6-month consequences of COVID-19 in patients discharged from hospital: a cohort study.

BACKGROUND: The long-term health consequences of COVID-19 remain largely unclear. The aim of this study was to describe the long-term health consequences of patients with COVID-19 who have been discharged from hospital and investigate the associated risk factors, in particular disease severity. METHODS: We did an ambidirectional cohort study of patients with confirmed COVID-19 who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7 and May 29, 2020. Patients who died before follow-up; patients for whom follow-up would be difficult because of psychotic disorders, dementia, or readmission to hospital; those who were unable to move freely due to concomitant osteoarthropathy or immobile before or after discharge due to diseases such as stroke or pulmonary embolism; those who declined to participate; those who could not be contacted; and those living outside of Wuhan or in nursing or welfare homes were all excluded. All patients were interviewed with a series of questionnaires for evaluation of symptoms and health-related quality of life, underwent physical examinations and a 6-min walking test, and received blood tests. A stratified sampling procedure was used to sample patients according to their highest seven-category scale during their hospital stay as 3, 4, and 5-6, to receive pulmonary function test, high resolution CT of the chest, and ultrasonography. Enrolled patients who had participated in the Lopinavir Trial for Suppression of SARS-CoV-2 in China received SARS-CoV-2 antibody tests. Multivariable adjusted linear or logistic regression models were used to evaluate the association between disease severity and long-term health consequences. FINDINGS: In total, 1733 of 2469 discharged patients with COVID-19 were enrolled after 736 were excluded. Patients had a median age of 57·0 years (IQR 47·0-65·0) and 897 (52%) were male and 836 (48%) were female. The follow-up study was done from June 16 to Sept 3, 2020, and the median follow-up time after symptom onset was 186·0 days (175·0-199·0). Fatigue or muscle weakness (52%, 855 of 1654) and sleep difficulties (26%, 437 of 1655) were the most common symptoms. Anxiety or depression was reported among 23% (367 of 1616) of patients. The proportions of 6-min walking distance less than the lower limit of the normal range were 17% for those at severity scale 3, 13% for severity scale 4, and 28% for severity scale 5-6. The corresponding proportions of patients with diffusion impairment were 22% for severity scale 3, 29% for scale 4, and 56% for scale 5-6, and median CT scores were 3·0 (IQR 2·0-5·0) for severity scale 3, 4·0 (3·0-5·0) for scale 4, and 5·0 (4·0-6·0) for scale 5-6. After multivariable adjustment, patients showed an odds ratio (OR) of 1·61 (95% CI 0·80-3·25) for scale 4 versus scale 3 and 4·60 (1·85-11·48) for scale 5-6 versus scale 3 for diffusion impairment; OR 0·88 (0·66-1·17) for scale 4 versus scale 3 and OR 1·76 (1·05-2·96) for scale 5-6 versus scale 3 for anxiety or depression, and OR 0·87 (0·68-1·11) for scale 4 versus scale 3 and 2·75 (1·61-4·69) for scale 5-6 versus scale 3 for fatigue or muscle weakness. Of 94 patients with blood antibodies tested at follow-up, the seropositivity (96·2% vs 58·5%) and median titres (19·0 vs 10·0) of the neutralising antibodies were significantly lower compared with at the acute phase. 107 of 822 participants without acute kidney injury and with an estimated glomerular filtration rate (eGFR) of 90 mL/min per 1·73 m2 or more at acute phase had eGFR less than 90 mL/min per 1·73 m2 at follow-up. INTERPRETATION: At 6 months after acute infection, COVID-19 survivors were mainly troubled with fatigue or muscle weakness, sleep difficulties, and anxiety or depression. Patients who were more severely ill during their hospital stay had more severe impaired pulmonary diffusion capacities and abnormal chest imaging manifestations, and are the main target population for intervention of long-term recovery. FUNDING: National Natural Science Foundation of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, and Peking Union Medical College Foundation.

Risk factors associated with indoor transmission during home quarantine of COVID-19 patients.

