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<title>24 May, 2022</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Prosocial behavior in emergencies: Evidence from blood donors recruitment and retention during the COVID-19 pandemic</strong> -
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The impact of COVID-19 represents a specific challenge for voluntary transfusional systems sustained by the intrinsic motivations of blood donors. In general, health emergencies can stimulate altruistic behaviors. However, in this context, the same prosocial motivations, besides the personal health risks, could foster the adherence to social distancing rules to preserve collective health and, therefore, discourage blood donation activities. In this work, we investigate the consequences of the pandemic shock on the dynamics of new donors exploiting the individual-level longitudinal information contained in administrative data on the Italian region of Tuscany. We compare the change in new donors’ recruitment and retention during 2020 with respect to the 2017-2019 period, considering donors’ and their municipalities of residence characteristics. Our results show an increment of new donors, with higher growth for older donors. Moreover, we demonstrate that the quality of new donors, as proxied by the frequency of subsequent donations, increased with respect to previous years. Finally, we show that changes in extrinsic motivations, such as the possibility of obtaining a free antibody test or overcoming movement restrictions, cannot explain the documented improvement in performances.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/6t72b/" target="_blank">Prosocial behavior in emergencies: Evidence from blood donors recruitment and retention during the COVID-19 pandemic</a>
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<li><strong>Using a reverse genetics system to generate recombinant SARS-CoV-2 expressing robust levels of reporter genes</strong> -
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Reporter-expressing recombinant virus represents an excellent option and a powerful tool to investigate, among others, viral infection, pathogenicity, and transmission, as well as to identify therapeutic compounds that inhibit viral infection and prophylactic vaccines. To combat the still ongoing coronavirus disease 2019 (COVID-19) pandemic, we have established a robust bacterial artificial chromosome (BAC)-based reverse genetics (RG) system to rapidly generate recombinant severe acute respiratory syndrome coronavirus 2 (rSARS-CoV-2) to study the contribution of viral proteins in viral pathogenesis. In addition, we have also engineered reporter-expressing recombinant viruses in which we place the reporter genes upstream of the viral nucleocapsid (N) gene to promote high levels of reporter gene expression that facilitates the study of SARS-CoV-2 in vitro and in vivo. Although successful, the genetic manipulation of the BAC containing the entire SARS-CoV-2 genome of ~30,000 nucleotides, is challenging. Herein, we depict the technical details to engineer rSARS-CoV-2 expressing reporter genes using the BAC-based RG approach. We describe i) assembly of the full- length (FL) SARS-CoV-2 genome sequences into the empty pBeloBAC, ii) verification of the pBeloBAC-FL, iii) cloning of a Venus reporter gene into the pBeloBAC-FL, and iv) recovery of the Venus-expressing rSARS-CoV-2. By following this protocol, researchers with basic molecular biology and gene engineering techniques knowledge will be able to generate wild-type and reporter-expressing rSARS-CoV-2.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.21.492922v1" target="_blank">Using a reverse genetics system to generate recombinant SARS-CoV-2 expressing robust levels of reporter genes</a>
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</div></li>
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<li><strong>Reduced Neutralization of SARS-CoV-2 Omicron Variant in Sera from SARS-CoV-1 Survivors after 3-dose of Vaccination</strong> -
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Recent studies found that Omicron variant escapes vaccine-elicited immunity. Interestingly, potent cross-clade pan- sarbecovirus neutralizing antibodies were found in survivors of the infection by SARS-CoV-1 after BNT162b2 mRNA vaccination (N Engl J Med. 2021 Oct 7;385(15):1401-1406). These pan-sarbecovirus neutralizing antibodies were observed to efficiently neutralize the infection driven by the S protein from both SARS-CoV and multiple SARS-CoV-2 variants of concern (VOC) including B.1.1.7 (Alpha), B.1.351 (Beta), and B.1.617.2 (Delta) (N Engl J Med. 2021 Oct 7;385(15):1401-1406). However, whether these cross-reactive antibodies could neutralize the Omicron variant is still unknown. Based on the data collected from a cohort of SARS-CoV-1 survivors received 3-dose of immunization, our studies reported herein showed that a high level of neutralizing antibodies against both SARS-CoV-1 and SARS-CoV-2 were elicited by a 3rd-dose of booster vaccination of protein subunit vaccine ZF2001. However, a dramatically reduced neutralization of SARS-CoV-2 Omicron Variant (B.1.1.529) is observed in sera from these SARS-CoV-1 survivors received 3-dose of Vaccination. Our results indicates that the rapid development of pan-variant adapted vaccines is warranted.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.21.492903v1" target="_blank">Reduced Neutralization of SARS-CoV-2 Omicron Variant in Sera from SARS-CoV-1 Survivors after 3-dose of Vaccination</a>
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<li><strong>The SARS-CoV-2 spike protein binds and modulates estrogen receptors</strong> -
