Exploring links between pathogen avoidance motivation, COVID-19 case counts, and immune function.

OBJECTIVES: The selection pressures exerted by pathogens have played important roles in shaping the biology and behavior of animals, including humans. Immune systems recognize and respond to cues of infection or damage by coordinating cellular, humoral, and metabolic shifts that promote recovery. Moreover, animals also possess a repertoire of behavioral tools to help combat the threat of pathogens, often referred to as the behavioral immune system. Recently, researchers have begun to examine how cognitive, affective, and behavioral disease avoidance mechanisms interact with the biological immune system. METHODS: The present study explored relationships among individual differences in behavioral immune system activity (e.g., pathogen disgust), shifts in SARS-CoV-2 infection risk (i.e., 7-day case averages), and immune function in a community cohort from McLennan County, Texas, USA (n = 387). RESULTS: Levels of disease concern were not consistently associated with immune markers. However, serum levels of IFN-γ, TNF-α, IL-2, and IL-8, as well as serum killing ability of Escherichia coli, each varied with case counts. Additional analyses found that case counts also predicted changes in stress physiology, but not subjective measures of distress. However, follow-up mediation models did not provide evidence that relationships between case counts and immunological outcomes were mediated through levels of stress. CONCLUSIONS: The present project provides initial evidence that markers of immune function may be sensitive to changes in infection risk during the COVID-19 pandemic. This adds to the growing body of research finding relationships among behavioral and biological pathogen management mechanisms.

Waco COVID Survey: A Community-Based SARS-CoV-2 Serological Surveillance Study in Central Texas.

In early-2020, the epidemiology of the SARS-CoV-2 virus was still in discovery and initial reports about the role of asymptomatic individuals were developing. The Waco COVID Survey was implemented in mid-2020 with targeted serological surveillance to assess relationships among risk factors and asymptomatic transmission in McLennan County, Texas, USA. Because large-scale random sampling of the population was not feasible, a targeted and repeated sampling of specific clustered groups of asymptomatic individuals was employed. This included four waves (initial intake [n = 495], two follow-ups separated by a month [n = 348; n = 287], and a final follow-up one year later [n = 313]) of sampling participants in different risk categories: (a) healthcare workers (e.g., physicians, nurses, etc.) and first responders, (b) essential service employees (e.g., convenience and grocery stores, restaurants focused on delivery and carry-out), (c) employees whose businesses began reopening on May 1 (e.g., dine-in restaurants, churches, etc.) including church attendees, and (d) individuals that practiced intensive isolation. The survey collected information on demographics, compliance with public health recommendations, satisfaction with government responses, health history, attitudes regarding the SARS-CoV-2 virus and COVID-19 disease, health behaviors, personality, stress, and general affect. Results illustrate pandemic fatigue over time, the influence of political leniency on opinions and behaviors, the importance of face coverings in preventing infection, and the positive impact of vaccination in the community. This project remains one of the largest longitudinal SARS-CoV-2 antibody seroprevalence surveys in the US, and details for successful implementation and community involvement are discussed.

Dynamics of temperature change during experimental respiratory virus challenge: Relationships with symptoms, stress hormones, and inflammation.

Thermoregulation is a complex, dynamic process involving coordination between multiple autonomic, endocrine, and behavioral mechanisms. In the context of infection, this intricate machinery generates fever, a process believed to serve vital functions in the body's defense against pathogens. In addition to increasing core temperature, infection can lead to changes in the dynamic fluctuations in body temperature over time. The patterns of these deviations may convey information about the health of the body and the course of illness. Here, we utilized dynamic structural equation modeling to explore patterns of body temperature change following an experimental respiratory virus challenge in an aggregated, archival dataset of human participants (N = 1,412). We also examined whether temperature dynamics during infection were related to symptom severity, as well as individual differences in biomarkers of inflammation and stress. We found that individuals meeting the criteria for infection exhibited higher but less stable body temperatures over time compared to those not meeting criteria of infection. While temperature parameters did not reliably predict symptom severity, higher levels of nasal proinflammatory cytokines were associated with lower, more consistent temperatures during the study period. Further, levels of salivary cortisol and urinary catecholamines measured at the beginning of the study appeared to have disparate effects on temperature change. In sum, this research highlights the utility of dynamic time series modeling as a framework for studying body temperature change and lends novel insights into how stress may interact with infection to influence patterns of thermoregulation.

