Covid-19 Sentry

Contents

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

From Preprints

• Involvement of a serotonin/GLP-1 circuit in adolescent isolation-induced diabetes -
  In 2020, stay-at-home orders were implemented to stem the spread of SARS-CoV-2 worldwide. Social isolation can be particularly harmful to children and adolescents during the pandemic, the prevalence of obesity increased by ~37% in persons aged 2-19. Obesity is often comorbid with type 2 diabetes, which was not assessed in this human pandemic cohort. Here, we investigated whether male mice isolated throughout adolescence develop type 2 diabetes in a manner consistent with human obesity-induced diabetes, and explored neural changes that may underlie such an interaction. We find that isolating C57BL/6J mice throughout adolescence is sufficient to induce type 2 diabetes. We observed fasted hyperglycemia, diminished glucose clearance in response to an insulin tolerance test, decreased insulin signaling in skeletal muscle, decreased insulin staining of pancreatic islets, increased nociception, and diminished plasma cortisol levels compared to group-housed control mice. Using Promethion metabolic phenotyping chambers, we observed dysregulation of sleep and eating behaviors, as well as a time-dependent shift in respiratory exchange ratio of the adolescent-isolation mice. We profiled changes in neural gene transcription from several brain areas and found that a neural circuit between serotonin-producing and GLP-1-producing neurons is affected by this isolation paradigm. Overall, spatial transcription data suggest decreased serotonin neuron activity (via decreased GLP-1-mediated excitation) and increased GLP-1 neuron activity (via decreased serotonin-mediated inhibition). This circuit may represent an intersectional target to further investigate the relationship between social isolation and type 2 diabetes, as well as a pharmacologically-relevant circuit to explore the effects of serotonin and GLP-1 receptor agonists.
  🖺 Full Text HTML: Involvement of a serotonin/GLP-1 circuit in adolescent isolation-induced diabetes
• Keeping Kids Busy: Family Factors Associated with Hands-on Play and Screen Time During the COVID-19 Pandemic -
  Parent-child interactions are crucial for child development. The COVID-19 pandemic has negatively affected mental health and increased parenting challenges impacting parent-child functioning. The aim of the current study was to examine the relationship between parent factors and child activities to identify parental needs. A convenience sample of parents (N = 708), primarily mothers (n = 610; 87.4%) aged 35.59 years old (SD = 5.59; range = 21-72), with children ages 2-8 years completed an online questionnaire between April 14-June 1, 2020. Participants mostly resided in Canada and had an income of >$100,000. Parent-child activities were measured as total weekly time and combined time across activities within two categories: hands-on play and screen time. Bivariate correlations informed block-wise linear regression models. For families with childcare needs, parental anxiety was associated with higher total hands-on play (F(3,142) = 14.01, p < .001), combined hands-on play (F(2,85) = 6.82, p = .011), and combined screen time (F(2,82) = 6.25, p = .014). Families without childcare needs indicated parenting stress was associated with lower total hands-on play (F(3,212) = 7.95, p < .005) and combined hands-on play (F(2,110) = 5.67, p = .019), and higher supervised screen time (F(3,138) = 6.14, p = .014). Family structure and indices of socioeconomic status were also predictive of activities across childcare needs and child ages. To promote high-quality parent-child interactions and positive developmental outcomes in the pandemic, policy makers should support childcare needs, parent mental health and stress, and provide evidence-based guidelines for child screen time.
  🖺 Full Text HTML: Keeping Kids Busy: Family Factors Associated with Hands-on Play and Screen Time During the COVID-19 Pandemic
• Community occurrence of metapneumovirus, influenza A, and respiratory syncytial virus (RSV) inferred from wastewater solids during the winter 2022-2023 tripledemic -

  Wastewater monitoring can provide insights into respiratory disease occurrence in communities that contribute to the wastewater system. Using daily measurements of RNA of influenza A (IAV), respiratory syncytial virus (RSV), and human metapneumovirus (HMPV), as well as SARS-CoV-2 in wastewater solids from eight publicly owned treatment works in the Greater San Francisco Bay Area of California between July 2022 until early May 2023, we identify a “tripledemic” when concentrations of IAV, RSV, and SARS-CoV-2 peaked at approximately the same time. HMPV was also widely circulating. We designed novel hydrolysis probe RT-PCR assays for different IAV subtype makers to discern that the dominant circulating IAV subtype was H3N2. We show that wastewater data can be used to identify onset and offset of wastewater disease occurrence events that can provide insight into disease epidemiology and timely, localized information to inform hospital staffing and clinical decision making to respond to circulating viruses. Whereas RSV and IAV wastewater events were mostly regionally coherent, HMPV events displayed localized occurrence patterns.

