COVID-19 mRNA Vaccination Generates Greater Immunoglobulin G Levels in Women Compared to Men.

We investigated whether the antibody response to coronavirus disease 2019 (COVID-19) mRNA vaccination is similar in women and men. In a community cohort without prior COVID-19, first vaccine dose produced higher immunoglobulin G (IgG) levels and percent inhibition of spike-ACE2 receptor binding, a surrogate measure of virus neutralization, in women compared to men (7.0 µg/mL, 51.6% vs 3.3 µg/mL, 36.4%). After 2 doses, IgG levels remained significantly higher for women (30.4 µg/mL) compared to men (20.6 µg/mL), while percent inhibition was similar (98.4% vs 97.7%). Sex-specific antibody response to mRNA vaccination informs future efforts to understand vaccine protection and side effects.

Accelerated senescence as a cost of reproduction: Testing associations between oxidative stress and reproductive effort in rural and urban women.

OBJECTIVES: Oxidative stress is hypothesized to contribute to age-related somatic deterioration. Both reproductive and ecological context may necessitate tradeoffs that influence this outcome. We examined whether measures of lifetime reproductive effort were related to levels of oxidative stress biomarkers in peri- and post-menopausal women and whether associations were moderated by rural or urban residence. METHODS: We surveyed 263 healthy women (age 62.1 ± 10.0 SD) from rural (N = 161) and urban Poland (N = 102), collecting sociodemographic data and urine samples to analyze biomarkers of oxidative stress (8-oxo-2'-deoxyguanosine, 8-OHdG) and antioxidative defense (copper-zinc superoxide dismutase, Cu-Zn SOD). Linear regression models, adjusted for residence, were used to test for associations between reproductive effort and 8-OHdG and Cu-Zn SOD. RESULTS: Univariate models demonstrated significant associations between gravidity and the biomarkers of oxidative stress (8-OHdG: R2  = 0.042, P ≤ .001; Cu-Zn SOD: R2  = 0.123, P ≤ .001). Multivariate models incorporating potential confounding variables, as well as cross-product interaction terms, indicated that gravidity was associated with 8-OHdG (P < .01, R2 adj  = 0.067) and Cu-Zn SOD (P = .01, R2 adj  = 0.159). Residence (ie, urban vs rural) did not significantly moderate the associations between the biomarkers and reproductive effort. CONCLUSIONS: Higher lifetime reproductive effort contributes to increases in oxidative stress and antioxidative defenses. Our results provide evidence of potential mechanisms underlying the physiological tradeoffs influencing senescence for women with high reproductive effort. We illustrate the value of applying an evolutionary perspective to elucidate variation in human health and senescence.

C-reactive protein, Epstein-Barr virus, and cortisol trajectories in refugee and non-refugee youth: Links with stress, mental health, and cognitive function during a randomized controlled trial.

Experiencing childhood adversity has been associated with significant changes in inflammation, cell-mediated immunocompetence, and cortisol secretion. Relatively few studies have examined, longitudinally, alterations to inflammatory processes during adolescence, especially outside Western contexts; none have evaluated biomarker trajectories for at-risk youth in response to a structured behavioral intervention. We conducted a randomized controlled trial evaluating the efficacy of a humanitarian intervention targeting stress-alleviation, with 12-18 year-old Syrian refugees (n = 446) and Jordanian non-refugees (n = 371) living side-by-side in war-affected communities in Jordan. We measured C-reactive protein (CRP), Epstein-Barr virus antibodies (EBV), and hair cortisol concentration (HCC) at three timepoints (pre/post intervention and 11 month follow-up), and assessed three main outcomes (psychosocial stress, mental health, and cognitive function). Using growth mixture models, regressions, and growth curve models, we identified three distinct trajectories for CRP, two for EBV, and three for HCC, and examined their associations with age, gender, BMI, poverty, and trauma. We found associations with BMI for CRP, refugee status for EBV, and BMI and gender with HCC trajectory. In terms of health outcomes, we found associations between rising CRP levels and perceived stress (B =  -2.92, p = .007), and between HCC hypersecretion and insecurity (B = 7.21, p = .017). In terms of responses to the intervention, we observed no differential impacts by CRP or EBV trajectories, unlike HCC. These results suggest that commonly-assayed biomarkers do not associate with health outcomes and respond to targeted interventions in straightforward ways. Our study is the first to examine multiple biomarker trajectories in war-affected adolescents, in order to better evaluate the extent, timing, and malleability of the biological signatures of poverty, conflict, and forced displacement.

