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<title>15 December, 2022</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Development and validation of MedDRA Tagger: a tool for extraction and structuring medical information from clinical notes</strong> -
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Rapid and automated extraction of clinical information from patients9 notes is a desirable though difficult task. Natural language processing (NLP) and machine learning have great potential to automate and accelerate such applications, but developing such models can require a large amount of labeled clinical text, which can be a slow and laborious process. To address this gap, we propose the MedDRA tagger, a fast annotation tool that makes use of industrial level libraries such as spaCy, biomedical ontologies and weak supervision to annotate and extract clinical concepts at scale. The tool can be used to annotate clinical text and obtain labels for training machine learning models and further refine the clinical concept extraction performance, or to extract clinical concepts for observational study purposes. To demonstrate the usability and versatility of our tool, we present three different use cases: we use the tagger to determine patients with a primary brain cancer diagnosis, we show evidence of rising mental health symptoms at the population level and our last use case shows the evolution of COVID-19 symptomatology throughout three waves between February 2020 and October 2021. The validation of our tool showed good performance on both specific annotations from our development set (F1 score 0.81) and open source annotated data set (F1 score 0.79). We successfully demonstrate the versatility of our pipeline with three different use cases. Finally, we note that the modular nature of our tool allows for a straightforward adaptation to another biomedical ontology. We also show that our tool is independent of EHR system, and as such generalizable.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.14.22283470v1" target="_blank">Development and validation of MedDRA Tagger: a tool for extraction and structuring medical information from clinical notes</a>
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</div></li>
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<li><strong>Bayesian uncertainty quantification to identify population level vaccine hesitancy behaviours</strong> -
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When effective vaccines are available, vaccination programs are typically one of the best defences against the spread of an infectious disease. Unfortunately, vaccination rates may be suboptimal for a prolonged duration as a result of slow uptake of vaccines by the public. Key factors driving slow vaccination uptake can be a complex interaction of vaccine roll-out policies and logistics, and vaccine hesitancy behaviours potentially caused by an inflated sense of risk in adverse reactions in some populations or community complacency in communities that have not yet experienced a large outbreak. In the recent COVID-19 pandemic, public health responses around the world began to include vaccination programs from late 2020 to early 2021 with an aim of relaxing non-pharmaceutical interventions such as lockdowns and travel restrictions. For many jurisdictions there have been challenges in getting vaccination rates high enough to enable the relaxation of restrictions based on non-pharmaceutical interventions. A key concern during this time was vaccine hestitancy behaviours potentially caused by vaccine safety concerns fuelled by misinformation and community complacency in jurisdictions that had seen very low COVID-19 case numbers throughout 2020, such as Australia and New Zealand. We develop a novel stochastic epidemiological model of COVID-19 transmission that incorporates changes in population behaviour relating to responses based on non-pharmaceutical interventions and community vaccine uptake as functions of the reported COVID-19 cases, deaths, and vaccination rates. Through a simulation study, we develop a Bayesian analysis approach to demonstrate that different factors inhibiting the uptake of vaccines by the population can be isolated despite key model parameters being subject to substantial uncertainty. In particular, we are able to identify the presence of vaccine hesitancy in a population using reported case, death and vaccination count data alone. Furthermore, our approach provides insight as to whether the dominant concerns driving hesitancy are related to vaccine safety or complacency. While our simulation study is inspired by the COVID-19 pandemic, our tools and techniques are general and could be enable vaccination programs of various infectious diseases to be adapted rapidly in response to community behaviours moving forward into the future.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.13.22283297v1" target="_blank">Bayesian uncertainty quantification to identify population level vaccine hesitancy behaviours</a>
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<li><strong>Milk antibody response after 3rd dose of COVID-19 mRNA vaccine and SARS-CoV-2 breakthrough infection and implications for infant protection</strong> -
