Introduction Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection produces more severe symptoms and a higher mortality in men than in women. The role of biological sex in the immune response to SARS-CoV-2 is believed to explain this sex disparity. However, the contribution of gender factors that influence health protective behaviors and therefore health outcomes, remains poorly explored. Methods We assessed the contributions of gender in attitudes towards the COVID-19 pandemic, using a hypothetical influenza pandemic data from the 2014 Taiwan Social Change Survey. Participants were selected through a stratified, three-stage probability proportional-to-size sampling from across the nation, to fill in questionnaires that asked about their perception of the hypothetical pandemic, and intention to adopt health protective behaviors. Results A total of 1,990 participants (median age 45.92 years, 49% women) were included. Significant gender disparities (p<0.001) were observed. The risk perception of pandemic (OR=1.28, 95% CI=1.21-1.35, p<0.001), older age (1.06, 95%=1.05-1.07, p<0.001), female gender (OR = 1.18, 95% CI = 1.09‐1.27, p<0.001), higher education (OR=1.10, 95% CI=1.06-1.13, p<0.001), and larger family size (OR=1.09, 95% CI=1.06-1.15, p<0.001) were positively associated with health protective behaviors. The risk perception of pandemic (OR=1.25, 95% CI=1.15-1.36), higher education (OR=1.07, 95% CI=1.02-1.13, p<0.05), being married (OR=1.17, 95% CI=1.01-1.36, p<0.05), and larger family size (OR=1.33, 95% CI=1.25-1.42, p<0.001), were positively associated with intention to receive a vaccine. However, female gender was negatively associated with intention to receive a vaccine (OR=0.85, 95% CI=0.75-0.90, p<0.01) and to comply with contact-tracing (OR=0.95, 95% CI=0.90-1.00, p<0.05) compared to men. Living with children was also negatively associated with intention to receive vaccines (OR=0.77, 95% CI=0.66-0.90, p<0.001). Conclusion This study unveils gender differences in risk perception, health protective behaviors, vaccine hesitancy, and compliance with contact-tracing using a hypothetical viral pandemic. Gender-specific health education raising awareness of health protective behaviors may be beneficial to prevent future pandemics.

Until recently, most genetic studies of headache have been conducted on participants with European ancestry. We therefore conducted a large-scale genome-wide association study of self-reported headache in individuals of East Asian ancestry (specifically those who were identified as Han Chinese). In this study, 108,855 participants were enrolled, including 12,026 headache cases from the Taiwan Biobank. For broadly-defined headache phenotype, we identified a locus on chromosome 17, with the lead single nucleotide polymorphism (SNP) rs8072917 (odds ratio 1.08, p = 4.49 × 10–8) mapped to two protein-coding genes RNF213 and ENDOV. For severe headache phenotype, we found a strong association on chromosome 8, with the lead SNP rs13272202 [odds ratio 1.30, p = 1.02 × 10–9], mapped to gene RP11-1101K5.1. We then conducted a conditional analysis and a statistical fine mapping of the broadly-defined headache-associated loci and identified a single credible set of loci with rs8072917 supporting that this lead variant was the true causal variant on RNF213 gene region. RNF213 replicated the result of previous studies and played important roles in the biological mechanism of broadly-defined headache. On the basis of the previous results found in the Taiwan biobank, we conducted phenome-wide association studies for the lead variants using data from the UK biobank, and found that the causal variant (SNP rs8072917) was associated with muscle symptoms, cellulitis and abscess of face and neck, and cardiogenic shock. Our findings foster the genetic architecture of headache in individuals of East Asian ancestry. Our study can be replicated using genomic data linked to electronic health records from a variety of countries, therefore affecting a wide range of ethnicities globally. Our genome-phenome association study may facilitate the development of new genetic tests and novel drug mechanisms.

