Covid-19 Sentry

Contents

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

From Preprints

• Comparison of different isolation periods for preventing the spread of COVID-19: a rapid systematic review and a modelling study -

  Background: The optimal isolation duration for COVID-19 patients remains unclear. To support an update of WHO Living Clinical management guidelines for COVID-19 (https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2022.2), this rapid systematic review and modelling study addresses the effects of different isolation periods for preventing onward transmission leading to hospitalization and death among secondary cases. Methods: We searched World Health Organization (WHO) COVID-19 database for clinical studies evaluating the impact of isolation periods for COVID-19 patients up to July 28, 2022. We performed random-effects meta-analyses to summarize testing rates of persistent test positivity rates after COVID-19 infection. We developed a model to compare the effects of the five-day isolation and removal of isolation based on a negative antigen test with ten-day isolation on onward transmission leading to hospitalization and death. We assumed that patients with a positive test are infectious and those with a negative test are not. If the test becomes negative, patients will stay negative. The model included estimates of test positivity rates, effective reproduction number, and hospitalization rate or case fatality rate. Findings: Twelve studies addressing persistent test positivity rates including 2799 patients proved eligible. Asymptomatic patients (27.1%, 95% CI: 15.8% to 40.0%) had a significantly lower rapid antigen test (RAT) positive rate than symptomatic patients (68.1%, 95% CI: 40.6% to 90.3%) on day 5. The RAT positive rate was 21.5% (95% CI: 0 to 64.1%; moderate certainty) on day 10. Our modelling study suggested that the risk difference (RD) for asymptomatic patients between five-day isolation and ten-day isolation in hospitalization (2 more hospitalizations of secondary cases per 1000 patients isolated, 95% uncertainty interval (UI) 2 more to 3 more) and mortality (1 more per 1000 patients, 95% UI 0 to 1 more) of secondary cases proved very small (very low certainty). For symptomatic patients, the potential impact of five- versus ten-day isolation was much greater in hospitalizations (RD 19 more per 1000 patients, 95% UI 14 more to 24 more; very low certainty) and mortality (RD 5 more per 1000 patients, 95% UI 4 more to 6 more; very low certainty). There may be no difference between removing isolation based on a negative antigen test and ten-day isolation in the onward transmission leading to hospitalization or death, but the average isolation period (mean difference -3 days) will be shorter for the removal of isolation based on a negative antigen test (moderate certainty). Interpretation: Five versus 10 days of isolation in asymptomatic patients may result in a small amount of onward transmission and negligible hospitalization and mortality, but in symptomatic patients concerning transmission and resulting hospitalization and mortality. The evidence is, however, very uncertain.

  🖺 Full Text HTML: Comparison of different isolation periods for preventing the spread of COVID-19: a rapid systematic review and a modelling study
• The role of SARS-CoV-2 variants of concern in children and adolescents with COVID-19: a systematic review -

  Background: Infections by SARS-CoV-2 variants of concern (VOCs) might affect children and adolescents differently than earlier viral lineages. We aimed to address five questions about SARS-CoV-2 VOC infections in children and adolescents: i) symptoms and severity, ii) risk factors for severe disease, iii) the risk of becoming infected, iv) the risk of transmission and v) long-term consequences following a VOC infection. Methods: We carried out a systematic review. We searched the COVID-19 Open Access Project database up to 1 March 2022 and PubMed up to 9 May 2022 for observational epidemiological studies about alpha, beta, gamma, delta and omicron VOCs among 0 to 18 year olds. We synthesised data for each question descriptively and assessed the risks of bias at the outcome level. Results: We included 53 articles, of which 47% were from high-income countries and none were from low-income countries, according to World Bank categories. Most children with any VOC infection presented with mild disease, with more severe disease being described with the delta or the gamma VOC. Diabetes and obesity were reported as risk factors for severe disease during the whole pandemic period. The risk of becoming infected with a SARS-CoV-2 VOC seemed to increase with age, while in daycare settings the risk of onward transmission of VOCs was higher for younger than older children or at least partially vaccinated adults. Long-term symptoms or signs following an infection with a VOC were described in <5% of children and adolescents. Conclusion: Overall patterns of SARS-CoV-2 VOC infections in children and adolescents are similar to those of earlier lineages. Comparisons between different pandemic periods, countries and age groups should be improved with complete reporting of relevant contextual factors, including VOCs, vaccination status of study participants and the risk of exposure of the population to SARS-CoV-2.

