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192 lines
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<title>05 April, 2023</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>Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses</strong> -
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We measured brain injury markers, inflammatory mediators, and autoantibodies in 203 participants with COVID-19; 111 provided acute sera (1-11 days post admission) and 56 with COVID-19-associated neurological diagnoses provided subacute/convalescent sera (6-76 weeks post-admission). Compared to 60 controls, brain injury biomarkers (Tau, GFAP, NfL, UCH-L1) were increased in acute sera, significantly more so for NfL and UCH-L1, in patients with altered consciousness. Tau and NfL remained elevated in convalescent sera, particularly following cerebrovascular and neuroinflammatory disorders. Acutely, inflammatory mediators (including IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) were higher in participants with altered consciousness, and correlated with brain injury biomarker levels. Inflammatory mediators were lower than acute levels in convalescent sera, but levels of CCL2, CCL7, IL-1RA, IL-2Rα, M-CSF, SCF, IL-16 and IL-18 in individual participants correlated with Tau levels even at this late time point. When compared to acute COVID-19 patients with a normal GCS, network analysis showed significantly altered immune responses in patients with acute alteration of consciousness, and in convalescent patients who had suffered an acute neurological complication. The frequency and range of autoantibodies did not associate with neurological disorders. However, autoantibodies against specific antigens were more frequent in patients with altered consciousness in the acute phase (including MYL7, UCH-L1, GRIN3B, and DDR2), and in patients with neurological complications in the convalescent phase (including MYL7, GNRHR, and HLA antigens). In a novel low-inoculum mouse model of SARS-CoV-2, while viral replication was only consistently seen in mouse lungs, inflammatory responses were seen in both brain and lungs, with significant increases in CCL4, IFNγ, IL-17A, and microglial reactivity in the brain. Neurological injury is common in the acute phase and persists late after COVID-19, and may be driven by a para-infectious process involving a dysregulated host response.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.03.23287902v1" target="_blank">Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses</a>
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<li><strong>A second update on mapping the human genetic architecture of COVID-19</strong> -
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Investigating the role of host genetic factors in COVID-19 severity and susceptibility can inform our understanding of the underlying biological mechanisms that influence adverse outcomes and drug development. Here we present a second updated genome-wide association study (GWAS) on COVID-19 severity and infection susceptibility to SARS-CoV-2 from the COVID-19 Host Genetic Initiative (data release 7). We performed a meta-analysis of up to 219,692 cases and over 3 million controls, identifying 51 distinct genome-wide significant loci—adding 28 loci from the previous data release. The increased number of candidate genes at the identified loci helped to map three major biological pathways involved in susceptibility and severity: viral entry, airway defense in mucus, and type I interferon.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.24.22283874v2" target="_blank">A second update on mapping the human genetic architecture of COVID-19</a>
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<li><strong>SARS-CoV-2 infection and post-acute risk of non-Covid-19 infectious disease hospitalizations: a nationwide cohort study of Danish adults aged ≥50 years</strong> -
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Reports suggest that the potential long-lasting health consequences of SARS-CoV-2 infection may involve persistent dysregulation of some immune populations, but the potential clinical implications are unknown. In a nationwide cohort of 2,430,694 50+-year-olds, we compared the rates of non-Covid-19 infectious disease inpatient hospitalizations (of ≥5 hours) following the acute phase of SARS-CoV-2 infection in 930,071 individuals with rates among SARS-CoV-2 uninfected from 1 January 2021 to 10 December 2022. The post-acute phase of SARS-CoV-2 infection was associated with an incidence rate ratio of 0.90 (95% confidence interval 0.88-0.92) for any infectious disease hospitalization. Findings were similar for upper- (1.08, 0.97-1.20), lower respiratory tract (0.90, 0.87-0.93), influenza (1.04, 0.94-1.15), gastrointestinal (1.28, 0.78-2.09), skin (0.98, 0.93-1.03), urinary tract (1.01, 0.96-1.08), certain invasive bacterial (0.96, 0.91-0.1.01), and other (0.96, 0.92-1.00) infectious disease hospitalizations and in subgroups. Our study does not support an increased susceptibility to non-Covid-19 infectious disease hospitalization following SARS-CoV-2 infection.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.03.23288102v1" target="_blank">SARS-CoV-2 infection and post-acute risk of non-Covid-19 infectious disease hospitalizations: a nationwide cohort study of Danish adults aged ≥50 years</a>
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<li><strong>Spatial Variation in Excess Mortality Across Europe: A Cross-sectional Study of 561 Regions in 21 Countries</strong> -
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Objective: To measure the burden of the COVID-19 pandemic in 2020 at the subnational level by estimating excess mortality, defined as the increase in all-cause mortality relative to an expected baseline mortality level. Design: Statistical and demographic analyses of regional all-cause mortality data. Setting: The vital statistics systems of 21 European countries. Participants: The entire population of 561 spatial units in 21 European countries. Main Outcome Measures: Losses of life expectancy at ages 0 and 60 for males and females. Results: Evidence was found of a loss in life expectancy in 391 regions, while only three regions exhibit notable gains in life expectancy in 2020. For 12 regions, losses of life expectancy amounted to more than 2 years, and three regions showed losses greater than 3 years. Geographic clusters of high mortality were found in Northern Italia, Spain and Poland, while clusters of low mortality were found in Western France, Germany/Denmark and Norway/Sweden. Conclusions: Regional differences of loss of life expectancy are impressive, ranging from a loss of more than 4 years to a gain of 8 months. These findings provide a strong rationale for regional analysis, as national estimates hide significant regional disparities.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.04.23284990v1" target="_blank">Spatial Variation in Excess Mortality Across Europe: A Cross-sectional Study of 561 Regions in 21 Countries</a>
