Covid-19 Sentry

Contents

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

From Preprints

• What can be impact of civil authorities faulty mortality registration on COVID-19 mortality count in the state of Bihar, India- Evidence from NFHS-5 -
  Several local / global / national / international agencies have been estimating the impact of COVID-19 pandemic on mortality count in different regions. On 30 January 2020 the World Health Organization (WHO) declared COVID-19 a Public Health Emergency of International Concern (PHEIC). Death toll was only 171 on 30-01-2020 and by 31 -12- 2020, this figure increased to 1 813 188. The estimates of global deaths attributable to the COVID-19 pandemic in 2020 as published by WHO is at least 3 million, which is 1.2 million more than officially reported. Objective of this research study is to find out number of deaths in the household in the three years preceding the survey registered with the civil authorities’ with another objective of this research study is to estimate the excess mortality due to COVID-19 in a simple way to be understood by most of the readers. The total sample size was 35,834 households, 42,483 women of age 15-49 (including 6,350 women interviewed in PSUs in the state module), and 4,897 men of age 15-54 for the state of Bihar. This sample size was based on the size needed to produce reliable indicator estimates for each district. Household questionnaire regarding number of deaths in the household in the three years preceding the survey were collected and utilized to produce information in 19 languages using CAPI (Computer Assisted Personal Interviewing). This cross sectional survey study revealed that only 37.1 percent of deaths of households members due to any cause were registered with the civil authorities in the three years preceding the survey, of which 28 percent of deaths are at age 0-4, 45 percent of deaths occurred at age 25-34, and 41 percent of deaths occurred at age 35 and above (see table-1 and 2 for more details).
  🖺 Full Text HTML: What can be impact of civil authorities faulty mortality registration on COVID-19 mortality count in the state of Bihar, India- Evidence from NFHS-5
• Tixagevimab/cilgavimab pre-exposure prophylaxis is associated with lower breakthrough infection risk in vaccinated solid organ transplant recipients during the Omicron wave -

  The neutralizing monoclonal antibody combination of tixagevimab/cilgavimab has been shown to reduce the risk of SARS-CoV-2 infection in unvaccinated individuals during the Alpha (B.1.1.7) and Delta (B.1.617.2) waves. However, data on efficacy and safety of tixagevimab/cilgavimab in vaccinated solid organ transplant recipients during the Omicron wave is limited. To address this, we conducted a retrospective cohort study comparing 222 solid organ transplant recipients who received tixagevimab/cilgavimab for pre-exposure prophylaxis and 222 age-matched vaccinated solid organ transplant recipients who did not receive tixagevimab/cilgavimab. Subjects were followed for a mean of 67 (standard deviation 18) days. Kaplan-Meier estimates of the 60-day incidence of breakthrough infection were 1.8% in the tixagevimab/cilgavimab group and 4.7% in the control group (P = 0.045). Adverse events were uncommon, occurring in 4% of our cohort and most were mild. There was no significant change in serum creatinine or liver chemistries in kidney and liver transplant recipients respectively. In conclusion, we found that tixagevimab/cilgavimab use is safe and associated with a lower risk of breakthrough SARS-CoV-2 infection in vaccinated solid organ transplant recipients during the Omicron wave.