  🖺 Full Text HTML: Community occurrence of metapneumovirus, influenza A, and respiratory syncytial virus (RSV) inferred from wastewater solids during the winter 2022-2023 tripledemic
• Polygenic risk of idiopathic pulmonary fibrosis and COVID-19 severity -

  Introduction. Coronavirus disease 2019 (COVID-19) survivors can develop residual lung abnormalities consistent with lung fibrosis. A shared genetic component between COVID-19 and idiopathic pulmonary fibrosis (IPF) has been shown. However, genetic overlap studies of IPF and COVID-19 have primarily concentrated on the IPF genome-wide significant risk variants that have been previously identified, rather than combined into a genome-wide polygenic risk. Here we used IPF genome-wide association study (GWAS) results to calculate polygenic risk scores (PRSs) and study their association with COVID-19 severity. Methods. We used results from the largest meta-GWAS of clinically defined IPF risk (base dataset; n=24,589) and individual-level imputed data from the SCOURGE study of patients with COVID-19 (target dataset; n=15,024). We calculated IPF PRSs using PRSice-2 and assessed their association with COVID-19 hospitalisation, severe illness, and critical illness. We also evaluated the effect of age and sex stratification. Results were validated using an independent PRS method. Enrichment analyses and pathway-specific PRSs were performed to study biological pathways associated with COVID-19 severity. Results. IPF PRSs were significantly associated with COVID-19 hospitalisation and severe illness. The strongest association was found in patients aged <60 years, especially among younger males (OR=1.16; 95%CI=1.08-1.25; p=6.39x10-5). A pathway enrichment analysis of the variants included in the best model fit and subsequent pathway-specific PRSs analyses supported the link of Cadherin and Integrin signalling pathways to COVID-19 severity when stratified by age and sex. Conclusion. Our results suggest that there is genome-wide genetic overlap between IPF and severe COVID-19 that is dependent on age and sex and adds further support that the pathogenesis of both IPF and severe COVID-19 share underlying biological mechanisms. This could imply that individuals with a high IPF genetic risk are at an overall increased risk of developing lung sequelae resulting from severe COVID-19.

  🖺 Full Text HTML: Polygenic risk of idiopathic pulmonary fibrosis and COVID-19 severity
• Association of COVID-19 vaccination with risks of hospitalization due to cardiovascular and other diseases: A study of the UK Biobank -

  Background Vaccines for COVID-19 represent a major breakthrough. However, worries about adverse effects led to vaccine hesitancy in some people. On the other hand, as COVID-19 may be associated with various sequelae, vaccination may protect against such sequelae via the prevention of infections and severe disease. Methods We leveraged the UK-Biobank (UKBB) and studied associations of at least one dose of COVID-19 vaccination (BioNTech-BNT162b2 or Oxford-AstraZeneca-ChAdOx1) with short-term hospitalizations from cardiovascular and other selected diseases(N=393,544; median follow-up=54 days among vaccinated). Multivariable Cox and Poisson regression analyses were performed. We also performed adjustments using prescription-time distribution matching (PTDM) and prior-event rate ratio (PERR). PERR minimizes unmeasured confounding by comparing event hazards before introduction of vaccination. Results We observed that COVID-19 vaccination(at least one dose), when compared to no vaccination, was associated with reduced short-term risks of hospitalizations from stroke(hazard ratio[HR]=0.178, 95% CI: 0.127-0.250, P=1.50e-23), venous thromboembolism (VTE) (HR=0.426, CI: 0.270-0.673, P=2.51e-4), dementia(HR=0.114, CI: 0.060-0.216; P=2.24e-11), non-COVID-19 pneumonia(NCP) (HR=0.108, CI: 0.080-0.145; P=2.20e-49), coronary artery disease (CAD) (HR=0.563, CI: 0.416-0.762; P=2.05e-4), chronic obstructive pulmonary disease (COPD) (HR=0.212, CI: 0.126-0.357; P=4.92e-9), type-2 diabetes (T2DM) (HR=0.216, CI: 0.096-0.486, P=2.12e-4), heart failure (HR=0.174, CI: 0.118-0.256, P=1.34e-18) and renal failure (HR=0.415, CI: 0.255- 0.677, P=4.19e-4), based on Cox regression models. Among the above results, reduced hospitalizations for stroke, heart failure, NCP and dementia were consistently observed across all analyses, including regression/PTDM/PERR. Conclusions Taken together, this study provides further support to the safety and benefits of COVID-19 vaccination, and such benefits may extend beyond reduction of infection risk or severity per se. However, causal relationship cannot be concluded and further studies are required to verify the findings.

