To the Editor: The spread of the coronavirus disease-2019 (COVID-19) remains a worsening global health crisis. Although many studies have reported risk factors for severe COVID-19, asthma characterization in COVID-19 is still controversial, with different early reports from China and recent reports from the Europe and United States.1 Prolonged viral shedding is not only a risk factor for poor outcome of COVID-19, but also clues to host immune response against the virus. However, there is limited data on this except for results from relative small group studies.2 In this study, 2 200 adult patients hospitalized for COVID-19 in Daegu were evaluated for prevalence of asthma and clinical outcomes with COVID-19 according to asthma. In addition, the risk factors for delayed viral clearance were evaluated.The prevalence of asthma in patients with COVID-19 was 3.2% which was not different from its prevalence in the Korea National Health and Nutrition Examination Survey (KNHANES) (Figure 1A and Table S1). By age group, the prevalence of asthma showed a similar U-shaped pattern as the general prevalence pattern in Korea. However, the prevalence of asthma in the 19–29-year age group (2.1%) was lower than that of KNHANES (Figure 1B).Table S2 compares the characteristics between the asthma group and the non-asthma group. Older age, overweight, and comorbidity of chronic obstructive pulmonary disease, and initial symptoms of dyspnea and nausea/vomiting were more common in the asthma group. Compared with the non-asthma group, the asthma group had a greater risk of death (13.6%vs. 6.4%, P = 0.02) and a greater need for high-flow oxygen therapy (18.2% vs . 10.5%, P = 0.048) (Figure 1C and Table S3). The higher mortality rate in asthma patients compared with non-asthmatic patients was particularly noticeable in female and overweight patients. Older patients (> 65 years) with asthma tended to have a higher mortality rate than those without asthma (Figure 1D). After adjusting for potential confounders, asthma had no significant association with clinical outcomes of COVID-19 (Figure 1E and Table S4). Meanwhile, older age, male gender, and comorbid diseases including overweight, diabetes, chronic kidney disease, cancer, autoimmune disease, dementia, and other psychological disorder were significant risk factors for mortality (Tables S5 and S6).Asthma is considered to have a lower risk of death than other well-known risk factors.3, 4 However, asthma is a heterogeneous disease and is often associated with atopic and eosinophilic asthma in younger patients. Meanwhile, obese asthma and elderly asthma are known to have common neutrophilic phenotypes.5, 6 The recent results of higher expression of COVID-19 receptors in respiratory specimens with neutrophilic asthma phenotype compared with the eosinophilic asthma phenotype.7 Considering prevalence and clinical outcome results, it is possible that neutrophilic asthma is a risk factor for infection and poor prognosis of COVID-19 rather than eosinophilic asthma.When delayed viral clearance was divided into two groups based on 30 days, 906 patients were included in the non-delayed viral clearance group and 415 patients in the delayed viral clearance group. After adjusting for potential confounders, delayed viral clearance was not significantly associated with asthma (Figure 1E and Table S4). However, older age >65 years (Odds ratio (OR) 2.002, 95% Confidence interval (CI) 1.292–3.101; P = 0.002), comorbid diseases including dementia (OR 3.123, 95% CI 1.833–5.321; P<0.001), and other psychological disorder (OR 2.084, 95% CI 1.178–3.687; P = 0.012), initial symptom of skin rash (OR 15.943, 95% CI 1.613–157.535; P = 0.018), and initial laboratory abnormalities including hemoglobin <10 g/dL (OR 2.156, 95% CI 1.161–4.003; P = 0.015) and C-reactive protein (CRP) ≥1.0 mg/dL (OR 1.588, 95% CI 1.061–2.377; P = 0.025) were significant risk factors for delayed viral clearance. On the other hand, male sex (OR 0.752, 95% CI 0.567–0.997; P = 0.047), hypertension (OR 0.704, 95% CI 0.519–0.953; P = 0.023), and initial symptom of headache (OR 0.673, 95% CI 0.485–0.932; P = 0.017) were significant protective factors for delayed viral clearance (Figure 2A and Table S7). In particular, when limited to the mild COVID-19 group classified as no activity limitations in the outcome parameters, older age, dementia, initial symptoms of skin rash and headache, and initial hemoglobin <10 g/dL showed significant differences (Figure 2B, Table S8).Several factors related to the nervous system were identified as important risk factors for delayed viral clearance. Previous studies have shown that the coronavirus can initially invade the peripheral nerves and enter the central nervous system through a synapse path.8 It is hypothesized that the ability of the immune system to find and remove viruses that have penetrated the nervous system is important for virus clearance. Male sex, hypertension and elevated CRP did not show a significant difference when analyzed only mild patients, and these may be indicators associated with severity rather than a direct effect on viral clearance.Anti-inflammatory drugs such as hydroxychloroquine and systemic steroid were shown to be risk factors for mortality and delayed viral clearance (Table S6 and S8). These medications were used more often when the hospitalization period was extended or when showing poor prognosis factors. Notwithstanding these, our results suggest that anti-inflammatory drugs need to be used with proper consideration of appropriate indications.On May 9, 2020, there were 6,859 patients with PCR-confirmed COVID-19 in Daegu. This data excluded asymptomatic or minimal symptomatic patients who did not require hospitalization. However, our study covered almost all hospitalized patients diagnosed with COVID-19 in Daegu from February to May ,therefore, selection bias is minimized.9 In Korea, most hospitals decided to terminate the quarantine by repeating PCR every week. In addition, the Korea Centers for Disease Control & Prevention (KCDC) thoroughly managed the criteria for quarantine termination and PCR results. Through this, in our study, we were able to perform a large-scale study to confirm the risk factors for delayed viral clearance.In summary, despite the positivity of differences depending on phenotypes, the prevalence of asthma was not significantly different in patients with COVID-19, and asthma did not affect the outcomes of COVID-19. Age, dementia, and initial presentations of headache, skin rash, and anemia were independently associated with viral clearance.

