Why did air quality experience little improvement during the COVID-19 lockdown in megacities, northeast China?

To inhibit the COVID-19 (Coronavirus disease 2019) outbreak, unprecedented nationwide lockdowns were implemented in China in early 2020, resulting in a marked reduction of anthropogenic emissions. However, reasons for the insignificant improvement in air quality in megacities of northeast China, including Shenyang, Changchun, Jilin, Harbin, and Daqing, were scarcely reported. We assessed the influences of meteorological conditions and changes in emissions on air quality in the five megacities during the COVID-19 lockdown (February 2020) using the WRF-CMAQ model. Modeling results indicated that meteorology contributed a 14.7% increment in Air Quality Index (AQI) averaged over the five megacities, thus, the local unfavorable meteorology was one of the causes to yield little improved air quality. In terms of emission changes, the increase in residential emissions (+15%) accompanied by declining industry emissions (-15%) and transportation (-90%) emissions resulted in a slight AQI decrease of 3.1%, demonstrating the decrease in emissions associated with the lockdown were largely offset by the increment in residential emissions. Also, residential emissions contributed 42.3% to PM2.5 concentration on average based on the Integrated Source Apportionment tool. These results demonstrated the key role residential emissions played in determining air quality. The findings of this study provide a scenario that helps make appropriate emission mitigation measures for improving air quality in this part of China.

Utility of Epstein-Barr Virus DNA in Nasopharynx Swabs as a Reflex Test to Triage Seropositive Individuals in Nasopharyngeal Carcinoma Screening Programs.

BACKGROUND: Epstein-Barr virus (EBV) DNA detection in the nasopharynx is considered a biomarker for nasopharyngeal carcinoma (NPC). We evaluated its performance as a reflex test to triage EBV seropositives within an NPC screening program in China. METHODS: The study population was embedded within an ongoing NPC screening trial and included 1111 participants who screened positive for anti-EBV VCA (antibodies against EBV capsid antigens)/EBNA1 (EBV nuclear antigen1)-IgA antibodies (of 18 237 screened). Nasopharynx swabs were collected/tested for EBNA1 gene EBV DNA load. We evaluated performance of EBV DNA in the nasopharynx swab as a reflex test to triage EBV serological high-risk (those referred to endoscopy/MRI) and medium-risk (those referred to accelerated screening) individuals. RESULTS: By the end of 2019, we detected 20 NPC cases from 317 serological high-risk individuals and 4 NPC cases from 794 medium-risk individuals. When used to triage serological high-risk individuals, nasopharynx swab EBV DNA was detected in 19/20 cases (positivity rate among cases: 95.0%; 95% CI, 75.1%-99.9%), with a referral rate of 63.4% (201/317, 95% CI, 57.8%-68.7%) and NPC detection rate among positives of 9.5% (19/201, 95% CI, 5.8%-14.4%). The performance of an algorithm that combined serology with triage of serology high-risk individuals using EBV DNA testing yielded a sensitivity of 72.4% (95% CI, 3.0%-81.4%) and specificity of 97.6% (95% CI, 97.2%-97.9%). When used to triage EBV serological medium-risk individuals, the positivity rate among cases was 75.0% (95% CI, 19.4%-99.4%), with a referral rate of 61.8% (95% CI, 58.4%-65.2%) and NPC detection rate among positives of 0.6% (95% CI, 0.1%-1.8%). CONCLUSIONS: Nasopharynx swab EBV DNA showed promise as a reflex test to triage serology high-risk individuals, reducing referral by ca. 40% with little reduction in sensitivity compared to a serology-only screening program.

Bullet screen in pre-clinical undergraduate pharmacology education: a survey study.

