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<title>13 November, 2022</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Pandemic panic? Results of a 6-month longitudinal study on fear of COVID-19</strong> -
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Fear is an evolutionary adaptive emotion that serves to protect the organism from harm. Once a threat diminishes, fear should also dissipate as otherwise fear may become chronic and pathological. While threat (i.e., number of infections, hospitalizations and deaths) during the ongoing COVID-19 pandemic has substantially varied over time, it remains unclear whether fear has followed a similar pattern. To examine the development of fear of COVID-19 and investigate potential predictors for chronic fear, we conducted a large online longitudinal study (N = 2000) using the Prolific platform. Participants represented unselected residents of 34 different countries. The Fear of the Coronavirus Questionnaire (FCQ) and several other demographic and psychological measures were completed monthly between March and August 2020. Overall, we find that fear steadily decreased after a peak in April 2020. Additional analyses showed that elevated fear was predicted by region (i.e., North America), anxious traits, and media use.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/xtu3f/" target="_blank">Pandemic panic? Results of a 6-month longitudinal study on fear of COVID-19</a>
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<li><strong>Crystal structure and activity profiling of deubiquitinating inhibitors-bound to SARS-CoV-2 papain like protease revealed new allosteric sites for antiviral therapies</strong> -
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Emerging variants of SARS-CoV-2 still threaten the effectiveness of currently deployed vaccines, and antivirals can prove to be an effective therapeutic option for attenuating it. The papain-like protease (PLpro) is an attractive target due to its sequence conservation and critical role in the replication and pathogenesis of SARS-CoV-2. PLpro also plays very important role in modulation of host immune responses by deubiquitinating (DUBs) or deISGylating host proteins. Thus, targeting PLpro serves as a two-pronged approach to abate SARS-CoV-2. Due to its structural and functional similarities with the host DUB enzymes, an in-house library of DUB inhibitors was constituted in this study. Five promising compounds exhibiting high binding affinities with the substrate binding site of PLpro were identified from a library of 81 compounds with in silico screening, docking, and simulation studies. Interestingly, lithocholic acid, linagliptin, teneligliptin, and flupenthixol significantly inhibited the proteolytic activity of PLpro. Each of these compounds abrogated in vitro replication of SARS-CoV-2 with EC50 values in the range of 5-21 micro M. In addition, crystal structure of SARS-CoV-2 PLpro and its complex with inhibitors have been determined that revealed their inhibitory mechanism. The findings of this study provide the proof-of-principle that the DUB inhibitors hold high potential as a new class of therapeutics against SARS-CoV-2. Additionally, this is the first study that has opened a new avenue towards not only targeting PLpro active site but also simultaneously directing towards restoration of antiviral immune response of the host for deterring SARS-CoV-2.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.11.11.516107v1" target="_blank">Crystal structure and activity profiling of deubiquitinating inhibitors-bound to SARS-CoV-2 papain like protease revealed new allosteric sites for antiviral therapies</a>
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<li><strong>Attenuated humoral responses in HIV infection after SARS-CoV-2 vaccination are linked to global B cell defects and cellular immune profiles</strong> -
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People living with HIV (PLWH) on suppressive antiretroviral therapy (ART) can have residual immune dysfunction and often display poorer responses to vaccination. We assessed in a cohort of PLWH (n=110) and HIV negative controls (n=64) the humoral and spike-specific B-cell responses following 1, 2 or 3 SARS-CoV-2 vaccine doses. PLWH had significantly lower neutralizing antibody (nAb) titers than HIV-negative controls at all studied timepoints. Moreover, their neutralization breadth was reduced with fewer individuals developing a neutralizing response against the Omicron variant (BA.1) relative to controls. We also observed a delayed development of neutralization in PLWH that was underpinned by a reduced frequency of spike-specific memory B cells (MBCs) and pronounced B cell dysfunction. Improved neutralization breadth was seen after the third vaccine dose in PLWH but lower nAb responses persisted and were associated with global, but not spike-specific, MBC dysfunction. In contrast to the inferior antibody responses, SARS-CoV-2 vaccination induced robust T cell responses that cross-recognized variants in PLWH. Strikingly, a subset of PLWH with low or absent neutralization had detectable functional T cell responses. These individuals had reduced numbers of circulating T follicular helper cells and an enriched population of CXCR3+CD127+CD8+ T cells after two doses of SARS-CoV-2 vaccination, which may compensate for sub-optimal serological responses in the event of infection. Therefore, normalisation of B cell homeostasis could improve serological responses to vaccines in PLWH and evaluating T cell immunity could provide a more comprehensive immune status profile in these individuals and others with B cell imbalances.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.11.11.516111v1" target="_blank">Attenuated humoral responses in HIV infection after SARS-CoV-2 vaccination are linked to global B cell defects and cellular immune profiles</a>
