Covid-19 Sentry

Contents

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

From Preprints

• Medication Use Patterns in COVID-19 Positive Patients in a large state-wide health system by Age Group, Comorbidity, and Month During the Pandemic in 2020 -

  Objectives: Main objective was to systematically determine most frequently used medications among COVID-19 patients overall and by hospitalization status. Secondary objective was to measure use patterns of medications considered potential therapeutic options Design: Retrospective cohort study. Setting: The five academic medical centers of University of California Health. Participants: University of California COVID Research Data Set (UC CORDS) patients between March 10, 2020 and December 31, 2020. Exposure(s): Confirmed COVID-19 positive by SARS-CoV-2 nucleic acid amplification. Main Outcome(s) and Measure(s): Main outcomes were percentages of patients prescribed medications, overall, by age group, and by comorbidity based on hospitalization status. Use percentage by month of COVID-19 diagnosis was measured. Cumulative count of potential therapeutic options was measured over time. Results: Dataset included 22897 unique patients with COVID-19 (mean [SD] age, 42.4 [20.4] years; 12154 [53%] female). Among the sample, 6326 28%) were non-Hispanic White, 8475 (37%) were Hispanic, 1562 (7%) Asian, and 1313 (6%) Black. A COVID-related hospitalization occurred in 3546 patients. Of the hospitalized patients, more than 30% had baseline comorbidities of hypertension (48%), hyperlipidemia (37%), and type 2 diabetes (35%). Most frequently used medications in patients overall were acetaminophen (21.2%), albuterol (14.9%), ondansetron (13.9%), and enoxaparin (10.8%). Medications used were generally similar across ages and comorbidities. Prior to May, dexamethasone was rarely used, with well under 50 COVID-19 patients that had been hospitalized to that point receiving the medication. By mid-August, more than 500 patients to that point had received dexamethasone. Hydroxychloroquine use effectively halted in COVID-19 hospitalized patients after May. Throughout the period of March to December 2020, enoxaparin was used in the most patients to that point at any instance. By mid-December, more than 2000 in the analysis cohort of hospitalized patients had received enoxaparin. Conclusions and Relevance: In this retrospective cohort study, across age and comorbidity groups, predominant utilization was for supportive care therapy. Dexamethasone and remdesivir experienced large increases in use. Conversely, hydroxychloroquine and azithromycin use markedly dropped. Medication utilization rapidly shifted towards more evidence-concordant treatment of patients with COVID-19 as rigorous study findings emerged.

  🖺 Full Text HTML: Medication Use Patterns in COVID-19 Positive Patients in a large state-wide health system by Age Group, Comorbidity, and Month During the Pandemic in 2020
• “I Think It’ll All Blow Over in the End”: How Young People Perceive the Impact of COVID-19 on Their Future Orientations - July 2021 -
  Since the beginning of 2020, the coronavirus disease (COVID-19) and its lockdowns have changed the current lives of young people drastically. Given the importance of future orientations for young people’s mental well-being, it is important to investigate if and how this lockdown affected young people’s future orientations. This study interviewed 34 Dutch young people (aged 16-24) with diverse backgrounds in the lockdown of spring 2020 in the Netherlands. Results showed that young people experienced effects of COVID-19 on their current lives and short-term futures, but young people’s long-term futures were not affected by the first COVID-19 lockdown. This may be explained by young people’s assumed temporality of the pandemic, their general optimistic attitudes, two-track thinking, strong feelings of agency, and flexibility.
  🖺 Full Text HTML: “I Think It’ll All Blow Over in the End”: How Young People Perceive the Impact of COVID-19 on Their Future Orientations - July 2021
• Wastewater SARS-CoV-2 Concentration and Loading Variability from Grab and 24-Hour Composite Samples -

  The ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires a significant, coordinated public health response. Assessing case density and spread of infection is critical and relies largely on clinical testing data. However, clinical testing suffers from known limitations, including test availability and a bias towards enumerating only symptomatic individuals. Wastewater-based epidemiology (WBE) has gained widespread support as a potential complement to clinical testing for assessing COVID-19 infections at the community scale. The efficacy of WBE hinges on the ability to accurately characterize SARS-CoV-2 RNA concentrations in wastewater. To date, a variety of sampling schemes have been used without consensus around the appropriateness of grab or composite sampling. Here we address a key WBE knowledge gap by examining the variability of SARS-CoV-2 RNA concentrations in wastewater grab samples collected every 2 hours for 72 hours compared with three corresponding 24-hour flow-weighted composite samples collected over the same period. Results show relatively low variability (respective means for N1, N2, N3 assays = 608, 847.9, 768.4 copies 100 mL-1, standard deviations = 501.4, 500.3, 505.8 copies 100 mL-1) for grab sample concentrations, and good agreement between most grab samples and their respective composite (mean deviation from composite = 159 copies 100 mL-1). When SARS-CoV-2 RNA concentrations are used to calculate viral load (RNA concentration * total influent flow the sample day), the discrepancy between grabs (log10 range for all grabs = 11.9) or a grab and its associated 24-hour composite (log10 difference = 11.6) are amplified. A similar effect is seen when estimating carrier prevalence in a catchment population with median estimates based on grabs ranging 63-1885 carriers. Findings suggest that grab samples may be sufficient to characterize SARS-CoV-2 RNA concentrations, but additional calculations using these data may be sensitive to grab sample variability and warrant the use of flow- weighted composite sampling. These data inform future WBE work by helping determine the most appropriate sampling scheme and facilitate sharing of datasets between studies via consistent methodology.

