Ratiometric fluorescence immunoassay of SARS-CoV-2 nucleocapsid protein via Si-FITC nanoprobe-based inner filter effect

The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has necessitated rapid, easy-to-use, and accurate diagnostic methods to monitor the virus infection. Herein, a ratiometric fluorescence enzyme-linked immunosorbent assay (ELISA) was developed using Si-fluorescein isothiocyanate nanoparticles (FITC NPs) for detecting SARS-CoV-2 nucleocapsid (N) protein. Si-FITC NPs were prepared by a one-pot hydrothermal method using 3-aminopropyl triethoxysilane (APTES)-FITC as the Si source. This method did not need post-modification and avoided the reduction in quantum yield and stability. The p-nitrophenyl (pNP) produced by the alkaline phosphatase (ALP)-mediated hydrolysis of p-nitrophenyl phosphate (pNPP) could quench Si fluorescence in Si-FITC NPs via the inner filter effect. In ELISA, an immunocomplex was formed by the recognition of capture antibody/N protein/reporter antibody. ALP-linked secondary antibody bound to the reporter antibody and induced pNPP hydrolysis to specifically quench Si fluorescence in Si-FITC NPs. The change in fluorescence intensity ratio could be used for detecting N protein, with a wide linearity range (0.01–10.0 and 50–300 ng/mL) and low detection limit (0.002 ng/mL). The concentration of spiked SARS-CoV-2 N protein could be determined accurately in human serum. Moreover, this proposed method can accurately distinguish coronavirus disease 2019 (COVID-19) and non-COVID-19 patient samples. Therefore, this simple, sensitive, and accurate method can be applied for the early diagnosis of SARS-CoV-2 virus infection. Electronic Supplementary Material Supplementary material (characterization of Si-FITC NPs (FTIR spectrum, XRD spectra, and synchronous fluorescence spectra);condition optimization of ALP response (fluorescence intensity ratio change);mechanism investigation of ALP response (fluorescence lifetime decay curves and UV—vis absorption spectra);detection of N protein using commercial ELISA Kit;analytical performance of assays for ALP detection or SARS-CoV-2 N protein detection;and determination results of SARS-CoV-2 N protein in human serum) is available in the online version of this article at 10.1007/s12274-022-4740-5.

DrugDevCovid19: An Atlas of Anti-COVID-19 Compounds Derived By Computer-Aided Drug Design (preprint)

Since the outbreak of SARS-CoV-2, numerous compounds against COVID-19 have been derived by computer-aided drug design (CADD) studies. They are valuable resources for the development of COVID-19 therapeutics. In this work, we reviewed these studies and analyzed 779 compounds against 16 target proteins from 181 CADD publications. We performed unified docking simulations and neck-to-neck comparison with the solved co-crystal structures. We computed their chemical features and classified these compounds aiming to provide insights for subsequent drug design. Through detailed analyses, we recommended a batch of compounds that are worth further study. Moreover, we organized all the abundant data and constructed a freely available database, DrugDevCovid19 (http://clab.labshare.cn/covid/php/index.php), to facilitate the development of COVID-19 therapeutics.

Asymmetric Differential Privacy (preprint)

Differential privacy (DP) is getting attention as a privacy definition when publishing statistics of a dataset. This paper focuses on the limitation that DP inevitably causes two-sided error, which is not desirable for epidemic analysis such as how many COVID-19 infected individuals visited location A. For example, consider publishing misinformation that many infected people did not visit location A, which may lead to miss decision-making that expands the epidemic. To fix this issue, we propose a relaxation of DP, called asymmetric differential privacy (ADP). We show that ADP can provide reasonable privacy protection while achieving one-sided error. Finally, we conduct experiments to evaluate the utility of proposed mechanisms for epidemic analysis using a real-world dataset, which shows the practicality of our mechanisms.

