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226 lines
64 KiB
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<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
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<title>07 December, 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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<ul>
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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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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Fluorescence signatures of SARS CoV-2 spike S1 proteins and an human ACE-2: excitation-emission maps and fluorescence lifetimes</strong> -
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<div>
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Significance: Fast and reliable detection of infectious SARS-CoV-2 virus loads is an important issue. Fluorescence spectroscopy is a sensitive tool to do so in clean environments. This presumes a comprehensive knowledge of fluorescence data. Aim: This work aims at providing fully featured information on wavelength and time-dependent data of the fluorescence of the SARS-CoV-2 spike protein S1 subunit, its receptor binding domain (RBD) and the human angiotensinconverting enzyme 2 (hACE2), specially with respect to possible optical detection schemes. Approach: Spectrally resolved excitation-emission maps of the involved proteins and measurements of fluorescence lifetimes were recorded for excitations from 220 to 295 nm. The fluorescence decay times were extracted by using a bi-exponential kinetic approach. The binding process in the SARS-CoV-2 RBD was likewise examined for spectroscopic changes. Results: Distinct spectral features for each protein are pointed out in relevant spectra extracted from the excitation emission maps. We also identify minor spectroscopic changes under the binding process. The decay times in the bi-exponential model are found to be <span class="math inline">(2.0 ± 0.1)</span> ns and <span class="math inline">(8.0 ± 1.0)</span> ns. Conclusions: Specific material data serve as important background information for the design of optical detection and testing methods for SARS-CoV-2 loaded media.
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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/10.1101/2021.05.20.444935v2" target="_blank">Fluorescence signatures of SARS CoV-2 spike S1 proteins and an human ACE-2: excitation-emission maps and fluorescence lifetimes</a>
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</div></li>
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<li><strong>COV-Drug Target interaction server for Covid-19 Drug Repurposing</strong> -
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The outbreak of the novel coronavirus disease COVID-19, caused by the SARS-CoV-2 virus has killed over 5 million people to date. So, there is an urgent requirement for new and effective medications that can treat the disease caused by SARS-CoV-2. To find new drugs, identification of drug targets is necessary (Chen et al., 2016). Number of research studies have identified therapeutic targets such as helicases, transmembrane serine protease 2, cathepsin L, cyclin G-associated kinase, adaptor associated kinase 1, two-pore channel, viral virulence factors, 3-chymotrypsin-like protease, suppression of excessive inflammatory response, inhibition of viral membrane, nucleocapsid, envelope, and accessory proteins, and inhibition of endocytosis. Here we present a web enabled tool which helps in ranking the COVID-19 drugs based upon underlying molecular targets. The users are allowed to give drugs in SMILE format and the tools will provide the list of relevant targets related to COVID-19.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/gejwq/" target="_blank">COV-Drug Target interaction server for Covid-19 Drug Repurposing</a>
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</div></li>
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<li><strong>Predictions of the SARS-CoV-2 Omicron Variant (B.1.1.529) Spike Protein Receptor-Binding Domain Structure and Neutralizing Antibody Interactions</strong> -
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The genome of the SARS-CoV-2 Omicron variant (B.1.1.529) was released on November 22, 2021, which has caused a flurry of media attention due the large number of mutations it contains. These raw data have spurred questions around vaccine efficacy. Given that neither the structural information nor the experimentally-derived antibody interaction of this variant are available, we have turned to predictive computational methods to model the mutated structure of the spike protein’s receptor binding domain and posit potential changes to vaccine efficacy. In this study, we predict some structural changes in the receptor-binding domain that may reduce antibody interaction, but no drastic changes that would completely evade existing neutralizing antibodies (and therefore current vaccines).
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.12.03.471024v1" target="_blank">Predictions of the SARS-CoV-2 Omicron Variant (B.1.1.529) Spike Protein Receptor-Binding Domain Structure and Neutralizing Antibody Interactions</a>
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<li><strong>Interactions of SARS-CoV-2 protein E with cell junctions and polarity PDZ-containing proteins</strong> -
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The C-terminus of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protein E contains a PBM (PDZ binding motif) targeting PDZ (PSD-95/Dlg/ZO-1) domains identical to the PBM of SARS-CoV. The latter is involved in the pathogenicity of the virus. Recently, we identified ten human PDZ-containing proteins showing significant interactions with SARS-CoV-2 protein E PBM. We selected several of them involved in cellular junctions and cell polarity (TJP1, PARD3, MLLT4, LNX2) and MPP5/Pals1 previously shown to interact with SARS-CoV E PBM. Targeting cellular junctions and polarity components is a common strategy by viruses to hijack cell machinery to their advantage. In this study, we showed that these host PDZ domains TJP1, PARD3, MLLT4, LNX2 and MPP5/PALS1 interact in a PBM-dependent manner in vitro and colocalize with the full-length E protein in cellulo, sequestrating the PDZ domains to the Golgi compartment. We solved three crystal structures of complexes between human LNX2, MLLT4 and MPP5 PDZs and SARS-CoV-2 E PBM highlighting its binding preferences for several cellular targets. Finally, we showed different affinities for the PDZ domains with the original SARS-CoV-2 C-terminal sequence containing the PBM and the one of the beta variant that contains a mutation close to the PBM. The acquired mutations in E protein localized near the PBM might have important effects both on the structure and the ion-channel activity of the E protein and on the host machinery targeted by the variants during the infection.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.12.04.471219v1" target="_blank">Interactions of SARS-CoV-2 protein E with cell junctions and polarity PDZ-containing proteins</a>
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</div></li>
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<li><strong>Critical Negatively Charged Residues Are Important for the Activity of SARS-CoV-1 and SARS-CoV-2 Fusion Peptides</strong> -