BACKGROUND: The lack of interaction and communication in pharmacology courses, especially since the onset of the coronavirus disease 2019 (COVID-19) pandemic, which required a fast shift to remote learning at medical schools, leads to an unsatisfactory learning outcome. New interactive teaching approaches are required to improve pharmacology learning attention and interaction in remote education and traditional classrooms. METHODS: We introduced bullet screens to pharmacology teaching. Then, a survey was distributed to first-, second- and third-year pre-clinical undergraduate medical and nursing students at the Shanghai Jiao Tong University School of Medicine from November 2020 to March 2022. We evaluated the essential features, instructional effectiveness, and entertainment value of bullet screens. Responses to structured and open-ended questions about the strengths and weaknesses of the bullet screen and overall thoughts were coded and compared between medical and nursing students. RESULTS: In terms of essential features, bullet screens have a high degree of acceptability among students, and this novel instructional style conveniently increased classroom interaction. Considering instructional effectiveness, bullet screen may stimulate students' in-depth thinking. Meanwhile, students tended to use bullet-screen comments as a way to express their support rather than to make additional comments or to express their different viewpoints. The entertainment value of bullet screen was noteworthy. The lack of ideas might lead to relative differences between medical and nursing students, indicating that guiding the appropriate use of bullet screen is necessary. CONCLUSIONS: The bullet screen may be popularized as an auxiliary teaching approach to promote interaction between teachers and students in the classroom as well as during remote education. It is an interesting and beneficial tool in pharmacology courses, yet there are several aspects of this device that should be improved for popularization.

Caspase-1 and Gasdermin D Afford the Optimal Targets with Distinct Switching Strategies in NLRP1b Inflammasome-Induced Cell Death.

Inflammasomes are essential complexes of innate immune system, which form the first line of host defense against pathogens. Mounting evidence accumulates that inflammasome signaling is highly correlated with coronavirus disease 2019 (COVID-19). However, there remains a significant gap in our understanding of the regulatory mechanism of inflammasome signaling. Combining mathematical modeling with experimental analysis of NLRP1b inflammasome signaling, we found that only the expression levels of caspase-1 and GSDMD have the potential to individually switch cell death modes. Reduction of caspase-1 or GSDMD switches cell death from pyroptosis to apoptosis. Caspase-1 and GSDMD present different thresholds and exert distinct pathway choices in switching death modes. Pyroptosis switches to apoptosis with an extremely low threshold level of caspase-1, but with a high threshold of GSDMD. Caspase-1-impaired cells employ ASC-caspase-8-dependent pathway for apoptosis, while GSDMD-impaired cells primarily utilize caspase-1-dependent pathway. Additionally, caspase-1 and GSDMD can severally ignite the cooccurrence of pyroptosis and apoptosis. Landscape topography unravels that the cooccurrence is dramatically different in caspase-1- and GSDMD-impaired cells. Besides pyroptosis state and apoptosis state, a potential new "coexisting" state in single cells is proposed when GSDMD acts as the driving force of the landscape. The "seesaw model" is therefore proposed, which can well describe the death states that are controlled by caspase-1 or GSDMD in single cells. Our study sheds new light on NLRP1b inflammasome signaling and uncovers the switching mechanisms among various death modes, providing potential clues to guide the development of more rational control strategies for diseases.

Combinational benefit of antihistamines and remdesivir for reducing SARS-CoV-2 replication and alleviating inflammation-induced lung injury in mice.

COVID-19 is an immune-mediated inflammatory disease caused by SARS-CoV-2 infection, the combination of anti-inflammatory and antiviral therapy is predicted to provide clinical benefits. We recently demonstrated that mast cells (MCs) are an essential mediator of SARS-CoV-2-initiated hyperinflammation. We also showed that spike protein-induced MC degranulation initiates alveolar epithelial inflammation for barrier disruption and suggested an off-label use of antihistamines as MC stabilizers to block degranulation and consequently suppress inflammation and prevent lung injury. In this study, we emphasized the essential role of MCs in SARS-CoV-2-induced lung lesions in vivo, and demonstrated the benefits of co-administration of antihistamines and antiviral drug remdesivir in SARS-CoV-2-infected mice. Specifically, SARS-CoV-2 spike protein-induced MC degranulation resulted in alveolar-capillary injury, while pretreatment of pulmonary microvascular endothelial cells with antihistamines prevented adhesion junction disruption; predictably, the combination of antiviral drug remdesivir with the antihistamine loratadine, a histamine receptor 1 (HR1) antagonist, dampened viral replication and inflammation, thereby greatly reducing lung injury. Our findings emphasize the crucial role of MCs in SARS-CoV-2-induced inflammation and lung injury and provide a feasible combination antiviral and anti-inflammatory therapy for COVID-19 treatment.