  🖺 Full Text HTML: Wastewater SARS-CoV-2 Concentration and Loading Variability from Grab and 24-Hour Composite Samples
• Using time use diaries to track changing behavior across successive stages of COVID-19 social restrictions -

  How did people change their behavior over the different phases of the UK COVID-19 restrictions, and how did these changes affect their risk of being exposed to infection? Time use diary surveys are unique in providing a complete chronicle of daily behavior; 24-hour continuous records of the populations9 activities, their social context and their location. We present results from four such surveys, collected in real time from representative UK samples, both before, and at three points over the course of the current pandemic. Comparing across the four waves, we find evidence of substantial changes in the UK population9s behavior relating to activities, locations and social context. We assign different levels of risk to combinations of activities, locations and copresence, to compare risk-related behavior across successive 9lockdowns9. We find evidence that during the second lockdown (November 2020) there was an increase in high-risk behaviors relative to the first (starting March 2020). This increase is shown to be associated with more paid work time in the workplace. At a time when capacity is still limited both in respect of immunization and track-trace technology, governments must continue to rely on changes in people9s daily behaviors to contain the spread of COVID-19 and similar viruses. Time use diary information of this type, collected in real time across the course of the COVID-19 pandemic, can provide policy-makers with information to assess and quantify changes in daily behaviors, and the impact they are likely to have on overall behavioral-associated risks.

  🖺 Full Text HTML: Using time use diaries to track changing behavior across successive stages of COVID-19 social restrictions
• Evaluating discharges and readmissions using a COVID Virtual Ward model: a retrospective data study assessing patient outcomes and the likely staffing commitment -

  Background: COVID-19 has placed a catastrophic burden on acute hospitals. In an attempt to reduce admissions and enable safe early discharge, a COVID virtual ward (CVW) care pathway has been supported by NHS England. This includes discharging people who meet objective criteria based on acuity scores and oxygen saturations, with pulse oximeters and daily phone calls for up to 14 days. Observational studies have reported the safety of this system, but without describing the outcomes from usual care. Methods: A retrospective study using routinely collected health data from all adults with a confirmed positive severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) swab result between 1st June 2020 and 31st Jan 2021 who attended the Emergency Department or Acute Medical Unit at QEHB, which does not have a CVW service. Criteria for CVW were applied using data from the first 24 hours of presentation to hospital and subsequent health outcomes were included for 28 days, including re-presentation, re-admission, ITU escalation and death. Results were compared to reported studies based in secondary care. Results: During the study period, 26,127 patients presented to QEHB hospital. 2301 had a positive SARS-CoV-2 swab. Of these, 1730 (75.2%) did not meet the criteria for the CVW and 571 (24.8%) did. Of the 571, 325 (56.9%) were discharged home within 24 hours and 246 (43.1%) were admitted for 24 hours or longer. Those admitted were older, with increased co-morbidities, 80.9% required hospital-supported acute therapies after the first 24 hours and 10.6% died. Of the 325 discharged, 44 were readmitted (13.5%), 30 (9.2%) with COVID-related symptoms, 5 (1.5%) required ITU and 1 patient (0.3%) died. These results were comparable to published studies with a CVW service. Discussion: In the current study, discharging patients without a CVW did not confer a greater risk of re- presentation, re-admission, ITU escalation or death. The majority of patients who remained in hospital despite meeting the CVW criteria did so for the provision of treatments or acute assessments. It remains uncertain whether a CVW delivers improvements in hard outcomes, and further research is needed.

