Covid-19 Sentry

Contents

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

From Preprints

• The COVID States Project #57: Social media news consumption and COVID-19 vaccination rates -
  Earlier this month, we witnessed a vigorous back and forth between the White House and Facebook regarding the role of the company in circulating health misinformation. On the White House side, the Surgeon General released an Advisory declaring misinformation a public health threat to the nation, highlighting, in part, the role of social media. This was followed the next day by a pointed statement by President Biden– “They’re killing us!” Facebook responded with a blog entry, Moving Past the Finger Pointing, asserting that it was not responsible for the plateauing vaccination rates in the US. The company pointed to the fact that 85% of Facebook users in a large survey by Carnegie Mellon (supported by Facebook) reported being vaccinated or wanting to be vaccinated. This exchange begs an obvious question: who has it right? Answering this question is tricky; but at minimum, rebutting the President’s accusation would require more information than is provided in Facebook’s blog post. For one thing, it fails to compare Facebook users to non-users. It also does not provide information on vaccination rates among those Facebook users who actually get information regarding COVID-19 from Facebook. As most Americans use Facebook, the vaccination rates among users will inevitably be similar to those of the general population. But only a subset of those users go to Facebook specifically to get news and information about COVID-19. These are the people who the Biden administration worries are at risk of exposure to vaccine misinformation.
  🖺 Full Text HTML: The COVID States Project #57: Social media news consumption and COVID-19 vaccination rates
• Relaxed peripheral tolerance drives broad de novo autoreactivity in severe COVID-19. -

  An emerging feature of COVID-19 is the identification of autoreactivity in patients with severe disease that may contribute to disease pathology, however the origin and resolution of these responses remain unclear. Previously, we identified strong extrafollicular B cell activation as a shared immune response feature between both severe COVID-19 and patients with advanced rheumatic disease. In autoimmune settings, this pathway is associated with relaxed peripheral tolerance in the antibody secreting cell compartment and the generation of de novo autoreactive responses. Investigating these responses in COVID-19, we performed single-cell repertoire analysis on 7 patients with severe disease. In these patients, we identify the expansion of a low-mutation IgG1 fraction of the antibody secreting cell compartment that are not memory derived, display low levels of selective pressure, and are enriched for autoreactivity-prone IGHV4-34 expression. Within this compartment, we identify B cell lineages that display specificity to both SARS-CoV-2 and autoantigens, including pathogenic autoantibodies against glomerular basement membrane, and describe progressive, broad, clinically relevant autoreactivity within these patients correlated with disease severity. Importantly, we identify anti-carbamylated protein responses as a common hallmark and candidate biomarker of broken peripheral tolerance in severe COVID-19. Finally, we identify the contraction of this pathway upon recovery, and re-establishment of tolerance standards coupled with a concomitant loss of acute-derived ASCs irrespective of antigen specificity. In total, this study reveals the origins, breadth, and resolution of acute-phase autoreactivity in severe COVID-19, with significant implications in both early interventions and potential treatment of patients with post-COVID sequelae.

  🖺 Full Text HTML: Relaxed peripheral tolerance drives broad de novo autoreactivity in severe COVID-19.
• Can we clinically identify pre-symptomatic and asymptomatic COVID-19? -

  Objectives: COVID-19 has had a severe impact on morbidity and mortality among nursing home (NH) residents. Earlier detection of SARS-CoV-2 may position us to better mitigate risk of spread. Both asymptomatic or pre-symptomatic transmission are common in outbreaks, and threshold temperatures, such as 38C, for screening for infection could miss timely detection in the majority. Design: Retrospective cohort study using electronic health records Methods: We hypothesized that in long-term care residents, temperature trends with SARS-CoV-2 infection could identify infection in pre-symptomatic and asymptomatic individuals earlier. We collected information about age and other demographics, baseline temperature, and specific comorbidities. We created standardized definitions, and an alternative hypothetical model to test measures of temperature variation and compare outcomes to the VA reality. Settings and participants: Our subjects were 6,176 residents of the VA NHs who underwent SARS-CoV-2 trigger testing. Results: We showed that a change from baseline of >0.4C identifies 47% of the SARS-CoV-2 positive NH residents early, and achieves earlier detection by 42.2 hours. Range improves early detection to 55% when paired with a 37.2C cutoff, and achieves earlier detection by 44.4 hours. Temperature elevation >0.4C from baseline, when combined with a 0.7C range, would detect 52% early, leading to earlier detection by more than 3 days in 22% of the residents. This earlier detection comes at the expense of triggering 57,793 tests, as compared to the number of trigger tests ordered in the VA system of 40,691. Conclusion and implications: Our model suggests that current clinical screening for SARS-CoV-2 in NHs can be substantially improved upon by triggering testing using a patient-derived baseline temperature with a 0.4C degree relative elevation or temperature variability of 0.7C trigger threshold for SARS-CoV2 testing. Such triggers could be automated in facilities that track temperatures in their electronic records.