Network modeling-based identification of the switching targets between pyroptosis and secondary pyroptosis.

The newly identified cell death type, pyroptosis plays crucial roles in various diseases. Most recently, mounting evidence accumulates that pyroptotic signaling is highly correlated with coronavirus disease 2019 (COVID-19). Thus, understanding the induction of the pyroptotic signaling and dissecting the detail molecular control mechanisms are urgently needed. Based on recent experimental studies, a core regulatory model of the pyroptotic signaling is constructed to investigate the intricate crosstalk dynamics between the two cell death types, i.e., pyroptosis and secondary pyroptosis. The model well reproduces the experimental observations under different conditions. Sensitivity analysis determines that only the expression level of caspase-1 or GSDMD has the potential to individually change death modes. The decrease of caspase-1 or GSDMD level switches cell death from pyroptosis to secondary pyroptosis. Besides, eight biochemical reactions are identified that can efficiently switch death modes. While from the viewpoint of bifurcation analysis, the expression level of caspase-3 is further identified and twelve biochemical reactions are obtained. The coexistence of pyroptosis and secondary pyroptosis is predicted to be observed not only within the bistable range, but also within proper monostable range, presenting two potential different control mechanisms. Combined with the landscape theory, we further explore the stochastic dynamic and global stability of the pyroptotic system, accurately quantifying how each component mediates the individual occurrence probability of pyroptosis and secondary pyroptosis. Overall, this study sheds new light on the intricate crosstalk of the pyroptotic signaling and uncovers the regulatory mechanisms of various stable state transitions, providing potential clues to guide the development for prevention and treatment of pyroptosis-related diseases.

Extracorporeal Membrane Oxygenation for SARS-CoV-2 Acute Respiratory Distress Syndrome: A Retrospective Study From Hubei, China.

Background: The data on long-term outcomes of patients infected by SARS-CoV-2 and treated with extracorporeal membrane oxygenation (ECMO) in China are merely available. Methods: A retrospective study included 73 patients infected by SARS-CoV-2 and treated with ECMO in 21 intensive care units in Hubei, China. Data on demographic information, clinical features, laboratory tests, ECMO durations, complications, and living status were collected. Results: The 73 ECMO-treated patients had a median age of 62 (range 33-78) years and 42 (63.6%) were males. Before ECMO initiation, patients had severe respiratory failure on mechanical ventilation with a median PO2/FiO2 of 71.9 [interquartile range (IQR), 58.6-87.0] mmHg and a median PCO2 of 62 [IQR, 43-84] mmHg on arterial blood analyses. The median duration from symptom onset to invasive mechanical ventilation, and to ECMO initiation was19 [IQR, 15-25] days, and 23 [IQR, 19-31] days. Before and after ECMO initiation, the proportions of patients receiving prone position ventilation were 58.9 and 69.9%, respectively. The median duration of ECMO support was 18.5 [IQR 12-30] days. During the treatments with ECMO, major hemorrhages occurred in 31 (42.5%) patients, and oxygenators were replaced in 21 (28.8%) patients. Since ECMO initiation, the 30-day mortality and 60-day mortality were 63.0 and 80.8%, respectively. Conclusions: In Hubei, China, the ECMO-treated patients infected by SARS-CoV-2 were of a broad age range and with severe hypoxemia. The durations of ECMO support, accompanied with increased complications, were relatively long. The long-term mortality in these patients was considerably high.

