Objectives Hygiene behaviours had been an essential component of attempts to slow the spread of SARS-CoV-2. Most data on adherence to these behaviours is collected via self-reporting, which can differ from observed behaviours. We quantified this discrepancy among a university sample and tested the impact of simple intervention on observed behaviour. Study design Cross-sectional questionnaire of behaviour on campus compared to direct observation on one day without, and one day with, additional signage. Methods We circulated an email inviting all staff and students at our university to complete a questionnaire asking how often they wear a mark or practice hand hygiene when entering campus buildings, and how often they practiced social distancing within campus buildings. We observed all entrants to the main building on one campus on a baseline day and on a day after installing a large sign reminding people that these behaviours were mandatory. Results In our survey, 172 out of 252 respondents (68%) reported always cleaning their hands, 225 out of 251 (90%) reported always wearing a face covering, and 124 out of 252 (49%) reported always maintaining social distancing. On the baseline day of observation, 50 out of 311 people (16.1%) cleaned their hands and 256 (82.3%) wore a face covering correctly. Out of 119 people whom we could assess, 9 (7%) maintained social distance from others. The signage was associated with significant improvements for cleaning hands (104 / 375 people: 27.7%), wearing a face covering (374 / 375; 99.8%) and maintaining social distance (79 / 144; 54.8%). Conclusions Greater use of observational methods will provide a more accurate measure of behaviour than the current reliance on self-report and allow interventions to be robustly tested.
Objective: We assessed the Brazilian health system9s ability to respond to the challenges imposed by the Covid-19 pandemic considering hospital capacity in the 450 Health Regions of the country in 2020. Hospital capacity referred to the availability of hospital beds, equipment, and human resources. Methods: Data came from National Register of Health Facilities on the availability of Covid-19 resources in inpatient facilities from January to December,2020. Assessed resources were health professionals, hospital beds, and medical equipment. A synthetic indicator, Installed Capacity Index (ICI) was calculated using Principal Component Analysis. Results: There was an increase in all selected indicators between January and December 2020. We observed differences between the Northeast, North regions, and the other regions of the country. Most Health Regions presented low ICI. The ICI increased especially in regions with considerably high baseline capacity in January 2020. The Northeast and North had a higher concentration of low ICI regions. Conclusion: The information here provided may be used by health authorities, providers, and managers in planning and adjusting for future Covid-19 care and in dimensioning the adequate supply of hospital beds, health care professionals, and devices in Health Regions to reduce associated morbidity and mortality.
Background: Restrictions due to the COVID-19 pandemic have led to everyday reliance on digitalisation of life, including access to health care services. People with severe mental ill health (SMI, e.g., bipolar or psychosis spectrum disorders) are at greater risk for digital exclusion and it is unknown to what extent they are able to adapt to online service delivery. This study explored use of the Internet and digital devices during the pandemic restrictions and its association with physical and mental health changes. Methods: 367 adults with an SMI diagnosis completed a survey (online or offline) and provided information on access to Internet connection and devices, internet skills, online activities, and barriers to using the Internet. They also self-reported changes in mental and physical health. Results: During the pandemic restrictions 61.6% were limited or non-users of the Internet. The majority had access to the Internet and digital devices but around half reported knowledge deficits. Most common activities were accessing information and entertainment (88.9%), staying in touch with friends and families (84.8%), and purchasing goods (other than food) (84.3%). Most common barriers were finding the Internet 9not interesting9 (28.3%) or 9too difficult9 (27.9%), as well as 9security concerns9 (22.1% to 24.3%). Using the Internet 9a lot9 (vs 9just a bit or not at all9) during the pandemic was associated with younger age (Adj ORs = 4.76 and 6.39, Ps < .001), having a diagnosis of bipolar disorder (compared to psychosis; Adj OR = 3.88, P < .001), or reporting a decline in mental health (compared to no decline; Adj OR = 1.92, P = .01). Conclusion: Most people with SMI were limited or non-users of the Internet during the pandemic, which seems to be mainly attributable to lack of interest and skills, rather than lack of devices or connectivity. Older adults with psychosis should be the focus of interventions to support digital engagement in people with SMI.
