Covid-19 Sentry

Contents

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

From Preprints

• An exploration of psychological trauma and positive adaptation in adults with congenital heart disease during the COVID-19 pandemic. -
  Introduction: The growing population of adults with congenital heart disease (CHD) often have lifelong experience of dealing with potentially traumatic health crises and medical uncertainty whilst facing increased vulnerability to post-traumatic stress disorder (PTSD). The COVID-19 pandemic presents additional challenges for this population including increased risk of health complications, shielding and strict social distancing, changes to medical care provision and social stigma. Despite such challenges, adults with CHD have the potential to also experience positive changes, yet little is known as to what helps cultivate positive adaptation and post-traumatic growth (PTG) within this context. Methods: The current study comprised a cross-sectional, anonymous, online study exploring psychosocial measures of traumatic experiences as well as protective factors that mitigate the risks to mental health on the mental health for adults with CHD (n=236) during the pandemic. Closed and open-ended questions and a series of standardised psychosocial measures of traumatic experiences, coping mechanisms, emotional regulation and PTG were measured. Results: Findings suggest the CHD population are at increased risk of PSTD which may be exacerbated by the COVID-19 pandemic. However, positive adaptation may promote post traumatic growth. In particular, health adversity is associated with greater appreciation whilst emotional regulation is associated with post-traumatic growth. Conclusions: We recommend a growth-focused, psychologically and trauma-informed approach to medicine and public health, recognising the importance of supporting mental health and promoting living well with CHD during the COVID-19 pandemic and beyond. These findings are likely generalisable to other lifelong health conditions and shielding populations.
  🖺 Full Text HTML: An exploration of psychological trauma and positive adaptation in adults with congenital heart disease during the COVID-19 pandemic.
• High viral SARS-CoV-2 load in placenta of patients with hypertensive disorders after COVID-19 during pregnancy -

  Introduction: Studies described an increased frequency of hypertensive disorders of pregnancy after a COVID-19 episode. There is limited evidence about SARS-CoV-2 viral load in placenta. This study aimed to investigate the relationship between SARS-CoV-2 viral load in placenta and clinical development of HDP after COVID-19 throughout different periods of gestation. Methods: This was a case-control study in women with and without gestational hypertensive disorders (HDP) after SARS-CoV-2 infection diagnosed by RT-PCR during pregnancy. Patients were matched by gestational age at the moment of COVID-19 diagnosis. We performed an analysis of SARS-CoV-2 RNA levels in placenta. Results: A total of 28 women were enrolled. Sixteen patients were diagnosed with COVID-19 during the third trimester and the remaining twelve patients in the others trimesters. Ten placentas (35.7%) were positive for SARS-CoV-2, nine of them (90%) belonged to the HDP group versus one (10%) in control group (p=0.009). Those cases with the highest loads of viral RNA developed severe-preeclampsia. Conclusion: The presence of SARS-CoV-2 was more frequent in placentas of patients with HDP after COVID-19. There seems to be a relationship between high viral load in the placenta and the development of hypertensive disorders. We found SARS-CoV-2 viral load in placenta after birth in mothers infected at the first half of pregnancy, but with negative nasopharyngeal RT-PCR at delivery. Our data suggest that SARS-CoV-2 infection during pregnancy could trigger gestational hypertensive disorders through placenta-related mechanisms.

  🖺 Full Text HTML: High viral SARS-CoV-2 load in placenta of patients with hypertensive disorders after COVID-19 during pregnancy
• Evaluation of commercially available high-throughput SARS-CoV-2 serological assays for serosurveillance and related applications -

  SARS-CoV-2 serosurveys can estimate cumulative incidence for monitoring epidemics but require characterization of employed serological assays performance to inform testing algorithm development and interpretation of results. We conducted a multi-laboratory evaluation of 21 commercial high-throughput SARS-CoV-2 serological assays using blinded panels of 1,000 highly-characterized blood-donor specimens. Assays demonstrated a range of sensitivities (96%-63%), specificities (99%-96%) and precision (IIC 0.55-0.99). Durability of antibody detection in longitudinal samples was dependent on assay format and immunoglobulin target, with anti-spike, direct, or total Ig assays demonstrating more stable, or increasing reactivity over time than anti-nucleocapsid, indirect, or IgG assays. Assays with high sensitivity, specificity and durable antibody detection are ideal for serosurveillance. Less sensitive assays demonstrating waning reactivity are appropriate for other applications, including characterizing antibody responses after infection and vaccination, and detection of anamnestic boosting by reinfections and vaccine breakthrough infections. Assay performance must be evaluated in the context of the intended use.

