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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>
</ul>
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
<ul>
<li><strong>Finding a Needle in the Haystack: Design and Implementation of a Digital Site-less Clinical Study of Serial Rapid Antigen Testing to Identify Asymptomatic SARS-CoV-2 Infection</strong> -
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Background: Over-the-counter rapid antigen tests for SARS-CoV-2 with an Emergency Use Authorization (EUA) in the United States generally include a condition of authorization to evaluate the test9s performance in asymptomatic individuals when used serially. A goal of this study was to investigate the performance of SARS-CoV-2 antigen serial testing and generate data to support regulatory decisions. Objective: To describe a novel study design to evaluate serial use of rapid antigen tests in detecting SARS-CoV-2 virus among asymptomatic individuals. Design: Prospective cohort study using a decentralized approach. Eligible participants from across the U.S. could enroll and complete this study from their home environment through a study app. Participant enrollment was prioritized based on regional 7-day case rates, participants9 vaccination status, and sociodemographic characteristics prior to enrollment. Prioritization criteria were adjusted on a daily or weekly basis. Enrolled participants were mailed rapid antigen tests and molecular comparator collection kits and asked to test every 48 hours for 15 days. Three companies9 rapid antigen tests were used in the study; assignment of participant to a test was criteria-based and non-random, precluding head-to-head comparison between the tests. Participants: Mainland United States residents over 2 years old with no reported COVID-19 symptoms in the 14 days prior to study enrollment. Main Measures: Participant demographics, COVID-19 vaccination status, and geographic distribution were used to understand the impact of the site-less recruitment and enrollment strategy. Key Results: A total of 7,361 participants enrolled in the study between October 18, 2021 and February 15, 2022. Throughout the study, 369 participants tested positive for SARS-CoV-2, including 167 who were asymptomatic and tested negative on SARS-CoV-2 molecular assays to start the study. This exceeded the initial enrollment goals of 60 positive participants. We enrolled participants from 44 of the 48 mainland U.S. states, and geographic distribution of participants shifted in accordance with the changing COVID-19 prevalence nationwide. Conclusions: The novel, digital site-less approach employed in the 9Test Us At Home9 study enabled rapid, efficient, and rigorous evaluation of rapid diagnostics for COVID-19, and can be adapted across research disciplines to optimize study enrollment and accessibility.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.04.22278274v1" target="_blank">Finding a Needle in the Haystack: Design and Implementation of a Digital Site-less Clinical Study of Serial Rapid Antigen Testing to Identify Asymptomatic SARS-CoV-2 Infection</a>
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<li><strong>Overuse in US Medicare during the COVID-19 pandemic: 2020 versus 2019</strong> -
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Background: The COVID-19 pandemic and March 2020 shutdown in the US reduced the volume of healthcare services, but the impact on overuse has not been investigated. Objective: To examine the change in overuse rates and volumes through 2020. Design: A retrospective cohort study using Medicare fee-for-service claims. Setting: Outpatient and inpatient claims. Participants: Patients who met the criteria for one of 10 overuse measures with a claim between January 1 2019 to December 31 2020. Measurements: Overuse volumes were reported as patients with claims meeting overuse metric criteria per 100,000 Medicare beneficiaries. Overuse rates were measured by the same overuse cohort per 100 patients meeting the denominator criteria of the metric. Rates in 2020 were compared to the same date period in 2019 using incidence rate ratios (IRRs) estimated from Poisson regressions. Results: In 2019, 302,379 patients had an overuse claim (14.72% of 2,053,792 patients in the cohort) versus 234,481 (13.79% of 1,699,807) in 2020. The overall cohort included 2,112,904 (61.0%) women and a mean (SD) age of 76.5 (8.1) years. There was a 52.3% decrease in overall cohort volume during the COVID-19 shutdown; 2,341,017 patients in 2020 versus 4,912,453 in 2019. There was a 72.57% decrease in patients with an overuse procedure between April 2019 (N = 11,794) and 2020 (N = 3,220) (IRR 0.27 (95% CI 0.25 to 0.3; p &lt;0.001)), including spinal fusion/laminectomy, carotid endarterectomy, knee arthroscopy, hysterectomy and vertebroplasty. Limitations: This study uses claim-based measures of overuse and is limited to the first ten months of the COVID-19 pandemic. Conclusions: The shutdown period during March through May in 2020 had a drastic impact on both the overuse volume and rates for these 10 overuse metrics.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.25.22275006v2" target="_blank">Overuse in US Medicare during the COVID-19 pandemic: 2020 versus 2019</a>