  🖺 Full Text HTML: Can we clinically identify pre-symptomatic and asymptomatic COVID-19?
• ETAS(R)50 Attenuates SARS-CoV-2 Spike Protein-Induced IL-6 and IL-1β Production by Suppressing p44/42 MAPK and Akt Phosphorylation in Murine Primary Macrophages -
  Excessive host inflammation following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with severity and mortality in coronavirus disease 2019 (COVID-19). We recently reported that the SARS- CoV-2 spike protein S1 subunit (S1) induces pro-inflammatory responses by activating toll-like receptor 4 (TLR4) signaling in macrophages. ETAS(R)50, a standardized extract of Asparagus officinalis stem, is a unique functional food that elicits anti-photoaging effects by suppressing pro-inflammatory signaling in hydrogen peroxide- and ultraviolet B-exposed skin fibroblasts. To elucidate its potential in preventing excessive inflammation in COVID-19, we examined the effects of ETAS(R)50 on pro-inflammatory responses in S1-stimulated murine peritoneal exudate macrophages. Co-treatment of the cells with ETAS(R)50 significantly attenuated S1-induced secretion of interleukin (IL)-6 in a concentration- dependent manner without reducing cell viability. ETAS(R)50 also markedly suppressed the S1-induced transcription of IL-6 and IL-1{beta}. However, among the TLR4 signaling proteins, ETAS(R)50 did not affect the degradation of inhibitor {kappa}B, nuclear translocation of nuclear factor-{kappa}B p65 subunit, and phosphorylation of c-Jun N-terminal kinase p54 subunit after S1 exposure. In contrast, ETAS(R)50 significantly suppressed S1-induced phosphorylation of p44/42 mitogen-activated protein kinase (MAPK) and Akt. Attenuation of S1-induced transcription of IL-6 and IL-1{beta} by the MAPK kinase inhibitor U0126 was greater than that by the Akt inhibitor perifosine, and the effects were potentiated by simultaneous treatment with both inhibitors. These results suggest that ETAS(R)50 attenuates S1-induced IL-6 and IL-1{beta} production by suppressing p44/42 MAPK and Akt signaling in macrophages. Therefore, ETAS(R)50 may be beneficial in regulating excessive inflammation in patients with COVID-19.
  🖺 Full Text HTML: ETAS(R)50 Attenuates SARS-CoV-2 Spike Protein-Induced IL-6 and IL-1β Production by Suppressing p44/42 MAPK and Akt Phosphorylation in Murine Primary Macrophages
• Protection of human ACE2 transgenic Syrian hamsters from SARS CoV-2 variants by human polyclonal IgG from hyper- immunized transchromosomic bovines -
  Pandemic SARS CoV-2 has been undergoing rapid evolution during spread throughout the world resulting in the emergence of many Spike protein variants, some of which appear to either evade antibody neutralization, transmit more efficiently, or potentially exhibit increased virulence. This raises significant concerns regarding the long-term efficacy of protection elicited after primary infection and/or from vaccines derived from single virus Spike (S) genotypes, as well as the efficacy of anti-S monoclonal antibody based therapeutics. Here, we used fully human polyclonal human IgG (SAB-185), derived from hyperimmunization of transchromosomic bovines with DNA plasmids encoding the SARS-CoV-2 Wa-1 strain S protein or purified ectodomain of S protein, to examine the neutralizing capacity of SAB-185 in vitro and the protective efficacy of passive SAB-185 antibody (Ab) transfer in vivo. The Ab preparation was tested for neutralization against five variant SARS-CoV-2 strains: Munich (Spike D614G), UK (B.1.1.7), Brazil (P.1) and SA (B.1.3.5) variants, and a variant isolated from a chronically infected immunocompromised patient (Spike del144-146). For the in vivo studies, we used a new human ACE2 (hACE2) transgenic Syrian hamster model that exhibits lethality after SARS-Cov-2 challenge and the Munich, UK, SA and del144-146 variants. SAB-185 neutralized each of the SARS-CoV-2 strains equivalently on Vero E6 cells, however, a control convalescent human serum sample was less effective at neutralizing the SA variant. In the hamster model, prophylactic SAB-185 treatment protected the hamsters from fatal disease and minimized clinical signs of infection. These results suggest that SAB-185 may be an effective treatment for patients infected with SARS CoV-2 variants.
  🖺 Full Text HTML: Protection of human ACE2 transgenic Syrian hamsters from SARS CoV-2 variants by human polyclonal IgG from hyper-immunized transchromosomic bovines
• Increased aerosol transmission for B.1.1.7 (alpha variant) over lineage A variant of SARS-CoV-2 -
  Airborne transmission, a term combining both large droplet and aerosol transmission, is thought to be the main transmission route of SARS-CoV-2. Here we investigated the relative efficiency of aerosol transmission of two variants of SARS-CoV-2, B.1.1.7 (alpha) and lineage A, in the Syrian hamster. A novel transmission caging setup was designed and validated, which allowed the assessment of transmission efficiency at various distances. At 2 meters distance, only particles <5 micrometer traversed between cages. In this setup, aerosol transmission was confirmed in 8 out of 8 (N = 4 for each variant) sentinels after 24 hours of exposure as demonstrated by respiratory shedding and seroconversion. Successful transmission occurred even when exposure time was limited to one hour, highlighting the efficiency of this transmission route. Interestingly, the B.1.1.7 variant outcompeted the lineage A variant in an airborne transmission chain after mixed infection of donors. Combined, this data indicates that the infectious dose of B.1.1.7 required for successful transmission may be lower than that of lineage A virus. The experimental proof for true aerosol transmission and the increase in the aerosol transmission potential of B.1.1.7 underscore the continuous need for assessment of novel variants and the development or preemptive transmission mitigation strategies.
  🖺 Full Text HTML: Increased aerosol transmission for B.1.1.7 (alpha variant) over lineage A variant of SARS-CoV-2
• Multivariate mining of an alpaca immune repertoire identifies potent cross-neutralising SARS-CoV-2 nanobodies -
  Conventional approaches to isolate and characterize nanobodies are laborious and cumbersome. Here we combine phage display, multivariate enrichment, and novel sequence analysis techniques to annotate an entire nanobody repertoire from an immunized alpaca. We combine this approach with a streamlined screening strategy to identify numerous anti-SARS-CoV-2 nanobodies, and use neutralization assays and Hydrogen/Deuterium exchange coupled to mass spectrometry (HDX-MS) epitope mapping to characterize their potency and specificity. Epitope mapping revealed that the binding site is a key determinant of neutralization potency, rather than affinity alone. The most potent nanobodies bind to the receptor binding motif of the RBD, directly preventing interaction with the host cell receptor ACE2, and we identify two exceptionally potent members of this category (with monomeric IC50s around 13 and 16 ng/ml). Other nanobodies bind to a more conserved epitope on the side of the RBD, and are able to potently neutralize the SARS-CoV-2 founder virus (42 ng/ml), the beta variant (B.1.351/501Y.V2) (35 ng/ml), and also cross-neutralize the more distantly related SARS-CoV-1 (0.46 g/ml). The approach presented here is well suited for the screening of phage libraries to identify functional nanobodies for various biomedical and biochemical applications.
  🖺 Full Text HTML: Multivariate mining of an alpaca immune repertoire identifies potent cross-neutralising SARS-CoV-2 nanobodies
• Immunization with synthetic SARS-CoV-2 S glycoprotein virus-like particles protects Macaques from infection -
