Covid-19 Sentry

Contents

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

From Preprints

• SARS-CoV-2 accessory proteins involvement in inflammatory and profibrotic processes through IL11 signaling -
  SARS-CoV-2, the cause of the COVID19 pandemic, possesses eleven accessory proteins encoded in its genome. Their roles during infection are still not completely understood. Transcriptomic analysis revealed that both WNT5A and IL11 were significantly up-regulated in A549 cells expressing individual accessory proteins ORF6, ORF8, ORF9b or ORF9c from SARS-CoV-2 (Wuhan-Hu-1 isolate). IL11 signaling-related genes were also differentially expressed. Bioinformatics analysis disclosed that both WNT5A and IL11 were involved in pulmonary fibrosis idiopathic disease. Functional assays confirmed their association with profibrotic cell responses. Subsequently, data comparison with lung cell lines infected with SARS-CoV-2 or lung biopsies from patients with COVID19 evidenced altered gene expression that matched those obtained in this study. Our results show ORF6, ORF8, ORF9b and ORF9c involvement in inflammatory and profibrotic responses. Thus, these accessory proteins could be targeted by new therapies against COVID19 disease.
  🖺 Full Text HTML: SARS-CoV-2 accessory proteins involvement in inflammatory and profibrotic processes through IL11 signaling
• Shedding light on human olfaction: electrophysiological recordings from sensory neurons in acute slices of olfactory epithelium -
  The COVID-19 pandemic brought attention to our limited understanding of human olfactory physiology. While the cellular composition of the human olfactory epithelium is similar to that of other vertebrates, its functional properties are largely unknown. We prepared acute slices of human olfactory epithelium from nasal biopsies and used the whole-cell patch-clamp technique to record electrical properties of cells. We measured voltage-gated currents in human olfactory sensory neurons and supporting cells, and action potentials in neurons. Additionally, inward currents and action potentials responses of neurons to a phosphodiesterase inhibitor indicated that the transduction cascade involves cAMP as a second messenger. Furthermore, responses to odorant mixtures demonstrated that the transduction cascade was intact in this preparation. This study provides the first electrophysiological characterization of olfactory sensory neurons in acute slices of the human olfactory epithelium, paving the way for future research to expand our knowledge of human olfactory physiology.
  🖺 Full Text HTML: Shedding light on human olfaction: electrophysiological recordings from sensory neurons in acute slices of olfactory epithelium
• A Complement Atlas identifies interleukin 6 dependent alternative pathway dysregulation as a key druggable feature of COVID-19 -

  To improve COVID-19 therapy, it is essential to understand the mechanisms driving critical illness. The complement system is an essential part of innate host defense that can also contribute to injury. All complement pathways have been implicated in COVID-19 pathogenesis, however the upstream drivers and downstream consequences on tissue injury remain ill-defined. Here, we demonstrate that complement activation is mediated by the alternative pathway and we provide a comprehensive atlas of the alterations in complement around the time of respiratory deterioration. Proteome and single-cell sequencing mapping across cell types and tissues reveals a division of labor between lung epithelial, stromal and myeloid cells in the production of complement, in addition to liver-derived factors. Upstream, IL-6 drives complement responses, linking complement dysregulation to approved COVID-19 therapies. In an exploratory proteomic study, C5 inhibition improves epithelial damage and markers of disease severity. Collectively, these results identify complement dysregulation as a key druggable feature of COVID-19.

  🖺 Full Text HTML: A Complement Atlas identifies interleukin 6 dependent alternative pathway dysregulation as a key druggable feature of COVID-19
• Sequential viral introductions and spread of BA.1 drove the Omicron wave across Pakistani provinces -

  Background: COVID-19 waves caused by specific SARS-CoV-2 variants have occurred globally at different times. We focused on Omicron variants to understand the genomic diversity and phylogenetic relatedness of SARS-CoV-2 strains in various regions of Pakistan. Methods: We studied 276,525 COVID-19 cases and 1,041 genomes sequenced from December 2021 to August 2022. Sequences were analyzed and visualized using phylogenetic trees. Results: The highest case numbers and deaths were recorded in Sindh and Punjab, the most populous provinces in Pakistan. Omicron variants comprised 95% of all genomes, with BA.2 (34.2%) and BA.5 (44.6%) predominating. The first Omicron wave was associated with the sequential identification of BA.1 in Sindh, then Islamabad Capital Territory, Punjab, Khyber Pakhtunkhwa (KP), Azad Jammu Kashmir (AJK), Gilgit-Baltistan (GB) and Balochistan. Phylogenetic analysis revealed Sindh to be the source of BA.1 and BA.2 introductions into Punjab and Balochistan during early 2022. BA.4 was first introduced in AJK and BA.5 in Punjab. Most recent common ancestor (MRCA) analysis revealed relatedness between the earliest BA.1 genome from Sindh with Balochistan, AJK, Punjab and ICT, and that of first BA.1 from Punjab with strains from KPK and GB. Conclusions: Phylogenetic analysis provides insights into the introduction and transmission dynamics of the Omicron variant in Pakistan, identifying Sindh as a hotspot for viral dissemination. Such data linked with public health efforts can help limit surges of new infections.

