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180 lines
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<title>10 June, 2022</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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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li>**Spike-Induced Disturbances (SPAS*): An Analysis of Common Suspected Adverse Experiences Associated With Covid-19 Vaccines** -
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<div>
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This review/analysis gives a first impression of numerous adverse events related to Covid-19 vaccination, which have received little attention to date, are often unexplained, but are nevertheless very distressing. Frequently observed organ-related ADRs after Covid-19 vaccination were such of the nervous system, musculoskeletal system, gastrointestinal tract, and skin. The involvement of almost all organs in the side effect spectrum of Covid-19 vaccines demonstrates their systemic efficacy. As shown by the ADRs occurrence even after numerous days to weeks, the duration of spike production obviously lasts longer than claimed. The key role is played by the interaction between the spike subunit S1 and the membrane-bound enzyme ACE2, the receptor for SARS-CoV. Downregulation of ACE2 by spikes and following activation of RAAS can lead to numerous clinically relevant disorders, such as vasoconstriction, tissue ischemia, induction of proliferative processes, increased oxidative stress, inflammation, or coagulation disorders, as previously shown for cardiovascular reactions. It is proposed to use the collective term “SPAS” (in German: Spike ausgelöste Störungen) - spike induced disturbances for side effects based on this mode of action. The common mode of action and only slightly different frequencies of adverse events and fatal outcomes do not indicate any principal differences in adverse event profiles of the individual spike-based Covid-19 vaccines. A class-specific side effect profile can be assumed. Knowledge and awareness of the comprehensive adverse event profile of the novel Covid-19 vaccines and their potential dangerousness may improve vaccine safety.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/q94bn/" target="_blank">Spike-Induced Disturbances (SPAS*): An Analysis of Common Suspected Adverse Experiences Associated With Covid-19 Vaccines</a>
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</div></li>
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<li><strong>A cellular assay for spike/ACE2 fusion: quantification of fusion-inhibitory antibodies after COVID-19 and vaccination</strong> -
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<div>
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Not all antibodies against SARS-CoV-2 inhibit viral entry and hence infection. Neutralizing antibodies are more likely to reflect real immunity, however certain of these tests investigate protein/protein interaction rather than the fusion event. Viral and pseudoviral entry assays detect functionally active antibodies, however they are cumbersome and burdened by biosafety and standardization issues. We have developed a Spike/ACE2-dependant cell-to-cell fusion assay, based on a split luciferase. Hela cells stably transduced with Spike and a large fragment of luciferase were co-cultured with Hela cells transduced with ACE2 and the complementary small fragment of luciferase. Within 24h, cell fusion occured allowing the measurement of luminescence. Light emission was abolished in the absence of Spike and reduced in the presence of an inhibitor of Spike-processing proteases. Serum samples from COVID-19-negative, non-vaccinated individuals, or sera from patients at the moment of first symptoms did not lead to a significant reduction of fusion. In contrast, sera from COVID-19-positive patients as well as sera from vaccinated individuals reduced the fusion. In conclusion, we report a new method measuring fusion-inhibitory antibodies in serum, combining the advantage of a functional full Spike/ACE2 interaction with a high degree of standardization, easily allowing automation in a standard bio-safety environment.
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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://www.biorxiv.org/content/10.1101/2022.06.09.495433v1" target="_blank">A cellular assay for spike/ACE2 fusion: quantification of fusion-inhibitory antibodies after COVID-19 and vaccination</a>
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</div></li>
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<li><strong>Tracking infectious entry routes of SARS-CoV-2</strong> -
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<div>
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SARS-CoV-2 cell entry starts with membrane attachment and ends with spike-protein (S) catalyzed membrane fusion depending on two cleavage steps, one usually by furin in producing cells and the second by TMPRSS2 on target cells. Endosomal cathepsins can carry out both. Using real-time 3D single virion tracking, we show fusion and genome penetration requires virion exposure to an acidic milieu of pH 6.2-6.8, even when furin and TMPRSS2 cleavages have occurred. We detect the sequential steps of S1-fragment dissociation, fusion, and content release from the cell surface in TMPRRS2 overexpressing cells only when exposed to acidic pH. We define a key role of an acidic environment for successful infection, found in endosomal compartments and at the surface of TMPRSS2 expressing cells in the acidic milieu of the nasal cavity.
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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://www.biorxiv.org/content/10.1101/2022.06.09.495472v1" target="_blank">Tracking infectious entry routes of SARS-CoV-2</a>
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</div></li>
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<li><strong>Binding and unbinding pathways of peptide substrate on SARS-CoV-2 3CL protease</strong> -
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<div>
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Based on many crystal structures of ligand complexes, much study has been devoted to understanding the molecular recognition of SARS-CoV-2 3C-like protease (3CLpro), a potent drug target for COVID-19. In this research, to extend this present static view, we examined the kinetic process of binding/unbinding of an eight-residue substrate peptide to/from 3CLpro by evaluating the path ensemble with the weighted ensemble simulation. The path ensemble showed the mechanism of how a highly flexible peptide folded into the bound form. At the early stage, the dominant motion was the diffusion on the protein surface showing a broad distribution, whose centre was led into the cleft of the Chymotrypsin fold. We observed a definite sequential formation of the hydrogen bonds at the later stage occurring in the cleft, initiated between Glu166 (3CLpro) and P3_Val (peptide), followed by binding to the oxyanion hole and completed by the sequence-specific recognition at P1_Gln.
