Covid-19 Sentry

Contents

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

From Preprints

• How to coordinate vaccination and social distancing to mitigate SARS-CoV-2 outbreaks -

  Most countries have started vaccinating people against COVID-19. However, due to limited production capacities and logistical challenges it will take months/years until herd immunity is achieved. Therefore, vaccination and social distancing have to be coordinated. In this paper, we provide some insight on this topic using optimization-based control on an age-differentiated compartmental model. For real-life decision making, we investigate the impact of the planning horizon on the optimal vaccination/social distancing strategy. We find that in order to reduce social distancing in the long run, without overburdening the healthcare system, it is essential to vaccinate the people with the highest contact rates first. That is also the case if the objective is to minimize fatalities provided that the social distancing measures are sufficiently strict. However, for short-term planning it is optimal to focus on the high-risk group.

  🖺 Full Text HTML: How to coordinate vaccination and social distancing to mitigate SARS-CoV-2 outbreaks
• Ruxolitinib versus Dexamethasone in Hospitalized Adults with Covid-19: multicenter matched-controlled study -

  Background: Several anti-cytokine therapies were tested in the randomized trials in hospitalized patients with severe acute respiratory syndrome coronavirus 2 infection (COVID-19). Both janus kinase (JAK) inhibitor, baricitinib, and dexamethasone demonstrated the reduction of mortality. In this matched control study we compared dexamethasone to another JAK inhibitor, ruxolitinib. Methods: The study included 146 hospitalized patients with COVID-19 and oxygen support requirement. The control group was selected 1:1 from 1355 dexamethasone-treated patients and was matched by 29 clinical and laboratory parameters predicting survival. Results: Ruxolitinib treatment in the general cohort of patients was associated with equivalent to dexamethasone mortality rate: 9,6% (95% CI 4,6-14,6%) vs 13,0% (95% CI 7,5-18,5%, superiority p=0.35, non-inferiority p=0.0137), respectively. Time to discharge without oxygen support requirement was also not different between these groups: 13 vs 11 days (p=0.13). Subgroup analysis without adjustment for multiple comparisons demonstrated reduced mortality in ruxolitnib-treated patients with febrile fever (OR 0.33, 95%CI 0.11-1.00). Except higher incidence of grade 1 thrombocytopenia (37% vs 23%, p=0.042), ruxolitinib therapy was associated with better safety profile due to reduced rate of severe cardiovascular adverse events (6.8% vs 15%, p=0.025). Conclusions: Ruxolitinib may be an alternative anti-cytokine therapy with comparable efficacy in patients with potential risks of steroid administration. Patients with febrile fever at admission may benefit from ruxolitinib administration. Funding: Ruxolitinib was obtained from Novartis through Managed Access Program (MAP).

  🖺 Full Text HTML: Ruxolitinib versus Dexamethasone in Hospitalized Adults with Covid-19: multicenter matched-controlled study
• Identification of clinical features associated with mortality in COVID-19 patients -

  Background To prevent infectious diseases, it is necessary to understand how they are spread and their clinical features. Early identification of risk factors and clinical features is needed to identify critically ill patients, provide suitable treatments, and prevent mortality. Methods We conducted a prospective study on COVID-19 patients referred to a tertiary hospital in Iran between March and November 2020. Of the 3008 patients (mean age 59.3 years, range 1 to 100 years), 1324 were women. We investigated COVID-19 related mortality and its association with clinical features including headache, chest pain, symptoms on CT, hospitalization, time to infection, history of neurological disorders, having a single or multiple risk factors, fever, myalgia, dizziness, seizure, abdominal pain, nausea, vomiting, diarrhoea and anorexia. Findings There was a significant association between COVID-19 mortality and old age, headache, chest pain, respiratory distress, low respiratory rate, oxygen saturation less than 93%, need for a mechanical ventilator, having symptoms on CT, hospitalization, time to infection, history of hypertension, neurological disorders, cardiovascular diseases and having a risk factor or multiple risk factors. In contrast, there was no significant association between mortality and gender, fever, myalgia, dizziness, seizure, abdominal pain, nausea, vomiting, diarrhoea and anorexia. Interpretation Our results might help identify early symptoms related to COVID-19 and better manage patients clinically.

  🖺 Full Text HTML: Identification of clinical features associated with mortality in COVID-19 patients
• Prevalence of severe adverse events in health professionals after receiving the first dose of the COVID-19 vaccination in Togo, March 2021 -