  🖺 Full Text HTML: The role of SARS-CoV-2 variants of concern in children and adolescents with COVID-19: a systematic review
• Microfluidics-enabled fluorescence-activated cell sorting of single pathogen-specific antibody secreting cells for the rapid discovery of monoclonal antibodies -
  Monoclonal antibodies are increasingly used to prevent and treat viral infections, playing a pivotal role in pandemic response efforts. Antibody secreting cells (ASCs, plasma cells and plasmablasts) are an excellent source of high-affinity antibodies with therapeutic potential. Current methodologies to study antigen-specific ASCs either have low throughput, require expensive and labour-intensive screening or are technically demanding and therefore not accessible to the wider research community. Here, we present a straightforward technology for the rapid discovery of monoclonal antibodies from ASCs: we combine microfluidic encapsulation of single cells into an antibody capture hydrogel with antigen bait sorting by conventional flow cytometry. With our technology, we screened millions of mouse and human ASCs and obtained anti-SARS-CoV-2 monoclonal antibodies with high affinity (pM) and neutralising capacity (<100 ng/mL) in two weeks with a high hit rate (>85%). By facilitating access into the underexplored ASC compartment, we enable fast and efficient antibody discovery as well as immunological studies into the generation of protective antibodies.
  🖺 Full Text HTML: Microfluidics-enabled fluorescence-activated cell sorting of single pathogen-specific antibody secreting cells for the rapid discovery of monoclonal antibodies
• Independent regulation of Z-lines and M-linesduring sarcomere assembly in cardiac myocytesrevealed by the automatic image analysis software sarcApp -
  Sarcomeres are the basic contractile units within cardiac myocytes, and the collective shortening of sarcomeres aligned along myofibrils generates the force driving the heartbeat. The alignment of the individual sarcomeres is important for proper force generation, and misaligned sarcomeres are associated with diseases including cardiomyopathies and COVID-19. The actin bundling protein, -actinin-2, localizes to the Z-Bodies of sarcomere precursors and the Z-Lines of sarcomeres, and has been used previously to assess sarcomere assembly and maintenance. Previous measurements of -actinin-2 organization have been largely accomplished manually, which is time-consuming and has hampered research progress. Here, we introduce sarcApp, an image analysis tool that quantifies several components of the cardiac sarcomere and their alignment in muscle cells and tissue. We first developed sarcApp to utilize deep learning- based segmentation and real space quantification to measure -actinin-2 structures and determine the organization of both precursors and sarcomeres/myofibrils. We then expanded sarcApp to analyze M-Lines using the localization of myomesin and a protein that connects the Z-Lines to the M-Line (titin). sarcApp produces 33 distinct measurements per cell and 24 per myofibril that allow for precise quantification of changes in sarcomeres, myofibrils, and their precursors. We validated this system with perturbations to sarcomere assembly. Surprisingly, we found perturbations that affected Z-Lines and M-Lines differently, suggesting that they may be regulated independently during sarcomere assembly.
  🖺 Full Text HTML: Independent regulation of Z-lines and M-linesduring sarcomere assembly in cardiac myocytesrevealed by the automatic image analysis software sarcApp
• A Phase 2/3 study of S-217622 in participants with SARS-CoV-2 infection (Phase 3 part) -

