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BackgroundSince December 2020, public health agencies have implemented a variety of vaccination strategies to curb the spread of SARS-CoV-2, along with pre-existing Nonpharmaceutical Interventions (NPIs). Initial strategy focused on vaccinating the elderly to prevent hospitalizations and deaths. With vaccines becoming available to the broader population, we aimed to determine the optimal strategy to enable the safe lifting of NPIs while avoiding virus resurgence. MethodsWe developed a compartmental deterministic SEIR model to simulate the lifting of NPIs under different vaccination rollout scenarios. Using case and vaccination data from Toronto, Canada between December 28, 2020 and May 19, 2021, we estimated transmission throughout past stages of NPI escalation/relaxation to compare the impact of lifting NPIs on different dates on cases, hospitalizations, and deaths, given varying degrees of vaccine coverages by 20-year age groups, accounting for waning immunity. ResultsWe found that, once coverage among the elderly is high enough (80% with at least one dose), the main age groups to target are 20-39 and 40-59 years, whereby first-dose coverage of at least 70% by mid-June 2021 is needed to minimize the possibility of resurgence if NPIs are to be lifted in the summer. While a resurgence was observed for every scenario of NPI lifting, we also found that under an optimistic vaccination coverage (70% by mid-June, postponing reopening from August 2021 to September 2021can reduce case counts and severe outcomes by roughly 80% by December 31, 2021. ConclusionsOur results suggest that focusing the vaccination strategy on the working-age population can curb the spread of SARS-CoV-2. However, even with high vaccination coverage in adults, lifting NPIs to pre-pandemic levels is not advisable since a resurgence is expected to occur, especially with earlier reopening.
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The spread of SARS-CoV-2 through direct transmission (person-to-person) has been the focus of most studies on the dynamics of COVID-19. The efficacy of social distancing and mask usage at reducing the risk of direct transmission of COVID-19 has been studied by many researchers. Little or no attention is given to indirect transmission of the virus through shared items, commonly touch surfaces and door handles. The impact of the persistence of SARS-CoV-2 on hard surfaces and in the environment, on the dynamics of COVID-19 remain largely unknown. Also, the current increase in the number of cases despite the strict non-pharmaceutical interventions suggests a need to study the indirect transmission of COVID-19 while incorporating testing of infected individuals as a preventive measure. Assessing the impact of indirect transmission of the virus may improve our understanding of the overall dynamics of COVID-19. We developed a novel deterministic susceptible-exposed-infected-removed-virus-death compartmental model to study the impact of indirect transmission pathway on the spread of COVID-19, the sources of infection, and prevention/control. We fitted the model to the cumulative number of confirmed cases at episode date in Toronto, Canada using a Markov Chain Monte Carlo optimization algorithm. We studied the effect of indirect transmission on the epidemic peak, peak time, epidemic final size and the effective reproduction number, based on different initial conditions and at different stages. Our findings revealed an increase in cases with indirect transmission. Our work highlights the importance of implementing additional preventive and control measures involving cleaning of surfaces, fumigation, and disinfection to lower the spread of COVID-19, especially in public areas like the grocery stores, malls and so on. We conclude that indirect transmission of SARS-CoV-2 has a significant effect on the dynamics of COVID-19, and there is need to consider this transmission route for effective mitigation, prevention and control of COVID-19 epidemic.
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Efforts to mitigate the COVID-19 pandemic have relied heavily on non-pharmaceutical interventions (NPIs), including physical distancing, hand hygiene, and mask-wearing. However, an effective vaccine is essential to containing the spread of the virus. The first doses were distributed at the end of 2020, but the efficacy, period of immunity it will provide, and percentage of coverage still remain unclear. We developed a compartment model to examine different vaccine strategies for controlling the spread of COVID-19. Our framework accounts for testing rates, test-turnaround times, and vaccination waning immunity. Using reported case data from the city of Toronto, Canada between Mar-Dec, 2020 we defined epidemic phases of infection using contact rates, which depend on individuals duration of time spent within the household, workplace/school, or community settings, as well as the probability of transmission upon contact. We investigated the impact of vaccine distribution by comparing different permutations of waning immunity, vaccine coverage and efficacy throughout various stages of NPIs relaxation in terms of cases, deaths, and household transmission, as measured using the basic reproduction number (R0). We observed that widespread vaccine coverage substantially reduced the number of cases and deaths. In order for NPIs to be relaxed 8 months after vaccine distribution, infection spread can be kept under control with either 60% vaccine coverage, no waning immunity, and 70% efficacy, or with 60% coverage with a 12-month waning immunity and 90% vaccine efficacy. Widespread virus resurgence can result when the immunity wanes under 3 months and/or when NPIs are relaxed in concomitance with vaccine distribution. In addition to vaccination, our analysis of R0 showed that the basic reproduction number is reduced by decreasing the tests turnaround time and transmission in the household. While we found that household transmission can decrease following the introduction of a vaccine, public health efforts to reduce test turnaround times remain important for virus containment. Our findings suggest that vaccinating two-thirds of the population with a vaccine that is at least 70% effective may be sufficient for controlling COVID-19 spread, as long as NPIs are not immediately relaxed.
