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194 lines
51 KiB
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<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
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<title>20 February, 2021</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Age-related heterogeneity in Neutralising antibody responses to SARS-CoV-2 following BNT162b2 vaccination</strong> -
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Background Vaccines remain the cornerstone for containing the SARS-CoV-2 pandemic. mRNA vaccines provide protection in clinical trials using a two-dose approach, separated by a three to four week gap. UK policy in 2021 is to extend the dosing interval from three to twelve weeks. There is a paucity of data in the elderly, even though these individuals are the first to receive vaccines due to risk of severe disease. Here we assessed real world immune responses following vaccination with mRNA-based vaccine BNT162b2. Methods: We did a prospective cohort study of individuals presenting for first dose vaccination. Following the first and second doses of the BNT162b2 vaccine, we measured IFNgamma; T cell responses, as well as binding antibody (IgA, IgG and IgG1-4) responses to Spike and Spike RBD. We also measured neutralising antibody responses to Spike in sera using a lentiviral pseudotyping system. We correlated age with immune responses and compared responses after the first and second doses. Findings Median age was 63.5 years amongst 42 participants. Three weeks after the first dose a lower proportion of participants over 80 years old achieved adequate neutralisation titre of >1:20 for 50% neutralisation as compared to those under 80 (8/17 versus 19/24, p=0.03). Geometric mean neutralisation titres in this age group after the first dose were lower than in younger individuals (p<0.001). Binding IgA and IgG1 and 3 responses developed post vaccination, as observed in natural infection. T- cell responses were not different in those above or below 80 years. Following the second dose, 50% neutralising antibody titres were above 1:20 in all individuals and there was no longer a difference by age grouping. Interpretation A high proportion of individuals above the age of 80 have suboptimal neutralising antibody responses following first dose vaccination with BNT162b2, cautioning against extending the dosing interval in this high risk population.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.02.03.21251054v3" target="_blank">Age-related heterogeneity in Neutralising antibody responses to SARS-CoV-2 following BNT162b2 vaccination</a>
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</div></li>
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<li><strong>Combined Metabolic Activators accelerates recovery in mild-to-moderate COVID-19</strong> -
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There is a need to treat COVID-19 patients suffering from respiratory problems, resulting in decreased oxygen levels and thus leading to mitochondrial dysfunction and metabolic abnormalities. Here, we investigated if a high oral dose of a mixture of Combined Metabolic Activators (CMA) can restore metabolic function and thus aid the recovery of COVID-19 patients. We conducted a placebo-controlled, open-label phase 2 study and a double-blinded phase 3 clinical trials to investigate the time of symptom-free recovery on ambulatory patients using a mixture of CMA consisting of NAD+ and glutathione precursors. The results of both studies showed that the time to complete recovery was significantly shorter in the CMA group (6.6 vs 9.3 days) in phase 2 and (5.7 vs 9.2 days) in phase 3 trials. A comprehensive analysis of the blood metabolome and proteome showed that the plasma levels of proteins and metabolites associated with inflammation and antioxidant metabolism are significantly improved in patients treated with the metabolic activators as compared to placebo. The results show that treating patients infected with COVID-19 with a high dose of CMAs leads to a more rapid symptom-free recovery, suggesting a role for such a therapeutic regime in the treatment of infections leading to respiratory problems.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.10.02.20202614v2" target="_blank">Combined Metabolic Activators accelerates recovery in mild-to-moderate COVID-19</a>
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<li><strong>Coroless, effective ingredient isolated from traditional Chinese medicine for the prevention and treatment of Covid-19</strong> -
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<div>
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We believe that a good medicine for the prevention and treatment of Covid-19 requires three points: 1. Effectively inhibit the cells from being infected by Covid-19; 2. Quickly repair lung damage; 3. Non-toxic and harmless. Fortunately, from the treasure depot of Chinese traditional medicine, we found Kyllinga brevifolia Rottb, which is sufficient for three points and can be used for prevention, treatment and rehabilitation. Not only that, we have isolated the active ingredient of the Kyllinga brevifolia Rottb, named it Coroless, and verified that Coroless inhibits the Covid-19 from infecting cells through in vitro cell experiments.
