Changes in prevalence of anxiety and depression among COVID-19 patients during a two-year recovery period: A systematic review and meta-analysis.

OBJECTIVE: To analyze the temporal trend of anxiety and depression prevalences up to 2 years of follow-up for COVID-19 patients during the recovery period and to compare regional differences. METHODS: We performed a systematic review from PubMed, Embase, Web of Science, CNKI, Wanfang, and VIP using keywords such as "COVID-19", "anxiety", "depression", and "cohort study". Meta-analysis was performed to estimate the pooled prevalence of anxiety and depression at five follow-up time intervals. Subgroup analyses were conducted by different regions. RESULTS: 34 cohort studies were included in the meta-analyses. The pooled anxiety prevalence rates at 0-1 month, 1-3 months, 3-6 months, 6-12 months and 12-24 months were 18% (95% CI: 11% to 28%), 18% (95% CI: 12% to 28%), 22% (95% CI: 16% to 29%), 15% (95% CI: 11% to 21%), and 10% (95% CI: 0.05% to 20%), respectively, and the pooled depression prevalence rates were 22% (95%CI: 15% to 33%), 19% (95% CI: 13% to 29%), 21% (95% CI: 15% to 28%), 15% (95% CI: 11% to 20%), and 9% (95% CI: 0.4% to 21%) respectively. The prevalence of depression in Asian and non-Asian countries was statistically different at 0-1 month (χ2 = 15.248, P < 0.001) and 1-3 months (χ2 = 28.298, P < 0.001), and prevalence of anxiety was statistically different at 3-6 months (χ2 = 9.986, P = 0.002) and 6-12 months (χ2 = 7.378, P = 0.007). CONCLUSION: The prevalence of anxiety and depression in COVID-19 patients generally tends to decrease after 2 years of recovery, but may temporarily increase at 3-6 months. There are regional differences in the changes in prevalence of anxiety and depression.

IGF2BP2­dependent STIM1 inhibition protects against LPS­induced pneumonia in vitro by alleviating endoplasmic reticulum stress and the inflammatory response.

Pneumonia is a disease caused by inflammation and has high morbidity and mortality rates. Stromal interaction molecule 1 (STIM1) is involved in the regulation of inflammatory processes. However, to the best of the authors' knowledge, the role of STIM1 in pneumonia has not yet been reported. In the present study, lipopolysaccharide (LPS) was administered to A549 cells to construct a cell damage model. The expression of STIM1 in the model cells was detected by western blotting and reverse transcription-quantitative PCR. Then, STIM1 expression was inhibited and cell survival was detected by Cell Counting Kit-8 and flow cytometry. The expression of inflammatory factors was detected by enzyme-linked immunosorbent assay and endoplasmic reticulum stress (ERS)-related proteins were detected by immunofluorescence and western blotting. Subsequently, the relationship between insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) and STIM1 was verified by RNA-binding protein immunoprecipitation assay and actinomycin D treatment. Finally, the regulatory mechanism of IGF2BP2 and STIM1 in LPS-induced A549 cells was further investigated. The results of the present study demonstrated that STIM1 expression was increased in LPS-induced A549 cells and that STIM1 knockdown inhibited LPS-induced A549 cell apoptosis and alleviated LPS-induced A549 cell inflammation and ERS. In addition, IGF2BP2 enhanced the stability of STIM1 mRNA and knockdown of IGF2BP2-regulated STIM1 expression alleviated LPS-induced ERS and inflammatory responses in A549 cells. In conclusion, knockdown of IGF2BP2-regulated STIM1 improved cell damage in the LPS-induced pneumonia cell model by alleviating ERS and the inflammatory response.

Annual incidence and fatality rates of notifiable infectious diseases in southeast China from 1950 to 2022 and relationship to socioeconomic development.

