight separations and whether qualities of the pair relationship mediate these effects are unknown. In this study, we investigated the effects of overnight separations on the urinary cortisol concentration of 20 differentially paired adult female rhesus macaques (Macaca mulatta) at the California National Primate Research Center. These females were initially kept in either continuous (no overnight separation) or intermittent (with overnight separation) pair-housing and then switched to the alternate pair-housing condition part way through the study. Each study subject was observed for 5 weeks, during which we collected measures of affiliative, aggressive, anxious, abnormal, and activity-state behaviors in both pair-housing conditions. Additionally, up to three urine samples were collected from each subject per week and assayed for urinary free cortisol and creatinine. Lastly, the behavioral observer scored each pair on four relationship quality attributes ("Anxious," "Tense," "Well-meshed," and "Friendly") using a seven-point scale. Data were analyzed using a generalized linear model with gamma distribution and an information theoretic approach to determine the best model set. An interaction between the intermittent pairing condition and tense pair adjective rating was in the top three models of the best model set. Dominance and rates of affiliation were also important for explaining urinary cortisol variation. Our results suggest that to prevent significant changes in HPA-axis activation in rhesus macaque females, which could have unintended effects on research outcomes, pairs with "Tense" relationships and overnight separations preventing tactile contact should be avoided.

Preference for novel faces in male infant monkeys predicts cerebrospinal fluid oxytocin concentrations later in life.

The ability to recognize individuals is a critical skill acquired early in life for group living species. In primates, individual recognition occurs predominantly through face discrimination. Despite the essential adaptive value of this ability, robust individual differences in conspecific face recognition exist, yet its associated biology remains unknown. Although pharmacological administration of oxytocin has implicated this neuropeptide in face perception and social memory, no prior research has tested the relationship between individual differences in face recognition and endogenous oxytocin concentrations. Here we show in a male rhesus monkey cohort (N = 60) that infant performance in a task used to determine face recognition ability (specifically, the ability of animals to show a preference for a novel face) robustly predicts cerebrospinal fluid, but not blood, oxytocin concentrations up to five years after behavioural assessment. These results argue that central oxytocin biology may be related to individual face perceptual abilities necessary for group living, and that these differences are stable traits.

Depressive-like behavior, its sensitization, social buffering, and altered cytokine responses in rhesus macaques moved from outdoor social groups to indoor housing.

Psychosocial stressors appear to promote the onset of depressive illness through activation and sensitization of inflammatory mechanisms. Here, adult male rhesus monkeys brought from large outdoor social groups to indoor housing for 8 days reliably exhibited a hunched, depressive-like posture. When rehoused indoors a second 8 days about 2 weeks later, monkeys housed alone, but not those with an affiliative partner, showed sensitization of the depressive-like hunched posture. Housing indoors also affected circulating pro-inflammatory cytokines: IL-1ß showed increased responsiveness to immune challenge, and IL-1ß and TNF-α showed reduced suppression by dexamethasone. Sensitivity of the anti-inflammatory cytokine IL-10 to immune challenge exhibited a relative increase from the first to the second round of indoor housing in animals housed in pairs, and a relative decrease in animals housed alone. Cytokine levels during indoor housing were positively correlated with duration of depressive-like behavior. Plasma cortisol levels increased but did not differentiate housing conditions or rounds. Results demonstrate a rapid induction and sensitization of depressive-like behavior to indoor individual housing, social buffering of sensitization, and associated inflammatory responses. This paradigm may provide a practical nonhuman primate model for examining inflammatory-mediated consequences of psychosocial stressors on depression and possible social buffering of these effects.

Developmental consequences of behavioral inhibition: a model in rhesus monkeys (Macaca mulatta).