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🖺 Full Text HTML: <a href="https://osf.io/6myat/" target="_blank">Coroless, effective ingredient isolated from traditional Chinese medicine for the prevention and treatment of Covid-19</a>
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<li><strong>Adequate knowledge of COVID-19 impacts good practices amongst health profession students in the Philippines</strong> -
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Background: The spread of the coronavirus disease 2019 (COVID-19) in the Philippines started with its first suspected case on January 22, 2020. The government reacted by imposing several measures including community quarantine, class suspensions, drug therapy and vaccine development, and travel restrictions. This online survey was done amongst Filipino health professions undergraduate students to uncover the relationship between their knowledge, attitude, and practice during this pandemic. Methods: Cross-sectional data were obtained from an online survey done on students of medicine, dentistry, optometry, rehabilitative sciences, and pharmacy. Results: At a response rate of 100% (n=1257), the results show that healthcare profession students in the Philippines have good knowledge (87.6%) and practices (63.6%) regarding COVID-19, yet attitude (63.6%) was just passable. This study also shows that a strong correlation exists between knowledge and practice concerning the current pandemic, r(2) = 0.08, P = 0.004. Conclusion: Adequate knowledge of COVID-19 impacts good practices of avoiding crowded places and misuse of steam inhalation amongst health profession students in the Philippines. Knowledge and practice pertaining to the current pandemic have been found to be good, but attitude remains low.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.02.18.431919v1" target="_blank">Adequate knowledge of COVID-19 impacts good practices amongst health profession students in the Philippines</a>
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</div></li>
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<li><strong>SARS-CoV-2 variant evolution in the United States: High accumulation of viral mutations over time likely through serial Founder Events and mutational bursts.</strong> -
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Since the first case of COVID-19 in December 2019 in Wuhan, China, SARS-CoV-2 has spread worldwide and within a year has caused 2.29 million deaths globally. With dramatically increasing infection numbers, and the arrival of new variants with increased infectivity, tracking the evolution of its genome is crucial for effectively controlling the pandemic and informing vaccine platform development. Our study explores evolution of SARS-CoV-2 in a representative cohort of sequences covering the entire genome in the United States, through all of 2020 and early 2021. Strikingly, we detected many accumulating Single Nucleotide Variations (SNVs) encoding amino acid changes in the SARS-CoV-2 genome, with a pattern indicative of RNA editing enzymes as major mutators of SARS-CoV-2 genomes. We report three major variants through October of 2020. These revealed 14 key mutations that were found in various combinations among 14 distinct predominant signatures. These signatures likely represent evolutionary lineages of SARS-CoV-2 in the U.S. and reveal clues to its evolution such as a mutational burst in the summer of 2020 likely leading to a homegrown new variant, and a trend towards higher mutational load among viral isolates, but with occasional mutation loss. The last quartile of 2020 revealed a concerning accumulation of mostly novel low frequency replacement mutations in the Spike protein, and a hypermutable glutamine residue near the putative furin cleavage site. Finally, the end of the year data revealed the presence of known variants of concern including B.1.1.7, which has acquired additional Spike mutations. Overall, our results suggest that predominant viral sequences are dynamically evolving over time, with periods of mutational bursts and unabated mutation accumulation. This high level of existing variation, even at low frequencies and especially in the Spike-encoding region may be become problematic when superspreader events, akin to serial Founder Events in evolution, drive these rare mutations to prominence.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.02.19.431311v1" target="_blank">SARS-CoV-2 variant evolution in the United States: High accumulation of viral mutations over time likely through serial Founder Events and mutational bursts.</a>
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<li><strong>Probing the SAM Binding Site of SARS-CoV-2 nsp14 in vitro Using SAM Competitive Inhibitors Guides Developing Selective bi-substrate Inhibitors</strong> -
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<div>
