Covid-19 Sentry

Contents

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

From Preprints

• Dichotomy of neutralizing antibody, B cell and T cell responses to SARS-CoV-2 vaccination and protection in healthy adults -
  Heterogeneity in SARS-CoV-2 vaccine responses is not understood. Here, we identify four patterns of live-virus neutralizing antibody responses: individuals with hybrid immunity (with confirmed prior infection); rare individuals with low responses (paucity of S1-binding antibodies); and surprisingly, two further groups with distinct serological repertoires. One group - broad responders - neutralize a range of SARS-CoV-2 variants, whereas the other - narrow responders - neutralize fewer, less divergent variants. This heterogeneity does not correlate with Ancestral S1-binding antibody, rather the quality of the serological response. Furthermore, IgDlowCD27-CD137+ B cells and CCR6+ CD4+ T cells are enriched in broad responders before dose 3. Notably, broad responders have significantly longer infection-free time after their third dose. Understanding the control and persistence of these serological profiles could allow personalized approaches to enhance serological breadth after vaccination.
  🖺 Full Text HTML: Dichotomy of neutralizing antibody, B cell and T cell responses to SARS-CoV-2 vaccination and protection in healthy adults
• Longitudinal host transcriptional responses to SARS-CoV-2 infection in adults with extremely high viral load -
  Current understanding of viral dynamics of SARS-CoV-2 and host responses driving the pathogenic mechanisms in COVID-19 is rapidly evolving. Here, we conducted a longitudinal study to investigate gene expression patterns during acute SARS-CoV-2 illness. Cases included SARS-CoV-2 infected individuals with extremely high viral loads early in their illness, individuals having low SARS-CoV-2 viral loads early in their infection, and individuals testing negative for SARS-CoV-2. We could identify widespread transcriptional host responses to SARS-CoV-2 infection that were initially most strongly manifested in patients with extremely high initial viral loads, then attenuating within the patient over time as viral loads decreased. Genes correlated with SARS-CoV-2 viral load over time were similarly differentially expressed across independent datasets of SARS-CoV-2 infected lung and upper airway cells, from both in vitro systems and patient samples. We also generated expression data on the human nose organoid model during SARS-CoV-2 infection. The human nose organoid-generated host transcriptional response captured many aspects of responses observed in the above patient samples while suggesting the existence of distinct host responses to SARS-CoV-2 depending on the cellular context, involving both epithelial and cellular immune responses. Our findings provide a catalog of SARS-CoV-2 host response genes changing over time.
  🖺 Full Text HTML: Longitudinal host transcriptional responses to SARS-CoV-2 infection in adults with extremely high viral load
• Vascular Endothelial-derived SPARCL1 Exacerbates Viral Pneumonia Through Pro-Inflammatory Macrophage Activation -
  Inflammation upon infectious lung injury is a double-edged sword: while tissue-infiltrating immune cells and cytokines are necessary to control infection, these same factors often aggravate injury. Full appreciation of both the sources and targets of inflammatory mediators is required to facilitate strategies to maintain antimicrobial effects while minimizing off-target epithelial and endothelial damage. Recognizing that the vasculature is centrally involved in tissue responses to injury and infection, we observed that pulmonary capillary endothelial cells (ECs) exhibit dramatic transcriptomic changes upon influenza injury punctuated by profound upregulation of Sparcl1. Endothelial deletion and overexpression of SPARCL1 implicated this secreted matricellular protein in driving key pathophysiologic symptoms of pneumonia, which we demonstrate result from its effects on macrophage polarization. SPARCL1 induces a shift to a pro-inflammatory "M1-like" phenotype (CD86+CD206-), thereby increasing associated cytokine levels. Mechanistically, SPARCL1 acts directly on macrophages in vitro to induce the pro-inflammatory phenotype via activation of TLR4, and TLR4 inhibition in vivo ameliorates inflammatory exacerbations caused by endothelial Sparcl1 overexpression. Finally, we confirmed significant elevation of SPARCL1 in COVID-19 lung ECs in comparison with those from healthy donors. Survival analysis demonstrated that patients with fatal COVID-19 had higher levels of circulating SPARCL1 protein compared to those who recovered, indicating the potential of SPARCL1 as a biomarker for prognosis of pneumonia and suggesting that personalized medicine approaches might be harnessed to block SPARCL1 and improve outcomes in high-expressing patients.
  🖺 Full Text HTML: Vascular Endothelial-derived SPARCL1 Exacerbates Viral Pneumonia Through Pro-Inflammatory Macrophage Activation
• The landscape of biomedical research -
