Social axioms and psychological toll: A study of emotional, behavioral, and cognitive responses across 35 cultures during the COVID-19 pandemic.

The COVID-19 pandemic has significantly affected the psychological well-being of individuals worldwide. Previous research has indicated that values and beliefs, particularly social axioms, are associated with psychological responses during crises. However, most of the studies have focused on specific regions; the impact of social axioms on a global scale remains unclear. We conducted a multinational study comprising stratified samples of 18,171 participants from 35 cultures. Using multilevel modeling, we examined the associations between social axioms, personal worry, normative concerns, trust, and individuals' psychological responses to the pandemic. The results showed that greater personal worry and normative concerns predicted more negative psychological responses. Furthermore, the study also identified significant buffering effects at the societal level, as cultures with higher overall levels of fate control, religiosity, or reward for application exhibited weaker associations between personal worry and negative responses. Our findings reveal the influence of social axioms on psychological responses during the pandemic, with varying effects across cultures. The buffering effects of fate control, religiosity, and reward for application underscore the importance of considering cultural differences and individual variability when examining the impact of social axioms on psychological outcomes.

Efficient evolution of human antibodies from general protein language models.

Natural evolution must explore a vast landscape of possible sequences for desirable yet rare mutations, suggesting that learning from natural evolutionary strategies could guide artificial evolution. Here we report that general protein language models can efficiently evolve human antibodies by suggesting mutations that are evolutionarily plausible, despite providing the model with no information about the target antigen, binding specificity or protein structure. We performed language-model-guided affinity maturation of seven antibodies, screening 20 or fewer variants of each antibody across only two rounds of laboratory evolution, and improved the binding affinities of four clinically relevant, highly mature antibodies up to sevenfold and three unmatured antibodies up to 160-fold, with many designs also demonstrating favorable thermostability and viral neutralization activity against Ebola and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudoviruses. The same models that improve antibody binding also guide efficient evolution across diverse protein families and selection pressures, including antibiotic resistance and enzyme activity, suggesting that these results generalize to many settings.

SARS-COV-2 Omicron variants conformationally escape a rare quaternary antibody binding mode.

The ongoing evolution of SARS-CoV-2 into more easily transmissible and infectious variants has provided unprecedented insight into mutations enabling immune escape. Understanding how these mutations affect the dynamics of antibody-antigen interactions is crucial to the development of broadly protective antibodies and vaccines. Here we report the characterization of a potent neutralizing antibody (N3-1) identified from a COVID-19 patient during the first disease wave. Cryogenic electron microscopy revealed a quaternary binding mode that enables direct interactions with all three receptor-binding domains of the spike protein trimer, resulting in extraordinary avidity and potent neutralization of all major variants of concern until the emergence of Omicron. Structure-based rational design of N3-1 mutants improved binding to all Omicron variants but only partially restored neutralization of the conformationally distinct Omicron BA.1. This study provides new insights into immune evasion through changes in spike protein dynamics and highlights considerations for future conformationally biased multivalent vaccine designs.

Social media trust predicts lower COVID-19 vaccination rates and higher excess mortality over 2 years.

Trust plays a crucial role in implementing public health interventions against the COVID-19 pandemic. We examined the prospective associations of interpersonal, institutional, and media trust with vaccination rates and excess mortality over time in two multinational studies. In study 1, we investigated the country-level relationships between interpersonal trust, vaccination rates, and excess mortality across 54 countries. Interpersonal trust at the country level was calculated by aggregating data of 80,317 participants from the World Values Survey in 2017-20. Data on vaccination rates and excess mortality were obtained from the World Health Organization. Our findings indicated that higher levels of interpersonal trust were linked to higher vaccination rates and lower excess mortality rates in both 2020 and 2021. In study 2, we collected data from 18,171 adults in 35 countries/societies, stratified by age, gender, and region of residence. At the country/society level, interpersonal trust and trust in local healthcare facilities, local healthcare services, and healthcare professionals were associated with higher vaccination rates and lower excess mortality, whereas social media trust was associated with lower vaccination rates and higher excess mortality across three time points over 2 years. Our findings are robust when controlling for country-level covariates of the government stringency index, population density, and medical resources (i.e. critical care beds) in both studies.

Who do we trust and how do we cope with COVID-19? A mixed-methods sequential exploratory approach to understanding supportive messages across 35 cultures.