  Introduction: Covid-19 vaccines can cause adverse events (AE) that can lead to increased hesitation or fear of vaccination. This study aims at estimating the prevalence of severe adverse events (SAEs) and their associated factors among health professionals (HPs) vaccinated with COVISHIELD(TM) vaccine in Togo. Methods: A cross-sectional study was conducted from March 13th to 19th, 2021 in Togo among HPs who received the first dose of vaccine. An online self-administered questionnaire was used to collect data on sociodemographic characteristics and vaccination. SAEs were defined as one resulting in hospitalization, medical consultation, or inability to work the day following the administration of the vaccine. Regression analysis were performed to assess factors associated with SAEs. Results: A total of 1,639 HP (70.2% male) with a median age [IQR] of 32 years [27-40] participated. At least one AE was reported among 71.6% (95%CI= [69.3-73.8]). The most commonly reported AEs were pain at the injection site (91.0%), asthenia (74.3%), headache (68.7%), soreness (55.0%), and fever (47.5%). An increased libido was also reported in 3.0% of HP. Among HP who experienced AEs, 18.2% were unable to go to work the day after vaccination, 10.5% consulted a medical doctor, and 1.0% were hospitalized. The SAE prevalence was 23.8% (95%CI= [21.8-25.9]). Being <30 years (aOR=5.54; p<0.001), or 30-49 years (aOR=3.62; p<0.001) and being female (aOR=1.97; p<0.001) were associated with SAEs. Conclusion: Despite the occurrence of SAEs, current data collected in Togo about adverse events are reassuring with COVISHIELD(TM) vaccine and how they could be managed. Keywords: Severe adverse event, COVID-19, vaccine, prevalence, health professionals, Togo.

  🖺 Full Text HTML: Prevalence of severe adverse events in health professionals after receiving the first dose of the COVID-19 vaccination in Togo, March 2021
• Mixed Emotions, But Not Positive or Negative Emotions, Facilitate Legitimate Virus-Prevention Behaviors and Eudaimonic Outcomes in the Emergence of the COVID-19 Crisis -
  We report four studies (N=1419) examining emotional reactions from March to April 2020, when COVID-19 exhibited exponentially increasing infections and fatalities. Specifically, we examined associations between emotions with self-reported intentions to enact virus-prevention behaviors that protect oneself from COVID-19 and eudaimonic functioning. Study 1A, 1B, and Study 2 provided naturalistic evidence that mixed emotions predicted legitimate virus-prevention behaviors and eudaimonic functioning in the United States and Singapore, and Study 2 also supported receptivity as a mediator. Finally, Study 3 provided experimental evidence that mixed emotions causally increased legitimate virus-prevention behaviors relative to neutral, positive emotion, and negative emotion conditions, whereas eudaimonic functioning was increased only relative to the neutral condition. Across all studies, positive and negative emotions were unrelated to legitimate virus-prevention behaviors, while relationships with eudaimonic functioning were inconsistent. While self-reported measures do not represent actual behaviors, the findings suggest a potential role for mixed emotions in pandemic-related outcomes.
  🖺 Full Text HTML: Mixed Emotions, But Not Positive or Negative Emotions, Facilitate Legitimate Virus-Prevention Behaviors and Eudaimonic Outcomes in the Emergence of the COVID-19 Crisis
• Emergence of the novel SARS-CoV-2 lineage P.4.1 and massive spread of P.2 in South Brazil -

  South Brazil has been the novel epicenter of Coronavirus Disease 2019 (COVID-19) in 2021, accounting for the greatest number of cumulative cases and deaths (per 100 thousand inhabitants in a week) worldwide. In this study, we analyzed 340 whole genomes of SARS-CoV-2, which were sampled between April and November 2020 in 33 cities in South Brazil. We demonstrated the circulation of two novel emergent lineages, described here as P.4 and P.4.1 (provisionally termed VUI-NP13L), and seven lineages that had already been assigned (B.1.1.33, B.1.1.28, P.2, B.1.91, B.1.1.94, B.1.195 and B.1.212). P.2 and P.4.1 demonstrated massive spread from approximately September/October 2020. Constant and consistent genomic surveillance is crucial to identify newly emerging SARS-CoV-2 lineages in Brazil and to guide decision making in the Brazilian Public Healthcare System.

  🖺 Full Text HTML: Emergence of the novel SARS-CoV-2 lineage P.4.1 and massive spread of P.2 in South Brazil
• Simulation of aerosol and droplet spread during upper airway and gastrointestinal endoscopy -

  Objective: Aerosols and droplets are the main vectors in transmission of highly contagious SARS-Cov-2. Invasive diagnostic procedures like upper airway and gastrointestinal endoscopy have been declared as aerosol generating procedures. Protection of health care workers is crucial in times of COVID-19 pandemic. Methods: We simulated aerosol and droplet spread during upper airway and gastrointestinal endoscopy with and without physico-mechanical barriers using a simulation model. Results: A clear plastic drape as used for central venous access markedly reduced visualized aerosol and droplet spread during endoscopy. Conclusion: A simple and cheap drape has the potential to reduce aerosol and droplet spread during endoscopy. In terms of health care worker protection, this may be important particularly in low- or moderate-income countries.

