Risk of severe COVID-19 increases with age, is greater in males, and is associated with lymphopenia, but not with higher burden of SARS-CoV-2. It is unknown whether effects of age and sex on abundance of specific lymphoid subsets explain these correlations. This study found that the abundance of ILCs decreases more than 7-fold over the human lifespan and is lower in males than in females. After accounting for age and sex, innate lymphoid cells (ILCs), but not T cells, were lower in adults hospitalized with COVID-19, independent of lymphopenia. Among SARS-CoV-2-infected adults, ILC abundance correlated inversely with odds and duration of hospitalization, and with severity of inflammation. ILCs were also uniquely decreased in pediatric COVID-19 and did not recover during follow-up. In contrast, individuals with MIS-C had depletion of both ILCs and T cells, and both cell types increased during follow-up. In both pediatric COVID-19 and MIS-C, ILC abundance correlated inversely with inflammation. Blood ILC mRNA and phenotype tracked more closely with ILCs from lung than from other organs. Importantly, blood ILCs produced amphiregulin, a protein implicated in disease tolerance and tissue homeostasis, and the percentage of amphiregulin-producing ILCs was higher in females. These results suggest that, by promoting disease tolerance, homeostatic ILCs decrease morbidity and mortality associated with SARS-CoV-2 infection, and that lower ILC abundance accounts for increased COVID-19 severity with age and in males.
Abstract There is a great demand for more rapid tests for SARS-COV-2 detection to reduce waiting time, boost public health strategies for combating disease, decrease costs, and prevent overwhelming laboratory capacities. This study was conducted to assess the performance of 10 lateral flow device viral antigen immunoassays for the detection of SARS-CoV-2 in nasopharyngeal swab specimens. We analyzed 231 nasopharyngeal samples collected from October 2020-December 2020, from suspected COVID-19 cases and contacts of positive cases at Biotechnology Research Center laboratories, Tripoli, Libya. The performance of 10 COVID-19 Antigen (Ag) rapid test devices for the detection of SARS-CoV-2 antigen was compared to RT-qPCR. In this study 161 cases had symptoms consistent with COVID-19. The mean duration from symptom onset was 6.6 days. The median cycle threshold (Ct) of positive samples was 25. Among the 108 positive samples detected by RT-qPCR, the COVID-19 antigen (Ag) tests detected 83 cases correctly. All rapid Ag test devices used in this study showed 100% specificity. While tests from 6 manufacturers had an overall sensitivity range from 75-100%, the remaining 4 tests had sensitivity of 50-71.43%. Sensitivity during the first 6 days of symptoms and in samples with high viral loads (Ct<25), was 100% in all but 2 of the test platforms. False negative samples had a median Ct of 34 and an average duration of onset of symptoms of 11.3 days (range=5-20 days). Antigen test diagnosis has high sensitivity and specificity in early disease when patients present less than 7 days of symptom onset. Patients are encouraged to test as soon as they get COVID-19 related symptoms within 1 week and to seek medical advice within 24 hrs. if they develop disturbed smell/taste. The use of rapid antigen tests is important for controlling COVID-19 pandemic and reducing burden on molecular diagnostic laboratories. Keywords: Rapid antigen tests, SARS-CoV-2, COVID-19 diagnosis, Surveillance
The first case of COVID-19 in India was reported on January 30, 2020 [1]. The number of infections rose steeply and preventative measures such as lockdowns were implemented to slow down the spread of the disease. Infections peaked around mid-September the same year and the cases gradually started declining. Following the relaxation of lockdown and the appearance of mutant strains of the virus, a much severe second wave of COVID-19 emerged starting mid-February. For characterization and comparison of both the waves, a SIQR (Susceptible-Infected-Quarantined-Removed) model is used in this paper. The results indicate that a single patient can infect approximately 2.44 individuals in the population. The epidemic doubling time was calculated to be 11.8 days. It is predicted that the actual number of infected patients is grossly underestimated (by a factor of 16) by current testing methods.