Objectives- The aim of this study is to identify socio-demographic and the use of basic maternal health care services associated with mobile use to receive health care services (antenatal care, transport in the facility and postnatal care for mother and newborn). Design– This a cross-sectional study Setting- Data were collected from eight districts in Bangladesh- Barishal, Chattogram, Dhaka, Mymensingh, Khulna, Rajshahi, Rangpur, and Sylhet by Bangladesh Demographic and Health Survey (BDHS) 2014 Sample- 4494 women aged 14-49 with children were involved in the research. Methods-Data were collected using questionnaire. Models of logistic regression were used for association determination. Results- The total woman using the mobile phone was reported 22.23%. Among those 29.9% using the mobile phone to obtain health service or advice and 70.1% did not obtain health information. Women who had higher education with a mobile phone to received more health care (secondary and higher: OR=1.922, 95%CI=1.225-3.014; primary: OR=1.982, 95%CI=1.738-2.654), socio-economic status (rich: OR=1.228, 95%CI=1.009-1.494; middle: OR=1.691, 95%CI=1.256-2.333), prenatal care (yes: OR=1.993, 95%CI=1.425-1.987), antenatal care (yes: OR=1.951, 95%CI=1.765-1.998) and after delivery to check up health status (yes: OR=1.966, 95%CI=1.639-2.357). Conclusions– The results of this study showed that women who have completed higher education, high-income families, young age groups, residence in urban areas are more likely to use mobile phones to receive health care facilities in Bangladesh. Intervention studies are essential for recognizing the instrument by which mobile phone-based facility improves maternal health care application.

Objectives: To assess the characteristics and forecasting of respiratory viruses epidemic among young children with acute respiratory tract infection (ARTI) in west China. Methods: This study retrospected the epidemic characteristics of respiratory viruses among 11813 pediatric patients with ARTI between March 2018 and March 2020. Results: 11813 samples were collected, with a mean age of 2.25 years. The ratio of the boy: the girl was 1.36. The two predominant viruses were influenza (Flu) A and respiratory syncytial virus (RSV), with Flu A accounting for 47.3% (n=1099), 47.5% (n=1333) and RSV accounting for 32.7% (n=760), 24.7% (n=692) of the positive samples in the two respective years. The positive rate of Flu B was 10.9% and 13.1%, and the other four viruses were <7%. The most common virus was RSV in the <5 years group and Flu A in the 5-10 years group. Flu A and RSV demonstrated pronounced seasonality, and their infection rates increased from October. During the pandemic of SARS-CoV-2, isolation measures led to a decline in the number of ARTI. Conclusions: The study provided surveillance of respiratory viruses in west China. It will provide guidance for medical staff to implement the necessary prevention and management strategies before the outbreak of the virus in the future.

Background: The pandemic caused by Coronavirus disease 2019, has caused great impact worldwide. Risk factors for severe outcomes have been identified, but asthma seems not to be one of them. Objectives: Our principal purpose is to analyze personal characteristics in severe asthma patients, in treatment with monoclonal antibody, belonging to the Health Department of Castellon, in order to see if these variables affect the probability of being infected by SARS-Cov-2. Methods: This is an observational study. Patients recruited had severe asthma in treatment with monoclonal antibody. A questionnaire was elaborated. Aspects evaluated were: COVID-19 symptoms, asthma control, exposition to the disease, and lifestyle before the pandemic. Serological tests were done by using total SARS-Cov-2 antibody test. Results: 108 patients were enrolled in the study, of whom 106 patients were included. 11 patients declared suggestive COVID-19 symptoms. A total of 21 patients had a serology test done, giving positive results 2 of them. 27 patients needed medical attention, being asthma exacerbation the most common symptom. 71,7% of patients had a normal or high level of social activity before the pandemic. Statistic significance was achieved for medical assistance, asthma control and contact with SARS-Cov-2 positive patients. Conclusion: Personal external factors in severe asthma patients do not influence the probability of being affected by the disease. We can hypothesize that these patients do not have an increased susceptibility for being infected by the virus. Bad asthma control was the main reason for medical assistance during the pandemic.

Background: Little is known about the clinical course of chronic urticaria (CU) and predictors of its prognosis. We evaluated CU patient clusters based on medication scores for the initial 3 months of treatment to investigate time to remission and relapse rates and to identify predictors for CU remission. Methods: In total, 4552 patients (57.9% female; mean age of 38.6 years) with CU were included in this retrospective cohort study. The K-medoids algorithm was used for clustering CU patients. Kaplan-Meier survival analysis with Cox regression was applied to identify predictors of CU remission. Results: Four distinct clusters were identified: patients with consistently low disease activity (cluster 1, n = 1786), with medium-to-low disease activity (cluster 2, n = 1031), with consistently medium disease activity (cluster 3, n = 1332), or with consistently high disease activity (cluster 4, n = 403). Mean age, treatment duration, peripheral neutrophil counts, total IgE, and complements levels were significantly higher for cluster 4 than the other three clusters. Median times to remission were also different among the four clusters (2.1 vs 3.3 vs 6.4 vs 9.4 years, respectively, P < .001). Sensitization to house dust mites (≥ class 3) and female sex were identified as significant predictors of CU remission. Around 20% of patients who achieved CU remission experienced relapse. Conclusion: In this study, we identified four CU patient clusters by analyzing medication scores during the first 3 months of treatment and found that sensitization to house dust mites and female sex can affect CU prognosis.