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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://www.biorxiv.org/content/10.1101/2022.06.08.495396v1" target="_blank">Binding and unbinding pathways of peptide substrate on SARS-CoV-2 3CL protease</a>
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</div></li>
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<li><strong>SARS-CoV-2-neutralizing humoral IgA response occurs earlier but modest and diminishes faster compared to IgG response.</strong> -
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<div>
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Secretory immunoglobulin A (IgA) plays a crucial role in the mucosal immunity for preventing the invasion of the exogenous antigens, however, little has been understood about the neutralizing activity of serum IgA. Here, to examine the role of IgA antibodies against COVID-19 illnesses, we determined the neutralizing activity of serum/plasma IgG and IgA purified from previously SARS-CoV-2-infected and COVID-19 mRNA-vaccine-receiving individuals. We found that serum/plasma IgA possesses substantial but rather modest neutralizing activity against SARS-CoV-2 compared to IgG with no significant correlation with the disease severity. Neutralizing IgA and IgG antibodies achieved the greatest activity at approximately 25 and 35 days after symptom onset, respectively. However, neutralizing IgA activity quickly diminished and went down below the detection limit approximately 70 days after onset, while substantial IgG activity was observed till 200 days after onset. The total neutralizing activity in sera/plasmas of those with COVID-19 largely correlated with that in purified-IgG and purified-IgA and levels of anti-SARS-CoV-2-S1-binding IgG and anti-SARS-CoV-2-S1-binding IgA. In individuals who were previously infected with SARS-CoV-2 but had no detectable neutralizing IgA activity, a single dose of BNT162b2 or mRNA-1273 elicited potent serum/plasma neutralizing IgA activity but the second dose did not further strengthen the neutralization antibody response. The present data show that the systemic immune stimulation with natural infection and COVID-19 mRNA-vaccines elicit both SARS-CoV-2-specific neutralizing IgG and IgA response in serum, but the IgA response is modest and diminishes faster compared to IgG response.
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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://www.biorxiv.org/content/10.1101/2022.06.09.495422v1" target="_blank">SARS-CoV-2-neutralizing humoral IgA response occurs earlier but modest and diminishes faster compared to IgG response.</a>
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</div></li>
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<li><strong>ARF6 is an important host factor for SARS-CoV-2 infection in vitro</strong> -
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<div>
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SARS-CoV-2 is a newly emerged beta-coronavirus that enter cells via two routes, direct fusion at the plasma membrane or endocytosis followed by fusion with the late endosome/lysosome. While the viral receptor, ACE2, multiple entry factors, and the mechanism of fusion of the virus at the plasma membrane have been extensively investigated, viral entry via the endocytic pathway is less understood. By using a human hepatocarcinoma cell line, Huh-7, which is resistant to the antiviral action of the TMPRSS2 inhibitor camostat, we discovered that SARS-CoV-2 entry is not dependent on dynasore but dependent on cholesterol. ADP-ribosylation factor 6 (ARF6) has been described as a host factor for SARS-CoV2 replication and it is involved in the entry and infection of several pathogenic viruses. By CRISPR-Cas9 genetic deletion, we found that ARF6 is important for SARS-CoV-2 uptake and infection in Huh-7. In addition, the ARF6 inhibitor NAV-2729, and the ARF6 agonist AA147, showed a dose-responsive inhibition or enhancement of viral infection, respectively. Importantly, ARF6 inhibition reduced SARS-CoV-2 viral loads also in more physiologic models of infection: Calu-3 and kidney organoids, suggesting a role also in post-entry steps. Together, these experiments points to a ARF6 as a putative target to develop antiviral strategies against SARS-CoV-2.
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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://www.biorxiv.org/content/10.1101/2022.06.09.495482v1" target="_blank">ARF6 is an important host factor for SARS-CoV-2 infection in vitro</a>
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<li><strong>The Pandemic as a Portal: Reimagining Psychological Science as Truly Open and Inclusive</strong> -
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Psychological science is at an inflection point: The COVID-19 pandemic has already begun to exacerbate inequalities that stem from our historically closed and exclusive culture. Meanwhile, reform efforts to change the future of our science are too narrow in focus to fully succeed. In this paper, we call on psychological scientists—focusing specifically on those who use quantitative methods in the United States as one context for such conversations—to begin reimagining our discipline as fundamentally open and inclusive. First, we discuss who our discipline was designed to serve and how this history produced the inequitable reward and support systems we see today. Second, we highlight how current institutional responses to address worsening inequalities are inadequate, as well as how our disciplinary perspective may both help and hinder our ability to craft effective solutions. Third, we take a hard look in the mirror at the disconnect between what we ostensibly value as a field and what we actually practice. Fourth and finally, we lead readers through a roadmap for reimagining psychological science in whatever roles and spaces they occupy, from an informal discussion group in a department to a formal strategic planning retreat at a scientific society.