  🖺 Full Text HTML: Evaluation of commercially available high-throughput SARS-CoV-2 serological assays for serosurveillance and related applications
• Emergence of SARS-CoV-2 Resistance with Monoclonal Antibody Therapy -

  Resistance mutations to monoclonal antibody (mAb) therapy has been reported, but in the non-immunosuppressed population, it is unclear if in vivo emergence of SARS-CoV-2 resistance mutations alters either viral replication dynamics or therapeutic efficacy. In ACTIV-2/A5401, non-hospitalized participants with symptomatic SARS-CoV-2 infection were randomized to bamlanivimab (700mg or 7000mg) or placebo. Treatment-emergent resistance mutations were significantly more likely detected after bamlanivimab 700mg treatment than placebo (7% of 111 vs 0% of 112 participants, P=0.003). There were no treatment-emergent resistance mutations among the 48 participants who received bamlanivimab 7000mg. Participants with emerging mAb resistant virus had significantly higher pre-treatment nasopharyngeal and anterior nasal viral load. Intensive respiratory tract viral sampling revealed the dynamic nature of SARS-CoV-2 evolution, with evidence of rapid and sustained viral rebound after emergence of resistance mutations, and worsened symptom severity. Participants with emerging bamlanivimab resistance often accumulated additional polymorphisms found in current variants of concern/interest and associated with immune escape. These results highlight the potential for rapid emergence of resistance during mAb monotherapy treatment, resulting in prolonged high level respiratory tract viral loads and clinical worsening. Careful virologic assessment should be prioritized during the development and clinical implementation of antiviral treatments for COVID-19.

  🖺 Full Text HTML: Emergence of SARS-CoV-2 Resistance with Monoclonal Antibody Therapy
• GlycoSHIELD: a versatile pipeline to assess glycan impact on protein structures -
  More than 75% of surface and secreted proteins are modified by covalent addition of complex sugars through N- and O-glycosylation. Unlike proteins, glycans do not typically adopt specific secondary structures and remain very mobile, influencing protein dynamics and interactions with other molecules. Glycan conformational freedom impairs complete structural elucidation of glycoproteins. Computer simulations may be used to model glycan structure and dynamics. However, such simulations typically require thousands of computing hours on specialized supercomputers, thus limiting routine use. Here, we describe a reductionist method that can be implemented on personal computers to graft ensembles of realistic glycan conformers onto static protein structures in a matter of minutes. Using this open-source pipeline, we reconstructed the full glycan cover of SARS-CoV-2 Spike protein (S-protein) and a human GABAA receptor. Focusing on S-protein, we show that GlycoSHIELD recapitulates key features of extended simulations of the glycosylated protein, including epitope masking, and provides new mechanistic insights on N-glycan impact on protein structural dynamics.
  🖺 Full Text HTML: GlycoSHIELD: a versatile pipeline to assess glycan impact on protein structures
• Explaining daily total energy demand in British housing using linked smart meter and socio-technical data in a bottom-up statistical model -
  This paper investigates factors associated with variation in daily total energy consumption in domestic buildings using linked pre-COVID-19 smart meter, weather, building thermal characteristics, and socio-technical survey data covering appliance ownership, demographics, behaviours, and attitudes for a sub-sample of 617 British households selected from the Smart Energy Research Laboratory (SERL) Observatory panel. Linear mixed effects modelling resulted in marginal/conditional R2 of 0.68/0.83 and root mean squared error of 17.7 kWh/day, for daily gas and electricity use combined. Increased daily energy consumption was significantly associated (p-value<0.05) with: households living in buildings with larger floor area, more rooms, that are older, have lower energy efficiency, and experience colder or less sunny weather; households with more adult occupants, more children, older adult occupants, fewer adults with qualifications, higher heating temperature setpoints, that do not try to save energy, and that do not put on more clothes rather than turning the heating on. The results demonstrate the value of smart meter data linked with contextual data for improving understanding of energy demand in British housing. Accredited UK researchers are invited to apply to access the data which has recently been updated to include over 13,000 households from across Great Britain.
  🖺 Full Text HTML: Explaining daily total energy demand in British housing using linked smart meter and socio-technical data in a bottom-up statistical model
• Development of a novel, pan-variant aerosol intervention for COVID-19 -
  To develop a universal strategy to block SARS-CoV-2 cellular entry and infection represents a central aim for effective COVID-19 therapy. The growing impact of emerging variants of concern increases the urgency for development of effective interventions. Since ACE2 is the critical SARS-CoV-2 receptor and all tested variants bind to ACE2, some even at much increased affinity (see accompanying paper), we hypothesized that aerosol administration of clinical grade soluble human recombinant ACE2 (APN01) will neutralize SARS-CoV-2 in the airways, limit spread of infection in the lung and mitigate lung damage caused by deregulated signaling in the renin-angiotensin (RAS) and Kinin pathways. Here we show that intranasal administration of APN01 in a mouse model of SARS-CoV-2 infection dramatically reduced weight loss and prevented animal death. As a prerequisite to a clinical trial, we evaluated both virus binding activity and enzymatic activity for cleavage of Ang II following aerosolization. We report successful aerosolization for APN01, retaining viral binding as well as catalytic RAS activity. Dose range-finding and IND-enabling repeat-dose aerosol toxicology testing were conducted in dogs. Twice daily aerosol administration for two weeks at the maximum feasible concentration revealed no notable toxicities. Based on these results, a Phase I clinical trial in healthy volunteers can now be initiated, with subsequent Phase II testing in individuals with SARS-CoV-2 infection. This strategy could be used to develop a viable and rapidly actionable therapy to prevent and treat COVID-19, against all current and future SARS-CoV-2 variants.