Purpose: The study aimed to identify potential risk factors for family transmission and to provide precautionary guidelines for the general public during novel Coronavirus disease 2019 (COVID-19) waves. Methods: A retrospective cohort study with numerous COVID-19 patients recruited was conducted in Shanghai. Epidemiological data including transmission details, demographics, vaccination status, symptoms, comorbidities, antigen test, living environment, residential ventilation, disinfection and medical treatment of each participant were collected and risk factors for family transmission were determined. Results: A total of 2,334 COVID-19 patients participated. Compared with non-cohabitation infected patients, cohabitated ones were younger (p = 0.019), more commonly unvaccinated (p = 0.048) or exposed to infections (p < 0.001), and had higher rates of symptoms (p = 0.003) or shared living room (p < 0.001). Risk factors analysis showed that the 2019-nCov antigen positive (OR = 1.86, 95%CI 1.40-2.48, p < 0.001), symptoms development (OR = 1.86, 95%CI 1.34-2.58, p < 0.001), direct contact exposure (OR = 1.47, 95%CI 1.09-1.96, p = 0.010) were independent risk factors for the cohabitant transmission of COVID-19, and a separate room with a separate toilet could reduce the risk of family transmission (OR = 0.62, 95%CI 0.41-0.92, p = 0.018). Conclusion: Patients showing negative 2019-nCov antigen tests, being asymptomatic, living in a separate room with a separate toilet, or actively avoiding direct contact with cohabitants were at low risk of family transmission, and the study recommended that avoiding direct contact and residential disinfection could reduce the risk of all cohabitants within the same house being infected with COVID-19.

Pathogenicity, tissue tropism and potential vertical transmission of SARSr-CoV-2 in Malayan pangolins.

Malayan pangolin SARS-CoV-2-related coronavirus (SARSr-CoV-2) is closely related to SARS-CoV-2. However, little is known about its pathogenicity in pangolins. Using CT scans we show that SARSr-CoV-2 positive Malayan pangolins are characterized by bilateral ground-glass opacities in lungs in a similar manner to COVID-19 patients. Histological examination and blood gas tests are indicative of dyspnea. SARSr-CoV-2 infected multiple organs in pangolins, with the lungs the major target, and histological expression data revealed that ACE2 and TMPRSS2 were co-expressed with viral RNA. Transcriptome analysis indicated that virus-positive pangolins were likely to have inadequate interferon responses, with relative greater cytokine and chemokine activity in the lung and spleen. Notably, both viral RNA and viral proteins were detected in three pangolin fetuses, providing initial evidence for vertical virus transmission. In sum, our study outlines the biological framework of SARSr-CoV-2 in pangolins, revealing striking similarities to COVID-19 in humans.

Early-stage predictors of deterioration among 3145 nonsevere SARS-CoV-2-infected people community-isolated in Wuhan, China: A combination of machine learning algorithms and competing risk survival analyses.

OBJECTIVE: To determine which early-stage variables best predicted the deterioration of coronavirus disease 2019 (COVID-19) among community-isolated people infected with severe acute respiratory syndrome coronavirus 2 and to test the performance of prediction using only inexpensive-to-measure variables. METHODS: Medical records of 3145 people isolated in two Fangcang shelter hospitals (large-scale community isolation centers) from February to March 2020 were accessed. Two complementary methods-machine learning algorithms and competing risk survival analyses-were used to test potential predictors, including age, gender, severity upon admission, symptoms (general symptoms, respiratory symptoms, and gastrointestinal symptoms), computed tomography (CT) signs, and comorbid chronic diseases. All variables were measured upon (or shortly after) admission. The outcome was deterioration versus recovery of COVID-19. RESULTS: More than a quarter of the 3145 people did not present any symptoms, while one-third ended isolation due to deterioration. Machine learning models identified moderate severity upon admission, old age, and CT ground-glass opacity as the most important predictors of deterioration. Removing CT signs did not degrade the performance of models. Competing risk models identified age ≥ 35 years, male gender, moderate severity upon admission, cough, expectoration, CT patchy opacity, CT consolidation, comorbid diabetes, and comorbid cardiovascular or cerebrovascular diseases as significant predictors of deterioration, while a stuffy or runny nose as a predictor of recovery. CONCLUSIONS: Early-stage prediction of COVID-19 deterioration can be made with inexpensive-to-measure variables, such as demographic characteristics, severity upon admission, observable symptoms, and self-reported comorbid diseases, among asymptomatic people and mildly to moderately symptomatic patients.