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<li><strong>A broad-spectrum macrocyclic peptide inhibitor of the SARS-CoV-2 spike protein</strong> -
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The ongoing COVID-19 pandemic has had great societal and health consequences. Despite the availability of vaccines, infection rates remain high due to immune evasive Omicron sublineages. Broad-spectrum antivirals are needed to safeguard against emerging variants and future pandemics. We used mRNA display under a reprogrammed genetic code to find a spike-targeting macrocyclic peptide that inhibits SARS-CoV-2 Wuhan strain infection and also pseudoviruses containing spike proteins of SARS-CoV-2 variants or related sarbecoviruses. Structural and bioinformatic analyses reveal a conserved binding pocket between the receptor binding domain and other domains, distal to the ACE2 receptor-interaction site. Collectively, our data reveal a hitherto unexplored site of vulnerability in sarbecoviruses that can be targeted by peptides and potentially other drug-like molecules.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.11.11.516114v1" target="_blank">A broad-spectrum macrocyclic peptide inhibitor of the SARS-CoV-2 spike protein</a>
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<li><strong>Selection of long COVID symptoms influences prevalence estimates in a prospective cohort</strong> -
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Background: Studies on long COVID differ in the selection of symptoms used to define the condition. We aimed to assess to what extent symptom selection impacts prevalence estimates of long COVID. Methods: In a prospective cohort of patients who experienced mild to critical coronavirus disease 2019 (COVID-19), we used longitudinal data on the presence of 20 different symptoms to evaluate changes in the prevalence of long COVID over time when altering symptom selection. Results: Changing symptom selection resulted in wide variation in long COVID prevalence, even within the same study population. Long COVID prevalence at 12 months since illness onset ranged from 39.6% (95%CI=33.4-46.2) when using a limited selection of symptoms to 80.6% (95%CI=74.8-85.4) when considering any reported symptom to be relevant. Conclusions: Comparing the occurrence of long COVID is already complex due to heterogeneity in study design and population. Disparate symptom selection may further hamper comparison of long COVID estimates between populations. Harmonised data collection tools could be one means to achieve greater reproducibility and comparability of results.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.09.22282120v1" target="_blank">Selection of long COVID symptoms influences prevalence estimates in a prospective cohort</a>
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<li><strong>Year-round RSV Transmission in the Netherlands Following the COVID-19 Pandemic - A Prospective Nationwide Observational and Modeling Study</strong> -
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A nationwide prospective study showed year-round RSV transmission in the Netherlands after an initial 2021 summer outbreak. The pattern was unprecedented and distinct from neighboring countries. Our dynamic simulation model suggests that this transmission pattern could be associated with waning immunity because of low RSV circulation during the COVID-19 pandemic.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.10.22282132v1" target="_blank">Year-round RSV Transmission in the Netherlands Following the COVID-19 Pandemic - A Prospective Nationwide Observational and Modeling Study</a>
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<li><strong>Screening, diagnosis and hospitalization of breast and cervical cancer in Brazil from 2010 to 2022: a time-series study</strong> -
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In Brazil, during the pandemic caused by COVID-19, screening for breast and cervical cancers was postponed or interrupted due to the prevailing health conditions. These neoplasms, however, are responsible for high morbidity and mortality among women in Brazil and have a major impact on the quality of life of this population and on public health. Thus, this study aims to evaluate the epidemiological behavior of hospitalization for cervical and breast cancer in Brazilian women, as well as the trend of screening tests and diagnosis of breast and cervical cancer in the years 2010 to 2022 in Brazil. This is an ecological research of time series, based on secondary data obtained from information systems of the country, about hospital admissions for breast and cervical cancer and screening methods used for these tumors. The data were analyzed in the Joinpoint Regression Program, to obtain the linear regression and temporal analysis of the variables. As results, there is a decrease in hospitalization rates for cervical cancer between the years 2010 and 2015 and a subsequent increase in 2019. Regarding breast cancer, there was an increase in hospitalizations, until reaching a peak in 2019. For both, in the pandemic years, between 2020 and 2022, there is a decrease in Brazil and in all its regions. As for the tracking of these diseases, it was observed that the performance of mammograms and preventive tests showed a similar behavior, in which there is a higher supply of these tests until 2019 and a drop during the pandemic period. This leads to the conclusion that even though Brazil has several policies for screening and early diagnosis of these diseases, there is still instability in the offer of tests and that there was a precariousness in this area during the pandemic.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.09.22282147v1" target="_blank">Screening, diagnosis and hospitalization of breast and cervical cancer in Brazil from 2010 to 2022: a time-series study</a>
