Covid-19 Sentry

Contents

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

From Preprints

• The Effects of Non-pharmaceutical Interventions on COVID-19 Mortality: A Generalized Synthetic Control Approach Across 169 Countries -
  Importance: Governments have introduced non-pharmaceutical interventions (NPIs) in response to the pandemic outbreak of Coronavirus disease (COVID-19). While NPIs aim at preventing fatalities related to COVID-19, the previous literature on their efficacy has focused on infections and on data of the first half of 2020. Still, findings of early NPI studies may be subject to underreporting and missing timeliness of reporting of cases. Moreover, the low variation in treatment timing during the first wave makes identification of robust treatment effects difficult.
  🖺 Full Text HTML: The Effects of Non-pharmaceutical Interventions on COVID-19 Mortality: A Generalized Synthetic Control Approach Across 169 Countries
• China’s research evaluation reform: what are the consequences for global science? -
  In the 1990s, China created a research evaluation system based on publications indexed in the Science Citation Index (SCI) and on the Journal Impact Factor. Such a system helped the country become the largest contributor to the scientific literature and increased the position of Chinese universities in international rankings. Although the system had been criticized by many because of its adverse effects, the policy reform for research evaluation crawled until the breakout of the COVID-19 pandemic, which accidentally accelerates the process of policy reform. This paper highlights the background and principles of this reform provides evidence of its effects and discusses the implications for global science.
  🖺 Full Text HTML: China’s research evaluation reform: what are the consequences for global science?
• Inferring the true number of SARS-CoV-2 infections in Japan -

  Introduction. In Japan, as of December 31, 2021, more than 1.73 million laboratory-confirmed cases have been reported. However, the actual number of infections is likely to be under-ascertained due to the epidemiological characteristics such as mild and subclinical infections and limited testing availability in the early days of the pandemic. In this study, we infer the true number of infections in Japan between January 16, 2020, and December 31, 2021 , using a statistical modelling framework that combines data on reported cases and fatalities. Methods. We used reported daily COVID-19 deaths stratified into 8 distinct age-groups and age-specific infection fatality ratios (IFR) to impute the true number of infections. Estimates of IFR were informed from published studies as well seroprevalence studies conducted in Japan. To account for the uncertainty in IFR estimates, we sampled values from relevant distributions. Results. We estimated that as of December 31, 2021, 2.90 million (CrI: 1.77 to 4.27 million) people had been infected in Japan, which is 1.68 times higher than the 1.73 million reported cases. Our meta-analysis confirmed that these findings were consistent with the intermittent seroprevalence studies conducted in Japan. Conclusions. We have estimated that a substantial number of COVID-19 infections in the country were unreported, particularly in adults. Our approach provides a more realistic assessment of the true underlying burden of COVID-19. The results of this study can be used as fundamental components to strengthen population health control and surveillance measures.

  🖺 Full Text HTML: Inferring the true number of SARS- CoV-2 infections in Japan
• Epidemiological topology data analysis links severe COVID-19 to RAAS and hyperlipidemia associated metabolic syndrome conditions -

  The emergence of COVID19 created incredible worldwide challenges but offers unique opportunities to understand the physiology of its risk factors and their interactions with complex disease conditions, such as metabolic syndrome. Epidemiological analysis powered by topological data analysis (TDA) is a novel approach to uncover these clinically relevant interactions. Here TDA utilized Explorys data to discover associations among severe COVID19 and metabolic syndrome, and it explored the probative value of drug prescriptions to capture the involvement of RAAS and hypertension with COVID19 as well as modification of risk factor impact by hyperlipidemia on severe COVID19.

