Covid-19 Sentry

Contents

• From Preprints
• From Clinical Trials
• From PubMed
• From Patent Search

From Preprints

• Effect of surfactants on SARS-CoV-2: Molecular Dynamics Simulations -
  Surfactants are commonly used as disinfection agents in personal care products against bacteria and viruses, including SARS-CoV-2. However, there is a lack of understanding of the molecular mechanisms of the inactivation of viruses by surfactants. Here, we employ coarse grain (CG) and all-atom (AA) molecular dynamics simulations to investigate the interaction between general families of surfactants and the SARS-CoV-2 virus. To this end, we considered a CG model of a full virion. Overall, we found that surfactants have only a small impact over the virus envelope, being inserted into the envelope without dissolving it or generating pores, at the conditions considered here. However, we found that surfactants may induce a deep impact on the spike protein of the virus (responsible for its infectivity), easily covering it and inducing its collapse over the envelope surface of the virus. AA simulations confirmed that both negatively and positively charged surfactants are able to extensively adsorb over the spike protein and get inserted into the virus envelope. Our results suggest that the best strategy for the design of surfactants as virucidal agents will be to focus on those strongly interacting with the spike protein.
  🖺 Full Text HTML: Effect of surfactants on SARS-CoV-2: Molecular Dynamics Simulations
• Characterizing and Predicting Post-Acute Sequelae of SARS CoV-2 infection (PASC) in a Large Academic Medical Center in the US -

  Objective: The growing number of Coronavirus Disease-2019 (COVID-19) survivors who are affected by Post-Acute Sequelae of SARS CoV-2 infection (PACS) represent a worldwide public health challenge. Yet, the novelty of this condition and the resulting limited data on underlying pathomechanisms so far hampered the advancement of effective therapies. Using electronic health records (EHR) data, we aimed to characterize PASC-associated diagnoses and develop risk prediction models. Methods: In our cohort of 63,675 COVID-19-positive patients seen at Michigan Medicine, 1,724 (2.7 %) had a recorded PASC diagnosis. We used a case-control study design comparing PASC cases with 17,205 matched controls and performed phenome-wide association studies (PheWASs) to characterize enriched phenotypes of the post-COVID-19 period and potential PASC pre-disposing phenotypes of the pre-, and acute-COVID-19 periods. We also integrated PASC-associated phenotypes into Phenotype Risk Scores (PheRSs) and evaluated their predictive performance. Results: In the post-COVID-19 period, cases were significantly enriched for known PASC symptoms (e.g., shortness of breath, malaise/fatigue, and cardiac dysrhythmias) but also many musculoskeletal, infectious, and digestive disorders. We found seven phenotypes in the pre-COVID-19 period (irritable bowel syndrome, concussion, nausea/vomiting, shortness of breath, respiratory abnormalities, allergic reaction to food, and circulatory disease) and 69 in the acute-COVID-19 period (predominantly respiratory, circulatory, neurological, digestive, and mental health phenotypes) that were significantly associated with PASC. The derived pre-COVID-19 PheRS and acute-COVID-19 PheRS had low accuracy to differentiate cases from controls; however, they stratified risk well, e.g., a combination of the two PheRSs identified a quarter of the COVID-19 positive cohort at 2.9-fold increased risk for PASC compared to the bottom 50% of their distributions. Conclusions: Our agnostic screen of time-stamped EHR data uncovered a plethora of PASC-associated diagnoses across many categories and highlighted a complex arrangement of presenting and likely pre-disposing features - the latter with potential for risk stratification approaches. Yet, considerably more work will need to be done to better characterize PASC and its subtypes, especially long-term consequences, and to consider more comprehensive risk models. Methods: In our cohort of 63,675 COVID-19 positive patients seen at Michigan Medicine, 1,724 (2.7 %) had a recorded PASC diagnosis. We used a case control study design comparing PASC cases with 17,205 matched controls and performed phenome-wide association studies (PheWASs) to characterize enriched phenotypes of the post-COVID-19 period and potential PASC pre-disposing phenotypes of the pre-, and acute-COVID-19 periods. We also integrated PASC-associated phenotypes into Phenotype Risk Scores (PheRSs) and evaluated their predictive performance. Results: In the post-COVID-19 period, cases were significantly enriched for known PASC symptoms (e.g., shortness of breath, malaise/fatigue, and cardiac dysrhythmias) but also many musculoskeletal, infectious, and digestive disorders. We found seven phenotypes in the pre-COVID-19 period (irritable bowel syndrome, concussion, nausea/vomiting, shortness of breath, respiratory abnormalities, allergic reaction to food, and circulatory disease) and 69 phenotypes in the acute-COVID-19 period (predominantly respiratory, circulatory, neurological, digestive, and mental health phenotypes) that were significantly associated with PASC. The derived pre-COVID-19 PheRS and acute-COVID-19 PheRS had low accuracy to differentiate cases from controls; however, they stratified risk well, e.g., a combination of the two PheRSs identified a quarter of the COVID-19 positive cohort at a 3.5-fold increased risk for PASC compared to the bottom 50% of their distributions. Conclusions: Our agnostic screen of time stamped EHR data uncovered a plethora of PASC-associated diagnoses across many categories and highlighted a complex arrangement of presenting and likely pre-disposing features — the latter with a potential for risk stratification approaches. Yet, considerably more work will need to be done to better characterize PASC and its subtypes, especially long-term consequences, and to consider more comprehensive risk models.

