Quantifying the spatial spillover effects of non-pharmaceutical interventions on pandemic risk.

BACKGROUND: Non-pharmaceutical interventions (NPIs) implemented in one place can affect neighboring regions by influencing people's behavior. However, existing epidemic models for NPIs evaluation rarely consider such spatial spillover effects, which may lead to a biased assessment of policy effects. METHODS: Using the US state-level mobility and policy data from January 6 to August 2, 2020, we develop a quantitative framework that includes both a panel spatial econometric model and an S-SEIR (Spillover-Susceptible-Exposed-Infected-Recovered) model to quantify the spatial spillover effects of NPIs on human mobility and COVID-19 transmission. RESULTS: The spatial spillover effects of NPIs explain [Formula: see text] [[Formula: see text] credible interval: 52.8-[Formula: see text]] of national cumulative confirmed cases, suggesting that the presence of the spillover effect significantly enhances the NPI influence. Simulations based on the S-SEIR model further show that increasing interventions in only a few states with larger intrastate human mobility intensity significantly reduce the cases nationwide. These region-based interventions also can carry over to interstate lockdowns. CONCLUSIONS: Our study provides a framework for evaluating and comparing the effectiveness of different intervention strategies conditional on NPI spillovers, and calls for collaboration from different regions.

Ultrasound combined with glial cell line-derived neurotrophic factor-loaded microbubbles for the targeted treatment of drug addiction.

Drug addiction is a serious problem globally, recently exacerbated by the COVID-19 pandemic. Glial cell-derived neurotrophic factor (GDNF) is considered a potentially effective strategy for the treatment of addiction. Previous animal experiments have proven that GDNF has a good therapeutic effect on drug addiction, but its clinical application is limited due to its poor blood-brain barrier (BBB) permeability. Low-frequency focused ultrasound, combined with microbubbles, is a non-invasive and reversible technique for locally-targeted BBB opening. In the present study, magnetic resonance imaging-guided low-frequency focused ultrasound, combined with GDNF microbubbles, was used to target BBB opening in the ventral tegmental area (VTA) region. The effects of GDNF on morphine-induced conditioned place preference (CPP) and acute withdrawal symptoms in rats after a partially opened BBB were evaluated by behavioral observation. Western blot was used to detect changes in tyrosine hydroxylase (TH) expression levels in the VTA region after different treatments, and high performance liquid chromatography was used to detect the changes in monoamine neurotransmitter content. The results showed that ultrasound combined with GDNF microbubbles targeted and opened the BBB in the VTA region, and significantly increased GDNF content, destroyed morphine-induced CPP, and reduced the withdrawal symptoms of morphine addiction in rats. Furthermore, the up-regulation of TH expression and the increase of norepinephrine and dopamine content induced by morphine were significantly reversed, and the increase of 5-hydroxytryptamine content was partially reversed. Therefore, ultrasound combined with GDNF microbubbles to target and open the BBB can effectively increase the content of central GDNF, thus playing a therapeutic role in morphine addiction. Our study provides a new approach to locally open the BBB and target delivery of neurotrophic factors, such as GDNF, to treat brain diseases like addiction.

Investigating time, strength, and duration of measures in controlling the spread of COVID-19 using a networked meta-population model.

Policy makers around the world are facing unprecedented challenges in making decisions on when and what degrees of measures should be implemented to tackle the COVID-19 pandemic. Here, using a nationwide mobile phone dataset, we developed a networked meta-population model to simulate the impact of intervention in controlling the spread of the virus in China by varying the effectiveness of transmission reduction and the timing of intervention start and relaxation. We estimated basic reproduction number and transition probabilities between health states based on reported cases. Our model demonstrates that both the time of initiating an intervention and its effectiveness had a very large impact on controlling the epidemic, and the current Chinese intense social distancing intervention has reduced the impact substantially but would have been even more effective had it started earlier. The optimal duration of the control measures to avoid resurgence was estimated to be 2 months, although would need to be longer under less effective controls.

A Toll-like Receptor-Activating, Self-Adjuvant Glycan Nanocarrier.

The global pandemic of COVID-19 highlights the importance of vaccination, which remains the most efficient measure against many diseases. Despite the progress in vaccine design, concerns with suboptimal antigen immunogenicity and delivery efficiency prevail. Self-adjuvant carriers-vehicles that can simultaneously deliver antigens and act as adjuvants-may improve efficacies in these aspects. Here, we developed a self-adjuvant carrier based on an acetyl glucomannan (acGM), which can activate toll-like receptor 2 (TLR2) and encapsulate the model antigen ovalbumin (OVA) via a double-emulsion process. In vitro tests showed that these OVA@acGM-8k nanoparticles (NPs) enhanced cellular uptake and activated TLR2 on the surface of dendritic cells (DCs), with increased expression of co-stimulatory molecules (e.g. CD80 and CD86) and pro-inflammatory cytokines (e.g. TNF-α and IL12p70). In vivo experiments in mice demonstrated that OVA@acGM-8k NPs accumulated in the lymph nodes and promoted DCs' maturation. The immunization also boosted the humoral and cellular immune responses. Our findings suggest that this self-adjuvant polysaccharide carrier could be a promising approach for vaccine development.

