Covid-19 Sentry

Contents

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

From Preprints

• 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
• Men have approximately 2- to 3-fold greater overdose mortality than women for synthetic opioids, heroin and psychostimulants including cocaine across the lifespan: Analysis of state-level CDC data for 2020-2021 -

  Drug overdoses are an escalating cause of mortality in the United States, with potential sex differences across the lifespan. The objective of this study was to use state-level nationally representative data that includes the COVID-19 pandemic period to determine overdose mortality for specific drug categories across the lifespan of men and women. We used Centers for Disease Control and Prevention (CDC) Multiple Cause of Death 2020-2021 data on overdose mortality, for 50 states and District of Columbia, across 10-year age bins (age range: 15-74). The outcome measure was sex-specific crude overdose death rate (per 100,000) for: synthetic opioids excluding methadone (ICD-10 code: T40.4; e.g., fentanyl), heroin (T40.1), psychostimulants with abuse potential (T43.6; e.g., methamphetamine), and cocaine (T40.5). Multiple regression analyses adjusted for ethnic-cultural background and household net worth from Census data, and sex-specific rate of misuse of the relevant substances, from the National Survey on Drug Use and Health (2019-2020). For each of these major drug categories, men had greater overall overdose mortality than women. Although overall rates of mortality differed across jurisdictions, the sex ratio of mortality for each drug category was relatively stable (≈2- to 3-fold greater mortality in men vs women). These findings survived adjustment for state-level ethnic-cultural and economic variables, and for sex-specific misuse of each drug type (especially in the 25-34, 35-44, 45-54 and 55-64 age bins). These findings underscore the need for research into sex- and gender-based mechanisms underlying differential vulnerability in overdose mortality for these drugs, based on their diverse pharmacodynamics and pathophysiology.

  🖺 Full Text HTML: Men have approximately 2- to 3-fold greater overdose mortality than women for synthetic opioids, heroin and psychostimulants including cocaine across the lifespan: Analysis of state-level CDC data for 2020-2021
• HPV and HBV vaccine hesitancy, intention and uptake in the era of social media and COVID-19: A review -

  Prior to the COVID-19 pandemic, the World Health Organization named vaccine hesitancy as one of the top 10 threats to global health. The impact of hesitancy on uptake of human papillomavirus (HPV) vaccines was of particular concern, given the markedly lower uptake compared to other adolescent vaccines in some countries, notably the United States. With the recent approval of COVID-19 vaccines coupled with the widespread use of social media, concerns regarding vaccine hesitancy have grown. However, the association between COVID-related vaccine hesitancy and cancer vaccines such as HPV is unclear. To examine the potential association, we performed two reviews using Ovid Medline and APA PsychInfo. Our aim was to answer two questions: (1) Is COVID-19 vaccine hesitancy, intention, or uptake associated with HPV or HBV vaccine hesitancy, intention, or uptake? and (2) Is exposure to COVID-19 vaccine misinformation on social media associated with HPV or HBV vaccine hesitancy, intention, or uptake? Our review identified few published empirical studies that addressed these questions. Our results highlight the urgent need for studies that can shift through the vast quantities of social media data to better understand the link between COVID-19 vaccine misinformation and disinformation and its impact on uptake of cancer vaccines.

  🖺 Full Text HTML: HPV and HBV vaccine hesitancy, intention and uptake in the era of social media and COVID-19: A review
• Country Learning on Maintaining Quality Essential Health Services (EHS) during COVID-19 in Timor-Leste: A mixed methods qualitative analysis -

  Objective: This research study examines the enabling factors, strengths, and challenges experienced by the Timor-Leste health system as it sought to maintain quality essential health services (EHS) during the COVID-19 pandemic. Design: A mixed methods qualitative analysis Setting: National, municipal, facility levels in Baucau, Dili and Ermera Municipalities in TLS Participants Key informant interviews (n=40) and focus group discussions (n=6) working to maintain quality EHS in TLS. Results: A reduction in people accessing general health services was observed in 2020, reportedly due to fears of contracting COVID-19 in healthcare settings, limited resources (eg. human resources, personal protective equipment, clinical facilities, etc) and closure of health services. However, improvements in maternal child health services simultaneously improved in the areas of skilled birth attendants, prenatal coverage, and vitamin A distribution, for example. Five themes emerged as enabling factors for maintaining quality EHS including 1) high level strategy for maintaining quality EHS, 2) implementation of quality activities across the three levels of the health system, 3) measurement for quality and factors affecting service utilization 4) the positive impact of quality improvement leadership in health facilities during COVID-19, and 5) learning from each other for maintaining quality EHS now and for the future. Other countries may benefit from the challenges, strengths and enablers found on planning for quality. Conclusion: The maintenance of quality essential health services (EHS) is critical to mitigate adverse health effects from the COVID-19 pandemic. When quality health services are delivered prior to and maintained during public health emergencies, they build trust within the health system and promote healthcare seeking behavior. Planning for quality as part of emergency preparedness can facilitate a high standard of care by ensuring health services continue to provide a safe environment, reduce harm, improve clinical care, and engage patients, facilities, and communities.