  The SARS-CoV-2 pandemic causes an ongoing global health crisis, which requires efficient and safe vaccination programs. Here, we present synthetic SARS-CoV2 S glycoprotein-coated liposomes that resemble in size and surface structure virus-like particles. Soluble S glycoprotein trimers were stabilized by formaldehyde cross-linking and coated onto lipid vesicles (S-VLP). Immunization of cynomolgus macaques with S-VLPs induced high antibody titers and TH1 CD4+ biased T cell responses. Although antibody responses were initially dominated by RBD specificity, the third immunization boosted non-RBD antibody titers. Antibodies showed potent neutralization against the vaccine strain and the Alpha variant after two immunizations and robust neutralization of Beta and Gamma strains. Challenge of animals with SARS-CoV-2 protected all vaccinated animals by sterilizing immunity. Thus, the S-VLP approach is an efficient and safe vaccine candidate based on a proven classical approach for further development and clinical testing.
  🖺 Full Text HTML: Immunization with synthetic SARS- CoV-2 S glycoprotein virus-like particles protects Macaques from infection
• Differential Interactions Between Human ACE2 and Spike RBD of SARS-CoV-2 Variants of Concern -
  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current coronavirus disease 2019 (COVID-19) pandemic. It is known that the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 interacts with the human angiotensin-converting enzyme 2 (ACE2) receptor, initiating the entry of SARS-CoV-2. Since its emergence, a number of SARS-CoV-2 variants have been reported, and the variants that show high infectivity are classified as the variants of concern according to the US CDC. In this study, we performed both all-atom steered molecular dynamics (SMD) simulations and microscale thermophoresis (MST) experiments to characterize the binding interactions between ACE2 and RBD of all current variants of concern (Alpha, Beta, Gamma, and Delta) and two variants of interest (Epsilon and Kappa). We report that the RBD of the Alpha (N501Y) variant requires the highest amount of force initially to be detached from ACE2 due to the N501Y mutation in addition to the role of N90-glycan, followed by Beta/Gamma (K417N/T, E484K, and N501Y) or Delta (L452R and T478K) variant. Among all variants investigated in this work, the RBD of the Epsilon (L452R) variant is relatively easily detached from ACE2. Our results combined SMD simulations and MST experiments indicate what makes each variant more contagious in terms of RBD and ACE2 interactions. This study could help develop new drugs to inhibit SARS-CoV-2 entry effectively.
  🖺 Full Text HTML: Differential Interactions Between Human ACE2 and Spike RBD of SARS-CoV-2 Variants of Concern
• N-glycosylation profiles of the SARS-CoV-2 spike D614G mutant and its ancestral protein characterized by advanced mass spectrometry -
  N-glycosylation plays an important role in the structure and function of membrane and secreted proteins. The spike protein on the surface of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, is heavily glycosylated and the major target for developing vaccines, therapeutic drugs and diagnostic tests. The first major SARS-CoV-2 variant carries a D614G substitution in the spike (S-D614G) that has been associated with altered conformation, enhanced ACE2 binding, and increased infectivity and transmission. In this report, we used mass spectrometry techniques to characterize and compare the N-glycosylation of the wild type (S-614D) or variant (S-614G) SARS-CoV-2 spike glycoproteins prepared under identical conditions. The data showed that half of the N-glycosylation sequons changed their distribution of glycans in the S-614G variant. The S-614G variant showed a decrease in the relative abundance of complex-type glycans (up to 45%) and an increase in oligomannose glycans (up to 33%) on all altered sequons. These changes led to a reduction in the overall complexity of the total N-glycosylation profile. All the glycosylation sites with altered patterns were in the spike head while the glycosylation of three sites in the stalk remained unchanged between S-614G and S-614D proteins.
  🖺 Full Text HTML: N-glycosylation profiles of the SARS-CoV-2 spike D614G mutant and its ancestral protein characterized by advanced mass spectrometry
• Mutations in two SARS-CoV-2 variants of concern reflect two distinct strategies of antibody escape -
  Understanding the factors that contribute to antibody escape of SARS-CoV-2 and its variants is key for the development of drugs and vaccines that provide broad protection against a variety of virus variants. Using microfluidic diffusional sizing, we determined the dissociation constant ((KD)) for the interaction between receptor binding domains (RBDs) of SARS-CoV-2 in its original version (WT) as well as alpha and beta variants with the host-cell receptor angiotensin converting enzyme 2 (ACE2). For RBD-alpha, the ACE2-binding affinity was increased by a factor of ten when compared with RBD-WT, while ACE2-binding of RBD-beta was largely unaffected. However, when challenged with a neutralizing antibody that binds to both RBD-WT and RBD-alpha with low nanomolar (KD) values, RBD-beta displayed no binding, suggesting a substantial epitope change. In SARS-CoV-2 convalescent sera, RBD-binding antibodies showed low nanomolar affinities to both wild-type and variant RBD proteins–strikingly, the concentration of antibodies binding to RBD-beta was half that of RBD-WT and RBD-alpha, again indicating considerable epitope changes in the beta variant. Our data therefore suggests that one factor contributing to the higher transmissibility and antibody evasion of SARS-CoV-2 alpha and beta is a larger fraction of viruses that can form a complex with ACE2. However, the two variants employ different mechanisms to achieve this goal. While SARS-CoV-2 alpha RBD binds with greater affinity to ACE2 and is thus more difficult to displace from the receptor by neutralizing antibodies, RBD-beta is less accessible to antibodies due to epitope changes which increases the chances of ACE2-binding and infection.
  🖺 Full Text HTML: Mutations in two SARS-CoV-2 variants of concern reflect two distinct strategies of antibody escape
• SARS-CoV-2 Delta variant pathogenesis and host response in Syrian hamsters -
  B.1.617 lineage is becoming a dominant SARS-CoV-2 lineage worldwide and was the dominant lineage reported in second COVID-19 wave in India, which necessitated studying the properties of the variant. We evaluated the pathogenicity and virus shedding of B.1.617.2 (Delta) and B.1.617.3 lineage of SARS-CoV-2 and compared with that of B.1, an early virus isolate with D614G mutation in Syrian hamster model. Viral load, antibody response and lung disease were studied. No significant difference in the virus shedding pattern was observed among these variants studied. A significantly high SARS-CoV-2 sub genomic RNA could be detected in the respiratory tract of hamsters infected with Delta variant for 14 days. Delta variant induced lung disease of moderate severity in 40% of infected animals. The neutralizing capability of the B.1, Delta and B.1.617.3 variant infected animals were found significantly lower with the B.1.351 (Beta variant). The findings of the study support the attributed disease severity and the increased transmission potential of the Delta variant.
  🖺 Full Text HTML: SARS-CoV-2 Delta variant pathogenesis and host response in Syrian hamsters
• The efficacy of vaccines in the context of COVID-19 and its variants: Role of Spatio-temporal boundary -