  The number of publications in biomedicine and life sciences has rapidly grown over the last decades, with over 1.5 million papers now published every year. This makes it difficult to keep track of new scientific works and to have an overview of the evolution of the field as a whole. Here we present a 2D atlas of the entire corpus of biomedical literature, and argue that it provides a unique and useful overview of the life sciences research. We base our atlas on the abstract texts of 21 million English articles from the PubMed database. To embed the abstracts into 2D, we use a large language model PubMedBERT, combined with t-SNE tailored to handle samples of our size. We use our atlas to study the emergence of the Covid-19 literature, the evolution of the neuroscience discipline, the uptake of machine learning, and the distribution of gender imbalance in academic authorship. Furthermore, we present an interactive web version of our atlas that allows easy exploration and will enable further insights and facilitate future research.
  🖺 Full Text HTML: The landscape of biomedical research
• Learning virus genotype-fitness landscape in embedding space -
  Predicting the SARS-CoV-2 epidemic and “immune escape” mutations remain crucial problems. We present a theoretical framework called Phenotype-Embedding (P-E) theorem and prove that the virus fitness can calculate by selecting appropriate sequence embedding under the VAE framework. Starting from the P-E theorem and based on a modified Transformer model, we obtain a calculable quantitative relationship between “immune escape” mutations and the fitness of the virus lineage and plot a genotype-fitness landscape in the embedded space. We accurately calculated the viral fitness and basic replication number (R0) using only the sequence data of SARS-CoV-2 spike protein. In addition, our model can simulate viral neutral evolution and spatio-temporal selection, decipher the effects of epistasis and recombination, and more accurately predict viral mutations associated with immune escape. Our work provides a theoretical framework for constructing genotype-phenotype landscapes and a paradigm for the interpretability of deep learning in virus evolution research.
  🖺 Full Text HTML: Learning virus genotype-fitness landscape in embedding space
• Modeling spatial intercellular communication and multilayer signaling regulations using stMLnet -
  Multicellular organisms require intercellular and intracellular signaling to coordinately regulate different cell functions. Although many methods of cell-cell communication (CCC) inference have been developed, they seldom account for both the intracellular signaling responses and global spatial information. The recent advancement of spatial transcriptomics (ST) provides unprecedented opportunities to better decipher CCC signaling and functioning. In this paper, we propose an ST-based multilayer network method, stMLnet, for inferring spatial intercellular communication and multilayer signaling regulations by quantifying distance-weighted ligand-receptor signaling activity based on diffusion and mass action models and mapping it to intracellular targets. We benchmark stMLnet with existing methods using simulation data and 8 real datasets of cell type-specific perturbations. Furthermore, we demonstrate the applicability of stMLnet on six ST datasets acquired with four different technologies (e.g., seqFISH+, Slide-seq v2, MERFIS and Visium), showing its effectiveness and reliability on ST data with varying spatial resolutions and gene coverages. Finally, stMLnet identifies positive feedback circuits between alveolar epithelial cells, macrophages, and monocytes via multilayer signaling pathways within a COVID-19 microenvironment. Our proposed method provides an effective tool for predicting multilayer signaling regulations between interacting cells, which can advance the mechanistic and functional understanding of spatial CCCs.
  🖺 Full Text HTML: Modeling spatial intercellular communication and multilayer signaling regulations using stMLnet
• The impact of RSV/SARS-CoV-2 co-infection on clinical disease and viral replication: insights from a BALB/c mouse model -
  RSV and SARS-CoV-2 are prone to co-infection with other respiratory viruses. In this study, we use RSV/SARS-CoV-2 co-infection to evaluate changes to clinical disease and viral replication in vivo. To consider the severity of RSV infection, effect of sequential infection, and the impact of infection timing, mice were co-infected with varying doses and timing. Compared with a single infection of RSV or SARS-CoV-2, the co-infection of RSV/SARS-CoV-2 and the primary infection of RSV followed by SARS-CoV-2 results in protection from SARS-CoV-2-induced clinical disease and reduces SARS-CoV-2 replication. Co-infection also augmented RSV replication at early timepoints with only the low dose. Additionally, the sequential infection of RSV followed by SARS-CoV-2 led to improved RSV clearance regardless of viral load. However, SARS-CoV-2 infection followed by RSV results in enhanced SARS-CoV-2-induced disease while protecting from RSV-induced disease. SARS-CoV-2/RSV sequential infection also reduced RSV replication in the lung tissue, regardless of viral load. Collectively, these data suggest that RSV and SARS-CoV-2 co-infection may afford protection from or enhancement of disease based on variation in infection timing, viral infection order, and/or viral dose. In the pediatric population, understanding these infection dynamics will be critical to treat patients and mitigate disease outcomes.
  🖺 Full Text HTML: The impact of RSV/SARS-CoV-2 co-infection on clinical disease and viral replication: insights from a BALB/c mouse model
• Within-host SARS-CoV-2 viral kinetics informed by complex life course exposures reveals different intrinsic properties of Omicron and Delta variants -

