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208 lines
54 KiB
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<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
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<title>17 April, 2021</title>
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div.column{display: inline-block; vertical-align: top; width: 50%;}
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Decline in rate of divorce and separation filings in Denmark in 2020 compared to previous years</strong> -
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<div>
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The radical changes to everyday life brought on by the COVID-19 pandemic and the closure of non-family social spheres in particular may have impacted marriage dynamics. We provide evidence on the monthly rates of initiation of divorce and separation filings in Denmark for the period 2016-2020 to examine how filing behavior changed during 2020 compared to the four previous years. Because filing rates precedes a divorce, rates reflect more precise the temporal dynamic of divorce initiation. Rates of initiation of divorce filings declined in 2020 to the lowest level in the period 2016-2020. On average, monthly rates in 2020 were 7 percent lower than 2019 rates and 20 percent lower than 2016 rates. There is little indication of the COVID-19 pandemic having an immediate influence on divorce dynamics, although the filing rate was more depressed during lockdown periods.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/hprjb/" target="_blank">Decline in rate of divorce and separation filings in Denmark in 2020 compared to previous years</a>
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<li><strong>Convalescent Plasma Use in the United States was inversely correlated with COVID-19 Mortality: Did Convalescent Plasma Hesitancy cost lives?</strong> -
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Background. The US Food and Drug Administration authorized Convalescent Plasma (CCP) therapy for hospitalized COVID-19 patients with via the Expanded Access Program (EAP) and the Emergency Use Authorization (EUA), leading to its use in some 500,000 patients during the first year of the pandemic. Methods. We tracked the number of CCP units dispensed to hospitals by blood banking organizations and correlated that usage with hospital admission and mortality data over the course of the year. Results. CCP usage per admission peaked in Fall 2020, with > 40% of inpatients estimated to have received CCP between late September and early November 2020. However, after randomized controlled trials failed to show a reduction in mortality, usage/admissions declined steadily to a nadir of < 10% in March 2021. We found a strong inverse correlation (Pearsons correlation coefficient of -0.52 with P = 0.002) between CCP usage/hospital admission and deaths occurring two weeks after admission, and this finding was robust to examination of deaths taking place one, two or three weeks after admission. Changes in the number of hospital admissions, prevalence of variants, and age of patients could not explain these findings. The retreat from CCP usage might have resulted in as many as 29,000 excess deaths from mid-November 2020 to February 2021. Conclusions. A strong inverse correlation between CCP use and mortality per admission in the USA provides population level evidence consistent the notion that CCP reduces mortality in COVID-19 and suggests that the recent decline in usage could have resulted in excess deaths.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.04.07.21255089v2" target="_blank">Convalescent Plasma Use in the United States was inversely correlated with COVID-19 Mortality: Did Convalescent Plasma Hesitancy cost lives?</a>
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</div></li>
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<li><strong>Changes in eating habits and sedentary behavior during the COVID-19 pandemic in adolescents with chronic conditions</strong> -
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Purpose: To report on the impact of the COVID-19 outbreak on eating habits and sedentary behavior among adolescents with multiple chronic conditions (n=347) from a tertiary, referral hospital vs. healthy peers. Methods: This observational study was conducted in Sao Paulo (Brazil) between July and October 2020, period in which a set of social distancing measures to contain the pandemic. Results: The main findings of this study were that adolescents with chronic conditions showed important changes in eating habits (e.g., less often consumption of convenience foods and more often eating in front of television than before quarantine). Also, 86.8% of adolescents with chronic conditions reported increasing screen time during pandemic. No major differences were observed between patients and controls. Conclusions: Adolescents with chronic conditions exposed to pandemic showed substantial changes in lifestyle, stressing the need for specific care to mitigate poor eating habits and excessive sedentary behavior in this group.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.04.16.21255582v1" target="_blank">Changes in eating habits and sedentary behavior during the COVID-19 pandemic in adolescents with chronic conditions</a>
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<li><strong>More than a year after the onset of the CoVid-19 pandemic in the UK: lessons learned from a minimalistic model capturing essential features including social awareness and policy making</strong> -