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BackgroundThe closure of communities, including schools, has been adopted to control the coronavirus disease 2019 (COVID-19) epidemic in most countries. Operating schools safely during the pandemic requires a balance between health risks and the need for in-person learning. We use compartmental models to explore school reopening scenarios. MethodsUsing demographic and epidemiological data between July 31 and November 23, 2020 from the city of Toronto, we developed a Susceptible-Exposed-Asymptomatic-Infectious-Recovered-Hospitalized-Isolated model. Our model with age, household, and community transmission allow us to study the impact of schools open in September 2020. The model mimics the transmission in households, the community, and schools, accounting for differences in infectiousness between adults and children and youth and adults working status. We assessed the extent to which school opening may have contributed to COVID-19 resurgence in the fall and simulated scenarios for the safe reopening of schools up to May 31, 2021. We further considered the impact of the introduction of the new variant of concern. FindingsThough a slight increase in infections among adults (2.8%) and children (5.4%) is anticipated by the end of the year, safe school opening is possible with stringent nonpharmaceutical interventions (NPIs) decreasing the risk of transmission in the community and the household. We found that while school reopening was not the key driver in virus resurgence, but rather it was community spread that determined the outbreak trajectory, brief school closures did reduce infections when transmission risk within the home was low. When considered possible cross-infection amongst households, communities, and schools, we found that home transmission was crucial for mitigating the epidemic and safely operating schools. Simulating the introduction of a new strain with higher infectiousness, we observed substantial increases in infections, even when both schools and communities are closed. InterpretationSchools can open safely under strict maintenance of strict public health measures in the community. The gradual opening of schools and communities can only be achieved by maintaining NPIs and mitigating household transmission risk to avoid the broader escape of infections acquired in schools into the community via households. If the new COVID-19 strain is more infectious for children, public spaces, including schools, should be closed, and additional NPIs, including the use of masks, should be extended to toddlers. FundingThis research was supported by Canadian Institutes of Health Research (CIHR), Natural Sciences and Engineering Research Council of Canada, and York University Research Chair program. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThe design of a gradual school reopening strategy remains at the heart of decision-making on reopening after shut-downs to control the epidemic. Although available studies have assessed the risk of school reopening by modelling the transmission across schools and communities, it remains unclear whether the risk is due to increased transmission in adults or children and youth.We used GoogleScholar and PubMed searches to identify previous published works. We used te following terms: "school closure", "covid 19 school closure", "reopening schools", "reopening screening school", "school household second wave model". The search of the studies ended in January 2021. Papers in other languages than English and letters were excluded from the search. Two modelling studies examined the effects of screening and delayed school reopening, two other agent-based modelling studies explored the epidemic spread across different age groups. Added-value of this studyWe find that the resurgence of COVID-19 in Toronto in fall 2020 mainly resulted from the increase of contact rate among adults in the community, and that the degree of in-person attendance had the most significant impact on transmission in schools. To our knowledge, our work is the first to investigate the resurgence in infections following school reopening and the impact of risk mitigation measures in schools operation during the pandemic. Our novel and comprehensive model considers the age and household structure, but also considers three different settings, school, household and community. We further examined the effects of self-screening procedures, class size, and schooling days on transmission, which enabled us to compare scenarios of school reopening separately for both adults and children and youth, and model the cross-infection between them to avoid potential underestimation. We found that after schools opened, reducing household transmission was crucial for mitigating the epidemic since it can reduce cross-infection amongst households, communities and schools. Lastly, given the recent report of SARS-CoV-2 variant (VOC202012/01), we investigated the impact of the new variant that may be more infectious in children and youth. Implications of all the available evidenceOur analysis can inform policymakers of planning the safe reopening of schools during COVID-19. We suggest that integrating strict NPIs and school control measures are crucial for safe reopening. When schools are open, reducing transmission risk at home and community is paramount in curbing the spread of COVID-19. Lastly, if children are more susceptible to the new COVID-19 VOC, both schools and community must be closed, the time children spend in essential services locations minimized, and NPIs for those aged less than three years enforced.
