Novel genes and sex differences in COVID-19 severity

Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.Instituto de Salud Carlos III (COV20_00622 to A.C., COV20/00792 to M.B., COV20_00181 to C.A., COV20_1144 to M.A.J.S., PI20/00876 to C.F.); European Union (ERDF) ‘A way of making Europe’. Fundación Amancio Ortega, Banco de Santander (to A.C.), Estrella de Levante S.A. and Colabora Mujer Association (to E.G.-N.) and Obra Social La Caixa (to R.B.); Agencia Estatal de Investigación (RTC-2017-6471-1 to C.F.), Cabildo Insular de Tenerife (CGIEU0000219140 ‘Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19’ to C.F.) and Fundación Canaria Instituto de Investigación Sanitaria de Canarias (PIFIISC20/57 to C.F.)

Cohort profile: the Siyakhula cohort, rural South Africa

No abstract available

Use of personal child health records in the UK: findings from the millennium cohort study.

OBJECTIVES: The personal child health record (PCHR) is a record of a child's growth, development, and uptake of preventive health services, designed to enhance communication between parents and health professionals. We examined its use throughout the United Kingdom with respect to recording children's weight and measures of social disadvantage and infant health. DESIGN: Cross sectional survey within a cohort study. SETTING: UK. PARTICIPANTS: Mothers of 18,503 children born between 2000 and 2002, living in the UK at 9 months of age. MAIN OUTCOME MEASURES: Proportion of mothers able to produce their child's PCHR; proportion of PCHRs consulted containing record of child's last weight; effective use of the PCHR (defined as production, consultation, and child's last weight recorded). RESULTS: In all, 16,917 (93%) mothers produced their child's PCHR and 15,138 (85%) mothers showed effective use of their child's PCHR. Last weight was recorded in 97% of PCHRs consulted. Effective use was less in children previously admitted to hospital, and, in association with factors reflecting social disadvantage, including residence in disadvantaged communities, young maternal age, large family size (four or more children; incidence rate ratio 0.87; 95% confidence interval 0.83 to 0.91), and lone parent status (0.88; 0.86 to 0.91). CONCLUSIONS: Use of the PCHR is lower by women living in disadvantaged circumstances, but overall the record is retained and used by a high proportion of all mothers throughout the UK in their child's first year of life. PCHR use is endorsed in the National Service Framework for Children and has potential benefits which extend beyond the direct care of individual children

An ecological systems approach to examining risk factors for early childhood overweight: findings from the UK Millennium Cohort Study

Objective: To use an ecological systems approach to examine individual-, family-, community- and area-level risk factors for overweight (including obesity) in 3-year-old children. Methods: A prospective nationally representative cohort study conducted in England, Wales, Scotland, Northern Ireland. Participants included 13 188 singleton children aged 3 years in the Millennium Cohort Study, born between 2000 and 2002, who had complete height/weight data. The main outcome measure was childhood overweight (including obesity) defined by the International Obesity TaskForce cut-offs for body mass index. Results: 23.0% of 3-year-old children were overweight or obese. In the fully adjusted model, primarily individual- and family-level factors were associated with early childhood overweight: birthweight z-score (adjusted odds ratio, 1.36, 95% CI 1.30 to 1.42), black ethnicity (1.41, 1.11 to 1.80) (compared with white), introduction to solid foods or =21 hours/week (1.23, 1.10 to 1.37) (compared with never worked). Breastfeeding > or =4 months (0.86, 0.76 to 0.97) (compared with none) and Indian ethnicity (0.63, 0.42 to 0.94) were associated with a decreased risk of early childhood overweight. Children from Wales were also more likely to be overweight than children from England. Conclusions: Most risk factors for early childhood overweight are modifiable or would allow at-risk groups to be identified. Policies and interventions should focus on parents and providing them with an environment to support healthy behaviours for themselves and their children

Maternal employment and early childhood overweight: findings from the UK Millennium Cohort Study

Background: In most developed countries, maternal employment has increased rapidly. Changing patterns of family life have been suggested to be contributing to the rising prevalence of childhood obesity. Objectives: Our primary objective was to examine the relationship between maternal and partner employment and overweight in children aged 3 years. Our secondary objective was to investigate factors related to early childhood overweight only among mothers in employment. Design: Cohort study. Subjects: A total of 13 113 singleton children aged 3 years in the Millennium Cohort Study, born between 2000 and 2002 in the United Kingdom, who had complete height/weight data and parental employment histories. Measurements: Parents were interviewed when the child was aged 9 months and 3 years, and the child's height and weight were measured at 3 years. Overweight (including obesity) was defined by the International Obesity Task Force cut-offs. Results: A total of 23% (3085) of children were overweight at 3 years. Any maternal employment after the child's birth was associated with early childhood overweight (odds ratio (OR) [95% confidence interval (CI)]; 1.14 [1.00, 1.29]), after adjustment for potential confounding and mediating factors. Children were more likely to be overweight for every 10 h a mother worked per week (OR [95% CI]; 1.10 [1.04, 1.17]), after adjustment. An interaction with household income revealed that this relationship was only significant for children from households with an annual income of pound33 000 ($57 750) or higher. There was no evidence for an association between early childhood overweight and whether or for how many hours the partner worked, or with mothers' or partners' duration of employment. These relationships were also evident among mothers in employment. Independent risk factors for early childhood overweight were consistent with the published literature. Conclusions: Long hours of maternal employment, rather than lack of money may impede young children's access to healthy foods and physical activity. Policies supporting work-life balance may help parents reduce potential barriers