Based upon a mixed-methods follow-up exploratory model, we examined the link between trust and coping during the early outbreak of the COVID-19 pandemic at the society level. Qualitative data were collected from the supportive messages written by 10,072 community adults across 35 societies. Trust and coping were used as the two pre-defined themes in the conceptual content analysis. Five subthemes emerged from the theme trust, depicting five distinct trusted targets: God, a larger us, country/government, science/healthcare, and the affected. Six subthemes emerged from the theme coping, depicting six distinct coping strategies: interpersonal/social coping, religious/spiritual coping, acceptance, blame, wishful thinking, and strength-based coping. A follow-up quantitative investigation also showed that four society-level factors (viz., individualism, cultural tightness, globalization, and severity of pandemic) had differential effects on people's trusted targets and ways of coping with the pandemic. Our study made both methodological and practical contributions to cross-cultural research on COVID-19 by using a mixed-methods approach in a multinational study and demonstrating the importance of making meaningful virtual connection during a time of physical distancing.

MultiSero: An Open-Source Multiplex-ELISA Platform for Measuring Antibody Responses to Infection.

A multiplexed enzyme-linked immunosorbent assay (ELISA) that simultaneously measures antibody binding to multiple antigens can extend the impact of serosurveillance studies, particularly if the assay approaches the simplicity, robustness, and accuracy of a conventional single-antigen ELISA. Here, we report on the development of multiSero, an open-source multiplex ELISA platform for measuring antibody responses to viral infection. Our assay consists of three parts: (1) an ELISA against an array of proteins in a 96-well format; (2) automated imaging of each well of the ELISA array using an open-source plate reader; and (3) automated measurement of optical densities for each protein within the array using an open-source analysis pipeline. We validated the platform by comparing antibody binding to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) antigens in 217 human sera samples, showing high sensitivity (0.978), specificity (0.977), positive predictive value (0.978), and negative predictive value (0.977) for classifying seropositivity, a high correlation of multiSero determined antibody titers with commercially available SARS-CoV-2 antibody tests, and antigen-specific changes in antibody titer dynamics upon vaccination. The open-source format and accessibility of our multiSero platform can contribute to the adoption of multiplexed ELISA arrays for serosurveillance studies, for SARS-CoV-2 and other pathogens of significance.

Global Consciousness Predicts Behavioral Responses to the COVID-19 Pandemic: Empirical Evidence From 35 Cultures.

COVID-19 has drastically changed human behaviors and posed a threat to globalism by spurring a resurgence of nationalism. Promoting prosocial behavior within and across borders is of paramount importance for global cooperation to combat pandemics. To examine both self-report and actual prosocial behavior, we conducted the first empirical test of global consciousness theory in a multinational study of 35 cultures (N = 18,171 community adults stratified by age, gender, and region of residence). Global consciousness encompassed cosmopolitan orientation, identification with all humanity, and multicultural acquisition, whereas national consciousness reflected ethnic protection. Both global consciousness and national consciousness positively predicted perceived risk of coronavirus and concern about coronavirus, after controlling for interdependent self-construal. While global consciousness positively predicted prosocial behavior in response to COVID-19, national consciousness positively predicted defensive behavior. These findings shed light on overcoming national parochialism and provide a theoretical framework for the study of global unity and cooperation.

CAR-T Cell-Mediated B-Cell Depletion in Central Nervous System Autoimmunity.