Travel medicine meets conservation medicine in St. Kitts: Disinhibition, cognitive-affective inconsistency, and disease risk among vacationers around green monkeys (Chlorocebus sabaeus).

Despite concern about environmental protection, travelers often underestimate the contribution they may have to disease transmission to other species, as well as the risk of becoming infected themselves. Tourists in general tend to accept more physical risks when traveling than when at home, and much of this can be blamed on the temporary loss of situational awareness and loss of inhibition with a corresponding relaxed attitude toward safety. To better understand environmental attitudes and travel health knowledge and behaviors, a detailed survey of adult tourists was distributed on the island of St. Kitts, home to many green monkeys. Data from 1097 respondents were collected at two locations where cruise ship passengers typically visit the island. Results revealed that even though individuals with more positive environmental attitudes were more willing to take steps to mitigate tourism-related disease transmission, they were also more likely to report wanting to touch or feed a monkey/ape. Similarly, those more willing to prevent the spread of diseases (e.g., wear a mask and report any illnesses to park authorities) were actually more likely to want to touch or feed a monkey/ape. The human desire for physical contact with other species may be partly the result of biophilia, emotionally arousing events (like contact with exotic species) that can lead to further disinhibition, and social media platforms that provide opportunities for exhibitionism. The attitude-behavior incongruency identified here may also be explained through cognitive-affective inconsistency: environmentally-oriented individuals believe that it is prudent to take steps to prevent zoonotic disease transmission but also desire to touch or feed exotic species as it may be emotionally rewarding. Individuals for whom physically interacting with monkeys/apes may be emotionally rewarding may not alter their behavior in response to cognitive means of persuasion; techniques aimed at appealing to emotions may be more effective.

Religiosity/Spirituality and Physiological Markers of Health.

The long-standing interest in the effects of religiosity and spirituality (R/S) on health outcomes has given rise to a large and diverse literature. We conducted a meta-analysis on research involving R/S and physiological markers of health to elucidate both the scope and mechanism(s) of this phenomenon. A combined analysis found a significant, but small, beneficial effect. Subgroup analyses found that some measures of both extrinsic and intrinsic religiosity were significantly associated with health. Several outcome measures, including blood pressure, C-reactive protein, and cardiovascular health markers, were significantly associated with R/S. Our findings suggest that R/S benefits health, perhaps through minimizing the disruptive effects of stress/depression on inflammation. We hope that researchers can use these results to guide efforts aimed at elucidating the true mechanism(s) linking religious/spiritual beliefs and physical health.

Short-term resource allocation during extensive athletic competition.

OBJECTIVES: Following predictions from life history theory, we sought to identify acute trade-offs between reproductive effort (as measured by psychological arousal) and somatic maintenance (via functional measures of innate immunity) during conditions of severe energetic imbalance. METHODS: Sixty-six male ultramarathon runners (ages 20 to 37 years) were sampled before and after a lengthy race. Saliva and sera were collected for testosterone and immunological analyses (hemolytic complement activity and bacterial killing ability). Lean body mass was assessed by bioelectrical impedance, and libido was measured using a slideshow of arousing and neutral images. RESULTS: Following predictions, there was a significant decrease in salivary testosterone levels (109.59 pg/mL versus 97.61 pg/mL, P < .001) and arousal scores in response to provocative images (5.40 versus 4.89, P = .001) between prerace and postrace time points. Additionally, participant bacterial killing ability (P = .035) and hemolytic complement activity (P = .021) increased between prerace and postrace. CONCLUSIONS: Decreased libido and testosterone with concomitant heightened innate immune responses suggest a shift in energetic priorities away from reproduction and toward maintenance/defense during a period of energetic stress.

Primates on display: Potential disease consequences beyond bushmeat.

