Covid-19 Sentry

Contents

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

From Preprints

• Identification of a molnupiravir-associated mutational signature in SARS-CoV-2 sequencing databases -

  Molnupiravir, an antiviral medication that has been widely used against SARS-CoV-2, acts by inducing mutations in the virus genome during replication. Most random mutations are likely to be deleterious to the virus, and many will be lethal. Molnupiravir-induced elevated mutation rates have been shown to decrease viral load in animal models. However, it is possible that some patients treated with molnupiravir might not fully clear SARS-CoV-2 infections, with the potential for onward transmission of molnupiravir-mutated viruses. We set out to systematically investigate global sequencing databases for a signature of molnupiravir mutagenesis. We find that a specific class of long phylogenetic branches appear almost exclusively in sequences from 2022, after the introduction of molnupiravir treatment, and in countries and age-groups with widespread usage of the drug. We calculate a mutational spectrum from the AGILE placebo-controlled clinical trial of molnupiravir and show that its signature, with elevated G-to-A and C-to-T rates, largely corresponds to the mutational spectrum seen in these long branches. Our data suggest a signature of molnupiravir mutagenesis can be seen in global sequencing databases, in some cases with onwards transmission.

  🖺 Full Text HTML: Identification of a molnupiravir-associated mutational signature in SARS-CoV-2 sequencing databases
• Early risk-assessment of pathogen genomic variants emergence -

  Accurate, reliable, and timely estimates of pathogen variant risk are essential for informing effective public health responses to infectious diseases. Despite decades of use for influenza vaccine strain selection and PCR-based molecular diagnostics, data on pathogen variant prevalence and growth advantage has only risen to its current prominence during the SARS-CoV-2 pandemic. However, such data are still often sparse: novel variants are initially rare or a region has limited sequencing. To ensure real-time estimates of risk are available in these types of data-sparse conditions, we develop a hierarchical modeling approach that estimates variant fitness advantage and prevalence by pooling data across geographic regions. We apply this method to estimate SARS-CoV-2 variant dynamics at the country-level and assess its stability with retrospective validation. Our results show that more stable and robust estimates can be obtained even when sequencing data are sparse, as compared to established, single-country estimation approaches. We discuss how this method can inform risk assessment of novel emerging variants and provide situational awareness on currently circulating variants, for a range of pathogens and use-cases.

  🖺 Full Text HTML: Early risk-assessment of pathogen genomic variants emergence
• Bayesian Prediction of Severe Outcomes in the LabMarCS: Laboratory Markers of COVID-19 Severity - Bristol Cohort -

  Objectives: To develop cross-validated prediction models for severe outcomes in COVID-19 using blood biomarker and demographic data; Demonstrate best practices for clinical data curation and statistical modelling decisions, with an emphasis on Bayesian methods. Design: Retrospective observational cohort study. Setting: Multicentre across National Health Service (NHS) trusts in Southwest region, England, UK. Participants: Hospitalised adult patients with a positive SARS-CoV 2 by PCR during the first wave (March - October 2020). 843 COVID-19 patients (mean age 71, 45% female, 32% died or needed ICU stay) split into training (n=590) and validation groups (n=253) along with observations on demographics, coinfections, and 30 laboratory blood biomarkers. Primary outcome measures: ICU admission or death within 28-days of admission to hospital for COVID-19 or a positive PCR result if already admitted. Results: Predictive regression models were fit to predict primary outcomes using demographic data and initial results from biomarker tests collected within 3 days of admission or testing positive if already admitted. Using all variables, a standard logistic regression yielded an internal validation median AUC of 0.7 (95% Interval [0.64,0.81]), and an external validation AUC of 0.67 [0.61, 0.71], a Bayesian logistic regression using a horseshoe prior yielded an internal validation median AUC of 0.78 [0.71, 0.85], and an external validation median AUC of 0.70 [0.68, 0.71]. Variable selection performed using Bayesian predictive projection determined a four variable model using Age, Urea, Prothrombin time and Neutrophil-Lymphocyte ratio, with a median AUC of 0.74 [0.67, 0.82], and external validation AUC of 0.70 [0.69, 0.71]. Conclusions: Our study reiterates the predictive value of previously identified biomarkers for COVID-19 severity assessment. Given the small data set, the full and reduced models have decent performance, but would require improved external validation for clinical application. The study highlights a variety of challenges present in complex medical data sets while maintaining best statistical practices with an emphasis on showcasing recent Bayesian methods.

