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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-preprints">From Preprints</a></li>
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
<li><a href="#from-pubmed">From PubMed</a></li>
<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>U.S. CDC support to international SARS-CoV-2 seroprevalence surveys, May 2020February 2022</strong> -
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SARS-CoV-2 seroprevalence surveys provide critical information to assess the burden of COVID-19, describe population immunity, and guide public health strategies. Early in the pandemic, most of these surveys were conducted within high-income countries, leaving significant knowledge gaps in low-and middle-income (LMI) countries. To address this gap, the U.S. Centers for Disease Control and Prevention (CDC) is supporting serosurveys internationally. We conducted a descriptive analysis of international serosurveys supported by CDC during May 12, 2020February 28, 2022, using an internal tracker including data on the type of assistance provided, study design, population surveyed, laboratory testing performed, and status of implementation. Since the beginning of the pandemic, CDC has supported 72 serosurveys (77 serosurvey rounds) in 35 LMI countries by providing technical assistance (TA) on epidemiologic, statistical, and laboratory methods, financial assistance (FA), or both. Among these serosurvey rounds, the majority (61%) received both TA and FA from CDC, 30% received TA only, 3% received only FA, and 5% were part of informal reviews. Fifty-four percent of these serosurveys target the general population, 13% sample pregnant women, 7% sample healthcare workers, 7% sample other special populations (internally displaced persons, patients, students, and people living with HIV), and 18% assess multiple or other populations. These studies are in different stages of implementation, ranging from protocol development to dissemination of results. They are conducted under the leadership of local governments, who have ownership over the data, in collaboration with international partners. Thirty-four surveys rounds have completed data collection. CDC TA and FA of SARS-CoV-2 seroprevalence surveys will enhance the knowledge of the COVID-19 pandemic in almost three dozen LMI countries. Support for these surveys should account for current limitations with interpreting results, focusing efforts on prospective cohorts, identifying, and forecasting disease patterns over time, and helping understand antibody kinetics and correlates of protection.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.01.22275786v1" target="_blank">U.S. CDC support to international SARS-CoV-2 seroprevalence surveys, May 2020February 2022</a>
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<li><strong>Vaccine effectiveness against SARS-CoV-2 reinfection during periods of Alpha (B.1.1.7), Delta (B.1.617.2) or Omicron (B.1.1.529) dominance: A Danish nationwide study</strong> -
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Introduction Individuals with a prior severe acute respiratory corona virus 2 (SARS-CoV-2) infection have a moderate to high degree of protection against reinfection, though seemingly less so when the Omicron variant of SARS-CoV-2 started to circulate. The aim of this study was to evaluate the vaccine effectiveness (VE) against SARS-CoV-2 reinfection, that is, in individuals with prior SARS-CoV-2 infection, during periods with different dominant SARS-CoV-2 variants. Methods A nationwide cohort study design including all individuals with a confirmed SARS-CoV-2 infection, who were alive and residing in Denmark between 1 January 2020 and 31 January 2022 were used. Using Danish nationwide registries, we obtained information on SARS-CoV-2 infections, Coronavirus Disease 2019 (COVID-19) vaccination, age, sex, comorbidity, staying at hospital and region of affiliation. The study population included were individuals with prior SARS-CoV-2 infection. Crude and adjusted estimates of VE against SARS-CoV-2 reinfection with 95% confidence intervals (CIs) were calculated using Poisson and Cox regression models, respectively. The VE estimates were calculated separately for three periods with different dominant SARS-CoV-2 variants (Alpha (B.1.1.7), Delta (B.1.617.2), or Omicron (B.1.1.529)) and by time since vaccination using unvaccinated as the reference. Findings The study population comprised of 209,814 individuals infected before or during the Alpha period, 292,978 before or during the Delta period and 245,530 before or during the Omicron period. Of these, 40,281 individuals had completed their primary vaccination series during the Alpha period (19.2%), 190,026 during the Delta period (64.9%) and 158,563 during the Omicron period (64.6%). VE against reinfection following any COVID-19 vaccine type administered in Denmark, peaked at 85% (95% CI: 37% to 97%) at 104 days or more after vaccination during the Alpha period, 88% (95% CI: 81% to 92%) 14-43 days after vaccination during the Delta period and 60% (95% CI: 58% to 62%) 14-43 days after vaccination during the Omicron period. Waning immunity was observed, and was most pronounced during the Omicron period. Interpretation This study shows that, in previously infected individuals, completing a primary vaccination series was associated with a significant protection against SARS-CoV-2 reinfection compared with no vaccination for all three variant periods. Even though vaccination seems to protect to a lesser degree against reinfection with the Omicron variant, these findings are of public health relevance as they show that previously infected individuals still benefit from COVID-19 vaccination in all three variant periods.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.01.22275858v1" target="_blank">Vaccine effectiveness against SARS-CoV-2 reinfection during periods of Alpha (B.1.1.7), Delta (B.1.617.2) or Omicron (B.1.1.529) dominance: A Danish nationwide study</a>
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<li><strong>COVID-19 is not an Independent Cause of Death</strong> -
