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1.
Emerg Infect Dis ; 28(12)2022 Nov 02.
Article in English | MEDLINE | ID: covidwho-2099066

ABSTRACT

We report results from serologic surveillance for exposure to SARS-CoV-2 among 1,237 wild rodents and small mammals across Europe. All samples were negative, with the possible exception of 1. Despite suspected potential for human-to-rodent spillover, no evidence of widespread SARS-CoV-2 circulation in rodent populations has been reported to date.Esitämme tulokset serologisesta tutkimuksesta, jossa seulottiin SARS-CoV-2 tartuntojen varalta 1,237 luonnonvaraista jyrsijää ja piennisäkästä eri puolilta Eurooppaa. Kaikki näytteet olivat negatiivisia, yhtä näytettä lukuun ottamatta. SARS-CoV-2:n läikkymisen ihmisistä jyrsijöihin on arveltu olevan mahdollista, mutta todisteet viruksen laajamittaisesta leviämisestä jyrsijäpopulaatioissa puuttuvat.

2.
Advances in 21st Century Human Settlements ; : 145-176, 2022.
Article in English | Scopus | ID: covidwho-2075311

ABSTRACT

Mumbai, the financial capital of India, has been severely impacted by the COVID-19 pandemic not only in terms of health but also in terms of economic and other spheres. This chapter initiates with the preliminary analysis of the COVID-19 situation and its related challenges in Mumbai megacity and further presents an outline of the journey that the metro-city has trailed during the COVID-19 era. With the advent of the pandemic, several restrictive measures were imposed resulting in abrupt loss of jobs, salary reductions, unavailability of public health infrastructure, closure of finance and educational institutions, closure of economic hubs and transportation systems had severely derailed the ‘business as usual’ of Mumbai, thereby impacting the health and well-being of its citizens. This chapter highlights the impact of restrictive measures such as lockdown, night curfew, containment and quarantine and self-isolation. The impacts of the local and state government initiatives and participation of private enterprises and non-profit organisations in order to curb the crisis, with a focus on special models such as ‘4-T model’ ‘chase the virus’ mission implemented on the mega-slum of Dharavi, were studied. The major difficulties and hurdles that were exposed during this period included dwindling health infrastructure, overcrowding and hyper-density, lack of habitable spaces and sanitation facilities. Lastly, the ‘urban restart’ approaches and innovative initiatives taken by the city development authorities in order to reinvigorate the balance between work and life have also been portrayed on the other hand. © 2022, The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

3.
Preprint in English | bioRxiv | ID: ppbiorxiv-502439

ABSTRACT

We report serological surveillance for exposure to SARS-CoV-2 in 1,237 wild rodents and other small mammals across Europe. All samples were negative with the possible exception of one. Given the ongoing circulation of this virus in humans and potential host jumps, we suggest such surveillance be continued.

4.
Topics in Antiviral Medicine ; 30(1 SUPPL):175, 2022.
Article in English | EMBASE | ID: covidwho-1880389

ABSTRACT

Background: Camostat, an oral protease inhibitor, blocks entry and replication of SARS-CoV-1 and SARS-CoV-2 in vitro. It is approved for therapy of recurrent pancreatitis in several countries. Camostat has an excellent safety profile and repurposing for COVID-19 treatment was proposed. Methods: We conducted a Phase II randomized, placebo-controlled trial of camostat in adult outpatients with confirmed COVID-19 and one or more risk factors for severe disease (including age ≥65 years, severe obesity, hypertension, diabetes, chronic lung, heart or liver disease). Participants were randomized 2:1 to oral camostat 200 mg or matching placebo four times a day for 14 days. Exclusion criteria were end-stage liver disease, severe renal impairment, oxygen saturation ≤94% on room air, and experimental treatment for COVID-19. The primary efficacy endpoint was hospitalization or death within 28 days. Secondary efficacy included positivity for SARS-CoV-2 by PCR on mid-nasal turbinate swabs on days 7 and 15 compared to baseline. Results: We enrolled 295 participants, 57.3% were female, 15.6% Black and 60% Latinx. Mean age was 51 years (18-93 years). Most (75.3%) were randomized ≤5 days after symptom onset. Common risk factors were hypertension (63.4%), chronic lung disease (33.2%) and diabetes (25.4%), with 46.8% having >1 risk factor. With a lower than anticipated event rate, the primary endpoint of hospitalization or death was not significantly different in the camostat (5.3%, 10/194) and placebo groups (6.1%, 6/99;p=0.78). In the intention-to-treat population, there was a trend towards a lower proportion of PCR positivity in the camostat compared to the placebo group at day 7 (65.2% vs. 75.7%, p=0.12) and day 15 (22.0% vs. 34.3%, p=0.06). Similarly, in a post hoc as treated population, fewer participants in the camostat than in the placebo group remained PCR positive at day 7 (64.7%, 88/136 vs. 76.8%, 53/96;p=0.077) and day 15 (21.8%, 29/133, vs. 34.8%, 23/66;p=0.05). Adverse events occurred in 13% of participants in the placebo and 9% in the camostat group. All severe adverse events (5% in both groups) were related to COVID-19. Conclusion: With a low overall event rate, we did not observe a decrease in risk of hospitalization or death in camostat treated outpatients with COVID-19 at risk for severe disease. SARS-CoV-2 PCR turned negative faster on camostat treatment. Camostat was well tolerated.

