Evaluating Different Measures for Social Distancing with Simulation

The following sections are included: • Introduction • Literature Review • Covid-ABS Model • Overview • Parameter Setting • Simulation Dynamics • A1 Mobility Patterns • Healthcare System Capacity • Contagion Spreading • Economic Transactions • Summary • Scenarios and Results • Scenarios Setting • Scenario 0 (Baseline): No Covid-19 Pandemic • Scenario 1: Take no Measures • Scenario 2: Work in Groups Every Other Week • Scenario 3: Work in Groups Every Other Week and Partial Lockdown • Scenario 4: Work in Groups Every Other Day • Scenario 5: Work in Groups Every Other Day and Partial Lockdown • Comparisons Among the Scenarios • Impact on the Supply Chain • Conclusion • References. © 2023 by World Scientific Publishing Co. Pte. Ltd.

New Insights from Chemical Biology: Molecular Basis of Transmission, Diagnosis, and Therapy of SARS-CoV-2

Coronavirus disease 2019 (COVID-19) is caused by a novel strain of coronavirus, designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has caused a global pandemic rapidly sweeping across all countries, bringing social and economic hardship to millions. Most countries have implemented early warning measures to detect, isolate, and treat patients infected with SARS-CoV-2. This minireview summarizes some of those steps, in particular, testing methods and drug development in the context of chemical biology, and discusses the molecular basis of COVID-19's virulent transmissibility.

Effectiveness of Non-pharmaceutical Interventions on Suppressing the 1st Wave of COVID-19 Epidemic in Shenzhen: An Agent-based Modelling Study

Many cities in China have adopted a series of Non-Pharmaceutical Interventions (NPIs) and rapidly suppressed the 1 st wave of COVID-19 epidemic in 2020. It is critical to evaluate the effectiveness of these NPIs for future epidemic control. However, as a variety of NPIs were applied together in practice, it is difficult to evaluate the effectiveness of a single type of intervention by epidemiological observation. Taking Shenzhen city as an example, this study used a spatially explicit agent-based model by integrating mobile phone location data, travel survey data, building survey data and other multi-source spatiotemporal big data to evaluate the effectiveness of different types of NPIs in the suppression of the 1 st wave of COVID-19 epidemic in Shenzhen. The simulation results show that the peak of the epidemic would have appeared on the 127 th day since Jan 1st of 2020, resulting in an average of 72.26% of the population to be infected without any interventions. In the 1 st wave of Shenzhen epidemic, except for the hospitalization of confirmed cases and intercity traffic restrictions, the stay-at-home order was the most effective one, followed by comprehensive isolation and quarantine measures (for close contacts, imported population and suspected cases), mask wearing, and orderly resumption of work. The stay-at-home order and comprehensive isolation and quarantine measures can effectively control the large-scale outbreak of the COVID-19, which are identified as the core measures;Mask wearing and orderly resumption of work can only reduce the overall infection size and delay the epidemic peak, which are identified as secondary measures. Considering the socioeconomic costs and the receding compliance to interventions in the post-epidemic period, this study suggests that the core measures and secondary measures should be combined to control the sporadic cases. Specifically, the local government can give the highest priority to isolation and quarantine measures for confirmed cases and high-risk individuals, complemented by mask wearing. In addition, our model can reveal the high-risk infection areas at a community level, which can help deploy control measures within an urban environment. In summary, this study demonstrated the advantages of integrating spatiotemporal big data and agent-based models to simulate the spread processes of infectious diseases in an urban environment: it can not only simulate the evolving processes of an epidemic at a fine-grained scale, but also evaluate the effectiveness of the NPIs at an individual level and for activity-travel behaviors, which can be useful for precise intervention. 2021, Science Press. All right reserved.

Centralized remote and risk-based monitoring in the influenza vaccine to effectively stop cardiothoracic events and decompensated heart failure trial: A cost-effective and easy-to-implement approach

