Covid-19 Sentry

Contents

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

From Preprints

• SIRT-1 is required for release of enveloped picornaviruses -
  Enterovirus D68 is a re-emerging enterovirus that causes acute respiratory illness in infants and has recently been linked to Acute Flaccid Myelitis. Here, we show that the histone deacetylase, SIRT-1, is essential for autophagy and EV-D68 infection. Knockdown of SIRT-1 blocks autophagy and reduces EV-D68 extracellular titers. The proviral activity of SIRT-1 does not require its deacetylase activity or functional autophagy. SIRT-1’s proviral activity is, we demonstrate, mediated through the repression of ER stress. Inducing ER stress through thapsigargin treatment or SERCA2A knockdown in SIRT-1 knockdown cells had no additional effect on EV-D68 extracellular titers. Knockdown of SIRT-1 also decreases poliovirus and SARS-CoV-2 titers but not coxsackievirus B3. In non-lytic conditions, EV-D68 is primarily released in an enveloped form, and SIRT-1 is required for this process. Our data show that SIRT-1, through its translocation to the cytosol, is critical to promote the release of enveloped EV-D68 viral particles.
  🖺 Full Text HTML: SIRT-1 is required for release of enveloped picornaviruses
• The Online Customer Decision-Making Styles as Marketing Innovation Strategies for the New Normal -
  Purpose. This research contributed to the customer decision-making style (CDMS) theory in the online framework (eCDMS) to unravel new orientations and segmentation to generate marketing innovation strategies for the new normal firms. Methodology. It is based on a literature review designing a model and questionnaire applied to 400 Mexican online customers (May-Aug, 2021). The dataset is analyzed under Covariance-Based Structural Equation Modelling (CB-SEM), Cluster Analysis, and one-way-ANOVA multivariate methods. Findings and Originality. The obtention of an empirical model with 9 factors, 24 indicators as new online customer decision-making styles orientations (eCDMS orientation), being quality, brand, and customer experience the most relevant. Besides, we obtained four new online customer groups (eCDMS Segmentation) that we called: marketing followers, price searchers, convenience shoppers, ethics& reputation keepers. The originality is based on a framework proposal about the discussion of new online consumers after the COVID-19 pandemic as the first insights to conform to an online customer decision-making style (eCDMS) theory.
  🖺 Full Text HTML: The Online Customer Decision-Making Styles as Marketing Innovation Strategies for the New Normal
• ATG5 suppresses type I IFN-dependent neutrophil swarming and NETosis -
  Inflammation is critical for controlling infections, but when left unchecked can cause tissue damage and disease. For tuberculosis, the leading cause of death due to infection, host inflammation is responsible for the clinical symptoms, morbidity, and mortality. Specifically, neutrophil-dominated inflammation is associated with tuberculosis disease progression. Therefore, understanding how neutrophil functions are regulated during infection is important for developing ways to prevent disease. Atg5 was the first gene shown to specifically function within neutrophils to promote control of Mycobacterium tuberculosis, the causative agent of tuberculosis. ATG5 is best studied for its role in autophagy, however, the protective activity of ATG5 in neutrophils was unexpectedly independent of other autophagy proteins and remained elusive. We report here that ATG5, but not other autophagy proteins, is required in neutrophils to suppress neutrophil NETosis and swarming that occur due to elevated type I interferon levels during M. tuberculosis infection. The elevated level of NETosis that results from loss of ATG5 expression contributes to the early susceptibility of Atg5fl/fl-LysM-Cre mice during M. tuberculosis infection. NETosis is associated with poor disease outcomes in tuberculosis and COVID-19 patients, as well as during other inflammatory diseases in humans. Our studies identify an essential regulator of NETosis and elucidate previously unappreciated roles for ATG5 during infection, which may inform the design of host-directed therapeutics modulating these pathways.
  🖺 Full Text HTML: ATG5 suppresses type I IFN-dependent neutrophil swarming and NETosis
• Risk factors for SARS-CoV-2 infection: A test-negative case-control study with additional population controls -

  ABSTRACT Objectives: To assess risk factors for SARS-CoV-2 infection by first comparing positive cases with negative controls as determined by polymerase chain reaction (PCR) testing and then comparing these two groups with an additional population control group. Design and setting: Test-negative design (TND), multicentre case-control study with additional population controls in South Eastern Norway. Participants: Adults who underwent SARS-CoV-2 PCR testing between February and December 2020. PCR-positive cases, PCR-negative controls, and additional age-matched population controls. Primary outcome measures: The associations between various risk factors based on self- reported questionnaire and SARS-CoV-2 infection comparing PCR positive cases and PCR- negative controls. Using subgroup analysis, the risk factors were then compared with a population control group. Univariate and multivariate regression analyses were performed. Results: In total, 400 SARS-CoV-2 PCR-positive cases, 719 PCR-negative controls, and 14,509 population controls were included. Male sex was associated with the risk of SARS- CoV-2 infection when PCR-positive cases were compared with PCR-negative controls (OR 1.9, 95% CI 1.4 to 2.6). Age, education level, comorbidities (asthma, diabetes, hypertension), an exercise were not associated with the risk of SARS-CoV-2 infection when PCR-positive cases were compared with PCR-negative controls. In the subgroup analysis comparing PCR- positive cases with age-matched population controls, asthma was associated with the risk of SARS-CoV-2 infection (OR 1.6, 95% CI 1.1 to 2.1). Daily or occasional smoking was negatively associated with the risk of SARS-CoV-2 infection in both analyses (OR 0.5, 95% CI 0.3 to 0.8 and OR 0.55, 95% CI 0.35, to 0.82, respectively). Conclusions: Male sex was a possible risk factor, whereas smoking was negatively associated with the risk of SARS-CoV-2 infection, when comparing PCR-positive cases and PCR- negative controls. Asthma was associated with the risk of SARS-CoV-2 infection when PCR- positive cases were compared with population controls.

