We describe a novel assay method: reverse-transcription reverse-complement polymerase chain reaction (RT-RC-PCR), which rationalises reverse transcription and NGS library preparation into a single closed tube reaction. By simplifying the analytical process and cross-contamination risks, RT-RC-PCR presents disruptive scalability MESHD and economy while using NGS and LIMS infrastructure widely available across health service, institutional and commercial laboratories. We present a validation of RT-RC-PCR for the qualitative detection of SARS-CoV-2 RNA by NGS. The limit of detection is comparable to real-time RT-PCR, and no obvious difference in sensitivity was detected between extracted nasopharyngeal swab ( NPS MESHD) RNA and native saliva samples. The end point measurement of RT-RC-PCR is NGS of amplified sequences within the SARS-CoV-2 genome; we demonstrated its capacity to detect different variants using amplicons containing delH69-V70 and N501Y, both of which emerged in the UK Variant of Concern B.1.1.7 in 2020. In summary, RT-RC-PCR has potential to facilitate accurate mass testing at disruptive scale and cost, with concurrent detection of variants of concern.

The COVID-19 pandemic MESHD has proved to be one of the most disruptive public health emergencies MESHD in recent memory. Among non-pharmaceutical interventions, social distancing and lockdown measures are some of the most common tools employed by governments around the world to combat the disease. While mathematical models of COVID-19 MESHD are ubiquitous, few have leveraged network theory in a general way to explain the mechanics of social distancing. In this paper, we build on existing network models for heterogeneous, clustered networks with random link activation/deletion dynamics to put forth realistic mechanisms of social distancing using piecewise constant activation/deletion rates. We find our models are capable of rich qualitative behavior, and offer meaningful insight with relatively few intervention parameters. In particular, we find that the severity of social distancing interventions and when they begin have more impact than how long it takes for the interventions to take full effect.

The SARS-CoV-2 pandemic triggered substantial economic and social disruptions MESHD. Mitigation policies varied across countries based on resources, political conditions, and human behavior. In the absence of widespread vaccination able to induce herd immunity, strategies to coexist with the virus while minimizing risks of surges are paramount, which should work in parallel with reopening societies. To support these strategies, we present a predictive control system coupled with a nonlinear model able to optimize the level of policies to stop epidemic growth. We applied this system to study the unfolding of COVID-19 MESHD in Bahia, Brazil, also assessing the effects of varying population compliance. We show the importance of finely tuning the levels of enforced measures to achieve SARS-CoV-2 containment, with periodic interventions emerging as an optimal control strategy in the long-term. One-sentence summaryWe present an adaptive predictive control algorithm to provide optimal public health measures to slow the COVID-19 MESHD transmission rate.

Background. The COVID-19 pandemic MESHD has induced historic educational disruptions MESHD. In December 2020, at least two-thirds of US public school students were not attending full-time in-person education. The Biden Administration has expressed that reopening schools is a priority. Objective. To compare risks of SARS-COV-2 transmission in schools across different school-based prevention strategies and levels of community transmission. Design. We developed an agent-based network model to simulate transmission in elementary and high school communities, including home, school, and inter-household interactions. Setting. We parameterized school structure based on average US classrooms, with elementary schools of 638 students and high schools of 1,451 students. We varied daily community incidence from 1 to 100 cases per 100,000 population. Patients (or Participants). We simulated students, faculty/staff, and adult household members. Interventions. We evaluated isolation of symptomatic individuals, quarantine of an infected individual's contacts, reduced class sizes, alternative schedules, staff vaccination, and weekly asymptomatic screening. Measurements. We projected transmission among students, staff and families during one month following introduction of a single infection into a school. We also calculated the number of infections expected for a typical 8-week quarter, contingent on community incidence rate. Results. School transmission risk varies according to student age and community incidence and is substantially reduced with effective, consistent mitigation measures. Nevertheless, when transmission occurs, it may be difficult to detect without regular, frequent testing due to the subclinical nature of most infections in children. Teacher vaccination can reduce transmission to staff, while asymptomatic screening both improves understanding of local circumstances and reduces transmission, facilitating five-day schedules at full classroom capacity. Limitations. There is uncertainty about susceptibility and infectiousness of children and low precision regarding the effectiveness of specific prevention measures, particularly with emergence of new variants. Conclusion. With controlled community transmission and moderate school-based prevention measures, elementary schools can open with few in-school transmissions, while high schools require more intensive mitigation. Asymptomatic screening can both reduce transmission and provide useful information for decision-makers.