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<li><strong>Longitudinal Analysis of Humoral and Cellular Immune Response Following SARS-CoV-2 Vaccination Supports Utilizing Point-Of-Care Tests to Enhance COVID-19 Booster Uptake.</strong> -
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Individuals with weaker neutralizing responses show reduced protection with SARS-CoV-2 variants. Booster vaccines are recommended for vaccinated individuals, but the uptake is low. We present the feasibility of utilizing point-of-care tests (POCT) to support evidence-based decision-making around COVID-19 booster vaccinations. Using infectious virus neutralization, ACE2 blocking, spike binding, and TCR sequencing assays, we investigated the dynamics of changes in the breadth and depth of blood and salivary antibodies as well as T-cell clonal response following mRNA vaccination in a cohort of healthcare providers. We evaluated the accuracy of two POCTs utilizing either blood or saliva to identify those in whom humoral immunity was inadequate. >4 months after two doses of mRNA vaccine, SARS-CoV-2 binding and neutralizing Abs (nAbs) and T-cell clones declined 40-80%, and 2/3rd lacked Omicron nAbs. After the third mRNA booster, binding and neutralizing Abs increased overall in the systemic compartment; notably, individuals with previously weak nAbs gained sharply. The third dose failed to stimulate secretory IgA, but salivary IgG closely tracked systemic IgG levels. Vaccine boosting increased Ab breadth against a divergent bat sarbecovirus, SHC014, although the TCR-beta sequence breadth was unchanged. Post 3rd booster dose, Ab avidity increased for the Wuhan and Delta strains, while avidity against Omicron and SHC014 increased to levels seen for Wuhan after the second dose. Negative results on POCTs strongly correlated with a lack of functional humoral immunity. The third booster dose helps vaccinees gain depth and breadth of systemic Abs against evolving SARS-CoV-2 and related viruses. Our findings show that POCTs are useful and easy-to-access tools to inform inadequate humoral immunity accurately. POCTs designed to match the circulating variants can help individuals with booster vaccine decisions and could serve as a population-level screening platform to preserve herd immunity.
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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/10.1101/2023.04.03.23287498v1" target="_blank">Longitudinal Analysis of Humoral and Cellular Immune Response Following SARS-CoV-2 Vaccination Supports Utilizing Point-Of-Care Tests to Enhance COVID-19 Booster Uptake.</a>
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<li><strong>Early Treatment with Hydroxychloroquine and Azithromycin: A Real-Life Monocentric Retrospective Cohort Study of 30,423 COVID-19 Patients</strong> -
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Objective To estimate the comparative effectiveness of combination therapy with hydroxychloroquine (HCQ) and azithromycin for coronavirus disease 2019 (COVID-19)-related death based on a large monocentric cohort independent of investigators putative biases in a real-world setting. Design Retrospective monocentric cohort study, with comprehensive data collection authenticated by an external bailiff and death reports from a national database (French National Death Registry). Setting Institut Hospitalo-Universitaire Mediterranee Infection Center in Marseille, France. Participants All adults older than 18 years with PCR-proven COVID-19 who were treated directly in our centre between 2 March 2020 and 31 December 2021 and did not refuse the use of their data. Interventions HCQ and azithromycin (HCQ-AZ) as a reference treatment were compared to other regimens containing HCQ, ivermectin and azithromycin alone, combined, or none of these three drugs. The effect of vaccination was also evaluated. Main outcome measures 6-week all-cause mortality. Multivariable logistic regression estimated treatment effectiveness with adjustments for age, sex, comorbidities, vaccination, period of infection or virus variant, and outpatient or inpatient care. Results Total 30,423 COVID-19 patients were analysed (86 refused the analysis of their data) including 30,202 with available treatment data, and 535 died (1.77%). All-cause mortality was very low among patients < 50 years (8/15,925 (0.05%)) and among outpatients treated with HCQ-AZ (21 deaths out of 21,135 (0.1%), never exceeding 0.2% regardless of epidemic period). HCQ-AZ treatment was associated with a significantly lower mortality rate than no HCQ-AZ after adjustment for sex, age, period and patient care setting (adjusted OR (aOR) 95% confidence interval (CI) 0.55, 0.45-0.68). The effect was greater among outpatients (71% death protection rate) than among inpatients (45%). In a subset of 16,063 patients with available comorbidities and vaccinations status, obesity (2.01, 1.23-3.29), chronic respiratory disease (2.93, 1.29-6.64), and immunodeficiency (4.01, 1.69-9.50), on the one hand, and vaccination (0.29, 0.12-0.67) and HCQ-AZ treatment (0.47, 0.29-0.76), on the other hand, were independent factors associated with mortality. HCQ, alone or in any association, was associated with significant protection from death among outpatients (0.41, 0.21-0.79) and inpatients (0.59, 0.47-0.73). Conclusions HCQ prescribed early or late protects in part from COVID-19-related death. During pandemic health crises, financial stakes are enormous. Authentication of the data by an independent external judicial officer should be required. Public sharing of anonymized databases, ensuring their verifiability, should be mandatory in this context to avoid fake publications.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.03.23287649v1" target="_blank">Early Treatment with Hydroxychloroquine and Azithromycin: A Real-Life Monocentric Retrospective Cohort Study of 30,423 COVID-19 Patients</a>