  🖺 Full Text HTML: Risk factors for SARS-CoV-2 infection: A test-negative case-control study with additional population controls
• Genomic surveillance reveals dynamic shifts in the connectivity of COVID-19 epidemics -

  The maturation of genomic surveillance in the past decade has enabled tracking of the emergence and spread of epidemics at an unprecedented level. During the COVID-19 pandemic, for example, genomic data revealed that local epidemics varied considerably in the frequency of SARS-CoV-2 lineage importation and persistence, likely due to a combination of COVID-19 restrictions and changing connectivity. Here, we show that local COVID-19 epidemics are driven by regional transmission, including across international boundaries, but can become increasingly connected to distant locations following the relaxation of public health interventions. By integrating genomic, mobility, and epidemiological data, we find abundant transmission occurring between both adjacent and distant locations, supported by dynamic mobility patterns. We find that changing connectivity significantly influences local COVID-19 incidence. Our findings demonstrate a complex meaning of 9local9 when investigating connected epidemics and emphasize the importance of collaborative interventions for pandemic prevention and mitigation.

  🖺 Full Text HTML: Genomic surveillance reveals dynamic shifts in the connectivity of COVID-19 epidemics
• The effects of COVID-19 on cognitive performance in a community-based cohort: A COVID Symptom Study Biobank observational study -

  Background Cognitive impairment has been reported after many types of infection, including SARS-CoV-2. Whether deficits following SARS-CoV-2 improve over time is unclear. Studies to date have focused on hospitalised individuals with up to a year follow-up. The presence, magnitude, persistence and correlations of effects in community-based cases remain relatively unexplored. Methods Cognitive performance (working memory, attention, reasoning, motor control) was assessed in participants of a voluntary biobank in July, 2021 (Round 1), and April, 2022 (Round 2). Participants, drawn from the COVID Symptom Study smartphone app, comprised individuals with and without SARS-CoV-2 infection and varying symptom duration. Effects of COVID-19 exposures on cognitive accuracy and reaction time scores were estimated using multivariable ordinary least squares linear regression models weighted for inverse probability of participation, adjusting for potential confounders and mediators. The role of ongoing symptoms after COVID-19 infection was examined stratifying for self-perceived recovery. Longitudinal analysis assessed change in cognitive performance between rounds. Findings 3335 individuals completed Round 1, of whom 1768 also completed Round 2. At Round 1, individuals with previous positive SARS-CoV-2 tests had lower cognitive accuracy (N = 1737, β = -0.14 standard deviations, SDs) than negative controls. Deficits were largest for positive individuals with ≥ 12 weeks of symptoms (N = 495, β = -0.22 SDs). Effects were comparable to hospital presentation during illness (N = 281, β = -0.31 SDs), and 10 years age difference (60-70 years vs. 50-60 years, β = -0.21 SDs) in the whole study population. Stratification by self-reported recovery revealed that deficits were only detectable in SARS-CoV-2 positive individuals who did not feel recovered from COVID-19, whereas individuals who reported full recovery showed no deficits. Longitudinal analysis showed no evidence of cognitive change over time, suggesting that cognitive deficits for affected individuals persisted at almost 2 years since initial infection. Interpretation Cognitive deficits following SARS-CoV-2 infection were detectable nearly two years post infection, and largest for individuals with longer symptom durations, ongoing symptoms, and/or more severe infection. However, no such deficits were detected in individuals who reported full recovery from COVID-19. Further work is needed to monitor and develop understanding of recovery mechanisms for those with ongoing symptoms. Funding Chronic Disease Research Foundation, Wellcome Trust, National Institute for Health and Care Research, Medical Research Council, British Heart Foundation, Alzheimer9s Society, European Union, COVID-19 Driver Relief Fund, French National Research Agency.