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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://psyarxiv.com/gdzue/" target="_blank">The Pandemic as a Portal: Reimagining Psychological Science as Truly Open and Inclusive</a>
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<li><strong>Out-of-hospital Cardiac Arrest Before and During the COVID-19 Pandemic in the South Bronx</strong> -
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Background: Out-of-hospital cardiac arrest (OHCA) is a major health challenge; the impact of the COVID-19 pandemic on OHCA in the South Bronx is unknown. The aim of this study was to determine differences between return of spontaneous circulation(ROSC), witnessed arrest, bystander CPR and survival to discharge, prior to and during the COVID-19 pandemic to improve ROSC and survival. Methods: Single-center retrospective study of non-traumatic OHCA adult patients admitted to Lincoln Medical Center between 8/2019 to 6/2021, 3/2020 being the first established date of the COVID-19 pandemic in New York City. International Classification of Diseases (ICD) coding was used to identify cardiac arrests and collect information. Statistical analysis was performed using IBM-SPSS. Results: ROSC time pre COVID-19 was 26 minutes, during the COVID-19 pandemic it was 25 minutes 54 seconds. A significant difference in witnessed arrests in the pre COVID-19 period compared to the COVID-19 period (86% vs 55% p = 0.03). Bystander CPR occurred 36% of the time in the pre COVID-19 period contrasting to 19% during. Prior to the COVID-19 pandemic the overall survival to discharge in OHCA ROSC cases was 28.5% comparing to 29% during the pandemic. ROSC was 18 minutes among survivors during the pandemic, compared to 21 minutes in survivors prior to COVID (p = 0.2). Conclusion: There was a non-significant difference in ROSC, bystander CPR and survival to discharge in non-traumatic OHCA prior to and during the COVID-19 pandemic in the South Bronx. There was a significant difference in witnessed vs unwitnessed OHCA prior to and during the COVID-19 pandemic.
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</p>
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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://www.medrxiv.org/content/10.1101/2022.06.08.22276169v1" target="_blank">Out-of-hospital Cardiac Arrest Before and During the COVID-19 Pandemic in the South Bronx</a>
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</div></li>
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<li><strong>Environmental circulation of adenovirus 40/41 and SARS-CoV-2 in the context of the emergence of acute hepatitis of unknown origin</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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The recent surge of hepatitis of unknown origin in children is hypothesized to be caused by adenovirus 41 and/or SARS-CoV-2 infections. A relatively high proportion of patients testing positive for these viruses concomitantly with the development of acute hepatitis supports this hypothesis. To formally incriminate these viral infections as causative agents of hepatitis, both a plausible physiopathological pathway and supporting epidemiological dynamics in the community need demonstration. In this study, we measured the level of circulation of adenovirus 40/41 and SARS-CoV-2 in the general population of the city of Leuven in Belgium using wastewater monitoring between December 2020 and May 2022 and indoor air sampling in day care centers between November 2021 and May 2022. We also retrospectively analyzed medical records of 12.672 children attending a tertiary hospital draining the same region between January 2019 and April 2022. Our results demonstrate a recent but modest increase in hepatitis of unknown origin concomitant with a surge of circulating adenovirus 41 and SARS-CoV-2 in the general population, including in children under 5.