BACKGROUND: The coronavirus disease-2019 (COVID-19) is still rapidly spreading worldwide, and remains a global health crisis. We investigated the impact of asthma on the prevalence and outcomes of COVID-19 and identify the risk factors for delayed viral clearance. METHODS: Adult patients with COVID-19 admitted to 10 hospitals in Daegu were retrospectively registered, and their clinical information was collected. Delayed viral clearance was divided into two groups based on 30 days. RESULTS: A total of 2,200 patents were evaluated, and the prevalence of asthma in COVID-19 was 3.2%. Compared with Korea nationwide survey data, there were no differences in asthma prevalence. In the univariate analysis, the risk of death (13.6% vs 6.4%, P = 0.021) and high flow oxygen therapy (18.2% vs 10.5%, P = 0,048) was increased in asthma patients, with a stronger tendency among elderly, women, and overweight patients. However, in a multivariate analysis using the logistic regression model, any clinical outcomes according to asthma was not significant. The risk factors for delayed viral clearance were older age >65 years (Odds ratio [95% confidence interval] 2.002 [1.292–3101]), dementia (3.123 [1.833–5.321]), skin rash (15.943 [1.613–157.535]), and anemia (2.156 [1.061–2.377]), whereas headache (0.673 [0.485–0.932]) lowered the risk. CONCLUSIONS: There may be a difference depending on phenotypes, but asthma prevalence was not significantly different in patients with COVID-19, and asthma did not affect outcomes of COVID-19. Older age, dementia, headache, skin rash, and anemia were independently associated with delayed viral clearance.

A valid measurement of the SARS-CoV-2 incubation period is needed for case definitions and for adapting appropriate isolation measures but is challenging in an emergency context. The objective was to systematically review recent literature of reported estimates of the distribution of incubation period of SARS-CoV-2 for describing the distribution and its variability and dispersion through meta-analysis. A systematic review search was carried out up to July 1st 2020 of all identified references available reporting the SARS-CoV-2 incubation. Individual mean and standard deviation were used to produce the pooled estimate. Heterogeneity was also assessed using I2 statistics and sources of heterogeneity were explored using a meta-regression. The main outcome was the SARS-CoV-2 incubation period defined as the time from exposure to onset of clinical illness. In total, 43 studies were eligible, including 12 (27.9%) cohorts and 31 (72.1%) case reports and series. The pooled estimate of the mean incubation period across the studies was 6.24 days, 95% CI [5.80;6.69] ranging from 2.33 to 17.60 days. Shorter incubation periods were reported in cohorts compared to case series (p<0.01) and among studies with high proportions of males (p<0.05). The mean incubation period will help for identification times of exposure but determinants of its variations/range might be explored for potential links with clinical outcome or early pathogenic steps. The impact of individuals with extreme values of incubation on the outbreak dynamic should be evaluated taking account for the basic reproductive number. A real time of meta-analysis, called the InCoVid Lyon, is proposed.

Background: There is a known female predominance in immunological conditions. Gender differences have also been demonstrated in perioperative hypersensitivity. The aim of this study was to investigate gender differences in the incidence of perioperative allergic reactions in Norway from 1997 to 2017. Methods: Spontaneous reports on allergic reactions during anesthesia were collected, and information about demographic, clinical and laboratory findings were recorded. Results: Women account for 66% of reported cases, and gender difference was most pronounced in fertile women (ages 14 to 51), where 74% of reports were from women. After withdrawal of the only pholcodine containing cough syrup on the market in 2007, the female predominance fell from 72 to 60% in all age groups. We found no differences in severity of the reaction or in laboratory findings between men and women. Conclusions: Women are at increased risk of suffering perioperative hypersensitivity reactions. The gender difference was less pronounced after the withdrawal of pholcodine.

Abstract Background: the survival of Wilms tumor is very low when evaluated in 2008. The impact of establishing pediatric oncology service on survival is studied, and the obstacles of treating Wilms tumor patients were identified. Procedure: All Wilms tumor patients from 2005 to 2014 were analyzed retrospectively. Patients received treatment based on the NWTS IV protocol. Patients were analyzed for overall survival, and event-free survival, and these outcomes were correlated with age, sex, stage at presentation, and histology. Results: We analyzed 143 files of Wilms tumor. The male to female ratio is 1.75. The mean age of patients at diagnosis is 3.5. The follow-up period is five years. Most patients (83%) had advanced disease stage 3, and 4.There is a very high abandonment rate (37%). The event-free survival among patients who completed treatment is 75.6%, and the overall survival is 43.4% Conclusions: There is a remarkable improvement in Wilms tumor survival from 11% to 43 % and 75.6%. Much needs to be done to reduce abandonment rates and establish a surgical pediatric oncology service.

Endometriosis is a common health condition affecting women of reproductive age who often present with chronic pelvic pain and/or infertility. There is wide variation in the estimates of endometriosis prevalence. Accurate reporting of the disease prevalence is hampered by multiple factors including long delay in diagnosis due to natural fluctuation in symptoms severity, lack of a reliable non-surgical diagnostic tool, polymorphic appearance of endometriosis lesions at laparoscopy, inability to achieve histological confirmation is all suspected cases and tendency for disease recurrence. Therefore, a longitudinal, rather than cross-sectional, cohort study design spanning an extended follow-up period is better suited to assess endometriosis prevalence. In this issue of BJOG, Rowlands and colleagues (2020) linked longitudinal survey data to three administrative health databases to identify the prevalence of endometriosis among 13,508 young Australian women followed up for nearly 20 years. The study reported a 6% cumulative prevalence of clinically-confirmed endometriosis and an additional 5.4% of clinically-suspected endometriosis. If these figures reflect the true prevalence of endometriosis, then one in nine women will be diagnosed with endometriosis at some point during their reproductive years up to the age of 44 with a peak at 30-34 years, thus underscoring the significant impact of the disease on the well-being and quality of life in young women and the enormous burden on healthcare resources needed to diagnose and treat endometriosis and its sequelae.The data presented in the study of Rowlands and colleagues (BJOG 2020) included patients who could have been diagnosed with adenomyosis but their condition was coded as endometriosis. This is unlikely to have significantly over-estimated the prevalence of endometriosis as recent evidence suggests adenomyosis prevalence to be only 1% with a considerable proportion of those patients having co-existing endometriosis (Yu et al, Am J Obstet Gynecol 2020; 223: 94.e1-10). The same can not be said about the 5.4% of clinically-suspected endometriosis cases. Symptoms review, clinical examination and various imaging modalities, including ultrasound scanning and magnetic resonance imaging, represent the cornerstone of non-invasive diagnosis of endometriosis. Current evidence suggests that the predictive accuracy of those non-invasive methods in the diagnosis of endometriosis compared to laparoscopy and histological confirmation is modest (Nisenblat et al, Cochrane Database Syst Rev, 2016 (2): CD009591) and depends on the combination of diagnostic tools used as well as the site and extent of the endometriosis lesions (Reid et al, Eur J Obstet Gynecol Reprod Biol 2019; 234: 171-178). These data are not provided in the study of Rowlands and colleagues. It is therefore difficult to accurately estimate the prevalence of endometriosis whether it’s the 6% clinically-confirmed rate or the full 11.4% confirmed and suspected rate. The truth probably lies somewhere in the middle! Future epidemiological studies should endeavour to elucidate on the distinction between the different methods used in the diagnosis of endometriosis with reference to the predictive accuracy of each diagnostic modality to help advance our understanding of the incidence and risk factors associated with this debilitating gynaecological condition.Mr. Tarek A El-ToukhyAssisted Conception Unit, Guys and St. Thomas Hospital NHS Trust11th Floor, Tower Wing,Guys Hospital,St. Thomas Street tarekeltoukhy@hotmail.com