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The COVID-19 pandemic has had overwhelming global impacts with deleterious social, economic, and health consequences. To assess the COVID-19 death toll researchers have estimated declines in 2020 life expectancy at birth. Because data are often available only for COVID-19 deaths, the risks of dying from COVID-19 are assumed to be independent of those from other causes. We explore the soundness of this assumption based on data from the US and Brazil, the countries with the largest number of reported COVID-19 deaths. We use three methods. One estimates the difference between 2019 and 2020 life tables and therefore does not require the assumption of independence. The other two assume independence to simulate scenarios in which COVID-19 mortality is added to 2019 death rates or is eliminated from 2020 rates. Our results reveal that COVID-19 is not independent of other causes of death. The assumption of independence can lead to either an overestimate (Brazil) or an underestimate (US) of the decline in e0, depending on how the number of other reported causes of death changed in 2020.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.01.22275878v1" target="_blank">COVID-19 is not an Independent Cause of Death</a>
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<li><strong>Artificial intelligence tool for the study of COVID-19 microdroplet spread across the human diameter and airborne space</strong> -
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The 2019 novel coronavirus (SARS-COV2 / COVID-19), with a point of origin in Wuhan, China, has spread rapidly all over the world. It turned into a raging pandemic wrecking havoc on health care facilities, world economy and affecting everyones life to date. With every new variant, rate of transmission, spread of infections and the number of cases continues to rise at an international level and scale. There are limited reliable researches that study microdroplets spread and transmissions from human sneeze or cough in the airborne space. In this paper, we propose an intelligent technique to visualize, detect, measure the distance of the spread in a real-world settings of microdroplet transmissions in airborne space, called ”COVNET45”. In this paper, we investigate the microdroplet transmission and validate the measurements accuracy compared to published researches, by examining several microscopic and visual images taken to investigate the novel coronavirus (SARS-COV2 / COVID-19). The ultimate contribution is to calculate the spread of the microdroplets measurements precisely with graphical presentation.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.01.22275872v1" target="_blank">Artificial intelligence tool for the study of COVID-19 microdroplet spread across the human diameter and airborne space</a>
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<li><strong>Symptom variation, correlations, and relationship to physical activity in Long Covid: intensive longitudinal study</strong> -
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Background People with Long Covid (Post-Acute Sequelae of Covid-19) describe multiple symptoms which vary between and within individuals over relatively short time intervals. We aimed to describe the real-time associations between different symptoms and between symptoms and physical activity at the individual patient level. Methods and Findings Intensive longitudinal study of 82 adults with self-reported Long Covid (median duration 12-18 months). Data collection involved a smartphone app with 5 daily entries over 14 days and continuous wearing of a wrist accelerometer. Data items included 7 symptoms (Visual Analog Scales) and perceived demands in the preceding period (Likert scales). Activity was measured using mean acceleration in the 3-hour periods preceding and following app data entry. Analysis used within-person correlations of symptoms pairs and both pooled and individual symptom networks derived from graphical vector autoregression. App data was suitable for analysis from 74 participants (90%) comprising 4022 entries representing 77.6% of possible entries. Symptoms varied substantially within individuals and were only weakly auto-correlated. The strongest between-subject symptom correlations were of fatigue with pain (partial coefficient 0.5) and cognitive difficulty with light-headedness (0.41). Pooled within-subject correlations showed fatigue correlated with cognitive difficulty (partial coefficient 0.2) pain (0.19) breathlessness (0.15) and light-headedness (0.12) but not anxiety. Cognitive difficulty was correlated with anxiety and light-headedness (partial coefficients 0.16 and 0.17). Individual participant correlation heatmaps and symptom networks showed no clear patterns indicative of distinct phenotypes. Symptoms, including fatigue, were inconsistently correlated with prior or subsequent physical activity: this may reflect adjustment of activity in response to symptoms. Delayed worsening of symptoms after the highest activity peak was observed in 7 participants. Conclusion: Symptoms of Long Covid vary within individuals over short time scales, with heterogenous patterns of symptom correlation. The findings are compatible with altered central symptom processing as an additional factor in Long Covid.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.31.22275746v1" target="_blank">Symptom variation, correlations, and relationship to physical activity in Long Covid: intensive longitudinal study</a>
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<li><strong>Severe acute respiratory syndrome coronavirus 2 breakthrough infections in healthcare workers vaccinees with BNT162b2 (Pfizer-BioNtech) in Bogota, Colombia</strong> -
