Anti-synthetase syndrome masquerading as recurrent pneumonia.

Anti-synthetase syndrome (ASS) is a rare inflammatory myopathy with a wide variety of clinical presentations. ASS-related interstitial lung disease (ASS-ILD) presents with rapid onset and progression, which could often be confused with other more common acute processes such as pneumonia, especially when ILD can be the sole manifestation. A woman in her 50s presented with recurrent dyspnoea for 2 months requiring multiple hospital admissions, and each time, she was diagnosed with multifocal pneumonia and treated with antibiotics. On admission, the evaluation revealed a markedly elevated creatine kinase level at 3258 U/L and a CT scan of the chest revealed worsening scattered ground-glass opacities. Given the concern for ILD as the cause of antibiotic failure, she underwent bronchoscopy with bronchoalveolar lavage which revealed non-specific interstitial pneumonia. A subsequent myositis panel revealed a positive anti-Jo-1 antibody, and she was diagnosed with ASS-ILD. She completed a course of intravenous immunoglobulin and methylprednisolone and experienced significant clinical improvement with the resolution of hypoxaemia and improved polyarthralgia.ASS could often be misdiagnosed as other more common acute lung processes, as a clinically subtle course can escape detection given its rarity, as well as its non-specific and highly variable presentations. This case highlights the importance of early suspicion and consideration of performing specific autoantibody testing when evaluating patients with a suspicion of undifferentiated autoimmune condition.

Multi-omics characterization of RNA binding proteins reveals disease comorbidities and potential drugs in COVID-19.

The COVID-19 has led to a devastating global health crisis, which emphasizes the urgent need to deepen our understanding of the molecular mechanism and identifying potential antiviral drugs. Here, we comprehensively analyzed the transcriptomic and proteomic profiles of 178 COVID-19 patients, ranging from asymptomatic to critically ill. Our analyses found that the RNA binding proteins (RBPs) were likely to be perturbed in infection. Interactome analysis revealed that RBPs interact with virus proteins and the viral interacting RBPs were likely to locate in central regions of human protein-protein interaction network. Functional enrichment analysis revealed that the viral interacting RBPs were likely to be enriched in RNA transport, apoptosis and viral genome replication-related pathways. Based on network proximity analyses of 299 human complex-disease genes and COVID-19-related RBPs in the human interactome, we revealed the significant associations between complex diseases and COVID-19. Network analysis also implicated potential antiviral drugs for treatment of COVID-19. In summary, our integrative characterization of COVID-19 patients may thus help providing evidence regarding pathophysiology and potential therapeutic strategies for COVID-19.

Data analysis guidelines for single-cell RNA-seq in biomedical studies and clinical applications.

The application of single-cell RNA sequencing (scRNA-seq) in biomedical research has advanced our understanding of the pathogenesis of disease and provided valuable insights into new diagnostic and therapeutic strategies. With the expansion of capacity for high-throughput scRNA-seq, including clinical samples, the analysis of these huge volumes of data has become a daunting prospect for researchers entering this field. Here, we review the workflow for typical scRNA-seq data analysis, covering raw data processing and quality control, basic data analysis applicable for almost all scRNA-seq data sets, and advanced data analysis that should be tailored to specific scientific questions. While summarizing the current methods for each analysis step, we also provide an online repository of software and wrapped-up scripts to support the implementation. Recommendations and caveats are pointed out for some specific analysis tasks and approaches. We hope this resource will be helpful to researchers engaging with scRNA-seq, in particular for emerging clinical applications.

COVID-19 Vaccine Booster-Induced Dermatographism.

The urgent requirement for a preventative vaccination became more pressing due to the severe repercussions that the SARS-CoV-2 (COVID-19) virus had on society and the economy. The deployment of the COVID-19 vaccination program had to be expedited. As with all vaccinations, adverse events have been recorded with the COVID-19 vaccine. Some patients may experience cutaneous reactions such as rashes, itching, hives, and swelling after receiving the COVID-19 vaccine, but it is unclear how common these events are or how frequently they recur. This article discusses an unusual case of a young man who got chronic severe dermatographism after receiving a booster shot of the Moderna vaccine (Moderna, Inc., Cambridge, Massachusetts).

Development of a Handheld Nano-centrifugal Device for Visual Virus Detection.