  🖺 Full Text HTML: Association of COVID-19 vaccination with risks of hospitalization due to cardiovascular and other diseases: A study of the UK Biobank
• A comparative analysis of state-of-the-art AI-based protein folding applied to SARS-CoV-2 -
  This paper discusses the importance of identifying and understanding the Variants of Concern (VOC) of COVID-19, which are mutations of the SARS-CoV-2 virus that have the potential to increase transmission, severity of disease, or the ability to evade immune responses. Protein modeling can be used to understand the structure of SARS-CoV-2 and its components, such as the spike protein. This paper presents a comparative study between the current state-of-the-art software for protein folding by applying them to different variants of the spike protein of SARS-CoV-2 and showcasing the resulting TM-scores.
  🖺 Full Text HTML: A comparative analysis of state-of-the-art AI-based protein folding applied to SARS-CoV-2
• SARS CoV-2 Envelope protein alters calcium signaling via SERCA interactions -
  The clinical management of severe COVID-19 cases is not yet well resolved. Therefore, it is important to identify and characterize cell signaling pathways involved in virus pathogenesis that can be targeted therapeutically. Envelope (E) protein is a structural protein of the virus, which is known to be highly expressed in the infected host cell and is a key virulence factor, however, its role is poorly characterized. The E protein is a single-pass transmembrane protein that can assemble into a pentamer forming a viroporin, perturbing Ca2+ homeostasis. Because it is structurally similar to regulins such as, for example, phospholamban, that regulate the sarco/endoplasmic reticulum calcium ATPases (SERCA), we investigated whether the SARS-CoV-2 E protein affects the SERCA system as an exoregulin. Using FRET experiments we demonstrate that E protein can form oligomers with regulins, and thus can alter the monomer/multimer regulin ratio and consequently influence their interactions with SERCAs. We also confirmed that a direct interaction between E protein and SERCA2b results in a decrease in SERCA-mediated ER Ca2+ reload. Structural modeling and molecular dynamics of the complexes indicates an overlapping interaction site for E protein and endogenous regulins. Our results reveal novel links in the host-virus interaction network that play an important role in viral pathogenesis and may provide a new therapeutic target for managing severe inflammatory responses induced by SARS-CoV-2.
  🖺 Full Text HTML: SARS CoV-2 Envelope protein alters calcium signaling via SERCA interactions
• Assessment of the relationship between Google Trend search data on clinical symptoms and cases reported during the first wave of the COVID-19 outbreak in India. -

  Infodemiology and infoveillance approaches have been extensively used in recent years to support traditional epidemiology and disease surveillance. Hence, the present study aimed to explore the association between Google Trends (GTs) search of clinical symptoms and cases reported during the first wave of COVID-19. The GT data from January 30, 2020, to September 30, 2020, and daily COVID-19 cases in India and a few selected states were collected from the Ministry of Health and Family Welfare, Government of India. Correlation analysis was performed between the GT index values and the number of confirmed cases. Followed by, the COVID-19 cases were predicted using Bayesian regression and classical linear regression models. A strong association was observed between the search index of clinical symptoms and reported COVID-19 cases (cold: R=0.41, headache: R=0.46, fever: R=0.66, loss of taste: R=0.78, loss of smell R=0.86) across India. Similarly, lagged correlations were also observed (loss of smell, loss of taste, loss of taste and loss of smell, fever and headache show 3, 9, 1, 9, and 13 days lag periods respectively). Besides this, the Bayesian regression model was outperformed (MAE: 0.331164, RMSE: 0.411087) for predicting the COVID-19 cases in India and regionally than the frequentist linear regression (MAE: 0.33134, RMSE: 0.411316). The study helps health authorities better prepare and planning of health care facility timely to avoid adverse impacts.

  🖺 Full Text HTML: Assessment of the relationship between Google Trend search data on clinical symptoms and cases reported during the first wave of the COVID-19 outbreak in India.
• Neurodivergence as a risk factor for Post-Covid-19 Syndrome -

  Neurodivergent (ND) individuals (e.g., Autistic people) are more likely to experience health problems that are characterised by central sensitisation9. Recent research suggests that a so-called Long-COVID syndrome might also be explained by a heightened response to internal physiological stimuli, much like in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Using a standardised assessment tool, we examined whether traits associated with Autism would predict long-term COVID-19 symptoms in 267 Healthcare Workers (HCW).. Higher autistic traits predicted COVID-19 symptoms that lasting more than 12 weeks regardless of formal autism diagnosis. A personality measure also showed that negative affect was associated with experiencing COVID-19 symptoms for 4-12 weeks, though the direction of causality in this case is uncertain. Limitations of the present study are 1) the retrospective nature of COVID-19 symptom reporting; 2) likely self-selection bias given the high number of HCWs who reported long-term COVID-19 symptoms; and 3) the gender-bias towards females in our sample.