  The emergence of successive SARS-CoV-2 variants of concern (VOC) during 2020-22, each exhibiting increased epidemic growth relative to earlier circulating variants, has created a need to understand the drivers of such growth. However, both pathogen biology and changing host characteristics - such as varying levels of immunity - can combine to influence replication and transmission of SARS-CoV-2 within and between hosts. Disentangling the role of variant and host in individual-level viral shedding of VOCs is essential to inform COVID-19 planning and response, and interpret past epidemic trends. Using data from a prospective observational cohort study of healthy adult volunteers undergoing weekly occupational health PCR screening, we developed a Bayesian hierarchical model to reconstruct individual-level viral kinetics and estimate how different factors shaped viral dynamics, measured by PCR cycle threshold (Ct) values over time. Jointly accounting for both inter-individual variation in Ct values and complex host characteristics - such as vaccination status, exposure history and age - we found that age and number of prior exposures had a strong influence on peak viral replication. Older individuals and those who had at least five prior antigen exposures to vaccination and/or infection typically had much lower levels of shedding. Moreover, we found evidence of a correlation between the speed of early shedding and duration of incubation period when comparing different VOCs and age groups. Our findings illustrate the value of linking information on participant characteristics, symptom profile and infecting variant with prospective PCR sampling, and the importance of accounting for increasingly complex population exposure landscapes when analysing the viral kinetics of VOCs.

  🖺 Full Text HTML: Within-host SARS-CoV-2 viral kinetics informed by complex life course exposures reveals different intrinsic properties of Omicron and Delta variants
• Primary Care Post-COVID syndrome Diagnosis and Referral Coding -

  Introduction - Guidelines for diagnosing and managing Post-COVID syndrome have been rapidly developed. Consistency of the application of these guidelines in primary care is unknown. Electronic health records provide an opportunity to review the use of codes relating to Post-COVID syndrome. This paper explores the use of primary care records as a surrogate uptake measure for NICEs rapid guideline managing the long-term effects of COVID-19 by measuring the use of Post-COVID syndrome diagnosis and referral codes in the pathway. Method - With the approval of NHS England we used routine clinical data from the OpenSafely-EMIS/-TPP platforms. Counts of Post-COVID syndrome diagnosis and referral codes were generated from a cohort of all adults, establishing numbers of diagnoses and referrals following diagnosis. The relationship between Post-COVID syndrome diagnosis and referral codes was explored with reference to NICEs rapid guideline. Results - Of over 45 million patients, 69,220 (0.15%) had a Post-COVID syndrome diagnostic code, and 67,741 (0.15%) had a referral code. 78% of referral codes did not have an associated diagnosis code. 79% of diagnosis codes had no subsequent referral code. Only 18,633 (0.04%) had both. There were higher rates of both diagnosis and referral in those who were more deprived, female and some ethnic groups. Discussion - This study demonstrates variation in diagnosis and referral coding rates for Post-COVID syndrome across different patient groups. The results, with limited crossover of referral and diagnostic codes, suggest only one type of code is usually recorded. Recording one code limits the use of routine data for monitoring Post-COVID syndrome diagnosis and management, but suggests several areas for improvement in coding. Post-COVID syndrome coding, particularly diagnosis coding, needs to improve before administrators and researchers can use it to evaluate care pathways.

  🖺 Full Text HTML: Primary Care Post-COVID syndrome Diagnosis and Referral Coding
• Psychiatric hospital admissions and linkages to ambulatory services in the Western Cape Province of South Africa (2015-2022): trends, risk factors, the impact of the COVID-19 pandemic and possible opportunities for intervention -