  🖺 Full Text HTML: Bayesian Prediction of Severe Outcomes in the LabMarCS: Laboratory Markers of COVID-19 Severity - Bristol Cohort
• Infection of equine bronchial epithelial cells with a SARS-CoV-2 pseudovirus -
  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of COVID-19, can infect animals by binding to the angiotensin-converting enzyme 2 (ACE2). Equine infection appears possible due to high homology ({approx}97%) between human and equine ACE2, evidence of in vitro infection in cell lines expressing equine ACE2, and evidence of seroconversion in horses after exposure to persons infected with SARS-CoV-2. Our objective was to examine susceptibility of cultured primary equine bronchial epithelial cells (EBECs) to a SARS-CoV-2 pseudovirus relative to human bronchial epithelial cells (HBECs; positive control). ACE2 expression in EBECs detected by immunofluorescence, western immunoblotting, and flow cytometry was lower in EBECs than in HBECs. EBECs were transduced with a lentivirus pseudotyped with the SARS-CoV-2 spike protein that binds to ACE2 and expresses the enhanced green fluorescent protein (eGFP) as a reporter. Cells were co-cultivated with the pseudovirus at a multiplicity of infection of 0.1 for 6 hours, washed, and maintained in media. After 96 hours, eGFP expression in EBECs was demonstrated by fluorescence microscopy, and mean {Delta} Ct values from quantitative PCR were significantly (P < 0.0001) higher in HBECs (8.78) than HBECs (3.24) indicating lower infectivity in EBECs. Equine respiratory tract cells were susceptible to infection with a SARS-CoV-2 pseudovirus. Lower replication efficiency in EBECs suggests that horses are unlikely to be an important zoonotic host of SARS-CoV-2, but viral mutations could render some strains more infectious to horses. Serological and virological monitoring of horses in contact with persons shedding SARS-CoV-2 is warranted.
  🖺 Full Text HTML: Infection of equine bronchial epithelial cells with a SARS-CoV-2 pseudovirus
• The lung employs an intrinsic surfactant-mediated inflammatory response for viral defense -
  Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) causes an acute respiratory distress syndrome (ARDS) that resembles surfactant deficient RDS. Using a novel multi-cell type, human induced pluripotent stem cell (hiPSC)-derived lung organoid (LO) system, validated against primary lung cells, we found that inflammatory cytokine/chemokine production and interferon (IFN) responses are dynamically regulated autonomously within the lung following SARS-CoV-2 infection, an intrinsic defense mechanism mediated by surfactant proteins (SP). Single cell RNA sequencing revealed broad infectability of most lung cell types through canonical (ACE2) and non-canonical (endocytotic) viral entry routes. SARS-CoV-2 triggers rapid apoptosis, impairing viral dissemination. In the absence of surfactant protein B (SP-B), resistance to infection was impaired and cytokine/chemokine production and IFN responses were modulated. Exogenous surfactant, recombinant SP-B, or genomic correction of the SP-B deletion restored resistance to SARS-CoV-2 and improved viability.
  🖺 Full Text HTML: The lung employs an intrinsic surfactant-mediated inflammatory response for viral defense
• The Omicron variant BQ.1* with mutations at positions 28,311 and 28,312 in the SARS-CoV-2 N gene have minimal impact on CDC N1 target detection -
  Ensuring COVID-19 testing remains accurate and reliable is of critical importance as the SARS-CoV-2 virus continues to evolve. Currently, a number of Omicron variants are dominating infection across the globe in including BQ.1 and XBB. Both variants and their sublineages (BQ.1* and XBB) contain a 28,311 C/U mutation inherited from the original Omicron variant (BA.1). This mutation overlaps with a commonly used fluorescent probe for N gene detection in many Emergency Use Authorization (EUA) assays, as this target was originally established by the U.S. Centers for Disease Control and Prevention (CDC) in their EUA test for COVID-19 (2019-nCoV_N1). This C to U mutation was previously shown to have no impact on CDC N1 target detection. The rise of Omicron sublineages has increased the likelihood of additional point mutations occurring within the same assay target. A subpopulation of BQ.1 has an additional 28,312 C/U mutation within the CDC 2019_nCoV_N1 fluorescent probe in addition to the 28,311 C/U mutation. The double mutation could adversely affect the ability of diagnostic assays to detect the virus in patient samples and therefore it is important to verify the impacts of this additional mutation. Using in vitro transcribed (IVT) N gene RNA representing the wildtype (GenBank/GISAID ID MN908947.3) and Omicron BQ.1.1 variant (BQ.1, GISAID ID EPI_ISL_ 15155651), we evaluated the performance of two different amplification protocols, both of which include the CDC 2019-nCoV_N1 primer-probe set. Both assays successfully detected the mutant N gene sequence efficiently even at 10 copies of input, although the double mutation caused a 0.5~1 Cq delay on average when compared to the wild-type sequence. These data suggest that circulating BQ.1* lineage viruses with this double mutation likely have minimal impact on diagnostic assays that use the 2019-nCoV-N1 primer-probe.
  🖺 Full Text HTML: The Omicron variant BQ.1* with mutations at positions 28,311 and 28,312 in the SARS-CoV-2 N gene have minimal impact on CDC N1 target detection
• Emotional responses to COVID-19 stressors increase avoidance of health information and access to care -
  The COVID-19 pandemic, like other crises, has had direct and indirect impacts on people’s lives, many of which have been negative. However, there is little evidence about how COVID-19 affects decision-making. Emotional responses to COVID-19- related stressors, such as local cases and income loss, provide a pathway for these stressors to affect decision-making. In this study, we examine linkages between exposure to COVID-19-related stressors—focusing on temporally specific local case counts and loss of income due to the pandemic—and behaviors for important health decisions with both individual (accessing health care) and societal (accessing information about antimicrobial resistance (AMR)) relevance. In the analysis of two health behaviors that use data from 1) a custom AMR survey and 2) the U.S. Census’s Household Pulse Survey, which asked about accessing healthcare, we find that exposure to COVID-19 stressors significantly increases feelings of hopelessness. Higher levels of hopelessness are associated with an increased probability of avoiding health information about AMR and foregoing or delaying needed medical care. Mediation analysis confirms that hopelessness is an important pathway through which COVID-19-related stressors affect avoidance behaviors. Our results suggest that large- scale crises may diminish action on other important personal and societal health issues facing humanity through emotion-mediated changes in decision-making.
  🖺 Full Text HTML: Emotional responses to COVID-19 stressors increase avoidance of health information and access to care
• Identification of a molnupiravir-associated mutational signature in SARS-CoV-2 sequencing databases -