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<li><strong>Comparative pathogenicity of SARS-CoV-2 Omicron subvariants including BA.1, BA.2, and BA.5</strong> -
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Unremitting emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants imposes us to continuous control measurement. Given the rapid spread, new Omicron subvariant named BA.5 is urgently required for characterization. Here we analyzed BA.5 with the other Omicron variants BA.1, BA.2, and ancestral B.1.1 comprehensively. Although in vitro growth kinetics of BA.5 is comparable among the Omicron subvariants, BA.5 become much more fusogenic than BA.1 and BA.2. The airway-on-a-chip analysis showed that the ability of BA.5 to disrupt the respiratory epithelial and endothelial barriers is enhanced among Omicron subvariants. Furthermore, in our hamster model, in vivo replication of BA.5 is comparable with that of the other Omicrons and less than that of the ancestral B.1.1. Importantly, inflammatory response against BA.5 is strong compared with BA.1 and BA.2. Our data suggest that BA.5 is still low pathogenic compared to ancestral strain but evolved to induce enhanced inflammation when compared to prior Omicron subvariants.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.05.502758v1" target="_blank">Comparative pathogenicity of SARS-CoV-2 Omicron subvariants including BA.1, BA.2, and BA.5</a>
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<li><strong>SARS-CoV-2 entry route impacts a range of downstream viral and cellular processes</strong> -
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SARS-CoV-2 entry is promoted by both cell-surface TMPRSS2 and endolysosomal cathepsins. To investigate the impact of differentially routed virions on host and viral processes, lung epithelial cells expressing distinct combinations of entry factors were infected with authentic viruses. Entry route determined early rates of viral replication and transcription, egress and inhibitor sensitivity, with differences observed between virus strains. Transcriptional profiling revealed that induction of innate immunity was correlated to viral genome and transcript abundance in infected cells. Surface entry triggered early activation of antiviral responses, reducing cumulative virion production, while endolysosomal entry delayed antiviral responses and prolonged virus shedding due to extended cell viability. The likely molecular footprints of escape from antiviral effector targeting were also recorded in viral genomes and correlated with entry route-dependent immune status of cells. TMPRSS2 orthologues from diverse mammals, but not zebra fish, facilitated infection enhancement, which was more pronounced for ancestral strains. Leveraging RNA-seq and scRNA-seq datasets from SARS-CoV-2 infected hamsters, we validate aspects of our model in vivo. In summary, we demonstrate that distinct cellular and viral processes are linked to viral entry route, collectively modulating virus shedding, cell-death rates and viral genome evolution.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.05.502936v1" target="_blank">SARS-CoV-2 entry route impacts a range of downstream viral and cellular processes</a>
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<li><strong>mRNA vaccines and hybrid immunity use different B cell germlines to neutralize Omicron BA.4 and BA.5</strong> -
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SARS-CoV-2 omicron BA.4 and BA.5, characterized by high transmissibility and ability to escape natural and vaccine induced immunity, are rampaging worldwide. To understand the escape mechanisms, we tested the neutralizing activity against omicron BA.4 and BA.5 of a panel of 482 human monoclonal antibodies that had been isolated from people who received two or three mRNA vaccine doses or from people that had been vaccinated after infection. None of the antibodies isolated after two vaccine doses neutralized omicron BA.4 and BA.5, while these variants were neutralized by approximately 15% of antibodies obtained from people that received three doses or had been vaccinated after infection. Remarkably, the antibodies isolated after three vaccine doses targeted mainly the receptor binding domain (RBD) Class 1/2 epitope region and were encoded by the IGHV1-69 and IGHV3-66 B cell germlines, while the antibodies isolated after infection recognized mostly the RBD Class 3 epitope region and the NTD, and were encoded by the IGHV2-5;IGHJ4-1 and IGHV1-24;IGHJ4-1 germlines. The observation that mRNA vaccination and hybrid immunity elicit a different immunity against the same antigen is intriguing and its understanding may help to design the next generation of therapeutics and vaccines against COVID-19.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.04.502828v1" target="_blank">mRNA vaccines and hybrid immunity use different B cell germlines to neutralize Omicron BA.4 and BA.5</a>
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<li><strong>The COVID-19 Pandemic and US Presidential Elections</strong> -