Gold nanoparticles (AuNPs) colorimetric assays based on distance-dependent optical characteristics have been widely employed for bioanalysis. However, this assay is not effective for visually detecting low-concentration targets due to the faint color change. Here, we developed a handheld nano-centrifugal device which could separate the crosslinked and non-crosslinked AuNPs. Results showed that the handheld nano-centrifugal device could easily reach more than 6000 r/min within 10 s simply by stretching and tightening the coiled rope in an appropriate rhythm. Further, combined with the CRISPR/Cas12a nucleic acids recognition system, a field-deployable colorimetric platform termed handheld nano-centrifugal device assisted CRISPR/Cas12a (Hand-CRISPR) has been validated. Moreover, clinical diagnostics applications for Epstein-Barr virus (EBV) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) detection with high sensitivity and accuracy (100% consistency with reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) test results) have been demonstrated. Overall, the Hand-CRISPR platform showed great promise in point-of-care-test (POCT) application, expected to become a powerful supplement to the standard nucleic acid testing method in remote or poverty-stricken areas. Supplementary Information: The online version contains supplementary material available at 10.1007/s41664-022-00232-0.

Comprehensive characterization of human-virus protein-protein interactions reveals disease comorbidities and potential antiviral drugs.

The protein-protein interactions (PPIs) between human and viruses play important roles in viral infection and host immune responses. Rapid accumulation of experimentally validated human-virus PPIs provides an unprecedented opportunity to investigate the regulatory pattern of viral infection. However, we are still lack of knowledge about the regulatory patterns of human-virus interactions. We collected 27,293 experimentally validated human-virus PPIs, covering 8 virus families, 140 viral proteins and 6059 human proteins. Functional enrichment analysis revealed that the viral interacting proteins were likely to be enriched in cell cycle and immune-related pathways. Moreover, we analysed the topological features of the viral interacting proteins and found that they were likely to locate in central regions of human PPI network. Based on network proximity analyses of diseases genes and human-virus interactions in the human interactome, we revealed the associations between complex diseases and viral infections. Network analysis also implicated potential antiviral drugs that were further validated by text mining. Finally, we presented the Human-Virus Protein-Protein Interaction database (HVPPI, http://bio-bigdata.hrbmu.edu.cn/HVPPI), that provides experimentally validated human-virus PPIs as well as seamlessly integrates online functional analysis tools. In summary, comprehensive understanding the regulatory pattern of human-virus interactome will provide novel insights into fundamental infectious mechanism discovery and new antiviral therapy development.

Some characteristics of clinical sequelae of COVID-19 survivors from Wuhan, China: A multi-center longitudinal study.

BACKGROUND: The pandemic of COVID-19 has a persistent impact on global health, yet its sequelae need to be addressed at a wide scale around the globe. This study aims to investigate the characteristics, prevalence, and risk factors for mid-term (>6 months) clinical sequelae in a cohort of COVID-19 survivors. METHODS: Totally 715 COVID-19 survivors discharged before April 1, 2020, from three medical centers in Wuhan, China, were included. The longitudinal study was conducted by telephone interviews based on a questionnaire including the clinical sequelae of general, respiratory, and cardiovascular systems. Demographics and some characteristics of clinical sequelae of the survivors were recorded and analyzed. Multivariate logistic regression analysis was applied to explore the risk factors for the sequelae. RESULTS: The median time interval from discharge to telephone interview was 225.0 days. The COVID-19 survivors' median ages were 69 years, and 51.3% were male. Among them, 29.9% had at least one clinical sequela. There were 19.2%, 22.7%, and 5.0% of the survivors reporting fatigue, respiratory symptoms, and cardiovascular symptoms, respectively. Comorbidities, disease severity, the application of mechanical ventilation and high-flow oxygen therapy, and the history of re-admission were associated with the presence of clinical sequelae. CONCLUSIONS: Our study provides further evidence for the prevalence and characteristics of clinical sequelae of COVID-19 survivors, suggesting long-term monitoring and management is needed for their full recovery.

Recombinant angiopoietin-like protein 4 attenuates intestinal barrier structure and function injury after ischemia/reperfusion.

