Background: Countermeasures against COVID-19 outbreak such as lockdown and voluntary restrictions against going out adversely affect human stress and economic activity. Particularly, this stress might lead to suicide. Object: We examined excess mortality attributable to suicide caused by COVID-19. Method: We applied the NIID model to suicide deaths from October 2009 through September, 2020 for the whole of Japan for both genders. Effects of the great earthquake that struck in eastern Japan on March 11, 2011 were incorporated into the estimation model. Results: Significant excess mortality in suicide was found in July, August and September in 2020 for both genders. It was greater among females than among males. In total, 810 excess cases of mortality were identified. Discussion and Conclusion: Excess mortality during the two months was 1.4 times greater than the number of COVID-19 deaths confirmed by PCR testing. Countermeasures against COVID-19 should be chosen carefully in light of suicide effects.
Vaccination elicits immune responses capable of potently neutralizing SARS-CoV-2. However, ongoing surveillance has revealed the emergence of variants harboring mutations in spike, the main target of neutralizing antibodies. To understand the impact of globally circulating variants, we evaluated the neutralization potency of 48 sera from BNT162b2 and mRNA-1273 vaccine recipients against pseudoviruses bearing spike proteins derived from 10 strains of SARS- CoV-2. While multiple strains exhibited vaccine-induced cross-neutralization comparable to wild- type pseudovirus, 5 strains harboring receptor-binding domain mutations, including K417N/T, E484K, and N501Y, were highly resistant to neutralization. Cross-neutralization of B.1.351 variants was weak and comparable to SARS-CoV and bat-derived WIV1-CoV, suggesting that a relatively small number of mutations can mediate potent escape from vaccine responses. While the clinical impact of neutralization resistance remains uncertain, these results highlight the potential for variants to escape from neutralizing humoral immunity and emphasize the need to develop broadly protective interventions against the evolving pandemic.
Background: Little is known about the role of artificial intelligence (AI) as a decisive technology in the clinical management of COVID-19 patients. We aimed to systematically review and critically appraise the current evidence on AI applications for COVID-19 in intensive care and emergency settings, focusing on methods, reporting standards, and clinical utility. Methods: We systematically searched PubMed, Embase, Scopus, CINAHL, IEEE Xplore, and ACM Digital Library databases from inception to 1 October 2020, without language restrictions. We included peer-reviewed original studies that applied AI for COVID-19 patients, healthcare workers, or health systems in intensive care, emergency or prehospital settings. We assessed predictive modelling studies using PROBAST (prediction model risk of bias assessment tool) and a modified TRIPOD (transparent reporting of a multivariable prediction model for individual prognosis or diagnosis) statement for AI. We critically appraised the methodology and key findings of all other studies. Results: Of fourteen eligible studies, eleven developed prognostic or diagnostic AI predictive models, all of which were assessed to be at high risk of bias. Common pitfalls included inadequate sample sizes, poor handling of missing data, failure to account for censored participants, and weak validation of models. Studies had low adherence to reporting guidelines, with particularly poor reporting on model calibration and blinding of outcome and predictor assessment. Of the remaining three studies, two evaluated the prognostic utility of deep learning-based lung segmentation software and one studied an AI-based system for resource optimisation in the ICU. These studies had similar issues in methodology, validation, and reporting. Conclusions: Current AI applications for COVID-19 are not ready for deployment in acute care settings, given their limited scope and poor quality. Our findings underscore the need for improvements to facilitate safe and effective clinical adoption of AI applications, for and beyond the COVID-19 pandemic.