  In recent years, hospital managers have reported increasing numbers of psychiatric hospital admissions in the Western Cape Province of South Africa, driven by poverty and substance use. We aimed to examine this trend, and the impact of the COVID-19 pandemic, as well as assess factors associated with linkage to ambulatory services following hospital discharge and repeat psychiatric admissions. Using electronic health data from the Provincial Health Data Centre, a consolidated routine service database, all psychiatric hospital admissions in the Western Cape public sector from 2015 to 2022 were analyzed, stratified by hospital level. Mixed effects logistic regression was used in this cohort study to determine the factors associated with successful linkage to ambulatory services within 30 days following hospital discharge, and repeat psychiatric admission within 30 and 90 days. We found that psychiatric hospital admissions, particularly at the district/acute level, were increasing prior to 2020 and an increasing proportion of diagnoses were substance related. 40% of admissions at the district level had not been seen at a primary health care facility in the year before the admission. Male patients and those with substance use disorders were less likely to be successfully linked to outpatient services following discharge. Successful linkage was one of the most protective factors against readmission within 90 days with an adjusted odds ratio of 0.76 (95%CI 0.73-0.79) and 0.45 (95%CI 0.42-0.49) at district/acute and specialized hospitals respectively. Improving linkage to ambulatory services by mental health patients post-discharge is likely to avert hospital readmissions.

  🖺 Full Text HTML: Psychiatric hospital admissions and linkages to ambulatory services in the Western Cape Province of South Africa (2015-2022): trends, risk factors, the impact of the COVID-19 pandemic and possible opportunities for intervention
• Posttraumatic stress disorder symptom trajectories in a 16-month COVID-19 pandemic period -
  In the aftermath of mass trauma, posttraumatic stress disorder (PTSD) symptoms follow prototypical trajectories of resilience, recovery, or chronic distress. The coronavirus disease 2019 (COVID-19) pandemic represented an unheralded opportunity to better understand heterogeneous trajectories of PTSD symptoms across a prolonged period of social disruption and stress. We tracked the PTSD symptoms of trauma-exposed individuals in the U.S., sought to identify population-based variability in PTSD symptom trajectories, and understand what, if any, early pandemic experiences would predict their membership in one trajectory over others. As part of a large-scale longitudinal study of U.S. residents during the pandemic, participants who reported at least one potentially traumatic event in their lifetime (N = 1206) at Wave 1 (April 2020) were included in the current study. PTSD symptoms were assessed with the PTSD Checklist for DSM-5 at four time points extending to July 2021. Latent growth mixture modeling was used to identify heterogeneous symptom trajectories. Trajectory membership was regressed on baseline demographics and experiences from the early stage of the pandemic as measured by the Epidemic-Pandemic Impacts Inventory. Four trajectories (Resilient [73%], Recurring [13.3%], Recovering [8.3%], and Chronic [5.5%] were identified. Age, trauma load, and early pandemic experiences (emotional/physical health problems and positive changes) were each significant predictors of trajectory membership. Predictors primarily differentiated the Resilient from each of the other three trajectories. Distinct PTSD symptom trajectories during the COVID-19 pandemic point to the need for targeted efforts helping those at most risk for ongoing distress.
  🖺 Full Text HTML: Posttraumatic stress disorder symptom trajectories in a 16-month COVID-19 pandemic period
• Experiences, impacts and mental health functioning during a COVID-19 outbreak and lockdown: Data from a diverse New York City sample of college students -
  In March 2020, New York City (NYC) experienced an outbreak of coronavirus disease 2019 (COVID-19) which resulted in a 78-day mass confinement of all residents other than essential workers. The aims of the current study were to (1) document the breadth of COVID-19 experiences and their impacts on college students of a minority-serving academic institution in NYC; (2) explore associations between patterns of COVID-19 experiences and psychosocial functioning during the prolonged lockdown, and (3) explore sex and racial/ethnic differences in COVID-19-related experiences and mental health correlates. A total of 909 ethnically and racially diverse students completed an online survey in May 2020. Findings highlight significant impediments to multiple areas of students’ daily life during this period (i.e., home life, work life, social environment, and emotional and physical health) and a vast majority reported heightened symptoms of depression and generalized anxiety. These life disruptions were significantly related to poorer mental health. Moreover, those who reported the loss of a close friend or loved one from COVID-19 (17%) experienced significantly more psychological distress than counterparts with other types of infection-related histories. Nonetheless, the majority (96%) reported at least one positive experience since the pandemic began. Our findings add to a growing understanding of COVID-19 impacts on psychological health and contribute the important perspective of the North American epicenter of the pandemic during the time frame of this investigation. We discuss how the results may inform best practices to support students’ well-being and serve as a benchmark for future studies of US student populations facing COVID-19 and its aftermath.
  🖺 Full Text HTML: Experiences, impacts and mental health functioning during a COVID-19 outbreak and lockdown: Data from a diverse New York City sample of college students
• Information bias of vaccine effectiveness estimation due to informed consent for national registration of COVID-19 vaccination: estimation and correction using a data augmentation model -

