Engineering customized viral receptors for various coronaviruses (preprint)

Coronaviruses display versatile receptor usage, yet in-depth characterization of coronaviruses lacking known receptor identities has been impeded by the absence of feasible infection models. Here, we developed an innovative strategy to engineer functional customized viral receptors (CVRs). The modular design relies on building receptor frameworks comprising various function modules and generating specific epitope-targeting viral binding domains. We showed the key factors for CVRs to efficiently facilitate spike cleavage, membrane fusion, pseudovirus entry, and authentic virus amplification for various coronaviruses, resembling their native receptors. Applying this strategy, we delineated the accessible receptor binding epitopes for functional SARS-CoV-2 CVR design and elucidated the mechanism of entry supported by an amino-terminus domain (NTD) targeting S2L20-CVR. Furthermore, we created CVR-expressing cells for assessing antibodies and inhibitors against 12 representative coronaviruses from six subgenera, most of which lacking known receptors. Notably, a pan-sarbecovirus CVR supported entry of various sarbecoviruses, as well as amplification of a replicable HKU3 pseudovirus and the authentic strain RsHuB2019A. Through combining an HKU5-specific CVR with reverse genetics, we successfully rescued and cultured wild-type and fluorescence protein-incorporated HKU5, a receptor-unidentified merbecovirus. Our study demonstrated the great potential of CVR strategy in establishing native receptor-independent infection models, paving the way for studying various viruses that are challenging to culture due to the lack of susceptible cells.

Deep spatial proteomic exploration of severe COVID-19-related pulmonary injury in post-mortem specimens (preprint)

The lung, as a primary target of SARS-CoV-2, exhibits heterogeneous microenvironment accompanied by various histopathological changes following virus infection. However, comprehensive insight into the protein basis of COVID-19-related pulmonary injury with spatial resolution is currently deficient. Here, we generated a region-resolved quantitative proteomic atlas of seven major pathological structures within the lungs of COVID-19 victims by integrating histological examination, laser microdissection, and ultrasensitive proteomic technologies. Over 10,000 proteins were quantified across 71 dissected FFPE post-mortem specimens. By comparison with control samples, we identified a spectrum of COVID-19-induced protein and pathway dysregulations in alveolar epithelium, bronchial epithelium, and pulmonary blood vessels, providing evidence for the proliferation of transitional-state pneumocytes. Additionally, we profiled the region-specific proteomes of hallmark COVID-19 pulmonary injuries, including bronchiole mucus plug, pulmonary fibrosis, airspace inflammation, and hyperplastic alveolar type 2 cells. Bioinformatic analysis revealed the enrichment of cell-type and functional markers in these regions (e.g. enriched TGFBI in fibrotic region). Furthermore, we identified the up-regulation of proteins associated with viral entry, host restriction, and inflammatory response in COVID-19 lungs, such as FURIN and HGF. Collectively, this study provides spatial proteomic insights for understanding COVID-19-caused pulmonary injury, and may serve as a valuable reference for improving therapeutic intervention for severe pneumonia.

CBPH assay for the highest sensitive detection of SARS-COV-2 in the semen.

BACKGROUND: Great concerns have been raised on SARS-CoV-2 impact on men's andrological well-being, and many studies have attempted to determine whether SARS-CoV-2 is present in the semen and till now the data are unclear and somehow ambiguous. However, these studies used quantitative real-time (qRT) PCR, which is not sufficiently sensitive to detect nucleic acids in clinical samples with a low viral load. METHODS: The clinical performance of various nucleic acid detection methods (qRT-PCR, OSN-qRT-PCR, cd-PCR, and CBPH) was assessed for SARS-CoV-2 using 236 clinical samples from laboratory-confirmed COVID-19 cases. Then, the presence of SARS-CoV-2 in the semen of 12 recovering patients was investigated using qRT-PCR, OSN-qRT-PCR, cd-PCR, and CBPH in parallel using 24 paired semen, blood, throat swab, and urine samples. RESULTS: The sensitivity and specificity along with AUC of CBPH was markedly higher than the other 3methods. Although qRT-PCR, OSN-qRT-PCR and cdPCR detected no SARS-CoV-2 RNA in throat swab, blood, urine, and semen samples of the 12 patients, CBPH detected the presence of SARS-CoV-2 genome fragments in semen samples, but not in paired urine samples, of 3 of 12 patients. The existing SARS-CoV-2 genome fragments were metabolized over time. CONCLUSIONS: Both OSN-qRT-PCR and cdPCR had better performance than qRT-PCR, and CBPH had the highest diagnostic performance in detecting SARS-CoV-2, which contributed the most improvement to the determination of the critical value in gray area samples with low vrial load, which then provides a rational screening strategy for studying the clearance of coronavirus in the semen over time in patients recovering from COVID-19. Although the presence of SARS-CoV-2 fragments in the semen was demonstrated by CBPH, COVID-19 is unlikely to be sexually transmitted from male partners for at least 3 months after hospital discharge.