Insecurity, distress and mental health: experimental and randomized controlled trials of a psychosocial intervention for youth affected by the Syrian crisis.

BACKGROUND: Strengthening the evidence base for humanitarian interventions that provide psychosocial support to war-affected youth is a key priority. We tested the impacts of an 8-week programme of structured activities informed by a profound stress attunement (PSA) framework (Advancing Adolescents), delivered in group-format to 12-18 year-olds in communities heavily affected by the Syrian crisis. We included both Syrian refugee and Jordanian youth. METHODS: We followed an experimental design, comparing treatment youth and wait-list controls over two programme implementation cycles, randomizing to study arm in cycle 2 (ClinicalTrials.gov ID: NCT03012451). We measured insecurity, distress, mental health difficulties, prosocial behaviour and post-traumatic stress symptoms at three time-points: baseline (n = 817 youth; 55% Syrian, 43% female), postintervention (n = 463; 54% Syrian, 47% female), and follow-up (n = 212, 58% Syrian, 43% female). Regression models assessed: prospective intervention impacts, adjusting for baseline scores, trauma exposure, age, and gender; differential impacts across levels of trauma exposure and activity-based modality; and sustained recovery 1 year later. We analysed cycle-specific and cycle-pooled data for youth exclusively engaged in Advancing Adolescents and for the intent-to-treat sample. RESULTS: We found medium to small effect sizes for all psychosocial outcomes, namely Human Insecurity (ß = -7.04 (95% CI: -10.90, -3.17), Cohen's d = -0.4), Human Distress (ß = -5.78 (-9.02, -2.54), d = -0.3), and Perceived Stress (ß = -1.92 (-3.05, -0.79), d = -0.3); and two secondary mental health outcomes (AYMH: ß = -3.35 (-4.68, -2.02), d = -0.4; SDQ: ß = -1.46 (-2.42, -0.50), d = -0.2). We found no programme impacts for prosocial behaviour or post-traumatic stress reactions. Beneficial impacts were stronger for youth with exposure to four trauma events or more. While symptoms alleviated for both intervention and control groups over time, there were sustained effects of the intervention on Human Insecurity. CONCLUSIONS: Findings strengthen the evidence base for mental health and psychosocial programming for a generation affected by conflict and forced displacement. We discuss implications for programme implementation and evaluation research.

The cost of reproduction in women: Reproductive effort and oxidative stress in premenopausal and postmenopausal American women.

OBJECTIVES: Life history theory predicts a trade-off between female investment in reproduction and somatic maintenance, which can result in accelerated senescence. Oxidative stress has been shown to be a causal physiological mechanism for accelerated aging and a possible contributor to this trade-off. We aimed to test the hypothesis for the existence of significant associations between measures of reproductive effort and the level of oxidative stress biomarkers in premenopausal and postmenopausal American women. METHODS: Serum samples and questionnaire data were collected from 63 premenopausal and postmenopausal women (mean age 53.4 years), controls in the Connecticut Thyroid Health Study, between May 2010 and December 2013. Samples were analyzed for levels of 8-OHdG and Cu/Zn-SOD using immunoassay method. RESULTS: Levels of oxidative damage (8-OHdG) but not oxidative defense (Cu/Zn-SOD) were negatively associated with parity and number of sons in premenopausal women (r = -0.52 for parity, r = -0.52 for number of sons, P < .01). Together, measures of reproductive effort, women's BMI, age, and menopausal status explained around 15% of variance in level of 8-OHdG. No association between reproductive effort characteristics and oxidative damage was found for postmenopausal women. CONCLUSIONS: We found no evidence of a trade-off between somatic maintenance as measured by 8-OHdG and reproductive effort in women from this American population. On the contrary, higher gravidity and parity in premenopausal women was associated with lower damage to cellular DNA caused by oxidative stress. These results highlight the importance of population variation and environmental conditions when testing the occurrence of life-history trade-offs.