  Molnupiravir, an antiviral medication that has been widely used against SARS-CoV-2, acts by inducing mutations in the virus genome during replication. Most random mutations are likely to be deleterious to the virus, and many will be lethal. Molnupiravir-induced elevated mutation rates have been shown to decrease viral load in animal models. However, it is possible that some patients treated with molnupiravir might not fully clear SARS-CoV-2 infections, with the potential for onward transmission of molnupiravir-mutated viruses. We set out to systematically investigate global sequencing databases for a signature of molnupiravir mutagenesis. We find that a specific class of long phylogenetic branches appear almost exclusively in sequences from 2022, after the introduction of molnupiravir treatment, and in countries and age-groups with widespread usage of the drug. We calculate a mutational spectrum from the AGILE placebo-controlled clinical trial of molnupiravir and show that its signature, with elevated G-to-A and C-to-T rates, largely corresponds to the mutational spectrum seen in these long branches. Our data suggest a signature of molnupiravir mutagenesis can be seen in global sequencing databases, in some cases with onwards transmission.

  🖺 Full Text HTML: Identification of a molnupiravir-associated mutational signature in SARS-CoV-2 sequencing databases
• Clinical Characteristics and Outcomes of Laboratory-Confirmed SARS-CoV-2 Cases Infected with Omicron subvariants and XBB recombinant variant -

  Background: The SARS-CoV-2 has evolved to produce new variants causing successive waves of infection. Currently, six variants are being monitored by the World Health Organization that are replacing BA.5. These include BQ.1, BA.5 with one or several of five mutations (R346X, K444X, V445X, N450D, N460X), BA.2.75, XBB, BA.4.6, and BA.2.30.2. BQ.1 and XBB variants are more immune evasive and have spread quickly throughout the world. With the concern of the potential severity of infections caused by these variants, the present study describes the clinical characteristics and outcomes of these major variants in Maharashtra. Material and Methods: A total of 1039 Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) positive SARS-CoV-2 samples, with a cycle threshold value (Ct) less than 25, were processed for SARS-CoV-2 whole genome sequencing between 10th July 2022 and 10th December 2022. All corresponding demographic and clinical data were recorded and analyzed using MicrosoftTM ExcelTM and Epi InfoTM. Results: Out of 1039 samples sequenced, 829 (79.79%) were assigned Pango lineages, of which BA.2.75 (67.31%) was the predominant Omicron variant, followed by the XBB (17.13%), BA.2.38* (5.43%), BA.2.10* (3.62%) and BA.5* (3.50%). A total of 494 cases were contacted telephonically, of which 455 (92.11%) were symptomatic with mild symptoms. Fever (78.46%) was the most common symptom, followed by rhinorrhoea (46.37%), cough (42.20%), myalgia (19.56%) and fatigue (18.24%). Of the 494 cases, 379 (76.72%) cases recovered at home, and 115 (23.28%) were institutionally quarantined/ hospitalized. Among the home-isolated and hospitalized cases, 378 (99.74%) and 101 (87.83%) recovered with symptomatic treatment, whereas 01 (0.26%) and 14 (12.17%) succumbed to the disease, respectively. Of the 494 cases, 449 (90.89%) were vaccinated with at least one dose of the COVID-19 vaccine, 40 (8.10%) were unvaccinated, and for 05 (1.01%) cases, vaccine data was not available. Conclusion: The current study indicates that the XBB* variant is causing mild disease in India. However, as XBB* possess both immune-escape and infectivity-enhancing mutations, it has the potential to spread to other parts of the world rapidly.