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<li><strong>Heterogeneity and Risk-of-Biases are No Longer the Issues to Conclude the Effectiveness of Baricitinib in Reducing COVID-19 Related Mortality: A Systematic Review and Meta-Analysis of Eight Randomised Controlled Trials</strong> -
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Background: Due to high heterogeneity and risk of bias (RoB) in previously published meta-analysis, a concrete conclusion on the efficacy of baricitinib in reducing mortality in COVID-19 patients was unable to form. Methods: Search engines PubMed/MEDLINE, ScienceDirect and other sources like preprints and reference lists were searched with appropriate keywords. The included evidence was graded with GRADEpro. The RoB, heterogeneity and meta-analysis were studied through RevMan 5.4.1 software. The heterogeneity was evaluated based on the generated p-value or I2 test. Results: Eight (8) RCTs were included in current analysis. Five studies had low RoB. Based on grading the evidence, the inclusion and exclusion of high RoB articles led to moderate and high certainty of evidence, respectively. Based on 8 RCTs (with high RoB), baricitinib statistically significantly reduced mortality where the risk ratio (RR) = 0.84 [95% CI: 0.76 to 0.92; p = 0.0002; I2 = 23%; p = 0.25]. The heterogeneity was insignificant but the RoB was high. We did subgroup analysis of low and high RoB articles and found out baricitinib statistically significantly reduced mortality with the RR = 0.68 [95% CI: 0.56 to 0.82; p < 0.0001; I2 = 0%; p = 0.85] and RR = 0.89 [95% CI: 0.80 to 0.99; p = 0.04; I2 = 0%; p = 0.43], respectively. The heterogeneity was 0% with insignificant p-values in both subgroup analyses. The percentage of mortality reduction was 31.31% and 7.79%, respectively whereas it was 13.95% in main group analysis. Conclusion: With the presence of optimal sample size of 3944 from 5 low RoB studies which represents a minimum of 300 million population of people and with 0% of heterogeneity, the effectiveness of baricitinib in reducing the mortality in COVID-19 patients is concretely proven.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.07.22282055v1" target="_blank">Heterogeneity and Risk-of-Biases are No Longer the Issues to Conclude the Effectiveness of Baricitinib in Reducing COVID-19 Related Mortality: A Systematic Review and Meta-Analysis of Eight Randomised Controlled Trials</a>
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<li><strong>Cotranslational formation of disulfides guides folding of the SARS CoV-2 receptor binding domain</strong> -
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Many secreted proteins contain multiple disulfide bonds. How disulfide formation is coupled to protein folding in the cell remains poorly understood at the molecular level. Here, we combine experiment and simulation to address this question as it pertains to the SARS-CoV-2 receptor binding domain (RBD). We show that, whereas RBD can refold reversibly when its disulfides are intact, their disruption causes misfolding into a nonnative molten-globule state that is highly prone to aggregation and disulfide scrambling. Thus, non-equilibrium mechanisms are needed to ensure disulfides form prior to folding in vivo. Our simulations suggest that co-translational folding may accomplish this, as native disulfide pairs are predicted to form with high probability at intermediate lengths, ultimately committing the RBD to its metastable native state and circumventing nonnative intermediates. This detailed molecular picture of the RBD folding landscape may shed light on SARS-CoV-2 pathology and molecular constraints governing SARS-CoV-2 evolution.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.11.10.516025v1" target="_blank">Cotranslational formation of disulfides guides folding of the SARS CoV-2 receptor binding domain</a>
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<li><strong>A pan-variant mRNA-LNP T cell vaccine protects HLA transgenic mice from mortality after infection with SARS-CoV-2 Beta</strong> -