BACKGROUND AND OBJECTIVES: Anti-CD20 monoclonal antibody (mAb) B-cell depletion is a remarkably successful multiple sclerosis (MS) treatment. Chimeric antigen receptor (CAR)-T cells, which target antigens in a non-major histocompatibility complex (MHC)-restricted manner, can penetrate tissues more thoroughly than mAbs. However, a previous study indicated that anti-CD19 CAR-T cells can paradoxically exacerbate experimental autoimmune encephalomyelitis (EAE) disease. We tested anti-CD19 CAR-T cells in a B-cell-dependent EAE model that is responsive to anti-CD20 B-cell depletion similar to the clinical benefit of anti-CD20 mAb treatment in MS. METHODS: Anti-CD19 CAR-T cells or control cells that overexpressed green fluorescent protein were transferred into C57BL/6 mice pretreated with cyclophosphamide (Cy). Mice were immunized with recombinant human (rh) myelin oligodendrocyte protein (MOG), which causes EAE in a B-cell-dependent manner. Mice were evaluated for B-cell depletion, clinical and histologic signs of EAE, and immune modulation. RESULTS: Clinical scores and lymphocyte infiltration were reduced in mice treated with either anti-CD19 CAR-T cells with Cy or control cells with Cy, but not with Cy alone. B-cell depletion was observed in peripheral lymphoid tissue and in the CNS of mice treated with anti-CD19 CAR-T cells with Cy pretreatment. Th1 or Th17 populations did not differ in anti-CD19 CAR-T cell, control cell-treated animals, or Cy alone. DISCUSSION: In contrast to previous data showing that anti-CD19 CAR-T cell treatment exacerbated EAE, we observed that anti-CD19 CAR-T cells ameliorated EAE. In addition, anti-CD19 CAR-T cells thoroughly depleted B cells in peripheral tissues and in the CNS. However, the clinical benefit occurred independently of antigen specificity or B-cell depletion.

Relationships between global orientations and attitudes toward integration policies: A sequential explanatory mixed methods approach.

OBJECTIVES: Based upon a mixed methods follow-up explanation model, the present research examined the relationships between global orientations and the attitudes toward integration policies among both locals (majority group) and South Asians (minority group) in Hong Kong. METHODS: In Study 1, quantitative data were collected from a community sample of 1,614 adults comprising 1,007 locals and 607 South Asians in three minority groups (Indians, Nepalese, and Pakistanis). In Study 2, a follow-up explanation phase of qualitative investigation was conducted, with 12 in-depth semistructured focus group discussions among seven locals and 49 South Asians, generating three main themes and six subthemes. RESULTS: Quantitative results showed that the positive link between multicultural acquisition and instrumental integration policies was significantly stronger for South Asians than for locals, and that ethnic protection was negatively associated with a positive attitude toward symbolic integration policies in the majority group but had no effects in the minority group. The three main themes generated from the qualitative results include alleviating minority disadvantage, preserving majority privilege, and embracing diversity for the common good. CONCLUSIONS: The combined quantitative and qualitative results suggest that the differential relationships of multicultural acquisition and ethnic protection with support for specific integration policies can be understood with the underlying structural power asymmetry between the majority and minority groups. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

A Comprehensive Review of Non-Energy-Based Treatments for Atrophic Acne Scarring.

Scarring is a dire consequence of acne vulgaris. Particularly, atrophic acne scarring is highly prevalent among young adults, and its physical and psychological effects can persist throughout their lives if left untreated. This literature review will analyze various non-energy-based approaches to treating atrophic acne scarring, emphasizing recent advances within the last 5 to 10 years. To accomplish this, we performed a PubMed search for various acne scar treatments such as chemical peels, dermabrasion, microdermabrasion, subcision, microneedling, punch techniques, dermal fillers, and thread lifting. Our findings and analysis show that there is no panacean solution to treating atrophic acne scars, which explains the evolving trend towards developing unique combinatorial treatments. Although a fair comparison of each treatment approach is difficult to achieve due to the studies' varying sample sizes, strength of evidence, treatment execution, etc, there still remains a level of consensus on what treatments are well suited for particular scar types.

Who donates? Patterns of blood donation and donor characteristics at a university-affiliated hospital-based donor center.

BACKGROUND: Blood donors are a crucial element of the blood supply chain. Optimal recruitment strategies built upon the robust understanding of local donor behavior and demographics-specifically, the donor characteristics of our university-affiliated hospital-based donor center-improve outreach and retention of donors. STUDY DESIGN AND METHODS: This retrospective study analyzed blood donors' genders, ethnicities, and donation frequencies at a university-affiliated hospital-based donor center from 2014-2019, stratified into seven age cohorts. Donor ethnicity demographics were compared to the reported student, employee, and LA County population. RESULTS: Female donors outnumbered male donors in all age cohorts. The majority of donors self-identified (SI) as White (36.7%), Hispanic/Latino (21.6%), or Asian (19.1%). Older donors (age > 25) donated more frequently (4.1 vs. 2.3 donations per donor) than younger donors (age ≤ 25). Repeat donors who donated in multiple years during the study period were more likely to donate multiple times each year than those donors who only donated during 1 year. DISCUSSION: Our donor demographics more closely reflect the university student and employee demographics than LA County demographics, demonstrating the broad local efforts of recruitment by student groups and donor center recruitment staff. However, non-White populations continue to be underrepresented. The majority of donors only donated once during the study period. Recruitment strategies to increase donor engagement among underrepresented populations and increase the proportion of repeat donors are likely to prove most beneficial.