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<li><strong>Stratification of Pediatric COVID-19 cases by inflammatory biomarker profiling and machine learning</strong> -
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An objective method to identify imminent or current Multi-inflammatory Syndrome in Children (MIS-C) infected with SARS-CoV-2 is highly desirable. The aims were to define an algorithmically interpreted novel cytokine/chemokine assay panel providing such an objective classification. This study was conducted on 4 groups of patients seen at multiple sites of Texas Childrens Hospital, Houston, TX who consented to provide blood samples to our COVID-19 Biorepository. Standard laboratory markers of inflammation and a novel cytokine/chemokine array were measured in blood samples of all patients. Group 1 consisted of 72 COVID-19, 66 MIS-C and 63 uninfected control patients seen between May 2020 and January 2021 and predominantly infected with pre-alpha variants. Group 2 consisted of 29 COVID-19 and 43 MIS-C patients seen between January-May 2021 infected predominantly with the alpha variant. Group 3 consisted of 30 COVID-19 and 32 MIS-C patients seen between August-October 2021 infected with alpha and/or delta variants. Group 4 consisted of 20 COVID-19 and 46 MIS-C patients seen between October 2021- January 2022 infected with delta and/or omicron variants. Group 1 was used to train a L1-regularized logistic regression model which was validated using 5-fold cross validation, and then separately validated against the remaining naive groups. The area under receiver operating curve (AUROC) and F1-score were used to quantify the performance of the algorithmically interpreted cytokine/chemokine assay panel. Standard laboratory markers predict MIS-C with a 5-fold cross-validated AUROC of 0.86 ± 0.05 and an F1 score of 0.78±0.07, while the cytokine/chemokine panel predicted MIS-C with a 5-fold cross-validated AUROC of 0.95 ± 0.02 and an F1 score of 0.91 ± 0.04, with only sixteen of the forty-five cytokines/chemokines sufficient to achieve this performance. Tested on Group 2 the cytokine/chemokine panel yielded AUROC =0.98, F1=0.93, on Group 3 it yielded AUROC=0.89 , F1 = 0.89, and on Group 4 AUROC= 0.99, F1= 0.97. Adding standard laboratory markers to the cytokine/chemokine panel did not improve performance. A top-10 subset of these 16 cytokines achieved equivalent performance on the validation data sets. Our findings demonstrate that a sixteen-cytokine/chemokine panel as well as the top ten subset provide a sensitive, specific method to identify MIS-C in patients infected with SARS-CoV-2 in all the major variants identified to date.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.04.23288117v1" target="_blank">Stratification of Pediatric COVID-19 cases by inflammatory biomarker profiling and machine learning</a>
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<li><strong>Beyond dry eye: the greater extent of Sjögren’s systemic disease symptoms, impact of COVID-19 and perceptions towards Telemedicine identified through a patient co-designed study</strong> -
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Background: Sjögren’s (“SHOW-grins”) is a chronic debilitating autoimmune disease characterised by dry eyes and dry mouth, secondary to reduced exocrine function of both the lacrimal and salivary glands. The persistent, severe and serious systemic complications of Sjögren’s are poorly understood and often unappreciated, resulting in significant morbidity and treatment burden. This study aimed to explore experiences of those living with Sjögren’s, specifically access to healthcare and attitude towards telemedicine. Additionally, we sought to collect information regarding the impact of the pandemic on their quality of life (QoL). Methods: Attendees (n=194) of an Irish Sjögren’s Webinar were invited to participate in two online surveys. The first survey gathered information related to demographics, disease, and experiences during the COVID-19 pandemic. A combination of bespoke items and validated questionnaires (EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI), COV19-QoL) was used. The second survey consisted of a shortened Telehealth Usability Questionnaire. Both were prepared in collaboration with a patient advocate. Results: Survey 1: n=76; response rate=39.2%. Thirty-one respondents (41.4%) to Survey 1 reported a delay of ≥5 years between the onset of symptoms and diagnosis. Dry mouth was the most common symptom experienced (76.8% n=63), followed by dry eye (74.4% n=61), fatigue (57.3%, n=47) and joint pain (53.7% n=44), but a range of other symptoms were also reported. COV19-QoL results indicated that the pandemic had a detrimental effect on participants’ overall QoL (4.0 ± 1.0) and physical health (4.0 ± 0.8) in particular. COV19-QoL and ESSPRI scores were moderately correlated (0.36, p=0.002). Over 70% of respondents had a medical appointment cancelled, delayed or rescheduled (n=60). Survey 2: n=57; response rate=29.4%. Those that had interacted with telemedicine reported largely positive experiences with the virtual model. Conclusion: Clinicians should be aware of the range of symptoms experienced by patients with Sjögren’s beyond those of sicca and fatigue. COVID-19 has negatively influenced the self-reported health and well-being of those with Sjögren’s, particularly those with higher symptom scores. It is vital that optimised telemedicine models are implemented to ensure continuity in the provision of healthcare for those with chronic illness such as Sjögren’s and in preparation for possible future pandemics. Patient or Public Contribution: A group of people living with Sjögren’s co-designed the structure and content of the webinar where the survey was shared. A PPI contributor also collaborated in the selection of questionnaires used in the study ensuring that the questions asked would best reflect the priorities of patients. They contributed to the writing of this manuscript as co-authors. Additionally, the research team and Sjögren’s patients who contributed to this work have gone on to establish Sjögren’s Research Ireland, a collaboration between patient advocates, researchers, and PPI facilitators.