  🖺 Full Text HTML: Tixagevimab/cilgavimab pre-exposure prophylaxis is associated with lower breakthrough infection risk in vaccinated solid organ transplant recipients during the Omicron wave
• Variation in the ACE2 receptor has limited utility for SARS-CoV-2 host prediction -
  Transmission of SARS-CoV-2 from humans to other species threatens wildlife conservation and may create novel sources of viral diversity for future zoonotic transmission. A variety of computational heuristics have been developed to pre-emptively identify susceptible host species based on variation in the ACE2 receptor used for viral entry. However, the predictive performance of these heuristics remains unknown. Using a newly-compiled database of 96 species we show that, while variation in ACE2 can be used by machine learning models to accurately predict animal susceptibility to sarbecoviruses (accuracy = 80.2%, binomial confidence interval [CI]: 70.8 - 87.6%), the sites informing predictions have no known involvement in virus binding and instead recapitulate host phylogeny. Models trained on host phylogeny alone performed equally well (accuracy = 84.4%, CI: 75.5 - 91.0%) and at a level equivalent to retrospective assessments of accuracy for previously published models. These results suggest that the predictive power of ACE2-based models derives from strong correlations with host phylogeny rather than processes which can be mechanistically linked to infection biology. Further, biased availability of ACE2 sequences misleads projections of the number and geographic distribution of at-risk species. Models based on host phylogeny reduce this bias, but identify a very large number of susceptible species, implying that model predictions must be combined with local knowledge of exposure risk to practically guide surveillance. Identifying barriers to viral infection or onward transmission beyond receptor binding and incorporating data which are independent of host phylogeny will be necessary to manage the ongoing risk of establishment of novel animal reservoirs of SARS-CoV-2.
  🖺 Full Text HTML: Variation in the ACE2 receptor has limited utility for SARS-CoV-2 host prediction
• Unsupervised outlier detection applied to SARS-CoV-2 nucleotide sequences can identify sequences of common variants and other variants of interest -
  As of February 2022, the GISAID database contains more than one million SARS-CoV-2 genomes, including several thousand nucleotide sequences for the most common variants such as delta or omicron. These SARS-CoV-2 strains have been collected from patients around the world since the beginning of the pandemic. We start by assessing the similarity of all pairs of nucleotide sequences using the Jaccard index and principal component analysis. As shown previously in the literature, an unsupervised cluster analysis applied to the SARS-CoV-2 genomes results in clusters of sequences according to certain characteristics such as their strain or their clade. Importantly, we observe that nucleotide sequences of common variants are often outliers in clusters of sequences stemming from variants identified earlier on during the pandemic. Motivated by this finding, we are interested in applying outlier detection to nucleotide sequences. We demonstrate that nucleotide sequences of common variants (such as alpha, delta, or omicron) can be identified solely based on a statistical outlier criterion. We argue that outlier detection might be a useful surveillance tool to identify emerging variants in real time as the pandemic progresses.
  🖺 Full Text HTML: Unsupervised outlier detection applied to SARS-CoV-2 nucleotide sequences can identify sequences of common variants and other variants of interest
• Differential Evasion of Delta and Omicron Immunity and Enhanced Fusogenicity of SARS-CoV-2 Omicron BA.4/5 and BA.2.12.1 Subvariants -
  The rising case numbers of the SARS-CoV-2 Omicron BA.4, BA.5, and BA.2.12.1 subvariants has generated serious concern about the course of the pandemic. Here we examine the neutralization resistance, infectivity, processing, and fusogenicity of spike from the BA.4/5 and BA.2.12.1 SARS-CoV-2 variants compared with other Omicron subvariants and Delta. Critically, we found that the new Omicron subvariants BA.4/5 and BA.2.12.1 were more resistant to neutralization by mRNA-vaccinated and boosted health care worker sera and Omicron-BA.1-wave patient sera than were the BA.1 and BA.2 variants. Interestingly, Delta-wave patient sera neutralized more efficiently against not only Delta but also BA.4/5 and BA.2.12.1 variants that also contain substitutions at position L452, similar to Delta. The BA.4/5 and BA.2.12.1 variants also exhibited higher fusogenicity, and increased spike processing, dependent on the L452 substitution. These results highlight the key role of the L452R and L452Q mutations in BA.4/5 and BA.2.12.1 subvariants.
  🖺 Full Text HTML: Differential Evasion of Delta and Omicron Immunity and Enhanced Fusogenicity of SARS-CoV-2 Omicron BA.4/5 and BA.2.12.1 Subvariants
• Prophylactic treatment of Glycyrrhiza glabra mitigates COVID-19 pathology through inhibition of pro-inflammatory cytokines in the hamster model and NETosis. -
  Severe coronavirus disease (COVID-19) is accompanied with acute respiratory distress syndrome & pulmonary pathology, and is presented mostly with inflammatory cytokine release, dysregulated immune response, skewed neutrophil/ lymphocyte ratio, and hypercoagulable state. Though vaccinations have proved effective in reducing the COVID-19 related mortality, the limitation of use of vaccine against immunocompromised, comorbidity, and emerging variants remains a concern. In the current study we investigate for the first-time the efficacy of Glycyrrhiza glabra (GG) extract, a potent immunomodulator, against SARS-CoV-2 infection in hamsters. Prophylactic treatment with GG showed protection against loss in body weight and 35-40% decrease in lung viral load along with reduced lung pathology in the hamster model. Remarkably, GG reduced the mRNA expression of pro-inflammatory cytokines and Plasminogen activator inhibito-1 (PAI-1). In-vitro, GG acted as potent immunomodulator by reducing Th2 and Th17 differentiation and IL-4 and IL-17A cytokine production. In addition, GG also showed robust potential to suppress ROS, mtROS and NETs generation in a concentration dependent manner in both human polymorphonuclear neutrophils (PMNs) and murine bone marrow derived neutrophils (BMDNs). Taken together, we provide evidence for the protective efficacy of GG against COVID-19 and its putative mechanistic insight, which might be developed as a future immunomodulatory approach against various pathologies with high cytokine production, aberrant neutrophil activation including coronavirus infection.
  🖺 Full Text HTML: Prophylactic treatment of Glycyrrhiza glabra mitigates COVID-19 pathology through inhibition of pro-inflammatory cytokines in the hamster model and NETosis.
• SARS-CoV-2 accessory proteins ORF7a and ORF3a use distinct mechanisms to downregulate MHC-I surface expression -
  Major histocompatibility complex class I (MHC-I) molecules, which are dimers of a glycosylated polymorphic transmembrane heavy chain and the small protein {beta}2-microglobulin ({beta}2m), bind peptides in the endoplasmic reticulum that are generated by the cytosolic turnover of cellular proteins. In virus-infected cells these peptides may include those derived from viral proteins. Peptide-MHC-I complexes then traffic through the secretory pathway and are displayed at the cell surface where those containing viral peptides can be detected by CD8+ T lymphocytes that kill infected cells. Many viruses enhance their in vivo survival by encoding genes that downregulate MHC-I expression to avoid CD8+ T cell recognition. Here we report that two accessory proteins encoded by SARS-CoV-2, the causative agent of the ongoing COVID-19 pandemic, downregulate MHC-I expression using distinct mechanisms. One, ORF3a, a viroporin, reduces global trafficking of proteins, including MHC-I, through the secretory pathway. The second, ORF7a, interacts specifically with the MHC-I heavy chain, acting as a molecular mimic of {beta}2m to inhibit its association. This slows the exit of properly assembled MHC-I molecules from the endoplasmic reticulum. We demonstrate that ORF7a reduces antigen presentation by the human MHC-I allele HLA-A*02:01. Thus, both ORF3a and ORF7a act post-translationally in the secretory pathway to lower surface MHC-I expression, with ORF7a exhibiting a novel and specific mechanism that allows immune evasion by SARS-CoV-2.
  🖺 Full Text HTML: SARS-CoV-2 accessory proteins ORF7a and ORF3a use distinct mechanisms to downregulate MHC-I surface expression
• Excess all-cause mortality across counties in the United States, March 2020 to December 2021 -

