Non-pharmacological interventions for asthma prevention and management across the life course: Umbrella review.

BACKGROUND: The impact of non-pharmacological interventions (NPIs) on asthma prevention and management is insufficiently examined. We aim to comprehensively evaluate and synthesize existing evidence regarding the effectiveness of various NPIs throughout the life course. METHODS: We conducted a systematic search and screening of reviews that examined the effectiveness of various NPIs on asthma prevention and control in the Cochrane Library, PubMed, Embase, and Ovid databases. Data extraction was performed by considering the type of NPIs and the life course stages of the target population. Recommendations were provided by considering the quality of review assessed using the AMSTAR2 tool and the consistency of findings across reviews. RESULTS: We identified 145 reviews and mapped the evidence on the impact of 25 subtypes of NPIs on asthma prevention and control based on five stages of life course. Reviews indicated a shift of focus and various impacts of major NPIs on asthma prevention and control across life courses, while a few types of NPIs, such as physical exercise, appeared to be beneficial in children, adolescents and adults. Consistent and high-level evidence was observed only for psychological intervention on asthma control and quality of life among adults and older adults. Potential benefit with high-level evidence was reported on certain NPIs, such as vitamin D in reducing risk of developing asthma in offsprings in the prenatal stage, digital health interventions in improving asthma control from childhood to older adulthood, and breathing exercise in improving quality of life, asthma-related symptoms and lung function in adulthood and older adulthood. CONCLUSION: This study emphasizes the significance of delivering NPIs to improve asthma prevention and management and highlights the heterogeneity regarding the impact of NPIs across life courses. High-quality research is urgently needed to further strengthen the evidence base of NPIs and tailored interventions should be considered in guideline development.

Recurrent and persistent fever after SARS-CoV-2 infection in patients with follicular lymphoma: A case series.

Although persistent or recurrent COVID-19 infection is well described in some immunosuppressed patient cohort, to date, there have been no reports of this phenomenon in the context of repeatedly negative SARS-CoV-2 testing in the upper respiratory tract. We reported six patients with follicular lymphoma who developed recurrent symptomatic COVID-19 infection. They tested persistently negative for SARS-CoV-2 on pharyngeal swabs and ultimately confirmed by bronchoalveolar lavage fluid metagenomics next-generation sequencing. All six patients presented with lymphopenia and B-cell depletion, and five of them received the anti-cluster of differentiation 20 treatment in the last year. Persistent fever was the most common symptom and bilateral ground-glass opacities were the primary pattern on chest computed tomography. A relatively long course of unnecessary and ineffective antibacterial and/or antifungal treatments was administered until the definitive diagnosis. Persistent fever subsided rapidly with nirmatrelvir/ritonavir treatment. Our case highlighted that recurrent COVID-19 infection should be suspected in immunocompromised patients with persistent fever despite negative pharyngeal swabs, and urgent bronchoalveolar lavage fluid testing is necessary. Treatment with nirmatrelvir/ritonavir appeared to be very effective in these patients.

Risk factors associated with functional decline in older hospital survivors with acute lower respiratory tract infections: a prospective cohort study.

OBJECTIVE: To evaluate the dynamics of basic activity of daily living (BADL) in older patients with acute lower respiratory tract infections (LRTIs) during acute phase and to investigate risk factors associated with decreased physical function at discharge. METHODS: We conducted a prospective cohort study of patients aged 65 years and older who were hospitalized for acute LRTIs between April 15, 2020 and January 15, 2023. All patients received geriatric assessment at admission, including emotion, cognition, frailty, physical function status and so on. The BADL was also evaluated by the Barthel Index (BI) at two weeks before admission by recall (baseline status), at admission and at discharge. Based on the BI grades at baseline and at discharge, patients were classified into two groups: ADL decline and no ADL decline. Multivariable adjusted logistic regression models were used to evaluate the risk factors of decreased physical function. RESULTS: A total of 364 older survivors with LRTIs were included in the analysis. The median age was 74 years (IQR 61.0-82.0), 231 (62.6%) were male, the median length of stay was 10 days. In the geriatric assessment, 139 patients (38.2%) were classified as frailty, 137 patients (37.6%) experienced insomnia, 60 patients (16.5%) exhibited cognitive impairments, and 37 patients (10.2%) were defined as malnutrition. Additionally, 30 patients (8.2%) dealt with emotional disorders. On average, patients were taking 3 medications, and Charlson Comorbidity Index score was 4. 72 patients (19.8%) had function decline at discharge. In the multivariable analysis, frailty status had an odds ratio of 4.25 (95% CI 1.31-19.26) for decreased physical function and cognitive impairment had an odds ratio of 2.58 (95% CI 1.27-5.19). CONCLUSIONS: About 20% older patients with LRTIs experienced functional decline at discharge. Compared to age, severity of diseases and length of stay, frailty and cognitive impairment performed better at predicting the function decline. The apply of geriatric assessment may contribute to enhance the quality of management and treatment for patients with the older with LRTIs.