Biocultural research in global mental health: mapping idioms of distress onto blood pressure in a population survey.

OBJECTIVES: Biocultural research remains a challenge in the field of global mental health. We sought to test associations between blood pressure and idioms of distress in a population survey. METHODS: We drew on a randomly selected sample of 991 adults (498 men, 493 women) in Afghanistan, for whom physiological and psychosocial data were systematically collected. Assessment of mental health (Self-Reported Questionnaire, Afghan Symptom Checklist) included conceptualizations of distress related to pressure (fishar), anxiety, and dysphoria, as well as dimensions of negative affect and aggression. We used principal component analysis to map survey responses to fishar, and multiple regressions to examine associations with systolic/diastolic blood pressure, controlling for age, body mass index, and wealth, and differentiating by gender, mental health, and medication. RESULTS: The Afghan sample averaged 129/80 mmHg, with 27.14% of hypertensive individuals. SBP showed inverse associations with reports of low fishar (ß = -4.58, P < .001) and high fishar (ß = 6.90, P < .001), as did DPB with low fishar (ß = -1.55, P < .001) and high fishar (ß = 3.77, P < .001). Low and high fishar responses accounted for substantial proportions of SBP data variation (R2 = 20% and R2 = 24%), especially in adults on blood pressure medication (R2 = 58% and R2 = 49%). CONCLUSIONS: Subjective reports of fishar map onto physiological blood pressure more robustly than other conceptualizations of mental distress related to anxiety, dysphoria, negative affect, or aggression. Our results point to the utility of mapping biological and cultural measures of stress and distress, advancing biopsychosocial understandings of wellbeing in global mental health surveys.

Physical activity patterns and biomarkers of cardiovascular disease risk in hunter-gatherers.

OBJECTIVES: Time spent in moderate-to-vigorous physical activity (MVPA) is a strong predictor of cardiovascular health, yet few humans living in industrialized societies meet current recommendations (150 min/week). Researchers have long suggested that human physiological requirements for aerobic exercise reflect an evolutionary shift to a hunting and gathering foraging strategy, and a recent transition to more sedentary lifestyles likely represents a mismatch with our past in terms of physical activity. The goal of this study is to explore this mismatch by characterizing MVPA and cardiovascular health in the Hadza, a modern hunting and gathering population living in Northern Tanzania. METHODS: We measured MVPA using continuous heart rate monitoring in 46 participants recruited from two Hadza camps. As part of a larger survey of health in the Hadza, we measured blood pressure (n = 198) and biomarkers of cardiovascular health (n = 23) including C-reactive protein, cholesterol (Total, HDL, and LDL), and triglycerides. RESULTS: We show that Hadza participants spend large amounts of time in MVPA (134.92 ± 8.6 min/day), and maintain these activity levels across the lifespan. In fact, the Hadza engage in over 14 times as much MVPA as subjects participating in large epidemiological studies in the United States. We found no evidence of risk factors for cardiovascular disease in this population (low prevalence of hypertension across the lifespan, optimal levels for biomarkers of cardiovascular health). CONCLUSIONS: Our results provide evidence that the hunting and gathering foraging strategy involves high levels of MVPA, supporting the evolutionary medicine model for the relationship between MVPA and cardiovascular health.

Comparing the validity of the self reporting questionnaire and the Afghan symptom checklist: dysphoria, aggression, and gender in transcultural assessment of mental health.