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<div>
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Coronaviruses are a major infectious disease threat, and include the human pathogens of zoonotic origin SARS-CoV (“SARS-1”), SARS-CoV-2 (“SARS-2”) and MERS-CoV (“MERS”). Entry of coronaviruses into host cells is mediated by the viral spike (S) protein. Previously, we identified that the domain immediately downstream of the S2’ cleavage site is the bona fide FP (amino acids 798-835) for SARS-1 using ESR spectroscopy technology. We also found that the SARS-1 FP induces membrane ordering in a Ca2+ dependent fashion. In this study, we want to know which residues are involved in this Ca2+ binding, to build a topological model and to understand the role of the Ca2+. We performed a systematic mutation study on the negatively charged residues on the SARS-1 FP. While all six negatively charged residues contributes to the membrane ordering activity of the FP to some extent, D812 is the most important residue. We provided a topological model of how the FP binds Ca2+ ions: both FP1 and FP2 bind one Ca2+ ion, and there are two binding sites in FP1 and three in FP2. We also found that the corresponding residue D830 in the SARS-2 FP plays a similar critical role. ITC experiments show that the binding energies between the FP and Ca2+ as well as between the FP and membranes also decreases for all mutants. The binding of Ca2+, the folding of FP and the ordering activity correlated very well across the mutants, suggesting that the function of the Ca2+ is to help to folding of FP in membranes to enhance its activity. Using a novel pseudotyped virus particle (PP)-liposome methodology, we monitored the membrane ordering induced by the FPs in the whole S proteins in its trimer form in real time. We found that the SARS-1 and SARS-2 PPs also induce membrane ordering as the separate FPs do, and the mutations of the negatively charged residues also greatly reduce the membrane ordering activity. However, the difference in kinetic between the PP and FP indicates a possible role of FP trimerization. This finding could lead to therapeutic solutions that either target the FP-calcium interaction or block the Ca2+ channel to combat the ongoing COVID-19 pandemic.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.11.03.467161v1" target="_blank">Critical Negatively Charged Residues Are Important for the Activity of SARS-CoV-1 and SARS-CoV-2 Fusion Peptides</a>
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<li><strong>Estimation of heterogeneous instantaneous reproduction numbers with application to characterize SARS-CoV-2 transmission in Massachusetts counties</strong> -
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The reproductive number is an important metric that has been widely used to quantify the infectiousness of communicable diseases. The time-varying instantaneous reproductive number is useful for monitoring the real time dynamics of a disease to inform policy making for disease control. Local estimation of this metric, for instance at a county or city level, allows for more targeted interventions to curb transmission. However, simultaneous estimation of local reproductive numbers must account for potential sources of heterogeneity in these time-varying quantities – a key element of which is human mobility. We develop a statistical method that incorporates human mobility between multiple regions for estimating region-specific instantaneous reproductive numbers. The model also can account for exogenous cases imported from outside of the regions of interest. We propose two approaches to estimate the reproductive numbers, with mobility data used to adjust incidence in the first approach and to inform a formal priori distribution in the second (Bayesian) approach. Through a simulation study, we show that region-specific reproductive numbers can be well estimated if human mobility is reasonably well approximated by available data. We use this approach to estimate the instantaneous reproductive numbers of COVID-19 for 14 counties in Massachusetts using CDC case report data and the human mobility data collected by SafeGraph. We found that, accounting for mobility, our method produces estimates of reproductive numbers that are distinct across counties. In contrast, independent estimation of county-level reproductive numbers tends to produce similar values, as trends in county case-counts for the state are fairly concordant. These approaches can also be used to estimate any heterogeneity in transmission, for instance, age-dependent instantaneous reproductive number estimates. As people are more mobile and interact frequently in ways that permit transmission, it is important to account for this in the estimation of the reproductive number.
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</p>
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<div class="article-link article- html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.12.02.21267164v2" target="_blank">Estimation of heterogeneous instantaneous reproduction numbers with application to characterize SARS- CoV-2 transmission in Massachusetts counties</a>
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<li><strong>Healthcare worker risk of COVID-19: A 20-month analysis of protective measures from vaccination and beyond</strong> -
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Background: As the COVID-19 pandemic continues and new variants such as Omicron emerge, we aimed to re-evaluate vaccine effectiveness as well as impacts of rigorously implemented infection control, public health and occupational health measures in protecting healthcare workers (HCWs). Methods: Following a cohort of 21,242 HCWs in Vancouver, British Columbia, Canada, for 20 months since the pandemic started, we used Cox regression and test-negative design to examine differences in SARS-COV-2 infection rates compared to community counterparts, and within the HCW workforce, assessing the role of occupation, testing accessibility, vaccination rates, and vaccine effectiveness over time. Results: Nurses, allied health professionals and medical staff in this jurisdiction had a significantly lower rate of infection compared to their age-group community counterparts, at 47.4, 41.8, and 55.3% reduction respectively; controlling for vaccine-attributable reductions, the protective impact was still substantial, at 33.4, 28.0, and 36.5% respectively. Licensed practical nurses and care aides had the highest risk of infection among HCWs, more than double that of medical staff. However, even considering differences in vaccination rates, no increase in SARS-CoV-2 infection was found compared to community rates, with combined protective measures beyond vaccination associated with a 17.7% reduced SARS-COV-2 rate in the VCH workforce overall. There was also no evidence of waning immunity within at least 200 days after second dose. Conclusion: Rigorously implemented occupational health, public health and infection control measures results in a well-protected healthcare workforce with infection rates at or below rates in community counterparts. Greater accessibility of vaccination worldwide is essential; however, as implementing measures to protect this workforce globally also requires considerable health system strengthening in many jurisdictions, we caution against overly focusing on vaccination to the exclusion of other crucial elements for wider protection of HCWs, especially in facing ongoing mutations which may escape current vaccines.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.12.02.21267190v2" target="_blank">Healthcare worker risk of COVID-19: A 20-month analysis of protective measures from vaccination and beyond</a>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Pulmonary thromboembolism in COVID-19 Patients on CT Pulmonary Angiography - A Single-Centre Retrospective Cohort Study in the United Arab Emirates</strong> -