  Background: Limited treatment options exist for patients with mild-to-moderate coronavirus disease 2019 (COVID-19), irrespective of vaccination history or risk status. Ensitrelvir is a novel oral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3C-like protease inhibitor. While phase 2 studies of ensitrelvir have demonstrated promising results in treating mild-to-moderate COVID-19, evaluation of its clinical efficacy due to shifting vaccination status and emergence of the Omicron variant represents significant challenges. Here, we describe the protocol for a phase 3 study designed to evaluate the efficacy and safety of ensitrelvir in patients with mild-to-moderate COVID-19, regardless of risk status or vaccination history. Methods: This is a multicenter, randomized, double-blind, placebo-controlled, phase 3 study. Patients with mild-to-moderate COVID-19 within 120 hours from onset will be randomized in a 1:1:1 ratio into 3 treatment arms-ensitrelvir 125 mg (375 mg loading dose on Day 1), ensitrelvir 250 mg (750 mg loading dose on Day 1), and placebo. The study interventions will be administered orally, once daily, for 5 days. The primary endpoint will be the time to resolution of 5 symptoms of COVID-19 (stuffy or runny nose, sore throat, cough, feeling hot or feverish, and low energy or tiredness), and the key secondary endpoints will include the change from baseline on Day 4 in the amount of SARS-CoV-2 viral RNA and the time to first negative SARS-CoV-2 viral titer. The primary population for the primary and key secondary endpoints will be patients with <72 hours from COVID-19 onset to randomization and, subsequently, patients in entire patient population (<120 hours) in the ensitrelvir 125 mg group. Closed testing procedure will be used for the primary and key secondary endpoints in both the primary and entire patient populations. All safety assessments and adverse events will be reported. Discussion: In a post hoc analysis of the phase 2b study, compared with placebo, ensitrelvir demonstrated a reduced time to resolution of 5 symptoms in patients with mild-to-moderate COVID-19. Through this study, we intend to validate and establish the efficacy and safety of ensitrelvir in patients with mild-to-moderate COVID-19. Trial registration: Japan Registry of Clinical Trials (https://jrct.niph.go.jp): jRCT2031210350.

  🖺 Full Text HTML: A Phase 2/3 study of S-217622 in participants with SARS-CoV-2 infection (Phase 3 part)
• Vectored Immunoprophylaxis and Treatment of SARS-CoV-2 Infection -
  Vectored immunoprophylaxis was first developed as a means to establish engineered immunity to HIV through the use of an adeno-associated viral vector expressing a broadly neutralizing antibody. We have applied this concept to establish long-term prophylaxis against SARS-CoV-2 by adeno-associated and lentiviral vectors expressing a high affinity ACE2 decoy receptor. Administration of decoy-expressing AAV vectors based on AAV2.retro and AAV6.2 by intranasal instillation or intramuscular injection protected mice against high-titered SARS-CoV-2 infection. AAV and lentiviral vectored immunoprophylaxis was durable and active against recent SARS-CoV-2 Omicron subvariants. The AAV vectors were also effective when administered up to 24 hours post-infection. Vectored immunoprophylaxis could be of value for immunocompromised individuals for whom vaccination is not practical and as a means to rapidly establish protection from infection. Unlike monoclonal antibody therapy, the approach is expected to remain active despite continued evolution viral variants.
  🖺 Full Text HTML: Vectored Immunoprophylaxis and Treatment of SARS-CoV-2 Infection
• The natural tannins oligomeric proanthocyanidins and punicalagin are potent inhibitors of infection by SARS-CoV-2 in vitro -
  The COVID-19 pandemic continues to infect people worldwide. While the vaccinated population has been increasing, the rising breakthrough infection persists in the vaccinated population. For living with the virus, the dietary guidelines to prevent virus infection are worthy of and timely to develop further. Tannic acid has been demonstrated to be an effective inhibitor of coronavirus and is under clinical trial. Here we found that two other members of the tannins family, oligomeric proanthocyanidins (OPCs) and punicalagin, are also potent inhibitors against SARS-CoV-2 infection with different mechanisms. OPCs and punicalagin showed inhibitory activity against omicron variants of SARS-CoV-2 infection. The water extractant of the grape seed was rich in OPCs and also exhibited the strongest inhibitory activities for viral entry of wild-type and other variants in vitro. Moreover, we evaluated the inhibitory activity of grape seed extractants (GSE) supplementation against SARS-CoV-2 viral entry in vivo and observed that serum samples from the healthy human subjects had suppressive activity against different variants of SARS-CoV-2 vpp infection after taking GSE capsules. Our results suggest that natural tannins acted as potent inhibitors against SARS-CoV-2 infection, and GSE supplementation could serve as healthy food for infection prevention.
  🖺 Full Text HTML: The natural tannins oligomeric proanthocyanidins and punicalagin are potent inhibitors of infection by SARS-CoV-2 in vitro
• Intranasal mRNA-LNP vaccination protects hamsters from SARS-CoV-2 infection -
  Intranasal vaccination represents a promising approach for preventing disease caused by respiratory pathogens by eliciting a mucosal immune response in the respiratory tract that may act as an early barrier to infection and transmission. This study investigated immunogenicity and protective efficacy of intranasally administered messenger RNA (mRNA)-lipid nanoparticle (LNP) encapsulated vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Syrian golden hamsters. Intranasal mRNA-LNP vaccination systemically induced spike-specific binding (IgG and IgA) and neutralizing antibodies with similar robustness to intramuscular controls. Additionally, intranasal vaccination decreased viral loads in the respiratory tract, reduced lung pathology, and prevented weight loss after SARS-CoV-2 challenge. This is the first study to demonstrate successful immunogenicity and protection against respiratory viral infection by an intranasally administered mRNA-LNP vaccine.
  🖺 Full Text HTML: Intranasal mRNA-LNP vaccination protects hamsters from SARS-CoV-2 infection
• 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
• DISPOSITION OF ADOLESCENTS TOWARD RECEIVING COVID-19 VACCINATIONS IN VILLAVICENCIO: MYTHS AND BELIEFS -

