S-RBD-modified and miR-486-5p-engineered exosomes derived from mesenchymal stem cells alleviate radiation-induced lung injury and long-term pulmonary fibrosis via suppression of ferroptosis (preprint)

Background Radiation-induced pulmonary fibrosis (RIPF) is a late-stage complication of therapeutic radiation, associated with poor prognosis and limited therapeutic options. Radiation-induced lung injury (RILI) is an early manifestation of RIPF, and intervention of RILI is an effective method for preventing long-term RIPF. Mesenchymal stem cell (MSC)-derived exosomes exhibit regenerative activity in injured lungs and are effective drug-delivery nanoparticles. SARS-CoV-2-S-RBD enables ACE2+ cell targeting of MSC extracellular vesicles. miR-486-5p is a multifunctional miRNA with angiogenic and anti-fibrotic activities and is enriched in MSC-derived exosomes. In this study, we investigated the therapeutic effects of miR-486-5p and SARS-COV-2-S-RBD-engineered MSC exosomes on RIPF in vitro and in vivo.Results Adenovirus-mediated gene modification led to the overexpression of miR-486-5p in umbilical cord MSCs (UC-MSCs), which further enriched miR-486-5p in UC-MSCs-derived exosomes. MiR-486-5p-engineered MSC exosomes (miR-486-MSC-Exo) promoted the proliferation and migration of irradiated MLE-12 cells in vitro and inhibited RILI in vivo. An in vitro assay revealed the occurrence of ferroptosis, a major form of cell death during radiation injury, indicated by the upregulated expression of fibrosis-related genes. miR-486-MSC-Exo effectively reversed these changes. MiR-486-MSC-Exo strongly reversed the upregulated expression of MLE-12 fibrosis-related genes induced by TGF in vitro and improved pathological fibrosis in the RIPF model in vivo. The distribution of RBD-VSVG-MSC exosomes labeled with DiR dye in hACE2CKI/CKI Sftpc-Cre+ mice demonstrated that the fluorescence of RBD-VSVG exosomes remained in the lungs for a long time. miR-486-RBD-MSC-exosomes significantly improved the survival rate and pathological changes in hACE2CKI/CKI Sftpc-Cre+ RIPF mice. Furthermore, miR-486-MSC-Exo exerted anti-fibrotic effects through targeted inhibition of SMAD2 and activation of Akt phosphorylation.Conclusions Here, miR-486-MSC-Exo inhibited lung injury and alleviated fibrosis in vivo and in vitro. Surface modification with COVID-S-RBD conferred engineered exosomes with the ability to target the lungs of animal models. The therapeutic effects of miR-486-5p and COVID-S-RBD-engineered MSC exosomes on RIPF were significantly enhanced. MSC-derived exosomes modified with recombinant COVID-S-RBD enabled targeted delivery of miR-486-5p, which is an effective approach for the treatment of RIPF.

A Prediction Model for Spot LNG Prices Based on Machine Learning Algorithms to Reduce Fluctuation Risks in Purchasing Prices