  The vaccine efficacy is a crucial determining factor in choosing a vaccine candidate for human use. When the choices of vaccines are many, the decision-making becomes difficult. General public resorts to the media and news, which talks about efficacies of various vaccines as observed for COVID-19. In this paper, for the first time, a concise mathematical framework for analyzing the efficacy of vaccines is introduced based on the standard definition of vaccine efficacy. The framework is then generalized to incorporate multi-variants. Finally, we introduce the idea of combined efficacy to characterize a vaccine efficacy as obtained from various clinical trials carried out across the world for Covid-19. We show that the efficacy reported by vaccine manufacturers from clinical trial data need not always directly translate to percentage efficacy. The efficacy of a vaccine is inherently a spatio-temporal statistical measure that characterizes a vaccine, which depends on the geographical location, the sample size, and the time of the clinical trials. Here, the dependence of efficacy on spatio-temporal parameters is expounded in detail, using hypothetical clinical trials conducted for different regions at different time intervals using real-world data.

  🖺 Full Text HTML: The efficacy of vaccines in the context of COVID-19 and its variants: Role of Spatio-temporal boundary
• THE US MIDLIFE MORTALITY CRISIS CONTINUES: INCREASED DEATH RATES FROM CAUSES OTHER THAN COVID-19 DURING 2020 -