  🖺 Full Text HTML: Sequential viral introductions and spread of BA.1 drove the Omicron wave across Pakistani provinces
• Facility-based and virtual cardiac rehabilitation in young patients with heart disease during the COVID-19 era -

  Background: Cardiac rehabilitation (CR) is an important tool for improving fitness and quality of life in those with heart disease (HD). Few pediatric centers use CR to care for these patients, and virtual CR is rarely used. Additionally, it is unclear how the COVID-19 era has changed CR outcomes. Objectives: This study assessed fitness improvements in young HD patients participating in both facility-based and virtual CR during the COVID-19 pandemic. Methods: This retrospective single-center cohort study included new patients who completed CR from March 2020 through July 2022. CR outcomes included physical, performance, and psychosocial measures. Comparison between serial testing was performed with a paired t-test with P<0.05 was considered significant. Data are reported as mean±standard deviation. Results: There were 47 patients (19±7.3 years-old; 49% male) who completed CR. Improvements were seen in peak oxygen consumption (VO2, 62.3±16.1 v 71±18.2% of predicted, p=0.0007), 6-minute walk (6MW) distance (401±163.8 v 480.7±119.2 meters, p=<0.0001), sit to stand (16.2±4.9 v 22.1±6.6 repetitions; p=<0.0001), Patient Health Questionnaire-9 (PHQ-9) (5.9±4.3 v 4.4± 4.2; p=0.002), and Physical Component Score (39.9±10.1 v 44.9± 8.8; p=0.002). Facility-based CR enrollees were less likely to complete CR than virtual patients (60%, 33/55 v 80%, 12/15; p=0.005). Increases in peak VO2 (60±15.3 v 70.2±17.8 % of predicted; p=0.002) were seen among those that completed facility-based CR; this was not observed in the virtual group. Both groups demonstrated improvement in 6MW distance, sit-to-stand repetitions, and sit-and-reach distance. Conclusions: Completion of a CR program resulted in fitness improvements during the COVID-19 era regardless of location.

  🖺 Full Text HTML: Facility-based and virtual cardiac rehabilitation in young patients with heart disease during the COVID-19 era
• The impact of BNT162b2 mRNA vaccine on adaptive and innate immune responses -

  The mRNA-based BNT162b2 protects against severe disease and mortality caused by SARS-CoV-2 through induction of specific antibody and T-cell responses. Much less is known about its broad effects on immune responses against other pathogens. In the present study, we investigated the specific adaptive immune responses induced by BNT162b2 vaccination against various SARS-CoV-2 variants, as well as its effects on the responsiveness of human immune cells upon stimulation with heterologous viral, bacterial, and fungal pathogens. BNT162b2 vaccination induced effective humoral and cellular immunity against SARS-CoV-2 that started to wane after six months. We also observed long-term transcriptional changes in immune cells after vaccination, as assessed by RNA sequencing. Additionally, vaccination with BNT162b2 modulated innate immune responses as measured by the production of inflammatory cytokines when stimulated with various microbial stimuli other than SARS-CoV-2, including higher IL-1/IL-6 release and decreased production of IFN-α. Altogether, these data expand our knowledge regarding the overall immunological effects of this new class of vaccines and underline the need of additional studies to elucidate their effects on both innate and adaptive immune responses.

  🖺 Full Text HTML: The impact of BNT162b2 mRNA vaccine on adaptive and innate immune responses
• AI-Designed, Mutation-Resistant Broad Neutralizing Antibodies Against Multiple SARS-CoV-2 Strains -
  In this study, we generated a Digital Twin for SARS-CoV-2 by integrating data and meta-data with multiple data types and processing strategies, including machine learning, natural language processing, protein structural modeling, and protein sequence language modeling. This approach enabled the computational design of broadly neutralizing antibodies against over 1300 different historical strains of SARS-COV-2 containing 64 mutations in the receptor binding domain (RBD) region. The AI-designed antibodies were experimentally validated in real-virus neutralization assays against multiple strains including the newer Omicron strains that were not included in the initial design base. Many of these antibodies demonstrate strong binding capability in ELISA assays against the RBD of multiple strains. These results could help shape future therapeutic design for existing strains, as well as predicting hidden patterns in viral evolution that can be learned by AI for developing future antiviral treatments.
  🖺 Full Text HTML: AI-Designed, Mutation-Resistant Broad Neutralizing Antibodies Against Multiple SARS-CoV-2 Strains
• Trends in STI testing, diagnoses, and use of online chlamydia self-sampling services among young people during the first year of the COVID-19 pandemic in England -