Quantifying the Privacy-Utility Trade-offs in COVID-19 Contact Tracing Apps (preprint)

How to contain the spread of the COVID-19 virus is a major concern for most countries. As the situation continues to change, various countries are making efforts to reopen their economies by lifting some restrictions and enforcing new measures to prevent the spread. In this work, we review some approaches that have been adopted to contain the COVID-19 virus such as contact tracing, clusters identification, movement restrictions, and status validation. Specifically, we classify available techniques based on some characteristics such as technology, architecture, trade-offs (privacy vs utility), and the phase of adoption. We present a novel approach for evaluating privacy using both qualitative and quantitative measures of privacy-utility assessment of contact tracing applications. In this new method, we classify utility at three (3) distinct levels: no privacy, 100% privacy, and at k where k is set by the system providing the utility or privacy.

PCT-TEE: Trajectory-based Private Contact Tracing System with Trusted Execution Environment (preprint)

Existing Bluetooth-based Private Contact Tracing (PCT) systems can privately detect whether people have come into direct contact with COVID-19 patients. However, we find that the existing systems lack functionality and flexibility, which may hurt the success of the contact tracing. Specifically, they cannot detect indirect contact (e.g., people may be exposed to coronavirus because of used the same elevator even without direct contact); they also cannot flexibly change the rules of "risky contact", such as how many hours of exposure or how close to a COVID-19 patient that is considered as risk exposure, which may be changed with the environmental situation. In this paper, we propose an efficient and secure contact tracing system that enables both direct contact and indirect contact. To address the above problems, we need to utilize users' trajectory data for private contact tracing, which we call trajectory-based PCT. We formalize this problem as Spatiotemporal Private Set Intersection. By analyzing different approaches such as homomorphic encryption that could be extended to solve this problem, we identify that Trusted Execution Environment (TEE) is a proposing method to achieve our requirements. The major challenge is how to design algorithms for spatiotemporal private set intersection under limited secure memory of TEE. To this end, we design a TEE-based system with flexible trajectory data encoding algorithms. Our experiments on real-world data show that the proposed system can process thousands of queries on tens of million records of trajectory data in a few seconds.

Spinal surgery and related management on patients with COVID-19: experience of a regional medical centre in Wuhan.

During the pandemic of COVID-19, some patients with COVID-19 may need emergency surgeries. As spine surgeons, it is our responsibility to ensure appropriate treatment to the patients with COVID-19 and spinal diseases. A protocol for spinal surgery and related management on patients with COVID-19 has been reviewed. Patient preparation for emergency surgeries, indications, and contraindications of emergency surgeries, operating room preparation, infection control precautions and personal protective equipments (PPE), anesthesia management, intraoperative procedures, postoperative management, medical waste disposal, and surveillance of healthcare workers were reviewed. It should be safe for surgeons with PPE of protection level 2 to perform spinal surgeries on patients with COVID-19. Standardized and careful surgical procedures should be necessary to reduce the exposure to COVID-19.

Invasive Mechanical Ventilation May Be an Important Factor of Mortality in Severe/Critical COVID-19 Pneumonia: A Retrospective Cohort Study (preprint)

Background: Many of severe COVID-19 patients are admitted to the hospital or even to the Intensive Care Unit(ICU). The present study was aimed to investigated the risk factors in death from COVID-19.Methods: In this retrospective study, all inpatients confirmed severe or critical COVID-19 from two tertiary hospital in Huangshi were included, who had been discharged or died by March19,2020. Demographic,clinical,treatment,laboratory data and information were extracted from electronic medical records and compared between survivors group and non-survivors group. The univariable and multivariable logistic regression analysis was used to analyze the risk factors associated with in-hospital death.Results: 81 patients were included in this study, of whom 55 were discharged and 26 died in hospital. In all patients, 36(44.4%) patients had comorbidity, including hypertension(27[33.3%]), diabetes(11[13.6%]) and coronary heart disease (CHD)(11[13.6%]), and 16(19.8%) patients accompanied with more than 2 kinds of underlying diseases. The proportion of CHD in non-survivors group was significantly higher than that in survivors group(26.9% vs 7.3%, P=0.032), but there were no differences in hypertension, diabetes and COPD between the non-survivors group and the survivors group. Multivariable logistic regression analysis showed increasing odds of in-hospital death associated with aspartate aminotransferase(AST) and invasive mechanical ventilation (IMV) (P<0.001)(P=0.017）.Conclusions: Invasive Mechanical Ventilation may contribute to mortality of severe/critical COVID-19 pneumonia, and with higher AST at admission was one of the indicators of poor prognosis.Trial registration: Chinese Clinical Trial Registration; ChiCTR2000031494; Registered 02 April 2020; http://www.medresman.org