  🖺 Full Text HTML: Evaluating discharges and readmissions using a COVID Virtual Ward model: a retrospective data study assessing patient outcomes and the likely staffing commitment
• HLA-dependent variation in SARS-CoV-2 CD8+ T cell cross-reactivity with human coronaviruses -
  Pre-existing T cell immunity to SARS-CoV-2 in individuals without prior exposure to SARS-CoV-2 has been reported in several studies. While emerging evidence hints toward prior exposure to common-cold human coronaviruses (HCoV), the extent of- and conditions for- cross-protective immunity between SARS-CoV-2 and HCoVs remain open. Here, by leveraging a comprehensive pool of publicly available functionally evaluated SARS-CoV-2 peptides, we report 126 immunogenic SARS- CoV-2 peptides with high sequence similarity to 285 MHC-presented target peptides from at least one of four HCoV, thus providing a map describing the landscape of SARS-CoV-2 shared and private immunogenic peptides with functionally validated T cell responses. Using this map, we show that while SARS-CoV-2 immunogenic peptides in general exhibit higher level of dissimilarity to both self-proteome and -microbiomes, there exist several SARS-CoV-2 immunogenic peptides with high similarity to various human protein coding genes, some of which have been reported to have elevated expression in severe COVID-19 patients. We then combine our map with a SARS-CoV-2-specific TCR repertoire data from COVID-19 patients and healthy controls and show that whereas the public repertoire for the majority of convalescent patients are dominated by TCRs cognate to private SARS-CoV-2 peptides, for a subset of patients, more than 50% of their public repertoires that show reactivity to SARS-CoV-2, consist of TCRs cognate to shared SARS-CoV-2-HCoV peptides. Further analyses suggest that the skewed distribution of TCRs cognate to shared and private peptides in COVID-19 patients is likely to be HLA- dependent. Finally, by utilising the global prevalence of HLA alleles, we provide 10 peptides with known cognate TCRs that are conserved across SARS-CoV-2 and multiple human coronaviruses and are predicted to be recognised by a high proportion of the global population. Overall, our work indicates the potential for HCoV-SARS-CoV-2 reactive CD8+ T cells, which is likely dependent on differences in HLA-coding genes among individuals. These findings may have important implications for COVID-19 heterogeneity and vaccine-induced immune responses as well as robustness of immunity to SARS- CoV-2 and its variants.
  🖺 Full Text HTML: HLA-dependent variation in SARS-CoV-2 CD8+ T cell cross-reactivity with human coronaviruses
• Previously unrecognized non-reproducible antibody-antigen interactions and their implications for diagnosis of viral infections including COVID-19 -
  Antibody-antigen (Ab-Ag) interactions are canonically described by a model which exclusively accommodates non- interaction (0) or reproducible-interaction (RI) states, yet this model is inadequate to explain often-encountered non- reproducible signals. Here, by monitoring diverse experimental systems and confirmed COVID-19 clinical sera using a peptide microarray, we observed that non-specific interactions (NSI) comprise a substantial proportion of non- reproducible antibody-based results. This enabled our discovery and capacity to reliably identify non-reproducible Ab-Ag interactions (NRI), as well as our development of a powerful explanatory model (“0-RI-NRI-Hook four-state model”) that is [mAb]-dependent, regardless of specificity, which ultimately shows that both NSI and NRI are not predictable yet certain-to-happen. In experiments using seven FDA-approved mAb drugs, we demonstrated the use of NSI counts in predicting epitope type. Beyond challenging the centrality of Ab-Ag interaction specificity data in serology and immunology, our discoveries also facilitated the rapid development of a serological test with uniquely informative COVID-19 diagnosis performance.
  🖺 Full Text HTML: Previously unrecognized non- reproducible antibody-antigen interactions and their implications for diagnosis of viral infections including COVID-19
• Forecasting admissions in psychiatric hospitals before and during Covid-19 -

  Introduction The COVID-19 pandemic has strong effects on most health care systems and individual services providers. Forecasting of admissions can help for the efficient organisation of hospital care. We aimed to forecast the number of admissions to psychiatric hospitals before and during the COVID-19 pandemic and we compared the performance of machine learning models and time series models. This would eventually allow to support timely resource allocation for optimal treatment of patients. Methods We used admission data from 9 psychiatric hospitals in Germany between 2017 and

2020. We compared machine learning models with time series models in weekly, monthly and yearly forecasting before and during the COVID-19 pandemic. Our models were trained and validated with data from the first two years and tested in prospectively sliding time-windows in the last two years. Results A total of 90,686 admissions were analysed. The models explained up to 90% of variance in hospital admissions in 2019 and 75% in 2020 with the effects of the COVID-19 pandemic. The best models substantially outperformed a one-step seasonal naive forecast (seasonal mean absolute scaled error (sMASE) 2019: 0.59, 2020: 0.76). The best model in 2019 was a machine learning model (elastic net, mean absolute error (MAE): 7.25). The best model in 2020 was a time series model (exponential smoothing state space model with Box-Cox transformation, ARMA errors and trend and seasonal components, MAE: 10.44), which adjusted more quickly to the shock effects of the COVID-19 pandemic. Models forecasting admissions one week in advance did not perform better than monthly and yearly models in 2019 but they did in 2020. The most important features for the machine learning models were calendrical variables. Conclusion Model performance did not vary much between different modelling approaches before the COVID-19 pandemic and established forecasts were substantially better than one-step seasonal naive forecasts. However, weekly time series models adjusted quicker to the COVID-19 related shock effects. In practice, different forecast horizons could be used simultaneously to allow both early planning and quick adjustments to external effects.

• Modeling shield immunity to reduce COVID-19 transmission in long-term care facilities -

  Nursing homes and other long-term care facilities in the United States have experienced severe COVID-19 outbreaks and elevated mortality rates, often following upon the inadvertent introduction of SARS-CoV-2. Following FDA emergency use approval, widespread distribution of vaccines has resulted in rapid reduction in COVID-19 cases in vulnerable, older populations. Yet, vaccination coverage remains incomplete amongst residents and healthcare workers. As such, mitigation and prevention strategies are needed to reduce the ongoing risk of transmission and mortality amongst vulnerable, nursing home populations. One such strategy is that of ′shield immunity′, in which recovered individuals increase their contact rates and therefore shield individuals who remain susceptible to infection. Here, we adapt recent population-scale shield immunity models to a network context. To do so, we evaluate network-based shield immunity by evaluating how restructured interactions in a bipartite network (e.g., between healthcare workers and long-term care residents) affects SARS-CoV-2 epidemic dynamics. First, we identify a series of rewiring principles that leverage viral testing, antibody testing, and vaccination information to reassign immunized healthcare workers to care for infected residents while retaining workload balance amidst an outbreak. We find a significant reduction in outbreak size when using infection and immune-based cohorting as a weekly intervention. Second, we also identify a preventative strategy using shield-immunity rewiring principles, by assigning susceptible healthcare workers to care for cohorts of immunized residents; this strategy reduces the risk that an inadvertent introduction of SARS-CoV-2 into the facility via a healthcare worker spreads to susceptible residents. Network-based epidemic modeling reveals that preventative rewiring can control the size of outbreaks at levels similar to that of isolation of infectious healthcare workers. Overall, this assessment of shield immunity provides further support for leveraging infection and immune status in network-based interventions to control and prevent the spread of COVID-19.