Lockdown in Chinese university dormitories: Significant increase in negative feelings and time perception distortion.

The COVID-19 pandemic has led to a global crisis resulting in lockdowns worldwide. Studies found that these could amplify negative affects predictive of disturbances in time perception. However, all existing studies on this topic concentrated on the general population during a lockdown at home. There was no research on university students living in dormitories. This study fills a gap in the literature by investigating the affective states and awareness of the passage of time of Chinese university students during an exceptional dormitory lockdown. Using a snowball sampling approach, this web-based study recruited 225 volunteers (136 girls, 17-27 years old) during a dormitory lockdown. The online survey consisted of questions on demographic information, affective states (the Chinese version of the depression anxiety stress scales-21 (DASS-21) on depression, anxiety, and stress), and sense of the passage of time (the translated version of the assessment of passage of time over daily, weekly and yearly periods). The researchers shared the questionnaire link via the social media application WeChat. The study applied descriptive statistics and column charts to represent students' affective states and sense of the passage of time under extreme conditions and Pearson's correlation analysis to examine the impact of affective states on their sense of time. The study's results indicate that the dormitory lockdown caused a significant increase in all depression, anxiety, and stress categories of the DASS-21, as well as a distortion of the sense of time passing. However, the direction of the distortion differed from that in previous studies. Moreover, a Pearson correlation analysis showed that none of the three negative affects could be associated with students' sense of time. The findings of this study indicate an increased vulnerability of students due to the lockdown. Their emotions were strongly affected, requiring particular interventions to preserve their mental well-being. In addition, they showed a different distortion direction of time passage. Finally, they differed in the correlations between negative affect and the sense of passage of time compared to the general population in lockdown at home. This shows a need to investigate the impact of psychological states on students' routines and quality of life in emergencies. This study's scope should be expanded by incorporating additional factors pertaining to the passage of time and by integrating cross-cultural comparisons.

An ultra-sensitive one-pot RNA-templated DNA ligation rolling circle amplification-assisted CRISPR/Cas12a detector assay for rapid detection of SARS-CoV-2

Rapid, sensitive, and one-pot diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays an extremely important role in point-of-care testing (POCT). Herein, we report an ultra-sensitive and rapid one-pot enzyme-catalyzed rolling circle amplification-assisted CRISPR/FnCas12a assay, termed OPERATOR. OPERATOR employs a single well-designed single-strand padlock DNA, containing a protospacer adjacent motif (PAM) site and a sequence complementary to the target RNA which procedure converts and amplifies genomic RNA to DNA by RNA-templated DNA ligation and multiply-primed rolling circle amplification (MRCA). The MRCA amplicon of single-stranded DNA is cleaved by the FnCas12a/crRNA complex and detected via a fluorescence reader or lateral flow strip. OPERATOR presents outstanding advantages including ultra-sensitivity (1.625 copies per reaction), high specificity (100%), rapid reaction speed (∼30 min), easy operation, low cost, and on-spot visualization. Furthermore, we established a POCT platform by combining OPERATOR with rapid RNA release and a lateral flow strip without professional equipment. The high performance of OPERATOR in SARS-CoV-2 tests was confirmed using both reference materials and clinical samples, and the results suggest that is readily adaptable for point-of-care testing of other RNA viruses.

An ultra-sensitive one-pot RNA-templated DNA ligation rolling circle amplification-assisted CRISPR/Cas12a detector assay for rapid detection of SARS-CoV-2.