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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein binds angiotensin-converting enzyme 2 (ACE2) at the cell surface, which constitutes the primary mechanism driving SARS-CoV-2 infection. Molecular interactions between the transduced S and endogenous proteins likely occur post-infection, but such interactions are not well understood. We used an unbiased primary screen to profile the binding of full-length S against >9,000 human proteins and found significant S-host protein interactions, including one between S and human estrogen receptor alpha (ER). After confirming this interaction in a secondary assay, we used bioinformatics, supercomputing, and experimental assays to identify a highly conserved and functional nuclear receptor coregulator (NRC) LXD-like motif on the S2 subunit and an S-ER binding mode. In cultured cells, S DNA transfection increased ER cytoplasmic accumulation, and S treatment induced ER-dependent biological effects and ACE2 expression. Noninvasive multimodal PET/CT imaging in SARS- CoV-2-infected hamsters using [18F]fluoroestradiol (FES) localized lung pathology with increased ER lung levels. Postmortem experiments in lung tissues from SARS-CoV-2-infected hamsters and humans confirmed an increase in cytoplasmic ER expression and its colocalization with S protein in alveolar macrophages. These findings describe the discovery and characterization of a novel S-ER interaction, imply a role for S as an NRC, and are poised to advance knowledge of SARS- CoV-2 biology, COVID-19 pathology, and mechanisms of sex differences in the pathology of infectious disease.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.21.492920v1" target="_blank">The SARS-CoV-2 spike protein binds and modulates estrogen receptors</a>
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<li><strong>Intranasal pediatric parainfluenza virus-vectored SARS-CoV-2 vaccine candidate is protective in macaques</strong> -
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Pediatric SARS-CoV-2 vaccines are needed that elicit immunity directly in the airways, as well as systemically. Building on pediatric parainfluenza virus vaccines in clinical development, we generated a live-attenuated parainfluenza virus-vectored vaccine candidate expressing SARS-CoV-2 prefusion-stabilized spike (S) protein (B/HPIV3/S-6P) and evaluated its immunogenicity and protective efficacy in rhesus macaques. A single intranasal/intratracheal dose of B/HPIV3/S-6P induced strong S-specific airway mucosal IgA and IgG responses. High levels of S-specific antibodies were also induced in serum, which efficiently neutralized SARS-CoV-2 variants of concern. Furthermore, B/HPIV3/S-6P induced robust systemic and pulmonary S-specific CD4+ and CD8+ T-cell responses, including tissue-resident memory cells in lungs. Following challenge, SARS-CoV-2 replication was undetectable in airways and lung tissues of immunized macaques. B/HPIV3/S-6P will be evaluated clinically as pediatric intranasal SARS-CoV-2/parainfluenza virus type 3 vaccine.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.21.492923v1" target="_blank">Intranasal pediatric parainfluenza virus-vectored SARS-CoV-2 vaccine candidate is protective in macaques</a>
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<li><strong>Modeling suggests that multiple immunizations or infections will reveal the benefits of updating SARS-CoV-2 vaccines</strong> -
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When should vaccines to evolving pathogens such as SARS-CoV-2 be updated? Our computational models address this focusing on updating SARS-CoV-2 vaccines to the currently circulating Omicron variant. Current studies typically compare the antibody titers to the new variant following a single dose of the original-vaccine versus the updated-vaccine in previously immunized individuals. These studies find that the updated-vaccine does not induce higher titers to the vaccine-variant compared with the original-vaccine, suggesting that updating may not be needed. Our models recapitulate this observation but suggest that vaccination with the updated-vaccine generates qualitatively different humoral immunity, a small fraction of which is specific for unique epitopes to the new variant. Our simulations suggest that these new variant-specific responses could dominate following subsequent vaccination or infection with either the currently circulating or future variants. We suggest a two-dose strategy for determining if the vaccine needs updating and for vaccinating high-risk individuals.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.21.492928v1" target="_blank">Modeling suggests that multiple immunizations or infections will reveal the benefits of updating SARS-CoV-2 vaccines</a>
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<li><strong>Anti-chemokine antibodies after SARS-CoV-2 infection correlate with favorable disease course</strong> -
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Infection by SARS-CoV-2 leads to diverse symptoms, which can persist for months. While antiviral antibodies are protective, those targeting interferons and other immune factors are associated with adverse COVID-19 outcomes. Instead, we discovered that antibodies against specific chemokines are omnipresent after COVID-19, associated with favorable disease, and predictive of lack of long COVID symptoms at one year post infection. Anti-chemokine antibodies are present also in HIV-1 and autoimmune disorders, but they target different chemokines than those in COVID-19. Finally, monoclonal antibodies derived from COVID-19 convalescents that bind to the chemokine N-loop impair cell migration. Given the role of chemokines in orchestrating immune cell trafficking, naturally arising anti-chemokine antibodies associated with favorable COVID 19 may be beneficial by modulating the inflammatory response and thus bear therapeutic potential.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.23.493121v1" target="_blank">Anti-chemokine antibodies after SARS- CoV-2 infection correlate with favorable disease course</a>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Patient satisfaction with telemedicine in the Philippines during the COVID-19 pandemic</strong> -