  COVID-19 prematurely ended many lives, particularly among the oldest Americans, but the pandemic also had an indirect effect on health and non-COVID mortality among the working-age population, who suffered the brunt of the economic consequences. This analysis investigates whether monthly excess mortality in the US during 2020 varied by age and cause of death. The data comprise national-level monthly death counts by age group and selected causes of death for 1999-2020 combined with annual mid-year population estimates over the same period. A negative binomial regression model was used to estimate monthly cause-specific excess mortality during 2020 controlling for the pre-pandemic mortality patterns by age, calendar year, and seasonality. The model included interactions between broad age groups and a dichotomous indicator for the pandemic (March-December) period of 2020 to test whether excess mortality varied by age. In relative terms, excess all cause mortality (including COVID-19) peaked in December at ages 45-64 (RR=1.27, 95% CI=1.24-1.31). The results reveal notable excess mortality during April-December 2020 for influenza/pneumonia, external causes, diabetes, heart disease, and a residual category of other causes, but the vast majority of those excess deaths were among working-age (25-64) Americans. The largest share of non-COVID excess deaths resulted from external causes, nearly 80% of which occurred at working ages. Although misclassified COVID-19 deaths may explain some excess non-COVID mortality, neither misclassification nor an atypical flu season that disproportionately affected younger people is likely to explain the increase in external mortality. Exploratory analyses suggest that drug-related mortality may be driving the rise in external mortality. The social and economic upheaval resulting from the pandemic may have exacerbated the drug epidemic, but drug overdoses were already increasing for a year prior to the pandemic. Even if it were possible to vaccinate everyone and eradicate the SARS-CoV-2 virus, the drug problem will persist. The oldest Americans bore the brunt of COVID-19 mortality, but working-age Americans suffered the vast majority of excess non-COVID deaths, most commonly from external causes.