10553 Background: Human papillomavirus (HPV) screening has been implemented to monitor both cervical cancer and head and neck cancer. In this prospective cohort study, we determined sociodemographic, behavioral, and infectious etiology for head and neck squamous cell carcinoma (HNSCC) in Taiwan using data collected from an anonymous sexually transmitted infections screening program. Methods: An anonymous sexually transmitted infections screening program was conducted at a medical center during 2016, in which sociodemographic characteristics including gender, age, marital status, education level, and occupation; medical history regarding underlying comorbidities and history of receiving HPV and other vaccines; lifestyle determinants including betel quid chewing, drug using, and sexual behaviors, were inquired. Blood, anal swab, and penile swab samples were collected to determine viral infections using polymerase chain reaction (PCR). With PCR, 37 HPV genotypes were detected. Regular follow-ups were made for patients enrolled in the screening program until end of 2020, during which all suspected malignancies were recorded upon referrals to oncologists. From this prospective cohort, odds ratios (ORs) of HNSCC for sociodemographic, lifestyle, and infectious variables were derived with logistic regression (R version 4.0.1). P < 0.05 was considered statistically significant. Results: A total of 376 patients were enrolled. Most patients were men (n = 372), with a median age of 27 years. There were 124 (32.98%) HPV-positive patients and 78 (20.74%) HIV-positive patients. Among HPV-positive patients, 20 (25.64%) were of high-risk genotypes. During the follow-up, 44 patients developed HNSCC and all received radiotherapy. Multivariate analysis revealed that patients who were single (OR = 1.43, 95% CI = 1.12-1.83, P = 0.01) or widowed (OR = 2.47, 95% CI = 1.88-3.25, P < 0.001) had higher risk of HNSCC than patients who were married. Patients aged 51-60 (OR = 2.93, 95% CI = 2.10-4.09, P < 0.001) and over 60 (OR = 1.89, 95% CI = 1.45-2.47, P < 0.001) presented higher risks of HNSCC, compared with those aged below 20. Patients addicted to betel quid chewing had high HNSCC risk (OR = 1.29, 95% CI = 1.11 – 1.50, P < 0.001). However, patients with HPV infections did not present with higher HNSCC risks (OR = 0.925, 95% CI = 0.852 – 1.003, P = 0.058). Conclusions: In this prospective cohort study, the elderly, unmarried patients, and patients addicted to betel quid chewing, presented with high HNSCC incidence. On the contrary, the association between HPV infection and HNSCC was insignificant. As both betel nut-chewing and HPV infection could be prevented, we advocate for comprehensive screening and patient education for HNSCC prevention.

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BACKGROUND:Multiple trauma deserves early prognostication and stratification. Copeptin, a precursor of vasopressin, is produced in response to stress. We examined the association between serum levels of copeptin and mortality risk in patients with multiple trauma. We aimed to also enhance the previously established Trauma-Related Injury Severity Score (TRISS) and Mechanism, GCS, Age, and Arterial Pressure (MGAP) score with the additional consideration of copeptin levels. METHODS:This single-center prospective cohort study enrolled patients who presented to the emergency department with potential major injuries. The serum levels of copeptin were measured, and the correlation to clinical severity in terms of 30-day mortality and requirement of intensive care management was analyzed. By combining copeptin levels with TRISS or MGAP, comparison between performance of the original models with the copeptin-enhanced models was performed via discrimination, calibration, and reclassification analyses. RESULTS:There was a significant increase in copeptin levels in patients who died within 30 days (median 644.4 pg/L, interquartile range [472.5, 785.9]) or were admitted to intensive care units (233.8 pg/L, [105.7, 366.4]), compared with those who survived (37.49 pg/L, [17.88, 77.68]). Adding the natural log of copeptin levels to the established TRISS and MGAP models improved the AUC of TRISS from 0.89 to 0.96, and that of MGAP from 0.82 to 0.95. Both calibrations as measured by Brier's scores and reclassification as measured by net reclassification improvement or integrated discrimination improvement demonstrated significant improvements. A Web-based calculator was built to generate predicted mortality rates of various models for convenient clinical use. CONCLUSION:Admission serum copeptin levels were correlated with clinical severity in multiple trauma. Coupling copeptin with preexisting trauma severity scores improved prediction accuracy. Copeptin shows promise as a novel biomarker for the prediction of trauma outcome.