Rapid, sensitive, and one-pot diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays an extremely important role in point-of-care testing (POCT). Herein, we report an ultra-sensitive and rapid one-pot enzyme-catalyzed rolling circle amplification-assisted CRISPR/FnCas12a assay, termed OPERATOR. OPERATOR employs a single well-designed single-strand padlock DNA, containing a protospacer adjacent motif (PAM) site and a sequence complementary to the target RNA which procedure converts and amplifies genomic RNA to DNA by RNA-templated DNA ligation and multiply-primed rolling circle amplification (MRCA). The MRCA amplicon of single-stranded DNA is cleaved by the FnCas12a/crRNA complex and detected via a fluorescence reader or lateral flow strip. OPERATOR presents outstanding advantages including ultra-sensitivity (1.625 copies per reaction), high specificity (100%), rapid reaction speed (∼30 min), easy operation, low cost, and on-spot visualization. Furthermore, we established a POCT platform by combining OPERATOR with rapid RNA release and a lateral flow strip without professional equipment. The high performance of OPERATOR in SARS-CoV-2 tests was confirmed using both reference materials and clinical samples, and the results suggest that is readily adaptable for point-of-care testing of other RNA viruses.

The city-wide full-scale interactive application of sewage surveillance programme for assisting real-time COVID-19 pandemic control - A case study in Hong Kong.

The paper discusses the implementation of Hong Kong's tailor-made sewage surveillance programme led by the Government, which has demonstrated how an efficient and well-organized sewage surveillance system can complement conventional epidemiological surveillance to facilitate the planning of intervention strategies and actions for combating COVID-19 pandemic in real-time. This included the setting up of a comprehensive sewerage network-based SARS-CoV-2 virus surveillance programme with 154 stationary sites covering 6 million people (or 80 % of the total population), and employing an intensive monitoring programme to take samples from each stationary site every 2 days. From 1 January to 22 May 2022, the daily confirmed case count started with 17 cases per day on 1 January to a maximum of 76,991 cases on 3 March and dropped to 237 cases on 22 May. During this period, a total of 270 "Restriction-Testing Declaration" (RTD) operations at high-risk residential areas were conducted based on the sewage virus testing results, where over 26,500 confirmed cases were detected with a majority being asymptomatic. In addition, Compulsory Testing Notices (CTN) were issued to residents, and the distribution of Rapid Antigen Test kits was adopted as alternatives to RTD operations in areas of moderate risk. These measures formulated a tiered and cost-effective approach to combat the disease in the local setting. Some ongoing and future enhancement efforts to improve efficacy are discussed from the perspective of wastewater-based epidemiology. Forecast models on case counts based on sewage virus testing results were also developed with R2 of 0.9669-0.9775, which estimated that up to 22 May 2022, around 2,000,000 people (~67 % higher than the total number of 1,200,000 reported to the health authority, due to various constraints or limitations) had potentially contracted the disease, which is believed to be reflecting the real situation occurring in a highly urbanized metropolis like Hong Kong.

Toward Trustworthy AI: Blockchain-Based Architecture Design for Accountability and Fairness of Federated Learning Systems

Federated learning is an emerging privacy-preserving AI technique where clients (i.e., organizations or devices) train models locally and formulate a global model based on the local model updates without transferring local data externally. However, federated learning systems struggle to achieve trustworthiness and embody responsible AI principles. In particular, federated learning systems face accountability and fairness challenges due to multistakeholder involvement and heterogeneity in client data distribution. To enhance the accountability and fairness of federated learning systems, we present a blockchain-based trustworthy federated learning architecture. We first design a smart contract-based data-model provenance registry to enable accountability. Additionally, we propose a weighted fair data sampler algorithm to enhance fairness in training data. We evaluate the proposed approach using a COVID-19 X-ray detection use case. The evaluation results show that the approach is feasible to enable accountability and improve fairness. The proposed algorithm can achieve better performance than the default federated learning setting in terms of the model's generalization and accuracy.

Adenovirus-mediated Over-Expression of FcγRIIB Attenuates Pulmonary Inflammation and Fibrosis.