  🖺 Full Text HTML: Characterizing and Predicting Post-Acute Sequelae of SARS CoV-2 infection (PASC) in a Large Academic Medical Center in the US
• Infectiousness of SARS-CoV-2 breakthrough infections and reinfections during the Omicron wave -

  SARS-CoV-2 breakthrough infections in vaccinated individuals and reinfections among previously infected individuals have become increasingly common. Such infections highlight a broader need to understand the contribution of vaccination, including booster doses, and natural immunity to the infectiousness of persons with SARS-CoV-2 infections, especially in high-risk populations with intense transmission such as prisons. Here, we show that both vaccine-derived and naturally acquired immunity independently reduce the infectiousness of persons with Omicron variant SARS-CoV-2 infections in a prison setting. Analyzing SARS-CoV-2 surveillance data from December 2021 to May 2022 across 35 California state prisons with a predominately male population, we estimate that unvaccinated Omicron cases had a 36% (95% confidence interval (CI): 31-42%) risk of transmitting infection to close contacts, as compared to 28% (25-31%) risk among vaccinated cases. In adjusted analyses, we estimated that any vaccination, prior infection alone, and both vaccination and prior infection reduced an index case9s risk of transmitting infection by 22% (6-36%), 23% (3-39%) and 40% (20-55%), respectively. Receipt of booster doses and more recent vaccination further reduced infectiousness among vaccinated cases. These findings suggest that although vaccinated and/or previously infected individuals remain highly infectious upon SARS-CoV-2 infection in this prison setting, their infectiousness is reduced compared to individuals without any history of vaccination or infection, underscoring some benefit of vaccination to reduce but not eliminate transmission.

  🖺 Full Text HTML: Infectiousness of SARS-CoV-2 breakthrough infections and reinfections during the Omicron wave
• Resistance of Omicron subvariants BA.2.75.2, BA.4.6 and BQ.1.1 to neutralizing antibodies -
  Convergent evolution of SARS-CoV-2 Omicron BA.2, BA.4 and BA.5 lineages has led to the emergence of several new subvariants, including BA.2.75.2, BA.4.6. and BQ.1.1. The subvariants BA.2.75.2 and BQ.1.1 are expected to become predominant in many countries in November 2022. They carry an additional and often redundant set of mutations in the spike, likely responsible for increased transmissibility and immune evasion. Here, we established a viral amplification procedure to easily isolate Omicron strains. We examined their sensitivity to 6 therapeutic monoclonal antibodies (mAbs) and to 72 sera from Pfizer BNT162b2-vaccinated individuals, with or without BA.1/BA.2 or BA.5 breakthrough infection. Ronapreve (Casirivimab and Imdevimab) and Evusheld (Cilgavimab and Tixagevimab) lost any antiviral efficacy against BA.2.75.2 and BQ.1.1, whereas Xevudy (Sotrovimab) remained weakly active. BQ.1.1 was also resistant to Bebtelovimab. Neutralizing titers in triply vaccinated individuals were low to undetectable against BQ.1.1 and BA.2.75.2, 4 months after boosting. A BA.1/BA.2 breakthrough infection increased these titers, which remained about 18-fold lower against BA.2.75.2 and BQ.1.1, than against BA.1. Reciprocally, a BA.5 breakthrough infection increased more efficiently neutralization against BA.5 and BQ.1.1 than against BA.2.75.2. Thus, the evolution trajectory of novel Omicron subvariants facilitated their spread in immunized populations and raises concerns about the efficacy of most currently available mAbs.
  🖺 Full Text HTML: Resistance of Omicron subvariants BA.2.75.2, BA.4.6 and BQ.1.1 to neutralizing antibodies
• Free energy perturbation calculations of mutation effects on SARS-CoV-2 RBD::ACE2 binding affinity -
  The strength of binding between human angiotensin converting enzyme 2 (ACE2) and the receptor binding domain (RBD) of viral spike protein plays a role in the transmissibility of the SARS-CoV-2 virus. In this study we focus on a subset of RBD mutations that have been frequently observed in infected individuals and probe binding affinity changes to ACE2 using surface plasmon resonance (SPR) measurements and free energy perturbation (FEP) calculations. Our SPR results are largely in accord with previous studies but discrepancies do arise due to differences in experimental methods and to protocol differences even when a single method is used. Overall, we find that FEP performance is superior to that of other computational approaches examined as determined by agreement with experiment and, in particular, by its ability to identify stabilizing mutations. Moreover, the calculations successfully predict the observed cooperative stabilization of binding by the Q498R N501Y double mutant present in Omicron variants and offer a physical explanation for the underlying mechanism. Overall, our results suggest that despite the significant computational cost, FEP calculations may offer an effective strategy to understand the effects of interfacial mutations on protein-protein binding affinities and in practical applications such as the optimization of neutralizing antibodies.
  🖺 Full Text HTML: Free energy perturbation calculations of mutation effects on SARS-CoV-2 RBD::ACE2 binding affinity
• Family experiences during illness outbreaks: A systematic review -

