Covid-19 Sentry

Contents

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

From Preprints

• Aripiprazole as a candidate treatment of COVID-19 identified through genomic analysis -

  Background: Antipsychotics suppress expression of inflammatory cytokines and inducible inflammatory enzymes. Elopiprazole (a phenylpiperazine antipsychotic drug in phase 1) has been characterized as a therapeutic drug to treat SARS-CoV-2 infection in a repurposing study. We aim to investigate the potential effects of aripiprazole (an FDA approved phenylpiperazine) on COVID19-related immunological parameters. Methods: Differential gene expression profiles of non-COVID versus COVID RNA-Seq samples (CRA002390 project in GSA database) and drug-naive patients with psychosis at baseline and after three months of aripiprazole treatment was identified. An integrative analysis between COVID and aripiprazole immunomodulatory antagonist effects was performed. Findings: 82 out the 377 genes (21.7%) with expression significantly altered by aripiprazole have also their expression altered in COVID-19 patients and in 93.9% of these genes their expression is reverted by aripiprazole. The number of common genes with expression altered in both analyses is significantly higher than expected (Fisher9s Exact Test, two tail; P value=3.2e-11). 11 KEGG pathways were significantly enriched with genes with altered expression both in COVID-19 patients and aripiprazole medicated schizophrenia patients (P adj<0.05). The most significant pathways were associated to the immune system such as the inflammatory bowel disease (IBD) (the most significant pathway with a P adj of 0.00021), Th1 and Th2 cell differentiation and B cell receptor signaling pathway, all three related to the defense against infections. Interpretation: This exploratory investigation may provide further support to the notion that protective effect is exerted by phenylpiperazine by modulating the immunological dysregulation associated to COVID-19. Along with many ongoing studies and clinical trials, repurposing available medications could be of use in countering SARS-CoV-2 infection, but require further studies and trials.

  🖺 Full Text HTML: Aripiprazole as a candidate treatment of COVID-19 identified through genomic analysis
• Mask exposure during COVID-19 changes emotional face processing -
  Faces are one of the key ways that we obtain social information about others. They allow people to identify individuals, understand conversational cues, and make judgements about other’s mental states. When the COVID-19 pandemic hit the United States, widespread mask-wearing practices were implemented, causing a shift in the way Americans typically interact. This introduction of masks into social exchanges posed a potential challenge – how would people make these important inferences about others when a large source of information was no longer available? We conducted two studies that investigated the impact of mask exposure on emotion perception. In particular, we measured how participants used facial landmarks (visual cues) and the expressed valence and arousal (affective cues), to make similarity judgements about pairs of emotion faces. Study 1 found that participants with higher levels of mask exposure used cues from the eyes to a greater extent when judging emotion similarity than participants with less mask exposure. Study 2 measured participants’ emotion perception in both April and September 2020 – before and after widespread mask adoption – in the same group of participants to examine changes in the use of facial cues over time. Results revealed an overall increase in the use of visual cues from April to September. Further, as mask exposure increased, people with the most social interaction showed the largest increase in the use of visual facial cues. These results provide evidence that a shift has occurred in how people process faces such that the more people are interacting with others that are wearing masks, the more they have learned to focus on visual cues from the eye area of the face.
  🖺 Full Text HTML: Mask exposure during COVID-19 changes emotional face processing
• Parental Social Isolation and Child Maltreatment Risk During the COVID-19 Pandemic -
  Background: On March 11, 2020, COVID-19 was declared a pandemic by the World Health Organization. The social isolation and economic stress resulting from pandemic have the potential to exacerbate child abuse and neglect. Objective: This study examines the association of parents’ perceived social isolation and recent employment loss to risk for child maltreatment (neglect, verbal aggression, and physical punishment) in the early weeks of the COVID-19 pandemic. Participants and Setting: Participants (N = 283) were adults living in the U.S. who were parents of at least one child 0-12 years of age. Methods: Participants completed an online survey approximately 2 weeks after the World Health Organization declared that COVID-19 was a pandemic. The survey asked about recent changes (i.e., in the past 2 weeks) to employment status, parenting behaviors, use of discipline, use of spanking, and depressive symptoms. Results: Parents’ perceived social isolation and recent employment loss were associated with self-report of physical and emotional neglect and verbal aggression against the child, even after statistically controlling for parental depressive symptoms, income, and sociodemographic factors. Parents’ perceived social isolation was associated with parental report of changes in discipline, specifically, using discipline and spanking more often in the past 2 weeks. Associations were robust to analyses that included two variables that assessed days spent social distancing and days spent in “lockdown.” Conclusions: Study results point to the need for mental health supports to parents and children to ameliorate the strain created by COVID-19.
  🖺 Full Text HTML: Parental Social Isolation and Child Maltreatment Risk During the COVID-19 Pandemic
• Diverse Functional Autoantibodies in Patients with COVID-19 -

  COVID-19 manifests with a wide spectrum of clinical phenotypes that are characterized by exaggerated and misdirected host immune responses. While pathological innate immune activation is well documented in severe disease, the impact of autoantibodies on disease progression is less defined. Here, we used a high-throughput autoantibody discovery technique called Rapid Extracellular Antigen Profiling (REAP) to screen a cohort of 194 SARS-CoV-2 infected COVID-19 patients and healthcare workers for autoantibodies against 2,770 extracellular and secreted proteins (the "exoproteome"). We found that COVID-19 patients exhibit dramatic increases in autoantibody reactivities compared to uninfected controls, with a high prevalence of autoantibodies against immunomodulatory proteins including cytokines, chemokines, complement components, and cell surface proteins. We established that these autoantibodies perturb immune function and impair virological control by inhibiting immunoreceptor signaling and by altering peripheral immune cell composition, and found that murine surrogates of these autoantibodies exacerbate disease severity in a mouse model of SARS-CoV-2 infection. Analysis of autoantibodies against tissue-associated antigens revealed associations with specific clinical characteristics and disease severity. In summary, these findings implicate a pathological role for exoproteome-directed autoantibodies in COVID-19 with diverse impacts on immune functionality and associations with clinical outcomes.