Monitoring of clinical trials is crucial for the protection of human subjects, the integrity of the study, validity of the data, and for safeguarding the highest standards in clinical research. It is required by good clinical practice, but the expense of traditional on-site monitoring can be prohibitive. Striking a balance between the level of monitoring needed and meeting the good clinical practice requirements while remaining fiscally viable is a delicate act, but can be successfully achieved with a targeted use of resources. This paper details the use of a cost-effective strategy of using a risk-based remote monitoring model adopted in the INfluenza Vaccine to Effectively Stop cardio Thoracic Events and Decompensated heart failure trial (ClinicalTrials.gov Identifier: NCT02787044), a pragmatic large simple trial, conducted in the United States and Canada. These strategies provide protection to human subjects and ensure the enrollment of eligible patients to the trial, two areas deemed most critical for INfluenza Vaccine to Effectively Stop cardio Thoracic Events and Decompensated heart failure as a pragmatic trial. When combined appropriately strategies common to centralized, remote, and risk-based monitoring ensure the safety of participants, study quality, and allow the study to remain within budgetary constraints. The INfluenza Vaccine to Effectively Stop cardio Thoracic Events and Decompensated heart failure trial is monitored without a single planned on-site visit. The monitors use the electronic trial master file used in the study along with low-tech and easy to implement, yet secure methods to review the informed consent. The monitors also use an electronic data capture system in the study and a secure cloud-based system to access and share protected health information-redacted medical records to verify eligibility of enrolled patients. The key to the successful remote monitoring of the trial is based on the low-tech methodologies that all sites could easily access and implement while still providing a high level of security for the subjects' protected health information. The processes developed for INfluenza Vaccine to Effectively Stop cardio Thoracic Events and Decompensated heart failure allowed for the study teams to react quickly to any issues, while still ensuring highquality monitoring at a much lower cost than on-site monitoring. The strategies for monitoring the INfluenza Vaccine to Effectively Stop cardio Thoracic Events and Decompensated heart failure trial could be feasible for other clinical trials similar in design and risk especially during the COVID-19 pandemic and in the future. The INfluenza Vaccine to Effectively Stop cardio Thoracic Events and Decompensated heart failure trial was supported by the National Heart, Lung, and Blood Institute under cooperative agreements U01HL130163 and U01HL130204 and by Sanofi Pasteur to the INfluenza Vaccine to Effectively Stop cardio Thoracic Events and Decompensated heart failure Clinical Coordinating Center and the INfluenza Vaccine to Effectively Stop cardio Thoracic Events and Decompensated heart failure Data Coordinating Center.

Apatinib in combination with camrelizumab, a humanized immunoglobulin G4 monoclonal antibody against programmed cell death-1, in patients with metastatic acral melanoma

Background: Patients(pts) with metastatic acral melanoma respond poorly to anti-PD-1 monotherapy. Apatinib, a vascular endothelial growth factor (VEGF) inhibitor, is a kind of antiangiogenic drugs which have shown synergistic therapeutic effects in combination with PD-1 blockade. We conducted this single-center, open label phase trial to evaluate the safety and efficacy of camrelizumab in combination with apatinib in advanced treatment-naïve acral melanoma pts. Methods: Eligible participants were adult pts (aged 18 to 75) with histologically confirmed unresectable stage or distant metastatic acral melanoma. Exclusion criterion included unknown primary melanoma, brain metastatic disease or previous use of anti PD-1 ab. Pts received camrelizumab at 200mg intravenous infusion every 2 weeks, in combination with apatinib 250 mg orally once a day. The primary endpoint was ORR according to RECIST 1.1 criteria, and the secondary endpoints were safety and RFS. Results: Thirty pts were enrolled from April 2019 to January 2021. Basic characteristics: the mean age was 56.7 years, 22 pts were at stage, 33.3% had an elevated LDH level. Median tumor burden was 45mm (10-187). Gene mutation: Nras 4, cKit 3, Braf 2. Up to January 2021, 27 pts could be evaluated, in which 2 pts got CR, 4 pts achieved PR, and 63% experienced tumor shrinkage. The ORR and DCR were 22.2% and 77.8%, respectively. With a median follow up time of 8.3 months, the median PFS was 8.0 months (95% CI, 3.68, 10.19), the one-year durable response rate was 83.3% and the duration of response time was still not reached. Univariate analysis showed high LDH level was negatively associated with PFS. Whole exome data of baseline tumor biopsies revealed a positive correlation between high copy number variation (CNV) plus high mutational load (TMB) and efficacy, and all of the 4pts with MDC1 gene mutation got tumor shrink and 2 got PR. 96.7% pts experienced treatment-related AEs (TRAEs), including hand foot syndrome in 40%, proteinuria in 40%, liver dysfunction in 36.7%, and hypothyroidism in 30%. The grade 3-4 TRAEs were 33.3%. AE-related permanent discontinuation occurred in only 13.3% pts. 6 pts had delays of treatment due to the COVID-19 epidemic. No dose-limiting toxicities and suspected unexpected AEs were observed in the combination. Conclusions: The combination of apatinib plus camrelizumab was tolerable and showed promising antitumor activities and PFS improvement in pts with treatment-naïve metastatic acral melanoma. The survival is still in follow up.