  Background: During the pandemic and associated lockdowns, many families from around the world experienced financial and confinement stress and the reorganisation of family caregiving responsibilities. Several studies have been conducted about the impact of the pandemic on family wellbeing. The aim of this systematic review was to identify, synthesize and critique relevant studies in this field. Methods: Following Cochrane Collaboration and PRISMA guidelines, a systematic search was performed in databases including MEDLINE, PsycINFO, Embase, SocINDEX and PubMed. Peer-reviewed studies that examined the experiences of families during infectious disease outbreaks were included. Quality assessment was undertaken using the Mixed Methods Appraisal Tool. A narrative synthesis approach was employed. Results: Eighty-four papers were found, all conducted during the Covid-19 pandemic, with the majority from the USA and presented from the perspective of parents/caregivers. Synthesized results focused on how family experiences, the dyad relationship and parenting behaviours were impacted during Covid-19. Conclusion: Although some families reported positive growth, socially and financially vulnerable families were more negatively impacted than others during the pandemic. The review highlights the important role of families during times of stress and possible intervention targets. Keywords: family, parenting, pandemic, infectious disease, covid-19

  🖺 Full Text HTML: Family experiences during illness outbreaks: A systematic review
• VACtrac: Enhancing access immunization registry data for population outreach using Bulk Fast Interoperable Healthcare Resource (FHIR) protocol -

  COVID-19 vaccination uptake has been suboptimal, even in high-risk populations. This paper describes work to extend the Bulk Fast Healthcare Interoperability Resource (FHIR) standard for use in querying state Immunization Information Systems (IIS). We also describe a population vaccination outreach tool that uses both Bulk FHIR and automated single queries to access IIS data. Bulk FHIR protocols needed to be extended to support IIS responses for care outside an institution resulting in the addition of Group and Master Data Management FHIR profile functionalities to Bulk FHIR queries to support more accurate and easier retrieval of data. While real-world testing of Bulk FHIR queries using the vaccination outreach system was not possible, we tested an automated single-query tool in a focused effort to reach 1500 high-risk patients. Results confirmed the potential for performance problems during periods of high demand that could be resolved by Bulk FHIR asynchronous retrieval methods.

  🖺 Full Text HTML: VACtrac: Enhancing access immunization registry data for population outreach using Bulk Fast Interoperable Healthcare Resource (FHIR) protocol
• Global spatiotemporal trends and determinants of COVID-19 vaccine acceptance on Twitter: a multilingual deep learning study in 135 countries and territories -

  Background: COVID-19 vaccination has faced a range of challenges from supply-side barriers such as insufficient vaccine supply and negative information environment and demand-side barriers centring on public acceptance and confidence in vaccines. This study assessed global spatiotemporal trends in demand- and supply-side barriers to vaccine uptake using COVID-19-related social media data and explored the country-level determinants of vaccine acceptance. Methods: We accessed a total of 13,093,406 tweets sent between November 2020 and March 2022 about the COVID-19 vaccine in 90 languages from 135 countries using Meltwater (a social listening platform). Based on 8,125 manually-annotated tweets, we fine-tuned multilingual deep learning models to automatically annotate all 13,093,406 tweets. We present spatial and temporal trends in four key spheres: (1) COVID-19 vaccine acceptance; (2) confidence in COVID-19 vaccines; (3) the online information environment regarding the COVID-19 vaccine; and (4) perceived supply-side barriers to COVID-19 vaccination. Using univariate and multilevel regressions, we evaluated the association between COVID-19 vaccine acceptance on Twitter and (1) country-level characteristics regarding governance, pandemic preparedness, trust, culture, social development, and population demographics; (2) country-level COVID-19 vaccine coverage; and (3) Google search trends on adverse vaccine events. Findings: COVID-19 vaccine acceptance was high among Twitter users in Southeast Asian, Eastern Mediterranean, and Western Pacific countries, including India, Indonesia, and Pakistan. In contrast, acceptance was relatively low in high-income nations like South Korea, Japan, and the Netherlands. Spatial variations were correlated with country-level governance, pandemic preparedness, public trust, culture, social development, and demographic determinants. At the country level, vaccine acceptance sentiments expressed on Twitter predicted higher vaccine coverage. We noted the declining trend of COVID-19 vaccine acceptance among global Twitter users since March 2021, which was associated with increased searches for adverse vaccine events. Interpretation: In future pandemics, new vaccines may face the potential low-level and declining trend in acceptance, like COVID-19 vaccines, and early responses are needed. Social media mining represents a promising surveillance approach to monitor vaccine acceptance and can be validated against real-world vaccine uptake data. Keywords: COVID-19, vaccine confidence, vaccine acceptance, vaccine hesitancy, social media, machine learning