  Background: Registration in the Dutch national COVID-19 vaccination register requires consent from the vaccinee. This causes misclassification of non-consenting vaccinated persons as being unvaccinated. We quantified and corrected the resulting information bias in the estimation of vaccine effectiveness (VE). Methods: National data were used for the period dominated by the SARS-CoV-2 Delta variant (11 July to 15 November 2021). VE ((1-relative risk)*100%) against COVID-19 hospitalization and ICU admission was estimated for individuals 12-49, 50-69, and ≥70 years of age using negative binomial regression. Anonymous data on vaccinations administered by the Municipal Health Services were used to determine informed consent percentages and estimate corrected VEs by iterative data augmentation. Absolute bias was calculated as the absolute change in VE; relative bias as uncorrected / corrected relative risk. Results: A total of 8,804 COVID-19 hospitalizations and 1,692 COVID-19 ICU admissions were observed. The bias was largest in the 70+ age group where the non-consent proportion was 7.0% and observed vaccination coverage was 87%: VE of primary vaccination against hospitalization changed from 75.5% (95% CI 73.5-77.4) before to 85.9% (95% CI 84.7-87.1) after correction (absolute bias -10.4 percentage point, relative bias 1.74). VE against ICU admission in this group was 88.7% (95% CI 86.2-90.8) before and 93.7% (95% CI 92.2-94.9) after correction (absolute bias -5.0 percentage point, relative bias 1.79). Conclusions: VE estimates can be substantially biased with modest non-consent percentages for registration of vaccination. Data on covariate specific non-consent percentages should be available to correct this bias.

  🖺 Full Text HTML: Information bias of vaccine effectiveness estimation due to informed consent for national registration of COVID-19 vaccination: estimation and correction using a data augmentation model
• Emotional overeating affected nine in ten female students during the COVID-19 University closure: A cross-sectional study in France -

  Objectives: To estimate the proportion of female university students reporting overeating (EO) in response to emotions during the COVID-19 university closures, and to investigate social and psychological factors associated with this response to stress. Design: Online survey gathered sociodemographic data, alcohol/drugs use disorders, boredom proneness and impulsivity using validated questionnaires, and EO using the Emotional Overeating Questionnaire (EOQ) assessing eating in response to six emotions (anxiety, sadness, loneliness, anger, fatigue, happiness), whose structure remains to be determined. Participants: Sample of 302 female students from Rennes University, France. Main Outcome Measure: Frequencies of emotional overeating. Analysis: The frequency of emotional overeating was expressed for each emotion as percentages. Exploratory Factor analyses (EFA) were used to determine EOQ structure and provide an index of all EOQ items used for further analysis. Linear regression models were used to explore relationships between EO and others covariates. Results: Nine in ten participants reported intermittent EO in the last 28 days, mostly during 6 to 12 days, in response to Anxiety (75.5%), Sadness (64.5%), Happiness (59.9%), Loneliness (57.9%), Tiredness (51.7%), and to a lesser extent to Anger (31.1%). EFA evidenced a one-factor latent variable reflecting “Distress-Induced Overeating” positively correlated with internal boredom proneness, tobacco use, attentional impulsivity, inability to resist emotional cues, and loss of control over food intake, and negatively with age and well-being. EO was unrelated to body mass index or substance abuse. Conclusion and Implications: Nine in ten female students reported emotional overeating during the COVID-19 university closure. This response to stress was related to eating tendencies typical of young women, but also to personality/behavioral patterns such as boredom and impulsivity proneness. Better understanding of the mechanisms underlying EO in response to stress and lack of external/social stimulation would improve preventive interventions.

  🖺 Full Text HTML: Emotional overeating affected nine in ten female students during the COVID-19 University closure: A cross-sectional study in France
• Wastewater Surveillance for SARS-CoV-2 in an Atlanta, Georgia Jail: A study of the feasibility of wastewater monitoring and correlation of building wastewater and individual testing results. -