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What is the effect of the COVID-19 pandemic on the 2020 U.S. presidential election? Guided by a pre-analysis plan, we estimate the effect of COVID-19 cases and deaths on the change in county-level voting for Donald Trump between 2016 and 2020. To account for potential confounders, we include a large number of COVID-19-related controls as well as demographic and socioeconomic variables. Moreover, we instrument the numbers of cases and deaths with the share of workers employed in meat-processing factories to sharpen our identification strategy. We find that COVID-19 cases negatively affected Trumps vote share. The estimated effect appears strongest in urban counties, in swing states, and in states that Trump won in 2016. A simple counterfactual analysis suggests that Trump would likely have won re-election if COVID-19 cases had been 5 percent lower. Our paper contributes to the literature of retrospective voting and demonstrates that voters hold leaders accountable for their (mis-)handling of negative shocks.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/metaarxiv/sxajv/" target="_blank">The COVID-19 Pandemic and US Presidential Elections</a>
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<li><strong>One Health Genomic Surveillance and Response to a University-Based Outbreak of the SARS-CoV-2 Delta AY.25 Lineage, Arizona, 2021</strong> -
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Large scale outbreaks of the SARS-CoV-2 Delta variant have occurred in numerous settings, including universities. An outbreak of the SARS-CoV-2 Delta AY.25 lineage associated with a university campus with multiple transmission events was identified; genomic analyses characterized this outbreak and complemented contract tracing and wastewater surveillance strategies that strengthened overall public health response actions. Epidemiologic and clinical data routinely gathered through contact tracing and public health investigations was matched to genomic sequencing of SARS-CoV-2 positive samples belonging to a suspect cluster identified through ongoing phylogenomic analyses. Continued phylogenetic analyses were conducted to describe the AY.25 outbreak. Wastewater collected twice weekly from sites across campus was tested for SARS-CoV-2 by RT-qPCR, and subsequently sequenced to identify variants. The AY.25 outbreak was defined by a single mutation (C18804T) and comprised 379 genomes from SARS-CoV-2 positive cases associated with the university and community. Several undergraduate student gatherings and congregate living settings on campus likely contributed to the rapid spread of COVID-19 across the university with secondary transmission into the community. The clade defining mutation was also found in wastewater samples collected from around student dormitories during “move-in”, a week before the semester began, and 9 days before cases were identified. Genomic, epidemiologic, and wastewater surveillance provided evidence that an AY.25 clone was likely imported into the university setting just prior to the onset of the Fall 2021 semester, rapidly spread through a subset of the student population, and then subsequent spillover occurred in the surrounding community. The university and local public health department worked closely together to facilitate timely reporting of cases, identification of close contacts, and other necessary response and mitigation strategies. The emergence of new SARS-CoV-2 variants and potential threat of other infectious disease outbreaks on university campuses presents an opportunity for future comprehensive One Health genomic data driven, targeted interventions.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.02.22278212v2" target="_blank">One Health Genomic Surveillance and Response to a University-Based Outbreak of the SARS-CoV-2 Delta AY.25 Lineage, Arizona, 2021</a>
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<li><strong>COVID-19 convalescent plasma for the treatment of immunocompromised patients: a systematic review.</strong> -
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Immunosuppressed patients have increased risk for morbidity and mortality from COVID-19 because they less frequently mount antibody responses to vaccines and often cannot tolerate small-molecule antivirals. The Omicron variant of concern of SARS-CoV-2 has progressively defeated anti-Spike mAbs authorized so far, paving the way to a return to COVID-19 convalescent plasma (CCP) therapy. In this systematic review we performed a metanalysis of 6 controlled studies (including 2 randomized controlled trials; totaling 368 treated patients and 1119 control), an individual patient data analysis of 125 case reports/series (totaling 265 patients), and a descriptive analysis of 13 uncontrolled large case series without individual patient data available (totaling 358 patients). The metanalysis showed a risk ratio for mortality of 0.61 in treatment with CCP versus standard of care for immunosuppressed COVID-19 patients. On the basis of this evidence, we encourage initiation of high-titer CCP from vaccinees (hybrid plasma) in immunocompromised patients.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.03.22278359v2" target="_blank">COVID-19 convalescent plasma for the treatment of immunocompromised patients: a systematic review.</a>
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<li><strong>An observational study of the association between COVID-19 vaccination rates and entry into the “Million Dollar Vax” competition</strong> -