  🖺 Full Text HTML: Clinical Characteristics and Outcomes of Laboratory-Confirmed SARS-CoV-2 Cases Infected with Omicron subvariants and XBB recombinant variant
• SPEAR: a Sparse Supervised Bayesian Factor Model for Multi-omic Integration -
  Motivation: Unsupervised factor modeling, which preserves the primary sources of data variation through low-dimensional factors, is commonly applied to integrate high-dimensional multi-omics data. However, the resulting factors are suboptimal for prediction tasks due to the separation between factor construction and prediction model learning. A supervised factor model that effectively utilizes the responses while accounting for structural heterogeneity across omics is needed. Results: We present SPEAR, a supervised variational Bayesian framework that decomposes multi-omics data into latent factors with predictive power. The method adaptively determines factor rank, emphasis on factor structure, data relevance and feature sparsity. SPEAR improves reconstruction of underlying factors in synthetic examples and prediction accuracy of COVID-19 severity and breast cancer tumor subtypes. Availability: SPEAR is a publicly available R-package hosted at https://bitbucket.org/kleinstein/SPEAR.
  🖺 Full Text HTML: SPEAR: a Sparse Supervised Bayesian Factor Model for Multi-omic Integration
• First virological and pathological study of Göttingen Minipigs with Dippity Pig Syndrome (DPS) -
  Dippity Pig Syndrome (DPS) is a well-known but rare complex of clinical signs affecting minipigs, which has not been thoroughly investigated yet. Clinically affected animals show acute appearance of red, exudating lesions across the spine. The lesions are painful, evidenced by arching of the back (dipping), and the onset of clinical symptoms is generally sudden. In order to understand the pathogenesis, histological and virological investigations were performed in affected and unaffected Gottingen Minipigs (GoMPs). The following DNA viruses were screened for using PCR-based methods: Porcine cytomegalovirus (PCMV), which is a porcine roseolovirus (PCMV/PRV), porcine lymphotropic herpesviruses (PLHV-1, PLHV-2, PLHV-3), porcine circoviruses (PCV1, PCV2, PCV3, PCV4), porcine parvovirus 1 (PPV1), and Torque Teno sus virus (TTSuV1, TTSuV2). Screening was also performed for integrated porcine endogenous retroviruses (PERV-A, PERV-B, PERV-C) and recombinant PERV-A/C and their expression as well as for the RNA viruses hepatitis E virus (HEV) and SARS-CoV-2. Eight clinically affected and one unaffected GoMPs were analyzed. Additional unaffected minipigs had been analyzed in the past. The analyzed GoMPs contained PERV-A and PERV-B integrated in the genome, which are present in all pigs and PERV-C, which is present in most, but not all pigs. In one affected GoMPs recombinant PERV-A/C was detected in blood. In this animal a very high expression of PERV mRNA was observed. PCMV/PRV was found in three affected animals, PCV1 was found in three animals with DPS and in the healthy minipig, and PCV3 was detected in two animals with DPS and in the unaffected minipig. Most importantly, in one animal only PLHV-3 was detected. It was found in the affected and unaffected skin, and in other organs. Unfortunately, PLHV-3 could not be studied in all other affected minipigs. None of the other viruses were detected and using electron microscopy, no virus particles were found in the affected skin. This data identified some virus infections in GoMPs with DPS and assign a special role to PLHV-3. Since PCMV/PRV, PCV1, PCV3 and PLHV-3 were also found in unaffected animals, a multifactorial cause of DPS is suggested. However, elimination of the viruses from GoMPs may prevent DPS.
  🖺 Full Text HTML: First virological and pathological study of Göttingen Minipigs with Dippity Pig Syndrome (DPS)
• Antibody escape, the risk of serotype formation, and rapid immune waning: modeling the implications of SARS-CoV-2 immune evasion -