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Purpose. Our aim is to identify the prevalence and distribution of pulmonary thromboembolism in COVID-19 infected patients in our hospital. Materials and Methods. Data of all patients with COVID-19 infection either on RT-PCR testing or non-contrast high resolution CT(HRCT) who had CT pulmonary angiography (CTPA) from April to June 2020 were included. 133 patients were initially included in the study, 7 were excluded according to exclusion criteria, leaving a total number of 126 patients. Results. Twenty (15.8%) patients had evidence of pulmonary embolism (PE) on CTPA with mean age of 50 years (range 31-85) of which 95% were males. The mean D-dimer was 5.61mcg/mL among the PE-negative and 14.49 mcg/mL in the PE-positive groups respectively. Among the patients with evidence of pulmonary embolism on CTP, almost half required admission to intensive care unit in comparison to only one-fifth with negative CTPA. One-fourth died among the PE positive group with only 5% died among the PE negative group. There was a 33% reduction in the development of PE in the COVID-19 patients who had received low molecular weight heparin (LMWH) prior to their CTPA study versus those who had not. Conclusion. D-dimer correlates well with the incidence of pulmonary embolism among COVID-19 patients. Our data suggest that majority of our patients, developed pulmonary embolisms within 5 days into their hospital stay, accounting to almost two thirds of all positive cases diagnosed by CTPA. Those with PE among COVID-19 patients have high chances of ICU admission and mortality. Use of thromboprophylaxis early on might reduce the incidence of PE.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.11.14.21266214v3" target="_blank">Pulmonary thromboembolism in COVID-19 Patients on CT Pulmonary Angiography - A Single-Centre Retrospective Cohort Study in the United Arab Emirates</a>
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<li><strong>Functional and microstructural brain abnormalities, fatigue, and cognitive dysfunction after mild COVID-19</strong> -
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Although post-acute cognitive dysfunction and neuroimaging abnormalities have been reported after hospital discharge in patients recovered from COVID-19, little is known about persistent, long-term alterations in patients who did not require hospitalization. Therefore, we conducted a cross-sectional study of 87 consecutive, non-hospitalized recovered individuals, with a median of 54 days after the laboratory confirmation of COVID-19. We performed structured interviews, neurological examination, and 3T-MRI scans. The MRI study included white matter investigation with diffusion tensor images (DTI) and seed-based resting-state functional MRI (fMRI) connectivity analyses of the default mode network (DMN). In addition, we used validated instruments to examine fatigue, symptoms of anxiety and depression, somnolence, language, memory, and cognitive flexibility. Individuals self-reported a high frequency of headaches (40%) and memory difficulties (33%). The quantitative analyses confirmed symptoms of fatigue (68% of participants), excessive somnolence (35%), symptoms of anxiety (29%), impaired cognitive flexibility (40%) and language dysfunction (33%). In addition, we observed a correlation between DTI fractional anisotropy (FA) and abnormal attention and cognitive flexibility measured by the Trail Making Test part B. The resting-state fMRI study of the DMN showed an association between higher connectivity of the posterior cingulate cortex (PCC) and higher levels of fatigue and somnolence. While greater connectivity of the PCC with bilateral angular gyri was associated with higher fatigue levels, the elevated levels of somnolence correlated with higher connectivity between the PCC and both the left thalamus and putamen.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.03.20.21253414v2" target="_blank">Functional and microstructural brain abnormalities, fatigue, and cognitive dysfunction after mild COVID-19</a>
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<li><strong>‘Trained immunity’ from Mycobacterium spp. (environmental or BCG) exposure predicts protection from Coronavirus disease 2019 (COVID-19)</strong> -
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Endeavors to identify potentially protective variables for COVID-19 impact on certain populations have remained a priority. Multiple attempts have been made to attribute the reduced COVID-19 impact on populations to their bacillus Calmette-Guerin (BCG) vaccination coverage ignoring the fact that the effect of childhood BCG vaccination wanes within 5 years while most of the COVID-19 cases and deaths have occurred in aged with comorbidities. Since the supposed protection being investigated could come from heterologous ′trained immunity′ (TI) conferred by exposure to <i>Mycobacterium</i> spp. (<i>i.e.</i>, environmental and BCG), it is argued that the estimates of the prevalence of TI of populations currently available as latent tuberculosis infection (LTBI) prevalence would be a better variable to evaluate such assertions. Indeed, when we analyze the European populations (twenty-four), and erstwhile East and West Germany populations completely disregarding their BCG vaccination coverage, the populations with higher TI prevalence consistently display reduced COVID-19 impact as compared to their lower TI prevalence neighbors. The TI estimates of the populations not the BCG coverage per se, negatively correlated with pandemic phase-matched COVID-19 incidences (<i>r</i>(24): -0.79 to -0.57; p-value: <0.004), mortality (<i>r</i>(24): -0.63 to -0.45; p-value: <0.03), and interim case fatality rates(i-CFR) data. To decisively arrive at dependable conclusions about the potential protective benefit gained from BCG vaccination in COVID-19, the ongoing/planned randomized controlled trials should consciously consider including measures of TI as - a) all individuals immunized do not respond equally, b) small study groups from higher background TI could fail to indicate any protective effect.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.02.11.20233593v2" target="_blank">‘Trained immunity’ from Mycobacterium spp. (environmental or BCG) exposure predicts protection from Coronavirus disease 2019 (COVID-19)</a>
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<li><strong>Bringing testing closer to you. Barriers and Facilitators in Implementing HIV Self-Testing among Filipino Men Having Sex with Men and Transgender Women in National Capital Region (NCR), Philippines: A Qualitative Study</strong> -