  🖺 Full Text HTML: Neurodivergence as a risk factor for Post-Covid-19 Syndrome
• Comparison of incidence and prognosis of myocardial injury in patients with COVID-19-related respiratory failure and other pulmonary infections: a contemporary cohort study -

  Background: Myocardial injury (MI) is frequent in critically ill patients with COVID-19, but its pathogenesis remains unclear. We hypothesized that MI is not solely due to viral infection by SARS-CoV-2, but rather due to the common pathophysiological mechanisms associated with severe pulmonary infections and respiratory failure. Methods: Contemporary and comparative cohort study designed to compare the incidence of MI in patients with acute respiratory failure caused by COVID-19 to that of patients with other pulmonary infections. In addition, we aim to investigate whether MI is a distinct risk factor for in-hospital mortality in patients with COVID-19-related respiratory failure compared to those with non-COVID-19 infections. Results: The study included 1444 patients with COVID-19 [55.5% men; age 58 (46;68) years] and 182 patients with other pulmonary infections [46.9% men; age 62 (44;73) years]. The incidence of MI at ICU admission was lower in COVID-19 patients (36.4%) compared to non-COVID-19 patients (56%), and this difference persisted after adjusting for age, sex, coronary artery disease, heart failure, SOFA score, lactate, and C-reactive protein [RR 0.84 (95% CI, 0.71-0.99)]. MI at ICU admission was associated with a 59% increase in mortality [RR 1.59 (1.36-1.86); P<0.001], and there was no significant difference in the mortality between patients with COVID-19 and those with other pulmonary infections (P=0.271). Conclusion: Myocardial injury is less frequent in patients with critical COVID-19 pneumonia and respiratory failure compared to those with other types of pneumonia. The occurrence of MI is a significant risk factor for in-hospital mortality, regardless of the etiology of the pulmonary infection.

  🖺 Full Text HTML: Comparison of incidence and prognosis of myocardial injury in patients with COVID-19-related respiratory failure and other pulmonary infections: a contemporary cohort study
• Large scale phenotyping of long COVID inflammation reveals mechanistic subtypes of disease -

  One in ten SARS-CoV-2 infections result in prolonged symptoms termed “long COVID”, yet disease phenotypes and mechanisms are poorly understood. We studied the blood proteome of 719 adults, grouped by long COVID symptoms. Elevated markers of monocytic inflammation and complement activation were associated with increased likelihood of all symptoms. Elevated IL1R2, MATN2 and COLEC12 associated with cardiorespiratory symptoms, fatigue, and anxiety/depression, while elevated MATN2 and DPP10 associated with gastrointestinal (GI) symptoms, and elevated C1QA was associated with cognitive impairment (the proteome of those with cognitive impairment and GI symptoms being most distinct). Markers of neuroinflammation distinguished cognitive impairment whilst elevated SCG3, indicative of brain-gut axis disturbance, distinguished those with GI symptoms. Women had a higher incidence of long COVID and higher inflammatory markers. Symptoms did not associate with respiratory inflammation or persistent virus in sputum. Thus, persistent inflammation is evident in long COVID, distinct profiles being associated with specific symptoms.

  🖺 Full Text HTML: Large scale phenotyping of long COVID inflammation reveals mechanistic subtypes of disease
• Start Smart, Then Focus: Antimicrobial Stewardship Practice at One NHS Foundation Trust in England Before and During the COVID-19 Pandemic -