Background and Purpose: Various neurological complications have been reported in association with COVID-19. We report our experience of COVID-19 with stroke at a single center over a period of eight months spanning 1 March to 31 October 2020. Methods: We recruited all patients admitted to Internal Medicine with an acute stroke, who also tested positive for COVID-19 on RTPCR. We included all stroke cases in our analysis for prediction of in-hospital mortality, and separately analyzed arterial infarcts for vascular territory of ischemic strokes. Results: There were 62 stroke cases among 3923 COVID-19 admissions (incidence 1.6%). Data was available for 58 patients {mean age 52.6 years; age range 17 − 91; F/M=20/38; 24% (14/58) aged ≤ 40; 51% (30/58) hypertensive; 36% (21/58) diabetic; 41% (24/58) with O2 saturation <95% at admission; 32/58 (55.17 %) in-hospital mortality}. Among 58 strokes, there were 44 arterial infarcts, seven bleeds, three arterial infarcts with associated cerebral venous sinus thrombosis, two combined infarct and bleed, and two of indeterminate type. Among the total 49 infarcts, Carotid territory was the commonest affected (36/49; 73.5%), followed by vertebrobasilar (7/49; 14.3%) and both (6/49; 12.2%). Concordant arterial block was seen in 61% (19 of 31 infarcts with angiography done). 9Early stroke9 (within 48 hours of respiratory symptoms) was seen in 82.7% (48/58) patients. Patients with poor saturation at admission were older (58 vs 49 years) and had more comorbidities and higher mortality (79% vs 38%). Mortality was similar in young strokes and older patients, although the latter required more intense respiratory support. Logistic regression analysis showed that low GCS and requirement for increasing intensity of respiratory support predicted in-hospital mortality. Conclusions: We had a 1.6% incidence of COVID-19 related stroke of which the majority were carotid territory infarcts. In-hospital mortality was 55.17%, predicted by low GCS at admission.
Shelter-in-place mandates and closure of non-essential businesses have been central to COVID-19 response strategies including in Toronto, Canada. Approximately half of the working population in Canada are employed in occupations that do not allow for remote work suggesting potentially limited impact of some of the strategies proposed to mitigate COVID-19 acquisition and onward transmission risks and associated morbidity and mortality. We compared per-capita rates of COVID-19 cases and deaths from January 23, 2020 to January 24, 2021, across neighborhoods in Toronto by proportion of the population working in essential services. We used person-level data on laboratory-confirmed COVID-19 community cases (N=74,477) and deaths (N=2319), and census data for neighborhood-level attributes. Cumulative per-capita rates of COVID-19 cases and deaths were 3-fold and 2.5-fold higher, respectively, in neighborhoods with the highest versus lowest concentration of essential workers. Findings suggest that the population who continued to serve the essential needs of society throughout COVID-19 shouldered a disproportionate burden of transmission and deaths. Taken together, results signal the need for active intervention strategies to complement restrictive measures to optimize both the equity and effectiveness of COVID-19 responses.
Large Phase 3 clinical trials of the two FDA-authorized COVID-19 vaccines, mRNA-1273 (Moderna) and BNT162b2 (Pfizer/BioNTech), have demonstrated efficacies of 94.1% (n = 30,420, 95% CI: 89.3-96.8) and 95% (n = 43,448, 95% CI: 90.3-97.6) in preventing symptomatic COVID-19, respectively. Given the ongoing vaccine rollout to healthcare personnel and residents of long-term care facilities, here we provide a preliminary assessment of real-world vaccination efficacy in 62,138 individuals from the Mayo Clinic and associated health system (Arizona, Florida, Minnesota, Wisconsin) between December 1st 2020 and February 8th 2021. Our retrospective analysis contrasts 31,069 individuals receiving at least one dose of either vaccine with 31,069 unvaccinated individuals who are propensity-matched based on demographics, location (zip code), and number of prior SARS-CoV-2 PCR tests. 8,041 individuals received two doses of a COVID-19 vaccine and were at risk for infection at least 36 days after their first dose. Administration of two COVID-19 vaccine doses was 88.7% effective in preventing SARS-CoV-2 infection (95% CI: 68.4-97.1%) with onset at least 36 days after the first dose. Furthermore, vaccinated patients who were subsequently diagnosed with COVID-19 had significantly lower 14-day hospital admission rates than propensity-matched unvaccinated COVID-19 patients (3.7% vs. 9.2%; Relative Risk: 0.4; p-value: 0.007). Building upon the previous randomized trials of these vaccines, this study demonstrates their real-world effectiveness in reducing the rates of SARS-CoV-2 infection and COVID-19 severity among individuals at highest risk for infection.