  🖺 Full Text HTML: Diverse Functional Autoantibodies in Patients with COVID-19
• Addressing Personal Protective Equipment (PPE) Decontamination: Methylene Blue and Light Inactivates SARS-CoV-2 on N95 Respirators and Masks with Maintenance of Integrity and Fit -

  Background: The coronavirus disease 2019 (COVID-19) pandemic has resulted in severe shortages of personal protective equipment (PPE) necessary to protect front-line healthcare personnel. These shortages underscore the urgent need for simple, efficient, and inexpensive methods to decontaminate SARS-CoV-2-exposed PPE enabling safe reuse of masks and respirators. Efficient decontamination must be available not only in low-resourced settings, but also in well-resourced settings affected by PPE shortages. Methylene blue (MB) photochemical treatment, hitherto with many clinical applications including those used to inactivate virus in plasma, presents a novel approach for widely applicable PPE decontamination. Dry heat (DH) treatment is another potential low-cost decontamination method. Methods: MB and light (MBL) and DH treatments were used to inactivate coronavirus on respirator and mask material. We tested three N95 filtering facepiece respirators (FFRs), two medical masks (MMs), and one cloth community mask (CM). FFR/MM/CM materials were inoculated with SARS-CoV-2 (a Betacoronavirus), murine hepatitis virus (MHV) (a Betacoronavirus), or porcine respiratory coronavirus (PRCV) (an Alphacoronavirus), and treated with 10 μM MB followed by 50,000 lux of broad-spectrum light or 12,500 lux of red light for 30 minutes, or with 75°C DH for 60 minutes. In parallel, we tested respirator and mask integrity using several standard methods and compared to the FDA-authorized vaporized hydrogen peroxide plus ozone (VHP+O3) decontamination method. Intact FFRs/MMs/CM were subjected to five cycles of decontamination (5CD) to assess integrity using International Standardization Organization (ISO), American Society for Testing and Materials (ASTM) International, National Institute for Occupational Safety and Health (NIOSH), and Occupational Safety and Health Administration (OSHA) test methods. Findings: Overall, MBL robustly and consistently inactivated all three coronaviruses with at least a 4-log reduction. DH yielded similar results, with the exception of MHV, which was only reduced by 2-log after treatment. FFR/MM integrity was maintained for 5 cycles of MBL or DH treatment, whereas one FFR failed after 5 cycles of VHP+O3. Baseline performance for the CM was variable, but reduction of integrity was minimal. Interpretation: Methylene blue with light and DH treatment decontaminated masks and respirators by inactivating three tested coronaviruses without compromising integrity through 5CD. MBL decontamination of masks is effective, low-cost and does not require specialized equipment, making it applicable in all-resource settings. These attractive features support the utilization and continued development of this novel PPE decontamination method.

  🖺 Full Text HTML: Addressing Personal Protective Equipment (PPE) Decontamination: Methylene Blue and Light Inactivates SARS-CoV-2 on N95 Respirators and Masks with Maintenance of Integrity and Fit
• Social and racial inequalities in COVID-19 risk of hospitalisation and death across Sao Paulo state, Brazil -

  Background: Little evidence exists on the differential health effects of COVID-19 on disadvantaged population groups. Here we characterise the differential risk of hospitalisation and death in Sao Paulo state, Brazil and show how vulnerability to COVID-19 is shaped by socioeconomic inequalities. Methods: We conducted a cross-sectional study using hospitalised severe acute respiratory infections (SARI) notified from March to August 2020, in the Sistema de Monitoramento Inteligente de Sao Paulo (SIMI-SP) database. We examined the risk of hospitalisation and death by race and socioeconomic status using multiple datasets for individual-level and spatio-temporal analyses. We explained these inequalities according to differences in daily mobility from mobile phone data, teleworking behaviour, and comorbidities. Findings: Throughout the study period, patients living in the 40% poorest areas were more likely to die when compared to patients living in the 5% wealthiest areas (OR: 1.60, 95% CI: 1.48 - 1.74) and were more likely to be hospitalised between April and July, 2020 (OR: 1.08, 95% CI: 1.04 - 1.12). Black and Pardo individuals were more likely to be hospitalised when compared to White individuals (OR: 1.37, 95% CI: 1.32 - 1.41; OR: 1.23, 95% CI: 1.21 - 1.25, respectively), and were more likely to die (OR: 1.14, 95% CI: 1.07 - 1.21; 1.09, 95% CI: 1.05 - 1.13, respectively). Interpretation: Low-income and Black and Pardo communities are more likely to die with COVID-19. This is associated with differential access to healthcare, adherence to social distancing, and the higher prevalence of comorbidities.