Clinical manifestations of respiratory syncytial virus infection and the risk of wheezing and recurrent wheezing illness: a systematic review and meta-analysis.

BACKGROUND: Respiratory syncytial virus (RSV) infection in infants is a global health priority. We aimed to investigate the common manifestations of RSV infection by age group and human development index (HDI) level and to assess its association with the development of wheezing and recurrent wheezing illness. METHODS: We searched the literature published between January 1, 2010 and June 2, 2022 in seven databases. Outcomes included common manifestations and long-term respiratory outcomes of RSV infection in children. Random- and fixed-effect models were used to estimate the effect size and their 95% confidence intervals. Subgroup analysis was conducted by age and HDI levels. This review was registered in PROSPERO (CRD42022379401). RESULTS: The meta-analysis included 47 studies. The top five manifestations were cough (92%), nasal congestion (58%), rhinorrhea (53%), shortness of breath (50%), and dyspnea (47%). The clinical symptoms were most severe in infants. In our analysis, compared to very high and high HDI countries, fewer studies in medium HDI countries reported related manifestations, and no study in low HDI countries reported that. The RSV-infected infants were more likely to develop wheezing than the non-infected infants [odds ratio (OR), 3.12; 95% CI, 2.59-3.76] and had a higher risk of developing wheezing illnesses after recovery (OR, 2.60; 95% CI, 2.51-2.70). CONCLUSIONS: Cough and shortness of breath are common manifestations of RSV infection. More attention should be given to infants and areas with low HDI levels. The current findings confirm an association between RSV infection and wheezing or recurrent wheezing illness.

Place of death among individuals with chronic respiratory diseases in China: Trends and associated factors between 2014 and 2020.

Background: Chronic respiratory disease (CRD) is a common cause of mortality in China, but little is known about the place of death (POD) among individuals with CRD. Methods: Information about CRD-caused deaths was obtained from the National Mortality Surveillance System (NMSS) in China, covering 605 surveillance points in 31 provinces, autonomous regions, and municipalities. Both individual- and provincial-level characteristics were measured. Multilevel logistic regression models were built to evaluate correlates of hospital CRD deaths. Results: From 2014 to 2020, a total of 1,109,895 individuals who died of CRD were collected by the NMSS in China, among which home was the most common POD (82.84%), followed by medical and healthcare institutions (14.94%), nursing homes (0.72%), the way to hospitals (0.90%), and unknown places (0.59%). Being male, unmarried, having a higher level of educational attainment, and being retired personnel were associated with increased odds of hospital death. Distribution of POD differed across the provinces and municipalities with different development levels, also presenting differences between urban and rural. Demographics and individual socioeconomic status (SES) explained a proportion of 23.94% of spatial variations at the provincial level. Home deaths are the most common POD (>80%) among patients with COPD and asthma, which are the two major contributors to CRD deaths. Conclusion: Home was the leading POD among patients with CRD in China in the study period; therefore, more attention should be emphasized to the allocation of health resources and end-of-life care in the home setting to meet the increasing needs among people with CRD.

Spatial, temporal and demographic patterns in asthma mortality in China: A systematic analysis from 2014 to 2020.

Background: Asthma is an important contributor to the burden of non-communicable diseases in China. Understanding spatial, temporal, and demographic patterns in asthma mortality is relevant to the design and implementation of targeted interventions. Methods: This study collected information on asthma deaths occurring across 605 disease surveillance points (DSPs) as recorded in the population-based national mortality surveillance system (NMSS) of China. Asthma was defined according to the International Classification of Diseases, 10th Revision code J45-J46. Estimates of age-standardized mortality rates and total national asthma deaths were calculated based on yearly population data. Statistical analysis was performed to investigate the influence of various factors on asthma mortality. Results: Between 2014 and 2020, a total of 40 116 asthma deaths occurred in DSPs. Standardized asthma mortality per 100 000 people decreased from 1.79 (95% CI: 1.74-1.83) in 2014 to 1.07 (95% CI: 1.03-1.10) in 2020 in China. In 2020, the overall asthma mortality rate was higher for male patients than for female patients, and asthma mortality rates increased substantially with age. Age-standardized asthma mortality per 100,000 people exhibited significant geographic variation, ranging from 0.93 (95% CI: 0.89-0.98) in Eastern China to 1.04 (95% CI: 0.98-1.10) in Central China and 1.37 (95% CI: 1.29-1.45) in Western China in 2020. Asthma mortality in urban areas appeared to be higher than in rural areas. Socioeconomic factors, including gross domestic product per capita and density of hospital beds per 10,000 population, may be related to asthma mortality. Male asthma patients who lived in rural areas and were aged 65 years and above were generally at high risk of asthma-related mortality. Conclusions: This study found a spatial and temporal trend for a reduction in asthma deaths over seven years in China; however, there remain important sociodemographic groups that have not secured the same decrease in mortality rates. Trial registration: This was a purely observational study and thus registration was not required.