  🖺 Full Text HTML: Modeling shield immunity to reduce COVID-19 transmission in long-term care facilities
• Modelling infectious disease transmission potential as a function of human behaviour -

  Mathematical modelling is an important public health tool for aiding understanding the spread of respiratory infectious diseases, such as influenza or COVID-19, and for quantifying the effects of behavioural interventions. However, such models rarely explicitly appeals to theories of human behaviour to justify model assumptions. Here we propose a novel mathematical model of disease transmission via fomites (luggage trays) at airport security screening during an outbreak. Our model incorporates the self-protective behaviour of using hand sanitiser gel in line with the extended parallel processing model (EPPM) of behaviour. We find that changing model assumptions of human behaviour in line with the EPPM gives qualitatively different results on the optimal placement of hand sanitiser gels within an airport compared to the model with naive behavioural assumptions. Specifically, that it is preferable to place hand sanitiser gels after luggage screening in most scenarios, however in situations where individuals perceive high threat and low efficacy this strategy may need to be reviewed. This model demonstrates how existing behavioural theories can be incorporated into mathematical models of infectious disease.

  🖺 Full Text HTML: Modelling infectious disease transmission potential as a function of human behaviour
• SARS-CoV-2 seroprevalence in Chattogram, Bangladesh before a National Lockdown, March-April 2021 -

  The absence of population-based seroprevalence estimates in Bangladesh have impeded efforts to understand the relatively low reported mortality and incidence rates of SARS-CoV-2 in this country. We report findings of a representative serosurvey of the Sitakunda subdistrict in the Chattogram division of Bangladesh before a nationwide lockdown in April 2021. After adjusting for age, sex, household clustering and test performance using a Bayesian modeling approach, we estimate the seroprevalence of SARS-CoV-2 to have been 63.1% (56.2-60.8%) in Sitakunda during this period. These results illustrate that going into the national lockdown in April 2021, the majority of this population had already been infected despite a relatively low incidence of medically attended COVID-19.

  🖺 Full Text HTML: SARS-CoV-2 seroprevalence in Chattogram, Bangladesh before a National Lockdown, March-April 2021
• Potential applications of the rapid COVID-19 antibody test kit screening in comparison to the RT-PCR in patients and personnel at the Department of Obstetrics and Gynecology. -

  Objective To explore potential applications of the rapid antibody test for COVID-19 screening, in comparison to RT-PCR, for emergency obstetric and gynecological procedures, and medical personnel in the Department of Obstetrics and Gynecology. Methods A cross-sectional study was conducted in expected 290 participants: 230 patients and 60 medical staff, during the four-month national COVID-19 outbreak period (Aug-Sep 2020, and Dec 2020-Jan 2021). All participants underwent both rapid antibody tests and RT-PCR (at admission for patients). Results A total of 270 participants completed the study. Fever and URI symptoms were present in 6/210 patients (2.8%) while one patient (0.5%) had a history of traveling to a high-risk area. However, only two (1%) asymptomatic patients had positive IgM results. Concerning the medical personnel, 10% fell into the patient under investigation (PUI) category. 4/60 (6.7%) IgM positive was observed in the staff cohort in which 3/4 came from non-PUI participants. Neither participant had RT-PCR positive demonstrating a 1.9% total false positive rate. Conclusion Rapid point-of-care antibody test can be used to screen either a pregnant coming for delivery, a patient who requires urgent/emergency operative procedures, or medical personnel, at least in the defined lower-prevalence COVID-19 situation.

  🖺 Full Text HTML: Potential applications of the rapid COVID-19 antibody test kit screening in comparison to the RT-PCR in patients and personnel at the Department of Obstetrics and Gynecology.
• The SARS-CoV-2 reproduction number R0 in cats -
  Domestic cats are susceptible to SARS-CoV-2 virus infection and given that they are in close contact with people, assessing the potential risk cats represent for the transmission and maintenance of SARS-CoV-2 is important. Assessing this risk implies quantifying transmission from humans-to-cats, from cats-to-cats and from cats-to-humans. Here we quantified the risk of cat-to-cat transmission by reviewing published literature describing transmission either experimentally or under natural conditions in infected households. Data from these studies were collated to quantify the SARS-CoV-2 reproduction number R0 among cats. The estimated R0 was significantly higher than 1, hence cats could play a role in the transmission and maintenance of SARS-CoV-2. Questions that remain to be addressed are the risk of transmission from humans-to-cats and cats-to-humans. Further data on household transmission and data on virus levels in both the environment around infected cats and their exhaled air could be a step towards assessing these risks.