Progressive fibrosing interstitial lung diseases (PF-ILDs) result in high mortality and lack effective therapies. The pathogenesis of PF-ILDs involves macrophages driving inflammation and irreversible fibrosis. Fc-gamma receptors (FcγRs) regulate macrophages and inflammation, but their roles in PF-ILDs remain unclear. We characterized the expression of FcγRs and found up-regulated FcγRIIB in human and mouse lungs following exposure to silica. FcγRIIB deficiency aggravated lung dysfunction, inflammation and fibrosis in silica-exposed mice. Using single-cell transcriptomics and in vitro experiments, FcγRIIB was found in alveolar macrophages, where it regulated the expression of fibrosis-related genes Spp1 and Ctss. In mice with macrophage-specific over-expression of FcγRIIB, and in mice treated with adenovirus by intra-tracheal instillation to up-regulate FcγRIIB, silica-induced functional and histological changes were ameliorated. Our data from three genetic models and a therapeutic model suggest that FcγRIIB plays a protective role that can be enhanced by adenoviral over-expression, representing a potential therapeutic strategy for PF-ILDs.

Lockdown in Chinese university dormitories: Significant increase in negative feelings and time perception distortion

The COVID‐19 pandemic has led to a global crisis resulting in lockdowns worldwide. Studies found that these could amplify negative affects predictive of disturbances in time perception. However, all existing studies on this topic concentrated on the general population during a lockdown at home. There was no research on university students living in dormitories. This study fills a gap in the literature by investigating the affective states and awareness of the passage of time of Chinese university students during an exceptional dormitory lockdown. Using a snowball sampling approach, this web‐based study recruited 225 volunteers (136 girls, 17−27 years old) during a dormitory lockdown. The online survey consisted of questions on demographic information, affective states (the Chinese version of the depression anxiety stress scales‐21 (DASS‐21) on depression, anxiety, and stress), and sense of the passage of time (the translated version of the assessment of passage of time over daily, weekly and yearly periods). The researchers shared the questionnaire link via the social media application WeChat. The study applied descriptive statistics and column charts to represent students' affective states and sense of the passage of time under extreme conditions and Pearson's correlation analysis to examine the impact of affective states on their sense of time. The study's results indicate that the dormitory lockdown caused a significant increase in all depression, anxiety, and stress categories of the DASS‐21, as well as a distortion of the sense of time passing. However, the direction of the distortion differed from that in previous studies. Moreover, a Pearson correlation analysis showed that none of the three negative affects could be associated with students' sense of time. The findings of this study indicate an increased vulnerability of students due to the lockdown. Their emotions were strongly affected, requiring particular interventions to preserve their mental well‐being. In addition, they showed a different distortion direction of time passage. Finally, they differed in the correlations between negative affect and the sense of passage of time compared to the general population in lockdown at home. This shows a need to investigate the impact of psychological states on students' routines and quality of life in emergencies. This study's scope should be expanded by incorporating additional factors pertaining to the passage of time and by integrating cross‐cultural comparisons. Practitioner Points 1. The dormitory lockdown caused a significant increase in all depression, anxiety, and stress categories of the DASS‐21.2. The dormitory lockdown caused a distortion of the sense of time passing, which differed from that in previous studies.3. None of the three negative affects could be associated with students' sense of time.

Influence of circadian clocks on adaptive immunity and vaccination responses.

The adaptive immune response is under circadian control, yet, why adaptive immune reactions continue to exhibit circadian changes over long periods of time is unknown. Using a combination of experimental and mathematical modeling approaches, we show here that dendritic cells migrate from the skin to the draining lymph node in a time-of-day-dependent manner, which provides an enhanced likelihood for functional interactions with T cells. Rhythmic expression of TNF in the draining lymph node enhances BMAL1-controlled ICAM-1 expression in high endothelial venules, resulting in lymphocyte infiltration and lymph node expansion. Lymph node cellularity continues to be different for weeks after the initial time-of-day-dependent challenge, which governs the immune response to vaccinations directed against Hepatitis A virus as well as SARS-CoV-2. In this work, we present a mechanistic understanding of the time-of-day dependent development and maintenance of an adaptive immune response, providing a strategy for using time-of-day to optimize vaccination regimes.