• SARS-CoV-2 infection fatality rates in India: systematic review, meta-analysis and model-based estimation -

  Introduction Fervorous investigation and dialogue surrounding the true number of SARS-CoV-2 related deaths and implied infection fatality rates in India have been ongoing throughout the pandemic, and especially pronounced during the nations devastating second wave. We aim to synthesize the existing literature on the true SARS-CoV-2 excess deaths and infection fatality rates (IFR) in India, through a systematic search followed by viable meta-analysis. We then provide updated epidemiological model-based estimates of the wave 1, wave 2 and combined IFRs using an extension of the Susceptible-Exposed-Infected-Removed (SEIR) model, using data from April 1, 2020 to June 30, 2021. Methods Following PRISMA guidelines, the databases PubMed, Embase, Global Index Medicus, as well as BioRxiv, MedRxiv, and SSRN for preprints (accessed through iSearch), were searched on July 3, 2021 (with results verified through August 15, 2021). Altogether using a two-step approach, 4,765 initial citations were screened resulting in 37 citations included in the narrative review and 19 studies with 41 datapoints included in the quantitative synthesis. Using a random effects model with DerSimonian-Laird estimation, we meta-analyze IFR1 which is defined as the ratio of the total number of observed reported deaths divided by the total number of estimated infections and IFR2 (which accounts for death underreporting in the numerator of IFR1). For the latter, we provide lower and upper bounds based on the available range of estimates of death undercounting, often arising from an excess death calculation. The primary focus is to estimate pooled nationwide estimates of IFRs with the secondary goal of estimating pooled regional and state-specific estimates for SARS-CoV-2 related IFRs in India. We also try to stratify our empirical results across the first and the second wave. In tandem, we present updated SEIR model estimates of IFRs for waves 1, 2, and combined across the waves with observed case and death count data from April 1, 2020 to June 30, 2021. Results For India countrywide, underreporting factors (URF) for cases (sourced from serosurveys) range from 14.3-29.1 in the four nationwide serosurveys; URFs for deaths (sourced from excess deaths reports) range from 4.4-11.9 with cumulative excess deaths ranging from 1.79-4.9 million (as of June 2021). Nationwide pooled IFR1 and IFR2 estimates for India are 0.097% (95% confidence interval [CI]: 0.067 - 0.140) and 0.365% (95% CI: 0.264 - 0.504) to 0.485% (95% CI: 0.344 - 0.685), respectively, again noting that IFR2 changes as excess deaths estimates vary. Among the included studies in this meta-analysis, the IFR1 generally appear to decrease over time from the earliest study end date to the latest study end date (from 4 June 2020 to 6 July 2021, IFR1 changed from 0.199 to 0.055%), whereas a similar trend is not as readily evident for IFR2 due to the wide variation in excess death estimates (from 4 June 2020 to 6 July 2021, IFR2 ranged from (0.290-1.316) to (0.241-0.651) %). Nationwide SEIR model-based combined estimates for IFR1 and IFR2 are 0.101% (95% CI: 0.097 - 0.116) and 0.367% (95% CI: 0.358 - 0.383), respectively, which largely reconcile with the empirical findings and concur with the lower end of the excess death estimates. An advantage of such epidemiological models is the ability to produce daily estimates with updated data with the disadvantages being that these estimates are subject to numerous assumptions, arduousness of validation and not directly using the available excess death data. Whether one uses empirical data or model-based estimation, it is evident that IFR2 is at least 3.6 times more than IFR1. Conclusion When incorporating case and death underreporting, the meta- analyzed cumulative infection fatality rate in India varies from 0.36%-0.48%, with a case underreporting factor ranging from 25-30 and a death underreporting factor ranging from 4-12. This implies, by June 30, 2021, India may have seen nearly 900 million infections and 1.7-4.9 million deaths when the reported numbers stood at 30.4 million cases and 412 thousand deaths (covid19india.org) with an observed case fatality rate (CFR) of 1.35%. We reiterate the need for timely and disaggregated infection and fatality data to examine the burden of the virus by age and other demographics. Large degrees of nationwide and state-specific death undercounting reinforce the call to improve death reporting within India.

  🖺 Full Text HTML: SARS-CoV-2 infection fatality rates in India: systematic review, meta-analysis and model-based estimation
• Low dose hydroxychloroquine prophylaxis for COVID-19 - a prospective study -