  Background Antimicrobial Resistance (AMR), a major global public health threat causing 1.2 million deaths, calls for immediate action. Antimicrobial stewardship (AMS) promotes judicious antibiotic use, but the COVID-19 pandemic increased AMR by 15%. Our study evaluated AMS implementation and inappropriate antibiotic prescribing before-the-pandemic (PD) and during-the-pandemic (DP). Methods This retrospective study examined medical records of adult patients (age 25 and above) admitted to an NHS Foundation Trust in England for respiratory tract infections (RTIs) or pneumonia in 2019 and 2020. Our objective was to evaluate antibiotic prescribing practices BP and DP in 2019 and 2020. Primary outcomes included evaluating the prevalence of inappropriate antibiotic prescribing and assessing the implementation of AMS using Public Health England9s 9Start Smart, Then Focus9 (SSTF) toolkit. Reliable data extraction was ensured by two independent reviewers using a validated data extraction tool. Results A total of 640 patient records (320 from 2019 and 320 from 2020) were analysed. The mean age of enrolled adults was 74.3 years in 2019 and 76.2 years in 2020. COVID pneumonia showed a significantly higher odds ratio (OR) of 20.24 (95% CI 5.82 to 128.19, p-value<0.001). Inappropriate antibiotic prescribing, as per local guidelines, increased from 36% in 2019 to 64% in 2020 for the second course of antibiotics DP. Differences were observed in AMS interventions, with an OR of 3.36 (95% CI 1.30-9.25, p=0.015) for 9Continue Antibiotics9 and an OR of 2.77 (95% CI 1.37-5.70, p=0.005) for 9De-escalation9. Conclusion The COVID-19 pandemic significantly impacted antibiotic prescribing, increasing inappropriate use and posing risks of antimicrobial resistance. Factors influencing prescribing practices must be considered, and proactive measures, including updating the SSTF toolkit and developing an AMS roadmap, are needed to address the challenges of AMR in the context of evolving infectious diseases.

  🖺 Full Text HTML: Start Smart, Then Focus: Antimicrobial Stewardship Practice at One NHS Foundation Trust in England Before and During the COVID-19 Pandemic
• SARS-CoV-2 Nonstructural Proteins 3 and 4 tune the Unfolded Protein Response -
  Coronaviruses (CoV), including SARS-CoV-2, modulate host proteostasis through activation of stress-responsive signaling pathways such as the Unfolded Protein Response (UPR), which remedies misfolded protein accumulation by attenuating translation and increasing protein folding capacity. While CoV nonstructural proteins (nsps) are essential for infection, little is known about the role of nsps in modulating the UPR. We characterized the impact of SARS-CoV-2 nsp4, a key driver of replication, on the UPR using quantitative proteomics to sensitively detect pathway-wide upregulation of effector proteins. We find nsp4 preferentially activates the ATF6 and PERK branches of the UPR. Previously, we found an N-terminal truncation of nsp3 (nsp3.1) can suppress pharmacological ATF6 activation. To determine how nsp3.1 and nsp4 tune the UPR, their co-expression demonstrated that nsp3.1 suppresses nsp4-mediated PERK, but not ATF6 activation. Re-analysis of SARS-CoV-2 infection proteomics data revealed time-dependent activation of PERK targets early in infection, which subsequently fades. This temporal regulation suggests a role for nsp3 and nsp4 in tuning the PERK pathway to attenuate host translation beneficial for viral replication while avoiding later apoptotic signaling caused by chronic activation. This work furthers our understanding of CoV-host proteostasis interactions and highlights the power of proteomic methods for systems-level analysis of the UPR.
  🖺 Full Text HTML: SARS-CoV-2 Nonstructural Proteins 3 and 4 tune the Unfolded Protein Response
• Low Dose Naltrexone use for the management of post acute sequelae of COVID 19 -

  Post-Acute Sequelae of SARS-CoV-2 (PASC), also known as Long COVID, is globally estimated to have affected up to 40-50% of individuals who were infected with SARS-CoV-2. The causes of PASC are being investigated, and there are no established therapies. One of the leading hypotheses for the cause of PASC is the persistent activation of innate immune cells with increased systemic inflammation. Naltrexone is a medication with anti-inflammatory and immunomodulatory properties that has been used in other conditions that overlap with PASC. In this study we performed retrospective review of a clinical cohort of 59 patients at a single academic center who received low-dose naltrexone (LDN) off-label as a potential therapeutic intervention for PASC. The use of LDN was associated with improved clinical symptoms (fatigue, brain fog, post exertional malaise/PEM, unrefreshing sleep, sleep pattern, and headache), fewer number of symptoms, and better functional status. This observational finding warrants further testing in rigorous, randomized, placebo-controlled clinical trials.

  🖺 Full Text HTML: Low Dose Naltrexone use for the management of post acute sequelae of COVID 19
• Global seasonal activities of respiratory syncytial virus before the COVID-19 pandemic: a systematic review -