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Anti-SARS-CoV-2 antibodies have been found in human-milk after COVID-19 infection and vaccination. However, little is known about their persistence in milk after booster vaccination and breakthrough infection. In this study, human-milk, saliva and blood samples were collected from 33 lactating individuals before and after mRNA-based vaccination and COVID-19 breakthrough infections. Antibody levels were measured using ELISA and symptoms were assessed using questionnaires. Evaluation of maternal and infant symptomatology revealed that infected mothers reported more symptoms than vaccinated mothers. We found that after vaccination, human-milk anti-SARS-CoV-2 antibodies persisted for up to 8 months. In addition, distinct patterns of human milk IgA and IgG production we observed after breakthrough infection compared to 3-dose vaccination series alone, indicating a differential central and mucosal immune profiles in hybrid compared with vaccine-induced immunity. To investigate passively-derived milk antibody protection in infants, we examined the persistence of these antibodies in infant saliva after breastfeeding. We found that IgA was more abundant in infant saliva compared to IgG and persist in infant saliva longer after feeding. Our results delineate the differences in milk antibody response to vaccination as compared to breakthrough infection and emphasize the importance of improving the secretion of IgA antibodies to human milk after vaccination to improve the protection of breastfeeding infants.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.12.22283367v1" target="_blank">Milk antibody response after 3rd dose of COVID-19 mRNA vaccine and SARS-CoV-2 breakthrough infection and implications for infant protection</a>
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<li><strong>COVID-19 Outbreak Control Strategies and their Impact on the Provision of Essential Health Services in Ghana: An Explanatory-Sequential Study</strong> -
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Background The COVID-19 pandemic has led to substantial interruptions in critical health services, with 90% of countries reporting interruptions in routine vaccinations, maternal health care and chronic disease management. The use of non-pharmaceutical interventions (NPIs) such as lockdowns and self-isolation had implications on the provision of essential health services (EHS). We investigated exemplary COVID-19 outbreak control strategies and explored the extent to which the adoption of these NPIs affected the provision of EHS including immunization coverage and facility-based deliveries. Finally, we document core health system strategies and practices adopted to maintain EHS during the early phase of the pandemic. Methods This study used an explanatory sequential study design. First, we utilized data from routine health management information systems to quantify the impact of the pandemic on the provision of EHS using interrupted time series models. Second, we explored exemplary strategies and health system initiatives that were adopted to prevent the spread of COVID-19 infections while maintaining the provision of EHS using in-depth interviews with key informants including policymakers and healthcare providers. Results The COVID-19 pandemic and the interventions that were implemented disrupted the provision of EHS. In the first month of the COVID-19 pandemic, Oral Polio and pentavalent vaccination coverage reduced by 15.2% [95% CI = -22.61, -7.87, p<0.001] and 12.4% [95% CI = 17.68, -7.13; p<0.001] respectively. The exemplary strategies adopted in maintaining the provision of EHS while also responding to the spread of infections include the development of new policy guidelines that were disseminated with modified service delivery models, new treatment and prevention guidelines, healthcare workforce capacity building on outbreak control strategies, the use of telemedicine and medical drones to provide EHS and facilitate rapid testing of suspected cases. Conclusion The implementation of different NPIs during the peak phase of the pandemic disrupted the provision of EHS. However, the Ministry of Health leveraged the resilient health system and deployed efficient, all-inclusive, and integrated infectious disease management and infection prevention control strategies to maintain the provision of EHS while responding to the spread of infections.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.12.22283342v1" target="_blank">COVID-19 Outbreak Control Strategies and their Impact on the Provision of Essential Health Services in Ghana: An Explanatory-Sequential Study</a>
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<li><strong>The effects of sleep disturbance on dyspnoea and impaired lung function following COVID-19 hospitalisation: a prospective multi-centre cohort study</strong> -