  Global efforts regarding the COVID-19 pandemic have been focused on preventive activities, such as vaccination, since the disease is expected to become endemic. Adolescents were among the last population groups to be included in the vaccination program in Colombia, and adequate coverage has not yet been achieved in this group and in infants. It is important to understand their motivations to improve the willingness of this population to be vaccinated. A cross-sectional study was designed via an online survey in adolescents aged 14–19 years in Villavicencio Meta after validation of the survey and informed consent. The following options were provided for the question on vaccine disposition: willing, undecided, and unwilling. We described the disposition toward receiving COVID-19 vaccine using graphs and absolute and relative frequencies based on age group. A multinomial regression model was used to assess the relationship between our predictor variables and vaccine disposition in adolescents.  In this study, 288 adolescents were surveyed. The risk variables for unwillingness to be vaccinated were being male (odds ratio [OR] 2.18, 95% confidence interval [CI] 0.8–5.7, p = 0.62), belonging to low social stratum (OR 2.29, 95% CI 0.9–5.88, p = 0.19), having a monthly  family income of less than 1 million Colombian pesos (250 USD) (OR 2.01, 95% CI 0.8–5.16, p = 0.19), and having basic education (OR 2.59, 95% CI 0.33–20.14, p = 0.18). Unproven myths and beliefs exert a profound influence on adolescents, which results in an unwillingness to be vaccinated. Hence, innovative public health strategies should be designed to improve the disposition to be vaccinated in this population group.