Optimization and Operations Research in Mitigation of a Pandemic

The pandemic of COVID-19 initiated in 2019 and spread all over the world in 2020 has caused significant damages to the human society, making troubles to all aspects of our daily life. Facing the serious outbreak of the virus, we consider possible solutions from the perspectives of both governments and enterprises. Particularly, this paper discusses several applications of supply chain management, public resource allocation, and pandemic prevention using optimization and machine learning methods. Some useful insights in mitigating the pandemic and economy reopening are provided at the end of this paper. These insights might help governments to reduce the severity of the current pandemic and prevent the next round of outbreak. They may also improve companies’ reactions to the increasing uncertainties appearing in the business operations. Although the coronavirus imposes challenges to the entire society at the moment, we are confident to develop new techniques to prevent and eradicate the disease.

`Development of a rapid neutralizing antibody test for SARS-CoV-2 and its application for neutralizing antibody screening and vaccinated serum testing

Background : Since the outbreak of coronavirus disease (COVID-19), the high infection rate and mutation frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent, have contributed to the ongoing global pandemic. Vaccination has become the most effective means of controlling COVID-19. Traditional neutralizing tests of sera are complex and labor-intensive, therefore, a rapid test for detecting neutralizing antibodies and antibody status post-immunization is needed. Methods : Based on the fact that antibodies exhibit neutralizing activity by blocking the binding of the S protein receptor-binding domain (S-RBD) to ACE2, we developed a rapid neutralizing antibody test, ACE2-Block-ELISA. To evaluate the sensitivity and specificity, we used 54 positive and 84 negative serum samples. We also tested the neutralizing activities of monoclonal antibodies (mAbs) and 214 sera samples from healthy individuals immunized with the inactivated SARS-CoV-2 vaccine. Results : The sensitivity and specificity of the ACE2-Block ELISA were 96.3% and 100%, respectively. For neutralizing mAb screening, ch-2C5 was selected for its ability to block the ACE2–S-RBD interaction. A plaque assay confirmed that ch-2C5 neutralized SARS-CoV-2, with NT50 values of 4.19, 10.63, and 1.074 μg/mL against the SARS-CoV-2 original strain, and the Beta and Delta variants, respectively. For the immunized sera samples, the neutralizing positive rate dropped from 82.14% to 32.16% within 4 months post-vaccination. Conclusions : This study developed and validated an ACE2-Block-ELISA to test the neutralizing activities of antibodies. As a rapid, inexpensive and easy-to-perform method, this ACE2-Block-ELISA has potential applications in rapid neutralizing mAb screening and SARS-CoV-2 vaccine evaluation.

The change of myopic prevalence in children and adolescents before and after COVID-19 pandemic in Suqian, China.

PURPOSE: The aim of this study was to investigate the change of myopic prevalence in students with different demographic characteristics before and after the COVID-19 pandemic in Suqian, China. METHODS: A retrospective, cross-sectional study was conducted. Student data from 52 schools in 2019 and 2020 were collected from the electronic medical records database through cluster sampling. Ophthalmic examinations were conducted on students from September to December in 2019 and 2020. Measurements of uncorrected visual acuity (UCVA) and noncycloplegic autorefraction were included to obtain the spherical equivalent refraction (SER) and prevalence of myopia. The difference in the rate of myopia and SER of students ages 6 to 18 with various demographic characteristics was compared between the two years. RESULTS: Records from 118,479 students in 2019 and the 121,881 students in 2020 were obtained. In 2019 and 2020, the prevalence of overall myopia increased from 43.1% to 48.9% (5.8 percentage point), and a substantial shift in myopic rate occurred in grades 4 to 6 (6.9 percentage point). The change in the prevalence of myopia in girls (5.9 percentage point) was approximately equal to that in boys (5.8 percentage point) and it was more common in rural students (5.9 percentage point) than in urban students (5.1 percentage point). The prevalence of low myopia increased more in children, and the prevalence of moderate myopia increased more in adolescents. The mean spherical equivalent refraction (SER) (-1.34±2.03 D) was lower in 2020 than in 2019 (-1.16±1.92 D), while SER decreased mainly at ages 7 to 15. The SER presented myopic status at the age of 9 (-0.55±1.26 D in 2019, -0.71±1.42 D in 2020), and attained moderate myopia at the age of 15 (-3.06±2.41 D in 2019, -3.22±2.40 D in 2020). CONCLUSIONS: After the COVID-19 pandemic, myopia increased in this population with variable rates of increase in different demographic groups. The change of myopia in children was comparatively greater than that in adolescents. Therefore, we should take measures to prevent and control the development of myopia after the COVID-19 pandemic, especially for younger students.