BACKGROUND: Intestinal barrier breakdown, a frequent complication of intestinal ischemia-reperfusion (I/R) including dysfunction and the structure changes of the intestine, is characterized by a loss of tight junction and enhanced permeability of the intestinal barrier and increased mortality. To develop effective and novel therapeutics is important for the improvement of outcome of patients with intestinal barrier deterioration. Recombinant human angiopoietin-like protein 4 (rhANGPTL4) is reported to protect the blood-brain barrier when administered exogenously, and endogenous ANGPTL4 deficiency deteriorates radiation-induced intestinal injury. AIM: To identify whether rhANGPTL4 may protect intestinal barrier breakdown induced by I/R. METHODS: Intestinal I/R injury was elicited through clamping the superior mesenteric artery for 60 min followed by 240 min reperfusion. Intestinal epithelial (Caco-2) cells and human umbilical vein endothelial cells were challenged by hypoxia/ reoxygenation to mimic I/R in vitro. RESULTS: Indicators including fluorescein isothiocyanate-conjugated dextran (4 kilodaltons; FD-4) clearance, ratio of phosphorylated myosin light chain/total myosin light chain, myosin light chain kinase and loss of zonula occludens-1, claudin-2 and VE-cadherin were significantly increased after intestinal I/R or cell hypoxia/reoxygenation. rhANGPTL4 treatment significantly reversed these indicators, which were associated with inhibiting the inflammatory and oxidative cascade, excessive activation of cellular autophagy and apoptosis and improvement of survival rate. Similar results were observed in vitro when cells were challenged by hypoxia/reoxygenation, whereas rhANGPTL4 reversed the indicators close to normal level in Caco-2 cells and human umbilical vein endothelial cells significantly. CONCLUSION: rhANGPTL4 can function as a protective agent against intestinal injury induced by intestinal I/R and improve survival via maintenance of intestinal barrier structure and functions.

Post-infection cognitive impairments in a cohort of elderly patients with COVID-19.

BACKGROUND: Understanding the long-term effects of coronavirus disease 2019 (COVID-19) on cognitive function is essential for monitoring the cognitive decline in the elderly population. This study aims to assess the current cognitive status and the longitudinal cognitive decline in elderly patients recovered from COVID-19. METHODS: This cross-sectional study recruited 1539 COVID-19 inpatients aged over 60 years who were discharged from three COVID-19-designated hospitals in Wuhan, China, from February 10 to April 10, 2020. In total, 466 uninfected spouses of COVID-19 patients were selected as controls. The current cognitive status was assessed using a Chinese version of the Telephone Interview of Cognitive Status-40 (TICS-40) and the longitudinal cognitive decline was assessed using an Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Cognitive assessments were performed 6 months after patient discharge. RESULTS: Compared with controls, COVID-19 patients had lower TICS-40 scores and higher IQCODE scores [TICS-40 median (IQR): 29 (25 to 32) vs. 30 (26 to 33), p < 0.001; IQCODE median (IQR): 3.19 (3.00 to 3.63) vs. 3.06 (3.00 to 3.38), p < 0.001]. Severe COVID-19 patients had lower TICS-40 scores and higher IQCODE scores than non-severe COVID-19 patients [TICS-40 median (IQR): 24 (18 to 28) vs. 30 (26 to 33), p < 0.001; IQCODE median (IQR): 3.63 (3.13 to 4.31) vs. 3.13 (3.00 to 3.56), p < 0.001] and controls [TICS-40 median (IQR): 24 (18 to 28) vs. 30 (26 to 33), p < 0.001; IQCODE median (IQR) 3.63 (3.13 to 4.31) vs. 3.06 (3.00 to 3.38), p < 0.001]. Severe COVID-19 patients had a higher proportion of cases with current cognitive impairment and longitudinal cognitive decline than non-severe COVID-19 patients [dementia: 25 (10.50 %) vs. 9 (0.69 %), p < 0.001; Mild cognitive impairment (MCI): 60 (25.21 %) vs. 63 (4.84 %), p < 0.001] and controls [dementia: 25 (10.50 %) vs. 0 (0 %), p < 0.001; MCI: 60 (25.21 %) vs. 20 (4.29 %), p < 0.001)]. COVID-19 severity, delirium and COPD were risk factors of current cognitive impairment. Low education level, severe COVID-19, delirium, hypertension and COPD were risk factors of longitudinal cognitive decline. CONCLUSIONS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with an increased risk of long-term cognitive decline in elderly population. COVID-19 patients, especially severe patients, should be intensively monitored for post-infection cognitive decline.

Diffuse Alveolar Hemorrhage With Avelumab Maintenance Therapy.

Immune checkpoint blockade is a rapidly expanding therapeutic modality in oncology. However, its adverse effects extend beyond the cytotoxicity of conventional chemotherapy. Pneumotoxicity associated with immune checkpoint therapy presents a diagnostic conundrum that has been further complicated by the COVID-19 pandemic. We report a case of a patient with metastatic urothelial carcinoma who developed diffuse alveolar hemorrhage (DAH) following treatment with avelumab.

Exploring Strategies for Improving Green Open Spaces in Old Downtown Residential Communities from the Perspective of Public Health to Enhance the Health and Well-Being of the Aged.