  🖺 Full Text HTML: The effects of COVID-19 on cognitive performance in a community-based cohort: A COVID Symptom Study Biobank observational study
• Remote work as a new dimension of polarisation: Individual and contextual determinants of the relationship between working from home and job quality -
  This chapter provides an empirical overview of the extent and distribution of working from home across EU member states and the changes due to its sharp rise following the start of the Covid-19 pandemic. The chapter describes working from a home as an increasingly important dimension in the way new digital technologies reinforce inequalities among already existing lines. Neither the possibility to move tasks remotely nor the probability of being offered the option by your employer are equally distributed. Unfortunately, they tend to be higher for those already doing better on the labour market: those in digitally advanced sectors and larger firms, those with higher skills and doing more abstract and complex tasks, and those on standard employment contracts. On top of this unevenness in access, working from home itself also carries benefits that may increase productivity and wages. Both through access and benefits a rise in working from home then risks widening the polarisation on the labour market. This chapter shows that indeed, remote work growth mainly benefited those more advantaged on the labour market, and is itself associated with better working conditions and higher wages, although also with higher working hours. Importantly, there is substantial variation in how unequally telework grows between sectors and countries. Digital intensity increases this polarisation by working from home further, while stronger worker representation through greater union density can curtail some of this inequality.
  🖺 Full Text HTML: Remote work as a new dimension of polarisation: Individual and contextual determinants of the relationship between working from home and job quality
• Effect of Andrographis paniculata treatment for patients with early-stage COVID-19 on the prevention of pneumonia: A retrospective cohort study -

  There is a need for safe and cost-effective treatments for COVID-19. Andrographis paniculata (AP) is an herbal plant that has been used for centuries to treat upper respiratory tract infections. Andrographolide is the major active component of AP that inhibits intracellular SARS-CoV-2 replication and has anti-inflammatory action. We performed a retrospective cohort study to evaluate the therapeutic and adverse effects of oral AP-products on COVID-19 by using the risk of pneumonia diagnosed by chest radiography as an indicator. This study included patients 15 to 60 years of age with laboratory-confirmed early-stage (asymptomatic or mild) COVID-19 without comorbidities at seven hospitals in three adjacent provinces in Thailand, between December 2020 and March 2021. Patients were treated for five days with either AP-extract (60 mg andrographolide, 3 times daily) or crude-AP (48 mg andrographolide, 3 times daily), when available. Patient information was prospectively recorded in the structured medical records and retrospectively reviewed. All eligible patients who received AP-treatment were included and control patients who did not receive AP-treatment were randomly selected using a ratio of approximately 1:1. Pneumonia occurred in 1/243 AP-treatment patients and 69/285 control patients. The risks of pneumonia after adjusting for confounding effects were 0.3% (95%CI, 0%-0.9%) and 24.3% (95%CI, 19.0%-29.7%) in the AP-treatment and control groups, respectively. The number needed to treat to avoid pneumonia development in one patient was four (95% CI, 3-5). Eight patients developed mild adverse events. AP-treatment regimens are acceptably safe and associated with highly reduced rates of pneumonia for patients with early-stage COVID-19.

  🖺 Full Text HTML: Effect of Andrographis paniculata treatment for patients with early-stage COVID-19 on the prevention of pneumonia: A retrospective cohort study
• Protection against symptomatic SARS-CoV-2 BA.5 infection conferred by the Pfizer-BioNTech Original/BA.4-5 bivalent vaccine compared to the mRNA Original (ancestral) monovalent vaccines - a matched cohort study in France -

  This cohort study aimed to evaluate the protection against symptomatic SARS-CoV-2 infection conferred by the Pfizer-BioNTech Original/BA.4-5 bivalent vaccine compared to mRNA Original (ancestral) monovalent vaccines. Individuals of ≥60 years old who received a booster dose between 03/10/2022 and 06/11/2022, when both the bivalent and monovalent vaccines were used in France, were included. Individuals who received a booster dose with (1) a monovalent Original mRNA vaccine (Pfizer- BioNTech or Moderna) or (2) the bivalent Pfizer-BioNTech Original/BA.4-5 vaccine were  matched. The outcome of interest was a positive SARS-CoV-2 RT-PCR or antigenic test associated to self-reported symptoms, at least seven days after receiving the booster dose. Data were analysed with a Cox Proportional-Hazards model adjusted for the presence of previous infection, age, sex, and the presence of medium risk comorbidities. A total of 136 852 individuals were included and followed for a median period of 77 days. The bivalent vaccine conferred an additional protection of 8% [95% CI: 0% - 16%, p=0.045] against symptomatic SARS-CoV-2 infection compared to the monovalent vaccines.