BACKGROUND: The relative performance of local and international assessment instruments is subject to ongoing discussion in transcultural research on mental health and psychosocial support. We examined the construct and external validity of two instruments, one developed for use in Afghanistan, the other developed by the World Health Organization for use in resource-poor settings. METHODS: We used data collected on 1003 Afghan adults (500 men, 503 women) randomly sampled at three sites in Afghanistan. We compared the 22-item Afghan Symptom Checklist (ASCL), a culturally-grounded assessment of psychosocial wellbeing, with Pashto and Dari versions of the 20-item Self-Reporting Questionnaire (SRQ-20). We derived subscales using exploratory and confirmatory factor analyses (EFA and CFA) and tested total and subscale scores for external validity with respect to lifetime trauma and household wealth using block model regressions. RESULTS: EFA suggested a three-factor structure for SRQ-20--somatic complaints, negative affect, and emotional numbing--and a two-factor structure for ASCL--jigar khun (dysphoria) and aggression. Both factor models were supported by CFA in separate subsamples. Women had higher scores for each of the five subscales than men (p < 0.001), and larger bivariate associations with trauma (rs .24 to .29, and .10 to .19, women and men respectively) and household wealth (rs -.27 to -.39, and .05 to -.22, respectively). The three SRQ-20 subscales and the ASCL jigar khun subscale were equally associated with variance in trauma exposures. However, interactions between gender and jigar khun suggested that, relative to SRQ-20, the jigar khun subscale was more strongly associated with household wealth for women; similarly, gender interactions with aggression indicated that the aggression subscale was more strongly associated with trauma and wealth. CONCLUSIONS: Two central elements of Afghan conceptualizations of mental distress--aggression and the syndrome jigar khun--were captured by the ASCL and not by the SRQ-20. The appropriateness of the culturally-grounded instrument was more salient for women, indicating that the validity of instruments may be gender-differentiated. Transcultural validation processes for tools measuring mental distress need to explicitly take gender into account. Culturally relevant measures are worth developing for long-term psychosocial programming.

Nigeria healthcare worker SARS-CoV-2 serology study: Results from a prospective, longitudinal cohort.

Healthcare workers, both globally and in Nigeria, have an increased risk for SARS-CoV-2 infection compared with the general population due to higher risk contacts, including occupational exposures. In addition, primary healthcare workers represent an important group for estimating prior infection to SARS-CoV-2 because they work at the first point-of-contact for most patients yet have not been included in prior COVID-19 seroepidemiology research in Nigeria. We sought to evaluate baseline seroprevalence, rates of seroconversion (IgG- to IgG+) and seroreversion (IgG+ to IgG-), change in IgG concentration at 3- and 6-month follow-up, and factors associated with seropositivity. From June 2020 to December 2020, we conducted a longitudinal seroepidemiology study among frontline health care workers in Nigeria using a validated dried blood spot assay. Among 525 participants, mean (SD) age was 39.1 (9.7) years, 61.0% were female, and 45.1% were community health workers. The six-month follow-up rate was 93.5%. Seropositivity rates increased from 31% (95% CI: 27%, 35%) at baseline to 45% (95% CI: 40%, 49%) at 3-month follow-up, and 70% (95% CI: 66%, 74%) at 6-month follow-up. There was a corresponding increase in IgG levels from baseline (median = 0.18 ug/mL) to 3-month (median = 0.35 ug/mL) and 6-month follow-up (median = 0.59 ug/mL, Ptrend < .0001). A minority of participants reported symptoms from February 2020 until baseline (12.2%) or during 3-month (6.6%) or 6-month (7.5%) follow-up. only 1 participant was hospitalized. This study demonstrated high baseline, 3-month and 6-month follow-up prevalence of IgG antibodies to SARS-CoV-2 during the first two waves of the COVID-19 pandemic in Nigeria among a cohort of unvaccinated frontline healthcare workers, including primary healthcare workers despite low symptomatology. These results may have implications in state- and national-level disease pandemic modeling. Trial registration: NCT04158154.

mRNA intramuscular vaccination produces a robust IgG antibody response in advanced neuromuscular disease.

SARS-CoV-2 vaccines protect against symptomatic and severe COVID-19. The BNT162b2/Pfizer and mRNA-1273/Moderna vaccines represent new vaccine technology relying on administration of mRNA encoding SARS-CoV-2 viral spike protein encased in lipid nanoparticles. The vaccines are administered as two doses into muscle, which elicits a strong response, typically within 14 days after the second dose. Neuromuscular diseases are characterized by the progressive loss of muscle and are often treated with chronic glucocorticoid steroids, both of which may contribute to a blunted immune response to vaccination. Here, we measured IgG antibody content and neutralizing antibody response after mRNA COVID-19 vaccination in non-ambulatory neuromuscular disease patients. After two doses of mRNA COVID-19 vaccine, median anti-receptor binding domain IgG and percent surrogate viral neutralization in non-ambulatory neuromuscular disease samples were significantly elevated similar to healthy vaccinated controls. As in healthy controls, COVID-19 vaccines produce greater antibody levels compared to those with a history of outpatient COVID-19 infection. This data documents that non-ambulatory neuromuscular disease patients respond well to two doses of mRNA COVID-19 vaccine despite low muscle mass and even chronic steroid use.