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The healthcare workers are considered as a high-risk group for infection with SARS-CoV-2, so they were included in the first stage of the National Plan for Vaccination against COVID-19 in Colombia. An ongoing prospective cohort study to evaluate immune response to vaccination included 490 workers from health institutions in Bogota, Colombia, vaccinated between March and June 2021 with BNT162b2 (Pfizer-BioNtech). Multiple samples were collected during a follow-up period of 6 months after immunization. We report cases of asymptomatic and symptomatic SARS-CoV-2 infections detected in this cohort. For each participant demographic data, vaccination dates, results for SARS-CoV-2 RT-PCR, and detection of antibody (IgG) tests during the follow-up period were collected. SARS-CoV-2 infection was detected in 38 (7.7 %) volunteers. Of these, 81.6% had a positive RT-PCR for SARS-CoV-2, and 18.4% were confirmed by detection of IgG anti-SARS-CoV-2 nucleoprotein; 76.3% of infections occurred after 7 days of second dose. A total of 57.9% of the cases were asymptomatic. No hospitalizations or deaths were registered. When infection occurred, 81.6% of infected participants had presence of IgG anti-S antibodies. In 12 samples in which genomic characterization was achieved, 83.4% corresponded to the variant Mu, 8.3% Gamma, and 8.3% Delta. All findings agree with other reports in different studies that show the benefit of COVID-19 vaccines, protecting specially against severe disease but not against infection or re-infection.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.31.22274501v1" target="_blank">Severe acute respiratory syndrome coronavirus 2 breakthrough infections in healthcare workers vaccinees with BNT162b2 (Pfizer-BioNtech) in Bogota, Colombia</a>
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<li><strong>Antiviral immune responses, cellular metabolism and adhesion are differentially modulated by SARS-CoV-2 ORF7a or ORF7b</strong> -
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SARS-CoV-2, the causative agent of the present COVID-19 pandemic, possesses eleven accessory proteins encoded in its genome, and some have been implicated in facilitating infection and pathogenesis through their interaction with cellular components. Among these proteins, accessory protein ORF7a and ORF7b functions are poorly understood. In this study, A549 cells were transduced to express ORF7a and ORF7b, respectively, to explore more in depth the role of each accessory protein in the pathological manifestation leading to COVID-19. Bioinformatic analysis and integration of transcriptome results identified defined canonical pathways and functional groupings revealing that after expression of ORF7a or ORF7b, the lung cells are potentially altered to create conditions more favorable for SARS-CoV-2, by inhibiting the IFN-I response, increasing proinflammatory cytokines release, and altering cell metabolic activity and adhesion. Based on these results, it is reasonable to suggest that ORF7a and ORF7b could be targeted by new therapies or used as future biomarkers during this pandemic.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.06.01.494101v1" target="_blank">Antiviral immune responses, cellular metabolism and adhesion are differentially modulated by SARS-CoV-2 ORF7a or ORF7b</a>
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<li><strong>SUMOylation of SARS-CoV-2 Nucleocapsid protein enhances its interaction affinity and plays a critical role for its nuclear translocation</strong> -
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Viruses, such as SARS-CoV-2, infect hosts and take advantages of host cellular machinery for their genome replication and new virion production. Identification and elucidation of host pathways for viral infection are critical for understanding the viral life cycle and novel therapeutics development. SARS-CoV-2 N protein is critical for viral RNA(vRNA) genome packaging in new virion formation, Here, we report that identification of SUMOylation sites of SARS-CoV-2 N protein and role of SUMO modification in N protein interaction affinity with itself using our qFRET/MS coupled method. We found, for the first time, that the SUMO modification of N protein can significantly increase its interaction affinity with itself and may support its oligomer formation. One of the identified Lys residues, K65 was critical for N protein translocation to nucleus, where the vRNA replication and packaging take place. The in vitro assessment of the affinity of N protein to N protein with SUMO mutants provides insight of the oligomerized N protein formation after SUMO modification. These results suggest that the host human SUMOylation pathway may be very critical for N protein functions in viral replication. The host SUMOylation pathway may be a critical host factor for the SARS-CoV-2 virus life cycle. Identification and inhibition of critical host SUMOylation could provide a novel strategy for future anti-viral therapeutics development, such as SARS-CoV-2 and other viruses.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.31.494262v1" target="_blank">SUMOylation of SARS-CoV-2 Nucleocapsid protein enhances its interaction affinity and plays a critical role for its nuclear translocation</a>
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<li><strong>Malinformation an emergent problem for medical journals and scientific communication</strong> -
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Background: Misinformation and disinformation are problems increasingly recognized in medicine. However, much less attention has been paid to their insidious relative, malinformation, the presentation of curated facts in manner that presents a false narrative and/or creates a misleading impression by leaving out important context. Unlike its better-known relatives, malinformation depends not on false information but instead employs cherry-picked facts and deliberate omissions to mislead. Medical journals are the vanguards of new research and analysis in biomedicine; yet results and commentary published in them can easily be misrepresented to produce malinformation. These distortions can be introduced by third parties interpreting the research, the authors themselves, or both. Methods: We present a case study of the article about a COVID-19 vaccine with the highest Altmetric score in history. Employing Altmetric and sentiment analysis to quantify its context, spread and interpretation, we analyzed how the presentation of the article is likely to adversely affect future public understanding of science and trust in the safety of COVID-19 vaccines. Results: Our analysis suggests the selective and leading presentation made this an especially powerful piece of malinformation, in large part because the imprimatur of a respected medical journal gave it a veneer of legitimacy. Sentiment analysis suggests it has been chiefly amplified by antivaccine activists and conspiracy theorists worldwide, with negative ramifications for vaccine acceptance. Conclusion: To maintain public trust in medical science, authors, editors, and reviewers need be aware of the potential for malinformation and decontextualized misappropriation of bona fide results.