  🖺 Full Text HTML: Simulation of aerosol and droplet spread during upper airway and gastrointestinal endoscopy
• Study Pre-protocol for ‘BronchStart - The Impact of the COVID-19 Pandemic on the Timing, Age and Severity of Respiratory Syncytial Virus (RSV) Emergency Presentations; a Multi-Centre Prospective Observational Cohort Study’ -

  Background Bronchiolitis (most frequently caused by Respiratory Syncytial Virus; RSV) is a common winter disease predominantly affecting children under one year of age. It is a common reason for presentations to an Emergency Department (ED) and frequently results in hospital admission, contributing to paediatric units approaching or exceeding capacity each winter. During the SARS-CoV-2 pandemic, the circulation of RSV was dramatically reduced in the United Kingdom and Ireland. Evidence from the Southern Hemisphere and other European countries suggests that as social distancing restrictions for SARS-CoV-2 are relaxed, RSV infection returns, causing delayed or even summer epidemics, with different age distributions. Study question The ability to track, anticipate and respond to a surge in RSV cases is critical for planning acute care delivery. There is an urgent need to understand the onset of RSV spread at the earliest opportunity. This will influence service planning, to inform clinicians whether the population at risk is a wider age range than normal, and whether there are changes in disease severity. This information is also needed to inform decision on the timing of passive immunisation of children at higher risk of hospitalisation, intensive care admission or death with RSV infection, which is a public health priority. Methods and likely impact This multi-centre prospective observational cohort study will use a well-established research network (Paediatric Emergency Research in the UK and Ireland, PERUKI) to report in real time cases of RSV infection in children aged under two years, through the collection of essential, but non-identifying patient information. Forty centres will gather initial data on age, index of multiple deprivation quintile, clinical features on presentation, and co-morbidities. Each case will be followed up at 7 days to identify treatment, viral diagnosis and outcome. Information be released on a weekly basis and used to support clinical decision making.

  🖺 Full Text HTML: Study Pre-protocol for ‘BronchStart - The Impact of the COVID-19 Pandemic on the Timing, Age and Severity of Respiratory Syncytial Virus (RSV) Emergency Presentations; a Multi-Centre Prospective Observational Cohort Study’
• Health Belief, Planned Behavior, or Psychological Antecedents: What predicts COVID-19 Vaccine Hesitancy better among the Bangladeshi Adults? -

  Background This study aimed to determine the prevalence and investigate the constellations of psychological determinants of the COVID-19 vaccine hesitancy among the Bangladeshi adult population utilizing the health belief model-HBM (perceived susceptibility to and severity of COVID-19, perceived benefits of and barriers to COVID-19 vaccination, and cues to action), the theory of planned behavior-TPB (attitude toward COVId-19 vaccine, subjective norm, perceived behavioral control, and anticipated regret), and the novel 5C psychological antecedents (confidence, constraints, complacency, calculation, and collective responsibility). We compared the predictability of these theoretical frameworks to see which framework explains the highest variance in COVID-19 vaccine hesitancy. Methods This study adopted a cross-sectional research design. We collected data from a nationally representative sample of 1497 respondents through both online and face-to-face interviews. We employed multiple linear regression analysis to assess the predictability of each model of COVID-19 vaccine hesitancy. Results We found a 41.1% prevalence of COVID-19 vaccine hesitancy among our study respondents. After controlling the effects of socio-economic, demographic, and other COVID-19 related covariates, we found that the TPB has the highest predictive power (adjusted R2=0.43), followed by the 5C psychological antecedents of vaccination (adjusted R2=0.32) and the HBM (adjusted R2=0.31) in terms of explaining total variance in the COVID-19 vaccine hesitancy among the adults of Bangladesh. Conclusions This study provides evidence that theoretical frameworks like the HBM, the TPB, and the 5C psychological antecedents can be used to explore the psychological determinants of vaccine hesitancy, where the TBP has the highest predictability. Our findings can be used to design targeted interventions to reduce vaccine hesitancy and increase vaccine uptake.

  🖺 Full Text HTML: Health Belief, Planned Behavior, or Psychological Antecedents: What predicts COVID-19 Vaccine Hesitancy better among the Bangladeshi Adults?
• Infants have lower RT-PCR cycle threshold for SARS-CoV-2 in comparison with older children and adults -

  Background: The viral dynamics and the role of children in the spread of SARS-CoV-2 are not completely understood. Our aim was to evaluate how RT-PCR Ct values among children with confirmed SARS-CoV-2 compared with that of adult subjects. Methods: Patients (aged from 2 months to ≤18 years, and adults) with signs and symptoms of acute SARS-CoV-2 infection for less than 7 days, were prospectively enrolled in the study from May to November 2020. All participants performed RT-PCR assay for SARS-CoV-2 detection; Ct values of ORF1ab, N, and S gene-targets, and the average of all the three probes were used as surrogates of viral load. Results: Of the total of 376 participants with confirmed SARS-CoV-2 infection there were 21 infants, 62 children and 293 adults. The RT-PCR Ct values of children under 18 were not significantly different from that of adults, as observed by the analyzed probes (namely ORF1ab, N, and S), and by the mean of all 3 gene-targets. However, infants had significantly lower Ct values compared to children and adults (P = 0.044). Discussion: Ct values for children were not significantly different than that of adults with positive SARS-CoV-2. Interestingly, infants had even lower Ct values when compared to older children and adults. Although viral load is not the only determinant of transmission, infants may play a significant role in the spread of SARS-CoV-2 in the community, especially if or when this population returns to regular daycare activities.

