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1.
Interactive Journal of Medical Research ; 16:16, 2022.
Artigo em Inglês | MEDLINE | ID: covidwho-2022412

RESUMO

BACKGROUND: Academic institutions are central hubs for young adults, laden with academic and social interactions, and communal living arrangements, heightening the risk of transmission of many communicable diseases, including COVID-19. Shortly after the start of the Fall 2020 academic year, institutions of higher learning were identified as hotspots for rises in COVID-19 incidence among young adults. OBJECTIVE: This analysis aims to identify the characteristics of student SARS-CoV-2 cases, identify the extent to which the student population adhered to preventative strategies, and examine behaviors that would put them at higher risk of contracting or spreading COVID-19. METHODS: This observational study comprises 1,175 university students at The George Washington University (GWU) in Washington, DC, with a confirmed COVID-19 diagnosis between August 3, 2020, and November 30, 2021. Case investigation and contact tracing tools were developed by the Campus COVID-19 Support Team and captured in REDCap. Trained case investigators were notified of a case and attempted to contact all cases within 24 hours of the case receiving their lab result. Associations between case characteristics and number of contacts were examined using Wilcoxon Rank Sum tests. Knowledge of exposure, behaviors since exposure, and student residence status, and fraternity and sorority life affiliation were examined using Chi-Square tests. RESULTS: Positive student cases reported a median of three close contacts and 84.6% reported at least one symptom with a median of four COVID-19 symptoms. Congestion (53.4%), cough (45.1%), and headache (41.2%) were the most frequently reported symptoms. Thirty-six percent reported that they did not know how they were exposed to the virus. Among those aware of contact with a COVID-19 confirmed case, 55.1% reported the contact was a close friend or family member and 25.3% reported that it was someone with whom they lived. Athletes (vs. non-athletes), on-campus (vs. off-campus), and undergraduate (vs. graduate) students all reported a significantly higher number of contacts (P<.01). Students living on campus were more likely to report attending campus events in the two days prior to symptom onset or positive test result (P=.004). Students with fraternity/sorority affiliation were more likely to report attending campus events in the two days prior to symptom onset or positive test result (P<.001). CONCLUSIONS: COVID-19 cases have not yet stabilized to a predictable state, but this study provides case characteristics and insights for how academic institutions might prepare to mitigate outbreaks on their campuses as the world plans for the transition from pandemic to endemic COVID-19. Clinicaltrial:

2.
Virologie ; 26(2):142-143, 2022.
Artigo em Inglês | EMBASE | ID: covidwho-1912894

RESUMO

Bronchi of the upper respiratory tract are considered the site of SARSCoV- 2 infection initiation from where a possible spread to the lower respiratory tract can cause acute respiratory distress syndrome with a high degree of mortality in elderly patients. Here we established functional reconstituted primary bronchial epithelia (BE) derived from donors including both adults and children to study SARS-CoV-2 infection dynamics in a physiologically relevant model. We identified multi-ciliated cells as the primary target cells for SARS-CoV-2 in our reconstituted BE. We further observed rapid viral spread throughout the entire BE within 24-48hours. Within 3-4 days, we observed syncytia formation between ciliated cells and basal cells which accumulate at the apical side of the BE. We show that infected cells including syncytia are released into the apical lumen and contribute to the transmittable virus dose. Interestingly, some BE mainly reconstituted from young donor, showed an intrinsic resistance to infection and virus spread. This restricted infection phenotype correlated with a faster release of type-III interferon secretion. Moreover, exogenous type-III interferon treatment to permissive epithelia installed infection restriction while interferon gene knockout promoted infection. Taken together our data uncover syncytia formation as possible contribution to tissue or environmental SARS-CoV-2 dissemination and the type-III IFN response as a central contributor to SARS-CoV-2 resistance in BE, which may explain epidemiological observations that SARS-CoV-2 fatality is age dependent.