The coronavirus SARS-CoV-2 (SCV2) causes acute respiratory distress, termed COVID-19 disease, with substantial morbidity and mortality. As SCV2 is related to previously-studied coronaviruses that have been shown to have the capability for brain invasion, it seems likely that SCV2 may be able to do so as well. To date, although there have been many clinical and autopsy-based reports that describe a broad range of SCV2-associated neurological conditions, it is unclear what fraction of these have been due to direct CNS invasion versus indirect effects caused by systemic reactions to critical illness. Still critically lacking is a comprehensive tissue-based survey of the CNS presence and specific neuropathology of SCV2 in humans. We conducted an extensive neuroanatomical survey of RT-PCR-detected SCV2 in 16 brain regions from 20 subjects who died of COVID-19 disease. Targeted areas were those with cranial nerve nuclei, including the olfactory bulb, medullary dorsal motor nucleus of the vagus nerve and the pontine trigeminal nerve nuclei, as well as areas possibly exposed to hematogenous entry, including the choroid plexus, leptomeninges, median eminence of the hypothalamus and area postrema of the medulla. Subjects ranged in age from 38 to 97 (mean 77) with 9 females and 11 males. Most subjects had typical age-related neuropathological findings. Two subjects had severe neuropathology, one with a large acute cerebral infarction and one with hemorrhagic encephalitis, that was unequivocally related to their COVID-19 disease while most of the 18 other subjects had non-specific histopathology including focal B-amyloid precursor protein white matter immunoreactivity and sparse perivascular mononuclear cell cuffing. Four subjects (20%) had SCV2 RNA in one or more brain regions including the olfactory bulb, amygdala, entorhinal area, temporal and frontal neocortex, dorsal medulla and leptomeninges. The subject with encephalitis was SCV2-positive in a histopathologically-affected area, the entorhinal cortex, while the subject with the large acute cerebral infarct was SCV2-negative in all brain regions. Like other human coronaviruses, SCV2 can inflict acute neuropathology in susceptible patients. Much remains to be understood, including what viral and host factors influence SCV2 brain invasion and whether it is cleared from the brain subsequent to the acute illness.
Background The District of Columbia (DC), a major metropolitan area, continues to see community transmission of SARS CoV 2. While serologic testing does not indicate current SARS CoV 2 infection, it can indicate prior infection and help inform local policy and health guidance. The DC Department of Health (DC Health) conducted a community based survey to estimate DC SARS CoV 2 seroprevalence and identify seropositivity associated factors. Methods A mixed-methods cross-sectional serology survey was conducted among a convenience sample of DC residents during July 27 through August 21, 2020. Free serology testing was offered at three public test sites. Participants completed an electronic questionnaire on household and demographic characteristics, COVID like illness (CLI) since January 1, 2020, comorbidities, and SARS-CoV-2 exposures. Univariate and bivariate analyses were conducted to describe the sample population and assess factors associated with seropositivity. Results Among a sample of 671 participants, 51 individuals were seropositive, yielding an estimated seroprevalence of 7.6%. More than half (56.9%) of the seropositive participants reported no prior CLI; nearly half (47.1%) had no prior SARS-CoV-2 testing. Race/ethnicity, prior SARS-CoV-2 testing, prior CLI, employment status, and contact with confirmed COVID-19 cases were associated with seropositivity (P<0.05). Among those reporting prior CLI, loss of taste or smell, duration of CLI, fewer days between CLI and serology test, or prior viral test were associated with seropositivity (P≤0.006). Conclusions These findings indicate many seropositive individuals reported no symptoms consistent with CLI since January or any prior SARS-CoV-2 testing. This underscores the potential for cases to go undetected in the community and suggests wider-spread transmission than previously reported in DC.
Background: New SARS-CoV-2 variants with increased transmissibility, like B.1.1.7 from England or B1.351 from South Africa, have caused considerable concern worldwide. In order to contain the spread of these lineages, it is of utmost importance to have rapid, sensitive and high-throughput detection methods at hand. Methods: Analytical sensitivity was assessed for both wild-type SARS-CoV-2 and B.1.1.7 lineage by serial dilution. A total of 141 clinical samples were subjected to the test and results compared to a commercial manual typing-PCR assay and NGS. Results: The multiplex assay is highly sensitive for detection of SARS-CoV-2 RNA in clinical samples, with an LoD of 25.82 cp/ml (CI: 11.61 - 57.48). LoDs are slightly higher for the HV68/70 deletion (111.36 cp/ml; CI: 78.16 - 158.67) and the N501Y SNP (2548.04 cp/ml, CI: 1592.58 - 4076.73). A total of 141 clinical samples were tested with the assay, including 16 samples containing SARS-CoV-2 of the B.1.1.7 lineage. Three non-B.1.1.7 samples contained a HV69/70 deletion. All were correctly identified by the multiplex assay. Conclusion: We describe here a highly sensitive, fully automated multiplex PCR assay for the simultaneous detection of del-HV69/70 and N501Y that can distinguish between lineages B.1.1.7 and B1.351. The assay allows for high-throughput screening for relevant variants in clinical samples prior to sequencing.