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Objectives: Our study identified barriers and facilitators in implementing HIV Self-Testing (HIVST), including the perceptions of men-having-sex-with-men (MSM) and transgender women on HIVST. Furthermore, we explored the current knowledge, practices, and potential of HIVST among the MSM and TGW populations. Design: Key Informant Interviews (KIIs) were administered using semi-structured interviews administered in both English and Filipin. Thematic analysis of the findings was done after transcribing all audio recordings. Setting: The study was done in the National Capital Region (NCR), Philippines using online video conferencing platforms due to mobility restrictions caused by the COVID-19 pandemic. Participants: All study participants were either MSM or TGW, 18 to 49 years old, and residing/working in NCR. Exclusion criteria include biologically born female and/or currently on pre-exposure prophylaxis (PrEP), antiretroviral therapy (ART) medications, or an HIV-positive diagnosis. Results: Twenty informants were interviewed, of which 75% were MSM, and most of them preferred the use of HIVST. Facilitators and barriers to the use of HIVST were grouped into three main themes: Acceptability, distribution, and monitoring and tracking. Convenience and confidentiality, overcoming fears, and normalization of HIV testing services (HTS) in the country were why the participants preferred HIVST. Social media was recognized as a powerful tool in promoting HIVST. The use of a welcoming tone and positive language should be taken into consideration due to the prevalent HIV stigma. Informants also highlighted that confidentiality must be maintained throughout the whole HIVST process. Conclusions: The identified facilitators and barriers from the study may be considered by the Philippine HTS program implementers. The HIVST strategy may complement the current HTS. It will be very promising to involve the MSM and TGW communities and other key populations to know their HIV status by bringing testing closer to them.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.09.25.21264098v2" target="_blank">Bringing testing closer to you. Barriers and Facilitators in Implementing HIV Self-Testing among Filipino Men Having Sex with Men and Transgender Women in National Capital Region (NCR), Philippines: A Qualitative Study</a>
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<li><strong>COVID-19 vaccination and menstrual cycle changes: A United Kingdom (UK) retrospective case-control study</strong> -
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<b>Background</b>. There has been increasing public concern that COVID-19 vaccines cause menstrual cycle disturbances, yet there is currently limited data to evaluate the impact of vaccination on menstrual health. Our objectives were (1) to evaluate the prevalence of menstrual changes following vaccination against COVID-19, (2) to test potential risk factors for any such changes, and (3) to identify patterns of symptoms in participants9 written accounts. <b>Methods</b>. We performed a secondary analysis of a retrospective online survey titled <i>The Covid-19 Pandemic and Women9s Reproductive Health</i>, conducted in March 2021 in the UK before widespread media attention regarding potential impacts of SARS-CoV-2 vaccination on menstruation. Participants were recruited via a Facebook ad campaign in the UK and eligibility criteria for survey completion were age greater than 18 years, having ever menstruated and currently living in the UK. In total, 26,710 people gave consent and completed the survey. For this analysis we selected 4,989 participants who were pre-menopausal and vaccinated. These participants were aged 28 to 43, predominantly from England (81%), of white background (95%) and not using hormonal contraception (58%). <b>Findings</b>. Among pre-menopausal vaccinated individuals (n=4,989), 80% did not report any menstrual cycle changes up to 4 months after their first COVID-19 vaccine injection. Current use of combined oral contraceptives was associated with lower odds of reporting any changes by 48% (OR = 0.52, 95CI = [0.34 to 0.78], P<0.001). Odds of reporting any menstrual changes were increased by 44% for current smokers (OR = 1.44, 95CI = [1.07 to 1.94], P<0.01) and by more than 50% for individuals with a positive COVID status [Long Covid (OR = 1.61, 95CI = [1.28 to 2.02], P<0.001), acute COVID (OR = 1.54, 95CI = [1.27 to 1.86], P<0.001)]. The effects remain after adjusting for self-reported magnitude of menstrual cycle changes over the year preceding the survey. Written accounts report diverse symptoms; the most common words include 9cramps9, 9late9, 9early9, 9spotting9, 9heavy9 and 9irregular9, with a low level of clustering among them. <b>Conclusions</b>. Following vaccination for COVID-19, menstrual disturbance occurred in 20% of individuals in a UK sample. Out of 33 variables investigated, smoking and a previous history of SARS-CoV-2 infection were found to be risk factors while using oestradiol-containing contraceptives was found to be a protective factor. Diverse experiences were reported, from menstrual bleeding cessation to heavy menstrual bleeding.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.11.23.21266709v3" target="_blank">COVID-19 vaccination and menstrual cycle changes: A United Kingdom (UK) retrospective case-control study</a>
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<li><strong>Inflammasome-related markers at the ICU admission are not associated with outcome in the critically ill COVID-19 patients.</strong> -
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Purpose: Development of targeted biological therapies for COVID-19 requires reliable biomarkers that could help indicate the responding patients. Hyperactivation of the inflammasome by SARS-CoV2 virus is hypothesized to contribute to severe course of the COVID-19 disease. Therefore, we aimed to evaluate the prognostic value of several inflammasome- related cytokines and proteins at the admission to the intensive care unit (ICU). Patients and methods: Plasma samples were obtained from 45 critically ill COVID-19 patients and from 10 patients any without any signs of infection (TBI, traumatic brain injury) on admission to the ICU. The concentration of IL-1𝛼, IL-1𝛽, IL-18, IL-1RA, galectin-1, ASC, LDH, ferritin, and gasdermin D were analyzed. A novel cell-free caspase-1 plasma assay was developed by inhibitor-based immunoprecipitation followed by Western Blot. Demographic and clinical characteristics were recorded. Results: In-hospital mortality in COVID-19 patients reached 62%. Galectin-1 was 1.8-fold lower in COVID-19 than in TBI patients (17101.84 vs. 30764.20 pg/ml, p=0.007), but other inflammasome-related biomarkers were at similar concentrations. Patients with SOFA score of >9 on admission who were at high risk of death had significantly higher galectin-1 but lower IL-1RA in comparison to low-risk patients (25551.3 pg/ml vs 16302.7 pg/ml, p=0.014; 14.5 pg/ml vs 39.4 pg/ml, p=0.04, respectively). Statistically significant correlations were observed between: IL-1𝛼 and platelets (r=-0.37), IL-1𝛽 and platelets (r=-0.36), ferritin and INR (r=0.39). Activated caspase-1 p35 was detectable in 12/22 COVID-19 patients but in none of the TBI patients. Its presence was related with higher fibrinogen and lower D-dimers. Moreover, the densitometric analysis showed a significantly higher amount of p35 in patients with SOFA> 9. Conclusion: Our results indicate that the systemic markers of activation of the inflammasome in critically ill COVID-19 patients is not directly related with outcome. Therefore, potential interventions aimed at the inflammasome pathway in this group of patients may be of limited effectiveness and should be biomarker-guided.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.10.30.21265662v2" target="_blank">Inflammasome-related markers at the ICU admission are not associated with outcome in the critically ill COVID-19 patients.</a>