  Background: Since the outbreak of COVID-19 pandemic, the world began a frantic search for possible prophylactic options. While trials on hydroxychloroquine (HCQ) prophylaxis are ongoing, concrete evidence is lacking. The study aimed to determine the relative efficacy of various doses of oral HCQ in prophylaxis and mitigating the severity of COVID-19 in healthcare workers. Methods: This was a prospective cohort with four arms (high, medium, low dose, and control) of HCQ prophylaxis, used by healthcare workers at a tertiary care center in India. Participants were grouped as per their opting for any one arm on a voluntary basis as per institute policy under the Government guidance. The outcomes studied were COVID-19 positivity by RT-PCR and its severity assessed by WHO COVID-19 severity scale. Results: Total 486 participants were enrolled, of which 29 (6%) opted for low dose, 2 (<1%) medium dose, and none for high dose HCQ while 455 (93.6%) were in the control arm. Of the 164 participants who underwent RT-PCR, 96 (58.2%) tested positive. Out of these 96 positive cases, the majority of them (79 of 96 [82.3%]) were ambulatory and were managed conservatively at home. Only 17.7% (17 of 96) participants, all of them from the control group, required hospitalization with the mild- moderate disease. None of the participants had severe disease, COVID-related complications, ICU stay, or death. The difference in the outcome assessed amongst the various arms was statistically insignificant (p value >0.05). Conclusion: This single-center study demonstrated that HCQ prophylaxis in healthcare workers does not cause a significant reduction in COVID-19 as well as mitigating its severity in those infected. At present, most of the trials have not shown any benefit. The debate continues to rage, should HCQ prophylaxis be given to healthcare workers for chemoprophylaxis?

  🖺 Full Text HTML: Low dose hydroxychloroquine prophylaxis for COVID-19 - a prospective study
• Mitoxantrone dihydrochloride, an FDA approved drug, binds with SARS-CoV-2 NSP1 C-terminal -
  One of the major virulence factors of SARS-CoV-2, NSP1, is a vital drug target due to its role in host immune evasion through multiple pathways. NSP1 protein is associated with inhibiting host mRNA translation by binding to the small subunit of ribosome through its C-terminal region. Previously, we have shown the structural dynamics of NSP1 C-terminal region (NSP1-CTR) in different physiological environments. So, it would be very interesting to investigate the druggable compounds that could bind with NSP1-CTR. Here, in this article, we have performed the different spectroscopic technique-based binding assays of an anticancer drug Mitoxantrone dihydrochloride (MTX) against the NSP1-CTR. We have also performed molecular docking followed by computational simulations with two different forcefields up to one microsecond. Overall, our results have suggested good binding between NSP1-CTR and MTX and may have implications in developing therapeutic strategies targeting NSP1 protein of SARS-CoV-2.
  🖺 Full Text HTML: Mitoxantrone dihydrochloride, an FDA approved drug, binds with SARS-CoV-2 NSP1 C-terminal
• Effect of ORF7 of SARS-CoV-2 on the chemotaxis of monocytes and neutrophils in vitro -
  Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the most significant public health threats in worldwide. Patients with severe COVID-19 usually have pneumonia concomitant with local inflammation and sometimes a cytokine storm. Specific components of the SARS-CoV-2 virus trigger lung inflammation, and recruitment of immune cells to the lungs exacerbates this process, although much remains unknown about the pathogenesis of COVID-19. Our study of lung type II pneumocyte cells (A549) demonstrated that ORF7, an open reading frame (ORF) in the genome of SARS-CoV-2, induced the production of CCL2, a chemokine that promotes the chemotaxis of monocytes, and decreased the expression of IL-8, a chemokine that recruits neutrophils. A549 cells also had an increased level of IL-6. The results of our chemotaxis transwell assay suggested that ORF7 augmented monocyte infiltration and reduced the number of neutrophils. We conclude that the ORF7 of SARS-CoV-2 may have specific effects on the immunological changes in tissues after infection. These results suggest that the functions of other ORFs of SARS- CoV-2 should also be comprehensively examined.
  🖺 Full Text HTML: Effect of ORF7 of SARS-CoV-2 on the chemotaxis of monocytes and neutrophils in vitro
• Prolific Induction of IL-6 in Human Cells by SARS-CoV-2-derived Peptide is Attenuated by Recombinant Human Anti- inflammatory Cytokines made in planta. -
  Development of efficient therapies for COVID-19 is the focus of intense research. The cytokine release syndrome was underlined as a culprit for severe outcomes in COVID-19 patients. Interleukin-6 (IL-6) plays a crucial role in human immune responses and elevated IL-6 plasma levels have been associated with the exacerbated COVID-19 pathology. Since non-structural protein 10 (NSP10) of SARS-CoV-2 has been implicated in the induction of IL-6, we designed Peptide (P)1, containing sequences corresponding to amino acids 68-96 of NSP10, and examined its effect on cultured human cells. Treatment with P1 strongly increased IL-6 secretion by the lung cancer cell line NCI-H1792 and the breast cancer cell line MDA-MB-231 and revealed profound cytotoxic activity on Caco-2 colorectal adenocarcinoma cells. Treatment with P2, harbouring a mutation in the zinc knuckle motif of NSP10, caused no IL-6 induction and no cytotoxicity. Pre-treatment with plant-produced human anti-inflammatory cytokines IL-37b and IL-38 effectively mitigated the induction of IL-6 secretion. Our results suggest a role for the zinc knuckle motif of NSP10 in the onset of increased IL-6 plasma levels of COVID-19 patients and for IL-37b and IL-38 as therapeutics aimed at attenuating the cytokine release syndrome.