• CRISPR screens for host factors critical for infection by SARS-CoV-2 variants of concern identify GATA6 as a central modulator of ACE2. -
  The global spread of SARS-CoV-2 lead to the most challenging pandemic in this century, posing major economic and health challenges worldwide. Revealing host genes essential for infection by multiple variants of SASR-CoV-2 can provide insights into the virus pathogenesis, and facilitates the development of novel broad-spectrum host-directed therapeutics. Here, employing genome-scale CRISPR screens, we provide a comprehensive data-set of cellular factors that are exploited by WT-SARS-CoV-2 as well as two additional recently emerged variants of concerns (VOCs), Alpha and Beta. These screens identified known and novel host factors critical for SARS-CoV-2 infection, including various components belonging to the Clathrin-dependent transport pathway, ubiquitination and Heparan sulfate biogenesis. In addition, the host metabolic pathways pertaining to mitochondrial activity as well as phosphatidylglycerol biosynthesis processes appeared to have major anti-viral functions. Comparative analysis between the different VOCs revealed the receptor KREMEN2 as unique gene required only to the Alpha variant, providing a possible explanation for the increased infectivity of this variant. Furthermore, the analysis identified GATA6, a zinc finger transcription factor, as an essential pro-viral gene for all variants inspected. We reveal that GATA6 directly regulates ACE2 transcription and is accordingly, critical for SARS-CoV-2 cell entry. Analysis of clinical samples collected from SARS-CoV-2 infected individuals showed an elevated level of GATA6, indicating the important role GATA6 may be playing in COVID-19 pathogenesis. Finally, pharmacological inhibition of GATA6 results in down-modulation of ACE2 and consequently to inhibition of the viral infectivity. Overall, we show GATA6 represents a target for the development of anti-SARS-CoV-2 therapeutic strategies and reaffirm the value of the CRISPR loss-of-function screens in providing a list of potential new targets for therapeutic interventions.
  🖺 Full Text HTML: CRISPR screens for host factors critical for infection by SARS-CoV-2 variants of concern identify GATA6 as a central modulator of ACE2.
• The SARS-CoV-2 Spike protein disrupts human cardiac pericytes function through CD147-receptor-mediated signalling: a potential non-infective mechanism of COVID-19 microvascular disease -
  Severe coronavirus disease 2019 (COVID-19) manifests as a life-threatening microvascular syndrome. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the Spike (S) protein to engage with its receptors and infect host cells. To date, it is still not known whether heart vascular pericytes (PCs) are infected by SARS-CoV-2, and if the S protein alone provokes PC dysfunction. Here, we aimed to investigate the effects of the S protein on primary human cardiac PC signalling and function. Results show, for the first time, that cardiac PCs are not permissive to SARS-CoV-2 infection in vitro, whilst a recombinant S protein alone elicits functional alterations in PCs. This was documented as:

1. increased migration, (2) reduced ability to support endothelial cell (EC) network formation on Matrigel, (3) secretion of pro-inflammatory molecules typically involved in the cytokine storm, and (4) production of pro-apoptotic factors responsible for EC death. Next, adopting a blocking strategy against the S protein receptors angiotensin- converting enzyme 2 (ACE2) and CD147, we discovered that the S protein stimulates the phosphorylation/activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) through the CD147 receptor, but not ACE2, in PCs. The neutralisation of CD147, either using a blocking antibody or mRNA silencing, reduced ERK1/2 activation and rescued PC function in the presence of the S protein. In conclusion, our findings suggest that circulating S protein prompts vascular PC dysfunction, potentially contributing to establishing microvascular injury in organs distant from the site of infection. This mechanism may have clinical and therapeutic implications.
   🖺 Full Text HTML: The SARS-CoV-2 Spike protein disrupts human cardiac pericytes function through CD147-receptor-mediated signalling: a potential non-infective mechanism of COVID-19 microvascular disease

From Clinical Trials

• A Study of PF-07321332/Ritonavir in Nonhospitalized High Risk Adult Participants With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: PF-07321332;   Drug: Ritonavir;   Drug: Placebo
  Sponsor:   Pfizer
  Not yet recruiting

• Building Resiliency and Vital Equity (BRAVE) Project: Understanding Native Americans’ Perceptions/Beliefs About COVID-19 Testing and Vaccination Study - Condition:   Covid19 Virus Infection
  Intervention:   Behavioral: Protect Your Elders Campaign
  Sponsors:   North Carolina Central University;   Lumbee Tribe of North Carolina;   University of North Carolina at Pembroke
  Recruiting

• Study on Sequential Immunization of Inactivated COVID-19 Vaccine and Recombinant COVID-19 Vaccine (Ad5 Vector) - Condition:   COVID-19
  Interventions:   Biological: Recombinant SARS-CoV-2 Ad5 vectored vaccine;   Biological: Inactive SARS-CoV-2 vaccine (Vero cell)
  Sponsors:   Jiangsu Province Centers for Disease Control and Prevention;   CanSino Biologics Inc.
  Not yet recruiting

• Vaccination for Recovered Inpatients With COVID-19 (VATICO) - Condition:   Covid19
  Interventions:   Biological: Moderna mRNA-1273 COVID-19 vaccine;   Biological: Pfizer BNT162b2 COVID-19 vaccine
  Sponsors:   International Network for Strategic Initiatives in Global HIV Trials (INSIGHT);   University of Minnesota;   National Institute of Allergy and Infectious Diseases (NIAID);   University of Copenhagen;   Kirby Institute;   Washington D.C. Veterans Affairs Medical Center;   AIDS Clinical Trials Group;   National Heart, Lung, and Blood Institute (NHLBI);   US Department of Veterans Affairs;   Prevention and Early Treatment of Acute Lung Injury (PETAL);   Cardiothoracic Surgical Trials Network (CTSN);   Medical Research Council
  Not yet recruiting