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🖺 Full Text HTML: <a href="https://osf.io/6r8nd/" target="_blank">Beyond dry eye: the greater extent of Sjögren’s systemic disease symptoms, impact of COVID-19 and perceptions towards Telemedicine identified through a patient co-designed study</a>
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<li><strong>Head-to head comparison of anterior nares and nasopharyngeal swabs for SARS-CoV-2 antigen detection in a community drive-through test centre in the UK</strong> -
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Objective: To conduct a head-to-head diagnostic accuracy evaluation of professionally taken anterior nares (AN) and nasopharyngeal (NP) swabs for SARS-CoV-2 antigen detection using rapid diagnostic tests (Ag-RDT). Methods: NP swabs for SARS-CoV-2 reverse transcription quantitative polymerase chain reaction (RT-qPCR) testing and paired AN and NP swabs for the antigen detection were collected from symptomatic participants enrolled at a community drive-through COVID-19 test centre in Liverpool. Two Ag-RDT brands were evaluated: Sure-Status (PMC, India) and Biocredit (RapiGEN, South Korea). The visual read out of the Ag-RDT test band was quantitative scored and the 50% and 95% limit of detection (LoD) of both Ag-RDT brands using AN and NP swabs was calculated using a probabilistic logistic regression model. Results: A total of 604 participants were recruited of which 241 (40.3%) were SARS-CoV-2 positive by RT-qPCR. Sensitivity and specificity of AN swabs was equivalent to the obtained with NP swabs: 83.2% (75.2-89.4%) and 98.8% (96.5-99.6%) utilising NP swabs and 84.0% (76.2-90.1%) and 99.2% (97.0-99.8%) with AN swabs for Sure-Status and; 81.2% (73.1-87.7%) and 99.0% (94.7-86.5%) with NP swabs and 79.5% (71.3-86.3%) and 100% (96.5-100%) with AN swabs for Biocredit. The agreement of the AN and NP swabs was high for both brands with an inter-rater relatability (K) of 0.918 and 0.833 for Sure-Status and Biocredit, respectively. The overall 50% LoD and 95% LoD was 0.9-2.4 x 104 and 3.0-3.2 x 108 RNA copies/mL for NP swabs and 0.3- 1.1 x 105 and 0.7-7.9 x 107 RNA copies/mL and for AN swabs with no significant difference on LoD for any of the swabs types or test brands. Quantitative read-out of test line intensity was more often higher when using NP swabs with significantly higher scores for both Ag-RDT brands. Conclusions: the diagnostic accuracy of the two SARS-CoV-2 Ag-RDTs brands evaluated in this study was equivalent using AN swabs than NP swabs. However, test line intensity was lower when using AN swabs which could influence negatively the interpretation of the Ag-RDT results for lay users. Studies on Ag-RDT self-interpretation using AN and NP swabs are needed to ensure accurate test use in the wider community.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.06.22279637v2" target="_blank">Head-to head comparison of anterior nares and nasopharyngeal swabs for SARS-CoV-2 antigen detection in a community drive-through test centre in the UK</a>
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<li><strong>The re-emergence of influenza following the COVID-19 pandemic in Victoria, Australia</strong> -
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Background: COVID-19 pandemic mitigation measures, including travel restrictions, effectively limited global circulation of influenza viruses. In Australia, travel bans for non-residents and quarantine requirements for returned travellers were eased in November 2021, providing pathways for influenza viruses to be re-introduced. Methods: From 1 November 2021 to 30 April 2022 we conducted an epidemiological study to investigate the re-establishment of influenza in Victoria, Australia. We analyzed case notification data from the Victorian Department of Health to describe case demographics, interviewed the first 200 cases to establish probable routes of virus reintroduction, and examined phylogenetic and antigenic data to understand virus diversity and susceptibility to current vaccines. Results: Overall, 1598 notifications and 1064 positive specimens were analyzed. The majority of cases occurred in the 15-34 year age group. Case interviews revealed a higher incidence of international travel exposure during the first month of case detections and high levels of transmission in university residential colleges associated with the return to campus. Influenza A(H3N2) was the dominant subtype, with a single lineage predominating despite multiple importations. Conclusions: Enhanced testing for respiratory viruses during the COVID-19 pandemic provided a more complete picture of influenza virus transmission compared to previous seasons. Returned international travellers were important drivers of the re-emergence of influenza, as were young adults, a group whose role has previously been under-recognised in the establishment of seasonal influenza epidemics. Targeting interventions, including vaccination, to these groups could reduce influenza transmission in the future.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.02.23288053v1" target="_blank">The re-emergence of influenza following the COVID-19 pandemic in Victoria, Australia</a>
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<li><strong>Risk of Adverse Maternal and Fetal Outcomes Associated with COVID-19 Variants of Concern: A Sequential Prospective Meta-Analysis</strong> -
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Introduction The main objective of this study is to conduct an individual patient data meta-analysis with collaborators from various countries to identify SARS-CoV-2 variants of concern associated with adverse maternal and neonatal outcomes. Methods Eligible studies included registries and single- or multi-site cohort studies that recruited pregnant and recently postpartum women with confirmed COVID-19. Studies must have enrolled at least 25 women within a defined catchment area. Studies also had to have data that overlapped more than a single COVID-19 variant time period. We invited principal investigators already participating in an ongoing sequential, prospective meta-analysis of perinatal COVID-19. Investigators shared individual patient data (IPD) with the technical team for review and analysis. We examined 31 outcomes related to: i) COVID-19 severity (n=5); ii) maternal morbidities including adverse birth outcomes (n=14); iii) fetal and neonatal morbidity and mortality (n=5) and iv) adverse birth outcomes (n=8). SARS-CoV-2 strains that have been identified as variants of concern (VOC) by