  🖺 Full Text HTML: Infants have lower RT-PCR cycle threshold for SARS-CoV-2 in comparison with older children and adults
• Corticosteroids for Severe Coronavirus Disease 2019: High Time for High Dose Clinical Trials? -
  Over 3 million deaths into the COVID-19 pandemic, low dose corticosteroids are still the chief therapeutic intervention to decrease mortality in critically ill COVID-19 patients. However, the persistently high mortality rate (approximately 30%) and the global surge in cases in 2021 associated with new more contagious variants of SARS-CoV-2 underscore the urgent need to evaluate whether the current corticosteroid regimens achieve the best possible outcomes. Our review of clinical, virological, and immunological data suggest that corticosteroids reduce COVID-19 mortality more when initiated in the second or third weeks after symptom onset, after viral infectivity has waned and SARS-CoV-2 immunopathology is maximal. At this time, clinical deterioration is driven by aberrant hyperinflammation. To counteract the hyperinflammation, we present credible arguments that high dose corticosteroids, defined in this Perspective as intravenous (i.v.) methylprednisolone 500-1000 mg/day for 3-7 days or the equivalent doses of other corticosteroids, can be administered with little or no risk of worsening viral replication and with expected benefits that greatly outweigh potential harm. Since the 1970s, the strategy of administering supraphysiologic doses of i.v. methylprednisolone (termed ‘pulse’ therapy) over a short period to enhance therapeutic benefit while decreasing harmful effects has become an accepted standard of care to effectively suppress inflammation in many autoimmune and immune-mediated disorders. It is particularly useful in conditions requiring rapid immunosuppression and anti-inflammatory effect and has recently been used to control inflammation in SARS-CoV-2 related complications, including multisystem inflammatory syndrome in children (MIS-C) and organizing pneumonia. In aggregate, awareness of the need for more aggressive immunosuppression and lessons learned over a half-century from the successful treatment of various inflammatory disorders, provide a sound scientific and ethics rationale for expeditiously conducting high dose corticosteroid randomized clinical trials (RCTs) in critically ill patients with COVID-19.
  🖺 Full Text HTML: Corticosteroids for Severe Coronavirus Disease 2019: High Time for High Dose Clinical Trials?
• Inactivation of SARS-CoV-2 in chlorinated swimming pool water -
  SARS-CoV-2 transmission remains a global problem which exerts a significant direct cost to public health. Additionally, other aspects of physical and mental health can be affected by limited access to social and exercise venues as a result of lockdowns in the community or personal reluctance due to safety concerns. Swimming pools have reopened in the UK as of April 12th, but the effect of swimming pool water on inactivation of SARS-CoV-2 has not yet been directly demonstrated. Here we demonstrate that water which adheres to UK swimming pool guidelines is sufficient to reduce SARS-CoV-2 infectious titre by at least 3 orders of magnitude.
  🖺 Full Text HTML: Inactivation of SARS-CoV-2 in chlorinated swimming pool water
• Ultrapotent SARS-CoV-2 neutralizing antibodies with protective efficacy against newly emerged mutational variants -
  Accumulating mutations in the SARS-CoV-2 Spike (S) protein can increase the possibility of immune escape, challenging the present COVID-19 prophylaxis and clinical interventions. Here, 3 receptor binding domain (RBD) specific monoclonal antibodies (mAbs), 58G6, 510A5 and 13G9, with high neutralizing potency blocking authentic SARS-CoV-2 virus displayed remarkable efficacy against authentic B.1.351 virus. Each of these 3 mAbs in combination with one neutralizing Ab recognizing non-competing epitope exhibited synergistic effect against authentic SARS-CoV-2 virus. Surprisingly, structural analysis revealed that 58G6 and 13G9, encoded by the IGHV1-58 and the IGKV3-20 germline genes, both recognized the steric region S470-495 on the RBD, overlapping the E484K mutation presented in B.1.351. Also, 58G6 directly bound to another region S450-458 in the RBD. Significantly, 58G6 and 510A5 both demonstrated prophylactic efficacy against authentic SARS-CoV-2 and B.1.351 viruses in the transgenic mice expressing human ACE2 (hACE2), protecting weight loss and reducing virus loads. These 2 ultrapotent neutralizing Abs can be promising candidates to fulfill the urgent needs for the prolonged COVID-19 pandemic.
  🖺 Full Text HTML: Ultrapotent SARS-CoV-2 neutralizing antibodies with protective efficacy against newly emerged mutational variants
• Drug repurposing to face Covid-19: Celastrol, a potential leading drug capable of inhibiting SARS-CoV-2 replication and induced inflammation -
  The global emergence of Covid-19 has caused huge human casualties. Clinical manifestations of the disease vary from asymptomatic to lethal, and the symptomatic form can be associated with cytokine storm and non-homeostatic inflammatory response. In face of the urgent demand for effective drugs to treat Covid-19, we have searched for candidate compounds using a drug repurposing approach based on in silico analysis followed by biological validation. Here we identified celastrol, a pentacyclic triterpene isolated from Tripterygium wilfordii Hook F - a plant used in traditional Chinese medicine - as one of the best compounds out of 39 repurposed drug candidates. Celastrol reverted gene expression signature from SARS-CoV-2-infected cells; bound with high-affinity energy to viral molecular targets such as main protease (Mpro) and receptor-biding domain (RBD); inhibited SARS-CoV-2 replication in monkey (Vero and Vero-ACE2) and human (Caco-2 and Calu-3) cell lines; and decreased interleukin-6 (IL-6) secretion in SARS-CoV-2-infected human cell lines. Interestingly, celastrol acted in a concentration-dependent manner, with undetectable signs of cytotoxicity. Therefore, celastrol is a promising lead drug candidate to treat Covid-19 due to its ability to suppress SARS-CoV-2 replication and IL-6 production in infected cells, two critical events in the pathophysiology of this disease.
  🖺 Full Text HTML: Drug repurposing to face Covid-19: Celastrol, a potential leading drug capable of inhibiting SARS-CoV-2 replication and induced inflammation
• Comparison of Mucosal and Intramuscular Immunization against SARS-CoV-2 with Replication-Defective and Replicating Single-cycle Adenovirus Vaccines -
  SARS-CoV-2 enters the body at mucosal surfaces, such as the nose and lungs. These events involve a small number of virions at these mucosal barriers and are therefore a strategic point to stop a COVID-19 infection before it starts. Despite this, most vaccines against COVID-19 are being injected into the muscle where they will not generate the highest levels of mucosal protection. The vaccines that are approved for use in humans are all replication-defective (RD) mRNA, DNA, or adenovirus (Ad) vaccines that do not amplify antigen transgenes. We developed single cycle adenovirus (SC-Ad) vectors that replicate antigen genes up to 10,000-fold in human cells, but that are disabled from producing infectious Ad particles. We show here that SC-Ad expressing the full-length SARS-CoV-2 spike protein produces 100-fold more spike protein than a matched RD-Ad-Spike vector. When Ad-permissive hamsters were immunized with these vaccines by intranasal (IN) or intramuscular (IM) routes, SC-Ad produced significantly stronger antibody responses as compared to RD-Ad against the spike protein that rose over 14 weeks after one immunization. Single IN or IM immunizations generated significant antibody responses in serum and in bronchoalveolar lavages (BALs). IN priming, but not IM priming, generated HLA-restricted CD8 T cell responses in BALs. SC-Ad-Spike generated antibodies that retain binding to spike receptor binding domains (RBDs) with mutations from new viral variants. These data suggest empowering the genomes of gene-based vaccines with the ability to amplify antigen genes can increase potency. This may be particularly advantageous when applying mucosal vaccines to combat mucosal pathogens like SARS-CoV-2.
  🖺 Full Text HTML: Comparison of Mucosal and Intramuscular Immunization against SARS-CoV-2 with Replication-Defective and Replicating Single-cycle Adenovirus Vaccines