  🖺 Full Text HTML: Protection against symptomatic SARS-CoV-2 BA.5 infection conferred by the Pfizer-BioNTech Original/BA.4-5 bivalent vaccine compared to the mRNA Original (ancestral) monovalent vaccines - a matched cohort study in France
• Demographic and co-morbidity characteristics of patients tested for SARS-CoV-2 from March 2020 to January 2022 in a national clinical research network: results from PCORnet® -

  Background Prior studies have documented differences in the age, racial, and ethnic characteristics among patients with SARS-CoV-2 infection. However, little is known about how these characteristics changed over time during the pandemic and whether racial, ethnic, and age disparities evident early in the pandemic were persistent over time. This study reports on trends in SARS-CoV-2 infections among U.S. adults from March 1, 2020 to January, 31 2022, using data from electronic health records. Methods and Findings We captured repeated cross-sectional information from 43 large healthcare systems in 52 U.S. States and territories, participating in PCORnet®, the National Patient-Centered Clinical Research Network. Using distributed queries executed at each participating institution, we acquired information for all patients ≥ 20 years of age who were tested for SARS-CoV-2 (both positive and negative results), including care setting, age, sex, race, and ethnicity by month as well as comorbidities (assessed with diagnostic codes). During this time period, 1,325,563 patients had positive (13% inpatient) and 6,705,868 patients had negative (25% inpatient) viral tests for SARS-CoV-2. Disparities in testing positive were present across racial and ethnic groups, especially in the inpatient setting. Compared to White patients, Black or African American and other race patients had relative risks for testing positive of 1.5 or greater in the inpatient setting for 12 of the 23-month study period. Compared to nonHispanic patients, Hispanic patients had relative risks for testing positive in the inpatient setting of 1.5 or greater for 16 of 23. Ethnic and racial differences were present in emergency department and ambulatory settings but were less common across time than in inpatient settings. Trends in infections by age group demonstrated higher test positivity for older patients in the inpatient setting only for most months, except for June and July of 2020, April to August 2021, and January 2022. Comorbidities were common, with much higher rates among those hospitalized; hypertension (38% of patients SARS-CoV-2 positive vs. 29% for those negative) and type 2 diabetes mellitus (22% vs. 13%) were the most common. Conclusion and Relevance Racial and ethnic disparities changed over time among persons infected with SARS-CoV-2. These trends highlight potential underlying mechanisms, such as poor access to care and differential vaccination rates, that may have contributed to greater disparities, especially early in the pandemic. Monitoring data on characteristics of patients testing positive in real time could allow public health officials and policymakers to tailor interventions to ensure that patients and communities most in need are receiving adequate testing, mitigation strategies, and treatment.

  🖺 Full Text HTML: Demographic and co-morbidity characteristics of patients tested for SARS-CoV-2 from March 2020 to January 2022 in a national clinical research network: results from PCORnet®
• Chest CT findings and outcomes of COVID-19 in second wave: A cross-sectional study in a tertiary care centre in Northern India -

  Introduction: The COVID19 pandemic has posed a serious threat to global health, with developing nations like India being amongst the worst affected. Chest CT scans play a pivotal role in the diagnosis and evaluation of COVID19, and certain CT features may aid in predicting the prognosis of COVID19 illness. Methods: This was a single center, hospital based, cross sectional study conducted at a tertiary care center in Northern India during the second wave of the COVID19 pandemic from May June 2021. The study included 473 patients who tested positive for COVID-19. A high resolution chest CT scan was performed within five days of hospitalization, and patientrelated information was extracted retrospectively from medical records. Univariable and Multivariable analysis was done to study the predictors of poor outcome. Results: A total of 473 patients were included in the study, with 75.5% being males. The mean total CT score was 29.89 ± 9.06. Fibrosis was present in 17.1% of patients, crazy paving in 3.6%, pneumomediastinum in 8.9%, and pneumothorax in 3.6%. Males had a significantly higher total score, while the patients who survived (30.00 ± 9.55 vs 35.00 v 6.21, p value <.001), received Steroids at day 2 (28.04 ± 9.71 vs 31.66 ± 7.12, p value 0.002) or Remdesivir had lower total scores (28.04 ± 9.71 vs 31.66 ± 7.12, p value 0.002). Total CT score (aHR 1.05, 95% CI 1.02 1.08, p 0.001), pneumothorax (aHR 1.38, 95 % CI 0.67 2.87, p 0.385), pneumomediastinum (aHR 1.20, 95% CI 0.71 2.03, p 0.298) and cardiovascular accident (CVA, aHR 4.75, 95% CI 0.84 26.72, p 0.077) were associated with increased mortality, but the results were not significant after adjusting with other variables on multiple regression analysis. Conclusion: This study identifies several radiological parameters, including fibrosis, crazy paving, pneumomediastinum, and pneumothorax, that are associated with poor prognosis in COVID19. These findings highlight the role of CT thorax in COVID19 illness and the importance of timely identification and interventions in severe and critical cases of COVID19 to reduce mortality and morbidity.