  Official Covid-19 death counts have underestimated the mortality impact of the Covid-19 pandemic in the United States. Excess mortality, which compares observed deaths to deaths expected in the absence of the pandemic, is a useful measure for assessing the total effect of the pandemic on mortality levels. In the present study, we produce county- level estimates of excess mortality for 3,127 counties between March 2020 and December 2021. We fit two hierarchical linear models to county-level death rates from January 2015 to December 2019 and predict expected deaths for each month during the pandemic. We compare observed deaths to these estimates to obtain excess deaths for each county-month. An estimated 936,911 excess deaths occurred during 2020 and 2021, of which 171,168 (18.3%) were not assigned to Covid-19 on death certificates as an underlying cause of death. Urban counties in the Far West, Great Lakes, Mideast, and New England experienced a substantial mortality disadvantage in 2020, whereas rural counties in these regions had higher mortality in 2021. In the Southeast, Southwest, Rocky Mountain, and Plains regions, there was a rural mortality disadvantage in 2020, which was exacerbated in 2021. The proportion of excess deaths assigned to Covid-19 was lower in 2020 (76.3%) than in 2021 (87.0%), suggesting that a larger fraction of excess deaths was assigned to Covid-19 later in the pandemic. However, in rural areas and in the Southeast and Southwest a large share of excess deaths was still not assigned to Covid-19 during 2021.