  🖺 Full Text HTML: THE US MIDLIFE MORTALITY CRISIS CONTINUES: INCREASED DEATH RATES FROM CAUSES OTHER THAN COVID-19 DURING 2020
• The U.S. COVID-19 Trends and Impact Survey, 2020-2021: Continuous real-time measurement of COVID-19 symptoms, risks, protective behaviors, testing and vaccination -

  The U.S. COVID-19 Trends and Impact Survey (CTIS) is a large, cross-sectional, Internet-based survey that has operated continuously since April 6, 2020. By inviting a random sample of Facebook active users each day, CTIS collects information about COVID-19 symptoms, risks, mitigating behaviors, mental health, testing, vaccination, and other key priorities. The large scale of the survey – over 20 million responses in its first year of operation – allows tracking of trends over short timescales and allows comparisons at fine demographic and geographic detail. The survey has been repeatedly revised to respond to emerging public health priorities. In this paper, we describe the survey methods and content and give examples of CTIS results that illuminate key patterns and trends and help answer high-priority policy questions relevant to the COVID-19 epidemic and response. These results demonstrate how large online surveys can provide continuous, real-time indicators of important outcomes that are not subject to public health reporting delays and backlogs. The CTIS offers high value as a supplement to official reporting data by supplying essential information about behaviors, attitudes toward policy and preventive measures, economic impacts, and other topics not reported in public health surveillance systems.

  🖺 Full Text HTML: The U.S. COVID-19 Trends and Impact Survey, 2020-2021: Continuous real-time measurement of COVID-19 symptoms, risks, protective behaviors, testing and vaccination

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

• Phase II/III Study of AZD2816, for the Prevention of COVID-19 in Adults - Conditions:   COVID-19;   SARS-CoV-2
  Interventions:   Biological: AZD1222;   Biological: AZD2816
  Sponsor:   AstraZeneca
  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

• Effects of Respiratory Muscle Training in Patients With Post COVID-19 - Condition:   Covid19
  Interventions:   Other: Exercise training group;   Other: Control training group
  Sponsor:   Gazi University
  Completed

• 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

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

• Saliva-based COVID-19 DNA Aptamer Test - Condition:   Covid19
  Intervention:   Device: AptameX
  Sponsors:   Achiko AG;   Udayana University
  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

• Coenzyme Q10 as Treatment for Long Term COVID-19 - Conditions:   Covid19;   Long Term Covid19
  Interventions:   Drug: Coenzyme Q10;   Drug: Placebo
  Sponsors:   Aarhus University Hospital;   University of Aarhus;   Pharma Nord
  Recruiting

• Evaluation of The Efficacy of Triazavirin Versus Oseltamivir in Egyptian Patients Infected With COVID-19 - Condition:   Covid19
  Intervention:   Drug: standard treatment COVID-19 + Triazavirin
  Sponsor:   Ain Shams University
  Recruiting

• Hidroxicloroquina With Azitromicina Versus Hidroxicloroquina and Placebo Int Patients With Mild COVID-19 - Condition:   Covid19
  Intervention:   Drug: Hydroxychloroquine with Azithromycin
  Sponsors:   Coordinación de Investigación en Salud, Mexico;   Ultra Laboratorios SA. de CV.
  Recruiting

• MANS-NRIZ Trial for COVID-19 Treatment : Extension Study - Condition:   COVID-19 Pneumonia
  Intervention:  
  Drug: Ivermectin,ribavirin ,nitazoxanide and zinc
  Sponsor:   Mansoura University
  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

• BinaxNow COVID-19 IgG Rapid Test Device and Antibody Self Test - Condition:   COVID-19 Respiratory Infection
  Intervention:   Diagnostic Test: The BinaxNOW™ Antibody Tests measure IgG antibodies against SARS-CoV-2.
  Sponsor:   Abbott Rapid Diagnostics Jena GmbH
  Recruiting

From PubMed

• Identification of FDA approved drugs against SARS-CoV-2 RNA dependent RNA polymerase (RdRp) and 3-chymotrypsin-like protease (3CLpro), drug repurposing approach - The RNA-dependent RNA polymerase (RdRp) and 3C-like protease (3CLpro) from SARS-CoV-2 play crucial roles in the viral life cycle and are considered the most promising targets for drug discovery against SARS-CoV-2. In this study, FDA- approved drugs were screened to identify the probable anti-RdRp and 3CLpro inhibitors by molecular docking approach. The number of ligands selected from the PubChem database of NCBI for screening was 1760. Ligands were energy minimized using Open Babel. The RdRp and…

