LSR is a cell-intrinsic defence factor against SARS-CoV-2 infection in small intestine (preprint)

The identification of host factors with antiviral potential is important for developing effective prevention as well as therapeutic strategies against SARS-CoV-2. Here, we have identified the lipolysis-stimulated lipoprotein receptor (LSR) as a crucial host-defense factor against SARS-CoV-2 infection in small intestine using immortalized cell lines, intestinal organoids, ex vivo intestinal tissues, and humanized ACE2 mouse model as proof-of-principle systems. Loss of endogenous LSR enhances ACE2-dependent infection by pseudotyped virus and authentic SARS-CoV-2 virus, and exogenous administration of LSR protect against viral infection. Mechanistically, LSR interacts with ACE2 both in cis and in trans, preventing its binding to Spike protein, and thus blocking viral entry and restricting Spike-mediated cell-cell fusion. These results identify both a previously unknown function for LSR and an associated antiviral host defense mechanism against SARS-CoV-2. The capacity of a small LSR-derived peptide to block Spike binding to the ACE2 receptor holds promise for pan-variant therapeutic interventions.

A Transformer-based representation-learning model with unified processing of multimodal input for clinical diagnostics (preprint)

During the diagnostic process, clinicians leverage multimodal information, such as chief complaints, medical images, and laboratory-test results. Deep-learning models for aiding diagnosis have yet to meet this requirement. Here we report a Transformer-based representation-learning model as a clinical diagnostic aid that processes multimodal input in a unified manner. Rather than learning modality-specific features, the model uses embedding layers to convert images and unstructured and structured text into visual tokens and text tokens, and bidirectional blocks with intramodal and intermodal attention to learn a holistic representation of radiographs, the unstructured chief complaint and clinical history, structured clinical information such as laboratory-test results and patient demographic information. The unified model outperformed an image-only model and non-unified multimodal diagnosis models in the identification of pulmonary diseases (by 12% and 9%, respectively) and in the prediction of adverse clinical outcomes in patients with COVID-19 (by 29% and 7%, respectively). Leveraging unified multimodal Transformer-based models may help streamline triage of patients and facilitate the clinical decision process.

Analysis on SARS-CoV-2 contamination in the environment exposure to the SARS-CoV-2 cases in Huangpu District of Shanghai in 2022

Objective: To analyze the detection of SARS-CoV-2 in household environment and public place environment of Huangpu District, and describe the feature of SARS-CoV-2 contamination in the environment exposure to the infected cases, so as to support the control strategies such as disinfection and health communication.

Influence of A Public Health Emergency On Care For Patients With Duchenne Muscular Dystrophy: An Online, Cross-Sectional Survey (preprint)

Background: The public health emergency has created challenges for the care of patients, particularly those with chronic diseases such as Duchenne muscular dystrophy. To elucidate the challenges faced by Chinese patients with Duchenne muscular dystrophy during the public health emergency coronavirus disease 2019 pandemic, we conducted an online cross-sectional survey, the responses of which were collected between March 27 and June 30, 2021. Results: : In total, valid questionnaire responses were obtained from 2,105 patients, of whom 49 lived in pandemic lockdown areas. Of the 2,056 responders from non-lockdown areas, 42.8% reduced their outside daily activities, 49.4% reduced their use of rehabilitation services, 39.7% postponed regular follow-up appointments, and 40.8% complained of accelerated declines in motor function over the previous year. The corresponding figures for the 49 participants from lockdown areas were almost all higher, with 67.3% reducing outside daily activities, 44.9% reducing their use of rehabilitation services, 79.6% postponing regular follow-up appointments, and 55.1% complaining of accelerated declines in motor function. When asked whether they expected more assistance from society than they had received before the pandemic, 60.8% of patients in non-lockdown areas and 87.8% of those in lockdown areas responded affirmatively. When asked whether they felt more anxious than they had before the pandemic and needed psychological counseling, 11.5% of respondents in non-lockdown areas and 18.4% of respondents in lockdown areas responded affirmatively. In non-lockdown areas, 76% of respondents had at least one telemedicine visit, and 71% of them thought that telemedicine was helpful. In lockdown areas, 91.8% had used telemedicine at least once, and 66.7% of them found it helpful. Conclusions: : These public health emergency control measures have affected the care of patients with chronic diseases worldwide, particularly pronounced in lockdown areas. It is imperative that healthcare workers assist patients and establish more robust chronic disease management systems. Telemedicine is an effective model for providing healthcare to such patients.