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The COVID-19 pandemic has clearly brought the healthcare systems world-wide to a breaking point along with devastating socioeconomic consequences. The SARS-CoV-2 virus which causes the disease uses RNA capping to evade the human immune system. Non-structural protein (nsp) 14 is one of the 16 nsps in SARS-CoV-2 and catalyzes the methylation of the viral RNA at N7-guanosine in the cap formation process. To discover small molecule inhibitors of nsp14 methyltransferase (MT) activity, we developed and employed a radiometric MT assay to screen a library of 161 in house synthesized S-adenosylmethionine (SAM) competitive methyltransferase inhibitors and SAM analogs. Among seven identified screening hits, SS148 inhibited nsp14 MT activity with an IC50 value of 70 {+/-} 6 nM and was selective against 20 human protein lysine methyltransferases indicating significant differences in SAM binding sites. Interestingly, DS0464 with IC50 value of 1.1 {+/-} 0.2 M showed a bi-substrate competitive inhibitor mechanism of action. Modeling the binding of this compound to nsp14 suggests that the terminal phenyl group extends into the RNA binding site. DS0464 was also selective against 28 out of 33 RNA, DNA, and protein methyltransferases. The structure-activity relationship provided by these compounds should guide the optimization of selective bi-substrate nsp14 inhibitors and may provide a path towards a novel class of antivirals against COVID-19, and possibly other coronaviruses.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.02.19.424337v1" target="_blank">Probing the SAM Binding Site of SARS-CoV-2 nsp14 in vitro Using SAM Competitive Inhibitors Guides Developing Selective bi-substrate Inhibitors</a>
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<li><strong>Viral genetic sequencing identifies staff transmission of COVID-19 is important in a community hospital outbreak</strong> -
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Background Whole-genome sequencing has been used successfully to provide additional information for transmission pathways in infectious spread. We report and interpret genomic sequencing results in clinical context from a large outbreak of COVID-19 with 46 cases across staff and patients in a community hospital in the UK. Methods Following multiple symptomatic cases within a two-week period, all staff and patients were screened by RT-PCR and staff subsequently had serology tests. Findings Thirty staff (25%) and 16 patients (62%) tested positive for COVID-19. Genomic sequencing data showed significant overlap of viral haplotypes in staff who had overlapping shift patterns. Patient haplotypes were more distinct from each other but had overlap with staff haplotypes. Interpretation This study includes clinical and genomic epidemiological detail that demonstrates the value of a combined approach. Viral genetic sequencing has identified that staff transmission of COVID-19 was important in this community hospital outbreak.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.02.18.21250737v1" target="_blank">Viral genetic sequencing identifies staff transmission of COVID-19 is important in a community hospital outbreak</a>
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<li><strong>Antiviral activity of influenza A virus defective interfering particles against SARS-CoV-2 replication in vitro through stimulation of innate immunity</strong> -
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SARS-CoV-2 causing COVID-19 emerged in late 2019 and resulted in a devastating pandemic. Although the first approved vaccines were already administered by the end of 2020, vaccine availability is still limited. Moreover, immune escape variants of the virus are emerging against which the current vaccines may confer only limited protection. Further, existing antivirals and treatment options against COVID-19 only show limited efficacy. Influenza A virus (IAV) defective interfering particles (DIPs) were previously proposed not only for antiviral treatment of the influenza disease but also for pan-specific treatment of interferon (IFN)-sensitive respiratory virus infections. To investigate the applicability of IAV DIPs as an antiviral for the treatment of COVID-19, we conducted in vitro co-infection experiments with produced, cell culture-derived DIPs and the IFN-sensitive SARS-CoV-2. We show that treatment with IAV DIPs leads to complete abrogation of SARS-CoV-2 replication. Moreover, this inhibitory effect was dependent on janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling. These results suggest an unspecific stimulation of the innate immunity by IAV DIPs as a major contributor in suppressing SARS-CoV-2 replication. Thus, we propose IAV DIPs as an effective antiviral agent for treatment of COVID-19, and potentially also for suppressing the replication of new variants of SARS-CoV-2.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.02.19.431972v1" target="_blank">Antiviral activity of influenza A virus defective interfering particles against SARS-CoV-2 replication in vitro through stimulation of innate immunity</a>
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<li><strong>Resveratrol-Zinc Combination for COVID-19 Management: Could it be the Holy Grail?</strong> -
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In this manuscript we provide the scientific basis to adopt a novel combination of resveratrol and zinc in management of COVID-19. Resveratrol, a well-known antioxidant and anti-inflammatory triphenolic stilbene, is abundant in red grapes, red wine, dark chocolate, and peanut butter. Furthermore, we recommend performing of clinical trials to assess the potential of this combination as a monotherapy for mild COVID-19 with a potential to prevent its progression to moderate-severe disease for which we also recommend its trial as an adjuvant therapy.