From Clinical Trials

• Oestrogen Treatment for COVID-19 Symptoms - Condition:   COVID-19
  Intervention:   Drug: Transdermal estradiol gel
  Sponsors:   Hamad Medical Corporation;   Laboratoires Besins International
  Not yet recruiting

• Clinical Study in the Treatment of Patients With Moderate Course of COVID-19 - Condition:   COVID-19
  Interventions:   Drug: COVID-globulin;   Drug: Placebo
  Sponsor:   Microgen
  Recruiting

• The Effects of a Multi-factorial Rehabilitation Program for Healthcare Workers Suffering From Post-COVID-19 Fatigue Syndrome - Condition:   COVID-19
  Intervention:   Other: Exercise
  Sponsor:   Medical University of Vienna
  Recruiting

• Omega-3 Oil Use in COVID-19 Patients in Qatar - Condition:   COVID-19
  Intervention:   Drug: Omega 3 fatty acid
  Sponsor:   Hamad Medical Corporation
  Recruiting

• Safety and Immunogenicity of the Inactivated Koçak-19 Inaktif Adjuvanlı COVID-19 Vaccine Compared to Placebo - Condition:   COVID-19 Vaccine
  Interventions:   Biological: Koçak-19 Inaktif Adjuvanlı COVID-19 Vaccine 4 µg/0.5 ml Vaccine;   Biological: Koçak-19 Inaktif Adjuvanlı COVID-19 Vaccine 6 µg/0.5 ml Vaccine;   Biological: Placebo
  Sponsor:   Kocak Farma
  Recruiting

• Study of Intravenous Ampion in Adult COVID-19 Patients Requiring Supplemental Oxygen - Condition:   COVID-19
  Interventions:   Biological: Ampion;   Other: Saline
  Sponsor:   Ampio Pharmaceuticals. Inc.
  Recruiting

• A Study to Evaluate the Efficacy, Safety and Immunogenicity of SARS-CoV-2 Vaccine (Vero Cells), Inactivated in Healthy Adults Aged 18 Years and Older (COVID-19) - Condition:   COVID-19
  Interventions:   Biological: SARS-CoV-2 Vaccine (Vero Cells), Inactivated;   Biological: Placebo
  Sponsors:   Shenzhen Kangtai Biological Products Co., LTD;   Beijing Minhai Biotechnology Co., Ltd
  Not yet recruiting