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</p>
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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://www.medrxiv.org/content/10.1101/2022.06.08.22276091v1" target="_blank">Environmental circulation of adenovirus 40/41 and SARS-CoV-2 in the context of the emergence of acute hepatitis of unknown origin</a>
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</div></li>
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<li><strong>Validity of self-testing at home with rapid SARS-CoV-2 antibody detection by lateral flow immunoassay</strong> -
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Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody lateral flow immunoassays (LFIA) can be carried out in the home and have been used as an affordable and practical approach to large-scale antibody prevalence studies. However, assay performance differs from that of high-throughput laboratory-based assays which can be highly sensitive. We explore LFIA performance under field conditions compared to laboratory-based ELISA and assess the potential of LFIAs to identify people who lack functional antibodies following infection or vaccination. Methods: Field evaluation of a self-administered LFIA test (Fortress, NI) among 3758 participants from the REal-time Assessment of Community Transmission-2 (REACT-2) study in England selected based on vaccination history and previous LFIA result to ensure a range of antibody titres. In July 2021, participants performed, at home, a self-administered LFIA on finger-prick blood, reported and submitted a photograph of the result, and provided a self-collected capillary blood sample (Tasso-SST) for serological assessment of IgG antibodies to the spike protein using the Roche Elecsys Anti-SARS-CoV-2 assay. We compared the self-administered and reported LFIA result to the quantitative Roche assay and checked the reading of the LFIA result with an automated image analysis (ALFA). In a subsample of 250 participants, we compared the results to live virus neutralisation. Results: Almost all participants (3593/3758, 95.6%) had been vaccinated or reported prior infection, with most having received one (862, 22.9%) or two (2430, 64.7%) COVID-19 vaccine doses. Overall, 2777/3758 (73.9%) were positive on self-reported LFIA, 2811/3457 (81.3%) positive by LFIA when ALFA-reported, and 3622/3758 (96.4%) positive on Roche anti-S (using the manufacturer reference standard threshold for positivity of 0.8 U ml-1). Live virus neutralisation was detected in 169 of 250 randomly selected samples (67.6%); 133/169 were positive with self-reported LFIA (sensitivity 78.7%; 95% CI 71.8, 84.6), 142/155 (91.6%; 86.1, 95.5) with ALFA, and 169 (100%; 97.8, 100.0) with Roche anti-S. There were 81 samples with no detectable virus neutralisation; 47/81 were negative with self-reported LFIA (specificity 58.0%; 95% CI 46.5, 68.9), 34/75 (45.3%; 33.8, 57.3) with ALFA, and 0/81 (0%; 0.0, 4.5) with Roche anti-S. All 250 samples remained positive with Roche anti-S when the threshold was increased to 1000U ml-1. Conclusions: Self-administered LFIA can provide insights into population patterns of infection and vaccine response, and sensitivity can be improved with automated reading of the result. The LFIA is less sensitive than a quantitative antibody test, but the positivity in LFIA correlates better than the quantitative ELISA with virus neutralisation.
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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/10.1101/2022.06.08.22276154v1" target="_blank">Validity of self-testing at home with rapid SARS-CoV-2 antibody detection by lateral flow immunoassay</a>
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<li><strong>Seroprevalence of SARS-CoV-2 and risk factors in Bantul Regency, Yogyakarta, Indonesia</strong> -
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COVID-19 case counts in Indonesia inevitably underestimate the true cumulative incidence of infection due to limited barriers to testing accessibility and asymptomatic infections. Therefore, community-based serological data are essential for understanding the true prevalence of infections. This study aims to estimate the seroprevalence of SARS-CoV-2 infection and factors related to the seropositivity in Bantul Regency, Yogyakarta, Indonesia. A cross-sectional study involving 425 individuals in 40 clusters was conducted between March and April 2021. Participants were interviewed using an e-questionnaire developed in the Kobo toolbox to collect information on socio-demographic, COVID-19 suggestive symptoms, history of COVID-19 diagnosis and COVID-19 vaccination status. A venous blood sample was collected from each participant and tested for immunoglobulin G (Ig-G) SARS-CoV-2 antibody titers using the enzyme-linked immunosorbent assay (ELISA). Seroprevalence was 31.1% in the Bantul Regency: 34.2% in semi-urban and 29.9% in urban villages. However, there is no significant proportion difference between both areas. A significant difference was reported in the age group. Participants in the 55-64 age group demonstrated the highest seroprevalence (43.7%; p=0.00), with a higher risk compared to the other age group (aOR= 3.79; 95% CI, 1.46-9.85, p<0.05). Seroprevalence in the unvaccinated participants was 29.9%. Family clusters accounted for 10.6% of the total seropositive cases. No significant difference was observed between individual preventive actions and their mobility with seropositivity status. This study observed a discrepancy with COVID-19 confirmed cumulative incidence data reported in the same period (11 out of 1000 population), indicating silent transmission may have occurred within the community. Higher seroprevalence in semi-urban areas rather than urban areas suggests a gap in health services access. Surveillance improvement through testing, tracing, and treatment, particularly in areas with lower access to health services, are necessary, along with more robust implementations of health protocols.