  🖺 Full Text HTML: Social and racial inequalities in COVID-19 risk of hospitalisation and death across Sao Paulo state, Brazil
• Longitudinal Analysis of Short-term Changes in Relationship Conflict During COVID-19: A Risk and Resilience Perspective -
  This study uses a risk and resilience framework to examine short-term self-reported changes in relationship conflict early in the COVID-19 pandemic (March and April 2020). Longitudinal data from U.S. adults in a romantic relationship (N = 291) were collected via three waves of an online survey. Participants self-reported anxiety, depression, increased alcohol use, and dyadic coping since the pandemic. Relationship conflict variables included whether the participant reported that they and their partner “had disagreements related to the Coronavirus,” “had more disagreements than usual,” “had more verbal fights than usual,” and “had more physical fights than usual” in the past 2 weeks. Analyses controlled for sociodemographic characteristics as well as days spent in lockdown and employment change due to COVID-19. Results indicated that couples’ disagreement and verbal fighting scores increased from Time 1 to Time 2, but disagreements related to COVID-19 and physical fighting did not. Couples with higher levels of dyadic coping reported fewer fights and disagreements on average. However, dyadic coping did not buffer participants from increases in relationship conflict. Increased alcohol use since the pandemic was positively associated with disagreements related to COVID-19, disagreement scores, and verbal fighting scores. More days spent in lockdown was associated with increases in disagreements related to COVID-19. The conditions created by COVID-19 may contribute to worsening relationship conflict, even among couples who start with high levels of dyadic coping. Depression and alcohol use may contribute to poorer relationship quality during the pandemic. There is need for enhanced intervention and mental health supports to mitigate the potential effects of the pandemic on couples’ relationship functioning.
  🖺 Full Text HTML: Longitudinal Analysis of Short-term Changes in Relationship Conflict During COVID-19: A Risk and Resilience Perspective
• The MERS-CoV receptor gene is among COVID-19 risk factors inherited from Neandertals -
  In the current SARS-CoV-2 pandemic, two genetic regions derived from Neandertals have been shown to increase and decrease, respectively, the risk of falling severely ill upon infection. Here, we show that 2-8% of people in Eurasia carry a variant promoter region of the DPP4 gene inherited from Neandertals. This gene encodes an enzyme that serves as a receptor for the coronavirus MERS-CoV and is currently not believed to be a receptor for SARS-CoV-2. However, the Neandertal DPP4 variant doubles the risk to become critically ill in COVID-19.
  🖺 Full Text HTML: The MERS-CoV receptor gene is among COVID-19 risk factors inherited from Neandertals
• Millisecond-scale molecular dynamics simulation of spike RBD structure reveals evolutionary adaption of SARS-CoV-2 to stably bind ACE2 -
  The Receptor Binding Domain (RBD) of the SARS-CoV-2 surface spike (S) protein interacts with host angiotensin converting enzyme 2 (ACE2) to gain entry to host cells and initiate infection 1-3. Detailed, accurate understanding of key interactions between S RBD and ACE2 provides critical information that may be leveraged in the development of strategies for the prevention and treatment of COVID-19. Utilizing the published sequences and cryo-EM structures of both the viral S RBD and ACE2 4,5, we performed in silico molecular dynamics (MD) simulations of free S RBD and of its interaction with ACE2 over the exceptionally long durations of 2.9 and 2 milliseconds, respectively, to elucidate the nature and relative affinity of S RBD surface residues for the ACE2 binding region. Our findings reveal that free S RBD has assumed an optimized ACE2 binding-ready conformation, incurring little entropic penalty for binding, an evolutionary adaptation that contributes to its high affinity for the receptor 6. We further identified high probability molecular binding interactions that inform both vaccine design and therapeutic development, which may include recombinant ACE2-based spike decoys 7 and/or allosteric S RBD-ACE2 binding inhibitors 8,9 to prevent or arrest infection and thus disease.
  🖺 Full Text HTML: Millisecond-scale molecular dynamics simulation of spike RBD structure reveals evolutionary adaption of SARS-CoV-2 to stably bind ACE2
• COVID-19 and Wellbeing: Demographics, Individual Differences, and Leadership Help Explain Pandemic Impact -
  Across the globe, COVID-19 continues to disrupt everyday lives, with serious consequences for individuals' health and wellbeing. This retrospective, multinational survey study draws upon the Personal Resource Allocation (PRA) framework to explore how various demographic factors, individual differences, and leadership determine the perceived and actual impact of COVID-19 on health (mental, physical) and wellbeing (work, home, general) across five countries: Canada, France, Germany, the United Kingdom, and the United States. Having dependents under 12, working more hours since the onset, and having essential worker status led to better wellbeing outcomes. All three individual differences (adaptivity, resilience, remote work training) were positively related to engagement, with resilience and remote work also relating to better health for these individuals. Lastly, perceptions of COVID impact on mental and physical health had negative consequences for general wellbeing, while effective leadership perceptions predicted work engagement. No differences were found between the five countries. Findings highlight the importance of personal resources in determining the pandemic’s impact on wellbeing.
  🖺 Full Text HTML: COVID-19 and Wellbeing: Demographics, Individual Differences, and Leadership Help Explain Pandemic Impact
• Simultaneous Detection and Mutation Surveillance of SARS-CoV-2 and co-infections of multiple respiratory viruses by Rapid field-deployable sequencing -

  Strategies for monitoring the COVID-19 infection are crucial for combating the pandemic. Here we describe a method for multiplex isothermal amplification-based sequencing and real-time analysis of multiple viral genomes. It can simultaneously detect SARS-CoV-2 and co-infecting respiratory viruses, and monitor mutations for up to 96 samples in real time. The method, termed NIRVANA for Nanopore sequencing of Isothermal Rapid Viral Amplification for Near real-time Analysis, showed high sensitivity and specificity for SARS-CoV-2 in 70 clinical samples. It also simultaneously detected other viral pathogens (e.g. influenza A) in clinical and municipal wastewater samples. It provides a rapid field-deployable solution of COVID-19 and co-infection detection and surveillance of the evolution of pandemic strains.

