Evaluation of an automated CRISPR-based diagnostic tool for rapid detection of COVID-19.

The performance of an automated commercial CRISPR/Cas based technology was evaluated and compared with routine RT-PCR testing to diagnose COVID-19. Suspected and discharged COVID-19 cases were included and tested with CRISPR-based SARS-CoV-2 test and RT-PCR assay using throat swab and sputum specimens. The diagnostic yield was calculated and compared using the McNemar test. A total of 437 patients were included for analysis, including COVID-19 (n = 171), discharged cases (n = 155), and others (n = 111). For the diagnosis of COVID-19, the CRISPR-SARS-CoV-2 test had a sensitivity and specificity of 98.2% (168/171) and 100.0% (266/266), respectively; the RT-PCR test had a sensitivity and specificity of 100.0% (171/171) and 100.0% (266/266), respectively. No significant difference was found in the sensitivity of CRISPR-SARS-CoV-2 and RT-PCR. In conclusion, the CRISPR-SARS-CoV-2 test had a comparable performance with RT-PCR and showed several advantages, such as short assay time, low cost, and no requirement for expensive equipment.

Comparing airborne infectious aerosol exposures in sparsely occupied large spaces utilizing large-diameter ceiling fans

In sparsely occupied large industrial and commercial buildings, large-diameter ceiling fans1 (LDCFs) are commonly utilized for comfort cooling and destratification;however, a limited number of studies were conducted to guide the operation of these devices during the COVID-19 pandemic. This study conducted 223 parametrical computational-fluid-dynamics (CFD) simulations of LDCFs in the U.S. Department of Energy warehouse reference building to compare the impacts of fan operations, index-person, and worker-packing-line locations on airborne exposures to infectious aerosols under both summer and winter conditions. The steady-state airflow fields were modeled while transient exposures to particles of varying sizes (0.5–10 μm) were evaluated over an eight-hour period. Both the airflow and aerosol models were validated by measurement data from the literature. It was found that it is preferable to create a breeze from LDCFs for increased airborne dilution into a sparsely occupied large warehouse, which is more similar to an outdoor scenario than a typical indoor scenario. Operation of fans at the highest feasible speed while maintaining thermal-comfort requirements consistently outperformed the other options in terms of airborne exposures. There is no substantial evidence that fan reversal is beneficial in the current large space of interest. Reversal flow direction to create upward flows at higher fan speeds generally reduced performance compared with downward flows, as there was less airflow through the fan blades at the same rotational speed. Reversing flow at lower fan speeds decreased airflow speeds and dilution in the space and, thus, increased whole-warehouse concentrations.

Potential links between COVID-19 and periodontitis: a bioinformatic analysis based on GEO datasets.

BACKGROUND: 2019 Coronavirus disease (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The COVID-19 pandemic has already had a serious influence on human existence, causing a huge public health concern for countries all around the world. Because SARS-CoV-2 infection can be spread by contact with the oral cavity, the link between oral illness and COVID-19 is gaining traction. Through bioinformatics approaches, we explored the possible molecular mechanisms linking the COVID-19 and periodontitis to provide the basis and direction for future research. METHODS: Transcriptomic data from blood samples of patients with COVID-19 and periodontitis was downloaded from the Gene Expression Omnibus database. The shared differentially expressed genes were identified. The analysis of Gene Ontology, Kyoto Encyclopedia of Genesand Genomes pathway, and protein-protein interaction network was conducted for the shared differentially expressed genes. Top 5 hub genes were selected through Maximal Clique Centrality algorithm. Then mRNA-miRNA network of the hub genes was established based on miRDB database, miRTarbase database and Targetscan database. The Least absolute shrinkage and selection operator regression analysis was used to discover possible biomarkers, which were then investigated in relation to immune-related genes. RESULTS: Fifty-six shared genes were identified through differential expression analysis in COVID-19 and periodontitis. The function of these genes was enriched in regulation of hormone secretion, regulation of secretion by cell. Myozenin 2 was identified through Least absolute shrinkage and selection operator regression Analysis, which was down-regulated in both COVID-19 and periodontitis. There was a positive correlation between Myozenin 2 and the biomarker of activated B cell, memory B cell, effector memory CD4 T cell, Type 17 helper cell, T follicular helper cell and Type 2 helper cell. CONCLUSION: By bioinformatics analysis, Myozenin 2 is predicted to correlate to the pathogenesis and immune infiltrating of COVID-19 and periodontitis. However, more clinical and experimental researches are needed to validate the function of Myozenin 2.