Association between ambient sulfur dioxide pollution and asthma mortality: Evidence from a nationwide analysis in China.

There is a lack of research on the effects of acute exposure to ambient sulfur dioxide (SO2) on mortality caused by asthma, especially nationwide research in China. To explore the acute effect of exposure to ambient SO2 on asthma mortality using nationwide dataset in China from 2015 to 2020 and further evaluate the associations in subgroups with different geographical and demographic characteristics. We used data from China's Disease Surveillance Points system with 29,553 asthma deaths in China during 2015-2020. The exposure variable was the daily mean concentrations of SO2 from the ChinaHighSO2 10 km × 10 km daily grid dataset. Bilinear interpolation was used to estimate each individual's exposure to air pollutants and meteorological variables. We used a time-stratified case crossover design at the individual level to analyze the exposure response relationship between short-term exposure to SO2 and asthma mortality. Stratified analyses were carried out by sex, age group, marital status, warm season and cold season, urbanicity and region. Significant associations between short-term exposure to ambient SO2 and increased asthma mortality were found in this nationwide study. The excess risk (ER) for each 10 µg/m3 increase in SO2 concentrations at lag07 was 7.78 % (95 % CI, 4.16-11.52 %). Season appeared to significantly modify the association. The associations were stronger in cold season (ER 9.78 %, 95 % CI:5.82 -13.89 %). The association remained consistent using different lag periods, adjusting for other pollutants, and in the analysis during pre-Corona Virus Disease 2019 (COVID-19) period. Our study indicates increased risk of asthma mortality with acute exposures to SO2 in Chinese population. The current study lends support for greater awareness of the harmful effect of SO2 in China and other countries with high SO2 pollution.

Extension of mepolizumab injection intervals as potential of saving costs in well controlled patients with severe eosinophilic asthma.

Background: Present guidelines recommend a life-long therapy with mepolizumab in patients suffering from severe eosinophilic asthma as several studies proved the disadvantages of treatment cessation. This study evaluated the possibility of extending the dosage intervals of mepolizumab in those patients with severe eosinophilic asthma after being well controlled. Methods: Eighteen patients diagnosed with severe eosinophilic asthma were started on treatment with mepolizumab in regular 4-week intervals. Symptom control was measured using the asthma control test (ACT) and pulmonary function test every 3 months. The amount of oral corticosteroids needed to maintain symptom control was monitored at every visit. After achieving good symptom control, defined as well controlled ACT ≥20, injection intervals were prolonged from 4 up to 6 to 8 weeks. The evaluation of this data was approved by the ethics committee. Results: ACT and pulmonary function values significantly improved after initiating therapy with mepolizumab on a regular 4-weekly injection interval. After extending the dosage intervals, both ACT and pulmonary function remained on a stable level without significant changes during the follow-up visits for 1 year. Median dosage of prednisolone declined significantly in the studied group under mepolizumab therapy and stayed on a low level during the follow-up visits with only a single patient using prednisolone after 1 year. Conclusion: In patients with fully or well controlled eosinophilic asthma treated with mepolizumab extending the dosage intervals between the injections up to 8 weeks bears the potential to save costs for the health care system.

Particulate matter pollution and asthma mortality in China: A nationwide time-stratified case-crossover study from 2015 to 2020.