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Objectives: To examine the association between financial incentives from entry into a vaccine competition with the probability of vaccination for COVID19. Design: A cross sectional study with adjustment for covariates using logistic regression Setting: October and November 2021, Australia. Participants: 2,375 respondents of the Taking the Pulse of the Nation Survey Primary and secondary outcome measures The proportion of respondents who had any vaccination, a first dose only, or second dose after the competition opened. Results: Those who entered the competition were 2.27 times more likely to be vaccinated after the competition opened on October 1st than those who did not enter, an increase in the probability of having any dose of 0.16 percentage points. This increase was mostly driven by those receiving second doses. Entrants were 2.39 times more likely to receive their second dose after the competition opened. Conclusions Those who entered the Million Dollar Vax competition were more likely to receive a vaccination after the competition opened compared to those who did not enter the competition, with this effect dominated by those receiving second doses. Strengths and limitations of this study We use a nationally representative sample of individual self reported vaccination status and timings. We distinguish between the association between competition entry and first and second doses. We adjust for a rich set of individual characteristics associated with vaccination status, and examine the factors influencing competition entry The strong association for second dose vaccinations may reflect some individuals who had already scheduled their second dose after the competition opened, potentially leading to an overestimate of the association.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.03.02.22271734v3" target="_blank">An observational study of the association between COVID-19 vaccination rates and entry into the “Million Dollar Vax” competition</a>
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<li><strong>Analysis of anti-Omicron neutralizing antibody titers in different convalescent plasma sources.</strong> -
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The latest SARS-CoV-2 variant of concern Omicron, with its immune escape from therapeutic anti-Spike monoclonal antibodies and vaccine-elicited sera, demonstrates the continued relevance of COVID19 convalescent plasma (CCP) therapies. Lessons learnt from previous usage of CCP suggests focusing on outpatients and immunocompromised recipients, with high neutralizing antibody (nAb) titer units. In this analysis we systematically reviewed Omicron neutralizing plasma activity data, and found that approximately 50% (426/911) of CCP from unvaccinated donors neutralizes Omicron with a very low geometric mean of geometric mean titers for 50% neutralization (GM(GMT50)) of about 17, representing a more than 24-fold reduction from paired WA-1 neutralization. Two doses of mRNA vaccines in nonconvalescent subjects had a similar 50% percent neutralization with Omicron neutralization GM(GMT(50)) about 24. However, CCP from vaccinees recovered from previous variants of concern or third-dose uninfected vaccinees was nearly 100% neutralizing with Omicron GM(GMT(50)) over 200, a 12-fold Omicron neutralizing antibody increase compared to unvaccinated convalescents from former VOCs. These findings have implications for both CCP stocks collected in prior pandemic periods and plans to restart CCP collections. Thus, CCP from vaccinated donors provides an effective tool to combat variants that defeat therapeutic monoclonal antibodies.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.12.24.21268317v4" target="_blank">Analysis of anti-Omicron neutralizing antibody titers in different convalescent plasma sources.</a>
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<li><strong>Pregnancies and contraceptive use in four African countries during the COVID-19 pandemic</strong> -
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The COVID-19 pandemic and the public health measures adopted in response to it have triggered plenty of speculation about the potential impact on fertility in different regions of the globe. This study provides evidence on the fertility response in four sub-Saharan African countries during the first year of the pandemic. Using harmonized data on women of childbearing age from the Performance Monitoring for Action (PMA) data series, this study compares pregnancy rates at the turn of the year 2020/21 to a pre-pandemic baseline. There is no indication of a general increase in pregnancy rates after the beginning of the pandemic. In some of the sample countries, pregnancy rates during this phase of the COVID-19 pandemic instead fell significantly among the youngest and the least educated women of childbearing age, respectively. The findings also indicate that over this period, rates of modern contraceptive usage rose significantly among the surveyed female populations in several sample countries.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/av7ec/" target="_blank">Pregnancies and contraceptive use in four African countries during the COVID-19 pandemic</a>