The mRNA vaccine BNT162b2 has proven highly effective and currently many millions are being vaccinated. There are limited and conflicting data from immunogenicity studies on the effects of age, gender, vaccination side effects (VSE), risk factors for severe COVID-19 (RFS-COV), obesity (BMI) and previous SARS-CoV-2 (Pr-CoV) Moreover, immunogenicity data from COVID-19 patients comparing various disease categories of natural infection i.e. asymptomatic vs mild vs moderate vs severe infection are sparse, and include limited number of individuals. This study included 871 vaccinated health care workers (HCW) and 181 patients with natural infection. Immunogenicity was assessed by a quantative assay measuring anti-SARS-CoV-2 against the RBD domain of the spike protein (anti-RBD) and anti-SARS-CoV-2 against nucleocapsid protein (anti-N). Samples were collected 1-2 weeks after completion of the 2nd dose in the vaccinated HCWs and 15-59 days post symptoms onset in patients with natural infection. The concentration of anti-RBD in vaccinated individuals after multivariable analysis was significantly associated with age, gender, VSE and Pr-CoV. Specifically, anti-RBD median levels (95% CI) were lower by 2,466 (651-5,583), 6,228 (3,254-9,203) and 7,651 (4,479-10,823) AU/ml in 35-44, 45-54, 55-70 yrs respectively, compared with 18-34 yrs group. In females, median levels of anti-RBD were higher by 2,823 (859-4,787) compared with males, in individuals with VSE were higher by 5,024 (3,122-6,926) compared with no VSE, and in HCWs with Pr-CoV were higher by 9,971 (5,158-14,783) AU/ml compared with HCWs without Pr-CoV. Among individuals with natural infection, the median anti-RBD levels were 14.8 times higher in patients with critical COVID-19 infection compared with non-hospitalized individuals. The ratio of anti-RBD in vaccinated individuals versus those with natural infection varied from 1.0 up to 19.4 according to the clinical subgroup of natural infection. This study proves the high immunogenicity of BNT162b2 vaccine although its sustainability remains to be seen. The use of comparative data from natural infection serological panels, expressing the clinical heterogeneity of natural infection may facilitate early decisions for vaccine evaluation in clinical trials.
SARS-CoV-2 infection results in highly heterogeneous outcomes, from cure without symptoms to acute respiratory distress and death. While immunological correlates of disease severity have been identified, how they act together to determine the outcomes is unknown. Here, using a new mathematical model of within-host SARS-CoV-2 infection, we analyze diverse clinical datasets and predict that a subtle interplay between innate and CD8 T-cell responses underlies disease heterogeneity. Our model considers essential features of these immune arms and immunopathology from cytokines and effector cells. Model predictions provided excellent fits to patient data and, by varying the strength and timing of the immune arms, quantitatively recapitulated viral load changes in mild, moderate, and severe disease, and death. Additionally, they explained several confounding observations, including viral recrudescence after symptom loss, prolonged viral positivity before cure, and mortality despite declining viral loads. Together, a robust conceptual understanding of COVID-19 outcomes emerges, bearing implications for interventions.
Glucocorticoids have been shown to improve outcomes of patients with severe cases of Covid-19. However, criteria for prescribing glucocorticoids are currently limited. To identify potential for targeting, we perform an observational analysis of mortality of hospitalized patients. Our results agree with current clinical understanding that glucocorticoids benefit patients with severe cases of Covid-19, and that elevated Neutrophil/Lymphocyte Ratio (NLR) is associated with mortality. Furthermore, our results suggest that glucocorticoids could be targeted to patients with elevated NLR (especially in the range 6-25) at time of admission. Finally, we note there are also high-risk patients with low NLR, suggesting varying presentations of severe Covid-19.
Since the beginning of the Covid-19 pandemics, variants have emerged. Whereas most of them have no to limited selective advantage, some display increased transmissibility and/or resistance to immune response. To date, most of the mutations involved in the functional adaptation are found in the Receptor Binding Module (RBM), close to the interface with the human receptor ACE2. In this study, we thus developed and validated a fast and simple molecular assay allowing the detection and partial identification of the mutations in the RBM coding sequence. After the amplification of the region of interest, the amplicon is heat-denatured and hybridized with an amplicon of reference. The presence of a mutation in the heteroduplex can be cleaved by a mismatch-specific endonuclease and the cleavage pattern is analysed by capillary electrophoresis. The approach was first validated on viral RNA purified different SARS-CoV-2 variants produced in the lab before being implemented for clinical samples. The results highlighted the performance of the assay for the detection of mutations in the RBM from clinical samples. The procedure can be easily set up for high throughput identification of the presence of mutations and serve as a first-line screening to select the samples for full genome sequencing.