  Purpose: Measures to control COVID-19 reduced face-to-face appointments and walk-ins at sexual health services (SHSs). Remote access to SHSs through online self-sampling for STIs was increased. This analysis assesses how these changes affected service use and STI testing among young people in England. Methods: Data on all chlamydia, gonorrhoea and syphilis tests from 2019-2020 amongst English-resident 15-24 year olds (hereafter referred to as young people) were obtained from national STI surveillance datasets. We calculated proportional differences in tests and diagnoses for each STI, by demographic characteristics including age and socioeconomic deprivation, between 2019 and 2020. Among those tested for chlamydia, we used binary logistic regression to determine crude and adjusted odds ratios (OR) between demographic characteristics and being tested for chlamydia by an online service. Results: Compared to 2019, there were declines in testing (30% for chlamydia, 26% for gonorrhoea, 36% for syphilis) and diagnoses (31% for chlamydia, 25% for gonorrhoea and 23% for syphilis) among young people in 2020. These reductions were greater amongst 15-19 year-olds (vs. 20-24 year-olds). Among young people tested for chlamydia, those living in the least deprived areas were more likely to be tested using an online self-sampling kit compared to those living in the most deprived areas (males; OR=1.24[1.22-1.26], females; OR=1.28[1.27-1.30]). Conclusion: The first year of the COVID-19 pandemic in England saw declines in STI testing and diagnoses in young people and disparities in the use of online chlamydia self-sampling which risk widening existing health inequalities.

  🖺 Full Text HTML: Trends in STI testing, diagnoses, and use of online chlamydia self-sampling services among young people during the first year of the COVID-19 pandemic in England
• A gene network implicated in the joint-muscle pain, brain fog, chronic fatigue, and bowel irregularity of Ehlers-Danlos and “long” COVID19 syndromes. -

  Objectives Characterization of tissue laxity and dysautonomia symptoms in Ehlers-Danlos syndrome (EDS) uncovered similarities with those of post-infectious SARS-CoV-2 or long COVID19, prompting detailed comparison of their findings and influencing genes. Methods Holistic assessment of 1261 EDS outpatients for 120 history-physical findings populated a deidentified database that includes 568 patients with 317 variant genes obtained by commercial NextGen sequencing. Findings were compared to 15 of long COVID19 compiled in an extensive review, genes to 104 associated with COVID19 severity in multiple molecular studies. Results Fifteen symptoms common to Ehlers-Danlos versus long COVID19 ranged from brain fog (27-80 versus 30-70%), chronic fatigue (38-91; 30-60%), dyspnea (32-52; 29-52%) to irritable bowel (67-89; 14-78%), muscle weakness (22-49; 15-25%), and arthritis (32-94; 15-27%). Genes relevant to EDS included 6 identical to those influencing COVID19 severity (F2, LIFR, NLRP3, STAT1, T1CAM1, TNFRSF13B) and 18 similar including POLG-POLD4, SLC6A2-SLC6A20, and NFKB1-NFKB2. Both gene sets had broad genomic distribution, many mitochondrial genes influencing EDS and many involved with immunity-inflammation modifying COVID19 severity. Recurring DNA variants in EDS that merit evaluation in COVID19 resistance include those impacting connective tissue elements–51 in COL5 (joint), 29 in COL1/2/9/11 (bone), 13 in COL3 (vessel), and 18 in FBN1 (vessel-heart)–or neural function–93 in mitochondrial DNA, 28 in COL6/12, 16 in SCN9A/10A/11A, 14 in POLG, and 11 in genes associated with porphyria. Conclusions Holistic ascertainment of finding pattern and exome variation in EDS defined tissue laxity, neuromuscular, and autonomic correlations that transcend single abnormalities or types. Implied networks of nuclear and mitochondrial genes are linked to findings like brain fog, fatigue, and frailty in EDS, their similarity to long COVID19 supporting shared therapies for disorders affecting a minimum 0.1% of the global population.