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<li><strong>COVID-19 patient serum less potently inhibits ACE2-RBD binding for various SARS-CoV-2 RBD mutants</strong> -
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As global vaccination campaigns against SARS-CoV-2 proceed, there is particular interest in the longevity of immune protection, especially with regard to increasingly infectious virus variants. Neutralizing antibodies (Nabs) targeting the receptor binding domain (RBD) of SARS-CoV-2 are promising correlates of protective immunity and have been successfully used for prevention and therapy. As SARS-CoV-2 variants of concern (VOCs) are known to affect binding to the ACE2 receptor and by extension neutralizing activity, we developed a bead-based multiplex ACE2-RBD inhibition assay (RBDCoV-ACE2) as a highly scalable, time-, cost-, and material-saving alternative to infectious live-virus neutralization tests. By mimicking the interaction between ACE2 and the RBD, this serological multiplex assay allows the simultaneous analysis of ACE2 binding inhibition to the RBDs of all SARS-CoV-2 VOCs and variants of interest (VOIs) in a single well. Following validation against a classical virus neutralization test and comparison of performance against a commercially available assay, we analyzed 266 serum samples from 168 COVID-19 patients of varying severity. ACE2 binding inhibition was reduced for ten out of eleven variants examined compared to wild-type, especially for those displaying the E484K mutation such as VOCs beta and gamma. ACE2 binding inhibition, while highly individualistic, positively correlated with IgG levels. ACE2 binding inhibition also correlated with disease severity up to WHO grade 7, after which it reduced.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.08.20.21262328v2" target="_blank">COVID-19 patient serum less potently inhibits ACE2-RBD binding for various SARS-CoV-2 RBD mutants</a>
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<li><strong>COVID-19 infections post-vaccination by HIV status in the United States</strong> -
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Importance: Recommendations for additional doses of COVID vaccine are restricted to people with HIV who have advanced disease or unsuppressed HIV viral load. Understanding SARS-CoV-2 infection risk post-vaccination among PWH is essential for informing vaccination guidelines. Objective: Estimate the risk of breakthrough infections among fully vaccinated people with (PWH) and without (PWoH) HIV in the US. Design, setting, and participants: The Corona-Infectious- Virus Epidemiology Team (CIVET)-II cohort collaboration consists of 4 longitudinal cohorts from integrated health systems and academic health centers. Each cohort identified individuals ≥18 years old, in-care, and fully vaccinated for COVID-19 through 30 June 2021. PWH were matched to PWoH on date fully vaccinated, age group, race/ethnicity, and sex at birth. Incidence rates per 1,000 person-years and cumulative incidence of breakthrough infections with 95% confidence intervals ([,]) were estimated by HIV status. Cox proportional hazards models estimated adjusted hazard ratios (aHR) of breakthrough infections by HIV status adjusting for demographic factors, prior COVID-19 illness, vaccine type (BNT162b2, [Pfizer], mRNA-1273 [Moderna], Jansen Ad26.COV2.S [J&J]), calendar time, and cohort. Risk factors for breakthroughs among PWH, were also investigated. Exposure: HIV infection Outcome: COVID-19 breakthrough infections, defined as laboratory evidence of SARS-CoV-2 infection or COVID-19 diagnosis after an individual was fully vaccinated. Results: Among 109,599 individuals (31,840 PWH and 77,759 PWoH), the rate of breakthrough infections was higher in PWH versus PWoH: 44 [41, 48] vs. 31 [29, 33] per 1,000 person-years. Cumulative incidence at 210 days after date fully vaccinated was low, albeit higher in PWH versus PWoH overall (2.8% versus 2.1%, log-rank p<0.001, risk difference=0.7% [0.4%, 1.0%]) and within each vaccine type. Breakthrough infection risk was 41% higher in PWH versus PWoH (aHR=1.41 [1.28, 1.56]). Among PWH, younger age (18-24 versus 45-54), history of COVID-19 prior to fully vaccinated date, and J&J vaccination (versus Pfizer) were associated with increased risk of breakthroughs. There was no association of breakthrough with HIV viral load suppression or CD4 count. Conclusions and Relevance: COVID-19 vaccination is effective against infection with SARS-CoV-2 strains circulating through 30 Sept 2021. PWH have an increased risk of breakthrough infections compared to PWoH. Recommendations for additional vaccine doses should be expanded to all PWH.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.12.02.21267182v1" target="_blank">COVID-19 infections post- vaccination by HIV status in the United States</a>
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</div></li>
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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>Allogenic UCMSCs as Adjuvant Therapy for Severe COVID-19 Patients</strong> - <b>Condition</b>: Covid 19<br/><b>Interventions</b>: Biological: Normoxic Allogenic UCMSC; Other: Normal saline solution<br/><b>Sponsors</b>: Kementerian Riset dan Teknologi / Badan Riset dan Inovasi Nasional, Indonesia; Dr. Moewardi General Hospital, Surakarta, Indonesia; Dr. Sardjito General Hospital, Yogyakarta, Indonesia; Dr. Hasan Sadikin General Hospital, Bandung, Indonesia; PT Bifarma Adiluhung<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>Physical Fitness in Young Healthy Adults After COVID-19 Infection</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Other: Physical Activity Level; Other: Evaluation of knee extension and elbow flexion muscle strength; Other: Evaluation of functional strength of trunk muscles; Other: Muscle Endurance; Other: Flexibility; Other: Balance; Other: Fatigue<br/><b>Sponsor</b>: <br/>
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Baskent University<br/><b>Enrolling by invitation</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Using MOST to Optimize an Intervention to Increase COVID-19 Testing for Frontline Essential Workers</strong> - <b>Conditions</b>: COVID-19; COVID-19 Testing<br/><b>Interventions</b>: Behavioral: Motivational interviewing</li>
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</ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">counseling; Behavioral: Text messages (TMs) and quiz questions (QQs); Behavioral: Peer education; Behavioral: Access to COVID testing<br/><b>Sponsor</b>: New York University<br/><b>Not yet recruiting</b></li>
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</ol>