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Clinically licensed COVID-19 vaccines ameliorate viral infection by inducing vaccinee production of neutralizing antibodies that bind to the SARS-CoV-2 Spike protein to inhibit viral cellular entry (Walsh et al., 2020; Baden et al., 2021), however the clinical effectiveness of these vaccines is transitory as viral variants arise that escape antibody neutralization (Tregoning et al., 2021; Willett et al., 2022). Vaccines that solely rely upon a T cell response to combat viral infection could be transformational because they can be based on highly conserved short peptide epitopes that hold the potential for pan-variant immunity, but a mRNA-LNP T cell vaccine has not been shown to be sufficient for effective antiviral prophylaxis. Here we show that a mRNA-LNP vaccine based on highly conserved short peptide epitopes activates a CD8+ and CD4+ T cell response that prevents mortality in HLA-A*02:01 transgenic mice infected with the SARS-CoV-2 Beta variant of concern (B.1.351). In mice vaccinated with the T cell vaccine, 24% of the nucleated cells in lung were CD8+ T cells on day 7 post infection. This was 5.5 times more CD8+ T cell infiltration of the lungs in response to infection compared to the Pfizer-BioNTech Comirnaty(R) vaccine. Between days 2 and 7 post infection, the number of CD8+ T cells in the lung increased in mice vaccinated with the T cell vaccine and decreased in mice vaccinated with Comirnaty(R). The T cell vaccine did not produce neutralizing antibodies, and thus our results demonstrate that SARS-CoV-2 viral infection can be controlled by a T cell response alone. Our results suggest that further study is merited for pan-variant T cell vaccines, and that T cell vaccines may be relevant for individuals that cannot produce neutralizing antibodies or to help mitigate Long COVID.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.09.23.509206v3" target="_blank">A pan-variant mRNA-LNP T cell vaccine protects HLA transgenic mice from mortality after infection with SARS-CoV-2 Beta</a>
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<li><strong>Health, socioeconomic and genetic predictors of COVID-19 vaccination uptake: a nationwide machine-learning study</strong> -
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Reduced participation in COVID-19 vaccination programs is a key societal concern. Understanding factors associated with vaccination uptake can help in planning effective immunization programs. We considered 2,890 health, socioeconomic, familial, and demographic factors measured on the entire Finnish population aged 30 to 80 (N=3,192,505) and genome-wide information for a subset of 273,765 individuals. Risk factors were further classified into 12 thematic categories and a machine learning model was trained for each category. The main outcome was uptaking the first COVID-19 vaccination dose by 31.10.2021, which has occurred for 90.3% of the individuals. The strongest predictor category was labor income in 2019 (AUC evaluated in a separate test set = 0.710, 95% CI: 0.708-0.712), while drug purchase history, including 376 drug classes, achieved a similar prediction performance (AUC = 0.706, 95% CI: 0.704-0.708). Higher relative risks of being unvaccinated were observed for some mental health diagnoses (e.g. dissocial personality disorder, OR=1.26, 95% CI : 1.24-1.27 ) and when considering vaccination status of first-degree relatives (OR=1.31, 95% CI:1.31-1.32 for unvaccinated mothers) We derived a prediction model for vaccination uptake by combining all the predictors and achieved good discrimination (AUC = 0.801, 95% CI: 0.799-0.803). The 1% of individuals with the highest risk of not vaccinating according to the model predictions had an average observed vaccination rate of only 18.8%. We identified 8 genetic loci associated with vaccination uptake and derived a polygenic score, which was a weak predictor of vaccination status in an independent subset (AUC=0.612, 95% CI: 0.601-0.623). Genetic effects were replicated in an additional 145,615 individuals from Estonia (genetic correlation=0.80, 95% CI: 0.66-0.95) and, similarly to data from Finland, correlated with mental health and propensity to participate in scientific studies. Individuals at higher genetic risk for severe COVID-19 were less likely to get vaccinated (OR=1.03, 95% CI: 1.02-1.05). Our results, while highlighting the importance of harmonized nationwide information, not limited to health, suggest that individuals at higher risk of suffering the worst consequences of COVID-19 are also those less likely to uptake COVID-19 vaccination. The results can support evidence-informed actions for COVID-19 and other areas of national immunization programs.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.11.22282213v1" target="_blank">Health, socioeconomic and genetic predictors of COVID-19 vaccination uptake: a nationwide machine-learning study</a>
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<li><strong>Assessing the spatial-temporal risks of SARS-CoV-2 infection for healthcare-workers in the hospital using behavioural indices from routine data</strong> -
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The COVID-19 pandemic has emphasised the need to rapidly assess infection risks for healthcare workers within the hospital environment. Using data from the first year of the pandemic, we investigated whether an individuals COVID-19 test result was associated with behavioural markers derived from routinely collected hospital data two weeks prior to a test. The temporal and spatial context of behaviours were important, with the highest risks of infection during the first wave, for staff in contact with a greater number of patients and those with greater levels of activity on floors handling the majority of COVID-19 patients. Infection risks were higher for BAME staff and individuals working more shifts. Night shifts presented higher risks of infection between waves of COVID-19 patients. Our results demonstrate the epidemiological relevance of deriving markers of staff behaviour from electronic records, which extend beyond COVID-19 with applications for other communicable diseases and in supporting pandemic preparedness.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.10.22282176v1" target="_blank">Assessing the spatial-temporal risks of SARS-CoV-2 infection for healthcare-workers in the hospital using behavioural indices from routine data</a>