  Background: Varied seasonal patterns of respiratory syncytial virus (RSV) have been reported worldwide. We aimed to review the patterns of RSV activity globally before the COVID-19 pandemic and to explore factors potentially associated with RSV seasonality. Methods: We conducted a systematic review on articles identified in PubMed reporting RSV seasonality based on data collected before 1 January 2020. Information on the timing of the start, peak, and end of an RSV season, study location, study period, and details in study methods were extracted. RSV seasonal patterns were examined by geographic location, calendar month, analytic method and meteorological factors including temperature and absolute humidity. Correlation and regression analyses were conducted to explore the relationship between RSV seasonality and study methods and characteristics of study locations. Results: RSV seasons were reported in 209 articles published in 1973-2023 for 317 locations in 77 countries. Variations were identified in types of data, data collection and analytical methods across the studies. Regular RSV seasons were similarly reported in countries in temperate regions, with highly variable seasons identified in subtropical and tropical countries. Durations of RSV seasons were relatively longer in subtropical and tropical regions than from temperate regions. Longer durations of RSV seasons were associated with a higher daily average mean temperature and daily average mean absolute humidity. Conclusions: The global seasonal patterns of RSV provided important information for optimizing interventions against RSV infection. Heterogeneity in study methods highlighted the importance of developing and applying standardized approaches in RSV surveillance and data reporting.

  🖺 Full Text HTML: Global seasonal activities of respiratory syncytial virus before the COVID-19 pandemic: a systematic review

From Clinical Trials

• Extracorporeal Photopheresis as a Possible Therapeutic Approach to Adults With Severe and Critical COVID-19 - Condition:   COVID-19
  Intervention:   Procedure: Extracorporeal photopheresis
  Sponsor:   Del-Pest Central Hospital - National Institute of Hematology and Infectious Diseases
  Recruiting

• A Clinical Trial on Booster Immunization of Two COVID-19 Vaccines Constructed From Different Technical Routes - Condition:   COVID-19
  Interventions:   Biological: Prototype and Omicron BA.4/5 Bivalent Recombinant COVID-19 Vaccine(Adenovirus Type 5 Vector) For Inhalation;   Biological: Bivalent COVID-19 mRNA Vaccine;   Biological: Recombinant COVID-19 Vaccine (Adenovirus Type 5 Vector) For Inhalation
  Sponsors:   Zhongnan Hospital;   Institute of Biotechnology, Academy of Military Medical Sciences, PLA of China
  Recruiting

• Community-engaged Optimization of COVID-19 Rapid Evaluation And TEsting Experiences - Conditions:   COVID-19;   COVID-19 Pandemic
  Interventions:   Behavioral: COVID-19 walk-up, on-site testing strategy;   Behavioral: Community Health Worker (CHW) leading testing navigation and general preventive care reminders;   Behavioral: No-cost self-testing kit vending machines
  Sponsors:   University of California, San Diego;   San Ysidro Health Center
  Not yet recruiting

• Safety Study of COVID19 Vaccine on the Market - Condition:   COVID-19
  Intervention:   Biological: Recombinant new coronavirus vaccine (CHO cell)
  Sponsors:   Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.;   Hunan Provincial Center for Disease Control and Prevention;   Guizhou Center for Disease Control and Prevention;   Hainan Center for Disease Control & Prevention
  Recruiting

• ACTIV-6: COVID-19 Study of Repurposed Medications - Arm F (Montelukast) - Condition:   Covid19
  Interventions:   Other: Placebo;   Drug: Montelukast
  Sponsors:   Susanna Naggie, MD;   National Center for Advancing Translational Sciences (NCATS);   Vanderbilt University Medical Center
  Recruiting

• ACTIV-6: COVID-19 Study of Repurposed Medications - Arm B (Fluvoxamine) - Condition:   Covid19
  Interventions:   Drug: Fluvoxamine;   Other: Placebo
  Sponsors:   Susanna Naggie, MD;   National Center for Advancing Translational Sciences (NCATS);   Vanderbilt University Medical Center
  Completed

• ACTIV-6: COVID-19 Study of Repurposed Medications - Arm D (Ivermectin 600) - Condition:   Covid19
  Interventions:   Drug: Ivermectin;   Other: Placebo
  Sponsors:   Susanna Naggie, MD;   National Center for Advancing Translational Sciences (NCATS);   Vanderbilt University Medical Center
  Completed

• ACTIV-6: COVID-19 Study of Repurposed Medications - Arm E (Fluvoxamine 100) - Condition:   Covid19
  Interventions:   Drug: Fluvoxamine;   Other: Placebo
  Sponsors:   Susanna Naggie, MD;   National Center for Advancing Translational Sciences (NCATS);   Vanderbilt University Medical Center
  Completed

• Evaluation of Home Use COVID-19 Frequent Antigen Testing and Data Reporting - Condition:   COVID-19 Respiratory Infection
  Intervention:   Diagnostic Test: SARS CoV-2 antigen tests
  Sponsors:   IDX20 Inc;   National Institute on Minority Health and Health Disparities (NIMHD)
  Recruiting