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🖺 Full Text HTML: <a href="https://osf.io/2ngqj/" target="_blank">Resveratrol-Zinc Combination for COVID-19 Management: Could it be the Holy Grail?</a>
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<li><strong>Predicting the zoonotic capacity of mammal species for SARS-CoV-2</strong> -
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Spillback transmission from humans to animals, and secondary spillover from animal hosts back into humans, have now been documented for SARS-CoV-2. In addition to threatening animal health, virus variants arising from novel animal hosts have the potential to undermine global COVID-19 mitigation efforts. Numerous studies have therefore investigated the zoonotic capacity of various animal species for SARS-CoV-2, including predicting both species’ susceptibility to infection and their capacities for onward transmission. A major bottleneck to these studies is the limited number of sequences for ACE2, a key cellular receptor in chordates that is required for viral cell entry. Here, we combined protein structure modeling with machine learning of species’ traits to predict zoonotic capacity of SARS-CoV-2 across 5,400 mammals. High accuracy model predictions were strongly corroborated by in vivo empirical studies, and identify numerous mammal species across global COVID-19 hotspots that should be prioritized for surveillance and experimental validation.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.02.18.431844v1" target="_blank">Predicting the zoonotic capacity of mammal species for SARS-CoV-2</a>
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<li><strong>Decreased neutralization of SARS-CoV-2 global variants by therapeutic anti-spike protein monoclonal antibodies</strong> -
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Monoclonal antibodies against the SARS-CoV-2 spike protein, notably, those developed by Regeneron Pharmaceuticals and Eli Lilly and Company have proven to provide protection against severe COVID-19. The emergence of SARS-CoV-2 variants with heavily mutated spike proteins raises the concern that the therapy could become less effective if any of the mutations disrupt epitopes engaged by the antibodies. In this study, we tested monoclonal antibodies REGN10933 and REGN10987 that are used in combination, for their ability to neutralize SARS-CoV-2 variants B.1.1.7, B.1.351, mink cluster 5 and COH.20G/677H. We report that REGN10987 maintains most of its neutralization activity against viruses with B.1.1.7, B.1.351 and mink cluster 5 spike proteins but that REGN10933 has lost activity against B.1.351 and mink cluster 5. The failure of REGN10933 to neutralize B.1.351 is caused by the K417N and E484K mutations in the receptor binding domain; the failure to neutralize the mink cluster 5 spike protein is caused by the Y453F mutation. The REGN10933 and REGN10987 combination was 9.1-fold less potent on B.1.351 and 16.2-fold less potent on mink cluster 5, raising concerns of reduced efficacy in the treatment of patients infected with variant viruses. The results suggest that there is a need to develop additional monoclonal antibodies that are not affected by the current spike protein mutations.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.02.18.431897v1" target="_blank">Decreased neutralization of SARS-CoV-2 global variants by therapeutic anti-spike protein monoclonal antibodies</a>
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<li><strong>ESC - a comprehensive resource for SARS-CoV-2 immune escape variants</strong> -
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Ever since the breakout of COVID-19 disease, ceaseless genomic research to inspect the epidemiology and evolution of the pathogen has been undertaken globally. Large scale viral genome sequencing and analysis have uncovered the functional impact of numerous genetic variants in disease pathogenesis and transmission. Emerging evidence of mutations in spike protein domains escaping antibody neutralization is reported. We have a precise collation of manually curated variants in SARS-CoV-2 from literature with potential escape mechanisms from a range of neutralizing antibodies. This comprehensive repository encompasses a total of 532 variants accounting for 146 unique variants tested against 75 antibodies and patient convalescent plasma. This resource enables the user to gain access to an extensive annotation of SARS-CoV-2 escape mutations which we hope would contribute to exploring and understanding the underlying mechanisms of immune response against the pathogen. The resource is available at http://clingen.igib.res.in/esc/. Keywords : COVID-19, SARS-CoV-2, Neutralizing antibodies, Escape mutations, Genomes
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.02.18.431922v1" target="_blank">ESC - a comprehensive resource for SARS-CoV-2 immune escape variants</a>
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<li><strong>The epidemiological characteristics of the primary health care based COVID-19 swabbed persons in Qatar, March- October 2020</strong> -