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Introduction: The capacity to deliver essential health services has been negatively impacted by the COVID-19 pandemic particularly due to lockdown restrictions. Telemedicine provides a safe, efficient, and effective solution that addresses the needs of patients and the health system. However, there remain implementation challenges and barriers to patient adoption in resource-limited settings as in the Philippines. This study thus aimed to describe patient perspectives and experiences with telemedicine services, and explore the factors that influence telemedicine use and satisfaction. Methods: This study used a mixed-methods design through online surveys and in-depth interviews. An online survey using Consumer Assessment of Healthcare Providers and Systems (CAHPS) Clinician & Group Adult Visit Survey 4.0 (beta) and Telehealth Usability Questionnaire (TUQ) was accomplished by 200 participants aged 18 to 65 years. A subsample of 16 participants was interviewed to provide insights to the quantitative data. We used descriptive statistics to analyze survey data and grounded theory to analyze data from interviews. Results: Participants were generally satisfied with telemedicine services, with most reporting that this was an efficient and convenient alternative to face-to-face consultations. However, only 2 in 5 perceived telemedicine as affordable. Our quantitative findings suggest that participants preferred telemedicine services rather than in-person consultations, especially in cases where they feel that their condition is not urgent and does not need extensive physical examination. Safety against COVID-19, and the availability of multiple communication platforms contributed to patient satisfaction with telemedicine. Negative perceptions of patients on their telemedicine provider, perceived higher costs, poor connectivity and other technological issues were found to be barriers to patient satisfaction. Discussion: Telemedicine is viewed as a safe and efficient alternative to receiving care. Continued adoption of telemedicine will require improvements in technology and better patient communication related to their telemedicine provider and the associated costs.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.21.22274939v1" target="_blank">Patient satisfaction with telemedicine in the Philippines during the COVID-19 pandemic</a>
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<li><strong>Variant-specific symptoms of COVID-19 among 1,542,510 people in England</strong> -
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Infection with SARS-CoV-2 virus is associated with a wide range of symptoms. The REal-time Assessment of Community Transmission -1 (REACT-1) study has been monitoring the spread and clinical manifestation of SARS-CoV-2 among random samples of the population in England from 1 May 2020 to 31 March 2022. We show changing symptom profiles associated with the different variants over that period, with lower reporting of loss of sense of smell and taste for Omicron compared to previous variants, and higher reporting of cold-like and influenza-like symptoms, controlling for vaccination status. Contrary to the perception that recent variants have become successively milder, Omicron BA.2 was associated with reporting more symptoms, with greater disruption to daily activities, than BA.1. With restrictions lifted and routine testing limited in many countries, monitoring the changing symptom profiles associated with SARS- CoV-2 infection and induced changes in daily activities will become increasingly important.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.21.22275368v1" target="_blank">Variant-specific symptoms of COVID-19 among 1,542,510 people in England</a>
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<li><strong>Safety of the BNT162b2 mRNA COVID-19 Vaccine in Children below 5 Years in Germany (CoVacU5): An Investigator- initiated Retrospective Cohort Study</strong> -
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Background The safety of SARS-CoV-2 vaccines is unknown in children aged <5 years. Here, we retrospectively evaluated the safety of BNT162b2 vaccine used off-label in children of this age group in Germany. Methods An investigator-initiated retrospective cohort study (CoVacU5) included parents or caregivers having children aged <5 years registered for SARS-CoV-2 vaccination in outpatient care facilities in Germany. Reported short-term safety data of 1-3 doses of 3-10ug BNT162b2 in children aged 0 to <60 months are presented. Co-primary outcomes were the frequencies of 11 categories of symptoms post-vaccination with bivariate analyses and regression models adjusting for age, sex, weight and height. On-label non-SARS-CoV-2 vaccines served as controls in an active-comparator design. Results The study included 7806 representing a 41% response rate of 19,000 registered children. 