  As the COVID-19 pandemic progresses, widespread community transmission of SARS-CoV-2 has ushered in a volatile era of viral immune evasion rather than the much-heralded stability of “endemicity” or “herd immunity.” At this point, an array of viral variants has rendered essentially all monoclonal antibody therapeutics obsolete and strongly undermined the impact of vaccinal immunity on SARS-CoV-2 transmission. In this work, we demonstrate that antigenic drift resulting in evasion of pre-existing immunity is highly evolutionarily favored and likely to cause waves of short-term transmission. In the long-term, invading variants that induce weak cross-immunity against pre-existing strains may co-circulate with those pre-existing strains. This would result in the formation of serotypes that increase disease burden, complicate SARS-CoV-2 control and raise the potential for increases in viral virulence. Less durable immunity does not drive positive selection as a trait, but such strains may transmit at high levels if they establish. Overall, our results draw attention to the importance of inter-strain cross-immunity as a driver of transmission trends and the importance of early immune evasion data to predict the trajectory of the pandemic.

  🖺 Full Text HTML: Antibody escape, the risk of serotype formation, and rapid immune waning: modeling the implications of SARS-CoV-2 immune evasion
• LY6E protects mice from pathogenic effects of murine coronavirus and SARS-CoV-2 -
  LY6E is an antiviral protein that inhibits coronavirus entry. Its expression in immune cells allows mice to control murine coronavirus infection. However, it is not known which immune cell subsets mediate this control or whether LY6E protects mice from SARS-CoV-2. In this study, we used tissue-specific Cre recombinase expression to ablate Ly6e in distinct immune compartments or in all epiblast-derived cells, and bone marrow chimeras to target Ly6e in a subset of radioresistant cells. Mice lacking Ly6e in Lyz2-expressing cells and radioresistant Vav1 expressing cells were more susceptible to lethal murine coronavirus infection. Mice lacking Ly6e globally developed clinical disease when challenged with the Gamma (P.1) variant of SARS-CoV-2. By contrast, wildtype mice and mice lacking type I and type III interferon signaling had no clinical symptoms after SARS-CoV-2 infection. Transcriptomic profiling of lungs from SARS-CoV-2-infected wildtype and Ly6e knockout mice revealed a striking reduction of secretory cell-associated genes in infected knockout mice, including Muc5b, an airway mucin-encoding gene that may protect against SARS-CoV-2-inflicted respiratory disease. Collectively, our study reveals distinct cellular compartments in which Ly6e confers cell intrinsic antiviral effects, thereby conferring resistance to disease caused by murine coronavirus and SARS-CoV-2.
  🖺 Full Text HTML: LY6E protects mice from pathogenic effects of murine coronavirus and SARS-CoV-2
• Rapid engineering of SARS-CoV-2 therapeutic antibodies to increase breadth of neutralization including XBB.1.5 and BQ.1.1 -
  An antibody panel that broadly neutralizes currently circulating Omicron variants was obtained by in vitro affinity maturation using phage display. Starting from a single parent clone, antibody engineering was performed in iterative stages in real time as variants emerged using a proprietary technology called STage-Enhanced Maturation (STEM). Humanized from a rabbit antibody, the parent clone showed undetectable neutralization of later Omicron variants, while an early stage IgG possessing only an engineered light chain potently neutralizes some BA.2 but not BA.4/BA.5 lineage variants. However, the final heavy and light chain engineered mAbs show potent neutralization of XBB.1.5 and BQ.1.1 by surrogate virus neutralization test, and biolayer interferometry shows pM KD affinity for both variants. Our work not only details novel therapeutic candidates but also validates a unique general strategy to create broadly neutralizing mAbs to current and future SARS-CoV-2 variants.
  🖺 Full Text HTML: Rapid engineering of SARS-CoV-2 therapeutic antibodies to increase breadth of neutralization including XBB.1.5 and BQ.1.1
• Incident autoimmune diseases in association with a SARS-CoV-2 infection: A matched cohort study -