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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/10.1101/2022.06.07.22276128v1" target="_blank">Seroprevalence of SARS-CoV-2 and risk factors in Bantul Regency, Yogyakarta, Indonesia</a>
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<li><strong>Estimating the within-person change in dental service access measures during the COVID-19 Pandemic</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Background: American adults delay dental care more than any other healthcare service. Unfortunately, the COVID-19 pandemic may have stalled efforts to address dental service delays. Early evidence has suggested substantial declines in dental service visits in the early phase of the pandemic, however our study is among the first to measure within-person changes from 2019 to 2020 and conduct subgroup analyses to examine if changing dental patterns were mediated by exposure to the pandemic, risk of adverse COVID-19 outcomes, or dental insurance. Methods: We analyzed a National Health Interview Survey panel of individuals initially surveyed in 2019, with subsequent follow up in 2020. The outcomes included dental service access measures and the interval of a most recent dental visit. By constructing a probability weighted linear regression model with fixed-effects, we estimated the average within-person change from 2019 to 2020. Robust standard errors were clustered within each respondent. Results: Overall, adults in 2020 were 4.6%-points less likely to visit the dentist compared to 2019 (p < 0.001). Significantly higher declines were found in Northeast/West regions compared to Midwest/South. We find no evidence that declining dental services in 2020 were associated with more chronic diseases, older age, or lack of dental insurance coverage. Adults did not report more financial or non-financial access barriers to dental care in 2020 compared to 2019. Conclusions: The long-term effects of the COVID-19 pandemic on delayed dental care warrants continued monitoring as policymakers aim to mitigate the pandemic9s negative consequences on oral health equity.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.08.22276174v1" target="_blank">Estimating the within-person change in dental service access measures during the COVID-19 Pandemic</a>
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<li><strong>Effects of Covid-19 Pandemic on Online Shopping Behavior in Iran</strong> -
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Purpose - the main purpose of this study is to investigate the impact of Covid-19 pandemic on online shopping behavior in Iran. Design/methodology/approach - 484 customers of Digi Kala were selected by simple random sampling. The present study is applied objectively. The present study is a descriptive research in terms of how to collect data and it is a field research in terms of data collection. Structural equation modeling and SPSS 23 and SMARTPLS3 software were used to analyze the data. Findings - our results indicated that Covid-19 pandemic had a positive and significant effect on online shopping behavior in Iran. The level of health and economic fears during Covid-19 pandemic had a positive and significant effect on online shopping behavior in Iran. According to the moderating role of generational differences, Covid-19 pandemic and the level of health fears during the pandemic had a positive and significant effect on online shopping behavior in Iran. Nevertheless, the level of economic fears during Covid-19 pandemic had no significant effect on online shopping behavior in Iran according to the moderating role of generational differences. Originality/value - this work provides a guidance for the researchers and academicians in the field of marketing. Correspondingly, retailers and marketers should train themselves to survive during the global pandemics, and learn innovative approaches to supply the needs according to the changes in customers shopping behavior.
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🖺 Full Text HTML: <a href="https://osf.io/f9wng/" target="_blank">Effects of Covid-19 Pandemic on Online Shopping Behavior in Iran</a>
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<li><strong>Efficient reconciliation of genomic datasets of high similarity</strong> -
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We apply Invertible Bloom Lookup Tables (IBLTs) to comparison of k-mer sets originated from large DNA sequence datasets. We show that for similar datasets, IBLTs provide a more space-efficient and, at the same time, more accurate method for estimating Jaccard similarity of underlying k-mer sets, compared to MinHash which is a go-to sketching technique for efficient pairwise similarity estimation. This is achieved by combining IBLTs with k-mer sampling based on syncmers, which constitute a context-independent alternative to minimizers and provide an unbiased estimator of Jaccard similarity. A key property of our method is that involved data structures take space proportional to the difference of k-mer sets and are independent of the size of sets themselves. As another application, we show how our ideas can be applied in order to efficiently compute (an approximation of) k-mers that differ between two datasets, still using a space only proportional to their number. We experimentally illustrate our results on both simulated and real data (SARS-CoV-2 and Streptococcus Pneumoniae genomes).
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.06.07.495186v1" target="_blank">Efficient reconciliation of genomic datasets of high similarity</a>
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<li><strong>Microbial Risk Score for Capturing Microbial Characteristics, Integrating Multi-omics Data, and Predicting Disease Risk</strong> -