The ongoing Russia–Ukraine conflict has exacerbated the global crisis of natural gas supply, particularly in Europe. During the winter season, major importers of liquefied natural gas (LNG), such as South Korea and Japan, were directly affected by fluctuating spot LNG prices. This study aimed to use machine learning (ML) to predict the Japan Korea Marker (JKM), a spot LNG price index, to reduce price fluctuation risks for LNG importers such as the Korean Gas Corporation (KOGAS). Hence, price prediction models were developed based on long short-term memory (LSTM), artificial neural network (ANN), and support vector machine (SVM) algorithms, which were used for time series data prediction. Eighty-seven variables were collected for JKM prediction, of which eight were selected for modeling. Four scenarios (scenarios A, B, C, and D) were devised and tested to analyze the effect of each variable on the performance of the models. Among the eight variables, JKM, national balancing point (NBP), and Brent price indexes demonstrated the largest effects on the performance of the ML models. In contrast, the variable of LNG import volume in China had the least effect. The LSTM model showed a mean absolute error (MAE) of 0.195, making it the best-performing algorithm. However, the LSTM model demonstrated a decreased in performance of at least 57% during the COVID-19 period, which raises concerns regarding the reliability of the test results obtained during that time. The study compared the ML models' prediction performances with those of the traditional statistical model, autoregressive integrated moving averages (ARIMA), to verify their effectiveness. The comparison results showed that the LSTM model's performance deviated by an MAE of 15–22%, which can be attributed to the constraints of the small dataset size and conceptual structural differences between the ML and ARIMA models. However, if a sufficiently large dataset can be secured for training, the ML model is expected to perform better than the ARIMA. Additionally, separate tests were conducted to predict the trends of JKM fluctuations and comprehensively validate the practicality of the ML models. Based on the test results, LSTM model, identified as the optimal ML algorithm, achieved a performance of 53% during the regular period and 57% d during the abnormal period (i.e., COVID-19). Subject matter experts agreed that the performance of the ML models could be improved through additional studies, ultimately reducing the risk of price fluctuations when purchasing spot LNG. [ FROM AUTHOR] Copyright of Energies (19961073) is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Parallel use of human stem cell lung and heart models provide insights for SARS-CoV-2 treatment.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily infects the respiratory tract, but pulmonary and cardiac complications occur in severe coronavirus disease 2019 (COVID-19). To elucidate molecular mechanisms in the lung and heart, we conducted paired experiments in human stem cell-derived lung alveolar type II (AT2) epithelial cell and cardiac cultures infected with SARS-CoV-2. With CRISPR-Cas9-mediated knockout of ACE2, we demonstrated that angiotensin-converting enzyme 2 (ACE2) was essential for SARS-CoV-2 infection of both cell types but that further processing in lung cells required TMPRSS2, while cardiac cells required the endosomal pathway. Host responses were significantly different; transcriptome profiling and phosphoproteomics responses depended strongly on the cell type. We identified several antiviral compounds with distinct antiviral and toxicity profiles in lung AT2 and cardiac cells, highlighting the importance of using several relevant cell types for evaluation of antiviral drugs. Our data provide new insights into rational drug combinations for effective treatment of a virus that affects multiple organ systems.

Precise Control of Digital Dental Unit to Reduce Aerosol and Splatter Production: New Challenges for Future Epidemics (preprint)

Background During dental procedures, critical parameters, such as cooling condition, speed of the rotary dental turbine (handpiece), and distance and angle from pollution sources, were evaluated for transmission risk of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), simulated by spiking in a plasmid encoding a modified viral spike protein, HexaPro (S6P), in droplets and aerosols.Methods To simulate routine operation in dental clinics, dental procedures were conducted on a dental manikin within a digital dental unit, incorporating different dental handpiece speeds and cooling conditions. The tooth model was immersed in Coomassie brilliant blue dye and was pre-coated with 100 µL water spiked-in with S6P-encoding plasmid. Furthermore, the manikin was surrounded by filter papers and Petri dishes positioned at different distances and angles. Subsequently, the filter papers and Petri dishes were collected to evaluate the aerosol splash points and the viral load of S6P-encoding plasmid in aerosols and splatters generated during the dental procedure.Results Aerosol splashing generated a localized pollution area extended up to 60 cm, with heightened contamination risks concentrated within a 30 cm radius. Significant differences in aerosol splash points and viral load by different turbine handpiece speeds under any cooling condition (P < 0.05) were detected. The highest level of aerosol splash points and viral load were observed when the handpiece speed was set at 40,000 rpm. Conversely, the lowest level of aerosol splash point and viral load were found at a handpiece speed of 10,000 rpm. Moreover, the aerosol splash points with higher viral load were more prominent in the positions of the operator and assistant compared to other positions. Additionally, the position of the operator exhibited the highest viral load among all positions.Conclusions To minimize the spread of aerosol and virus in clinics, dentists are supposed to adopt the minimal viable speed of a dental handpiece with limited cooling water during dental procedures. In addition, comprehensive personal protective equipment is necessary for both dental providers and dental assistants.

Video-Assisted Versus Traditional Problem-Based Learning: A Quasi-Experimental Study Among Pediatric Nursing Students.