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The number of new daily SARS-CoV-2 infections experienced an abrupt increase during the last quarter of 2020 in almost every European country. The phenomenological explanation offered was a new mutation of the virus, first identified in the UK. We use publicly available data in combination with a time-delayed controlled SIR model, which captures the effects of preventive measures and concomitant social response on the spreading of the virus. The model, which has a unique transmission rate, enables us to reproduce the waves of infection occurred in the UK. This suggests that the new SARS-CoV-2 UK variant is as transmissible as previous strains. Our findings reveal that the sudden surge in cases was in fact related to the relaxation of preventive measures and social awareness. We also simulate the combined effects of restrictions and vaccination campaigns in 2021, demonstrating that lockdown policies are not fully effective to flatten the curve; fully effective mitigation can only be achieved via a vigorous vaccination campaign. As a matter of fact, incorporating recent data about vaccine efficacy, our simulations advocate that the UK might have overcome the worse of the CoVid-19 pandemic, provided that the vaccination campaign maintains a rate of approximately 140k jabs per day.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.04.15.21255510v1" target="_blank">More than a year after the onset of the CoVid-19 pandemic in the UK: lessons learned from a minimalistic model capturing essential features including social awareness and policy making</a>
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</div></li>
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<li><strong>SARS-CoV-2 RNA load in the lower respiratory tract, viral RNAemia and N-antigenemia in critically ill adult COVID-19 patients: relationship with biomarkers of disease severity</strong> -
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Background: Little is known about the comparative kinetics of SARS-CoV-RNA load in the lower respiratory tract and in blood compartment in patients admitted to the intensive care unit, and how these relate to biomarkers of COVID-19 severity. Methods: Seventy-three consecutive critically ill COVID-19 patients (median age, 65 years) were recruited. Serial lower respiratory tract (n=165) and plasma (n=340) specimens were collected. RT-PCR and lateral flow immunochromatography assay were used for SARS-CoV-2 RNA quantitation and N protein detection in plasma, respectively. Serum levels of inflammatory and tissue-damage biomarkers in paired specimens were analyzed. Results: SARS-CoV-RNA was detected in the lower respiratory tract of most patients (92%). Viral RNAemia and N-antigenemia were documented in 35.6% and 40.1% of patients, respectively. Viral RNAemia and N-antigenemia cleared at a faster rate than SARS-CoV-2 RNA in tracheal aspirates (TA). SARS-CoV-2 RNA load was higher (P<0.001) in TA than in plasma, and correlated significantly (Rho, 0.41; P<0.001). A modest correlation was found between SARS-CoV-2 RNA load in TA and plasma and levels of ferritin and lactose dehydrogenase (Rho≤0.3; P≤0.008) in paired serum specimens. Neither the dynamics of SARS-CoV-2 RNA load in TA and plasma, nor N-antigenemia detection rate differed between surviving and deceased patients. Yet, a trend towards a higher mortality was seen in patients with viral RNAemia (OR; 2.82; 95% CI, 0.94-8.47; P=0.06).
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.04.16.21255601v1" target="_blank">SARS-CoV-2 RNA load in the lower respiratory tract, viral RNAemia and N-antigenemia in critically ill adult COVID-19 patients: relationship with biomarkers of disease severity</a>
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<li><strong>Longitudinal detection of SARS-CoV-2-specific antibody responses with different serological methods</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Serological testing for anti-SARS-CoV-2 antibodies is used to detect ongoing or past SARS-CoV-2 infections. To study the kinetics of anti-SARS-CoV-2 antibodies and to assess the diagnostic performances of eight serological assays, we used 129 serum samples collected on known days post symptom onset (dpso) from 42 patients with PCR-confirmed COVID-19 and 54 serum samples from healthy blood donors, and children infected with seasonal coronaviruses. The sera were analyzed for the presence of IgG, IgM and IgA antibodies using indirect immunofluorescence testing (IIFT) based on SARS-CoV-2-infected cells. They were further tested for antibodies against the S1 domain of the SARS-CoV-2 spike protein (IgG, IgA) and against the viral nucleocapsid protein (IgG, IgM) using ELISA. The assay specificities were 94.4%-100%. The sensitivities varied largely between assays, reflecting their respective purposes. The sensitivities of IgA and IgM assays were highest between 11 and 20 dpso, whereas the sensitivities of IgG assays peaked between 20 and 60 dpso. IIFT showed highest sensitivities due to the use of the whole SARS-CoV-2 as substrate and provided information whether or not the individual has been infected with SARS-CoV-2. ELISAs provided further information about both the prevalence and concentration of specific antibodies against selected antigens of SARS-CoV-2.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.04.16.21255608v1" target="_blank">Longitudinal detection of SARS-CoV-2-specific antibody responses with different serological methods</a>
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<li><strong>IL-1 Mediates Tissue Specific Inflammation and Severe Respiratory Failure In Covid-19: Clinical And Experimental Evidence</strong> -