Low Levels of Neutralizing Antibodies After Natural Infection With Severe Acute Respiratory Syndrome Coronavirus 2 in a Community-Based Serological Study.

BACKGROUND: Confidence in natural immunity after infection with severe acute respiratory syndrome coronavirus 2 is one reason for vaccine hesitancy. METHODS: We measured antibody-mediated neutralization of spike protein-ACE2 receptor binding in a large community-based sample of seropositive individuals who differed in severity of infection (N = 790). RESULTS: A total of 39.8% of infections were asymptomatic, 46.5% were symptomatic with no clinical care, 13.8% were symptomatic with clinical care, and 3.7% required hospitalization. Moderate/high neutralizing activity was present after 41.3% of clinically managed infections, in comparison with 7.9% of symptomatic and 1.9% of asymptomatic infections. CONCLUSIONS: Prior coronavirus disease 2019 infection does not guarantee a high level of antibody-mediated protection against reinfection in the general population.

No difference in anti-spike antibody and surrogate viral neutralization following SARS-CoV-2 booster vaccination in persons with HIV compared to controls (CO-HIV Study).

Background: Understanding the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination will enable accurate counseling and inform evolving vaccination strategies. Little is known about antibody response following booster vaccination in people living with HIV (PLWH). Methods: We enrolled SARS-CoV-2 vaccinated PLWH and controls without HIV in similar proportions based on age and comorbidities. Participants completed surveys on prior SARS-CoV-2 infection, vaccination, and comorbidities, and provided self-collected dried blood spots (DBS). Quantitative anti-spike IgG and surrogate viral neutralization assays targeted wild-type (WT), Delta, and Omicron variants. We also measured quantitative anti-nucleocapsid IgG. The analysis population had received full SARS-CoV-2 vaccination plus one booster dose. Bivariate analyses for continuous outcomes utilized Wilcoxon tests and multivariate analysis used linear models. Results: The analysis population comprised 140 PLWH and 75 controls with median age 58 and 55 years, males 95% and 43%, and DBS collection on 112 and 109 days after the last booster dose, respectively. Median CD4 count among PLWH was 760 cells/mm3 and 91% had an undetectable HIV-1 viral load. Considering WT, Delta, and Omicron variants, there was no significant difference in mean quantitative anti-spike IgG between PLWH (3.3, 2.9, 1.8) and controls (3.3, 2.9, 1.8), respectively (p-values=0. 771, 0.920, 0.708). Surrogate viral neutralization responses were similar in PLWH (1.0, 0.9, and 0.4) and controls (1.0, 0.9, 0.5), respectively (p-values=0.594, 0.436, 0.706). Conclusions: PLWH whose CD4 counts are well preserved and persons without HIV have similar anti-spike IgG antibody levels and viral neutralization responses after a single SARS-CoV-2 booster vaccination.

COVID-19 symptom severity predicts neutralizing antibody activity in a community-based serological study.

Serological testing for SARS-CoV-2 IgG antibodies is used to assess their presence in blood samples from exposed individuals and provides a measure of the magnitude of immune response to infection. The measurement of neutralizing antibodies (NAbs) in particular provides information about the severity of prior infection and level of protective immunity against re-infection. Much of the work investigating the association between prior infection severity and NAb levels has been conducted among clinical populations, and less is known about this relationship in the general population. Accordingly, we utilize data from a large (n = 790) community-based cohort of unvaccinated, seropositive participants. We analyzed the association between NAb response, measured via surrogate virus neutralization assay, with patterns of symptoms and household exposure. Our results indicate no detectable NAb activity in 63.8% of the seropositive participants (n = 504). Those with detectable NAb levels demonstrated a positive relationship between NAb activity and both self-reported previous symptom severity and household exposure. These findings are significant in light of recent concerns about degree of protective immunity conferred by prior infection or vaccination, and we highlight the value of community-based research for investigating variation in immune response.