338 children received the first dose of BNT162b2 at age 0-<12 months, n=1272 at age 12-24 months and n=5629 at age ≥24 to <60 months. A 10ug dosage was more frequently associated with injection-site symptoms compared to lower dosages. The probability of any symptoms (OR: 1.62 [95% confidence interval (CI): 1.36-1.94]), injection-site, musculoskeletal, dermatological or otolaryngological symptom categories were modestly elevated after BNT12b2 compared to non-SARS-CoV-2 vaccines, whereas the probabilities of general symptoms (OR: 0.74 [95% CI: 0.64-0.85]) and fever (OR: 0.43 [95% CI: 0.35-0.51]) were lower after BNT162b2. Symptoms requiring hospitalization (n=10) were reported only at BNT162b2 dosages higher than 3ug. Conclusions The symptoms reported after BNT162b2 administration were overall comparable to on-label non-SARS-CoV-2 vaccines in this cohort of children aged <5 years.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.17.22275005v1" target="_blank">Safety of the BNT162b2 mRNA COVID-19 Vaccine in Children below 5 Years in Germany (CoVacU5): An Investigator-initiated Retrospective Cohort Study</a>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 symptoms and duration of direct antigen test positivity at a community testing and surveillance site, January 2021-2022</strong> -
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Importance: Characterizing clinical symptoms and evolution of community- based SARS Co-V-2 infections can inform health practitioners and public health officials in a rapidly changing landscape of population immunity and viral variants. Objective: To characterize COVID-19 symptoms during the Omicron period compared to pre-Delta and Delta variant periods and assess the duration of COVID-19 BinaxNOW rapid antigen test positivity during the Omicron variant surge. Design, Setting, and Participants: This public health surveillance study was undertaken between January 2021- January 2022, at a walk-up community COVID-19 testing site in San Francisco, California. Testing with BinaxNOW rapid antigen tests was available regardless of age, vaccine status, or symptoms throughout. Main Outcomes and Measures: We characterized the prevalence of specific symptoms for people with a positive BinaxNOW test during the Omicron period and compared it to the pre-Delta and Delta periods. During the Omicron period, we examined differences in symptoms by age and vaccine status. Among people returning for repeat testing during Omicron period, we estimated the proportion with a positive BinaxNOW antigen test between 4-14 days from symptom onset or since first positive test if asymptomatic. Results: Of 63,277 persons tested, 18,301 (30%) reported symptoms and 4,568 (25%) tested positive for COVID-19. During the Omicron period, 41.6% (3032/7283) of symptomatic testers tested positive, and the proportion reporting cough (67.4%) and sore throat (43.4%) was higher than during Delta and pre-Delta periods. Congestion was higher during Omicron (38.8%) than during the pre-Delta period and loss of taste/smell (5.3%) and fever (30.4%) were less common. Fevers and myalgias were less common among persons who had received boosters compared to unvaccinated people or those who received the primary series. Five days after symptom onset, 31.1% of people with COVID-19 stated their symptoms were similar or worsening. An estimated 80.2% of symptomatic re-testers remained positive five days after symptom onset and 60.5% after ten days. Conclusions and Relevance: COVID-19 upper respiratory tract symptoms were more commonly reported during the Omicron period compared to pre-Delta and Delta periods, with differences by vaccination status. Antigen test positivity remained high after 5 days, supporting guidelines requiring a negative test to shorten the isolation period.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.19.22274968v1" target="_blank">COVID-19 symptoms and duration of direct antigen test positivity at a community testing and surveillance site, January 2021-2022</a>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Low testing rates limit the ability of genomic surveillance programs to monitor SARS-CoV-2 variants: a mathematical modelling study</strong> -
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Background Genomic surveillance is essential for monitoring the emergence and spread of SARS-CoV-2 variants. SARS-CoV-2 diagnostic testing is the starting point for SARS-CoV-2 genomic sequencing. However, testing rates in many low- and middle-income countries (LMICs) are low (mean = 27 tests/100,000 people/day) and global testing rates are falling in the post-crisis phase of the pandemic, leading to spatiotemporal biases in sample collection. Various public health agencies and academic groups have produced recommendations on sample sizes and sequencing strategies for effective genomic surveillance. However, these recommendations assume very high volumes of diagnostic testing that are currently well beyond reach in most LMICs. Methods To investigate how testing rates, sequencing strategies and the degree of spatiotemporal bias in sample collection impact variant detection and monitoring outcomes, we used an individual-based model to simulate COVID-19 epidemics in a prototypical LMIC. Within the model, we simulated a range of testing rates, accounted for likely testing demand and applied various genomic surveillance strategies, including sentinel surveillance. Findings Diagnostic testing rates play a substantially larger role in monitoring the prevalence and emergence of new variants than the proportion of samples sequenced. To enable timely detection and monitoring of emerging variants, programs should achieve average testing rates of at least 100 tests/100,000 people/day and sequence 5-10% of test-positive specimens, which may be accomplished through sentinel or other routine surveillance systems. Under realistic assumptions, this averages to ~10 samples for sequencing/1,000,000 people/week. Interpretation For countries where testing capacities are low and sample collection is spatiotemporally biased, surveillance programs should prioritize investments in wider access to diagnostic testing to enable more representative sampling, ahead of simply increasing quantities of sequenced samples. Funding European Research Council, the Rockefeller Foundation, and the Governments of Germany, Canada, UK, Australia, Norway, Saudi Arabia, Kuwait, Netherlands and Portugal.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.20.22275319v1" target="_blank">Low testing rates limit the ability of genomic surveillance programs to monitor SARS-CoV-2 variants: a mathematical modelling study</a>