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Background: Acute respiratory distress syndrome (ARDS) in COVID-19 has been associated with dysregulated immune responses leading to catastrophic inflammation. The activation pathways remain to be fully elucidated. We investigated the ability of circulating to induce dysregulated immune responses. Materials & Methods: Calprotectin and high mobility group box 1 (HMGB1) were associated with ARDS in 60 COVID-19 patients. In a second cohort of 40 COVID-19 patients calprotectin at hospital admission was associated with serum levels of soluble urokinase plasminogen activator receptor (suPAR). A COVID-19 animal model was developed by intravenous injection of plasma from healthy volunteers or patients with COVID-19 ARDS into C57/BL6 mice once daily for 3 consecutive days. In separate experiments, mice were treated with a) the IL-1 receptor antagonist Anakinra or vehicle and b) Flo1-2a anti-murine anti-IL-1α monoclonal antibody or the specific anti-human IL-1α antibody XB2001, or isotype controls. Mice were sacrificed on day 4. Cytokines and myeloperoxidase (MPO) in tissues were measured. Results: Calprotectin, but not HMGB1, was elevated ARDS. Higher suPAR readouts indicated higher calprotectin levels. CHallenge of mice with COVID-19 plasma led to inflammatory reactions in murine lung and intestines as evidenced by increased levels of TNFα, IL-6, IFNγ and MPO. Anakinra treatment brought these levels down. Similar decrease was found in mice treated with Flo1-2a but not with XB2001. Conclusion: Circulating alarmins, specifically calprotectin, of critically ill COVID-19 patients induces tissue-specific inflammatory responses through an IL-1α mediated mechanism. This could be attenuated through inhibition of IL-1 receptor or specific inhibition of IL-1α.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.04.09.21255190v2" target="_blank">IL-1 Mediates Tissue Specific Inflammation and Severe Respiratory Failure In Covid-19: Clinical And Experimental Evidence</a>
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<li><strong>Improved screening of COVID-19 cases through a Bayesian network symptoms model and psychophysical olfactory test</strong> -
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The infectiousness and presymptomatic transmission of SARS-CoV-2 hinder pandemic control efforts worldwide. Therefore, the frequency of testing, accessibility, and immediate results are critical for reopening societies until an effective vaccine becomes available for a substantial proportion of the population. The loss of sense of smell is among the earliest, most discriminant, and prevalent symptoms of COVID-19, with 75-98% prevalence when clinical olfactory tests are used. Frequent screening for olfactory dysfunction could substantially reduce viral spread. However, olfactory dysfunction is generally self-reported, which is problematic as partial olfactory impairment is broadly unrecognized. To address this limitation, we developed a rapid psychophysical olfactory test (KOR) deployed on a web platform for automated reporting and traceability based on a low-cost (about USD 0.50/test), six-odor olfactory identification kit. Based on test results, we defined an anosmia score -a classifier for olfactory impairment-, and a Bayesian Network (BN) model that incorporates other symptoms for detecting COVID-19. We trained and validated the BN model on two samples: suspected COVID-19 cases in five healthcare centers (n=926; 32% COVID-19 prevalence) and healthy (asymptomatic) mining workers (n=1,365; 1.1% COVID-19 prevalence). All participants had COVID-19 assessment by RT-PCR assay. Using the BN model, we predicted COVID-19 status with 76% accuracy (AUC=0.79 [0.75-0.82]) in the healthcare sample and 84% accuracy (AUC=0.71 [0.63-0.79]) among miners. The KOR test and BN model enabled the detection of COVID-19 cases that otherwise appeared asymptomatic. Our results confirmed that olfactory dysfunction is the most discriminant symptom to predict COVID-19 status when based on olfactory function measurements. Overall, this work highlights the potential for low-cost, frequent, accessible, routine testing for COVID-19 surveillance to aid society9s reopening.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.01.18.21249821v2" target="_blank">Improved screening of COVID-19 cases through a Bayesian network symptoms model and psychophysical olfactory test</a>
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<li><strong>SARS-CoV-2 Immunogenicity in individuals infected before and after COVID-19 vaccination: Israel, January-March 2021: Implications for vaccination policy</strong> -
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Between December 2020-March 2021 we measured anti-SARS-CoV-2 IgG titers post-vaccination with the BNT162b2 vaccine among 725 Israeli hospital workers. Previously infected individuals who received one dose had higher IgG titres than fully vaccinated, never-infected workers. Post-vaccination infection did not increase IgG titres. Individuals infected post-dose one should receive the second.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.04.11.21255273v1" target="_blank">SARS-CoV-2 Immunogenicity in individuals infected before and after COVID-19 vaccination: Israel, January-March 2021: Implications for vaccination policy</a>
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<li><strong>The impact of the COVID-19 pandemic on influenza, respiratory syncytial virus, and other seasonal respiratory virus circulation in Canada</strong> -