3.
PubMed; 2021.
Preprint em Inglês | PubMed | ID: ppcovidwho-334715

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant quickly rose to dominance in mid-2021, displacing other variants, including Alpha. Studies using data from the United Kingdom and India estimated that Delta was 40-80% more transmissible than Alpha, allowing Delta to become the globally dominant variant. However, it was unclear if the ostensible difference in relative transmissibility was due mostly to innate properties of Delta's infectiousness or differences in the study populations. To investigate, we formed a partnership with SARS-CoV-2 genomic surveillance programs from all six New England US states. By comparing logistic growth rates, we found that Delta emerged 37-163% faster than Alpha in early 2021 (37% Massachusetts, 75% New Hampshire, 95% Maine, 98% Rhode Island, 151% Connecticut, and 163% Vermont). We next computed variant-specific effective reproductive numbers and estimated that Delta was 58-120% more transmissible than Alpha across New England (58% New Hampshire, 68% Massachusetts, 76% Connecticut, 85% Rhode Island, 98% Maine, and 120% Vermont). Finally, using RT-PCR data, we estimated that Delta infections generate on average ~6 times more viral RNA copies per mL than Alpha infections. Overall, our evidence indicates that Delta's enhanced transmissibility could be attributed to its innate ability to increase infectiousness, but its epidemiological dynamics may vary depending on the underlying immunity and behavior of distinct populations.

4.
PubMed; 2021.
Preprint em Inglês | PubMed | ID: ppcovidwho-330706

RESUMO

With the emergence of SARS-CoV-2 variants that may increase transmissibility and/or cause escape from immune responses 1-3 , there is an urgent need for the targeted surveillance of circulating lineages. It was found that the B.1.1.7 (also 501Y.V1) variant first detected in the UK 4,5 could be serendipitously detected by the ThermoFisher TaqPath COVID-19 PCR assay because a key deletion in these viruses, spike DELTA69-70, would cause a "spike gene target failure" (SGTF) result. However, a SGTF result is not definitive for B.1.1.7, and this assay cannot detect other variants of concern that lack spike DELTA69-70, such as B.1.351 (also 501Y.V2) detected in South Africa 6 and P.1 (also 501Y.V3) recently detected in Brazil 7 . We identified a deletion in the ORF1a gene (ORF1a DELTA3675-3677) in all three variants, which has not yet been widely detected in other SARS-CoV-2 lineages. Using ORF1a DELTA3675-3677 as the primary target and spike DELTA69-70 to differentiate, we designed and validated an open source PCR assay to detect SARS-CoV-2 variants of concern 8 . Our assay can be rapidly deployed in laboratories around the world to enhance surveillance for the local emergence spread of B.1.1.7, B.1.351, and P.1.

5.
MEDLINE;
Preprint em Inglês | MEDLINE | ID: ppcovidwho-326567

RESUMO

Since its emergence and detection in Wuhan, China in late 2019, the novel coronavirus SARS-CoV-2 has spread to nearly every country around the world, resulting in hundreds of thousands of infections to date. The virus was first detected in the Pacific Northwest region of the United States in January, 2020, with subsequent COVID-19 outbreaks detected in all 50 states by early March. To uncover the sources of SARS-CoV-2 introductions and patterns of spread within the U.S., we sequenced nine viral genomes from early reported COVID-19 patients in Connecticut. Our phylogenetic analysis places the majority of these genomes with viruses sequenced from Washington state. By coupling our genomic data with domestic and international travel patterns, we show that early SARS-CoV-2 transmission in Connecticut was likely driven by domestic introductions. Moreover, the risk of domestic importation to Connecticut exceeded that of international importation by mid-March regardless of our estimated impacts of federal travel restrictions. This study provides evidence for widespread, sustained transmission of SARS-CoV-2 within the U.S. and highlights the critical need for local surveillance.

6.
Obesity ; 29(SUPPL 2):86, 2021.
Artigo em Inglês | EMBASE | ID: covidwho-1616064

RESUMO

Background: Growing interest in very low carbohydrate diets, and in particular the ketogenic diet, has been met with some resistance. Important gaps exist regarding what diet to compare to the ketogenic diet. The objective of this study was to compare a Well Formulated Ketogenic Diet (WFKD) with a Mediterranean-Plus diet (Med-Plus;Mediterranean with emphasis on eliminating added sugars and refined grains), in a crossover study, stratified by diabetes status (T2D vs Prediabetes). Methods: The intervention involved having participants follow the WFKD and Med-Plus, for 12 weeks each, in random order. All meals were provided for the first 4 weeks of each diet phase (food delivery);then participants were responsible for purchasing and preparing their own foods (self-provided). The primary outcome was glycosylated hemoglobin (HbA1c). Secondary outcomes included weight, glucose as measured by continuous glucose monitor (CGM), and cardiometabolic risk factors, such as fasting insulin, glucose, and lipids. Results: Among participants randomized (n = 42), 33 had complete data at both diet phases (some missing data attributable to COVID disruptions). Participants were 60 ± 9 (mean ± sd) years of age, 61% men, with BMI 31 ± 5 kg/m2. Adherence for both diets was higher during the food delivery than the self-provided phase, but similar between diets for both phases. HbA1c concentrations were not significantly different between diets, but average CGM glucose levels were significantly lower during the WFKD compared to Med-Plus (p = 0.03). Additionally, WFKD induced a significantly greater decrease in triglycerides (-16% vs -5%, p = 0.02) and greater increase in LDL-C levels (10% vs -5%, p = 0.01), compared to Med-Plus. Weight change on WFKD vs Med-Plus was -8% vs -7% (p = 0.05). Sensitivity analyses largely confirmed the main findings. Conclusions: Participants improved in glucose control and weight management on both diets relative to baseline;however, glucose control was superior on the WFKD. Some caution is warranted when interpreting these results due to pandemic disruptions and a small sample size. A fair comparison of the two diets should also take into consideration non-glycemic effects.