  🖺 Full Text HTML: DISPOSITION OF ADOLESCENTS TOWARD RECEIVING COVID-19 VACCINATIONS IN VILLAVICENCIO: MYTHS AND BELIEFS
• Mortality rates among hospitalized patients with COVID-19 treated with convalescent plasma: A Systematic review and meta-analysis -

  Abstract IMPORTANCE. Many hospitalized patients with COVID-19 have been treated with convalescent plasma. However, it is uncertain whether this therapy lowers mortality and if so, if the mortality benefit is larger among specific subgroups, such as recipients of plasma with high antibody content and patients treated early in the disease course. OBJECTIVE. To examine the association of COVID-19 convalescent plasma transfusion with mortality and the differences between subgroups in hospitalized patients with COVID-19. DATA SOURCES. On October 26, 2022, a systematic search was performed for clinical studies of COVID-19 convalescent plasma in the literature. STUDY SELECTION. Randomized clinical trials and matched cohort studies investigating COVID-19 convalescent plasma transfusion compared with standard of care treatment or placebo among hospitalized patients with confirmed COVID-19 were included. The electronic search yielded 3,841 unique records, of which 744 were considered for full-text screening. The selection process was performed independently by a panel of five reviewers. DATA EXTRACTION AND SYNTHESIS. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data were extracted by 5 independent reviewers in duplicate and pooled using inverse-variance random-effects model. MAIN OUTCOMES AND MEASURES. Prespecified end point was all-cause mortality during hospitalization. RESULTS. Thirty-nine randomized clinical trials enrolling 21,529 participants and 70 matched cohort studies enrolling 50,160 participants were included in the systematic review. Separate meta-analyses demonstrated that transfusion of COVID-19 convalescent plasma was associated with a significant decrease in mortality compared with the control cohort for both randomized clinical trials (odds ratio (OR), 0.87 [95% CI, 0.76-1.00]) and matched cohort studies (OR, 0.77 [95% CI, 0.64-0.94]). Meta-analysis of subgroups revealed two important findings. First, treatment with convalescent plasma containing high antibody levels was associated with a decrease in mortality compared to convalescent plasma containing low antibody levels (OR, 0.85 [95% CI, 0.73 to 0.99]). Second, earlier treatment with COVID-19 convalescent plasma was associated with a significant decrease in mortality compared with the later treatment cohort (OR, 0.63 [95% CI, 0.48 to 0.82]). CONCLUSIONS AND RELEVANCE. COVID-19 convalescent plasma use was associated with a 13% reduced risk in mortality, implying a mortality benefit for hospitalized patients with COVID-19, particularly those treated with convalescent plasma containing high antibody levels treated earlier in the disease course.

  🖺 Full Text HTML: Mortality rates among hospitalized patients with COVID-19 treated with convalescent plasma: A Systematic review and meta-analysis
• COVID-19 Policies’ Impact on House Cleaners’ Workplace Precarity -
  The COVID-19 pandemic increased the volume of precarious work (i.e. work that is unstable, often without social/legal protections) across many industries, including for domestic workers. House cleaners face particularly precarious conditions due to being predominantly marginalized (i.e. lower socio-economic status, racial/ethnic minorities, non-native English speakers) women, often with informal contracts. The present grounded-theory qualitative study elucidates how COVID-19 policies in two different US cities (Boston, MA and Dallas, TX) affected precarity in house cleaners’ work. Dallas had far less strict COVID-19 policies (e.g., shorter mask mandates and quicker business re-openings) compared to Boston. In each city, house cleaners (n=10 in Dallas and n=8 in Boston) participated in 15-35 minute semi-structured interviews over Zoom or phone. Participants were asked about their working relationships during COVID-19, as well as how they coped with health safety and payments. House cleaners reported that the COVID-19 increased the precarity of their work in three essential ways: (1) furloughs and firings without protections (2) duress around their health and safety while at work, and (3) increased awareness of existing power structures in their employer-employee relationships. However, Dallas house cleaners reported shorter furloughs, higher rates of discomfort around safety, and more instances of a new awareness in power structures than their Boston counterparts, demonstrating differences in precarity based on local COVID-19 policies and employer attitudes. Importantly, precarity in work can result in negative psychological outcomes such as anxiety and depression and a lack of dignity.
  🖺 Full Text HTML: COVID-19 Policies’ Impact on House Cleaners’ Workplace Precarity
• COVID-19 NFL Injury Prevalence Analysis, A Follow-Up Study -