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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>GlowTest COVID-19 Antigen Home Test Kit QRI Use Study</strong> - <b>Condition</b>: Covid 19<br/><b>Intervention</b>: Diagnostic Test: GlowTest COVID-19 Antigen Home Test<br/><b>Sponsors</b>: Arion Bio; CSSi Life Sciences<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 of Different COVID-19 Vaccine Combinations in Inducing Long-term Humoral Immunity [PRIBIVAC]</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Homologous mRNA booster vaccine; Biological: Heterologous mRNA booster vaccine; Biological: Non-mRNA booster vaccine A; Biological: Non- mRNA booster vaccine B; Biological: Non-mRNA booster vaccine C<br/><b>Sponsors</b>: Tan Tock Seng Hospital; A*Star; Duke-NUS Graduate Medical School; KK Women’s and Children’s Hospital<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>Inhaled Recombinant Non-immunogenic Staphylokinase vs Placebo in Patients With COVID-19 - FORRIF Trial</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Recombinant nonimmunogenic staphylokinase; Drug: Placebo<br/><b>Sponsors</b>: Supergene, LLC; Russian Academy of Medical Sciences<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>Safety and Immunogenicity of COVID-19 Vaccine, Inactivated in Healthy Population Aged From 3 to 11 Years</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: COVID-19 Vaccine,Inactivated<br/><b>Sponsor</b>: Sinovac Biotech Co., Ltd<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>Nutritional Supplementation of Vitamin D, Quercetin and Curcumin With Standard of Care for Managing Mild Early Symptoms of COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Standard of care; Dietary Supplement: Investigational treatment<br/><b>Sponsor</b>: King Edward Medical University<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>Study of Immunogenicity Equivalence of a Homologous Third Dose of Covid-19 (Recombinante) Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: Covid -19 (recombinante) vaccine<br/><b>Sponsor</b>: The Immunobiological Technology Institute (Bio-Manguinhos) / Oswaldo Cruz Foundation (Fiocruz)<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>Study to Evaluate the Safety and Efficacy of a Monoclonal Antibody Cocktail for the Prevention of COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: ADM03820; Other: Placebo<br/><b>Sponsors</b>: <br/>
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Ology Bioservices; Enabling Biotechnologies (EB)<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>Usefulness of DORNASE in COVID-19 on HFNO</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Intervention</b>: Procedure: inhalations<br/><b>Sponsor</b>: <br/>
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University Medical Centre Ljubljana<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>The Immune Response of Heterologous Boost Third Dose of mRNA and Protein COVID-19 Vaccine: a Single-blind, and Randomized Study</strong> - <b>Conditions</b>: COVID-19; Breakthrough Infection<br/><b>Interventions</b>: Biological: BNT162b2; Biological: mRNA-1273; Biological: MCV COVID-19 vaccine<br/><b>Sponsors</b>: Chang Gung Memorial Hospital; Medigen Vaccine Biologics Corp.<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 VACCINE SAFETY AND EFFECTIVENESS</strong> - <b>Condition</b>: SARS-CoV-2 Infection<br/><b>Intervention</b>: Biological: ChAdOx1 nCoV-19 vaccine (AZD1222)<br/><b>Sponsors</b>: Federal University of Espirito Santo; Instituto René Rachou/Fiocruz<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>Phase Ⅱ and Ⅲ Trial of a SARS-CoV-2 Vaccine LYB001</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: LYB001; Biological: Placebo<br/><b>Sponsor</b>: Yantai Patronus Biotech Co., Ltd.<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>Safety and Immunogenicity of Recombinant Protein RBD Fusion Dimer Vaccine Against the Virus That Cause COVID-19, Known as Severe Acute Respiratoy Syndrome Coronavirus 2 (SARS-CoV-2)</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2 Acute Respiratory Disease<br/><b>Interventions</b>: <br/>
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Biological: COVID-19 Vaccine HIPRA; Biological: Cominarty (Pfizer-BioNtech)<br/><b>Sponsors</b>: <br/>
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Hipra Scientific, S.L.U; Laboratorios Hipra, S.A.; National Institute of Hygiene and Epidemiology, Vietnam<br/><b>Recruiting</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>Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients</strong> - Azvudine (FNC) is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase (RdRp). Recently, we discovered FNC an agent against SARS-CoV-2, and have taken it into Phase III trial for COVID-19 patients. FNC monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC(50) between 1.2 and 4.3 μM, depending on viruses or cells, and selective index (SI) in 15-83 range. Oral administration of FNC in rats revealed a substantial thymus-homing feature, with FNC triphosphate…</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>Pharmacologic profiling reveals lapatinib as a novel antiviral against SARS-CoV-2 in vitro</strong> - The emergence of SARS-CoV-2 virus has resulted in a worldwide pandemic, but effective antiviral therapies are not widely available. To improve treatment options, we conducted a high-throughput screen to uncover compounds that block SARS- CoV-2 infection. A minimally pathogenic human betacoronavirus (OC43) was used to infect physiologically-relevant human pulmonary fibroblasts (MRC5) to facilitate rapid antiviral discovery in a preclinical model. Comprehensive profiling was conducted on more than…</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>Genome-scale CRISPR screen identifies TMEM41B as a multi-function host factor required for coronavirus replication</strong> - Emerging coronaviruses (CoVs) pose a severe threat to human and animal health worldwide. To identify host factors required for CoV infection, we used α-CoV transmissible gastroenteritis virus (TGEV) as a model for genome-scale CRISPR knockout (KO) screening. Transmembrane protein 41B (TMEM41B) was found to be a bona fide host factor involved in infection by CoV and three additional virus families. We found that TMEM41B is critical for the internalization and early-stage replication of TGEV….</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>Insights into Fibrinogen-Mediated COVID-19 Hypercoagubility in Critically Ill Patients</strong> - Coronavirus disease-2019 (COVID-19) is associated with hypercoagulability that may cause thromobembolic complications. We describe our recent studies investigating the mechanisms of hypercoagulability in patients with severe COVID-19 requiring mechanical ventilation during the COVID-19 crisis in New York City in spring 2020. Using rotational thombelastometry we found that almost all patients with severe COVID-19 had signs of hypercoagulability compared with non-COVID-19 controls. Specifically,…</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>Metabolic reprograming shapes neutrophil functions in severe COVID-19</strong> - To better understand the mechanisms at the basis of neutrophil functions during SARS-CoV-2 we studied patients with severe COVID-19 pneumonia. They had high blood proportion of degranulated neutrophils and elevated plasma levels of myeloperoxidase (MPO), elastase and MPO-DNA complexes, which are typical markers of neutrophil extracellular traps (NET). Their neutrophils display dysfunctional mitochondria, defective oxidative burst, increased glycolysis, glycogen accumulation in the cytoplasm, 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>Teriflunomide: A possible effective drug for the comprehensive treatment of COVID-19</strong> - The coronavirus disease 2019 (COVID-19) pandemic has undoubtedly become a global crisis. Consequently, discovery and identification of new or known potential drug candidates to solve the health problems caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have become an urgent necessity. This current research study sheds light on the possible direct repurposing of the antirheumatic drug teriflunomide to act as an effective and potent anti-SARS- CoV-2 agent. Herein, an…</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>Can NLRP3 inhibitors improve on dexamethasone for the treatment of COVID-19?