  🖺 Full Text HTML: Simultaneous Detection and Mutation Surveillance of SARS-CoV-2 and co-infections of multiple respiratory viruses by Rapid field-deployable sequencing
• Hunt Regional Medical Center Policy for Dapsone administration of ARDS by SARS-CoV-2 -
  A covid-19 committee at Hunt regional Medical centre reviewed the use of Dapsone use as an off label medication based upon treatment adjuncts and inflammasome thesis. It recommends that any physician can write this prescription. However, to ensure safe, appropriate, and accurate administration. Following general guidance is recommended.
  🖺 Full Text HTML: Hunt Regional Medical Center Policy for Dapsone administration of ARDS by SARS-CoV-2
• Chest CT versus RT-PCR for the Detection of COVID-19: Systematic Review and Meta-analysis of Comparative Studies -

  Objectives To compare the performance of chest computed tomography (CT) scan versus reverse transcription polymerase chain reaction (RT-PCR) as the reference standard in the initial diagnostic assessment of coronavirus disease 2019 (COVID-19) patients. Design A systematic review and meta-analysis were performed as per the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A search of electronic information was conducted using the following databases: MEDLINE, EMBASE, EMCARE, CINAHL and the Cochrane Central Register of Controlled Trials (CENTRAL). Setting Studies that compared the diagnostic performance within the same patient cohort of chest CT scan versus RT-PCR in COVID-19 suspected patients. Participants Thirteen non-randomised studies enrolling 4092 patients were identified. Main Outcome Measures Sensitivity, specificity and accuracy were primary outcome measures. Secondary outcomes included other test performance characteristics and discrepant findings between both investigations. Results Chest CT had a sensitivity, specificity and accuracy of 0.91 (0.82-0.98), 0.775 (0.25-1.00) and 0.87 (0.68-0.99), respectively, with RT-PCR as the reference. Importantly, early small, China-based studies tended to favour chest CT versus later larger, non-China studies. Conclusions A relatively high false positive rate can be expected with chest CT. It may still be useful, however, in patients with a suspicious clinical presentation of COVID-19 and a negative initial SARS-CoV-2 RT-PCR. In acute cardiorespiratory presentations, negative CT scan and RT-PCR tests is likely to be reassuring.

  🖺 Full Text HTML: Chest CT versus RT-PCR for the Detection of COVID-19: Systematic Review and Meta-analysis of Comparative Studies
• Diverse Functional Autoantibodies in Patients with COVID-19 -

  COVID-19 manifests with a wide spectrum of clinical phenotypes that are characterized by exaggerated and misdirected host immune responses. While pathological innate immune activation is well documented in severe disease, the impact of autoantibodies on disease progression is less defined. Here, we used a high-throughput autoantibody discovery technique called Rapid Extracellular Antigen Profiling (REAP) to screen a cohort of 194 SARS-CoV-2 infected COVID-19 patients and healthcare workers for autoantibodies against 2,770 extracellular and secreted proteins (the "exoproteome"). We found that COVID-19 patients exhibit dramatic increases in autoantibody reactivities compared to uninfected controls, with a high prevalence of autoantibodies against immunomodulatory proteins including cytokines, chemokines, complement components, and cell surface proteins. We established that these autoantibodies perturb immune function and impair virological control by inhibiting immunoreceptor signaling and by altering peripheral immune cell composition, and found that murine surrogates of these autoantibodies exacerbate disease severity in a mouse model of SARS-CoV-2 infection. Analysis of autoantibodies against tissue-associated antigens revealed associations with specific clinical characteristics and disease severity. In summary, these findings implicate a pathological role for exoproteome-directed autoantibodies in COVID-19 with diverse impacts on immune functionality and associations with clinical outcomes.

  🖺 Full Text HTML: Diverse Functional Autoantibodies in Patients with COVID-19
• Effective post-exposure prophylaxis of Covid-19 is associated with use of hydroxychloroquine: Prospective re-analysis of a public dataset incorporating novel data. -