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Background: With the rapid accumulation of microbiome-wide association studies, a great amount of microbiome data are available to study the microbiome’s role in human disease and advance the microbiome’s potential use for disease prediction. However, the unique features of microbiome data hinder its utility for disease prediction. Methods: Motivated from the polygenic risk score framework, we propose a microbial risk score (MRS) framework to aggregate the complicated microbial profile into a summarized risk score that can be used to measure and predict disease susceptibility. Specifically, the MRS algorithm involves two steps: 1) identifying a sub-community consisting of the signature microbial taxa associated with disease, and 2) integrating the identified microbial taxa into a continuous score. The first step is carried out using the existing sophisticated microbial association tests and pruning and thresholding method in the discovery samples. The second step constructs a community-based MRS by calculating alpha diversity on the identified sub-community in the validation samples. Moreover, we propose a multi-omics data integration method by jointly modeling the proposed MRS and other risk scores constructed from other omics data in disease prediction. Results: Through three comprehensive real data analyses using the NYU Langone Health COVID-19 cohort, the gut microbiome health index (GMHI) multi-study cohort, and a large type 1 diabetes cohort separately, we exhibit and evaluate the utility of the proposed MRS framework for disease prediction and multi-omics data integration. In addition, the disease-specific MRSs for colorectal adenoma, colorectal cancer, Crohn’s disease, and rheumatoid arthritis based on the relative abundances of 5, 6, 12, and 6 microbial taxa respectively are created and validated using the GMHI multi-study cohort. Especially, Crohn’s disease MRS achieves AUCs of 0.88 ([0.85-0.91]) and 0.86 ([0.78-0.95]) in the discovery and validation cohorts, respectively. Conclusions: The proposed MRS framework sheds light on the utility of the microbiome data for disease prediction and multi-omics integration, and provides great potential in understanding the microbiome’s role in disease diagnosis and prognosis.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.06.07.495127v1" target="_blank">Microbial Risk Score for Capturing Microbial Characteristics, Integrating Multi-omics Data, and Predicting Disease Risk</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>Phase I Clinical Trial of GEN2-Recombinant COVID-19 Vaccine (CHO Cells) in Healthy People Aged 18 and Above</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Interventions</b>: Biological: Experimental Vaccine 1; Biological: Experimental Vaccine 2; Biological: Experimental Vaccine 3; Biological: placebo<br/><b>Sponsors</b>: National Vaccine and Serum Institute, China; Lanzhou Institute of Biological Products Co., Ltd; Beijing Institute of Biological Products 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>COVID-19 Algorithm Treatment at Home</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Recommended treatment schedule; Drug: Usual care<br/><b>Sponsor</b>: Mario Negri Institute for Pharmacological Research<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>Eucalyptus Oil as Adjuvant Therapy for Coronavirus Disease 19 (COVID-19)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Eucalyptus Oil; Drug: Standard COVID medication<br/><b>Sponsors</b>: Hasanuddin University; Ministry of Agriculture, Republic of Indonesia<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>Study of Oral High/Low-dose Cepharanthine Compared With Placebo in Non Hospitalized Adults With COVID-19</strong> - <b>Condition</b>: Asymptomatic COVID-19<br/><b>Interventions</b>: Drug: Cepharanthine; Drug: Placebo<br/><b>Sponsors</b>: Shanghai Jiao Tong University School of Medicine; YUNNAN BAIYAO GROUP 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>Epidemiological Monitoring of COVID-19 Patients Hospitalized on Reunion Island</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: telephone interview 24 months after hospitalization for Covid-19<br/><b>Sponsor</b>: Centre Hospitalier Universitaire de la Réunion<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>α-synuclein Seeding Activity in the Olfactory Mucosa in COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: Real-time Quaking-Induced Conversion (RT-QuIC)<br/><b>Sponsor</b>: Medical University Innsbruck<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>Randomized, Single-blinded, Multicenter Trial Comparing the Immune Response to a 2nd Booster Dose of COVID-19 mRNA Vaccine (Pfizer-BioNTech) or Sanofi /GSK B.1.351 Adjuvanted Vaccine in Adults</strong> - <b>Condition</b>: COVID-19 Vaccines<br/><b>Interventions</b>: Biological: 2nd booster with Comirnaty® (Pfizer-BioNTech); Biological: CoV2 preS dTM adjuvanted vaccine (B.1.351), Sanofi/GSK<br/><b>Sponsors</b>: Assistance Publique - Hôpitaux de Paris; IREIVAC/COVIREIVAC Network<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>Immunogenicity and Safety of a Third Dose of COVID-19 Vaccine(Vero Cell), Inactivated in the Elderly</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: COVID-19 Vaccine (Vero cell), Inactivated<br/><b>Sponsor</b>: Sinovac Life Sciences Co., Ltd.