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🖺 Full Text HTML: <a href="https://osf.io/g4jwr/" target="_blank">Malinformation an emergent problem for medical journals and scientific communication</a>
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<li><strong>Anti-COVID-19 Activity of FDA Approved Drugs through RNA G-quadruplex Binding</strong> -
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The COVID-19 pandemic caused by SARS-CoV-2 has caused millions of infections and deaths worldwide. Limited treatment options and the threat from emerging variants underline the need for novel and widely accessible therapeutics. G-quadruplexes (G4s) are nucleic acid secondary structures known to affect many cellular processes including viral replication and transcription. We identified heretofore not reported G4s with remarkably low mutation frequency across &gt;4 million SARS-CoV-2 genomes. The G4 structure was targeted using FDA approved drugs that can bind G4s - Chlorpromazine (CPZ) and Prochlorperazine (PCZ). We found significant inhibition in lung pathology and lung viral load of SARS-CoV-2 challenged hamsters when treated with CPZ, PCZ that was comparable to the widely used antiviral drug Remdesivir. In support, in vitro G4 binding, inhibition of reverse transcription from RNA isolated from COVID-infected humans, and attenuated viral replication and infectivity in vero cell cultures were clear in case of both CPZ/PCZ. Apart from the wide accessibility of CPZ/PCZ, targeting relatively invariant nucleic acid structures poses an attractive strategy against fast mutating viruses like SARS-CoV-2.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.31.493843v1" target="_blank">Anti-COVID-19 Activity of FDA Approved Drugs through RNA G-quadruplex Binding</a>
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<li><strong>SARS-CoV-2 Variant Spike and accessory gene mutations alter pathogenesis</strong> -
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The ongoing COVID-19 pandemic is a major public health crisis. Despite the development and deployment of vaccines against SARS-CoV-2, the pandemic persists. The continued spread of the virus is largely driven by the emergence of viral variants, which can evade the current vaccines through mutations in the Spike protein. Although these differences in Spike are important in terms of transmission and vaccine responses, these variants possess mutations in the other parts of their genome which may affect pathogenesis. Of particular interest to us are the mutations present in the accessory genes, which have been shown to contribute to pathogenesis in the host through innate immune signaling, among other effects on host machinery. To examine the effects of accessory protein mutations and other non-spike mutations on SARS-CoV-2 pathogenesis, we synthesized viruses where the WA1 Spike is replaced by each variant spike genes in a SARS-CoV-2/WA-1 infectious clone. We then characterized the in vitro and in vivo replication of these viruses and compared them to the full variant viruses. Our work has revealed that non-spike mutations in variants can contribute to replication of SARS-CoV-2 and pathogenesis in the host and can lead to attenuating phenotypes in circulating variants of concern. This work suggests that while Spike mutations may enhance receptor binding and entry into cells, mutations in accessory proteins may lead to less clinical disease, extended time toward knowing an infection exists in a person and thus increased time for transmission to occur.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.31.494211v1" target="_blank">SARS-CoV-2 Variant Spike and accessory gene mutations alter pathogenesis</a>
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<li><strong>Adults Health-Related Problem Solving Is Facilitated by Number Lines, But Not Risk Ladders and Icon Arrays</strong> -
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Visual displays, such as icon arrays and risk ladders, are often used to communicate numerical health information. Number lines improve reasoning with rational numbers but are seldom used in health contexts. College students compared rates for information related to COVID-19 (e.g., number of deaths and number of cases) in one of four randomly-assigned conditions: icon arrays, risk ladders, number lines, or no accompanying visual display. As predicted, number lines facilitated performance on these problems the number line condition outperformed the other visual display conditions, which did not perform any better than the no visual display condition. In addition, higher performance on the health-related math problems was associated with higher COVID-19 worry for oneself and others, higher perceptions of COVID-19 severity, and higher endorsement of intentions to engage in preventive health behaviors, even when controlling for baseline math skills. These findings have important implications for effectively presenting health statistics.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/h3stw/" target="_blank">Adults Health-Related Problem Solving Is Facilitated by Number Lines, But Not Risk Ladders and Icon Arrays</a>
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<li><strong>Effectiveness of a Fourth Dose of COVID-19 Vaccine among Long-Term Care Residents in Ontario, Canada: Test-Negative Design Study</strong> -