  🖺 Full Text HTML: Excess all-cause mortality across counties in the United States, March 2020 to December 2021
• Racial differences in vaccine acceptance in a rural southern US state -

  Introduction: To assess vaccine acceptance among adults living in a largely rural Southern state. Methods: Data were collected between October 3 and October 17, 2020 using random digit dialing. Participants included residents aged 18+, able to understand English or Spanish, and provide informed consent. The primary outcome was a multi- dimensional COVID-19 vaccine acceptance measure. Scores varied between -3 to +3. Results: The sample (n=1,164) was weighted to be representative of the state9s population. Black participants had the lowest overall vaccine acceptance (0.5) compared to White participants (1.2). Hispanic participants had the highest scores (1.4). In adjusted models, Black participants had 0.81 points lower acceptance than White participants, and Hispanic participants had 0.35 points higher acceptance. Hispanic participants had the highest scores for all five vaccine acceptance dimensions, relatively equivalent to White participants. Black participants had consistently lower scores, especially perceived vaccine safety (mean -0.2, SD 0.1). Conclusions: The lowest vaccine acceptance rates were among Black participants particularly on perceived vaccine safety. While Black participants had the lowest acceptance scores, Hispanic participants had the highest. This variability shows the value of a multi-dimensional vaccine acceptance measure to inform COVID-19 vaccination campaign strategies.

  🖺 Full Text HTML: Racial differences in vaccine acceptance in a rural southern US state
• SARS-CoV-2 Spike evolution influences GBP and IFITM sensitivity -
  SARS-CoV-2 spike requires proteolytic processing for viral entry. The presence of a polybasic furin-cleavage site (FCS) in spike, and evolution towards an optimised FCS by dominant variants of concern (VOCs), are linked to enhanced infectivity and transmission. Here we show that interferon-inducible antiviral restriction factors Guanylate binding proteins (GBP) 2 and 5 interfere with furin-mediated cleavage of SARS-CoV-2 spike and inhibit the infectivity of early- lineage Wuhan-Hu-1, while VOCs Alpha and Delta have evolved to escape restriction. Strikingly, we find Omicron is unique amongst VOCs, being restricted by GBP2/5, and also IFITM1, 2 and 3. Replacing the spike S2 domain in Omicron with Delta shows S2 is the determinant of entry route and IFITM sensitivity. We conclude that VOC evolution under different selective pressures has influenced sensitivity to spike-targeting restriction factors, with Omicron selecting spike changes that not only mediate antibody escape, and altered tropism, but also sensitivity to innate immunity.
  🖺 Full Text HTML: SARS-CoV-2 Spike evolution influences GBP and IFITM sensitivity
• Neuropathic symptoms with SARS-CoV-2 vaccination -

  Background and Objectives: Various peripheral neuropathies, particularly those with sensory and autonomic dysfunction may occur during or shortly after acute COVID-19 illnesses. These appear most likely to reflect immune dysregulation. If similar manifestations can occur with the vaccination remains unknown. Results: In an observational study, we studied 23 patients (92% female; median age 40years) reporting new neuropathic symptoms beginning within 1 month after SARS-CoV-2 vaccination. 100% reported sensory symptoms comprising severe face and/or limb paresthesias, and 61% had orthostasis, heat intolerance and palpitations. Autonomic testing in 12 identified seven with reduced distal sweat production and six with positional orthostatic tachycardia syndrome. Among 16 with lower-leg skin biopsies, 31% had diagnostic/subthreshold epidermal neurite densities (≤5%), 13% were borderline (5.01-10%) and 19% showed abnormal axonal swelling. Biopsies from randomly selected five patients that were evaluated for immune complexes showed deposition of complement C4d in endothelial cells. Electrodiagnostic test results were normal in 94% (16/17). Together, 52% (12/23) of patients had objective evidence of small-fiber peripheral neuropathy. 58% patients (7/12) treated with oral corticosteroids had complete or near-complete improvement after two weeks as compared to 9% (1/11) of patients who did not receive immunotherapy having full recovery at 12 weeks. At 5-9 months post-symptom onset, 3 non-recovering patients received intravenous immunoglobulin with symptom resolution within two weeks. Conclusions: This observational study suggests that a variety of neuropathic symptoms may manifest after SARS-CoV-2 vaccinations and in some patients might be an immune-mediated process.