Control strategies that employ real time polymerase chain reaction (RT-PCR) tests for the diagnosis and surveillance of COVID-19 epidemic are inefficient in fighting the epidemic due to high cost, delays in obtaining results, and the need of specialized personnel and equipment for laboratory processing. Cheaper and faster alternatives, such as antigen and paper-strip tests, have been proposed. They return results rapidly, but have lower sensitivity thresholds for detecting virus. To quantify the effects of the tradeoffs between sensitivity, cost, testing frequency, and delay in test return on the overall course of an outbreak, we built a multi-scale immuno-epidemiological model that connects the virus profile of infected individuals with transmission and testing at the population level. We investigated various randomized testing strategies and found that, for fixed testing capacity, lower sensitivity tests with shorter return delays slightly flatten the daily incidence curve and delay the time to the peak daily incidence. However, compared with RT-PCR testing, they do not always reduce the cumulative case count at half a year into the outbreak. When testing frequency is increased to account for the lower cost of less sensitive tests, we observe a large reduction in cumulative case counts, from 57% to as low as 1.5% half a year into the outbreak and to 3.2% three years into the outbreak. The improvement is preserved even when the testing budget is reduced by one half or one third. Our results predict that surveillance testing that employs low-sensitivity tests at high frequency is an effective tool for epidemic control.
Vaccine allocation is a national concern especially for countries such as the Philippines that have limited resources in acquiring COVID-19 vaccines. As such, certain groups are suggested to be prioritized for vaccination to protect the most vulnerable before vaccinating others. Our model suggests an allocation of vaccines such that COVID-19 deaths are minimized while the prioritization framework is satisfied. Results of the model show that a vaccine coverage of at least 50 to 70% of the population can be enough for a community with limited supplies, and an increase in vaccine supply is beneficial if initial coverage is less than the specified target range. Also, among the vaccines considered in the study, the one with 89.9% effectiveness and has a 183 Philippine peso (Php) price per dose projected the least number of deaths. Compared to other model variations and common allocation approaches, the model has achieved both an optimal and equitable allocation. This will be helpful for policymakers in determining a vaccine distribution for a resource-constrained community.
Study to Evaluate the Safety and Efficacy of a Single Dose of STI-2020 (COVI-AMG™) to Treat COVID-19 - Condition: Covid19
Interventions: Biological: COVI-AMG; Drug: Placebo
Sponsor: Sorrento Therapeutics, Inc.
Not yet recruiting
An Effectiveness Study of the Sinovac’s Adsorbed COVID-19 (Inactivated) Vaccine - Condition: Covid19
Intervention: Biological: Adsorbed COVID-19 (Inactivated) Vaccine
Sponsor: Butantan Institute
Enrolling by invitation
Telerehabilitation in Covid-19 After Hospital Discharge - Condition: Covid19
Interventions: Other: Standard Physiotherapy program; Other: Telerehabilitation
Sponsor: Universidad de Granada
Not yet recruiting
Study of the Kinetics of COVID-19 Antibodies for 24 Months in Patients With Confirmed SARS-CoV-2 Infection - Conditions: Covid19; SARS-CoV 2
Intervention: Other: Sampling by venipuncture
Sponsor: Centre Hospitalier Régional d’Orléans
Recruiting
Effect of Prone Position onV/Q Matching in Non-intubated Patients With COVID-19 - Condition: Covid19
Intervention: Other: prone position
Sponsor: Southeast University, China
Not yet recruiting
COVID-19 Convalescent Plasma Therapy - Conditions: SARS-CoV-2 Infection; COVID-19 Infection
Intervention: Biological: Convalescent plasma
Sponsors: Angelica Samudio; Consejo Nacional de Ciencias y Tecnología, Paraguay; Ministerio de Salud Pública y Bienestar Social, Paraguay; Centro de información y recursos para el desarrollo, Paraguay
Completed
Oxidative Stress Parameters, Trace Element and Quality of Life in Women Before and After Covid-19 Vaccines - Condition: Covid-19 Vaccine