Background: Over the past 70 years, China has advanced significantly in the prevention and treatment of infectious diseases while simultaneously undergoing a socioeconomic transformation, making it a useful source of data for analysing relationships between public health policy and the control of infectious diseases. Methods: We collected data on the incidence of notifiable infectious diseases and associated fatalities in Jiangsu province in southeast China from the Provincial Center for Disease Control and Prevention, Provincial Institute of Parasitic Diseases, and the Nationwide Notifiable Infectious Diseases Reporting Information System. We compared data from different historical periods using descriptive statistical methods, joinpoint regression, and correlation analysis. Results: During 1950-2022, 75 754 008 cases of 46 notifiable infectious diseases were reported in Jiangsu, with an average annual incidence was 1679.49 per 100 000 population and a fatality rate of 1.82 per 1000 persons. The incidence of classes A-B decreased (average annual percent change (AAPC) = -2.1) during the entire study period, while the incidence of class C increased (AAPC = 10.8) after 2004. The incidence of intestinal diseases (AAPC = -4.4) and vector-borne and zoonotic diseases (AAPC = -8.1) decreased rapidly, while the incidence of sexually transmitted and blood-borne diseases (AAPC = 1.8) increased. The number of medical and health institutions and the per capita gross domestic product correlated negatively with the annual incidence of diseases in classes A-B, but not with fatality rates. Conclusions: Although the annual incidence of many severe infectious diseases has decreased in Jiangsu since 1950, the incidence of sexually transmitted and blood-borne diseases increased. Socioeconomic growth and sustainable investment in health systems are associated with better control of infectious diseases.

Unveiling a New Perspective on Distinguishing Omicron Breakthrough Cases and Postimmune COVID-19-Naive Individuals: Insights from Antibody Profiles.

In the situation of mass vaccination against COVID-19, few studies have reported on the early kinetics of specific antibodies (IgG/IgM/IgA) of vaccine breakthrough cases. There is still a lack of epidemiological evidence about the value of serological indicators in the auxiliary diagnosis of COVID-19 infection, especially when the nucleic acid results were undetectable. Omicron breakthrough cases post-inactivated vaccination (n = 456) and COVID-19-naive individuals with two doses of inactivated vaccination (n = 693) were enrolled. Blood samples were collected and tested for SARS-CoV-2 antibody levels based on the magnetic chemiluminescence enzyme immunoassay. Among Omicron breakthrough cases, the serum IgG antibody level was 36.34 Sample/CutOff (S/CO) (95% confidence interval [CI], 31.89 to 40.79) in the acute phase and 88.45 S/CO (95% CI, 82.79 to 94.12) in the recovery phase. Serum IgA can be detected in the first week post-symptom onset (PSO) and showed an almost linear increase within 5 weeks PSO. Compared with those of breakthrough cases, IgG and IgA titers of the postimmune group were much lower (4.70 S/CO and 0.46 S/CO, respectively). Multivariate regression showed that serum IgG and IgA levels in Omicron breakthrough cases were mainly affected by the weeks PSO (P < 0.001). Receiver operating characteristic ROC0 curve analysis showed that the area under the curve (AUC) was 0.744 and 0.806 when the cutoff values of IgA and IgG were 1 S/CO and 15 S/CO, respectively. Omicron breakthrough infection can lead to a further increase in IgG and IgA levels relative to those of the immunized population. When nucleic acid real-time PCR was negative, we would use the kinetics of IgG and IgA levels to distinguish the breakthrough cases from the immunized population. IMPORTANCE This study fills a gap in the epidemiological evidence by investigating the value of serological indicators, particularly IgG and IgA levels, in the auxiliary diagnosis of COVID-19 infections when nucleic acid results are undetectable. The findings reveal that among Omicron breakthrough cases, both IgG and IgA antibody levels exhibit significant changes. Serum IgG levels increase during the acute phase and rise further in the recovery phase. Serum IgA can be detected as early as the first week post-symptom onset (PSO), showing a consistent linear increase within 5 weeks PSO. Furthermore, receiver operating characteristic (ROC) curve analysis demonstrates the potential of IgG and IgA cutoff values as diagnostic markers. The study's conclusion underscores the importance of monitoring IgG and IgA kinetics in distinguishing Omicron breakthrough cases from vaccinated individuals. These findings contribute to the development of more accurate diagnostic approaches and help inform public health strategies during the ongoing COVID-19 pandemic.

Dynamic characteristics of a COVID-19 outbreak in Nanjing, Jiangsu province, China.

Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage B.1.617.2 (also named the Delta variant) was declared as a variant of concern by the World Health Organization (WHO). This study aimed to describe the outbreak that occurred in Nanjing city triggered by the Delta variant through the epidemiological parameters and to understand the evolving epidemiology of the Delta variant. Methods: We collected the data of all COVID-19 cases during the outbreak from 20 July 2021 to 24 August 2021 and estimated the distribution of serial interval, basic and time-dependent reproduction numbers (R0 and Rt), and household secondary attack rate (SAR). We also analyzed the cycle threshold (Ct) values of infections. Results: A total of 235 cases have been confirmed. The mean value of serial interval was estimated to be 4.79 days with the Weibull distribution. The R0 was 3.73 [95% confidence interval (CI), 2.66-5.15] as estimated by the exponential growth (EG) method. The Rt decreased from 4.36 on 20 July 2021 to below 1 on 1 August 2021 as estimated by the Bayesian approach. We estimated the household SAR as 27.35% (95% CI, 22.04-33.39%), and the median Ct value of open reading frame 1ab (ORF1ab) genes and nucleocapsid protein (N) genes as 25.25 [interquartile range (IQR), 20.53-29.50] and 23.85 (IQR, 18.70-28.70), respectively. Conclusions: The Delta variant is more aggressive and transmissible than the original virus types, so continuous non-pharmaceutical interventions are still needed.

A dynamic model for individualized prognosis prediction in patients with avian influenza A H7N9.

Background: Avian influenza A H7N9 progresses rapidly and has a high case fatality rate. However, few models are available to predict the survival of individual patients with H7N9 infection in real-time. This study set out to construct a dynamic model for individual prognosis prediction based on multiple longitudinal measurements taken during hospitalization. Methods: The clinical and laboratory characteristics of 96 patients with H7N9 who were admitted to hospitals in Jiangsu between January 2016 and May 2017 were retrospectively investigated. A random forest model was applied to longitudinal data to select the biomarkers associated with prognostic outcome. Finally, a multivariate joint model was used to describe the time-varying effects of the biomarkers and calculate individual survival probabilities. Results: The random forest selected a set of significant biomarkers that had the lowest classification error rates in the feature selection phase, including C-reactive protein (CRP), blood urea nitrogen (BUN), procalcitonin (PCT), base excess (BE), lymphocyte count (LYMPH), white blood cell count (WBC), and creatine phosphokinase (CPK). The multivariate joint model was used to describe the effects of these biomarkers and characterize the dynamic progression of the prognosis. Combined with the covariates, the joint model displayed a good performance in discriminating survival outcomes in patients within a fixed time window of 3 days. During hospitalization, the areas under the curve were stable at 0.75. Conclusions: Our study has established a novel model that is able to identify significant indicators associated with the prognostic outcomes of patients with H7N9, characterize the time-to-event process, and predict individual-level daily survival probabilities after admission.

Influenza virus subtype/lineage-specific seasonal patterns and age-related infection risk, in Eastern China.

INTRODUCTION: Differences in seasonal pattern and age-related infection risk have been reported between Influenza type A and B, but have not been elaborated at subtype/lineage level. METHODOLOGY: All laboratory-confirmed influenza cases reported in the influenza surveillance system of Jiangsu Province, China from January 2011 to August 2019 were analyzed. Influenza seasonality was characterized using the Seasonal Decomposition method. Binary and multinomial logistic regressions were employed to calculate the odds ratios of influenza subtypes/lineages in relation to age. RESULTS: A total of 28,772 confirmed influenza cases were included. Among them, a majority (64.1%) were influenza A infections. One annual peak was observed for A (H1N1) pdm and B-Yamagata in winter months, and for B-Victoria in spring months, while biannual peaks were observed for A (H3N2) in winter and summer months. Using all ages as the reference, children younger than 5 years and adults of 25-59 years were more likely to infect with A (H1N1) pdm. Older children aged 5-14 years had significantly higher odds of infection with influenza B of both lineages, while individuals aged 15-24 years had higher odds for A (H3N2) and B-Victoria. The elderly (60 years or older) were prone to be infected with A (H3N2) and B-Yamagata. For a specific age group, their likelihood of getting infected with an influenza subtype or lineage was related to the co-circulating influenza subtype or lineage. CONCLUSIONS: Influenza viruses have divergent seasonal peak times and age-related infection risk at subtype/lineage level.

Clinical practice guidelines for the treatment of allergic rhinitis in children with traditional Chinese medicine.