Secure and Efficient Trajectory-Based Contact Tracing using Trusted Hardware (preprint)

The COVID-19 pandemic has prompted technological measures to control the spread of the disease. Private contact tracing (PCT) is one of the promising techniques for the purpose. However, the recently proposed Bluetooth-based PCT has several limitations in terms of functionality and flexibility. The existing systems are only able to detect direct contact (i.e., human-human contact), but cannot detect indirect contact (i.e., human-object, such as the disease transmission through surface). Moreover, the rule of risky contact cannot be flexibly changed with the environmental situation and the nature of the virus. In this paper, we propose a secure and efficient trajectory-based PCT system using trusted hardware. We formalize trajectory-based PCT as a generalization of the well-studied Private Set Intersection (PSI), which is mostly based on cryptographic primitives and thus insufficient. We solve the problem by leveraging trusted hardware such as Intel SGX and designing a novel algorithm to achieve a secure, efficient and flexible PCT system. Our experiments on real-world data show that the proposed system can achieve high performance and scalability. Specifically, our system (one single machine with Intel SGX) can process thousands of queries on 100 million records of trajectory data in a few seconds.

Impacts of the COVID-19 epidemic on the department of stomatology in a tertiary hospital: a case study in the General Hospital of the Central Theater Command, Wuhan, China (preprint)

Objectives: The aim of this study is to depict the impacts of COVID-19 pandemic on the clinical services and academic activities in the department of stomatology of a tertiary hospitals in Wuhan, China. Methods: We obtained historical data of the Department of Stomatology from the Health Information System of the General Hospital of Central Theater Command, Wuhan, China between January 2018 and June 2020. Line plots were used to illustrate temporal trend of the variables. Mean {+/-} standard deviation and median with interquartile range were used to summarize the variables. The Kruskal-Wallis equality-of-populations rank test was used to compare the difference between groups. Results: A significant decrease was noted in the monthly average number of patients seeking the outpatient services for the year 2020. The monthly numbers of patients seeking outpatient services were decreased by two thirds from 2018 to 2020. The number of emergency cases also decreased significantly by 64% in 2020. The monthly number of teaching hours decreased from 3.8 {+/-} 1.5 in 2018 and 4.7 {+/-} 1.4 in 2019 to 1.7 {+/-} 1.9 in 2020. The number of interns also decreased more than 70% in 2020. Conclusions: The impacts of COVID 19 in the stomatology clinic were significant with notable decreases in clinical services and education offered to the stomatology students. We must find solutions to keep as many as needed dental profession stay on thriving and to remain on the frontline of healthcare.

Clinical Characteristics and Short-Term Outcomes of Severe Patients With COVID-19 in Wuhan, China.