  BACKGROUND: A recent trial (NCT04308668) found that post-exposure prophylaxis with hydroxychloroquine (HCQ) was associated with a reduced incidence of Covid-19 by 17% overall; 36% in younger subjects, 31% in household contacts and 49% given within one day. To understand these trends, we re-analyzed the released dataset. METHODS: Our protocol conformed to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT). We compared the incidence of Covid-19 after HCQ or placebo, stratifying by intervention lag, age, and gender. RESULTS: Requesting additional data, we found that 52% of subjects received medication 1-2 days after the intended overnight delivery; 19% of them outside the intended four-day intervention lag. After re-analysis, there was a reduced incidence of Covid-19 associated with HCQ compared with placebo (9.6% vs. 16.5%) when received Early (up to 3 days) after exposure (RR 0.58, 95%CI 0.35 - 0.97; p=0.044; NNT 14.5) but not Late (RR 1.22, 95%CI 0.72 - 2.04). We found a significant HCQ-associated Covid-19 reduction in subjects 18 to 45 years old with Early (RR 0.54, 95%CI 0.29-0.97; p=0.0448, NNT 11.5) but not Late (RR 1.02, 95%CI 0.55-1.89) prophylaxis, attenuated in older subjects (RR 0.75, 95%CI 0-27-2.05) and by co-morbidities. There were reductions associated with Early prophylaxis in household contacts (RR 0.35, 95%CI 0.13-0.89; p=0.025, NNT 5.7) and Health Care Workers (RR 0.74, 95%CI 0.4-1.38). We did not detect effects of gender, folate, zinc, or ascorbic acid. CONCLUSIONS: Using novel data with a prospective post hoc re-analysis, hydroxychloroquine, in an age-dependent manner, was associated with reduced illness compatible with Covid-19 or confirmed infection when supplied for post-exposure prophylaxis between 1 and 3 days after high-risk or moderate-risk exposure, at higher loading and maintenance doses than in similar studies. This finding warrants prospective confirmation. Registered with the Open Science Framework (last revised September 27, 2020, osf.io/fqtnw). Plain Language Summary A recent clinical trial examined the ability of hydroxychloroquine (HCQ) to prevent Covid-19 just after an exposure to a person confirmed to have Covid-19. There was an HCQ-associated reduction of Covid-19 by an overall 17%; 36% in younger subjects, and 49% in subjects given HCQ within one day of being exposed. Likely because the study had too few patients to find what may have been a medically and economically meaningful, reduction, this effect was not statistically significant. Studying the trial data, we discovered an unintended and variable delay in the delivery of study drug which may have masked any drug effect. The investigators provided further information at our request that confirmed our theory. About half of the participants received drugs one or two days later than intended, about a fifth beyond the four days the investigators thought the drug might work. When we factored in this new information, we found that if HCQ was given early (up to three days after exposure), it was associated with a statistically significant 42% reduction of Covid-19. Giving HCQ later had no effect. There was a greater effect in younger (less than 45 years) rather than older subjects (47% vs. 25%). Gender did not seem to affect the results, but there was a greater HCQ-associated reduction (65%) when it was given early to people exposed to Covid-19 in a household environment rather than to health care workers (26%). The effects associated with HCQ were better in people without co-existing conditions. These re-calculations are important because the study, as originally analyzed, was the only randomized study that dealt with preventing Covid-19 cited by FDA to support a key public health decision made in June 2020 regarding HCQ. Although other studies have shown that the drug is not effective to treat established cases of Covid-19, our research suggests that that it is effective for prevention. Other prevention studies have failed to show a benefit of HCQ, possibly because they have used lower doses or have estimated the timing of dosing differently. Our research paves the way for our result to be confirmed under clinical trial conditions and for a re-examination of public health policy regarding this drug. Even with the introduction of vaccination, there remains a need for approaches like this to prevent Covid-19 while individual and community immunity develops, especially in subjects given a lower priority for vaccination. Short Summary A prospective re-analysis of a public dataset integrated with novel data found an HCQ-associated reduction of illness compatible with Covid-19 when received between 1 and 3 days after a high-risk or moderate-risk exposure (RR 0.58, 95% CI 0.35-0.97, p=0.044, NNT14.5).

  🖺 Full Text HTML: Effective post-exposure prophylaxis of Covid-19 is associated with use of hydroxychloroquine: Prospective re-analysis of a public dataset incorporating novel data.

From Clinical Trials

• Evaluating Safety, Pharmacokinetics and Clinical Benefit of Silmitasertib (CX-4945) in Subjects With Moderate COVID-19 - Condition:   Covid19
  Interventions:   Drug: Silmitasertib;   Drug: SOC
  Sponsor:   Chris Recknor, MD
  Recruiting

• Convalescent Plasma for Treatment of COVID-19: An Open Randomised Controlled Trial - Condition:   Covid19
  Interventions:   Biological: SARS-CoV-2 convalescent plasma;   Other: Standard of care
  Sponsors:   Joakim Dillner;   Karolinska Institutet;   Danderyd Hospital;   Falu Hospital
  Not yet recruiting

• Phase II / III Study of COVID-19 DNA Vaccine (AG0302-COVID19) - Condition:   COVID-19
  Interventions:   Biological: Group A (AG0302-COVID19);   Biological: Group A (Placebo);   Biological: Group B (AG0302-COVID19);   Biological: Group B (Placebo)
  Sponsors:   AnGes, Inc.;   Japan Agency for Medical Research and Development
  Recruiting

• Use of BCG Vaccine as a Preventive Measure for COVID-19 in Health Care Workers - Condition:   COVID 19 Vaccine
  Intervention:   Biological: BCG vaccine
  Sponsors:   Universidade Federal do Rio de Janeiro;   Ministry of Science and Technology, Brazil
  Recruiting

• At-Home Infusion Using Bamlanivimab in Participants With Mild to Moderate COVID-19 - Condition:   Covid19
  Intervention:   Drug: bamlanivimab
  Sponsors:   Daniel Griffin, MD PhD;   Eli Lilly and Company;   Optum, Inc.
  Not yet recruiting

• Efficacy and Safety of High-dose Vitamin C Combined With Chinese Medicine Against Coronavirus Pneumonia (COVID-19) - Condition:   COVID-19
  Interventions:   Drug: Alpha-interferon alpha, abidol, ribavirin, Buzhong Yiqi plus and minus formula, Huhuang Detoxicity Paste, Baimu Qingre Jiedu Paste, fumigation/inhalation of vitamin C;   Drug: Alpha-interferon, abidol, ribavirin, Buzhong Yiqi plus and minus formula, Huhuang Detoxicity Paste, Baimu Qingre Jiedu Paste and 5% glucose;   Drug: Alpha-interferon, abidol, ribavirin, Buzhong Yiqi plus and minus formula, Huhuang Detoxicity Paste, Baimu Qingre Jiedu Paste and high-dose vitamin C treatment
  Sponsor:   Xi'an International Medical Center Hospital
  Active, not recruiting