BACKGROUND: The text-assisted problem-based, methods traditionally used to teach nursing students cannot adequately simulate holistic clinical situations and patient symptoms. Although video-assisted, problem-based learning methods combined with text have shown positive results in terms of improving comprehension and cognitive abilities, some studies have shown these methods to be inferior to text-assisted methods in terms of promoting deep critical thinking in medical students. PURPOSE: This study was designed to assess the benefits in nursing education of video-assisted, problem-based learning using online multimedia technologies compared with text-assisted, problem-based learning using traditional face-to-face classes. METHODS: A quasi-experimental, nonequivalent control group, preintervention-and-postintervention design was used. The experimental group ( n = 31) received video-assisted, problem-based learning materials with multimedia technologies (video scenarios, Google Docs worksheets, Google slides, Zoom cloud meetings, and e-learning management system) and weekly online lectures (100 minutes) for 4 weeks. The control group ( n = 35) received text-assisted, problem-based learning materials with traditional face-to-face classes and weekly lectures (100 minutes) for 4 weeks. The study data were analyzed using chi-square, Fisher's exact, and independent t tests as well as analysis of variance. RESULTS: At posttest, learning motivation ( t = 3.25, p = .002), academic self-efficacy ( t = 2.41, p = .019), and self-directed learning ( t = 3.08, p = .003) were significantly higher in the experimental group than in the control group. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Video-assisted, problem-based learning using multimedia technologies was shown to be effective in increasing learning motivation, academic self-efficacy, and self-directed learning in nursing students. These findings have implications for the development and planning of contactless classes in response to the coronavirus pandemic. Notably, no intergroup differences were found in terms of problem-solving skills. Future studies should include in-depth reviews and assessments of the difficulties faced in producing problem scenarios as well as the methods of instruction.

Impact of the COVID-19 Pandemic on Neonatal Nursing Practicum and Extended Reality Simulation Training Needs: A Descriptive and Cross-Sectional Study.

This study investigated the neonatal intensive care unit (NICU) clinical practicum status during the COVID-19 pandemic and the need for extended reality (XR)-based training for neonatal care. A structured questionnaire was distributed to 132 prelicensing nursing students. Data were analyzed using importance-performance analysis and Borich needs analysis. Students wanted to use XR to learn about treating high-risk preterm infants. COVID-19 limited clinical training in NICUs, and most students preferred training in XR programs to improve their nursing competency for neonates. There is a large demand for nursing skills concerning high-risk newborns and hands-off training.

Negative conversion, lymphocyte/monocyte ratio, and bilirubinemia in COVID-19 with mental disorders (preprint)

This retrospective study explored the changes in biomarkers indicators and prognosis in COVID-19 patients with mental disorders (n = 60) from the author’ Hospital between 2/13/2020 and 4/15/2020. Significant differences before and after negative conversion were observed in lymphocytes, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, aspartate aminotransferase, albumin, albumin/globulin ratio, direct bilirubin, alkaline phosphatase, uric acid, high-density lipoprotein cholesterol, and ApoA1 (all P < 0.05). Compared with the patients who had a negative conversion within 3 weeks, those who did not turn negative within 3 weeks had a higher frequency of cardiovascular diseases (27.3% vs. 4.2%, P = 0.040), a higher lymphocyte-to-monocyte ratio (median, 4.72 vs. 3.35, P = 0.003), and higher total bilirubin levels (median, 12.0 vs. 8.6 µmol/L, P = 0.031). The results present the changes in laboratory parameters in COVID-19 patients with a mental disorder. Cardiovascular diseases and higher lymphocyte-to-monocyte ratio, and total bilirubin levels could be associated with the amount of time required for negative conversion.

A myeloid program associated with COVID-19 severity is decreased by therapeutic blockade of IL-6 signaling (preprint)