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<li><strong>Comparative effectiveness of sotrovimab and molnupiravir for prevention of severe COVID-19 outcomes in non- hospitalised patients: an observational cohort study using the OpenSAFELY platform</strong> -
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Objective: To compare the effectiveness of sotrovimab (a neutralising monoclonal antibody) vs. molnupiravir (an antiviral) in preventing severe COVID-19 outcomes in non-hospitalised high-risk COVID-19 adult patients. Design: With the approval of NHS England, we conducted a real-world cohort study using the OpenSAFELY-TPP platform. Setting: Patient- level electronic health record data were obtained from 24 million people registered with a general practice in England that uses TPP software. The primary care data were securely linked with data on COVID-19 infection and therapeutics, hospital admission and death within the OpenSAFELY-TPP platform, covering a period where both medications were frequently prescribed in community settings. Participants: Non-hospitalised adult COVID-19 patients at high-risk of severe outcomes treated with sotrovimab or molnupiravir between December 16, 2021 and February 10, 2022. Interventions: Sotrovimab or molnupiravir administered in the community by COVID-19 Medicine Delivery Units. Main outcome measure: COVID-19 related hospitalisation or COVID-19 related death within 28 days after treatment initiation. Results: Patients treated with sotrovimab (n=3288) and molnupiravir (n=2663) were similar with respect to most baseline characteristics. The mean age of all 5951 patients was 52 (SD=16) years; 59% were female, 89% White and 87% had three or more COVID-19 vaccinations. Within 28 days after treatment initiation, 84 (1.4%) COVID-19 related hospitalisations/deaths were observed (31 treated with sotrovimab and 53 with molnupiravir). Cox proportional hazards models stratified by area showed that after adjusting for demographics, high-risk cohort categories, vaccination status, calendar time, body mass index and other comorbidities, treatment with sotrovimab was associated with a substantially lower risk than treatment with molnupiravir (hazard ratio, HR=0.53, 95% CI: 0.32-0.88; P=0.014). Consistent results were obtained from propensity score weighted Cox models (HR=0.51, 95% CI: 0.31-0.83; P=0.007) and when restricted to fully vaccinated people (HR=0.52, 95% CI: 0.30-0.90; P=0.020). No substantial effect modifications by other characteristics were detected (all P values for interaction>0.10). Conclusion: In routine care of non- hospitalised high-risk adult patients with COVID-19 in England, those who received sotrovimab were at lower risk of severe COVID-19 outcomes than those receiving molnupiravir.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.22.22275417v1" target="_blank">Comparative effectiveness of sotrovimab and molnupiravir for prevention of severe COVID-19 outcomes in non-hospitalised patients: an observational cohort study using the OpenSAFELY platform</a>
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<li><strong>Does directly integrating health information exchange (HIE) data with the electronic health record increase HIE use by clinicians in the emergency department?</strong> -
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Objective: Develop and evaluate the effect of a Fast Healthcare Interoperability Resources (FHIR) app, Health Dart, integrating information from Indianas community health information exchange (HIE), the Indiana Network for Patient Care (INPC), directly with Cerner, an electronic health record (EHR) Materials and Methods: Health Dart was implemented in 14 Indiana University Health emergency departments (ED) using a stepped-wedge study design. We analyzed rates of INPC use in 286,175 ED encounters between October 1, 2019 and December 31, 2020. Logistic regression was used to model the probability of INPC use given the implementation context, such as user interface (UI) enhancements and the COVID-19 pandemic. Results: INPC use increased by 131% across all encounters (from 3.6% to 8.3%; p<0.001) after Health Dart implementation. INPC use increased by144% (from 3.6% to 8.8%; p<0.001) more than two months post-implementation. After UI enhancements, post-implementation INPC use increased 123% (from 3.5% to 7.8%) compared to 181% (from 3.6% to 10.1%; p<0.001) in post-implementation encounters that occurred before UI enhancements. During the pandemic, post- implementation INPC use increased by 135% (from 3.4% to 8.0%; p<0.001) compared to 178% (from 3.6% to 10%; p<0.001) in post-implementation encounters that occurred before the pandemic. Statistical significance was determined using 95% confidence intervals (α=0.05). Discussion: Direct integration of HIE information into an EHR substantially increased frequency of HIE use, but the effect was weakened by the UI enhancements and pandemic. Conclusion: HIE information integrated into EHRs in the form of dashboards can potentially make information retrieval more efficient and effective for clinicians.
