Integrated Organ Immunity: Antigen-specific CD4-T cell-derived IFN-γ induced by BCG imprints prolonged lung innate resistance against respiratory viruses (preprint)

Bacille Calmette-Guerin (BCG) vaccination can confer non-specific protection against heterologous pathogens. However, the underlying mechanisms remain mysterious. Here, we show that mice immunized intravenously with BCG exhibited reduced weight loss and/or improved viral clearance when challenged with SARS-CoV-2 and influenza. Protection was first evident between 14 - 21 days post vaccination, and lasted for at least 42 days. Remarkably, BCG induced a biphasic innate response in the lung, initially at day 1 and a subsequent prolonged phase starting at ~15 days post vaccination, and robust antigen-specific Th1 responses. MyD88-dependent TLR signaling was essential for the induction of the innate and Th1 responses, and protection against SARS-CoV-2. Depletion of CD4+ T cells or IFN-{gamma} activity prior to infection obliterated innate activation and protection. Single cell and spatial transcriptomics revealed CD4-dependent expression of interferon-stimulated genes (ISGs) in myeloid, type II alveolar and lung epithelial cells. Thus, BCG elicits "integrated organ immunity" where CD4+ T cells act on local myeloid and epithelial cells to imprint prolonged antiviral innate resistance.

Using Contactless Facial Image Recognition Technology to Detect Blood Oxygen Saturation.

Since the outbreak of COVID-19, as of January 2023, there have been over 670 million cases and more than 6.8 million deaths worldwide. Infections can cause inflammation in the lungs and decrease blood oxygen levels, which can lead to breathing difficulties and endanger life. As the situation continues to escalate, non-contact machines are used to assist patients at home to monitor their blood oxygen levels without encountering others. This paper uses a general network camera to capture the forehead area of a person's face, using the RPPG (remote photoplethysmography) principle. Then, image signal processing of red and blue light waves is carried out. By utilizing the principle of light reflection, the standard deviation and mean are calculated, and the blood oxygen saturation is computed. Finally, the effect of illuminance on the experimental values is discussed. The experimental results of this paper were compared with a blood oxygen meter certified by the Ministry of Health and Welfare in Taiwan, and the experimental results had only a maximum error of 2%, which is better than the 3% to 5% error rates in other studies The measurement time was only 30 s, which is better than the one minute reported using similar equipment in other studies. Therefore, this paper not only saves equipment expenses but also provides convenience and safety for those who need to monitor their blood oxygen levels at home. Future applications can combine the SpO2 detection software with camera-equipped devices such as smartphones and laptops. The public can detect SpO2 on their own mobile devices, providing a convenient and effective tool for personal health management.

[Clinical features of severe acute respiratory syndrome coronavirus 2 Omicron variant infection in children: an analysis of 201 cases]. / 201ä¾‹å„¿ç«¥æ–°åž‹å† çŠ¶ç— æ¯’Omicronå˜å¼‚æ ªæ„ŸæŸ“çš„ä¸´åºŠç‰¹å¾åˆ†æž.

OBJECTIVES: To study the clinical features of children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection. METHODS: A retrospective analysis was performed on the medical data of 201 children with coronavirus disease 2019 (COVID-19) who were hospitalized and diagnosed with SARS-CoV-2 Omicron variant infection in Quanzhou First Hospital from March 14 to April 7, 2022. Among the 201 children, there were 34 children with asymptomatic infection and 167 with symptomatic infection. The two groups were compared in terms of clinical features, results of experimental examinations, and outcome. RESULTS: Of all the 201 children, 161 (80.1%) had a history of exposure to COVID-19 patients and 132 (65.7%) had a history of COVID-19 vaccination. Among the 167 children with symptomatic infections, 151 had mild COVID-19 and 16 had common COVID-19, with no severe infection or death. Among the 101 children who underwent chest CT examination, 16 had ground glass changes and 20 had nodular or linear opacities. The mean time to nucleic acid clearance was (14±4) days for the 201 children with Omicron variant infection, and the symptomatic infection group had a significantly longer time than the asymptomatic infection group [(15±4) days vs (11±4) days, P<0.05]. The group vaccinated with one or two doses of COVID-19 vaccine had a significantly higher positive rate of IgG than the group without vaccination (P<0.05). The proportions of children with increased blood lymphocyte count in the symptomatic infection group was significantly lower than that in the asymptomatic infection group (P<0.05). Compared with the asymptomatic infection group, the symptomatic infection group had significantly higher proportions of children with increased interleukin-6, increased fibrinogen, and increased D-dimer (P<0.05). CONCLUSIONS: Most of the children with Omicron variant infection have clinical symptoms, which are generally mild. The children with symptomatic infection are often accompanied by decreased or normal blood lymphocyte count and increased levels of interleukin-6, fibrinogen, and D-dimer, with a relatively long time to nucleic acid clearance. Some of them had ground glass changes on chest CT.