Background: Randomised Evaluation of COVID-19 Therapy (RECOVERY) demonstrated that tocilizumab reduces mortality in hospitalized COVID-19 patients. However, substantial uncertainty remains whether tocilizumab9s effect is similar across clinically relevant subgroups. Whether this uncertainty can be resolved with Bayesian methods is unknown. Design, Setting, Participants, and Interventions: RECOVERY was a controlled, open-label, platform UK trial that randomized (1:1) 4116 adults with oxygen saturation <92% on room air or receiving oxygen therapy with C-reactive protein ≥75 mg/L to either usual care or tocilizumab plus usual care. Main outcome measures: Mortality and hospital discharge within 28 days. Methods: Using Bayesian methods, we combined RECOVERY with evidence-based priors incorporating previous COVID-19 tocilizumab RCTs. The probability of tocilizumab9s benefit for respiratory support and corticosteroid subgroups and sensitivity analyses were performed with different prior distributions and baseline risks. Results: For all-cause mortality, the posterior probabilities of decreased deaths with tocilizumab were >99% and 19% in patients using and not using corticosteroids, respectively. In patients on simple oxygen only, non-invasive ventilation and invasive mechanical ventilation, the probabilities of decreased mortality were 96%, >99% and 77%, respectively. The probabilities for a clinically significant mortality reduction, as assessed by an absolute risk difference > 3% (number needed to treat ≤ 33), were 77%, 96%, 56%, respectively. Sensitivity analyses highlighted the uncertainty and lack of conclusive evidence for tocilizumab9s effect in patients on invasive mechanical ventilation and those without concurrent corticosteroids. Posterior probabilities of benefit for hospital discharge outcome were high and consistent across most subgroups. Conclusions: In this Bayesian reanalysis, COVID-19 hospitalized patients exposed to corticosteroids or on non-invasive ventilation have a high probability of a clinically meaningful mortality benefit from tocilizumab. Tocilizumab also likely improves discharge from hospital in most subgroups. Future research should further address if patients on invasive mechanical ventilation can also benefit from tocilizumab.
Vaccinations are widely credited with reducing death rates from COVID-19 but the underlying host-viral mechanisms/interactions for morbidity and mortality of SARS-CoV-2 infection remain poorly understood. Acute respiratory distress syndrome (ARDS) describes the severe lung injury, which is pathologically associated with alveolar damage, inflammation, non-cardiogenic edema, and hyaline membrane formation. Because proteostatic pathways play central roles in cellular protection, immune modulation, protein degradation and tissue repair, we examined the pathological features for the unfolded protein response (UPR) using the surrogate biomarker glucose regulated protein 78 (GRP78) and co-receptor for SARS-CoV-2. At autopsy, immunostaining of COVID-19 lungs showed highly elevated expression of GRP78 in both pneumocytes and macrophages compared to non-COVID control lungs. GRP78 expression was detected in both SARS-CoV-2 infected and un-infected pneumocytes as determined by multiplexed immunostaining for nucleocapsid protein. In macrophages, immunohistochemical staining for GRP78 from deceased COVID-19 patients was increased but overlapped with GRP78 expression taken from surgical resections of non-COVID-19 controls. In contrast, the robust in situ GRP78 immunostaining of pneumocytes from COVID-19 autopsies exhibited no overlap and was independent of age, race/ethnicity and gender compared with non-COVID-19 controls. Our findings bring new insights for stress-response pathways involving the proteostatic network implicated for host resilience and suggest that targeting of GRP78 expression might afford an alternative therapeutic strategy to modulate host-viral interactions during SARS-CoV-2 infections.
Most COVID-19 patients can build effective humoral immunity against SARS-CoV-2 after recovery . However, it remains unknown how long the protection can maintain and how efficiently it can protect people from the reinfection of the emerging SARS-CoV-2 variants. Here we evaluated the sera from 248 COVID-19 convalescents around one year post-infection in Wuhan, the earliest epicenter of SARS-CoV-2. We demonstrated that the SARS-CoV-2 immunoglobulin G (IgG) maintains at a high level and potently neutralizes the infection of the original strain (WT) and the B.1.1.7 variant in most patients. However, they showed varying degrees of efficacy reduction against the other variants of concern (P.1, B.1.525, and especially B.1.351) in a patient-specific manner. Mutations in RBD including K417N, E484K, and E484Q/L452R (B.1.617) remarkably impair the neutralizing activity of the convalescents9 sera. Encouragingly, we found that a small fraction of patients9 sera showed broad neutralization potency to multiple variants and mutants, suggesting the existence of broadly neutralizing antibodies recognizing the epitopes beyond the mutation sites. Our results suggest that the SARS-CoV-2 vaccination effectiveness relies more on the timely re-administration of the epitope-updated vaccine than the durability of the neutralizing antibodies.