Intervention: Biological: CoronoVac Vaccine
Sponsors: Izmir Bakircay University; Cigli Regional Training Hospital; Muğla Sıtkı Koçman University
Not yet recruiting
Effectiveness of Ivermectin in SARS-CoV-2/COVID-19 Patients - Condition: Covid19
Intervention: Drug: Ivermectin
Sponsor: FMH College of Medicine and Dentistry
Completed
COVID Antithrombotic Rivaroxaban Evaluation - Condition: COVID-19
Intervention: Drug: Rivaroxaban 10 mg
Sponsors: Hospital Alemão Oswaldo Cruz; Bayer; Hospital Israelita Albert Einstein; Hospital do Coracao; Hospital Sirio-Libanes; Hospital Moinhos de Vento; Brazilian Research In Intensive Care Network; Brazilian Clinical Research Institute
Recruiting
AGILE (Early Phase Platform Trial for COVID-19) - Condition: Covid19
Interventions: Drug: CST-2: EIDD-2801; Drug: CST-2: Placebo
Sponsors: University of Liverpool; University of Southampton; Liverpool School of Tropical Medicine; Lancaster University; Liverpool University Hospitals NHS Foundation Trust
Recruiting
A Study to Evaluate the Efficacy and Safety of Prothione™ Capsules for Mild to Moderate Coronavirus Disease 2019 (COVID-19) - Condition: Coronavirus Disease 2019 (COVID-19)
Interventions: Drug: Placebo; Drug: Prothione™ (6g)
Sponsor: Prothione, LLC
Not yet recruiting
Pulmonary Rehabilitation of Patients With a History of COVID-19 - Condition: Covid19
Intervention: Procedure: Pulmonary rehabilitation
Sponsor: University of Rzeszow
Enrolling by invitation
Ivermectin Role in Covid-19 Clinical Trial - Condition: Covid19
Interventions: Drug: ivermectin; Drug: hydroxychloroquine; Drug: Placebo
Sponsors: Elaraby Hospital; Shebin-Elkom Teaching Hospital
Completed
Safety, Tolerability and Efficacy Of S-1226 in Moderate Severity Covid-19 Bronchiolitis/Pneumonia - Conditions: Covid19; SARS-CoV-2 Infection
Intervention: Drug: S-1226
Sponsor: SolAeroMed Inc.
Not yet recruiting
Community Network-driven COVID-19 Testing of Vulnerable Populations in the Central US - Condition: Covid19
Intervention: Other: Social Network Strategy + COVID-19 messaging
Sponsor: University of Chicago
Not yet recruiting
Photosynthetically Controlled Spirulina, but Not Solar Spirulina, Inhibits TNF-alpha Secretion: Potential Implications for COVID-19-Related Cytokine Storm Therapy - An array of infections, including the novel coronavirus (SARS-CoV-2), trigger macrophage activation syndrome (MAS) and subsequently hypercytokinemia, commonly referred to as a cytokine storm (CS). It is postulated that CS is mainly responsible for critical COVID-19 cases, including acute respiratory distress syndrome (ARDS). Recognizing the therapeutic potential of Spirulina blue-green algae (Arthrospira platensis), in this in vitro stimulation study, LPS-activated macrophages and monocytes were…
Artificially expanded genetic information systems (AEGISs) as potent inhibitors of the RNA-dependent RNA polymerase of the SARS-CoV-2 - The recent outbreak of the SARS-CoV-2 infection has affected the lives and economy of more than 200 countries. The unavailability of virus-specific drugs has created an opportunity to identify potential therapeutic agents that can control the rapid transmission of this pandemic. Here, the mechanisms of the inhibition of the RNA-dependent RNA polymerase (RdRp), responsible for the replication of the virus in host cells, are examined by different ligands, such as Remdesivir (RDV), Remdesivir…
Role of the SphK-S1P-S1PRs pathway in invasion of the nervous system by SARS-CoV-2 Infection - Global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still ongoing. Before an effective vaccine is available, the development of potential treatments for resultant coronavirus disease 2019 (COVID-19) is crucial. One of disease hallmarks is hyper-inflammatory responses, which usually leads to a severe lung disease. Patients with COVID-19 also frequently suffered from neurological symptoms such as acute diffuse encephalomyelitis, brain injury and psychiatric…
The basis of a more contagious 501Y.V1 variant of SARS-COV-2 - Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) is causing a world-wide pandemic. A variant of SARS-COV-2 (20I/501Y.V1) recently discovered in the United Kingdom has a single mutation from N501 to Y501 within the receptor binding domain (Y501-RBD), of the Spike protein of the virus. This variant is much more contagious than the original version (N501-RBD). We found that this mutated version of RBD binds to human Angiotensin Converting Enzyme 2 (ACE2) a ~10 times more tightly…