  Background In 2020, COVID-19 spread across the world and brought the world to a halt, causing the shutdown of nearly everything in order to prevent its spread. The NFL, like most of the world, faced shutdowns leaving athletes unable to train in some of the most advanced facilities with many of the best trainers in the world. Through a previous study, COVID-19 Return to Sport Injury Prevalence Analysis, it was determined that there was increased injury prevalence during the 2020 season likely due to decreased physiological adaptations within athletes bodies that resulted from facility shutdowns. Understanding injury epidemiology is vital in the prevention of injuries and the development of return-to-play protocols. Objective: The objective of this study is to perform a follow up study to COVID-19 Return to Sport Injury Prevalence Analysis in order to to examine the longitudinal effects of the COVID-19 pandemic on injury epidemiology. This study will examine if there was a recovery to baseline or lingering effects from the COVID-19 pandemic-induced spike in injuries. Methods Injury tallies collected from the 17-week-long 2020 NFL regular season, played after COVID-19 restrictions, were compared with the injury tallies collected from the 18-week-long NFL regular seasons (2021, 2022), in order to determine if there was a change in injury prevalence. An unpaired t-test was conducted to compare the mean injuries per team per week between each of the 2020, 2021, and 2022 regular seasons. Results The 2022 and 2021 NFL regular seasons produced lower numbers of total injuries than the 2020 NFL regular season that was impacted by COVID-19. The comparison of the mean number of injuries per team per week of the 2020 season compared with the 2021 regular season was statistically significant (P=.03). The comparison of the 2020 and 2022 regular seasons was also statistically significant (P=.02). Conclusions The results of this follow-up study and our previous study show that extended training interruptions have the ability to induce detraining and lead to increased injuries. Additionally, the results of this study show that retraining can occur and lead to injury protective factors. This is the first large scale opportunity to demonstrate the effects of these principles and how they are important to understanding injury epidemiology.

  🖺 Full Text HTML: COVID-19 NFL Injury Prevalence Analysis, A Follow-Up Study
• Safety and Efficacy of Oral administrated Cepharathine in Non-hospitalized, asymptomatic or mild COVID-19 patients: A Double-blind, Randomized, Placebo-controlled Trial -

  Cepharanthine (CEP) is a natural remedy that potently inhibits SARS-CoV-2 activity both in vitro and in vivo. We conducted a proof-of-concept, double-blind, randomized, placebo-controlled trial among adults with asymptomatic or mild coronavirus disease 2019 (COVID-19). Patients were stratified randomly to de novo infection or viral rebound, and assigned in a 1:1:1 ratio to receive 60 mg/day or 120 mg/day of CEP or placebo. Primary outcome the time from randomization to negative nasopharyngeal swab, and safety were evaluated. A total of 262 de novo infected and 124 viral rebound patients underwent randomization. In the 188 de novo patients included in modified intention-to-treat (mITT) population, when compared with placebo, 60 mg/day CEP slightly shortened the time to negative (difference=-0.77 days, hazard ratio (HR)=1.40, 95% CI 0.97 to 2.01, p=0.072), and 120 mg/day CEP did not show the trend. Among de novo patients in the per-protocol set (PPS), 60 mg/day CEP significantly shortened the time to negative (difference=-0.87 days, HR=1.56, 95% CI 1.03 to 2.37, p=0.035). Among viral rebound patients in the mITT population, neither 120 mg/day nor 60 mg/day CEP significantly shortened the time to negative compared to placebo. Adverse events were not different among the three groups, and no serious adverse events occurred. Treatment of asymptomatic or mild Covid-19 with 120 mg/day or 60 mg/day CEP did not shorten the time to negative compared with placebo, without evident safety concerns. Among de novo infected patients with good compliance, 60 mg/day CEP significantly shortened the time to negative compared with placebo (NCT05398705).