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Background Sleep disturbance is common following hospitalisation both for COVID-19 and other causes. The clinical associations are poorly understood, despite it altering pathophysiology in other scenarios. We, therefore, investigated whether sleep disturbance is associated with dyspnoea along with relevant mediation pathways. Methods Sleep parameters were assessed in a prospective cohort of patients (n=2,468) hospitalised for COVID-19 in the United Kingdom in 39 centres using both subjective and device-based measures. Results were compared to a matched UK biobank cohort and associations were evaluated using multivariable linear regression. Findings 64% (456/714) of participants reported poor sleep quality; 56% felt their sleep quality had deteriorated for at least 1-year following hospitalisation. Compared to the matched cohort, both sleep regularity (44.5 vs 59.2, p<0.001) and sleep efficiency (85.4% vs 88.5%, p<0.001) were lower whilst sleep period duration was longer (8.25h vs 7.32h, p<0.001). Overall sleep quality (effect estimate 4.2 (3.0-5.5)), deterioration in sleep quality following hospitalisation (effect estimate 3.2 (2.0-4.5)), and sleep regularity (effect estimate 5.9 (3.7-8.1)) were associated with both dyspnoea and impaired lung function (FEV1 and FVC). Depending on the sleep metric, anxiety mediated 13-42% of the effect of sleep disturbance on dyspnoea and muscle weakness mediated 29-43% of this effect. Interpretation Sleep disturbance is associated with dyspnoea, anxiety and muscle weakness following COVID-19 hospitalisation. It could have similar effects for other causes of hospitalisation where sleep disturbance is prevalent.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.13.22283391v1" target="_blank">The effects of sleep disturbance on dyspnoea and impaired lung function following COVID-19 hospitalisation: a prospective multi-centre cohort study</a>
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<li><strong>A cross-sectional survey of material deprivation and suicide-related ideation among Vietnamese technical interns in Japan in 2021</strong> -
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Background: Many technical intern trainees in Japan are economically impoverished because of the need to send money back to their home country, debts from the intermediaries that arranged their arrival in Japan, and reduced working hours because of the coronavirus disease 2019 (COVID-19) pandemic. In addition, there is concern that COVID-19 may cause mental instability in response to the life changes experienced by interns. The purpose of this study was to elucidate the experience of material deprivation and the relationship between the state of material deprivation and suicidal ideation among Vietnamese intern trainees in Japan. Methods: A cross-sectional study was conducted from September to October 2021. Of 310 Vietnamese technical intern trainees who responded, we analyzed data from 200 individuals with no missing or abnormal values. The questionnaire obtained information about gender, age, length of residence in Japan, Japanese language proficiency, changes in income related to the COVID-19 pandemic, material deprivation status, and suicidal ideation. The ninth item of the Patient Health Questionnaire-9 was used to examine suicidal ideation. Logistic regression analysis was used to analyze the relationship between material deprivation items and suicidal ideation. Results: Respondents mean age was 26.0 ± 5.1 years, and 62.0% (n = 124) were male. Regarding material deprivation items, food was reported in 82 (41.0%) cases, cellphone bills were reported in 49 (24.5%) cases, and medical expenses were reported in 34 (22.0%) cases. Forty-six (23.0%) respondents reported experiencing suicidal ideation, and the prevalence was associated with age (p = 0.031, odds ratio [OR] = 0.889, 95% confidence interval [CI] = 0.799-0.990), deprivation regarding food expenses (p = 0.003, OR = 3.897, 95% CI = 1.597-9.511), and deprivation regarding cellphone usage (p = 0.021, OR = 3.671, 95% CI = 1.217-11.075). Conclusions: Vietnamese technical intern trainees in Japan experienced material deprivation in multiple ways, and exhibited a high prevalence of serious psychological problems. Factors contributing to suicidal ideation included age, experience of deprivation in relation to food expenses, and deprivation in relation to cellphone bills. Inability to pay cellphone bills may have increased isolation among Vietnamese trainees during the COVID-19 pandemic.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.14.22283455v1" target="_blank">A cross-sectional survey of material deprivation and suicide-related ideation among Vietnamese technical interns in Japan in 2021</a>
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<li><strong>Difference in presentation, outcomes, and hospital epidemiologic trend of COVID-19 among first, second, and third waves in Dhaka Medical College</strong> -
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Background This study aimed to examine the differences in epidemiologic and disease aspects among patients with COVID 19 Methods: We reviewed the hospital records between April 2020 and September 2021 and followed up on the patients for post COVID complications. Findings: Older adult patients were predominantly affected during the first and second waves, followed by middle-aged patients. Men were predominantly admitted, considering the three waves; although more women were admitted in the second wave. Cough was more common in the second and third waves than in the first wave 522 (59.7%). Respiratory distress was the most common in the third wave, 251(67.1%), and least common in the first wave 403 (46.1%). Anosmia was more common in the third