• Efficacy of Amantadine Treatment in COVID-19 Patients - Condition:   Patients With Moderate or Severe COVID-19
  Intervention:   Drug: Amantadine
  Sponsors:   Noblewell;   Medical Research Agency (ABM);   Leszek Giec Upper-Silesian Medical Centre of the Silesian Medical University in Katowice
  Recruiting

• Internet-based Multidisciplinary Rehabilitation for Longterm COVID-19 Syndrome - Condition:   Long COVID-19
  Intervention:   Behavioral: Multidisciplinary Rehabilitation
  Sponsors:   Danderyd Hospital;   St Göran Hospital, Stockholm
  Recruiting

• Enabling Family Physicians to Reduce Vaccine Hesitancy and Increase Covid-19 Vaccine Uptake - Conditions:   Covid19;   COVID-19 Vaccine
  Interventions:  
  Behavioral: Tailored COVID-19 vaccine messages;   Other: Other health messages
  Sponsors:  
  Hopital Montfort;   Public Health Agency of Canada (PHAC);   Eastern Ontario Health Unit
  Not yet recruiting

• COVID-19 and Lung Ultrasound Utility - Condition:   Covid19
  Intervention:   Device: Device: Butterfly iQ
  Sponsor:  
  Rocket Doctor Inc.
  Recruiting

• A Different Use of The Aerosol Box in COVID-19 Patients; Internal Jugular Vein Cannulation - Condition:   COVID-19 Pneumonia
  Intervention:   Procedure: Internal jugular vein cannulation
  Sponsor:   Bakirkoy Dr. Sadi Konuk Research and Training Hospital
  Completed

• Reconditioning Exercise for COVID-19 Patients Experiencing Residual sYmptoms - Condition:   Covid19
  Intervention:   Other: Exercise Therapy
  Sponsor:  
  Wake Forest University Health Sciences
  Not yet recruiting

• Lipid Emulsion Infusion and COVID-19 Patients - Condition:   Covid19
  Interventions:   Drug: SMOFlipid;   Other: 0.9% saline
  Sponsor:   Assiut University
  Recruiting

• Baricitinib in Hospitalized Covid-19 Patients With Diabetes Mellitus - Condition:   COVID-19 Pneumonia
  Interventions:   Drug: Baricitinib;   Drug: Dexamethasone;   Drug: Remdesivir
  Sponsor:   Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders
  Recruiting

• Short Term, High Dose Vitamin D Supplementation in Moderate to Severe COVID-19 Disease - Condition:   Covid19
  Intervention:   Drug: cholecalciferol 6 lakh IU
  Sponsor:  
  Postgraduate Institute of Medical Education and Research
  Not yet recruiting

• Immunogenicity and Safety of an Inactivated COVID-19 Vaccine - Condition:   COVID-19
  Interventions:   Biological: Inactivated COVID-19 Vaccine;   Biological: 23-valent pneumococcal polysaccharide vaccine;   Biological: Inactivated Hepatitis A Vaccine
  Sponsor:  
  Sinovac Research and Development Co., Ltd.
  Not yet recruiting

• Evaluation of the RD-X19 Treatment Device in Individuals With Mild to Moderate COVID-19 - Condition:   COVID19
  Interventions:   Device: RD-X19;   Device: Sham
  Sponsor:  
  EmitBio Inc.
  Recruiting

From PubMed

• Syncing sustainable urban mobility with public transit policy trends based on global data analysis - Unforeseeable developments will accompany progressive COVID-19 recovery globally. Similarly, science will inform changes amidst its own progress. Social isolation and distancing imposed by the pandemic are likely to result in changed habits, behavior, and thinking paradigms. Inevitably, this should affect the tremendous confusion inhibiting automated urban mobility’s evolution. While mobility often seems magnanimously resistant to change, using international data, this analysis shows road…

• Masitinib is a broad coronavirus 3CL inhibitor that blocks replication of SARS-CoV-2 - There is an urgent need for antiviral agents that treat SARS-CoV-2 infection. We screened a library of 1,900 clinically safe drugs against OC43, a human beta-coronavirus that causes the common cold and evaluated the top hits against SARS- CoV-2. Twenty drugs significantly inhibited replication of both viruses in vitro. Eight of these drugs inhibited the activity of the SARS-CoV-2 main protease, 3CLpro, with the most potent being masitinib, an orally bioavailable tyrosine kinase inhibitor. X-ray…

• Preventive behaviours and family inequalities during the COVID-19 pandemic: a cross-sectional study in China - CONCLUSIONS: Inequalities in COVID-19 prevention behaviours exist between families and inadequate adoption of prevention by vulnerable groups are noteworthy. This study expands the research perspective by emphasizing the role of household factors in preventive behaviours and by focusing on family inequalities. The government should use traditional media as a platform to enhance residents’ public health knowledge. Targeted additional wage subsidies, investments in affordable housing, financial…

• Before the 2020 Pandemic: an observational study exploring public knowledge, attitudes, plans, and preferences towards death and end of life care in Wales - CONCLUSIONS: People are ready to talk about death and dying and COVID-19 has increased awareness. A combination of top- down and bottom-up initiatives across levels and settings can increase awareness, knowledge, and service-utilisation- drivers to support health professionals and people towards shared decisions which align with people’s end of life wishes and preferences.