• Transcription factor NF-kappaB as target for SARS-CoV-2 drug discovery efforts using inflammation-based QSAR screening model - NF-κB is a central regulator of immunity and inflammation. It is suggested that the inflammatory response mediated by SARS-CoV-2 is predominated by NF-κB activation. Thus, NF-κB inhibition is considered a potential therapeutic strategy for COVID-19. The aim of this study was to identify potential anti-inflammation lead molecules that target NF-κB using a quantitative structure-activity relationships (QSAR) model of currently used and investigated anti-inflammatory drugs as the basis for…

• Computational modeling predicts potential effects of the herbal infusion “horchata” against COVID-19 - Bioactive plant-derived molecules have emerged as therapeutic alternatives in the fight against the COVID-19 pandemic. In this investigation, principal bioactive compounds of the herbal infusion “horchata” from Ecuador were studied as potential novel inhibitors of the SARS-CoV-2 virus. The chemical composition of horchata was determined through a HPLC- DAD/ESI-MS^(n) and GC-MS analysis while the inhibitory potential of the compounds on SARS-CoV-2 was determined by a computational prediction using…

• The potential role of thymoquinone in preventing the cardiovascular complications of COVID-19 - A new virus strain detected in late 2019 and not previously described in humans is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes corona virus disease (COVID-19). While potential therapeutic approaches for COVID-19 are being investigated, significant initiatives are being made to create protective drugs and study various antiviral agents to cure the infection. However, an effective treatment strategy against COVID-19 is worrisome inadequate. The objective of the…

• Glucagon-Like Peptide 1 Receptor Agonist Usage in Type 2 Diabetes in Primary Care for the UK and Beyond: A Narrative Review - The scientific landscape of treatments for type 2 diabetes (T2D) has changed rapidly in the last decade with newer treatments becoming available. However, a large proportion of people with T2D are not able to achieve glycaemic goals because of clinical inertia. The majority of T2D management is in primary care, where clinicians (medical, nursing and pharmacist staff) play an important role in addressing patient needs and achieving treatment goals. However, management of T2D is challenging…

• Design and in silico investigation of novel Maraviroc analogues as dual inhibition of CCR-5/SARS-CoV-2 M(pro) - A sudden increase in life-threatening COVID-19 infections around the world inflicts global crisis and emotional trauma. In current study two druggable targets, namely SARS-COV-2 M^(pro) and CCR-5 were selected due to their significant nature in the viral life cycle and cytokine molecular storm respectively. The systematic drug repurposing strategy has been utilized to recognize inhibitory mechanism through extensive in silico investigation of novel Maraviroc analogues as promising inhibitors…

• Target-Based In Silico Screening for Phytoactive Compounds Targeting SARS-CoV-2 - Coronavirus disease 2019 (COVID-19), resulting from infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can cause severe and fatal pneumonia along with other life-threatening complications. The COVID-19 pandemic has taken a heavy toll on the healthcare system globally and has hit the economy hard in all affected countries. As a result, there is an unmet medical need for both the prevention and treatment of COVID-19 infection. Several herbal remedies have claimed to…

• Phytocompounds of Rheum emodi, Thymus serpyllum, and Artemisia annua Inhibit Spike Protein of SARS-CoV-2 Binding to ACE2 Receptor: In Silico Approach - COVID-19, the disease caused by SARS-CoV-2, has been declared as a global pandemic. Traditional medicinal plants have long history to treat viral infections. Our in silico approach suggested that unique phytocompounds such as emodin, thymol and carvacrol, and artemisinin could physically bind SARS-CoV-2 spike glycoproteins (6VXX and 6VYB), SARS-CoV-2 B.1.351 South Africa variant of Spike glycoprotein (7NXA), and even with ACE2 and prevent the SARS-CoV-2 binding to the host ACE2, TMPRSS2 and…

• Inhibition of SARS CoV Envelope Protein by Flavonoids and Classical Viroporin Inhibitors - Severe acute respiratory syndrome coronavirus (SARS-CoV), an enveloped single-stranded positive-sense RNA virus, is a member of the genus Betacoronavirus, family Coronaviridae. The SARS-CoV envelope protein E is a small (∼8.4 kDa) channel-forming membrane protein whose sequence is highly conserved between SARS-CoV and SARS-CoV-2. As a viroporin, it is involved in various aspects of the virus life cycle including assembly, budding, envelope formation, virus release, and inflammasome activation….