wave 116 (31.2%). In the third wave, patients presenting in a critical state 23 (6.2%) and severe disease 152 (40.8%) were more common. The hospital admission median (IQR) was longer in the first wave, 12 (8–20), than in other waves. More patients were admitted in the first wave (52%) than in the other waves, and patients received more oxygen in the third wave (75%) than in the other waves. Death occurred more commonly in the first wave (51%) than in the other waves. Patients were investigated more commonly in the first and third waves than in the second wave. The positivity rate was high in the third wave (22.8%) than in other waves. In the third wave, the positivity rate was higher in women (24.3%) than in men. Post COVID cough increased in the second wave and fatigue was higher in the third wave than in other waves. Tiredness and memory loss was greater during the second wave than in other waves. Conclusion: This study revealed that the presenting symptoms, outcomes, and epidemiologic trends differed during the COVID 19 waves.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.14.22283379v1" target="_blank">Difference in presentation, outcomes, and hospital epidemiologic trend of COVID-19 among first, second, and third waves in Dhaka Medical College</a>
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<li><strong>COVID-19db linkage maps of cell surface proteins and transcription factors in immune cells</strong> -
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The highly contagious SARS-CoV-2 and its associated disease (COVID-19) are a threat to global public health and economies. To develop effective treatments for COVID-19, we must understand the host cell types, cell states and regulators associated with infection and pathogenesis such as dysregulated transcription factors (TFs) and surface proteins, including signaling receptors. To link cell surface proteins with TFs, we recently developed SPaRTAN (Single-cell Proteomic and RNA-based Transcription factor Activity Network) by integrating parallel single-cell proteomic and transcriptomic data based on Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-seq), which contains gene cis-regulatory information. We apply SPaRTAN to CITE-seq datasets from patients with varying degrees of COVID-19 severity and healthy controls to identify the associations between surface proteins and TFs in host immune cells. Here, we present COVID-19db of Immune Cell States (https://covid19db.streamlit.app/), a web server containing cell surface protein expression, SPaRTAN-inferred TF activities, and their associations with major host immune cell types. The data include four high-quality COVID-19 CITE-seq datasets with a toolset for user-friendly data analysis and visualization. We provide interactive surface protein and TF visualizations across major immune cell types for each dataset, allowing comparison between various patient severity groups for the discovery of potential therapeutic targets and diagnostic biomarkers.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.14.520411v1" target="_blank">COVID-19db linkage maps of cell surface proteins and transcription factors in immune cells</a>
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<li><strong>2-Thiouridine is a broad-spectrum antiviral nucleoside analogue against positive-strand RNA viruses</strong> -
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes significant morbidity and mortality worldwide, seriously impacting not only human health but also the global economy. Furthermore, over 1 million cases of newly emerging or re-emerging viral infections, specifically dengue virus (DENV), are known to occur annually. Because no virus-specific and fully effective treatments against these and many other viruses have been approved, they continue to be responsible for large-scale epidemics and global pandemics. Thus, there is an urgent need for novel, effective therapeutic agents. Here, we identified 2-thiouridine (s2U) as a broad-spectrum antiviral nucleoside analogue that exhibited antiviral activity against SARS-CoV-2 and its variants of concern, including the Delta and Omicron variants, as well as a number of other positive-sense single-stranded RNA (ssRNA+) viruses, including DENV. s2U inhibits RNA synthesis catalyzed by viral RNA-dependent RNA polymerase, thereby reducing viral RNA replication, which improved the survival rate of mice infected with SARS-CoV-2 or DENV in our animal models. Our findings demonstrate that s2U is a potential broad-spectrum antiviral agent not only against SARS-CoV-2 and DENV but other ssRNA+ viruses.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.14.520006v1" target="_blank">2-Thiouridine is a broad-spectrum antiviral nucleoside analogue against positive-strand RNA viruses</a>
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<li><strong>COVID-19 Vaccination in Pregnancy: The Impact of Multimorbidity and Smoking Status on Vaccine Hesitancy, a Cohort Study of 25,111 Women in Wales, UK</strong> -