Nausea and vomiting in pregnancy (NVP) is not just 'Morning Sickness' : data from a prospective cohort study

Background: Nausea and vomiting in pregnancy is usually called ‘morning sickness’. This is felt by sufferers to trivialise the condition. Symptoms have been described as occurring both before and after noon, but daily symptom patterns have not been clearly described and statistically modelled to enable the term ‘morning sickness’ to be accurately analysed. Aim: To describe the daily variation in nausea and vomiting symptoms during early pregnancy in a group of sufferers. Design and setting: A prospective cohort study of females recruited from 15 May 2014 to 17 February 2017 by Swiss Precision Diagnostics (SPD) Development Company Limited, which was researching hormone levels in early pregnancy and extended its study to include the description of pregnancy symptoms. Method: Daily symptom diaries of nausea and vomiting were kept by females who were trying to conceive. They also provided daily urine samples, which when analysed enabled the date of ovulation to be determined. Data from 256 females who conceived during the first month of the study are included in this article. Daily symptom patterns and changes in daily patterns by week of pregnancy were modelled. Functional data analysis was used to produce estimated symptom probability functions. Results: There was a peak probability of nausea in the morning, a lower but sustained probability of nausea throughout the day, and a slight peak in the evening. Vomiting had a defined peak incidence in the morning. Conclusion: Referring to nausea and vomiting in pregnancy as simply ‘morning sickness’ is inaccurate, simplistic, and therefore unhelpful

Feasibility of collecting oral fluid samples in the home setting to determine seroprevalence of infections in a large-scale cohort of preschool-aged children

Oral fluid is a non-invasive biological sample, which can be returned by post, making it suitable for large-scale epidemiological studies in children. We report our experience of oral fluid collection from 14 373 preschool-aged children in the UK Millennium Cohort Study. Samples were collected by mothers in the home setting following the guidance of trained interviewers, and posted to the laboratory. Samples were received from 11698 children (81.4 %). Children whose mothers were of Black Caribbean ethnicity and who lived in non-English-speaking households were less likely to provide a sample, and those with a maternal history of asthma more likely to provide a sample [adjusted risk ratio (95 % CI) 0.85 (0.73-0.98), 0.87 (0.77-0.98) and 1.03 (1.00-1.05) respectively]. Collection of oral fluid samples is feasible and acceptable in large-scale child cohort studies. Formal interpreter support may be required to increase participation rates in surveys that collect biological samples from ethnic minorities

Evaluation of In-Hospital Management for Febrile Illness\ud in Northern Tanzania before and after 2010 World Health\ud Organization Guidelines for the Treatment of Malaria

In 2010, the World Health Organization (WHO) published updated guidelines emphasizing and expanding recommendations for a parasitological confirmation of malaria before treating with antimalarials. This study aimed to assess differences in historic (2007–2008) (cohort 1) and recent (2011–2012) (cohort 2) hospital cohorts in the diagnosis and treatment of febrile illness in a low malaria prevalence area of northern Tanzania. We analyzed data from two prospective cohort studies that enrolled febrile adolescents and adults aged $13 years. All patients received quality-controlled aerobic blood cultures and malaria smears. We compared patients’ discharge diagnoses, treatments, and outcomes to assess changes in the treatment of malaria and bacterial infections. In total, 595 febrile inpatients were enrolled from two referral hospitals in Moshi, Tanzania. Laboratory-confirmed malaria was detected in 13 (3.2%) of 402 patients in cohort 1 and 1 (0.5%) of 193 patients in cohort 2 (p = 0.041). Antimalarials were prescribed to 201 (51.7%) of 389 smear-negative patients in cohort 1 and 97 (50.5%) of 192 smearnegative patients in cohort 2 (p = 0.794). Bacteremia was diagnosed from standard blood culture in 58 (14.5%) of 401 patients in cohort 1 compared to 18 (9.5%) of 190 patients in cohort 2 (p = 0.091). In cohort 1, 40 (69.0%) of 58 patients with a positive blood culture received antibacterials compared to 16 (88.9%) of 18 patients in cohort 2 (p = 0.094). In cohort 1, 43 (10.8%) of the 399 patients with known outcomes died during hospitalization compared with 12 (6.2%) deaths among 193 patients in cohort 2 (p = 0.073). In a setting of low malaria transmission, a high proportion of smear-negative patients were diagnosed with malaria and treated with antimalarials despite updated WHO guidelines on malaria treatment. Improved laboratory diagnostics for non-malaria febrile illness might help to curb this practice.\u