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Background: As of December 30, 2021, Ontario long-term care (LTC) residents who received a third dose of COVID-19 vaccine ≥84 days previously were offered a fourth dose to prevent a surge in COVID-19-related morbidity and mortality due to the Omicron variant. Methods: We used a test-negative design and linked databases to estimate the marginal effectiveness (4 versus 3 doses) and vaccine effectiveness (VE; 2, 3, or 4 doses versus no doses) of mRNA vaccines among Ontario LTC residents aged ≥60 years who were tested for SARS-CoV-2 between December 30, 2021 and April 27, 2022. Outcome measures included any Omicron infection, symptomatic infection, and severe outcomes (hospitalization or death). Results: We included 13,654 Omicron cases and 205,862 test-negative controls. The marginal effectiveness of a fourth dose (with 95% of fourth dose vaccine recipients receiving mRNA-1273) ≥7 days after vaccination versus a third dose received ≥84 days prior was 19% (95% Confidence Interval [CI], 12-26%) against infection, 31% (95%CI, 20-41%) against symptomatic infection, and 40% (95%CI, 24-52%) against severe outcomes. VE (compared to an unvaccinated group) increased with each additional dose, and for a fourth dose was 49% (95%CI, 43-54%), 69% (95%CI, 61-76%), and 86% (95%CI, 81-90%), against infection, symptomatic infection, and severe outcomes, respectively. Conclusions: Our findings suggest that compared to a third dose received ≥84 days ago, a fourth dose improved protection against infection, symptomatic infection, and severe outcomes caused by Omicron among long-term care residents. Compared to unvaccinated individuals, fourth doses provide strong protection against severe outcomes, but the duration of protection remains unknown.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.15.22273846v2" target="_blank">Effectiveness of a Fourth Dose of COVID-19 Vaccine among Long-Term Care Residents in Ontario, Canada: Test-Negative Design Study</a>
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<li><strong>Trends, variation and clinical characteristics of recipients of antivirals and neutralising monoclonal antibodies for non-hospitalised COVID-19: a descriptive cohort study of 23.4 million people in OpenSAFELY</strong> -
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Objectives Ascertain patient eligibility status and describe coverage of antivirals and neutralising monoclonal antibodies (nMAB) as treatment for COVID-19 in community settings in England. Design Cohort study, approved by NHS England. Setting Routine clinical data from 23.4m people linked to data on COVID-19 infection and treatment, within the OpenSAFELY-TPP database. Participants Non-hospitalised COVID-19 patients at high-risk of severe outcomes. Interventions Nirmatrelvir/ritonavir (Paxlovid), sotrovimab, molnupiravir, casirivimab or remdesivir, administered in the community by COVID-19 Medicine Delivery Units. Results We identified 102,170 non-hospitalised patients with COVID-19 between 11th December 2021 and 28th April 2022 at high-risk of severe outcomes and therefore potentially eligible for antiviral and/or nMAB treatment. Of these patients, 18,210 (18%) received treatment; sotrovimab, 9,340 (51%); molnupiravir, 4,500 (25%); Paxlovid, 4,290 (24%); casirivimab, 50 (&lt;1%); and remdesivir, 20 (&lt;1%). The proportion of patients treated increased from 8% (180/2,380) in the first week of treatment availability to 22% (420/1870) in the latest week. The proportion treated varied by high risk group, lowest in those with Liver disease (12%; 95% CI 11 to 13); by treatment type, with sotrovimab favoured over molnupiravir/Paxlovid in all but three high risk groups: Down syndrome (36%; 95% CI 31 to 40), Rare neurological conditions (46%; 95% CI 44 to 48), and Primary immune deficiencies (49%; 95% CI 48 to 51); by ethnicity, from Black (10%; 95% CI 9 to 11) to White (18%; 95% CI 18 to 19); by NHS Region, from 11% (95% CI 10 to 12) in Yorkshire and the Humber to 23% (95% CI 22 to 24) in the East of England); and by deprivation level, from 12% (95% CI 12 to 13) in the most deprived areas to 21% (95% CI 21 to 22) in the least deprived areas. There was also lower coverage among unvaccinated patients (5%; 95% CI 4 to 7), those with dementia (5%; 95% CI 4 to 6) and care home residents (6%; 95% CI 5 to 6). Conclusions Using the OpenSAFELY platform we were able to identify patients who were potentially eligible to receive treatment and assess the coverage of these new treatments amongst these patients. Targeted activity may be needed to address apparent lower treatment coverage observed among certain groups, in particular (at present): different NHS regions, socioeconomically deprived areas, and care homes.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.03.07.22272026v2" target="_blank">Trends, variation and clinical characteristics of recipients of antivirals and neutralising monoclonal antibodies for non-hospitalised COVID-19: a descriptive cohort study of 23.4 million people in OpenSAFELY</a>
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<li><strong>Diagnostic accuracy of the Panbio™ COVID-19 Antigen rapid test device for SARS-CoV-2 detection in Kenya, 2021: A field evaluation</strong> -