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Abstract Background Multimorbidity and pregnancy are two risk factors for more severe outcomes after a SARS-CoV-2 infection, thus vaccination uptake is important for pregnant women living with multimorbidity. This study aimed to examine the impact of multimorbidity, smoking status, and demographics (age, ethnic group, area of deprivation) on vaccine hesitancy among pregnant women in Wales using electronic health records (EHR) linkage. Methods This cohort study utilised routinely collected, individual-level, anonymised population-scale linked data within the Secure Anonymised Information Linkage (SAIL) Databank. Pregnant women were identified from 13th April 2021 to 31st December 2021. Survival analysis was utilised to examine and compare the length of time to vaccination uptake in pregnancy by multimorbidity and smoking status, as well as depression, diabetes, asthma, and cardiovascular conditions independently. Variation in uptake by; multimorbidity, smoking status, and demographics was examined jointly and separately for the independent conditions using hazard ratios (HR) from the Cox regression model. A bootstrapping internal validation was conducted to assess the performance of the models. Results Within the population cohort, 8,203 (32.7%) received at least one dose of the COVID-19 vaccine during pregnancy, with 8,572 (34.1%) remaining unvaccinated throughout the follow-up period, and 8,336 (33.2%) receiving the vaccine postpartum. Women aged 30 years or older were more likely to have the vaccine in pregnancy. Those who had depression were slightly but significantly more likely to have the vaccine compared to those without depression (HR = 1.08, 95% CI 1.03 to 1.14, p = 0.02). Women living with multimorbidity (> 1 health condition) were 1.12 times more likely to have the vaccine compared to those living without multimorbidity (HR = 1.12, 95% CI 1.04 to 1.19, p = 0.001). Vaccine uptakes were significantly lower among both current smokers and former smokers compared to never smokers (HR = 0.87, 95% CI 0.81 to 0.94, p < 0.001 and HR = 0.92, 95% CI 0.85 to 0.98, p = 0.015 respectively). Uptake was also lower among those living in the most deprived areas compared to those living in the most affluent areas (HR = 0.89, 95% CI 0.83 to 0.96, p = 0.002). The validated model had similar performance and revealed that multimorbidity, smoking status, age, and deprivation level together have a significant impact on vaccine hesitancy (p < 0.05 for all). Conclusion Younger women, living without multimorbidity (zero or only one health condition), current and former smokers, and those living in the more deprived areas are less likely to have the vaccine, thus, a targeted approach to vaccinations may be required for these groups. Women living with multimorbidity are slightly but significantly less likely to be hesitant about COVID-19 vaccination when pregnant.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.12.22283200v1" target="_blank">COVID-19 Vaccination in Pregnancy: The Impact of Multimorbidity and Smoking Status on Vaccine Hesitancy, a Cohort Study of 25,111 Women in Wales, UK</a>
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<li><strong>Robust SARS-CoV-2 antibody and T cell immunity following three COVID-19 vaccine doses in inflammatory bowel disease patients receiving anti-TNF or alternative treatments</strong> -
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BACKGROUND AND AIMS: Vaccine-mediated immune responses in patients with inflammatory bowel disease (IBD) may be influenced by IBD therapies. We investigated in-depth humoral and T-cell responses to SARS-CoV-2 vaccination in IBD patients following three COVID-19 vaccine doses. METHODS: Immune responses of 100 SARS-CoV-2-uninfected IBD patients on varying treatments were compared to healthy controls (n=35). Anti-S1/2 and anti-RBD SARS-CoV-2-specific antibodies, CD4+ and CD8+ T-cell responses were measured at baseline and at five time-points after COVID-19 vaccination. RESULTS: Anti-S1/2 and anti-RBD antibody concentrations at ~1 month after second dose vaccination were significantly lower in anti-TNF-treated patients compared to non-TNF IBD patients and healthy controls (126.4 vs 262.1 and 295.5, p<0.0001). Anti-S1/2 antibodies remained reduced in anti-TNF treated patients before and after the third dose (285.7 vs 365.3, p=0.03), although anti-RBD antibodies reached comparable titres to non-TNF patients. Anti-RBD antibodies were higher in the vedolizumab group than controls after second dose (4.2 vs 3.6, p=0.003). Anti-TNF monotherapy was associated with increased CD4+ and CD8+ T-cell activation compared to combination anti-TNF patients after second dose, but comparable after third dose. Overall, IBD patients demonstrated similar CD4+/CD8+ T-cell responses compared to healthy controls regardless of treatment regimen. CONCLUSIONS: Anti-TNFs impaired antibody concentrations when compared to non-TNF patients and controls after two vaccine doses. These differences were not observed after the third vaccine dose. However, vaccine induced SARS-CoV-2-specific T cell responses are robust in anti-TNF-treated patients. Our study supports the need for timely booster vaccination particularly in anti-TNF treated patients to minimise the risk of severe SARS-CoV-2 infection.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.13.22283434v1" target="_blank">Robust SARS-CoV-2 antibody and T cell immunity following three COVID-19 vaccine doses in inflammatory bowel disease patients receiving anti-TNF or alternative treatments</a>