To the Editor,The proportion of the population with allergic diseases has increased rapidly in recent decades1, 2. In addition to affecting the quality of life, a significant economic burden of these diseases was transferred to society and the national health care system1. China is a large country with a rapidly developing economy, wide geography, and diverse climate and lifestyles, which may lead to significantly regional differences in the distribution of allergens. Although a series of studies have explored the prevalence of allergen sensitization in China, the majority of them focus on one part of geography in China3-5. In 2009, a study6 was conducted to estimate the prevalence of common aeroallergens among patients with allergic asthma and/or rhinitis in mainland China. Although the study investigated the differences of the prevalence in different regions of China, it divided China into only four geographical regions, which may neglect detailed information about the characteristics of sensitization prevalence in different places in China. In that study, the skin prick test (SPT) was used to detect the sensitization to allergens. The method has low accuracy for positive results because it is heavily affected by certain factors, such as the skill of the tester, reagent used, interpretation of results and so on. Our research has the following different characteristics compared with previous studies: 1) covering a variety of allergic diseases, 2) exploring both aeroallergens and food allergens simultaneously, 3) including a large set of data from all the seven regions of mainland China, and 4) using an internationally recognized method of sIgE testing, ImmunoCAP, to detect sensitization. These advantages may help us obtain more accurate and reliable results and conclusions.Here, we conducted a large multicenter study on the prevalence patterns of serum allergen-specific IgE (sIgE) sensitization to the four most common food allergens (i.e., egg whites, cow’s milk, crab, and shrimp) and five aeroallergens (i.e., house dust mite, German cockroach, tree pollen mix, mold mix, dog dander) among 44156 patients with allergic symptoms in 52 cities from 26 provinces of all the seven geographical regions in mainland China from July 2015 to June 2018. The sIgE sensitization was tested by a certified third-party laboratory service provider with uniform and standardized procedures. This study was approved by the ethics committee of the First Affiliated Hospital of Guangzhou Medical University (Approval number: GYFYY-2017-18). Details about the methods were in the supplementary materials .Our study showed that the overall prevalence of positive sIgE responses to the 9 allergens across mainland China from the highest to the lowest was 33.74% for house dust mites, 24.5% for cockroaches, 19.97% for shrimp, 17.31% for crab, 11.62% for cow’s milk, 10.92% for egg whites, 9.35% for tree pollen mix, 4.02% for dog dander and 3.92% for mold mix (Table 1 ). Our study confirmed that an observation shown in several previous studies based on certain specific areas in China3-5 that the positive cases in sIgE fell mainly in the two low classes (i.e., classes 1 and 2) was also held in all the seven regions in mainland China (Table 1 ).Our study revealed the distinctive patterns in the prevalence of allergen sensitization among regions, gender, age groups and seasons. Geographically, there is a significant difference in the prevalence among regions for all 9 allergens except for the mold mix (Table S1 ). House dust mites were the allergen with the highest prevalence of sensitization in all seven regions, with the highest in South China (40.79%) and the lowest in Northeast China (11.21%). Allergies to German cockroaches had a higher prevalence in southern regions (Southwest China, South China and East China) than in northern regions (North China and Northeast China). The prevalence of sIgE responses to dog dander was the highest in North China and was very close to each other in the southern regions. The prevalence of the egg whites and milk in Central China, East China and South China was higher than in Southwest China, North China and Northeast China, which means that patients living in eastern, coastal and/or southern areas were more sensitive to egg whites and cow’s milk. The prevalence of crab and shrimp sensitization in Southwest China and South China was higher than that in the northern regions (North China and Northeast China). The heatmap (Figure 1 ) displays the distribution of the prevalence of the sIgE response to allergens in different regions of mainland China.The prevalence of sensitization to all nine allergens was higher overall in males than in females (Table 1 and Figure S1 ) although that may not be true in each age group for each allergen as shown in the forest plot in Figure S1 . Our study showed that, whereas the sensitization to egg whites and milk was the highest in children, the sensitization to other allergens tended to be the highest in teenagers and young adults (Figure S2 ). Figure S3displays he prevalence pattern of allergens by months across years. The prevalence of dog dander and mold mix was very stable across months; however, the prevalence of other allergens fluctuated from January to December. The prevalence of house dust mites, German cockroach, shrimp and crab were higher in the summer months (from June to August) than in other months. The prevalence of tree pollen mix was much higher in April and October than in other months.This should be the first large study to investigate the prevalence of allergen sensitization in the patients with allergic symptoms from all the seven geographic regions of mainland China. Based on this study, we found that the prevalence of sIgE sensitization to allergens displayed obvious and distinctive patterns among regions, gender, age groups and seasons. The reasons for these patterns may include lifestyle factors, socioeconomic factors, genetic predispositions, climate, sexual hormones, cross-reactivity and so on3,4,6-9. Please refer to the supplementary materials for the detailed discussion on the factors that influenced these variations. Our findings may help clinicians find effective individualized treatments for unique patient groups and direct researchers to conduct further studies on the epidemiology of allergic diseases.