BACKGROUND: A national and comprehensive evaluation is lacking on the relationship between short-term exposure to submicron particulate matter (PM1) pollution and asthma mortality. METHODS: Data was obtained from 29,553 asthma deaths from the China National Mortality Surveillance System from 2015 to 2020. We used a bilinear interpolation approach to estimate each participant's daily ambient particulate matter pollution and meteorological variables exposure based on their geocoded residential address and a 10 km × 10 km grid from China High Air Pollutants and the fifth generation of European ReAnalysis-Land reanalysis data set. The associations were estimated using a time-stratified case-crossover design and conditional logistic regressions. RESULTS: Our results revealed significant associations between short-term exposure to various particulate matter and asthma mortality. The 5-day moving average of particulate matter exposure produced the most pronounced effect. Compared to fine particulate matter (PM2.5) and inhalable particulate matter (PM10), significantly stronger effects on asthma mortality related to PM1 pollution were noted. The ERs% for asthma mortality associated with each interquartile range (IQR) increase of exposures to PM1 (IQR: 19.2 µg/m3) was 5.59% (95% CI: 2.11-9.19), which is 14% and 22% higher than that for PM2.5 (IQR: 32.0 µg/m3, 4.82% (95% CI: 1.84-7.90)) and PM10 (IQR: 52.2 µg/m3, 4.37% (95% CI: 1.16-7.69)), respectively. The estimates remained consistent in various sensitivity analyses. CONCLUSIONS: Our study provided national evidence that acute exposures to various ambient particulate matter pollution can increase mortality due to asthma in China, highlighting stronger associations with ambient PM1 than PM2.5 and PM10. China needs to adjust the current ambient air quality standards urgently and pay greater attention to the adverse health effects of PM1.

Concomitant Medication Use With Xiyanping Injection and the Risk of Suspected Allergic Reactions: A Nested Case-Control Study Based on China's National Medical Insurance Database.

Introduction: Xiyanping injection (XYP), a type of Traditional Chinese Medicine, is widely used and often applied in combination with other medications in treating bronchitis, tonsillitis, and bacillary dysentery in China. In recent years, an elevated risk of allergic reactions has been observed following XYP, but whether concomitant medication use contributes to this risk is still unknown. Objective: This study aims to investigate the association between the concomitant use of XYP and the 25 most frequently co-applied medications with suspected allergic reactions for China's patients receiving XYP. Methods: A nested case-control study was conducted using the sampling data from 2015 China's Urban Employees Basic Medical Insurance and Urban Residents Basic Medical Insurance database. Four anti-allergic marker drugs were used to evaluate suspected allergic reactions. Univariate analyses and multivariable conditional logistic regression were conducted, and results were reported as odds ratios (ORs) with a 95% confidence interval (CI). Sensitivity analyses were performed on the expanded sample by including those prescribed with anti-allergic marker drugs on the same day as XYP and then stopped XYP on the next day. Results: Out of 57,612 participants with XYP prescription, we obtained 949 matched case-control pairs. Multivariable conditional logistic regression revealed that seven concomitant medications including gentamicin [OR = 4.29; 95% CI (2.52, 7.30)], cefoperazone-sulbactam [OR = 4.26; 95% CI (1.40, 13.01)], lidocaine [OR = 2.76; 95% CI (1.79, 4.25)], aminophylline [OR = 1.73; 95% CI (1.05, 2.85)], ribavirin [OR = 1.54; 95% CI (1.13, 2.10)], potassium chloride [OR = 1.45; 95% CI (1.10, 1.91)], and vitamin C [OR = 1.32; 95% CI (1.03, 1.70)] were associated with increased risk, while cefathiamidine [OR = 0.29; 95% CI (0.16, 0.51)] was associated with reduced risk. Sensitivity analysis on 2,438 matched pairs revealed similar findings. Conclusion: Increased risks for suspected allergic reactions were found for the concomitant use of XYP with seven medications. Our data suggest that gentamicin, cefoperazone-sulbactam, lidocaine, and ribavirin should be applied with precautions for patients receiving XYP, and further studies on drug interactions and allergy mechanisms are warranted.

Peripheral Blood Microbiome Analysis via Noninvasive Prenatal Testing Reveals the Complexity of Circulating Microbial Cell-Free DNA.