The COVID-19 pandemic in Brazil is extremely severe, and Brazil has the third-highest number of cases in the world. The goal of the study is to identify the prevalence rates and several predictors of depression and anxiety in Brazil during the initial outbreak of COVID-19. We surveyed 482 adults in 23 Brazilian states online on 9-22 May 2020, and found 70.3% of the adults (N=339) had depressive symptoms and 67.2% (N=320) had anxiety symptoms. The results of multi-class logistic regression models revealed that females, younger adults and those with fewer children had a higher likelihood of depression and anxiety symptoms; adults who worked as employees were more likely to have anxiety symptoms than those who were self-employed or unemployed; adults who spent more time browsing COVID-19 information online were more likely to have depression and anxiety symptoms. Our results provide preliminary evidence and early warning for psychiatrists and healthcare organizations to better identify and focus on the more vulnerable sub-populations in Brazil during the ongoing COVID-19 pandemic. Keywords: COVID-19; Brazil; anxiety; depression; predictors; risk factors
Objectives: To estimate the effectiveness of BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), and ChAdOx1 (AstraZeneca) vaccines against symptomatic SARS-CoV-2 infection and severe outcomes (COVID-19 hospitalization or death) caused by the Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2) variants of concern (VOCs) during December 2020 to May 2021. Methods: We conducted a test-negative design study using linked population-wide vaccination, laboratory testing, and health administrative databases in Ontario, Canada. Results: Against symptomatic infection caused by Alpha, vaccine effectiveness with partial vaccination (≥14 days after dose 1) was higher for mRNA-1273 than BNT162b2 and ChAdOx1. Full vaccination (≥7 days after dose 2) increased vaccine effectiveness for BNT162b2 and mRNA-1273 against Alpha. Protection against symptomatic infection caused by Beta/Gamma was lower with partial vaccination for ChAdOx1 than mRNA-1273. Against Delta, vaccine effectiveness after partial vaccination tended to be lower than against Alpha for BNT162b2 and mRNA-1273, but was similar to Alpha for ChAdOx1. Full vaccination with BNT162b2 increased protection against Delta to levels comparable to Alpha and Beta/Gamma. Vaccine effectiveness against hospitalization or death caused by all studied VOCs was generally higher than for symptomatic infection after partial vaccination with all three vaccines. Conclusions: Our findings suggest that even a single dose of these 3 vaccine products provide good to excellent protection against symptomatic infection and severe outcomes caused by the 4 currently circulating variants of concern, and that 2 doses are likely to provide even higher protection.
Traditional contact tracing for COVID-19 tests the direct contacts of those who test positive even if the contacts do not show any symptom. But, by the time an infected individual is tested, the infection starting from the person may have infected a chain of individuals. Hence, why should the testing stop at direct contacts, and not test secondary, tertiary contacts or even contacts further down? One deterrent in testing long chains of individuals right away may be that it substantially increases the testing load, or does it? We investigate the costs and benefits of such multi-hop contact tracing for different number of hops. Considering a large number of contact topologies, spanning synthetic networks of divergent characteristics and those constructed from recorded interactions, we show that the cost-benefit tradeoff can be characterized in terms of a single measurable attribute, the initial epidemic growth rate. Once this growth rate crosses a threshold, multi-hop contact tracing substantially reduces the outbreak size compared to traditional contact tracing. Multi-hop even incurs a lower cost compared to the traditional contact tracing for a large range of values of the growth rate. The cost-benefit tradeoffs and the choice of the number of hops can be classified into three phases, with sharp transitions between them, depending on the value of the growth rate. The need for choosing a larger number of hops becomes greater as the growth rate increases or the environment becomes less conducive toward containing the disease.
Previous studies have described RT-LAMP methodology for the rapid detection of SARS-CoV-2 in nasopharyngeal/oropharyngeal swab and saliva samples. Here we describe the validation of an improved simple sample preparation method for Direct SARS-CoV-2 RT-LAMP, removing the need for RNA extraction, using 559 swabs and 86,760 saliva samples from asymptomatic and symptomatic individuals across multiple healthcare settings. Using this improved method we report a diagnostic sensitivity (DSe) of 70.35% (95% CI 63.48-76.60%) on swabs and 84.62% (79.50-88.88%) on saliva, with diagnostic specificity (DSp) 100% (98.98-100.00%) on swabs and 100% (99.72-100.00%) on saliva when compared to RT-qPCR. Analysing samples with RT-qPCR ORF1ab CT values of <25 and <33 (high and medium-high viral loads, respectively), we found DSe of 100% (96.34-100%) and 77.78% (70.99-83.62%) for swabs, and 99.01% (94.61-99.97%) and 87.32% (80.71-92.31%) for saliva. We also describe RNA RT-LAMP (on extracted RNA) performed on 12,619 swabs and 12,521 saliva samples to provide updated performance data with DSe and DSp of 95.98% (92.74-98.06%) and 99.99% (99.95-100%) for swabs, and 80.65% (73.54-86.54%) and 99.99% (99.95-100%) for saliva, respectively. We also report on daily samples collected from one individual from symptom onset where both Direct and RNA RT-LAMP detected SARS-CoV-2 in saliva collected on all six days where symptoms were recorded, with RNA RT-LAMP detecting SARS-CoV-2 for an additional further day. The findings from these studies demonstrate that RT-LAMP testing of swabs and saliva is potentially applicable to a variety of use-cases, including frequent, interval-based testing of saliva from asymptomatic individuals via Direct RT-LAMP that may be missed using symptomatic testing alone.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly in the global population since its emergence in humans in late 2019. Replication of SARS-CoV-2 is characterised by transcription and replication of genomic length RNA and shorter subgenomic RNAs to produce virus proteins and ultimately progeny virions. Here we explore the pattern of both genome-length and subgenomic RNAs and positive and negative strand SARS-CoV-2 RNAs in diagnostic nasopharyngeal swabs using sensitive probe based PCR assays as well as Ampliseq panels designed to target subgenomic RNAs. Using these assays, we measured the ratios of genomic to subgenomic RNAs as well as the ratios of positive to negative strand RNAs in SARS-CoV-2 positive nasopharyngeal swab samples. We found that while subgenomic RNAs and negative strand RNA can be readily detected in swab samples taken up to 19 and 17 days post symptom onset respectively, and therefore their detection alone is not likely an indicator of active SARS-CoV-2 replication. However, the ratios of genomic-length to subgenomic RNA and also of positive to negative strand RNA were elevated in some swabs, particularly those collected around the onset of clinical symptoms or in an individual with decreasing PCR Cts in successive swab samples. We tentatively conclude that it may be possible to refine such molecular assays to help determine if active replication of virus is occurring and progeny virions likely present in a SARS-CoV-2 positive individual. Assays targeting subgenomic N or ORF7a RNAs as well as strand specific ORF7a total genome-length and subgenomic RNAs may be the most sensitive for this purpose as these targets were consistently the most abundant in the swab samples.