• SARS-CoV-2 Spike Protein Regulation of Angiotensin Converting Enzyme 2 and Tissue Renin-Angiotensin Systems: Influence of Biologic Sex -
  Angiotensin converting enzyme 2 (ACE2) is an enzyme that limits activity of the renin-angiotensin system (RAS) and also serves as a receptor for the SARS-CoV-2 Spike (S) protein. Binding of S protein to ACE2 causes internalization which activates local RAS. ACE2 is on the X chromosome and its expression is regulated by sex hormones. In this study, we defined ACE2 mRNA abundance and examined effects of S protein on ACE2 activity and/or angiotensin II (AngII) levels in pivotal tissues (lung, adipose) from male and female mice. In lung, ACE2 mRNA abundance was reduced following gonadectomy (GDX) of male and female mice and was higher in XX than XY mice of the Four Core Genotypes (FCG). Reductions in lung ACE2 mRNA abundance by GDX occurred in XX, but not XY FCG female mice. Lung mRNA abundance of ADAM17 and TMPRSS2, enzymes that shed cell surface ACE2 and facilitate viral cell entry, was reduced by GDX in male but not female mice. For comparison, adipose ACE2 mRNA abundance was higher in female than male mice and higher in XX than XY FCG mice. Adipose ADAM17 mRNA abundance was increased by GDX of male and female mice. S protein reduced ACE2 activity in alveolar type II epithelial cells and 3T3-L1 adipocytes. Administration of S protein to male and female mice increased lung AngII levels and decreased adipose ACE2 activity in male but not female mice. These results demonstrate that sex differences in ACE2 expression levels may impact local RAS following S protein exposures.
  🖺 Full Text HTML: SARS-CoV-2 Spike Protein Regulation of Angiotensin Converting Enzyme 2 and Tissue Renin-Angiotensin Systems: Influence of Biologic Sex
• BNT162b2-Elicited Neutralization of Delta Plus, Lambda, and Other Variants -
  BNT162b2-elicited human sera are known to neutralize the currently dominant Delta SARS-CoV-2 variant. Here, we report the ability of 20 human sera, drawn 2 or 4 weeks after two doses of BNT162b2, to neutralize USA-WA1/2020 SARS- CoV-2 bearing variant spikes from Delta plus (Delta-AY.1, Delta-AY.2), Delta-{triangleup}144 (Delta with the Y144 deletion of the Alpha variant), Lambda, and B.1.1.519 lineage viruses. Geometric mean plaque reduction neutralization titers against Delta-AY.1, Delta-AY.2, and Delta-{triangleup}144 viruses are slightly lower than against USA-WA1/2020, but all sera neutralize the variant viruses to titers of [≥]80. Neutralization titers against Lambda and B.1.1.519 variants and against USA-WA1/2020 are equivalent. The susceptibility of Delta plus, Lambda, and other variants to neutralization by the sera indicates that antigenic change has not led to virus escape from vaccine-elicited neutralizing antibodies and supports ongoing mass immunization with BNT162b2 to control the variants and to minimize the emergence of new variants.
  🖺 Full Text HTML: BNT162b2-Elicited Neutralization of Delta Plus, Lambda, and Other Variants
• Protective Efficacy of Gastrointestinal SARS-CoV-2 Delivery Against Intranasal and Intratracheal SARS-CoV-2 Challenge in Rhesus Macaques -
  Live oral vaccines have been explored for their protective efficacy against respiratory viruses, particularly for adenovirus serotypes 4 and 7. The potential of a live oral vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), however, remains unclear. In this study, we assessed the immunogenicity of live SARS-CoV-2 delivered to the gastrointestinal tract in rhesus macaques and its protective efficacy against intranasal and intratracheal SARS- CoV-2 challenge. Post-pyloric administration of SARS-CoV-2 by esophagogastroduodenoscopy resulted in limited virus replication in the gastrointestinal tract and minimal to no induction of mucosal antibody titers in rectal swabs, nasal swabs, and bronchoalveolar lavage. Low levels of serum neutralizing antibodies were induced and correlated with modestly diminished viral loads in nasal swabs and bronchoalveolar lavage following intranasal and intratracheal SARS-CoV-2 challenge. Overall, our data show that post-pyloric inoculation of live SARS-CoV-2 is weakly immunogenic and confers partial protection against respiratory SARS-CoV-2 challenge in rhesus macaques.
  🖺 Full Text HTML: Protective Efficacy of Gastrointestinal SARS-CoV-2 Delivery Against Intranasal and Intratracheal SARS- CoV-2 Challenge in Rhesus Macaques

From Clinical Trials

• Finding Treatments for COVID-19: A Trial of Antiviral Pharmacodynamics in Early Symptomatic COVID-19 (PLATCOV) - Condition:   COVID-19
  Interventions:   Drug: Favipiravir;   Drug: Monoclonal antibodies;   Drug: Ivermectin;   Other: No treatment;   Drug: Remdesivir
  Sponsor:   University of Oxford
  Not yet recruiting