In children, behavioral inhibition is characterized by a disposition to withdraw in the presence of strangers and novel situations. Later in life, behavioral inhibition can result in an increased risk for anxiety and depression and a decrease in social behavior. We selected rhesus monkeys that, during infancy, showed evidence of behavioral inhibition in response to separation, and contrasted them with non-inhibited peers. To understand the development of behavioral inhibition at juvenile age, we collected behavioral data in response to relocation; in response to a human intruder challenge; and in naturalistic outdoor field corrals. At 4 years of age (young adulthood), we again collected behavioral data in the outdoor field corrals to understand the adult social consequences of behavioral inhibition. We also included sex, dominance rank, and number of available kin in our analyses. Finally, to understand the consistency in behavior in behaviorally inhibited animals, we conducted exploratory analyses contrasting behaviorally inhibited animals that showed high vs. low durations of non-social behaviors as adults. At juvenile age, behaviorally inhibited animals continued to show behavioral differences in the novel testing room and during the human intruder challenge, generally showing evidence of greater anxiety and emotionality compared to non-inhibited controls. In their outdoor corrals, behaviorally inhibited juveniles spent more time alone and less time in proximity and grooming with mother and other adult females. In young adulthood, we found that behavioral inhibition was not related to time spent alone. We did find that duration of time alone in adulthood was related to time alone exhibited as juveniles; sex, dominance rank, or the number of kin were not influential in adult non-social duration, either as main effects or as moderators. Finally, exploratory analyses revealed that behaviorally inhibited females that were more sociable (less time spent alone) as adults had spent more time grooming as juveniles, suggesting that high-quality social interaction at a young age might mitigate the social consequences of behavioral inhibition. Overall, we believe that the many similarities with the human data that we found suggest that this monkey model of naturally occurring behavioral inhibition can be valuable for understanding social development.

Myeloid differentiation architecture of leukocyte transcriptome dynamics in perceived social isolation.

To define the cellular mechanisms of up-regulated inflammatory gene expression and down-regulated antiviral response in people experiencing perceived social isolation (loneliness), we conducted integrative analyses of leukocyte gene regulation in humans and rhesus macaques. Five longitudinal leukocyte transcriptome surveys in 141 older adults showed up-regulation of the sympathetic nervous system (SNS), monocyte population expansion, and up-regulation of the leukocyte conserved transcriptional response to adversity (CTRA). Mechanistic analyses in a macaque model of perceived social isolation confirmed CTRA activation and identified selective up-regulation of the CD14(++)/CD16(-) classical monocyte transcriptome, functional glucocorticoid desensitization, down-regulation of Type I and II interferons, and impaired response to infection by simian immunodeficiency virus (SIV). These analyses identify neuroendocrine-related alterations in myeloid cell population dynamics as a key mediator of CTRA transcriptome skewing, which may both propagate perceived social isolation and contribute to its associated health risks.

Behavioral inhibition in rhesus monkeys (Macaca mulatta) is related to the airways response, but not immune measures, commonly associated with asthma.

Behavioral inhibition reflects a disposition to react warily to novel situations, and has been associated with atopic diseases such as asthma. Retrospective work established the relationship between behavioral inhibition in rhesus monkeys (Macaca mulatta) and airway hyperresponsiveness, but not atopy, and the suggestion was made that behavioral inhibition might index components of asthma that are not immune-related. In the present study, we prospectively examined the relationship between behavioral inhibition and airway hyperresponsiveness, and whether hormonal and immune measures often associated with asthma were associated with behavioral inhibition and/or airway hyperresponsiveness. In a sample of 49 yearling rhesus monkeys (mean=1.25 years, n=24 behaviorally inhibited animals), we measured in vitro cytokine levels (IL-4, IL-10, IL-12, IFN-γ) in response to stimulation, as well as peripheral blood cell percentages, cortisol levels, and percentage of regulatory T-cells (CD3+CD4+CD25+FOXP3+). Airway reactivity was assessed using an inhaled methacholine challenge. Bronchoalveolar lavage was performed and the proportion of immune cells was determined. Behaviorally inhibited monkeys had airway hyperresponsiveness as indicated by the methacholine challenge (p=0.031), confirming our earlier retrospective result. Airway hyperresponsiveness was also associated with lower lymphocyte percentages in lavage fluid and marginally lower plasma cortisol concentrations. However, none of the tested measures was significantly related to both behavioral inhibition and airway hyperresponsiveness, and so could not mediate their relationship. Airway hyperresponsiveness is common to atopic and non-atopic asthma and behavioral inhibition has been related to altered autonomic activity in other studies. Our results suggest that behavioral inhibition might index an autonomically mediated reactive airway phenotype, and that a variety of stimuli (including inflammation within lung tissue that is not specifically associated with behavioral inhibition) may trigger the airways response.