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Objective:To explore the differences of immune reconstitution between peripheral blood stem cell transplantation and umbilical cord blood transplantation.Methods:A total of 300 patients (aged 18 (8, 33), 163 males and 137 females) with malignant hematological diseases who received allogeneic hematopoietic stem cell transplantation in the First Affiliated Hospital of University of Science and Technology of China from January 2018 to March 2020 were enrolled in this study, including 255 cases of umbilical cord blood transplantation and 45 cases of peripheral blood stem cell transplantation. Multicolor flow cytometry was applied to analyze lymphocyte subsets of the percentages and absolute counts in the two donor types and peripheral blood of patients after receiving hematopoietic stem cell transplantation. The differences between the two grafts were compared, and the lymphocyte subsets results were evaluated at 1, 2, 3, 4, 6, 9, 12, and 18 months after transplantation. 18-month disease-free survival (DFS) within the 300 patients under the two transplantation types were retrospectively analyzed.Results:1. The proportion of NKT cells in peripheral blood group was significantly higher than that in cord blood group (2.79% vs 0.24%, P<0.001). 2. The proportion of helper T cells in the UCBT group was higher than that in the PBSCT group, as well as the counts 6 months after transplantation ( P<0.05). 3. The proportion of NK1 cells (3 rd to 9 th month) and count (4 th to 12 th month) in UCBT group were significantly higher than those in PBSCT group ( P<0.05). 4. NKT cells in the UCBT group were lower than those in the PBSCT group (proportion and count) throughout the monitoring process ( P≤0.001). 5. The proportion of DNT cells (within 1 year) and count (within 6 months) in the UCBT group were significantly lower than those in the PBSCT group ( P<0.05). Conclusions:Compared with the peripheral blood stem cell transplantation group, the umbilical cord blood transplantation patients had a faster rate of lymphocyte reconstitution, and patients received umbilical cord blood transplantation had a stronger ability of immune reconstitution and could achieve long-term hematopoiesis.
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BackgroundIn many parts of the world, restrictive non-pharmaceutical interventions (NPI) that aim to reduce contact rates, including stay-at-home orders, limitations on gatherings, and closure of public places, are being lifted, with the possibility that the epidemic resurges if alternative measures are not strong enough. Here we aim to capture the combination of use of NPIs and reopening measures which will prevent an infection rebound. MethodsWe employ an SEAIR model with household structure able to capture the stay-at-home policy (SAHP). To reflect the changes in the SAHP over the course of the epidemic, we vary the SAHP compliance rate, assuming that the time to compliance of all the people requested to stay-at-home follows a Gamma distribution. Using confirmed case data for the City of Toronto, we evaluate basic and instantaneous reproduction numbers and simulate how the average household size, the stay-at-home rate, the efficiency and duration of SAHP implementation, affect the outbreak trajectory. FindingsThe estimated basic reproduction number R_0 was 2.36 (95% CI: 2.28, 2.45) in Toronto. After the implementation of the SAHP, the contact rate outside the household fell by 39%. When people properly respect the SAHP, the outbreak can be quickly controlled, but extending its duration beyond two months (65 days) had little effect. Our findings also suggest that to avoid a large rebound of the epidemic, the average number of contacts per person per day should be kept below nine. This study suggests that fully reopening schools, offices, and other activities, is possible if the use of other NPIs is strictly adhered to. InterpretationOur model confirmed that the SAHP implemented in Toronto had a great impact in controlling the spread of COVID-19. Given the lifting of restrictive NPIs, we estimated the thresholds values of maximum number of contacts, probability of transmission and testing needed to ensure that the reopening will be safe, i.e. maintaining an Rt < 1. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSA survey on published articles was made through PubMed and Google Scholar searches. The search was conducted from March 1 to August 13, 2020 and all papers published until the end of this research were considered. The following terms were used to screen articles on mathematical models: "household structure", "epidemic model", "SARS-CoV-2", "COVID-19", "household SIR epidemic", "household SIS epidemic", "household SEIR epidemic", "quarantine, isolation model", "quarantine model dynamics", "structured model isolation". Any article showing, in the title, application of epidemic models in a specific country/region or infectious diseases rather than SARS-CoV-2 were excluded. Articles in English were considered. Added value of this studyWe develop an epidemic model with household structure to study the effects of SAHP on the infection within households and transmission of COVID-19 in Toronto. The complex model provides interesting insights into the effectiveness of SAHP, if the average number of individuals in a household changes. We found that the SAHP might not be adequate if the size of households is relatively large. We also introduce a new quantity called symptomatic diagnosis completion ratio (d_c). This indicator is defined as the ratio of cumulative reported cases and the cumulative cases by episode date at time t, and it is used in the model to inform the implementation of SAHP. If cases are diagnosed at the time of symptom onset, isolation will be enforced immediately. A delay in detecting cases will lead to a delay in isolation, with subsequent increase in the transmission of the infection. Comparing different scenarios (before and after reopening phases), we were able to identify thresholds of these factors which mainly affect the spread of the infection: the number of daily tests, average number of contacts per individual, and probability of transmission of the virus. Our results show that if any of the three above mentioned factors is reduced, then the other two need to be adjusted to keep a reproduction number below 1. Lifting restrictive closures will require the average number of contacts a person has each day to be less than pre-COVID-19, and a high rate of case detection and tracing of contacts. The thresholds found will inform public health decisions on reopening. Implications of all the available evidenceOur findings provide important information for policymakers when planning the full reopening phase. Our results confirm that prompt implementation of SAHP was crucial in reducing the spread of COVID-19. Also, based on our analyses, we propose public health alternatives to consider in view of a full reopening. For example, for different post-reopening scenarios, the average number of contacts per person needs to be reduced if the symptomatic diagnosis completion ratio is low and the probability of transmission increases. Namely, if fewer tests are completed and the usage of NPIs decreases, then the epidemic can be controlled only if individuals can maintain contact with a maximum average number of 4-5 people per person per day. Different recommendations can be provided by relaxing/strengthening one of the above-mentioned factors.
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Objective To investigate the cytogenetic and clinical features of acute myeloid leukemia (AML) with CD7 positive. Methods Among 788 AML patients in the First Affiliated Hospital of USTC from January 2008 to December 2012, a total of 140 AML patients with CD7 positive were enrolled, and their clinical and cytogenetic characteristics were analyzed respectively. Results According to French-American-British (FAB) classification systems, M5[47.1 % (66/140)] and M2[27.1 % (38/140)] were often detected in 140 AML patients with CD7 positive. The positive rate of CD7 in M0patients [(60.9±13.2) %] was the highest, followed by (53.1±29.5) % in M1patient. Karyotype analysis showed that 72 (51.4 %) AML patients with CD7 positive had unfavorable karyotypes. Thirty-one (22.1 %) AML patients with CD7 positive simultaneously showed the expressions of lymphoid antigens. Clinically, some AML patients with CD7 positive was accompanied by hyperleukocytosis [75.0 % (105/140)] (white blood count ≥20×109/L) and hepatosplenomegaly [82.1 % (115/140)]. The proportion of elder patients (above 65 years old) and complete remission rate of AML with CD7 positive were lower than those of AML with CD7 negative [25.7 % (36/140) vs. 39.4 % (255/648);12.1 % (17/140) vs. 24.7 % (160/648), respectively], and there were statistical differences (χ 2＝ 8.62, P＝0.03; χ 2＝ 9.70, P＝ 0.01, respectively). Conclusion AML patients with CD7 positive have specific cytogenetic and clinical characteristics, and poor prognosis.