the WHO were analyzed using the publicly available strain frequency data by Nextstrain.org and strains were classified as dominant when they were more than half of sequences in a given geographic area. We applied a 2-stage IPD meta-analytic framework to generate pooled relative risks, with 95% CI for each dominant variant and outcome pair when there were one or more studies with available data. Results Our data show that the Delta wave, compared to Omicron, was associated with a higher risk of all adverse COVID-19 severity outcomes in pregnancy including risk of hospitalization [RR 4.02 (95% CI 1.10, 14.69), n=1 study], risk of ICU admissions [RR 2.59 (95% CI 1.26, 5.30, n=3 studies], risk of critical care admission [RR 2.52 (95% CI 1.25, 5.08, n=3 studies], risk of needing ventilation [RR 3.96 (95% CI 1.47, 10.71), n=3 studies] and risk of pneumonia [RR 6.73 (95% CI 2.17, 20.90), n=3 studies]. The majority of maternal morbidity and mortality indicators were not at increased risk during any of the COVID-19 variant waves except hemorrhage, any Cesarean section, intrapartum Cesarean section and maternal composite outcome, although data was limited. Risk of fetal and neonatal morbidity and mortality did not show significant increases in risks during any of the COVID-19 waves except stillbirth and perinatal death during the Delta wave ([RR 4.84 (95% CI 1.37, 17.05, n=3 studies], [RR 6.03 (95%CI 1.63, 22.34), n=3 studies], respectively) when compared to the Pre-alpha wave. Adverse birth outcomes including very low birthweight and very preterm birth also showed increased risks during the Delta wave compared to the Pre-alpha wave. Discussion During periods of Delta strain predominance, all COVID-19 severity outcomes were more severe among pregnant women, compared to periods when other COVID-19 strains predominated. In addition, there are limited data comparing the impact of different variants on pregnancy outcomes. This highlights the importance of ongoing genomic surveillance among special populations.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.03.23287260v1" target="_blank">Risk of Adverse Maternal and Fetal Outcomes Associated with COVID-19 Variants of Concern: A Sequential Prospective Meta-Analysis</a>
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<li><strong>GILEA: GAN Inversion-enabled latent eigenvalue analysis for phenome profiling and editing</strong> -
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Modeling heterogeneous disease states by data-driven methods has great potential to advance biomedical research. However, a comprehensive analysis of phenotypic heterogeneity is often challenged by the complex nature of biomedical datasets and emerging imaging methodologies. Here, we propose a novel GAN Inversion-enabled Latent Eigenvalue Analysis (GILEA) framework and apply it to phenome profiling and editing. As key use cases for fluorescence and natural imaging, we demonstrate the power of GILEA using publicly available SARS-CoV-2 datasets stained with the multiplexed fluorescence cell-painting protocol as well as real-world medical images of common skin lesions captured by dermoscopy. The quantitative results of GILEA can be biologically supported by editing latent representations and simulating dynamic phenotype transitions between physiological and pathological states. In conclusion, GILEA represents a new and broadly applicable approach to the quantitative and interpretable analysis of biomedical image data.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.10.528026v3" target="_blank">GILEA: GAN Inversion-enabled latent eigenvalue analysis for phenome profiling and editing</a>
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<li><strong>Using macromolecular electron densities to improve the enrichment of active compounds in virtual screening</strong> -
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The quest for more effective virtual screening algorithms is hindered by the scarcity of training data, calling for innovative approaches. This study presents the first use of experimental electron density (ED) data for improving active compound enrichment in virtual screening, supported by ED’s ability to reflect the time-averaged behavior of ligands and solvents in the binding pocket. Experimental ED-based grid matching score (ExptGMS) was developed to score compounds by measuring the degree of matching between their binding conformations and a series of multi-resolution experimental ED grids. The efficiency of ExptGMS was validated using both in-silico tests with the Directory of Useful Decoys-Enhanced dataset and wet-lab tests on Covid-19 3CLpro-inhibitors. ExptGMS improved the active compound enrichment in top-ranked molecules by approximately 20%. Furthermore, ExptGMS helped identify four new and active inhibitors of 3CLpro, with the top showing an IC50 value of 1.9 uM. To facilitate the use of ExptGMS, we developed an online database containing experimental ED grids for over 17,000 proteins.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.04.535535v1" target="_blank">Using macromolecular electron densities to improve the enrichment of active compounds in virtual screening</a>
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<li><strong>The Functional RNA Identification (FRID) Pipeline: Identification of Potential Pseudoknot-Containing RNA Elements as Therapeutic Targets for SARS-CoV-2</strong> -
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The COVID-19 pandemic persists despite the development of effective vaccines. As such, it remains crucial to identify new targets for antiviral therapies. The causative virus of COVID-19, SARS-CoV-2, is a positive-sense RNA virus with RNA structures that could serve as therapeutic targets. One such RNA with established function is the frameshift stimulatory element (FSE), which promotes programmed ribosomal frameshifting. To accelerate identification of additional functional RNA elements, we introduce a novel computational approach termed the Functional RNA Identification (FRID) pipeline. The guiding principle of our pipeline, which uses established component programs as well as customized component programs, is that functional RNA elements have conserved secondary and pseudoknot structures that facilitate function. To assess the presence and conservation of putative functional RNA elements in SARS-CoV-2, we compared over 6,000 SARS-CoV-2 genomic isolates. We identified 22 functional RNA elements from the SARS-CoV-2 genome, 14 of which have conserved pseudoknots and serve as potential targets for small molecule or antisense oligonucleotide therapeutics. The FRID pipeline is general and can be applied to identify pseudoknotted RNAs for targeted therapeutics in genomes or transcriptomes from any virus or organism.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.03.535424v1" target="_blank">The Functional RNA Identification (FRID) Pipeline: Identification of Potential Pseudoknot-Containing RNA Elements as Therapeutic Targets for SARS-CoV-2</a>