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Background: In March 2020, Qatar started reporting increased numbers of COVID-19 positive cases. National preventive measures were put in place and testing plan has been developed to respond to the pandemic with the primary health care as the main provider. The study aims to describe the epidemiological characteristics of COVID-19 at the primary health care level in Qatar and to examine the factors associated with the positivity rate. Method: Retrospective data analysis for all the cases screened for COVID-19 at the primary health care level in Qatar between the 11th of March and 31st of October 2020. The study analyzed the demographic characteristics of the tested persons and non-communicable disease burden, positivity rate by month, nationality, and age-group, factors associated with the positivity rate. Results: Between the 11th of March and the 31st of October 2020, 285,352 persons were tested for SARS-CoV-2, with a median age (IQR) of 32 (22-43) years. 59.9% were from the Middle East and North Africa region and 29.6% originally from Asia. Overall, among them, 11.2% had diabetes mellitus and 11.4% had hypertension. The epidemiological curve showed a steep increase in positivity rate from March till June 2020 at the highest rate of 21.4% in June 2020. The highest positivity rate was observed among Asian males at 20.3%. The positivity rates were almost the same among the tested persons for SARS-CoV-2 in the main three age-groups (0-18, 19-39, 40-59) at 13%, 14.5%, and 14.0%, respectively. In a multi regression model, being a male was associated with a higher risk (OR 1.16; 95% CI 1.13 to 1.18). Persons originally from Asia were at higher risk than those originally from the Middle East and North Africa (OR 1.5; 95% CI 147 to 1.54). COVID-19 infection was higher among those presenting with clinical symptoms than those asymptomatic (OR. 4.16; 95% CI 4.05 to 4.28). Conclusion: The epidemic predominantly affected younger ages and males namely coming from Asia. At the primary health care level, COVID-19 infection rate was higher among those who presented with clinical symptoms. The scale-up of the testing at the primary health care level helped in detecting more cases and was reflected in a steady increase in the positivity rate to be flattened afterward.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.02.17.21251722v1" target="_blank">The epidemiological characteristics of the primary health care based COVID-19 swabbed persons in Qatar, March- October 2020</a>
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<li><strong>The unexpected dynamics of COVID-19 in Manaus, Brazil: Herd immunity versus interventions</strong> -
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The arrival of SARS-COV-2 in late March 2020 in the state of Amazonas, Brazil, captured worldwide attention and concern. The rapid growth of the epidemic, a health system that had collapsed, and mass gravesites for coping with growing numbers of dead, were broadcast by the media around the world. Moreover, a majority of the local Amazonian indigenous communities were physically distant from appropriate medical services, to the point where warnings of genocide were issued. In a recent Science paper (December 2020), Buss et al. reported that some 76% of the residents of the city of Manaus, the capital of Amazonas, had been infected by October 2020. This estimate of the COVID-19 attack rate was based on a seroprevalence analysis of blood donor data, which despite its shortcomings was thought to be a sufficiently reliable proxy of the larger population. An attack rate of this magnitude (76%) implied that herd immunity had already been reached and the community was relatively protected from further infection. Yet in December 2020, a harsh second wave of COVID-19 struck Manaus, and currently appears to be even larger than the first wave. Here we use mathematical modelling of mortality data in Manaus, and in various states of Brazil, to understand why a second wave appeared against all expectations. Our analysis is based on estimating a “flexible” reproductive number R_0 (t) from the mortality data, as it changes in time over the epidemic.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.02.18.21251809v1" target="_blank">The unexpected dynamics of COVID-19 in Manaus, Brazil: Herd immunity versus interventions</a>
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<li><strong>Early pandemic molecular diversity of SARS-CoV-2 in children</strong> -
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Background In the US, community circulation of the SARS-CoV-2 virus likely began in February 2020 after mostly travel-related cases. Children9s Hospital of Philadelphia began testing on 3/9/2020 for pediatric and adult patients, and for all admitted patients on 4/1/2020, allowing an early glimpse into the local molecular epidemiology of the virus. Methods We obtained 169 SARS-CoV-2 samples (83 from patients <21 years old) from March through May and produced whole genome sequences. We used genotyping tools to track variants over time and to test for possible genotype associated clinical presentations and outcomes in children. Results Our analysis uncovered 13 major lineages that changed in relative abundance as cases peaked in mid-April in Philadelphia. We detected at least 6 introductions of distinct viral variants into the population. As a group, children had more diverse virus genotypes than the adults tested. No strong differences in clinical variables were associated with genotypes. Conclusions Whole genome analysis revealed unexpected diversity, and distinct circulating viral variants within the initial peak of cases in Philadelphia. Most introductions appeared to be local from nearby states. Although limited by sample size, we found no evidence that different genotypes had different clinical impacts in children in this study.