Characterization of Newly Diagnosed Type 1 Diabetes in Children and Adolescents from 2017–2022 in China: A Single-center Analysis (preprint)

OBJECTIVE This study investigated the characteristics of newly diagnosed type 1 diabetes mellitus (T1DM) related to autoimmunity and the frequency of diabetic ketoacidosis (DKA) in children and adolescents from 2017–2022 in China.RESEARCH DESIGN AND METHODS Single-center regional data from the Department of Pediatric Endocrinology, Tongji Hospital, were used to compare 88 children and adolescents newly diagnosed with T1DM from 2020 to 2022 (i.e. during the COVID-19 pandemic in China) and 76 children and adolescents diagnosed with T1DM from 2017 to 2019. Auto-antibodies, including glutamic acid decarboxylase-65 and insulin auto-antibodies, were detected by enzyme-linked immunoassays. DKA was defined as a pH < 7.3 and/or a bicarbonate level < 15 mmol/L.RESULTS The median age of the 164 children and adolescents newly diagnosed with T1DM from 2017 to 2022 was 7.0 years (interquartile range [IQR]: 3.8–10.0 years; 51.83% male). The mean annual incidence of T1DM was 4.25/100,000. The estimated frequency of auto-antibody positivity was 51.22% (n = 84), and there was no difference between the 2020–2022 group and 2017–2019 group (55.68% [n = 49] vs. 46.5% [n = 35]; p = 0.219). The incidence of DKA among the entire cohort was 57.93% (n = 95). The frequency of DKA was not significantly higher in the 2020–2022 group compared with the 2017–2019 group (60.23% [n = 53] vs. 55.26% [n = 42]; p = 0.521). We found no significant difference in the frequency of DKA between patients who were negative vs. positive for auto-antibodies in the 2020–2022 group (64.10% [n = 25] vs. 57.14% [n = 28], p > 0.05). The C-peptide level and HbA1c (%) were positively correlated with onset age (R1 = 0.389, p < 0.01; R2 = 0.371, p < 0.01), and the estimated mean C-peptide level was 0.26 ng/ml (IQR: 0.2–0.4 ng/ml) in patients with DKA and 0.370 ng/ml (IQR: 0.2–0.6 ng/ml) in patients without DKA (p = 0.044).CONCLUSIONS This study showed the annual incidence of T1DM was 4.25/100,000, gradually increased over the study period, and there was no significant increase in T1DM with auto-antibody positivity in children and adolescents newly diagnosed from 2020–2022 in China compared with the previous 3 years. Furthermore, the frequencies of DKA were not significantly different between patients who were negative vs. positive for auto-antibodies.

Personal Protective Equipment Waste Management Behavior of Undergraduates in Xi'an City: Extended Theory of Value-Identity-Personal Norm Model (preprint)

The COVID-19 pandemic has changed people’s lives, with the most prominent change being the use of personal protective equipment (PPE). In this study, we used the extended Value-Identity-Personal (VIP) norm model to empirically analyze the influencing factors of pro-environmental behavior (PEB) among college students in Xi 'an, China, while considering the usage of PPE as an example of PEB. We proposed nine hypothetical questions, and the VIP model was established through the SmartPLS software to test the valid questionnaires of 414 college students. The verification results indicated that all the nine hypotheses were supported statistically, with personal environmental social responsibility and personal norms showing the most significant direct impact on PEB; notably, personal norms were also strongly influenced by environmental personal social responsibility. Biosphere values affected PEB indirectly, through self-identity and individual norms. This study proposes viable countermeasures and suggestions for college students to improve PEB; our findings can serve as a reference for policymakers and stakeholders to ensure the effective waste management of personal safety equipment.