  🖺 Full Text HTML: Safety and Efficacy of Oral administrated Cepharathine in Non-hospitalized, asymptomatic or mild COVID-19 patients: A Double-blind, Randomized, Placebo-controlled Trial
• Effectiveness of second booster compared to first booster and protection conferred by previous SARS CoV-2 infection against symptomatic Omicron BA.2 and BA.4/5 in France -

  In face of evidence of rapid waning of vaccine effectiveness against Omicron and its sub-lineages, a second booster with mRNA vaccines was recommended for the most vulnerable in France. We used a test negative design to estimate the effectiveness of the second booster relative to the first booster and the protection conferred by a previous SARS-CoV-2 infection, against symptomatic Omicron BA.2 or BA.4/5. We included symptomatic ≥60 years old individuals tested for SARS-CoV-2 in March 21-October 30, 2022. Compared to a 181-210 days old first booster, a second booster restored protection with an effectiveness of 39% [95%CI: 38% - 41%], 7-30 days post-vaccination This gain in protection was lower than the one observed with the first booster, at equal time points since vaccination. High levels of protection were associated to previous SARS-CoV-2 infection, especially if the infection was recent and occurred when an antigenic-related variant was dominant.

  🖺 Full Text HTML: Effectiveness of second booster compared to first booster and protection conferred by previous SARS CoV-2 infection against symptomatic Omicron BA.2 and BA.4/5 in France

From Clinical Trials

• Postural Changes and Severe COVID-19 - Condition:   COVID-19
  Intervention:   Behavioral: Postural interventions based on pulmonary imaging
  Sponsor:   Wuhan Union Hospital, China
  Not yet recruiting

• 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

• Study on the Safety and Efficacy of Meplazumab for Injection in Severe Patients With COVID-19 - Condition:   COVID-19
  Interventions:   Biological: Meplazumab for injection;   Other: Normal saline
  Sponsor:   Jiangsu Pacific Meinuoke Bio Pharmaceutical Co Ltd
  Not yet 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

• Study on the Safety and Efficacy of Meplazumab for Injection in Adults With Mild and Moderate COVID-19 Infections - Condition:   COVID-19
  Interventions:   Biological: Meplazumab foe injection;   Other: Normal saline
  Sponsor:   Jiangsu Pacific Meinuoke Bio Pharmaceutical Co Ltd
  Not yet recruiting

• 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

• UC-MSCs in the Treatment of Severe and Critical COVID-19 Patients - Conditions:   Mesenchymal Stem Cell;   COVID-19 Pneumonia
  Interventions:   Biological: umbilical cord mesenchymal stem cells;   Drug: paxlovid
  Sponsor:   Shanghai East Hospital
  Recruiting

• An Investigator Initiated, Randomized, Double-blinded, Placebo-controlled Clinical Trial to Evaluate the Safety, Immunogenicity and Efficacy of the Recombinant Two-component COVID-19 Vaccine (CHO Cell) in Adults Aged 18 Years and Older - Condition:   Prevention of COVID-19 Caused by SARS-CoV-2
  Intervention:   Biological: randomized, double-blinded, placebo-controlled
  Sponsor:   Yu Qin
  Active, not recruiting

• Evaluate the Efficacy and Safety of Azvudine in Preventing SARS-Cov-2 Infection in Ousehold in China - Condition:   COVID-19
  Interventions:   Drug: Azvudine;   Drug: Placebo
  Sponsors:   Shanghai Henlius Biotech;   Huashan Hospital;   Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.;   HeNan Sincere Biotech Co., Ltd
  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

From PubMed

• Toll-Like Receptor 4-Dependent Platelet-Related Thrombosis in SARS-CoV-2 Infection - CONCLUSIONS: The study identifies 2 TLR4-dependent and independent pathways promoting platelet-dependent thrombus growth and suggests inhibition of TLR4. or p47phox as a tool to counteract thrombosis in SARS-CoV-2.