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<li><strong>Chemical-guided SHAPE sequencing (cgSHAPE-seq) informs the binding site of RNA-degrading chimeras targeting SARS-CoV-2 5’ untranslated region</strong> -
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One of the hallmarks of RNA viruses is highly structured untranslated regions (UTRs) in their genomes. These conserved RNA structures are often essential for viral replication, transcription, or translation. In this report, we discovered and optimized a new coumarin derivative C30 that binds to a four-way RNA helix called SL5 in the 5’ UTR of the SARS-CoV-2 RNA genome. To locate the binding site, we developed a novel sequencing-based method namely cgSHAPE-seq, in which the acylating chemical probe was directed to crosslink with the 2’-OH groups of ribose at the ligand binding site. This crosslinked RNA could then create read-through mutations during reverse transcription (i.e., primer extension) at single-nucleotide resolution to uncover the acylation locations. cgSHAPE-seq unambiguously determined that a bulged G in SL5 was the primary binding site of C30 in the SARS-CoV-2 5’ UTR, which was validated through mutagenesis and in vitro binding experiments. C30 was further used as a warhead in RNA-degrading chimeras (RIBOTACs) to reduce viral RNA expression levels. We demonstrated that replacing the acylating moiety in the cgSHAPE probe with ribonuclease L recruiter (RLR) moieties yielded RNA degraders active in the in vitro RNase L degradation assay and SARS-CoV-2 5’ UTR expressing cells. We further explored another RLR conjugation site on the E ring of C30 and discovered potent activity in vitro and in cells. The optimized RIBOTAC C64 inhibited live virus replication in lung epithelial carcinoma cells.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.03.535453v1" target="_blank">Chemical-guided SHAPE sequencing (cgSHAPE-seq) informs the binding site of RNA-degrading chimeras targeting SARS-CoV-2 5’ untranslated region</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of Safety & Efficacy of MIR 19 ® Inhalation Solution in Patients With Mild COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: MIR 19 ®; Combination Product: Standard therapy<br/><b>Sponsor</b>: National Research Center - Institute of Immunology Federal Medical-Biological Agency of Russia<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>LACTYFERRIN™ Forte and ZINC Defense™ and Standard of Care (SOC) vs SOC in the Treatment of Non-hospitalized Patients With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Sesderma LACTYFERRIN™ Forte and Sesderma ZINC Defense™; Drug: Placebo<br/><b>Sponsors</b>: Jose David Suarez, MD; Sesderma S.L.; Westchester General Hospital Inc. DBA Keralty Hospital Miami; MGM Technology Corp<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>MP0420 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: MP0420; Drug: Placebo; Biological: Remdesivir<br/><b>Sponsors</b>: National Institute of Allergy and Infectious Diseases (NIAID); International Network for Strategic Initiatives in Global HIV Trials (INSIGHT); University of Copenhagen; Medical Research Council; Kirby Institute; Washington D.C. Veterans Affairs Medical Center; AIDS Clinical Trials Group; National Heart, Lung, and Blood Institute (NHLBI); US Department of Veterans Affairs; Prevention and Early Treatment of Acute Lung Injury (PETAL); Cardiothoracic Surgical Trials Network (CTSN); Molecular Partners AG; University of Minnesota<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>AZD7442 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: AZD7442; Biological: Placebo; Biological: Remdesivir<br/><b>Sponsors</b>: National Institute of Allergy and Infectious Diseases (NIAID); International Network for Strategic Initiatives in Global HIV Trials (INSIGHT); University of Copenhagen; Medical Research Council; Kirby Institute; Washington D.C. Veterans Affairs Medical Center; AIDS Clinical Trials Group; National Heart, Lung, and Blood Institute (NHLBI); US Department of Veterans Affairs; Prevention and Early Treatment of Acute Lung Injury (PETAL); Cardiothoracic Surgical Trials Network (CTSN); AstraZeneca; University of Minnesota<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>PF-07304814 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: PF-07304814; Drug: Placebo; Biological: Remdesivir<br/><b>Sponsors</b>: National Institute of Allergy and Infectious Diseases (NIAID); International Network for Strategic Initiatives in Global HIV Trials (INSIGHT); University of Copenhagen; Medical Research Council; Kirby Institute; Washington D.C. Veterans Affairs Medical Center; AIDS Clinical Trials Group; National Heart, Lung, and Blood Institute (NHLBI); US Department of Veterans Affairs; Prevention and Early Treatment of Acute Lung Injury (PETAL); Cardiothoracic Surgical Trials Network (CTSN); Pfizer; University of Minnesota<br/><b>Suspended</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>VIR-7831 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: VIR-7831; Biological: Placebo; Biological: Remdesivir<br/><b>Sponsors</b>: National Institute of Allergy and Infectious Diseases (NIAID); International Network for Strategic Initiatives in Global HIV Trials (INSIGHT); University of Copenhagen; Medical Research Council; Kirby Institute; Washington D.C. Veterans Affairs Medical Center; AIDS Clinical Trials Group; National Heart, Lung, and Blood Institute (NHLBI); US Department of Veterans Affairs; Prevention and Early Treatment of Acute Lung Injury (PETAL); Cardiothoracic Surgical Trials Network (CTSN); Vir Biotechnology, Inc.; GlaxoSmithKline; University of Minnesota<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>BRII-196/BRII-198 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: BRII-196; Biological: BRII-198; Biological: Placebo; Biological: Remdesivir<br/><b>Sponsors</b>: National Institute of Allergy and Infectious Diseases (NIAID); International Network for Strategic Initiatives in Global HIV Trials (INSIGHT); University of Copenhagen; Medical Research Council; Kirby Institute; Washington