Myopia of primary school students in Suqian before and after COVID-19 epidemic

Objective: To compare myopia prevalence among primary school students in Suqian before and after COVID-19 epidemic, so as to provide a reference for prevention and scientific propaganda of myopia.

Risk Factors and Outcomes of Acute Kidney Injury in Critically Ill Patients with Coronavirus Disease 2019.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has emerged as a major global health threat with a great number of deaths worldwide. Acute kidney injury (AKI) is a common complication in patients admitted to the intensive care unit. We aimed to assess the incidence, risk factors and in-hospital outcomes of AKI in COVID-19 patients admitted to the intensive care unit. METHODS: We conducted a retrospective observational study in the intensive care unit of Tongji Hospital, which was assigned responsibility for the treatments of severe COVID-19 patients by the Wuhan government. AKI was defined and staged based on Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Mild AKI was defined as stage 1, and severe AKI was defined as stage 2 or stage 3. Logistic regression analysis was used to evaluate AKI risk factors, and Cox proportional hazards model was used to assess the association between AKI and in-hospital mortality. RESULTS: A total of 119 patients with COVID-19 were included in our study. The median patient age was 70 years (interquartile range, 59-77) and 61.3% were male. Fifty-one (42.8%) patients developed AKI during hospitalization, corresponding to 14.3% in stage 1, 28.6% in stage 2 and 18.5% in stage 3, respectively. Compared to patients without AKI, patients with AKI had a higher proportion of mechanical ventilation mortality and higher in-hospital mortality. A total of 97.1% of patients with severe AKI received mechanical ventilation and in-hospital mortality was up to 79.4%. Severe AKI was independently associated with high in-hospital mortality (OR: 1.82; 95% CI: 1.06-3.13). Logistic regression analysis demonstrated that high serum interleukin-8 (OR: 4.21; 95% CI: 1.23-14.38), interleukin-10 (OR: 3.32; 95% CI: 1.04-10.59) and interleukin-2 receptor (OR: 4.50; 95% CI: 0.73-6.78) were risk factors for severe AKI development. CONCLUSIONS: Severe AKI was associated with high in-hospital mortality, and inflammatory response may play a role in AKI development in critically ill patients with COVID-19.

Early prediction model for progression and prognosis of severe patients with coronavirus disease 2019.

ABSTRACT: Coronavirus disease 2019 (COVID-19) has been a rampant worldwide health threat and we aimed to develop a model for early prediction of disease progression.This retrospective study included 124 adult inpatients with COVID-19 who presented with severe illness at admission and had a definite outcome (recovered or progressed to critical illness) during February 2020. Eighty-four patients were used as training cohort and 40 patients as validation cohort. Logistic regression analysis and receiver operating characteristic curve (ROC) analysis were used to develop and evaluate the prognostic prediction model.In the training cohort, the mean age was 63.4 ±â€Š1.5 years, and male patients (48, 57%) were predominant. Forty-three (52%) recovered, and 41 (49%) progressed to critical. Decreased lymphocyte count (LC, odds ratio [OR] = 4.40, P = .026), elevated lactate dehydrogenase levels (LDH, OR = 4.24, P = .030), and high-sensitivity C-reactive protein (hsCRP, OR = 1.01, P = .025) at admission were independently associated with higher odds of deteriorated outcome. Accordingly, we developed a predictive model for disease progression based on the levels of the 3 risk factors (LC, LDH, and hsCRP) with a satisfactory performance in ROC analysis (area under the ROC curve [AUC] = 0.88, P < .001) and the best cut-off value was 0.526 with the sensitivity and specificity of 75.0% and 90.7%, respectively. Then, the model was internally validated by leave-one-out cross-validation with value of AUC 0.85 (P < .001) and externally validated in another validation cohort (26 recovered patients and 14 progressed patients) with AUC 0.84 (P < .001).We identified 3 clinical indicators of risk of progression and developed a severe COVID-19 prognostic prediction model, allowing early identification and intervention of high-risk patients being critically illness.

The Incidence, Risk Factors, and Prognosis of Acute Kidney Injury in Adult Patients with Coronavirus Disease 2019.