Altered myeloid inflammation and lymphopenia are hallmarks of severe infections, including with SARS-CoV-2. Here, we identified a gene program, defined by correlation with EN-RAGE (S100A12) gene expression, which was up-regulated in airway and blood myeloid cells from COVID-19 patients. The EN-RAGE program was expressed in 7 cohorts and observed in patients with both COVID-19 and acute respiratory distress syndrome (ARDS) from other causes. This program was associated with greater clinical severity and predicted future mechanical ventilation and death. EN-RAGE+ myeloid cells express features consistent with suppressor cell functionality, with low HLA-DR and high PD-L1 surface expression and higher expression of T cell-suppressive genes. Sustained EN-RAGE signature expression in airway and blood myeloid cells correlated with clinical severity and increasing expression of T cell exhaustion markers, such as PD-1. IL-6 treatment of monocytes in vitro upregulated many of the severity-associated genes in the EN-RAGE gene program, along with potential mediators of T cell suppression, such as IL-10. Blockade of IL-6 signaling by tocilizumab in a placebo-controlled clinical trial led to a rapid normalization of ENRAGE and T cell gene expression. This identifies IL-6 as a key driver of myeloid dysregulation associated with worse clinical outcomes in COVID-19 patients and provides insights into shared pathophysiological mechanisms in non-COVID-19 ARDS.

Parallel use of pluripotent human stem cell lung and heart models provide new insights for treatment of SARS-CoV-2 (preprint)

SARS-CoV-2 primarily infects the respiratory tract, but pulmonary and cardiac complications occur in severe COVID-19. To elucidate molecular mechanisms in the lung and heart, we conducted paired experiments in human stem cell-derived lung alveolar type II (AT2) epithelial cell and cardiac cultures infected with SARS-CoV-2. With CRISPR-Cas9 mediated knock-out of ACE2, we demonstrated that angiotensin converting enzyme 2 (ACE2) was essential for SARS-CoV-2 infection of both cell types but further processing in lung cells required TMPRSS2 while cardiac cells required the endosomal pathway. Host responses were significantly different; transcriptome profiling and phosphoproteomics responses depended strongly on the cell type. We identified several antiviral compounds with distinct antiviral and toxicity profiles in lung AT2 and cardiac cells, highlighting the importance of using several relevant cell types for evaluation of antiviral drugs. Our data provide new insights into rational drug combinations for effective treatment of a virus that affects multiple organ systems.

The effects of neonatal resuscitation gamification program using immersive virtual reality: A quasi-experimental study.

BACKGROUND: Clinical practice in neonatal intensive care units for nursing college students has been restricted due to the COVID-19 pandemic outbreak; thus, the gamification program has emerged as an alternative learning method. Consequently, there is a need to examine the effectiveness of such alternative learning methods to enhance the response to high-risk newborn emergencies. OBJECTIVES: To examine the effects (neonatal resuscitation nursing knowledge, problem-solving and clinical reasoning ability, self-confidence in practical performance, degree of anxiety, and learning motivation) of a neonatal resuscitation gamification program using immersive virtual reality based on Keller's ARCS model. DESIGN: A non-randomized controlled simulation study with a pretest-posttest design. SETTING: Lab and lecture rooms of two universities in South Korea, from June to November 2021. PARTICIPANTS: Prelicensure nursing students. METHODS: The virtual reality group (n = 29) underwent a neonatal resuscitation gamification program using virtual reality based on Keller's ARCS model. The simulation group (n = 28) received high-fidelity neonatal resuscitation simulations and online neonatal resuscitation program lectures. The control group (n = 26) only received online neonatal resuscitation program lectures. Changes in scores among these groups were compared using analysis of variance and analysis of covariance with SPSS for Windows version 27.0. RESULTS: Post intervention, neonatal resuscitation knowledge [F(2) = 3.83, p = .004] and learning motivation [F(2) = 1.79, p = .025] were significantly higher in the virtual reality and simulation groups than in the control group, whereas problem-solving ability [F(2) = 2.07, p = .038] and self-confidence [F(2) = 6.53, p < .001] were significantly higher in the virtual reality group than in the simulation and control groups. Anxiety [F(2) = 16.14, p < .001] was significantly lower in the simulation group than in the virtual reality and control groups. CONCLUSIONS: The neonatal resuscitation gamification program using immersive virtual reality was found to be effective in increasing neonatal resuscitation knowledge, problem-solving ability, self-confidence, and learning motivation of the nursing students who participated in the trial application process.