Assessment of integrated patterns of human-animal-environment health: a holistic and stratified analysis.

BACKGROUND: Data-driven research is a very important component of One Health. As the core part of the global One Health index (GOHI), the global One Health Intrinsic Drivers index (IDI) is a framework for evaluating the baseline conditions of human-animal-environment health. This study aims to assess the global performance in terms of GOH-IDI, compare it across different World Bank regions, and analyze the relationships between GOH-IDI and national economic levels. METHODS: The raw data among 146 countries were collected from authoritative databases and official reports in November 2021. Descriptive statistical analysis, data visualization and manipulation, Shapiro normality test and ridge maps were used to evaluate and identify the spatial and classificatory distribution of GOH-IDI. This paper uses the World Bank regional classification and the World Bank income groups to analyse the relationship between GOH-IDI and regional economic levels, and completes the case studies of representative countries. RESULTS: The performance of One Health Intrinsic Driver in 146 countries was evaluated. The mean (standard deviation, SD) score of GOH-IDI is 54.05 (4.95). The values (mean SD) of different regions are North America (60.44, 2.36), Europe and Central Asia (57.73, 3.29), Middle East and North Africa (57.02, 2.56), East Asia and Pacific (53.87, 5.22), Latin America and the Caribbean (53.75, 2.20), South Asia (52.45, 2.61) and sub-Saharan Africa (48.27, 2.48). Gross national income per capita was moderately correlated with GOH-IDI (R2 = 0.651, Deviance explained = 66.6%, P < 0.005). Low income countries have the best performance in some secondary indicators, including Non-communicable Diseases and Mental Health and Health risks. Five indicators are not statistically different at each economic level, including Animal Epidemic Disease, Animal Biodiversity, Air Quality and Climate Change, Land Resources and Environmental Biodiversity. CONCLUSIONS: The GOH-IDI is a crucial tool to evaluate the situation of One Health. There are inter-regional differences in GOH-IDI significantly at the worldwide level. The best performing region for GOH-IDI was North America and the worst was sub-Saharan Africa. There is a positive correlation between the GOH-IDI and country economic status, with high-income countries performing well in most indicators. GOH-IDI facilitates researchers' understanding of the multidimensional situation in each country and invests more attention in scientific questions that need to be addressed urgently.

Multi-resource collaborative scheduling problem of automated terminal considering the AGV charging effect under COVID-19.

Since the COVID-19 ravaged the global terminals, the Automated Container Terminal (ACT) has become one of important approach to promote the stronger quick response capacity to deal with the uncertainty that COVID-19 brought to the terminal. This research takes Automated Guided Vehicle (AGV) and their effects into account the multi-resource collaborative scheduling model to tradeoff ACT operational efficiency and energy savings. Firstly, the dual-cycle strategy of QC and the pooling strategy of AGV are given, which coordinates the scheduling of Quay Cranes (QCs), Yard Cranes (YCs) and other equipment. Furthermore, a multi-resource collaborative scheduling optimization model is proposed which roots from the principle of the Blocking-type Hybrid Flow Shop Problem (B-HFSP) with the objectives of minimizing the makespan of QC and the transportation energy consumption. And simultaneously, a mixed algorithm SA-GA is designed for solving this mixed integer programming model by an optimizing effect of Simulated Annealing on Genetic algorithms. Numerical experiments show that the model in this research is effective. The convergence of SA-GA is effective for small-scale cases and superior for large-scale cases. Considering both goals of high efficiency and energy saving, the Pareto solution set and collaborative scheduling solution take a priority to ensure that the bottlenecked QC runs efficiently. Here and now the average idle rate of QC is about [14%, 35%] lower than that of other equipment. The collaborative scheduling model constructed above not only has reference value for other multi-device and multi-stage scheduling problem, but also enhance the integrated decision-making ability of the ACT in the post-epidemic era.