5.
Topics in Antiviral Medicine ; 30(1 SUPPL):41, 2022.
Article in English | EMBASE | ID: covidwho-1880388

ABSTRACT

Background: Camostat, a serine protease inhibitor, prevents activation of the SARS-CoV-2 spike protein and blocks SARS-CoV-2 infection in vitro. We studied the safety and antiviral and clinical efficacy of orally administered camostat in non-hospitalized adults with mild-moderate COVID-19. Methods: ACTIV-2/A5401 is a platform trial to evaluate therapies for non-hospitalized adults with mild-moderate COVID-19. In a Phase II portion of the study, participants were enrolled within 10 days of COVID-19 related symptom onset and randomized to camostat 200 mg orally every 6 hours for 7 days or the pooled placebo group. Objectives were to evaluate the safety and efficacy of camostat to reduce the duration of COVID-19 symptoms and increase the proportion of participants with SARS-CoV-2 RNA below the lower limit of quantification (LLoQ) from nasopharyngeal (NP) swabs on days 3, 7, and 14. Participants completed a study diary from day 0 to day 28 scoring COVID-19 symptoms as absent, mild, moderate, or severe. Results: Of the 224 participants enrolled from 54 US sites, 215 participants (108 camostat, 107 placebo) initiated study intervention and formed the modified intent-to-treat population. Fifty-four percent were female, >99% cis-gender, 85% White, 9% Black, and 51% Latinx. Median age was 37 years;47% reported ≤5 days of symptoms at study entry and 26% met the protocol definition of higher risk of progression to severe COVID-19. Most frequent symptoms on day 0 were cough (86%), fatigue (85%), nasal obstruction/congestion (71%) and body/muscle aches (71%). There was no significant difference between camostat and placebo arms in grade 3 or higher adverse events (7.4% vs. 6.5%, respectively). Median (Q1, Q3) time to symptom improvement was 9 days for both camostat (5, 20) and placebo (6, 19). There were no significant differences in the proportion of participants with NP SARS-CoV-2 RNA<="" div=""> Conclusion: Camostat was well-tolerated. Despite compelling in vitro data, camostat did not show evidence of antiviral or clinical efficacy in ACTIV-2/A5401. This highlights the critical importance of randomized controlled trials in the evaluation of therapies for COVID-19.

6.
PubMed; 2022.
Preprint in English | PubMed | ID: ppcovidwho-329197

ABSTRACT

Using molecular dynamic simulations we study whether amyloidogenic regions in viral proteins can initiate and modulate formation of α-synuclein aggregates, thought to be the disease-causing agent in Parkinson's Disease. As an example we choose the nine-residue fragment SFYVYSRVK (SK9), located on the C-terminal of the Envelope protein of SARS-COV-2. We probe how the presence of SK9 affects the conformational ensemble of α-synuclein monomers and the stability of two resolved fibril polymorphs. We find that the viral protein fragment SK9 may alter α-synuclein amyloid formation by shifting the ensemble toward aggregation-prone and preferentially rod-like fibril seeding conformations. However, SK9 has only little effect of the stability of pre-existing or newly-formed fibrils.

7.
PubMed; 2022.
Preprint in English | PubMed | ID: ppcovidwho-329196

ABSTRACT

Using molecular dynamic simulations we study whether amyloidogenic regions in viral proteins can initiate and modulate formation of alpha-synuclein aggregates, thought to be the disease-causing agent in Parkinson's Disease. As an example we choose the nine-residue fragment SFYVYSRVK (SK9), located on the C-terminal of the Envelope protein of SARS-COV-2. We probe how the presence of SK9 affects the conformational ensemble of alpha-synuclein monomers and the stability of two resolved fibril polymorphs. We find that the viral protein fragment SK9 may alter alpha-synuclein amyloid formation by shifting the ensemble toward aggregation-prone and preferentially rod-like fibril seeding conformations. However, SK9 has only little effect of the stability of pre-existing or newly-formed fibrils.