Information on the cumulative incidence of SARS-CoV-2 in East Africa is scarce. We conducted serosurveillance of anti-SARS-CoV-2 antibodies among pregnant women attending their first antenatal care visit in three health facilities in eastern Ethiopia. We collected questionnaire data and a blood sample from 3,312 pregnant women between April 1, 2020 and March 31, 2021 at health facilities in Haramaya, Awoday and Harar. We selected 1,447 blood samples at random and assayed these for anti-SARS-CoV-2 antibodies at Hararghe Health Research laboratory using WANTAI SARS-CoV-2 Rapid Test for total immunoglobulin. Temporal trends in seroprevalence were analysed with a X2 test for trend and multivariable binomial regression. Among 1,447 sera tested, 83 were positive for anti-SARS-CoV-2 antibodies giving a crude seroprevalence of 5.7% (95% CI 4.6%, 7.0%). Of 160 samples tested in April-May, 2020, none was seropositive; the first seropositive sample was identified in June and seroprevalence rose steadily thereafter (X2 test for trend;p=0.003) reaching a peak of 11.8% in February, 2021. In the multivariable model, seroprevalence was approximately 3% higher in first-trimester mothers compared to later presentations, and rose by 0.75% (95% CI 0.31%, 1.20%) per month of calendar time. This clinical convenience sample illustrates the dynamic of the SARS-CoV-2 epidemic in young adults in eastern Ethiopia; infection was rare before June 2020 but it spread in a linear fashion thereafter, rather than following intermittent waves, and reached 10% by the beginning of 2021. After one year of surveillance, most pregnant mothers remained susceptible.
Although SARS-CoV-2 surface contamination has been investigated in temperate climates, few studies have been conducted in the tropics. Here, we investigated the presence of SARS-CoV-2 on high-touch surfaces in a large city in Brazil. A total of 400 surface samples were collected in February 2021 in the City of Recife, Northeastern Brazil. A total of 97 samples (24.2%) tested positive for SARS-CoV-2 by RT-qPCR using the CDC-USA protocol. All the collection sites, except one (18/19, 94.7%) had at least one environmental surface sample contaminated. SARS-CoV-2 positivity was higher in public transport terminals (47/97, 48.4%), followed by health care units (26/97, 26.8%), public parks (14/97, 14.4%), public markets (4/97, 4.1%), and beach areas (4/97, 4.1%). Toilets, ATMs, handrails, playground, and outdoor gym were identified as fomites with the highest rates of viral contamination. Regarding the type of material, SARS-CoV-2 RNA was found more commonly on metal (45/97, 46.3%), followed by plastic (18/97, 18.5%), wood (12/97, 12.3%), rock (10/97, 10.3%), concrete (8/97, 8.2%), and glass (2/97, 2.0%). Taken together, our data indicated extensive SARS-CoV-2 contamination in public surfaces and identified critical control points that need to be targeted to break SARS-CoV-2 transmission chains.
The rapid emergence of wastewater based surveillance has led to a wide array of SARS-CoV-2 RNA quantification methodologies being employed. Here we compare methods to store samples, inactivate viruses, capture/concentrate viruses, and extract/measure viral RNA from primary influent into wastewater facilities. We found that heat inactivation of the viruses led to a 1-3 log10 decrease compared to chemical inactivation. Freezing influent prior to concentration caused a 1-4 log10 decrease compared to processing fresh samples, but viral capture by membrane adsorption prior to freezing was robust to freeze-thaw variability. Concentration vs. direct extraction, and PCR platform also affected outcome, but by a smaller amount. The choice of nucleocapsid gene target had nearly no effect. Pepper mild-mottle virus was much less sensitive to these methodological differences than was SARS-CoV-2, which challenges its use as a population-level control among studies using different methods. Better characterizing the variability associated with different methodologies, in particular the impact of methods on sensitivity, will aid decision makers in following the effects of vaccination campaigns, early detection of future outbreaks, and potentially monitoring the appearance of SARS-CoV-2 variants in the population.
