Covid-19 Sentry

Contents

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

From Preprints

• Everyday Emotional Functioning in COVID-19 Lockdowns -
  Throughout the COVID-19 pandemic, policy makers have tried to balance the effectiveness of lockdowns (i.e., stay-at-home orders) with their potential mental health costs. Yet, several years into the pandemic, policy makers lack solid evidence about the toll of lockdowns on daily emotional functioning. Using data from two intensive longitudinal studies conducted in Australia in 2021, we compared the intensity, persistence, and regulation of emotions on days in and out of lockdown. Participants (N = 441, observations = 14,511) completed a 7-day study either entirely in lockdown, entirely out of lockdown, or both in and out of lockdown. We assessed emotions in general (Dataset 1) and in the context of social interactions (Dataset 2). Lockdowns took an emotional toll, but this toll was relatively mild: In lockdown, people experienced slightly more negative and less positive emotion; returned to a mildly negative emotional state more quickly; and used low-effort emotion regulation strategies (i.e., distraction). There are three interpretations for our findings, which are not mutually exclusive. First, people may be relatively resilient to the emotional challenges posed by repeated lockdowns. Second, lockdowns may not compound the emotional challenges of the pandemic. Third, because we found effects even in a mostly childless and well-educated sample, lockdowns may take a greater emotional toll in samples with less pandemic privilege. Indeed, the high level of pandemic privilege of our sample limits the generalizability of our findings (e.g., to people with caregiving roles).
  🖺 Full Text HTML: Everyday Emotional Functioning in COVID-19 Lockdowns
• Inspiration of SARS-CoV-2 envelope protein mutations on pathogenicity of Omicron XBB -
  Predicting pathogenicity of Omicron sub-variants is critical for assessing disease dynamics and developing public health strategies. As an important virulence factor, SARS-CoV-2 envelope protein (2-E) causes cell death and acute respiratory distress syndrome (ARDS)-like pathological damages. Evaluation of 2-E mutations might offer clues to pathogenicity forecast. Here, the frequency and cell lethality of 92 mutations of 2-E in five early “variants of concern” (VOCs, Alpha, Beta, Gamma, Delta, and Omicron BA.1, BA.2, BA.3, BA.4, and BA.5) were analyzed, which could be divided into three classes. Most (87) mutations belong to Class I, no obvious frequency changes. Class II consists of 2 mutations, exhibiting enhanced cell lethality but decreased frequency. The rest 3 mutations in Class III were characterized by attenuated cell lethality and increased frequency. Remarkably, the Class II mutations are always observed in the VOCs with high disease severity while the Class III mutations are highly conserved in the VOCs with weakened pathogenicity. For example, P71L, the most lethal mutation, dropped to nearly 0.00% in the milder Omicrons from 99.12% in Beta, while the less lethal mutation T9I, sharply increased to 99.70% in BA.1 and is highly conserved in BA.1-5. Accordingly, we proposed that some key 2-E mutations are pathogenicity markers of the virus. Notably, the highly contagious Omicron XBB retained T9I also. In addition, XBB gained a new dominant-negative mutation T11A with frequency 90.52%, exhibiting reduced cell lethality, cytokine induction and viral production capabilities in vitro, and particularly weakened lung damages in mice. No mutations with enhanced cell lethality were observed in XBB. These clues imply a further weakened pathogenicity of XBB among Omicron sub-variants.
  🖺 Full Text HTML: Inspiration of SARS-CoV-2 envelope protein mutations on pathogenicity of Omicron XBB
• Human iPS cell-derived sensory neurons can be infected by SARS-CoV-2 strain WA1/2020 as well as variants delta and omicron. -
  COVID-19 has impacted billions of people in the world since 2019 and unfolded a major healthcare crisis. With an increasing number of deaths and the emergence of more transmissible variants, it is crucial to better understand the biology of the disease-causing virus, the SARS-CoV-2. Peripheral neuropathies appeared as a specific COVID-19 symptom occurring at later stages of the disease. In order to understand the impact of SARS-CoV-2 on the peripheral nervous system, we generated human sensory neurons from induced pluripotent stem cells that we infected with the SARS-CoV-2 strain WA1/2020 and the variants delta and omicron. Using single cell RNA sequencing, we found that human sensory neurons can be infected by SARS-CoV-2 but are unable to produce new viruses. Our data suggests that sensory neurons can be infected by the original WA1/2020 strain of SARS-CoV-2 as well as the delta and omicron variants.
  🖺 Full Text HTML: Human iPS cell-derived sensory neurons can be infected by SARS-CoV-2 strain WA1/2020 as well as variants delta and omicron.
• Effectiveness of nirmatrelvir-ritonavir against hospital admission or death: a cohort study in a large US healthcare system -