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.02.17.21251960v1" target="_blank">Early pandemic molecular diversity of SARS-CoV-2 in children</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An Effectiveness Study of the Sinovac’s Adsorbed COVID-19 (Inactivated) Vaccine</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Biological: Adsorbed COVID-19 (Inactivated) Vaccine<br/><b>Sponsor</b>: Butantan Institute<br/><b>Enrolling by invitation</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Telerehabilitation in Covid-19 After Hospital Discharge</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Other: Standard Physiotherapy program; Other: Telerehabilitation<br/><b>Sponsor</b>: Universidad de Granada<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study of the Kinetics of COVID-19 Antibodies for 24 Months in Patients With Confirmed SARS-CoV-2 Infection</strong> - <b>Conditions</b>: Covid19; SARS-CoV 2<br/><b>Intervention</b>: Other: Sampling by venipuncture<br/><b>Sponsor</b>: Centre Hospitalier Régional d’Orléans<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effect of Prone Position onV/Q Matching in Non-intubated Patients With COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Other: prone position<br/><b>Sponsor</b>: Southeast University, China<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 Convalescent Plasma Therapy</strong> - <b>Conditions</b>: SARS-CoV-2 Infection; COVID-19 Infection<br/><b>Intervention</b>: Biological: Convalescent plasma<br/><b>Sponsors</b>: 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<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Oxidative Stress Parameters, Trace Element and Quality of Life in Women Before and After Covid-19 Vaccines</strong> - <b>Condition</b>: Covid-19 Vaccine<br/><b>Intervention</b>: Biological: CoronoVac Vaccine<br/><b>Sponsors</b>: Izmir Bakircay University; Cigli Regional Training Hospital; Muğla Sıtkı Koçman University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID Antithrombotic Rivaroxaban Evaluation</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Rivaroxaban 10 mg<br/><b>Sponsors</b>: 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<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>AGILE (Early Phase Platform Trial for COVID-19)</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: CST-2: EIDD-2801; Drug: CST-2: Placebo<br/><b>Sponsors</b>: University of Liverpool; University of Southampton; Liverpool School of Tropical Medicine; Lancaster University; Liverpool University Hospitals NHS Foundation Trust<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety and Immunogenicity Study in Adults of AZD1222 and rAd26-S Administered as Heterologous Prime Boost Regimen for the Prevention of Coronavirus Disease 2019 (COVID-19)</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Biological: AZD1222; Biological: rAd26-S<br/><b>Sponsors</b>: R-Pharm; AstraZeneca<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Efficacy and Safety of Prothione™ Capsules for Mild to Moderate Coronavirus Disease 2019 (COVID-19)</strong> - <b>Condition</b>: Coronavirus Disease 2019 (COVID-19)<br/><b>Interventions</b>: Drug: Placebo; Drug: Prothione™ (6g)<br/><b>Sponsor</b>: Prothione, LLC<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Pulmonary Rehabilitation of Patients With a History of COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Procedure: Pulmonary rehabilitation<br/><b>Sponsor</b>: University of Rzeszow<br/><b>Enrolling by invitation</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ivermectin Role in Covid-19 Clinical Trial</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: ivermectin; Drug: hydroxychloroquine; Drug: Placebo<br/><b>Sponsors</b>: Elaraby Hospital; Shebin El-Kom Teaching Hospital<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Community Network-driven COVID-19 Testing of Vulnerable Populations in the Central US</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Other: Social Network Strategy + COVID-19 messaging<br/><b>Sponsor</b>: University of Chicago<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Enriched Heparin Anti COVID-19 Trial</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Heparin sodium; Drug: Placebo<br/><b>Sponsor</b>: UPECLIN HC FM Botucatu Unesp<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy and Safety of Tofacitinib in Patients With COVID-19 Pneumonia</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Tofacitinib<br/><b>Sponsor</b>: I.M. Sechenov First Moscow State Medical University<br/><b>Completed</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Development of a large volume concentration method for recovery of coronavirus from wastewater</strong> - Levels of severe acute respiratory coronavirus type 2 (SARS CoV 2) RNA in wastewater could act as an effective means to monitor coronavirus disease 2019 (COVID-19) within communities. However, current methods used to detect SARS CoV 2 RNA in wastewater are limited in their ability to process sufficient volumes of source material, inhibiting our ability to assess viral load. Typically, viruses are concentrated from large liquid volumes using two stage concentration, primary and