D.C. Veterans Affairs Medical Center; AIDS Clinical Trials Group; National Heart, Lung, and Blood Institute (NHLBI); US Department of Veterans Affairs; Prevention and Early Treatment of Acute Lung Injury (PETAL); Cardiothoracic Surgical Trials Network (CTSN); Brii Biosciences Limited; University of Minnesota<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>LY3819253 (LY-CoV555) for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: LY3819253; Biological: Placebo; Biological: Remdesivir<br/><b>Sponsors</b>: National Institute of Allergy and Infectious Diseases (NIAID); International Network for Strategic Initiatives in Global HIV Trials (INSIGHT); University of Copenhagen; Medical Research Council; Kirby Institute; Washington D.C. Veterans Affairs Medical Center; AIDS Clinical Trials Group; National Heart, Lung, and Blood Institute (NHLBI); US Department of Veterans Affairs; Prevention and Early Treatment of Acute Lung Injury (PETAL); Cardiothoracic Surgical Trials Network (CTSN); Eli Lilly and Company; University of Minnesota<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 Nasal Treatment for COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Optate; Drug: Placebo<br/><b>Sponsor</b>: Indiana University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effect of a Health Pathway for People With Persistent Symptoms Covid-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Other: usual care and follow-up by a nurse; Other: Personalized Multifactorial Intervention (IMP)<br/><b>Sponsor</b>: Centre Hospitalier Universitaire de Saint Etienne<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>RCT for Yinqiaosan-Maxingganshitang in the Treatment of COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Chinese Herb; Diagnostic Test: Placebo<br/><b>Sponsor</b>: Chinese University of Hong Kong<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 Understand the Effect and Safety of the Study Medicine PF-07817883 in Adults Who Have Symptoms of COVID-19 But Are Not Hospitalized.</strong> - <b>Condition</b>: SARS-CoV-2 Infection<br/><b>Interventions</b>: Drug: PF-07817883; Drug: Placebo<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>Traditional Chinese Medicine or Low-dose Dexamethasone in COVID-19 Pneumonia</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Interventions</b>: Other: conventional western medicine treatment; Drug: Dexamethasone oral tablet; Other: Traditional Chinese medicine decoction<br/><b>Sponsor</b>: China-Japan Friendship 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>A Clinical Study on Safety and Effectiveness of Mesenchymal Stem Cell Exosomes for the Treatment of COVID-19.</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Intervention</b>: Biological: Extracellular Vesicles from Mesenchymal Stem Cells<br/><b>Sponsor</b>: First Affiliated Hospital of Wenzhou Medical University<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 of the Safety, Tolerability and Efficacy of NP-101 in Treating High Risk Participants Who Are Covid-19 Positive.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: NP-101; Other: Placebo<br/><b>Sponsor</b>: Novatek Pharmaceuticals<br/><b>Recruiting</b></p></li>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Comprehensive structural analysis reveals broad-spectrum neutralizing antibodies against SARS-CoV-2 Omicron variants</strong> - The pandemic of COVID-19 caused by SARS-CoV-2 continues to spread around the world. Mutant strains of SARS-CoV-2 are constantly emerging. At present, Omicron variants have become mainstream. In this work, we carried out a systematic and comprehensive analysis of the reported spike protein antibodies, counting the epitopes and genotypes of these antibodies. We further comprehensively analyzed the impact of Omicron mutations on antibody epitopes and classified these antibodies according to their…</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>Phosphatidylglycerol-specific phospholipase C from Amycolatopsis sp. NT115 strain: purification, characterization, and gene cloning</strong> - Recently, phosphatidylglycerol (PG) focused on its important role in chloroplast photosynthesis, mitochondrial function of the sperm, an inhibitory effect on SARS-CoV-2 ability to infect naïve cells and reducing lung inflammation caused by COVID-19. To develop an enzymatic PG determination method as the high-throughput analysis of PG, a PG-specific phospholipase C (PG-PLC) was found in the culture supernatant of Amycolatopsis sp. NT115. PG-PLC (54 kDa by SDS-PAGE) achieved the maximal activity…</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>Antiviral Activity of Cell Membrane-Bound Amphiphilic Polymers</strong> - We demonstrate that cholesterol-modified polyethylene glycol has antiviral activity, exerted by anchoring to plasma membranes and sterically inhibiting viruses from entering cells. These polymers distribute sparsely on cell membranes even at binding saturation. However, the polymers have sufficient elastic repulsion energy to repel various kinds of viruses with sizes larger than the mean distances between anchored polymers, including SARS-CoV-2 pseudoparticles. Our strategy can be applied to…</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>Effects of Omicron Infection and Changes in Serum Antibody Response to Wild-Type, Delta, and Omicron After a Booster Dose With BNT163b2 Vaccine in Korean Healthcare Workers</strong> - CONCLUSION: Booster vaccination with BNT162b2 was significantly less effective for the neutralizing antibody responses to omicron variant compared to the wild-type or delta variant in healthy population. Humoral immunogenicity was sustained significantly high after 4 months of booster vaccine in the infected population after booster vaccination. Further studies are needed to understand the characteristics of immunogenicity in these populations.</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>Cyanometabolites: molecules with immense antiviral potential</strong> - Cyanometabolites are active compounds derived from cyanobacteria that include small low molecular weight peptides, oligosaccharides, lectins, phenols, fatty acids, and alkaloids. Some of these compounds may pose a threat to human and environment. However, majority of them are known to have various health benefits with antiviral properties against pathogenic viruses including Human immunodeficiency virus (HIV), Ebola virus (EBOV), Herpes simplex virus (HSV), Influenza A virus (IAV) etc….