  Background: In the United States, oral nirmatrelvir-ritonavir (PaxlovidTM) is authorized for use among patients aged 12+ years with mild-to-moderate SARS-CoV-2 infection who are at risk for progression to severe COVID-19, including hospitalization. However, effectiveness under current real-world prescribing practices in outpatient settings is unclear. Methods: We undertook a matched observational cohort study of non-hospitalized cases with SARS-CoV-2 infection to compare outcomes among those who received or did not receive nirmatrelvir-ritonavir within the Kaiser Permanente Southern California healthcare system. Cases were matched on testing date, age, sex, clinical status (including care received, presence or absence of acute COVID-19 symptoms at testing, and time from symptom onset to testing), history of vaccination, Charlson comorbidity index, prior-year healthcare utilization, and body mass index. Primary analyses evaluated effectiveness of nirmatrelvir-ritonavir in preventing hospital admission or death within 30 days after a positive test. Secondary analyses evaluated effectiveness against intensive care unit admission, mechanical ventilation, or death within 60 days after a positive test. We measured treatment effectiveness as (1-adjusted hazards ratio [aHR])*100%, estimating the aHR via Cox proportional hazards models. Results: Analyses included 7,274 nirmatrelvir-ritonavir recipients and 126,152 non-recipients with positive results from SARS-CoV-2 tests undertaken in outpatient settings between 8 April and 7 October, 2022. Overall, 114,208 (85.6%) and 81,739 (61.3%) of 133,426 participants had received 2+ and 3+ COVID-19 vaccine doses, respectively. A total of 111,489 (83.6% of 133,426) cases were symptomatic at the point of testing, with 5,472 (75.2% of 7,274) treatment recipients and 84,657 (67.1% of 126,152) non-recipients testing within 0-5 days after symptom onset. Effectiveness in preventing hospital admission or death within 30 days after a positive test was 79.6% (95% confidence interval: 33.9% to 93.8%) for cases dispensed nirmatrelvir-ritonavir within 0-5 days after symptom onset; within the subgroup of cases tested 0-5 days after symptom onset and dispensed treatment on the day of their test, effectiveness was 89.6% (50.2% to 97.8%). Effectiveness declined to 43.8% (-33.3% to 81.7%) for treatment course dispensed 6+ days after symptom onset or to cases who were not experiencing acute clinical symptoms. Overall, for cases dispensed treatment at any time within their clinical course, effectiveness was 53.6% (6.6% to 77.0%). Effectiveness in preventing the secondary endpoint of intensive care unit admission, mechanical ventilation, or death within 60 days after a positive test was 89.2% (-25.0% to 99.3%) for cases dispensed treatment 0-5 days after symptom onset and 84.1% (18.8% to 96.9%) for cases dispensed treatment at any time. Subgroup analyses identified similar effectiveness estimates among cases who had received 2+ or 3+ COVID-19 vaccine doses. Implications: In a setting with high levels of COVID-19 vaccine and booster uptake, receipt of nirmatrelvir-ritonavir 0-5 days after symptom onset was associated with substantial reductions in risk of hospital admission or death within 30 days after a positive outpatient SARS-CoV-2 test.