• IFN-beta 1b and Remdesivir for COVID19 - Condition:   Covid19
  Interventions:   Drug: Interferon beta-1b;   Drug: Remdesivir
  Sponsor:   The University of Hong Kong
  Recruiting

• COVID-19 And Geko Evaluation: The CAGE Study - Condition:   Covid19
  Intervention:   Device: geko T3
  Sponsor:   Lawson Health Research Institute
  Not yet recruiting

• A Clinical Safety Study on AT-100 in Treating Adults With Severe COVID-19 Infection - Condition:   Covid19
  Intervention:   Biological: AT-100
  Sponsor:   Airway Therapeutics, Inc.
  Not yet recruiting

• LYT-100 in Post-acute COVID-19 Respiratory Disease - Condition:   Covid19
  Interventions:   Drug: LYT-100;   Other: Placebo
  Sponsors:   PureTech;   Clinipace Worldwide;   Novotech (Australia) Pty Limited
  Not yet recruiting

• Resolving Inflammatory Storm in COVID-19 Patients by Omega-3 Polyunsaturated Fatty Acids - - Condition:   COVID-19
  Interventions:   Drug: Omegaven®;   Drug: Sodium chloride
  Sponsor:   Karolinska University Hospital
  Recruiting

• WHO COVID-19 Solidarity Trial for COVID-19 Treatments - Condition:   Covid19
  Interventions:   Drug: Remdesivir;   Drug: Acalabrutinib;   Drug: Interferon beta-1a;   Other: Standard of Care
  Sponsor:   The University of The West Indies
  Not yet recruiting

• COVID-19 Thrombosis Prevention Trials: Post-hospital Thromboprophylaxis - Condition:   Covid19
  Interventions:   Drug: Apixaban 2.5 MG;   Drug: Placebo
  Sponsors:   Thomas Ortel, M.D., Ph.D.;   National Heart, Lung, and Blood Institute (NHLBI)
  Not yet recruiting

• Urine Alkalinisation to Prevent AKI in COVID-19 - Condition:   Covid19
  Intervention:   Drug: Sodium Bicarbonate 150Meq/L/D5W Inj
  Sponsor:   Guy's and St Thomas' NHS Foundation Trust
  Not yet recruiting

• COVID-19 Outpatient Pragmatic Platform Study (COPPS) - Master Protocol - Condition:   Covid19
  Interventions:   Drug: Acebilustat;   Drug: Camostat
  Sponsor:   Stanford University
  Not yet recruiting

From PubMed

• Candidate Binding Sites for Allosteric Inhibition of the SARS-CoV-2 Main Protease from the Analysis of Large-Scale Molecular Dynamics Simulations - We analyzed a 100 μs MD trajectory of the SARS-CoV-2 main protease by a non-parametric data analysis approach which allows characterizing a free energy landscape as a simultaneous function of hundreds of variables. We identified several conformations that, when visited by the dynamics, are stable for several hundred nanoseconds. We explicitly characterize and describe these metastable states. In some of these configurations, the catalytic dyad is less accessible. Stabilizing them by a suitable...

• Coronavirus disease 2019 (COVID-19), human erythrocytes and the PKC-alpha/-beta inhibitor chelerythrine -possible therapeutic implication - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19. Until now, diverse drugs have been used for the treatment of COVID-19. These drugs are associated with severe side effects, e.g. induction of erythrocyte death, named eryptosis. This massively affects the oxygen (O(2)) supply of the organism. Therefore, three elementary aspects should be considered simultaneously: (1) a potential drug should directly attack the virus, (2) eliminate virus-infected host cells and (3)...

• First Report of Tocilizumab Use in a Cohort of Latin American Patients Hospitalized for Severe COVID-19 Pneumonia - Introduction/objectives: An interleukin-6 inhibition strategy could be effective in selected COVID-19 patients. The objective is to present our experience of tocilizumab use in patients with severe COVID-19. Methods: Observational retrospective cohort study. Hospitalized patients were evaluated by our multidisciplinary team for eventual use of tocilizumab. Patients with progressive ventilatory impairment and evidence of a hyperinflammatory state despite usual treatment received tocilizumab 8...

• Repurposing Known Drugs as Covalent and Non-covalent Inhibitors of the SARS-CoV-2 Papain-Like Protease - In the absence of an approved vaccine, developing effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antivirals is essential to tackle the current pandemic health crisis due to the coronavirus disease 2019 (COVID-19) spread. As any traditional drug discovery program is a time-consuming and costly process requiring more than one decade to be completed, in silico repurposing of existing drugs is the preferred way for rapidly selecting promising clinical candidates. We present a...

• Proton pump inhibitors and the risk of severe COVID-19: a post-hoc analysis from the Korean nationwide cohort - No abstract

• Silybin B and Cianidanol Inhibit M pro and Spike Protein of SARS-CoV-2: Evidence from in Silico Molecular Docking Studies - CONCLUSION: Silybin B and Cianidanol showed excellent binding and ADME properties compared with the currently endeavored drugs and can be exploited as therapeutic options against SARS-CoV-2 infection after experimental validation and clinical trials.

• Natural Products Homoharringtonine and Emetine Alkaloids for SARSCoV-2 Treatment Options - CONCLUSION: This review specifically focuses on the recent findings of these alkaloids against coronaviruses and possible treatment options for SARS-CoV-2. It is expected that natural products as alkaloids from herbal plants could be considered as novel and valuable candidates for the new antiviral drugs against SARS-CoV-2.