Introduction: In 2019, an alarming number of cases coined as e-cigarette, or vaping, product use associated lung injury (EVALI) was described in adolescents ranging from mild respiratory distress to fulminant respiratory failure. Limited data has been published on outcomes at short term follow-up. We aimed to describe pulmonary manifestations, function and radiologic findings after corticosteroid therapy in a cohort of adolescent patients. Methods: A retrospective chart review of all patients presenting to our institution between July and December 2019 with EVALI was conducted. Patients who had pulmonary follow-up were included. Spirometry was performed prior to discharge from the hospital and during outpatient follow-up. A paired t-test was used to compare serial spirometry data between visits. Results: Eight patients (6 males) were included. Two patients required intubation with mechanical ventilation, 2 required bilevel positive airway pressure (BPAP), and 3 required oxygen supplementation. All patients received glucocorticoids (3 receiving pulse dosing). Initial spirometry revealed decreased forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) with clinically and statistically significant improvement at follow-up. Diffusing capacity of the lungs for carbon monoxide (DLCO) was decreased in 2/6 patients initially and in 4/5 at follow-up. Radiographic manifestations also improved after vaping was discontinued. Conclusion: In our cohort of patients with EVALI, at short term follow up, all normalized their spirometry parameters. However, most did not normalize their DLCO on follow up, raising concern for risk of developing chronic lung disease later in life.

To the Editor, A COVID-19 epidemic started in China and then disseminated to other Asian countries before becoming a pandemic. It appears that the pandemic has so far resulted in proportionately fewer deaths in China and most Eastern Asian countries. Many reasons can explain this picture.1 One of them is the type of diet in the low mortality countries. 2This paper is the sixth of a series attempting to understand the role of diet in the differences of COVID-19 death rates between and within countries with the aim to identify potential preventive measures against COVID-19. The concept paper 2 was followed by two ecological studies comparing death rates in European countries and the consumption of vegetables or fermented foods. 3,4 We then proposed that sulforaphane from cruciferous vegetables1 and lactobacilli from fermented foods (submitted) were possibly involved in the reduction of insulin resistance in COVID-19.It is noteworthy that fermented foods are largely used in Asia.5,6 It is therefore important to check whether some commonly eaten fermented foods in these countries may explain geographic differences in COVID-19. Kimchi will be used as a model of fermented cabbage.

Background: As pregnancy is a physiological prothrombotic state, pregnant women may be at increased risk of developing coagulopathic and/or thromboembolic complications associated with COVID-19. Objectives: To investigate the occurrence of haemostatic and thrombo-embolic complications in pregnant women with COVID-19. Search Strategy: Two biomedical databases were searched between September 2019 and June 2020 for case reports and series of pregnant women with COVID-19. Additional registry cases known to the authors were included. Steps were taken to minimise duplicate patients. Selection criteria: Pregnant women with COVID-19 based either on a positive swab or high clinical suspicion e.g. symptoms and radiographic evidence. Data Collection and Analysis: Information on coagulopathy based on abnormal coagulation test results or clinical evidence of disseminated intravascular coagulation (DIC), and on arterial or venous thrombosis, were extracted using a standard form. If available, detailed laboratory results and information on maternal outcomes were analysed. Main Results: 1063 women met the inclusion criteria, of which three (0.28%) had arterial and/or venous thrombosis, seven (0.66%) had DIC, and a further three (0.28%) had coagulopathy without meeting the definition of DIC. Five hundred and thirty-seven women (56%) had been reported as having given birth and 426 (40%) as having an ongoing pregnancy. There were 17 (1.6%) maternal deaths in which DIC was reported as a factor in two. Conclusions: Our data suggests that coagulopathy and thromboembolism are both increased in pregnancies affected by COVID-19. Detection of the former may be useful in the identification of women at risk of deterioration.

Objective: To investigate the prognostic factors to developing parotid and neck metastasis in locally advanced and relapsed cutaneous squamous cell carcinoma (CSCC) of the head and neck region. Study Design: Retrospective cohort study. Setting: Single-center study enrolling consecutive patients with advanced CSCC from 2009 to 2019. Subjects and Methods: Seventy-four cases were identified. Study variables demographic data, clinical skin tumor stage, neck stage, parotid stage (P stage), surgical treatment features, and parotid, regional, and distant metastases. Survival measures: overall survival (OS) and disease-specific survival (DSS). Results: The study group included 72.9% men (median age, 67 years); 67.5% showed T2/T3 tumors, 90.5% comorbidities, 20.2% immunosuppressed, with median follow-up: 35.8 months. The most frequent skin primary were auricular and eyelid regions, 75% underwent primary resection with flap reconstruction. Parotid metastasis was present in 50%, 32.4% showing parotid extracapsular spread, multivariate analysis found OR=37.6 of positive parotid metastasis evolve into positive neck metastasis, p=0.001. Occult neck metastasis, neck metastasis, and neck extracapsular spread were observed in 13.5%, 51.3%, and 37.8%, respectively. Kaplan-Meier survival: Clinical T4 and T1, p=0.028, P1 stage: 30% and 5% survival at 5 and 10 years, P3 stage: 0%, p=0.016; OS and DSS showed negative survival for the parotid metastasis group, p=0.0283. Conclusion: Our outcomes support a surgically aggressive approach for locally advanced and relapsed CSCC, with partial parotidectomy for P0, total parotidectomy for P1-3, selective I-III neck dissection for all patients and adjuvant radiochemotherapy to appropriately treat patients with advanced CSCC of the head and neck region.