• Efficacy and Safety of Oral Immunotherapy With GcMAF in Hospitalized Patients With COVID-19 Pneumonia - Condition:   COVID-19 Pneumonia
  Intervention:   Dietary Supplement: Saisei Maf capsules
  Sponsor:   Dr. Spadera Lucrezia
  Recruiting

• Safety and Efficacy of Hyperbaric Oxygen Therapy for Long COVID Syndrome - Condition:   COVID-19
  Interventions:   Drug: Hyperbaric oxygen;   Procedure: Sham treatment
  Sponsors:   Karolinska University Hospital;   Karolinska Institutet;   Karolinska Trial Alliance
  Not yet recruiting

• A Phase 2 Study to Evaluate Biomarker Change, Efficacy, Pharmacokinetics, Safety and Tolerability of Telacebec (Q203) in Covid-19 Patients - Condition:   COVID-19 Virus Infection
  Interventions:   Drug: Telacebec;   Drug: COVID-19 Standard of care
  Sponsor:   Qurient Co., Ltd.
  Not yet recruiting

• Virgin Coconut Oil as Adjunctive Therapy for Hospitalized COVID-19 Patients - Condition:   Covid19
  Intervention:   Drug: Virgin Coconut Oil
  Sponsors:   University of the Philippines;   Philippine Coconut Authority;   Philippine Council for Health Research & Development
  Recruiting

• Rehabilitation for Patients With Persistent Symptoms Post COVID-19 - Condition:   Covid19
  Intervention:   Other: Concentrated rehabilitation for patients with persistent symptoms post COVID-19
  Sponsors:   Western Norway University of Applied Sciences;   Helse-Bergen HF
  Recruiting

• Safety and Immunogenicity of Demi-dose of Two Covid-19 mRNA Vaccines in Healthy Population - Condition:   Covid19
  Intervention:   Diagnostic Test: immunogenicity after first and second dose
  Sponsors:   Sciensano;   Mensura EDPB;   Institute of Tropical Medicine, Belgium;   Erasme University Hospital
  Not yet recruiting

• Efficacy of FES Cycling After a Severe Form of COVID-19 - Condition:   Person With a Severe Form of COVID-19 That Caused an Acute Distress Respiratory Syndrome Treated by Mechanical Ventilation in Intensive Care Unit
  Interventions:   Behavioral: Physical therapy that include a standardized cycling training with functional electrical stimulation;   Behavioral: Physical therapy that include a standardized cycling training with no additional functional electrical stimulation
  Sponsor:   Hospices Civils de Lyon
  Not yet recruiting

• A Phase III Clinical Study of a SARS-CoV-2 Messenger Ribonucleic Acid (mRNA) Vaccine Candidate Against COVID-19 in Population Aged 18 Years and Above - Conditions:   COVID-19;   SARS-CoV-2
  Interventions:   Biological: SARS-CoV-2 mRNA Vaccine;   Biological: Placebo
  Sponsors:   Walvax Biotechnology Co., Ltd.;   Abogen Biosciences Co., Ltd.;   Yuxi Walvax Biotechnology Co., Ltd.
  Not yet recruiting

From PubMed

• Successful treatment of vaccine-induced prothrombotic immune thrombocytopenia (VIPIT) - Cases of unusual thrombosis and thrombocytopenia after administration of the ChAdOx1 nCoV-19 vaccine (AstraZeneca) have been reported. The term vaccine-induced prothrombotic immune thrombocytopenia (VIPIT) was coined to reflect this new phenomenon. In vitro experiments with VIPIT patient sera indicated that high dose intravenous immunoglobulins (IVIG) competitively inhibit the platelet activating properties of ChAdOx1 nCoV-19 vaccine induced antibodies. Here, we report a case of a 62-year-old…

• Antibody Affinity Governs the Inhibition of SARS-CoV-2 Spike/ACE2 Binding in Patient Serum - The humoral immune response plays a key role in suppressing the pathogenesis of SARS-CoV-2. The molecular determinants underlying the neutralization of the virus remain, however, incompletely understood. Here, we show that the ability of antibodies to disrupt the binding of the viral spike protein to the angiotensin-converting enzyme 2 (ACE2) receptor on the cell, the key molecular event initiating SARS-CoV-2 entry into host cells, is controlled by the affinity of these antibodies to the viral…

• A crystallography-based investigation of weak interactions for drug design against COVID-19 - Interactions between proteins and small molecules play important roles in the inhibition of protein function. However, a lack of proper knowledge about non-covalent interactions can act as a barrier towards gaining a complete understanding of the factors that control these associations. To find effective molecules for COVID-19 inhibition, we have quantitatively investigated 143 X-ray crystal structures of the SARS-CoV-2 M^(pro) protein of coronavirus with covalently or non-covalently bound small…

• The role of IL-6 and IL-6 blockade in COVID-19 - INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a dysregulated hyperinflammatory response.