  🖺 Full Text HTML: Chest CT findings and outcomes of COVID-19 in second wave: A cross-sectional study in a tertiary care centre in Northern India
• A general computational design strategy for stabilizing viral class I fusion proteins -
  Many pathogenic viruses, including influenza virus, Ebola virus, coronaviruses, and Pneumoviruses, rely on class I fusion proteins to fuse viral and cellular membranes. To drive the fusion process, class I fusion proteins undergo an irreversible conformational change from a metastable prefusion state to an energetically more favorable and stable postfusion state. An increasing amount of evidence exists highlighting that antibodies targeting the prefusion conformation are the most potent. However, many mutations have to be evaluated before identifying prefusion-stabilizing substitutions. We therefore established a computational design protocol that stabilizes the prefusion state while destabilizing the postfusion conformation. As a proof of concept, we applied this principle to the fusion protein of the RSV, hMPV, and SARS-CoV-2 viruses. For each protein, we tested less than a handful of designs to identify stable versions. Solved structures of designed proteins from the three different viruses evidenced the atomic accuracy of our approach. Furthermore, the immunological response of the RSV F design compared to a current clinical candidate in a mouse model. While the parallel design of two conformations allows identifying and selectively modifying energetically less optimized positions for one conformation, our protocol also reveals diverse molecular strategies for stabilization. We recaptured many approaches previously introduced manually for the stabilization of viral surface proteins, such as cavity-filling, optimization of polar interactions, as well as postfusion-disruptive strategies. Using our approach, it is possible to focus on the most impacting mutations and potentially preserve the immunogen as closely as possible to its native version. The latter is important as sequence re-design can cause perturbations to B and T cell epitopes. Given the clinical significance of viruses using class I fusion proteins, our algorithm can substantially contribute to vaccine development by reducing the time and resources needed to optimize these immunogens.
  🖺 Full Text HTML: A general computational design strategy for stabilizing viral class I fusion proteins
• Antibodies generated in vitro and in vivo elucidate design of a thermostable ADDomer COVID-19 nasal nanoparticle vaccine -
  COVID-19 continues to damage populations, communities and economies worldwide. Vaccines have reduced COVID-19-related hospitalisations and deaths, primarily in developed countries. Persisting infection rates, and highly transmissible SARS-CoV-2 Variants of Concern (VOCs) causing repeat and breakthrough infections, underscore the ongoing need for new treatments to achieve a global solution. Based on ADDomer, a self-assembling protein nanoparticle scaffold, we created ADDoCoV, a thermostable COVID-19 candidate vaccine displaying multiple copies of a SARS-CoV-2 receptor binding motif (RBM)-derived epitope. In vitro generated neutralising nanobodies combined with molecular dynamics (MD) simulations and electron cryo-microscopy (cryo-EM) established authenticity and accessibility of the epitopes displayed. A Gigabody comprising multimerized nanobodies prevented SARS-CoV-2 virion attachment with picomolar EC50. Antibodies generated by immunising mice cross-reacted with VOCs including Delta and Omicron. Our study elucidates nasal administration of ADDomer-based nanoparticles for active and passive immunisation against SARS-CoV-2 and provides a blueprint for designing nanoparticle reagents to combat respiratory viral infections.
  🖺 Full Text HTML: Antibodies generated in vitro and in vivo elucidate design of a thermostable ADDomer COVID-19 nasal nanoparticle vaccine
• How have mathematical models contributed to understanding the transmission and control of SARS-CoV-2 in healthcare settings? A systematic search and review -

  Background: Since the onset of the COVID-19 pandemic, mathematical models have been widely used to inform public health recommendations regarding COVID-19 control in healthcare settings. Objectives: To systematically review SARS-CoV-2 transmission models in healthcare settings, and summarise their contributions to understanding nosocomial COVID-19. Methods: Systematic search and review. Data sources: Published articles indexed in PubMed. Study eligibility criteria: Modelling studies describing dynamic inter-individual transmission of SARS-CoV-2 in healthcare settings, published by mid-February 2022. Participants and interventions: Any population and intervention described by included models. Assessment of risk of bias: Not appropriate for modelling studies. Methods of data synthesis: Structured narrative review. Results: Models have mostly focused on acute care and long-term care facilities in high-income countries. Models have quantified outbreak risk across different types of individuals and facilities, showing great variation across settings and pandemic periods. Regarding surveillance, routine testing - rather than symptom-based testing - was highlighted as essential for COVID-19 prevention due to high rates of silent transmission. Surveillance impacts were found to depend critically on testing frequency, diagnostic sensitivity, and turn-around time. Healthcare re-organization was also found to have large epidemiological impacts: beyond obvious benefits of isolating cases and limiting inter-individual contact, more complex strategies such as staggered staff scheduling and immune-based cohorting reduced infection risk. Finally, vaccination impact, while highly effective for limiting COVID-19 burden, varied substantially depending on assumed mechanistic impacts on infection acquisition, symptom onset and transmission. Studies were inconsistent regarding which individuals to prioritize for interventions, probably due to the high diversity of settings and populations investigated. Conclusions: Modelling results form an extensive evidence base that may inform control strategies for future waves of SARS-CoV-2 and other viral respiratory pathogens. We propose new avenues for future models of healthcare-associated outbreaks, with the aim of enhancing their efficiency and contributions to decision-making.

