PurposeTo determine the potential associations between physical activity and risk of SARS-CoV-2 infection, severe illness from COVID-19 and COVID-19 related death using a nationwide cohort from South Korea.MethodsData regarding 212 768 Korean adults (age ≥20 years), who tested for SARS-CoV-2, from 1 January 2020 to 30 May 2020, were obtained from the National Health Insurance Service of South Korea and further linked with the national general health examination from 1 January 2018 to 31 December 2019 to assess physical activity levels. SARS-CoV-2 positivity, severe COVID-19 illness and COVID-19 related death were the main outcomes. The observation period was between 1 January 2020 and 31 July 2020.ResultsOut of 76 395 participants who completed the general health examination and were tested for SARS-CoV-2, 2295 (3.0%) were positive for SARS-CoV-2, 446 (0.58%) had severe illness from COVID-19 and 45 (0.059%) died from COVID-19. Adults who engaged in both aerobic and muscle strengthening activities according to the 2018 physical activity guidelines had a lower risk of SARS-CoV-2 infection (2.6% vs 3.1%; adjusted relative risk (aRR), 0.85; 95% CI 0.72 to 0.96), severe COVID-19 illness (0.35% vs 0.66%; aRR 0.42; 95% CI 0.19 to 0.91) and COVID-19 related death (0.02% vs 0.08%; aRR 0.24; 95% CI 0.05 to 0.99) than those who engaged in insufficient aerobic and muscle strengthening activities. Furthermore, the recommended range of metabolic equivalent task (MET; 500–1000 MET min/week) was associated with the maximum beneficial effect size for reduced risk of SARS-CoV-2 infection (aRR 0.78; 95% CI 0.66 to 0.92), severe COVID-19 illness (aRR 0.62; 95% CI 0.43 to 0.90) and COVID-19 related death (aRR 0.17; 95% CI 0.07 to 0.98). Similar patterns of association were observed in different sensitivity analyses.ConclusionAdults who engaged in the recommended levels of physical activity were associated with a decreased likelihood of SARS-CoV-2 infection, severe COVID-19 illness and COVID-19 related death. Our findings suggest that engaging in physical activity has substantial public health value and demonstrates potential benefits to combat COVID-19.

IMPORTANCEAntidepressant use is increasing worldwide. Yet, contrasting evidence on the safety of antidepressants is available from meta-analyses, and the credibility of these findings has not been quantified. OBJECTIVE To grade the evidence from published meta-analyses of observational studies that assessed the association between antidepressant use or exposure and adverse health outcomes.

Background. Since people with mental illness more likely die from cancer, we assessed whether people with mental illness undergo less cancer screening versus the general population. Methods. Systematic review and meta-analysis of observational studies. Primary outcome was Odds Ratio (OR) of cancer screening in people with mental illness versus the general population. Secondary outcome was prevalence of cancer screening in mental illness. Sensitivity and subgroup analyses considered specific mental illness, diagnostic criteria, confounder adjustment, country/region, and program vs. opportunistic screening. Newcastle-Ottawa Scale was used to assess study quality. This study is registered with PROSPERO, number CRD42018114781.

Background Numerous studies have identified the potential risk factors and biomarkers for autism spectrum disorder (ASD). We aim to study the strength and validity of the suggested environmental risk factors or biomarkers of ASD. Methods We conducted an umbrella review and systematically appraised the relevant meta-analyses of observational studies (PROSPERO registration: CRD42018091704). We searched PubMed, Embase, and Cochrane Database of Systematic Reviews from inception to 10/17/2018 and screened the reference list of relevant articles. We obtained the summary effect, 95% confidence interval (CI), heterogeneity, and 95% prediction intervals. We examined small study effects and excess significance. We performed analyses under credibility ceilings. Findings A total of 46 eligible articles yielded data on 67 environmental risk factors (cases=544212, population=81708787) and 52 biomarkers (cases=15614, controls=15417). Evidence of association was convincing for greater maternal age (RR=1•31, 95% CI=1•18 to 1•45), maternal chronic hypertension (OR=1•48, 95% CI=1•29 to 1•70), maternal gestational hypertension (OR=1•37, 95% CI=1•21 to 1•54), maternal overweight (RR=1•28, 95% CI=1•19 to 1•36), preeclampsia (RR=1•32, 95% CI=1•20 to 1•45), pre-pregnancy maternal antidepressant exposure (RR=1•48, 95% CI=1•29 to 1•71), and selective serotonin reuptake inhibitor (SSRI) exposure during pregnancy (OR=1•84, 95% CI=1•60 to 2•11). Only two associations, maternal overweight and SSRI during pregnancy, retained high level of evidence under subset sensitivity analyses. Evidence from biomarkers was limited. Interpretation Convincing evidence suggests that maternal factors such as age and features of metabolic syndrome are associated with risk of ASD. SSRI use during pregnancy was also convincingly associated with risk of ASD when exposed and non-exposed groups were compared. However, there is a possibility that the association is affected by other confounding factors, considering that pre-pregnancy maternal antidepressant exposure was also convincingly associated with higher risk of ASD. Findings from prior studies suggest that one possible confounding factor is underlying maternal psychiatric disorders.