  Background Wastewater-based surveillance (WBS) on an institutional level was implemented during the COVID-19 pandemic, including carceral facilities. In this study of a mega-jail, we examined the relationship between COVID-19 diagnostic test results from jail residents and the PCR signal for SARS-CoV-2 detection in weekly samples of jail wastewater over a 28-week period. Methods This study in a Georgia Jail (average population ~2,700) was conducted October 2021-May 2022. Weekly on-site wastewater samples were collected (Moore Swabs) and tested for SARS-CoV-2 RNA using RTqPCR. The source of wastewater was identified using a tracer dye. The jail offered residents rapid antigen testing at entry. We conducted periodic mass screenings via RT-PCR of nasal swabs. We aggregated individual test data, calculated the Spearman correlation coefficient, and performed logistic regression to examine the relationship between the strength of the SARS-CoV-2 PCR signal (Ct value) in wastewater and the proportion of the jail population that tested positive for COVID-19. Results Overall, 3770 individual nasal specimens were collected; 3.4% were COVID-positive. Weekly diagnostic test positivity ranged from 0%-29.5%. Dye tests demonstrated that a single wastewater collection point was sufficiently representative of the jails aggregate viral load. Twenty-five wastewater samples were collected. RT-qPCR Ct values for wastewater samples with SARS-CoV-2 RNA ranged from 28.1-39.9. A strong inverse correlation was observed between diagnostic test positivity and Ct value (r= -0.67, p < 0.01). Conclusion WBS was shown to be an effective strategy for surveilling COVID-19 in a large jail. Strong partnerships with the jail administration are essential to the success of WBS surveillance.

  🖺 Full Text HTML: Wastewater Surveillance for SARS-CoV-2 in an Atlanta, Georgia Jail: A study of the feasibility of wastewater monitoring and correlation of building wastewater and individual testing results.

From Clinical Trials

• Investigation of the Effect on Cognitive Skills of COVID-19 Survivors - Condition:   COVID-19
  Intervention:   Other: green walking and intelligence gam
  Sponsors:   Bayburt University;   Karadeniz Technical University
  Completed

• Conducting Clinical Trials of the Medicine “Rutan Tablets 0.1g” No. 10 in the Complex Therapy of COVID-19 - Condition:   Patients With COVID-19
  Interventions:   Drug: The drug “Rutan 0.1”.;   Other: Basic treatment
  Sponsor:   Research Institute of Virology, Ministry of Health of the Republic of Uzbekistan
  Completed

• Evaluation of Safety, Tolerability, Reactogenicity, Immunogenicity of Baiya SARS-CoV-2 Vax 2 as a Booster for COVID-19 - Conditions:   COVID-19 Vaccine;   COVID-19
  Interventions:   Biological: 50 μg Baiya SARS-CoV-2 Vax 2;   Other: Placebo
  Sponsor:   Baiya Phytopharm Co., Ltd.
  Not yet recruiting

• The Effect of Special Discharge Training in the COVID-19 - Condition:   COVID-19 Pneumonia
  Intervention:   Other: COVID-19 Discharge Education
  Sponsor:   Kilis 7 Aralik University
  Completed

• Physiotherapy in Mutated COVID-19 Patients - Condition:   COVID-19 Pandemic
  Intervention:   Behavioral: Physiotherapy
  Sponsor:   Giresun University
  Completed

• Studying the Efficiency of the Natural Preparation Rutan in Children in the Treatment of COVID-19, ARVI - Condition:   COVID-19 Respiratory Infection
  Interventions:   Drug: Rutan 25 mg;   Other: Control group
  Sponsor:   Research Institute of Virology, Ministry of Health of the Republic of Uzbekistan
  Completed

• A Pilot Study Evaluating the Efficacy of the Vielight Neuro RX Gamma in the Treatment of Post COVID-19 Cognitive Impairment - Condition:   Post COVID-19 Cognitive Impairment
  Interventions:   Device: Vielight Neuro RX Gamma active device;   Device: Vielight Neuro RX Gamma sham device
  Sponsor:   Vielight Inc.
  Not yet recruiting

• To Explore the Regulatory Effect of Combined Capsule FMT on the Levels of Inflammatory Factors in Peripheral Blood of Patients With COVID-19 During Treatment. - Conditions:   Fecal Microbiota Transplantation;   COVID-19 Infection
  Intervention:   Procedure: Fecal microbiota transplantation
  Sponsor:   Shanghai 10th People’s Hospital
  Completed

• Use of a Hypochlorous Acid Spray Solution in the Treatment of COVID-19 Patients : COVICONTROL Study . - Condition:   SARS CoV 2 Infection
  Interventions:   Other: Spray with Hypochlorous Acid Group;   Other: Spray with Placebo Group
  Sponsor:   University of Monastir
  Recruiting

• Telerehabilitation Program and Detraining in Patients With Post-COVID-19 Sequelae - Condition:   COVID-19 Acute Respiratory Distress Syndrome
  Intervention:   Other: Telerehabilitation program
  Sponsor:   Campus docent Sant Joan de Déu-Universitat de Barcelona
  Completed