Epidemiological characteristics of traumatic spinal cord injuries in a multicenter retrospective study in northwest China, 2017-2020.

Background: Traumatic spinal cord injuries (TSCIs) are worldwide public health problems that are difficult to cure and impose a substantial economic burden on society. There has been a lack of extensive multicenter review of TSCI epidemiology in northwest China during the Corona Virus Disease 2019 (COVID-19) pandemic. Method: A multicenter retrospective study of 14 selected hospitals in two provinces in northwest China was conducted on patients admitted for TSCI between 2017 and 2020. Variables assessed included patient demographics, etiology, segmental distribution, treatment, waiting time for treatment, and outcomes. Results: The number of patients with TSCI showed an increasing trend from 2017 to 2019, while there were 12.8% fewer patients in 2020 than in 2019. The male-to-female ratio was 3.67:1, and the mean age was 48 ± 14.9 years. The primary cause of TSCI was high falls (38.8%), slip falls/low falls (27.7%), traffic accidents (23.9%), sports (2.6%), and other factors (7.0%). The segmental distribution showed a bimodal pattern, peak segments were C6 and L1 vertebra, L1 (14.7%), T12 (8.2%), and C6 (8.2%) were the most frequently injured segments. In terms of severity, incomplete injury (72.8%) occurred more often than complete injury (27.2%). The American Spinal Injury Association impairment scale of most patients did not convert before and after treatment in the operational group (71.6%) or the conservative group (80.6%). A total of 975 patients (37.2%) from urban and 1,646 patients (62.8%) from rural areas were included; almost all urban residents could rush to get treatment after being injured immediately (<1 h), whereas most rural patients get the treatment needed 4-7 h after injury. The rough annual incidence from 2017 to 2020 is 112.4, 143.4, 152.2, and 132.6 per million people, calculated by the coverage rate of the population of the sampling hospital. Conclusion: The incidence of TSCI in northwest China is high and on the rise. However, due to pandemic policy reasons, the incidence of urban residents decreased in 2020. The promotion of online work may be an effective primary prevention measure for traumatic diseases. Also, because of the further distance from the good conditional hospital, rural patients need to spend more time there, and the timely treatment of patients from remote areas should be paid attention to.

A single-nucleus and spatial transcriptomic atlas of the COVID-19 liver reveals topological, functional, and regenerative organ disruption in patients (preprint)

The molecular underpinnings of organ dysfunction in acute COVID-19 and its potential long-term sequelae are under intense investigation. To shed light on these in the context of liver function, we performed single-nucleus RNA-seq and spatial transcriptomic profiling of livers from 17 COVID-19 decedents. We identified hepatocytes positive for SARS-CoV-2 RNA with an expression phenotype resembling infected lung epithelial cells. Integrated analysis and comparisons with healthy controls revealed extensive changes in the cellular composition and expression states in COVID-19 liver, reflecting hepatocellular injury, ductular reaction, pathologic vascular expansion, and fibrogenesis. We also observed Kupffer cell proliferation and erythrocyte progenitors for the first time in a human liver single-cell atlas, resembling similar responses in liver injury in mice and in sepsis, respectively. Despite the absence of a clinical acute liver injury phenotype, endothelial cell composition was dramatically impacted in COVID-19, concomitantly with extensive alterations and profibrogenic activation of reactive cholangiocytes and mesenchymal cells. Our atlas provides novel insights into liver physiology and pathology in COVID-19 and forms a foundational resource for its investigation and understanding.