  🖺 Full Text HTML: Effectiveness of nirmatrelvir-ritonavir against hospital admission or death: a cohort study in a large US healthcare system
• HOGVAX: Exploiting Peptide Overlaps to Maximize Population Coverage in Vaccine Design with Application to SARS-CoV-2 -
  Peptide vaccines present a safe and cost-efficient alternative to traditional vaccines. Their efficacy depends on the peptides included in the vaccine and the ability of major histocompatibility complex (MHC) molecules to bind and present these peptides. Due to the high diversity of MHC alleles, their diverging peptide binding specificities, and physical constraints on the maximum length of peptide vaccine constructs, choosing a set of peptides that effectively achieve immunization across a large proportion of the population is challenging. Here, we present HOGVAX, a combinatorial optimization approach to select peptides that maximize population coverage. The key idea behind HOGVAX is to exploit overlaps between peptide sequences to include a large number of peptides in limited space and thereby also cover rare MHC alleles. We formalize the vaccine design task as a theoretical problem, which we call the Maximum Scoring k-Superstring Problem (MSKS). We show that MSKS is NP-hard, reformulate it into a graph problem using the hierarchical overlap graph (HOG), and present a haplotype-aware variant of MSKS to take linkage disequilibrium between MHC loci into account. We give an integer linear programming formulation for the graph problem and provide an open source implementation. We demonstrate on a SARS-CoV-2 case study that HOGVAX-designed vaccine formulations contain significantly more peptides than vaccine sequences built from concatenated peptides. We predict over 98% population coverage and high numbers of per-individual presented peptides, leading to robust immunity against new pathogens or viral variants.
  🖺 Full Text HTML: HOGVAX: Exploiting Peptide Overlaps to Maximize Population Coverage in Vaccine Design with Application to SARS-CoV-2
• Hamsters are a model for post-COVID-19 alveolar regeneration mechanisms: an opportunity to understand post-acute sequelae of SARS-CoV-2 -
  A relevant number of coronavirus disease 2019 (COVID-19) survivors suffers from post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PASC). Current evidence suggests a dysregulated alveolar regeneration in COVID-19 as a possible explanation for respiratory PASC symptoms, a phenomenon which deserves further investigation in a suitable animal model. This study investigates morphologic and transcriptomic features of alveolar regeneration in SARS-CoV-2 infected Syrian golden hamsters. We demonstrate that CK8+ alveolar differentiation intermediate (ADI) cells accumulate following SARS-CoV-2-induced diffuse alveolar damage. A subset of ADI cells shows nuclear accumulation of TP53 at 6- and 14-days post infection (dpi), indicating a prolonged arrest in the ADI state. Transcriptome data shows the expression of gene signatures driving ADI cell senescence, epithelial-mesenchymal transition, and angiogenesis. Moreover, we show that multipotent CK14+ airway basal cell progenitors migrate out of terminal bronchioles, aiding alveolar regeneration. At 14 dpi, persistence of ADI cells, peribronchiolar proliferates, M2-type macrophages, and sub-pleural fibrosis is observed, indicating incomplete alveolar restoration. The results demonstrate that the hamster model reliably phenocopies indicators of a dysregulated alveolar regeneration of COVID-19 patients. The study provides a suitable translational model for future research on the pathomechanims of PASC and testing of prophylactic and therapeutical approaches.
  🖺 Full Text HTML: Hamsters are a model for post-COVID-19 alveolar regeneration mechanisms: an opportunity to understand post-acute sequelae of SARS-CoV-2
• SARS-CoV-2 nucleocapsid protein inhibits the PKR-mediated integrated stress response through RNA-binding domain N2b -
  The nucleocapsid protein N of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enwraps and condenses the viral genome for packaging but is also an antagonist of the innate antiviral defense. It suppresses the integrated stress response (ISR), purportedly by interacting with stress granule (SG) assembly factors G3BP1 and 2, and inhibits type I interferon responses. To elucidate its mode of action, we systematically deleted and over-expressed distinct regions and domains. We show that N via domain N2b blocks PKR-mediated ISR activation, as measured by suppression of ISR-induced translational arrest and SG formation. N2b mutations that prevent dsRNA binding abrogate these activities also when introduced in the intact N protein. Substitutions reported to block post-translation modifications of N or its interaction with G3BP1/2 did not have a detectable additive effect. In an encephalomyocarditis virus-based infection model, N2b - but not a derivative defective in RNA binding - prevented PKR activation, inhibited {beta}-interferon expression and promoted virus replication. Apparently, SARS-CoV-2 N inhibits innate immunity by sequestering dsRNA to prevent activation of PKR and RIG-I-like receptors. Similar observations were made for the N protein of human coronavirus 229E, suggesting that this may be a general trait conserved among members of other orthocoronavirus (sub)genera.
  🖺 Full Text HTML: SARS-CoV-2 nucleocapsid protein inhibits the PKR-mediated integrated stress response through RNA-binding domain N2b
• Analysis of recurrent research pathways for assessing and improving effectiveness in life sciences laboratories -

  Background Life sciences research often turns out to be ineffective. Our aim was to develop a method for mapping repetitive research processes, detecting practice variations, and exploring inefficiencies. Methods Three samples of R&I projects were used: companion diagnostics of cancer treatments, identification of COVID-19 variants, and COVID-19 vaccine development. Major steps involved: defined starting points, desired end points; measurement of transition times and success rates; exploration of variations, and recommendations for improved efficiency. Results Over 50% of CDX developments failed to reach market simultaneously with new drugs. There were significant variations among phases of co-development (Bartlett test P<0.001). Length of time in vaccine development also shows variations (P<0.0001). Similarly, subject participation indicates unexplained variations in trials (Phase I: 489.7 (±461.8); Phase II: 857.3 (±450.1); Phase III: 35402 (±18079). Conclusion Analysis of repetitive research processes can highlight inefficiencies and show ways to improve quality and productivity in life sciences.