Background: A novel pneumonia (COVID-19) spread rapidly throughout worldwide, in December, 2019. Most of the deaths have occurred in severe and critical cases, but information on prognostic risk factors for severely ill patients is incomplete. Further research is urgently needed to guide clinicians, and we therefore prospectively evaluate the clinical outcomes of 114 severely ill patients with COVID-19 for short-term at the Union Hospital in Wuhan, China. Methods: In this single-centered, prospective, and observational study, we enrolled 114 severely ill patients with confirmed COVID-19 from Jan 23, 2020, to February 22, 2020. Epidemiological, demographic, laboratory, treatment, and outcome data were recorded, and the risk factors for poor outcome were analyzed. Results: Among the 114 enrolled patients with a mean age of 63.96 ± 13.41 years, 94 (82.5%) patients were classified as a good outcome group. Common clinical manifestations included fever, cough, and fatigue. Compared with the good outcome group, 20 (17.5%) patients in the poor outcome group more frequently exhibited lymphopenia, and lower levels of albumin, partial arterial oxygen pressure, higher levels of lactate dehydrogenase, creatine kinase, hypersensitive troponin I, C-reactive protein, ferritin, blood urea nitrogen, and D-dimer, as well as markedly higher levels of IL-6 and IL-10. Absolute numbers of T lymphocytes, CD8 + T cells, decreased in almost all the patients and were markedly lower in the poor outcome group than the good outcome group. We also found that traditional Chinese medicine can significantly improve the patient's condition, which is conducive to the transformation from a severe to mild condition. In addition, univariate and multivariate Cox analyses of potential factors for poor outcome patients indicated that cytokine storms and uncontrolled inflammation responses as well as liver, kidney, and cardiac dysfunction are related to the development of a poor outcome. Conclusion: In summary, we reported this single-centered, prospective, and observational study for short-term outcome in severe patients with COVID-19. We found that cytokine storms and uncontrolled inflammation responses as well as liver, kidney, and cardiac dysfunction may play important roles in the final outcome of severely ill patients with COVID-19. Our study will allow clinicians to benefit and rapidly estimate the likelihood of a short-term poor outcome for severely ill patients.

Psychological and behavioral responses of nursing interns from 12 Chinese universities during the COVID-19 epidemic: a knowledge, attitude and practice survey (preprint)

Background: Coronavirus disease 2019 (COVID-19) has spread globally and resulted in the COVID-19 pandemic worldwide. To depict the psychological and behavioral responses, and knowledge of nursing interns who are facing the COVID-19 epidemic in China, we conducted a knowledge, attitude, and practice (KAP) survey using a convenience sample in the First People’s Hospital of Lianyungang, Kangda College of Nanjing Medical University, Jiangsu Province, China.Methods: A combination of a face-to-face questionnaire survey and an online survey was used for nursing interns from 12 Chinese universities. The Symptom Checklist 90 was used to investigate anxiety and depression of the nursing interns during the COVID-19 epidemic. Self-designed questionnaires were used to investigate behavioral responses, COVID-19-related knowledge, and preventive measures.Results: During the COVID-19 epidemic, the mean score of anxiety of 237 surveyed nursing interns were not statistically significantly different with that of the Chinese norm (1.42 vs. 1.39, P = 0.354). However, the mean score of depression of them were lower than that of the Chinese norm (1.22 vs. 1.50, P < 0.001). However, no statistically significant difference in the anxiety or depression was found between demographic subgroups. The most common way for the nursing interns to seek for help was asking for instructor or other medical professionals (89.45%). When the nursing interns had suspected symptoms, they will most likely go to the hospital for treatment (97.89%). The nursing interns have good knowledge regarding the origin and prevention of COVID-19 (correct percentage > 94%), however less knowledge regarding treatment and incubation (correct percentage < 10%).Conclusion: The nursing interns showed relative lower depression in the face of COVID-19 public health emergencies, and took proper preventive measures during the epidemic, however, were lack of certain epidemiology knowledge about COVID-19.

Work characteristics of orthopaedic surgeons during the COVID-19 pandemic: A single center analysis.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has resulted in widespread cancellation of elective orthopaedic surgeries. During the pandemic period, many orthopaedic surgeons had been working at the front line to fight against COVID-19 in China, and the number of orthopaedic surgeries performed in our hospital decreased sharply. METHODS: The work characteristics of orthopaedic surgeons was evaluated by the workplaces of orthopaedic surgeons, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rate of orthopaedic surgeons and the number of orthopaedic surgeries performed. January 23-April 7 in 2020, January 23-April 8 in 2019, and April 8-June 22 in 2020 was defined as the pandemic period, non-pandemic period and post-pandemic period, respectively. The number and types of orthopaedic surgeons during the pandemic period, non-pandemic period, and post-pandemic period was compared and summarized. RESULTS: During the pandemic period, 65.56% of the orthopaedic surgeons had been working at the front line to fight against COVID-19. The SARS-CoV-2 infection rate of the orthopaedic surgeons who worked at the front line in January and since February was 18.18% and 0.00%, respectively (P=0.003). The number of orthopaedic surgeries performed per day during the pandemic period decreased 95.74% compared with the same period in the past year (P<0.001). The number of orthopaedic surgeries performed during the post-pandemic period was 13.10 times that of the pandemic period (P<0.001), and 55.71% of the non-pandemic period (P<0.001). CONCLUSIONS: The work characteristics of orthopaedic surgeons greatly changed during the COVID-19 pandemic.