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<li><strong>Human endogenous retrovirus-R envelope is a host restriction factor against severe acute respiratory syndrome-coronavirus-2</strong> -
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Coronavirus induced disease-19 (COVID-19), caused by the SARS-CoV-2 remains a major global health challenge. Human endogenous retroviruses (HERVs) represent retroviral elements that got integrated into the ancestral human genome. HERVs are important in development and diseases, including cancer, inflammation and viral infections. Here, we analyzed the expression of several HERVs in SARS-CoV-2 infected cells and observed increased activity of HERV-E, HERV-V, HERV-FRD, HERV-MER34, HERV-W and HERV-K-HML2. In contrast, HERV-R-envelope was downregulated in cell-based models and COVID-19 patient PBMCs. HERV-R overexpression inhibited SARS-CoV-2 replication, suggesting its antiviral action. Further studies demonstrated the role of extracellular signal-regulated kinase (ERK) in regulating HERV-R antiviral activity. Cross-talk between the ERK and p38 MAPK controls HERV-R envelope synthesis, which in turn modulates the replication of SARS-CoV-2. These findings establish the importance of HERV-R envelope as a host restriction factor against SARS-CoV-2 and illustrate the advantage of integration and evolutionary maintenance of retroviral-elements in the human genome.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.05.502940v1" target="_blank">Human endogenous retrovirus-R envelope is a host restriction factor against severe acute respiratory syndrome-coronavirus-2</a>
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<li><strong>Viral Kinetics of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Omicron Infection in mRNA-Vaccinated Individuals Treated and Not Treated with Nirmatrelvir-Ritonavir</strong> -
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We measured viral kinetics of SARS-CoV-2 Omicron infection in 36 mRNA-vaccinated individuals, 11 of whom were treated with nirmatrelvir-ritonavir (NMV-r). We found that NMV-r was associated with greater incidence of viral rebound compared to no treatment. For those that did not rebound, NMV-r significantly reduced time to PCR conversion.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.04.22278378v1" target="_blank">Viral Kinetics of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Omicron Infection in mRNA-Vaccinated Individuals Treated and Not Treated with Nirmatrelvir-Ritonavir</a>
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<li><strong>SARS-CoV-2 BA.4/5 Spike recognition and neutralization elicited after the third dose of mRNA vaccine</strong> -
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The SARS-CoV-2 Omicron BA.4 and BA.5 subvariants have recently emerged, with BA.5 becoming the dominant circulating strain in many countries. Both variants share the same Spike glycoprotein sequence which contains a large number of mutations, raising concerns about vaccine efficacy. In this study, we evaluated the ability of plasma from a cohort of individuals that received three doses of mRNA vaccine to recognize and neutralize the BA.4/5 Spike. We observed that BA.4/5 Spike is markedly less recognized and neutralized compared to the D614G and Omicron BA.2 Spike variants. Individuals who have been infected before or after vaccination present better humoral responses than SARS-CoV-2 naive vaccinated individuals, thus indicating that hybrid immunity generates better humoral responses against this subvariant.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.03.22278386v1" target="_blank">SARS-CoV-2 BA.4/5 Spike recognition and neutralization elicited after the third dose of mRNA vaccine</a>
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<li><strong>Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is common in post-acute sequelae of SARS-CoV-2 infection (PASC): Results from a post-COVID-19 multidisciplinary clinic.</strong> -
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Background The global prevalence of PASC is estimated to be present in 0.43 and based on the WHO estimation of 470 million worldwide COVID-19 infections, corresponds to around 200 million people experiencing long COVID symptoms. Despite this, its clinical features are not well defined. Methods We collected retrospective data from 140 patients with PASC in a post-COVID-19 clinic on demographics, risk factors, illness severity (graded as one-mild to five-severe), functional status, and 29 symptoms and principal component symptoms cluster analysis. The Institute of Medicine (IOM) 2015 criteria were used to determine the ME/CFS phenotype. Findings The median age was 47 years, 59.0% were female; 49.3% White, 17.2% Hispanic, 14.9% Asian, and 6.7% Black. Only 12.7% required hospitalization. Seventy-two (53.5%) patients had no known comorbid conditions. Forty-five (33.9%) were significantly debilitated. The median duration of symptoms was 285.5 days, and the number of symptoms was 12. The most common symptoms were fatigue (86.5%), post-exertional malaise (82.8%), brain fog (81.2%), unrefreshing sleep (76.7%), and lethargy (74.6%). Forty-three percent fit the criteria for ME/CFS. Interpretations Most PASC patients evaluated at our clinic had no comorbid condition and were not hospitalized for acute COVID-19. One-third of patients experienced a severe decline in their functional status. About 43% had the ME/CFS subtype.