Human interactions with nonhuman primates vary tremendously, from daily cultural engagements and food commodities, to pet ownership and tourist encounters. These interactions provide opportunities for the exchange of pathogenic organisms (both zoonoses and anthroponoses). As exposures are not limited to areas where bushmeat usage continues to be a major problem, we must work to understand better our motivations for engaging in activities like owning primates as pets and having direct physical contact with wild primates within the context of nature-based tourism. These topics, and the theoretical potential for pathogen transmission, are reviewed in the present manuscript. This is followed by a case study utilizing 3845 survey responses collected from four international locations known for primate-based tourism, with results indicating that while a majority of people understand that they can give/get diseases to/from wild primates, a surprising percentage would still touch or feed these animals if given the opportunity. Many people still choose to touch and/or own primates, as their drive to bond with animals outweighs some basic health behaviors. Desires to tame, control, or otherwise establish emotional connections with other species, combined with the central role of touch for exploring our environment, necessitate the development of better communication and educational campaigns to minimize risks of emerging infectious diseases.

Accelerated diversification of nonhuman primate malarias in Southeast Asia: adaptive radiation or geographic speciation?

Although parasitic organisms are found worldwide, the relative importance of host specificity and geographic isolation for parasite speciation has been explored in only a few systems. Here, we study Plasmodium parasites known to infect Asian nonhuman primates, a monophyletic group that includes the lineage leading to the human parasite Plasmodium vivax and several species used as laboratory models in malaria research. We analyze the available data together with new samples from three sympatric primate species from Borneo: The Bornean orangutan and the long-tailed and the pig-tailed macaques. We find several species of malaria parasites, including three putatively new species in this biodiversity hotspot. Among those newly discovered lineages, we report two sympatric parasites in orangutans. We find no differences in the sets of malaria species infecting each macaque species indicating that these species show no host specificity. Finally, phylogenetic analysis of these data suggests that the malaria parasites infecting Southeast Asian macaques and their relatives are speciating three to four times more rapidly than those with other mammalian hosts such as lemurs and African apes. We estimate that these events took place in approximately a 3-4-Ma period. Based on the genetic and phenotypic diversity of the macaque malarias, we hypothesize that the diversification of this group of parasites has been facilitated by the diversity, geographic distributions, and demographic histories of their primate hosts.

Towards an integrative picture of human sickness behavior.

Sickness behavior, a coordinated set of behavioral changes during infection and elicited by the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß), is well studied in non-human animals. Over the last two decades, several papers have expanded this research to include humans. However, these studies use a variety of research designs, and typically focus on a single cytokine and only a few of the many behavioral changes constituting sickness behavior. Therefore, our understanding of human sickness behavior remains equivocal. To generate a more holistic, integrative picture of this phenomenon, a meta-analysis of the human sickness behavior literature was conducted. Full model results show that both IL-6 and IL-1ß have significant relationships with sickness behavior, and the strength of these relationships is affected by a number of study parameters, such as type of immune stimulus and inclusion of controls. In addition to research design heterogeneity, other issues to address in future studies include an unequal focus on different cytokines and different sickness behaviors.

Human sickness behavior: Ultimate and proximate explanations.

Sickness behavior, a coordinated set of behavioral changes in response to infection, lies at the intersection of immunology, endocrinology, and evolutionary biology. Sickness behavior is elicited by pro-inflammatory cytokines, is thought to be an adaptive means of redirecting energy away from disadvantageous behaviors and toward mounting an effective immune response, and may be modulated by hormones, including testosterone and oxytocin. Research on sickness behavior in humans has lagged behind non-human animal research due to methodological complexities. Here we review what is known about sickness behavior in humans, the effects of various hormones on sickness behavior, the possible role of cytokine gene variation in influencing sickness behavior responses, and the ways in which culture and gender norms could similarly influence these behavioral changes. We also propose methodologies for advancing further studies of sickness behavior in humans.

Mood, behavior, testosterone, cortisol, and interleukin-6 in adults during immune activation: a pilot study to assess sickness behaviors in humans.