Durability of antibody response to vaccination and surrogate neutralization of emerging variants based on SARS-CoV-2 exposure history.

Two-dose messenger RNA vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are highly effective in preventing symptomatic COVID-19 infection. However, the durability of protection is not known, nor is the effectiveness against emerging viral variants. Additionally, vaccine responses may differ based on prior SARS-CoV-2 exposure history. To investigate protection against SARS-CoV-2 variants we measured binding and neutralizing antibody responses following both vaccine doses. We document significant declines in antibody levels three months post-vaccination, and reduced neutralization of emerging variants, highlighting the need to identify correlates of clinical protection to inform the timing of and indications for booster vaccination.

A surrogate virus neutralization test to quantify antibody-mediated inhibition of SARS-CoV-2 in finger stick dried blood spot samples.

The spike protein of SARS-CoV-2 engages the human angiotensin-converting enzyme 2 (ACE2) receptor to enter host cells, and neutralizing antibodies are effective at blocking this interaction to prevent infection. Widespread application of this important marker of protective immunity is limited by logistical and technical challenges associated with live virus methods and venous blood collection. To address this gap, we validated an immunoassay-based method for quantifying neutralization of the spike-ACE2 interaction in a single drop of capillary whole blood, collected on filter paper as a dried blood spot (DBS) sample. Samples are eluted overnight and incubated in the presence of spike antigen and ACE2 in a 96-well solid phase plate. Competitive immunoassay with electrochemiluminescent label is used to quantify neutralizing activity. The following measures of assay performance were evaluated: dilution series of confirmed positive and negative samples, agreement with results from matched DBS-serum samples, analysis of results from DBS samples with known COVID-19 status, and precision (intra-assay percent coefficient of variation; %CV) and reliability (inter-assay; %CV). Dilution series produced the expected pattern of dose-response. Agreement between results from serum and DBS samples was high, with concordance correlation = 0.991. Analysis of three control samples across the measurement range indicated acceptable levels of precision and reliability. Median % surrogate neutralization was 46.9 for PCR confirmed convalescent COVID-19 samples and 0.1 for negative samples. Large-scale testing is important for quantifying neutralizing antibodies that can provide protection against COVID-19 in order to estimate the level of immunity in the general population. DBS provides a minimally-invasive, low cost alternative to venous blood collection, and this scalable immunoassay-based method for quantifying inhibition of the spike-ACE2 interaction can be used as a surrogate for virus-based assays to expand testing across a wide range of settings and populations.

Gendered movement ecology and landscape use in Hadza hunter-gatherers.

Understanding how gendered economic roles structure space use is critical to evolutionary models of foraging behaviour, social organization and cognition. Here, we examine hunter-gatherer spatial behaviour on a very large scale, using GPS devices worn by Hadza foragers to record 2,078 person-days of movement. Theory in movement ecology suggests that the density and mobility of targeted foods should predict spatial behaviour and that strong gender differences should arise in a hunter-gatherer context. As predicted, we find that men walked further per day, explored more land, followed more sinuous paths and were more likely to be alone. These data are consistent with the ecology of male- and female-targeted foods and suggest that male landscape use is more navigationally challenging in this hunter-gatherer context. Comparisons of Hadza space use with space use data available for non-human primates suggest that the sexual division of labour likely co-evolved with increased sex differences in spatial behaviour and landscape use.

Comparison of IgG and neutralizing antibody responses after one or two doses of COVID-19 mRNA vaccine in previously infected and uninfected individuals.