• Low neutralizing antibody responses in WM, CLL and NHL patients after the first dose of the BNT162b2 and AZD1222 vaccine - Vaccination against SARS-CoV-2 is considered as the most important preventive strategy against COVID-19, but its efficacy in patients with hematological malignancies is largely unknown. We investigated the development of neutralizing antibodies (NAbs) against SARS-CoV-2 in patients with Waldenstrom Macroglobulinemia (WM), Chronic Lymphocytic Leukemia (CLL) and Non-Hodgkin Lymphoma (NHL). After the first dose of the vaccine, on D22, WM/CLL/NHL patients had lower NAb titers compared to controls:…

• Mouthwashes with CPC Reduce the Infectivity of SARS-CoV-2 Variants In Vitro - Oral mouthwashes decrease the infectivity of several respiratory viruses including SARS-CoV-2. However, the precise agents with antiviral activity in these oral rinses and their exact mechanism of action remain unknown. Here we show that cetylpyridinium chloride (CPC), a quaternary ammonium compound in many oral mouthwashes, reduces SARS-CoV-2 infectivity by inhibiting the viral fusion step with target cells after disrupting the integrity of the viral envelope. We also found that CPC-containing…

• Water-soluble tocopherol derivatives inhibit SARS-CoV-2 RNA-dependent RNA polymerase - The recent emergence of a novel coronavirus, SARS-CoV-2, has led to the global pandemic of the severe disease COVID-19 in humans. While efforts to quickly identify effective antiviral therapies have focused largely on repurposing existing drugs ^(1-4) , the current standard of care, remdesivir, remains the only authorized antiviral intervention of COVID-19 and provides only modest clinical benefits ⁵ . Here we show that water-soluble derivatives of α-tocopherol have potent antiviral activity and…

• Xeno-nucleic Acid (XNA) 2’-Fluoro-Arabino Nucleic Acid (FANA) Aptamers to the Receptor Binding Domain of SARS-CoV-2 S Protein Block ACE2 Binding - The causative agent of COVID-19, SARS-CoV-2, gains access to cells through interactions of the receptor binding domain (RBD) on the viral S protein with angiotensin converting enzyme 2 (ACE2) on the surface of human host cells. Systematic Evolution of Ligands by Exponential Enrichment (SELEX) was used to generate aptamers (nucleic acids selected for high binding affinity to a target) to the RBD made from 2’-fluoroarabinonucleic acid (FANA). The best selected ~ 79 nucleotide aptamers bound the…

• The Role of Micronutrient and Immunomodulation effect in the vaccine era of COVID-19 - Different dietary nutrients have distinct effects, including enhancing immune response activity and supporting mucous membrane integrity. These effects are critical in fighting against pathogenic agents, which cover COVID-19, the coronavirus disease that shuts down globally. Recent researches have shown that micronutrient deficiency is commonly associated with compromised immune responses, respiratory tract infections, or even susceptibility to COVID-19. The relationship between Vit A and…

• Molecular Mechanisms of Palmitic Acid Augmentation in COVID-19 Pathologies - The coronavirus disease 2019 (COVID-19) pandemic has claimed over 2.7 million lives globally. Obesity has been associated with increased severity and mortality of COVID-19. However, the molecular mechanisms by which obesity exacerbates COVID-19 pathologies are not well-defined. The levels of free fatty acids (FFAs) are elevated in obese subjects. This study was therefore designed to examine how excess levels of different FFAs may affect the progression of COVID-19. Biological molecules…

• Regulation of Mindfulness-Based Music Listening on Negative Emotions Related to COVID-19: An ERP Study - The current study aimed to explore the behavioral and neural correlates of mindfulness-based music listening regulation of induced negative emotions related to COVID-19 using the face-word Stroop task. Eighty-five young adults visited the laboratory and were randomly assigned to three groups: a calm music group (CMG: n = 28), a happy music group (HMG: n = 30), and a sad music group (SMG: n = 27). Negative emotions were induced in all participants using a COVID-19 video, followed by the music…

• Broad sarbecovirus neutralization by a human monoclonal antibody - The recent emergence of SARS-CoV-2 variants of concern (VOC)^(1-10) and the recurrent spillovers of coronaviruses^(11,12) in the human population highlight the need for broadly neutralizing antibodies that are not affected by the ongoing antigenic drift and that can prevent or treat future zoonotic infections. Here, we describe a human monoclonal antibody (mAb), designated S2X259, recognizing a highly conserved cryptic receptor-binding domain (RBD) epitope and cross-reacting with spikes from all…

• Structure-Based Discovery of Novel Nonpeptide Inhibitors Targeting SARS-CoV-2 M(pro) - The continual spread of novel coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), posing a severe threat to the health worldwide. The main protease (M^(pro), alias 3CL^(pro)) of SARS-CoV-2 is a crucial enzyme for the maturation of viral particles and is a very attractive target for designing drugs to treat COVID-19. Here, we propose a multiple conformation-based virtual screening strategy to discover inhibitors that can target SARS-CoV-2…

• Lentil lectin derived from Lens culinaris exhibit broad antiviral activities against SARS-CoV-2 variants - The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutated continuously and newly emerging variants escape from antibody-mediated neutralization raised great concern. S protein is heavily glycosylated and the glycosylation sites are relatively conserved, thus glycans on S protein surface could be a target for development of anti-SARS-CoV-2 strategies against variants. Here, we collected twelve plant-derived lectins with different carbohydrate specificity and…