• How to achieve carbon neutrality while maintaining economic vitality: An exploration from the perspective of technological innovation and trade openness - The significant drop in global carbon emissions in 2020 was credited to the enormous loss of economic activity from the impact of COVID-19. The challenge is now to reduce carbon emissions without causing massive disruption and damage to economic production. To achieve carbon neutrality while maintaining economic vitality, the impact of technological innovation and trade openness must be considered. This paper sets technological innovation and trade openness as core variables and establishes two…

• Molecular mechanisms in chloroquine-exposed muscle cells elucidated by combined proteomic and microscopic studies - CONCLUSION: We demonstrated that CQ exposure (secondarily) impacts biological processes beyond lysosomal function and linked a variety of proteins with known roles in the manifestation of other neuromuscular diseases.

• Predicting the systemic exposure and lung concentration of nafamostat using physiologically-based pharmacokinetic modeling - Nafamostat has been actively studied for its neuroprotective activity and effect on various indications, such as coronavirus disease 2019 (COVID-19). Nafamostat has low water solubility at a specific pH and is rapidly metabolized in the blood. Therefore, it is administered only intravenously, and its distribution is not well known. The main purposes of this study are to predict and evaluate the pharmacokinetic (PK) profiles of nafamostat in a virtual healthy population under various dosing…

• Pharmacokinetic/Pharmacodynamic Modeling of Dexamethasone Anti-Inflammatory and Immunomodulatory Effects in LPS-Challenged Rats: A Model for Cytokine Release Syndrome - Dexamethasone (DEX) is a potent synthetic glucocorticoid used for the treatment of variety of inflammatory and immune-mediated disorders. The RECOVERY clinical trial revealed benefits of DEX therapy in COVID-19 patients. Severe SARS-CoV-2 infection leads to an excessive inflammatory reaction commonly known as a cytokine release syndrome that is associated with activation of the toll like receptor 4 (TLR4) signaling pathway. The possible mechanism of action of DEX in the treatment of COVID-19 is…

• P2Y12 Inhibition Suppresses Proinflammatory Platelet-Monocyte Interactions - BACKGROUND: Monocyte-platelet aggregates (MPAs) represent the crossroads between thrombosis and inflammation, and targeting this axis may suppress thromboinflammation. While antiplatelet therapy (APT) reduces platelet-platelet aggregation and thrombosis, its effects on MPA and platelet effector properties on monocytes are uncertain.

• 4-Aminoquinolines modulate RNA structure and function: Pharmacophore implications of a conformationally restricted polyamine - RNA structure plays an important role in regulating cellular function and there is a significant emerging interest in targeting RNA for drug discovery. Here we report the identification of 4-aminoquinolines as modulators of RNA structure and function. Aminoquinolines have a broad range of pharmacological activities, but their specific mechanism of action is often not fully understood. Using electrophoretic mobility shift assays and enzymatic probing we identified 4-aminoquinolines that bind the…

• Sleep as a protective factor of children’s executive functions: A study during COVID-19 confinement - Confinements due to the COVID-19 outbreak affected sleep and mental health of adults, adolescents and children. Already preschool children experienced acutely worsened sleep, yet the possible resulting effects on executive functions remain unexplored. Longitudinally, sleep quality predicts later behavioral-cognitive outcomes. Accordingly, we propose children’s sleep behavior as essential for healthy cognitive development. By using the COVID-19 confinement as an observational-experimental…

• A Novel Y-Shaped, S-O-N-O-S-Bridged Cross-Link between Three Residues C22, C44, and K61 Is Frequently Observed in the SARS-CoV-2 Main Protease - As the COVID-19 pathogen, SARS-CoV-2 relies on its main protease (M^(Pro)) for pathogenesis and replication. During crystallographic analyses of M^(Pro) crystals that were exposed to the air, a uniquely Y-shaped, S-O-N-O-S-bridged post-translational cross-link that connects three residues C22, C44, and K61 at their side chains was frequently observed. As a novel covalent modification, this cross-link serves potentially as a redox switch to regulate the catalytic activity of M^(Pro), a…

• 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…

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