8.
Desidoc Journal of Library & Information Technology ; 41(3):175-183, 2021.
Article in English | Web of Science | ID: covidwho-1285573

ABSTRACT

In an academic set up the 'library' plays a pivotal role. It stores, analyses, interpret and disseminate information among the users to fulfil their information needs. It has been observed that recent technological advancement has revolutionised library services to a great extent. Now libraries are providing both physical as well as web-enabled library services to their users. In this context, library websites act as a major gateway in providing web-enabled library services. The sudden outbreak of the COVID-19 pandemic has disrupted the physical mode of library services. However, to support the ongoing teaching and learning process, libraries need to continue their services despite the lockdown. Therefore, the present study seeks to find out whether academic libraries are ready and adequately equipped to perform basic services during this critical juncture. The present study was directed towards exploring the readiness among the academic libraries by assessing their websites based on selected evaluation criteria. Hence, in this study top, 100 NIRF ranked institutes websites were examined by adopting 30-point evaluation criteria. These criteria were selected from the extant literature. These criteria were grouped into 04 categories i.e., basic website information, resource discovery, availability of resources and reference services. The readiness index of each library was calculated based on the availability and non-availability of the said criteria. The findings of the study reveal that 64 per cent of the libraries have failed to secure their score of 50 per cent on predefined criteria. It was also found that the preparedness index is independent of NIRF ranking. Overall findings of the study make it clear that academic libraries need to improve and up to date their web-based services to play a proactive role in the present and post-pandemic situation.

9.
Neurobiol Dis ; 146: 105131, 2020 12.
Article in English | MEDLINE | ID: covidwho-872391

ABSTRACT

As researchers across the globe have focused their attention on understanding SARS-CoV-2, the picture that is emerging is that of a virus that has serious effects on the vasculature in multiple organ systems including the cerebral vasculature. Observed effects on the central nervous system include neurological symptoms (headache, nausea, dizziness), fatal microclot formation and in rare cases encephalitis. However, our understanding of how the virus causes these mild to severe neurological symptoms and how the cerebral vasculature is impacted remains unclear. Thus, the results presented in this report explored whether deleterious outcomes from the SARS-CoV-2 viral spike protein on primary human brain microvascular endothelial cells (hBMVECs) could be observed. The spike protein, which plays a key role in receptor recognition, is formed by the S1 subunit containing a receptor binding domain (RBD) and the S2 subunit. First, using postmortem brain tissue, we show that the angiotensin converting enzyme 2 or ACE2 (a known binding target for the SARS-CoV-2 spike protein), is ubiquitously expressed throughout various vessel calibers in the frontal cortex. Moreover, ACE2 expression was upregulated in cases of hypertension and dementia. ACE2 was also detectable in primary hBMVECs maintained under cell culture conditions. Analysis of cell viability revealed that neither the S1, S2 or a truncated form of the S1 containing only the RBD had minimal effects on hBMVEC viability within a 48 h exposure window. Introduction of spike proteins to invitro models of the blood-brain barrier (BBB) showed significant changes to barrier properties. Key to our findings is the demonstration that S1 promotes loss of barrier integrity in an advanced 3D microfluidic model of the human BBB, a platform that more closely resembles the physiological conditions at this CNS interface. Evidence provided suggests that the SARS-CoV-2 spike proteins trigger a pro-inflammatory response on brain endothelial cells that may contribute to an altered state of BBB function. Together, these results are the first to show the direct impact that the SARS-CoV-2 spike protein could have on brain endothelial cells; thereby offering a plausible explanation for the neurological consequences seen in COVID-19 patients.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Blood-Brain Barrier/metabolism , Capillary Permeability/physiology , Endothelial Cells/metabolism , Inflammation/metabolism , Matrix Metalloproteinases/metabolism , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/physiology , Blood-Brain Barrier/drug effects , COVID-19 , Capillary Permeability/drug effects , Cell Adhesion Molecules/drug effects , Cell Adhesion Molecules/metabolism , Cell Survival/drug effects , Dementia/metabolism , Electric Impedance , Endothelial Cells/drug effects , Frontal Lobe/metabolism , Humans , Hypertension/metabolism , In Vitro Techniques , Intercellular Junctions/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , Lab-On-A-Chip Devices , Matrix Metalloproteinases/drug effects , Primary Cell Culture , Protein Domains , Protein Subunits/metabolism , Protein Subunits/pharmacology , RNA, Messenger/drug effects , RNA, Messenger/metabolism , Spike Glycoprotein, Coronavirus/pharmacology
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