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<li><strong>Trends in inequalities in avoidable hospitalisations across the COVID-19 pandemic: A cohort study of 23.5 million people in England</strong> -
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Background: The COVID-19 pandemic and associated national lockdowns created unprecedented disruption to healthcare, with reduced access to services and planned clinical encounters postponed or cancelled. It was widely anticipated that failure to obtain timely treatment would cause progression of illness and increased hospital admissions. Additional concerns were that social and spatial inequalities would widen given the disproportionate impacts of COVID-19 directly. The aim of our study is to determine whether this was observable in England. Methods: With the approval of NHS England we utilised individual-level electronic health records from OpenSAFELY, which covered ~40% of general practices in England (mean monthly population size 23.5 million people). We estimated crude and directly age-standardised rates for potentially preventable unplanned hospital admissions: ambulatory care sensitive conditions and urgent emergency sensitive conditions. We considered how trends in these outcomes varied by three measures of social and spatial inequality: neighbourhood socioeconomic deprivation, ethnicity, and geographical region. Findings: There were large declines in avoidable hospitalisations during the first national lockdown, which then reversed post-lockdown albeit never reaching pre-pandemic levels. While trends were consistent by each measure of inequality, absolute levels of inequalities narrowed throughout 2020 (especially during the first national lockdown) and remained lower than pre-pandemic trends. While the scale of inequalities remained similar into 2021 for deprivation and ethnicity, we found evidence of widening absolute and relative inequalities by geographic region in 2021 and 2022. Interpretation: The anticipation that healthcare disruption from the COVID-19 pandemic and lockdowns would result in more (avoidable) hospitalisations and widening social inequalities was wrong. However, the recent growing gap between geographic regions suggests that the effects of the pandemic has reinforced spatial inequalities.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.14.22283458v1" target="_blank">Trends in inequalities in avoidable hospitalisations across the COVID-19 pandemic: A cohort study of 23.5 million people in England</a>
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<li><strong>Trivalent SARS-CoV-2 S1 Subunit Protein Vaccination Induces Broad Humoral Responses in BALB/c Mice</strong> -
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This paper presents a novel approach for improving the efficacy of COVID-19 vaccines against emergent SARS-CoV-2 variants. We have evaluated the immunogenicity of unadjuvanted wild-type (WU S1-RS09cg) and variant-specific (Delta S1-RS09cg and OM S1-RS09cg) S1 subunit protein vaccines delivered either as a monovalent or a trivalent antigen in BALB/c mice. Our results show that a trivalent approach induced a broader humoral response with more coverage against antigenically distinct variants, especially when compared to monovalent Omicron-specific S1. This trivalent approach was also found to have increased or equivalent ACE2 binding inhibition, and increased S1 IgG endpoint titer at early timepoints, against SARS-CoV-2 spike variants when compared monovalent Wuhan, Delta, or Omicron S1. Our results demonstrate the utility of protein subunit vaccines against COVID-19 and provide insights into the impact of variant-specific COVID-19 vaccine approaches on the immune response in the current SARS-CoV-2 variant landscape. Particularly, our study provides insight into effects of further increasing valency of currently approved SARS-CoV-2 vaccines, a promising approach for improving protection to curtail emerging viral variants.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.12.520124v1" target="_blank">Trivalent SARS-CoV-2 S1 Subunit Protein Vaccination Induces Broad Humoral Responses in BALB/c Mice</a>
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<li><strong>Severe Acute Respiratory Syndrome Coronavirus 2 detection in induced sputum of asthmatic patients using saliva sampling device</strong> -
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Since the beginning of the severe acute respiratory syndrome coronavirus 2 pandemic, the potential contamination of the induced sputum obtained from asthmatic patients in routine is a question of concern. The goal of this study was to assess this contamination using a saliva sample collection device. One hundred seventy-five sputum samples of asthmatic patients without fever were tested. We did not identify any positive PCR on sputum samples from asthmatic patients reporting chronic/episodic respiratory symptoms similar to what is seen in case of COVID-19. This technique was useful to evaluate the contamination of sputum samples generated during the pandemic.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.12.22283341v1" target="_blank">Severe Acute Respiratory Syndrome Coronavirus 2 detection in induced sputum of asthmatic patients using saliva sampling device</a>