• Interleukin-6: obstacles to targeting a complex cytokine in critical illness - Circulating concentrations of the pleiotropic cytokine interleukin-6 (IL-6) are known to be increased in pro-inflammatory critical care syndromes, such as sepsis and acute respiratory distress syndrome. Elevations in serum IL-6 concentrations in patients with severe COVID-19 have led to renewed interest in the cytokine as a therapeutic target. However, although the pro-inflammatory properties of IL-6 are widely known, the cytokine also has a series of important physiological and…

• Interactions between SARS coronavirus 2 papain-like protease and immune system: a potential drug target for the treatment of COVID-19 - Coronaviruses (CoVs) are a large family of respiratory viruses which can cause mild to moderate upper respiratory tract infections. Recently, new coronavirus named as Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified which is a major threat to public health. Innate immune responses play a vital role in a host’s defense against viruses. Interestingly, CoVs have evolved elaborate strategies to evade the complex system of sensors and signaling molecules to suppress…

• Acute Cardiac Injury in Coronavirus Disease 2019 and Other Viral Infections-A Systematic Review and Meta-Analysis - CONCLUSIONS: Acute cardiac injury may be associated with whether the virus binds angiotensin-converting enzyme-2. Acute cardiac injury occurs in half of critically ill coronavirus disease 2019 patients, but only 12% of patients infected by viruses that do not bind to angiotensin-converting enzyme-2.

• A Multifunctional Peptide From Bacillus Fermented Soybean for Effective Inhibition of SARS-CoV-2 S1 Receptor Binding Domain and Modulation of Toll Like Receptor 4: A Molecular Docking Study - Fermented soybean products are traditionally consumed and popular in many Asian countries and the northeastern part of India. To search for potential agents for the interruption of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike glycoprotein 1 (S1) and human angiotensin-converting enzyme 2 (ACE2) receptor interactions, the in silico antiviral prospective of peptides identified from the proteome of kinema was investigated. Soybean was fermented using Bacillus licheniformis…

• Virtual screening by targeting proteolytic sites of furin and TMPRSS2 to propose potential compounds obstructing the entry of SARS-CoV-2 virus into human host cells - BACKGROUND AND AIM: The year 2020 begins with the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that cause the disease COVID-19, and continue till today. As of March 23, 2021, the outbreak has infected 124,313,054 worldwide with a total death of 2,735,707. The use of traditional medicines as an adjuvant therapy with western drugs can lower the fatality rate due to the COVID-19. Therefore, in silico molecular docking study was performed to search potential…

• MicroLet-7b Regulates Neutrophil Function and Dampens Neutrophilic Inflammation by Suppressing the Canonical TLR4/NF-κB Pathway - Sepsis is a heterogeneous syndrome caused by a dysregulated host response during the process of infection. Neutrophils are involved in the development of sepsis due to their essential role in host defense. COVID-19 is a viral sepsis. Disfunction of neutrophils in sepsis has been described in previous studies, however, little is known about the role of microRNA-let-7b (miR-let-7b), toll-like receptor 4 (TLR4), and nuclear factor kappa B (NF-κB) activity in neutrophils and how they participate in…

• Possible Potential Effects of Honey and Its Main Components Against Covid-19 Infection - Coronavirus disease 2019 (COVID-19) is a viral pneumonia that is spreading rapidly worldwide. The main feature of this disease is a severe acute respiratory syndrome and caused by coronavirus 2 (SARS-CoV-2). There are several unknowns about the pathogenesis and therapeutically treatment of COVID-19 infection. In addition, available treatment protocols have not been effective in managing COVID-19 infection. It is proposed that natural anti-oxidants such as lemon, green tea, saffron, curcuma…

• Discovery of anti-MERS-CoV small covalent inhibitors through pharmacophore modeling, covalent docking and molecular dynamics simulation - Middle east respiratory syndrome coronavirus (MERS-CoV) is a fatal pathogen that poses a serious health risk worldwide and especially in the middle east countries. Targeting the MERS-CoV 3-chymotrypsin-like cysteine protease (3CL^(pro)) with small covalent inhibitors is a significant approach to inhibit replication of the virus. The present work includes generating a pharmacophore model based on the X-ray crystal structures of MERS-CoV 3CL^(pro) in complex with two covalently bound inhibitors….

• In-silico pharmacophoric and molecular docking-based drug discovery against the Main Protease (Mpro) of SARS-CoV-2, a causative agent COVID-19 - COVID-19 (Coronavirus Disease 2019) caused by a novel ‘SARS-CoV-2’ virus resulted in public health emergencies across the world. An effective vaccine to cure this virus is not yet available, thus requires concerted efforts at various scales. In this study, we employed Computer-Aided Drug Design (CADD) based approach to identify the drug-like compounds - inhibiting the replication of the main protease (M^(pro)) of SARS-CoV-2. Our database search using an online tool “ZINC pharmer” retrieved ~1500…

• Babaodan controls excessive immune responses and may represent a cytokine-targeted agent suitable for COVID-19 treatment - It has become evident that the actions of pro-inflammatory cytokines and/or the development of a cytokine storm are responsible for the occurrence of severe COVID-19 during SARS-CoV-2 infection. Although immunomodulatory mechanisms vary among viruses, the activation of multiple TLRs that occurs primarily through the recruitment of adapter proteins such as MyD88 and TRIF contributes to the induction of a cytokine storm. Based on this, controlling the robust production of pro-inflammatory…