While circulating cell-free DNA (cfDNA) is becoming a powerful marker for noninvasive identification of infectious pathogens in liquid biopsy specimens, a microbial cfDNA baseline in healthy individuals is urgently needed for the proper interpretation of microbial cfDNA sequencing results in clinical metagenomics. Because noninvasive prenatal testing (NIPT) shares many similarities with the sequencing protocol of metagenomics, we utilized the standard low-pass whole-genome-sequencing-based NIPT to establish a microbial cfDNA baseline in healthy people. Sequencing data from a total of 107,763 peripheral blood samples of healthy pregnant women undergoing NIPT screening were retrospectively collected and reanalyzed for microbiome DNA screening. It was found that more than 95% of exogenous cfDNA was from bacteria, 3% from eukaryotes, and 0.4% from viruses, indicating the gut/environment origins of many microorganisms. Overall and regional abundance patterns were well illustrated, with huge regional diversity and complexity, and unique interspecies and symbiotic relationships were observed for TORCH organisms (Toxoplasma gondii, others [Treponema pallidum {causing syphilis}, hepatitis B virus {HBV}, and human parvovirus B19 {HPV-B19}], rubella virus, cytomegalovirus [CMV], and herpes simplex virus [HSV]) and another common virus, Epstein-Barr virus (EBV). To sum up, our study revealed the complexity of the baseline circulating microbial cfDNA and showed that microbial cfDNA sequencing results need to be interpreted in a more comprehensive manner. IMPORTANCE While circulating cell-free DNA (cfDNA) has been becoming a powerful marker for noninvasive identification of infectious pathogens in liquid biopsy specimens, a baseline for microbial cfDNA in healthy individuals is urgently needed for the proper interpretation of microbial cfDNA sequencing results in clinical metagenomics. Standard low-pass whole-genome-sequencing-based NIPT shares many similarities with the sequencing protocol for metagenomics and could provide a microbial cfDNA baseline in healthy people; thus, a reference cfDNA data set of the human microbiome was established with sequencing data from a total of 107,763 peripheral blood samples of healthy pregnant women undergoing NIPT screening. Our study revealed the complexity of circulating microbial cfDNA and indicated that microbial cfDNA sequencing results need to be interpreted in a more comprehensive manner, especially with regard to geographic patterns and coexistence networks.

Clinical features and risk factors of severely and critically ill patients with COVID-19.

BACKGROUND: As of June 1, 2020, over 370000 coronavirus disease 2019 (COVID-19) deaths have been reported to the World Health Organization. However, the risk factors for patients with moderate-to-severe or severe-to-critical COVID-19 remain unclear. AIM: To explore the characteristics and predictive markers of severely and critically ill patients with COVID-19. METHODS: A retrospective study was conducted at the B11 Zhongfaxincheng campus and E1-3 Guanggu campus of Tongji Hospital affiliated with Huazhong University of Science and Technology in Wuhan. Patients with COVID-19 admitted from 1st February 2020 to 8th March 2020 were enrolled and categorized into 3 groups: The moderate group, severe group and critically ill group. Epidemiological data, demographic data, clinical symptoms and outcomes, complications, laboratory tests and radiographic examinations were collected retrospectively from the hospital information system and then compared between groups. RESULTS: A total of 126 patients were enrolled. There were 59 in the moderate group, 49 in the severe group, and 18 in the critically ill group. Multivariate logistic regression analysis showed that age [odd ratio (OR) = 1.055, 95% (confidence interval) CI: 1.099-1.104], elevated neutrophil-to-lymphocyte ratios (OR = 4.019, 95%CI: 1.045-15.467) and elevated high-sensitivity cardiac troponin I (OR = 10.126, 95%CI: 1.088 -94.247) were high-risk factors. CONCLUSION: The following indicators can help clinicians identify patients with severe COVID-19 at an early stage: age, an elevated neutrophil-to-lymphocyte ratio and high sensitivity cardiac troponin I.

Factors Predicting Progression to Severe COVID-19: A Competing Risk Survival Analysis of 1753 Patients in Community Isolation in Wuhan, China.