  🖺 Full Text HTML: Epidemiological topology data analysis links severe COVID-19 to RAAS and hyperlipidemia associated metabolic syndrome conditions
• SARS-CoV-2 spike S375F mutation characterizes the Omicron BA.1 variant -
  Recent studies have revealed the unique virological characteristics of Omicron, the newest SARS-CoV-2 variant of concern, such as pronounced resistance to vaccine-induced neutralizing antibodies, less efficient cleavage of the spike protein, and poor fusogenicity. However, it remains unclear which mutation(s) in the spike protein determine the virological characteristics of Omicron. Here, we show that the representative characteristics of the Omicron spike are determined by its receptor-binding domain. Interestingly, the molecular phylogenetic analysis revealed that the acquisition of the spike S375F mutation was closely associated with the explosive spread of Omicron in the human population. We further elucidate that the F375 residue forms an interprotomer pi-pi interaction with the H505 residue in another protomer in the spike trimer, which confers the attenuated spike cleavage efficiency and fusogenicity of Omicron. Our data shed light on the evolutionary events underlying Omicron emergence at the molecular level.
  🖺 Full Text HTML: SARS-CoV-2 spike S375F mutation characterizes the Omicron BA.1 variant
• Dietary αKG inhibits SARS CoV-2 infection and rescues inflamed lungs to restore normal O2 saturation in animals -
  Our recent works described the rescue effect of -ketoglutarate (KG, a metabolite of Krebs cycle) on thrombosis and inflammation in animals. KG augments activity of prolyl hydroxylase 2 (PHD2), which in turn degrades proline residues of substrates like phosphorylated Akt (pAkt) and hypoxia inducible factor (HIF). Here we describe the inhibitory effect of octyl KG on pAkt as well as on HIF1/HIF2, and in turn decreasing SARS CoV-2 replication in Vero E6 cells. KG failed to inhibit the viral replication and Akt phosphorylation in PHD2-knockdown U937 cells transiently expressing ACE2. Contrastingly, triciribine (TCN, an Akt-inhibitor) inhibited viral replication alongside a downmodulation of pAkt in PHD2-KD cells. Dietary KG significantly inhibited viral infection and rescued hamsters from thrombus formation and inflammation in lungs, the known causes of acute respiratory distress syndrome (ARDS) in COVID-19. KG supplementation also reduced the apoptotic death of lung tissues in infected animals, alongside a downmodulation of pAkt and HIF2. KG supplementation neither affected IgG levels against SARS CoV-2 RBD protein nor altered the neutralization antibody response against SARS CoV-2. It did not interfere with the percentage of interferon-{gamma} positive (IFN{gamma}+) CD4+ and IFN{gamma}+CD8+ T cells in infected animals. The extended work in balb/c mice transiently expressing ACE2 showed a similar effect of KG in reducing accumulation of inflammatory immune cells and cytokines, including IL6, IL1{beta} and TNF, in lungs as well as in circulation of infected animals. Pro-thrombotic markers like platelet microparticles and platelet-leukocyte aggregates were reduced significantly in infected mice after KG supplementation. Importantly, KG supplementation restored the O2 saturation (SpO2) in circulation of SARS CoV-2 infected hamsters and mice, suggesting a potential therapeutic role of this metabolite in COVID-19 treatment.
  🖺 Full Text HTML: Dietary αKG inhibits SARS CoV-2 infection and rescues inflamed lungs to restore normal O2 saturation in animals
• Conformational Flexibility in Neutralization of SARS-CoV-2 by Naturally Elicited Anti-SARS-CoV-2 Antibodies -
  As new variants of SARS-CoV-2 continue to emerge, it is important to assess the neutralizing capabilities of naturally elicited antibodies against SARS-CoV-2. In the present study, we evaluated the activity of nine anti-SARS- CoV-2 monoclonal antibodies (mAbs), previously isolated from convalescent donors infected with the Wuhan-Hu-1 strain, against the SARS-CoV-2 variants of concern (VOC) Alpha, Beta, Gamma, Delta and Omicron. By testing an array of mutated spike receptor binding domain (RBD) proteins, cell-expressed spike proteins from VOCs, and neutralization of SARS-CoV-2 VOCs as pseudoviuses, or as the authentic viruses in culture, we show that mAbs directed against the ACE2 binding site (ACE2bs) are far more sensitive to viral evolution compared to anti-RBD non-ACE2bs mAbs, two of which kept their potency against all VOCs tested. At the second part of our study, we reveal the neutralization mechanisms at high molecular resolution of two anti-SARS-CoV-2 neutralizing mAbs by structural characterization. We solved the structures of the Delta-neutralizing ACE2bs mAb TAU-2303 with the SARS-CoV-2 spike trimer and RBD at 4.5 [A] and 2.42 [A], respectively, revealing a similar mode of binding to that between the RBD and the ACE2 receptor. Furthermore, we provide five additional structures (at resolutions of 5.54 [A], 7.76 [A], 6.47 [A], 3.45 [A], and 7.32 [A]) of a second antibody, non-ACE2bs mAb TAU-2212, complexed with the SARS-CoV-2 spike trimer. TAU-2212 binds an exclusively quaternary epitope, and exhibits a unique, flexible mode of neutralization that involves transitioning between five different conformations, with both arms of the antibody recruited for cross linking intra- and inter-spike RBD subunits. Our study provides new mechanistic insights about how antibodies neutralize SARS-CoV-2 and its emerging variants and provides insight about the likelihood of reinfections.
  🖺 Full Text HTML: Conformational Flexibility in Neutralization of SARS-CoV-2 by Naturally Elicited Anti-SARS-CoV-2 Antibodies
• Acute respiratory distress syndrome after SARS-CoV-2 infection on young adult population: international observational federated study based on electronic health records through the 4CE consortium ARDS after SARS-CoV-2 infection on young adult -

  Purpose : In young adults (18 to 49 years old), investigation of the acute respiratory distress syndrome (ARDS) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been limited. We evaluated the risk factors and outcomes of ARDS following infection with SARS-CoV-2 in a young adult population. Methods  : A retrospective cohort study was conducted between January 1st, 2020 and February 28th, 2021 using patient-level electronic health records (EHR),  across 241 United States hospitals and 43 European hospitals participating in the Consortium for Clinical Characterization of COVID-19 by EHR (4CE). To identify the risk factors associated with ARDS, we compared young patients with and without ARDS through a federated analysis. We further compared the outcomes between young and old patients with ARDS. Results  : Among the 75,377 hospitalized patients with positive SARS-CoV-2 PCR, 1001 young adults presented with ARDS ( 7.8% of young hospitalized adults). Their mortality rate at 90 days was 16.2% and they presented with a similar complication rate for infection than older adults with ARDS. Peptic ulcer disease, paralysis, obesity, congestive heart failure, valvular disease, diabetes, chronic pulmonary disease and liver disease were associated with a higher risk of ARDS. We described a high prevalence of obesity (53%), hypertension (38%- although not significantly associated with ARDS), and diabetes (32%). Conclusion : Trough an innovative method, a large international cohort study of young adults developing ARDS after SARS-CoV-2 infection has been gather. It demonstrated the poor outcomes of this population and associated risk factor.