Long-term outcomes in COVID-19 patients who recovered from the first wave of the pandemic.

This cross-sectional study evaluated the long-term health effects of coronavirus disease 2019 (COVID-19) in Jianghan District (Wuhan, China). The results showed that 61.4% of COVID-19 patients reported at least one symptom and 8.8% had depressive symptoms at the 17-month follow-up. The proportion of patients with chest radiographic abnormalities in Fangcang shelter hospitals and designated COVID-19 hospitals was 31.6% and 41.1%, respectively, and the proportion of patients with impaired pulmonary diffusion capacity in these hospitals was 52.8% and 60.9%, respectively. Female sex (odds ratio [OR] = 1.48, 95% confidence interval [CI]: 1.16-1.88), severe disease (OR = 1.46, 95% CI: 1.01-2.10) and a higher number of initial symptoms (OR = 1.31, 95% CI: 1.23-1.40) were associated with the development of sequelae symptoms at 17 months. This study involving community-dwelling COVID-19 adults may help determine the long-term effects of COVID-19 during the first pandemic wave. Nonetheless, larger follow-up studies are needed to characterize the post-COVID-19 condition.

Surface antimicrobial functionalization with polymers: fabrication, mechanisms and applications.

Undesirable adhesion of microbes such as bacteria, fungi and viruses onto surfaces affects many industries such as marine, food, textile, and healthcare. In particular in healthcare and food packaging, the effects of unwanted microbial contamination can be life-threatening. With the current global COVID-19 pandemic, interest in the development of surfaces with superior anti-viral and anti-bacterial activities has multiplied. Polymers carrying anti-microbial properties are extensively used to functionalize material surfaces to inactivate infection-causing and biocide-resistant microbes including COVID-19. This review aims to introduce the fabrication of polymer-based antimicrobial surfaces through physical and chemical modifications, followed by the discussion of the inactivation mechanisms of conventional biocidal agents and new-generation antimicrobial macromolecules in polymer-modified antimicrobial surfaces. The advanced applications of polymer-based antimicrobial surfaces on personal protective equipment against COVID-19, food packaging materials, biomedical devices, marine vessels and textiles are also summarized to express the research trend in academia and industry.

Animated, video entertainment-education to improve vaccine confidence globally during the COVID-19 pandemic: an online randomized controlled experiment with 24,000 participants.

BACKGROUND: Science-driven storytelling and entertainment-education (E-E) media demonstrate potential for promoting improved attitudes and behavioral intent towards health-related practices. Months after the outbreak of coronavirus disease 2019 (COVID-19), emerging research highlights the essential role of interventions to improve public confidence in the COVID-19 vaccine. To improve vaccine confidence, we designed three short, animated videos employing three research-informed pedagogical strategies. These can be distributed globally through social media platforms, because of their wordless and culturally accessible design. However, the effectiveness of short, animated storytelling videos, deploying various pedagogic strategies, needs to be explored across different global regions. METHODS/DESIGN: The present study is a multi-site, parallel group, randomized controlled trial (RCT) comparing the effectiveness of (i) a storytelling-instructional-humor approach, (ii) a storytelling-analogy approach, (iii) a storytelling-emotion-focused approach, and (iv) no video. For our primary outcomes, we will measure vaccine hesitancy, and for secondary outcomes, we will measure behavioral intent to seek vaccination and hope. Using online platforms, we will recruit 12,000 participants (aged 18-59 years) from the USA and China, respectively, yielding a total sample size of 24,000. DISCUSSION: This trial uses innovative online technology, reliable randomization algorithms, validated survey instruments, and list experiments to establish the effectiveness of three short, animated videos employing various research-informed pedagogical strategies. Results will be used to scientifically support the broader distribution of these short, animated video as well as informing the design of future videos for rapid, global public health communication. TRIAL REGISTRATION: German Clinical Trials Register DRKS #00023650 . Date of registration: 2021/02/09.