  🖺 Full Text HTML: Analysis of recurrent research pathways for assessing and improving effectiveness in life sciences laboratories
• Diminished responses to mRNA-based SARS-CoV-2 vaccines in individuals with rheumatoid arthritis on immune modifying therapies -

  Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes debilitating swelling and destruction of the joints. People with RA are treated with drugs that actively suppress one or more parts of their immune system, and these may alter their response to vaccination against SARS-CoV-2. In this study, we analyzed blood samples from a cohort of RA subjects after receiving a 2-dose mRNA COVID-19 vaccine regimen. Our data show that individuals on the CTLA4-Ig therapy abatacept have reduced levels of SARS-CoV-2-neutralizing antibodies after vaccination. At a cellular level, these subjects show reduced activation and class-switching of SARS-CoV-2-specific B cells, as well as reduced numbers and impaired helper cytokine production by SARS-CoV-2-specific CD4⁺ T cells. Individuals on methotrexate showed similar but less severe defects in vaccine response, whereas individuals on the B celldepleting therapy rituximab had a near-total loss of antibody production after vaccination. These data define a specific cellular phenotype associated with impaired response to SARS-CoV-2 vaccination in RA subjects on different immune-modifying therapies, and help inform efforts to improve vaccination strategies in this vulnerable population.

  🖺 Full Text HTML: Diminished responses to mRNA-based SARS-CoV-2 vaccines in individuals with rheumatoid arthritis on immune modifying therapies
• The incidence and mortality of COVID-19 related TB disease in Sub-Saharan Africa: A systematic review and meta-analysis -

  Background Coronavirus disease 2019 (COVID-19) is also associated with other co-morbidities in people who have previously or currently have pulmonary tuberculosis (PTB). PTB is a risk factor for COVID-19, both in terms of severity and mortality, regardless of HIV status. However, there is less information available on COVID-19 and PTB in terms of incidence and mortality rates in Sub-Saharan Africa (SSA), a high-burden TB region. This systematic review provided a data synthesis of available evidence on COVID-19/PTB incidence and case fatality rates, as well as mortality rates found in clinical and post-mortem COVID-19/PTB diagnostics in SSA. Methods We conducted an electronic search in the PubMed, Medline, Google Scholar, Medrxix, and COVID-19 Global literature on coronavirus disease databases for studies involving COVID-19 and PTB in Sub-Saharan Africa. The primary outcomes were the incidence proportion of people with COVID-19 who had current or previous PTB, as well as the case fatality rate associated with COVID-19/PTB. Based on methodological similarities in the included random effect model studies, the combination method was developed using Stata version 16 and Prometa 3 software. We also performed sensitivity analysis and meta-regression. Results From the 548 references extracted by the literature search, 25 studies were selected and included in the meta-analysis with a total of 191, 250 COVID-19 infected patients and 11, 480 COVID-19 deaths. The pooled COVID-19/PTB incidence was 3% [2%-5%] and a case fatality rate of 13% [4%-23%]. The pooled estimates for case fatality rate among COVID-19/PTB were 7% [1%-12%] for clinical PTB diagnostic and 25% [3%-47%] for post-mortem PTB diagnostic. Previous TB had the highest incidence and fatality rates with 46 [19-73] per 1, 000 population and 8% [3%-19%], respectively. Meta-regression model including the effect sizes and cumulative COVID-19 cases (P= 0.032), HIV prevalence (P= 0.041), and TB incidence (P= 0.002) to explain high heterogeneity between studies. Conclusion To summarize, the incidence of TB associated with COVID-19 is higher in SSA, as are the case fatality rates, when compared to the rest of the world. However, because the post-mortem TB diagnostic was higher, COVID-19 associated with TB may have been underreported in studies conducted in SSA. To confirm COVID-19/TB incidence and case fatality rates in SSA, large-scale cohort studies that adequately clear tools on previous and/or current TB diagnostic tools are required.