secondary. Here,…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Re(I) Tricarbonyl Complexes as Coordinate Covalent Inhibitors for the SARS-CoV-2 Main Cysteine Protease</strong> - Since its outbreak, the severe acute respiratory syndrome - coronavirus 2 (SARS-CoV-2) has impacted the quality of life and cost hundreds-of-thousands of lives worldwide. Based on its global spread and mortality, there is an urgent need for novel treatments which can combat this disease. To date, the 3-chymotrypsin-like protease (3CLpro), which is also known as the main protease, is considered among the most important pharmacological targets. The vast majority of investigated 3CLpro inhibitors…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Simultaneous Inhibition of SARS-CoV-2 Entry Pathways by Cyclosporine</strong> - The COVID-19 pandemic caused by SARS-CoV-2 represents a global public health emergency. The entry of SARS-CoV-2 into host cells requires the activation of its spike protein by host cell proteases. The serine protease, TMPRSS2, and cysteine proteases, Cathepsins B/L, activate spike protein and enable SARS-CoV-2 entry to the host cell through two completely different and independent pathways. Therefore, inhibiting either TMPRSS2 or cathepsin B/L may not sufficiently block the virus entry. We here…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Advances of Inorganic Materials in the Detection and Therapeutic Uses Against Coronaviruses</strong> - Coronaviruses (CoVs) are enveloped viruses with particle-like characteristics and a diameter of 60-140 nm, positively charged, and single-stranded RNA genomes which produce a major outbreak of human fatal pneumonia since the beginning of the 21st century. COVID-19 is currently considered as a continuous potential pandemic threat across the globe. Therefore, considerable efforts have been made to develop innovative methods and technologies for suppressing the spread of viruses as well as…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 M(pro) inhibitors with antiviral activity in a transgenic mouse model</strong> - The COVID-19 pandemic caused by the SARS-CoV-2 virus continually poses serious threats to global public health. The main protease (M^(pro)) of SARS-CoV-2 plays a central role in viral replication. We designed and synthesized 32 new bicycloproline-containing M^(pro) inhibitors derived from either Boceprevir or Telaprevir, both of which are approved antivirals. All compounds inhibited SARS-CoV-2 M^(pro) activity in vitro with IC(50) values ranging from 7.6 to 748.5 nM. The co-crystal structure of…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>3D culture models to study SARS-CoV-2 infectivity and antiviral candidates: From spheroids to bioprinting</strong> - The pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is receiving worldwide attention, due to the severity of the disease (COVID-19) that resulted in more than a million global deaths so far. The urgent need for vaccines and antiviral drugs is mobilizing the scientific community to develop strategies for studying the mechanisms of SARS-CoV-2 infection, replication kinetics, pathogenesis, host-virus interaction, and infection inhibition. In this work, we review the…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phyto-compounds from a rather poisonous plant, Strychnos nux-vomica, show high potency against SARS-CoV-2 RNA-dependent RNA polymerase</strong> - CONCLUSION: Sharing the same binding location as that of ATP and having high binding affinities, Ergotamine, Isosungucine, Sungucine and Strychnine N-oxide could be effective in controlling the SARS-CoV-2 virus replication by blocking the ATP and inhibiting the enzyme function.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The COVID-Kidney Controversy: Can SARS-CoV-2 Cause Direct Renal Infection?</strong> - Determining whether SARS-CoV-2 causes direct infection of the kidneys is challenging due to limitations in imaging and molecular tools. Subject of Review: A growing number of conflicting kidney biopsy and autopsy reports highlight this controversial issue. Second Opinion: Based on the collective evidence, therapies that improve hemodynamic stability and oxygenation, or dampen complement activation, are likely to ameliorate acute kidney injury in COVID-19. At this time, whether inhibition of…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Angiotensin-converting enzyme 2, coronavirus disease 2019 and abdominal aortic aneurysms</strong> - CONCLUSION: COVID-19 may theoretically influence AAA disease through multiple SARS-CoV-2-induced mechanisms. Further investigation and clinical follow-up will be necessary to determine whether and to what extent the COVID-19 pandemic will influence the prevalence, progression and lethality of AAA disease in the coming decade.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Development and Validation of Viral Load Assays to Quantitate SARS-CoV-2</strong> - SARS-CoV-2 has infected more than 30 million persons throughout the world. A subset of patients suffer serious consequences that require hospitalization and ventilator support. Current tests for SARS-CoV-2 generate qualitative results and are vital to make a diagnosis of the infection. However, they are not helpful to follow changes in viral loads after diagnosis. The ability to quantitatively assess viral levels is necessary to determine the effectiveness of therapy with anti-viral or immune…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ivermectin shows clinical benefits in mild to moderate COVID19: A randomised controlled double-blind, dose-response study in Lagos</strong> - CONCLUSIONS: 12 mg IV regime may have superior efficacy. IV should be considered for use in clinical management of SARS-Cov-2, and may find applications in community prophylaxis in high-risk areas.