• Protease-activated receptor 1 as a potential therapeutic target for COVID-19 - Acute respiratory disease caused by a novel coronavirus (SARS-CoV-2) has spread all over the world, since its discovery in 2019, Wuhan, China. This disease is called COVID-19 and already killed over 1 million people worldwide. The clinical symptoms include fever, dry cough, dyspnea, headache, dizziness, generalized weakness, vomiting, and diarrhea. Unfortunately, so far, there is no validated vaccine, and its management consists mainly of supportive care. Venous thrombosis and pulmonary embolism...

• Inhibition of SARS-CoV-2 Entry into Host Cells Using Small Molecules - Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a virus belonging to the Coronavirus family, is now known to cause Coronavirus Disease (Covid-19) which was first recognized in December 2019. Covid-19 leads to respiratory illnesses ranging from mild infections to pneumonia and lung failure. Strikingly, within a few months of its first report, Covid-19 has spread worldwide at an exceptionally high speed and it has caused enormous human casualties. As yet, there is no specific...

• Topoisomerase 1 inhibition therapy protects against SARS-CoV-2-induced inflammation and death in animal models - The ongoing pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is currently affecting millions of lives worldwide. Large retrospective studies indicate that an elevated level of inflammatory cytokines and pro-inflammatory factors are associated with both increased disease severity and mortality. Here, using multidimensional epigenetic, transcriptional, in vitro and in vivo analyses, we report that Topoisomerase 1 (Top1) inhibition suppresses lethal inflammation...

• Amilorides inhibit SARS-CoV-2 replication in vitro by targeting RNA structures - The SARS-CoV-2 pandemic, and the likelihood of future coronavirus pandemics, has rendered our understanding of coronavirus biology more essential than ever. Small molecule chemical probes offer to both reveal novel aspects of virus replication and to serve as leads for antiviral therapeutic development. The RNA-biased amiloride scaffold was recently tuned to target a viral RNA structure critical for translation in enterovirus 71, ultimately uncovering a novel mechanism to modulate positive-sense...

• Ca (2+) -dependent mechanism of membrane insertion and destabilization by the SARS-CoV-2 fusion peptide - Cell penetration after recognition of the SARS-CoV-2 virus by the ACE2 receptor, and the fusion of its viral envelope membrane with cellular membranes, are the early steps of infectivity. A region of the Spike protein (S) of the virus, identified as the "fusion peptide" (FP), is liberated at its N-terminal site by a specific cleavage occurring in concert with the interaction of the receptor binding domain of the Spike. Studies have shown that penetration is enhanced by the required binding of Ca...

• Repurposing the Ebola and Marburg Virus Inhibitors Tilorone, Quinacrine and Pyronaridine: In vitro Activity Against SARS-CoV-2 and Potential Mechanisms - SARS-CoV-2 is a newly identified virus that has resulted in over 1.3 M deaths globally and over 59 M cases globally to date. Small molecule inhibitors that reverse disease severity have proven difficult to discover. One of the key approaches that has been widely applied in an effort to speed up the translation of drugs is drug repurposing. A few drugs have shown in vitro activity against Ebola virus and demonstrated activity against SARS-CoV-2 in vivo . Most notably the RNA polymerase targeting...

• A proposed molecular mechanism for pathogenesis of severe RNA-viral pulmonary infections - Background: Certain riboviruses can cause severe pulmonary complications leading to death in some infected patients. We propose that DNA damage induced-apoptosis accelerates viral release, triggered by depletion of host RNA binding proteins (RBPs) from nuclear RNA bound to replicating viral sequences. Methods: Information theory-based analysis of interactions between RBPs and individual sequences in the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2), Influenza A (H3N1), HIV-1, and...

• Emerging role of artificial intelligence in therapeutics for COVID-19: a systematic review - To elucidate the role of artificial intelligence (AI) in therapeutics for coronavirus disease 2019 (COVID-19). Five databases were searched (December 2019-May 2020). We included both published and pre-print original articles in English that applied AI, machine learning or deep learning in drug repurposing, novel drug discovery, vaccine and antibody development for COVID-19. Out of 31 studies included, 16 studies applied AI for drug repurposing, whereas 10 studies utilized AI for novel drug...

From Patent Search

• "AYURVEDIC PROPRIETARY MEDICINE FOR TREATMENT OF SEVERWE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2." - AbstractAyurvedic Proprietary Medicine for treatment of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)In one of the aspect of the present invention it is provided that Polyherbal combinations called Coufex (syrup) is prepared as Ayurvedic Proprietary Medicine , Aqueous Extracts Mixing with Sugar Syrup form the following herbal aqueous extract coriandrum sativum was used for the formulation of protek.Further another Polyherbal combination protek as syrup is prepared by the combining an aqueous extract of the medicinal herbs including Emblica officinalis, Terminalia chebula, Terminalia belerica, Aegle marmelos, Zingiber officinale, Ocimum sanctum, Adatoda zeylanica, Piper lingum, Andrographis panivulata, Coriandrum sativum, Tinospora cordiofolia, cuminum cyminum,piper nigrum was used for the formulation of Coufex.

• Haptens, hapten conjugates, compositions thereof and method for their preparation and use - A method for performing a multiplexed diagnostic assay, such as for two or more different targets in a sample, is described. One embodiment comprised contacting the sample with two or more specific binding moieties that bind specifically to two or more different targets. The two or more specific binding moieties are conjugated to different haptens, and at least one of the haptens is an oxazole, a pyrazole, a thiazole, a nitroaryl compound other than dinitrophenyl, a benzofurazan, a triterpene, a urea, a thiourea, a rotenoid, a coumarin, a cyclolignan, a heterobiaryl, an azo aryl, or a benzodiazepine. The sample is contacted with two or more different anti-hapten antibodies that can be detected separately. The two or more different anti-hapten antibodies may be conjugated to different detectable labels.