A review on indoor airborne transmission of COVID-19– modelling and mitigation approaches

In the past few years, significant efforts have been made to investigate the transmission of COVID-19. This paper provides a review of the COVID-19 airborne transmission modeling and mitigation strategies. The simulation models here are classified into airborne transmission infectious risk models and numerical approaches for spatiotemporal airborne transmissions. Mathematical descriptions and assumptions on which these models have been based are discussed. Input data used in previous simulation studies to assess the dispersion of COVID-19 are extracted and reported. Moreover, measurements performed to study the COVID-19 airborne transmission within indoor environments are introduced to support validations for anticipated future modeling studies. Transmission mitigation strategies recommended in recent studies have been classified to include modifying occupancy and ventilation operations, using filters and air purifiers, installing ultraviolet (UV) air disinfection systems, and personal protection compliance, such as wearing masks and social distancing. The application of mitigation strategies to various building types, such as educational, office, public, residential, and hospital, is reviewed. Recommendations for future works are also discussed based on the current apparent knowledge gaps covering both modeling and mitigation approaches. Our findings show that different transmission mitigation measures were recommended for various indoor environments;however, there is no conclusive work reporting their combined effects on the level of mitigation that may be achieved. Moreover, further studies should be conducted to understand better the balance between approaches to mitigating the viral transmissions in buildings and building energy consumption.

Efficiency Droop and Degradation in AlGaN-Based UVB Light-Emitting Diodes

In this study, we found that the current droop (J-droop) in AlGaN-based UVB light-emitting diodes was more obvious at higher temperatures, despite both the main and parasitic peaks undergoing monotonic decreases in their intensity upon an increase in the temperature. The slower temperature droop (T-droop) did not occur when the forward current was increased to temperatures greater than 298 K. After an aging time of 6000 h, the emission wavelengths did not undergo any obvious changes, while the intensity of the parasitic peak barely changed. Thus, the degradation in the light output power during long-term operation was not obviously correlated to the existence of the parasitic peak.

Humanized mice for investigating SARS-CoV-2 lung infection and associated human immune responses.

There is an urgent need for animal models of coronavirus disease 2019 to study immunopathogenesis and test therapeutic intervenes. In this study, we showed that NOD/SCID IL2rg-/- (NSG) mice engrafted with human lung (HL) tissue (NSG-L mice) could be infected efficiently by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and that live virus capable of infecting Vero cells was found in the HL grafts and multiple organs from infected NSG-L mice. RNA-Sequencing identified a series of differentially expressed genes, which are enriched in viral defense responses, chemotaxis, IFN stimulation and pulmonary fibrosis, between HL grafts from infected and control NSG-L mice. Furthermore, when infected with SARS-CoV-2, humanized mice with both human immune system (HIS) and autologous HL grafts (HISL mice) had bodyweight loss and hemorrhage and immune cell infiltration in HL grafts, which were not observed in immunodeficient NSG-L mice, indicating the development of anti-viral immune responses in these mice. In support of this possibility, the infected HISL mice showed bodyweight recovery and lack of detectable live virus at the later time. These results demonstrate that NSG-L and HISL mice are susceptible to SARS-CoV-2 infection, offering a useful in vivo model for studying SARS-CoV-2 infection and the associated immune response and immunopathology, and testing anti-SARS-CoV-2 therapies.

The roles of inactivated vaccines in older patients with infection of Delta variant in Nanjing, China.