Most studies of coronavirus disease 2019 (COVID-19) progression have focused on the transfer of patients within secondary or tertiary care hospitals from regular wards to intensive care units. Little is known about the risk factors predicting the progression to severe COVID-19 among patients in community isolation, who are either asymptomatic or suffer from only mild to moderate symptoms. Using a multivariable competing risk survival analysis, we identify several important predictors of progression to severe COVID-19-rather than to recovery-among patients in the largest community isolation center in Wuhan, China from 6 February 2020 (when the center opened) to 9 March 2020 (when it closed). All patients in community isolation in Wuhan were either asymptomatic or suffered from mild to moderate COVID-19 symptoms. We performed competing risk survival analysis on time-to-event data from a cohort study of all COVID-19 patients (n = 1753) in the isolation center. The potential predictors we investigated were the routine patient data collected upon admission to the isolation center: age, sex, respiratory symptoms, gastrointestinal symptoms, general symptoms, and computed tomography (CT) scan signs. The main outcomes were time to severe COVID-19 or recovery. The factors predicting progression to severe COVID-19 were: male sex (hazard ratio (HR) = 1.29, 95% confidence interval (CI) 1.04-1.58, p = 0.018), young and old age, dyspnea (HR = 1.58, 95% CI 1.24-2.01, p < 0.001), and CT signs of ground-glass opacity (HR = 1.39, 95% CI 1.04-1.86, p = 0.024) and infiltrating shadows (HR = 1.84, 95% CI 1.22-2.78, p = 0.004). The risk of progression was found to be lower among patients with nausea or vomiting (HR = 0.53, 95% CI 0.30-0.96, p = 0.036) and headaches (HR = 0.54, 95% CI 0.29-0.99, p = 0.046). Our results suggest that several factors that can be easily measured even in resource-poor settings (dyspnea, sex, and age) can be used to identify mild COVID-19 patients who are at increased risk of disease progression. Looking for CT signs of ground-glass opacity and infiltrating shadows may be an affordable option to support triage decisions in resource-rich settings. Common and unspecific symptoms (headaches, nausea, and vomiting) are likely to have led to the identification and subsequent community isolation of COVID-19 patients who were relatively unlikely to deteriorate. Future public health and clinical guidelines should build on this evidence to improve the screening, triage, and monitoring of COVID-19 patients who are asymtomatic or suffer from mild to moderate symptoms.

Characteristics of peripheral white blood cells in COVID-19 patients revealed by a retrospective cohort study.

BACKGROUND: Peripheral hematological changes in severe COVID-19 patients may reflect the immune response during SARS-CoV-2 infection. Characteristics of peripheral white blood cells as early signals were needed to be investigated for clarifying its associations with the fatal outcomes in COVID-19 patients. METHODS: A retrospective cohort study was performed and the hospitalized COVID-19 patients were recruited in wards of Sino-French New City Branch of Tongji Hospital in Wuhan, Hubei province, China. Characteristics of peripheral white blood cells in survivors and non-survivors were analyzed. Comparison among patients with different level of eosinophils was performed. RESULTS: Of 198 patients included in this study, 185 were discharged and 13 died. Levels of eosinophils, lymphocytes and basophils in non-survivors were significantly lower than those in survivors. Death rate in low eosinophils group was higher and no patient died in normal eosinophils group (16.7% vs 0, P < 0.001). The proportion of patients in low eosinophils group who used glucocorticoids was higher than in normal eosinophils group, but glucocorticoids usage was not an indicator for death in subgroup analysis in low eosinophils patients. Moreover, positive correlation was found between the counts of lymphocytes and eosinophils in patients with glucocorticoids use but not in patients without the treatment. CONCLUSIONS: Hematological changes differed between survivors and non-survivors with COVID-19. Lymphopenia and eosinopenia could be predictors for poor prognosis of COVID-19 patients. Initial counts of eosinophils may guide us in usage of glucocorticoids for COVID-19 treatment.

Expert consensus on the use of omalizumab in chronic urticaria in China.

Chronic urticaria (CU) is a debilitating skin disease that lasts for more than 6 weeks with wheals and/or angioedema, including chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU). In China, the prevalence of this disease is high, more than 1%, and on the rise. CU has a major impact on the quality of life (QoL) of patients who frequently experience sleep disturbance, depression, and anxiety. Nearly one-third of patients with CSU, in China, are resistant to second-generation H1-antihistamines (sgAHs), even at a fourfold dose (second line; off-label). Omalizumab is approved for the treatment of CSU treatment in Europe and shows remarkable efficacy and safety. In China, regulatory approval for the use of omalizumab is pending, and its use in clinical practice varies widely. Consensus on omalizumab CU treatment in China is urgently needed. The aim of this article is to propose a practical omalizumab treatment algorithm for the management of antihistamine-resistant CSU and CIndU in adults and special population including children and adolescents, and pregnant or breast feeding women, to guide daily clinical practice in China. In the development of this consensus, an expert group including mainly dermatologists, allergists, but also pulmonologists, ENTs, immunologists, and pediatricians in Allergic Disease Prevention and Control Committee, Chinese Preventive Medicine Association, reviewed the existing evidence and developed consensus on the use of omalizumab in CU patients from China. The goal of this consensus is to assist clinicians in making rational decisions in the management of refractory CU with omalizumab. The key clinical questions covered by the treatment algorithm are: 1) Omalizumab treatment routine strategy in both CSU and CIndU patients; 2) Recommended dose and treatment duration for different age stratification; 3) Treatment duration for CU patients with other allergic comorbidities; 4) Recommendation on omalizumab stopping strategy.