Targeting CTP Synthetase 1 to Restore Interferon Induction and Impede Nucleotide Synthesis in SARS-CoV-2 Infection (preprint)

The newly emerged SARS-CoV-2 caused a global pandemic with astonishing mortality and morbidity. The mechanisms underpinning its highly infectious nature remain poorly understood. We report here that SARS-CoV-2 exploits cellular CTP synthetase 1 (CTPS1) to promote CTP synthesis and suppress interferon (IFN) induction. Screening a SARS-CoV-2 expression library identified ORF7b and ORF8 that suppressed IFN induction via inducing the deamidation of interferon regulatory factor 3 (IRF3). Deamidated IRF3 fails to bind the promoters of classic IRF3-responsible genes, thus muting IFN induction. Conversely, a shRNA-mediated screen focused on cellular glutamine amidotransferases corroborated that CTPS1 deamidates IRF3 to inhibit IFN induction. Functionally, ORF7b and ORF8 activate CTPS1 to promote de novo CTP synthesis while shutting down IFN induction. De novo synthesis of small-molecule inhibitors of CTPS1 enabled CTP depletion and IFN induction in SARS-CoV-2 infection, thus impeding SARS-CoV-2 replication. Our work uncovers a strategy that a viral pathogen couples immune evasion to metabolic activation to fuel viral replication. Inhibition of the cellular CTPS1 offers an attractive means for developing antiviral therapy that would be resistant to SARS-CoV-2 mutation.

CT-based Rapid Triage of COVID-19 Patients: Risk Prediction and Progression Estimation of ICU Admission, Mechanical Ventilation, and Death of Hospitalized Patients (preprint)

The wave of COVID-19 continues to overwhelm the medical resources, especially the stressed intensive care unit (ICU) capacity and the shortage of mechanical ventilation (MV). Here we performed CT-based analysis combined with electronic health records and clinical laboratory results on Cohort 1 (n = 1662 from 17 hospitals) with prognostic estimation for the rapid stratification of PCR confirmed COVID-19 patients. These models, validated on Cohort 2 (n = 700) and Cohort 3 (n = 662) constructed from 9 external hospitals, achieved satisfying performance for predicting ICU, MV and death of COVID-19 patients (AUROC 0.916, 0.919 and 0.853), even on events happened two days later after admission (AUROC 0.919, 0.943 and 0.856). Both clinical and image features showed complementary roles in events prediction and provided accurate estimates to the time of progression (p

The Psychological impact on the front-line medical staff during the recuperation after fighting against COVID-19 in China (preprint)

Background At the beginning of 2020, the novel corona virus disease (COVID-19) broke out in Wuhan (China) on a large scale. Medical staff from all over the country quickly supported Wuhan and put into combat. In May 2020, the epidemic has been effectively controlled, and medical staff withdrew from Wuhan and entered into recuperation. Methods During the recuperation in March and June, 2020, 441 medical staff were participated to investigate the psychological symptoms on SCL-90. Student's t-test and one-way analysis of variance were chosen to analyze the data. Results Of the 441 participants, the positive ratio (i ≥ 2) of the ten dimensions and the average score of SCL-90 was from 3.17% to 13.61%. Compared respectively with the medical staff in front-line and the Chinese norms, the scores obviously decreased during the recuperation. Gender, occupation, professional ranks and titles, working position in Wuhan and the patient’s condition affected the scores of SCL-90, age and educational attainment had little effect. Conclusions These results showed that the recuperation had the positive impact on the psychological status of the medical staff after fighting against COVID-19, which is worthy of further promotion. Our findings also showed that a small number of medical staff still had the risk on the mental problem, which need continuous attention and intervention.

Psychological symptoms of the front-line medical staff during the recuperation after fighting against COVID-19 in China (preprint)

BackgroundAt the beginning of 2020, COVID-19 broke out in Wuhan, China. Medical staff from all over the country quickly supported Wuhan and put into combat. In May 2020, the epidemic has been effectively controlled, and medical staff withdrew from Wuhan and entered into recuperation. MethodsDuring the recuperation in March and June, 2020, 441 medical staff were participated to investigate the psychological symptoms on SCL-90. Student's t-test and one-way analysis of variance were chosen to analyze the data. ResultsOf the 441 participants, the positive ratio (i ≥ 2) of the ten dimensions and the average score of SCL-90 was from 3.17% to 13.61%. Compared respectively with the medical staff in front-line and the Chinese norms, the scores obviously decreased during the recuperation. Gender, occupation, professional ranks and titles, working position in Wuhan and the patient’s condition affected the scores of SCL-90, age and educational attainment had little effect. ConclusionsThese results showed that the recuperation had the positive impact on the psychological status of the medical staff after fighting against COVID-19, which is worthy of further promotion. Our findings also showed that a small number of medical staff still had the risk on the mental problem, which need continuous attention and intervention.