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Background The ongoing coronavirus disease 2019 (COVID-19) pandemic has resulted in implementation of public health measures worldwide to mitigate disease spread, including; travel restrictions, lockdowns, messaging on handwashing, use of face coverings and physical distancing. As the pandemic progresses, exceptional decreases in seasonal respiratory viruses are increasingly reported. We aimed to evaluate the impact of the pandemic on circulation of influenza, respiratory syncytial virus and other seasonal respiratory viruses in Canada. Methods Epidemiologic data were obtained from the Canadian Respiratory Virus Detection Surveillance System. Weekly data from the week ending 30th August 2014 until the week ending the 13th February 2021 were analysed. We compared trends in laboratory detection and test volumes during the 2020/2021 influenza season with baseline pre-pandemic seasons from 2014 to 2019. Findings We observed a dramatically lower percentage of tests positive for all seasonal respiratory viruses during 2020-2021 compared to baseline. For influenza A and B the percent positive decreased to 0.0017 and 0.0061 times that of baseline respectively and for RSV, the percent positive dropped to 0.0145 times that of baseline. Ongoing detection of enterovirus/rhinovirus occurred, with regional variation in the epidemic patterns and intensity. Interpretation We report an effective absence of the annual seasonal epidemic of most seasonal respiratory viruses in 2020/2021. This dramatic decrease is likely related to implementation of multi-layered public health measures during the pandemic. The impact of such measures may have relevance for public health practice in mitigating seasonal respiratory virus epidemics and for informing responses to future respiratory virus pandemics.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.04.15.21255591v1" target="_blank">The impact of the COVID-19 pandemic on influenza, respiratory syncytial virus, and other seasonal respiratory virus circulation in Canada</a>
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<li><strong>Humoral and cellular immune responses against SARS-CoV-2 variants and human coronaviruses after single BNT162b2 vaccination.</strong> -
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Vaccine-induced neutralizing antibodies are key in combating the COVID-19 pandemic. However, delays of boost immunization due to limited availability of vaccines may leave individuals vulnerable to infection and disease for prolonged periods. The emergence of SARS-CoV-2 variants of concern (VOC), B.1.1.7 (United Kingdom), B.1.351 (South Africa) and P.1 (Brazil), may reinforce this issue with the latter two being able to evade control by antibodies. We assessed humoral and T cell responses against SARS-CoV-2 WT and VOC and endemic human coronaviruses (hCoV) that were induced after single and double vaccination with BNT162b2. Despite readily detectable IgG against the receptor-binding domain (RBD) of the SARS-CoV-2 S protein at day 14 after a single vaccination, inhibition of SARS-CoV-2 S-driven host cell entry was weak and particularly low for the B.1.351 variant. Frequencies of SARS-CoV-2 specific T cells were low in many vaccinees after application of a single dose and influenced by immunity against endemic hCoV. The second vaccination significantly boosted T cell frequencies reactive for WT, B.1.1.7 and B.1.351 variants. These results call into question whether neutralizing antibodies significantly contribute to protection against COVID-19 upon single vaccination and suggest that cellular immunity is central for the early defenses against COVID-19.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.04.16.21255412v1" target="_blank">Humoral and cellular immune responses against SARS-CoV-2 variants and human coronaviruses after single BNT162b2 vaccination.</a>
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<li><strong>Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2 mRNA vaccinated individuals</strong> -
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The SARS-CoV-2 pandemic has been raging for over a year, creating global detrimental impact. The BNT162b2 mRNA vaccine has demonstrated high protection levels, yet apprehension exists that several variants of concerns (VOCs) can surmount the immune defenses generated by the vaccines. Neutralization assays have revealed some reduction in neutralization of VOCs B.1.1.7 and B.1.351, but the relevance of these assays in real life remains unclear. Here, we performed a case-control study that examined whether BNT162b2 vaccinees with documented SARS-CoV-2 infection were more likely to become infected with B.1.1.7 or B.1.351 compared with unvaccinated individuals. Vaccinees infected at least a week after the second dose were disproportionally infected with B.1.351 (odds ratio of 8:1). Those infected between two weeks after the first dose and one week after the second dose, were disproportionally infected by B.1.1.7 (odds ratio of 26:10), suggesting reduced vaccine effectiveness against both VOCs under different dosage/timing conditions. Nevertheless, the B.1.351 incidence in Israel to-date remains low and vaccine effectiveness remains high against B.1.1.7, among those fully vaccinated. These results overall suggest that vaccine breakthrough infection is more frequent with both VOCs, yet a combination of mass-vaccination with two doses coupled with non-pharmaceutical interventions control and contain their spread.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.04.06.21254882v2" target="_blank">Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2 mRNA vaccinated individuals</a>
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<li><strong>Genomic epidemiology of SARS-CoV-2 in Russia reveals recurring cross-border transmission throughout 2020</strong> -
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SARS-CoV-2 has spread rapidly across the globe, with most nations failing to prevent or substantially delay its introduction. While many countries have imposed some limitations on trans-border passenger traffic, the effect of these measures on the spread of COVID-19 strains remains unclear. Here, we report an analysis of whole-genome sequencing of 3206 SARS-CoV-2 samples from 78 regions of Russia covering the period between March and November 2020. We describe recurring imports of multiple COVID-19 strains throughout this period, giving rise to 457 uniquely Russian transmission lineages, as well as repeated cross-border transmissions of local circulating variants out of Russia.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.03.31.21254115v2" target="_blank">Genomic epidemiology of SARS-CoV-2 in Russia reveals recurring cross-border transmission throughout 2020</a>