• Phase 3 Study of Novavax Vaccine(s) as Booster Dose After mRNA Vaccines - Condition:   COVID-19
  Interventions:   Biological: NVX-CoV2373;   Biological: SARS-CoV-2 rS antigen/Matrix-M Adjuvant
  Sponsor:   Novavax
  Active, not recruiting

• COVID-19 Vaccine Uptake Amongst Underserved Populations in East London - Conditions:   COVID-19;   Influenza;   Vaccination Refusal
  Intervention:   Device: Patient Engagement tool
  Sponsors:   Queen Mary University of London;   Social Action for Health
  Not yet recruiting

• REVERSE-Long COVID-19 With Baricitinib Pilot Study - Condition:   Post-Acute COVID-19 Syndrome
  Intervention:   Drug: Baricitinib 4 MG
  Sponsors:   Vanderbilt University Medical Center;   Emory University;   University of California, San Francisco;   University of Minnesota;   Vanderbilt University;   Yale University
  Not yet recruiting

• Dose Exploration Intramuscular/Intravenous Prophylaxis Pharmacokinetic Exposure Response Study - Condition:   COVID-19
  Interventions:   Drug: AZD3152;   Other: Placebo
  Sponsor:   AstraZeneca
  Not yet recruiting

• Study to Assess Safety, Reactogenicity and Immunogenicity of the repRNA(QTP104) Vaccine Against SARS-CoV-2(COVID-19) - Conditions:   COVID-19;   SARS-CoV-2
  Interventions:   Biological: QTP104 1ug;   Biological: QTP104 5ug;   Biological: QTP104 25ug
  Sponsor:   Quratis Inc.
  Active, not recruiting

From PubMed

• Optimizing the Cas13 antiviral train: cargo and delivery - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in 2020 highlighted the need for rapid, widespread responses against infectious disease. One such innovation uses CRISPR-Cas13 technology to directly target and cleave viral RNA, thereby inhibiting replication. Due to their programmability, Cas13-based antiviral therapies can be rapidly deployed to target emerging viruses, in comparison with traditional therapeutic development that takes at least 12-18 months, and often…

• In silico design and evaluation of a novel therapeutic agent against the spike protein as a novel treatment strategy for COVID-19 treatment - CONCLUSIONS: In silico studies can provide a good opportunity to study viral proteins and new drugs or compounds since they do not need direct exposure to infectious agents or equipped laboratories. The suggested therapeutic agent should be further characterized in vitro and in vivo.

• CD24-Siglec interactions in inflammatory diseases - CD24 is a small glycosylphosphatidylinositol (GPI)-anchored glycoprotein with broad expression in multiple cell types. Due to differential glycosylation, cell surface CD24 have been shown to interact with various receptors to mediate multiple physiological functions. Nearly 15 years ago, CD24 was shown to interact with Siglec G/10 to selectively inhibit inflammatory response to tissue injuries. Subsequent studies demonstrate that sialylated CD24 (SialoCD24) is a major endogenous ligand for…

• A linear B-cell epitope close to the furin cleavage site within the S1 domain of SARS-CoV-2 Spike protein discriminates the humoral immune response of nucleic acid- and protein-based vaccine cohorts - CONCLUSIONS: Understanding the exact function of antibodies recognizing amino acid region 657-671 of SARS-CoV-2 Spike glycoprotein and why nucleic acid-based vaccines elicit different responses from protein-based ones will be helpful for future vaccine design.

• Impacts of pregnancy and menopause on COVID-19 severity: A systematic review and meta-analysis of 4.6 million women - CONCLUSIONS: Pregnancy and menopause are protective and risk factors for severe COVID-19, respectively. The protective role of pregnancy on COVID-19 is minimal and could be counteracted or masked by prepregnancy or pregnancy comorbidities. The administration of estrogen and progesterone may prevent severe COVID-19.

• Effect of voluntary human mobility restrictions on vector-borne diseases during the COVID-19 pandemic in Japan: A descriptive epidemiological study using a national database (2016 to 2021) - The coronavirus disease 2019 (COVID-19) pandemic not only encouraged people to practice good hygiene but also caused behavioral inhibitions and resulted reduction in both endemic and imported infectious diseases. However, the changing patterns of vector-borne diseases under human mobility restrictions remain unclear. Hence, we aimed to investigate the impact of transborder and local mobility restrictions on vector-borne diseases through a descriptive epidemiological study. The analysis was…

• Effect of P2Y12 Inhibitors on Organ Support-Free Survival in Critically Ill Patients Hospitalized for COVID-19: A Randomized Clinical Trial - CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of critically ill participants hospitalized for COVID-19, treatment with a P2Y12 inhibitor did not improve the number of days alive and free of cardiovascular or respiratory organ support. The use of the P2Y12 inhibitor did not increase major bleeding compared with usual care. These data do not support routine use of a P2Y12 inhibitor in critically ill patients hospitalized for COVID-19.