Analysis of anti-SARS-CoV-2 antibodies can identify recent-onset or prior COVID-19 infection or vaccine-induced humoral immunity. We have developed a rapid point-of-care test for IgG, M, or A-class immunoglobulins that recognize the S1 domain of the SARS-CoV-2 spike protein (CovAb™). The test employs a lateral-flow strip design with a recombinant SARS-CoV-2 spike protein S1 domain capture antigen to detect anti-SARS-CoV-2 antibodies in oral fluid samples. Oral fluid samples are collected with a swab that captures the gingival crevicular fluid component of oral fluid that represents a plasma transudate and that is the primary source of oral fluid monomeric antibodies. The sensitivity of the CovAb™ test is 97.29% and the specificity is 98.13%, and the results obtained are similar to those obtained using matched fingerstick whole blood samples and in an EUA-approved commercial serology test. Oral fluid SARS-CoV-2 antibodies could be detected in subjects more than 7 months post-symptom onset. We also demonstrate the utility of the CovAb™ test in characterizing adaptive immune responses to vaccination in COVID-19-naive and exposed populations after first and second vaccine doses and show that significant heterogeneity in magnitude of antibody titers achieved is seen after both doses and that prior COVID-19 exposure increases the adaptive immune response to vaccination.
Introduction Long COVID, describing the long-term sequelae after SARS-CoV-2 infection, remains a poorly defined syndrome. There is uncertainty about its predisposing factors and the extent of the resultant public health burden, with estimates of prevalence and duration varying widely. Methods Within rounds 3-5 of the REACT-2 study, 508,707 people in the community in England were asked about a prior history of COVID-19 and the presence and duration of 29 different symptoms. We used uni- and multivariable models to identify predictors of persistence of symptoms (12 weeks or more). We estimated the prevalence of symptom persistence at 12 weeks, and used unsupervised learning to cluster individuals by symptoms experienced. Results Among the 508,707 participants, the weighted prevalence of self-reported COVID-19 was 19.2% (95% CI: 19.1,19.3). 37.7% of 76,155 symptomatic people post COVID-19 experienced at least one symptom, while 14.8% experienced three or more symptoms, lasting 12 weeks or more. This gives a weighted population prevalence of persistent symptoms of 5.75% (5.68, 5.81) for one and 2.22% (2.1, 2.26) for three or more symptoms. Almost a third of people 8,771/28,713 (30.5%) with at least one symptom lasting 12 weeks or more reported having had severe COVID-19 symptoms (9significant effect on my daily life9) at the time of their illness, giving a weighted prevalence overall for this group of 1.72% (1.69,1.76). The prevalence of persistent symptoms was higher in women than men (OR: 1.51 [1.46,1.55]) and, conditional on reporting symptoms, risk of persistent symptoms increased linearly with age by 3.5 percentage points per decade of life. Obesity, smoking or vaping, hospitalisation , and deprivation were also associated with a higher probability of persistent symptoms, while Asian ethnicity was associated with a lower probability. Two stable clusters were identified based on symptoms that persisted for 12 weeks or more: in the largest cluster, tiredness predominated, while in the second there was a high prevalence of respiratory and related symptoms. Interpretation A substantial proportion of people with symptomatic COVID-19 go on to have persistent symptoms for 12 weeks or more, which is age-dependent. Clinicians need to be aware of the differing manifestations of Long COVID which may require tailored therapeutic approaches. Managing the long-term sequelae of SARS-CoV-2 infection in the population will remain a major challenge for health services in the next stage of the pandemic.