  🖺 Full Text HTML: Global spatiotemporal trends and determinants of COVID-19 vaccine acceptance on Twitter: a multilingual deep learning study in 135 countries and territories
• ‘’Locating the Processes of Non-State Relief Work During the Covid-19 Lockdown in Delhi’’ -
  ‘Locating the Processes of Non-state Relief Work during the Covid-19 Lockdown in Delhi’, uses a gender-responsive intersectional framework to highlight the critical role played by communities and civil society in four slum areas of Delhi, in order to reduce human suffering during the Covid-19 lockdown. The study is also an effort to understand the various gendered and intersectional vulnerabilities that came to the fore, the mechanisms of relief work and care that were undertaken through local collective action, as well as the collaborations and networks that were locally built to respond to the crisis. Further, the study is centred on the concepts of social reproduction and care and aims to understand the critical role played by communities in extending care within the institutional framework represented by the ‘Care Diamond’. Thus, the study draws lessons from the experiences of local slum communities in responding to the care crisis during the lockdown and aims to throw light on the wider structural inequalities in society. The findings from the study respond to the policy needs of both the government and civil society in terms of averting a care crisis and/or addressing such a scenario.
  🖺 Full Text HTML: ‘’Locating the Processes of Non-State Relief Work During the Covid-19 Lockdown in Delhi’’
• COVID-19: A Continuing Education Activity -
  Coronavirus disease (COVID-19) is an infectious disease caused by the SARS-CoV-2 virus. Most people infected with the virus will experience mild to moderate respiratory illness and recover without requiring special treatment. However, some will become seriously ill and require medical attention. Older people and those with underlying medical conditions like cardiovascular disease, diabetes, chronic respiratory disease, or cancer are more likely to develop serious illness. Anyone can get sick with COVID-19 and become seriously ill or die at any age. The best way to prevent and slow down transmission is to be well-informed about the disease and how the virus spreads. Protect yourself and others from infection by staying at least 1 meter apart from others, wearing a properly fitted mask, and washing your hands or using an alcohol-based rub frequently. Get vaccinated when it’s your turn and follow local guidance. The virus can spread from an infected person’s mouth or nose in small liquid particles when they cough, sneeze, speak, sing or breathe. These particles range from larger respiratory droplets to smaller aerosols. It is important to practice respiratory etiquette, for example by coughing into a flexed elbow, and to stay home and self-isolate until you recover if you feel unwell.
  🖺 Full Text HTML: COVID-19: A Continuing Education Activity
• Supporting diabetic self-management behaviors during the COVID-19 pandemic -
  This study provides a qualitative analysis of the effects of the COVID-19 pandemic on the nutritional and physical activity self-management of adults with Type 2 diabetes (T2D). We conducted semi-structured interviews with 21 adults with T2D living in the United States, and recorded their experiences maintaining and/or modifying their self-management behaviors as they faced new challenges presented by the pandemic and social distancing (e.g., working from home, lack of access to gyms, online grocery shopping). Interview transcripts were coded using concepts based on the Behavior Change Wheel (BCW) framework. A thematic analysis was then performed to identify common challenges experienced by our participants, and common adjustments they made in an attempt to maintain healthy self-management behaviors. Drivers of behavior were also captured using the COM-B model framework. Based on these results, we propose categories of behavioral interventions and policy options to support self-management activities by Type 2 diabetic adults during the COVID-19 pandemic.
  🖺 Full Text HTML: Supporting diabetic self-management behaviors during the COVID-19 pandemic
• Financial Health of Private Equity-Backed Groups: Perspectives from Ophthalmology and Optometry -

  Purpose: To identify debt valuations of ophthalmology and optometry private equity –backed group (OPEG) practices, which are a proxy for financial performance. Design: Retrospective cohort study using the 2021 Business Development Company (BDC) Report and BDC quarterly/annual filings. Participants: BDCs holding one or more ophthalmology/optometry group debt instruments. Methods: The 2021 BDC Report was used to identify all BDCs actively filing annual reports (Form 10-Ks) and quarterly reports (Form 10–Qs) in 2021. The public filings of BDCs lending to OPEGs were searched from inception of a debt instrument in a BDC portfolio, and the amortized cost and fair value of each debt instrument were tabulated. A panel linear regression was used to evaluate temporal changes in debt valuations. Main Outcome Measures: Trends in total debt held by OPEGs, trends in valuation (premium or discount) of OPEGs. Results: A total of 2997 practice locations affiliated with 14 unique OPEGs and 17 BDCs were identified in 2021. Debt valuations of OPEGs decreased 0.46% per quarter over the study period (95% CI: –0.88 to –0.03, P = 0.036). In the COVID-19 pre-vaccine period (March 2020 – December 2020), there was an excess (additional) 4.93% decrease in debt valuations (95% CI: –8.63 to [ndash]1.24, P = 0.010) when compared to prepandemic debt valuations (March 2017 – December 2019). Effects of COVID–19 on valuations stabilized during the pandemic post-vaccine period (February 2021 – March 2022), with no change in excess debt valuation compared to pre-pandemic baseline (0.60, 95% CI: –4.59 to 5.78, P = 0.822). There was an increase in practices that reported average discounted debt valuations from 20 practices (1.6%) associated with 1 OPEG to 1213 practices (40.5%) (including 100% of newly acquired practices) associated with 9 OPEGs, despite stabilization of COVID–19 related excess (additional) debt. Conclusions: Valuations of OPEG debt have declined significantly post–PE investment from March 2017 to March 2022. An excess (additional) decline in valuations was observed during the COVID pre –vaccine period, with trends in excess debt valuations returning to baseline pre –pandemic levels by December 2021. Declining and discounted valuations of debt raise concerns about the financial viability of many PE–backed practices.