Few studies have investigated the real-life outcomes of interdisciplinary multimodal pain rehabilitation programs (IMMRP) for chronic pain. This study has four aims: investigate effect sizes (ES); analyse correlation patterns of outcome changes; define a multivariate outcome measure; and investigate whether the clinical self-reported presentation pre-IMMRP predicts the multivariate outcome. To this end, this study analysed chronic pain patients in specialist care included in the Swedish Quality Registry for Pain Rehabilitation for 22 outcomes (pain, psychological distress, participation, and health) on three occasions: pre-IMMRP, post-IMMRP, and 12-month follow-up. Moderate stable ES were demonstrated for pain intensity, interference in daily life, vitality, and health; most other outcomes showed small ES. Using a Multivariate Improvement Score (MIS), we identified three clusters. Cluster 1 had marked positive MIS and was associated with the overall worst situation pre-IMMRP. However, the pre-IMMRP situation could only predict 8% of the variation in MIS. Specialist care IMPRPs showed moderate ES for pain, interference, vitality, and health. Outcomes were best for patients with the worst clinical presentation pre-IMMRP. It was not possible to predict who would clinically benefit most from IMMRP.

The literature on non-genetic peripheral biomarkers for major mental disorders is broad, with conflicting results. An umbrella review of meta-analyses of non-genetic peripheral biomarkers for Alzheimer's disease, autism spectrum disorder, bipolar disorder (BD), major depressive disorder, and schizophrenia, including first-episode psychosis. We included meta-analyses that compared alterations in peripheral biomarkers between participants with mental disorders to controls (i.e., between-group meta-analyses) and that assessed biomarkers after treatment (i.e., withingroup meta-analyses). Evidence for association was hierarchically graded using a priori defined criteria against several biases. The Assessment of Multiple Systematic Reviews (AMSTAR) instrument was used to investigate study quality. 1161 references were screened. 110 met inclusion criteria, relating to 359 meta-analytic estimates and 733,316 measurements, on 162 different biomarkers. Only two estimates met a priori defined criteria for convincing evidence (elevated awakening cortisol levels in euthymic BD participants relative to controls and decreased pyridoxal levels in participants with schizophrenia relative to controls). Of 42 estimates which met criteria for highly suggestive evidence only five biomarker aberrations occurred in more than one disorder. Only 15 meta-analyses had a power >0.8 to detect a small effect size, and most (81.9%) meta-analyses had high heterogeneity. Although some associations met criteria for either convincing or highly suggestive evidence, overall the vast literature of peripheral biomarkers for major mental disorders is affected by bias and is underpowered. No convincing evidence supported the existence of a transdiagnostic biomarker. Adequately powered and methodologically sound future large collaborative studies are warranted.

Decades of research have revealed numerous risk factors for mental disorders beyond genetics, but their consistency and magnitude remain uncer tain. We conducted a "metaumbrella" systematic synthesis of umbrella reviews, which are systematic reviews of metaanalyses of individual studies, by searching international databases from inception to January 1, 2021. We included umbrella reviews on nonpurely genetic risk or protective factors for any ICD/DSM mental disorders, applying an established classification of the credibility of the evidence: class I (convinc ing), class II (highly suggestive), class III (suggestive), class IV (weak). Sensitivity analyses were conducted on prospective studies to test for temporality (reverse causation), TRANSD criteria were applied to test transdiagnosticity of factors, and A Measurement Tool to Assess Systematic Reviews (AMSTAR) was employed to address the quality of metaanalyses. Fourteen eligible umbrella reviews were retrieved, summarizing 390 metaanalyses and 1,180 associations between putative risk or protective factors and mental disorders. We included 176 class I to III evidence associations, relating to 142 risk/protective factors. The most robust risk factors (class I or II, from prospective designs) were 21. For dementia, they included type 2 diabetes mellitus (risk ratio, RR from 1.54 to 2.28), depression (RR from 1.65 to 1.99) and low frequency of social con tacts (RR=1.57). For opioid use disorders, the most robust risk factor was tobacco smoking (odds ratio, OR=3.07). For nonorganic psychotic disorders, the most robust risk factors were clinical high risk state for psychosis (OR=9.32), cannabis use (OR=3.90), and childhood adversities (OR=2.80). For depressive disorders, they were widowhood (RR=5.59), sexual dysfunction (OR=2.71), three (OR=1.99) or fourfive (OR=2.06) metabolic factors, childhood physical (OR=1.98) and sexual (OR=2.42) abuse, job strain (OR=1.77), obesity (OR=1.35), and sleep disturbances (RR=1.92). For autism spectrum disorder, the most robust risk factor was maternal overweight pre/during pregnancy (RR=1.28). For attention deficit/hyperactivity disorder (ADHD), they were maternal prepregnancy obesity (OR=1.63), maternal smoking during pregnancy (OR=1.60), and maternal overweight pre/during pregnancy (OR=1.28). Only one robust protective factor was detected: high physical activity (hazard ratio, HR=0.62) for Alzheimer's disease. In all, 32.9% of the associations were of high quality, 48.9% of medium quality, and 18.2% of low quality. Transdiagnostic class IIII risk/protective factors were mostly involved in the early neurodevelopmental period. The evidencebased atlas of key risk and protective factors identified in this study represents a benchmark for advancing clinical characterization and research, and for expand ing early intervention and preventive strategies for mental disorders.

Although almost 80% meta-analyses reported a nominally statistically significant finding favouring psychotherapy, only a few meta-analyses provided convincing evidence without biases.