  🖺 Full Text HTML: The incidence and mortality of COVID-19 related TB disease in Sub-Saharan Africa: A systematic review and meta-analysis
• Role of spike in the pathogenic and antigenic behavior of SARS-CoV-2 BA.1Omicron -
  The recently identified, globally predominant SARS-CoV-2 Omicron variant (BA.1) is highly transmissible, even in fully vaccinated individuals, and causes attenuated disease compared with other major viral variants recognized to date. The Omicron spike (S) protein, with an unusually large number of mutations, is considered the major driver of these phenotypes. We generated chimeric recombinant SARS-CoV-2 encoding the S gene of Omicron in the backbone of an ancestral SARS-CoV-2 isolate and compared this virus with the naturally circulating Omicron variant. The Omicron S-bearing virus robustly escapes vaccine-induced humoral immunity, mainly due to mutations in the receptor binding motif (RBM), yet unlike naturally occurring Omicron, efficiently replicates in cell lines and primary-like distal lung cells. In K18-hACE2 mice, while Omicron causes mild, non-fatal infection, the Omicron S-carrying virus inflicts severe disease with a mortality rate of 80%. This indicates that while the vaccine escape of Omicron is defined by mutations in S, major determinants of viral pathogenicity reside outside of S.
  🖺 Full Text HTML: Role of spike in the pathogenic and antigenic behavior of SARS-CoV-2 BA.1Omicron
• A Global Experiment on Motivating Social Distancing during the COVID-19 Pandemic -
  Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e. a controlling message) compared to no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly-internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared to the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly-internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing: Controlled motivation was associated with more defiance and less long-term behavioral intentions to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges.
  🖺 Full Text HTML: A Global Experiment on Motivating Social Distancing during the COVID-19 Pandemic
• In COVID-19 health messaging, loss framing increases anxiety with little-to-no concomitant benefits: Experimental evidence from 84 countries -
  The COVID-19 pandemic (and its aftermath) highlights a critical need to communicate health information effectively to the global public. Given that subtle differences in information framing can have meaningful effects on behavior, behavioral science research highlights a pressing question: Is it more effective to frame COVID-19 health messages in terms of potential losses (e.g., “If you do not practice these steps, you can endanger yourself and others”) or potential gains (e.g., “If you practice these steps, you can protect yourself and others”)? Collecting data in 48 languages from 15,929 participants in 84 countries, we experimentally tested the effects of message framing on COVID-19-related judgments, intentions, and feelings. Loss- (vs. gain-) framed messages increased self-reported anxiety among participants cross-nationally with little-to-no impact on policy attitudes, behavioral intentions, or information seeking relevant to pandemic risks. These results were consistent across 84 countries, three variations of the message framing wording, and 560 data processing and analytic choices. Thus, results provide an empirical answer to a global communication question and highlight the emotional toll of loss-framed messages. Critically, this work demonstrates the importance of considering unintended affective consequences when evaluating nudge-style interventions.
  🖺 Full Text HTML: In COVID-19 health messaging, loss framing increases anxiety with little-to-no concomitant benefits: Experimental evidence from 84 countries
• A global test of brief reappraisal interventions on emotions during the COVID-19 pandemic -
  The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion regulation strategy which modifies how one thinks about a situation. Participants from 87 countries/regions (N = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vs. both control conditions) had consistent effects in reducing negative emotions and increasing positive emotions across different measures. Reconstrual and repurposing had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world to build resilience during the pandemic and beyond.
  🖺 Full Text HTML: A global test of brief reappraisal interventions on emotions during the COVID-19 pandemic
• Genomic epidemiology reveals the dominance of Hennepin County in transmission of SARS-CoV-2 in Minnesota from 2020-2022 -

  SARS-CoV-2 has had an unprecedented impact on human health and highlights the need for genomic epidemiology studies to increase our understanding of the evolution and spread of pathogens and to inform policy decisions. Most efforts have focused on international or country-wide transmission, which are unable to highlight state-wide trends. We sequenced virus genomes from over 22,000 patients tested at Mayo Clinic Laboratories between 2020-2022 and leveraged detailed patient metadata to describe county-to-county spread in Minnesota. Our findings indicate that spread in the state was mostly dominated by viruses from Hennepin County, which contains the largest metropolis. For many counties, we found that state government restrictions eventually led to a decrease in the diversity of circulating viruses from other counties and that their complete removal in May of 2021 saw a drastic revert to levels at or greater than those observed during the months before. We also linked over 14,000 genomes with patient risk characteristics and infection-related phenotypes from the Mayo Clinic electronic health record. We found that the genetic relationship of Omicron viruses was structured by clinical outcomes when stratifying by patient risk factor and variant of concern. However, we were unable to identify nucleotide variants that drove this association.