</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>Heat shock protein 90 facilitates SARS-CoV-2 structural protein-mediated virion assembly and promotes virus-induced pyroptosis</strong> - Inhibition of heat shock protein 90 (Hsp90), a prominent molecular chaperone, effectively limits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but little is known about any interaction between Hsp90 and SARS-CoV-2 proteins. Here, we systematically analyzed the effects of the chaperone isoforms Hsp90α and Hsp90β on individual SARS-CoV-2 viral proteins. Five SARS-CoV-2 proteins, namely nucleocapsid (N), membrane (M), and accessory proteins Orf3, Orf7a, and Orf7b were…</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>CCL12 induces trabecular bone loss by stimulating RANKL production in BMSCs during acute lung injury</strong> - In the last three years, the capacity of health care systems and the public health policies of governments worldwide were challenged by the spread of SARS-CoV-2. Mortality due to SARS-CoV-2 mainly resulted from the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Moreover, millions of people who survived ALI/ARDS in SARS-CoV-2 infection suffer from multiple lung inflammation-induced complications that lead to disability and even death. The lung-bone axis refers…</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 synergistic effect of Cu-MOF nanoparticles and immunomodulatory agent on SARS-CoV-2 inhibition</strong> - In this work, HKUST-1 and Cu-BDC nanoparticles were used as delivery systems for the early anti-COVID-19 drug, hydroxychloroquine. The antiviral MOF/drug combinations significantly reduced the infectivity of SARS-CoV-2, which can be attributed to the nanometric size of the carriers, the presence of copper in the MOF nodes, and the semi-controlled release of the drug.</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 and <em>in vitro</em> evaluation of antiviral activity of wogonin against main protease of porcine epidemic diarrhea virus</strong> - The high mortality rate of weaned piglets infected with porcine epidemic diarrhea virus (PEDV) poses a serious threat to the pig industry worldwide, demanding urgent research efforts related to developing effective antiviral drugs to prevent and treat PEDV infection. Small molecules can possibly prevent the spread of infection by targeting specific vital components of the pathogen’s genome. Main protease (Mpro, also named 3CL protease) plays essential roles in PEDV replication and has emerged as…</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>G4-binding drugs, chlorpromazine and prochlorperazine, repurposed against COVID-19 infection in hamsters</strong> - The COVID-19 pandemic caused by SARS-CoV-2 has caused millions of infections and deaths worldwide. Limited treatment options and the threat from emerging variants underline the need for novel and widely accessible therapeutics. G-quadruplexes (G4s) are nucleic acid secondary structures known to affect many cellular processes including viral replication and transcription. We identified heretofore not reported G4s with remarkably low mutation frequency across >5 million SARS-CoV-2 genomes. The G4…</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>Heterologous prime-boost immunisation with mRNA- and AdC68-based 2019-nCoV variant vaccines induces broad-spectrum immune responses in mice</strong> - The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or 2019-nCoV) variants has been associated with the transmission and pathogenicity of COVID-19. Therefore, exploring the optimal immunisation strategy to improve the broad-spectrum cross-protection ability of COVID-19 vaccines is of great significance. Herein, we assessed different heterologous prime-boost strategies with chimpanzee adenovirus vector-based COVID-19 vaccines plus Wuhan-Hu-1 (WH-1) strain (AdW)…</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>Channel activity of SARS-CoV-2 viroporin ORF3a inhibited by adamantanes and phenolic plant metabolites</strong> - SARS-CoV-2 has been responsible for the major worldwide pandemic of COVID-19. Despite the enormous success of vaccination campaigns, virus infections are still prevalent and effective antiviral therapies are urgently needed. Viroporins are essential for virus replication and release, and are thus promising therapeutic targets. Here, we studied the expression and function of recombinant ORF3a viroporin of SARS-CoV-2 using a combination of cell viability assays and patch-clamp electrophysiology….</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>Effect of Famotidine on COVID-19: Killing Virus or Opposing ARDS?</strong> - Since the first detection of SARS-CoV-2 in China, COVID-19 (Corona Virus Disease 2019) has taken the lives of more than six million people. Although some antivirals seem proper for treatment, the investigation of finding the best therapeutic approach for COVID-19 is still continuing. Some observational research showed that famotidine has promising effects in addition to its acid-suppressing characteristics in the treatment of COVID-19. The definite viricidal effect of famotidine is not…</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 inhibitory and inducing effects of ritonavir on hepatic and intestinal CYP3A and other drug-handling proteins</strong> - Ritonavir, originally developed as HIV protease inhibitor, is widely used as a booster in several HIV pharmacotherapy regimens and more recently in Covid-19 treatment (e.g., Paxlovid). Its boosting capacity is due to the highly potent irreversible inhibition of the cytochrome P450 (CYP) 3 A enzyme, thereby enhancing the plasma exposure to coadministered drugs metabolized by CYP3A. Typically used booster doses of ritonavir are 100-200 mg once or twice daily. This review aims to address several…</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>Management of patients with advanced prostate cancer-metastatic and/or castration-resistant prostate cancer: report of the Advanced Prostate Cancer Consensus Conference (APCCC) 2022</strong> - CONCLUSIONS: These voting results in four specific areas from a panel of experts in advanced prostate cancer can help clinicians and patients navigate controversial areas of management for which high-level evidence is scant or conflicting and can help research funders and policy makers identify information gaps and consider what areas to explore further. However, diagnostic and treatment decisions always have to be individualised based on patient characteristics, including the extent and…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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