Using Explainable AI to Cross-Validate Socio-economic Disparities Among Covid-19 Patient Mortality (preprint)

This paper applies eXplainable Artificial Intelligence (XAI) methods to investigate the socioeconomic disparities in COVID patient mortality. An Extreme Gradient Boosting (XGBoost) prediction model is built based on a de-identified Austin area hospital dataset to predict the mortality of COVID-19 patients. We apply two XAI methods, Shapley Additive exPlanations (SHAP) and Locally Interpretable Model Agnostic Explanations (LIME), to compare the global and local interpretation of feature importance. This paper demonstrates the advantages of using XAI which shows the feature importance and decisive capability. Furthermore, we use the XAI methods to cross-validate their interpretations for individual patients. The XAI models reveal that Medicare financial class, older age, and gender have high impact on the mortality prediction. We find that LIME local interpretation does not show significant differences in feature importance comparing to SHAP, which suggests pattern confirmation. This paper demonstrates the importance of XAI methods in cross-validation of feature attributions.

True or false? Cognitive load when reading COVID-19 news headlines: an eye-tracking study (preprint)

Misinformation is an important topic in the Information Retrieval (IR) context and has implications for both system-centered and user-centered IR. While it has been established that the performance in discerning misinformation is affected by a person's cognitive load, the variation in cognitive load in judging the veracity of news is less understood. To understand the variation in cognitive load imposed by reading news headlines related to COVID-19 claims, within the context of a fact-checking system, we conducted a within-subject, lab-based, quasi-experiment (N=40) with eye-tracking. Our results suggest that examining true claims imposed a higher cognitive load on participants when news headlines provided incorrect evidence for a claim and were inconsistent with the person's prior beliefs. In contrast, checking false claims imposed a higher cognitive load when the news headlines provided correct evidence for a claim and were consistent with the participants' prior beliefs. However, changing beliefs after examining a claim did not have a significant relationship with cognitive load while reading the news headlines. The results illustrate that reading news headlines related to true and false claims in the fact-checking context impose different levels of cognitive load. Our findings suggest that user engagement with tools for discerning misinformation needs to account for the possible variation in the mental effort involved in different information contexts.

Towards a global One Health index: a potential assessment tool for One Health performance.

BACKGROUND: A One Health approach has been increasingly mainstreamed by the international community, as it provides for holistic thinking in recognizing the close links and inter-dependence of the health of humans, animals and the environment. However, the dearth of real-world evidence has hampered application of a One Health approach in shaping policies and practice. This study proposes the development of a potential evaluation tool for One Health performance, in order to contribute to the scientific measurement of One Health approach and the identification of gaps where One Health capacity building is most urgently needed. METHODS: We describe five steps towards a global One Health index (GOHI), including (i) framework formulation; (ii) indicator selection; (iii) database building; (iv) weight determination; and (v) GOHI scores calculation. A cell-like framework for GOHI is proposed, which comprises an external drivers index (EDI), an intrinsic drivers index (IDI) and a core drivers index (CDI). We construct the indicator scheme for GOHI based on this framework after multiple rounds of panel discussions with our expert advisory committee. A fuzzy analytical hierarchy process is adopted to determine the weights for each of the indicators. RESULTS: The weighted indicator scheme of GOHI comprises three first-level indicators, 13 second-level indicators, and 57 third-level indicators. According to the pilot analysis based on the data from more than 200 countries/territories the GOHI scores overall are far from ideal (the highest score of 65.0 out of a maximum score of 100), and we found considerable variations among different countries/territories (31.8-65.0). The results from the pilot analysis are consistent with the results from a literature review, which suggests that a GOHI as a potential tool for the assessment of One Health performance might be feasible. CONCLUSIONS: GOHI-subject to rigorous validation-would represent the world's first evaluation tool that constructs the conceptual framework from a holistic perspective of One Health. Future application of GOHI might promote a common understanding of a strong One Health approach and provide reference for promoting effective measures to strengthen One Health capacity building. With further adaptations under various scenarios, GOHI, along with its technical protocols and databases, will be updated regularly to address current technical limitations, and capture new knowledge.