SARS-CoV-2-Triggered Mast Cell Rapid Degranulation Induces Alveolar Epithelial Inflammation and Lung Injury (preprint)

SARS-CoV-2 infection-induced hyper-inflammation links to the acute lung injury and COVID-19 severity. Identifying the primary mediators that initiate the uncontrolled hypercytokinemia is essential for treatments. Mast cells (MCs) are strategically located at the mucosa and beneficially or detrimentally regulate immune inflammations. Here we showed that SARS-CoV-2-triggeed MC degranulation initiated alveolar epithelial inflammation and lung injury. SARS-CoV-2 challenge induced MC degranulation in ACE-2 humanized mice and rhesus macaques, and a rapid MC degranulation could be recapitulated with Spike-RBD binding to ACE2 in cells; MC degranulation alterred various signaling pathways in alveolar epithelial cells, particularly, led to the production of pro-inflammatory factors and consequential disruption of tight junctions. Importantly, the administration of clinical MC stabilizers for blocking degranulation dampened SARS-CoV-2-induced production of pro-inflammatory factors and prevented lung injury. These findings uncover a novel mechanism for SARS-CoV-2 initiating lung inflammation, and suggest an off-label use of MC stabilizer as immunomodulators for COVID-19 treatments.

The peak levels of highly sensitive troponin I predicts in-hospital mortality in COVID-19 patients with cardiac injury: a retrospective study.

AIMS: To investigate the association between levels of highly sensitive troponin I (hs-troponin I) and mortality in novel coronavirus disease 2019 (COVID-19) patients with cardiac injury. METHODS AND RESULTS: We retrospectively reviewed the medical records of all COVID-19 patients with increased levels of hs-troponin I from two hospitals in Wuhan, China. Demographic information, laboratory test results, cardiac ultrasonographic findings, and electrocardiograms were collected, and their predictive value on in-hospital mortality was explored using multivariable logistic regression. Of 1500 patients screened, 242 COVID-19 patients were enrolled in our study. Their median age was 68 years, and (48.8%) had underlying cardiovascular diseases. One hundred and seventy-six (72.7%) patients died during hospitalization. Multivariable logistic regression showed that C-reactive protein (>75.5 mg/L), D-dimer (>1.5 µg/mL), and acute respiratory distress syndrome were risk factors of mortality, and the peak hs-troponin I levels (>259.4 pg/mL) instead of the hs-troponin I levels at admission was predictor of death. The area under the receiver operating characteristic curve of the peak levels of hs-troponin I for predicting in-hospital mortality was 0.79 (95% confidence interval, 0.73-0.86; sensitivity, 0.80; specificity, 0.72; P < 0.0001). CONCLUSION: Our results demonstrated that the risk of in-hospital death among COVID-19 patients with cardiac injury can be predicted by the peak levels of hs-troponin I during hospitalization and was significantly associated with oxygen supply-demand mismatch, inflammation, and coagulation.

A Novel Risk-Stratification Models of the High-Flow Nasal Cannula Therapy in COVID-19 Patients With Hypoxemic Respiratory Failure.