Objective: Little is known about the demographic and clinical factors associated with SARS-CoV-2 infection in pregnant women in the United States. The objective of this study was to evaluate the factors associated with SARS-CoV-2 infection in women admitted for labor and delivery, in the context of universal screening. Design: Prospective cohort study. Setting: Four Boston-area hospitals. Population: Convenience sample of all women admitted for delivery (n= 1,153). Methods: We reviewed the health records of all women admitted for delivery at the largest health system in Massachusetts between April 19-May 16, 2020. Factors evaluated for potential association with SARS-CoV-2 infection included age, BMI, race, co-morbidities, zip code, infection in a household member, number of children in the household, occupation, and insurance type. Main Outcome Measures: Risk of SARS-CoV-2 infection and associations between SARS-CoV-2 infection and clinical characteristics. Results: A total of 32 patients (2.8%, 95% confidence interval 1.9-3.9) tested positive for SARS-CoV-2 infection on admission for delivery; 24 (75.0%) of the patients who tested positive were asymptomatic. Factors associated with SARS-CoV-2 infection included: younger age, obesity, African-American or Hispanic race/ethnicity, residence in heavily affected communities, household member with known infection, essential worker occupation, and Medicaid insurance. 93.5% of patients testing positive for SARS-CoV-2 had one or more factors associated with disease acquisition. Conclusions: In this large sample of deliveries, SARS-CoV-2 infection was largely concentrated in patients with distinct demographic characteristics. Understanding factors associated with infection may inform public health efforts directed towards at risk populations and serve in counseling pregnant women.

Objective To assess background rates of adverse pregnancy outcomes before implementation of a maternal pertussis immunisation programme in the Netherlands, to put into perspective the safety concerns about such outcomes following immunisation. Design Retrospective cross-sectional study. Setting and population Dutch pregnant women and their infants who were registered in the Dutch Perinatal Registry in the 2006-2018 period. Births of ≥500g birth weight and ≥24+0w gestational age were included. Methods Annual numbers of adverse outcomes were used to calculate incidence rates per 10,000. Trends with moving-average-lines over the past 3 years were plotted, with 95% confidence interval. Main Outcome Measures Adverse outcomes at maternal and neonatal level. Results From 2006 through 2018, yearly numbers of pregnancies ranged between 158,868-175,710. Numbers of newborns ranged between 161,307-178,874, of whom 160,838-178,177 were live-born. Most outcomes were stable over time. Between 2006-2011, occurrence of labour induction increased by 68%, and postpartum hemorrhage increased by 25%. Both stabilised from 2011 onwards. Perinatal mortality up to day 7 or 28 postpartum decreased by 38% and 37%, respectively. Occurrence of low Apgar score among preterm infants born before 37+0w gestational age and among term infants increased by 19% and 27%, respectively. Conclusions Our study on background incidences showed notable increases over time in occurrence of labour induction, postpartum hemorrhage and low Apgar score, while showing a considerable decrease in overall perinatal mortality. These findings should be considered when interpreting data on adverse events occurring since Tdap vaccination was implemented.

Background: Some studies have found a slowly increasing or decreasing trend of FA. However, the trends of FA in China are unknown. To investigate the prevalence of and characteristic changes in FA in children aged <2 years across 20 years. Methods: Data from three cross-sectional surveys on FA epidemiology conducted in 1999, 2009, and 2019 were assessed, and the outcomes were compared. The skin prick test was performed in all participants; open food challenge tests were used for diagnosis confirmation. Results: The prevalences of FA in 2009 and 2019 were significantly higher than that in 1999 (3.5% in 1999, 7.7% in 2009, 11.1% in 2019, P<0.001). However, there was no significant difference in prevalence between 2009 and 2019 (P=0.086). Cow’s milk protein allergy (5.7%) replaced egg allergy (5.5%) as the most common food allergy in infants as per the results of the 2019 survey. The incidence of skin symptoms did not differ significantly over the study period (90.9% in 1999, 87.1% in 2009, and 57.9% in 2019, P>0.05), while the incidence of gastrointestinal symptoms increased significantly over time (18.2% in 1999, 12.9% in 2009, and 43.9% in 2019, P<0.05). Conclusion: The prevalence of FA in infants rapidly increased after the 1990s and gradually stabilized after 2010. Cow’s milk protein has become the most common food allergen among infants in Chongqing, China. The incidence of gastrointestinal symptoms as a manifestation of FA has increased significantly since 2010.

Background: While a parental history of asthma has been widely reported as a risk factor for childhood asthma, less is known about the impact of multigenerational family history of asthma on the occurrence of asthma in children. Methods: From 2012 to 2013, a cross-sectional study was carried out in seven Chinese cities. Participants were randomly selected from 94 middle schools, elementary schools and kindergartens. Questionnaires, from which information on asthma, environmental exposure and family members (parents, paternal grandparents and maternal grandparents) affected by asthma were obtained, were completed by the children’s parents or guardians. Two-level logistic regressions were used to assess hereditary patterns of asthma, adjusted for potential confounding factors. Mediation analysis was performed to estimate the potential mediation effect of parents on the association between grandparental asthma and offspring asthma. Results: A paternal grandfather (OR: 2.59, 95%CI: 2.14-3.13), paternal grandmother (OR: 2.40, 95%CI: 1.93-2.99), maternal grandfather (OR: 2.08, 95%CI: 1.71-2.53) and maternal grandmother (OR: 2.08, 95%CI: 1.67-2.59) with asthma were associated with childhood asthma, independent of parental asthma. Of the children who had two family members with asthma, the risk of childhood asthma was highest when both parents had asthma (OR: 15.92, 95%CI: 4.66-54.45) or when both father and paternal grandfather had asthma (OR: 11.11, 95%CI: 5.77-21.38). Parents had a small proportion of mediation effect on the association between grandparental asthma and childhood asthma. Conclusions: A family history of grandparental asthma was associated with childhood asthma and parents only partially mediate the association.