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<li><strong>Cohort profile: A Quebec-based plasma donor biobank to study COVID-19 immunity (PlasCoV)</strong> -
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Purpose Long-term humoral immunity to COVID-19 is not well understood owing to the continuous emergence of new variants of concern, the evolving vaccine- and infection-induced immunity, and the limited follow-up of previous studies. As the blood service in Quebec (Canada), we established in April 2021 a COVID-19-focused biobank. Participants As of January 2022, included 86,229 plasma samples from 15,502 regular donors (age range=18-84 years, female %=49.7%), for an average of 5.6 donations per donor. Nearly two thirds (65.6%) of biobank donors made at least 2 donations, with many donors having provided samples pre- and post-vaccination (3061 [19.75%]) or pre- and post-infection (131 [0.85%]), thus allowing longitudinal studies on vaccine- and infection-induced immunity. Findings to date Comparative analysis of the immune response after the first and second dose of the BNT162b2 COVID-19 vaccine among SARS-CoV-2 naive and previously infected individuals revealed that a single vaccine dose administered to previously infected individuals yields a maximal immune response. In contrast, SARS-CoV-2 naive individuals required two vaccine doses to produce a maximal immune response. Furthermore, the results of a four-phase seroprevalence study indicate that the anti-N antibody response wanes quite rapidly, so that up to one third of previously infected donors were seronegative for anti-N. Future plans This plasma biobank from frequent and motivated donors, and the longitudinal nature of the biobank, will provide valuable insights into the anti-SARS-CoV-2 immune response and its persistence in time, and the effect of vaccination and of viral variants on the specificity of the antiSARS-CoV-2 immune response.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.09.22282156v1" target="_blank">Cohort profile: A Quebec-based plasma donor biobank to study COVID-19 immunity (PlasCoV)</a>
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<li><strong>A Digital Biomarker for Identifying Changes in Daily Activity Patterns</strong> -
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Malnutrition and dehydration are strongly associated with increased cognitive and functional decline in people living with dementia (PLWD), as well as an increased rate of hospitalisations in comparison to their healthy counterparts. Extreme changes in eating and drinking behaviours can often lead to malnutrition and dehydration, accelerating the progression of cognitive and functional decline and resulting in a marked reduction in quality of life. Unfortunately, there are currently no established methods by which to objectively detect such changes. Here, we present the findings of a quantitative analysis conducted on in-home monitoring data collected from 73 households of PLWD using Internet of Things technologies. The Coronavirus 2019 (COVID-19) pandemic has previously been shown to have dramatically altered the behavioural habits, particularly the eating and drinking habits, of PLWD. Using the COVID-19 pandemic as a natural experiment, we show that there were significant changes in kitchen activities at the group level within a subset of 21 households of PLWD that were continuously monitored for 499 days, with an overall increase in day-time activities and a decrease in night-time activity observed in both single and multiple occupancy households. We further present preliminary results suggesting it is possible to proactively detect episodic and gradual changes in behaviours using remote monitoring data as a proxy for behaviours that cannot be directly measured. Together, these results pave the way to introduce improvements into the monitoring of PLWD in naturalistic settings and for shifting from reactive to proactive care.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.25.22281467v2" target="_blank">A Digital Biomarker for Identifying Changes in Daily Activity Patterns</a>
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</div></li>
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<li><strong>Parents’ Work Arrangements and Gendered Time Use During the COVID-19 Pandemic</strong> -
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Objective: This study uses time diaries to examine how work arrangements shaped mothers’ and fathers’ time use at home and work during the COVID-19 pandemic. Background: The pandemic transformed home and work life for parents, disrupting employment and childcare. The shift to work from home offered more flexibility than the workplace to manage increased care burdens, but the lack of separation between work and family also likely contributed to more challenging work environments, especially among mothers. Method: This study relies on representative data from the 2017-2020 American Time Use Survey and matching to estimate changes in time use among parents working from home and the workplace in the pandemic relative to equivalent pre-pandemic parents. Results: Data showed no increase among working parents in activities in which childcare was the primary focus. Parents working from home during the pandemic, however, spent substantially more time on supervisory childcare, particularly in combination with paid work, and housework. Mothers working from home also changed their paid work schedules. Conclusion: Parents working from home responded to childcare demands through multitasking and schedule changes, especially mothers, with potential negative effects on work quality and stress. Parents in the workplace during the pandemic experienced smaller changes in time use, suggesting little flexibility to accommodate changes in family life. Implications: The pandemic has generated new inequalities between those with and without the flexibility to work from home, and potentially exacerbated gender inequalities among those working from home.