Importance While the mRNA BNT162b2 vaccine effectiveness was demonstrated in general population, the question of effectiveness given confirmed exposure has yet been answered, though it has policy implications, as the need for self-quarantine when exposed and protective measures for vaccinated in high-risk areas. Objective Assessing the BNT162b2 vaccine effectiveness in preventing SARS-CoV-2 infection given high-risk exposure, through analysis of household members of confirmed cases. Design Retrospective cohort study. Data of household members of confirmed SARS-CoV-2 cases between 20/12/2020 and 17/03/2021 were collected. Setting Nationally centralized database of Maccabi Healthcare Services (MHS), the second largest Healthcare Maintenance Organization in Israel. Participants 2.5 million MHS members were considered, of which we included only households with two adult members, given possible lower transmission and susceptibility among children. Households with no prior confirmed infections and a confirmed index case during the study period were included. Exposure Participants were classified into three vaccination groups in time of the index case (the confirmed exposure)- Unvaccinated; Fully Vaccinated(7 or more days post second dose) and a reference control group of Recently Vaccinated Once(0-7 days from the first dose, presumably still unprotected). Main Outcomes and Measures Assessing the probability of an additional SARS-CoV-2 infection in the household occurring within 10 days of an index case, calculated separately for the three vaccination groups. Main outcome was vaccine effectiveness given confirmed exposure. High testing rates among household members enabled us to estimate with a high degree of confidence effectiveness against asymptomatic SARS-CoV-2 infection as well. Results A total of 173,569 households were included, out of which 6,351 households had an index infection (mean [SD] age, 58.9 [13.5] years; 50% were women). Vaccine effectiveness of Fully Vaccinated compared to Unvaccinated participants was 80.0% [95% CI, 73.0-85.1] and 82.0% [95% CI, 75.5-86.7] compared to those Recently Vaccinated Once. Conclusion and Relevance The BNT162b2 vaccine is effective in a high-risk, real life, exposure scenario, but the protection rates afforded in these settings are lower than those previously described. Household members of COVID-19 patients and any individual with a confirmed exposure to COVID-19 are still at a considerable risk of being infected even if fully vaccinated.
Background More than 170 million cases of COVID-19 have been reported worldwide. It has been proposed that psychiatric disorders may be risk factors and/or consequences of COVID-19 infection. However, observational studies could be affected by confounding bias. Methods We performed bi-directional two-sample Mendelian randomization (MR) analysis to evaluate causal relationships between liability to COVID-19 (and severe/critical infection) and a wide range of neuropsychiatric disorders or traits. We employed the latest GWAS summary statistics from the COVID-19 Host Genetics Initiative. A variety of MR methods including those accounting for horizontal pleiotropy were used. Results Overall we observed evidence that liability to COVID-19 or severe infection may be causally associated with higher risks of post-traumatic stress disorder (PTSD), bipolar disorder (BD) (especially BD II), schizophrenia (SCZ), attention deficit hyperactivity disorder (ADHD) and suicidal thought (ST) when compared to the general population. On the other hand, liability to a few psychiatric traits/disorders, for example ADHD, alcohol and opioid use disorders may be causally associated with higher risks of COVID-19 infection or severe disease. In genetic correlation analysis, cannabis use disorder, ADHD, and anxiety showed significant and positive genetic correlation with critical or hospitalized infection. All the above findings passed multiple testing correction at a false discovery rate (FDR)<0.05. For pneumonia, in general we observed a different pattern of associations, with bi-directional positive associations with depression- and anxiety-related phenotypes. Conclusions In summary, this study provides evidence for tentative bi-directional causal associations between liability to COVID-19 (and severe infection) and a number of neuropsychiatric disorders. Further replications and prospective studies are required to verify the findings.
We report the emergence of a novel lineage of SARS-CoV-2 in South America, termed C.37. It presents a deletion in the ORF1a gene (Δ3675-3677), also found in variants of concern (VOCs) Alpha, Beta, and Gamma, and seven non-synonymous mutations in the Spike gene (Δ247-253, G75V, T76I, L452Q, F490S, T859N). Initially reported in Lima, Peru, in late December 2020, it now accounts for almost 100% of Peruvian genomes in April 2021. It is expanding in Chile and Argentina, and there is evidence of onward transmission in Colombia, Mexico, the USA, Germany, and Israel. On June 15, 2021, the World Health Organization designated C.37 as Variant of Interest (VOI) Lambda.