• Study on Safety and Clinical Efficacy of AZVUDINE in Initial Stage COVID-19 Patients (SARS-CoV-2 Infected) - Condition:   COVID-19
  Interventions:   Drug: AZVUDINE;   Drug: AZVUDINE placebo
  Sponsors:   HRH Holdngs Limited;   GALZU INSTITUTE OF RESEARCH, TEACHING, APPLIED SCIENCE AND TECHNOLOGY, Brazil;   SANTA CASA DE MISERICORDIA DE CAMPOS HOSPITAL (SCMCH), Brazil;   UNIVERSIDADE ESTADUAL DO NORTE FLUMINENSE (UENF), Brazil
  Not yet recruiting

• COVID-19 Morbidity in Healthcare Workers and Vitamin D Supplementation - Condition:   COVID-19 Respiratory Infection
  Intervention:   Drug: Vitamin D
  Sponsor:   Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health
  Completed

• TThe Safety and Efficacy of SCTV01C in Population Aged ≥18 Years Previously Vaccinated With Inactivated COVID-19 Vaccine.Healthy Population Aged ≥18 Years Previously Vaccinated With Inactivated COVID-19 Vaccine. - Conditions:   COVID-19;   SARS-CoV-2 Infection
  Interventions:   Biological: SCTV01C;   Other: Placebo
  Sponsor:   Sinocelltech Ltd.
  Not yet recruiting

• The Safety and Efficacy of SCTV01C in Population Aged ≥18 Years Previously Vaccinated With Inactivated COVID-19 Vaccine.Healthy Population Aged ≥18 Years Previously Vaccinated With Adenovirus Vectored or mRNA COVID-19 Vaccine. - Conditions:   COVID-19;   SARS-CoV-2 Infection
  Interventions:   Biological: SCTV01C;   Other: Placebo
  Sponsor:   Sinocelltech Ltd.
  Not yet recruiting

• Heterologous Prime-boost Immunization With an Aerosolised Adenovirus Type-5 Vector-based COVID-19 Vaccine (Ad5-nCoV) After Priming With an Inactivated SARS-CoV-2 Vaccine - Condition:   COVID-19
  Interventions:   Biological: inactive SARS-CoV-2 vaccine (Vero cell);   Biological: Low dose aerosolized Ad5-nCoV;   Biological: High dose aerosolized Ad5-nCoV
  Sponsor:   Jiangsu Province Centers for Disease Control and Prevention
  Not yet recruiting

• Text Message Nudges for COVID-19 Vaccination - Condition:   Covid19
  Intervention:   Behavioral: Text message
  Sponsor:  
  Ascension South East Michigan
  Not yet recruiting

• A Pilot Study of a PhysiOthErapy-based Tailored Intervention for Long Covid - Condition:   COVID-19
  Intervention:   Behavioral: Physiotherapy
  Sponsors:  
  University of Calgary;   Alberta Health Services
  Not yet recruiting

• Combined Antihistaminics Therapy in COVID 19 Patients - Condition:   Covid19
  Interventions:   Drug: Loratadine;   Drug: Famotidine
  Sponsors:   Ain Shams University;   Nasr City Insurance Hospital
  Not yet recruiting

• Prevention and Treatment of Patient Before, During, and After Covid-19 Infection - Condition:   Covid19
  Intervention:   Drug: AntiCov-220
  Sponsor:  
  Nguyen Thi Trieu, MD
  Active, not recruiting

• Quercetin in the Prevention of Covid-19 Infection - Condition:   Covid19
  Interventions:   Dietary Supplement: Quercetin;   Combination Product: Placebo
  Sponsor:   Azienda di Servizi alla Persona di Pavia
  Completed

• A Study to Evaluate Change in Viral Load After OPN-019 in Adults With COVID-19 - Condition:   Covid19
  Intervention:   Drug: OPN-019
  Sponsor:   Optinose US Inc.
  Recruiting

• Physical Activity and Smell Trainings to Help Individuals With Coronavirus Disease (COVID-19) Recover From Persistent Smell and Taste Impairments - A Pilot Study - Condition:   Covid19
  Interventions:   Behavioral: Physical activity;   Other: Smell training
  Sponsor:   Université de Montréal
  Not yet recruiting

• Phase 3 Study to Evaluate the Lot Consistency of a Recombinant Coronavirus-Like Particle COVID-19 Vaccine - Condition:   COVID-19
  Intervention:   Biological: CoVLP formulation
  Sponsor:  
  Medicago
  Not yet recruiting

• Safety and Efficacy of KOVIR in the Combination Regimen With Background Treatment in COVID-19 Patients (KOVIR) - Condition:   COVID-19
  Interventions:   Drug: KOVIR oral capsule;   Drug: Placebo oral capsule
  Sponsors:   Sunstar Joint Stock Company;   Big Leap Clinical Research Joint Stock Company
  Completed

From PubMed

• N-Terminal Modification of Gly-His-tagged Proteins with Azidogluconolactone - Site-specific protein modifications are vital for biopharmaceutical drug development. Gluconoylation is a non-enzymatic, post-translational modification of N-terminal HisTags. We report high-yield, site-selective in vitro α-aminoacylation of peptides, glycoproteins, antibodies, and Virus-like particles (VLPs) with azidogluconolactone at pH 7.5 in 1 h. Conjugates slowly hydrolyse, but diol-masking with borate esters inhibits reversibility. In an example, we multimerise azidogluconoylated…

• Influence of coronavirus disease 2019 on myopic progression in children treated with low-concentration atropine - CONCLUSIONS: The rates of myopic progression have increased substantially after the spread of COVID-19 with an increase in the home confinement of children. Therefore, it is necessary to control the environmental risk factors for myopia, even in children undergoing treatment for the inhibition of myopic progression.