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/xc9mw/" target="_blank">Parents’ Work Arrangements and Gendered Time Use During the COVID-19 Pandemic</a>
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</div></li>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 Bivalent Booster Megastudy</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: COVID Booster text messages<br/><b>Sponsor</b>: University of Pennsylvania<br/><b>Enrolling by invitation</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>Using a Community-level Just-in-Time Adaptive Intervention to Address COVID-19 Testing Disparities</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Behavioral: Multi-Level Multi-Component Intervention (MLI); Behavioral: Community Just-In-Time Adaptive Intervention (Community JITAI)<br/><b>Sponsors</b>: The University of Texas Health Science Center, Houston; National Center for Advancing Translational Sciences (NCATS)<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Examining How a Facilitated Self-Sampling Intervention and Testing Navigation Intervention Influences COVID-19 Testing</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Behavioral: Facilitated Self-Sampling Intervention (FSSI); Behavioral: Testing Navigation Intervention (TNI).; Behavioral: Control<br/><b>Sponsors</b>: The University of Texas Health Science Center, Houston; National Center for Advancing Translational Sciences (NCATS)<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>Assessing Performance of the Testing Done Simple Covid 19 Antigen Test</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Diagnostic Test: Testing Done Simple SARS CoV-2 Antigen Test<br/><b>Sponsors</b>: Testing Done Simple; Nao Medical Urgent Care<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 Phase III of COVID-19 Vaccine EuCorVac-19 in Healthy Adults Aged 18 Years and Older</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: EuCorVac-19; Biological: ChAdOx1<br/><b>Sponsor</b>: EuBiologics Co.,Ltd<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>Open Multicentre Study of the Safety and Efficacy Against COVID-19 of Nirmatrelvir/Ritonavir in the Adult Population</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: nirmatrelvir/ritonavir; Drug: Standard of care<br/><b>Sponsors</b>: Promomed, LLC; Sponsor GmbH<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study Evaluating GS-5245 in Participants With COVID-19 Who Have a High Risk of Developing Serious or Severe Illness</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: GS-5245; Drug: GS-5245 Placebo<br/><b>Sponsor</b>: Gilead Sciences<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>Recombinant COVID-19 Vaccine (CHO Cell, NVSI-06-09) Phase III Clinical Trial</strong> - <b>Conditions</b>: COVID-19; Coronavirus Infections<br/><b>Interventions</b>: Biological: LIBP-Rec-Vaccine; Biological: BIBP-Rec-Vaccine; Biological: placebo<br/><b>Sponsors</b>: National Vaccine and Serum Institute, China; China National Biotec Group Company Limited; Lanzhou Institute of Biological Products Co., Ltd; Beijing Institute of Biological Products Co Ltd.<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 Phase I/II Study of GLB-COV2-043 as a COVID-19 Vaccine Booster</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: GLB-COV2-043; Drug: BNT162b2/COMIRNATY®<br/><b>Sponsor</b>: GreenLight Biosciences, 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>Safety and Efficacy of Intranasal Administration of Avacc 10 Vaccine Against COVID-19 in Healthy Volunteers</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Avacc 10; Combination Product: Outer Membrane Vesicles (OMV) : OMV alone in vehicle; Other: Placebo<br/><b>Sponsors</b>: Intravacc B.V.; Novotech (Australia) Pty Limited<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Phase Ⅱ/Ⅲ Trial of LYB001</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: LYB001; Biological: Placebo<br/><b>Sponsor</b>: Yantai Patronus Biotech Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Nitric Oxide Nasal Spray (NONS) To Treat and Prevent the Exacerbation of Infection in Individuals With Mild COVID-19</strong> - <b>Condition</b>: SARS-CoV-2 Infection<br/><b>Intervention</b>: Drug: Nitric Oxide<br/><b>Sponsors</b>: Sanotize Research and Development corp.; Glenmark Pharmaceuticals Ltd. India<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase 1, Randomised, Double-blinded, Placebo-controlled, Dose-escalation Study to Evaluate the Safety and Immunogenicity of RH109 as Booster</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Interventions</b>: Biological: Lyophilized COVID-19 mRNA Vaccine; Drug: Sodium chloride<br/><b>Sponsors</b>: Wuhan Recogen Biotechnology Co., Ltd.; Shenzhen Rhegen Biotechnology Co., Ltd.; Wuhan Rhegen Biotechnology Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Role of Tele-physical Therapy in Patients With Type 2 Diabetes Mellitus Following COVID-19 Infection.