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AIM:Atherosclerotic calcification is highly linked with plaque instability and cardiovascular events .Adenosine monophosphate-activated protein kinase ( AMPK) has been involved in the pathogenesis of various cardiovascular disease .The contributions of AMPKαsubunits to the development of atherosclerotic calcification in vivo remained unknown .We hypothesized that AMPKαsubunits may play a role in the development of atherosclerotic calcification .METHODS: Atherosclerotic calcification was generated by 24-week fed of western diet in ApoE-/-background mice .Calcification was evaluated in aortic roots and innominate arteries of ApoE-/-mice or in mice with dual deficiencies of ApoE and AMPKαsubunits globally ( AMPKα1 and AMPKα2 ) , or vascular smooth muscle cell ( VSMC)-specific or macrophage-specific knockout of AMPKα1 with atherosclerotic calcification pone diet . The mechanism of AMPKα1 in regulating Runx2 was further explored in human aortic VSMC .RESULTS: Ablation of AMPKα1 but not AMPKα2 in ApoE-/-background promoted atherosclerotic calcification with increased Runt -related transcription factor ( Runx2 ) expression in VSMC compared with ApoE-/-mice.Conversely, chronic administration of metformin, which activated AMPK, markedly reduced ath-erosclerotic calcification and Runx2 expression in ApoE-/-mice but had less effects in ApoE-/-/AMPKα1 -/-mice.Furthermore, VSMC-but not macrophage-specific deficiency of AMPKα1 in ApoE-/-background promoted atherosclerotic calcification in vivo com-pared with the controls .AMPKα1 silencing in human aortic VSMC prevented Runx 2 from proteasome degradation to trigger osteoblastic differentiation of VSMC .Conversely , activation of AMPK led to Runx 2 instability by inducing its small ubiquitin-like modifier modifi-cation (SUMOylation).Protein inhibitor of activated STAT-1 (PIAS1), the SUMO E3-ligase of Runx2, was directly phosphorylated by AMPKα1 at serine 510, to enhance its SUMO E3-ligase activity.Ablation of PIAS1 serine 510 phosphorylation inhibited metformin-in-duced Runx2 SUMOylation, and subsequently prevented the effect of metformin on reducing oxLDL-triggered Runx2 expression in hu-man aortic VSMC.CONCLUSION:Deficiency of AMPKα1 in VSMC increases Runx2 expression and promotes atherosclerotic calcifi-cation in vivo.AMPKα1 phosphorylates PIAS1 to enhance Runx2 SUMOyalation and subsequent degradation .
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Purpose The aim is to obtain the cDNA sequence of encoding extramembrane human FL gene with high level expression in E.coli. Methods The primers were designed based on the known FL cDNA sequence. The total RNA was isolated from fetal liver cells , and then RT-PCR was performed. The fragment was cloned into pUC-18T vector, and further sequenced by automatic sequence analyzer. The gene was inserted into GST fusion expression vector between BamH Ⅰ and EcoR Ⅰ sites. The recombinant plasmid was transformed into E.coli strain DH5 α and induced with 1mmol/L IPTG.Results The 546bp DNA fragment was amplified by RT-PCR method from fetal liver cells and its sequence was identical to the published sequence encoding human FL. The expressed fusion protein, with molecular weight of about 22kD, was about 10% of the total bacteria protein by SDS-PAGE and densitometry analysis.Conclusion cDNA was cloned successfully. This study provided a basis for the further fundamental research and clinical application of FL.
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AIM: To further investagate the mechanism of thrombus formation and develop a new remedy of anti-thrombus formation. METHODS: The amplified DNA fragment of vWF-A1 domain was inserted into expression vector with 6?his taq (pQE-31), the recombinant expression vect or was transformed into E coli (strain M15) and induced by IPTG. The recombinant fragment, comprising residues 449-728 of mature vWF subunit, designate rvWF-A1. It was purified by Ni-NTA agarose column and renatured by Tris buffer containin g GSH and GSSG. FACS and platelet aggregometer were employed to analyse the rvWF -A1 function of binding to platelet glycoprotein Ib and inhibiting ristocetin-in duced platelet aggregation. RESULTS: The rvWF-A1 was expressed successfully in E coli, comin g up to 30% of total bacterial protein. Its purify was over 95% through Ni-NTA a garose. It was identified to have ability to bind to GPIb, its biologic activity to inhibit ristocetin-induced platelet aggregation was observed, and the inhibi tive rate was 84 7%. CONCLUSION: The above results indicated that high-level expressi on of rvWF-A1 was successfully achieved in E coli and rvWF-A1 may be an effectiv e antithromotic agent in preventing thrombus formation.
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Objective:To express the recombinant single chain Fv(scFv) in E.coli and reduce immunogenicity and molecular weight of a monoclonal antibody specific for human platelet.Methods:The variable regions of the heavy and light chains of platelet specific antibody SZ 2 were amplified by reverse transcription and polymerase chain reaction.VH and VL gene segments were cloned into pUC Tm and joined together with a (gly 4ser) 3 linker.The resulting scFv was expressed in PET expression system.The expressed recombinant protein was characterized by its size on SDS PAGE,by Western blot,by flow cytometry and its functions.Results:The VH and VL genes were homologous with the published gene sequences of mouse antibody variable region.The recombinant scFv was expressed mostly in the form of inclusion bodies,and the yield was up to 25% of the total cell proteins.Functional studies showed that SZ 2 scFv could bind to platelet and could suppress platelet aggregation induced by ristocatin and thrombin.Conclusion:A recombinant SZ 2 scFv specific against platelet was developed and characterized.