  🖺 Full Text HTML: Acute respiratory distress syndrome after SARS-CoV-2 infection on young adult population: international observational federated study based on electronic health records through the 4CE consortium ARDS after SARS-CoV-2 infection on young adult
• Clinical and Economic Impact of Differential COVID-19 Vaccine Effectiveness in the United States -

  Background: In the United States (US), three vaccines are currently available for primary vaccination and booster doses to prevent coronavirus disease 2019 (COVID-19), including the 2-dose messenger ribonucleic acid (mRNA) BNT162b2 (COMIRNATY®, Pfizer Inc) and mRNA-1273 (SPIKEVAX®, Moderna Inc) vaccines, which are preferred by the Centers for Disease Control and Prevention9s (CDC) Advisory Committee on Immunization Practice (ACIP), and the adenovirus vector Ad26.COV2.S (Johnson & Johnson) vaccine. A substantial body of evidence has now been published on the real-world effectiveness and waning of the primary series and booster doses against specific SARS-CoV2- variants. The study objective was to determine the clinical and economic impact of differences in effectiveness between mRNA-1273 and BNT162b2 booster vaccinations over one year (2022) in US adults ≥18 years. Methods: A decision analytic model was used to compare three mRNA booster market share scenarios: (1) Current Scenario, where the booster mix observed in December 2021 continues throughout 2022; (2) mRNA-1273 Scenario, where the only booster administered in 2022 is mRNA-1273, and

3. BNT162b2 Scenario, where the only booster administered in 2022 is BNT162b2. Analyses were performed from the US healthcare system perspective. Sensitivity analyses were performed to explore the impact of COVID-19 incidence in the unvaccinated population and vaccine effectiveness (VE) on model results. Results: In the Current Scenario, the model predicts 65.2 million outpatient visits, 3.4 million hospitalizations, and 636,100 deaths from COVID-19 in 2022. The mRNA-1273 Scenario reduced each of these outcomes compared to the Current Scenario. Specifically, 684,400 fewer outpatient visits, 48,700 fewer hospitalizations and 9,500 fewer deaths would be expected. Exclusive of vaccine costs, the mRNA-1273 Scenario is expected to decrease direct medical costs by $1.3 billion. Conversely, the BNT162b2 Scenario increased outcomes compared to the Current Scenario: specifically, 391,500 more outpatient visits, 34,500 more hospitalizations and 7,200 more deaths would be expected in 2022, costing an additional $946 million in direct medical costs. For both the mRNA-1273 and BNT162b2 booster scenarios, the percent change in direct treatment costs for COVID-19 is similar to the percent change in hospitalizations as the rate of hospitalizations is the driver of the overall costs. Changing the number of projected COVID-19 cases in 2022 by varying the incidence rate has a direct effect on model outcomes. Higher incidence rates leads to higher outpatient visits, hospitalizations and deaths for all scenarios. Varying VE has an inverse effect on model outcomes. All outcomes increase when VE is lower for all vaccines and decrease when VE is higher. In all cases, additional use of mRNA-1273 leads to fewer infection outcomes while additional use of BNT126b2 results to higher infection outcomes. Conclusion: As the real-world effectiveness evidence to date indicates that mRNA-1273 may be more effective at preventing COVID-19 infection and hospitalization over time than BNT-162b2, increasing the proportion of people receiving this as a booster are expected to reduce COVID-19-related outcomes and costs in 2022, regardless of COVID-19 incidence or variant.
   🖺 Full Text HTML: Clinical and Economic Impact of Differential COVID-19 Vaccine Effectiveness in the United States

• Transmission of SARS-CoV-2 in standardised First Few X cases and household transmission investigations: a systematic review and meta-analysis -

  First Few X cases (FFX) investigations and Household transmission investigations (HHTI) are essential epidemiological tools for early characterisation of novel infectious pathogens and their variants. We aimed to estimate the household secondary infection attack rate (hSAR) of SARS-CoV-2 in investigations aligned with the WHO Unity Studies HHTI protocol. We conducted a systematic review and meta-analysis according to PRISMA 2020 guidelines (PROSPERO registration: CRD42021260065). We searched Medline, Embase, Web of Science, Scopus and medRxiv/bioRxiv for Unity-aligned FFX and HHTI published between 1 December 2019 and 26 July 2021. Standardised early results were shared by WHO Unity Studies Collaborators (to 1 October 2021). We used a bespoke tool to assess investigation methodological quality. Values for hSAR and 95% confidence intervals (CIs) were extracted or calculated from crude data. Heterogeneity was assessed by visually inspecting overlap of CIs on forest plots and quantified in meta-analyses. Of 9988 records retrieved, 80 articles (64 from databases; 16 provided by WHO Unity Studies collaborators) were retained in the systematic review and 62 were included in the primary meta-analysis. hSAR point estimates ranged from 2%-90% (95% prediction interval: 3%-71%; I2 = 99.7%); I2 values remained >99% in subgroup analyses, indicating high, unexplained heterogeneity and leading to a decision not to report pooled hSAR estimates. The large, unexplained variance in hSAR estimates emphasises the need for improved standardisation in planning, conduct and analysis, and for clear and comprehensive reporting of FFX and HHTIs, to guide evidence-based pandemic preparedness and response efforts for SARS-CoV-2, influenza and future novel respiratory viruses.