  🖺 Full Text HTML: Country Learning on Maintaining Quality Essential Health Services (EHS) during COVID-19 in Timor-Leste: A mixed methods qualitative analysis
• Estimations of SARS-CoV-2 endemic characteristics -

  The fourth year of the COVID-19 pandemic without decreasing trends in the global numbers of new daily cases, high numbers of circulating SARS-CoV-2 variants and re-infections together with pessimistic predictions for the Omicron wave duration force studies about the endemic stage of the disease. The global trends were illustrated with the use the accumulated numbers of laboratory confirmed COVID-19 cases and deaths, the percentages of fully vaccinated people and boosters and the results of calculation of the effective reproduction number provided by Johns Hopkins University. The modified SIR model showed the presence of unsteady equilibrium. The global numbers of new daily cases will range between 300 thousand and one million, daily deaths between one and 3.3 thousand.

  🖺 Full Text HTML: Estimations of SARS-CoV-2 endemic characteristics
• Spatial and Temporal Origin of The Third SARS-Cov-2 Outbreak in Taiwan -
  Since the first report of SARS-CoV-2 in December 2019, Taiwan has gone through three local outbreaks. Unlike the first two outbreaks, the spatial and temporal origin of the third outbreak (April 20 to November 5, 2021) is still unclear. We assembled and analyzed a data set of more than 6,000 SARS-CoV-2 genomes, including 300 from Taiwan and 5812 related sequences downloaded from GISAID as of 2021/12/08. We found that the third outbreak in Taiwan was caused by a single virus lineage belonging to Alpha (B.1.1.7) strain. This lineage, T-III (the third outbreak in Taiwan), carries four distinct genetic fingerprints, including spike M1237I (S-M1237I) and three silent changes. The T-III is closest to the sequences derived from Turkey on February 8, 2021. The estimated age of the most recent common ancestor (TMRCA) of T-III is March 23, 2021 (95% highest posterior density [HPD] February 24 - April 13, 2021), almost one month before the first three confirmed cases on April 20, 2021. The effective population size of the T-III showed approximately 20-fold increase after the onset of the outbreak and reached a plateau in early June 2021. Our results reconcile several unresolved observations, including the occurrence of two infection clusters at the same time without traceable connection and several airline pilots who were PCR negative but serum IgM-/IgG+ for SARS-CoV-2 in late April. Therefore, in contrast to the general notion that the third SARS-CoV-2 outbreak in Taiwan was sparked by two imported cases from USA on April 20, 2021, which, in turn, was caused by the partial relaxation of entry quarantine measures in early April 2021, our comprehensive analyses demonstrated that the outbreak was most likely originated from Europe in February 2021.
  🖺 Full Text HTML: Spatial and Temporal Origin of The Third SARS-Cov-2 Outbreak in Taiwan
• Acute tubulointerstitial nephritis with or without uveitis: a novel form of post-acute COVID-19 syndrome in children -

  Background COVID-19 is a complex multisystem disease, frequently associated with kidney injury. Since the beginning of the COVID-19 pandemic, we observed a striking increase in the incidence of acute tubulointerstitial nephritis (aTIN) without or with uveitis (TINUs) among children. This prompted us to examine whether SARS-CoV-2 might be the underlying trigger. Methods We conducted a French nationwide retrospective cohort study. We included all consecutive children diagnosed with aTIN or TINUs of undetermined cause between April-2020 and March-2021. SARS-CoV-2 antibody responses were tested by a luciferase immunoprecipitation system and compared to age-matched controls. Immunohistochemistry, immunofluorescence and molecular microbiology analyses were performed on kidney biopsies. Results Forty-eight children were included with a median age at diagnosis of 14.7 years (9.4-17.6). aTIN and TINUs incidence rates increased 3-fold and 12-fold, respectively, compared to pre-pandemic years. All patients had impaired kidney function with a median eGFR of 31.9 ml/min/1.73m2 at diagnosis. Kidney biopsies showed lesions of acute tubulointerstitial nephritis and 25% of patients had fibrosis. No patient had concomitant acute COVID-19. All 16 children tested had high anti-N IgG titers and one had anti-S IgGs. Next-generation sequencing failed to detect any infectious agents in kidney biopsies. However, SARS-CoV-2 RNA was detected by PCR in two kidney samples supporting a potential direct link between SARS-CoV-2 and aTIN/TINUs. Conclusions We describe a novel form of post-acute COVID-19 syndrome in children, unique in its exclusive kidney and eye involvement, and its distinctive anti-SARS-CoV-2 N+/S- serological profile. Our results support a causal association linking SARS-CoV-2 infection to this newly-reported burst of renal/eye inflammation.