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.03.22278363v1" target="_blank">Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is common in post-acute sequelae of SARS-CoV-2 infection (PASC): Results from a post-COVID-19 multidisciplinary clinic.</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>A Study to Learn About a New COVID-19 RNA Vaccine Candidate as a Booster Dose in COVID-19 Vaccine-Experienced Healthy Adults</strong> - <b>Conditions</b>:   SARS-CoV-2 Infection;   COVID-19<br/><b>Interventions</b>:   Biological: BNT162b5 Bivalent (WT/OMI BA.2);   Biological: BNT162b2 Bivalent (WT/OMI BA.1)<br/><b>Sponsors</b>:   BioNTech SE;   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>Monitoring the Efficacy of a Probiotic Dietary Supplement SmartProbio C in Patients With Severe COVID-19 Infection</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Dietary Supplement: SmartProbio C;   Dietary Supplement: Placebo<br/><b>Sponsors</b>:   Medi Pharma Vision;   Veterinary Research Institute;   Brno University Hospital<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>A Study to Measure the Amount of Study Medicine in Blood in Adult Participants With COVID-19 and Severe Kidney Disease</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Drug: PF-07321332 (nirmatrelvir)/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>Physiotherapy in Post COVID-19 Syndrome Patients</strong> - <b>Condition</b>:   Post-COVID-19 Syndrome<br/><b>Interventions</b>:   Other: Cognitive behavioral principles-based treatment program;   Other: Control intervention<br/><b>Sponsor</b>:   Universidad de Granada<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>Rehabilitation for People With Post COVID-19 Syndrome</strong> - <b>Condition</b>:   Post-COVID-19 Syndrome<br/><b>Interventions</b>:   Other: Multidimensional intervention;   Other: Control intervention<br/><b>Sponsor</b>:   Universidad de Granada<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>Effect of Pulmonary Rehabilitation Program on Post Hospitalization Severe COVID- 19 Patients</strong> - <b>Condition</b>:   Post COVID-19 Condition<br/><b>Intervention</b>:   Combination Product: respiratory exercises - incentive spirometer - walking<br/><b>Sponsor</b>:   Fayoum University Hospital<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>Addressing Vaccine Hesitancy and Increasing COVID-19 Vaccine Uptake Among African American Young Adults in the South</strong> - <b>Conditions</b>:   COVID-19;   Vaccine Uptake<br/><b>Intervention</b>:   Behavioral: Tough Talks COVID<br/><b>Sponsors</b>:   University of North Carolina, Chapel Hill;   University of Alabama at Birmingham;   National Institute on Minority Health and Health Disparities (NIMHD)<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>rSIFN-co Among Healthy Subjects and Subjects With Mild or Asymptomatic COVID-19</strong> - <b>Conditions</b>:   COVID-19;   SARS-CoV-2<br/><b>Interventions</b>:   Drug: rSIFN-co Nasal Spray;   Drug: Placebo Nasal Spray<br/><b>Sponsor</b>:   Sichuan Huiyang Life Science and Technology Corporation<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 CHW Intervention to Identify and Decrease Barriers to COVID 19 Testing &amp; Vaccination</strong> - <b>Conditions</b>:   Vaccine Hesitancy;   COVID-19 Testing;   Community Health Workers<br/><b>Intervention</b>:   Behavioral: Community Health Worker led curriculum<br/><b>Sponsors</b>:   Charles Drew University of Medicine and Science;   Los Angeles County Department of Public Health;   National Library of Medicine (NLM)<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>Lollipop COVID-19 Testing Study</strong> - <b>Conditions</b>:   COVID-19;   SARS CoV 2 Infection;   COVID-19 Pandemic<br/><b>Intervention</b>:   Diagnostic Test: Lollipop Swab<br/><b>Sponsor</b>:   University of Wisconsin, Madison<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 Safety and Immunogenicity of the Recombinant ZR202-CoV and ZR202a-CoV Vaccines in Adults.</strong> - <b>Conditions</b>:   SARS-CoV-2 Infection;   COVID-19<br/><b>Interventions</b>:   Biological: ZR202-CoV;   Biological: ZR202a-CoV;   Biological: Comirnaty®<br/><b>Sponsor</b>:   Shanghai Zerun Biotechnology Co.,Ltd<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>Safety and Immunogenicity Study of a Booster Dose of the Investigational CV0501 mRNA COVID-19 Vaccine in Adults at Least 18 Years Old</strong> - <b>Condition</b>:   SARS-CoV-2<br/><b>Interventions</b>:   Biological: CV0501 (3 μg);   Biological: CV0501 (6 μg);   Biological: CV0501 (12 μg);   Biological: CV0501 (25 μg);   Biological: CV0501 (50 μg);   Biological: CV0501 (75 μg);   Biological: CV0501 (100 μg);   Biological: CV0501 (150 μg);   Biological: CV0501 (200 μg)<br/><b>Sponsor</b>:   GlaxoSmithKline<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 BBIBP-Corv Coadministered With PPV23 and IIV4 in Hemodialysis Population</strong> - <b>Conditions</b>:   Hemolysis;   COVID-19<br/><b>Interventions</b>:   Biological: coadministration;   Biological: COVID-19 vaccine;   Biological: IIV4+PPV23<br/><b>Sponsors</b>:   China National Biotec Group Company Limited;   Hunan Provincial Center for Disease Control