  🖺 Full Text HTML: Transmission of SARS-CoV-2 in standardised First Few X cases and household transmission investigations: a systematic review and meta- analysis
• Predictors of all-cause mortality among patients hospitalized with influenza, respiratory syncytial virus, or SARS- CoV-2 -

  Background: Identification of shared and divergent predictors of clinical severity across respiratory viruses may support clinical decision-making and resource planning in the context of a novel or re-emergent respiratory pathogen. Methods: We conducted a retrospective cohort study to identify predictors of 30-day all-cause mortality following hospitalization with influenza (N=45,749; 2011-09 to 2019-05), respiratory syncytial virus (RSV, N=24,345; 2011-09 to 2019-04), or SARS-CoV-2 (N=8,988; 2020-03 to 2020-12; pre-vaccine) using population-based health administrative data from Ontario, Canada. Multivariable modified Poisson regression was used to assess associations between potential predictors and mortality. We compared the direction, magnitude and confidence intervals of risk ratios to identify shared and divergent predictors of mortality. Results: 3,186 (7.0%), 697 (2.9%) and 1,880 (20.9%) patients died within 30 days of hospital admission with influenza, RSV, and SARS-CoV-2, respectively. Common predictors of increased mortality included: older age, male sex, residence in a long-term care home, and chronic kidney disease. Positive associations between age and mortality were largest for patients with SARS-CoV-2. Few comorbidities were associated with mortality among patients with SARS-CoV-2 as compared to those with influenza or RSV. Conclusions: Our findings may help identify patients at highest risk of illness secondary to a respiratory virus, anticipate hospital resource needs, and prioritize local preventions and therapeutics to communities with high prevalence of risk factors.

  🖺 Full Text HTML: Predictors of all-cause mortality among patients hospitalized with influenza, respiratory syncytial virus, or SARS-CoV-2
• Variation in National COVID-19 Mortality Rates Across Asian Subgroups in the United States, 2020 -

  Provisional U.S. national COVID-19 mortality data for the year 2020 analyzed by the CDC in March 2021 indicated that non-Hispanic Asians fared markedly better overall than other racial/ethnic minority groups-and marginally better than non-Hispanic Whites-in terms of age-adjusted mortality rates. However, Asians in the United States are composed of diverse array of origin subgroups with highly varying social, economic, and environmental experiences, which influence health outcomes. As such, lumping all Asians together into a single category can mask meaningful health disparities among more vulnerable Asian subgroups. To date, there has not been a national-level analysis of COVID-19 mortality outcomes between Asian subgroups. Utilizing final multiple cause of death data for 2020 and population projections from the U.S. Census Bureau9s Current Population Survey Annual Social and Economic Supplement for 2020, crude and age- adjusted national COVID-19 mortality rates, both overall and stratified by sex, were calculated for the six major single-race Asian origin subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, and Vietnamese) and a catch-all seventh category that comprises the remaining Asian subgroups (Other Asians), contrasting them to the corresponding mortality rates of other racial/ethnic groups. A substantially more nuanced picture emerges when disaggregating Asians into its diverse origin subgroups and stratifying by sex, with Filipino males and Asian males outside of the six major Asian subgroups in particular experiencing markedly higher age-adjusted mortality rates than their White male counterparts, whether comparisons were restricted to their non-Hispanic subsets or not. During the COVID-19 pandemic and in the post-pandemic recovery, it is imperative not to overlook the health needs of vulnerable Asian populations. Public health strategies to mitigate the effects of COVID-19 must avoid viewing Asians as a monolithic entity and recognize the heterogeneous risk profiles within the U.S. Asian population.

  🖺 Full Text HTML: Variation in National COVID-19 Mortality Rates Across Asian Subgroups in the United States, 2020
• High rate of BA.1, BA.1.1 and BA.2 in triple vaccinated -

  Background: Booster vaccine doses offer protection against severe COVID-19 caused by Omicron but are less effective against infection. Characteristics such as serological correlates of protection, viral abundance and clearance of Omicron infections in triple vaccinated individuals are scarce. Methods: We conducted a 4-week twice-weekly SARS- CoV-2 qPCR screening shortly after an mRNA vaccine booster in 375 healthcare workers. Anti-Spike IgG levels and neutralization titers were determined at study start. qPCR-positive participants were sampled repeatedly for two weeks and monitored for symptoms. Result: In total 82 (cumulative incidence 22%) Omicron infections were detected, divided between BA.1, BA.1.1 and BA.2. Only 10% of infected participants remained asymptomatic. Viral load peaked at day 3 and live virus could be detected for up to 9 days after first PCR-positive sample. Presence of symptoms correlated to elevated viral load (p<0.0001), but despite resolution of symptoms most participants showed Ct levels <30 at day

9. Post-booster antibody titers were similar in those with and without subsequent breakthrough infection (p>0.05), but high antibody titers were linked to reduced viral load (p<0.01) and time to viral clearance (p<0.01). No significant differences were observed for viral load and time to viral clearance between BA.1, BA.1.1 and BA.2 infected individuals. Conclusion: We report high incidence of Omicron infections despite a recent booster vaccination in triple vaccinated individuals. Vaccine-induced antibody titres seem to play a limited role in infection risk prediction. High viral load and detection of live virus for up to nine days enables spread in a triple vaccinated population.

• Does Metformin Decrease Mortality in Patients with Type 2 Diabetes Mellitus Hospitalized for COVID-19? A Multivariable and Propensity Score-adjusted Meta-analysis -

  Aims Coronavirus disease 2019 (COVID-19) is a new pandemic that the entire world is facing since December of