Streptococcus pneumoniae is the main bacterial pathogen causing respiratory infections. Since the COVID-19 pandemic emerged, less pneumococcal disease was identified by surveillance systems around the world. Measures to prevent transmission of SARS-CoV-2 also reduce transmission of pneumococci, but this would gradually lead to lower disease rates. Here, we explore additional factors that have contributed to the instant drop in pneumococcal disease cases captured in surveillance. Our observations on referral practices and other impediments to diagnostic testing indicate that residual IPD has likely occurred but remained undetected by conventional hospital-based surveillance. Depending on setting, we discuss alternative monitoring strategies that could improve sight on pneumococcal disease dynamics.
Cognitive and Psychological Disorders After Severe COVID-19 Infection - Condition: COVID 19
Interventions: Diagnostic Test: Cognitive assessment; Diagnostic Test: Imaging; Diagnostic Test: Routine care; Other: Psychiatric evaluation
Sponsors: Central Hospital, Nancy, France; Centre Hospitalier Universitaire de Besancon; University Hospital, Strasbourg, France; Centre Hospitalier Régional Metz-Thionville; Centre hospitalier Epinal; Hopitaux Civils de Colmar
Not yet recruiting
Phase 1 Study to Assess Safety, Tolerability, PD, PK, Immunogenicity of IV NTR-441 Solution in Healthy Volunteers and COVID-19 Patients - Condition: Covid19
Interventions: Drug: NTR-441; Drug: Placebo
Sponsor: Neutrolis
Recruiting
MP1032 Treatment in Patients With Moderate to Severe COVID-19 - Condition: COVID-19
Interventions: Drug: MP1032; Drug: Placebo
Sponsors: MetrioPharm AG; Syneos Health, LLC
Not yet recruiting
Study to Evaluate the Safety and Concentrations of Monoclonal Antibody Against Virus That Causes COVID-19 Disease. - Condition: COVID-19 Virus Disease
Interventions: Biological: MAD0004J08; Other: Placebo
Sponsors: Toscana Life Sciences Sviluppo s.r.l.; Cross Research S.A.
Active, not recruiting
Safety and Immunogenicity of LNP-nCOV saRNA-02 Vaccine Against SARS-CoV-2, the Causative Agent of COVID-19 - Condition: COVID-19
Intervention: Drug: LNP-nCOV saRNA-02 Vaccine
Sponsor: MRC/UVRI and LSHTM Uganda Research Unit
Not yet recruiting
Efficacy of Inhaled Therapies in the Treatment of Acute Symptoms Associated With COVID-19 - Condition: Covid19
Interventions: Drug: inhaled beclametasone; Drug: Inahaled beclomethasone / formoterol / glycopyrronium
Sponsors: UPECLIN HC FM Botucatu Unesp; Chiesi Farmaceutici S.p.A.
Not yet recruiting
Dapsone Coronavirus SARS-CoV-2 Trial (DAP-CORONA) COVID-19 - Condition: COVID-19
Interventions: Drug: Dapsone 85 mg PO BID; Drug: Placebo 85 mg PO BID
Sponsors: McGill University Health Centre/Research Institute of the McGill University Health Centre; Pulmonem Inc.
Not yet recruiting
Covid-19 Patients Management During Home Isolation - Condition: Covid19
Interventions: Procedure: Oxygen therapy and physical therapy; Device: Oxygen therapy
Sponsor: Cairo University
Not yet recruiting
Ivermectin Versus Standard Treatment in Mild COVID-19 - Condition: Covid19
Intervention: Drug: Ivermectin Tablets
Sponsor: Assiut University
Not yet recruiting
SCALE-UP Utah: Community-Academic Partnership to Address COVID-19 Testing Among Utah Community Health Centers - Condition: Covid19
Interventions: Behavioral: Text-Messaging (TM); Behavioral: Patient Navigation (PN)
Sponsors: University of Utah; Association for Utah Community Health; Utah Department of Health; National Institutes of Health (NIH)
Recruiting
SCALE-UP Utah: Community-Academic Partnership to Address COVID-19 Vaccination Rates Among Utah Community Health Centers - Condition: Covid19
Interventions: Behavioral: Text-Messaging (TM); Behavioral: Patient Navigation (PN)
Sponsors: University of Utah; Association for Utah Community Health; Utah Department of Health; National Institutes of Health (NIH)
Recruiting
Chinese Herbal Formula for COVID-19 - Condition: Covid19
Interventions: Drug: mQFPD; Drug: organic brown rice
Sponsor: University of California, San Diego