• Mitoquinone/Mitoquinol Mesylate as Oral and Safe Postexposure Prophylaxis for Covid-19 - Conditions:   SARS-CoV Infection;   COVID-19
  Interventions:   Drug: Mitoquinone/mitoquinol mesylate;   Other: Placebo
  Sponsor:   University of Texas Southwestern Medical Center
  Not yet recruiting

• Pycnogenol® in Post-COVID-19 Condition - Conditions:   Post COVID-19 Condition;   Long COVID
  Interventions:   Drug: Pycnogenol®;   Drug: Placebo
  Sponsor:   University of Zurich
  Recruiting

• Efficacy of Bailing Capsule on Pulmonary Fibrosis After COVID-19 - Conditions:   Pulmonary Fibrosis;   COVID-19 Pneumonia
  Intervention:   Drug: Bailing capsule
  Sponsor:   Second Affiliated Hospital, School of Medicine, Zhejiang University
  Not yet recruiting

• Evaluating Emetine for Viral Outbreaks (EVOLVE) - Condition:   COVID-19
  Interventions:   Drug: Emetine Hydrochloride;   Drug: Placebo
  Sponsors:   Johns Hopkins University;   Nepal Health Research Council;   Bharatpur Hospital Chitwan;   Stony Brook University;   Rutgers University
  Not yet recruiting

• Cupping Therapy on Immune System in Post Covid -19 - Condition:   Covid-19 Patients
  Interventions:   Combination Product: Cupping therapy with convential medical treatment;   Drug: Convential medical treatment
  Sponsor:   Cairo University
  Completed

• To Evaluate the Immunogenicity and Safety of Sequential Booster Immunization of Recombinant Novel Coronavirus Vaccine (CHO Cells) for SARS-CoV-2 - Condition:   COVID-19
  Intervention:   Biological: Recombinant Novel Coronavirus vaccine (CHO Cells)
  Sponsor:   Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.
  Completed

From PubMed

• Synthesis, Characterization, and Antibacterial Activity of New Isatin Derivatives - 1H-indol-2,3-dione (isatin) class of biologically active compounds have analgesic, anti-microbial, anti-inflammatory, anti-tubercular, anti-proliferative properties, and is also useful for the treatment of SARS-CoV. Schiff bases containing isatin moiety are known to have broad spectrum of biological activities like anti-viral, anti-tubercular, anti-fungal, and anti-bacterial. In this work, several Schiff base derivatives have been synthesized using two methods (synthetic and microwave) by…

• Mercapto-pyrimidines are reversible covalent inhibitors of the papain-like protease (PLpro) and inhibit SARS-CoV-2 (SCoV-2) replication - The papain-like protease (PLpro) plays a critical role in SARS-CoV-2 (SCoV-2) pathogenesis and is essential for viral replication and for allowing the virus to evade the host immune response. Inhibitors of PLpro have great therapeutic potential, however, developing them has been challenging due to PLpro’s restricted substrate binding pocket. In this report, we screened a 115 000-compound library for PLpro inhibitors and identified a new pharmacophore, based on a mercapto-pyrimidine fragment that…

• Sulfated Glycomimetic α-Helical Polypeptides for Antiviral Activity - In this work, we developed a library of sulfated glycomimetic polypeptides with a high sulfated degree (up to 99%) via a click reaction and sulfation modification, enabling control over the helicity, molecular weight, rigidity, and side-chain structure. Their potentials as the inhibitors of SARS-CoV-2 and common enterovirus were investigated, and the structure-activity relationship was explored in detail. The in vitro results revealed the crucial role of α-helical conformation and sulfated sugar…

• Stakeholder perspectives and experiences of the implementation of remote mental health consultations during the COVID-19 pandemic: a qualitative study - CONCLUSIONS: Remote mental health consultations were welcomed as a means to continue care during the COVID-19 pandemic. Their swift and necessary adoption placed pressure on providers and organisations to adapt quickly, navigating challenges and adjusting to a new way of working. This implementation created changes to workflows and dynamics that disrupted the traditional method of mental health care delivery. Further consideration of the importance of the therapeutic relationship and fostering…

• AEROSOLIZED SULFATED HYALURONAN DERIVATIVES PROLONG THE SURVIVAL OF K18 ACE2 MICE INFECTED WITH A LETHAL DOSE OF SARS-COV-2 - Despite several vaccines that are currently approved for human use to control the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is an urgent medical need for therapeutic and prophylactic options. SARS-CoV-2 binding and entry in human cells involves interactions of its spike (S) protein with several host cell surface factors, including heparan sulfate proteoglycans (HSPGs), transmembrane protease serine 2 (TMPRSS2), and angiotensin-converting enzyme 2…