BACKGROUND: Recent reports have suggested that among individuals previously infected with SARS-CoV-2, a single mRNA vaccine dose is sufficient to elicit high levels of immunity. METHODS: We compared anti-SARS-CoV-2 spike receptor binding domain (RBD) IgG antibody concentrations and antibody-mediated neutralization of spike-angiotensin-converting enzyme (ACE2) receptor binding in vitro following vaccination of non-hospitalized participants by sero-status and acute virus diagnosis history. Participants were analysed before and after mRNA vaccination (BNT162b2/Pfizer or mRNA-1273/Moderna) in a community-based, home-collected, longitudinal serosurvey in the Chicago area (USA); none reported hospitalization for COVID-19. Samples were collected in January and February 2021. Before vaccination, some reported prior positive acute viral diagnostic testing and were seropositive (COVID-19+); the others who did not report acute viral diagnostic testing were categorized as seropositive or seronegative based on anti-spike RBD IgG test results. FINDINGS: Of 307 unique vaccine recipients, 46 reported a prior COVID-19 diagnosis and were seropositive (COVID-19 +). Of the 261 with no history of acute viral diagnostic testing, 117 were seropositive and 144 seronegative before vaccination. The median age was 38 years (range 21-83) with 67 female and 33% male; 40% were non-White. Responses were evaluated after one (n = 142) or two (n = 191) doses of BNT162b2 or mRNA-1273 vaccine. After one dose, median post-vaccine IgG concentration and percent surrogate neutralization were each significantly higher among the COVID-19+ (median 48·2 µg/ml, IgG; > 99.9% neutralization) compared to the seropositives (3·6 µg /ml IgG; 56.5% neutralization) and seronegatives (2·6 µg /ml IgG; 38·3% neutralization). The latter two groups reached > 95% neutralization after the second vaccine dose. INTERPRETATION: After one dose of mRNA vaccine, individuals previously diagnosed with COVID-19 responded with high levels of anti-RBD IgG and surrogate neutralization of spike-ACE2 interaction. One dose of mRNA vaccine was not sufficient to generate comparably high responses among most persons previously infected with SARS-CoV-2 without a clinical COVID-19 diagnosis, nor among seronegative persons. FUNDING: National Science Foundation 2035114, NIH 3UL1TR001422-06S4, and Northwestern University Office of Research.

Oxidative stress as a hidden cost of attractiveness in postmenopausal women.

Perceived facial attractiveness, a putative marker of high biological fitness, is costly to maintain throughout a lifetime and may cause higher oxidative stress (OS). We investigated the association between the facial features of 97 postmenopausal women and their levels of OS biomarkers 8-hydroxy-2'-deoxyguanosine (8-OHdG), superoxide dismutase (Cu-Zn SOD), and thiobarbituric acid reactive substances (TBARS). In study 1, 966 judges rated the composites (facial averages) of women with higher OS as more attractive, healthier, younger, and less symmetric. In study 2, Geometric Morphometric analysis did not reveal significant differences in facial morphology depending on OS levels. In study 3, measured facial averageness and symmetry were weakly negatively related to 8-OHdG levels. Maintaining higher perceived facial attractiveness may be costly due to increased oxidative damage in the postmenopausal period. These costs may remain hidden during the reproductive period of life due to the protective mechanisms of oxidative shielding and revealed only after menopause when shielding has ceased.

Evidence for the Cost of Reproduction in Humans: High Lifetime Reproductive Effort Is Associated with Greater Oxidative Stress in Post-Menopausal Women.

Life history theory predicts trade-offs between reproductive effort and maternal survivorship in energy-restricted environments. However, empirical evidence for the positive association between maternal mortality and reproductive effort from energetically challenged human populations are mixed and physiological mechanisms that may underlie this association are poorly understood. We hypothesized that increases in aerobic metabolism during repeated periods of pregnancy and lactation result in increased oxidative stress that may contribute to somatic deterioration, vulnerability to illness, and accelerated aging. We therefore predicted that lifetime gravidity and parity would be related to levels of biomarkers of oxidative stress, as well as antioxidative defence enzymes in post-menopausal women. Our hypothesis was supported by positive linear associations between levels of 8-OHdG, a biomarker of DNA oxidative damage (ß = 0.21, p<0.05), levels of antioxidative defence enzyme Cu-Zn SOD (ß = 0.25, p<0.05), and number of lifetime pregnancies. Furthermore, independent of age and health status, post-menopausal women with higher gravidity and parity (> = 4 pregnancies per lifetime) had 20% higher levels of 8-OHdG and 60% higher levels of Cu-Zn SOD compared to women with lower gravidity and parity (<4 pregnancies per lifetime). Our results present the first evidence for oxidative stress as a possible cost of reproductive effort in humans.