BACKGROUND: The coronavirus disease 2019 (COVID-19) is spreading around the world. The COVID-19 vaccines may improve concerns about the pandemic. However, the roles of inactivated vaccines in older patients (aged ≥60 years) with infection of Delta variant were less studied. METHODS: We classified the older patients with infection of Delta variant into three groups based on the vaccination status: no vaccination (group A, n = 113), one dose of vaccination (group B, n = 46), and two doses of vaccination (group C, n = 22). Two inactivated COVID-19 vaccines (BBIBP-CorV or CoronaVac) were evaluated in this study. The demographic data, laboratory parameters, and clinical severity were recorded. RESULTS: A total of 181 older patients with infection of Delta variant were enrolled. 111 (61.3%) patients had one or more co-morbidities. The days of "turn negative" and hospital stay in Group C were lower than those in the other groups (P < 0.05). The incidences of multiple organ dysfunction syndrome (MODS), septic shock, acute respiratory distress syndrome (ARDS), acute kidney injury, and cardiac injury in Group A were higher than those in the other groups (P < 0.05). The MV-free days and ICU-free days during 28 days in Group A were also lower than those in the other groups (P < 0.05). In patients with co-morbidities, vaccinated cases had lower incidences of MODS (P = 0.015), septic shock (P = 0.015), and ARDS (P = 0.008). CONCLUSIONS: The inactivated COVID-19 vaccines were effective in improving the clinical severity of older patients with infection of Delta variant.

IFP35 as a promising biomarker and therapeutic target for the syndromes induced by SARS-CoV-2 or influenza virus.

Previous studies have shown that the high mortality caused by viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus primarily results from complications of a cytokine storm. Therefore, it is critical to identify the key factors participating in the cytokine storm. Here we demonstrate that interferon-induced protein 35 (IFP35) plays an important role in the cytokine storm induced by SARS-CoV-2 and influenza virus infection. We find that the levels of serum IFP35 in individuals with SARS-CoV-2 correlates with severity of the syndrome. Using mouse model and cell assays, we show that IFP35 is released by lung epithelial cells and macrophages after SARS-CoV-2 or influenza virus infection. In addition, we show that administration of neutralizing antibodies against IFP35 considerably reduces lung injury and, thus, the mortality rate of mice exposed to viral infection. Our findings suggest that IFP35 serves as a biomarker and as a therapeutic target in virus-induced syndromes.

VarEPS: an evaluation and prewarning system of known and virtual variations of SARS-CoV-2 genomes.

The genomic variations of SARS-CoV-2 continue to emerge and spread worldwide. Some mutant strains show increased transmissibility and virulence, which may cause reduced protection provided by vaccines. Thus, it is necessary to continuously monitor and analyze the genomic variations of SARS-COV-2 genomes. We established an evaluation and prewarning system, SARS-CoV-2 variations evaluation and prewarning system (VarEPS), including known and virtual mutations of SARS-CoV-2 genomes to achieve rapid evaluation of the risks posed by mutant strains. From the perspective of genomics and structural biology, the database comprehensively analyzes the effects of known variations and virtual variations on physicochemical properties, translation efficiency, secondary structure, and binding capacity of ACE2 and neutralizing antibodies. An AI-based algorithm was used to verify the effectiveness of these genomics and structural biology characteristic quantities for risk prediction. This classifier could be further used to group viral strains by their transmissibility and affinity to neutralizing antibodies. This unique resource makes it possible to quickly evaluate the variation risks of key sites, and guide the research and development of vaccines and drugs. The database is freely accessible at www.nmdc.cn/ncovn.

Antibody Response to COVID-19 Virus - Heilongjiang Province and Gansu Province, China, 2020.

WHAT IS ALREADY KNOWN ABOUT THIS TOPIC?: Coronavirus disease 2019 (COVID-19) has become a global pandemic, while the profile of antibody response against the COVID-19 virus has not been well clarified. WHAT IS ADDED BY THIS REPORT?: In this study, 210 serum samples from 160 confirmed COVID-19 cases with different disease severities were recruited. The IgM, IgA, IgG, and neutralizing antibodies (NAb) against COVID-19 virus were determined. Our findings indicated that four antibodies could be detectable at low levels within 2 weeks of disease onset, then rapidly increasing and peaking from the 3rd to 5th Weeks. NAb decreased between 5th and 9th Weeks, and a higher IgM/IgA level was observed in the groups with mild/moderate severity within 2 weeks (p<0.05), while all 4 types of antibodies were higher in the group with severe/critical severity after 4 weeks (p<0.05). WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE?: Our study on the dynamics of serological antibody responses against COVID-19 virus among COVID-19 patients complements the recognition regarding the humoral immune response to COVID-19 virus infection. The findings will help in the interpretation of antibody detection results for COVID-19 patients and be beneficial for the evaluation of vaccination effects.