Background To help control the spread of the coronavirus disease 2019 (COVID-19), the Japanese government declared a state of emergency (SoE) thrice. However, these were less stringent than other nations. It has not been assessed whether soft containment policies were sufficiently effective in promoting social distancing or reducing human contact. Methods Utilising the Google mobility index to assess social distancing behaviour in all Japanese prefectures between 15 February 2020 and 12 June 2021, mobility changes were assessed by an interrupted time-series analysis after adjusting for seasonality and various prefecture-specific fixed-effects and distinguishing potential heterogeneity across multiple SoEs and time passed after the declaration. Results The mobility index for retail and recreation showed an immediate decline after the declaration of the SoE by 12.78 percent-points (95%CI: -13.61 to -11.94) and a further decline after the initial period (beta: -0.93, 95%CI: -1.11 to -0.74), but gradually increased by 0.02 percent-points (95%CI: 0.02 to 0.02). This trend was similar for mobilities in other places. Among the three SoEs, the overall decline in human mobility outside the home in the third SoE was the least significant, suggesting that people were less compliant with social distancing measures during this period. Conclusion Although less stringent government responses to the pandemic may help promote social distancing by controlling human mobilities outside the home, their effectiveness may decrease if these interventions are repeated and enforced for extended periods, distorting one9s health belief by heuristics biases. By combining these with other measures (i.e. risk-communication strategies), even mild containment and closure policies can be effective in curbing the spread of the virus.
Ivermectin Treatment Efficacy in Covid-19 High Risk Patients - Condition: COVID-19
Intervention: Drug: Ivermectin 0.4mg/kg/day for 5 days
Sponsor: Clinical Research Centre, Malaysia
Not yet recruiting
Efficacy and Safety of XAV-19 for the Treatment of Moderate-to-severe COVID-19 - Condition: COVID-19
Interventions: Drug: XAV-19; Drug: Placebo
Sponsor: Xenothera SAS
Recruiting
Study of Codivir in Patients With COVID-19 - Condition: Covid19
Interventions: Drug: Covidir injections; Diagnostic Test: One Step Test; Diagnostic Test: IgM and IgG dosage; Diagnostic Test: RT-PCR SARS-CoV-2; Diagnostic Test: Screening blood test; Diagnostic Test: ECG; Diagnostic Test: Medical evaluation; Diagnostic Test: NEWS-2 score; Diagnostic Test: WHO score
Sponsors: Code Pharma; Zion Medical
Active, not recruiting
Clinical Trial With N-acetylcysteine and Bromhexine for COVID-19 - Condition: COVID-19
Interventions: Drug: Vitamin C; Drug: N-acetylcysteine (NAC); Drug: NAC + Bromhexine (BMX)
Sponsors: Universidade Federal do Ceara; Paulista School of Medicine-EPM, UNIFESP; Health Surveillance Secretariat - SVS; Central Laboratory of Public Health of Ceara - LACEN-CE; Leonardo da Vinci Hospital - HLV; São José Hospital for Infectious Diseases - HSJ; Ceará Health Secretariat - SESA; Municipal Health Secretary - SMS-Fortaleza
Not yet recruiting
Augmentation of Immune Response to COVID-19 mRNA Vaccination Through OMT With Lymphatic Pumps - Condition: Covid19
Intervention: Other: Osteopathic Manipulative Treatment (OMT)
Sponsors: Western University of Health Sciences; American College of Osteopathic Physicians; American Osteopathic Foundation; Osteopathic Physicians and Surgeons of California; Xavier-Nichols Foundation
Recruiting
Nervous System Symptoms Associated With COVID 19 - Condition: Covid19
Interventions: Other: NEURO +; Other: NEURO -
Sponsor: University Hospital, Toulouse
Completed
Tolerability,Safety of JS016 in SARS-CoV-2 (COVID-19) - Conditions: COVID-19; SARS-CoV-2
Intervention: Drug: Combination Product: JS016 (anti-SARS-CoV-2 monoclonal antibody)
Sponsor: Peking Union Medical College Hospital
Recruiting
Open Label, Single-Center Study Utilizing BIOZEK COVID-19 Antigen Rapid Test - Condition: Covid-19 Testing
Intervention: Diagnostic Test: Biozek Covid-19 Antigen Rapid Test (Saliva)
Sponsor: Mach-E B.V.