Treatment of Severe COVID-19 with Human Umbilical Cord Mesenchymal Stem Cells (preprint)

Background: COVID-19 is a highly infectious respiratory disease. No therapeutics have yet been proven effective for treating severe COVID-19. Objectives: To determine whether human umbilical cord mesenchymal stem cell infusion may be effective and safe for the treatment of severe COVID-19. Methods: Patients with severe COVID-19 were randomly divided into 2 groups: the standard treatment group and the standard treatment plus hUC-MSC infusion group. The incidence of progression from severe to critical illness, 28-day mortality, clinical symptom improvement, time to clinical symptom improvement, hematologic indicators including C-reactive protein, lymphocyte number, and interleukin 6, and imaging changes were observed and compared between the two groups. Measurements and Main Results: The incidence of progression from severe to critical illness and the 28-day mortality rate were 0 in the hUC-MSC treatment group, while 4 patients in the control group deteriorated to critical condition and received invasive ventilation; 3 of them died, and the 28-day mortality rate was 10.34% . In the hUC-MSC treatment group, the time to clinical improvement was shorter than that in the control group. Clinical symptoms of weakness and fatigue, shortness of breath, and low oxygen saturation obviously improved beginning on the third day of stem cell infusion and reached a significant difference on day 7. CRP and IL-6 levels were significantly lower from day 3 of infusion, the time for the lymphocyte count to return to the normal range was significantly faster, and lung inflammation absorption was significantly shorter on CT imaging in the hUC-MSC group than in the control group. Conclusions: Intravenous transplantation of hUC-MSCs is a safe and effective method that can be considered a salvage and priority treatment option for severe COVID-19.

COVID-19 case-fatality rate and demographic and socioeconomic influencers: a worldwide spatial regression analysis based on country-level data (preprint)

We used the COVID-19 dataset obtained from the Our World in Data website and investigated the associations between COVID-19 CFR and nine country-level indices of 209 countries/territories using the Matern correlation regression model. Spatial dependence among the data was controlled using the latitude and longitude of the centroid of the countries/territories. Stratified analyses were conducted by economic level and COVID-19 testing policy. The average of country/territory-specific COVID-19 CFR is about 2-3% worldwide, which is higher than previously reported at 0.7-1.3%. Statistically significant associations were observed between COVID-19 CFR and population size and proportion of female smokers. The open testing policies are associated with decreased CFR. Strictness of anti-COVID-19 measures was not statistically significantly associated with CFR overall, but the higher stringency index was associated with higher CFR in higher income countries with active testing policies. The statistically significant association between population size and COVID-19 CRF suggests the healthcare strain and lower treatment efficiency in countries with large populations. The observed association between smoking in females and COVID-19 CFR might be due to that the proportion of female smokers reflected broadly income level of a country. When testing is warranted and healthcare resources are sufficient, strict quarantine and/or lockdown measures might result in excess deaths in underprivileged populations.