  🖺 Full Text HTML: Genomic epidemiology reveals the dominance of Hennepin County in transmission of SARS-CoV-2 in Minnesota from 2020-2022

From Clinical Trials

• Efficacy and Safety of Jaktinib in Patients With COVID-19 Pneumoia - Condition:   COVID-19 Pneumonia
  Interventions:   Drug: Jaktinib;   Drug: Placebo
  Sponsor:   First Affiliated Hospital of Zhejiang University
  Not yet recruiting

• Awaken Prone Positioning Ventinlation in COVID-19 Patients - Condition:   COVID-19
  Intervention:   Procedure: Awaken prone positioning ventilation
  Sponsor:   Southeast University, China
  Enrolling by invitation

• Effect of a Traditional Chinese Medicine Formulation on COVID-19 Infection - Condition:   COVID-19
  Interventions:   Drug: Traditional Chinese Medicine Formulation;   Other: Placebo Treatment
  Sponsor:   First Affiliated Hospital Xi’an Jiaotong University
  Not yet recruiting

• Study of SHEN26 Capsule in Patients With Mild to Moderate COVID-19 - Condition:   COVID-19
  Interventions:   Drug: SHEN26 dose 1;   Drug: SHEN26 dose 2;   Drug: SHEN26 placebo
  Sponsor:   Shenzhen Kexing Pharmaceutical Co., Ltd.
  Recruiting

• Efficacy and Safety of SA58 Nasal Spray in Close Contact With COVID-19 People - Condition:   COVID-19
  Interventions:   Drug: SA58 Nasal Spray;   Drug: Placebo
  Sponsors:   Sinovac Life Sciences Co., Ltd.;   Beijing Ditan Hospital
  Recruiting

• Bright Light Therapy for Post-COVID-19 Fatigue - Condition:   Post COVID-19 Condition
  Interventions:   Device: Bright light therapy;   Device: Dim red light therapy
  Sponsor:   Chinese University of Hong Kong
  Not yet recruiting

• Immunogenicity of Heterologous Versus Homologous Prime Boost Schedule With mRNA and Inactivated COVID-19 Vaccines - Condition:   COVID-19
  Interventions:   Biological: CoronaVac/CoronaVac;   Biological: CoronaVac/BNT162b2
  Sponsor:   Institut Pasteur de Tunis
  Completed

• Evaluate the Efficacy and Safety of FB2001 for Inhalation in Patients With Mild to Moderate COVID-19 - Condition:   Mild to Moderate COVID-19
  Interventions:   Drug: FB2001;   Drug: FB2001 placebo
  Sponsor:   Frontier Biotechnologies Inc.
  Recruiting

• A Study of Positive Emotions With Long COVID-19 - Condition:   Post-Acute COVID-19 Syndrome
  Intervention:   Behavioral: Microdosing of mindfulness
  Sponsor:   University of California, Davis
  Not yet recruiting

• Efficacy and Safety of the Anti-COVID-19 Antibody SA55 for Injection in Patients With Hematological Malignancies Who Are Persistently Positive for COVID-19 - Conditions:   Hematological Malignancy;   COVID-19
  Intervention:   Biological: Anti-COVID-19 Antibody SA55 for Injection
  Sponsor:   Beijing Boren Hospital
  Recruiting

• A Vaccine Booster (GEO-CM04S1) for the Prevention of COVID-19 in Patients With Chronic Lymphocytic Leukemia - Conditions:   Chronic Lymphocytic Leukemia;   COVID-19 Infection
  Interventions:   Procedure: Biospecimen Collection;   Biological: mRNA COVID-19 Vaccine;   Biological: Synthetic MVA-based SARS-CoV-2 Vaccine COH04S1
  Sponsors:   City of Hope Medical Center;   National Cancer Institute (NCI)
  Not yet recruiting

• Sars-COV-2 Immunity in immunoCOmpromised Populations - Conditions:   SARS CoV 2 Infection;   COVID-19
  Intervention:   Diagnostic Test: Humoral immunity
  Sponsors:   Maria Goossens;   Université Libre de Bruxelles;   Institute of Tropical Medicine, Belgium;   Mensura EDPB;   Erasme hospital
  Not yet recruiting