• Antiviral strategies should focus on stimulating the biosynthesis of heparan sulfates, not their inhibition - Antiviral strategies for viruses that utilize proteoglycan core proteins (syndecans and glypicans) as receptors should focus on heparan sulfate (HS) biosynthesis rather than on inhibition of these sugar chains. Here, we show that heparin and certain xylosides, which exhibit in vitro viral entry inhibitory properties against HSV-1, HSV-2, HPV-16, HPV-31, HVB, HVC, HIV-1, HTLV-1, SARS-CoV-2, HCMV, DENV-1, and DENV-2, stimulated HS biosynthesis at the cell surface 2- to 3-fold for heparin and up to…

From Patent Search

• Compositions and methods for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection - - link

• 5-(4-TERT-BUTOXY PHENYL)-3-(4N-OCTYLOXYPHENYL)-4,5-DIHYDROISOXAZOLE MOLECULE (C-I): A PROMISING DRUG FOR SARS-COV-2 (TARGET I) AND BLOOD CANCER (TARGET II) - The present invention relates to a method ofmolecular docking of crystalline compound (C-I) with SARS-COV 2 proteins and its repurposing with proteins of blood cancer, comprising the steps of ; employing an algorithmto carry molecular docking calculations of the crystalized compound (C-I); studying the compound computationally to understand the effect of binding groups with the atoms of the amino acids on at least four target proteins of SARS-COV 2; downloading the structure of the proteins; removing water molecules, co enzymes and inhibitors attached to the enzymes; drawing the structure using Chem Sketch software; converting the mol file into a PDB file; using crystalized compound (C-I) for comparative and drug repurposing with two other mutated proteins; docking compound into the groove of the proteins; saving format of docked molecules retrieved; and filtering and docking the best docked results. - link

• AQUEOUS ZINC OXIDE NANOSPRAY COMPOSITIONS - Disclosed herein is aqueous zinc oxide nano spray compositions comprising zinc oxide nanoparticles and a synthetic surfactant for controlling the spread of Covid-19 virus. - link

• 一种肝素类药物组合物、喷鼻剂及其制备方法及应用 - 本发明公开了一种肝素类药物组合物、喷鼻剂及其制备方法及应用。该肝素类药物组合物包括肝素钠和阿比朵尔。本发明中的肝素类药物组合物首次采用肝素钠和阿比朵尔联合使用，普通肝素钠联合1μM/L以上的阿比朵尔病毒抑制效率显著高于单独普通肝素钠或单独阿比多尔组（p<0.05）。 - link

• USING CLINICAL ONTOLOGIES TO BUILD KNOWLEDGE BASED CLINICAL DECISION SUPPORT SYSTEM FOR NOVEL CORONAVIRUS (COVID-19) WITH THE ADOPTION OF TELECONFERENCING FOR THE PRIMARY HEALTH CENTRES/SATELLITE CLINICS OF ROYAL OMAN POLICE IN SULTANATE OF OMAN - - link

• 抗SARS-COV-2中和抗体 - 本公开提供了针对SARS‑COV‑2的新颖中和抗体和其抗原结合片段。还提供了包括其的药物组合物和试剂盒以及其用途。 - link

• Peptides and their use in diagnosis of SARS-CoV-2 infection - - link

• Method and compositions for treating coronavirus infection - A method of treating viral infection, such as viral infection caused by a virus of the Coronaviridae family, is provided. A composition having at least oleandrin is used to treat viral infection. - link

• **一种4-肟-5-（2-甲基丙酰基）尿苷的制备方法** - 本发明公开了一种4‑肟‑5‑（2‑甲基丙酰基）尿苷的制备方法，包括：S1：在酸存在条件下，使得化合物1和2,2‑二甲氧基丙烷在有机溶剂中反应得到化合物2；S2：在碱存在条件下，使得化合物2在有机溶剂中反应得到化合物3；S3：在羟胺水溶液存在条件下使化合物3在有机溶剂中反应得到化合物4；S4：在酸存在条件下使化合物4在有机溶剂中反应得到化合物I。本发明制备得到的结晶性能良好的固体，且制备条件简单，转化率以及原子经济性好。 - link

• 一种COVID-19假病毒及其制备方法和用途 - 本发明涉及生物技术领域，特别是涉及一种COVID‑19假病毒及其制备方法和用途本发明，所述COVID‑19假病毒由外壳蛋白质粒与辅助质粒经病毒包装而成，所述外壳蛋白质粒包括表达COVID‑19 S蛋白的质粒、表达COVID‑19 M蛋白的质粒和表达COVID‑19 E蛋白的质粒。本发明的COVID‑19假病毒采用三质粒系统包装，以S/M/E蛋白替代表达VSV‑G蛋白，比仅含有S蛋白的假病毒感染能力更强、灵敏度更高。而且，COVID‑19假病毒携带两种荧光报告基团，不同的荧光报告基团可应用于不同的场景，使得COVID‑19假病毒应用时更简便。 - link