BACKGROUND AND OBJECTIVES: Since December 2019, coronavirus disease 2019 (COVID-19) outbreak occurred and has rapidly spread worldwide. However, little information is available about the AKI in COVID-19. We aimed to evaluate the incidence, risk factors, and prognosis of AKI in adult patients with COVID-19. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a retrospective cohort study of 1392 patients with COVID-19 admitted to a tertiary teaching hospital. Clinical characteristics and laboratory data were extracted from electronic hospitalization and laboratory databases. AKI was defined and staged according to the 2012 Kidney Disease: Improving Global Outcomes criteria. Risk factors for AKI and the association of AKI with in-hospital mortality were assessed. RESULTS: A total of 7% (99 of 1392) of patients developed AKI during hospitalization, 40% (40 of 99) of which occurred within 1 week of admission. Factors associated with a higher risk of AKI include severe disease (odds ratio [OR], 2.25; 95% confidence interval [CI], 1.37 to 3.67), higher baseline serum creatinine (OR, 2.19; 95% CI, 1.17 to 4.11), lymphopenia (OR, 1.99; 95% CI, 1.12 to 3.53), and elevated D-dimer level (OR, 2.68; 95% CI, 1.07 to 6.70). The in-hospital mortality in patients with AKI stage 1, stage 2, and stage 3 was 62%, 77%, and 80%, respectively. AKI was associated with in-hospital mortality even after adjustment for confounders (OR, 5.12; 95% CI, 2.70 to 9.72). CONCLUSIONS: AKI is uncommon but carries high in-hospital mortality in patients with COVID-19.

Traditional Chinese medicine for symptoms of upper respiratory tract of COVID-19: A protocol for systematic review and meta-analysis.

BACKGROUND: Assessing the effectiveness and safety of traditional Chinese medicine (TCM) for symptoms of upper respiratory tract of coronavirus disease 2019 is the main purpose of this systematic review protocol. METHODS: The following electronic databases will be searched from inception to Sep 2020: the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, Web of Science, TCM, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scientific Journal Database (VIP database), and Wan-Fang Database. Search dates: from inception dates to June 2020. Language: English. Publication period: from inception dates to June 2020. The primary outcome is the time and rate of appearance of main symptoms (including coughing, pharyngalgia, and nasal obstruction). The secondary outcome is the length of hospital stay. Two independent reviewers will conduct the study selection, data extraction and assessment. RevMan V.5.3 will be used for the assessment of risk of bias and data synthesis. RESULTS: The results will provide a high-quality synthesis of current evidence for researchers in this subject area. CONCLUSION: The conclusion of our study will provide an evidence to judge whether TCM is effective and safe for the patients with symptoms of upper respiratory tract of coronavirus disease 2019. ETHICS AND DISSEMINATION: This protocol will not evaluate individual patient information or affect patient rights and therefore does not require ethical approval. Results from this review will be disseminated through peer-reviewed journals and conference reports. PROSPERO REGISTRATION NUMBER: CRD42020187422.

Kidney disease is associated with in-hospital death of patients with COVID-19.

In December 2019, a coronavirus 2019 (COVID-19) disease outbreak occurred in Wuhan, Hubei Province, China, and rapidly spread to other areas worldwide. Although diffuse alveolar damage and acute respiratory failure were the main features, the involvement of other organs needs to be explored. Since information on kidney disease in patients with COVID-19 is limited, we determined the prevalence of acute kidney injury (AKI) in patients with COVID-19. Further, we evaluated the association between markers of abnormal kidney function and death in patients with COVID-19. This was a prospective cohort study of 701 patients with COVID-19 admitted in a tertiary teaching hospital that also encompassed three affiliates following this major outbreak in Wuhan in 2020 of whom 113 (16.1%) died in hospital. Median age of the patients was 63 years (interquartile range, 50-71), including 367 men and 334 women. On admission, 43.9% of patients had proteinuria and 26.7% had hematuria. The prevalence of elevated serum creatinine, elevated blood urea nitrogen and estimated glomerular filtration under 60 ml/min/1.73m2 were 14.4, 13.1 and 13.1%, respectively. During the study period, AKI occurred in 5.1% patients. Kaplan-Meier analysis demonstrated that patients with kidney disease had a significantly higher risk for in-hospital death. Cox proportional hazard regression confirmed that elevated baseline serum creatinine (hazard ratio: 2.10, 95% confidence interval: 1.36-3.26), elevated baseline blood urea nitrogen (3.97, 2.57-6.14), AKI stage 1 (1.90, 0.76-4.76), stage 2 (3.51, 1.49-8.26), stage 3 (4.38, 2.31-8.31), proteinuria 1+ (1.80, 0.81-4.00), 2+∼3+ (4.84, 2.00-11.70), and hematuria 1+ (2.99, 1.39-6.42), 2+∼3+ (5.56,2.58- 12.01) were independent risk factors for in-hospital death after adjusting for age, sex, disease severity, comorbidity and leukocyte count. Thus, our findings show the prevalence of kidney disease on admission and the development of AKI during hospitalization in patients with COVID-19 is high and is associated with in-hospital mortality. Hence, clinicians should increase their awareness of kidney disease in patients with severe COVID-19.