Allergic rhinitis (AR) is one of the most common allergic diseases in children and it can lead to physical and mental health problems. Traditional Chinese medicine (TCM) plays an important role in understanding the phenotypes and treatment of AR. However, there are currently no normative clinical practice guidelines (CPGs) for the treatment of AR in children. The study aimed to develop an evidence-based CPG for the treatment of AR in children with TCM. Systematic literature research, expert questionnaire, and clinical evaluation after three rounds of surveys were adopted to form recommendations for treating children with AR using the Delphi method. Depending on the clinical manifestations, we finally recommended two decoctions with two Chinese patent medicines for an acute attack of AR and two decoctions for a chronic period of AR. For the acute attack of AR in children, Xinyi Qingfei decoction, Wenfei Zhiliu decoction, Xinqin granules, and Xinyi Biyan pills were suggested, whereas for the chronic period of AR, Buzhong Yiqi and Jingui Shenqi decoctions were recommended. The four external treatment methods suggested for the prevention and care of AR were body acupuncture, moxibustion, auricular point pressing, and acupoint application. The recommended levels of the suggested TCM strategies ranged from Grade B to D, indicating the weakness of the recommendations. TCM has the potential to offer new insights into phenotypes and the management of AR worldwide; however, more high-quality clinical studies are needed to improve the quality of evidence.

Epidemiology of 631 Cases of COVID-19 Identified in Jiangsu Province Between January 1st and March 20th 2020: Factors Associated with Disease Severity and Analysis of Zero Mortality.

BACKGROUND This retrospective study aimed to investigate the factors associated with disease severity and patient outcomes in 631 patients with COVID-19 who were reported to the Jiangsu Commission of Health between January 1 and March 20, 2020. MATERIAL AND METHODS We conducted an epidemiological investigation enrolling 631 patients with laboratory-confirmed COVID-19 from our clinic from January to March 2020. Patients' information was collected through a standard questionnaire. Then, we described the patients' epidemiological characteristics, analyzed risk factors associated with disease severity, and assessed causes of zero mortality. Additionally, some key technologies for epidemic prevention and control were identified. RESULTS Of the 631 patients, 8.46% (n=53) were severe cases, and no deaths were recorded (n=0). The epidemic of COVID-19 has gone through 4 stages: a sporadic phase, an exponential growth phase, a peak plateau phase, and a declining phase. The proportion of severe cases was significantly different among the 4 stages and 13 municipal prefectures (P<0.001). Factors including age >65 years old, underlying medical conditions, highest fever >39.0°C, dyspnea, and lymphocytopenia (<1.0×109/L) were early warning signs of disease severity (P<0.05). In contrast, earlier clinic visits were associated with better patient outcomes (P=0.029). Further, the viral load was a potentially useful marker associated with COVID-19 infection severity. CONCLUSIONS The study findings from the beginning of the COVID-19 epidemic in Jiangsu Province, China showed that patients who were more than 65 years of age and with comorbidities and presented with a fever of more than 39.0°C developed more severe disease. However, mortality was prevented in this initial patient population by early supportive clinical management.

Epidemiological and clinical characteristics of severe fever with thrombocytopenia syndrome bunyavirus human-to-human transmission.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) was listed as one of the most severe infectious disease by world health organization in 2017. It can mostly be transmitted by tick bite, while human-to-human transmission has occurred on multiple occasions. This study aimed to explore the epidemiological and clinical characteristics and make risk analysis of SFTS human-to-human transmission. METHODS: Descriptive and spatial methods were employed to illustrate the epidemiological and clinical characteristics of SFTS human-to-human transmission. The risk of SFTS human-to-human transmission was accessed through secondary attack rate (SAR) and basic reproductive number (R0). Logistic regression analysis was used to identify the associated risk factors. RESULTS: A total of 27 clusters of SFTS human-to-human transmission were reported in China and South Korea during 1996-2019. It mainly occurred among elder people in May, June and October in central and eastern China. The secondary cases developed milder clinical manifestation and better outcome than the index cases. The incubation period was 10.0 days (IQR:8.0-12.0), SAR was 1.72%-55.00%, and the average R0 to be 0.13 (95%CI:0.11-0.16). Being blood relatives of the index case, direct blood/bloody secretion contact and bloody droplet contact had more risk of infection (OR = 6.35(95%CI:3.26-12.37), 38.01 (95%CI,19.73-73.23), 2.27 (95%CI,1.01-5.19)). CONCLUSIONS: SFTS human-to-human transmission in China and South Korea during 1996-2019 had obvious spatio-temporal distinction. Ongoing assessment of this transmission risk is crucial for public health authorities though it continues to be low now.