• New Chalcone Derivatives as Effective Anti-SARS-CoV-2 Agents - CONCLUSIONS: Computational analyses identified eight compounds inhibiting each target, with binding affinity scores ranging from -4,370 to -2,748 kcal/mol along with their toxicological, ADME, and drug-like properties.

• Efficacy of Combination Therapy With The JAK Inhibitor Baricitinib In The Treatment of COVID-19 - CONCLUSIONS: These findings support the utility of immunosuppression via JAK inhibition in moderate to severe COVID-19 pneumonia.

• Social network-based cohorting to reduce the spread of SARS-CoV-2 in secondary schools: A simulation study in classrooms of four European countries - BACKGROUND: Operating schools safely under pandemic conditions is a widespread policy goal. We analyse the effectiveness of classroom cohorting, i.e., the decomposition of classrooms into smaller isolated units, in inhibiting the spread of SARS-CoV-2 in European secondary schools and compare different cohorting strategies.

• Telaprevir is a potential drug for repurposing against SARS-CoV-2: computational and in vitro studies - Drug repurposing is an important approach to the assignment of already approved drugs for new indications. This technique bypasses some steps in the traditional drug approval system, which saves time and lives in the case of pandemics. Direct acting antivirals (DAAs) have repeatedly repurposed from treating one virus to another. In this study, 16 FDA-approved hepatitis C virus (HCV) DAA drugs were studied to explore their activities against severe acute respiratory syndrome coronavirus 2…

• Endocytosis of abiotic nanomaterials and nanobiovectors: Inhibition of membrane trafficking - Humans are exposed to nanoscopical nanobiovectors (e.g. coronavirus SARS-CoV-2) as well as abiotic metal/carbon-based nanomaterials that enter cells serendipitously or intentionally. Understanding the interactions of cell membranes with these abiotic and biotic nanostructures will facilitate scientists to design better functional nanomaterials for biomedical applications. Such knowledge will also provide important clues for the control of viral infections and the treatment of virus-induced…

• Polymeric Materials as Potential Inhibitors Against SARS-CoV-2 - Recently discovered SARS-CoV-2 caused a pandemic that triggered researchers worldwide to focus their research on all aspects of this new peril to humanity. However, in the absence of specific therapeutic intervention, some preventive strategies and supportive treatment minimize the viral transmission as studied by some factors such as basic reproduction number, case fatality rate, and incubation period in the epidemiology of viral diseases. This review briefly discusses coronaviruses’ life cycle…

• Asunaprevir, a Potent Hepatitis C Virus Protease Inhibitor, Blocks SARS-CoV-2 Propagation - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has become a global health concern. Various SARS-CoV-2 vaccines have been developed and are being used for vaccination worldwide. However, no therapeutic agents against coronavirus disease 2019 (COVID-19) have been developed so far; therefore, new therapeutic agents are urgently needed. In the present study, we evaluated several hepatitis C virus direct-acting antivirals as potential candidates for drug repurposing against…

• Dehydrozingerone ameliorates Lipopolysaccharide induced acute respiratory distress syndrome by inhibiting cytokine storm, oxidative stress via modulating the MAPK/NF-kappaB pathway - CONCLUSION: This study demonstrates for the first time that DHZ has the potential to ameliorate LPS induced ARDS by inhibiting cytokine storm and oxidative through modulating the MAPK and NF-κB pathways. This data provides pre-clinical support to develop DHZ as a potential therapeutic agent against ARDS.

• Genomics-guided targeting of stress granule proteins G3BP1/2 to inhibit SARS-CoV-2 propagation - SARS-CoV-2 nucleocapsid (N) protein undergoes RNA-induced phase separation (LLPS) and sequesters the host key stress granule (SG) proteins, Ras-GTPase-activating protein SH3-domain-binding protein 1 and 2 (G3BP1 and G3BP2) to inhibit SG formation. This will allow viral packaging and propagation in host cells. Based on a genomic-guided meta-analysis, here we identify upstream regulatory elements modulating the expression of G3BP1 and G3BP2 (collectively called G3BP1/2). Using this strategy, we…

• Characterization of the NiRAN domain from RNA-dependent RNA polymerase provides insights into a potential therapeutic target against SARS-CoV-2 - Apart from the canonical fingers, palm and thumb domains, the RNA dependent RNA polymerases (RdRp) from the viral order Nidovirales possess two additional domains. Of these, the function of the Nidovirus RdRp associated nucleotidyl transferase domain (NiRAN) remains unanswered. The elucidation of the 3D structure of RdRp from the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), provided the first ever insights into the domain organisation and possible functional characteristics of…