  🖺 Full Text HTML: How have mathematical models contributed to understanding the transmission and control of SARS-CoV-2 in healthcare settings? A systematic search and review
• Relative vaccine effectiveness (rVE) of mRNA COVID-19 boosters in the UK vaccination programme, during the Spring-Summer (monovalent vaccine) and Autumn-Winter 2022 (bivalent vaccine) booster campaigns: a prospective test negative case-control study -

  Background Understanding the relative vaccine effectiveness (rVE) of new COVID-19 vaccine formulations against SARS-CoV-2 infection is an urgent public health priority. A precise comparison of the rVE of monovalent and bivalent boosters given during the 2022 Spring-Summer and Autumn-Winter campaigns, respectively, in a defined population has not been reported. We therefore assessed rVE against hospitalisation for the Spring-Summer (fourth vs third monovalent mRNA vaccine doses) and Autumn-Winter (fifth BA.1/ancestral bivalent vs fourth monovalent mRNA vaccine dose) boosters. Methods A prospective single-centre test-negative design case-control study of ≥75 year-olds hospitalised with COVID-19 or other acute respiratory disease. We conducted regression analyses controlling for age, gender, socioeconomic status, patient comorbidities, community SARS-CoV-2 prevalence, vaccine brand and time between baseline dose and hospitalisation. Results 682 controls and 182 cases were included in the Spring-Summer booster analysis; 572 controls and 152 cases for the Autumn-Winter booster analysis. A monovalent mRNA COVID-19 vaccine as fourth dose showed rVE 46∙9% (95% confidence interval [CI] 14∙4-67∙3) versus those not boosted. A bivalent mRNA COVID-19 vaccine as fifth dose had rVE 46∙4% (95%CI 17∙5-65), compared to a fourth monovalent mRNA COVID-19 vaccine dose. Interpretation Both fourth monovalent and fifth BA.1/ancestral mRNA bivalent COVID-19 vaccine doses demonstrated benefit as a booster in older adults. Bivalent mRNA boosters offer equivalent protection against hospitalisation with Omicron infection to monovalent mRNA boosters given earlier in the year. These findings support the current UK immunisation programme that advises the use of bivalent booster doses.

  🖺 Full Text HTML: Relative vaccine effectiveness (rVE) of mRNA COVID-19 boosters in the UK vaccination programme, during the Spring-Summer (monovalent vaccine) and Autumn-Winter 2022 (bivalent vaccine) booster campaigns: a prospective test negative case-control study

From Clinical Trials

• Clinical Performance Evaluation of the CareSuperb™ COVID-19 Antigen Home Test - Condition:   COVID-19
  Intervention:   Device: CareSuperb COVID-19 Antigen Home Test Kit
  Sponsor:   AccessBio, Inc.
  Recruiting

• Use of E-health Based Exercise Intervention After COVID-19 - Condition:   COVID-19
  Intervention:   Behavioral: Exercise training using an e-health tool
  Sponsors:   Norwegian University of Science and Technology;   University of Oslo
  Recruiting

• Effect Of Calcitriol On Neutrophil To Lymphocytes Ratio And High Sensitivity C-Reactive Protein Covid-19 Patients - Condition:   COVID-19
  Interventions:   Drug: Calcitriol;   Other: Placebo
  Sponsor:   Universitas Sebelas Maret
  Completed

• Clinical Study for the Efficacy and Safety of Ropeginterferon Alfa-2b in Moderate COVID19. - Condition:   COVID-19
  Interventions:   Drug: P1101 (Ropeginterferon alfa-2b);   Procedure: SOC
  Sponsor:   National Taiwan University Hospital
  Active, not recruiting

• Phase I Clinical Trial of Recombinant Variant COVID-19 Vaccine (Sf9 Cell) (WSK-V102) - Condition:   COVID-19
  Intervention:   Biological: Recombinant variant COVID-19 vaccine(Sf9 cell)
  Sponsor:   WestVac Biopharma Co., Ltd.
  Not yet recruiting

• A Phase II Clinical Trial of Recombinant Variant COVID-19 Vaccine (Sf9 Cell) (WSK-V102) - Condition:   COVID-19
  Interventions:   Biological: Recombinant variant COVID-19 vaccine (Sf9 cell);   Biological: Recombinant COVID-19 vaccine (CHO cell);   Biological: Recombinant COVID-19 vaccine (Sf9 cell)
  Sponsor:   WestVac Biopharma Co., Ltd.
  Not yet recruiting

• A Study to Compare QLS1128 With Placebo in Symptomatic Participants With Mild to Moderate COVID-19 - Condition:   COVID-19
  Interventions:   Drug: QLS1128;   Drug: Placebo
  Sponsor:   Qilu Pharmaceutical Co., Ltd.
  Not yet recruiting

• Short-term Effects of Transdermal Estradiol on Female COVID-19 Patients - Conditions:   COVID-19;   Hormone Replacement Therapy
  Interventions:   Drug: Climara 0.1Mg/24Hr Transdermal System;   Other: Hydrogel patch
  Sponsors:   Istanbul University - Cerrahpasa (IUC);   Turkish Menopause and Osteoporosis Society;   Karakoy Rotary Club;   Rebul Pharmacy
  Completed