  🖺 Full Text HTML: Neuropathic symptoms with SARS- CoV-2 vaccination
• Legal Restrictions and Mitigation Strategies Amongst People with Disabilities During COVID-19 -
  The impact of physical disability on protective behaviors during COVID-19 has been little studied. This retrospective study compared the 699 the self-declared behaviors of 699 people with disabilities before and after the relaxation of COVID-19 restrictions in England. We found that people with disabilities in England showed high compliance with protective behaviors and mitigation strategies during a period of legal restrictions. Following the lifting of restrictions, respondents engaged in less social mixing, fewer distancing and hygiene behaviors and were less likely to use face coverings. Hierarchical regressions revealed that socio-economic status, age, and gender moderated protective behaviors: while those with higher socio-economic status were more relaxed with regard to hygiene and distancing behaviors they were more cautious about mixing with others after the end of restrictions. Age, (male) gender, and being unvaccinated were positively associated with relaxation in the use of facemasks in public places, not needing a carer with fewer out-of-home visits. Taken together these findings suggest that the removal of restrictions had an unequal impact on the population of England, placing a disproportionate burden on some people with disabilities.
  🖺 Full Text HTML: Legal Restrictions and Mitigation Strategies Amongst People with Disabilities During COVID-19
• Providing normative information increases intentions to accept a COVID-19 vaccine -
  Despite the availability of multiple safe vaccines, vaccine hesitancy may present a challenge to successful control of the COVID-19 pandemic. As with many human behaviors, people’s vaccine acceptance may be affected by their beliefs about whether others will accept a vaccine (i.e., descriptive norms). However, information about these descriptive norms may have different effects depending on the actual descriptive norm, people’s baseline beliefs, and the relative importance of conformity, social learning, and free-riding. Here, using a pre-registered, randomized experiment (N=) embedded in an international survey (23 countries), we show that accurate information about descriptive norms can increase intentions to accept a vaccine for COVID-19. These effects are largely consistent across the 23 included countries, but are concentrated among people who were otherwise uncertain about accepting a vaccine. Providing normative information in vaccine communications partially corrects individuals’ underestimation of how many other people will accept a vaccine. These results suggest that presenting people with information about the widespread and growing acceptance of COVID-19 vaccines helps to increase vaccination intentions.
  🖺 Full Text HTML: Providing normative information increases intentions to accept a COVID-19 vaccine
• Persistence of disproportionate gender participation in virtual conference Q&A sessions -
  Due to the onset of the COVID-19 pandemic, virtual conferences have become not only more popular and widespread, but necessary. Virtual conferences come with big hopes for inclusion in science. At in-person conferences, there are large gender disparities in Q&A participation, and it is unclear how the shift to virtual would impact gendered Q&A participation. Gendered Q&A participation was tested in four virtual conferences that varied in gender representation and Q&A structured format. In virtual conferences, men continued to take a disproportionate amount of time and space in Q&A sessions. Disproportionate participation did not significantly vary between in-person and virtual formats and did not systematically vary by how the Q&A session was organized. In an all-chat virtual conference, gender differences in volubility were attenuated among higher status academics. Gendered participation and volubility were impacted by which sub-discipline the symposium was in. Future research should focus on the cultural factors that promote or mitigate gender disparities in participation.
  🖺 Full Text HTML: Persistence of disproportionate gender participation in virtual conference Q&A sessions
• The COVID States Project #87: Parent Information Sources and Children COVID Vaccination -
  The path to FDA authorization for vaccines in young children has been complex. On February 1, 2022 Pfizer and BioNTech responded to requests from the Food and Drug Administration (FDA) to seek emergency authorization of their COVID-19 vaccine for children ages 6 months through 4 years on a rolling basis. This authorization would have allowed children to begin receiving the first doses of the COVID-19 vaccine while data comparing two or three course vaccine regimens for children were still being collected. However, on February 11, 2022 the FDA reversed course and announced it would wait for data on the effectiveness of the third dose before granting emergency authorization. Most recently, Moderna announced it was seeking authorization for its vaccine for children under 6 and the FDA has laid out a timeline for examining the authorization requests and data in June. This back and forth has only added to the already confusing information environment for parents surrounding the entire COVID-19 pandemic and decisions about vaccination. Some parents of children under 5 reported frustration to The New York Times at the inconclusive and confusing nature of the vaccine approval process, along with the overall feeling of being left behind while the rest of the world opens up. Others were relieved that they could wait on the decision to vaccinate until more complete data were available. In light of this confusion, it is important to understand where parents are getting information about vaccinating their children against COVID-19. In this report we examine where parents are seeking information about their children’s health and vaccination decision-making, as well as who they discuss these important decisions with. We gathered this information by asking parents to select which sources they use from a list, as well as from an open-ended response question. We find that there is quite a bit of overlap in sources between these two methods.
  🖺 Full Text HTML: The COVID States Project #87: Parent Information Sources and Children COVID Vaccination