Functionalized biological metal-organic framework with nanosized coronal structure and hierarchical wrapping pattern for enhanced targeting therapy.

Inefficient tumor-targeted delivery and uncontrolled drug release are the major obstacles in cancer chemotherapy. Herein, inspired by the targeting advantage of coronavirus from its size and coronal structure, a coronal biological metal-organic framework nanovehicle (named as corona-BioMOF) is constructed for improving its precise cancer targeting ability. The designed corona-BioMOF is constructed as the carriers-encapsulated carrier model by inner coated with abundant protein-nanocaged doxorubicin particles and external decorated with high-affinity apoferritin proteins to form the spiky surface for constructing the specific coronal structure. The corona-BioMOF shows a higher affinity and an enhanced targeting ability towards receptor-positive cancer cells compared to that of MOF-drug composites without spiky surface. It also exhibits the hierarchical wrapping pattern-endowed controlled lysosome-specific drug release and remarkable tumor lethality in vivo. Moreover, water-induced surface defect-based protein handle mechanism is first proposed to shape the coronal-BioMOF. This work will provide a better inspiration for nanovehicle construction and be broadly useful for clinical precision nanomedicine.

Tongue and pulse features of 668 asymptomatic patients infected with the severe acute respiratory syndrome coronavirus 2 omicron variant in Shanghai.

OBJECTIVE: To characterize the tongue and pulse manifestations in asymptomatic coronavirus disease 2019 (COVID-19) cases in Shanghai. METHODS: We conducted a clinical study of 668 patients with asymptomatic infections in which we analyzed the tongue and pulse features in the Shanghai New International Expo Center mobile cabin hospital. The medical records of the patients, including tongue color, tongue coating, and pulse manifestations, were reviewed by healthcare workers. RESULTS: In total, 668 COVID-19 cases were included in the study. Patient age ranged from 5 to 96 years, with a median of 44.0 (IQR 33.0-53.0) years. Among the patients, 6.14% had comorbidities. The most common comorbid condition was diabetes (1.65%), followed by hypertension (0.89%), coronary heart disease (0.89%), thrombotic diseases (0.89%), congestive heart failure (0.60%), and stroke (0.45%). Pink-red (75.4%) was the most common tongue color, followed by red (23.4%) and pale red (1.2%). Tongue coating color and thickness were classified as white fur (9.28%), thin and yellow fur (48.65%), white greasy fur (8.98%), yellow greasy fur (24.70%), and less coating (8.39%). In addition, a large number of patients ( 300, 44.91%) presented superficial and rapid pulses, and 250 patients (37.4%) exhibited a slippery pulse. CONCLUSION: Our preliminary results showed that wind, heat, and dampness were the main etiologies of the severe acute respiratory syndrome coronavirus 2 Omicron (B.1.1.529) variant infection in traditional Chinese medicine. Furthermore, the main symptoms of the disease may be wind-heat invading the lung syndrome or damp-heat with the exuberance of virulence syndrome, which is of most significance in COVID-19 treatment.

