Association between acquiring SARS-CoV-2 during pregnancy and post-acute sequelae of SARS-CoV-2 infection: RECOVER electronic health record cohort analysis.

Background: Little is known about post-acute sequelae of SARS-CoV-2 infection (PASC) after acquiring SARS-CoV-2 infection during pregnancy. We aimed to evaluate the association between acquiring SARS-CoV-2 during pregnancy compared with acquiring SARS-CoV-2 outside of pregnancy and the development of PASC. Methods: This retrospective cohort study from the Researching COVID to Enhance Recovery (RECOVER) Initiative Patient-Centred Clinical Research Network (PCORnet) used electronic health record (EHR) data from 19 U.S. health systems. Females aged 18-49 years with lab-confirmed SARS-CoV-2 infection from March 2020 through June 2022 were included. Validated algorithms were used to identify pregnancies with a delivery at >20 weeks' gestation. The primary outcome was PASC, as previously defined by computable phenotype in the adult non-pregnant PCORnet EHR dataset, identified 30-180 days post-SARS-CoV-2 infection. Secondary outcomes were the 24 component diagnoses contributing to the PASC phenotype definition. Univariable comparisons were made for baseline characteristics between individuals with SARS-CoV-2 infection acquired during pregnancy compared with outside of pregnancy. Using inverse probability of treatment weighting to adjust for baseline differences, the association between SARS-CoV-2 infection acquired during pregnancy and the selected outcomes was modelled. The incident risk is reported as the adjusted hazard ratio (aHR) with 95% confidence intervals. Findings: In total, 83,915 females with SARS-CoV-2 infection acquired outside of pregnancy and 5397 females with SARS-CoV-2 infection acquired during pregnancy were included in analysis. Non-pregnant females with SARS-CoV-2 infection were more likely to be older and have comorbid health conditions. SARS-CoV-2 infection acquired in pregnancy as compared with acquired outside of pregnancy was associated with a lower incidence of PASC (25.5% vs 33.9%; aHR 0.85, 95% CI 0.80-0.91). SARS-CoV-2 infection acquired in pregnant females was associated with increased risk for some PASC component diagnoses including abnormal heartbeat (aHR 1.67, 95% CI 1.43-1.94), abdominal pain (aHR 1.34, 95% CI 1.16-1.55), and thromboembolism (aHR 1.88, 95% CI 1.17-3.04), but decreased risk for other diagnoses including malaise (aHR 0.35, 95% CI 0.27-0.47), pharyngitis (aHR 0.36, 95% CI 0.26-0.48) and cognitive problems (aHR 0.39, 95% CI 0.27-0.56). Interpretation: SARS-CoV-2 infection acquired during pregnancy was associated with lower risk of development of PASC at 30-180 days after incident SARS-CoV-2 infection in this nationally representative sample. These findings may be used to counsel pregnant and pregnant capable individuals, and direct future prospective study. Funding: National Institutes of Health (NIH) Other Transaction Agreement (OTA) OT2HL16184.

Risk factors for prostate cancer: An umbrella review of prospective observational studies and mendelian randomization analyses.

BACKGROUND: The incidence of prostate cancer is increasing in older males globally. Age, ethnicity, and family history are identified as the well-known risk factors for prostate cancer, but few modifiable factors have been firmly established. The objective of this study was to identify and evaluate various factors modifying the risk of prostate cancer reported in meta-analyses of prospective observational studies and mendelian randomization (MR) analyses. METHODS AND FINDINGS: We searched PubMed, Embase, and Web of Science from the inception to January 10, 2022, updated on September 9, 2023, to identify meta-analyses and MR studies on prostate cancer. Eligibility criteria for meta-analyses were (1) meta-analyses including prospective observational studies or studies that declared outcome-free at baseline; (2) evaluating the factors of any category associated with prostate cancer incidence; and (3) providing effect estimates for further data synthesis. Similar criteria were applied to MR studies. Meta-analysis was repeated using the random-effects inverse-variance model with DerSimonian-Laird method. Quality assessment was then conducted for included meta-analyses using AMSTAR-2 tool and for MR studies using STROBE-MR and assumption evaluation. Subsequent evidence grading criteria for significant associations in meta-analyses contained sample size, P values and 95% confidence intervals, 95% prediction intervals, heterogeneity, and publication bias, assigning 4 evidence grades (convincing, highly suggestive, suggestive, or weak). Significant associations in MR studies were graded as robust, probable, suggestive, or insufficient considering P values and concordance of effect directions. Finally, 92 selected from 411 meta-analyses and 64 selected from 118 MR studies were included after excluding the overlapping and outdated studies which were published earlier and contained fewer participants or fewer instrument variables for the same exposure. In total, 123 observational associations (45 significant and 78 null) and 145 causal associations (55 significant and 90 null) were categorized into lifestyle; diet and nutrition; anthropometric indices; biomarkers; clinical variables, diseases, and treatments; and environmental factors. Concerning evidence grading on significant associations, there were 5 highly suggestive, 36 suggestive, and 4 weak associations in meta-analyses, and 10 robust, 24 probable, 4 suggestive, and 17 insufficient causal associations in MR studies. Twenty-six overlapping factors between meta-analyses and MR studies were identified, with consistent significant effects found for physical activity (PA) (occupational PA in meta: OR = 0.87, 95% CI: 0.80, 0.94; accelerator-measured PA in MR: OR = 0.49, 95% CI: 0.33, 0.72), height (meta: OR = 1.09, 95% CI: 1.06, 1.12; MR: OR = 1.07, 95% CI: 1.01, 1.15, for aggressive prostate cancer), and smoking (current smoking in meta: OR = 0.74, 95% CI: 0.68, 0.80; smoking initiation in MR: OR = 0.91, 95% CI: 0.86, 0.97). Methodological limitation is that the evidence grading criteria could be expanded by considering more indices. CONCLUSIONS: In this large-scale study, we summarized the associations of various factors with prostate cancer risk and provided comparisons between observational associations by meta-analysis and genetically estimated causality by MR analyses. In the absence of convincing overlapping evidence based on the existing literature, no robust associations were identified, but some effects were observed for height, physical activity, and smoking.