Based on the trend of global aging, people are paying more and more attention to the health of the elderly and the improvement of green open spaces. However, few studies have focused on strategies to improve green spaces in response to this trend. Especially, with the outbreak of COVID-19, an urgent need to develop a sustainable system strategy to improve the health of the elderly in residential communities in old districts has emerged. Traditional improvement strategies based on current situation evaluation often focus on the most prominent practical problems. Therefore, the objective of this study was to provide theoretical research and practical improvement strategies for green open spaces in old downtown residential communities to improve the health and well-being of the elderly. In response to this problem, this research proposes an alternative method based on causality (FDM-DANP-mV model), by extracting 23 green open space elements that affect the health of the elderly and dividing them into three dimensions, to form a preliminary evaluation framework. On this basis, the more effective and feasible standard elements are screened out, and the influence relationship behind the elements is clarified. Then, the sustainable development strategy is systematically discussed in three practical cases. This allows for the analysis of the present situation to not only identify the current significant problems but also to capture the source of the influence behind the real problems based on the clarification of the dominant influence relationship. The actual value of this study is to provide a key design decision basis for the improvement of the green open spaces in old downtown residential communities, aiming at avoiding waste to the greatest extent under the premise of limited resources and gradually promoting the improvement of the urban built environment to promote the health and well-being of the elderly.

Coronavirus disease 2019 outbreak in Beijing's Xinfadi Market, China: a modeling study to inform future resurgence response.

BACKGROUND: A local coronavirus disease 2019 (COVID-19) case confirmed on June 11, 2020 triggered an outbreak in Beijing, China after 56 consecutive days without a newly confirmed case. Non-pharmaceutical interventions (NPIs) were used to contain the source in Xinfadi (XFD) market. To rapidly control the outbreak, both traditional and newly introduced NPIs including large-scale management of high-risk populations and expanded severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR-based screening in the general population were conducted in Beijing. We aimed to assess the effectiveness of the response to the COVID-19 outbreak in Beijing's XFD market and inform future response efforts of resurgence across regions. METHODS: A modified susceptible-exposed-infectious-recovered (SEIR) model was developed and applied to evaluate a range of different scenarios from the public health perspective. Two outcomes were measured: magnitude of transmission (i.e., number of cases in the outbreak) and endpoint of transmission (i.e., date of containment). The outcomes of scenario evaluations were presented relative to the reality case (i.e., 368 cases in 34 days) with 95% Confidence Interval (CI). RESULTS: Our results indicated that a 3 to 14 day delay in the identification of XFD as the infection source and initiation of NPIs would have caused a 3 to 28-fold increase in total case number (31-77 day delay in containment). A failure to implement the quarantine scheme employed in the XFD outbreak for defined key population would have caused a fivefold greater number of cases (73 day delay in containment). Similarly, failure to implement the quarantine plan executed in the XFD outbreak for close contacts would have caused twofold greater transmission (44 day delay in containment). Finally, failure to implement expanded nucleic acid screening in the general population would have yielded 1.6-fold greater transmission and a 32 day delay to containment. CONCLUSIONS: This study informs new evidence that in form the selection of NPI to use as countermeasures in response to a COVID-19 outbreak and optimal timing of their implementation. The evidence provided by this study should inform responses to future outbreaks of COVID-19 and future infectious disease outbreak preparedness efforts in China and elsewhere.

Comparison of patients hospitalized with COVID-19, H7N9 and H1N1.

BACKGROUND: There is an urgent need to better understand the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for that the coronavirus disease 2019 (COVID-19) continues to cause considerable morbidity and mortality worldwide. This paper was to differentiate COVID-19 from other respiratory infectious diseases such as avian-origin influenza A (H7N9) and influenza A (H1N1) virus infections. METHODS: We included patients who had been hospitalized with laboratory-confirmed infection by SARS-CoV-2 (n = 83), H7N9 (n = 36), H1N1 (n = 44) viruses. Clinical presentation, chest CT features, and progression of patients were compared. We used the Logistic regression model to explore the possible risk factors. RESULTS: Both COVID-19 and H7N9 patients had a longer duration of hospitalization than H1N1 patients (P < 0.01), a higher complication rate, and more severe cases than H1N1 patients. H7N9 patients had higher hospitalization-fatality ratio than COVID-19 patients (P = 0.01). H7N9 patients had similar patterns of lymphopenia, neutrophilia, elevated alanine aminotransferase, C-reactive protein, lactate dehydrogenase, and those seen in H1N1 patients, which were all significantly different from patients with COVID-19 (P < 0.01). Either H7N9 or H1N1 patients had more obvious symptoms, like fever, fatigue, yellow sputum, and myalgia than COVID-19 patients (P < 0.01). The mean duration of viral shedding was 9.5 days for SARS-CoV-2 vs 9.9 days for H7N9 (P = 0.78). For severe cases, the meantime from illness onset to severity was 8.0 days for COVID-19 vs 5.2 days for H7N9 (P < 0.01), the comorbidity of chronic heart disease was more common in the COVID-19 patients than H7N9 (P = 0.02). Multivariate analysis showed that chronic heart disease was a possible risk factor (OR > 1) for COVID-19, compared with H1N1 and H7N9. CONCLUSIONS: The proportion of severe cases were higher for H7N9 and SARS-CoV-2 infections, compared with H1N1. The meantime from illness onset to severity was shorter for H7N9. Chronic heart disease was a possible risk factor for COVID-19.The comparison may provide the rationale for strategies of isolation and treatment of infected patients in the future.