The Effects of Interactive AI Design on User Behavior: An Eye-tracking Study of Fact-checking COVID-19 Claims (preprint)

We conducted a lab-based eye-tracking study to investigate how the interactivity of an AI-powered fact-checking system affects user interactions, such as dwell time, attention, and mental resources involved in using the system. A within-subject experiment was conducted, where participants used an interactive and a non-interactive version of a mock AI fact-checking system and rated their perceived correctness of COVID-19 related claims. We collected web-page interactions, eye-tracking data, and mental workload using NASA-TLX. We found that the presence of the affordance of interactively manipulating the AI system's prediction parameters affected users' dwell times, and eye-fixations on AOIs, but not mental workload. In the interactive system, participants spent the most time evaluating claims' correctness, followed by reading news. This promising result shows a positive role of interactivity in a mixed-initiative AI-powered system.

Clinical Characteristics of Coronavirus Disease 2019 in China.

BACKGROUND: Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. METHODS: We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. RESULTS: The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. CONCLUSIONS: During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.).

COVID-19 and Tuberculosis Coinfection: An Overview of Case Reports/Case Series and Meta-Analysis.

Background: Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are two major infectious diseases posing significant public health threats, and their coinfection (aptly abbreviated COVID-TB) makes the situation worse. This study aimed to investigate the clinical features and prognosis of COVID-TB cases. Methods: The PubMed, Embase, Cochrane, CNKI, and Wanfang databases were searched for relevant studies published through December 18, 2020. An overview of COVID-TB case reports/case series was prepared that described their clinical characteristics and differences between survivors and deceased patients. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) for death or severe COVID-19 were calculated. The quality of outcomes was assessed using GRADEpro. Results: Thirty-six studies were included. Of 89 COVID-TB patients, 19 (23.46%) died, and 72 (80.90%) were male. The median age of non-survivors (53.95 ± 19.78 years) was greater than that of survivors (37.76 ± 15.54 years) (p < 0.001). Non-survivors were more likely to have hypertension (47.06 vs. 17.95%) or symptoms of dyspnea (72.73% vs. 30%) or bilateral lesions (73.68 vs. 47.14%), infiltrates (57.89 vs. 24.29%), tree in bud (10.53% vs. 0%), or a higher leucocyte count (12.9 [10.5-16.73] vs. 8.015 [4.8-8.97] × 109/L) than survivors (p < 0.05). In terms of treatment, 88.52% received anti-TB therapy, 50.82% received antibiotics, 22.95% received antiviral therapy, 26.23% received hydroxychloroquine, and 11.48% received corticosteroids. The pooled ORs of death or severe disease in the COVID-TB group and the non-TB group were 2.21 (95% CI: 1.80, 2.70) and 2.77 (95% CI: 1.33, 5.74) (P < 0.01), respectively. Conclusion: In summary, there appear to be some predictors of worse prognosis among COVID-TB cases. A moderate level of evidence suggests that COVID-TB patients are more likely to suffer severe disease or death than COVID-19 patients. Finally, routine screening for TB may be recommended among suspected or confirmed cases of COVID-19 in countries with high TB burden.

Progression of myopia in a natural cohort of Chinese children during COVID-19 pandemic.

PURPOSE: To determine myopia progression in children during the COVID-19 and the related factors associated with myopia. METHODS: All subjects underwent three-timepoint ocular examinations that were measured in July 2019, January, and August 2020. We compared the changes in uncorrected visual acuity (UCVA), mydriatic spherical equivalent (SE), and axial length (AL) between two periods (before and during COVID-19). A questionnaire was performed to investigate risk factors for myopia. RESULTS: Compared with before the COVID-19, the mean (S.D.) myopia progression during the COVID-19 was significantly higher in right eyes (- 0.93 (0.65) vs. - 0.33 (0.47) D; p < 0.001). However, the differences in UCVA changes and the axial elongation between two periods were clinically insignificant. Through logistic regressive analysis, we found the difference of the SE changes was associated with the baseline AL (P = 0.028; 95% confidence interval [CI], 1.058, 2.632), online education (P = 0.02; 95% CI, 1.587, 8.665), and time of digital screen (p < 0.005; 95% CI, 1.587, 4.450). CONCLUSIONS: Children were at higher risk of myopia progression during COVID-19, which was associated with the baseline AL, the longtime online learning, and digital screen reading.

Therapeutic Agents Rounding Up the Immunopathology of COVID-19.