Background: High-flow nasal cannula (HFNC) has been recommended as a suitable choice for the management of coronavirus disease 2019 (COVID-19) patients with acute hypoxemic respiratory failure before mechanical ventilation (MV); however, delaying MV with HFNC therapy is still a dilemma between the technique and clinical management during the ongoing pandemic. Methods: Retrospective analysis of COVID-19 patients treated with HFNC therapy from four hospitals of Wuhan, China. Demographic information and clinical variables before, at, and shortly after HFNC initiation were collected and analyzed. A risk-stratification model of HFNC failure (the need for MV) was developed with the 324 patients of Jin Yin-tan Hospital and validated its accuracy with 69 patients of other hospitals. Results: Among the training cohort, the median duration of HFNC therapy was 6 (range, 3-11), and 147 experienced HFNC failure within 7 days of HFNC initiation. Early predictors of HFNC failure on the basis of a multivariate regression analysis included age older than 60 years [odds ratio (OR), 1.93; 95% confidence interval (CI), 1.08-3.44; p = 0.027; 2 points], respiratory rate-oxygenation index (ROX) <5.31 (OR, 5.22; 95% CI, 2.96-9.20; p < 0.001; 5 points) within the first 4 h of HFNC initiation, platelets < 125 × 109/L (OR, 3.04; 95% CI, 1.46-6.35; p = 0.003; 3 points), and interleukin 6 (IL-6) >7.0 pg/mL (OR, 3.34; 95% CI, 1.79-6.23; p < 0.001; 3 points) at HFNC initiation. A weighted risk-stratification model of these predictors showed sensitivity of 80.3%, specificity of 71.2% and a better predictive ability than ROX index alone [area under the curve (AUC) = 0.807 vs. 0.779, p < 0.001]. Six points were used as a cutoff value for the risk of HFNC failure stratification. The HFNC success probability of patients in low-risk group (84.2%) was 9.84 times that in the high-risk group (34.8%). In the subsequent validation cohort, the AUC of the model was 0.815 (0.71-0.92). Conclusions: Aged patients with lower ROX index, thrombocytopenia, and elevated IL-6 values are at increased risk of HFNC failure. The risk-stratification models accurately predicted the HFNC failure and early stratified COVID-19 patients with HFNC therapy into relevant risk categories.

Lung ultrasound assessment of acute respiratory distress syndrome caused by coronavirus disease 2019: An observational study

Background:An outbreak of coronavirus disease 2019 (COVID-19) took place in Wuhan, China, by the end of 2019, and the disease continues to spread all over the world. The number of patients is increasing rapidly, a large number of infected patients is critically ill, and the mortality is high. However, information on COVID-19 patients is limited, and its clinical characteristics have not been fully studied.Objectives:To compare the performances of point-of-care lung ultrasound (LUS) and bedside chest X-ray in assessing the condition of COVID-19 patients with acute respiratory distress syndrome (ARDS).Methods:This observational study enrolled 42 COVID-19 patients with ARDS who were admitted to the Department of Critical Care Medicine of the Wuhan Union Hospital from February to April 2020. The point-of-care LUS characteristics of the COVID-19 patients with ARDS were summarized, and the performances of LUS and bedside chest X-ray in assessing the patient?s condition were compared.Results:Most of the 42 patients were elderly individuals with chronic clinical diseases. The proportion of patients older than 60?years old was 85.7%. All patients were given invasive mechanical ventilation;eight (19.0%) of them received venovenous extracorporeal membrane oxygenation support. LUS has evident advantages in detecting lung consolidation, patchy shadows, and pleural thickening, and pleural line changes in particular. The receiver operating characteristic analysis indicated that the sensitivity, Youden index, and kappa value for detecting COVID-19 patients with ARDS were higher for LUS than the chest X-ray.Conclusion:LUS has better diagnostic accuracy and sensitivity in COVID-19 patients with ARDS than the chest X-ray.

Clinical course and predictors of 60-day mortality in 239 critically ill patients with COVID-19: a multicenter retrospective study from Wuhan, China.