• Effect of Kinesio Tape Versus Diaphragmatic Breathing Exercise In Post COVID-19 - Condition:   Post COVID-19 Condition
  Interventions:   Other: Pursed lip breathing;   Other: Cognitive Behavior Therapy;   Other: Diaphragmatic breathing exercise;   Other: Kinesio tape
  Sponsor:   Cairo University
  Not yet recruiting

• Hydrogen-Oxygen Generator With Nebulizer for Adjuvant Treatment of Novel Coronavirus Disease 2019 (COVID-19) - Conditions:   Covid19;   Hydrogen-oxygen Gas;   AMS-H-03
  Interventions:   Device: Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03;   Device: OLO-1 Medical Molecular Sieve Oxygen Generator
  Sponsor:   Guangzhou Institute of Respiratory Disease
  Not yet recruiting

• Oxygen Atomizing Inhalation of EGCG in the Treatment COVID-19 Pneumonia in Cancer Patients - Conditions:   COVID-19 Pneumonia;   Neoplasms Malignant
  Interventions:   Drug: EGCG;   Drug: Placebo
  Sponsor:   Shandong Cancer Hospital and Institute
  Recruiting

• The Use of Photobiomodulation in the Treatment of Oral Complaints of Long COVID-19.A Randomized Controlled Trial. - Conditions:   Xerostomia;   COVID-19;   Long COVID;   Persistent COVID-19
  Interventions:   Combination Product: Institutional standard treatment for xerostomia and Long Covid;   Radiation: Photobiomodulation Therapy;   Radiation: Placebo Photobiomodulation Therapy
  Sponsor:   University of Nove de Julho
  Recruiting

• Balneotherapy for Patients With Post-acute Coronavirus Disease (COVID) Syndrome - Condition:   Post-COVID-19 Syndrome
  Intervention:   Other: Balneotherapy and aquatic exercises
  Sponsors:   Parc de Salut Mar;   Caldes de Montbui’s City Council;   Consorcio Centro de Investigación Biomédica en Red (CIBER);   European Regional Development Fund
  Completed

• A Study to Assess the Efficacy of HH-120 Nasal Spray for Prevention of SARS-CoV-2 Infection in Adult Close Contacts of Individuals Infected With SARS-CoV-2 - Condition:   SARS-CoV-2 Infection
  Interventions:   Drug: HH-120 nasal spray 1;   Drug: HH-120 nasal spray 2;   Drug: Placebo Comparator 1;   Drug: Placebo Comparator 2
  Sponsor:   Beijing Ditan Hospital
  Completed

• Lactoferrin for COVID-19-Induced Taste or Smell Abnormality - Conditions:   Covid19;   Taste Disorder, Secondary;   Taste Disorders;   Dysgeusia;   Smell Disorder;   Ageusia;   Anosmia
  Intervention:   Dietary Supplement: Lactoferrin
  Sponsor:   Wake Forest University Health Sciences
  Withdrawn

From PubMed

• A pharmacokinetic drug-drug interaction study between rosuvastatin and emvododstat, a potent anti-SARS-CoV-2 (COVID-19) DHODH (dihydroorotate dehydrogenase) inhibitor - A therapeutic agent that targets both viral replication and the hyper-reactive immune response would offer a highly desirable treatment for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19) management. Emvododstat (PTC299) was found to be a potent inhibitor of immunomodulatory and inflammation-related processes by the inhibition of dihydroorotate dehydrogenase (DHODH) to reduce SARS-CoV-2 replication. DHODH is the rate-limiting enzyme of the de novo pyrimidine nucleotide…

• Innovative, rapid, high-throughput method for drug repurposing in a pandemic-A case study of SARS-CoV-2 and COVID-19 - Several efforts to repurpose drugs for COVID-19 treatment have largely either failed to identify a suitable agent or agents identified did not translate to clinical use. Reasons that have been suggested to explain the failures include use of inappropriate doses, that are not clinically achievable, in the screening experiments, and the use of inappropriate pre-clinical laboratory surrogates to predict efficacy. In this study, we used an innovative algorithm, that incorporates dissemination and…

• Therapeutic developments for SARS-CoV-2 infection-Molecular mechanisms of action of antivirals and strategies for mitigating resistance in emerging variants in clinical practice - This article systematically presents the current clinically significant therapeutic developments for the treatment of COVID-19 by providing an in-depth review of molecular mechanisms of action for SARS-CoV-2 antivirals and critically analyzing the potential targets that may allow the selection of resistant viral variants. Two main categories of agents can display antiviral activity: direct-acting antivirals, which act by inhibiting viral enzymes, and host-directed antivirals, which target host…

• Multiple functions of stress granules in viral infection at a glance - Stress granules (SGs) are distinct RNA granules induced by various stresses, which are evolutionarily conserved across species. In general, SGs act as a conservative and essential self-protection mechanism during stress responses. Viruses have a long evolutionary history and viral infections can trigger a series of cellular stress responses, which may interact with SG formation. Targeting SGs is believed as one of the critical and conservative measures for viruses to tackle the inhibition of…

• Erastin inhibits porcine epidemic diarrhea virus replication in Vero cells - CONCLUSIONS: Since NRF2, ACSL4 and GPX4 are classical Ferroptosis genes, this study speculates that erastin may inhibit the replication of PEDV in Vero cells in part through the regulation of ferroptosis pathway, and erastin may be a potential drug for the treatment of PEDV infection.