Identification of the SHREK family of proteins as broad-spectrum host antiviral factors - Mucins and mucin-like molecules are highly glycosylated, high-molecular-weight cell surface proteins that possess a semi-rigid and highly extended extracellular domain. P-selectin glycoprotein ligand-1 (PSGL-1), a mucin-like glycoprotein, has recently been found to restrict HIV-1 infectivity through virion incorporation that sterically hinders virus particle attachment to target cells. Here, we report the identification of a family of antiviral cellular proteins, named the Surface-Hinged,…
Targeting CTP Synthetase 1 to Restore Interferon Induction and Impede Nucleotide Synthesis in SARS-CoV-2 Infection - The newly emerged SARS-CoV-2 caused a global pandemic with astonishing mortality and morbidity. The mechanisms underpinning its highly infectious nature remain poorly understood. We report here that SARS-CoV-2 exploits cellular CTP synthetase 1 (CTPS1) to promote CTP synthesis and suppress interferon (IFN) induction. Screening a SARS-CoV-2 expression library identified ORF7b and ORF8 that suppressed IFN induction via inducing the deamidation of interferon regulatory factor 3 (IRF3). Deamidated…
Discovery of re-purposed drugs that slow SARS-CoV-2 replication in human cells - BACKGROUND: The SARS-CoV-2 virus has caused the death of over 2 million people worldwide during the COVID-19 pandemic. Whilst effective vaccines have been developed and vaccination schedules are being rolled out, the identification of safe and inexpensive drugs to slow the replication of SARS-CoV-2 could help thousands of people worldwide whilst awaiting vaccination.
Structural modeling and analysis of the SARS-CoV-2 cell entry inhibitor camostat bound to the trypsin-like protease TMPRSS2 - The type II transmembrane serine protease TMPRSS2 facilitates the entry of coronaviruses, such as SARS-CoV-2, into host cells by cleaving the S(1)/S(2) interface of the viral spike protein. Based on structural data derived from X-ray crystallographic data of related trypsin-like proteases, a homology model of TMPRSS2 is described and validated using the broad spectrum COVID-19 drug candidate camostat as a probe. Both active site recognition and catalytic function are examined using quantum…
Tipiracil binds to uridine site and inhibits Nsp15 endoribonuclease NendoU from SARS-CoV-2 - SARS-CoV-2 Nsp15 is a uridine-specific endoribonuclease with C-terminal catalytic domain belonging to the EndoU family that is highly conserved in coronaviruses. As endoribonuclease activity seems to be responsible for the interference with the innate immune response, Nsp15 emerges as an attractive target for therapeutic intervention. Here we report the first structures with bound nucleotides and show how the enzyme specifically recognizes uridine moiety. In addition to a uridine site we present…
The polybasic cleavage site in the SARS-CoV-2 spike modulates viral sensitivity to Type I interferon and IFITM2 - The cellular entry of severe acute respiratory syndrome-associated coronaviruses types 1 and 2 (SARS-CoV-1 and -2) requires sequential protease processing of the viral spike glycoprotein. The presence of a polybasic cleavage site in SARS-CoV-2 spike at the S1/S2 boundary has been suggested to be a factor in the increased transmissibility of SARS-CoV-2 compared to SARS-CoV-1 by facilitating maturation of the spike precursor by furin-like proteases in the producer cells rather than endosomal…
Nucleoside Inhibitors of Coronaviruses - Coronaviruses (CoVs) belong to a large family of zoonotic supercapsid viruses, including about 40 species of RNA-containing viruses with several strains capable of causing damage to the lungs and respiratory tract. The severe acute respiratory syndrome coronavirus (SARS-CoV) was responsible for the worldwide SARS outbreak in 2003. The rapid global spread of SARS-CoV-2 has been the cause of significant health concern and thousands of deaths in 2019-2020 and outlined the need for novel antivirals….