and Prevention;   Sichuan Center for Disease Control and Prevention;   Guizhou Center for Disease Control and Prevention;   Xiangya Hospital of Central South University;   Beijing Institute of Biological Products Co Ltd.;   Chengdu Institute of Biological Products Co.,Ltd.;   Shanghai Institute Of Biological Products<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>The Effect Of Distraction Methods On Fear And Anxiety In Children Before The Covid 19 Test</strong> - <b>Conditions</b>:   Anxiety;   Fear<br/><b>Interventions</b>:   Behavioral: The Kaleidescope;   Behavioral: The visual illusion cards<br/><b>Sponsor</b>:   Ondokuz Mayıs University<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>A Phase 2 Study to Evaluate the Efficacy and Safety of TNX-102 SL in Patients With Multi-Site Pain Associated With Post-Acute Sequelae of SARS-CoV-2 Infection</strong> - <b>Conditions</b>:   Post-Acute Sequelae of SARS-CoV-2 (PASC) Infection;   COVID-19;   Long COVID;   Long Haul COVID<br/><b>Interventions</b>:   Drug: TNX-102 SL;   Drug: Placebo SL Tablet<br/><b>Sponsor</b>:   Tonix Pharmaceuticals, Inc.<br/><b>Recruiting</b></p></li>
</ul>
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</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 Nutritional Blend Suppresses the Inflammatory Response from Bronchial Epithelial Cells Induced by SARS-CoV-2</strong> - Even after virus elimination, numerous sequelae of coronavirus disease 2019 (COVID-19) persist. Based on accumulating evidence, large amounts of proinflammatory cytokines are released to drive COVID-19 progression, severity, and mortality, and their levels remain elevated after the acute phase of COVID-19, playing a central role in the disease sequelae. In this manner, bronchial epithelial cells are the first cells hyperactivated by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2),…</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>Jacareubin inhibits TLR4-induced lung inflammatory response caused by the RBD domain of SARS-CoV-2 Spike protein</strong> - CONCLUSIONS: S-RBD domain promotes lung TNF-α and IL-6 production in a TLR4-dependent fashion in C57BL6/J mice. Xanthone Jacareubin possesses potential anti-COVID-19 properties that, together with the previously tested anti-inflammatory activity, safety, and tolerance, make it a valuable drug to be further investigated for the treatment of cytokine production caused by SARS-CoV-2 infection.</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>Identification of Potential ACE2-Derived Peptide Mimetics in SARS-CoV-2 Omicron Variant Therapeutics using Computational Approaches</strong> - The COVID-19 pandemic has become a global health challenge because of the emergence of distinct variants. Omicron, a new variant, is recognized as a variant of concern (VOC) by the World Health Organization (WHO) because of its higher mutations and accelerated human infection. The infection rate is strongly dependent on the binding rate of the receptor binding domain (RBD) against human angiotensin converting enzyme-2 (ACE2^(human)) receptor. Inhibition of protein-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>Affinity selection-mass spectrometry in the discovery of anti-SARS-CoV-2 compounds</strong> - Small molecule therapeutic agents are needed to treat or prevent infections by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which is the cause of the COVID-19 pandemic. To expedite the discovery of lead compounds for development, assays have been developed based on affinity selection-mass spectrometry (AS-MS), which enables the rapid screening of mixtures such as combinatorial libraries and extracts of botanicals or other sources of natural products. AS-MS assays have been used…</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>Optimisation of anti-interleukin-6 therapy: Precision medicine through mathematical modelling</strong> - CONCLUSION: In clinical practice, IL-6 inhibition should be individualised based on pathophysiology to achieve full blockade of CRP production.</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>SARS-CoV-2 Epitopes following Infection and Vaccination Overlap Known Neutralizing Antibody Sites</strong> - Identification of epitopes targeted following virus infection or vaccination can guide vaccine design and development of therapeutic interventions targeting functional sites, but can be laborious. Herein, we employed peptide microarrays to map linear peptide epitopes (LPEs) recognized following SARS-CoV-2 infection and vaccination. LPEs detected by nonhuman primate (NHP) and patient IgMs after SARS-CoV-2 infection extensively overlapped, localized to functionally important virus regions, 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>Human milk inhibits some enveloped virus infections, including SARS-CoV-2, in an intestinal model</strong> - Human milk is important for antimicrobial defense in infants and has well demonstrated antiviral activity. We evaluated the protective ability of human milk against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a human fetal intestinal cell culture model. We found that, in this model, human milk blocks SARS-CoV-2 replication, irrespective of the presence of SARS-CoV-2 spike-specific antibodies. Complete inhibition of both enveloped Middle