COVID-19 pandemic has caused more than 3 million deaths globally during the past year. The direct attack from SARS-CoV-2 and hyperactivated immune response contribute to the progress and deterioration of COVID-19. After the virus invades, the activation and release of cytokines/chemokines cause "cytokine storm", leading to acute respiratory distress syndrome (ARDS) and multiple organs dysfunction syndrome (MODS). Eliminating virus and blocking cytokines are important checkpoints of COVID-19 therapy, and several agents targeting immunopathology, including interferons, thymosin, glucocorticoids and immunoglobulin, have shown therapeutic effects in severe patients with COVID-19. Herein, we reviewed the practice evidences and concluded that several agents rounding up the immunopathology of COVID-19 may be the alternative approaches under the scenario of the lacking of effective antiviral drugs.

Burden of Sleep Disturbance During COVID-19 Pandemic: A Systematic Review.

Coronavirus disease 2019 (COVID-19) pandemic may exert adverse impacts on sleep among populations, which may raise awareness of the burden of sleep disturbance, and the demand of intervention strategies for different populations. We aimed to summarize the current evidence for the impacts of COVID-19 on sleep in patients with COVID-19, healthcare workers (HWs), and the general population. We searched PubMed and Embase for studies on the prevalence of sleep disturbance. Totally, 86 studies were included in the review, including 16 studies for COVID-19 patients, 34 studies for HWs, and 36 studies for the general population. The prevalence of sleep disturbance was 33.3%-84.7%, and 29.5-40% in hospitalized COVID-19 patients and discharged COVID-19 survivors, respectively. Physiologic and psychological traumatic effects of the infection may interact with environmental factors to increase the risk of sleep disturbance in COVID-19 patients. The prevalence of sleep disturbance was 18.4-84.7% in HWs, and the contributors mainly included high workloads and shift work, occupation-related factors, and psychological factors. The prevalence of sleep disturbance was 17.65-81% in the general population. Physiologic and social-psychological factors contributed to sleep disturbance of the general population during COVID-19 pandemic. In summary, the sleep disturbance was highly prevalent during COVID-19 pandemic. Specific health strategies should be implemented to tackle sleep disturbance.

Earlier diagnosis improves COVID-19 prognosis: a nationwide retrospective cohort analysis.

BACKGROUND: Risk of adverse outcomes in COVID-19 patients by stratifying by the time from symptom onset to confirmed diagnosis status is still uncertain. METHODS: We included 1,590 hospitalized COVID-19 patients confirmed by real-time RT-PCR assay or high-throughput sequencing of pharyngeal and nasal swab specimens from 575 hospitals across China between 11 December 2019 and 31 January 2020. Times from symptom onset to confirmed diagnosis, from symptom onset to first medical visit and from first medical visit to confirmed diagnosis were described and turned into binary variables by the maximally selected rank statistics method. Then, survival analysis, including a log-rank test, Cox regression, and conditional inference tree (CTREE) was conducted, regarding whether patients progressed to a severe disease level during the observational period (assessed as severe pneumonia according to the Chinese Expert Consensus on Clinical Practice for Emergency Severe Pneumonia, admission to an intensive care unit, administration of invasive ventilation, or death) as the prognosis outcome, the dependent variable. Independent factors included whether the time from symptom onset to confirmed diagnosis was longer than 5 days (the exposure) and other demographic and clinical factors as multivariate adjustments. The clinical characteristics of the patients with different times from symptom onset to confirmed diagnosis were also compared. RESULTS: The medians of the times from symptom onset to confirmed diagnosis, from symptom onset to first medical visit, and from first medical visit to confirmed diagnosis were 6, 3, and 2 days. After adjusting for age, sex, smoking status, and comorbidity status, age [hazard ratio (HR): 1.03; 95% CI: 1.01-1.04], comorbidity (HR: 1.84; 95% CI: 1.23-2.73), and a duration from symptom onset to confirmed diagnosis of >5 days (HR: 1.69; 95% CI: 1.10-2.60) were independent predictors of COVID-19 prognosis, which echoed the CTREE models, with significant nodes such as time from symptom onset to confirmed diagnosis, age, and comorbidities. Males, older patients with symptoms such as dry cough/productive cough/shortness of breath, and prior COPD were observed more often in the patients who procrastinated before initiating the first medical consultation. CONCLUSIONS: A longer time from symptom onset to confirmed diagnosis yielded a worse COVID-19 prognosis.