From Clinical Trials

• The Role of Glutathione Deficiency and MSIDS Variables in Long COVID-19 - Condition:   COVID-19
  Intervention:   Dietary Supplement: NAC (N-acetyl cysteine) , Alpha lipoic acid (ALA), liposomal glutathione (GSH)
  Sponsors:   University of California, Irvine;   Hudson Valley Healing Arts Center
  Not yet recruiting

• Study to Evaluate the Efficacy of IN STI-9199 in Treating Symptomatic COVID-19 in Outpatient Adults and Adolescents - Condition:   COVID-19
  Interventions:   Drug: STI-9199;   Drug: Placebo
  Sponsor:  
  Sorrento Therapeutics, Inc.
  Not yet recruiting

• A Study to Evaluate the Safety and Immunogenicity of Omicron COVID-19 Vaccine (Vero Cell), Inactivated in Population 18 Years Old of Age and Above - Condition:   COVID-19
  Intervention:   Biological: Omicron COVID-19 Vaccine (Vero Cell), Inactivated
  Sponsors:   China National Biotec Group Company Limited;   Beijing Institute of Biological Products Co Ltd.;   Shulan (Hangzhou) Hospital
  Recruiting

• Study on Sequential Immunization of Omicron Inactivated COVID-19 Vaccine and Prototype Inactivated COVID-19 Vaccine in Population Aged 18 Years Old and Above - Condition:   COVID-19
  Interventions:   Biological: Omicron COVID-19 Vaccine (Vero Cell), Inactivated;   Biological: COVID-19 Vaccine (Vero Cell), Inactivated
  Sponsors:  
  China National Biotec Group Company Limited;   Beijing Institute of Biological Products Co Ltd.;   Hunan Provincial Center for Disease Control and Prevention
  Recruiting

• Neuro-inflammation and Post-infectious Fatigue in Individuals With and Without COVID-19 - Condition:   COVID-19
  Intervention:   Radiation: [18F]DPA-714 positron emission tomography (PET) scan
  Sponsors:   Amsterdam UMC, location VUmc;   ZonMw: The Netherlands Organisation for Health Research and Development
  Enrolling by invitation

• Phase II Safety Single-arm Study of CDK4/6 Inhibition With Palbociclib in Hospitalized, Moderate COVID-19 Cases to Prevent Thromboinflammation - Condition:   COVID-19
  Intervention:   Drug: Palbociclib
  Sponsor:   biotx.ai GmbH
  Active, not recruiting

• Phase I Clinical Trial of COVID-19 mRNA Vaccine in Adults Aged 18 Years and Older - Condition:   COVID-19
  Interventions:   Biological: COVID-19 mRNA vaccine;   Biological: Placebo
  Sponsor:   CanSino Biologics Inc.
  Not yet recruiting

• Phase II Clinical Trial of COVID-19 mRNA Vaccine in Adults Aged 18 Years and Older - Condition:   COVID-19
  Interventions:   Biological: COVID-19 mRNA vaccine;   Biological: Placebo
  Sponsor:   CanSino Biologics Inc.
  Not yet recruiting

• THEMBA II T-Cell Vaccine: Vaccination With saRNA COVID-19 Vaccines - Condition:   COVID-19
  Interventions:   Biological: AAHI-SC2 Vaccine;   Biological: AAHI- SC3 Vaccine;   Biological: EUA or approved vaccine
  Sponsor:   ImmunityBio, Inc.
  Recruiting

• To Evaluate SSD8432/Ritonavir in Adults With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: SSD8432 dose;   Drug: SSD8432 placebo
  Sponsor:   Jiangsu Simcere Pharmaceutical Co., Ltd.
  Not yet recruiting

• The Use of Chinese Herbal Medicine and Vitamin C by Hospital Care Workers in HK to Prevent COVID-19 - Condition:   COVID-19
  Intervention:   Drug: Chinese herbal medicine
  Sponsor:  
  Hong Kong Baptist University
  Not yet recruiting

• Evaluation of SSD8432 and Ritonavir in Adult Subjects With COVID-19 Placebo-Controlled, Phase II Clinical Study - Condition:   COVID-19
  Interventions:   Drug: SSD8432 dose1;   Drug: SSD8432 dose2;   Drug: SSD8432Placebo
  Sponsor:   Jiangsu Simcere Pharmaceutical Co., Ltd.
  Not yet recruiting