  🖺 Full Text HTML: Financial Health of Private Equity-Backed Groups: Perspectives from Ophthalmology and Optometry
• The prevalence of probable mental health disorders among hospital healthcare workers during COVID-19: A systematic review and meta-analysis -

  Abstract Objectives The mental health impacts of the COVID-19 pandemic continue to be documented worldwide with systematic reviews playing a pivotal role. Here we present updated findings from our systematic review and meta-analysis on the mental health impacts among hospital healthcare workers during COVID-19. Methods We searched MEDLINE, CINAHL, PsycINFO, Embase and Web Of Science Core Collection between 1st January 2000 to 17th February 2022 for studies using validated methods and reporting on the prevalence of diagnosed or probable mental health disorders in hospital healthcare workers during the COVID-19 pandemic. A meta-analysis of proportions and odds ratio was performed using a random effects model. Heterogeneity was investigated using test of subgroup differences and 95% prediction intervals. Results The meta-analysis included 401 studies, representing 458 754 participants across 58 countries. Pooled prevalence of depression was 28.5% (95%CI: 26.3-30.7), anxiety was 28.7% (95%CI: 26.5-31.0), PTSD was 25.5% (95%CI: 22.5-28.5), alcohol and substance use disorder was 25.3% (95%CI: 13.3-39.6) and insomnia was 24.4% (95%CI: 19.4-29.9). Prevalence rates were stratified by physicians, nurses, allied health, support staff and healthcare students, which varied considerably. There were significantly higher odds of probable mental health disorders in women, those working in high-risk units and those providing direct care. Limitations Majority of studies used self-report measures which reflected probable mental health disorders rather than actual diagnosis. Conclusions These updated findings have enhanced our understanding of at-risk groups working in hospitals. Targeted support and research towards these differences in mental health risks are recommended to mitigate any long-term consequences. Keywords: Mental health disorders, Hospital Healthcare Workers, COVID-19, Anxiety, Depression, Post-traumatic Stress Disorder (PTSD)

  🖺 Full Text HTML: The prevalence of probable mental health disorders among hospital healthcare workers during COVID-19: A systematic review and meta-analysis
• A single-centre, observational study to evaluate immune response to Covid-19 vaccines in immunocompromised patients with haematological disorders (COVAC-IC) -

  Abstract Objective: To evaluate immunological response to Covid-19 vaccines in immunocompromised haematology patients and compare with immunocompetent healthy controls Design: We compared total Anti SARS CoV 2 spike antibody and T cell response in 45 immunocompromised haematology patients with 30 healthy adults following 2 doses of Covid 19 vaccine for 3 to 5 months at 30 day intervals Setting: University Hospital, United Kingdom, Single Centre, March 2021 to December 2021 Main Outcome measures: Peak quantitative spike-specific antibody and cellular responses Results: We found 1. Non significant difference in T cell and total Anti SARS CoV 2 S antibody response between study and control group patients 2. Six (13%) study group participants did not have detectable Total Anti SARS Cov 2 S antibodies at any time point throughout the study monitoring period. 3. Three (7%) of the study group participants had no response, even after additional booster doses of Covid-19 vaccine. 4. All (100%) of the control group had detectable Anti SARS Cov 2 S antibodies after 2 doses of Covid 19 vaccine. 5. No participant died or was hospitalised due to severe Covid-19 infection during the study period. This included study group participants who had no antibody response at any time point. Conclusions: Though there was a non significant difference in T cell and total Anti SARS CoV 2 S antibody response between immunocompromised patients and healthy controls this did not result in any severe infection or Covid 19 related mortality in our study cohort. We did not identify any patient-specific factor (age, gender), specific haematological condition or treatment as determinant of response. Covid-19 vaccination was well tolerated without major side effects in both groups. What was already known about this topic: prior to starting this study there were no studies to confirm immunological response following Covid 19 vaccination in immunocompromised haematology patients. During the conduct of our study there have been publications from researchers confirming blunted serological response in 62-66% of immunocompromised haematology patients compared to 74 to 95% in healthy controls. What this study adds: Our study did not identify a significant difference in serological or T cell response between immunocompromised and healthy groups. Though 13% of immunocompromised patients had no response to Covid-19 vaccination none of them suffered from severe Covid-19 infection. We believe T cell response to Covid-19 vaccination has an important role in providing protective efficacy against Covid 19.