The Application of Tissue Glue in Eyelid Laceration Repair in Children During the Coronavirus Disease 2019 Pandemic Lockdown in Wuhan.

OBJECTIVE: To discuss a rapid and effective treatment used for children with eyelid lacerations during the COVID-19 lockdown in Wuhan to limit the risk of cross-infection. METHODS: A comparative study was conducted of forty-five patients with eyelid lacerations who attended the Ophthalmology Department of Wuhan Children's Hospital between January 23, 2020 and March 6, 2020. The tissue glue Histoacryl was used to bond the wounds in 24 cases, while the traditional suture method was used for 21 cases. The wound healing time, complications, treatment satisfaction, and number of visits of the two groups were compared. RESULTS: The two groups had similar baseline characteristics. The wound healing time (from wound disinfection to wound dressing) was shorter in the tissue glue group (4.35 ± 0.47min versus 11.71 ± 1.85 min, P< 0.01). There was 1 case of wound dehiscence in the tissue glue group. Twenty-two cases in the tissue glue group were satisfied, 2 cases were basically satisfied, and 0 were dissatisfied. Eleven cases in the traditional suture group were satisfied, 9 cases were basically satisfied, and 1 case was dissatisfied. The difference was statistically significant (P < 0.05). In terms of the number of visits, the tissue glue group visited (1.54 ± 0.88) times, while the traditional suture group visited (2.38 ± 0.59) times. The difference between the two groups was statistically significant (P < 0.01). The real-time reverse transcriptase polymerase chain tests for severe acute respiratory syndrome coronavirus 2 of all medical staff in the ophthalmology emergency room were negative. CONCLUSION: Compared with the traditional suture method, tissue glue used in eyelid laceration in children has the advantages of painlessness, shorter operation duration, higher safety and satisfaction, greater ease of care, and fewer hospital visits. Tissue glue can be widely used to reduce the risk of cross-infection.

A meta-analysis on the risk factors adjusted association between cardiovascular disease and COVID-19 severity (preprint)

Background Cardiovascular disease (CVD), one of the most common comorbidities of coronavirus disease 2019 (COVID-19), has been suspected to be associated with adverse outcomes in COVID-19 patients, but their correlation remains controversial.Method This is a quantitative meta-analysis on the basis of adjusted effect estimates. PubMed, Web of Science, MedRxiv, Scopus, Elsevier ScienceDirect, Cochrane Library and EMBASE were searched comprehensively to obtain a complete data source up to January 7, 2021. Pooled effects (hazard ratio (HR), odds ratio (OR)) and the 95% confidence intervals (CIs) were estimated to evaluate the risk of the adverse outcomes in COVID-19 patients with CVD. Heterogeneity was assessed by Cochran’s Q-statistic, I²test, and meta-regression. In addition, we also provided the prediction interval, which was helpful for assessing whether the variation across studies was clinically significant. The robustness of the results was evaluated by sensitivity analysis. Publication bias was assessed by Begg’s test, Egger’s test, and trim-and-fill method.Result Our results revealed that COVID-19 patients with pre-existing CVD tended more to adverse outcomes on the basis of 203 eligible studies with 24,033,838 cases (pooled ORs = 1.41, 95% CIs: 1.32–1.51, prediction interval: 0.84–2.39; pooled HRs = 1.34, 95% CIs: 1.23–1.46, prediction interval: 0.82–2.21). Further subgroup analyses stratified by age, the proportion of male, study design, disease types, sample size, region and disease outcomes also showed that pre-existing CVD was significantly associated with adverse outcomes among COVID-19 patients.Conclusion Our findings demonstrated that pre-existing CVD was an independent risk factor associated with adverse outcomes among COVID-19 patients.