  Objectives: To investigate whether the risk of developing an incident autoimmune disease is increased in patients with previous COVID-19 disease compared to people without COVID-19. Method: A cohort was selected from German routine health care data covering 38.9 million individuals. Based on documented diagnoses, we identified individuals with polymerase chain reaction (PCR)-confirmed COVID-19 through December 31, 2020. Patients were matched 1:3 to control patients without COVID-19. Both groups were followed up until June 30, 2021. We used the four quarters preceding the index date until the end of follow-up to analyze the onset of autoimmune diseases during the post-acute period. Incidence rates (IR) per 1000 person-years were calculated for each outcome and patient group. Poisson models were deployed to estimate the incidence rate ratios (IRRs) of developing an autoimmune disease conditional on a preceding diagnosis of COVID-19. Results: In total, 641,704 patients with COVID-19 were included. Comparing the incidence rates in the COVID-19 (IR=15.05, 95% CI: 14.69-15.42) and matched control groups (IR=10.55, 95% CI: 10.25-10.86), we found a 42.63% higher likelihood of acquiring autoimmunity for patients who had suffered from COVID-19. This estimate was similar for common autoimmune diseases, such as Hashimoto thyroiditis, rheumatoid arthritis, or Sjoegren syndrome. The highest IRR was observed for autoimmune disease of the vasculitis group. Patients with a more severe course of COVID-19 were at a greater risk for incident autoimmune diseases. Conclusions: SARS-CoV-2 infection is associated with an increased risk of developing new-onset autoimmune diseases after the acute phase of infection.

  🖺 Full Text HTML: Incident autoimmune diseases in association with a SARS-CoV-2 infection: A matched cohort study

From Clinical Trials

• Evaluation of Corfluvec Vaccine for the Prevention of COVID-19 in Healthy Volunteers - Condition:   COVID-19
  Interventions:   Biological: Corfluvec component 1 low dose;   Biological: Corfluvec component 2 low dose;   Biological: Corfluvec component 1 high dose;   Biological: Corfluvec component 2 high dose;   Biological: Corfluvec low dose;   Biological: Corfluvec high dose;   Biological: Placebo
  Sponsors:   Tatyana Zubkova;   MDP-CRO, LLC;   St. Petersburg State Pavlov Medical University
  Active, not recruiting

• COVID-19 Self-testing Study - Condition:   COVID-19
  Intervention:   Behavioral: SMARTest mobile app for COVID-19 self-testing
  Sponsor:   Columbia University
  Recruiting

• A Study of Efficacy and Safety of Azvudine vs. Nirmatrelvir-Ritonavir in the Treatment of COVID-19 Infection - Condition:   COVID-19
  Interventions:   Drug: Azvudine;   Drug: Nirmatrelvir-Ritonavir
  Sponsors:   Shandong Provincial Hospital;   Central hospital Affiliated to Shandong First Medical University;   The Second Affiliated Hospital of Shandong First Medical University;   The Affiliated Hospital Of Southwest Medical University;   Gansu Provincial Hospital
  Not yet recruiting

• A Chatbot to Enhance COVID-19 Knowledge - Condition:   COVID-19
  Interventions:   Device: chatbot;   Other: Printed educational booklet
  Sponsor:   Sun Yat-sen University
  Not yet recruiting

• Low-Dose Radiation Therapy for Severe COVID-19 Pneumonia - Condition:   COVID-19 Pneumonia
  Intervention:   Radiation: Low-Dose Radiation Therapy
  Sponsors:   Jiangsu Cancer Institute & Hospital;   Nanjing Chest Hospital;   The Affiliated BenQ Hospital of Nanjing Medical University;   Central South University;   Zhongda Hospital
  Not yet recruiting

• Tetrandrine Tablets Used in Hospitalized Adults With COVID-19 - Condition:   COVID-19
  Intervention:   Drug: Tetrandrine
  Sponsor:   Peking University Third Hospital
  Not yet recruiting

• A Phase 2 Study to Evaluate the Efficacy and Safety of QLS1128 Orally in Symptomatic Participants With Mild to Moderate COVID-19 - Condition:   COVID-19
  Interventions:   Drug: QLS1128;   Drug: Placebo
  Sponsor:   Qilu Pharmaceutical Co., Ltd.
  Recruiting

• Efficacy of Megadose Vitamin C in Severe and Critical Ill COVID-19 Patients. - Conditions:   Vitamin C;   COVID-19 Pneumonia
  Interventions:   Drug: Vitamin C;   Drug: Placebo
  Sponsor:   Zhujiang Hospital
  Recruiting

• Oropharyngeal Immunoprophylaxis With High Polyphenolic Olive Oil as Clinical Spectrum Mitigating Factor in COVID-19. - Condition:   COVID-19
  Intervention:   Dietary Supplement: High polyphenolic olive oil. (Early harvest olive oil).
  Sponsor:   Hospital General Nuestra Señora del Prado
  Completed

• A Randomized, Phase I Study of DNA Vaccine OC-007 as a Booster Dose of COVID-19 Vaccine - Conditions:   COVID-19 Respiratory Infection;   COVID-19 Vaccine Adverse Reaction
  Interventions:   Biological: DNA vaccine OC-007;   Other: Placebo
  Sponsor:   Matti Sällberg
  Not yet recruiting