The effect of COVID-19 school closures on adolescent sleep duration: an uncontrolled before-after study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic affected almost 1.6 billion students or more than 90% of learners globally. However, the effect of school closures during COVID-19 pandemic on adolescent sleep duration remains unclear. METHODS: We undertook a cross-sectional electronic survey in six junior and senior high schools in Shanghai, China from late June to early July 2020. We evaluated the changes of sleep duration on weekdays by comparing sleep duration hours and insufficient sleep (< 9 h for children aged 6-13 years or < 8 h for teenagers aged 14-17 years) in COVID-19 school closures and after school reopening. We also investigated possible sex differences in the changes of sleep duration. RESULTS: A total of 3265 students completed the survey, the mean age was 14.56 ± 1.99 years, 1567 (47.99%) were girls and 1344 (41.17%) were in grades 10-12. The overall sleep duration decreased from 8.88 h in school closures to 7.77 h after school reopening, and the change (difference: - 1.11 h; 95%CI: - 1.16, - 1.07; P < 0.001) was statistically significant. The prevalence of insufficient sleep increased sharply from 21.10 to 63.98%, and the change (ratio:3.03; 95%CI:2.84, 3.23; P < 0.001) was statistically significant. Besides, the changes were greater in girls than in boys. CONCLUSION: Results of this study revealed that sleep duration was longer and percentage of sufficient sleep was higher during COVID-19 school closures in adolescent students.

Association of liver abnormalities with in-hospital mortality in patients with COVID-19.

BACKGROUND & AIMS: The evolution and clinical significance of abnormal liver chemistries and the impact of hepatitis B infection on outcome in patients with COVID-19 is not well characterized. This study aimed to explore these issues. METHODS: This large retrospective cohort study included 2,073 patients with coronavirus disease 2019 (COVID-19) and definite outcomes in Wuhan, China. Longitudinal liver function tests were conducted, with associated factors and risk of death determined by multivariate regression analyses. A prognostic nomogram was formulated to predict the survival of patients with COVID-19. The characteristics of liver abnormalities and outcomes of patients with COVID-19, with and without hepatitis B, were compared after 1:3 propensity score matching. RESULTS: Of the 2,073 patients, 1,282 (61.8%) had abnormal liver chemistries during hospitalization, and 297 (14.3%) had a liver injury. The mean levels of aspartate aminotransferase (AST) and direct bilirubin (D-Bil) increased early after symptom onset in deceased patients and showed disparity compared to levels in discharged patients throughout the clinical course of the disease. Abnormal AST (adjusted hazard ratio [HR] 1.39; 95% CI 1.04-1.86, p = 0.027) and D-Bil (adjusted HR 1.66; 95% CI 1.22-2.26; p = 0.001) levels at admission were independent risk factors for mortality due to COVID-19. A nomogram was established based on the results of multivariate analysis and showed sufficient discriminatory power and good consistency between the prediction and the observation. HBV infection in patients did not increase the risk of poor COVID-19-associated outcomes. CONCLUSIONS: Abnormal AST and D-Bil levels at admission were independent predictors of COVID-19-related mortality. Therefore, monitoring liver chemistries, especially AST and D-Bil levels, is necessary in hospitalized patients with COVID-19. LAY SUMMARY: Liver test abnormalities (in particular elevations in the levels of aspartate aminotransferase [AST] and direct bilirubin [D-Bil]) were observed after symptom onset in patients who went on to die of coronavirus disease 2019 (COVID-19). Abnormal levels of AST and D-Bil at admission were independent predictors of COVID-19-related mortality. HBV infection in patients did not increase the risk of poor COVID-19-associated outcomes.

Fibrotic Changes Depicted by Thin-Section CT in Patients With COVID-19 at the Early Recovery Stage: Preliminary Experience.