Conceptualizing the Internet Compulsive-Buying Tendency: What We Know and Need to Know in the Context of the COVID-19 Pandemic

Over the past decade, new innovative products and services have been introduced into the marketplace using advanced technology. The enticement of new products lures consumers to buy compulsively. Because of the convenience and the characteristics of online shopping, it will increase the incidence of compulsive-buying behavior. Meanwhile, due to the fact that the COVID-19 pandemic is continuing to spread around the world, consumers may change their decision-making and behavior to shop online more frequently and intensively. The repetitive shopping online means more cardboard, delivery transportations, and vehicles and that more goods will be produced. It will result in an unfriendly result for the environment. Given the critical role of compulsive buying in the emerging Internet retail environment, it is necessary to develop and validate an instrument to measure the Internet compulsive-buying tendency (ICBT). Therefore, a rigorous measurement-scale-development procedure was applied to evaluate the initial 31 items. After two rounds of data collection and assessment, the final instrument contained 18 items that fall into four subconstructs: the tendency to spend online, feelings about online shopping and spending, dysfunctional online spending, and online post-purchase guilt. These factors can provide a basis for predicting tendencies toward Internet compulsive shopping and can be used to evaluate consumers’abnormal behavior in online-shopping circumstances.

Longitudinal single-cell epitope and RNA-sequencing reveals the immunological impact of type 1 interferon autoantibodies in critical COVID-19 (preprint)

Type I interferon (IFN-I) neutralizing autoantibodies have been found in some critical COVID-19 patients; however, their prevalence and longitudinal dynamics across the disease severity scale, and functional effects on circulating leukocytes remain unknown. Here, in 284 COVID-19 patients, we found IFN-I autoantibodies in 19% of critical, 6% of severe and none of the moderate cases. Longitudinal profiling of over 600,000 peripheral blood mononuclear cells using multiplexed single-cell epitope and transcriptome sequencing from 54 COVID-19 patients, 15 non-COVID-19 patients and 11 non-hospitalized healthy controls, revealed a lack of IFN-I stimulated gene (ISG-I) response in myeloid cells from critical cases, including those producing anti-IFN-I autoantibodies. Moreover, surface protein analysis showed an inverse correlation of the inhibitory receptor LAIR-1 with ISG-I expression response early in the disease course. This aberrant ISG-I response in critical patients with and without IFN-I autoantibodies, supports a unifying model for disease pathogenesis involving ISG-I suppression via convergent mechanisms.

A Systematic Review of the Clinical Applications of Traditional Chinese Medicine in Severe Epidemic Diseases SARS and COVID-19

2003年嚴重急性呼吸道症候群（SARS）肆虐全球，2019年12月在中國武漢發生的新型冠狀病毒肺炎（COVID-19），到6月下旬即已蔓延全球188國，感染逾一千萬人，將近五十萬人死亡。COVID-19與SARS兩者都屬新型冠狀病毒致病，都可引起嚴重肺炎而致死。WHO在2020年3月11日正式宣布COVID-19為全球性大流行（pandemic），目前仍無明確療效之藥物，而疫苗也仍處於研發階段。本文擬探討中醫藥治療與預防在COVID-19中的角色。透過搜尋資料庫包括PubMed、華藝線上圖書館及中國期刊全文數據庫，分析歷代典籍與當代國內外文獻，並參酌中國發布的SARS與COVID-19之診療方案，以探討SARS與COVID-19中醫臨床分期表現、病因、證型、病機及臨床治則與病程演變之關聯性比較。此外，本文亦分析COVID-19臨床通用方（清肺排毒湯）之組方機理，探討體質差異對於COVID-19等臨床表現之影響，並提出中醫介入治療COVID-19的關鍵時機，以截斷病勢，進而改善嚴重流行疫病（時疫）患者之預後。期望藉由本論文的發現能有助於加速中醫藥在COVID-19之相關研究，進一步擴展中醫在相關嚴重流行疫病之臨床應用。 The outbreak of severe acute respiratory syndrome (SARS) threatened the world in 2003. Almost two decades later, a novel Coronavirus Disease 2019 (COVID-19), which erupted in December 2019 in Wuhan, China, has spread to 188 countries and resulted in more than ten million cases infected and nearly 500,000 deaths worldwide in less than six months. Both of SARS and COVID-19 are all caused by novel coronavirus and can lead to severe pneumonia or death. Consequently, the World Health Organization (WHO) has officially announced that COVID-19 became pandemic on March 11th, 2020. Furthermore, no specific effective treatment for COVID-19 has been proved till now, and vaccines potentially useful for prophylaxis are still only in the clinical trial stage. In this study, we explored the roles of Traditional Chinese Medicine (TCM) in treatment and prevention of COVID-19. We retrieved the published articles from the online resources including PubMed, Airiti Library, and China Academic Journals Fulltext Database (CJFD). Subsequently, we analyzed the retrieved articles related to the SARS and COVID-19, and identified the clinical manifestations, etiologies, syndromes, pathogenesis, and therapeutic principles at different stages of the diseases based on the official reports of China Health authorities. We also evaluated the ingredients and the underlying therapeutic principle of the most commonly used Chinese herbal formula named ＂Qingfei Paidu Decoction＂ to treat COVID-19. Moreover, we identified the constitutional factors to explain the various clinical manifestations and outcomes of COVID-19 from the theory of TCM. Lastly, we proposed the opportune timing of TCM treatment to block the clinical progression and to improve the prognosis of COVID-19 patients. We expect our findings will contribute to vigorous progress on clinical treatment and research of TCM against COVID-19, and we are optimistic to see that TCM will play a more important role in the management of severe epidemic diseases in the future.