Epidemiologic characteristics and influencing factors of cluster infection of COVID-19 in Jiangsu Province.

To understand the characteristics and influencing factors related to cluster infections in Jiangsu Province, China, we investigated case reports to explore transmission dynamics and influencing factors of scales of cluster infection. The effectiveness of interventions was assessed by changes in the time-dependent reproductive number (Rt). From 25th January to 29th February, Jiangsu Province reported a total of 134 clusters involving 617 cases. Household clusters accounted for 79.85% of the total. The time interval from onset to report of index cases was 8 days, which was longer than that of secondary cases (4 days) (χ2 = 22.763, P < 0.001) and had a relationship with the number of secondary cases (the correlation coefficient (r) = 0.193, P = 0.040). The average interval from onset to report was different between family cluster cases (4 days) and community cluster cases (7 days) (χ2 = 28.072, P < 0.001). The average time interval from onset to isolation of patients with secondary infection (5 days) was longer than that of patients without secondary infection (3 days) (F = 9.761, P = 0.002). Asymptomatic patients and non-familial clusters had impacts on the size of the clusters. The average reduction in the Rt value in family clusters (26.00%, 0.26 ± 0.22) was lower than that in other clusters (37.00%, 0.37 ± 0.26) (F = 4.400, P = 0.039). Early detection of asymptomatic patients and early reports of non-family clusters can effectively weaken cluster infections.

COVID-19 outbreak following a single patient exposure at an entertainment site: An epidemiological study.

We investigated an outbreak of COVID-19 infection, which was traced back to a bathing pool at an entertainment venue, to explore the epidemiology of the outbreak, understand the transmissibility of the virus and analyse the influencing factors. Contact investigation and management were conducted to identify potential cases. Epidemiological investigation was carried out to determine the epidemiological and demographic characteristics of the outbreak. We estimated the secondary attack rate (SAR), incubation time and time-dependent reproductive number (Rt ) and explored the predisposing factors for cluster infection. The incubation time was 5.4 days and the serial interval (SI) was 4.4 days, with the rate of negative-valued SIs at 24.5%. The SAR at the bathing pool (3.3%) was relatively low due to its high temperature and humidity. The SAR was higher in the colleagues' cluster (20.5%) than in the family cluster (11.8%). Super-spreaders had a longer isolation delay time (p = .004). The Rt of the cluster decreased from the highest value of 3.88 on January 27, 2020 to 1.22 on February 6. Our findings suggest that the predisposing factors of the outbreak included close contact with an infected person, airtight and crowded spaces, temperature and humidity in the space and untimely isolation of patients and quarantine of contacts at the early stage of transmission. Measures to reduce the risk of infection at these gatherings and subsequent tracking of close contacts were effective.

Comparison of alternative full and brief versions of functional status scales among older adults in China.

BACKGROUND: Brief assessments of functional status for community-dwelling older adults are needed given expanded interest in the measurement of functional decline. METHODS: As part of a 2015 prospective cohort study of older adults aged 60-89 years in Jiangsu Province, China, 1506 participants were randomly assigned to two groups; each group was administered one of two alternative 20-item versions of a scale to assess activities of daily living (ADL) and instrumental activities of daily living (IADL) drawn from multiple commonly-used scales. One version asked if they required help to perform activities (ADL-IADL-HELP-20), while the other version provided additional response options if activities could be done alone but with difficulty (ADL-IADL-DIFFICULTY-20). Item responses to both versions were compared using the binomial test for differences in proportion (with Wald 95% confidence interval [CI]). A brief 9-item scale (ADL-IADL-DIFFICULTY-9) was developed favoring items identified as difficult or requiring help by ≥4%, with low redundancy and/or residual correlations, and with significant correlations with age and other health indicators. We repeated assessment of the measurement properties of the brief scale in two subsequent samples of older adults in Hong Kong in 2016 (aged 70-79 years; n = 404) and 2017 (aged 65-82 years; n = 1854). RESULTS: Asking if an activity can be done alone but with difficulty increased the proportion of participants reporting restriction on 9 of 20 items, for which 95% CI for difference scores did not overlap with zero; the proportion with at least one limitation increased from 28.6% to 34.2% or an absolute increase of 5.6% (95% CI = 0.9-10.3%), which was a relative increase of 19.6%. The brief ADL-IADL-DIFFICULTY-9 maintained excellent internal consistency (α = 0.93) and had similar ceiling effect (68.1%), invariant item ordering (H trans = .41; medium), and correlations with age and other health measures compared with the 20-item version. The brief scale performed similarly when subsequently administered to older adults in Hong Kong. CONCLUSIONS: Asking if tasks can be done alone but with difficulty can modestly reduce ceiling effects. It's possible that the length of commonly-used scales can be reduced by over half if researchers are primarily interested in a summed indicator rather than an inventory of specific types of deficits.