Tryptophan Metabolites and Aryl Hydrocarbon Receptor in Severe Acute Respiratory Syndrome, Coronavirus-2 (SARS-CoV-2) Pathophysiology - The metabolism of tryptophan is intimately associated with the differential regulation of diverse physiological processes, including in the regulation of responses to severe acute respiratory syndrome, coronavirus-2 (SARS-CoV-2) infection that underpins the COVID-19 pandemic. Two important products of tryptophan metabolism, viz kynurenine and interleukin (IL)4-inducible1 (IL41)-driven indole 3 pyruvate (I3P), activate the aryl hydrocarbon receptor (AhR), thereby altering the nature of immune…
SARS-CoV-2 infection is effectively treated and prevented by EIDD-2801 - All known recently emerged human coronaviruses probably originated in bats¹. Here we used a single experimental platform based on human lung-only mice (LoM) to demonstrate efficient in vivo replication of all recently emerged human coronaviruses (SARS-CoV, MERS-CoV and SARS-CoV-2) and two highly relevant endogenous pre-pandemic SARS-like bat coronaviruses. Virus replication in this model occurs in bona fide human lung tissue and does not require any type of adaptation of the virus or the host….
Carrageenan containing over-the-counter nasal and oral sprays inhibit SARS-CoV-2 infection of airway epithelial cultures - Pharmaceutical interventions are urgently needed to prevent SARS-CoV-2 infection and transmission. As SARS-CoV-2 infects and spreads via the nasopharyngeal airways, we analyzed the antiviral effect of selected nasal and oral sprays on virus infection in vitro. Two nose sprays showed virucidal activity but were cytotoxic precluding further analysis in cell culture. One nasal and one mouth spray suppressed SARS-CoV-2 infection of TMPRSS2-Vero E6 cells and primary differentiated human airway…
Aptamer Blocking Strategy Inhibits SARS-CoV-2 Virus Infection - The COVID-19 pandemic caused by SARS-CoV-2 is threating global health. Inhibiting interaction of the receptor-binding domain of SARS-CoV-2 S protein (S RBD) and human ACE2 receptor is a promising treatment strategy. However, SARS-CoV-2 neutralizing antibodies are compromised by their risk of antibody-dependent enhancement (ADE) and unfavorably large size for intranasal delivery. To avoid the limitations of neutralizing antibodies, we proposed and demonstrated an aptamer blocking strategy by…
Compositions and methods for detecting SARS-CoV-2 spike protein - - link