  🖺 Full Text HTML: A gene network implicated in the joint-muscle pain, brain fog, chronic fatigue, and bowel irregularity of Ehlers-Danlos and “long” COVID19 syndromes.
• COVID-19 Genome Surveillance: A Geographical Landscape and Mutational Mapping of SARS-CoV-2 Variants in Central India over Two Years -

  Reading the viral genome through whole genome sequencing enables the detection of changes in the viral genome. The rapid changes in the SARS-CoV-2 viral genome may cause immune escape leading to an increase in the pathogenicity or infectivity. Monitoring mutations through genomic surveillance helps understand the amino acid changes resulting from the mutation. These amino acid changes, especially in the spike glycoprotein, may have implications on the pathogenicity of the virus by rendering it immune-escape. The region of Vidarbha in Maharashtra represents 31.6% of the total area and 21.3% of the total population of the state. In total, 7457 SARS-CoV-2 positive samples belonging to 16 Indian States were included in the study, out of which 3002 samples passed the sequencing quality control criteria. The metadata of 7457 SARS-CoV-2 positive samples included in the study was sourced from the Integrated Health Information Platform. The metadata of 3002 sequenced samples, including the FASTA sequence, was submitted to the Global initiative on sharing Avian Influenza Data and the Indian biological data centre. This study identified 104 different SARS-CoV-2 pango-lineages classified into 19 clades. We have also analysed the mutation profiles of the variants found in the study, which showed eight mutations of interest, including L18F, K417N, K417T, L452R, S477N, N501Y, P681H, P681R, and mutation of concern E484K in the spike glycoprotein region. The study was from November 2020 to December 2022, making this study the most comprehensive genomic surveillance of SARS-CoV-2 conducted for the region.

  🖺 Full Text HTML: COVID-19 Genome Surveillance: A Geographical Landscape and Mutational Mapping of SARS-CoV-2 Variants in Central India over Two Years
• Evaluation of antiviral drugs against newly emerged SARS-CoV-2 Omicron variants -
  The ongoing emergence of SARS-CoV-2 Omicron subvariants and their rapid worldwide spread pose a threat to public health. From November 2022 to February 2023, newly emerged Omicron subvariants, including BQ.1.1, BF.7, BA.5.2, XBB.1, XBB.1.5, and BN.1.9, became prevalent global strains (>5% global prevalence). These Omicron subvariants are resistant to several therapeutic antibodies. Thus, the antiviral activities of current drugs such as remdesivir, molnupiravir, and nirmatrelvir, which target highly conserved regions of SARS-CoV-2, against newly emerged Omicron subvariants need to be evaluated. We assessed the antiviral efficacy of the drugs using half maximal inhibitory concentration (IC50) against human isolated 23 Omicron subvariants and four former SARS-CoV-2 variants of concern (VOC) and compared them with the antiviral efficacy of these drugs against the SARS-CoV-2 reference strain (hCoV/Korea/KCDC03/2020). Maximal IC50 fold changes of remdesivir, molnupiravir, and nirmatrelvir were 1.9- (BA.2.75.2), 1.2- (B.1.627.2), and 1.4-fold (BA.2.3), respectively, compared to median IC50 values of the reference strain. Moreover, median IC50-fold changes of remdesivir, molnupiravir, and nirmatrelvir against the Omicron variants were 0.96, 0.4, and 0.62, similar to 1.02, 0.88, and 0.67, respectively, of median IC50-fold changes for previous VOC. Although K90R and P132H in Nsp 5, and P323L, A529V, G671S, V405F, and ins823D in Nsp 12 mutations were identified, these amino acid substitutions did not affect drug antiviral activity. Altogether, these results indicated that the current antivirals retain antiviral efficacy against newly emerged Omicron subvariants, and provide comprehensive information on the antiviral efficacy of these drugs. Keywords: SARS-CoV-2, Omicron subvariant, remdesivir, molnupiravir, nirmatrelvir, antiviral activity
  🖺 Full Text HTML: Evaluation of antiviral drugs against newly emerged SARS-CoV-2 Omicron variants
• Non-invasive SARS-CoV-2 genome surveillance and its utility in resource-poor settings during the Delta wave of the COVID-19 pandemic -

  Voluntary participation of the public in disease surveillance can be encouraged by deploying user-friendly sample collection processes that can minimise the discomfort to the participants. This study evaluated the suitability of saline gargle-based sample collection for genomic surveillance of SARS-CoV-2, which included 589 SARS-CoV-2 positive samples collected from Nagpur city in central India from March to December 2021. The SARS-CoV-2 positive samples were subjected to whole genome sequencing (WGS) using the oxford nanopore technologies next-generation sequencing platform. Out of 589 samples, 500 samples qualified for the WGS, and the results revealed eight different clades of SARS-CoV-2 encompassing 37 different Pango-lineage types. The mutation mapping analysis of the variants identified in this study showed six mutations of interest and one mutation of concern E484K in the spike glycoprotein region. Our findings indicate that non-invasive gargle-based genomic surveillance is scalable and does not need significant changes to the existing workflow post-sample collection.