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Background: Accurate and timely diagnosis is essential in limiting the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Real-time reverse transcription-polymerase chain reaction (rRT-PCR), the reference standard, requires specialized laboratories, costly reagents, and a long turnaround time. Antigen rapid diagnostic tests (Ag RDTs) provide a feasible alternative to rRT-PCR since they are quick, relatively inexpensive, and do not require a laboratory. The WHO requires that Ag RDTs have a sensitivity ≥80% and specificity ≥97%. Methods: This evaluation was conducted at 11 health facilities in Kenya between March and July 2021. We enrolled persons of any age with respiratory symptoms and asymptomatic contacts of confirmed COVID-19 cases. We collected demographic and clinical information and two nasopharyngeal specimens from each participant for Ag RDT testing and rRT-PCR. We calculated the diagnostic performance of the Panbio™ Ag RDT against the US Centers for Disease Control and Prevention9s (CDC) rRT-PCR test. Results: We evaluated the Ag RDT in 2,245 individuals where 551 (24.5%, 95% CI: 22.8-26.3%) tested positive by rRT-PCR. Overall sensitivity of the Ag RDT was 46.6% (95% CI: 42.4-50.9%), specificity 98.5% (95% CI: 97.8-99.0%), PPV 90.8% (95% CI: 86.8-93.9%) and NPV 85.0% (95% CI: 83.4-86.6%). Among symptomatic individuals, sensitivity was 60.6% (95% CI: 54.3-66.7%) and specificity was 98.1% (95% CI: 96.7-99.0%). Among asymptomatic individuals, sensitivity was 34.7% (95% CI 29.3-40.4%) and specificity was 98.7% (95% CI: 97.8-99.3%). In persons with onset of symptoms &lt;5 days (594/876, 67.8%), sensitivity was 67.1% (95% CI: 59.2-74.3%), and 53.3% (95% CI: 40.0-66.3%) among those with onset of symptoms &gt;7 days (157/876, 17.9%). The highest sensitivity was 87.0% (95% CI: 80.9-91.8%) in symptomatic individuals with cycle threshold (Ct) values ≤30. Conclusion: The overall sensitivity and NPV of the Panbio™ Ag RDT were much lower than expected. The specificity of the Ag RDT was high and satisfactory; therefore, a positive result may not require confirmation by rRT-PCR. The kit may be useful as a rapid screening tool for only symptomatic patients in high-risk settings with limited access to RT-PCR. A negative result should be interpreted based on clinical and epidemiological information and may require retesting by rRT-PCR.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.23.22275439v2" target="_blank">Diagnostic accuracy of the Panbio™ COVID-19 Antigen rapid test device for SARS-CoV-2 detection in Kenya, 2021: A field evaluation</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Safety and Efficacy Study of Hymecromone Tablets for the Treatment of Patients With COVID-19.</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: Hymecromone tablets;   Other: Placebo<br/><b>Sponsor</b>:   Shanghai Zhongshan Hospital<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Assess the Safety and Immunogenicity of a COVID-19 Vaccine Booster in Healthy Adults</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Biological: Prime-2-CoV_Beta<br/><b>Sponsors</b>:   University Hospital Tuebingen;   FGK Clinical Research GmbH;   VisMederi srl;   Staburo GmbH;   Viedoc Technologies AB<br/><b>Not yet recruiting</b></p></li>
<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>
<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>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Learn About the Study Medicine (Called Nirmatrelvir/Ritonavir) in Pregnant Women With Mild or Moderate COVID-19.</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: nirmatrelvir;   Drug: ritonavir<br/><b>Sponsor</b>:   Pfizer<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of COVID-19 Vaccines Given as a Booster in Healthy Adults in Indonesia (MIACoV Indonesia)</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: Pfizer-BioNTech Standard dose;   Biological: AstraZeneca Standard dose;   Biological: Pfizer-BioNTech Fractional dose;   Biological: AstraZeneca Fractional dose;   Biological: Moderna Standard dose;   Biological: Moderna Fractional dose<br/><b>Sponsors</b>:   Murdoch Childrens Research Institute;   Universitas Padjadjaran (UNPAD);   Universitas Indonesia (UI);   Health Development Policy Agency, Ministry of Health Republic of Indonesia;   Coalition for Epidemic Preparedness Innovations;   The Peter Doherty Institute for Infection and Immunity<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Efficacy and Safety of DXP604 in Patients With Mild to Moderate COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Biological: DXP604<br/><b>Sponsor</b>:   Wuhan Institute of Biological Products Co., Ltd<br/><b>Not yet recruiting</b></p></li>
<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 Research and Development Co., Ltd.<br/><b>Active, not recruiting</b></p></li>
<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>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Sequential Immunization of Two Doses of Inactivated COVID-19 Vaccine (Omicron) in Vaccinated Population Aged 18 Years and Above</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: BIBP Omicron Inactivated COVID-19 vaccine (Vero Cell);   Biological: WIBP Omicron Inactivated COVID-19 vaccine (Vero Cell);   Biological: COVID-19 Vaccine (Vero Cell), Inactivated<br/><b>Sponsors</b>:   China National Biotec Group Company Limited;   Beijing Institute of Biological Products Co Ltd.;   Wuhan Institute of Biological Products Co., Ltd;   The University of Hong Kong<br/><b>Not yet recruiting</b></p></li>
<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 Booster Immunization of COVID-19 Vaccine (Vero Cell), Inactivated (Omicron Variant) in Healthy People Aged 18 Years and Above</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: COVID-19 Vaccine (Vero cell), Inactivated (Omicron variant);   Biological: COVID-19 Vaccine (Vero cell), Inactivated (CZ strain)<br/><b>Sponsor</b>:   Sinovac Research and Development Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