BACKGROUND: The global numbers of confirmed cases and deceased critically ill patients with COVID-19 are increasing. However, the clinical course, and the 60-day mortality and its predictors in critically ill patients have not been fully elucidated. The aim of this study is to identify the clinical course, and 60-day mortality and its predictors in critically ill patients with COVID-19. METHODS: Critically ill adult patients admitted to intensive care units (ICUs) from 3 hospitals in Wuhan, China, were included. Data on demographic information, preexisting comorbidities, laboratory findings at ICU admission, treatments, clinical outcomes, and results of SARS-CoV-2 RNA tests and of serum SARS-CoV-2 IgM were collected including the duration between symptom onset and negative conversion of SARS-CoV-2 RNA. RESULTS: Of 1748 patients with COVID-19, 239 (13.7%) critically ill patients were included. Complications included acute respiratory distress syndrome (ARDS) in 164 (68.6%) patients, coagulopathy in 150 (62.7%) patients, acute cardiac injury in 103 (43.1%) patients, and acute kidney injury (AKI) in 119 (49.8%) patients, which occurred 15.5 days, 17 days, 18.5 days, and 19 days after the symptom onset, respectively. The median duration of the negative conversion of SARS-CoV-2 RNA was 30 (range 6-81) days in 49 critically ill survivors that were identified. A total of 147 (61.5%) patients deceased by 60 days after ICU admission. The median duration between ICU admission and decease was 12 (range 3-36). Cox proportional-hazards regression analysis revealed that age older than 65 years, thrombocytopenia at ICU admission, ARDS, and AKI independently predicted the 60-day mortality. CONCLUSIONS: Severe complications are common and the 60-day mortality of critically ill patients with COVID-19 is considerably high. The duration of the negative conversion of SARS-CoV-2 RNA and its association with the severity of critically ill patients with COVID-19 should be seriously considered and further studied.

Clinical Characteristics of Children with Coronavirus Disease 2019 in Hubei, China.

Since December 2019, COVID-19 has occurred unexpectedly and emerged as a health problem worldwide. Despite the rapidly increasing number of cases in subsequent weeks, the clinical characteristics of pediatric cases are rarely described. A cross-sectional multicenter study was carried out in 10 hospitals across Hubei province. A total of 25 confirmed pediatric cases of COVID-19 were collected. The demographic data, epidemiological history, underlying diseases, clinical manifestations, laboratory and radiological data, treatments, and outcomes were analyzed. Of 25 hospitalized patients with COVID-19, the boy to girl ratio was 1.27:1. The median age was 3 years. COVID-19 cases in children aged <3 years, 3.6 years, and ≥6-years patients were 10 (40%), 6 (24%), and 9 (36%), respectively. The most common symptoms at onset of illness were fever (13 [52%]), and dry cough (11 [44%]). Chest CT images showed essential normal in 8 cases (33.3%), unilateral involvement of lungs in 5 cases (20.8%), and bilateral involvement in 11 cases (45.8%). Clinical diagnoses included upper respiratory tract infection (n=8), mild pneumonia (n=15), and critical cases (n=2). Two critical cases (8%) were given invasive mechanical ventilation, corticosteroids, and immunoglobulin. The symptoms in 24 (96%) of 25 patients were alleviated and one patient had been discharged. It was concluded that children were susceptible to COVID-19 like adults, while the clinical presentations and outcomes were more favorable in children. However, children less than 3 years old accounted for majority cases and critical cases lied in this age group, which demanded extra attentions during home caring and hospitalization treatment.

Masked Face Recognition Dataset and Application (preprint)

In order to effectively prevent the spread of COVID-19 virus, almost everyone wears a mask during coronavirus epidemic. This almost makes conventional facial recognition technology ineffective in many cases, such as community access control, face access control, facial attendance, facial security checks at train stations, etc. Therefore, it is very urgent to improve the recognition performance of the existing face recognition technology on the masked faces. Most current advanced face recognition approaches are designed based on deep learning, which depend on a large number of face samples. However, at present, there are no publicly available masked face recognition datasets. To this end, this work proposes three types of masked face datasets, including Masked Face Detection Dataset (MFDD), Real-world Masked Face Recognition Dataset (RMFRD) and Simulated Masked Face Recognition Dataset (SMFRD). Among them, to the best of our knowledge, RMFRD is currently theworld's largest real-world masked face dataset. These datasets are freely available to industry and academia, based on which various applications on masked faces can be developed. The multi-granularity masked face recognition model we developed achieves 95% accuracy, exceeding the results reported by the industry. Our datasets are available at: https://github.com/X-zhangyang/Real-World-Masked-Face-Dataset.