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<li><strong>Modelling the adjustment of COVID-19 response and exit from dynamic zero-COVID in China</strong> -
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Background Since the initial Wuhan outbreak, China has been containing COVID-19 outbreaks through its “dynamic zero-COVID” policy. Striking a balance between sustainability and cost-benefit, China has recently begun to adjust its COVID-19 response strategies, e.g. by announcing the “20 measures” on 11 November and further the “10 measures” on 7 December 2022. Strategies for safely exiting from dynamic zero-COVID (i.e. without catastrophically overburdening health systems and/or incurring unacceptably excessive morbidity and mortality) are urgently needed. Methods We use simulations to assess the respective and combined effectiveness of fourth-dose heterologous boosting, large-scale antiviral treatment and public health and social measures (PHSMs) that might allow China to further adjust COVID-19 response and exit from zero-COVID safely after 7 December 2022. We also assess whether local health systems can cope with the surge of COVID-19 cases posed by reopening, given that chunyun, a 40-day period with extremely high mobility across China associated with Spring Festival, will begin on 7 January 2023. Findings Reopening against Omicron transmission should be supported by the following interventions: 1) fourth-dose heterologous boosting 30-60 days before reopening by vaccinating 4-8% of the population per week with ≥85% uptake across all ages; 2) timely antiviral treatment with ≥60% coverage; 3) moderate PHSMs to reduce transmissibility by 47-69%. With fourth-dose vaccination coverage of 85% and antiviral coverage of 60%, the cumulative mortality burden would be reduced by 26-35% to 448-503 per million, compared with reopening without any of these interventions. Simultaneously reopening all provinces under current PHSMs would still lead to hospitalization demand that are 1.5-2.5 times of surge hospital capacity (2.2 per 10,000 population per day). Interpretation Although the surge of disease burden posed by reopening in December 2022-January 2023 would likely overload many local health systems across the country, the combined effect of vaccination, antiviral treatment and PHSMs could substantially reduce COVID-19 morbidity and mortality as China transits from dynamic-zero to normality. Planning for such a nationwide, coordinated reopening should be an urgent priority as part of the global exit from the acute phase of the COVID-19 pandemic.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.14.22283460v1" target="_blank">Modelling the adjustment of COVID-19 response and exit from dynamic zero-COVID in China</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study for Immunocompromised Patients for Pre Exposure Prophylaxis of COVID-19 With AZD5156.</strong> - <b>Condition</b>: COVID 19<br/><b>Interventions</b>: Biological: Placebo; Biological: AZD5156; Biological: AZD7442 (EVUSHELD™)<br/><b>Sponsor</b>: AstraZeneca<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>Animation Supported COVID-19 Education</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Intervention</b>: Other: Animation-Supported Education<br/><b>Sponsor</b>: Siirt University<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Pilot Clinical Trial to Explore Efficacy and Safety of Pyramax in Mild to Moderate COVID-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Pyramax<br/><b>Sponsor</b>: Shin Poong Pharmaceutical Co. Ltd.<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>COVID-19 Huashi Baidu Formula Clinical Study</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Huashi Baidu Granule; Drug: Monapiravir<br/><b>Sponsors</b>: Xiyuan Hospital of China Academy of Chinese Medical Sciences; Beijing YouAn Hospital; Kossamak Hospital; Kamuzu University of Health Sciences<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>Shaping Care Home COVID-19 Testing Policy</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Diagnostic Test: Lateral Flow Device<br/><b>Sponsor</b>: University College, London<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>Baldachin: Ceiling HEPA-filtration to Prevent Nosocomial Transmission of COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Device: Baldachin<br/><b>Sponsor</b>: University Hospital Inselspital, Berne<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>Asunercept for the Treatment of Patients With Moderate to Severe COVID-19 Disease</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Asunercept; Other: Placebo<br/><b>Sponsor</b>: Apogenix AG<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study in Adults to Assess the Safety and Efficacy of Inhaled IBIO123, for Post-exposure Prophylaxis of COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: IBIO123; Other: Placebo<br/><b>Sponsor</b>: Immune Biosolutions Inc<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Roles of Vitamin D and Microbiome in Children With Post-acute COVID-19 Syndromes (PACS) and Long COVID</strong> - <b>Condition</b>: Post-acute COVID-19 Syndromes<br/><b>Interventions</b>: Other: Vitamin D; Other: Placebo<br/><b>Sponsor</b>: China Medical University 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>The Efficacy of Azvudine and Paxlovid in High-risk Patients