7.
PubMed; 2020.
Preprint em Inglês | PubMed | ID: ppcovidwho-293591

RESUMO

To effectively track and eliminate COVID-19, it is critical to develop tools for rapid and accessible diagnosis of actively infected individuals. Here, we introduce a single-walled carbon nanotube (SWCNT)-based optical sensing approach towards these ends. We construct a nanosensor based on SWCNTs noncovalently functionalized with ACE2, a host protein with high binding affinity for the SARS-CoV-2 spike protein. Presence of the SARS-CoV-2 spike protein elicits a robust, two-fold nanosensor fluorescence increase within 90 min of spike protein exposure. We characterize the nanosensor stability and sensing mechanism, and passivate the nanosensor to preserve sensing response in saliva and viral transport medium. We further demonstrate that these ACE2-SWCNT nanosensors retain sensing capacity in a surface-immobilized format, exhibiting a 73% fluorescence turn-on response within 5 s of exposure to 35 mg/L SARS-CoV-2 virus-like particles. Our data demonstrate that ACE2-SWCNT nanosensors can be developed into an optical tool for rapid SARS-CoV-2 detection. Abstract Figure:

8.
PUBMED; 2021.
Preprint em Inglês | PUBMED | ID: ppcovidwho-293027

RESUMO

As SARS-CoV-2 continues to cause morbidity and mortality around the world, there is an urgent need for the development of effective medical countermeasures. Here, we assessed the antiviral capacity of a minimal RIG-I agonist, stem-loop RNA 14 (SLR14), in viral control, disease prevention, post-infection therapy, and cross-variant protection in mouse models of SARS-CoV-2 infection. A single dose of SLR14 prevented viral replication in the lower respiratory tract and development of severe disease in a type I interferon (IFN-I) dependent manner. SLR14 demonstrated remarkable protective capacity against lethal SARS-CoV-2 infection when used prophylactically and retained considerable efficacy as a therapeutic agent. In immunodeficient mice carrying chronic SARS-CoV-2 infection, SLR14 elicited near-sterilizing innate immunity by inducing IFN-I responses in the absence of the adaptive immune system. In the context of infection with variants of concern (VOC), SLR14 conferred broad protection and uncovered an IFN-I resistance gradient across emerging VOC. These findings demonstrate the therapeutic potential of SLR14 as a host-directed, broad-spectrum antiviral for early post-exposure treatment and for treatment of chronically infected immunosuppressed patients.

9.
BMJ Innovations ; 2021.
Artigo em Inglês | EMBASE | ID: covidwho-1255589

RESUMO

The COVID-19 pandemic has exposed the fragmentation of the healthcare delivery systems and highlighted the role of resilient primary healthcare systems for a robust public health response during health emergencies. Primary care while being the first point of contact between the citizens and the health systems has received scant attention or targeted investments over the past several decades. Through this narrative review, we aim to outline the potential role of telehealth in augmenting health systems capacity. While teleconsultations have increased exponentially during the pandemic, evidence suggests that utilisation of primary care for non-emergency and non-COVID-19 conditions such as chronic medical conditions has significantly decreased, suggesting that most telemedicine utilisation has been to address an immediate crisis. In countries with pre-existing national digital health framework and enabling regulatory environments, telehealth interventions while strengthening the public health response to COVID-19 also supported the continuum of care at the primary care level. Even after COVID-19 is controlled, telemedicine has the potential to address persistent obstacles to primary care in the South East Asia region, including scarcity of trained healthcare workers, access challenges and costs associated with in-person care. Telemedicine holds promise in strengthening primary care and has the potential to catalyse achieving universal health coverage.

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