Dental interns’ perception toward online learning of complete denture rehabilitation: a questionnaire survey (preprint)

Background: Students' internship year is critical for dental interns to develop the skills and knowledge to perform complete denture rehabilitation (CDR). Online learning is recommended because students can't go to the clinic with the outbreak of COVID-19. This study aims to assess students' intentions toward online learning to improve teaching quality and ensure students master the CDR. Methods: A questionnaire-based online survey was conducted to evaluate internship students’ background and attitudes to online learning of CDR. The questionnaire consists of three parts and 20 structured questions regarding students’ experience with online learning, students’ knowledge background about CDR, and students’ attitude about online learning CDR. 63 dental interns, including 19 male and 44 female undergraduate dental students, participated in this survey. Results: 93.65% of the 63 students have participated in online learning, 76.19% believe it is necessary to provide online instruction, and 80.95 % plan to join in the future. 71.42% of the students think they are ready for online learning on CDR. Then, we evaluated students’ knowledge background about CDR. Survey results indicate most students believe they are unprepared to perform CDR in the clinic and only a small percentage of students are familiar with the diagnosis, treatment process, and operation of CDR. Fortunately, interns are incredibly optimistic about the prospect of learning complete dentures online. According to our survey, 60.90% of students enjoy learning online, 71.43% are motivated to continue online learning, and 82.54% believe online learning of CDR is helpful. Conclusion: According to the survey results, adopting online learning may be a practical solution to guarantee students' quality of oral clinical placements and address the growing shortage of clinical placement opportunities worldwide. Furthermore, the effectiveness and efficiency of online learning need to be further evaluated to ensure they can enhance dental interns’ knowledge level and practical ability of CDR.

Epidemiological investigation on a cluster epidemic of COVID-19 in Taizhou, Zhejiang Province

Objective: To analyze the epidemiological characteristics of a family and workplace clustering of COVID-19, identify the source of infection and the transmission chain, and provide evidence for prevention and control of COVID-19 pandemic. Method: Field epidemiological method was used to conduct the investigation of confirmed cases and close contacts in this cluster. Data were analyzed with descriptive method. Real-time fluorescent quantitative PCR (RT-PCR) was used to detect the novel coronavirus nucleic acid in the collected respiratory tract samples.

A model of persistent post SARS-CoV-2 induced lung disease for target identification and testing of therapeutic strategies (preprint)

COVID-19 survivors develop post-acute sequelae of SARS-CoV-2 (PASC), but the mechanistic basis of PASC-associated lung abnormalities suffers from a lack of longitudinal samples. Mouse-adapted SARS-CoV-2 MA10 produces an acute respiratory distress syndrome (ARDS) in mice similar to humans. To investigate PASC pathogenesis, studies of MA10-infected mice were extended from acute disease through clinical recovery. At 15-120 days post-virus clearance, histologic evaluation identified subpleural lesions containing collagen, proliferative fibroblasts, and chronic inflammation with tertiary lymphoid structures. Longitudinal spatial transcriptional profiling identified global reparative and fibrotic pathways dysregulated in diseased regions, similar to human COVID-19. Populations of alveolar intermediate cells, coupled with focal upregulation of pro-fibrotic markers, were identified in persistently diseased regions. Early intervention with antiviral EIDD-2801 reduced chronic disease, and early anti-fibrotic agent (nintedanib) intervention modified early disease severity. This murine model provides opportunities to identify pathways associated with persistent SARS-CoV-2 pulmonary disease and test countermeasures to ameliorate PASC.

Assessment of the factors affecting health profession students' emergency transition during the COVID-19 pandemic: A cross-sectional study.

Objective: This study aimed to identify the factors that affected health profession students' emergency transition during the COVID-19 pandemic and to explore strategies that may help students be better prepared for any future health crises. Participants: This study population included 73 students that were originally enrolled in one online section (n = 49) and one face-to-face section (n = 24) of a healthcare administration course before the transition. Methods: The cross-sectional study was conducted and the anonymous survey data were analyzed using SPSS and a Man-Whitney U test. Results: Of the 73 students, 48 completed the survey, with a response rate of 66% (48/73). There was a statistically significant difference in the perceived COVID-19 impact (z=-3.339, p = 0.001) and difficulty transitioning during the pandemic (3-2.142, p = 0.032) between both groups. The top three hindering factors were stress and anxiety, difficulty focusing on studying at home, and time management due to uncertainty. Conclusions: The study findings suggest strategies that may help students with adequate knowledge and capabilities in managing stress, anxiety, and unprecedented challenges in the future.