With COVID-19: A Prospective Randomized Controlled Trial</strong> - <b>Condition</b>: SARS-CoV-2 Infection<br/><b>Interventions</b>: Drug: Azvudine; Drug: Paxlovid group<br/><b>Sponsors</b>: Southeast University, China; Hohhot First Hospital, Hohhot, Inner Mongolia, China<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>Post-COVID-19 Chronic Fatigue Syndrome</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome; Post-COVID Syndrome<br/><b>Intervention</b>: Drug: Synthetic Vitamin B1<br/><b>Sponsors</b>: ClinAmygate; As-Salam Center, Maadi, Cairo, Egypt<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>Effectiveness of Supportive Psychotherapy Through Internet-Based Teleconsultation on Psychological and Somatic Symptoms, Neutrophil-Lymphocyte Ratio, and Heart Rate Variability in Post Covid-19 Syndrome Patients</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Intervention</b>: Behavioral: Supportive Psychotherapy<br/><b>Sponsor</b>: Indonesia 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>A Study to Evaluate the Efficacy, Safety, and Immunogenicity of SARS-CoV-2 Variant (BA.4 /5) mRNA Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: ABO1020; Biological: Placebo<br/><b>Sponsor</b>: Suzhou Abogen Biosciences Co., Ltd.<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>Prednisolone and Vitamin B1/6/12 in Patients With Post-Covid-Syndrome</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Interventions</b>: Drug: Prednisolone 20 mg/ 5 mg; Drug: Vitamin B compound (100mg B1, 50 mg B6, 500 µg B12); Drug: Placebo for Vitamin B compound; Drug: Placebo for Prednisolon<br/><b>Sponsors</b>: Wuerzburg University Hospital; University Hospital Tuebingen; University Hospital Schleswig-Holstein<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>Evaluate the Efficacy and Safety of Azvudine in Preventing SARS-Cov-2 Infection in Household Contacts of Covid-19</strong> - <b>Condition</b>: SARS-CoV-2 Infection<br/><b>Interventions</b>: Drug: Azvudine; Drug: Placebo<br/><b>Sponsors</b>: Shanghai Henlius Biotech; Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.; HeNan Sincere Biotech Co., Ltd<br/><b>Not yet recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Dynamics and binding affinity of nucleoside and non-nucleoside inhibitors with RdRp of SARS-CoV-2: a molecular screening, docking, and molecular dynamics simulation study</strong> - No abstract</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 FDA-approved drugs cetilistat, abiraterone, diiodohydroxyquinoline, bexarotene, and remdesivir as potential inhibitors against RNA dependent RNA polymerase of SARS-CoV-2: A comparative in silico perspective</strong> - No abstract</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 Near-Infrared and blue laser light on Vero E6 cells SARS-CoV-2 infection model</strong> - No abstract</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 Upper Respiratory Tract Microbiome Network Impacted by SARS-CoV-2</strong> - No abstract</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>Reduced immunogenicity of BNT162b2 booster vaccination in combination with a tetravalent influenza vaccination: results of a prospective cohort study in 838 health workers</strong> - No abstract</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Design, synthesis, and pharmacological evaluations of pyrrolo[1,2-a]quinoxaline-based derivatives as potent and selective sirt6 activators</strong> - No abstract</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 structural optimization of 3-O-β-Chacotriosyl betulonic acid saponins as potent fusion inhibitors of Omicron virus infections</strong> - No abstract</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>Synergism of TNF-α and IFN-β triggers human airway epithelial cells death by apoptosis and pyroptosis</strong> - No abstract</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>Nirmatrelvir Plus Ritonavir for Early COVID-19 in a Large U.S. Health System : A Population-Based Cohort Study</strong> - No abstract</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>Phenotypic screening of 1,953 FDA-approved drugs reveals 26 hits with potential for repurposing for Peyronie’s disease</strong> - No abstract</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 preclinical discovery and development of molnupiravir for the treatment of SARS-CoV-2 (COVID-19)</strong> - No abstract</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>Inhibition of glycogen synthase kinase-3-beta (GSK3β) blocks nucleocapsid phosphorylation and SARS-CoV-2 replication</strong> - No abstract</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 properties of porous graphene, graphene oxide and graphene foam ultrafine fibers against Phi6 bacteriophage</strong> - No abstract</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>Enhancing motivation and psychological wellbeing in the workplace through conscious physical activity: Suggestions from a qualitative study examining workers’ experience</strong> - No abstract</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 Treatment by Antiviral Drugs Followed by Immunosuppressive Agents for COVID-19 Patients with Hematological Malignancy</strong> - No abstract</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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