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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/10.1101/2022.05.20.22275255v1" target="_blank">Does directly integrating health information exchange (HIE) data with the electronic health record increase HIE use by clinicians in the emergency department?</a>
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</div></li>
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<li><strong>A Mesoscale Agent Based Modeling Framework For Flow-mediated Infection Transmission In Indoor Occupied Spaces</strong> -
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The ongoing Covid-19 pandemic, and its associated public health and socioeconomic burden, has reaffirmed the necessity for a comprehensive understanding of flow-mediated infection transmission in occupied indoor spaces. This is an inherently multiscale problem, and suitable investigation approaches that can enable evidence-based decision-making for infection control strategies, interventions, and policies; will need to account for flow physics, and occupant behavior. Here, we present a mesoscale infection transmission model for human occupied indoor spaces, by integrating an agent-based human interaction model with a flow physics model for respiratory droplet dynamics and transport. We outline the mathematical and algorithmic details of the modeling framework, and demonstrate its validity using two simple simulation scenarios that verify each of the major sub-models. We then present a detailed case-study of infection transmission in a model indoor space with 60 human occupants; using a systematic set of simulations representing various flow scenarios. Data from the simulations illustrate the utility and efficacy of the devised mesoscale model in resolving flow-mediated infection transmission; and elucidate key trends in infection transmission dynamics amongst the human occupants.
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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/10.1101/2022.05.20.22275409v1" target="_blank">A Mesoscale Agent Based Modeling Framework For Flow-mediated Infection Transmission In Indoor Occupied Spaces</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>The Role of Glutathione Deficiency and MSIDS Variables in Long COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Dietary Supplement: NAC (N-acetyl cysteine) , Alpha lipoic acid (ALA), liposomal glutathione (GSH)<br/><b>Sponsors</b>: University of California, Irvine; Hudson Valley Healing Arts Center<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>Study to Evaluate the Efficacy of IN STI-9199 in Treating Symptomatic COVID-19 in Outpatient Adults and Adolescents</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: STI-9199; Drug: Placebo<br/><b>Sponsor</b>: <br/>
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Sorrento Therapeutics, 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>A Safety and Efficacy Study of Hymecromone Tablets for the Treatment of Patients With COVID-19.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Hymecromone tablets; Other: Placebo<br/><b>Sponsor</b>: Shanghai Zhongshan Hospital<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study on Sequential Immunization of Omicron Inactivated COVID-19 Vaccine and Prototype Inactivated COVID-19 Vaccine in Population Aged 18 Years Old and Above</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Omicron COVID-19 Vaccine (Vero Cell), Inactivated; Biological: COVID-19 Vaccine (Vero Cell), Inactivated<br/><b>Sponsors</b>: <br/>
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China National Biotec Group Company Limited; Beijing Institute of Biological Products Co Ltd.; Hunan Provincial Center for Disease Control and Prevention<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Neuro-inflammation and Post-infectious Fatigue in Individuals With and Without COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Radiation: [18F]DPA-714 positron emission tomography (PET) scan<br/><b>Sponsors</b>: Amsterdam UMC, location VUmc; ZonMw: The Netherlands Organisation for Health Research and Development<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>Phase II Safety Single-arm Study of CDK4/6 Inhibition With Palbociclib in Hospitalized, Moderate COVID-19 Cases to Prevent Thromboinflammation</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Palbociclib<br/><b>Sponsor</b>: biotx.ai GmbH<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>A Study to Learn About the Study Medicine (Called Nirmatrelvir/Ritonavir) in Pregnant Women With Mild or Moderate COVID-19.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: nirmatrelvir; Drug: ritonavir<br/><b>Sponsor</b>: Pfizer<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase I Clinical Trial of COVID-19 mRNA Vaccine in Adults Aged 18 Years and Older</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: COVID-19 mRNA vaccine; Biological: Placebo<br/><b>Sponsor</b>: CanSino Biologics 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>Phase II Clinical Trial of COVID-19 mRNA Vaccine in Adults Aged 18 Years and Older</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: COVID-19 mRNA vaccine; Biological: Placebo<br/><b>Sponsor</b>: CanSino Biologics 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>Evaluation of COVID-19 Vaccines Given as a Booster in Healthy Adults in Indonesia (MIACoV Indonesia)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Pfizer-BioNTech Standard dose; Biological: AstraZeneca Standard dose; Biological: Pfizer-BioNTech Fractional dose; Biological: AstraZeneca Fractional dose; Biological: Moderna Standard dose; Biological: Moderna Fractional dose<br/><b>Sponsors</b>: Murdoch Childrens Research Institute; Universitas Padjadjaran (UNPAD); Universitas Indonesia (UI); Health Development Policy Agency, Ministry of Health Republic of Indonesia; Coalition for Epidemic Preparedness Innovations; The Peter Doherty Institute for Infection and Immunity<br/><b>Not yet recruiting</b></p></li>