<br/><b>Active, not 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, Safety and Immunogenicity Study of the Recombinant Two-component COVID-19 Vaccine (CHO Cell)(Recov)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Recombinant two-component COVID-19 vaccine (CHO cell); Biological: Placebo<br/><b>Sponsor</b>: Jiangsu Rec-Biotechnology 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>Immunogenicity and Safety Study of Booster Vaccine With the COVID-19 Vaccine (Vero Cell), Inactivated, Omicron Strain</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: COVID-19 Vaccine (Vero Cell), Inactivated, Omicron Strain<br/><b>Sponsor</b>: Sinovac Biotech (Hong Kong) Limited<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 Phase 1a Trial to Evaluate the Safety and Immunogenicity of a SARS-CoV-2 mRNA Chimera Vaccine Against COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: RQ3013; Biological: Comirnaty<br/><b>Sponsors</b>: Walvax Biotechnology Co., Ltd.; Shanghai RNACure Biopharma 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>A Phase 1b Trial to Evaluate the Safety and Immunogenicity of a SARS-CoV-2 mRNA Chimera Vaccine Against COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: RQ3013; Biological: Comirnaty<br/><b>Sponsors</b>: Walvax Biotechnology Co., Ltd.; Shanghai RNACure Biopharma 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>Plerixafor in Acute Respiratory Distress Syndrome Related to COVID-19 (Phase IIb)</strong> - <b>Conditions</b>: COVID-19 Acute Respiratory Distress Syndrome; COVID-19<br/><b>Interventions</b>: Drug: Plerixafor 20 MG/ML [Mozobil]; Other: Placebo<br/><b>Sponsor</b>: 4Living Biotech<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>Effects of Telerehabilitative Aerobic and Relaxation Exercises Patients With Type 2 Diabetes With and Without COVID-19</strong> - <b>Conditions</b>: COVID-19; Type 2 Diabetes Mellitus<br/><b>Intervention</b>: Other: Aerobic and Relaxation Exercises<br/><b>Sponsor</b>: Bozyaka Training and Research Hospital<br/><b>Active, not 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>Long Haul COVID Rehabilitation & Recovery Research Program</strong> - <b>Condition</b>: Long Haul COVID or Post Acute Sequella of COVID - PASC (U09.9)<br/><b>Intervention</b>: Other: Virtual vs On Site Pulmonary Rehabilitation<br/><b>Sponsor</b>: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center<br/><b>Recruiting</b></p></li>
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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>Coronavirus Disease 2019 Vaccine Booster Effects Are Seen in Human Milk Antibody Response</strong> - Infants remain at high risk for severe coronavirus disease 2019 (COVID-19). Human milk contains high levels of protective SARS CoV-2 specific antibodies post-infection and primary vaccine series, but levels decline over time. We hypothesized that the COVID-19 booster vaccine augment antibody production and the protection afforded to human milk-fed infants. We prospectively enrolled pregnant or lactating mothers planning to receive COVID-19 vaccination. We measured human milk IgG, IgA, and IgM…</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>Molecular Modeling and Simulation Analysis of Antimicrobial Photodynamic Therapy Potential for Control of COVID-19</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can enter the host cells by binding the viral surface spike glycoprotein (SG) to angiotensin-converting enzyme 2. Since antiviral photodynamic therapy (aPDT) has been described as a new method for inhibiting viral infections, it is important to evaluate whether it can be used as a photoactivated disinfectant to control COVID-19. In this in silico study, SARS-CoV-2-SG was selected as a novel target for curcumin as a photosensitizer…</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>Transient Complete Recovery of Chronic Refractory Idiopathic Thrombocytopenic Purpura after Treatment with Monoclonal Antibody Targeting SARS-CoV-2 Spike Protein</strong> - Idiopathic thrombocytopenic purpura (ITP), also known as immune thrombocytopenic purpura, is an immune-mediated acquired disease characterized by transient or persistent decrease of the platelet count due to autoimmune-related destruction of platelets. Therapy for ITP relies on competing and inhibiting the autoantibody binding and destruction (intravenous immunoglobulin and anti-D immunoglobulin and spleen tyrosine kinase (Syk) inhibitor fostamatinib), augmenting platelet production…</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 an HPLC-UV Method for the Quantification of 4’-Hydroxydiclofenac Using Salicylic Acid: Future Applications for Measurement of In Vitro Drug-Drug Interaction in Rat Liver Microsomes</strong> - Salicylic acid is a key compound in nonsteroidal anti-inflammatory drugs that has been recently used for preventing the risk of hospitalization and death among COVID-19 patients and in preventing colorectal cancer (CRC) by suppressing two key proteins. Understanding drug-drug interaction pathways prevent the occurrence of adverse drug reactions in clinical trials. Drug-drug interactions can result in the variation of the pharmacodynamics and pharmacokinetic of the drug. Inhibition of 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>Isolation and Characterization of Werneria Chromene and Dihydroxyacidissimol from <em>Burkillanthus</em>&amp;nbsp;<em>malaccensis</em> (Ridl.) Swingle</strong> - The secondary metabolites of endemic plants from the Rutaceae family, such as Burkillanthusmalaccensis (Ridl.) Swingle from the rainforest of Malaysia, has not been studied. Burkillanthusmalaccensis (Ridl.) Swingle may produce antibacterial and antibiotic-potentiating secondary metabolites. Hexane, chloroform, and methanol extracts of leaves, bark, wood, pericarps, and endocarps were tested against bacteria by broth microdilution assay and their antibiotic-potentiating activities….</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>Role of Diet and Nutrients in SARS-CoV-2 Infection: Incidence on Oxidative Stress, Inflammatory Status and Viral Production</strong> - Coronavirus illness (COVID-19) is an infectious pathology generated by intense severe respiratory syndrome coronavirus 2 (SARS-CoV-2). This infectious disease has emerged in 2019. The COVID-19-associated pandemic has considerably affected the way of life and the economy in the world. It is consequently crucial to find solutions allowing remedying or alleviating the effects of this infectious disease. Natural products have been in perpetual application from immemorial time given that they are…</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 Third and Fourth mRNA-Based Booster Vaccinations on SARS-CoV-2 Neutralizing Antibody Titer Formation, Risk Factors for Non-Response, and Outcome after SARS-CoV-2 Omicron Breakthrough Infections in Patients on Chronic Hemodialysis: A Prospective Multicenter Cohort Study</strong> - CONCLUSIONS: Third and fourth mRNA-based booster vaccinations resulted in higher and longer lasting SARS-CoV-2 antibody levels as compared to after two dosages. The presence of immunosuppressive medication and repeat vaccinations are major potentially modifiable measures to increase antibody levels in non-or low-responders. Breakthrough infections with SARS-CoV-2 Omicron were associated with prolonged viral shedding but clinically mild disease courses.