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<li><strong>Characterising post-COVID syndrome more than 6 months after acute infection in adults; prospective longitudinal cohort study, England</strong> -
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Background Most individuals with COVID-19 will recover without sequelae, but some will develop long-term multi-system impairments. The definition, duration, prevalence and symptoms associated with long COVID, however, have not been established. Methods Public Health England (PHE) initiated longitudinal surveillance of clinical and non-clinical healthcare workers for monthly assessment and blood sampling for SARS-CoV-2 antibodies in March 2020. Eight months after enrolment, participants completed an online questionnaire including 72 symptoms in the preceding month. Symptomatic mild-to-moderate cases with confirmed COVID-19 were compared with asymptomatic, seronegative controls. Multivariable logistic regression was used to identify independent symptoms associated with long COVID. Findings All 2,147 participants were contacted and 1,671 (77.8%) completed the questionnaire, including 140 (8.4%) cases and 1,160 controls. At a median of 7.5 (IQR 7.1-7.8) months after infection, 20 cases (14.3%) had ongoing (4/140, 2.9%) or episodic (16/140, 11.4%) symptoms. We identified three clusters of symptoms associated with long COVID, those affecting the sensory (ageusia, anosmia, loss of appetite and blurred vision), neurological (forgetfulness, short-term memory loss and confusion/brain fog) and cardiorespiratory (chest tightness/pain, unusual fatigue, breathlessness after minimal exertion/at rest, palpitations) systems. The sensory cluster had the highest association with being a case (aOR 5.25, 95% CI 3.45-8.01). Dermatological, gynaecological, gastrointestinal or mental health symptoms were not significantly different between cases and controls. Interpretation Most persistent symptoms reported following mild COVID-19 were equally common in cases and controls. While all three clusters identified had a strong association with cases, the sensory cluster had the highest specificity and strength of association, and therefore, most likely to be characteristic of long COVID.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.03.18.21253633v2" target="_blank">Characterising post-COVID syndrome more than 6 months after acute infection in adults; prospective longitudinal cohort study, England</a>
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<li><strong>Viral neuroinvasion and neurotropism without neuronal damage in the hACE2 mouse model of COVID-19</strong> -
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Coronavirus disease 2019 (COVID-19) is a primarily respiratory disease with variable clinical courses for which animal models are needed to gather insights into the pathogenesis of its causative virus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), in human patients. SARS-CoV-2 not only affects the respiratory tract but also the central nervous system (CNS), leading to neurological symptoms such as loss of smell and taste, headache, fatigue or severe complications like cerebrovascular diseases. Transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) under the cytokeratin 18 promoter (K18-hACE2) represent a well-known model of SARS-CoV-2 infection. In the present study, it served to investigate the spatiotemporal distribution and pathomorphological features in the CNS following intranasal infection with relatively low SARS-CoV-2 doses and after prior influenza A virus infection. In K18-hACE2 mice, SARS-CoV-2 was found to frequently spread to and within the CNS during the later phase (day 7) of infection. Infection was restricted to neurons and appeared to first affect the olfactory bulb and spread from there mainly in basally orientated regions in the brain and into the spinal cord, in a dose dependent manner and independent of ACE2 expression. Neuronal infection was not associated with cell death, axonal damage or demyelination. However, microglial activation, microgliosis and a mild macrophage and T cell dominated inflammatory response was consistently observed. This was accompanied by apoptotic death of endothelial, microglial and immune cells, without evidence of viral infection of glial cells, endothelial cells and leukocytes. Taken together, microgliosis and immune cell apoptosis indicate a potential important role of microglial cells for the pathogenesis and viral effect in COVID-19 and possible impairment of neurological functions, especially in long COVID. These data may also be informative for the selection of therapeutic candidates, and broadly support investigation of agents with adequate penetration into relevant regions of the CNS.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.04.16.440173v1" target="_blank">Viral neuroinvasion and neurotropism without neuronal damage in the hACE2 mouse model of COVID-19</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>Clinical Study in the Treatment of Patients With Moderate Course of COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: COVID-globulin; Drug: Placebo<br/><b>Sponsor</b>: Microgen<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>Rehabilitation for Patients With Persistent Symptoms Post COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Other: Concentrated rehabilitation for patients with persistent symptoms post COVID-19<br/><b>Sponsors</b>: Western Norway University of Applied Sciences; Helse-Bergen HF<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>A Nurse-Community Health Worker-Family Partnership Model: Addressing Uptake of COVID-19 Testing and Control Measures</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: Nurse-Community-Family Partnership Intervention<br/><b>Sponsor</b>: New York University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy and Safety of Three Different Doses of an Anti SARS-CoV-2 Hyperimmune Equine Serum in COVID-19 Patients</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Biological: Anti SARS-CoV-2 equine hyperimmune serum; Biological: placebo<br/><b>Sponsors</b>: Caja Costarricense de Seguro Social; Universidad de Costa Rica; Ministry of Health Costa Rica<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>Viral Clearance, PK and Tolerability of Ensovibep in COVID-19 Patients</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Drug: ensovibep<br/><b>Sponsor</b>: Molecular Partners AG<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>A Clinical Study Evaluating Inhaled Aviptadil on COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Inhaled Aviptadil; Drug: Placebo<br/><b>Sponsors</b>: Centurion Pharma; Klinar CRO<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>ACTIV-3b: Therapeutics for Severely Ill Inpatients With COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Biological: Remdesivir; Drug: Remdesivir placebo; Biological: VIP; Drug: VIP Placebo; Drug: Corticosteroid<br/><b>Sponsors</b>: National Institute of Allergy and Infectious Diseases (NIAID); International Network for Strategic Initiatives in Global HIV Trials (INSIGHT); University of Copenhagen; Medical Research Council; Kirby Institute; Washington D.C. Veterans Affairs Medical Center; AIDS Clinical Trials Group; National Heart, Lung, and Blood Institute (NHLBI); US Department of Veterans Affairs; Prevention and Early Treatment of Acute Lung Injury (PETAL); Cardiothoracic Surgical Trials Network (CTSN); NeuroRx, Inc.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Effects of a Multi-factorial Rehabilitation Program for Healthcare Workers Suffering From Post-COVID-19 Fatigue Syndrome</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: Exercise<br/><b>Sponsor</b>: Medical University of Vienna<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety and Immunogenicity of the Inactivated Koçak-19 Inaktif Adjuvanlı COVID-19 Vaccine Compared to Placebo</strong> - <b>Condition</b>: COVID-19 Vaccine<br/><b>Interventions</b>: Biological: Koçak-19 Inaktif Adjuvanlı COVID-19 Vaccine 4 µg/0.5 ml Vaccine; Biological: Koçak-19 Inaktif Adjuvanlı COVID-19 Vaccine 6 µg/0.5 ml Vaccine; Biological: Placebo<br/><b>Sponsor</b>: Kocak Farma<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study on Sequential Immunization of Recombinant COVID-19 Vaccine (Ad5 Vector) and RBD-based Protein Subunit Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: recombinant Ad5 vectored COVID-19 vaccine; Biological: RBD-based protein subunit vaccine (ZF2001) against COVID-19; Biological: trivalent split influenza vaccine<br/><b>Sponsor</b>: Jiangsu Province Centers for Disease Control and Prevention<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>Total-Body Parametric 18F-FDG PET of COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Device: uEXPLORER/mCT<br/><b>Sponsor</b>: University of California, Davis<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>Cetirizine and Famotidine for COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Cetirizine and Famotidine; Drug: Placebo<br/><b>Sponsor</b>: Emory University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>TCB008 in Patients With COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Drug: TCB008<br/><b>Sponsor</b>: TC Biopharm<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>Omega-3 Oil Use in COVID-19 Patients in Qatar</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Omega 3 fatty acid<br/><b>Sponsor</b>: Hamad Medical Corporation<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>COVID-19 Supplemental Vaccine Boost to Enhance T Cell Protection in Those Who Have Already Received EUA S-Based Vaccines</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Biological: hAd5-S-Fusion+N-ETSD vaccine<br/><b>Sponsor</b>: ImmunityBio, Inc.<br/><b>Recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Novel inhibitors of the main protease enzyme of SARS-CoV-2 identified via molecular dynamics simulation-guided in vitro assay</strong> - For the COVID-19 pandemic caused by SARS-CoV-2, there are currently no effective drugs or vaccines to treat this coronavirus infection. In this study, we focus on the main protease enzyme of SARS-CoV-2, 3CL^(pro), which is critical for viral replication. We employ explicit solvent molecular dynamics simulations of about 150 compounds docked into 3CL^(pro)’s binding site and that had emerged as good main protease ligands from our previous in silico screening of over 1.2 million compounds. By…</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>Induction of Exaggerated Cytokine Production in Human Peripheral Blood Mononuclear Cells by a Recombinant SARS-CoV-2 Spike Glycoprotein S1 and Its Inhibition by Dexamethasone</strong> - An understanding of the pathological inflammatory mechanisms involved in SARS-CoV-2 virus infection is necessary in order to discover new molecular pharmacological targets for SARS-CoV-2 cytokine storm. In this study, the effects of a recombinant SARS-CoV-2 spike glycoprotein S1 was investigated in human peripheral blood mononuclear cells (PBMCs). Stimulation of PBMCs with spike glycoprotein S1 (100 ng/mL) resulted in significant elevation in the production of TNFα, IL-6, IL-1β and IL-8….</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>Polysulfates block SARS-CoV-2 uptake via electrostatic interactions</strong> - Here we report that negatively charged polysulfates can bind to the spike protein of SARS-CoV-2 via electrostatic interactions. Using a plaque reduction assay, we compare inhibition of SARS-CoV-2 by heparin, pentosan sulfate, linear polyglycerol sulfate (LPGS) and hyperbranched polyglycerol sulfate (HPGS). Highly sulfated LPGS is the optimal inhibitor, with a half-maximal inhibitory concentration (IC 50 ) of 67 μg/mL (approx. 