• Remdesivir Strongly Binds to RNA-Dependent RNA Polymerase, Membrane Protein, and Main Protease of SARS-CoV-2: Indication From Molecular Modeling and Simulations - Development of new drugs is a time-taking and expensive process. Comprehensive efforts are being made globally toward the search of therapeutics against SARS-CoV-2. Several drugs such as remdesivir, favipiravir, ritonavir, and lopinavir have been included in the treatment regimen and shown effective results in several cases. Among the existing broad- spectrum antiviral drugs, remdesivir is found to be more effective against SARS-CoV-2. Remdesivir has broad-spectrum antiviral action against many…

• Glycyrrhizic Acid: A Natural Plant Ingredient as a Drug Candidate to Treat COVID-19 - The total number of cumulative cases and deaths from the COVID-19 pandemic caused by SARS-CoV-2 is still increasing worldwide. Although many countries have actively implemented vaccination strategies to curb the epidemic, there is no specific efficient therapeutic drug for this virus to effectively reduce deaths. Therefore, the underappreciated macromolecular compounds have become the spotlight of research. Furthermore, the medicinal compounds in plants that provide myriad possibilities to treat…

• Exploring Phytochemicals of Traditional Medicinal Plants Exhibiting Inhibitory Activity Against Main Protease, Spike Glycoprotein, RNA-dependent RNA Polymerase and Non-Structural Proteins of SARS-CoV-2 Through Virtual Screening - Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) being a causative agent for global pandemic disease nCOVID’19, has acquired much scientific attention for the development of effective vaccines and drugs. Several attempts have been made to explore repurposing existing drugs known for their anti-viral activities, and test the traditional herbal medicines known for their health benefiting and immune-boosting activity against SARS-CoV-2. In this study, efforts were made to examine the…

• Coagulopathy in SARS-CoV-2 Infected Patients: Implication for the Management of COVID-19 - COVID-19 disease has led to an extraordinary inclusive health crisis globally. Elevation of D-dimer is the major remarkable abnormal coagulation test in seriously ill COVID-19 patients. In nearly 50% of COVID-19 patients, the value of D-dimer was significantly enhancing. Recent literature indicated that COVID-19 patients were at higher risk of developing disseminated intravascular coagulation. Pro-inflammatory cytokines and chemokines are some of the factors leading to these conditions. The…

• Flavonoids from Siparuna cristata as Potential Inhibitors of SARS-CoV-2 Replication - The novel coronavirus SARS-CoV-2 has been affecting the world, causing severe pneumonia and acute respiratory syndrome, leading people to death. Therefore, the search for anti-SARS-CoV-2 compounds is pivotal for public health. Natural products may present sources of bioactive compounds; among them, flavonoids are known in literature for their antiviral activity. Siparuna species are used in Brazilian folk medicine for the treatment of colds and flu. This work describes the isolation of…

• Seq12, Seq12m, and Seq13m, peptide analogues of the spike glycoprotein shows antiviral properties against SARS- CoV-2: An in silico study through molecular docking, molecular dynamics simulation, and MM-PB/GBSA calculations - At the very beginning of the new decade, the COVID-19 pandemic has badly hit modern human societies. SARS-CoV-2, the causative agent of COVID-19 acquiring mutations and circulating as new variants. Herein, we have found three new antiviral peptides (AVPs) against the SARS-CoV-2. These AVPs are analogous to the spike glycoprotein of the SARS-CoV-2. Antiviral peptides, i.e., Seq12, Seq12m, and Seq13m, can block the receptor-binding domain (RBD) of the SARS-CoV-2, which is necessary for…

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

• 一种包装重组流感病毒的重组载体和重组流感病毒及其构建方法和应用 - 本发明提供了一种包装重组流感病毒的重组载体和重组流感病毒及其构建方法和应用，涉及生物医药技术领域。本发明利用A型流感病毒八个基因片段为骨架包装出带有新型冠状病毒SARS‑CoV‑2表面刺突蛋白受体结合域（SARS‑CoV‑2_RBD）片段的重组流感病毒，此重组流感病毒可在复制过程中表达具有生物学活性和免疫原性的刺突蛋白受体结合区域RBD。本发明所述重组流感病毒rgH1N1（PR8）‑PA‑RBD可作为重组病毒类药物，用于2019新型冠状病毒肺炎（COVID‑19）的预防；也可作为体外SARS‑COV‑2 RBD等相关抗原表达和体内递呈系统。 - 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