Clinical features in pulmonary tuberculosis patients combined with diabetes mellitus in China: An observational study.

BACKGROUND: Consideration of the huge burden both of tuberculosis (TB) and diabetes mellitus (DM) in China as a major public health issue, research focused on the relationship between DM and TB was needed. METHODS: An observational study was conducted (2015-2018) in regional representative TB and lung disease hospitals in China. All the adult patients newly diagnosed of pulmonary TB were consecutively recruited in this study. RESULTS: A total of 1417 patients newly diagnosed pulmonary TB was recruited in this research, 312 (22.02%) of them had the history of type 2 DM. Majority of patients were with fatigue, loss of weight and mild anaemia in TB-DM group compared with TB-NDM group (58.3% vs 47.5%, p = .001; 8.21 ± 6.2 vs 5.74 ± 4.0 kg, p < .001, 88.9% vs 77.6% p = .021). TB-DM patients were with higher the proportion of TB severity score ≥3, compared with TB-NDM patients, but the distributions of drug susceptibility testing (DST) analysis were not significantly different between the two groups of patients. Remarkably, the sign of central shadow of pulmonary lobe distribution and cavity in TB-DM group presented significantly higher rate than it in TB-NDM group. Multivariable logistic regression showed that high uric acid level was an independent risk factor for thick wall cavity in TB-DM patients (OR 2.81, 95% CI 1.24-6.40), haemoptysis (OR 2.43, 95% CI 1.10-5.38) and chest pain (OR 5.22, 95% CI 1.38-19.70) were significantly associated with thick wall cavity. CONCLUSIONS: The clinical features of TB-DM patients are associated with cavities in CT scan, rather than DST results. It can help us recognition confounding variables, also may influence the treatment strategy and outcomes in TB-DM patients.

Clinical characteristics and outcome of influenza virus infection among adults hospitalized with severe COVID-19: a retrospective cohort study from Wuhan, China.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that rapidly spreads worldwide and co-infection of COVID-19 and influenza may occur in some cases. We aimed to describe clinical features and outcomes of severe COVID-19 patients with co-infection of influenza virus. METHODS: Retrospective cohort study was performed and a total of 140 patients with severe COVID-19 were enrolled in designated wards of Sino-French New City Branch of Tongji Hospital between Feb 8th and March 15th in Wuhan city, Hubei province, China. The demographic, clinical features, laboratory indices, treatment and outcomes of these patients were collected. RESULTS: Of 140 severe COVID-19 hospitalized patients, including 73 patients (52.14%) with median age 62 years were influenza virus IgM-positive and 67 patients (47.86%) with median age 66 years were influenza virus IgM-negative. 76 (54.4%) of severe COVID-19 patients were males. Chronic comorbidities consisting mainly of hypertension (45.3%), diabetes (15.8%), chronic respiratory disease (7.2%), cardiovascular disease (5.8%), malignancy (4.3%) and chronic kidney disease (2.2%). Clinical features, including fever (≥38 °C), chill, cough, chest pain, dyspnea, diarrhea and fatigue or myalgia were collected. Fatigue or myalgia was less found in COVID-19 patients with IgM-positive (33.3% vs 50/7%, P = 0.0375). Higher proportion of prolonged activated partial thromboplastin time (APTT) > 42 s was observed in COVID-19 patients with influenza virus IgM-negative (43.8% vs 23.6%, P = 0.0127). Severe COVID-19 Patients with influenza virus IgM positive have a higher cumulative survivor rate than that of patients with influenza virus IgM negative (Log-rank P = 0.0308). Considering age is a potential confounding variable, difference in age was adjusted between different influenza virus IgM status groups, the HR was 0.29 (95% CI, 0.081-1.100). Similarly, difference in gender was adjusted as above, the HR was 0.262 (95% CI, 0.072-0.952) in the COX regression model. CONCLUSIONS: Influenza virus IgM positive may be associated with decreasing in-hospital death.

Seroprevalence and humoral immune durability of anti-SARS-CoV-2 antibodies in Wuhan, China: a longitudinal, population-level, cross-sectional study.