A Universal Screening Strategy for SARS-CoV-2 Infection in Intensive Care Units: Korean Experience in a Single Hospital.

BACKGROUND: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection is not differentiated clinically from other respiratory infections, and intensive care units (ICUs) are vulnerable to in-hospital transmission due to interventions inducing respiratory aerosols. This study evaluated the effectiveness of universal SARS-CoV-2 screening in ICUs in terms of screened-out cases and reduction in anxiety of healthcare personnel (HCP). MATERIALS AND METHODS: This prospective single-armed observational study was conducted in 2 ICUs of a single hospital. The number of patients diagnosed with SARS-CoV-2 infection by the screening program and healthcare workers in ICUs that visited the SARS-CoV-2 screening clinic or infection clinic were investigated. RESULTS: During the 7-week study period, no positive screening case was reported among a total of 142 patients. Among 86 HCP in the ICUs, only 2 HCP sought medical consultation for SARS-CoV-2 infection during the initial 2 weeks. CONCLUSION: A universal screening program for SARS-CoV-2 infection in ICUs with the coordination of other countermeasures in the hospital was reasonably effective in preventing in-hospital transmission in a pandemic situation and making clinical practices and HCP stable.

Global Absence and Targeting of Protective Immune States in Severe COVID-19. (preprint)

While SARS-CoV-2 infection has pleiotropic and systemic effects in some patients, many others experience milder symptoms. We sought a holistic understanding of the severe/mild distinction in COVID-19 pathology, and its origins. We performed a whole-blood preserving single-cell analysis protocol to integrate contributions from all major cell types including neutrophils, monocytes, platelets, lymphocytes and the contents of serum. Patients with mild COVID-19 disease display a coordinated pattern of interferon-stimulated gene (ISG) expression across every cell population and these cells are systemically absent in patients with severe disease. Severe COVID-19 patients also paradoxically produce very high anti-SARS-CoV-2 antibody titers and have lower viral load as compared to mild disease. Examination of the serum from severe patients demonstrates that they uniquely produce antibodies with multiple patterns of specificity against interferon-stimulated cells and that those antibodies functionally block the production of the mild disease-associated ISG-expressing cells. Overzealous and auto-directed antibody responses pit the immune system against itself in many COVID-19 patients and this defines targets for immunotherapies to allow immune systems to provide viral defense. One Sentence SummaryIn severe COVID-19 patients, the immune system fails to generate cells that define mild disease; antibodies in their serum actively prevents the successful production of those cells.