With no end in sight to the convergence of COVID-19, countries are struggling with strategies to halt the “second wave” and mitigate economic decline. Estimated to account for around half of the infections, asymptomatic transmission of SARS-CoV-2 has been hampering the containment of the virus. A positive case rate of 10% was reported by Prabhu et al. among 625 pregnant women who were universally screened for SARS-CoV-2 on the day of admission for delivery at 3 institutions in New York City, of which 80% were asymptomatic at the time of testing including pre- and post-symptomatic patients. As evidence shows that virus sheds before symptoms appear and even after their cessation, these populations may have increased the chances of COVID-19 outbreak in the hospitals. Utilization of testing results for isolation practices was not mentioned in the report, possibly given the long turnaround time for the testing platforms at the time.While the risk of nosocomial transmission is affected by clinical settings, the intimate and prolonged nature of childbirth elevates the risk of cross-infection between midwives and women. The role of nosocomial transmission has been increasingly recognized, and its severity risk may be greater than those of community-acquired infections. A recent report has suggested facilities to consider testing pregnant women for SARS-CoV-2 at the time of admission (Rasmussen SA, et al. JAMA. 2020). International Confederation of Midwives has also called for governments to prioritize testing for all pregnant women and their care providers. Identification of infectious women prior to delivery could contribute to prevention of further transmission to patients and healthcare workers. Importance should also be emphasized on evaluating contact history due to the nature of false-negative PCR results (Woloshin S, et al. NEJM. 2020).Another significance of performing testing for SARS-CoV-2 on pregnant women is for the adequate medical management of the women and the fetuses. While outcome for mothers and neonates seems generally favorable, data suggest that pregnancy can be associated with increased risk for severity, including intensive care unit admission and receipt of mechanical ventilation (Ellington S, et al., MMWR Morb Mortal Wkly Rep 2020;69:769–775). Furthermore, a recent article has raised concerns over transplacental transmission of SARS-CoV-2 to the fetus (Vivanti AJ, et al. Nat Commun. 2020;11:3572). Collection of longitudinal data is crucial to understand the effects of SARS-CoV-2 infection on maternal and neonatal outcomes. Results of large-scale prospective cohort studies, such as INTERCOVID study, are expected to add high-quality evidence on the effects of COVID-19 in pregnancy on the health of the mothers, fetuses, and newborns.Screening a maternity population under a pandemic can be a way to provide a glimpse of the distribution of the population, since capacity constraints still impede widespread testing in many countries. Recent development of faster diagnostic testing could bring improvement, but test sensitivity will remain a challenge. Fundamental preventive measures and clinical management should be continued; that is, hygiene and social distancing practices for women themselves, and careful evaluation of each mother and fetus for care providers.

Objective: To evaluate the prevalence of dysmenorrhea in adolescents and its impact on daily living. Design: A cross-sectional, questionnaire-based study Setting: Multicenter study in eight randomly selected high schools in France. Population: Randomly selected post-menarche girl pupils 15 –19 years Methods: Each girl was asked to complete a 50-item questionnaire. Main Outcome Measures: Dysmenorrhea severity was assessed with the Numerical Rating Scale (NRS) and Verbal Multidimensional Scoring System Scale (VMSS). Results: Questionnaires from 953 girls were analyzed (mean age: 16.9 years). The prevalence of dysmenorrhea was 92.9 % with 8.9 % describing their pain as severe. Impact on quality of life was significant: 43.3% of the girls reported school absences because of dysmenorrhea, 74.9% difficulties in attending classes and 77.2% difficulties in sports activities. Risk factors of severe dysmenorrhea (VMSS grade 3) in multivariate analysis were heavy menstrual bleeding (OR 2.02, 95%CI [1.12 ; 3.63] p=0.0192), early menarche (OR 0.68, 95%CI [0.57 ; 0.81] p<0.0001), chronic pelvic pain (OR 2.60, 95%CI [1.10 ; 6.11] p=0.0274), BMI (BMI<18, OR 1.94, 95%CI [1.03 ; 3.66] p=0.0335). Of the 50.4% who had consulted a physician, 45.4% had seen a general practitioner. Among the girls who had not consulted a physician, 55.1% reported that menstruation was a “woman’s burden”. Conclusion: Dysmenorrhea is highly prevalent in adolescents in France and has a real impact on daily life activities. As such, it should be treated as a public health problem with educational and information campaigns targeting the girls themselves, their families and healthcare professionals.

Background: Anaphylaxis has been increasing in developed countries but there is very little published data on the burden of anaphylaxis and the pattern of adrenaline autoinjector (AAI) prescription from Asia. Objectives: We aim to determine the incidence rates of anaphylaxis and prescription rates of AAI over the past decade in Hong Kong. Methods: Using a centralized electronic database of Hong Kong’s sole public-funded healthcare provider, we obtained and analysed all patients between 2009 and 2019 with physician-reported diagnosis of anaphylaxis. Incidence rates were calculated using population statistics as the denominator. Patients’ prescriptions on discharge were collected to determine the AAI prescription rates. Results: The overall 10-year estimated incidence rate of anaphylaxis was 3.57 per 100,000 person-years. An increasing trend over time across both pediatric and adult populations from 2009 to 2019 was found which was more marked among the pediatric population. There was an overall increasing rates of AAI prescription for patients admitted for anaphylaxis, but the overall AAI prescription rate was less than 15% and was significantly less likely to be prescribed for the adult compared to pediatric patients (36.5% vs. 89.4%, p<0.001). Conclusions: An increasing trend of anaphylaxis incidence rates over the past decade is evident in Asian populations, with a discrepantly low rate of AAI prescription, particularly in the adult patients.