• β-Cyclodextrins as affordable antivirals to treat coronavirus infection - The SARS-CoV-2 pandemic made evident that there are only a few drugs against coronavirus. Here we aimed to identify a cost-effective antiviral with broad spectrum activity and high safety profile. Starting from a list of 116 drug candidates, we used molecular modelling tools to rank the 44 most promising inhibitors. Next, we tested their efficacy as antivirals against α and β coronaviruses, such as the HCoV-229E and SARS-CoV-2 variants. Four drugs, OSW-1, U18666A, hydroxypropyl-β-cyclodextrin…

• Novel SARS-CoV-2 entry inhibitors, 2-anilinoquinazolin-4(3H)-one derivatives, show potency as SARS-CoV-2 antivirals in a human ACE2 transgenic mouse model - The ongoing COVID-19 has not only caused millions of deaths worldwide, but it has also led to economic recession and the collapse of public health systems. The vaccines and antivirals developed in response to the pandemic have improved the situation markedly; however, the pandemic is still not under control with recurring surges. Thus, it is still necessary to develop therapeutic agents. In our previous studies, we designed and synthesized a series of novel 2-anilinoquinazolin-4(3H)-one…

• Antibody responses to mRNA versus non-mRNA COVID vaccines among the Mongolian population - CONCLUSIONS: The BNT162b2 vaccine showed the highest level of antibody against SARS-CoV-2, followed by the BBIBP-CorV, Gam-COVID-Vac, and ChAdOx1 n-CoV-19 vaccines. The level of antibodies was increased in people infected with SARS-CoV-2 after vaccination, as compared to uninfected but vaccinated individuals.

• Inhibiting C5 in patients with severe COVID-19-the incorrect target? - Authors’ reply - No abstract

• Inhibiting C5 in patients with severe COVID-19-the incorrect target? - No abstract

• Pharmacological properties and derivatives of saikosaponins-a review of recent studies - CONCLUSIONS: An increasing amount of data have indicated diverse SS pharmacological properties, indicating crucial clues for future studies and the production of novel saikosaponin-based anti-inflammatory, efficacious anticancer, and anti-novel-coronavirus agents with improved efficacy and reduced toxicity.

• Applications of advances in mRNA-based platforms as therapeutics and diagnostics in reproductive technologies - The recent COVID-19 pandemic led to many drastic changes in not only society, law, economics, but also in science and medicine, marking for the first time when drug regulatory authorities cleared for use mRNA-based vaccines in the fight against this outbreak. However, while indeed representing a novel application of such technology in the context of vaccination medicine, introducing RNA into cells to produce resultant molecules (proteins, antibodies, etc.) is not a novel principle. It has been…

• Biotransformation and brain distribution of the anti-COVID-19 drug molnupiravir and herb-drug pharmacokinetic interactions between the herbal extract Scutellaria formula-NRICM101 - The aim of this study was to explore the effects of herbal drug pharmacokinetic interactions on the biotransformation of molnupiravir and its metabolite β-D-N4-hydroxycytidine (NHC) in the blood and brain. To investigate the biotransformation mechanism, a carboxylesterase inhibitor, bis(4-nitrophenyl)phosphate (BNPP), was administered. Not only molnupiravir but also the herbal medicine Scutellaria formula-NRICM101 is potentially affected by coadministration with molnupiravir. However, the…

• Dicoumarol is an effective post-exposure prophylactic for SARS-CoV-2 Omicron infection in human airway epithelium - Repurposing existing drugs to inhibit SARS-CoV-2 infection in airway epithelial cells (AECs) is a quick way to find novel treatments for COVID-19. Computational screening has found dicoumarol (DCM), a natural anticoagulant, to be a potential SARS-CoV-2 inhibitor, but its inhibitory effects and possible working mechanisms remain unknown. Using air-liquid interface culture of primary human AECs, we demonstrated that DCM has potent antiviral activity against the infection of multiple Omicron…

• Binding properties of selective inhibitors of P323L mutated RdRp of SARS-CoV-2: a combined molecular screening, docking and dynamics simulation study - Since 2019 the SARS-CoV-2 and its variants caused COVID-19, such incidents brought the world in pandemic situation. This happened due to furious mutations in SARS-CoV-2, in which some variants had high transmissibility and infective, this led the virus emerged as virulent and worsened the COVID-19 situation. Among the variants, P323L is one of the important mutants of RdRp in SARS-CoV-2. To inhibit the erroneous function of this mutated RdRp, we have screened 943 molecules against the P323L…

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