• Efficient Inhibition of SARS-CoV-2 Using Chimeric oligonucleotides through RNase L Activation - Currently there is an urgent need to develop antiviral drugs and alleviate current COVID-19 pandemic. Although many candidates have been developed, we here designed and constructed chimeric oligonucleotides comprising a 2’-OMe modified antisense oligonucleotide and a 5’-phosphorylated 2’-5’ poly(A) 4 (4A 2-5 ) to degrade envelope and spike RNAs of SARS- CoV-2. The oligonucleotide was used for searching and recognizing target viral RNA sequence, and the conjugated 4A 2-5 was used for guided…

From Patent Search

• A SYSTEM AND METHOD FOR COVID- 19 DIAGNOSIS USING DETECTION RESULTS FROM CHEST X- RAY IMAGES - - link

• Advanced Machine Learning System combating COVID-19 virus Detection, Spread, Prevention and Medical Assistance. - - link

• Differential detection kit for common SARS-CoV-2 variants in COVID-19 patients - - link

• 一种新型冠状病毒的mRNA疫苗 - 本发明公开了一种新型冠状病毒的mRNA疫苗。本发明提供的疫苗，其活性成分为mRNA，如序列表的序列6所示。本发明还保护TF‑RBD蛋白，如序列表的序列2所示。本发明的发明人通过一系列序列设计和序列优化得到了特异DNA分子，进一步构建了特异重组质粒，将特异重组质粒进行体外转录，可以得到多聚化TF‑RBD mRNA。进一步的，发明人制备了负载TF‑RBD mRNA的脂质纳米粒。本发明对于新型冠状病毒的防控具有重大的应用推广价值。 - link

• 新型冠状病毒B．1．1．7英国突变株RBD的基因及其应用 - 本发明属于生物技术领域，具体涉及新型冠状病毒B．1．1．7英国突变株RBD的基因及其应用。本发明的新型冠状病毒B．1．1．7英国突变株RBD的基因，其核苷酸序列如SEQ ID NO.1或SEQ ID NO.6所示。本发明通过优化野生型新型冠状病毒B．1．1．7英国突变株RBD的基因序列，并结合筛选确定了相对最佳序列，优化后序列产生的克隆表达效率比野生型新型冠状病毒B．1．1．7英国突变株RBD序列表达效率大幅提高，从而，本发明的新型冠状病毒B．1．1．7英国突变株RBD的基因更有利于用于制备新型冠状病毒疫苗。 - link

• SARS-CoV-2 anti-viral therapeutic - - link

• 一种基于联邦学习的多用户协同训练人流统计方法及系统 - 本发明提供一种基于联邦学习的多用户协同训练人流统计方法，旨在利用联邦学习框架搭建一个新颖的人群计数模型，达到让多用户多设备同时训练的目的。各个客户端利用图像数据集对图像分类网络进行本地训练以获取本地模型；在各经过至少一次本地训练后，中心服务器从客户端获取本地模型的权值及附加层参数并进行聚合处理；中心服务器利用聚合处理后的权值及附加层参数更新全局模型，并将聚合处理后的权值参数及附加层参数返回给各个客户端；各个客户端利用中心服务器返回的权值以及ground truth值进行贝叶斯估计，计算loss值，并利用返回的权值参数及附加层参数更新本地模型；重复执行直至所有客户端的loss值均收敛，则完成人流统计全局模型和本地模型的训练。 - link

• A POLYHERBAL ALCOHOL FREE FORMULATION FOR ORAL CAVITY - The present invention generally relates to a herbal composition. Specifically, the present invention relates to a polyherbal alcohol free composition comprising of Glycyrrhiza glabra root extract, Ocimum sanctum leaf extract, Elettaria cardamomum fruit extract, Mentha spicata (Spearmint) oil and Tween 80 and method of preparation thereof. The polyherbal alcohol free composition of the present invention possesses excellent antimicrobial properties and useful for oral cavity. - link

• 新型冠状病毒B.1.351南非突变株RBD的基因及其应用 - 本发明属于生物技术领域，具体涉及新型冠状病毒B.1.351南非突变株RBD的基因及其应用。本发明的新型冠状病毒B.1.351南非突变株RBD的基因，其核苷酸序列如SEQIDNO.1或SEQIDNO.6所示。本发明通过优化野生型新型冠状病毒南非B.1.351南非突变株RBD的基因序列，并结合筛选确定了相对最佳序列，优化后序列产生的克隆表达效率比野生型新型冠状病毒B.1.351南非突变株RBD序列表达效率大幅提高，从而，本发明的新型冠状病毒B.1.351南非突变株RBD的基因可以用于制备新型冠状病毒疫苗。 - link

• 检测新型冠状病毒中和抗体的试剂盒及其应用 - 本发明涉及生物技术领域，具体而言，提供了一种检测新型冠状病毒中和抗体的试剂盒及其应用。本发明提供的检测新型冠状病毒中和抗体试剂盒，具体包括（a）或（b）两种方案：（a）示踪物标记的RBD三聚体抗原，包被在固体支持物上的ACE2，以及，含有0.2‑10mg/mL十二烷基二甲基甜菜碱的工作液；（b）示踪物标记的ACE2，包被在固体支持物上的RBD三聚体抗原，以及，含有0.2‑10mg/mL十二烷基二甲基甜菜碱的工作液；其中，RBD三聚体抗原利用二硫键将刺突蛋白的RBD与S2亚基完全交联得到。十二烷基二甲基甜菜碱会显著提高RBD三聚体抗原与新冠中和性抗体结合速度，提升阳性样本平均发光强度，缩短检测时间。 - link