2019. Increasing evidence has shown that metformin is linked to favorable outcomes in patients with COVID-19. The aim of this study was to address whether outpatient or inpatient metformin therapy offers low in-hospital mortality in patients with type 2 diabetes mellitus hospitalized for COVID-19. Methods We searched studies published in PubMed, Embase, Google Scholar and Cochrane Library up to October 1, 2021. Raw event data extracted from individual study were pooled using the Mantel-Haenszel approach. Odds ratio (OR) or hazard ratio (HR) adjusted for covariates that potentially confound the association using multivariable regression or propensity score matching was pooled by the inverse-variance method. Random effect models were applied for meta-analysis due to variation among studies. Results Nineteen retrospective observational studies were selected. The pooled unadjusted OR for outpatient metformin therapy and in- hospital mortality was 0.54 (95% CI, 0.42-0.68), whereas the pooled OR adjusted with multivariable regression or propensity score matching was 0.72 (95% CI, 0.47-1.12). The pooled unadjusted OR for inpatient metformin therapy and in- hospital mortality was 0.19 (95% CI, 0.10-0.36), whereas the pooled adjusted HR was 1.10 (95% CI, 0.38-3.15). Conclusions Our results suggest that there is a significant reduction of in-hospital mortality with metformin therapy in patients with type 2 diabetes mellitus hospitalized for COVID-19 in the unadjusted analysis, but this mortality benefit does not retain after adjustments for confounding bias.
      🖺 Full Text HTML: Does Metformin Decrease Mortality in Patients with Type 2 Diabetes Mellitus Hospitalized for COVID-19? A Multivariable and Propensity Score-adjusted Meta-analysis

• Transcriptional reprogramming from innate immune functions to a pro-thrombotic signature upon SARS-CoV-2 sensing by monocytes in COVID-19 -
  Alterations in the myeloid immune compartment have been observed in COVID-19, but the specific mechanisms underlying these impairments are not completely understood. Here we examined the functionality of classical CD14+ monocytes as a main myeloid cell component in well-defined cohorts of patients with mild and moderate COVID-19 during the acute phase of infection and compared them to that of healthy individuals. We found that ex vivo isolated CD14+ monocytes from mild and moderate COVID-19 patients display specific patterns of costimulatory and inhibitory receptors that clearly distinguish them from healthy monocytes, as well as altered expression of histone marks and a dysfunctional metabolic profile. Decreased NFkB activation in COVID-19 monocytes ex vivo is accompanied by an intact type I IFN antiviral response. Subsequent pathogen sensing ex vivo led to a state of functional unresponsiveness characterized by a defect in pro-inflammatory cytokine expression, NFkB-driven cytokine responses and defective type I IFN response in moderate COVID-19 monocytes. Transcriptionally, COVID-19 monocytes switched their gene expression signature from canonical innate immune functions to a pro-thrombotic phenotype characterized by increased expression of pathways involved in hemostasis and immunothrombosis. In response to SARS-CoV-2 or other viral or bacterial components, monocytes displayed defects in the epigenetic remodelling and metabolic reprogramming that usually occurs upon pathogen sensing in innate immune cells. These results provide a potential mechanism by which innate immune dysfunction in COVID-19 may contribute to disease pathology.
  🖺 Full Text HTML: Transcriptional reprogramming from innate immune functions to a pro-thrombotic signature upon SARS-CoV-2 sensing by monocytes in COVID-19

From Clinical Trials

• A Clinical Trial on Sequential Immunization of Recombinant COVID-19 Vaccine (CHO Cell, NVSI-06-09) and Inactivated COVID-19 Vaccine (Vero Cell) - Condition:   COVID-19
  Interventions:   Biological: Recombinant COVID-19 Vaccine (CHO cell，NVSI-06-09);   Biological: Inactivated COVID-19 vaccine (Vero cells)
  Sponsors:  
  National Vaccine and Serum Institute, China;   China National Biotec Group Company Limited;   Lanzhou Institute of Biological Products Co., Ltd;   Beijing Institute of Biological Products Co Ltd.
  Not yet recruiting

• Randomized Controlled Clinical Trial to Evaluate The Efficacy and Safety of Healthtone as Prophylaxis for COVID-19 - Condition:   COVID-19
  Intervention:   Dietary Supplement: Rhea® Health Tone
  Sponsor:   Indonesia University
  Completed

• Aerobic Exercise in People With Post-COVID-19 - Condition:   COVID-19
  Interventions:   Other: Conventional rehabilitation;   Other: Aerobic exercise
  Sponsor:   Istituti Clinici Scientifici Maugeri SpA
  Recruiting

• Acupressure and Qigong in Chronic Fatigue Post COVID-19. - Condition:   COVID-19
  Interventions:   Other: self- applied acupressure plus Qigong course plus advice literature;   Behavioral: advice literature with naturopathy
  Sponsors:  
  Charite University, Berlin, Germany;   Karl and Veronica Carstens Foundation
  Not yet recruiting

• A Study to Evaluate the Effectiveness and Safety of SCTV01E (a Recombinant Protein COVID-19 Vaccine) in Population Aged ≥12 Years - Conditions:   COVID-19;   SARS-CoV-2 Infection
  Interventions:   Biological: SCTV01E;   Biological: CoronaVac;   Biological: Sinopharm inactivated COVID-19 vaccine;   Biological: other approved COVID-19 vaccines
  Sponsor:   Sinocelltech Ltd.
  Not yet recruiting

• A Study to Evaluate the Immunogenicity and Safety of SCTV01C and SCTV01E (Two Recombinant Protein COVID-19 Vaccines) in Population Aged ≥12 Years - Conditions:   COVID-19;   SARS-CoV-2 Infection
  Interventions:   Biological: SCTV01C;   Biological: SCTV01E;   Biological: mRNA vaccine manufactured by Pfizer or Moderna;   Biological: Sinopharm inactivated COVID-19 vaccine
  Sponsor:   Sinocelltech Ltd.
  Not yet recruiting

• COVID-19 Treatment Cascade Optimization Study - Condition:   COVID-19
  Interventions:   Behavioral: Navigation Services;   Behavioral: Brief Counseling;   Behavioral: Critical Dialogue;   Behavioral: Referral and Digital Brochure
  Sponsors:   University of Illinois at Urbana-Champaign;   National Institute of Allergy and Infectious Diseases (NIAID);   Comprehensive Behavioral Health Center;   North Jersey Community Research Initiative;   University of Michigan
  Not yet recruiting