• To Evaluate SSD8432/ Ritonavir in Adults With COVID-19 - Condition:   COVID-19 Patients
  Interventions:   Drug: SSD8432 dose 1/Ritonavir;   Drug: SSD8432 dose 2/Ritonavir
  Sponsor:   Jiangsu Simcere Pharmaceutical Co., Ltd.
  Recruiting

• Safety, Reactogenicity, and Immunogenicity Study of a Lyophilized COVID-19 mRNA Vaccine - Condition:   COVID-19 Pandemic
  Interventions:   Biological: A Lyophilized COVID-19 mRNA Vaccine;   Biological: Placebo
  Sponsor:   Wuhan Recogen Biotechnology Co., Ltd.
  Not yet recruiting

• Home-based Exercise Program in Patients With the Post-COVID-19 Condition - Conditions:   Long COVID;   Post-acute COVID-19 Syndrome
  Intervention:   Other: Home- based physical training
  Sponsor:   University of Sao Paulo
  Not yet recruiting

From PubMed

• Computational studies on potential new anti-Covid-19 agents with a multi-target mode of action - A compound that could inhibit multiple targets associated with SARS-CoV-2 infection would prove to be a drug of choice against the virus. Human receptor-ACE2, receptor binding domain (RBD) of SARS-CoV-2 S-protein, Papain-like protein of SARS-CoV-2 (PLpro), reverse transcriptase of SARS-CoV-2 (RdRp) were chosen for in silico study. A set of previously synthesized compounds (1-5) were docked into the active sites of the targets. Based on the docking score, ligand efficiency, binding free energy,…

• Using cfRNA as a tool to evaluate clinical treatment outcomes in patients with metastatic lung cancers and other tumors - Aim: We report an exploratory analysis of cfRNA as a biomarker to monitor clinical responses in non-small cell lung cancer (NSCLC), breast cancer, and colorectal cancer (CRC). An analysis of cfRNA as a method for measuring PD-L1 expression with comparison to clinical responses was also performed in the NSCLC cohort. Methods: Blood samples were collected from 127 patients with metastatic disease that were undergoing therapy, 52 with NSCLC, 50 with breast cancer, and 25 with CRC. cfRNA was…

• RHAMNETIN IS A BETTER INHIBITOR OF SARS-COV-2 2’-O-METHYLTRANSFERASE THAN DOLUTEGRAVIR: A COMPUTATIONAL PREDICTION - CONCLUSION: Rhamnetin showed better inhibitory activity at the target’s active site than Dolutegravir.

• Nano drug (AgNPs capped with hydroxychloroquine): Synthesis, characterization, anti-covid-19 and healing the wound infected with S. aureus - Almost existing anti-viral drugs are only organic molecules that are able to circumvent the system the virus works with, which leaves it facing the immune system of our bodies and then kills it. Unfortunately, this type of pharmacological fight did not succeed in a way to overcome this virus, so it became necessary to think outside the box, to find a drug that would kill the virus or alter its protein structure. This research aims to prepare silver nanoparticle (AgNPs) by the green method…

• Antibody engineering improves neutralization activity against K417 spike mutant SARS-CoV-2 variants - CONCLUSION: Our studies have outlined a strategy to identify and engineer neutralizing antibodies against SARS-CoV-2 variants.

• Impact of renin-angiotensin-aldosterone system inhibitors on COVID-19 - Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, the possible roles of renin-angiotensin system (RAS) inhibitors in COVID-19 have been debated as favorable, harmful, or neutral. Angiotensin-converting enzyme 2 (ACE2) not only is the entry route of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection but also triggers a major mechanism of COVID-19 aggravation by promoting tissue RAS dysregulation, which induces a hyperinflammatory state in several organs,…

• Ultraviolet-coupled advanced oxidation processes for anti-COVID-19 drugs treatment: Degradation mechanisms, transformation products and toxicity evolution - Remdesivir (RDV), dexamethasone (DEX) and hydroxychloroquine (HCQ) were widely used in the treatment of COVID-19 pneumonia, possibly causing environmental risks and drug-resistance viruses. This study elucidated the degradation mechanisms and potential toxicity risks of the three anti-COVID-19 drugs by UV and ultraviolet-coupled advanced oxidation processes (UV/AOPs). All the drugs could be degraded by more than 98% within 3 min under the following optimal conditions: pH of 5.0 and…