Recruiting
Community-based Post-exposure Prophylaxis for COVID-19 - Condition: Covid19
Interventions: Other: Guduchi Ghanvati; Other: Standard guidelines
Sponsors: NMP Medical Research Institute; Aarogyam UK; Dr. Sarvepalli Radhakrishnan Rajasthan Ayurved University; Samta Ayurveda Prakoshtha, India; Padmanabhama Ayurveda Hospital and Research Centre
Completed
Vitamin A Supplementation in Children With Moderate to Severe COVID-19 - Condition: Covid19
Intervention: Dietary Supplement: Vitamin A supplement
Sponsor: Shiraz University of Medical Sciences
Not yet recruiting
Cerebral Autoregulation and COVID-19 - Conditions: COVID-19 Acute Respiratory Distress Syndrome; COVID-19 Pneumonia
Intervention: Other: NIRS (Near-Infrared Spectroscopy)
Sponsor: University of Athens
Not yet recruiting
Favipiravir +/- Nitazoxanide: Early Antivirals Combination Therapy in COVID-19 - Condition: Covid19
Interventions: Drug: Favipiravir; Drug: Nitazoxanide; Other: Nitazoxanide Placebo
Sponsors: Coordinación de Investigación en Salud, Mexico; University College, London; Centro de Investigacion y Estudios Avanzados del Instituto Politecnico Nacional (CINVESTAV); Universidad Autonoma de Guadalajara; Siegfried Rhein S.A. de C.V.; Strides Pharma Science Limited; Hakken Enterprise
Not yet recruiting
Safety and Efficacy of Dupilumab for Treatment of Hospitalized COVID-19 Patients - Condition: Covid19
Interventions: Biological: Dupilumab; Drug: Placebo
Sponsors: University of Virginia; PBM C19 Research, LLC (a COVID-19 research entity of the Paul Manning Foundation); Virginia Catalyst, Virginia Biosciences Health Research Corporation (VBHRC)
Recruiting
Impact of Moderate Exercise Training on Vitals and Peak VO2 in Different Age Categories of Adult in COVID-19. - Condition: Covid19
Interventions: Other: Moderate Exercise Training (Age Group 1; Young adult 17 -30 years); Other: Moderate Exercise Training (Age Group 2; 31 to 45 years); Other: Moderate Exercise Training (Age Group 3; Above 45 years)
Sponsor: Riphah International University
Recruiting
Infliximab in the Treatment of Patients With Severe COVID-19 Disease - Condition: COVID-19
Interventions: Drug: Infliximab; Other: Standard of Care
Sponsors: Jena University Hospital; German Federal Ministry of Education and Research; Celltrion
Not yet recruiting
Targeting Bruton’s Tyrosine Kinase in Inflammatory and Autoimmune Pathologies - Bruton’s tyrosine kinase (BTK) was discovered due to its importance in B cell development, and it has a critical role in signal transduction downstream of the B cell receptor (BCR). Targeting of BTK with small molecule inhibitors has proven to be efficacious in several B cell malignancies. Interestingly, recent studies reveal increased BTK protein expression in circulating resting B cells of patients with systemic autoimmune disease (AID) compared with healthy controls. Moreover, BTK…
Exploring the Psychological Effects of COVID-19 Home Confinement in China: A Psycho-Linguistic Analysis on Weibo Data Pool - CONCLUSION: Home confinement caused a decline in the use of positive emotion words. This indicates that home confinement can increase the frequency of negative emotions. The changes of exclusion words and inhibition words in high-endemic areas may be related to the high epidemic threat and the urgent need for social distancing in these areas.
Discovery of New Potent anti-MERS CoV Fusion Inhibitors - Middle East respiratory syndrome coronavirus (MERS-CoV), capable of zoonotic transmission, has been associated with emerging viral pneumonia in humans. In this study, a set of highly potent peptides were designed to prevent MERS-CoV fusion through competition with heptad repeat domain 2 (HR2) at its HR1 binding site. We designed eleven peptides with stronger estimated HR1 binding affinities than the wild-type peptide to prevent viral fusion with the cell membrane. Eight peptides showed strong…
“Surfactants - compounds for inactivation of SARS-CoV-2 and other enveloped viruses” - We provide here a general view on the interactions of surfactants with viruses, with a particular emphasis on how such interactions can be controlled and employed, for inhibiting the infectivity of enveloped viruses, including coronaviruses. The aim is to provide to interested scientists from different fields, including chemistry, physics, biochemistry, and medicine, an overview over the basic properties of surfactants and (corona)viruses, which are relevant to understanding the interactions…
COVID-19: In silico identification of potent alpha-ketoamide inhibitors targeting the main protease of the SARS-CoV-2 - The COVID-19 has been creating a global crisis, causing countless deaths and unbearable panic. Despite the progress made in the development of the vaccine, there is an urge need for the discovery of antivirals that may better work at different stages of SARS-CoV-2 reproduction. The main protease (M^(pro)) of the SARS-CoV-2 is a crucial therapeutic target due to its critical function in virus replication. The α-ketoamide derivatives represent an important class of inhibitors against the M^(pro)…
Fragment-based in silico design of SARS CoV-2 main protease inhibitors - 3CLpro is essential for SARS-CoV-2 replication and infection; its inhibition using small molecules is a potential therapeutic strategy. In this study, a comprehensive crystallography-guided fragment-based drug discovery approach was employed to design new inhibitors for SARS-CoV-2 3CLpro. All small molecules co-crystallized with SARS-CoV-2 3CLpro with structures deposited in the Protein Data Bank were used as inputs. Fragments sitting in the binding pocket (87) were grouped into eight…
Discovery and optimization of 2-((1H-indol-3-yl)thio)-N-benzyl-acetamides as novel SARS-CoV-2 RdRp inhibitors - The emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the global pandemic coronavirus disease (COVID-19), but no specific antiviral drug has been proven effective for controlling this pandemic to date. In this study, several 2-((indol-3-yl)thio)-N-benzyl-acetamides were identified as SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) inhibitors. After a two-round optimization, a new series of 2-((indol-3-yl)thio)-N-benzyl-acetamides was designed, synthesized,…
Imatinib in patients with severe COVID-19: a randomised, double-blind, placebo-controlled, clinical trial - BACKGROUND: The major complication of COVID-19 is hypoxaemic respiratory failure from capillary leak and alveolar oedema. Experimental and early clinical data suggest that the tyrosine-kinase inhibitor imatinib reverses pulmonary capillary leak.