</strong> - Dexamethasone, a corticosteroid, has been approved for use in the treatment of severe COVID-19, which is characterised by hyperinflammation and associated lung damage. However, dexamethasone shows no clinical benefit in the treatment of less severe disease, and prolonged treatment may lead to immunosuppression and an increased risk of opportunistic infections. Hence there is a need for more specific anti-inflammatory therapies which also prevent severe disease. The NLRP3 inflammasome is an…</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>Artificial intelligence-driven drug repurposing and structural biology for SARS-CoV-2</strong> - It has been said that COVID-19 is a generational challenge in many ways. But, at the same time, it becomes a catalyst for collective action, innovation, and discovery. Realizing the full potential of artificial intelligence (AI) for structure determination of unknown proteins and drug discovery are some of these innovations. Potential applications of AI include predicting the structure of the infectious proteins, identifying drugs that may be effective in targeting these proteins, and proposing…</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>Structure-Based Epitope Design: Toward a Greater Antibody-SARS-CoV-2 RBD Affinity</strong> - Efficient COVID-19 vaccines are widely acknowledged as the best way to end the global pandemic. SARS-CoV-2 receptor- binding domain (RBD) plays fundamental roles related to cell infection. Antibodies could be developed to target RBD and represent a potential approach for the neutralization of the virus. Epitopes used to produce antibodies are generally linear peptides and thus possess multiple confirmations that do not reflect the actual topology of the targeted part in the native protein. On 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>COVID-19 and renin angiotensin aldosterone system: Pathogenesis and therapy</strong> - CONCLUSION: Regarding the suggested potential therapies for COVID-19, there are many clinical trials whose results might change the treatment strategies of SARS-CoV-2 infection. So, the results of well-organized clinical trials on the efficacy and safety of the mentioned agents in the treatment of COVID-19 will be useful in the management and therapy of the disease.</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>Detection of Antibodies Against the SARS-CoV-2 Spike Protein and Analysis of the Peripheral Blood Mononuclear Cell Transcriptomic Profile, 15 Years After Recovery From SARS</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shows a high degree of homology with SARS-CoV. They share genes, protein sequences, clinical manifestations, and cellular entry patterns. Thus, SARS research may serve helpful in gaining a better understanding of the current coronavirus disease 2019 (COVID-19) pandemic. Serum antibodies from convalescent patients with SARS collected in 2018 were used to target the recombinant SARS-CoV-2 spike protein via a chemiluminescence microsphere…</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, Pre-Eclampsia, and Complement System</strong> - COVID-19 is characterized by virus-induced injury leading to multi-organ failure, together with inflammatory reaction, endothelial cell (EC) injury, and prothrombotic coagulopathy with thrombotic events. Complement system (C) via its cross-talk with the contact and coagulation systems contributes significantly to the severity and pathological consequences due to SARS-CoV-2 infection. These immunopathological mechanisms overlap in COVID-19 and pre-eclampsia (PE). Thus, mothers contracting…</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>Pre-Existing Cross-Reactive Antibody Responses Do Not Significantly Impact Inactivated COVID-19 Vaccine-Induced Neutralization</strong> - Recent exposure to seasonal coronaviruses (sCoVs) may stimulate cross-reactive antibody responses against severe acute respiratory syndrome CoV 2 (SARS-CoV-2). However, previous studies have produced divergent results regarding protective or damaging immunity induced by prior sCoV exposure. It remains unknown whether pre-existing humoral immunity plays a role in vaccine-induced neutralization and antibody responses. In this study, we collected 36 paired sera samples from 36 healthy volunteers…</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>Effects of beta-Blockers on the Sympathetic and Cytokines Storms in Covid-19</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a causative virus in the development of coronavirus disease 2019 (Covid-19) pandemic. Respiratory manifestations of SARS-CoV-2 infection such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) leads to hypoxia, oxidative stress, and sympatho-activation and in severe cases leads to sympathetic storm (SS). On the other hand, an exaggerated immune response to the SARS-CoV-2 invasion may lead to uncontrolled…</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>Moderate Intensity Aerobic Exercise Potential Favorable Effect Against COVID-19: The Role of Renin-Angiotensin System and Immunomodulatory Effects</strong> - The coronavirus disease (COVID-19) pandemic is caused by a novel coronavirus (CoV) named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As the angiotensin converting enzyme 2 (ACE2) is the cellular receptor of SARS- CoV-2, it has a strong interaction with the renin angiotensin system (RAS). Experimental studies have shown that the higher levels of ACE2 or increasing ACE2/ACE1 ratio improve COVID-19 outcomes through lowering inflammation and death. Aerobic moderate intensity…</p></li>
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</ul>