  🖺 Full Text HTML: Non-invasive SARS-CoV-2 genome surveillance and its utility in resource-poor settings during the Delta wave of the COVID-19 pandemic
• Immune responses and disease biomarker long-term changes following COVID-19 mRNA vaccination in a cohort of rheumatic disease patients -

  Objective. To evaluate seroreactivity and disease biomarkers after 2 or 3 doses of COVID-19 mRNA vaccines in a cohort of patients with rheumatic diseases. Methods. We collected biological samples longitudinally before and after 2-3 doses of COVID-19 mRNA vaccines from a cohort of patients with systemic lupus erythematosus (SLE), psoriatic arthritis, Sjogrens syndrome, ankylosing spondylitis, and inflammatory myositis. Anti-SARS-CoV-2 spike IgG and IgA and anti-dsDNA concentration were measured by ELISA. A surrogate neutralization assay was utilized to measure antibody neutralization ability. Lupus disease activity was measured by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Expression of type I interferon signature was measured by real-time PCR. The frequency of extrafollicular double negative 2 (DN2) B cells was measured by flow cytometry. Results. Most of the patients generated high SARS-CoV-2 spike-specific neutralizing antibodies comparable to those in healthy controls after 2 doses of mRNA vaccines. The antibody level declined over time but recovered after the third dose of the vaccine. Rituximab treatment substantially reduced antibody level and neutralization ability. Among SLE patients, no consistent increase in SLEDAI scores was observed post-vaccination. The changes in anti-dsDNA antibody concentration and expression of type I IFN signature genes were highly variable but did not show consistent or significant increases. Frequency of DN2 B cells remained largely stable. Conclusion. Rheumatic disease patients without rituximab treatment have robust antibody responses toward COVID-19 mRNA vaccination. Disease activity and disease-associated biomarkers remain largely stable over 3 doses of vaccines, suggesting that COVID-19 mRNA vaccines may not exacerbate rheumatic diseases.

  🖺 Full Text HTML: Immune responses and disease biomarker long-term changes following COVID-19 mRNA vaccination in a cohort of rheumatic disease patients
• Cell-type annotation with accurate unseen cell-type identification using multiple references -
  The recent advances in single-cell RNA sequencing (scRNA-seq) techniques have stimulated efforts to identify and characterize the cellular composition of complex tissues. With the advent of various sequencing techniques, automated cell-type annotation using a well-annotated scRNA-seq reference becomes popular but relies on the diversity of cell types in the reference. There are generally unseen cell l types in the query data of interest because most data atlases are obtained for different purposes and techniques. When annotating new query data, identifying unseen cell types is fundamental not only for improving annotation accuracy but also for novel biological discoveries. Here, we propose mtANN (multiple-reference-based scRNA-seq data annotation), a new method to automatically annotate query data while accurately identifying unseen cell types with the aid of multiple references. Key innovations of mtANN include the integration of deep learning and ensemble learning to improve prediction accuracy, and the introduction of a new metric defined from three complementary aspects to distinguish between unseen cell types and shared cell types. In addition, a data-driven method is provided to adaptively select threshold for unseen cell-type identification. We demonstrate the advantages of mtANN over state-of-the-art methods for unseen cell-type identification and cell-type annotation on two benchmark dataset collections, as well as its predictive power on a collection of COVID-19 datasets. The source code and tutorial are available at https://github.com/Zhangxf-ccnu/mtANN.
  🖺 Full Text HTML: Cell-type annotation with accurate unseen cell-type identification using multiple references
• Assessing the Impact of COVID-19 Pandemic on the Domestic Water Usage of Local Communities in Hanoi, Vietnam -
  This study aims to better understand the changes in the water usage behaviors of Hanoi communities in the current circumstance of preventing the spread of COVID-19 pandemic and developing the economy. The results of 206 survey responses conducted during April 2022 show that the main changes in the domestic water usage behavior of Hanoi communities come from hand washing, bathing/personal hygiene, house cleaning, and clothes washing. During the pandemic, 77% of the respondents had a habit of washing their hands for 30 seconds as recommended by the Ministry of Health and the frequency of daily hand washing increased 5-7 times compared to before the pandemic. The frequency of housing deep cleaning increased by 33% compared to before the pandemic, besides the frequency of floor mopping also increased about 3.5 times per week. The average frequency of clothes washing also changed from 2.43 times/week to 4.61 times/week. The total estimated moderate water use per person increased by 1.41% compared to its before the pandemic. Therefore, based on the total population of Hanoi city, the amount of domestic water increased by 471.457 m3/day. Statistical results show that there are differences in most of the water usage behaviors between the two groups of people living in apartments and houses.
  🖺 Full Text HTML: Assessing the Impact of COVID-19 Pandemic on the Domestic Water Usage of Local Communities in Hanoi, Vietnam