Influenza activity prediction using meteorological factors in a warm temperate to subtropical transitional zone, Eastern China.

Influenza activity is subject to environmental factors. Accurate forecasting of influenza epidemics would permit timely and effective implementation of public health interventions, but it remains challenging. In this study, we aimed to develop random forest (RF) regression models including meterological factors to predict seasonal influenza activity in Jiangsu provine, China. Coefficient of determination (R2) and mean absolute percentage error (MAPE) were employed to evaluate the models' performance. Three RF models with optimum parameters were constructed to predict influenza like illness (ILI) activity, influenza A and B (Flu-A and Flu-B) positive rates in Jiangsu. The models for Flu-B and ILI presented excellent performance with MAPEs <10%. The predicted values of the Flu-A model also matched the real trend very well, although its MAPE reached to 19.49% in the test set. The lagged dependent variables were vital predictors in each model. Seasonality was more pronounced in the models for ILI and Flu-A. The modification effects of the meteorological factors and their lagged terms on the prediction accuracy differed across the three models, while temperature always played an important role. Notably, atmospheric pressure made a major contribution to ILI and Flu-B forecasting. In brief, RF models performed well in influenza activity prediction. Impacts of meteorological factors on the predictive models for influenza activity are type-specific.

Tissue-Resident Macrophages Limit Pulmonary CD8 Resident Memory T Cell Establishment.

Tissue resident memory CD8 T cells (TRM) serve as potent local sentinels and contribute significantly to protective immunity against intracellular mucosal pathogens. While the molecular and transcriptional underpinnings of TRM differentiation are emerging, how TRM establishment is regulated by other leukocytes in vivo is largely unclear. Here, we observed that expression of PPAR-γ in the myeloid compartment was a negative regulator of CD8 TRM establishment following influenza virus infection. Interestingly, myeloid deficiency of PPAR-γ resulted in selective impairment of the tissue-resident alveolar macrophage (AM) compartment during primary influenza infection, suggesting that AM are likely negative regulators of CD8 TRM differentiation. Indeed, influenza-specific CD8 TRM cell numbers were increased following early, but not late ablation of AM using the CD169-DTR model. Importantly, these findings were specific to the parenchyma of infected tissue as circulating memory T cell frequencies in lung and TCM and TEM in spleen were largely unaltered following macrophage ablation. Further, the magnitude of the effector response could not explain these observations. These data indicate local regulation of pulmonary TRM differentiation is alveolar macrophage dependent. These, findings could aid in vaccine design aimed at increasing TRM density to enhance protective immunity, or deflating their numbers in conditions where they cause overt or veiled chronic pathologies.

Avian Influenza A Viruses among Occupationally Exposed Populations, China, 2014-2016.

To determine the seroprevalence and seroconversion of avian influenza virus (AIV) antibodies in poultry workers, we conducted a seroepidemiologic study in 7 areas of China during December 2014-April 2016. We used viral isolation and reverse transcription PCR to detect AIVs in specimens from live poultry markets. We analyzed 2,124 serum samples obtained from 1,407 poultry workers by using hemagglutination inhibition and microneutralization assays. We noted seroprevalence of AIV antibodies for subtypes H9N2, H7N9, H6N1, H5N1-SC29, H5N6, H5N1-SH199, and H6N6. In serum from participants with longitudinal samples, we noted seroconversion, with >4-fold rise in titers, for H9N2, H7N9, H6N1, H5N1-SC29, H6N6, H5N6, and H5N1-SH199 subtypes. We found no evidence of H10N8 subtype. The distribution of AIV antibodies provided evidence of asymptomatic infection. We found that AIV antibody prevalence in live poultry markets correlated with increased risk for H7N9 and H9N2 infection among poultry workers.