Not yet recruiting
Remdesivir- Ivermectin Combination Therapy in Severe Covid-19 - Condition: Covid19
Intervention: Drug: Ivermectin
Sponsor: Assiut University
Not yet recruiting
IRAK 4 Inhibitor (PF-06650833) in Hospitalized Patients With COVID-19 Pneumonia and Exuberant Inflammation. - Condition: COVID-19 Pneumonia
Interventions: Drug: PF-06650833; Drug: Matching Placebo
Sponsors: Giovanni Franchin, M.D, Ph.D; Pfizer
Recruiting
The Role of Chlorhexidine in Minimizing the Viral Load Among COVID-19 Patients - Condition: COVID-19
Intervention: Drug: Chlorhexidine digluconate, povidone iodine
Sponsor: King Abdulaziz University
Not yet recruiting
Protection of K18-hACE2 mice and ferrets against SARS-CoV-2 challenge by a single-dose mucosal immunization with a parainfluenza virus 5-based COVID-19 vaccine - Transmission-blocking vaccines are urgently needed to reduce transmission of SARS-CoV 2, the cause of the COVID-19 pandemic. The upper respiratory tract is an initial site of SARS-CoV-2 infection and, for many individuals, remains the primary site of virus replication. An ideal COVID-19 vaccine should reduce upper respiratory tract virus replication and block transmission as well as protect against severe disease. Here, we optimized a vaccine candidate, parainfluenza virus 5 (PIV5) expressing…
Small Molecule Therapeutics to Destabilize the ACE2-RBD Complex: a Molecular Dynamics Study - The ongoing COVID-19 pandemic has infected millions of people, claimed hundreds of thousands of lives, and made a worldwide health emergency. Understanding the SARS-CoV-2 mechanism of infection is crucial in the development of potential therapeutics and vaccines. The infection process is triggered by direct binding of the SARS-CoV-2 receptor-binding domain (RBD) to the host cell receptor, angiotensin-converting enzyme 2 (ACE2). Many efforts have been made to design or repurpose therapeutics to…
Famotidine inhibits Toll-like receptor 3-mediated inflammatory signaling in SARS-CoV2 infection - Apart from prevention using vaccinations, the management options for COVID-19 remain limited. In retrospective cohort studies, use of famotidine, a specific oral H2 receptor antagonist (antihistamine), has been associated with reduced risk of intubation and death in patients hospitalized with COVID-19. In a case series, non-hospitalized patients with COVID-19 experienced rapid symptom resolution after taking famotidine, but the molecular basis of these observations remains elusive. Here we show…
Phyllanthin and hypophyllanthin, the isolated compounds of Phyllanthus niruri inhibit protein receptor of corona virus (COVID-19) through in silico approach - CONCLUSIONS: In conclusion, phyllanthin and hypophyllanthin are predicted to have strong activity against COVID-19 through inhibiting spike glycoprotein and main protease under in silico study. Further research is needed to support the development of P. niruri as inhibitor agents of COVID-19 through bioassay studies.
Structure-Guided Design of Conformationally Constrained Cyclohexane Inhibitors of Severe Acute Respiratory Syndrome Coronavirus-2 3CL Protease - A series of nondeuterated and deuterated dipeptidyl aldehyde and masked aldehyde inhibitors that incorporate in their structure a conformationally constrained cyclohexane moiety was synthesized and found to potently inhibit severe acute respiratory syndrome coronavirus-2 3CL protease in biochemical and cell-based assays. Several of the inhibitors were also found to be nanomolar inhibitors of Middle East respiratory syndrome coronavirus 3CL protease. The corresponding latent aldehyde bisulfite…
Macrolactin A as a Novel Inhibitory Agent for SARS-CoV-2 M(pro): Bioinformatics Approach - COVID-19 is a disease that puts most of the world on lockdown and the search for therapeutic drugs is still ongoing. Therefore, this study used in silico screening to identify natural bioactive compounds from fruits, herbaceous plants, and marine invertebrates that are able to inhibit protease activity in SARS-CoV-2 (PDB: 6LU7). We have used extensive screening strategies such as drug likeliness, antiviral activity value prediction, molecular docking, ADME, molecular dynamics (MD) simulation,…