OBJECTIVES: Sickness behavior, a suite of behavioral changes subsequent to infection that includes depression, decreased social behaviors, and sleep disturbances, has been well described in model organisms. The phenomenon is relatively unexplored in humans due to methodological difficulties, and hormonal correlates of sickness behavior have not been studied. We therefore attempted to use a vaccine to elicit sickness behaviors outside of a clinical setting and uncover any correlations among testosterone, cortisol, and sickness behavior. METHODS: Eleven participants (five male, six female, mean age 22.8 years) naïve to the rabies vaccine were recruited from the School of Veterinary Medicine at Purdue University. Participants provided daily saliva and urine samples and completed questionnaires to assess mood and social behaviors for a period of 6 weeks. Saliva samples were assayed for cortisol and testosterone. Urine samples were assayed for interleukin-6 and creatinine. RESULTS: Analysis revealed an expected decrease in testosterone and an increase in cortisol. While mood did not differ, other behaviors, such as physical activity and hours slept, showed expected changes following vaccination. However, none of these results achieved statistical significance. CONCLUSION: Our results, while generally confirming previous research on sickness behavior and hormone changes during infection, are suggestive, but not statistically significant and so neither confirm nor contradict our hypotheses. We attribute this lack of significance to both the small sample size, as well as possible confounding factors, including the psychosocial stress of entering an intensive study program.

Dehydroepiandrosterone and multiple measures of functional immunity in young adults.

OBJECTIVES: Human immune function is strongly influenced by variation in hormone concentrations. The adrenal androgens dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DHEA-S) are thought to be beneficial to immune function and disease resistance, but physiologically interact with testosterone and cortisol. We predict that DHEA and DHEA-S will interact with these other hormones in determining immunological outcomes. Understanding the interactive effects of these hormones will aid in understanding variability in immunocompetence and clarify discrepancies in human studies of androgen-immune interactions. METHODS: Thirty-eight participants collected morning saliva over three days, from which concentrations of DHEA, DHEA-S, testosterone, and cortisol were measured, as well as salivary bacteria killing ability to measure innate immune function. From blood collection, serum was collected to measure innate immune function via a hemolytic complement assay, and whole blood collected and processed to measure proliferative responses of lymphocytes in the presence of mitogens. RESULTS: DHEA was negatively correlated with T cell proliferation, and positively correlated with salivary bacteria killing in male participants. Additionally, using regression models, DHEA-S was negatively associated with hemolytic complement activity, but interaction variables did not yield statistically significant relationships for any other outcome measure. CONCLUSIONS: While interactions with other hormones did not significantly relate with immune function measures in this sample, DHEA and DHEA-S did differentially impact multiple branches of the immune system. Generally characterized as immunosupportive in action, DHEA is shown to inhibit certain facets of innate and cell-mediated immunity, suggesting a more complex role in regulating immunocompetence.

Androgens and innate immunity in rehabilitated semi-captive orangutans (Pongo pygmaeus morio) from Malaysian Borneo.

Despite the implications for the development of life-history traits, endocrine-immune trade-offs in apes are not well studied. This is due, in part, to difficulty in sampling wild primates, and lack of methods available for immune measures using samples collected noninvasively. Evidence for androgen-mediated immune trade-offs in orangutans is virtually absent, and very little is known regarding their pattern of adrenal development and production of adrenal androgens. To remedy both of these deficiencies, sera were collected from orangutans (Pongo pygmaeus morio) (N = 38) at the Sepilok Orangutan Rehabilitation Centre, Sabah, Malaysia, during routine health screenings. Testosterone, dehydroepiandrosterone (DHEA), and dehydroepiandrosterone-sulfate (DHEA-S) were assayed, along with two measures of functional innate immunity. DHEA-S concentrations, but not DHEA, increased with age in this sample of 1-18 year old animals. DHEA concentrations were higher in animals with higher levels of serum bacteria killing ability, while DHEA-S and testosterone concentrations were higher in animals with reduced complement protein activity. Patterns of DHEA-S concentration in this sample are consistent with patterns of adrenarche observed in other apes. Results from this study suggest that in addition to testosterone, DHEA and DHEA-S may have potent effects on immunological activity in this species.

Lower testosterone levels are associated with higher risk of death in men.