• SARS-COV-2 M(pro) conformational changes induced by covalently bound ligands - SARS-CoV-2’s main protease (M^(pro)) interaction with ligands has been explored with a myriad of crystal structures, most of the monomers. Nonetheless, M^(pro) is known to be active as a dimer but the relevance of the dimerization in the ligand-induced conformational changes has not been fully elucidated. We systematically simulated different M^(pro)-ligand complexes aiming to study their conformational changes and interactions, through molecular dynamics (MD). We focused on covalently bound…

• Targeted Redesign of Suramin Analogs for Novel Antimicrobial Lead Development - The emergence of new viral infections and drug-resistant bacteria urgently necessitates expedient therapeutic development. Repurposing and redesign of existing drugs against different targets are one potential way in which to accelerate this process. Suramin was initially developed as a successful antiparasitic drug but has also shown promising antiviral and antibacterial activities. However, due to its high conformational flexibility and negative charge, suramin is considered quite promiscuous…

• Remdesivir: A Closer Look at Its Effect in COVID-19 Pandemic - BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiology of COVID-19 pandemic, resulted in significant harm to the affected countries in every aspect of life. The virus infected over 139 million patients and resulted in over 2.9 million deaths until April 16, 2021. New variants of this virus were identified that spread rapidly worldwide.

From Patent Search

• MACHINE LEARNING TECHNIQUE TO ANALYSE THE CONDITION OF COVID-19 PATIENTS BASED ON THEIR SATURATION LEVELS - - link

• A HERB BASED COMPOSITION ANTI VIRAL MEDICINE FOR TREATMENT OF SARS COV 2 AND A METHOD FOR TREATING A PERSON INFECTED BY THE SARS COV 2 VIRUS - A Herbal composition, viz., PONNU MARUNTHU essentially comprising of ALLUIUM CEPA extract. [concentrated to 30%] 75%, SAPINDUS MUKOROSSI - extract [Optimised] 10%, CITRUS X LIMON - extract in its natural form 05 TRACYSPERMUM AMMI (L) – extract 07%,ROSA HYBRIDA - extract 03%, PONNU MARUNTHU solution 50 ml, or as a capsulated PONNU MARUNTHU can be given to SARS cov2 positive Patients, three times a day that is ½ an hour before food; continued for 3 days to 5 days and further taking it for 2 days if need be there; It will completely cure a person. When the SARS cov2 test shows negative this medicine can be discontinued. This indigenous medicine and method for treating a person inflicted with SARS COV 2 viral infection is quite effective in achieving of much needed remedy for the patients and saving precious lives from the pangs of death and ensuring better health of people. - link

• Anti-Sars-Cov-2 Neutralizing Antibodies - - link

• Expression Vector for Anti-Sars-Cov-2 Neutralizing Antibodies - - link

• DEVELOPMENT OF CNN SCHEME FOR COVID-19 DISEASE DETECTION USING CHEST RADIOGRAPH - - link

• 一种检测新型冠状病毒的引物探针组合及其应用 - 本发明提供了一种检测新型冠状病毒的引物探针组合及其应用，所述检测新型冠状病毒的引物探针组合包括特异性扩增并检测2019‑nCoV的ORF1ab基因、核壳蛋白N基因和刺突蛋白S基因N501Y突变位点的特异性引物对和探针。本发明还提供了一种检测新型冠状病毒的试剂盒及其以非疾病诊断和/或治疗为目的的使用方法。本发明所述检测新型冠状病毒的引物探针组合具有良好的特异性与灵敏度，配合优化后的检测体系，可以对待测样本进行快速准确的检测，并可以对整个实验流程进行监控，降低假阳性以及假阴性检测结果的出现概率，具有重要的意义。 - link

• SARS-COV-2 BINDING PROTEINS - - link

• COVID-19胸部CT图像识别方法、装置及电子设备 - 本申请涉及一种COVID‑19胸部CT图像识别方法、装置及电子设备。所述方法获取COVID‑19的胸部CT图像，并针对胸部CT图像的特点，构建新冠肺炎CT识别网络，对该网络进行训练得到COVID‑19胸部CT图像识别模型，并利用该模型对待测CT图像进行分类。采用空洞卷积、深度卷积以及点卷积算子，减少冗余参数；采用并行结构连接方式，实现多尺度特征融合、降低模型复杂度；采用下采样方式，使用最大模糊池化以减少锯齿效应，保持信号的平移不变性；采用通道混洗操作，减少参数量与计算量，提高分类准确率，引入坐标注意力机制，使空间坐标信息与通道信息被关注，抑制不重要的信息，以解决资源匹配问题。 - link

• A PROCESS FOR PREPARING MONTELUKAST SODIUM FOR TREATING COVID 19 PATIENTS - - link

• IDENTIFICATION OF ANTI-COVID 19 AGENT SOMNIFERINE AS INHIBITOR OF MPRO & ACE2-RBD INTERACTION - - link