TRIM28 regulates SARS-CoV-2 cell entry by targeting ACE2 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019, it binds to angiotensin-converting enzyme 2 (ACE2) to enter into human cells. The expression level of ACE2 potentially determine the susceptibility and severity of COVID-19, it is thus of importance to understand the regulatory mechanism of ACE2 expression. Tripartite motif containing 28 (TRIM28) is known to be involved in multiple processes including antiviral restriction, endogenous…
From Cancer to COVID-19: A Perspective on Targeting Heparan Sulfate-Protein Interactions - Heparan sulfate (HS) is a complex, polyanionic polysaccharide ubiquitously expressed on cell surfaces and in the extracellular matrix. HS interacts with numerous proteins to mediate a vast array of biological and pathological processes. Inhibition of HS-protein interactions is thus an attractive approach for new therapeutic development for cancer and infectious diseases, including COVID-19; however, synthesis of well-defined native HS oligosaccharides remains challenging. This has aroused…
Activation of mTORC1 at late endosomes misdirects T cell fate decision in older individuals - The nutrient-sensing mammalian target of rapamycin (mTOR) is integral to cell fate decisions after T cell activation. Sustained mTORC1 activity favors the generation of terminally differentiated effector T cells instead of follicular helper and memory T cells. This is particularly pertinent for T cell responses of older adults who have sustained mTORC1 activation despite dysfunctional lysosomes. Here, we show that lysosome-deficient T cells rely on late endosomes rather than lysosomes as an…
Fear in the Chinese Population: Influential Patterns in the Early Stage of the COVID-19 Pandemic - Major global public health emergencies challenge public mental health. Negative emotions, and especially fear, may endanger social stability. To better cope with epidemics and pandemics, early emotional guidance should be provided based on an understanding of the status of public emotions in the given circumstances. From January 27 to February 11, 2020 (during which the cases of COVID-19 were increasing), a national online survey of the Chinese public was conducted. A total of 132,482…
An ACE2 Triple Decoy that neutralizes SARS-CoV-2 shows enhanced affinity for virus variants - The SARS-CoV-2 variants replacing the first wave strain pose an increased threat by their potential ability to escape pre-existing humoral protection. An angiotensin converting enzyme 2 (ACE2) decoy that competes with endogenous ACE2 for binding of the SARS-CoV-2 spike receptor binding domain (S RBD) and inhibits infection may offer a therapeutic option with sustained efficacy against variants. Here, we used Molecular Dynamics (MD) simulation to predict ACE2 sequence substitutions that might…
Melatonin and other indoles show antiviral activities against swine Coronaviruses in vitro at pharmacological concentrations - The current coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), highlights major gaps in our knowledge on the prevention control and cross-species transmission mechanisms of animal coronaviruses. Transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), and porcine delta-coronavirus (PDCoV) are three common swine coronaviruses and have similar clinical features. In absence of effective treatments, they…
Manipulation of the unfolded protein response: A pharmacological strategy against coronavirus infection - Coronavirus infection induces the unfolded protein response (UPR), a cellular signalling pathway composed of three branches, triggered by unfolded proteins in the endoplasmic reticulum (ER) due to high ER load. We have used RNA sequencing and ribosome profiling to investigate holistically the transcriptional and translational response to cellular infection by murine hepatitis virus (MHV), often used as a model for the Betacoronavirus genus to which the recently emerged SARS-CoV-2 also belongs….