• Molnupiravir inhibits SARS-CoV-2 variants including Omicron in the hamster model - The recent emergence of the SARS-CoV-2 Omicron variant of concern (VOC) containing a heavily mutated spike protein capable of escaping preexisting immunity identifies a continued need for interventional measures. Molnupiravir (MK-4482), an orally administered nucleoside analog, has demonstrated efficacy against earlier SARS-CoV-2 lineages and was recently approved for SARS-CoV-2 infections in high-risk adults. Here we assessed the efficacy of MK-4482 against the earlier Alpha, Beta and Delta…

• The potential of remdesivir to affect function, metabolism and proliferation of cardiac and kidney cells in vitro - Remdesivir is a prodrug of a nucleoside analog and the first antiviral therapeutic approved for coronavirus disease. Recent cardiac safety concerns and reports on remdesivir-related acute kidney injury call for a better characterization of remdesivir toxicity and understanding of the underlying mechanisms. Here, we performed an in vitro toxicity assessment of remdesivir around clinically relevant concentrations (C(max) 9 µM) using H9c2 rat cardiomyoblasts, neonatal mouse cardiomyocytes (NMCM),…

• Olverembatinib inhibits SARS-CoV-2-Omicron variant-mediated cytokine release in human peripheral blood mononuclear cells - No abstract

• Invalidation of dieckol and 1,2,3,4,6-pentagalloylglucose (PGG) as SARS-CoV-2 main protease inhibitors and the discovery of PGG as a papain-like protease inhibitor - The COVID-19 pandemic spurred a broad interest in antiviral drug discovery. The SARS-CoV-2 main protease (M^(pro)) and papain-like protease (PL^(pro)) are attractive antiviral drug targets given their vital roles in viral replication and modulation of host immune response. Structurally disparate compounds were reported as M^(pro) and PL^(pro) inhibitors from either drug repurposing or rational design. Two polyphenols dieckol and 1,2,3,4,6-pentagalloylglucose (PGG) were recently reported as…

• Synergistic deciphering of bioenergy production and electron transport characteristics to screen traditional Chinese medicine (TCM) for COVID-19 drug development - BACKGROUND: Traditional Chinese medicine (TCM) has been used as an “immune booster” for disease prevention and clinical treatment since ancient China. However, many studies were focused on the organic herbal extract rather than aqueous herbal extract (AHE; decoction). Due to the COVID-19 pandemics, this study tended to decipher phytochemical contents in the decoction of herbs and derived bioactivities (e.g., anti-oxidant and anti-inflammatory properties). As prior works revealed, the efficacy of…

• Molecular docking analysis reveals the functional inhibitory effect of Genistein and Quercetin on TMPRSS2: SARS- COV-2 cell entry facilitator spike protein - CONCLUSION: The compounds, Quercetin and Genistein, can inhibit the TMPRSS2 guided priming of the spike protein. The compounds could reduce the interaction of the host cell with the type I transmembrane glycoprotein to prevent the entry of the virus. The critical finding is that compared to Genistein, Quercetin exhibits higher binding affinity with the catalytic unit of TMPRSS2 and forms a stable complex with the target. Thus, enhancing our innate immunity by consuming foods rich in Quercetin…

• Famotidine activates the vagus nerve inflammatory reflex to attenuate cytokine storm - CONCLUSIONS: These observations reveal a previously unidentified vagus nerve-dependent anti-inflammatory effect of famotidine in the setting of cytokine storm which is not replicated by high dosages of other H2R antagonists in clinical use. Because famotidine is more potent when administered intrathecally, these findings are also consistent with a primarily central nervous system mechanism of action.

• Repurposing the natural compounds as potential therapeutic agents for COVID-19 based on the molecular docking study of the main protease and the receptor-binding domain of spike protein - Severe acute respiratory syndrome coronavirus (SARS-CoV-2) enters the cell by interacting with the human angiotensin- converting enzyme 2 (ACE2) receptor through the receptor-binding domain (RBD) of spike (S) protein. In the cell, the viral 3-chymotrypsin-like cysteine protease (3CLpro) enzyme is essential for its life cycle and controls coronavirus replication. Therefore, the S-RBD and 3CLpro are hot targets for drug discovery against SARS-CoV-2. This study was to identify repurposing drugs…

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