Prognostic Role of Neutrophil to Lymphocyte Ratio in COVID-19 Patients: Still Valid in Patients That Had Started Therapy? - COVID-19 may appear with a widely heterogeneous clinical expression. Thus, predictive markers of the outcome/progression are of paramount relevance. The neutrophil/lymphocyte ratio (NLR) has been suggested as a good predictive marker of disease severity and mortality. Accordingly, we found that NLR significantly increased in parallel with the WHO severity stage in COVID-19 patients during the I^(st) wave (March-May 2020; n = 49), due to the significant reduction of lymphocyte and the significant…
Investigation of a Model-Based Working Memory Training With and Without Distractor Inhibition and Its Comparative Efficacy: A Randomized Controlled Trial on Healthy Old Adults - Background: Various working memory (WM) trainings have been tested, but differences in experimental designs, the lack of theoretical background, and the need of identifying task-related processes such as filtering efficiency limit conclusions about their comparative efficacy. Objectives: In this study, we compared the efficacy of a model-based WM training with (MB^(+)) and without (MB) distractor inhibition on improving WM capacity to a dual n-back and active control condition. Methods: This…
The RNA sensor MDA5 detects SARS-CoV-2 infection - Human cells respond to infection by SARS-CoV-2, the virus that causes COVID-19, by producing cytokines including type I and III interferons (IFNs) and proinflammatory factors such as IL6 and TNF. IFNs can limit SARS-CoV-2 replication but cytokine imbalance contributes to severe COVID-19. We studied how cells detect SARS-CoV-2 infection. We report that the cytosolic RNA sensor MDA5 was required for type I and III IFN induction in the lung cancer cell line Calu-3 upon SARS-CoV-2 infection. Type I…
Postinfection treatment with a protease inhibitor increases survival of mice with a fatal SARS-CoV-2 infection - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to be a serious global public health threat. The 3C-like protease (3CLpro) is a virus protease encoded by SARS-CoV-2, which is essential for virus replication. We have previously reported a series of small-molecule 3CLpro inhibitors effective for inhibiting replication of human coronaviruses including SARS-CoV-2 in cell culture and in animal models. Here we generated a series of deuterated variants of a 3CLpro…
Potential In Vitro Inhibition of Selected Plant Extracts against SARS-CoV-2 Chymotripsin-Like Protease (3CL(Pro)) Activity - Antiviral treatments inhibiting Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication may represent a strategy complementary to vaccination to fight the ongoing Coronavirus disease 19 (COVID-19) pandemic. Molecules or extracts inhibiting the SARS-CoV-2 chymotripsin-like protease (3CL^(Pro)) could contribute to reducing or suppressing SARS-CoV-2 replication. Using a targeted approach, we identified 17 plant products that are included in current and traditional cuisines as…
Antiviral Activity of Vitis vinifera Leaf Extract against SARS-CoV-2 and HSV-1 - Vitis vinifera represents an important and renowned source of compounds with significant biological activity. Wines and winery bioproducts, such as grape pomace, skins, and seeds, are rich in bioactive compounds against a wide range of human pathogens, including bacteria, fungi, and viruses. However, little is known about the biological properties of vine leaves. The aim of this study was the evaluation of phenolic composition and antiviral activity of Vitis vinifera leaf extract against two…
Antiviral Effects of Green Tea EGCG and Its Potential Application against COVID-19 - (-)-Epigallocatechin-3-O-gallate (EGCG), the most abundant component of catechins in tea (Camellia sinensis (L.) O. Kuntze), plays a role against viruses through inhibiting virus invasiveness, restraining gene expression and replication. In this paper, the antiviral effects of EGCG on various viruses, including DNA virus, RNA virus, coronavirus, enterovirus and arbovirus, were reviewed. Meanwhile, the antiviral effects of the EGCG epi-isomer counterpart (+)-gallocatechin-3-O-gallate (GCG) were…