  🖺 Full Text HTML: A single-centre, observational study to evaluate immune response to Covid-19 vaccines in immunocompromised patients with haematological disorders (COVAC-IC)
• Prescription of anti-influenza drugs in Japan, 2014-2020: a retrospective study using open data from the national claims database -

  Background: Both physicians and patients are proactive towards managing seasonal influenza in Japan and six drugs are approved. We aimed to clarify the status of anti-influenza drug use by analyzing real-world data. Methods: This retrospective study analyzed open data from the National Database of Health Insurance Claims and Specific Health Checkups, which covers most claims data from national health insurance. We estimated the annual number of patients prescribed anti-influenza drugs, their age and sex distribution, drug costs, and regional disparities for the period 2014-2020. Results: For 2014-2019, an estimated 6.7-13.4 million patients per year were prescribed anti-influenza drugs, with an annual cost of 22.3-48.0 billion JPY (Japanese Yen). In addition, 21.1-32.0 million rapid antigen tests were performed at a cost of 30.1-47.1 billion JPY. In 2017, laninamivir was the most frequently prescribed anti-influenza drug (48%), followed by oseltamivir (36%), while in 2018, the newly introduced baloxavir accounted for 40.8% of prescriptions. After the emergence of COVID-19, the number of patients prescribed anti-influenza drugs in 2020 dropped to just 14,000. In 2018, 37.6% of prescriptions were for patients aged < 20 years compared with 12.2% for those aged ≥ 65 years. Prescriptions for inpatients accounted for 1.1%, and the proportion of prescriptions for inpatients increased with age. Male were more likely than female to be prescribed anti-influenza drugs for inpatient. Conclusions: Based on our clarification of how influenza is clinically managed in Japan, future work should evaluate the clinical and economic aspects of proactively prescribing anti-influenza drugs.

  🖺 Full Text HTML: Prescription of anti-influenza drugs in Japan, 2014-2020: a retrospective study using open data from the national claims database

From Clinical Trials

• COVID-19 Bivalent Booster Megastudy - Condition:   COVID-19
  Intervention:   Behavioral: COVID Booster text messages
  Sponsor:   University of Pennsylvania
  Enrolling by invitation

• A Study on Utilization, Adherence, and Acceptability of Voluntary Routine COVID-19 Self-testing Among Students, Staff and Health Workers at Two Institutions in Mizoram, India. - Condition:   COVID-19 Pandemic
  Intervention:   Diagnostic Test: COVID-19 Self testing and related messaging
  Sponsors:   PATH;   UNITAID;   Zoram Medical College;   Pacchunga University College;   ALERT India;   Government of Mizoram
  Not yet recruiting

• Using a Community-level Just-in-Time Adaptive Intervention to Address COVID-19 Testing Disparities - Condition:   COVID-19
  Interventions:   Behavioral: Multi-Level Multi-Component Intervention (MLI);   Behavioral: Community Just-In-Time Adaptive Intervention (Community JITAI)
  Sponsors:   The University of Texas Health Science Center, Houston;   National Center for Advancing Translational Sciences (NCATS)
  Active, not recruiting

• Examining How a Facilitated Self-Sampling Intervention and Testing Navigation Intervention Influences COVID-19 Testing - Condition:   COVID-19
  Interventions:   Behavioral: Facilitated Self-Sampling Intervention (FSSI);   Behavioral: Testing Navigation Intervention (TNI).;   Behavioral: Control
  Sponsors:   The University of Texas Health Science Center, Houston;   National Center for Advancing Translational Sciences (NCATS)
  Not yet recruiting

• Assessing Performance of the Testing Done Simple Covid 19 Antigen Test - Condition:   COVID-19
  Intervention:   Diagnostic Test: Testing Done Simple SARS CoV-2 Antigen Test
  Sponsors:   Testing Done Simple;   Nao Medical Urgent Care
  Recruiting

• A Study to Evaluate EDP-235 in Non-hospitalized Adults With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: EDP-235;   Drug: Placebo
  Sponsor:   Enanta Pharmaceuticals, Inc
  Recruiting

• The LAVA (Lateral Flow Antigen Validation and Applicability) 2 Study for COVID-19 - Condition:   SARS-CoV-2 Infection
  Intervention:   Diagnostic Test: Innova Lateral Flow Test
  Sponsor:   Alder Hey Children’s NHS Foundation Trust
  Completed

• Q-POC COVID-19 Clinical Evaluation - Condition:   COVID-19
  Interventions:   Diagnostic Test: RT-PCR Test;   Diagnostic Test: Real-time PCR Test
  Sponsors:   QuantuMDx Group Ltd;   EDP Biotech;   Paragon Rx Clinical;   PathAI;   PRX Research and Development
  Not yet recruiting

• Acute Rehabilitation in Patients With COVID-19 Pneumonia - Conditions:   COVID-19;   Rehabilitation;   Physical Medicine
  Intervention:   Procedure: Acute rehabilitation program
  Sponsor:   Institut za Rehabilitaciju Sokobanjska Beograd
  Recruiting