• Phase 1/2 Study to Evaluate the Efficacy and Safety of Inhaled IBIO123 in Participants With Mild to Moderate COVID-19 Illness - Condition:   COVID-19
  Interventions:   Biological: IBIO123;   Other: Placebo
  Sponsor:   Immune Biosolutions Inc
  Recruiting

• Compass Course: COVID-19 - Condition:   COVID-19
  Intervention:   Behavioral: Compass Course
  Sponsor:  
  Allina Health System
  Recruiting

• Improving COVID-19 Vaccine Uptake Among Black and Latino Youth - Condition:   COVID-19
  Interventions:   Behavioral: Culturally-Tailored COVID-19 Vaccine Uptake Intervention;   Behavioral: Standard Care
  Sponsors:   Nemours Children’s Health System;   National Institute of General Medical Sciences (NIGMS);   University of Delaware;   ChristianaCare
  Recruiting

• Phase 1&2 Study to Evaluate the Safety & Efficacy of Inhaled IBIO123 in Severe COVID-19 Illness - Condition:   COVID-19
  Interventions:   Biological: IBIO123;   Other: Placebo
  Sponsor:   Immune Biosolutions Inc
  Recruiting

• Clinical Evaluation of Rapid RNA Test for Covid-19 - Condition:   COVID-19
  Intervention:   Diagnostic Test: rapid RT-LAMP test to detect SARS-COV-2 RNA
  Sponsors:   University of Southampton;   West Hertfordshire Hospitals NHS Trust;   University of Oxford
  Completed

• Clinical Evaluation of Rapid Antibody Test for Covid-19 - Condition:   COVID-19
  Intervention:   Diagnostic Test: Livzon Rapid Antibody Test for COVID-19
  Sponsors:   University of Southampton;   West Hertfordshire Hospitals NHS Trust
  Completed

• ApTOLL for the Treatment of COVID-19 - Condition:   COVID-19
  Interventions:   Drug: ApTOLL;   Other: Saline
  Sponsors:  
  Macarena Hernández Jiménez;   Centro para el Desarrollo Tecnológico Industrial
  Recruiting

• Platform Trial to Compare Homologous Boost of Authorized COVID-19 Vaccines and Heterologous Boost With UB-612 Vaccine - Condition:   COVID-19 Vaccines
  Interventions:   Biological: UB-612;   Biological: BNT162b2 vaccine;   Biological: ChAdOx1-S vaccine;   Biological: Sinopharm BIBP
  Sponsors:   Vaxxinity, Inc.;   Syneos Health
  Recruiting

From PubMed

• A Spike Protein-Based Subunit SARS-CoV-2 Vaccine for Pets: Safety, Immunogenicity, and Protective Efficacy in Juvenile Cats - Whereas, multiple vaccine types have been developed to curb the spread of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) among humans, there are very few vaccines being developed for animals including pets. To combat the threat of human-to-animal, animal-to-animal, and animal-to-human transmission and the generation of new virus variants, we developed a subunit SARS-CoV-2 vaccine which is based on the recombinant spike protein extracellular domain expressed in insect cells and then…

• Host Cell Glycocalyx Remodeling Reveals SARS-CoV-2 Spike Protein Glycomic Binding Sites - Glycans on the host cell membrane and viral proteins play critical roles in pathogenesis. Highly glycosylated epithelial cells represent the primary boundary separating embedded host tissues from pathogens within the respiratory and intestinal tracts. SARS-CoV-2, the causative agent for the COVID-19 pandemic, reaches into the respiratory tract. We found purified human milk oligosaccharides (HMOs) inhibited the viral binding on cells. Spike (S) protein receptor binding domain (RBD) binding to…

• Multiple SARS-CoV-2 Variants Exhibit Variable Target Cell Infectivity and Ability to Evade Antibody Neutralization - The continuous emergence of SARS-coronavirus 2 (SARS-CoV-2) variants, especially the variants of concern (VOC), exacerbated the impact of the coronavirus disease 2019 (COVID-19) pandemic. As the key of viral entry into host cells, the spike (S) protein is the major target of therapeutic monoclonal antibodies (mAbs) and polyclonal antibodies elicited by infection or vaccination. However, the mutations of S protein in variants may change the infectivity and antigenicity of SARS-CoV-2, leading to…

• Interdisciplinarity for social justice enterprise: intersecting education, industry and community arts perspectives - The role of interdisciplinarity in achieving authentic and transformative learning outcomes is both contested and complex. At the same time, traditional disciplinary ways of being, doing and knowing have been further tested by the impact of COVID-19 on students, schools and communities. In Tasmania, already experiencing amongst the lowest levels of educational attainment in Australia, the educational implications of COVID-19 have been polarising. Preliminary reports have employed…

• Biological Activities of Some Natural Compounds and Their Cytotoxicity Studies against Breast and Prostate Cancer Cell Lines and Anti-COVID19 Studies - In this study, we investigated the inhibition effects of matairesinol, pregnanolone, hamamelitannin, secoisolariciresinol, and secoisolariciresinol diglicoside compounds on HMG-CoA reductase and urease enzymes. We have obtained results for the HMG-CoA reductase enzyme at the millimolar level, and for the urease enzyme at the micromolar level. Molecular docking calculations were made for their biological activities were compared. In docking calculations, proteins of experimentally used enzymes,…