Background and Objectives: Testosterone plays an important role in regulating male development, reproduction and health. Declining levels across the lifespan may reflect, or even contribute to, chronic disease and mortality in men. Methodology: Relationships between testosterone levels and male mortality were analyzed using data from multiple samples of the cross-sectional National Health and Nutrition Examination Survey (n = 10 225). Target outcomes included known deaths from heart disease, malignant neoplasms, chronic lower respiratory diseases, cerebrovascular diseases, Alzheimer's disease, diabetes mellitus, influenza and pneumonia, kidney diseases, and accidents or unintentional injuries. Results: Results of discrete-time hazard models revealed that lower levels of testosterone were related to higher mortality for the majority of disease categories in either an age-dependent or age-independent fashion. Analysis of all-cause mortality-which included deaths from any known disease-also revealed greater general risk for those with lower testosterone levels. For most disease categories, the hazard associated with low testosterone was especially evident at older ages when mortality from that particular ailment was already elevated. Notably, testosterone levels were not related to mortality risk for deaths unrelated to chronic disease (i.e. accidents and injuries). Conclusions and Implications: While the causal direction of relationships between testosterone and mortality risk remains unclear, these results may reflect the decline in testosterone that accompanies many disease states. Accordingly, the relationship between testosterone and male mortality may be indirect; ill individuals are expected to have both lower testosterone and higher mortality risk.

Survey of COVID-19 isolation cases at a major university campus in the United States.

Objective: Baylor University established a surveillance system to assess the needs of students and faculty in isolation from SARS-CoV-2 as well as any longer-term symptoms. Participants: Overall, there were 309 responses between March 20 and May 19, 2021. Methods: A survey covering experience in isolation, symptoms, vaccination, and demographic characteristics was emailed to individuals on Day 7 of isolation; a follow-up health survey was sent 30 days later. Results: Only 9.6% of respondents reported needing assistance while in isolation. Nearly 75% of respondents experienced COVID-19 symptoms in isolation, and 31.9% had remaining symptoms after isolation. Older age, being male, and more severe symptoms were associated with longer symptom duration. Those vaccinated had lower odds of developing symptoms and having symptoms remaining post-isolation. Conclusions: The present study adds to our understanding of long-COVID in young adult populations, while providing a framework for similar institutions to sustain operations during a global pandemic.

Tattooing as a phenotypic gambit.

OBJECTIVES: Tattooing is not an evolved behavior, but it may be a phenotypic gambit to highlight immunological health. Phenotypic gambits are traits or behaviors that appear costly but occur at high rates as a honing process of natural selection not constrained by genetics. Tattooing is an ancient practice that is increasing in popularity worldwide, but it involves wounding the body, which seems counterintuitive because it challenges the immune system and makes one more susceptible to infection. But tattooing may represent a costly honest signal of fitness by "upping the ante" in an era of hygiene or a means to stimulate the immune system in a way that improves and highlights underlying fitness. MATERIALS AND METHODS: We investigated this hypothesis by assessing bacteria killing activity (BKA) in saliva samples collected during two studies of tattooing (N = 40). We compared previous tattoo experience (extent of body tattooed and hours spent being tattooed) to BKA before and after getting a new tattoo. RESULTS: Tattoo experience positively predicts post-tattoo BKA (ß = 0.48, p = 0.01), suggesting that people with more tattoo experience have a relatively more immediate and active immune response than those with less tattoo experience. DISCUSSION: Tattoo experience may elevate innate immunological vigilance, which could aid in protecting against future dermal insults.

Longitudinal changes in COVID-19 concern and stress: Pandemic fatigue overrides individual differences in caution.

Background: Pandemic fatigue describes a phenomenon whereby individuals experience a decrease in COVID-19 concern over time, despite their risk for infection remaining stable, or even increasing. Individual differences in the experience of pandemic fatigue may have important implications for people's adherence to public health recommendations. Design and methods: Using data collected from a large community cohort in McLennan County, TX, longitudinal changes in COVID-19-related concern, stress, and affect across three appointments separated by approximately 4 weeks (July-November 2020) were examined. About 495, 349, and 286 participants completed one, two, and three appointments, respectively. Changes to stress physiology and local travel over time were also analyzed. Results: Results of a latent class growth analysis revealed four distinct classes of individuals: (a) low concern, low stress, (b) moderate concern, moderate stress, (c) moderate concern, low stress, and (d) high concern, high stress. Despite differences between latent classes in initial levels of concern, stress, and negative affect, levels of each variable decreased over time for all groups. While this reduction of concern did not coincide with changes in local travel, it was reflected in heart rate and blood pressure. Conclusions: Together, these results suggest a general trend of pandemic fatigue in the sample, even for those with moderate-to-high levels of initial COVID-19 stress and concern. Such findings may provide insights into the expected challenges of promoting compliance with public health recommendations as the pandemic continues.