From Clinical Trials

• Clinical Performance Evaluation of the CareSuperb™ COVID-19 Antigen Home Test - Condition:   COVID-19
  Intervention:   Device: CareSuperb COVID-19 Antigen Home Test Kit
  Sponsor:   AccessBio, Inc.
  Recruiting

• Evaluation of Safety & Efficacy of MIR 19 ® Inhalation Solution in Patients With Mild COVID-19 - Condition:   COVID-19
  Interventions:   Drug: MIR 19 ®;   Combination Product: Standard therapy
  Sponsor:   National Research Center - Institute of Immunology Federal Medical-Biological Agency of Russia
  Completed

• LACTYFERRIN™ Forte and ZINC Defense™ and Standard of Care (SOC) vs SOC in the Treatment of Non-hospitalized Patients With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Sesderma LACTYFERRIN™ Forte and Sesderma ZINC Defense™;   Drug: Placebo
  Sponsors:   Jose David Suarez, MD;   Sesderma S.L.;   Westchester General Hospital Inc. DBA Keralty Hospital Miami;   MGM Technology Corp
  Not yet recruiting

• MP0420 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial) - Condition:   COVID-19
  Interventions:   Drug: MP0420;   Drug: Placebo;   Biological: Remdesivir
  Sponsors:   National Institute of Allergy and Infectious Diseases (NIAID);   International Network for Strategic Initiatives in Global HIV Trials (INSIGHT);   University of Copenhagen;   Medical Research Council;   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);   Molecular Partners AG;   University of Minnesota
  Active, not recruiting

• AZD7442 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial) - Condition:   COVID-19
  Interventions:   Biological: AZD7442;   Biological: Placebo;   Biological: Remdesivir
  Sponsors:   National Institute of Allergy and Infectious Diseases (NIAID);   International Network for Strategic Initiatives in Global HIV Trials (INSIGHT);   University of Copenhagen;   Medical Research Council;   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);   AstraZeneca;   University of Minnesota
  Active, not recruiting

• PF-07304814 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial) - Condition:   COVID-19
  Interventions:   Drug: PF-07304814;   Drug: Placebo;   Biological: Remdesivir
  Sponsors:   National Institute of Allergy and Infectious Diseases (NIAID);   International Network for Strategic Initiatives in Global HIV Trials (INSIGHT);   University of Copenhagen;   Medical Research Council;   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);   Pfizer;   University of Minnesota
  Suspended

• VIR-7831 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial) - Condition:   COVID-19
  Interventions:   Biological: VIR-7831;   Biological: Placebo;   Biological: Remdesivir
  Sponsors:   National Institute of Allergy and Infectious Diseases (NIAID);   International Network for Strategic Initiatives in Global HIV Trials (INSIGHT);   University of Copenhagen;   Medical Research Council;   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);   Vir Biotechnology, Inc.;   GlaxoSmithKline;   University of Minnesota
  Completed

• BRII-196/BRII-198 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial) - Condition:   COVID-19
  Interventions:   Biological: BRII-196;   Biological: BRII-198;   Biological: Placebo;   Biological: Remdesivir
  Sponsors:   National Institute of Allergy and Infectious Diseases (NIAID);   International Network for Strategic Initiatives in Global HIV Trials (INSIGHT);   University of Copenhagen;   Medical Research Council;   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);   Brii Biosciences Limited;   University of Minnesota
  Completed

• LY3819253 (LY-CoV555) for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial) - Condition:   COVID-19
  Interventions:   Biological: LY3819253;   Biological: Placebo;   Biological: Remdesivir
  Sponsors:   National Institute of Allergy and Infectious Diseases (NIAID);   International Network for Strategic Initiatives in Global HIV Trials (INSIGHT);   University of Copenhagen;   Medical Research Council;   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);   Eli Lilly and Company;   University of Minnesota
  Completed

• Use of E-health Based Exercise Intervention After COVID-19 - Condition:   COVID-19
  Intervention:   Behavioral: Exercise training using an e-health tool
  Sponsors:   Norwegian University of Science and Technology;   University of Oslo
  Recruiting

• Clinical Study for the Efficacy and Safety of Ropeginterferon Alfa-2b in Moderate COVID19. - Condition:   COVID-19
  Interventions:   Drug: P1101 (Ropeginterferon alfa-2b);   Procedure: SOC
  Sponsor:   National Taiwan University Hospital
  Active, not recruiting