<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>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhaled Interferon α2b Treatment in Mild-to-moderate COVID-19 Infected Children</strong> - <b>Conditions</b>:   COVID-19;   Children<br/><b>Interventions</b>:   Drug: Inhaled Interferon α2b;   Other: Standard of Care<br/><b>Sponsors</b>:   Childrens Hospital of Fudan University;   RenJi Hospital;   Shanghai Childrens Hospital;   Shanghai Childrens Medical Center Affiliated to Shanghai Jiaotong University School of Medicine<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>INTEGrating Ag-RDTs for COVID in MNCH,HIV and TB Services in Cameroon and Kenya:A Cluster Randomized Trial of Two Models</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Diagnostic Test: Test all<br/><b>Sponsors</b>:   Elizabeth Glaser Pediatric AIDS Foundation;   UNITAID;   Kenya Ministry of Health;   Ministry of Public Health, Cameroon<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Paxlovid in the Treatment of COVID-19 Patients With Uremia</strong> - <b>Conditions</b>:   COVID-19;   Uremia<br/><b>Interventions</b>:   Drug: Paxlovid;   Drug: standard-of-care<br/><b>Sponsor</b>:   Ruijin Hospital<br/><b>Not yet 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>What Is an Antibody Test?Characteristics of Antibodies against SARS-CoV-2 and Their Tests</strong> - Antibodies play a major role in immune responses against viruses, which inhibit infection by binding to target viral antigen. Antibodies are induced by viral entry to the body and vaccination that artificially induces immune responses; therefore, antibody tests are used in research for infection history and evaluation of vaccine efficacy. Currently, antibody tests against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) by immunochromatography, enzyme-linked immunosorbent assay…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Suite of TMPRSS2 Assays for Screening Drug Repurposing Candidates as Potential Treatments of COVID-19</strong> - SARS-CoV-2 is the causative viral pathogen driving the COVID-19 pandemic that prompted an immediate global response to the development of vaccines and antiviral therapeutics. For antiviral therapeutics, drug repurposing allows for rapid movement of the existing clinical candidates and therapies into human clinical trials to be tested as COVID-19 therapies. One effective antiviral treatment strategy used early in symptom onset is to prevent viral entry. SARS-CoV-2 enters ACE2-expressing cells…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Synthetic Heparan Sulfate Mimetic Pixatimod (PG545) Potently Inhibits SARS-CoV-2 by Disrupting the Spike-ACE2 Interaction</strong> - Heparan sulfate (HS) is a cell surface polysaccharide recently identified as a coreceptor with the ACE2 protein for the S1 spike protein on SARS-CoV-2 virus, providing a tractable new therapeutic target. Clinically used heparins demonstrate an inhibitory activity but have an anticoagulant activity and are supply-limited, necessitating alternative solutions. Here, we show that synthetic HS mimetic pixatimod (PG545), a cancer drug candidate, binds and destabilizes the SARS-CoV-2 spike protein…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>High-Resolution Magic-Angle Spinning NMR Spectroscopy for Evaluation of Cell Shielding by Virucidal Composites Based on Biogenic Silver Nanoparticles, Flexible Cellulose Nanofibers and Graphene Oxide</strong> - Antiviral and non-toxic effects of silver nanoparticles onto in vitro cells infected with coronavirus were evaluated in this study using High-Resolution Magic-Angle Spinning Nuclear Magnetic Resonance (HR-MAS NMR) spectroscopy. Silver nanoparticles were designed and synthesized using an orange flavonoid-hesperetin (HST)-for reduction of silver(I) and stabilization of as obtained nanoparticles. The bio-inspired process is a simple, clean, and sustainable way to synthesize biogenic silver…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Unravelling the Therapeutic Potential of Botanicals Against Chronic Obstructive Pulmonary Disease (COPD): Molecular Insights and Future Perspectives</strong> - Background: COPD (chronic obstructive pulmonary disease) is a serious health problem worldwide. Present treatments are insufficient and have severe side effects. There is a critical shortage of possible alternative treatments. Medicinal herbs are the most traditional and widely used therapy for treating a wide range of human illnesses around the world. In several countries, different plants are used to treat COPD. Purpose: In this review, we have discussed several known cellular and molecular…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Binding of SARS-CoV-2 protein ORF9b to mitochondrial translocase TOM70 prevents its interaction with chaperone HSP90</strong> - The emergence of the COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a great threat to global health. ORF9b, an important accessory protein of SARS-CoV-2, plays a critical role in the viral host interaction, targeting TOM70, a member of the mitochondrial translocase of the outer membrane complex. The assembly between ORF9b and TOM70 is implicated in disrupting mitochondrial antiviral signaling, leading to immune evasion. We describe the…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>High-throughput drug screening allowed identification of entry inhibitors specifically targeting