SARS-CoV-2 anti-viral therapeutic - - link
폐마스크 밀봉 회수기 - 본 발명은 마스크 착용 후 버려지는 일회용 폐마스크를 비닐봉지에 넣은 후 밀봉하여 배출함으로써, 2차 감염을 예방하고 일반 생활폐기물과 선별 분리 배출하여 환경오염을 방지하는 데 그 목적이 있다. - link
COST EFFECTIVE PORTABLE OXYGEN CONCENTRATOR FOR COVID-19 - - link
METHOD OF IDENTIFYING SEVERE ACUTE RESPIRATORY SYNDROME CORONA VIRUS 2 (SARS-COV-2) RIBONUCLEIC ACID (RNA) - - link
Erweiterbare Desinfektionsvorrichtung, umfassend: einen Hauptkörper, der eine umgekehrt U-förmige Basisplatte aufweist, wobei die umgekehrt U-förmige Basisplatte mit einer Öffnung versehen ist und jeweils eine Seitenplatte sich von zwei Seiten der umgekehrt U-förmigen Basisplatte nach außen erstreckt; und mindestens eine Desinfektionslampe, die in den auf zwei Seiten des Hauptkörpers befindlichen Seitenplatten angeordnet ist und eine Lichtemissionseinheit, eine Erfassungseinheit, eine Steuereinheit und eine Stromversorgungseinheit umfasst.
Einfache Sterilisationsvorrichtung, mit einem Hauptkörper (11), der in Längsrichtung einen ersten Plattenabschnitt (111) und in Querrichtung einen zweiten Plattenabschnitt (112) aufweist, wobei der erste Plattenabschnitt (111) und der zweite Plattenabschnitt (112) L-förmig miteinander verbunden sind; und einer Sterilisationslampe (12), die an dem Hauptkörper (11) angeordnet ist und eine Lichtemissionseinheit (121), eine Sensoreinheit (122), eine Steuereinheit (123) und eine Stromeinheit (124) aufweist.
Klemmarme aufweisende Desinfektionsvorrichtung, umfassend: einen Hauptkörper; eine Desinfektionslampe, die im Hauptkörper angeordnet ist und eine Lichtemissionseinheit, eine Erfassungseinheit, eine Steuereinheit und eine Stromversorgungseinheit umfasst; einen Klemmabschnitt, der auf einer Seite des Hauptkörpers angeordnet ist, wobei der Klemmabschnitt zwei gegenüberliegende Greifbacken umfasst, wobei mindestens eine der beiden Greifbacken mit einer Schwenkachse versehen ist, wobei ein Klemmraum durch passgenaues Schließen der beiden Greifbacken entsteht und die beiden Greifbacken jeweils mit einem Durchgangsloch versehen sind; einen Befestigungsabschnitt, der durch die Durchgangslöcher der beiden Greifbacken hindurchgeführt ist;und ein Schild, das auf einer Seite des Klemmabschnitts angeordnet und mit einem Aufnahmeloch versehen ist.
Aufhängbare Sterilisationsvorrichtung, mit einem Hauptkörper (11); einer Sterilisationslampe (12), die an dem Hauptkörper (11) angeordnet ist und eine Lichtemissionseinheit (121), eine Sensoreinheit (122), eine Steuereinheit (123) und eine Stromeinheit (124) aufweist; einem Klemmabschnitt (13), der an einer Seite des Hautpkörpers (11) angeordnet ist und zwei gegenüberliegend angeordnete Klemmbacken (131) aufweist, wobei mindestens eine der beiden Klemmbacken (131) mit einem Achsbolzen (132) versehen ist, wobei die beiden Klemmbacken (131) beim Schließen einen Klemmraum (134) bilden, und wobei die beiden Klemmbacken (131) jeweils mit einem Durchgangsloch (135) versehen sind; und einem Befestigungselement (14), das durch die Durchgangslöcher (135) der beiden Klemmbacken (131) hindurchgeführt wird.
Sterilisationsvorrichtung zur Verbesserung der Desinfektionswirkung, umfassend: einen Hauptkörper, der eine erste Oberfläche, eine von der ersten Oberfläche abgewandte zweite Oberfläche und ein Aufnahmeloch aufweist, wobei die zwei Seiten des Hauptkörpers jeweils mit einem Durchgangsloch versehen sind, wobei die Durchgangslöcher mit dem Aufnahmeloch durchgängig verbunden sind; eine Desinfektionslampe, die auf der zweiten Oberfläche des Hauptkörpers angeordnet ist und eine Lichtemissionseinheit, eine Erfassungseinheit, eine Steuereinheit und eine Stromversorgungseinheit umfasst; und ein Befestigungsteil, das durch die Durchgangslöcher und das Aufnahmeloch des Hauptkörpers hindurchgeführt ist.