COVID-19 therapies for inpatients: a review and quality assessment of clinical guidelines.

Owing to condensed development processes, expanding evidence and differences in healthcare system characteristics, many COVID-19 guidelines differ in their quality and treatment recommendations, which has consequences for clinical practice. This review aimed to identify COVID-19 treatment guidelines, assess their quality and summarise their recommendations. Guidelines were identified for five therapies most commonly used among inpatients with COVID-19 (remdesivir, dexamethasone, tocilizumab, baricitinib and casirivimab/imdevimab) from 11 countries. Guideline quality was assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE-II) tool. Full details of recommendations and supporting evidence were analysed for high-quality guidelines, defined as those scoring ≥50% in Domain 3 (Rigour of Development) of AGREE-II. Overall, guidelines differed substantially in their quality and, even among high-quality guidelines using the same evidence, recommendations regarding specific therapeutics varied. Potential reasons for this heterogeneity, including the availability and consistency of clinical data, visibility of trial end-points and context-specific factors, are discussed.

Autoantibodies in immunodeficiency syndromes: The Janus faces of immune dysregulation.

Immunodeficiency syndromes represent a diverse group of inherited and acquired disorders, characterized by a spectrum of clinical manifestations, including recurrent infections, autoimmunity, lymphoproliferation and malignancy. Autoantibodies against various self-antigens reflect the immune dysregulation underlying these disorders, and could contribute to certain clinical findings, such as susceptibility to opportunistic infections, cytopenia of different hematopoietic lineages, and organ-specific autoimmune diseases. The mechanism of autoantibody production in the context of immunodeficiency remains largely unknown but is likely shaped by both intrinsic genetic aberrations and extrinsic exposures to possible infectious agents. These autoantibodies if harbor neutralizing activities and reach certain levels in the circulation, could disrupt the biological functions of their targets, resulting in specific clinical manifestations. Herein, we reviewed the prevalence of autoantibodies against cytokines, hematopoietic cells and organ-specific antigens in immunodeficiency syndromes and examined their associations with certain clinical findings. Moreover, the potential mechanism of autoantibody production was also discussed. These may shed light on the development of mechanism-based therapies to reset the dysregulated immune system in immunodeficient patients.

Assessment of the Effect on Thromboprophylaxis with Multifaceted Quality Improvement Intervention based on Clinical Decision Support System in Hospitalized Patients: A Pilot Study.

BACKGROUND: To explore the feasibility and effectiveness of multifaceted quality improvement intervention based on the clinical decision support system (CDSS) in VTE prophylaxis in hospitalized patients. METHODS: A randomized, department-based clinical trial was conducted in the department of respiratory and critical care medicine, orthopedic, and general surgery wards. Patients aged ≥18 years, without VTE in admission, were allocated to the intervention group and received regular care combined with multifaceted quality improvement intervention based on CDSS during hospitalization. VTE prophylaxis rate and the occurrence of hospital-associated VTE events were analyzed as primary and secondary outcomes. RESULTS: A total of 3644 eligible residents were enrolled in this trial. With the implementation of the multifaceted quality improvement intervention based on the CDSS, the VTE prophylaxis rate of the intervention group increased from 22.93% to 34.56% (p < 0.001), and the incidence of HA-VTE events increased from 0.49% to 1.00% (p = 0.366). In the nonintervention group, the VTE prophylaxis rate increased from 24.49% to 27.90% (p = 0.091), and the incidence of HA-VTE events increased from 0.47% to 2.02% (p = 0.001). CONCLUSIONS: Multifaceted quality improvement intervention based on the CDSS strategy is feasible and expected to facilitate implementation of the recommended VTE prophylaxis strategies and reduce the incidence of HA-VTE in hospital. However, it is necessary to conduct more multicenter clinical trials in the future to provide more reliable real-world evidence.