• Treatment of severe covid-19 with interleukin 6 receptor inhibition - No abstract

• Wearing N95 masks decreases the odor discrimination ability of healthcare workers: a self-controlled before-after study - CONCLUSION: Wearing N95 masks decreases the odor discrimination ability of healthcare workers. Therefore, we suggest that healthcare workers seek other clues when diagnosing disease with a characteristic odor.

• Structure-based computational screening of 470 natural quercetin derivatives for identification of SARS-CoV-2 M^pro inhibitor - Coronavirus disease 2019 (COVID-19) is a global pandemic infecting the respiratory system through a notorious virus known as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to viral mutations and the risk of drug resistance, it is crucial to identify new molecules having potential prophylactic or therapeutic effect against SARS-CoV-2 infection. In the present study, we aimed to identify a potential inhibitor of SARS-CoV-2 through virtual screening of a compound library of…

• In-silico studies of Momordica charantia extracts as potential candidates against SARS-CoV-2 targeting human main protease enzyme (M^pro) - Momordica charintia, a well-known plant called bitter melon, has been shown to have antibacterial, anti-diabetic, and antiviral properties against HIV infection. The goal of this work was to investigate the inhibitory effect of phytocompounds found in Momordica charintia leaf extracts on SARS-CoV-2 3CL protease (also known as the Main protease, M^(pro)) utilizing GC-MS analysis and molecular docking studies. The Crystal Structure of the SARS-CoV-2 3CL protease in complex with an inhibitor N3 was…

• The relationship between serum cytokine profile and vitamin D in calves with neonatal diarrhea - It is important to know the characteristics of the immunological response in newborn calf diarrhea, which is often caused by bacterial, viral and protozoal pathogens. Cytokinesare proteins that serve as chemical messengers to regulate theinnate and adaptive arms of theimmune response. Changes in circulatory cytokine levels provide valuable information for understanding the pathophysiological process and monitoring disease progression and inflammation. Vitamin D has important immunomodulatory…

• Xuanfei Baidu Decoction regulates NETs formation via CXCL2/CXCR2 signaling pathway that is involved in acute lung injury - Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening symptoms in Coronavirus Disease 2019 (COVID-19) patients. Xuanfei Baidu Decoction (XFBD) is a recommend first-line traditional Chinese medicine (TCM) formula therapeutic strategy for COVID-19 patients. Prior studies demonstrated the pharmacological roles and mechanisms of XFBD and its derived effective components against inflammation and infections through multiple model systems, which provided the…

• Digoxin and Standard-of-Care Therapy for Heart Failure Patients with COVID-19: Analysis of Data from the US Military Health System (MHS) Data Repository - CONCLUSION: The hypothesis of equivalent protection by digoxin treatment of HF patients in terms of susceptibility to COVID-19 infection appears to be supported by the data.

• Viral target- and metabolism-based rationale for combined use of recently authorized small molecule COVID-19 medicines: molnupiravir, nirmatrelvir and remdesivir - The COVID-19 pandemic remains a major health concern worldwide, and SARS-CoV-2 is continuously evolving. There is an urgent need to identify new antiviral drugs and develop novel therapeutic strategies. Combined use of newly authorized COVID-19 medicines including molnupiravir, nirmatrelvir and remdesivir, has been actively pursued. Mechanistically, nirmatrelvir inhibits SARS-CoV-2 replication by targeting the viral main protease (M^(pro) ), a critical enzyme in the processing of the immediately…

• SARS-CoV-2 NSP8 suppresses type I and III IFN responses by modulating the RIG-I/MDA5, TRIF, and STING signaling pathways - SARS-CoV-2 has developed a variety of approaches to counteract host innate antiviral immunity to facilitate its infection, replication and pathogenesis, but the molecular mechanisms that it employs are still not been fully understood. Here, we found that SARS-CoV-2 NSP8 inhibited the production of type I and III IFNs by acting on RIG-I/MDA5 and the signaling molecules TRIF and STING. Overexpression of NSP8 downregulated the expression of type I and III IFNs stimulated by poly (I:C) transfection…

• Acid sphingomyelinase (ASM) and COVID-19: A review of the potential use of ASM inhibitors against SARS-CoV-2 - In the last 2 years, different pharmacological agents have been indicated as potential inhibitors of SARS-CoV-2 in vitro. Specifically, drugs termed as functional inhibitors of acid sphingomyelinase (FIASMAs) have proved to inhibit the SARS-CoV-2 replication using different types of cells. Those therapeutic agents share several chemical structure characteristics and some well-known representatives are fluoxetine, escitalopram, fluvoxamine, and others. Most of the FIASMAs are primarily used as…

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