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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>THEMBA II T-Cell Vaccine: Vaccination With saRNA COVID-19 Vaccines</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: AAHI-SC2 Vaccine; Biological: AAHI- SC3 Vaccine; Biological: EUA or approved vaccine<br/><b>Sponsor</b>: ImmunityBio, Inc.<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>To Evaluate SSD8432/Ritonavir in Adults With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: SSD8432 750mg; Drug: SSD8432 placebo<br/><b>Sponsor</b>: Jiangsu Simcere Pharmaceutical Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Efficacy and Safety of DXP604 in Patients With Mild to Moderate COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: DXP604<br/><b>Sponsor</b>: <br/>
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Wuhan Institute of Biological Products Co., Ltd<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of SSD8432 and Ritonavir in Adult Subjects With COVID-19 Clinical Study</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: SSD8432 300mg; Drug: SSD8432 750mg; Drug: SSD8432Placebo<br/><b>Sponsor</b>: Jiangsu Simcere Pharmaceutical 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>Sequential Immunization of Two Doses of Inactivated COVID-19 Vaccine (Omicron) in Vaccinated Population Aged 18 Years and Above</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: BIBP Omicron Inactivated COVID-19 vaccine (Vero Cell); Biological: WIBP Omicron Inactivated COVID-19 vaccine (Vero Cell); Biological: COVID-19 Vaccine (Vero Cell), Inactivated<br/><b>Sponsors</b>: China National Biotec Group Company Limited; Beijing Institute of Biological Products Co Ltd.; Wuhan Institute of Biological Products Co., Ltd; The University of Hong Kong<br/><b>Not yet recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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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>Thiazole-based SARS-CoV-2 protease (COV M<sup>pro</sup> ) inhibitors: Design, synthesis, enzyme inhibition, and molecular modeling simulations</strong> - As an attempt to contribute to the efforts of combating the pandemic virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for COVID-19, new analogs of the repurposed drug nitazoxanide which showed promising inhibitory efficacy on a viral protease enzyme were designed, synthesized and evaluated for their inhibitory activity on the main protease of the SARS-CoV-2 virus, using the COV2-3CL protease inhibition assay. The obtained results showed that the…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Anti-SARS-CoV-2 activity of various PET-bottled Japanese green teas and tea compounds in vitro</strong> - The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) is a serious threat to global public health. The emergence of SARS-CoV-2 variants is a significant concern regarding the continued effectiveness of vaccines and antiviral therapeutics. Thus, natural products such as foods, drinks, and other compounds should be investigated for their potential to treat COVID-19. Here, we examined the in vitro antiviral activity against…</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>Highly polymerized proanthocyanidins (PAC) components from blueberry leaf and stem significantly inhibit SARS-CoV-2 infection via inhibition of ACE2 and viral 3CLpro enzymes</strong> - With the current worldwide pandemic of COVID-19, there is an urgent need to develop effective treatment and prevention methods against SARS-CoV-2 infection. We have previously reported that the proanthocyanidin (PAC) fraction in blueberry (BB) leaves has strong antiviral activity against hepatitis C virus (HCV) and human T-lymphocytic leukemia virus type 1 (HTLV-1). In this study, we used Kunisato 35 Gou (K35) derived from the rabbit eye blueberry (Vaccinium virgatum Aiton), which has a high PAC…</p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Copper(II) Schiff base complex derived from salen ligand: structural investigation, Hirshfeld surface analysis, anticancer and anti-SARS-CoV-2</strong> - This work deals with the synthesis and characterization of copper(II) complex <a href="1">Cu(salen)(H(2)O)</a> of salen-type Schiff base ligand derived from the condensation of 5-bromo-2-hydroxy-3-methoxybenzaldehyde and ethylenediamine in EtOH. This complex was characterized by different spectroscopic and physicochemical methods. Single crystal X-ray crystallography study revealed that Cu(II) in complex (1) is five-coordinate and adopts a distorted square pyramidal geometry. A DFT calculation was employed…</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>Discovery and Use of Long dsRNA Mediated RNA Interference to Stimulate Antiviral Protection in Interferon Competent Mammalian Cells</strong> - In invertebrate cells, RNA interference (RNAi) acts as a powerful immune defense that stimulates viral gene knockdown thereby preventing infection. With this pathway, virally produced long dsRNA (dsRNA) is cleaved into short interfering RNA (siRNA) by Dicer and loaded into the RNA-induced silencing complex (RISC) which can then destroy/disrupt complementary viral mRNA sequences. Comparatively, in mammalian cells it is believed that the type I interferon (IFN) pathway is the cornerstone of the…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Potential Drug Discovery for COVID-19 Treatment Targeting Cathepsin L Using a Deep Learning-Based Strategy</strong> - Cathepsin L (CTSL), a cysteine protease that can cleave and activate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, could be a promising therapeutic target for coronavirus disease 2019 (COVID-19). However, there is