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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>REAL-TIME REST BREAK MANAGEMENT SYSTEM FOR WORKPLACE</strong> - The present invention relates to a real-time rest break management system for workplace that comprises of a work desk, wherein first portion is incorporated with a biometric unit 4 for authenticating first user, and a second portion with a telescopic panel 2 associated with a weight sensor 6 and timer unit 7 calculating weight of head/hand manifesting user presence and their resting time period is mounted with an inflated cushion 5, an interactive primary display unit 1 attached over desk enables user to set first/second threshold time for sleeping/taking break, further linked with a tracking interface keeping track of activities and a vibrating unit crafted inside the cushion 5 which is linked to a secondary display unit 8 of second user, giving them access to actuate vibrating unit generating impulses to wake first user when threshold time period is exceeded by the first user. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN342791215">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>P2P 네트워크를 이용한 내장된 화상회의 시스템</strong> - 본 발명은 P2P 네트워크를 이용한 내장된 화상회의 시스템에 관한 것으로, 상태표시부(1), 영상송출부(2), 제어부(3), 광고부(4), 입력부(5)를 포함한다. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=KR342781397">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A DOORBELL SYSTEM FOR MONITORING AND RECORDING A PHYSIOLOGICAL DATA OF A PERSON</strong> - AbstractTitle: A doorbell system for monitoring and recording a physiological data of a person The present invention provides a doorbell system 500 for monitoring and recording a physiological data of a person. The doorbell system 500 having a transmitter module 100 and a receiving module 200. The transmitter module 100 is having a TOF sensor module 110, an ultrasound detector 120, and an infrared detector 130. Further, a speech recognition system 150, a facial recognition system 160, and a temperature detector 190 are provided for recognizing speech, face, and temperature of the person by comparing pre-stored data. A controlling module 180 is set with a predefined commands for communicating with the transmitter module 100 and receiving module 200. The collected facial and speech data is compared and matched with the pre-stored data then the temperature detector 190 triggers and the door opens when the captured body temperature of the person is matched within the predefined range of temperature.Figure 1 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN340503637">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A study of contemporary trends in investing patterns, household savings, and economic investment.</strong> - Because household savings and household investments are intertwined and interdependent, they are discussed briefly in this paper. Household savings account for more than half of a country’s capital formation, which fluctuates due to a variety of economic factors such as inflation and interest rates. Households should gradually shift their savings and investments from physical assets to financial assets to avoid a sudden change in wealth. They should also save and invest using a variety of platforms. Trends in investing and saving will be easier to track and measure this way. This year’s domestic saving rate in India is 2.3 percent lower than last year’s and 1.2 percent lower than the year before. Since 2011, general domestic savings have been steadily declining, with the trend continuing into the following year. According to official data, the GDP in 2020 shrank by 23.9%, the least in previous years and the least since the Covid-19 pandemic in previous years. As a result, the information presented in this paper is drawn from and evaluated from other sources - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN340502149">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>靶向刺激体液免疫和细胞免疫的新冠病毒mRNA疫苗</strong> - 本发明公开了一种靶向刺激体液免疫和细胞免疫的新冠病毒mRNA疫苗。本申请的第一方面提供一种分离的DNA分子组合，该DNA分子组合包括第一DNA分子和第二DNA分子和第三DNA分子中的至少一种。通过第一DNA分子以及第二DNA分子和/或第三DNA分子的组合，利用第一DNA分子最终合成的mRNA诱导高滴度的交叉中和抗体，利用第二DNA分子和/或第三DNA分子最终合成的mRNA诱导新冠病毒特异性的细胞毒性T淋巴细胞，从而高效地同时激活相对独立的体液免疫应答和细胞免疫应答，应对新冠病毒在流行传播过程中产生的突变毒株所引发的突破性感染。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN343418093">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>跨膜丝氨酸蛋白酶2抑制剂在制备治疗和/或预防冠状病毒感染药物中的用途</strong> - 本发明公开了跨膜丝氨酸蛋白酶2抑制剂在制备治疗和/或预防冠状病毒感染药物中的用途。本发明通过亲和垂钓及活性导向分离获得3种化合物，证实该类化合物可以直接地与跨膜丝氨酸蛋白酶2结合，KD<13μM，且能够显著抑制跨膜丝氨酸蛋白酶2的催化活性。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，表明该类化合物对于制备治疗和/或预防病毒感染药物具有非常积极的作用。化合物1 化合物2 化合物3。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN343418164">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>PROLIPOSOMAL DRY POWDER INHALER OF REMDESIVIR</strong> - The present invention is related to Proliposomal Dry Powder Inhaler of Remdesivir and its method thereof for the treatment of viral infections such Coronaviridae (including COVID-19 infection). - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN342291904">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Use of Diminazene Aceturate, Xanthenone, ACE 2 activators or analogs for the Treatment and therapeutic use of COVID-19 on human patients.</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU340325322">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>ACTIVE RIDER SAFETY SYSTEM FOR TWO WHEELERS</strong> - The present invention relates to an active rider safety system for two wheelers comprising, a protective case equipped by a user for riding, where the case is integrated with multiple piezoelectric sensor that determines fastening of the case by user, a processing unit linked to the sensor, where the unit detects absence of case upon fetching data from the sensor below a threshold value and thereby terminates operation of ignition by stopping a coupled motor operated via a radio frequency module, an alcohol detection sensor that detects presence of alcohol and send data to processing unit, a temperature sensor that measures temperature of the user, an accelerometer sensor that activates upon ignition us tuned on to determine presence of a crash and a navigation module that via communication module sends location of user to pre saved users and concerned authorities. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN340503361">link</a></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Medizintechnische Haltevorrichtung und Haltevorrichtungs-Kit jeweils zum Halten von allgemeinmedizinischen, chirurgischen oder diagnostischen Einrichtungen oder Instrumenten sowie deren Verwendung insbesondere zur Datenerfassung</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Medizintechnische Haltevorrichtung (10) eingerichtet zum Halten von allgemeinmedizinischen, chirurgischen oder diagnostischen Einrichtungen oder Instrumenten, insbesondere Diagnose-Einrichtungen oder -instrumenten für den Mund-/Rachenraum aus der folgenden Gruppe: Spatel (1), Abstrich-Einrichtung (2), Lichtquelle (3), Kamera (4); wobei die Haltevorrichtung (10) aufweist:</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">einen Kontaktbereich (15) zum manuellen Kontaktieren der Haltevorrichtung (10) durch einen Nutzer;</li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">wenigstens eine mit dem Kontaktbereich (15) verbundene Haltekupplung (11, 12, 13) zum reversiblen Kuppeln, insbesondere form- und/oder kraftschlüssigen Kuppeln, der jeweiligen Einrichtung oder des Instruments; dadurch gekennzeichnet, dass der Kontaktbereich (15) eine Mindest-Längserstreckung (x15) von 20cm aufweist, wobei die wenigstens eine Haltekupplung (11, 12) an einem Längs-Ende des Kontaktbereichs (15) angeordnet ist, und wobei der Kontaktbereich</li>
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</ul>
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<ol start="15" type="1">
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">zumindest teilweise aus Kupfer besteht oder Kupfer als Oberflächenmaterial/-werkstoff aufweist, wobei die medizintechnische Haltevorrichtung (10) eingerichtet ist zum Kuppeln einer/der Kamera im Kontaktbereich, insbesondere bei Verwendung einer Kamera mit einem Gehäuse mit integrierter Kuppelfunktion.</li>
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<li><a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=DE343577678">link</a></li>
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