EDITORIAL The average global temperatures on our planet are increasing due to rising anthropogenic greenhouse gases in the atmosphere, in particular carbon dioxide (CO2).1,2 There is an urgent need to call for action on global warming, which is resulting in extreme weather and related catastrophes.1 ,2 The Earth’s rising temperature is evidenced by warming of the oceans, melting glaciers, rising sea levels, and the diminished snow cover in the Northern Hemisphere. Climate-related factors can affect interactive atmospheric components (chemical and biological) and their interrelationship with human health.Climate change, a physics and meteorological event that affects health in the whole biosphere started to receive attention around the mid-twentieth century. Air pollution is the driving force of the Earth’s warming powered by the greenhouse effect (Figure 1). Environmental changes are occurring in frequency, intensity, type of precipitation, and extreme weather events, such as heatwaves, droughts, floods, blizzards, thunderstorms, sandstorms, and hurricanes. These are real and daunting challenges for the human and biosphere health, impacting the food and water supplies.1 ,2 Urbanization, with its high level of vehicle emissions and westernized lifestyle, is linked to the rising levels of particulate matter in the air, food supplies, soil, freshwater, and oceans. These environmental changes are correlated with the increased frequency of respiratory allergic diseases and bronchial asthma observed over recent decades in most industrialized countries and is continuously rising in developing countries.1-5This issue of Allergy focuses on the interrelationship between climate change, air pollution and human health.3-7Climate change is an important medical aspect in allergology as we are observing an increasing incidence of allergic diseases indirectly related to rising temperatures and are becoming a high socio-economic burden.1-3,8 Allergies and asthma appear to be at the front line of the sequelae of climate change along with infectious and cardiovascular diseases.1,5Cecchi et al. focus on the development and exacerbation of allergic diseases can be explained in terms of the exposome, a concept that includes all the environmental exposures from conception onwards. Multiple factors can trigger a pollen-induced respiratory allergy, such as airborne endotoxin levels and microbial composition of pollen, and these comprise a “pollen exposome”.4,9Susan Prescott has written an editorial in this issue bringing the attention to climate change and bidiversity aspects. At the time of Neil Armstrong’s lunar landing 50 years ago, Prof. Rene Dubos, a renowned microbiologist, delivered the seminal lecture “The Spaceship Earth”. He was ahead of his time and warned of an “altered immunity” driven by environmental problems and loss of biodiversity. Most of his predictions proved correct and we are now understanding at a molecular level the pathophysiological mechanisms involved in allergic diseases.8Climate change indirectly affects allergies by altering the pollen concentrations, allergenic potential, composition, migration of species and growth of new ones. Air pollution and climate change have resulted in the faster growth of allergenic plants, increasing the aeroallergen load for patients with inhalant allergy. Phenological studies indicate longer pollen seasons and emerge earlier in the year.1,4,5,8 Pollen and mold allergies are generally used to evaluate the interrelationship between air pollution and allergic respiratory diseases, such as rhinitis and asthma. Studies show that plants exhibit enhanced photosynthesis and reproductive effects and produce more pollen as a response to high atmospheric levels of CO2. 1,4,8 Pollen allergens have been demonstrated to trigger the release of pro-inflammatory and immunomodulatory mediators that accelerate the onset of allergy and the IgE-mediated sensitization. Lightning storms or wet conditions rupture the pollen grains releasing the allergenic proteins that cause asthma exacerbations in patients with pollinosis (thunderstorm-asthma).1,3,4,7,10 As a result of climate change, patients with seasonal allergic rhinoconjunctivitis and asthma have more intense symptoms and need stronger medication.1,4,8 In addition to respiratory illnesses, Fairweather et al. demonstrate the effect of environmental changes on cardiovascular, brain and mind, gastrointestinal, skin, immunologic and metabolic effects.1,3,4,7 The migration of stinging and biting insects to cooler climates has caused an increase in insect allergies in those areas.Prunicki et al. focus on the contribution of wildfires and deforestation and their contribution to global warming and immunological effects. It should be noted that in the last fifty years, half of the pluvial forests on Earth have been lost. Deforestation and forestation degradation is estimated to occur at a rate of 13 million hectares per year, mostly for agricultural purposes. Wildfires are becoming increasingly frequent, posing a serious risk to human health. The fine particulate matter (PM2.5) in wildfire smoke exacerbates asthma attacks, among other health problems. A study of 67 subjects demonstrated that those exposed to wildfire smoke had significantly higher levels of C-reactive protein and IL-1β compared with controls.6 The elevated levels of these two biomarkers are indicative of airway inflammation.Global warming and climate change need actions throughout the whole world with joined forces of all capabilities. These efforts are sometimes hampered by the unresponsiveness of governmental institutions and the general population, the lack of infrastructure and poverty. An action plan is needed to disseminate information on health-related problems associated with climate change. Patients with pollen allergies or asthma should be educated on the higher health risk during a thunderstorm or pollen season and the need for appropriate medication if staying outdoors. In collaboration with environmental organizations, physicians should take the lead to promote actions to mitigate air pollution and advocate the need to reduce global warming to protect our health.

Objective: To evaluate the relationship between adenomyosis severity and perinatal outcomes. Design: Pregnant women with adenomyosis were divided into two groups: the mild group (adenomyosis volume <500 cm3) and the severe group (adenomyosis volume ≥500 cm3). Setting: Tertiary care institution, Shanghai, China. Population: In total, 286 pregnancies complicated with adenomyosis, who attended routine prenatal check-ups between July 1, 2017, and June 30, 2019, at Shanghai First Maternity and Infant Hospital participated in the study. Methods: A total of 286 pregnant women with adenomyosis were analysed retrospectively. The three diameter lines (length, L; width, W; and thickness, T) of adenomyosis were measured by ultrasound during pregnancy. The volume of adenomyosis (V) was calculated by the formula V= L *W * T * 4 / 3 π. Pregnant women with adenomyosis were divided into a mild group (V<500 cm3) and a severe group (V≥500 cm3). Main outcome measures: The relationship between adenomyosis severity and perinatal outcomes. Results: Pregnant women in the severe group had higher preterm labour rate (18.5% versus 10.2%;odd ratio 1.991;95%CI0.969-4.090) , higher caesarean section rate (67.9% vs 49.8%; odd ratio 2.136;95%CI1.114-2.672) , and earlier gestational week at delivery (38+0 ± 2+1 versus 38+5±2+0).The new-born birth weight was significantly lower(3056.7 ± 523.8g versus 3216.9 ±546.4g) in the severe group. Severe adenomyosis didn’t increase postpartum hemorrhage significantly. Conclusion: Severe adenomyosis is related to adverse perinatal outcomes.