ObjectiveProper social participation and involvement in the daily activities of life increases the feeling of attachment, and increases a person's sense of worth, belonging, and dependence on society. Lack of social communication leads to anxiety, loneliness, depression MESHD, panic, mental. While COVID-19 MESHD has become a pandemic, public health measures to cut off human-to-human transmission may include quarantine and social isolation. Due to social distancing and quarantine practices, people's participation MESHD in many areas of social life and daily activities has been disrupted. The purpose of this study is to provide insight into the effects of the Covid 19 epidemic on integration into home activities, integration into the community and integration into productive activities, and overall determination of social participation during this epidemic.MethodsIn June 2020, the Social Integration Questionnaire (CIQ), which measures integration at home, integration in the community, and integration into purposeful and productive activities, was transcribed with the required demographic information in a web-based format. A total of 461 people (mean age 36.86±5.8 years) completed the social integration questionnaire in a cross-sectional study. The effects of Covid-19 MESHD on social interaction were then calculated by analyzing CIQ scores before and after the outbreak of COVID-19 MESHD and the data were analyzed using SPSS software version 22.ResultsComparing the participants score in the Community Integration Questionnaire before and after the COVID-19 pandemic MESHD showed that COVID-19 MESHD reduced home integration (from 4.6909±2.84 to 3.5938±2.80 , t= 11.151 p <0.000), social integration (from 8.6529±1.98 to 6.1150±2.10, t= 25.440, p <0.000), integration into productive and purposeful activities (from 5.3145±1.70 to 3.5098±2.02, t= 23.226, p <0.000) and total CIQ test score (from 18.6584±4.02 to 13.2185±4.56 , t= 29.022, p <0.000). These findings show how all three CIQ domains and their total scores decreased significantly after the outbreak of COVID-19 MESHD.ConclusionAfter the COVID-19 MESHD epidemic, people's social life is severely disrupted. The direct and indirect psychological and social effects of COVID- 19 are widespread and can affect mental health. Trial Registration: This study was registered and approved by the Ethic Committee of the University of Social Welfare and Rehabilitation Sciences, Tehran, Iran (IR.USWR.REC.1399.228).

Background The COVID-19 pandemic MESHD has had a disruptive MESHD effect on people with haematological cancers MESHD, who represent a high-risk population due to the nature of their disease and immunosuppressive treatments. We aimed to identify the psychological impacts of the COVID-19 pandemic MESHD on haematology patients and identify correlated factors to inform the development of appropriate supportive interventions.Methods 394 respondents volunteered their participation in response to a study advertisement distributed online through established haematology groups. Participants completed a self-report online survey exploring well-being, psychological distress, unmet supportive care needs, and fear of cancer MESHD recurrence.Results At least 1 in 3 respondents (35%) reported clinical levels of distress and nearly 1 in 3 (32%) identified at least one unmet need. Among respondents in remission (n = 134), clinical fear of cancer MESHD recurrence was reported by nearly all (95%). Unmet needs, pre-existing health conditions, younger age, financial concerns, and perceived risk of contracting COVID-19 MESHD were the dominant factors contributing to psychological distress during the pandemic. Psychological distress, lost income, perceived inadequate support from care team, perceived risk of contracting COVID-19 MESHD, and being a woman were significantly associated with unmet needs. Psychological distress and concern about the impact of COVID-19 MESHD on cancer MESHD management were significantly associated with fear of cancer MESHD recurrence among respondents in remission.Conclusion Results highlight the high psychological burden and unmet needs experienced by people with haematological cancers MESHD during the COVID-19 pandemic MESHD and indicate a need for innovative solutions to rapidly identify distress and unmet needs during, and beyond, pandemic times.

Abstract Importance: During the pandemic, healthcare workers on social media are sharing their challenges, including sleep disturbances MESHD. Objective: To assess sleep using validated measures among frontline healthcare workers on social media Design: A self-selection survey was distributed on Facebook, Twitter, and Instagram for 16 days (August 31-September 15, 2020) targeting healthcare workers (HCW) who were clinically active during the pandemic. Study participants completed the Pittsburgh Sleep Quality Index (PSQI), Insomnia MESHD Severity Index (ISI), and reported demographic/career information. Poor sleep quality was defined as PSQI>5. Moderate-to-severe insomnia MESHD was defined as an ISI>14. The mini-Z was used to measure burnout. Multivariate logistic regression tested associations between demographics, career characteristics, and sleep outcomes. Setting: Online self-selection survey on social media Participants: 963 surveys were completed. Participants were predominantly White (92.8%), female (73.4%), aged 30-49 (71.9%), and physicians (64.4%). Mean sleep duration was 6.1 (SD 1.2) hours. Nearly 90% reported poor sleep (PSQI). One third (33.0%) reported moderate or severe insomnia MESHD. Many (60%) experienced sleep disruptions MESHD due to device usage or had bad dreams at least once per week (45%). Over 50% reported burnout. In multivariable logistic regressions, non-physician (OR 2.4; CI: 1.7, 3.4), caring for COVID-19 MESHD patients (OR 1.8; CI 1.2, 2.8), Hispanic ethnicity (OR 2.2; CI: 1.4, 3.5), being female (OR 1.6; CI 1.1, 2.4), and having a sleep disorder MESHD (OR 4.3; CI 2.7,6.9) were associated with increased odds of insomnia MESHD. In open-ended comments (n=310), poor sleep mapped to four categories: children and family, work demands, personal health, and pandemic-related sleep disturbances. Conclusion: During the COVID-19 pandemic MESHD, 90% of frontline healthcare workers surveyed on social media reported poor sleep, over one-third reported insomnia MESHD, and over half reported burnout. Many also reported sleep disruptions MESHD due to device usage and nightmares. Sleep interventions for frontline healthcare workers are urgently needed.