• A Phase II Clinical Trial of Recombinant Variant COVID-19 Vaccine (Sf9 Cell) (WSK-V102) - Condition:   COVID-19
  Interventions:   Biological: Recombinant variant COVID-19 vaccine (Sf9 cell);   Biological: Recombinant COVID-19 vaccine (CHO cell);   Biological: Recombinant COVID-19 vaccine (Sf9 cell)
  Sponsor:   WestVac Biopharma Co., Ltd.
  Not yet recruiting

• Short-term Effects of Transdermal Estradiol on Female COVID-19 Patients - Conditions:   COVID-19;   Hormone Replacement Therapy
  Interventions:   Drug: Climara 0.1Mg/24Hr Transdermal System;   Other: Hydrogel patch
  Sponsors:   Istanbul University - Cerrahpasa (IUC);   Turkish Menopause and Osteoporosis Society;   Karakoy Rotary Club;   Rebul Pharmacy
  Completed

• Effect of Kinesio Tape Versus Diaphragmatic Breathing Exercise In Post COVID-19 - Condition:   Post COVID-19 Condition
  Interventions:   Other: Pursed lip breathing;   Other: Cognitive Behavior Therapy;   Other: Diaphragmatic breathing exercise;   Other: Kinesio tape
  Sponsor:   Cairo University
  Not yet recruiting

• Study of the Safety, Tolerability and Efficacy of NP-101 in Treating High Risk Participants Who Are Covid-19 Positive. - Condition:   COVID-19
  Interventions:   Drug: NP-101;   Other: Placebo
  Sponsor:   Novatek Pharmaceuticals
  Recruiting

From PubMed

• A theoretical survey to find potential natural compound for inhibition of binding the RBD domain to ACE2 receptor based on plant antivirals - The spike protein of coronavirus is crucial in binding and arrival of the virus to the human cell via binding to the human ACE2 receptor. In this study, at first 25 antiviral phytochemicals were docked into the RBD domain of spike protein, and then all complexes and free RBD domains were separately subjected to molecular dynamics simulation for 100 ns and MM/PBSA binding free energy calculation. In this phase, four ligands were chosen as hit compounds and a natural compound database (NPASS) was…

• Computational studies of potential antiviral compounds from some selected Nigerian medicinal plants against SARS-CoV-2 proteins - The challenges posed by COVID-19’s emergence have led to a search for its therapies. There is no cure for COVID-19 infection yet, but there is significant progress in vaccine formulation for prophylaxis and drug development (such as Paxlovid) for high-risk patients. As a contribution to the ongoing quest for solutions, this study shows potent phytocompounds identification as inhibitors of SARS-CoV-2 targets using in silico methods. We used virtual screening, molecular docking, and molecular…

• IBV QX affects the antigen presentation function of BMDCs through nonstructural protein16 - The gamma-coronavirus infectious bronchitis virus (IBV) has a high mutation rate and mainly invades the respiratory mucosa, making it difficult to prevent and causing great economic losses. Nonstructural protein 16 (NSP16) of IBV QX also not only plays an indispensable role in virus invading but also might hugely influence the antigen’s recognition and presentation ability of host BMDCs. Hence, our study tries to illustrate the underline mechanism of how NSP16 influences the immune function of…

• TNF/iNOS/NO pathway mediates host susceptibility to endothelial-dependent circulatory failure and death induced by betacoronavirus infection - Poor disease outcomes and lethality are directly related to endothelial dysfunction in betacoronavirus infections. Here, we investigated the mechanisms underlying the vascular dysfunction caused by the betacoronaviruses MHV-3 and SARS-CoV-2. Wild-type C57BL/6 (WT) and knockout mice for inducible nitric oxide synthase (iNOS-/-) or TNF receptor 1 (TNFR1-/-) were infected with MHV-3, and K18-hACE2 transgenic mice expressing human ACE2 were infected with SARS-CoV-2. Isometric tension was used to…

• An overview of the recent progress in Middle East Respiratory Syndrome Coronavirus (MERS-CoV) drug discovery - INTRODUCTION: The Middle East respiratory syndrome coronavirus (MERS-CoV) has remained a public health concern since it first emerged in 2012. Although many potential treatments for MERS-CoV have been developed and tested, none have had complete success in stopping the spread of this deadly disease. MERS-CoV replication comprises attachment, entry, fusion and replication steps. Targeting these events may lead to the creation of medications that effectively treat MERS-CoV infection.

• Abiotic Synthetic Antibody Inhibitor with Broad-Spectrum Neutralization and Antiviral Efficacy against Escaping SARS-CoV-2 Variants - The rapid emergence and spread of vaccine/antibody-escaping variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed serious challenges to our efforts in combating corona virus disease 2019 (COVID-19) pandemic. A potent and broad-spectrum neutralizing reagent against these escaping mutants is extremely important for the development of strategies for the prevention and treatment of SARS-CoV-2 infection. We herein report an abiotic synthetic antibody inhibitor as a…

• Qingfei Jiedu Granules fight influenza by regulating inflammation, immunity, metabolism, and gut microbiota - BACKGROUND AND AIM: Qingfei Jiedu Granules (QFJD) are a new Traditional Chinese Medicine (TCM) which has been clinically used against coronavirus pneumonia in China. In this study, the therapeutic effect and the underlying mechanisms of QFJD against influenza were investigated.

