Background: There is inconclusive and controversial evidence of the association between allergic diseases and the risk of adverse clinical outcomes of coronavirus disease 2019 (COVID-19). Objective: We sought to determine the association of allergic disorders with the likelihood of a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test result and with clinical outcomes of COVID-19 (admission to intensive care unit, administration of invasive ventilation, and death). Methods: A propensity-score-matched nationwide cohort study was performed in South Korea. Data obtained from the Health Insurance Review & Assessment Service of Korea from all adult patients (age, >20 years) who were tested for SARS-CoV-2 in South Korea between January 1, 2020, and May 15, 2020, were analyzed. The association of SARS-CoV-2 test positivity and allergic diseases in the entire cohort (n 5 219,959) and the difference in clinical outcomes of COVID-19 were evaluated in patients with allergic diseases and SARS-CoV-2 positivity (n 5 7,340). Results: In the entire cohort, patients who underwent SARS-CoV-2 testing were evaluated to ascertain whether asthma and allergic rhinitis were associated with an increased likelihood of SARS-CoV-2 test positivity. After propensity score matching, we found that asthma and allergic rhinitis were associated with worse clinical outcomes of COVID-19 in patients with SARS-CoV-2 test positivity. Patients with nonallergic asthma had a greater risk of SARS-CoV-2 test positivity and worse clinical outcomes of COVID-19 than patients with allergic asthma. Conclusions: In a Korean nationwide cohort, allergic rhinitis and asthma, especially nonallergic asthma, confers a greater risk of susceptibility to SARS-CoV-2 infection and severe clinical outcomes of COVID-19.

ObjectiveThe adverse effects of proton pump inhibitors (PPIs) have been documented for pneumonia; however, there is no consensus regarding whether the use of PPIs might be harmful regarding the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this regard, we aimed to measure the potential associations of the current use of PPIs with the infection rates of COVID-19 among patients who underwent SARS-CoV-2 testing.DesignData were derived from a Korean nationwide cohort study with propensity score matching. We included 132 316 patients older than 18 years who tested for SARS-CoV-2 between 1 January and 15 May 2020. Endpoints were SARS-CoV-2 positivity (primary) and severe clinical outcomes of COVID-19 (secondary: admission to intensive care unit, administration of invasive ventilation or death).ResultsIn the entire cohort, there were 111 911 non-users, 14 163 current PPI users and 6242 past PPI users. After propensity score matching, the SARS-CoV-2 test positivity rate was not associated with the current or past use of PPIs. Among patients with confirmed COVID-19, the current use of PPIs conferred a 79% greater risk of severe clinical outcomes of COVID-19, while the relationship with the past use of PPIs remained insignificant. Current PPI use starting within the previous 30 days was associated with a 90% increased risk of severe clinical outcomes of COVID-19.ConclusionPatients taking PPIs are at increased risk for severe clinical outcomes of COVID-19 but not susceptible to SARS-CoV-2 infection. This suggests that physicians need to assess benefit–risk assessments in the management of acid-related diseases amid the COVID-19 pandemic.

Background Evidence for the associations between mental illness and the likelihood of a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test result and the clinical outcomes of COVID-19 is scarce. We aimed to investigate these associations with data from a national register in South Korea. Methods A nationwide cohort study with propensity score matching was done in South Korea using data collected from the Health Insurance Review and Assessment Service of Korea. We defined mental illness as present if one of the relevant ICD-10 codes was recorded at least twice within 1 year for an outpatient or inpatient. Severe mental illness was considered as non-affective or affective disorders with psychotic features. We included all patients aged older than 20 years who were tested for SARS-CoV-2 through services facilitated by the Korea Centers for Disease Control and Prevention, the Health Insurance Review and Assessment Service of Korea, and the Ministry of Health and Welfare, South Korea. We investigated the primary outcome (SARS-CoV-2 test positivity) in the entire cohort and the secondary outcomes (severe clinical outcomes of COVID-19: death, admission to the intensive care unit, or invasive ventilation) among those who tested positive. Findings Between Jan 1 and May 15, 2020, 216 418 people were tested for SARS-CoV-2, of whom 7160 (3·3%) tested positive. In the entire cohort with propensity score matching, 1391 (3·0%) of 47 058 patients without a mental illness tested positive for SARS-CoV-2, compared with 1383 (2·9%) of 48 058 with a mental illness (adjusted odds ratio [OR] 1·00, 95% CI 0·93–1·08). Among the patients who tested positive for SARS-CoV-2, after propensity score matching, 109 (8·3%) of 1320 patients without a mental illness had severe clinical outcomes of COVID-19 compared with 128 (9·7%) of 1320 with a mental illness (adjusted OR 1·27, 95% CI 1·01–1·66). Interpretation Diagnosis of a mental illness was not associated with increased likelihood of testing positive for SARS-CoV-2. Patients with a severe mental illness had a slightly higher risk for severe clinical outcomes of COVID-19 than patients without a history of mental illness. Clinicians treating patients with COVID-19 should be aware of the risk associated with pre-existing mental illness. Funding National Research Foundation of Korea.

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Pediatric brain tumors are highly associated with epileptic seizures. However, their epileptogenic mechanisms remain unclear. Here, we show that the oncogenic BRAF somatic mutation p.Val600Glu (V600E) in developing neurons underlies intrinsic epileptogenicity in ganglioglioma, one of the leading causes of intractable epilepsy. To do so, we developed a mouse model harboring the BRAF somatic mutation during early brain development to reflect the most frequent mutation, as well as the origin and timing thereof. Therein, the BRAF mutation arising in progenitor cells during brain development led to the acquisition of intrinsic epileptogenic properties in neuronal lineage cells, whereas tumorigenic properties were attributed to high proliferation of glial lineage cells. RNA sequencing analysis of patient brain tissues with the mutation revealed that BRAF-induced epileptogenesis is mediated by RE1-silencing transcription factor (REST), which is a regulator of ion channels and neurotransmitter receptors associated with epilepsy. Moreover, we found that seizures in mice were significantly alleviated by an FDA-approved BRAF inhibitor, vemurafenib, as well as various genetic inhibitions of Rest. Accordingly, this study provides direct evidence of a BRAF somatic mutation contributing to the intrinsic epileptogenicity in pediatric brain tumors and suggests that BRAF and REST could be treatment targets for intractable epilepsy.

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Background: Although the different age groups had differences in sensitivity of asthma exacerbations (AEs) to environmental factors, no comprehensive study has examined the age-stratified effects of environmental factors on AEs. Objective: We sought to examine the short-term effects in agestratified groups (infants, preschool children, school-aged children, adults, and the elderly) of outdoor environmental factors (air pollutants, weather conditions, aeroallergens, and respiratory viral epidemics) on AEs. Methods: We performed an age-stratified analysis of the shortterm effects of 4 groups of outdoor environmental factors on AEs in Seoul Metropolitan City (Korea) from 2008 and 2012. The statistical analysis used a Poisson generalized linear regression model, with a distributed lag nonlinear model for identification of lagged and nonlinear effects and convergent cross-mapping for identification of causal associations. Results: Analysis of the total population (n 5 10,233,519) indicated there were 28,824 AE events requiring admission to an

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