• The Effect of Motivational Interviewing on the Adherence to Medication of Patients With COVID-19 Diagnosed at Home - Condition:   Drug Compliance
  Intervention:   Behavioral: motivational interview
  Sponsor:   Saglik Bilimleri Universitesi Gulhane Tip Fakultesi
  Completed

• Qigong for Post Acute Sequelae of COVID-19 Infection - Condition:   Long COVID
  Intervention:   Behavioral: External Qigong
  Sponsor:   University of California, Davis
  Recruiting

• Evaluating the Impact of Resource Navigators to Support LTC and RH Staff During and Beyond COVID-19 - Conditions:   Wellness;   Burnout, Caregiver;   Burnout, Professional;   COVID-19;   Vaccine Refusal
  Intervention:   Behavioral: Intervention
  Sponsors:   Unity Health Toronto;   Canadian Institutes of Health Research (CIHR);   University of Toronto
  Not yet recruiting

From PubMed

• Environmentally persistent free radicals enhance SARS-CoV-2 replication in respiratory epithelium - Epidemiological evidence links lower air quality with increased incidence and severity of COVID-19; however, mechanistic data have yet to be published. We hypothesized air pollution-induced oxidative stress in the nasal epithelium increased viral replication and inflammation. Nasal epithelial cells (NECs), collected from healthy adults, were grown into a fully differentiated epithelium. NECs were infected with the ancestral strain of SARS-CoV-2. An oxidant combustion by-product found in air…

• A computational study on the molecular mechanisms of panduratin A as a potential inhibitor on SARS-CoV-2 protein targets - Panduratin A from Boesebergia rotunda was recently reported as a potent anti-SARS-CoV-2 compound. However, the molecular mechanisms underlying the inhibition by Panduratin A and its target remained unclear. Molecular docking calculations were performed between panduratin A and five important proteins, i.e., main protease (Mpro), papain-like protease (PLpro), receptor binding domain (RBD) of spike proteins, RNA-dependent-RNA-polymerase (RdRp), and 2’-O-methyltransferase (MTase). The estimated…

• Anti-inflammatory and antiviral activities of flavone C-glycosides of Lophatherum gracile for COVID-19 - Lophatherum gracile (L. gracile) has long been used as a functional food and herbal medicine. Previous studies have demonstrated that extracts of L. gracile attenuate inflammatory response and inhibit SARS-CoV-2 replication; however, the underlying active constituents have yet to be identified. This study investigated the bioactive components of L. gracile. Flavone C-glycosides of L. gracile were found to dominate both anti-inflammatory and antiviral effects. A simple chromatography-based method…

• Hypercapnia alters stromal-derived Wnt production limiting β-catenin signaling and proliferation in alveolar type 2 cells - Persistent symptoms and radiographic abnormalities suggestive of failed lung repair are among the most common symptoms in patients with COVID-19 after hospital discharge. In mechanically ventilated patients with ARDS secondary to SARS-CoV-2 pneumonia, low tidal volumes to reduce ventilator-induced lung injury necessarily elevate blood CO2 levels, often leading to hypercapnia. The role of hypercapnia on lung repair after injury is not completely understood. Here, using a mouse model of…

• A simple in-host model for COVID-19 with treatments: model prediction and calibration - In this paper, we provide a simple ODEs model with a generic nonlinear incidence rate function and incorporate two treatments, blocking the virus binding and inhibiting the virus replication to investigate the impact of calibration on model predictions for the SARS-CoV-2 infection dynamics. We derive conditions of the infection eradication for the long-term dynamics using the basic reproduction number, and complement the characterization of the dynamics at short-time using the resilience and…

• The nanomolar affinity of C-phycocyanin from virtual screening of microalgal bioactive as potential ACE2 inhibitor for COVID-19 therapy - The global pandemic of COVID-19 caused by SARS-CoV-2 has caused more than 400 million infections with more than 5.7 million deaths worldwide, and the number of validated therapies from natural products for treating coronavirus infections needs to be increased. Therefore, the virtual screening of bioactive compounds from natural products based on computational methods could be an interesting strategy. Among many sources of bioactive natural products, compounds from marine organisms, particularly…

• Delivery of siRNAs against MERS-CoV in Vero and HEK-293 cells: A comparative evaluation of transfection reagents - CONCLUSION: Based on the results and data analysis, it is concluded that the use of two different transfection reagents was significantly effective. But the Lipofectamine™ 2000 was found to be a better transfection reagent than the JetPRIME^(R) for the delivery of siRNAs in both cell lines.