still no clinically available CTSL inhibitor that can be used. Here, we applied Chemprop, a newly trained directed-message passing deep neural network approach, to identify small molecules and FDA-approved drugs that can block CTSL activity to expand…</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>Targeted delivery of inhalable drug particles in a patient-specific tracheobronchial tree with moderate COVID-19: A numerical study</strong> - The coronavirus disease 2019 (COVID-19) pandemic has led to severe social and economic disruption worldwide. Although currently no consent has been reached on a specific therapy that can treat COVID-19 effectively, several inhalation therapy strategies have been proposed to inhibit SARS-CoV-2 infection. These strategies include inhalations of antiviral drugs, anti-inflammatory drugs, and vaccines. To investigate how to enhance the therapeutic effect by increasing the delivery efficiency (DE) of…</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>Fibrin clot characteristics and anticoagulant response in a SARS-CoV-2-infected endothelial model</strong> - Coronavirus disease 2019 (COVID-19) patients have increased thrombosis risk. With increasing age, there is an increase in COVID-19 severity. Additionally, adults with a history of vasculopathy have the highest thrombotic risk in COVID-19. The mechanisms of these clinical differences in risk remain unclear. Human umbilical vein endothelial cells (HUVECs) were infected with SARS-CoV-2, influenza A/Singapore/6/86 (H1N1) or mock-infected prior to incubation with plasma from healthy children, healthy…</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>Characterization of SARS-CoV-2 and host entry factors distribution in a COVID-19 autopsy series</strong> - CONCLUSIONS: This study portrays the impact of dispersed SARS-CoV-2 infection in diverse organ systems, thereby facilitating avenues for systematic therapeutic approaches.</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>Repurposing of Doxycycline to Hinder the Viral Replication of SARS-CoV-2: From <em>in silico</em> to <em>in vitro</em> Validation</strong> - Since the rapid spread of coronavirus disease (COVID-19) became a global pandemic, healthcare ministries around the world have recommended specific control methods such as quarantining infected peoples, identifying infections, wearing mask, and practicing hand hygiene. Since no effective treatment for COVID-19 has yet been discovered, a variety of drugs approved by Food and Drug Administration (FDA) have been suggested for repurposing strategy. In the current study, we predicted that doxycycline…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety and immunogenicity of Nanocovax, a SARS-CoV-2 recombinant spike protein vaccine: Interim results of a double- blind, randomised controlled phase 1 and 2 trial</strong> - BACKGROUND: Nanocovax is a recombinant severe acute respiratory syndrome coronavirus 2 subunit vaccine composed of full- length prefusion stabilized recombinant SARS-CoV-2 spike glycoproteins (S-2P) and aluminium hydroxide adjuvant.</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>Unraveling T Cell Responses for Long Term Protection of SARS-CoV-2 Infection</strong> - Due to the COVID-19 pandemic, the global need for vaccines to prevent the disease is imperative. To date, several manufacturers have made efforts to develop vaccines against SARS-CoV-2. In spite of the success of developing many useful vaccines so far, it will be helpful for future vaccine designs, targetting long-term disease protection. For this, we need to know more details of the mechanism of T cell responses to SARS-CoV-2. In this study, we first detected pairwise differentially expressed…</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>Generation of zinc ion-rich surface via in situ growth of ZIF-8 particle: Microorganism immobilization onto fabric surface for prohibit hospital-acquired infection</strong> - Viruses/bacteria outbreaks have motivated us to develop a fabric that will inhibit their transmission with high potency and long-term stability. By creating a metal-ion-rich surface onto polyester (PET) fabric, a method is found to inhibit hospital-acquired infections by immobilizing microorganisms on its surface. ZIF-8 and APTES are utilized to overcome the limitations associated with non-uniform distribution, weak biomolecule interaction, and ion leaching on surfaces. Modified surfaces…</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>Natural Compound ZINC12899676 Reduces Porcine Epidemic Diarrhea Virus Replication by Inhibiting the Viral NTPase Activity</strong> - Porcine epidemic diarrhea virus (PEDV) is an alphacoronavirus (α-CoV) that causes high mortality in suckling piglets, leading to severe economic losses worldwide. No effective vaccine or commercial antiviral drug is readily available. Several replicative enzymes are responsible for coronavirus replication. In this study, the potential candidates targeting replicative enzymes (PLP2, 3CLpro, RdRp, NTPase, and NendoU) were screened from 187,119 compounds in ZINC natural products library, and seven…</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>Promising Role of Emodin as Therapeutics to Against Viral Infections</strong> - Emodin is an anthraquinone derivative that is widely present in natural plants and has a wide spectrum of pharmacological effects, such as antibacterial, anti-inflammatory, anti-fibrotic and anticancer and so on. Through reviewing studies on antiviral effect of emodin in the past decades, we found that emodin exhibits ability of inhibiting the infection and replication of more than 10 viruses in vitro and in vivo, including herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), human…</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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