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Biomaterials-based formulations and surfaces to combat viral infectious diseases</strong> - Rapidly growing viral infections are potent risks to public health worldwide. Accessible virus-specific antiviral vaccines and drugs are therapeutically inert to emerging viruses, such as Zika, Ebola, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, discovering ways to prevent and control viral infections is among the foremost medical challenge of our time. Recently, innovative technologies are emerging that involve the development of new biomaterial-based…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Bepridil is potent against SARS-CoV-2 in vitro</strong> - Guided by a computational docking analysis, about 30 Food and Drug Administration/European Medicines Agency (FDA/EMA)-approved small-molecule medicines were characterized on their inhibition of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (M^(p) ^(ro)). Of these small molecules tested, six displayed a concentration that inhibits response by 50% (IC(50)) value below 100 μM in inhibiting M^(p) ^(ro), and, importantly, three, that is, pimozide, ebastine, and…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Potent, Novel SARS-CoV-2 PLpro Inhibitors Block Viral Replication in Monkey and Human Cell Cultures</strong> - Antiviral agents blocking SARS-CoV-2 viral replication are desperately needed to complement vaccination to end the COVID-19 pandemic. Viral replication and assembly are entirely dependent on two viral cysteine proteases: 3C-like protease (3CLpro) and the papain-like protease (PLpro). PLpro also has deubiquitinase (DUB) activity, removing ubiquitin (Ub) and Ub-like modifications from host proteins, disrupting the host immune response. 3CLpro is inhibited by many known cysteine protease…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Are vanadium complexes druggable against the main protease m(pro) of sars-cov-2? - a computational approach</strong> - In silico techniques helped explore the binding capacities of the SARS-CoV-2 main protease (M^(pro)) for a series of metalloorganic compounds. Along with small size vanadium complexes a vanadium-containing derivative of the peptide-like inhibitor N3 (N-[(5-methylisoxazol-3-yl)carbonyl]alanyl-l-valyl-N1-((1R,2Z)-4-(benzyloxy)-4-oxo-1-{[(3R)-2-oxopyrrolidin-3-yl] methyl }but-2-enyl)-l-leucinamide) was designed from the crystal structure with PDB entry code 6LU7. On theoretical grounds our…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-COV-2 BINDING PROTEINS</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU318004130">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Compositions and methods for detecting SARS-CoV-2 spike protein</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU317343760">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SELF-CLEANING AND GERM-KILLING REVOLVING PUBLIC TOILET FOR COVID 19</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU318003558">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Deep Learning Based System for the Detection of COVID-19 Infections</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU318003547">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>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</strong> - 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。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN317672956">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>陶瓷复合涂料、杀毒陶瓷复合涂料及其制备方法和涂层</strong> - 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30<sub>99.9%无机树脂、0.1</sub>70%氮化硅、0<sub>10%功能助剂、0</sub>18%无机颜料和0<sub>2%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1</sub>1.6：0.5~0.8：1。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。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN317672744">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 antibodies</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU315792577">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>利用BLI技术检测新型冠状病毒中和性抗体的方法</strong> - 本发明提供一种利用BLI技术检测新型冠状病毒中和性抗体的方法，先将同一浓度的人ACE2蛋白捕获到生物传感器表面上，再将新型冠状病毒棘突蛋白RBD分别与不同浓度的待测中和性抗体预混，再将各混合液分别与捕获到生物传感器表面上的人ACE2蛋白接触，根据基于BLI技术的分子互作仪器检测到的干涉光谱的相对位移强度变化计算抑制率，绘制抑制曲线，计算IC50。本发明操作简单，快速高效，检测全过程无需包被和反复加样、洗板，15min内即可得到实验结果。检测反应在黑色孔板中进行，可实现大批量样品的新冠中和抗体的检测，与传统定性检测不同，通过计算IC50值，可以快速比较不同新冠中和性抗体的抑制能力。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN317346970">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 antibodies</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU315792579">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>能够抑制冠状病毒Spike蛋白与ACE2相互作用的化合物的用途</strong> - 本发明公开了能够抑制冠状病毒Spike蛋白与ACE2相互作用的化合物的用途。结构如下，该类化合物在制备治疗和/或预防SARS‑CoV‑2新型冠状病毒感染的药物中的用途。同时，化合物不仅能够抑制冠状病毒Spike蛋白与ACE2蛋白的相互作用，IC50<1μM，同时能够促使Spike‑ACE2复合物的解离。在细胞水平上可以有效的抑制新型冠状病毒SARS‑CoV‑2假病毒入侵，IC50<2μM。所述化合物能特异性的结合在Spike蛋白的RBD区域，KD<6μM，表明该类化合物对于制备治疗和/或预防冠状病毒感染药物具有非常积极的作用。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN317346989">link</a></p></li>
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