• Polypropylene nanoplastic exposure leads to lung inflammation through p38-mediated NF-κB pathway due to mitochondrial damage - CONCLUSIONS: These results suggest that PP stimulation may contribute to inflammation pathogenesis via the p38 phosphorylation-mediated NF-κB pathway as a result of mitochondrial damage.

• Overcoming Pharmaceutical Bottlenecks for Nucleic Acid Drug Development - ConspectusThe outbreak of the coronavirus disease 2019 (COVID-19) pandemic and swift approval of two mRNA vaccines have put nucleic acid therapeutics in the spotlight of both the scientific community and the general public. Actually, in addition to mRNAs, multiple nucleic acid therapeutics have been successively commercialized over the past few years. The rapid development of nucleic acid drugs not only demonstrates their superior potency but also marks a new era of the field. Compared with…

• DDQ/Fe(NO₃)₃-Catalyzed Aerobic Synthesis of 3-Acyl Indoles and an In Silico Study for the Binding Affinity of N-Tosyl-3-acyl Indoles toward RdRp against SARS-CoV-2 - In the present study, we herein report a DDQ-catalyzed new protocol for the synthesis of substituted 3-acylindoles. Being a potential system for virtual hydrogen storage, introduction of catalytic DDQ in combination with Fe(NO(3))(3)·9H(2)O and molecular oxygen as co-catalysts offers a regioselective oxo-functionalization of C-3 alkyl-/aryllidine indolines even with scale-up investigations. Intermediate isolation, their spectroscopic characterization, and the density functional theory…

• A knowledge-based protein-protein interaction inhibition (KPI) pipeline: an insight from drug repositioning for COVID-19 inhibition - The inhibition of protein-protein interactions (PPIs) by small molecules is an exciting drug discovery strategy. Here, we aimed to develop a pipeline to identify candidate small molecules to inhibit PPIs. Therefore, KPI, a Knowledge-based Protein-Protein Interaction Inhibition pipeline, was introduced to improve the discovery of PPI inhibitors. Then, phytochemicals from a collection of known Middle Eastern antiviral herbs were screened to identify potential inhibitors of key PPIs involved in…

• SARS-CoV-2 Harnesses Host Translational Shutoff and Autophagy To Optimize Virus Yields: the Role of the Envelope (E) Protein - The SARS-CoV-2 virion is composed of four structural proteins: spike (S), nucleocapsid (N), membrane (M), and envelope (E). E spans the membrane a single time and is the smallest, yet most enigmatic of the structural proteins. E is conserved among coronaviruses and has an essential role in virus-mediated pathogenesis. We found that ectopic expression of E had deleterious effects on the host cell as it activated stress responses, leading to LC3 lipidation and phosphorylation of the translation…

• ‘Building back better’ or sustaining the unsustainable? The climate impacts of Bank of England QE in the Covid-19 pandemic - The environmental impacts of monetary policy received academic attention after the 2008 financial crisis and the ‘market neutral’ quantitative easing policies that followed. This article examines the Bank of England’s Corporate Covid Financing Facility (CCFF) and the Asset Purchasing Facility (APF) between June 2020 and June 2021 to assess whether the Bank’s response to the COVID-19 pandemic was aligned with the transition to sustainability. The data indicates that the Bank of England’s monetary…

• Inhibition of SARS-CoV2 viral infection with natural antiviral plants constituents: an in-silico approach - CONCLUSION: The phytoconstituents were found to hinder the early stages of infection, such as absorption and penetration, while ivermectin prevented the passage of genetic material from the cytoplasm to the nucleus. Additional research involving living tissues and clinical trials are suggested to corroborate the computational findings.

• Plant production of high affinity nanobodies that block SARS-CoV-2 spike protein binding with its receptor, human angiotensin converting enzyme - Nanobodies^(®) (V(HH) antibodies), are small peptides that represent the antigen binding domain, V(HH) of unique single domain antibodies (heavy chain only antibodies, HcAb) derived from camelids. Here, we demonstrate production of V(HH) nanobodies against the SARS-CoV-2 spike proteins in the solanaceous plant Nicotiana benthamiana through transient expression and their subsequent detection verified through western blot. We demonstrate that these nanobodies competitively inhibit binding between…

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