Observational and genetic analyses of the bidirectional relationship between depression and hypertension.

BACKGROUND: While the association between depression and hypertension has been extensively investigated, the pattern and nature of such association remain inconclusive. We sought to investigate the bidirectional relationship between depression and hypertension and its causal. METHODS: We first performed observational analyses using longitudinal data from the UK Biobank. We then performed genetic analyses leveraging summary statistics from large-scale genome-wide association studies (GWASs) conducted in European ancestry for depression and hypertension. RESULTS: Observational analysis suggested a significant bidirectional phenotypic association between depression and hypertension (Depression â†’ Hypertension: HR = 1.27, 95 % CI: 1.19, 1.36; Hypertension â†’ Depression: HR = 1.65, 95 % CI: 1.58, 1.72). Linkage disequilibrium score regression demonstrated a positive genetic correlation between the two conditions (rg=0.15, P = 5.75 × 10-10). Bidirectional two-sample Mendelian randomization (MR) suggested that genetic liability to depression was significantly associated with an increased risk of hypertension (OR = 1.27, 95 % CI: 1.12, 1.43), while the genetic liability to hypertension was not associated with the risk of depression (OR = 1.01, 95 % CI: 0.99, 1.03). Multivariate MR, after adjusting for smoking, drinking, and body mass index, further supported an independent causal effect of genetic liability to depression on hypertension risk (OR = 1.10, 95 % CI: 1.02, 1.18). LIMITATIONS: (1) interference of confounders, (2) absence of adequate statistical power, and (3) limitation to European populations. CONCLUSION: Our study indicates depression is a causal risk factor for hypertension, whereas the reverse maybe not. Findings support that prevention of depression might help in decreasing hypertension incidence.

Temporal relationship between sleep duration and obesity among Chinese Han people and ethnic minorities.

BACKGROUND: No studies have assessed the association between sleep duration and obesity in Chinese ethnic minorities. Whether the relationship between sleep duration and obesity is different between Chinese Han people and Chinese ethnic minorities remains unclear. The study aimed to explore the relationship between sleep duration and obesity among Chinese Han people and Chinese ethnic minorities. METHODS: We applied data from the Guizhou Population Health Cohort Study (GPHCS), which 9,280 participants were recruited in the baseline survey from 2010 to 2012, and 8,163 completed the follow-up survey from 2016 to 2020. A total of 5,096 participants (3,188 Han Chinese and 1,908 ethnic minorities) were included in the ultimate analysis. Information on sleep duration (total 24-hour sleep time), body mass index (BMI), and waist circumference (WC) was collected at the baseline and follow-up survey, respectively. Cross-lagged panel analyses were conducted to explore the temporal relationship between sleep duration and obesity for Han people and ethnic minorities. RESULTS: For Han people, the results from cross-lagged panel analyses indicated that baseline sleep duration was significantly associated with follow-up BMI (ßBMI = -0.041, 95% CIBMI: -0.072 ~ -0.009) and follow-up WC (ßWC = -0.070, 95%CIWC: -0.103 ~ -0.038), but baseline BMI (ßBMI = -0.016, 95% CIBMI: -0.050 ~ 0.018) and baseline WC (ßWC = -0.019, 95% CIWC: -0.053 ~ 0.016) were not associated with follow-up sleep duration. In addition, the relationship between baseline sleep duration and follow-up BMI was gender-specific and significant only in the Han people female (ßBMI = -0.047, 95% CIBMI: -0.090 ~ -0.003) but not in the Han people male (ßBMI = -0.029, 95% CIBMI: -0.075 ~ 0.016). For ethnic minorities, the results indicated that there was no relationship between sleep duration and obesity at all, either from sleep duration to obesity (ßBMI = 0.028, 95%CIBMI: -0.012 ~ 0.068; ßWC = 0.020, 95%CIWC: -0.022 ~ 0.062), or from obesity to sleep duration (ßBMI = -0.022, 95%CIBMI: -0.067 ~ 0.022; ßWC = -0.042, 95%CIWC: -0.087 ~ 0.003). CONCLUSION: The relationship pattern between sleep duration and obesity across Han people and ethnic minorities is different. Future sleep-aimed overweight and obesity intervention should be conducted according to population characteristics.