</strong> - <b>Conditions</b>: Type 2 Diabetes Mellitus; COVID-19<br/><b>Interventions</b>: Other: Tele physical therapy; Other: Patient educationa and Conventional exercises<br/><b>Sponsor</b>: Prince Sattam Bin Abdulaziz University<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity and Safety of ChulaCov19 BNA159 Vaccine as a Booster Dose in Adults</strong> - <b>Condition</b>: COVID-19, SARS CoV 2 Infection<br/><b>Interventions</b>: Biological: ChulaCov19 BNA159 vaccine (50 mcg); Biological: Pfizer/BNT vaccine (30 mcg)<br/><b>Sponsors</b>: Technovalia, Pty Ltd; Chulalongkorn University; Bionet Co., Ltd; Southern Star Research Pty Ltd.<br/><b>Not yet 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>Identification of novel inhibitors of high affinity iron permease (FTR1) through implementing pharmacokinetics index to fight against black fungus: An in silico approach</strong> - Mucormycosis is a life-threatening fungal infection, particularly in immunocompromised patients. Mucormycosis has been reported to show resistance to available antifungal drugs and was recently found in COVID-19 as a co-morbidity that demands new classes of drugs. In an attempt to find novel inhibitors against the high-affinity iron permease (FTR1), a novel target having fundamental importance on the pathogenesis of mucormycosis, 11,000 natural compounds were investigated in this study. Virtual…</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>Chicken interferon-induced transmembrane protein 1 promotes replication of coronavirus infectious bronchitis virus in a cell-specific manner</strong> - Interferon-induced transmembrane proteins (IFITMs) are broad-spectrum antiviral proteins that inhibit numerous virus infections by impeding viral entry into target cells. However, increasing evidence suggests diverse functions of IFITMs in virus infection, especially with the coronavirus. We analyzed the effect of chicken interferon-induced transmembrane proteins (chIFITMs) on coronavirus infectious bronchitis virus (IBV) infection in vitro. We demonstrated that the antiviral effects of IFITMs…</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>Design, Synthesis, and Biological Evaluation of Novel Ruxolitinib and Baricitinib Analogues for Potential Use Against COVID-19</strong> - The coronavirus pandemic known as COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), threatens public health worldwide. Approval of COVID-19 vaccines and antiviral drugs have greatly reduced the severe cases and mortality rate. However, the continues mutations of viruses are challenging the efficacies of vaccines and antiviral drugs. Drug repurposing campaign has identified two JAK1/2 inhibitors ruxolitinib and baricitinib as potential antiviral drugs. Ruxolitinib…</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 at the Human-Animal Interface: Implication for Global Public Health from an African Perspective</strong> - The coronavirus disease 2019 (COVID-19) pandemic has become the most far-reaching public health crisis of modern times. Several efforts are underway to unravel its root cause as well as to proffer adequate preventive or inhibitive measures. Zoonotic spillover of the causative virus from an animal reservoir to the human population is being studied as the most likely event leading to the pandemic. Consequently, it is important to consider viral evolution and the process of spread within zoonotic…</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 Short 5’triphosphate RNA nCoV-L Induces a Broad-Spectrum Antiviral Response by Activating RIG-I</strong> - Small molecular nucleic acid drugs produce antiviral effects by activating pattern recognition receptors (PRRs). In this study, a small molecular nucleotide containing 5’triphosphoric acid (5’PPP) and possessing a double-stranded structure was designed and named nCoV-L. nCoV-L was found to specifically activate RIG-I, induce interferon responses, and inhibit duplication of four RNA viruses (Human enterovirus 71, Human poliovirus 1, Human coxsackievirus B5 and Influenza A virus) in cells. In…</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>Canine Coronavirus Activates Aryl Hydrocarbon Receptor during In Vitro Infection</strong> - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that interacts with substrates, including microbial metabolites. Recent advances reveal that AhR is involved in the host response to coronaviruses (CoVs) infection. Particularly, AhR antagonists decrease the expression of angiotensin-converting enzyme 2 (ACE2) via AhR up-regulation, resulting in suppression of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in mammalian cells. Herein, we report…</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>An ACE2-Based Decoy Inhibitor Effectively Neutralizes SARS-CoV-2 Omicron BA.5 Variant</strong> - The recently circulating SARS-CoV-2 Omicron BA.5 is rampaging the world with elevated transmissibility compared to the original SARS-CoV-2 strain. Immune escape of BA.5 was observed after treatment with many monoclonal antibodies, calling for broad-spectrum, immune-escape-evading therapeutics. In retrospect, we previously reported Kansetin as an ACE2 mimetic and a protein antagonist against SARS-CoV-2, which proved potent neutralization bioactivity on the Reference, Alpha, Beta, Delta, 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>Immunogenicity of an mRNA-Based COVID-19 Vaccine among Adolescents with Obesity or Liver