BACKGROUND: Wuhan was the epicentre of the COVID-19 outbreak in China. We aimed to determine the seroprevalence and kinetics of anti-SARS-CoV-2 antibodies at population level in Wuhan to inform the development of vaccination strategies. METHODS: In this longitudinal cross-sectional study, we used a multistage, population-stratified, cluster random sampling method to systematically select 100 communities from the 13 districts of Wuhan. Households were systematically selected from each community and all family members were invited to community health-care centres to participate. Eligible individuals were those who had lived in Wuhan for at least 14 days since Dec 1, 2019. All eligible participants who consented to participate completed a standardised electronic questionnaire of demographic and clinical questions and self-reported any symptoms associated with COVID-19 or previous diagnosis of COVID-19. A venous blood sample was taken for immunological testing on April 14-15, 2020. Blood samples were tested for the presence of pan-immunoglobulins, IgM, IgA, and IgG antibodies against SARS-CoV-2 nucleocapsid protein and neutralising antibodies were assessed. We did two successive follow-ups between June 11 and June 13, and between Oct 9 and Dec 5, 2020, at which blood samples were taken. FINDINGS: Of 4600 households randomly selected, 3599 families (78·2%) with 9702 individuals attended the baseline visit. 9542 individuals from 3556 families had sufficient samples for analyses. 532 (5·6%) of 9542 participants were positive for pan-immunoglobulins against SARS-CoV-2, with a baseline adjusted seroprevalence of 6·92% (95% CI 6·41-7·43) in the population. 437 (82·1%) of 532 participants who were positive for pan-immunoglobulins were asymptomatic. 69 (13·0%) of 532 individuals were positive for IgM antibodies, 84 (15·8%) were positive for IgA antibodies, 532 (100%) were positive for IgG antibodies, and 212 (39·8%) were positive for neutralising antibodies at baseline. The proportion of individuals who were positive for pan-immunoglobulins who had neutralising antibodies in April remained stable for the two follow-up visits (162 [44·6%] of 363 in June, 2020, and 187 [41·2%] of 454 in October-December, 2020). On the basis of data from 335 individuals who attended all three follow-up visits and who were positive for pan-immunoglobulins, neutralising antibody levels did not significantly decrease over the study period (median 1/5·6 [IQR 1/2·0 to 1/14·0] at baseline vs 1/5·6 [1/4·0 to 1/11·2] at first follow-up [p=1·0] and 1/6·3 [1/2·0 to 1/12·6] at second follow-up [p=0·29]). However, neutralising antibody titres were lower in asymptomatic individuals than in confirmed cases and symptomatic individuals. Although titres of IgG decreased over time, the proportion of individuals who had IgG antibodies did not decrease substantially (from 30 [100%] of 30 at baseline to 26 [89·7%] of 29 at second follow-up among confirmed cases, 65 [100%] of 65 at baseline to 58 [92·1%] of 63 at second follow-up among symptomatic individuals, and 437 [100%] of 437 at baseline to 329 [90·9%] of 362 at second follow-up among asymptomatic individuals). INTERPRETATION: 6·92% of a cross-sectional sample of the population of Wuhan developed antibodies against SARS-CoV-2, with 39·8% of this population seroconverting to have neutralising antibodies. Our durability data on humoral responses indicate that mass vaccination is needed to effect herd protection to prevent the resurgence of the epidemic. FUNDING: Chinese Academy of Medical Sciences & Peking Union Medical College, National Natural Science Foundation, and Chinese Ministry of Science and Technology. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

The dynamic changes of serum IgM and IgG against SARS-CoV-2 in patients with COVID-19.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a worldwide pandemic since it emerged in December 2019. Previous studies have reported rapid antibody response to SARS-CoV-2 in the first 2 to 3 weeks after symptom onset. Here, we retrospectively described the dynamic changes of serum immunoglobulin M (IgM) and IgG specifically against SARS-CoV-2 in later weeks (mainly 4-10 weeks) in 97 hospitalized patients with COVID-19. We observed that serum IgM and IgG, especially in patients with moderate-to-high levels, declined significantly between week 4 to 10 after illness onset. Notably, IgG levels in high percentage of patients (77.5%, 31 of 40) rapidly declined by half, from 212.5 (range, 163.7-420.3) to 96.3 (range, 75.0-133.4) AU/mL, within 1 to 2 weeks in the second month and then sustained at around 100 AU/mL until discharge from hospital. Significant reduction of IgM was also observed as SARS-CoV-2 nucleic acid turned negative (P = .002). In the recovery stage, serum IgG declined significantly (early vs late recovery stage, n = 16, P = .003) with a median reduction of 50.0% (range, 3.7%-77.0%). Our results suggested that the decline of IgM may be an indicator of virus clearance and recovered patients may have a robust immunity against reinfection within at least 3 months after illness onset. Yet, the rapid reduction of IgG by half rises serious concerns on the robustness and sustainability of the humoral immune response in the period after discharge, which is crucial for immunity strategy and developing a vaccine.