• Isotyping and quantitation of the humoral immune response to SARS-CoV-2 - Understanding the immune response to SARS-CoV-2 is important for development of effective diagnostics and vaccines. We report here a broad antibody response to SARS-CoV-2 spike protein receptor binding domain (RBD) in 100 convalescent patient plasma samples. Antibody isotypes IgA, IgM, and IgG exhibited significantly higher anti-RBD titers when compared to SARS-CoV-2 negative controls. IgG subtyping indicated IgG1 and IgG3 to be most abundant. Greater than 90 % of SARS- CoV-2 positive plasma…

• Atorvastatin Effectively Inhibits Ancestral and Two Emerging Variants of SARS-CoV-2 in vitro - This article evaluated the in vitro antiviral effect of atorvastatin (ATV) against SARS-CoV-2 and identified the interaction affinity between this compound and two SARS-CoV-2 proteins. The antiviral activity of atorvastatin against this virus was evaluated by three different treatment strategies [(i) pre-post treatment, (ii) pre-infection treatment, and (iii) post-infection treatment] using Vero E6 and Caco-2 cells. The interaction of atorvastatin with RdRp (RNA- dependent RNA polymerase) and 3CL…

• Aberrant Cholesterol Metabolic Genes Regulation in a Negative Feedback Loop Induced by an Alphacoronavirus - Porcine epidemic diarrhea virus (PEDV) is an alphacoronavirus that causes acute inflammation and severe diarrhea in newborn piglets with a high mortality rate. Given that cholesterol is required for coronavirus infection in vitro, the role of endogenous cholesterol metabolism in regulating coronavirus infection and the mechanism behind it ought to be elucidated. In this study, we found that the levels of cholesterol and bile acids were both elevated in the livers of PEDV-infected piglets…

• A glimpse into the future of systemic lupus erythematosus - This viewpoint article on a forecast of clinically meaningful changes in the management of systemic lupus erythematosus (SLE) in the next 10 years is based on a review of the current state of the art. The groundwork has been laid by a robust series of classification criteria and treatment recommendations that have all been published since 2019. Building on this strong foundation, SLE management predictably will take significant steps forward. Assessment for lupus arthritis will presumably…

• Production, characteristics and applications of microbial heparinases - Heparinases are enzymes that selectively cleave heparin and heparan sulfate chains, via cleavage of the glycosidic linkage between hexosamines and uronic acids, producing disaccharide and oligosaccharide products. While heparin is well known as an anti-coagulant drug, heparin and heparan sulfate are also involved in biological processes such as inflammation, cancer and angiogenesis and viral and bacterial infections and are of growing interest for their therapeutic potential. Recently, potential…

• Effect of Aspirin on the prevention of pro-thrombotic states in hospitalized COVID-19 patients: Systematic review - CONCLUSIONS: Aspirin as an antiplatelet and anti-inflammatory agent may reduce the mortality rates in hospitalized patients with severe COVID-19. Further observational studies are necessary to determine the effect of aspirin on the prevention of prothrombotic states in hospitalized COVID-19 patients. The study was registered in the Systematic Review Registration: PROSPERO (pending registration ID: 300515).

• Clinical data mining reveals Gancao-Banxia as a potential herbal pair against moderate COVID-19 by dual binding to IL-6/STAT3 - CONCLUSIONS: This work provided some potential candidate Chinese medicine formulas for moderate COVID-19. Among them, Gancao-Banxia was considered the most potential herbal pair. Bioinformatic data demonstrated that Gancao-Banxia pair may achieve dual inhibition of IL-6-STAT3 via directly interacting with IL-6 and STAT3, suppressing the IL-6 amplifier. SARS-CoV-2 models will be needed to validate this possibility in the future.

• Diacerein ameliorates acetaminophen hepatotoxicity in rats via inhibiting HMGB1/TLR4/NF-kappaB and upregulating PPAR-gamma signal - CONCLUSIONS: This study demonstrated that DIA exerts anti-apoptotic, anti-inflammatory, and antioxidant properties against liver injury induced by APAP that is attributed to inhibition of the HMGB1/TLR4/NF-κB pathway, besides upregulation of the expression of PPAR-γ.

• Recent advances in carbon quantum dots for virus detection, as well as inhibition and treatment of viral infection - In the last decade, carbon quantum dots (CQDs), as a novel class of carbon-based nanomaterials, have received increasing attention due to their distinct properties. CQDs are ultimately small nanoparticles with an average size below 10 nm, possessing high water solubility, alluring photoluminescence, photostability, excellent biocompatibility, low/none toxicity, environmental friendliness, and high sustainability, etc. In history, there are intermittent threats from viruses to humans, animals and…

• High failure rate of ChAdOx1-nCoV19 immunization against asymptomatic infection in healthcare workers during a Delta variant surge - Immunization is expected to confer protection against infection and severe disease for vaccines while reducing risks to unimmunized populations by inhibiting transmission. Here, based on serial serological studies of an observational cohort of healthcare workers, we show that during a Severe Acute Respiratory Syndrome -Coronavirus 2 Delta-variant outbreak in Delhi, 25.3% (95% Confidence Interval 16.9-35.2) of previously uninfected, ChAdOx1-nCoV19 double vaccinated, healthcare workers were…

From Patent Search

• MACHINE LEARNING TECHNIQUE TO ANALYZE THE WORK PRESSURE OF PARAMEDICAL STAFF DURING COVID 19 - Machine learning technique to analyse the work pressure of paramedical staff during covid 19 is the proposed invention that focuses on identifying the stress levels of paramedical staff. The invention focuses on analysing the level of stress that is induced on the paramedical staff especially during pandemic. - link