新冠病毒疫苗表达抗原蛋白的电化学发光免疫检测试剂盒 - 本发明提供一种新冠病毒疫苗表达抗原蛋白的电化学发光免疫检测试剂盒，所述试剂盒至少包含：包被有链霉亲和素的孔板、生物素标记的抗新冠棘突蛋白抗体1、SULFO标记的抗新冠棘突蛋白抗体2、洗涤液、读数液、新冠病毒S蛋白标准品和新冠病毒RBD蛋白标准品。本发明以生物素标记的抗新冠棘突蛋白的抗体1与链霉亲和素板进行连接作为固定相，以新冠S蛋白、RBD蛋白作为参照品，可被SULFO标记的抗体2识别，从而检测新冠抗原的表达情况。该试剂盒能准确灵敏地定量检测不同基质中的新冠S蛋白、RBD蛋白，样品的前处理过程简单，耗时少，可同时检测大量样品。本发明对于大批量样品的新冠病毒疫苗表达抗原的检测具有重要意义。 - link
陶瓷复合涂料、杀毒陶瓷复合涂料及其制备方法和涂层 - 本发明是关于一种陶瓷复合涂料、杀毒陶瓷复合涂料及其制备方法和涂层。该涂料包括3099.9%无机树脂、0.170%氮化硅、010%功能助剂、018%无机颜料和02%其他功能助剂；无机树脂由有机烷氧基硅烷、有机溶剂和硅溶胶混合、反应，抽醇，添加去离子水获得；有机烷氧基硅烷、有机溶剂和硅溶胶的质量比为11.6：0.5~0.8：1。所要解决的技术问题是如何制备一种贮存稳定性好、可常温固化且膜层的物理化学性能优异的涂料；该涂料VOC含量低，具有良好的安全生产性，且涂料成膜过程中的VOC排放很低，利于环保；该膜层的硬度高、柔韧性好，不易开裂，且可以接触性杀灭病毒和细菌；该涂料既可常温固化，也可加热固化，无需现场两个剂型调配，施工方便，成本节约，从而更加适于实用。 - link
SARS-CoV-2 antibodies - - link
SARS-CoV-2 antibodies - - link
病毒核酸提取或保存试剂、引物探针组合、病毒扩增试剂、试剂盒及其应用 - 本发明涉及病毒检测领域，特别涉及病毒核酸提取或保存试剂、引物探针组合、病毒扩增试剂、试剂盒及其应用。本发明病毒检测装置提供了一种简单易行的病毒核酸提取方法，整个过程大约5‑15分钟，回收纯化的核酸，可用于病毒核酸的检测。包括PCR、NASBA、LAMP、RPA等。相比较于传统的病毒提取方法，本方法病毒核酸回收率高、用时少、操作方便、易于临床推广。本发明涉及单管同时检测新型冠状病毒COVID‑19 N和ORF基因以及人源内参基因的等温扩增引物、探针组合序列和反应缓冲液，该体系特异性好，灵敏度高（50 cp/mL），特异性高，只需20 min的检测时间，最快可在10 min左右报阳性。 - link
一种侧链修饰的聚氨基酸及其制备方法和用途 - 本发明提供了一种侧链修饰的聚氨基酸及其制备方法，所述侧链修饰的聚氨基酸具有如下优势：（1）主链和侧链结构及其连接方式都可以灵活选取，使制得的聚合物胶束具有良好生物相容性和靶向递送效率，（2）聚氨基酸主链的电荷极性为电正性，对主链的电荷调节促进胶束的pH值响应，帮助RNA从“溶酶体陷阱”中逃离进入胞浆，（3）通过量化侧链修饰脂肪链的链长、饱和度和脂肪链数量来控制侧链的疏水性部分，精确调节疏水部分的体积和缔合作用强度，（4）由于RNA和DNA在结构和负电性上的相似性，高效构建包裹和递送体，（5）通过双亲性功能高分子的侧链修饰引入不同的生物功能基团，实现递送体系对靶点组织和部位的特异性结合，提高靶向递送效果。 - link
靶向SARS-CoV-2冠状病毒的抗体及其诊断和检测用途 - 本发明涉及靶向SARS‑CoV‑2冠状病毒的抗体及其诊断和检测用途。具体涉及特异性结合冠状病毒S蛋白的抗体或其抗原结合片段和抗体对以及包含所述抗体或其抗原结合片段和抗体对的检测产品。本发明还涉及编码所述抗体或抗原结合片段的核酸及包含其的宿主细胞，以及制备所述抗体或抗原结合片段的方法。此外，本发明涉及所述抗体或其抗原结合片段、抗体对的预防、治疗或诊断用途。相较于常规的IgG/IgM检测，该检测方法直接检测样本中病毒的RBD蛋白，可以有效避免可能的样本中无关IgG/IgM对于检测的干扰，有效提高检测的灵敏度。所述抗体或抗体对可用于诊断和/或检测冠状病毒。 - link
A PHARMACEUTICAL COMPOSITION OF NITAZOXANIDE AND MEFLOQUINE AND METHOD THEREOF - A pharmaceutical composition for treating Covid-19 virus comprising a therapeutically effective amount of a nitazoxanide or its pharmaceutically acceptable salts thereof and an mefloquine or its pharmaceutically acceptable salts thereof is disclosed. The pharmaceutical composition comprises the nitazoxanide in the ratio of 0.05% to 66% w/v and the mefloquine in the ratio of 0.05% to 90% w/v. The composition is found to be effective for the treatment of COVID -19 (SARS-CoV2). The pharmaceutical composition of nitazoxanide and mefloquine has been found to be effective and is unexpectedly well tolerated with a low rate of side-effects, and equally high cure-rates than in comparable treatments. - link
TREATMENT OF COVID-19 WITH REBAMIPIDE - - link