• Immunosuppressants exert differential effects on pan-coronavirus infection and distinct combinatory antiviral activity with molnupiravir and nirmatrelvir - CONCLUSIONS: Different immunosuppressants have distinct effects on coronavirus replication, with 6-TG, MPA, tofacitinib and filgotinib possessing pan-coronavirus antiviral activity. The combinations of MPA, 6-TG, tofacitinib and filgotinib with antiviral drugs exerted an additive or synergistic antiviral activity. Thus, these findings provide an important reference for optimal management of immunocompromised patients infected with coronaviruses.

• Myricetin possesses the potency against SARS-CoV-2 infection through blocking viral-entry facilitators and suppressing inflammation in rats and mice - CONCLUSION: Our findings showed that myricetin inhibited HCoV-229E and SARS-CoV-2 replication in vitro, blocked SARS-CoV-2 virus entry facilitators and relieved inflammation through the RIPK1/NF-κB pathway, suggesting that this flavonol has the potential to be developed as a therapeutic agent against COVID-19.

• Promoting cognitive health: a virtual group intervention for community-living older adults - CONCLUSIONS: The synchronous virtual group intervention was shown to be feasible for the elderly in the community who participated in the study.

• SARS-CoV-2 RBD and Its Variants Can Induce Platelet Activation and Clearance: Implications for Antibody Therapy and Vaccinations against COVID-19 - The COVID-19 pandemic caused by SARS-CoV-2 virus is an ongoing global health burden. Severe cases of COVID-19 and the rare cases of COVID-19 vaccine-induced-thrombotic-thrombocytopenia (VITT) are both associated with thrombosis and thrombocytopenia; however, the underlying mechanisms remain inadequately understood. Both infection and vaccination utilize the spike protein receptor-binding domain (RBD) of SARS-CoV-2. We found that intravenous injection of recombinant RBD caused significant…

• HSPA5 Promotes Attachment and Internalization of Porcine Epidemic Diarrhea Virus through Interaction with the Spike Protein and the Endo-/Lysosomal Pathway - Porcine epidemic diarrhea virus (PEDV) has caused huge economic losses to the global pig industry. The swine enteric coronavirus spike (S) protein recognizes various cell surface molecules to regulate viral infection. In this study, we identified 211 host membrane proteins related to the S1 protein by pulldown combined with liquid-chromatography tandem mass spectrometry (LC-MS/MS) analysis. Among these, heat shock protein family A member 5 (HSPA5) was identified through screening as having a…

• Evaluation of the Inhibition Potency of Nirmatrelvir against Main Protease Mutants of SARS-CoV-2 Variants - SARS-CoV-2 continues to pose a threat to public health. Main protease (M^(pro)) is one of the most lucrative drug targets for developing specific antivirals against SARS-CoV-2 infection. By targeting M^(pro), peptidomimetic nirmatrelvir is able to inhibit viral replication of SARS-CoV-2 and reduce the risk for progression to severe COVID-19. However, multiple mutations in the gene encoding M^(pro) of emerging SARS-CoV-2 variants raise a concern of drug resistance. In the present study, we…

• Culture and pandemic control at cross-roads: navigating the burial guidelines for COVID-19-related deaths in a Ghanaian setting - CONCLUSIONS: Insensitivity to socio-cultural practices compromised the implementation of the COVID-19 pandemic control interventions, particularly, the COVID-19-related death and burial protocols. Some compromises that were not sanctioned by the protocols were reached to allow health officials and families respectfully bury their dead. These findings call for the need to prioritize the incorporation of sociocultural practices in future pandemic prevention and management strategies.

• Rational Design of Covalent Kinase Inhibitors by an Integrated Computational Workflow (Kin-Cov) - Covalent kinase inhibitors (CKIs) hold great promise for drug development. However, examples of computationally guided design of CKIs are still scarce. Here, we present an integrated computational workflow (Kin-Cov) for rational design of CKIs. The design of the first covalent leucine-zipper and sterile-α motif kinase (ZAK) inhibitor was presented as an example to showcase the power of computational workflow for CKI design. The two representative compounds, 7 and 8, inhibited ZAK kinase with…

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