• Study of RAY1216 Tablets Compared With Placebo in Patients With Mild to Moderate SARS-CoV-2 Infection - Condition:   Mild to Moderate COVID-19
  Interventions:   Drug: RAY1216;   Drug: Placebo
  Sponsor:   Guangdong Raynovent Biotech Co., Ltd
  Not yet recruiting

• Enhancing Protection Against Influenza and COVID-19 for Pregnant Women and Medically at Risk Children - Conditions:   Influenza;   COVID-19
  Intervention:   Behavioral: Nudge
  Sponsor:   University of Adelaide
  Recruiting

• A Trial Evaluate the Immunogenicity and Safety of Recombinant COVID-19 Omicron-Delta Variant Vaccine (CHO Cell) - Condition:   COVID-19
  Interventions:   Biological: Omicron-Delta Recombinant Novel Coronavirus Protein Vaccine (CHO cells);   Biological: Recombinant Novel Coronavirus Protein Vaccine (CHO cells)
  Sponsor:   Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.
  Recruiting

• COVID-19 Antibody Responses in Cystic Fibrosis - Conditions:   COVID-19;   Cystic Fibrosis
  Intervention:   Biological: Blood sample
  Sponsors:   Hospices Civils de Lyon;   Queen’s University, Belfast
  Recruiting

• A Phase 1, Randomised, Double-blinded, Placebo-controlled, Dose-escalation Study to Evaluate the Safety and Immunogenicity of RH109 as Booster - Condition:   COVID-19 Pandemic
  Interventions:   Biological: Lyophilized COVID-19 mRNA Vaccine;   Drug: Sodium chloride
  Sponsors:   Wuhan Recogen Biotechnology Co., Ltd.;   Shenzhen Rhegen Biotechnology Co., Ltd.;   Wuhan Rhegen Biotechnology Co., Ltd.
  Not yet recruiting

• Immunogenicity and Safety of ChulaCov19 BNA159 Vaccine as a Booster Dose in Adults - Condition:   COVID-19, SARS CoV 2 Infection
  Interventions:   Biological: ChulaCov19 BNA159 vaccine (50 mcg);   Biological: Pfizer/BNT vaccine (30 mcg)
  Sponsors:   Technovalia, Pty Ltd;   Chulalongkorn University;   BioNet-Asia;   Southern Star Research Pty Ltd.
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From PubMed

• Gastrointestinal, liver, pancreas, oral and psychological long-term symptoms of COVID-19 after recovery; A review - Due to the importance of control and prevention of COVID-19-correlated long-term symptoms, the present review article has summarized what has been currently known regarding the molecular and cellular mechanisms linking COVID-19 to important long-term complications including psychological complications, liver and gastrointestinal manifestations, oral signs as well as even diabetes. COVID-19 can directly affect the body cells through their Angiotensin-converting enzyme 2 [ACE-2] to induce…

• Pexidartinib (PLX3397) through restoring hippocampal synaptic plasticity ameliorates social isolation-induced mood disorders - Social behavior is essential for the well-being and survival of individuals. However, social isolation is a serious public health issue, especially during the COVID-19 pandemic, affecting a significant number of people worldwide, and can lead to serious psychological crises. Microglia, innate immune cells in the brain, are strongly implicated in the development of psychiatry. Although many microglial inhibitors have been used to treat depression, there is no literature report on pexidartinib…

• Discovery and mechanism of action of Thonzonium bromide from an FDA-approved drug library with potent and broad-spectrum inhibitory activity against main proteases of human coronaviruses - Although the effective drugs or vaccines have been developed to prevent the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), their efficacy may be limited for the viral evolution and immune escape. Thus, it is urgently needed to develop the novel broad-spectrum antiviral agents to control the coronavirus disease 2019 (COVID-19) global pandemic. The 3C-like protease (3CL^(pro)) is a highly conserved cysteine proteinase that plays a pivotal role in processing the viral…

• Diabetes medications and associations with Covid-19 outcomes in the N3C database: A national retrospective cohort study - CONCLUSIONS: There were clinically significant associations between metformin use and less severe COVID-19 compared to SU, but not compared to DPP4i. New-user studies and randomized trials are needed to assess early outpatient treatment and post-exposure prophylaxis with therapeutics that are safe in adults, children, pregnancy and available worldwide.

• A GABA-receptor agonist reduces pneumonitis severity, viral load, and death rate in SARS-CoV-2-infected mice - Gamma-aminobutyric acid (GABA) and GABA-receptors (GABA-Rs) form a major neurotransmitter system in the brain. GABA-Rs are also expressed by 1) cells of the innate and adaptive immune system and act to inhibit their inflammatory activities, and 2) lung epithelial cells and GABA-R agonists/potentiators have been observed to limit acute lung injuries. These biological properties suggest that GABA-R agonists may have potential for treating COVID-19. We previously reported that GABA-R agonist…

• Translation suppression underlies the restrained COVID-19 mRNA vaccine response in the high-risk immunocompromised group - CONCLUSIONS: This is the first study to demonstrate that ISs, sirolimus and mycophenolate inhibited Co-mV-induced Sp protein synthesis via translation repression. Selective use of tacrolimus or drug holiday of sirolimus can be a potential means to rescue translation-dependent Sp protein production. These findings lay a strong foundation for guiding future studies aimed at improving Co-mV responses in high-risk IC patients.