  🖺 Full Text HTML: Acute tubulointerstitial nephritis with or without uveitis: a novel form of post-acute COVID-19 syndrome in children
• Public attitudes to social care in Wales following the COVID-19 pandemic -
  Background. The COVID-19 pandemic has shone further light on some of the challenges facing social care in Wales, as in many countries, and looks to have exacerbated a crisis that was already extant. This has led to the intensification of longer-standing arguments that social reform is necessary and that the pandemic presents an added impetus and opportunity for reform. Methods. An online survey was completed by 2569 respondents between February 11th and March 11th, 2022. Additionally, online focus groups were conducted with a sample of 14 participants. The inclusion criteria were adults aged 18 years and over living in Wales. Results. Four-in-ten of those who felt that they or someone in their household or close family needed social care during the past two years did not receive or make use of it. The pandemic was cited as a major reason why many of those who may have needed social care didn’t access it Satisfaction with social care was variable, with approximately one-third either very or quite dissatisfied, and a little over half either very or quite satisfied with social care services for themselves or a household or close family member. Discussion. Social care policymakers and providers should seek to understand and address what people feel are the main barriers to accessing or using social care, including increasing provision for those who need it, encouraging and enabling those who feel they need social care to apply, consider broadening the eligibility criteria where appropriate, and simplifying the application process.
  🖺 Full Text HTML: Public attitudes to social care in Wales following the COVID-19 pandemic
• Framing COVID-19 preprint research as uncertain: A mixed-method study of public reactions -
  During the COVID-19 pandemic, journalists were encouraged to convey uncertainty surrounding preliminary scientific evidence, including mentioning when research is unpublished or unverified by peer review. To understand how public audiences interpret this information, we conducted a mixed method study with U.S. adults. Participants read a news article about preprint COVID-19 vaccine research in early April 2021, just as the vaccine was becoming widely available to the U.S. public. We modified the article to test two ways of conveying uncertainty (hedging of scientific claims and mention of preprint status) in a 2 × 2 between-participants factorial design. To complement this, we collected open-ended data to assess participants’ understanding of the concept of a scientific preprint. In all, participants who read hedged (vs. unhedged) versions of the article reported less favorable vaccine attitudes and intentions and found the scientists and news reporting less trustworthy. These effects were moderated by participants’ epistemic beliefs and their preference for information about scientific uncertainty. However, there was no impact of describing the study as a preprint, and participants’ qualitative responses indicated a limited understanding of the concept. We discuss implications of these findings for communicating initial scientific evidence to the public and we outline important next steps for research and theory-building.
  🖺 Full Text HTML: Framing COVID-19 preprint research as uncertain: A mixed-method study of public reactions
• In the name of health and illness: An inquiry into Covid-19 vaccination policy in postsecondary education in Canada -
  Since the launch of the Covid-19 global vaccination campaign in December of 2020, vaccination in postsecondary institutions has been a contested issue. International evidence indicates that these institutions have achieved high vaccination rates and Canadian public health agencies exclude them entirely from the list of institutions at risk of outbreaks. On the other hand, influential observers, and postsecondary institutions themselves insist that not only achieving, but also maintaining, “up-to-date” vaccination - through mandates if necessary – remains critical to contain the crisis. However, with the increasing recognition that vaccines do not stop viral spread, that young populations are at exceedingly low risk of severe Covid-19, hospitalization, and death - with a survival rate of over 99.98% - and that mandated medical interventions have a troubled history with repercussions to this day, the soundness of current vaccination policies in postsecondary institutions cannot be assumed. Drawing from the medicalization tradition and interpretive phenomenology, our study explores, through in-depth interviews, how vaccination policies within and beyond postsecondary institutions have shaped perceptions of the Covid-19 crisis, beliefs about the role, risks, and benefits of vaccination, and life choices and chances of students in Canada. We find that students largely comply with vaccination policies, whether by conviction, convenience, or coercion, and that the discourse and social practices promoted by the policies limit opportunities for free debate and exchange across vaccination statuses. Regardless of this status, students do resist, albeit very limitedly given the high cost of noncompliance. We discuss the implications of our findings for policy, equity, and for the power of medical social control in the Covid-19 era.
  🖺 Full Text HTML: In the name of health and illness: An inquiry into Covid-19 vaccination policy in postsecondary education in Canada

From Clinical Trials

• Digital Tools to Expand COVID-19 Testing in Exposed Individuals in Cameroon - Condition:   COVID-19
  Intervention:   Other: Digital based contact tracing
  Sponsors:   Elizabeth Glaser Pediatric AIDS Foundation;   Find
  Recruiting

• Evaluation of the Outcome of COVID-19 Patients Discharged Home on Oxygen Therapy - Condition:   COVID-19
  Intervention:   Other: Phone satisfaction questionnaire
  Sponsor:   Centre Hospitalier René Dubos
  Not yet recruiting

• 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

• 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

From PubMed

• 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…

• Evaluation of a biotin-based surrogate virus neutralization test for detecting postvaccination antibodies against SARS-CoV-2 variants in sera - A severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) surrogate virus neutralization test (sVNT) was used to determine the degree of inhibition of binding between human angiotensin converting enzyme 2 (hACE2) and the receptor binding domain (RBD) of spike protein by neutralizing antibodies in a biosafety level 2 facility. Here, to improve the sensitivity and specificity of the commercial sVNT, we developed a new biotin based sVNT using biotinylated RBD and HRP conjugated streptavidin…

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