SARS-CoV-2 antibody magnitude and detectability are driven by disease severity, timing, and assay.

Interpretation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serosurveillance studies is limited by poorly defined performance of antibody assays over time in individuals with different clinical presentations. We measured antibody responses in plasma samples from 128 individuals over 160 days using 14 assays. We found a consistent and strong effect of disease severity on antibody magnitude, driven by fever, cough, hospitalization, and oxygen requirement. Responses to spike protein versus nucleocapsid had consistently higher correlation with neutralization. Assays varied substantially in sensitivity during early convalescence and time to seroreversion. Variability was dramatic for individuals with mild infection, who had consistently lower antibody titers, with sensitivities at 6 months ranging from 33 to 98% for commercial assays. Thus, the ability to detect previous infection by SARS-CoV-2 is highly dependent on infection severity, timing, and the assay used. These findings have important implications for the design and interpretation of SARS-CoV-2 serosurveillance studies.

Citywide serosurveillance of the initial SARS-CoV-2 outbreak in San Francisco using electronic health records.

Serosurveillance provides a unique opportunity to quantify the proportion of the population that has been exposed to pathogens. Here, we developed and piloted Serosurveillance for Continuous, ActionabLe Epidemiologic Intelligence of Transmission (SCALE-IT), a platform through which we systematically tested remnant samples from routine blood draws in two major hospital networks in San Francisco for SARS-CoV-2 antibodies during the early months of the pandemic. Importantly, SCALE-IT allows for algorithmic sample selection and rich data on covariates by leveraging electronic health record data. We estimated overall seroprevalence at 4.2%, corresponding to a case ascertainment rate of only 4.9%, and identified important heterogeneities by neighborhood, homelessness status, and race/ethnicity. Neighborhood seroprevalence estimates from SCALE-IT were comparable to local community-based surveys, while providing results encompassing the entire city that have been previously unavailable. Leveraging this hybrid serosurveillance approach has strong potential for application beyond this local context and for diseases other than SARS-CoV-2.

multiSero: open multiplex-ELISA platform for analyzing antibody responses to SARS-CoV-2 infection.

Serology has provided valuable diagnostic and epidemiological data on antibody responses to SARS-CoV-2 in diverse patient cohorts. Deployment of high content, multiplex serology platforms across the world, including in low and medium income countries, can accelerate longitudinal epidemiological surveys. Here we report multiSero, an open platform to enable multiplex serology with up to 48 antigens in a 96-well format. The platform consists of three components: ELISA-array of printed proteins, a commercial or home-built plate reader, and modular python software for automated analysis (pysero). We validate the platform by comparing antibody titers against the SARS-CoV-2 Spike, receptor binding domain (RBD), and nucleocapsid (N) in 114 sera from COVID-19 positive individuals and 87 pre-pandemic COVID-19 negative sera. We report data with both a commercial plate reader and an inexpensive, open plate reader (nautilus). Receiver operating characteristic (ROC) analysis of classification with single antigens shows that Spike and RBD classify positive and negative sera with the highest sensitivity at a given specificity. The platform distinguished positive sera from negative sera when the reactivity of the sera was equivalent to the binding of 1 ng mL âˆ'1 RBD-specific monoclonal antibody. We developed normalization and classification methods to pool antibody responses from multiple antigens and multiple experiments. Our results demonstrate a performant and accessible pipeline for multiplexed ELISA ready for multiple applications, including serosurveillance, identification of viral proteins that elicit antibody responses, differential diagnosis of circulating pathogens, and immune responses to vaccines.

Divergent and self-reactive immune responses in the CNS of COVID-19 patients with neurological symptoms.