Identification of 13 Guanidinobenzoyl- or Aminidinobenzoyl-Containing Drugs to Potentially Inhibit TMPRSS2 for COVID-19 Treatment - Positively charged groups that mimic arginine or lysine in a natural substrate of trypsin are necessary for drugs to inhibit the trypsin-like serine protease TMPRSS2 that is involved in the viral entry and spread of coronaviruses, including SARS-CoV-2. Based on this assumption, we identified a set of 13 approved or clinically investigational drugs with positively charged guanidinobenzoyl and/or aminidinobenzoyl groups, including the experimentally verified TMPRSS2 inhibitors Camostat and…
Antimicrobial Peptides and Physical Activity: A Great Hope against COVID 19 - Antimicrobial peptides (AMPs), α- and β-defensins, possess antiviral properties. These AMPs achieve viral inhibition through different mechanisms of action. For example, they can: (i) bind directly to virions; (ii) bind to and modulate host cell-surface receptors, disrupting intracellular signaling; (iii) function as chemokines to augment and alter adaptive immune responses. Given their antiviral properties and the fact that the development of an effective coronavirus disease 2019 (COVID-19)…
Differential detection kit for common SARS-CoV-2 variants in COVID-19 patients - - link
SARS-CoV-2 anti-viral therapeutic - - link
A POLYHERBAL ALCOHOL FREE FORMULATION FOR ORAL CAVITY - The present invention generally relates to a herbal composition. Specifically, the present invention relates to a polyherbal alcohol free composition comprising of Glycyrrhiza glabra root extract, Ocimum sanctum leaf extract, Elettaria cardamomum fruit extract, Mentha spicata (Spearmint) oil and Tween 80 and method of preparation thereof. The polyherbal alcohol free composition of the present invention possesses excellent antimicrobial properties and useful for oral cavity. - link
一种新冠病毒肺炎重症化预测系统及方法 - 本发明涉及疾病预测技术领域，公开了一种新冠病毒肺炎重症化预测系统及方法，包括以下步骤：步骤一，采集患者血常规信息和用户信息；步骤二，将患者血常规信息按照用户信息进行等级分类；步骤三，将已经等级分类的患者血常规信息与对应等级的标准信息进行比较；步骤四，当患者血常规信息在标准信息范围内则判定患者为轻症患者，当患者血常规信息在标准信息范围外则判定患者为重症患者。本发明能够准确快速地区分轻症和重症。 - link
一种诊断标志物及其在COVID-19诊断及冠状病毒既往感染检测中的应用 - 本发明公开一种诊断标志物及在COVID‑19诊断及冠状病毒既往感染检测中的应用。所述诊断标志物包括肽段COVID19‑V001，所述肽段COVID19‑V001的氨基酸序列为：包含FKEELDKYFKNH中5个及5个以上连续氨基酸的序列；或所述肽段COVID19‑V001的氨基酸序列为：包含FKEELDKYFKNH中1个到几个氨基酸的取代或/和缺失或/和添加所形成的序列。基于本发明的诊断标志物应用间接法定性检测人血清中抗肽段的IgG抗体的水平。通过基于本发明所建立的检测试剂盒，可作为新型冠状病毒肺炎(COVID‑19)及诊断的一种辅助手段，还可作为区分感染和疫苗接种的手段。 - link
MEDIDOR DE SATURACION - - 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
백신 냉각 및 해동 기능을 갖는 백신 보관장치 - 본 발명은 백신 냉각 및 해동 기능을 갖는 백신 보관장치에 관한 것으로, 상, 하부하우징의 제1상, 하부누출방지공간에 냉각물질이 충입된 냉각파이프를 설치하되, 제2상, 하부누출방지공간에 가열물질이 충입된 가열파이프를 설치하여, 구획판부에 의해 구획된 백신냉각공간 및 백신해동공간 각각을 냉각 및 가열하고, 보조도어를 통해 백신냉각공간 내에 수용된 백신을 구획판부의 백신출구도어를 통해 백신해동공간으로 이동시켜, 백신해동공간 내에서 백신을 해동함으로써, 즉시 사용이 가능한 백신을 인출도어를 통해 인출할 수 있다. 본 발명에 따르면, 냉각파이프에 저장된 냉매에 의해 백신냉각공간 내의 온도가 극저온 상태로 변화되고, 극저온 상태를 유지하는 백신냉각공간 내에 백신을 저장하여, 안전하게 보관 할 수 있으며, 백신냉각공간 내의 백신을 백신해동공간 내로 이동시켜, 백신해동공간 내에서 백신을 해동할 수 있고, 이 해동된 백신을 인출도어를 통해 인출한 후 즉시 사용할 수 있어 백신을 해동하는 시간이 단축되며, 보조도어를 통해 백신냉각공간 내의 백신을 백신해동공간으로 이동시켜, 백신이 외기에 노출될 우려가 없으며, 백신냉각공간 내의 백신을 백신해동공간으로 이동시키거나 또는 인출도어를 통해 백신 인출시 정렬장치가 백신을 보조도어 및 인출도어 직하방에 자동 위치시킨다. - link
一种基于新型冠状病毒S蛋白的纳米抗体及其应用 - 本发明属于生物医药技术领域，尤其涉及一种基于新型冠状病毒S蛋白的纳米抗体及其应用。本发明利用纳米抗体文库，以2019新型冠状病毒的Spike S1+S2ECD为靶点，筛选获得一种针对2019新型冠状病毒的纳米抗体，经ELISA检测，不仅能够特异性识别2019新型冠状病毒的Spike S1+S2ECD靶点，还同时能够识别Spike RBD靶点，且结合信号较强。将相应抗体序列构建至原核表达载体中进行表达纯化，成功表达出目标抗体，纯化后纯度大于90％；且经VHH抗体ELISA检测发现，纯化后的纳米抗体对两种靶点均具有较高的亲和力。 - link
一种基于新型冠状病毒S蛋白S1亚基的纳米抗体及其应用 - 本发明属于生物医药技术领域，尤其涉及一种基于新型冠状病毒S蛋白S1亚基的纳米抗体及其应用。本发明利用纳米抗体文库，以2019新型冠状病毒的Spike RBD为靶点，筛选获得一种针对2019新型冠状病毒的纳米抗体，经ELISA检测，不仅能够特异性识别2019新型冠状病毒的Spike RBD靶点，还同时能够识别SPIKE S1+S2ECD靶点，且结合信号较强。将相应抗体序列构建至原核表达载体中进行表达纯化，成功表达出目标抗体，纯化后纯度大于90％；且经VHH抗体ELISA检测发现，纯化后的纳米抗体对两种靶点均具有较高的亲和力。 - link