The Blood-Brain Barrier is Dysregulated in COVID-19 and Serves as a CNS Entry Route for SARS-CoV-2 (preprint)

Neurological complications are common in COVID-19 patients. Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been detected in patients’ brain tissues, its entry routes and resulting consequences are not well understood. Here, we report that the blood-brain barrier (BBB) and its microenvironment show pronounced upregulation of interferon signaling pathways in fatal COVID-19. Moreover, human induced pluripotent stem cell (hiPSC)-derived brain capillary endothelial-like cells (BCECs) were susceptible to SARS-CoV-2 infection and recapitulated the transcriptional changes detected in vivo . While BCECs were not compromised in their paracellular tightness, we found SARS-CoV-2 in the basolateral compartment in transwell assays after apical infection, suggesting active transcytosis of the virus across the BBB in vitro . SARS-CoV-2 entry into BCECs could be reduced by anti-spike-, anti-ACE2- and anti-NRP1-specific antibodies or the TMPRSS2 inhibitor nafamostat. Together, our data provide direct evidence for SARS-CoV-2 brain entry across the BBB resulting in an increase in interferon signaling.

Postoperative Onset and Detection of SARS-CoV-2 in Surgically Resected Specimens From Gastrointestinal Cancer Patients With Pre/Asymptomatic COVID-19.

OBJECTIVE: To describe the epidemiologic features and clinical courses of gastrointestinal cancer patients with pre/asymptomatic COVID-19 and to explore evidence of SARS-CoV-2 in the surgically resected specimens. SUMMARY BACKGROUND DATA: The advisory of postponing or canceling elective surgeries escalated a worldwide debate regarding the safety and feasibility of performing elective surgical procedures during this pandemic. Limited data are available on gastrointestinal cancer patients with pre/asymptomatic COVID-19 undergoing surgery. METHODS: Clinical data were retrospectively collected and analyzed. Surgically resected specimens of the cases with confirmed COVID-19 were obtained to detect the expression of ACE2 and the presence of SARS-CoV-2. RESULTS: A total of 52 patients (male, 34) with a median age 62.5 years were enrolled. All the patients presented no respiratory symptoms or abnormalities on chest computed tomography before surgery. Six patients (11.5%) experienced symptom onset and were confirmed to be COVID-19. All were identified to be preoperatively pre/asymptomatic, as 5 were with SARS-CoV-2 presenting in cytoplasm of enterocytes or macrophages from the colorectal tissues and 1 had symptom onset immediately after surgery. The case fatality rate in patients with COVID-19 was 16.7%, much higher than those without COVID-19 (2.2%). CONCLUSIONS: Gastrointestinal cancer patients with pre/asymptomatic COVID-19 were at high risk of postoperative onset and death. At current pandemic, elective surgery should be postponed or canceled. It highlights the need for investigating the full clinical spectrum and natural history of this infection. The early colorectal tropism of SARS-CoV-2 may have major implications on prevention, diagnosis, and treatment of COVID-19.

A valid protective immune response elicited in rhesus macaques by an inactivated vaccine is capable of defending against SARS-CoV-2 infection (preprint)

With the relatively serious global epidemic outbreak of SARS-CoV-2 infection, public concerns focus on not only clinical therapeutic measures and public quarantine for this disease but also the development of vaccines. The technical design of our SARS-CoV-2 inactivated vaccine provides a viral antigen that enables the exposure of more than one structural protein based upon the antibody composition of COVID-19 patients convalescent serum. This design led to valid immunity with increasing neutralizing antibody titers and a CTL response detected post-immunization of this vaccine by two injections in rhesus macaques. Further, this elicited immunoprotection in macaques enables not only to restrain completely viral replication in tissues of immunized animals, compared to the adjuvant control and those immunized by an RBD peptide vaccine, but also to significantly alleviate inflammatory lesion in lung tissues in histo-pathologic detection, compared to the adjuvant control with developed interstitial pneumonia. The data obtained from these macaques immunized with the inactivated vaccine or RBD peptide vaccine suggest that immunity with a clinically protective effect against SARS-CoV-2 infection should include not only specific neutralizing antibodies but also specific CTL responses against at least the S and N antigens.