Macrophage PPAR-γ suppresses long-term lung fibrotic sequelae following acute influenza infection.

Influenza virus causes a heterogeneous respiratory infectious disease ranging from self-limiting symptoms to non-resolving pathology in the lungs. Worldwide, seasonal influenza infections claim ~500,000 lives annually. Recent reports describe pathologic pulmonary sequelae that result in remodeling the architecture of lung parenchyma following respiratory infections. These dysfunctional recovery processes that disproportionately impact the elderly have been understudied. Macrophages are involved in tissue remodeling and are critical for survival of severe influenza infection. Here, we found intrinsic deficiency of the nuclear receptor PPAR-γ in myeloid cells delayed the resolution of pulmonary inflammation following influenza infection. Mice with myeloid cell-specific PPAR-γ deficiency subsequently presented with increased influenza-induced deposition of pulmonary collagen compared to control mice. This dysfunctional lung remodeling was progressive and sustained for at least 3 months following infection of mice with myeloid PPAR-γ deficiency. These progressive changes were accompanied by a pro-fibrotic gene signature from lung macrophages and preceded by deficiencies in activation of genes involved with damage repair. Importantly similar aberrant gene expression patterns were also found in a secondary analysis of a study where macrophages were isolated from patients with fibrotic interstitial lung disease. Quite unexpectedly, mice with PPAR-γ deficient macrophages were more resistant to bleomycin-induced weight loss whereas extracellular matrix deposition was unaffected compared to controls. Therefore PPAR-γ expression in macrophages may be a pathogen-specific limiter of organ recovery rather than a ubiquitous effector pathway in response to generic damage.

PD-1hi CD8+ resident memory T cells balance immunity and fibrotic sequelae.

CD8+ tissue-resident memory T (TRM) cells provide frontline immunity in mucosal tissues. The mechanisms regulating CD8+ TRM maintenance, heterogeneity, and protective and pathological functions are largely elusive. Here, we identify a population of CD8+ TRM cells that is maintained by major histocompatibility complex class I (MHC-I) signaling, and CD80 and CD86 costimulation after acute influenza infection. These TRM cells have both exhausted-like phenotypes and memory features and provide heterologous immunity against secondary infection. PD-L1 blockade after the resolution of primary infection promotes the rejuvenation of these exhausted-like TRM cells, restoring protective immunity at the cost of promoting postinfection inflammatory and fibrotic sequelae. Thus, PD-1 serves to limit the pathogenic capacity of exhausted-like TRM cells at the memory phase. Our data indicate that TRM cell exhaustion is the result of a tissue-specific cellular adaptation that balances fibrotic sequelae with protective immunity.

Urine metabolic profiles in paediatric asthma.

BACKGROUND AND OBJECTIVE: Asthma is a global problem and complex disease suited for metabolomic profiling. This study explored the candidate biomarkers specific to paediatric asthma and provided insights into asthmatic pathophysiology. METHODS: Children (aged 6-11 years) meeting the criteria for healthy control (n = 29), uncontrolled asthma (n = 37) or controlled asthma (n = 43) were enrolled. Gas chromatography-mass spectrometry was performed on urine samples of the patients to explore the different types of metabolite profile in paediatric asthma. Additionally, we employed a comprehensive strategy to elucidate the relationship between significant metabolites and asthma-related genes. RESULTS: We identified 51 differential metabolites mainly related to dysfunctional amino acid, carbohydrate and purine metabolism. A combination of eight candidate metabolites, including uric acid, stearic acid, threitol, acetylgalactosamine, heptadecanoic acid, aspartic acid, xanthosine and hypoxanthine (adjusted P < 0.05 and fold-change >1.5 or <0.67), showed excellent discriminatory performance for the presence of asthma and the differentiation of poor-controlled or well-controlled asthma, and area under the curve values were >0.97 across groups. Enrichment analysis based on these targets revealed that the Fc receptor, intracellular steroid hormone receptor signalling pathway, DNA damage and fibroblast proliferation were involved in inflammation, immunity and stress-related biological progression of paediatric asthma. CONCLUSION: Metabolomic analysis of patient urine combined with network-biology approaches allowed discrimination of asthma profiles and subtypes according to the metabolic patterns. The results provided insight into the potential mechanism of paediatric asthma.