Anxiety and Depression of Nurses in a North West Province in China During the Period of Novel Coronavirus Pneumonia Outbreak.

PURPOSE: To investigate the anxiety and depression levels of frontline clinical nurses working in 14 hospitals in Gansu Province, China, during this period. DESIGN: A cross-sectional survey was conducted online between February 7 and 10, 2020, with a convenience sample of 22,034 nurses working in 14 prefecture and city hospitals in Gansu Province, located in northwest China. METHODS: A self-reported questionnaire with four parts (demographic characteristics, general questions related to novel coronavirus-infected pneumonia, self-rating anxiety scale, and self-rating depression scale) was administered. Descriptive statistics including frequencies, means, and SDs were computed. The associations between anxiety and depression with sociodemographic characteristics, work-related concerns, and impacts were analyzed, followed by multiple stepwise linear regression to identify factors that best predicted the nurses' anxiety and depression levels. FINDINGS: A total of 21,199 questionnaires were checked to be valid, with an effective recovery rate of 96.21%. The mean ± SD age of the respondents was 31.89 ± 7.084 years, and the mean ± SD length of service was 9.40 ± 7.638 years. The majority of the respondents were female (98.6%) and married (73.1%). Some demographic characteristics, related concerns, and impacts of COVID-19 were found to be significantly associated with both anxiety (p < .001) and depression (p < .001). Nurses who needed to take care of children or elderly relatives, took leave from work because they were worried about COVID-19, avoided contact with family and friends, and wanted to obtain more COVID-19-related knowledge had higher levels of both anxiety and depression. CONCLUSIONS: Results show that nurses faced with the COVID-19 outbreak are at risk for experiencing anxiety and depression. Demographic background, psychosocial factors, and work-related factors predicted the psychological responses. The family responsibilities and burdens of women may explain the higher levels of anxiety and depression among nurses with these obligations as compared to those without. On the other hand, nurses who chose not to take leave from work or who did not avoid going to work during this period were less anxious and depressed. CLINICAL RELEVANCE: Professional commitment might be a protective factor for adverse psychological responses. It is pertinent to provide emotional support for nurses and recognize their professional commitment in providing service to people in need.

An Atypical Presentation of Acute Pulmonary Embolism With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Pneumonia.

Clinical presentation and severity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) varies greatly amongst patients, as supported by recent literature. This poses an ongoing challenge in the diagnostic and therapeutic approach for managing these patients. Here, we would like to describe a case of acute bilateral pulmonary embolism (PE) presenting with atypical gastrointestinal symptoms in a patient with SARS-CoV-2 infection. This atypical presentation of PE is unique to our case and highlights the significance of a high index of clinical suspicion for SARS-CoV-2 and its associated thrombogenic effect, even in patients with atypical symptoms.

Mental Status and Psychological Needs of Chinese Police Officers in a Highly Impacted City during the COVID-19 Pandemic

The purpose of the study was to investigate the mental status and psychological needs of police officers during the COVID-19 outbreak in China. The Anti-Pandemic Public Mental Status Scale and self-administered Psychological Needs Scale were administered online to police officers in Y city, a significant sub-central city of Hubei Province, where was affected by the pandemic the most seriously. A total of 5,467 valid questionnaires were collected, of which female police accounted for 17.7%. Compared with the national public and Y city public data previously measured using the Anti-Pandemic Public Mental Status Scale, this study found that 24.6% of the Y city police suffered maladaptive problems. The mental status of the national public was the best, followed by the Y city police. The mental status of the Y city public was the worst. Moreover, there was a significant interaction between gender and unit type of Y city police (p = 0.02). The mental status of female police working in prisons was worse than their male counterparts (p = 0.01). Furthermore, psychological needs survey results showed that the police most wanted to learn the topics of self-adjustment and family relations. The most desired psychological assistances were relaxation and stress reduction, while the percentage of willingness to choose psychological counseling was low. During the pandemic, some police officers showed obvious psychological symptoms and the mental health services could be provided according to their psychological needs.