Sustaining University Operations During the COVID-19 Pandemic.

Colleges and universities around the world engaged diverse strategies during the COVID-19 pandemic. Baylor University, a community of ˜22,700 individuals, was 1 of the institutions which resumed and sustained operations. The key strategy was establishment of multidisciplinary teams to develop mitigation strategies and priority areas for action. This population-based team approach along with implementation of a "Swiss Cheese" risk mitigation model allowed small clusters to be rapidly addressed through testing, surveillance, tracing, isolation, and quarantine. These efforts were supported by health protocols including face coverings, social distancing, and compliance monitoring. As a result, activities were sustained from August 1 to December 8, 2020. There were 62,970 COVID-19 tests conducted with 1435 people testing positive for a positivity rate of 2.28%. A total of 1670 COVID-19 cases were identified with 235 self-reports. The mean number of tests per week was 3500 with approximately 80 of these positive (11/d). More than 60 student tracers were trained with over 120 personnel available to contact trace, at a ratio of 1 per 400 university members. The successes and lessons learned provide a framework and pathway for similar institutions to mitigate the ongoing impacts of COVID-19 and sustain operations during a global pandemic.

Beyond phytohaemagglutinin: assessing vertebrate immune function across ecological contexts.

1. Over the past decade, there has been a substantial increase in interest in the immune system and the role it plays in the regulation of disease susceptibility, giving rise to the field of eco-immunology. 2. Eco-immunology aims to understand changes in host immune responses in the broader framework of an organism's evolutionary, ecological and life-history contexts. 3. The immune system, however, is complex and multifaceted and can be intimidating for the nonimmunologist interested in incorporating immunological questions into their research. Which immune responses should one measure and what is the biological significance of these measures? 4. The focus of this review is to describe a wide range of eco-immunology techniques, from the simple to the sophisticated, with the goal of providing researchers with a range of options to consider incorporating in their own research programs. 5. These techniques were chosen because they provide relatively straightforward, biologically meaningful assessments of immune function, many of which can be performed across a range of ecological contexts (i.e. field vs. laboratory) and in a wide range of vertebrate animals without relying on species-specific reagents. 6. By incorporating assessments of immune function into their specific research questions, animal ecologists will gain a more comprehensive understanding of organism-environment interactions.

Unrealistic Optimism and Risk for COVID-19 Disease.

Risk perception and consequently engagement in behaviors to avoid illness often do not match actual risk of infection, morbidity, and mortality. Unrealistic optimism occurs when individuals falsely believe that their personal outcomes will be more favorable than others' in the same risk category. Natural selection could favor overconfidence if its benefits, such as psychological resilience, outweigh its costs. However, just because optimism biases may have offered fitness advantages in our evolutionary past does not mean that they are always optimal. The current project examined relationships among personal risk for severe COVID-19, risk perceptions, and preventative behaviors. We predicted that those with higher risk of severe COVID-19 would exhibit unrealistic optimism and behave in ways inconsistent with their elevated risk of morbidity and mortality. Clinical risk scores for severe COVID-19 were calculated and compared with COVID-19 threat appraisal, compliance with shelter-in-place orders (March 13-May 22, 2020) and travel restrictions, compliance with public health recommendations, and potential covariates like self-rated knowledge about COVID-19 in a robust dataset including 492 participants from McLennan County, TX, USA. While those with high clinical risk acknowledged their greater likelihood of experiencing severe illness if infected, they actually reported lower perceived likelihood of becoming infected in the first place. While it is possible that those with higher clinical risk scores truly are less likely to become infected, the pattern and significance of these results held after controlling for possible occupational exposure, household size, and other factors related to infection probability. Higher clinical risk also predicted more recent travel within Texas and lower distress during the pandemic (i.e., feeling less stressed, depressed, and helpless). Additional behavioral data suggested that those with higher clinical risk scores did not generally behave differently than those with lower scores during the shelter-in-place order. While unrealistic optimism may provide some short-term psychological benefits, it could be dangerous due to improper assessment of hazardous situations; inferring that optimism bias has evolutionary origins does not mean that unrealistic optimism is "optimal" in every situation. This may be especially true when individuals face novel sources (or scales) of risk, such as a global pandemic.