1.6 μM). This synthetic polysulfate exhibits more than 60-fold higher…</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>Wuhan to World: The COVID-19 Pandemic</strong> - COVID-19 is a Severe Acute Respiratory Syndrome (SARS), caused by SARS-CoV-2, a novel virus which belongs to the family Coronaviridae. It was first reported in December 2019 in the Wuhan city of China and soon after, the virus and hence the disease got spread to the entire world. As of February 26, 2021, SARS-CoV-2 has infected ~112.20 million people and caused ~2.49 million deaths across the globe. Although the case fatality rate among SARS-CoV-2 patient is lower (~2.15%) than its earlier…</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 of flexible electrochemical impedance spectroscopy-based biosensing platform for rapid screening of SARS-CoV-2 inhibitors</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the cells through the binding of its spike protein (S-protein) to the cell surface-expressing angiotensin-converting enzyme 2 (ACE2). Thus, inhibition of S-protein-ACE2 binding may impede SARS-CoV-2 cell entry and attenuate the progression of Coronavirus disease 2019 (COVID-19). In this study, an electrochemical impedance spectroscopy-based biosensing platform consisting of a recombinant ACE2-coated palladium nano-thin-film…</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 mutations acquired in mink reduce antibody-mediated neutralization</strong> - Transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from humans to farmed mink has been observed in Europe and the US. In the infected animals, viral variants arose that harbored mutations in the spike (S) protein, the target of neutralizing antibodies, and these variants were transmitted back to humans. This raised concerns that mink might become a constant source of human infection with SARS-CoV-2 variants associated with an increased threat to human health 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>Synergistic Inhibition of SARS-CoV-2 Replication Using Disulfiram/Ebselen and Remdesivir</strong> - The SARS-CoV-2 replication and transcription complex (RTC) comprising nonstructural protein (nsp) 2-16 plays crucial roles in viral replication, reducing the efficacy of broad-spectrum nucleoside analog drugs such as remdesivir and evading innate immune responses. Most studies target a specific viral component of the RTC such as the main protease or the RNA-dependent RNA polymerase. In contrast, our strategy is to target multiple conserved domains of the RTC to prevent SARS-CoV-2 genome…</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>Intriguing Antiviral Modified Nucleosides: A Retrospective View into the Future Treatment of COVID-19</strong> - Great pioneers of nucleic acid chemistry had elucidated nucleic acid functions and structures and developed various antiviral modified nucleoside drugs. It is possible in theory that antiviral modified nucleosides prevent viral replication by inhibiting viral polymerases. However, biological phenomena far exceed our predictions at times. We describe the characteristics of the approved antiviral modified nucleosides from an organic chemistry perspective. Also, based on our experiences 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>Angiotensin Receptor Blockers for COVID-19: Pathophysiological and Pharmacological Considerations About Ongoing and Future Prospective Clinical Trials</strong> - COVID-19 pandemic demands a swift response to find therapeutic tools that effectively reduce morbidity and mortality. Despite initial fears, evidence from retrospective observational studies supports the inhibition of the renin-angiotensin system as an emerging pathway to delay or moderate angiotensin II-driven lung inflammation. This has triggered several prospective clinical trials. In this commentary we provide an overview and analysis of current ongoing clinical trials aimed at evaluating…</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>Epstein-Barr virus lytic replication induces ACE2 expression and enhances SARS CoV-2 pseudotyped virus entry in epithelial cells</strong> - Understanding factors that affect the infectivity of SARS CoV-2 is central to combatting COVID-19. The virus surface spike protein of SARS CoV-2 mediates viral entry into cells by binding to the ACE2 receptor on epithelial cells and promoting fusion. We find that Epstein-Barr virus (EBV) induces ACE2 expression when it enters the lytic replicative cycle in epithelial cells. By using VSV particles pseudotyped with the SARS CoV-2 spike protein, we show that lytic EBV replication enhances…</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>C5aR inhibition of non-immune cells suppresses inflammation and maintains epithelial integrity in SARS-CoV-2-infected primary human airway epithelia</strong> - CONCLUSION: Crucially, we illustrate here for the first time, that targeting the anaphylotoxin receptors C3aR and C5aR in non-immune respiratory cells can prevent intrinsic lung inflammation and tissue damage. This opens up the exciting possibility in the treatment of COVID-19.