• Multicenter Randomized Double-blind Placebo-controlled Study to Investigate Azvudine in Symptomatic Adults With COVID-19 at Increased Risk of Progressing to Severe Illness - Condition:   COVID-19 Respiratory Infection
  Interventions:   Drug: Azvudine;   Drug: Placebo
  Sponsor:   Peking Union Medical College Hospital
  Not yet recruiting

• UC-MSCs in the Treatment of Severe and Critical COVID-19 Patients With Refractory Hypoxia - Conditions:   Mesenchymal Stem Cell;   COVID-19 Pneumonia
  Intervention:   Biological: UC-MSCs treatment
  Sponsors:   Shanghai East Hospital;   Sir Run Run Shaw Hospital
  Recruiting

• Safety and Efficacy of the Therapy With BREINMAX® for the Treatment of Patients With Asthenia After COVID-19 - Conditions:   Asthenia;   COVID-19
  Interventions:   Drug: Ethyl methyl hydroxypyridine succinate + Meldonium;   Drug: Placebo
  Sponsor:   Promomed, LLC
  Completed

• Aerosolized Versus Intravenous Colistin-based Antimicrobial Regimens in Hospitalized COVID-19 Patients With Bacterial Coinfection: A Randomized Controlled Trial - Condition:   Secondary Bacterial Infection in COVID-19 Patients
  Intervention:   Drug: Colistin
  Sponsor:   Beni-Suef University
  Completed

• Acupuncture as an Adjunctive Therapy for Covid-19 Omicron Randomised Controlled Trial in Patients With Moderate/Severe Pneumonia - Conditions:   Acupuncture;   Covid-19 Omicron;   Pulmonary Function
  Intervention:   Other: Acupuncture
  Sponsor:   The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine
  Recruiting

From PubMed

• Reducing Vaccinia virus transmission indoors within 60 seconds: Applying SAFEAIR-X aerosol with Iodine-V as a disinfectant - Iodine-V ((C26H39N4O15)x * (I2)y) demonstrates an in vitro virucidal activity by deactivating SARS-CoV-2 viral titers. It combines elemental iodine (I2) and fulvic acid (C14H12O8), forming a clathrate compound. The antiviral properties of Iodine-V reduce viral load in the air to inhibit viral transmission indoors. This antiviral property was applied to form a disinfectant solution called SAFEAIR-X Aerosol. The current study evaluates the antiviral efficacy of Iodine-V in aerosol form in a…

• Waning humoral and cellular immunity after COVID-19 vaccination in patients with psoriasis treated with methotrexate and biologics: a cohort study - CONCLUSIONS: Treatment with anti-TNF has an impact on the immunity elicited by mRNA-based COVID-19 vaccination in patients with psoriasis, resulting in a faster waning of humoral and cellular markers of immunity, however, the clinical implications are unknown.

• Identification of niclosamide as a novel antiviral agent against porcine epidemic diarrhea virus infection by targeting viral internalization - Porcine epidemic diarrhea virus (PEDV), an enteropathogenic coronavirus, has catastrophic impacts on the global pig industry. However, there remain no effective drugs against PEDV infection. In this study, we utilized a recombinant PEDV expressing renilla luciferase (PEDV-Rluc) to screen potential anti-PEDV agents from an FDA-approved drug library in Vero cells. Four compounds were identified that significantly decreased luciferase activity of PEDV-Rluc. Among them, Niclosamide was further…

• Hepatitis D virus interferes with hepatitis B virus RNA production via interferon-dependent and -independent mechanisms - CONCLUSIONS: Our data indicate that HDV interferes with HBV through both IFN-dependent and IFN-independent mechanisms. Specifically, we uncover a new viral interference mechanism in which proteins of a satellite virus affect RNA production of its helper virus. Exploiting these finding could pave the way to the development of new therapeutic strategies against HBV.

• Two pan-SARS-CoV-2 nanobodies and their multivalent derivatives effectively prevent Omicron infections in mice - With the widespread vaccinations against coronavirus disease 2019 (COVID-19), we are witnessing gradually waning neutralizing antibodies and increasing cases of breakthrough infections, necessitating the development of drugs aside from vaccines, particularly ones that can be administered outside of hospitals. Here, we present two cross-reactive nanobodies (R14 and S43) and their multivalent derivatives, including decameric ones (fused to the immunoglobulin M [IgM] Fc) that maintain potent…

• Thiopurine therapy in inflammatory bowel disease in the pandemic era: Safe or unsafe? - CONCLUSION: Emerging evidence suggests that TP therapy is safe during the current pandemic and does not carry an elevated risk when used as monotherapy on in combination with other IBD drugs. In-vitro studies demonstrate that TP is a potential therapeutic for present and future betacoronavirus pandemics.