East respiratory syndrome…</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>Discovery and Mechanistic Study of <em>Mycobacterium tuberculosis</em> PafA Inhibitors</strong> - Tuberculosis is caused by the bacterium Mycobacterium tuberculosis (Mtb) and is ranked as the second killer infectious disease after COVID-19. Proteasome accessory factor A (PafA) is considered an attractive target because of its low sequence conservation in humans and its role in virulence. In this study, we designed a mutant of Mtb PafA that enabled large-scale purification of active PafA. Using a devised high-throughput screening assay, two PafA inhibitors were discovered. ST1926 inhibited…</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>Pulmonary Surfactant Proteins are Inhibited by IgA Autoantibodies in Severe COVID-19</strong> - CONCLUSIONS: Our data suggest that patients with severe COVID-19 harbor IgA against pulmonary surfactant proteins B and C and that these antibodies block the function of lung surfactant, potentially contributing to alveolar collapse and poor oxygenation. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).</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>Proteolytic Processing of the Coronavirus Replicase Nonstructural Protein 14 Exonuclease Is Not Required for Virus Replication but Alters RNA Synthesis and Viral Fitness</strong> - Coronaviruses (CoVs) initiate replication by translation of the positive-sense RNA genome into the replicase polyproteins connecting 16 nonstructural protein domains (nsp1-16), which are subsequently processed by viral proteases to yield mature nsp. For the betacoronavirus murine hepatitis virus (MHV), total inhibition of translation or proteolytic processing of replicase polyproteins results in rapid cessation of RNA synthesis. The nsp5-3CLpro (Mpro) processes nsps7-16, which assemble into…</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>Inhibition of Glycolysis Impairs Retinoic Acid-Inducible Gene I-Mediated Antiviral Responses in Primary Human Dendritic Cells</strong> - Dendritic cells (DCs) are important mediators of the induction and regulation of adaptive immune responses following microbial infection and inflammation. Sensing environmental danger signals including viruses, microbial products, or inflammatory stimuli by DCs leads to the rapid transition from a resting state to an activated mature state. DC maturation involves enhanced capturing and processing of antigens for presentation by major histocompatibility complex (MHC) class I and class II,…</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>Breathability performance of antiviral cloth masks treated with silver nanoparticles for protection against COVID-19</strong> - The global widespread of coronavirus disease 2019 (COVID-19) has caused shortage of medical face masks and led to developing of various types of cloth masks with different levels of protection and comfort to meet the market demands. Breathing comfort is a significant aspect that should be considered during the design of cloth masks along with the filtration efficiency; otherwise, the wearer will feel suffocated. In this work, different types of cotton and polyester knitted fabrics blended with…</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>Mathematical modeling of plus-strand RNA virus replication to identify broad-spectrum antiviral treatment strategies</strong> - Plus-strand RNA viruses are the largest group of viruses. Many are human pathogens that inflict a socio-economic burden. Interestingly, plus-strand RNA viruses share remarkable similarities in their replication. A hallmark of plus-strand RNA viruses is the remodeling of intracellular membranes to establish replication organelles (so-called “replication factories”), which provide a protected environment for the replicase complex, consisting of the viral genome and proteins necessary for viral RNA…</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>SARS-CoV-2 Non-Structural Protein 1(NSP1) Mutation Virulence and Natural Selection: Evolutionary Trends in the Six Continents</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an unsegmented positivesense single-stranded RNA virus that belongs to the β-coronavirus . This virus was the cause of a novel severe acute respiratory syndrome in 2019 (COVID-19) that emerged in Wuhan, China at the early stage of the pandemic and rapidly spread around the world. Rapid transmission and reproduction of SARS-CoV-2 threaten worldwide health with a high mortality rate from the virus. According to the significant role of…</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>Ursolic acid and SARS-CoV-2 infection: a new horizon and perspective</strong> - SARS-CoV-2 (severe acute respiratory syndrome coronavirus type 2) has been identified as the source of a world coronavirus pandemic in 2019. Covid-19 is considered a main respiratory disease-causing viral pneumonia and, in severe cases, leads to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Although, extrapulmonary manifestations of Covid-19 like neurological, cardiovascular, and gastrointestinal have been confirmed. Exaggerated immune response and release of a high…</p></li>
</ul>
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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