IL10 and B cells cooperate to predict SARS-CoV-2 disease severity

Background: SARS-COV2 has infected more than 62 million people world-wide and led to almost 1.5 million deaths. Exacerbated inflammation, lymphopenia and coagulopathy are part of the complex cascade of events that can lead to death. Additionally, elevated B cells, antibody production and heightened IL-10 levels were associated with severe disease. Methods: We performed scRNAseq/CITEseq on matched peripheral blood mononuclear cells (PBMCs) and bronchoalveolar lavage (BAL) from 5 COVID-19 positive donors with different disease outcomes at time of hospitalization. B cell gene signatures and cytokine/chemokine levels in plasma and BAL fluid (BALF) were associated to live neutralizing antibodies (NAbs) as well as to viral load (VL) readouts. Results: Fourteen clusters of B cells were identified in PBMCs. They included subsets of naïve, memory B cells and plasmablasts. Ten clusters, comprising mature/effector B cells, were found in BAL while no naïve B cells were observed. Titers of NAbs in the BALF were significantly associated to memory B cell frequencies and were inversely correlated to VL. Systemic NAbs reflected Nabs titers in the BALF, supporting that antibody production in the site of infection impacted the circulating levels of Abs. Peripheral B cells were enriched in signatures associated to chemokine signaling which was positively correlated to the chemokines measured in BALF. This suggests that mature B cells in PBMCs could migrate from periphery to the lung to counteract infection. Importantly, B cells in COVID19 patients presented a strong inflammatory signature that included heightened levels of interferons and IL-10 signaling, the latter a marker of disease severity known to promote B cell differentiation and antibody production. Conclusion: While this work corroborates prior findings in the literature, it associates IL10 levels and B cell migration to disease severity. A detailed analysis of the antibody repertoire and B cell clonality induced upon infection is under way and would support the understanding of the role of B cells in SARS-CoV-2 pathogenesis and also lead to possible immune interventions to counteract severity.

[Source investigation on a familiar cluster of coronavirus disease 2019 in Dandong city of Liaoning Province].

To Track the source of the infection through an investigation of a clustering of coronavirus disease 2019(COVID-19), and provide scientific basis and Strategy for the effective control of the aggregated epidemic situation of COVID-19. Field epidemiological method was used to survey the cases and related close contacts in a family clustering epidemic of COVID-19 in Dandong city of Liaoning Province. We obtained survey data for a descriptive analysis.Real time RT-PCR technique was used to detect 2019-nCoV nucleic acid in samples collected from cases and related close contacts combined with serum specific antibody detection. A total of 3 confirmed cases and 2 asymptomatic infection cases were discovered in the clustering epidemic, with 34 close contacts.Of eight close family contacts visiting from other province, one patient was on the same flight as the confirmed case, and her antibody IgG was positive. The family clustering was caused by past infection case who visited her friend through Wuhan from other provinces to local area.

Using IL-2R/lymphocytes for predicting the clinical progression of patients with COVID-19.

Effective laboratory markers for the estimation of disease severity and predicting the clinical progression of coronavirus disease-2019 (COVID-19) is urgently needed. Laboratory tests, including blood routine, cytokine profiles and infection markers, were collected from 389 confirmed COVID-19 patients. The included patients were classified into mild (n = 168), severe (n = 169) and critical groups (n = 52). The leukocytes, neutrophils, infection biomarkers [such as C-reactive protein (CRP), procalcitonin (PCT) and ferritin] and the concentrations of cytokines [interleukin (IL)-2R, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α] were significantly increased, while lymphocytes were significantly decreased with increased severity of illness. The amount of IL-2R was positively correlated with the other cytokines and negatively correlated with lymphocyte number. The ratio of IL-2R to lymphocytes was found to be remarkably increased in severe and critical patients. IL-2R/lymphocytes were superior compared with other markers for the identification of COVID-19 with critical illness, not only from mild but also from severe illness. Moreover, the cytokine profiles and IL-2R/lymphocytes were significantly decreased in recovered patients, but further increased in disease-deteriorated patients, which might be correlated with the outcome of COVID-19. Lymphopenia and increased levels of cytokines were closely associated with disease severity. The IL-2R/lymphocyte was a prominent biomarker for early identification of severe COVID-19 and predicting the clinical progression of the disease.