PANDA: Policy-aware Location Privacy for Epidemic Surveillance (preprint)

In this demonstration, we present a privacy-preserving epidemic surveillance system. Recently, many countries that suffer from coronavirus crises attempt to access citizen's location data to eliminate the outbreak. However, it raises privacy concerns and may open the doors to more invasive forms of surveillance in the name of public health. It also brings a challenge for privacy protection techniques: how can we leverage people's mobile data to help combat the pandemic without scarifying our location privacy. We demonstrate that we can have the best of the two worlds by implementing policy-based location privacy for epidemic surveillance. Specifically, we formalize the privacy policy using graphs in light of differential privacy, called policy graph. Our system has three primary functions for epidemic surveillance: location monitoring, epidemic analysis, and contact tracing. We provide an interactive tool allowing the attendees to explore and examine the usability of our system: (1) the utility of location monitor and disease transmission model estimation, (2) the procedure of contact tracing in our systems, and (3) the privacy-utility trade-offs w.r.t. different policy graphs. The attendees can find that it is possible to have the full functionality of epidemic surveillance while preserving location privacy.

Neutrophil-to-Lymphocyte Ratio may Replace Chest Computed Tomography to Reflect the Degree of Lung Injury in Patients with Corona Virus Disease 2019 (COVID-19) (preprint)

Objectives To investigated the relationship between the neutrophil-to-lymphocyte ratio (NLR) and the severity of lung injury in corona virus disease 2019 (COVID-19) patients.Methods The clinical data, laboratory examination, and chest computed tomography (CT) findings of 167 patients with confirmed COVID-19 admitted to 5 hospitals in Chongqing, China from January 2020 to February 2020 were retrospectively reviewed. According to the diagnostic criteria sixth edition of the “Diagnosis and Treatment of New Coronavirus Pneumonitis” published by the China National Health Commission, the patients were stratified by the severity of their illness to 3 groups: mild (n = 17), moderate (n = 119), or severe (n = 31).Results Differences of the NLR among the three groups and between each of the groups were significant (all p < 0.001). The NLR and CT severity score were positively correlated (r = 0.823, p < 0.001). Receiver operating characteristic (ROC) curve analysis found that NLR had diagnostic and prognostic value in COVID-19 patients with either negative or positive CT results. The area under curve (AUC) was 0.819 (95% CI: 0.729-0.910, p < 0.001), the sensitivity was 61.3%, specificity was 94.1%, and the optimal NLR cutoff value was 3.634.Conclusion NLR reflected the degree of lung injury and predicted the progression of COVID-19. NLR is a low-cost, convenient, bedside alternative to chest CT scanning to indicate the severity of lung injury in patients with COVID-19, especially in relatively underdeveloped areas.

CT Imaging Changes of Corona Virus Disease 2019 (COVID-19):A multi-center study in Southwest China (preprint)

Background: Since the first case of a coronavirus disease 2019 (COVID-19) infection pneumonia was detected in Wuhan, China, a series of confirmed cases of the COVID-19 were found in Southwest China. The aim of this study was to describe the imaging manifestations of hospitalized patients with confirmed COVID-19 infection in southwest China. Methods: In this retrospective study, data were collected from 131 patients with confirmed coronavirus disease 2019 (COVID-19) from 3 Chinese hospitals. Their common clinical manifestations, as well as characteristics and evolvement features of chest CT images, were analyzed. Results: A total of 100 (76%) patients had a history of close contact with people living in Wuhan , Hubei. The clinical manifestations of COVID-19 included cough, fever. Most of the lesions identified in chest CT images were multiple lesions of bilateral lungs, lesions were more localized in the peripheral lung, 109 (83%) patients had more than two lobes involved,  20 (15%) patients presented with patchy ground glass opacities, patchy ground glass opacities and consolidation of lesions co-existing in 61 (47%) cases. Complications such as pleural thickening, hydrothorax, pericardial effusion, and enlarged mediastinal lymph nodes were detected but only in rare cases. For the follow-up chest CT examinations (91 cases), We found 66 (73%) cases changed very quickly, with an average of 3.5 days, 25 cases (27%) presented absorbed lesions, progression was observed in 41 cases (46%), 25 (27%) cases showed no significant changes. Conclusion: Chest CT plays an important role in diagnosing COVID-19. The imaging pattern of multifocal peripheral ground glass or mixed consolidation is highly suspicious of COVID-19, that can quickly change over a short period of time.