• A pan-variant mRNA-LNP T cell vaccine protects HLA transgenic mice from mortality after infection with SARS-CoV-2 Beta - Licensed COVID-19 vaccines ameliorate viral infection by inducing production of neutralizing antibodies that bind the SARS-CoV-2 Spike protein and inhibit viral cellular entry. However, the clinical effectiveness of these vaccines is transitory as viral variants escape antibody neutralization. Effective vaccines that solely rely upon a T cell response to combat SARS-CoV-2 infection could be transformational because they can utilize highly conserved short pan-variant peptide epitopes, but a…

• Discovery of therapeutic targets of quercetin for endometrial carcinoma patients infected with COVID-19 through network pharmacology - CONCLUSIONS: Taken together, this study provides new treatment option for UCEC patients infected with COVID-19. Quercetin may work by reducing the expression of ISG15 and participating in ubiquitination-related pathways.

• Effects of diarylbutane lignans from Schisandra chinensis fruit on SARS-CoV-2 3CL^pro and PL^pro and their in vitro anti-inflammatory properties - CONCLUSION: Our results suggest that compounds 63, 64, and 65 may be promising SARS-CoV-2 3CL^(pro) and PL^(pro) inhibitors and anti-inflammatory.

• Adamantanes for the treatment of neurodegenerative diseases in the presence of SARS-CoV-2 - Advent of the acute respiratory coronavirus SARS-CoV-2 has resulted in the search for novel antiviral agents and in the repurposing of existing agents with demonstrated efficacy against other known coronaviruses in the search for an agent with antiviral activity for use during the COVID-19 pandemic. Adamantanes including amantadine, rimantadine, and memantine have well-established benefit in the treatment of neurodegenerative diseases including Parkinson’s disease (PD), Alzheimer’s disease (AD)…

• Endogenous IFITMs boost SARS-coronavirus 1 and 2 replication whereas overexpression inhibits infection by relocalizing ACE2 - Opposing effects of interferon-induced transmembrane proteins (IFITMs 1, 2 and 3) on SARS-CoV-2 infection have been reported. The reasons for this are unclear and the role of IFITMs in infection of other human coronaviruses (hCoVs) remains poorly understood. Here, we demonstrate that endogenous expression of IFITM2 and/or IFITM3 is critical for efficient replication of SARS-CoV-1, SARS-CoV-2 and hCoV-OC43 but has little effect on MERS-, NL63-and 229E-hCoVs. In contrast, overexpression of IFITMs…

• Repurposing 1,2,4-oxadiazoles as SARS-CoV-2 PLpro inhibitors and investigation of their possible viral entry blockade potential - Although vaccines are obviously mitigating the COVID-19 pandemic diffusion, efficient complementary antiviral agents are urgently needed to combat SARS-CoV-2. The viral papain-like protease (PLpro) is a promising therapeutic target being one of only two essential proteases crucial for viral replication. Nevertheless, it dysregulates the host immune sensing response. Here we report repositioning of the privileged 1,2,4-oxadiazole scaffold as promising SARS-CoV-2 PLpro inhibitor with potential…

• Thalidomide interaction with inflammation in idiopathic pulmonary fibrosis - The “Thalidomide tragedy” is a landmark in the history of the pharmaceutical industry. Despite limited clinical trials, there is a continuous effort to investigate thalidomide as a drug for cancer and inflammatory diseases such as rheumatoid arthritis, lepromatous leprosy, and COVID-19. This review focuses on the possibilities of targeting inflammation by repurposing thalidomide for the treatment of idiopathic pulmonary fibrosis (IPF). Articles were searched from the Scopus database, sorted, and…

• Antiviral drugs block replication of highly immune-evasive Omicron subvariants ex vivo, but fail to reduce tissue inflammation - The identification of the SARS-CoV-2 Omicron variants BA.4/BA.5, BF.7 and BQ.1.1 immediately raised concerns regarding the efficacy of currently used monoclonal antibody therapies. Here we examined the activity of monoclonal antibody therapies and antiviral drugs against clinical specimens for SARS-CoV-2 Omicron BA.4/BA.5, BF.7 and BQ.1.1 employing an immunofluorescence neutralization assay. Further we explored treatment of BA.4/BA.5 infections with efficient antiviral drugs and monoclonal…

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