• CBD Covid 19 Protection - - link

• 沼泽红假单胞菌5-氨基乙酰丙酸合成酶突变体及应用 - 本发明公开了沼泽红假单胞菌5‑氨基乙酰丙酸合成酶突变体及应用，所述沼泽红假单胞菌5‑氨基乙酰丙酸合成酶突变体的氨基酸序列如SEQ ID NO.1所示。本发明的沼泽红假单胞菌5‑氨基乙酰丙酸合成酶突变体不仅相较于未突变的5‑氨基乙酰丙酸合成酶提高了酶活性，而且还提高了解调较高浓度血红素反馈抑制的能力，这使得本发明的宿主细胞生产5‑ALA的能力得到显著提升，约提升了40%。 - link

• 荚膜红细菌5-氨基乙酰丙酸合成酶突变体及应用 - 本发明提供了一种荚膜红细菌5‑氨基乙酰丙酸合成酶突变体及应用，荚膜红细菌5‑氨基乙酰丙酸合成酶突变体的氨基酸序列如SEQ ID NO.1所示。本发明的荚膜红细菌5‑氨基乙酰丙酸合成酶突变体与野生型的荚膜红细菌5‑氨基乙酰丙酸合成酶相比，在宿主细胞中对5‑氨基乙酰丙酸产量提升约22%；在20μM血红素存在下，突变型5‑氨基乙酰丙酸合成酶C201A能够保持较高的相对酶活。 - link

• METHOD AND SYSTEM FOR IMPLEMENTING IMPROVED GENERALIZED FUZZY PEER GROUP WITH MODIFIED TRILATERAL FILTER TO REMOVE MIXED IMPULSE AND ADAPTIVE WHITE GAUSSIAN NOISE FROM COLOR IMAGES - ABSTRACTMETHOD AND SYSTEM FOR IMPLEMENTING IMPROVED GENERALIZED FUZZY PEER GROUP WITH MODIFIED TRILATERAL FILTER TO REMOVE MIXED IMPULSE AND ADAPTIVE WHITE GAUSSIAN NOISE FROM COLOR IMAGESThe present invention provides a new approach is proposed that includes fuzzy-based approach and similarity function for filtering the mixed noise. In a peer group, the similarity function was adaptive to edge information and local noise level, which was utilized for detecting the similarity among pixels. In addition, a new filtering method Modified Trilateral Filter (MTF) with Improved Generalized Fuzzy Peer Group (IGFPG) is proposed to remove mixed impulse and Adaptive White Gaussian Noise from Color Images. The modified trilateral filter includes Kikuchi algorithm and loopy belief propagation to solve the inference issues on the basis of passing local message. In this research work, the images were collected from KODAK dataset and a few real time multimedia images like Lena were also used for testing the effectiveness of the proposed methodology. - link

• 一种病毒核酸提取无醇裂解液、试剂盒及提取方法 - 本发明公开了一种病毒核酸提取无醇裂解液、试剂盒及提取方法。本发明病毒核酸提取无醇裂解液由胍盐、无机盐、表面活性剂和缓冲液组成；所述胍盐为异硫氰酸胍和盐酸胍中的任一种或两种；所述无机盐为氯化钠和氯化钾中的任一种或两种；所述表面活性剂为聚乙二醇和吐温20；所述缓冲液的pH值为7.5~8.5。本发明可有效避免传统核酸提取裂解液中醇类挥发或刺激性气味对人体造成伤害；配制方法简单，无有毒化学试剂，安全无污染，既可手工操作提取，也可用于自动化平台；与有醇裂解液相比，病毒核酸检测的灵敏度相当，准确度一致，线性范围相当。 - link

• 用于预防SARS-CoV-2奥密克戎株的腺病毒载体疫苗 - 本发明涉及用于预防SARS‑CoV‑2奥密克戎株的腺病毒载体疫苗。本发明采用密码子偏好性进行优化得到新的S基因序列，其能高效在人源细胞内高效表达，免疫机体后可高效表达S抗原，产生针对奥密克戎株SARS‑CoV‑2的中和抗体，可以有效保护机体免受奥密克戎株的侵染。 - link

• 表达SARS-CoV-2奥密克戎突变株病毒抗原肽的核酸序列及其应用 - 本发明提供表达SARS‑CoV‑2奥密克戎突变株病毒抗原肽的核酸序列及其应用。奥密克戎株原始的S基因序列蛋白不能有效在细胞内高效表达；本发明采用密码子偏好性进行优化得到新的S基因序，使其能高效在人源细胞内高效表达，产生相应的多肽，诱导产生相应的免疫保护反应，为SARS‑CoV‑2奥密克戎株的疫苗的研发提供基础。 - link

• A STUDY ON MENTAL HEALTH, STRESS AND ANXIETY AMONG COLLEGE STUDENTS DURING COVID-19 - SARS-Cov-2 virus causes an infectious disease coronavirus(COVID-19).The Students life is made harder by COVID-19.The human reaction that happens normally to everyone through physical or emotional tension is stress. Feeling of angry, nervous and frustration caused through any thought or events leads to stress. As college closures and cancelled events, students are missing out on some of the biggest moments of their young lives as well as everyday moments like chatting with friend, participating in class and cultural programme. For students facing life changes due to the outbreak are feeling anxious, isolated and disappointed which lead them to feel all alone. We like to take the help of expert adolescent psychologist to find out the techniques to practice self-care and look after their mental health. We would like to find out whether techniques used reduce the anxiety and stress among Engineering Students. - link

• A METHOD FOR THE TREATMENT OF COVID-19 INFECTIONS WITH PALMITOYLETHANOLAMIDE - - link