</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>Hypoxic and pharmacological activation of HIF inhibits SARS-CoV-2 infection of lung epithelial cells</strong> - COVID-19, caused by the novel coronavirus SARS-CoV-2, is a global health issue with more than 2 million fatalities to date. Viral replication is shaped by the cellular microenvironment, and one important factor to consider is oxygen tension, in which hypoxia inducible factor (HIF) regulates transcriptional responses to hypoxia. SARS-CoV-2 primarily infects cells of the respiratory tract, entering via its spike glycoprotein binding to angiotensin-converting enzyme 2 (ACE2). We demonstrate that…</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>Vaccine-induced immune thrombotic thrombocytopenia (VITT): targeting pathomechanisms with Bruton tyrosine kinase inhibitors</strong> - A series of cases with rare thromboembolic incidents including cerebral sinus vein thrombosis (some of them fatal) and concomitant thrombocytopenia occurring shortly after vaccination with the COVID-19 vaccine AZD1222 (Vaxzevria) has caused significant concern and led to its temporary suspension in many countries. Immediate laboratory efforts in four of these patients have identified a tentative pathomechanism underlying this syndrome termed vaccine-induced prothrombotic immune thrombocytopenia…</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>Mendelian randomisation identifies alternative splicing of the FAS death receptor as a mediator of severe COVID-19</strong> - Severe COVID-19 is characterised by immunopathology and epithelial injury. Proteomic studies have identified circulating proteins that are biomarkers of severe COVID-19, but cannot distinguish correlation from causation. To address this, we performed Mendelian randomisation (MR) to identify proteins that mediate severe COVID-19. Using protein quantitative trait loci (pQTL) data from the SCALLOP consortium, involving meta-analysis of up to 26,494 individuals, and COVID-19 genome-wide association…</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>Structural basis for broad sarbecovirus neutralization by a human monoclonal antibody</strong> - The recent emergence of SARS-CoV-2 variants of concern (VOC) and the recurrent spillovers of coronaviruses in the human population highlight the need for broadly neutralizing antibodies that are not affected by the ongoing antigenic drift and that can prevent or treat future zoonotic infections. Here, we describe a human monoclonal antibody (mAb), designated S2×259, recognizing a highly conserved cryptic receptor-binding domain (RBD) epitope and cross-reacting with spikes from all sarbecovirus…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Compositions and methods for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU321590214">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>5-(4-TERT-BUTOXY PHENYL)-3-(4N-OCTYLOXYPHENYL)-4,5-DIHYDROISOXAZOLE MOLECULE (C-I): A PROMISING DRUG FOR SARS-COV-2 (TARGET I) AND BLOOD CANCER (TARGET II)</strong> - The present invention relates to a method ofmolecular docking of crystalline compound (C-I) with SARS-COV 2 proteins and its repurposing with proteins of blood cancer, comprising the steps of ; employing an algorithmto carry molecular docking calculations of the crystalized compound (C-I); studying the compound computationally to understand the effect of binding groups with the atoms of the amino acids on at least four target proteins of SARS-COV 2; downloading the structure of the proteins; removing water molecules, co enzymes and inhibitors attached to the enzymes; drawing the structure using Chem Sketch software; converting the mol file into a PDB file; using crystalized compound (C-I) for comparative and drug repurposing with two other mutated proteins; docking compound into the groove of the proteins; saving format of docked molecules retrieved; and filtering and docking the best docked results. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN320884617">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>AQUEOUS ZINC OXIDE NANOSPRAY COMPOSITIONS</strong> - Disclosed herein is aqueous zinc oxide nano spray compositions comprising zinc oxide nanoparticles and a synthetic surfactant for controlling the spread of Covid-19 virus. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN321836709">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>一种肝素类药物组合物、喷鼻剂及其制备方法及应用</strong> - 本发明公开了一种肝素类药物组合物、喷鼻剂及其制备方法及应用。该肝素类药物组合物包括肝素钠和阿比朵尔。本发明中的肝素类药物组合物首次采用肝素钠和阿比朵尔联合使用，普通肝素钠联合1μM/L以上的阿比朵尔病毒抑制效率显著高于单独普通肝素钠或单独阿比多尔组（p<0.05）。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN321712860">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>USING CLINICAL ONTOLOGIES TO BUILD KNOWLEDGE BASED CLINICAL DECISION SUPPORT SYSTEM FOR NOVEL CORONAVIRUS (COVID-19) WITH THE ADOPTION OF TELECONFERENCING FOR THE PRIMARY HEALTH CENTRES/SATELLITE CLINICS OF ROYAL OMAN POLICE IN SULTANATE OF OMAN</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU320796026">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>抗SARS-COV-2中和抗体</strong> - 本公开提供了针对SARS‑COV‑2的新颖中和抗体和其抗原结合片段。还提供了包括其的药物组合物和试剂盒以及其用途。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN321712812">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Peptides and their use in diagnosis of SARS-CoV-2 infection</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU319943278">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Method and compositions for treating coronavirus infection</strong> - A method of treating viral infection, such as viral infection caused by a virus of the Coronaviridae family, is provided. A composition having at least oleandrin is used to treat viral infection. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU319943054">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">**一种4-肟-5<code>-（2-甲基丙酰基）尿苷的制备方法** - 本发明公开了一种4‑肟‑5</code>‑（2‑甲基丙酰基）尿苷的制备方法，包括：S1：在酸存在条件下，使得化合物1和2,2‑二甲氧基丙烷在有机溶剂中反应得到化合物2；S2：在碱存在条件下，使得化合物2在有机溶剂中反应得到化合物3；S3：在羟胺水溶液存在条件下使化合物3在有机溶剂中反应得到化合物4；S4：在酸存在条件下使化合物4在有机溶剂中反应得到化合物I。本发明制备得到的结晶性能良好的固体，且制备条件简单，转化率以及原子经济性好。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN321712529">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>一种COVID-19假病毒及其制备方法和用途</strong> - 本发明涉及生物技术领域，特别是涉及一种COVID‑19假病毒及其制备方法和用途本发明，所述COVID‑19假病毒由外壳蛋白质粒与辅助质粒经病毒包装而成，所述外壳蛋白质粒包括表达COVID‑19 S蛋白的质粒、表达COVID‑19 M蛋白的质粒和表达COVID‑19 E蛋白的质粒。本发明的COVID‑19假病毒采用三质粒系统包装，以S/M/E蛋白替代表达VSV‑G蛋白，比仅含有S蛋白的假病毒感染能力更强、灵敏度更高。而且，COVID‑19假病毒携带两种荧光报告基团，不同的荧光报告基团可应用于不同的场景，使得COVID‑19假病毒应用时更简便。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN321712520">link</a></p></li>
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