Emerging in late 2019, the SARS-CoV-2 virus has had a devastating health and economic effects around the world forcing governments to enact restrictions on day to day life, resulting in severe economic and social disruption MESHD. The virus has stimulated new research in the fields of drug development, vaccinology and diagnostic testing. Here we present the basis for a simple, mass manufacturable saliva based electrochemical assay for the SARS-CoV-2 virus acheived through adsorption of the Angiotsnsin Converting Enzyme 2 (ACE2) into thiolated amphiphobic prefluoro monolayer assemled on a gold sensor surface. Following sensor preparation, it is possible to measure specific binding of recombinant spike protein PROTEIN and discriminate positive and negative samples of inactivated SARS-CoV-2 following 30 minutes incubation under ambient conditions. Representative calculations of limits of detection are made for recombinant spike protein PROTEIN (1.68 ng/ml) and inactivated virus (37.8 dC/mL). The assay as presented ultimately shows discrimination between positive and negative inactivated SARS-CoV-2 samples originating from clinical molecular standards kit intended for clinical and biomedical assay validation, and which is designed to mimic clinical samples through presence of cells and proteins in the sample medium. The simple design of the label free measurement and the selection of reagents involved means the assay has clear potential for transfer onto mass producible units such as screen-printed electrodes similar to glucose-format test strips, to enable widespread, low cost and rapid testing for SARS-CoV-2 in the general population

Background: Cervical cancer MESHD screening services in England have been disrupted by the COVID-19 pandemic MESHD COVID-19 pandemic MESHD. Methods: Using routine statistics we estimate number of women affected by delays to screening. We used published research to estimate the proportion of screening age women with high-grade cervical intraepithelial neoplasia MESHD and progression rates to cancer MESHD. Under two scenarios we estimate the impact of COVID-19 MESHD on cervical cancer MESHD over one screening cycle (3y at ages 25-49 and 5y at ages 50-64). The duration of disruption in both scenarios is six months. In the first scenario all women have their screening interval is extended by six months. In the second some women (those who would have been screened during the disruption MESHD) miss one screening cycle, but most women have no delay. Results: Both scenarios result in similar numbers of excess cervical cancers MESHD: 630 vs. 632 (both 4.3 per 100,000 women in the population). However the scenario in which some women miss one screening cycle creates inequalities - they would have much higher rates of excess cancer MESHD: 41.5 per 100,000 screened women compared to those with a six month delay (5.9 per 100,000 screened). Conclusion: To ensure equity for those affected by COVID-19 MESHD related screening delays additional screening capacity will need to be paired with prioritising the screening of overdue women.

Background: In less than a year from its zoonotic entry into the human population, SARS-CoV-2 has infected more than 45 million people, caused 1.2 million deaths, and induced widespread societal disruption MESHD. Leading SARS-CoV-2 vaccine candidates immunize with the viral spike protein PROTEIN delivered on viral vectors, encoded by injected mRNAs, or as purified protein. Here we describe a different approach to SARS-CoV-2 vaccine development that uses exosomes to deliver mRNAs that encode antigens from multiple SARS-CoV-2 structural proteins. Approach: Exosomes were purified and loaded with mRNAs designed to express (i) an artificial fusion protein, LSNME, that contains portions of the viral spike, nucleocapsid, membrane, and envelope proteins PROTEIN, and (ii) a functional form of spike. The resulting combinatorial vaccine, LSNME/SW1, was injected into thirteen weeks-old, male C57BL/6J mice, followed by interrogation of humoral and cellular immune responses to the SARS-CoV-2 nucleocapsid and spike proteins PROTEIN, as well as hematological and histological analysis to interrogate animals for possible adverse effects. Results: Immunized mice developed CD4+, and CD8+ T-cell reactivities that respond to both the SARS-CoV-2 nucelocapsid protein and the SARS-CoV-2 spike PROTEIN protein. These responses were apparent nearly two months after the conclusion of vaccination, as expected for a durable response to vaccination. In addition, the spike-reactive CD4+ T-cells response was associated with elevated expression of interferon gamma, indicative of a Th1 response, and a lesser induction of interleukin 4, a Th2-associated cytokine. Vaccinated mice showed no sign of altered growth, injection-site hypersensitivity MESHD, change in white blood cell profiles, or alterations in organ morphology. Consistent with these results, we also detected moderate but sustained anti-nucleocapsid and anti-spike antibodies in the plasma of vaccinated animals. Conclusion: Taken together, these results validate the use of exosomes for delivering functional mRNAs into target cells in vitro and in vivo, and more specifically, establish that the LSNME/SW1 vaccine induced broad immunity to multiple SARS-CoV-2 proteins.