Transplants</strong> - There are limited data regarding the immunogenicity of mRNA-based SARS-CoV-2 vaccine BNT162b2 among immunosuppressed or obese adolescents. We evaluated the humoral immune response in adolescents with obesity and adolescent liver transplant recipients (LTRs) after receiving two BNT162b2 doses. Sixty-eight participants (44 males; mean age 14.9 ± 1.7 years), comprising 12 LTRs, 24 obese, and 32 healthy adolescents, were enrolled. Immunogenicity was evaluated by anti-SARS-CoV-2 spike protein…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>In Silico Approach for the Evaluation of the Potential Antiviral Activity of Extra Virgin Olive Oil (EVOO) Bioactive Constituents Oleuropein and Oleocanthal on Spike Therapeutic Drug Target of SARS-CoV-2</strong> - Since there is an urgent need for novel treatments to combat the current coronavirus disease 2019 (COVID-19) pandemic, in silico molecular docking studies were implemented as an attempt to explore the ability of selected bioactive constituents of extra virgin olive oil (EVOO) to act as potent SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) antiviral compounds, aiming to explore their ability to interact with SARS-CoV-2 Spike key therapeutic target protein. Our results suggest 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>Identification of Doxorubicin as Repurposing Inhibitory Drug for MERS-CoV PLpro</strong> - Middle East respiratory syndrome coronavirus (MERS-CoV), belonging to the betacoronavirus genus can cause severe respiratory illnesses, accompanied by pneumonia, multiorgan failure, and ultimately death. CoVs have the ability to transgress species barriers and spread swiftly into new host species, with human-to-human transmission causing epidemic diseases. Despite the severe public health threat of MERS-CoV, there are currently no vaccines or drugs available for its treatment. MERS-CoV…</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>Impact of <em>TMPRSS2</em> Expression, Mutation Prognostics, and Small Molecule (CD, AD, TQ, and TQFL12) Inhibition on Pan-Cancer Tumors and Susceptibility to SARS-CoV-2</strong> - As a cellular protease, transmembrane serine protease 2 (TMPRSS2) plays roles in various physiological and pathological processes, including cancer and viral entry, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein, we conducted expression, mutation, and prognostic analyses for the TMPRSS2 gene in pan-cancers as well as in COVID-19-infected lung tissues. The results indicate that TMPRSS2 expression was highest in prostate cancer. A high expression of TMPRSS2 was…</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>Homology Modeling and Molecular Dynamics-Driven Search for Natural Inhibitors That Universally Target Receptor-Binding Domain of Spike Glycoprotein in SARS-CoV-2 Variants</strong> - The rapid spread of SARS-CoV-2 required immediate actions to control the transmission of the virus and minimize its impact on humanity. An extensive mutation rate of this viral genome contributes to the virus’ ability to quickly adapt to environmental changes, impacts transmissibility and antigenicity, and may facilitate immune escape. Therefore, it is of great interest for researchers working in vaccine development and drug design to consider the impact of mutations on virus-drug interactions….</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><em>Lentinus edodes</em> Polysaccharides Alleviate Acute Lung Injury by Inhibiting Oxidative Stress and Inflammation</strong> - Acute lung injury (ALI) is a kind of lung disease with acute dyspnea, pulmonary inflammation, respiratory distress, and non-cardiogenic pulmonary edema, accompanied by the mid- and end-stage characteristics of COVID-19, clinically. It is imperative to find non-toxic natural substances on preventing ALI and its complications. The animal experiments demonstrated that Lentinus edodes polysaccharides (PLE) had a potential role in alleviating ALI by inhibiting oxidative stress and inflammation, which…</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>Ultra-Large-Scale Screening of Natural Compounds and Free Energy Calculations Revealed Potential Inhibitors for the Receptor-Binding Domain (RBD) of SARS-CoV-2</strong> - The emergence of immune-evading variants of SARS-CoV-2 further aggravated the ongoing pandemic. Despite the deployments of various vaccines, the acquired mutations are capable of escaping both natural and vaccine-induced immune responses. Therefore, further investigation is needed to design a decisive pharmacological treatment that could efficiently block the entry of this virus into cells. Hence, the current study used structure-based methods to target the RBD of the recombinant variant…</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>Broad Antiviral Effects of <em>Echinacea purpurea</em> against SARS-CoV-2 Variants of Concern and Potential Mechanism of Action</strong> - SARS-CoV-2 variants of concern (VOCs) represent an alarming threat as they show altered biological behavior and may escape vaccination effectiveness. Broad-spectrum antivirals could play an important role to control infections. The activity of Echinacea purpurea (Echinaforce^(®) extract, EF) against (i) VOCs B1.1.7 (alpha), B.1.351.1 (beta), P.1 (gamma), B1.617.2 (delta), AV.1 (Scottish), B1.525 (eta), and B.1.1.529.BA1 (omicron); (ii) SARS-CoV-2 spike (S) protein-pseudotyped viral particles and…</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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