Objectives: To analyze follow-up CTs of patients recovering from COVID-19 in Wuhan, focusing on fibrotic change and its relevant risk factors. Methods: From January 13 to February 27, 2020, 166 hospitalized patients meeting our criteria were included. The scores of fibrotic patterns on follow-up CT were evaluated. Patients were designated as group 1 (with CT evidence of fibrotic pattern) and group 2 (without CT evidence of fibrotic pattern). Multivariate logistic regression was performed to explore risk factors for fibrotic change in patients with COVID-19. Results: The follow-up CTs were obtained on 56 days (median, IQR 51-63 days) after symptom onset. Of the 166 patients (mean age, 57 ± 15 years; 69/166 male), 46% (76/166) had CT evidence of fibrotic change and 77% (127/166) were severe or critical cases. Among patients with fibrotic change on CT, 84% (64/76) got a minimal or mild score of fibrosis. The high total score on peak CT, peak eosinophils, erythrocyte sedimentation rate (ESR) and advancing age were related to lung fibrotic change in patients with COVID-19. Conclusion: Forty six percentages of patients (mainly severe or critical cases) with COVID-19 showed fibrotic change on follow-up CT at early recovery phase, while the extent of fibrosis was not large. The advancing age, high total score on peak CT, peak eosinophils and ESR were associated with fibrotic change depicted by CT in patients recovering from COVID-19. An extended follow up by CT imaging and pulmonary function testing is necessary to fully assess the sequela of COVID-19.

Critically Ill Patients with Coronavirus Disease 2019 in a Designated ICU: Clinical Features and Predictors for Mortality.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a worldwide pandemic outbreak with a high mortality. Prognostic factors of critically ill patients with COVID-19 have not been fully elucidated yet. METHODS: In the present study, 59 patients with COVID-19 from the intensive care unit of the Caidian Branch of Tongji Hospital were enrolled. Epidemiological, demographic, clinical, laboratory, radiological, treatment data, and clinical outcomes were collected. Prognostic factors were statistically defined. RESULTS: Of the 59 patients studied (67.4±11.3 years), 38 patients were male, 51 had underlying diseases, and 41 patients died during admission. Compared with the survivors, the deceased patients were of older age, had more smoking history, severer fatigue, and diarrhea, a higher incidence of multiple organ injuries, more deteriorative lymphopenia and thrombocytopenia, remarkably impaired cellular immune response, and strengthened cytokine release. Age higher than 70 (OR=2.76, 95% CI=1.45-5.23), arrhythmia (OR=4.76, 95% CI=1.59-14.25), and a Sequential Organ Failure Assessment (SOFA) score above 4 (OR=5.16, 95% CI=1.29-20.55) were identified as risk factors for mortality of patients. CONCLUSION: Critically ill COVID-19 patients aged higher than 70, arrhythmia, or a SOFA score above 4 have a high risk of mortality, and need prior medical intervention.

Application of telemedicine during the coronavirus disease epidemics: a rapid review and meta-analysis.

BACKGROUND: As COVID-19 has become a global pandemic, early prevention and control of the epidemic is extremely important. Telemedicine, which includes medical advice given over telephone, Internet, mobile phone applications or other similar ways, may be an efficient way to reduce transmission and pressure on medical institutions. METHODS: We searched MEDLINE, Web of Science, Embase, Cochrane, CBM, CNKI and Wanfang databases for literature on the use of telemedicine for COVID-19, SARS and MERS from their inception to March 31st, 2020. We included studies about the content of the consultation (such as symptoms, therapy and prevention, policy, public service), screening of suspected cases, the provision of advice given to those people who may have symptoms or contact history. We conducted meta-analyses on the main outcomes of the studies. RESULTS: A total of 2,041 articles were identified after removing duplicates. After reading the full texts, we finally included nine studies. People were most concerned about symptoms (64.2%), epidemic situation and public problems (14.5%), and psychological problems (10.3%) during COVID-19 epidemic. During the SARS epidemic, the proportions of people asking for consultation for symptoms, prevention and therapy, and psychological problems were 35.0%, 22.0%, and 23.0%, respectively. Two studies demonstrated that telemedicine can be used to screen the suspected patients and give advice. One study emphasized the limited possibilities to follow up people calling hotlines and difficulties in identifying all suspect cases. CONCLUSIONS: Telemedicine services should focus on the issues that the public is most concerned about, such as the symptoms, prevention and treatment of the disease, and provide reasonable advice to patients with symptoms or people with epidemic history.