• SARS-CoV-2 modulates inflammatory responses of alveolar epithelial type II cells via PI3K/AKT pathway - CONCLUSION: The findings of our study, showed that SARS-CoV-2 S protein suppressed inflammatory responses in alveolar epithelial type II cells at early stages of infection through activation of the PI3K/AKT pathway. Thus, our results suggest that at early stages SARS-CoV-2 S protein signals inhibit immune responses to the virus allowing it to propagate the infection while in combination with TLR2 signals enhances PAI-1 expression, potentially affecting the local coagulation cascade.

• Nucleotide and nucleoside-based drugs: past, present, and future - Nucleotide and nucleoside-based analogue drugs are widely used for the treatment of both acute and chronic viral infections. These drugs inhibit viral replication due to one or more distinct mechanisms. It modifies the virus’s genetic structure by reducing viral capacity in every replication cycle. Their clinical success has shown strong effectiveness against several viruses, including ebolavirus, hepatitis C virus, HIV, MERS, SARS-Cov, and the most recent emergent SARS-Cov2. In this review,…

• User experience reevaluation and diffusion of technology in the context of compulsory usage illustrated by the example of telepsychotherapy-a literature review - CONCLUSIONS: Telepsychohtherapy has become an integral part of psychotherapeutic care. A hybrid system in close coordination between provider and patient may prevail, addressing individual needs of both parties to achieve optimal care and provider well-being. This requires transparent regulations, guidelines, and standards.

• Identification of a potent dual-function inhibitor for hIMPDH isoforms by computer-aided drug discovery approaches - Inosine monophosphate dehydrogenase (IMPDH) is a key enzyme in de novo biosynthesis of purine nucleotides. Due to this important role, it is a great target to drug discovery for a wide range of activities, especially immunosuppressant in heart and kidney transplantation. Both human IMPDH isoforms are expressed in stimulated lymphocytes. In addition to the side effects of existing drugs, previous studies have mainly focused on the type II isoform. In this study, virtual screening and…

• Herbo-mineral formulation, Divya-Swasari-Vati averts SARS-CoV-2 pseudovirus entry into human alveolar epithelial cells by interfering with spike protein-ACE 2 interaction and IL-6/TNF-α /NF-κB signaling - The herbo-mineral formulation, Divya-Swasari-Vati (DSV), is a well-known Ayurvedic medication for respiratory ailments. In a recent pre-clinical study, DSV rescued humanized zebrafish from SARS-CoV-2 S-protein-induced pathologies. This merited for an independent evaluation of DSV as a SARS-CoV-2 entry inhibitor in the human host cell and its effectiveness in ameliorating associated cytokine production. The ELISA-based protein-protein interaction study showed that DSV inhibited the interactions…

• Local Anesthetic Like Inhibition of the Cardiac Na⁺ Channel Nav1.5 by Chloroquine and Hydroxychloroquine - CONCLUSION: This study demonstrated that CQ and HCQ exert LA-typical effects on Nav1.5 involving the proposed LA binding site, thus contributing to their arrhythmogenic properties.

• XNAzymes targeting the SARS-CoV-2 genome inhibit viral infection - The unprecedented emergence and spread of SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic, underscores the need for diagnostic and therapeutic technologies that can be rapidly tailored to novel threats. Here, we show that site-specific RNA endonuclease XNAzymes - artificial catalysts composed of single-stranded synthetic xeno-nucleic acid oligonucleotides (in this case 2’-deoxy-2’-fluoro-β-D-arabino nucleic acid) - may be designed, synthesised and screened within days, enabling…

• AMPK directly phosphorylates TBK1 to integrate glucose sensing into innate immunity - Nutrient sensing and damage sensing are two fundamental processes in living organisms. While hyperglycemia is frequently linked to diabetes-related vulnerability to microbial infection, how body glucose levels affect innate immune responses to microbial invasion is not fully understood. Here, we surprisingly found that viral infection led to a rapid and dramatic decrease in blood glucose levels in rodents, leading to robust AMPK activation. AMPK, once activated, directly phosphorylates TBK1 at…

• Repositioning of anti-dengue compounds against SARS-CoV-2 as viral polyprotein processing inhibitor - A therapy for COVID-19 (Coronavirus Disease 19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) remains elusive due to the lack of an effective antiviral therapeutic molecule. The SARS-CoV-2 main protease (Mpro), which plays a vital role in the viral life cycle, is one of the most studied and validated drug targets. In Several prior studies, numerous possible chemical entities were proposed as potential Mpro inhibitors; however, most failed at various stages of drug…

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