• Discovery, synthesis and mechanism study of 2,3,5-substituted [1,2,4]-thiadiazoles as covalent inhibitors targeting 3C-Like protease of SARS-CoV-2 - The 3C-like protease (3CL^(pro)) is essential for the replication and transcription of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), making it a promising target for the treatment of corona virus disease 2019 (COVID-19). In this study, a series of 2,3,5-substituted [1,2,4]-thiadiazole analogs were discovered to be able to inhibit 3CL^(pro) as non-peptidomimetic covalent binders at submicromolar levels, with IC(50) values ranging from 0.118 to 0.582 μM. Interestingly, these…

• Exploration of Fuzheng Yugan Mixture on COVID-19 based on network pharmacology and molecular docking - After the World Health Organization declared coronavirus disease 2019 (COVID-19), as a global pandemic, global health workers have been facing an unprecedented and severe challenge. Currently, a mixturetion to inhibit the exacerbation of pulmonary inflammation caused by COVID-19, Fuzheng Yugan Mixture (FZYGM), has been approved for medical institution mixturetion notification. However, the mechanism of FZYGM remains poorly defined. This study aimed to elucidate the molecular and related…

• N-Phenylpyridine-3-Carboxamide and 6-Acetyl-1H-Indazole Inhibit the RNA Replication Step of the Dengue Virus Life Cycle - Dengue virus (DENV) is a Flavivirus that causes the most prevalent arthropod-borne viral disease. Clinical manifestation of DENV infection ranges from asymptomatic to severe symptoms that can lead to death. Unfortunately, no antiviral treatments against DENV are currently available. In order to identify novel DENV inhibitors, we screened a library of 1,604 chemically diversified fragment-based compounds using DENV reporter viruses that allowed quantification of viral replication in infected…

• Soluble epoxide hydrolase inhibition alleviates chemotherapy induced neuropathic pain - Chemotherapy induced peripheral neuropathy (CIPN) is a particularly pernicious form of neuropathy and the associated pain is the primary dose-limiting factor of life-prolonging chemotherapy treatment. The prevalence of CIPN is high and can last long after treatment has been stopped. Currently, late in the COVID-19 pandemic, there are still increased psychological pressures on cancer patients as well as additional challenges in providing analgesia for them. These include the risks of nonsteroidal…

• Growth of Executive Functions in Preschool-Age Children During the COVID-19 Lockdown: Empirical Evidence - CONCLUSION: Our findings illuminate the negative effects the pandemic-related social restrictions had on the growth of children’s cognitive flexibility and working memory. For working memory, the effect of social isolation varied depending on the child’s gender.

• Exploring novel targets of sitagliptin for type 2 diabetes mellitus: Network pharmacology, molecular docking, molecular dynamics simulation, and SPR approaches - CONCLUSION: This study used different methods to prove that ACE2 may be another novel target of sitagliptin for T2DM, which extended the application of ACE2 in improving diabetes mellitus.

• Luteolin-rich fraction from Perilla frutescens seed meal inhibits spike glycoprotein S1 of SARS-CoV-2-induced NLRP3 inflammasome lung cell inflammation via regulation of JAK1/STAT3 pathway: A potential anti-inflammatory compound against inflammation-induced long-COVID - CONCLUSION: The findings suggested that luteolin and PFEA can modulate the signaling cascades that regulate Spike S1-induced lung inflammation during the incidence of Long-COVID. Consequently, luteolin and P. frutescens may be introduced as potential candidates in the preventive therapeutic strategy for inflammation-related post-acute sequelae of COVID-19.

• Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Anti-C5a Antibody BDB-001 for Severe COVID-19: A Randomized, Double-Blind, Placebo-Controlled Phase 1 Clinical Trial in Healthy Chinese Adults - CONCLUSION: The results of this phase I study supported that BDB-001 is a potent anti-C5a inhibitor with safety, tolerability, and no immunogenicity. TRIAL REGISTRATION NUMBER: CTR20200429.

• A genetically encoded BRET-based SARS-CoV-2 M^pro protease activity sensor - The main protease, M^(pro), is critical for SARS-CoV-2 replication and an appealing target for designing anti-SARS-CoV-2 agents. Therefore, there is a demand for the development of improved sensors to monitor its activity. Here, we report a pair of genetically encoded, bioluminescence resonance energy transfer (BRET)-based sensors for detecting M^(pro) proteolytic activity in live cells as well as in vitro. The sensors were generated by sandwiching peptides containing the M^(pro) N-terminal…

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