• 疫苗融合蛋白 - 本申请涉及一种融合蛋白，所述融合蛋白包括SARS‑CoV‑2抗原多肽和鞭毛蛋白或其片段。本申请还提供了所述融合蛋白的制备方法和用途。本申请所述的融合蛋白能够诱导机体产生针对SARS‑CoV类病毒的抗原的细胞免疫反应。

• AN EFFICIENT METHODOLOGY TO MANAGE THE ADMISSIONS IN HOSPITALS DURING THE PANDEMICS SUCH AS COVID 19 -

• 一种SARS-CoV-2假病毒小鼠体内包装系统及其制备方法 - 本发明提供了一种假病毒小鼠体内包装系统的制备方法，包括以下步骤：S1基于慢病毒包装质粒系统和睡美人转座子系统构建SARS‑CoV‑2假病毒包装质粒系统，S2将步骤S1中SARS‑CoV‑2假病毒包装质粒系统与睡美人转座酶表达质粒混合通过水动力注射的方式转染小鼠肝细胞，然后睡美人转座子系统将SARS‑CoV‑2假病毒包装所需序列以剪切粘贴的方式整合到小鼠肝细胞的基因组。本发明可在小鼠体内持续制造分泌SARS‑CoV‑2假病毒，可模拟靶器官被SARS‑CoV‑2病毒持续侵入攻击的过程，从而可模拟出新冠肺炎（COVID‑19）的病理特征。基于SARS‑CoV‑2假病毒小鼠体内包装系统的动物模型安全性高，不需要P3级实验室就能开展研究。利用水动力注射的方式引入SARS‑CoV‑2假病毒包装质粒系统操作简单，成本低。

• 柴胡解毒药物组合物及其制备方法和应用 - 本发明属于中药领域，具体涉及一种柴胡解毒药物组合物及其制备方法和应用，所述柴胡解毒药物组合物以质量份计由如下原料组分制成：柴胡30_{60份，黄芩15}30份，法半夏15_{30份，生姜15}30份，大枣5_{10份，枳实20}40份，大黄10_{20份，桃仁10}20份，白芍15~30份。本发明的柴胡解毒药物组合物能够显著改善普通型COVID‑19引起的咳嗽；能改善疫毒闭肺型重型COVID‑19引起的咳嗽，显著改善疫毒闭肺型重型COVID‑19引起的胸闷、气短和乏力等主要症状。另外经大量临床观察，本发明的柴胡解毒药物组合物能够显著改善疫毒闭肺型重型COVID‑19引起的发热面红，咳嗽，痰黄粘少，或痰中带血，喘憋气促，疲乏倦怠，口干苦粘，大便不畅，小便短赤等症状。

• 一种新型冠状病毒RBD核苷酸序列、优化方法与应用 - 本发明公开了一种新型冠状病毒RBD核苷酸序列、优化方法与应用。属于基因工程技术领域。优化步骤：（1）对野生型新型冠状病毒RBD核苷酸序列进行初步优化；（2）将宿主细胞特异性高表达分泌蛋白信号肽序列进行优化；（3）将人IgG1‑Fc核苷酸序列进行优化；（4）将步骤（2）优化后的宿主细胞特异性高表达分泌蛋白信号肽核苷酸序列、步骤（1）得到的初步优化新型冠状病毒RBD核苷酸序列、连接子核苷酸序列和步骤（3）优化后的人IgG1‑Fc核苷酸序列依次连接即可。与现有技术相比，本发明的有益效果：产生的克隆表达效率比野生新型冠状病毒RBD序列提高了约12倍，比中国仓鼠密码子偏性优化序列克隆表达效率提高了2倍。

• ASSISTING COMPLEX FOR TAKING OF BIOMATERIAL FROM MOUTH IN PANDEMIC CONDITIONS - FIELD: medicine. SUBSTANCE: invention refers to medicine, namely to methods for contactless taking of biomaterial in tested person. Taking the biomaterial in the tested person is carried out in a room located in a dirty zone and separated by a partition from the clean zone, in which there is a laboratory assistant performing the procedure using a robotic complex. Complex includes digital controller, manipulator with tool unit, small manipulator, camera, monitor, control system of digital controller, manipulator, small manipulator, and complex control system. In the partition there are two holes: one – for installation and passage of the swab, the other – for the test tube installation. In the dirty zone there is a small manipulator having two actuators: one for movement of a test tube with a swab, and the second for positioning and placing a disposable mouthpiece. EFFECT: reduced risk of laboratory assistant and tested person infection by avoiding their direct contact. 17 cl, 1 dwg

• Antiinfektive Arzneiform zur Herstellung einer Nasenspülung gegen COVID-19 -

  Einzeldosierte, wasserlösliche oder wassermischbare Arzneiform, umfassend mindestens einen antiinfektiven Arzneistoff, zur Herstellung einer Nasenspülung und/oder zur Verwendung in der lokalen Behandlung des menschlichen Nasenraums.

• Antiinfektive Arzneiform zur Herstellung einer Nasenspülung gegen COVID-19 -

  Einzeldosierte, wasserlösliche oder wassermischbare Arzneiform, umfassend mindestens einen antiinfektiven Arzneistoff, zur Herstellung einer Nasenspülung und/oder zur Verwendung in der lokalen Behandlung des menschlichen Nasenraums.