Global Absence and Targeting of Protective Immune States in Severe COVID-19. (preprint)

While SARS-CoV-2 infection has pleiotropic and systemic effects in some patients, many others experience milder symptoms. We sought a holistic understanding of the severe/mild distinction in COVID-19 pathology, and its origins. We performed a wholeblood preserving single-cell analysis protocol to integrate contributions from all major cell types including neutrophils, monocytes, platelets, lymphocytes and the contents of serum. Patients with mild COVID-19 disease display a coordinated pattern of interferonstimulated gene (ISG) expression across every cell population and these cells are systemically absent in patients with severe disease. Severe COVID-19 patients also paradoxically produce very high anti-SARS-CoV-2 antibody titers and have lower viral load as compared to mild disease. Examination of the serum from severe patients demonstrates that they uniquely produce antibodies with multiple patterns of specificity against interferon-stimulated cells and that those antibodies functionally block the production of the mild disease-associated ISG-expressing cells. Overzealous and autodirected antibody responses pit the immune system against itself in many COVID-19 patients and this defines targets for immunotherapies to allow immune systems to provide viral defense.

Insulin Treatment Increased Fatality in COVID-19 Patients with Diabetes (preprint)

Background: COVID-19 epidemic continues to spread rapidly around the world, causing severe multi-organ injury and high mortality in a subset of patients. Individuals with diabetes mellitus are at a higher risk of SARS-CoV-2 infection and worse outcomes than the general population without diabetes. While glucose control was observed to be associated with attenuated mortality, limited evidence is available to determine whether glucose control by insulin was beneficial for COVID-19 patients with diabetes.Methods: This retrospective study focused on a cohort of 689 COVID-19 patients from Wuhan, China, diagnosed with diabetes, and assessed the clinical outcomes associated with insulin treatment. Kaplan-Meier survival analysis and proportional Cox regression were employed to analyze the influence of insulin treatment on all cause death.Results: Among the 689 diabetic patients infected with COVID-19, 106 patients died (fatality was 15.4%). The fatality of COVID-19 patients with diabetes treated with insulin was significantly higher than those without insulin treatment (27.2% vs. 3.5%, p < 0.001). The HR was 6.57 (95% CI 3.09 to 13.99; p < 0.001) after adjustment for age, gender, coronary heart disease, COPD, chronic kidney disease, pulse, respiratory rate, SpO2, lymphocyte count, albumin, NT-proBNP and glucose. Further survival analysis in several subgroups and critically ill group showed the similar effect of insulin on adverse outcome in COVID-19 patients with diabetes.Conclusion: According to this retrospective study, insulin treatment increases the mortality in COVID-19 patients with diabetes. Thus, close observation especially glucose and vital signs monitoring are very important when COVID-19 patients with diabetes treated with insulin.Funding: This work was supported in part by projects from Ministry of Science and Technology of China (No. 2020YFC0844500), Nature Science Foundation of China (Nos. 31130031), Emergency project fund of Chinese Academy of Sciences (No. 2020YJFK0105) and Chinese Academy of Engineering and Ma Yun Foundation (No. 2020-CMKYGG-05). Conflict of Interest: The authors have declared that no competing interests exist.Ethical Approval: This study was approved by the institutional review board of Tongji Hospital (IRBID: TJ-IRB20200229). The written informed consent was waived by the Ethics Committee because of the retrospective and anonymous nature of the data.

A Universal Screening Strategy for SARS-CoV-2 Infection in Intensive Care Units: Korean Experience in a Single Hospital

BACKGROUND: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection is not differentiated clinically from other respiratory infections, and intensive care units (ICUs) are vulnerable to in-hospital transmission due to interventions inducing respiratory aerosols. This study evaluated the effectiveness of universal SARS-CoV-2 screening in ICUs in terms of screened-out cases and reduction in anxiety of healthcare personnel (HCP). MATERIALS AND METHODS: This prospective single-armed observational study was conducted in 2 ICUs of a single hospital. The number of patients diagnosed with SARS-CoV-2 infection by the screening program and healthcare workers in ICUs that visited the SARS-CoV-2 screening clinic or infection clinic were investigated. RESULTS: During the 7-week study period, no positive screening case was reported among a total of 142 patients. Among 86 HCP in the ICUs, only 2 HCP sought medical consultation for SARS-CoV-2 infection during the initial 2 weeks. CONCLUSION: A universal screening program for SARS-CoV-2 infection in ICUs with the coordination of other countermeasures in the hospital was reasonably effective in preventing in-hospital transmission in a pandemic situation and making clinical practices and HCP stable.