different routes of SARS-CoV-2 Delta and Omicron/BA.1</strong> - The Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2) has continuously evolved, resulting in the emergence of several variants of concern (VOCs). To study mechanisms of viral entry and potentially identify specific inhibitors, we pseudotyped lentiviral vectors with different SARS-CoV-2 VOC spike variants (D614G, Alpha, Beta, Delta, Omicron/BA.1), responsible for receptor binding and membrane fusion. These SARS-CoV-2 lentiviral pseudoviruses were applied to screen 774 FDA-approved…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Exploration of potential inhibitors for SARS-CoV-2 Mpro considering its mutants via structure-based drug design, molecular docking, MD simulations, MM/PBSA and DFT calculations</strong> - The main protease (Mpro) of SARS-COV-2 plays a vital role in the viral life cycle and pathogenicity. Due to its specific attributes, this 3-chymotrypsin like protease (3Cl-P) can be a reliable target for the drug design to combat COVID-19. Since the advent of COVID-19, Mpro has undergone many mutations. Here, the impact of 10 mutations based on their frequency and 5 more based on their proximity to the active site was investigated. For comparison purposes, the docking process was also performed…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Performance of nasopharyngeal swab and saliva in detecting Delta and Omicron SARS-CoV-2 variants</strong> - A prospective cohort study was conducted during the Delta and Omicron SARS-CoV-2 epidemic waves from paired nasopharyngeal swab (NPS) and saliva samples taken from 624 participants. The study aimed to assess if any differences among participants from both waves could be observed and if any difference in molecular diagnostic performance could be observed among the two sample types. Samples were transported immediately to the laboratory to ensure the highest possible sample quality without any…</p></li>
<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 therapies: do we see substantial progress?</strong> - The appearance of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its spread all over the world is the cause of the coronavirus disease 2019 (COVID-19) pandemic, which has recently resulted in almost 400 million confirmed cases and 6 million deaths, not to mention unknown long-term or persistent side effects in convalescent individuals. In this short review, we discuss approaches to treat COVID-19 that are based on current knowledge of the mechanisms of viral cell receptor…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Structural and biochemical mechanism for increased infectivity and immune evasion of Omicron BA.2 variant compared to BA.1 and their possible mouse origins</strong> - The Omicron BA.2 variant has become a dominant infective strain worldwide. Receptor binding studies show that the Omicron BA.2 spike trimer exhibits 11-fold and 2-fold higher potency in binding to human ACE2 than the spike trimer from the wildtype (WT) and Omicron BA.1 strains. The structure of the BA.2 spike trimer complexed with human ACE2 reveals that all three receptor-binding domains (RBDs) in the spike trimer are in open conformation, ready for ACE2 binding, thus providing a basis for the…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Metformin: Is it a drug for all reasons and diseases?</strong> - Metformin was first used to treat type 2 diabetes in the late 1950s and in 2022 remains the first-choice drug used daily by approximately 150 million people. An accumulation of positive pre-clinical and clinical data has stimulated interest in re-purposing metformin to treat a variety of diseases including COVID-19. In polycystic ovary syndrome metformin improves insulin sensitivity. In type 1 diabetes metformin may help reduce the insulin dose. Meta-analysis and data from pre-clinical and…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Lianhuaqingwen alleviates p53-mediated apoptosis in alveolar epithelial cells to prevent LPS-induced ALI</strong> - CONCLUSION: Lianhuaqingwen inhibits p53-mediated apoptosis in alveolar epithelial cells, thereby preventing LPS-induced ALI.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Investigation on anti-Corona viral potential of Yarrow tea</strong> - Achillea millefolium (Yarrow) is a herbaceous plant of Greek origin noted to treat pneumonia, common cold, cough, and other respiratory disorders. The flowers and leaves are the core part used to prepare herbal tea that gains the worlds recognition as medicinal tea. Coronavirus disease is spreading across the globe, and numerous approaches are lodged to treat virus-induced lung inflammation. Here, we used the network pharmacology, metabolite analysis, docking and molecular simulation and…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Seeking antiviral drugs to inhibit SARS-CoV-2 RNA dependent RNA polymerase: A molecular docking analysis</strong> - COVID-19 outbreak associated with the severe acute respiratory syndrome coronavirus (SARS-CoV-2) raised health concerns across the globe and has been considered highly transmissible between people. In attempts for finding therapeutic treatment for the new disease, this work has focused on examining the polymerase inhibitors against the SARS-CoV-2 nsp12 and co-factors nsp8 and nsp7. Several polymerase inhibitors were examined against PDB ID: 6M71 using computational analysis evaluating the…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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