Individuals with coronavirus disease 2019 (COVID-19) frequently develop neurological symptoms, but the biological underpinnings of these phenomena are unknown. Through single-cell RNA sequencing (scRNA-seq) and cytokine analyses of cerebrospinal fluid (CSF) and blood from individuals with COVID-19 with neurological symptoms, we find compartmentalized, CNS-specific T cell activation and B cell responses. All affected individuals had CSF anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies whose target epitopes diverged from serum antibodies. In an animal model, we find that intrathecal SARS-CoV-2 antibodies are present only during brain infection and not elicited by pulmonary infection. We produced CSF-derived monoclonal antibodies from an individual with COVID-19 and found that these monoclonal antibodies (mAbs) target antiviral and antineural antigens, including one mAb that reacted to spike protein and neural tissue. CSF immunoglobulin G (IgG) from 5 of 7 patients showed antineural reactivity. This immune survey reveals evidence of a compartmentalized immune response in the CNS of individuals with COVID-19 and suggests a role of autoimmunity in neurologic sequelae of COVID-19.

Dual impacts of coronavirus anxiety on mental health in 35 societies.

The spread of coronavirus disease 2019 (COVID-19) has affected both physical health and mental well-being around the world. Stress-related reactions, if prolonged, may result in mental health problems. We examined the consequences of the COVID-19 pandemic on mental health in a multinational study and explored the effects of government responses to the outbreak. We sampled 18,171 community adults from 35 countries/societies, stratified by age, gender, and region of residence. Across the 35 societies, 26.6% of participants reported moderate to extremely severe depression symptoms, 28.2% moderate to extremely severe anxiety symptoms, and 18.3% moderate to extremely severe stress symptoms. Coronavirus anxiety comprises two factors, namely Perceived Vulnerability and Threat Response. After controlling for age, gender, and education level, perceived vulnerability predicted higher levels of negative emotional symptoms and psychological distress, whereas threat response predicted higher levels of self-rated health and subjective well-being. People in societies with more stringent control policies had more threat response and reported better subjective health. Coronavirus anxiety exerts detrimental effects on subjective health and well-being, but also has the adaptive function in mobilizing safety behaviors, providing support for an evolutionary perspective on psychological adaptation.

SARS-CoV-2 antibody magnitude and detectability are driven by disease severity, timing, and assay.

Serosurveillance studies are critical for estimating SARS-CoV-2 transmission and immunity, but interpretation of results is currently limited by poorly defined variability in the performance of antibody assays to detect seroreactivity over time in individuals with different clinical presentations. We measured longitudinal antibody responses to SARS-CoV-2 in plasma samples from a diverse cohort of 128 individuals over 160 days using 14 binding and neutralization assays. For all assays, we found a consistent and strong effect of disease severity on antibody magnitude, with fever, cough, hospitalization, and oxygen requirement explaining much of this variation. We found that binding assays measuring responses to spike protein had consistently higher correlation with neutralization than those measuring responses to nucleocapsid, regardless of assay format and sample timing. However, assays varied substantially with respect to sensitivity during early convalescence and in time to seroreversion. Variations in sensitivity and durability were particularly dramatic for individuals with mild infection, who had consistently lower antibody titers and represent the majority of the infected population, with sensitivities often differing substantially from reported test characteristics (e.g., amongst commercial assays, sensitivity at 6 months ranged from 33% for ARCHITECT IgG to 98% for VITROS Total Ig). Thus, the ability to detect previous infection by SARS-CoV-2 is highly dependent on the severity of the initial infection, timing relative to infection, and the assay used. These findings have important implications for the design and interpretation of SARS-CoV-2 serosurveillance studies.

Citywide serosurveillance of the initial SARS-CoV-2 outbreak in San Francisco.

Serosurveillance provides a unique opportunity to quantify the proportion of the population that has been exposed to pathogens. Here, we developed and piloted Serosurveillance for Continuous, ActionabLe Epidemiologic Intelligence of Transmission (SCALE-IT), a platform through which we systematically tested remnant samples from routine blood draws in two major hospital networks in San Francisco for SARS-CoV-2 antibodies during the early months of the pandemic. Importantly, SCALE-IT allows for algorithmic sample selection and rich data on covariates by leveraging electronic medical record data. We estimated overall seroprevalence at 4.2%, corresponding to a case ascertainment rate of only 4.9%, and identified important heterogeneities by neighborhood, homelessness status, and race/ethnicity. Neighborhood seroprevalence estimates from SCALE-IT were comparable to local community-based surveys, while providing results encompassing the entire city that have been previously unavailable. Leveraging this hybrid serosurveillance approach has strong potential for application beyond this local context and for diseases other than SARS-CoV-2.