</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>Inhibition of Respiratory Syncytial Virus Infection by Small Non-Coding RNA Fragments</strong> - Respiratory syncytial virus (RSV) causes acute lower respiratory tract infection in infants, immunocompromised individuals and the elderly. As the only current specific treatment options for RSV are monoclonal antibodies, there is a need for efficacious antiviral treatments against RSV to be developed. We have previously shown that a group of synthetic non-coding single-stranded DNA oligonucleotides with lengths of 25-40 nucleotides can inhibit RSV infection in vitro and in vivo. Based on this,…</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>Improvement in Quality of Life through Self-Management of Mild Symptoms during the COVID-19 Pandemic: A Prospective Cohort Study</strong> - The COVID-19 pandemic has inhibited people’s help-seeking behaviors (HSBs). In particular, older people in rural communities experienced limited access to medical care, which negatively affected their quality of life (QOL). Within HSB, self-management of mild symptoms may mitigate the difficulties experienced by older people in rural communities. However, few studies have examined the relationship between self-management and QOL. Therefore, we conducted a prospective cohort study to clarify this…</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 Neutralizing Antibodies Kinetics Postvaccination in Cancer Patients under Treatment with Immune Checkpoint Inhibition</strong> - Considering that COVID-19 could adversely affect cancer patients, several countries have prioritized this highly susceptible population for vaccination. Thus, rapidly generating evidence on the efficacy of SARS-CoV-2 vaccination in the subset of patients with cancer under active therapy is of paramount importance. From this perspective, we launched the present prospective observational study to comprehensively address the longitudinal dynamics of immunogenicity of both messenger RNA (mRNA) 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>Recombinant ACE2 protein protects against acute lung injury induced by SARS-CoV-2 spike RBD protein</strong> - CONCLUSION: This study is the first to prove that rACE2 plays a protective role against SARS-CoV-2 spike RBD protein-aggravated LPS-induced ALI in an animal model and illustrate the mechanism by which the ACE2-AngII-AT(1)R-NOX1/2 axis might contribute to SARS-CoV-2-induced ALI.</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>In Vivo Visualization and Quantification of Neutrophil Elastase in Lungs of COVID-19 Patients - A First-In-Human Positron Emission Tomography Study with <sup>11</sup>C-GW457427</strong> - COVID-19 can cause life-threatening lung-inflammation that is suggested to be mediated by neutrophils, whose effector mechanisms in COVID-19 is inexplicit. The aim of the present work is to evaluate a novel PET tracer for neutrophil elastase in COVID-19 patients and healthy controls. METHODS: In this open-label, First-In-Man study, four patients with hypoxia due to COVID-19 and two healthy controls were investigated with positron emission tomography (PET) using the new selective and specific…</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>Polypyridyl ruthenium complexes as bifunctional TAR RNA binders and HIV-1 reverse transcriptase inhibitors</strong> - Inhibitors of type 1 human immunodeficiency virus (HIV-1) reverse transcriptase are central to anti-HIV therapy. Most of their targets are enzymes, while very few could bind to viral RNA. Here we designed four new polypyridyl Ru(II) complexes, which could bind HIV-1 TAR RNA tightly and selectively by molecular recognition of hydrogen bonds, further stabilize the Ru(II)-RNA bound system by electrostatic attraction, and efficiently inhibit the Moloney murine leukemia virus (M-MuLV) and HIV-1…</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 interaction between anti-PF4 antibodies and anticoagulants in vaccine-induced thrombotic thrombocytopenia</strong> - Life-threatening thrombotic events at unusual sites have been reported after vector-based vaccinations against severe acute respiratory syndrome coronavirus 2. This phenomenon is now termed vaccine-induced immune thrombotic thrombocytopenia (VITT). The pathophysiology of VITT is similar to that of heparin-induced thrombocytopenia (HIT) and is associated with platelet-activating antibodies (Abs) against platelet factor 4 (PF4). Therefore, current guidelines suggest nonheparin anticoagulants to…</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>Investigating the Link between Alpha-1 Antitrypsin and Human Neutrophil Elastase in Bronchoalveolar Lavage Fluid of COVID-19 Patients</strong> - Neutrophils play a pathogenic role in COVID-19 by releasing Neutrophils Extracellular Traps (NETs) or human neutrophil elastase (HNE). Given that HNE is inhibited by α1-antitrypsin (AAT), we aimed to assess the content of HNE, α1-antitrypsin (AAT) and HNE-AAT complexes (the AAT/HNE balance) in 33 bronchoalveolar lavage fluid (BALf) samples from COVID-19 patients. These samples were submitted for Gel-Electrophoresis, Western Blot and ELISA, and proteins (bound to AAT or HNE) were identified by…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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