Third doses of COVID-19 vaccines were widely deployed following primary vaccine course waning and emergence of the Omicron-variant. We investigated protection from third-dose vaccines and previous infection against SARS-CoV-2 infection during Delta-variant and Omicron-variant (BA.1 & BA.2) waves in our frequently PCR-tested cohort of healthcare-workers. Relative effectiveness of BNT162b2 third doses and infection-acquired immunity was assessed by comparing the time to PCR-confirmed infection in boosted participants with those with waned dose-2 protection (≥254 days after dose-2). Follow-up time was divided by dominant circulating variant: Delta 07 September 2021 to 30 November 2021, Omicron 13 December 2021 to 28 February 2022. We used a Cox regression model with adjustment/stratification for demographic characteristics and staff-type. We explored protection associated with vaccination, infection and both. We included 19,614 participants, 29% previously infected. There were 278 primary infections (4 per 10,000 person-days of follow-up) and 85 reinfections (0.8/10,000 person-days) during the Delta period and 2467 primary infections (43/10,000 person-days) and 881 reinfections (33/10,000) during the Omicron period. Relative Vaccine Effectiveness (VE) 0-2 months post-3rd dose (V3) (3-doses BNT162b2) in the previously uninfected cohort against Delta infections was 63% (95% Confidence Interval (CI) 40%-77%) and was lower (35%) against Omicron infection (95% CI 21%-47%). For primary course ChAdOX1 recipients, BNT162b2 heterologous third doses were especially effective, with VE 0-2 months post-V3 over ≥68% higher for both variants. Third-dose protection waned rapidly against Omicron, with no significant difference between two and three BNT162b2 doses observed after 4-months. Previous infection continued to provide additional protection against Omicron (67% (CI 56%-75%) 3-6 months post-infection), but this waned to about 25% after 9-months, approximately three times lower than against Delta. Infection rates surged with Omicron emergence. Third doses of BNT162b2 vaccine provided short-term protection, with rapid waning against Omicron infections. Protection associated with infections incurred before Omicron was markedly diminished against the Omicron wave. Our findings demonstrate the complexity of an evolving pandemic with potential emergence of immune-escape variants and the importance of continued monitoring.
Introduction: During the COVID-19 pandemic, a digital transformation led to an expansion in telenursing practices and a shift in training to online learning. The aim of this study was to explore the impact of behavioral-related factors, based on both TAM and TPB variables, on the intention to use telenursing through videoconferencing and to compare the effect of frontal (before COVID-19) vs. online (during and after COVID-19) training in post-basic nursing courses on nursing attitudes to telenursing. Methods: A cross-sectional online survey was conducted in December 2022 among nurses working mainly at hospitals in Israel who underwent post-basic education training between January 2017 and December 2022. A multivariate ordinary least squares (OLS) regression analysis was used to investigate determinants of intention to use telenursing through videoconferencing Results: Nurses have a positive attitude towards telenursing technology via videoconferencing for remote patient care, regardless of whether they learned about it through face-to-face or online training. The ease of use and the perception of the technology9s importance by colleagues and supervisors were found to have the most significant impact on the attitude of both research groups towards the use of telelearning. Discussion: Successful implementation of new technology in healthcare requires organizational and collegial support. Therefore, managers should encourage the use of telenursing by providing appropriate training for nurses and the necessary resources and support.
During the pandemic of COVID-19, wastewater-based epidemiology has become a powerful epidemic surveillance tool widely used around the world. However, the development and application of this technology in Chinese Mainland are relatively lagging. Herein, we report the first case of community circulation of SARS-CoV-2 lineages monitored by WBE in Chinese Mainland during the infection outbreak at the end of 2022 after the comprehensive relaxation of epidemic prevention policies. During the peak period of infection, six precious sewage samples were collected from the manhole in the student dormitory area of Wangjiang Campus of Sichuan University. According to the results RT-qPCR, the six sewage samples were all positive for SARS-CoV-2 RNA. Based on multiplex PCR amplicon sequencing, the local transmission of SARS-CoV-2 variants at that time was analyzed. The results show that the main virus lineages in sewage have clear evolutionary genetic correlations. Furthermore, the sampling time is very consistent with the timeline of concern for these virus lineages and consistent with the timeline for uploading the nucleic acid sequences of the corresponding lineages in Sichuan to the database. These results demonstrate the reliability of the sequencing results of SARS-CoV-2 nucleic acid in wastewater. Multiplex PCR amplicon sequencing is by far the most powerful analytical tool of WBE, enabling quantitative monitoring of virus lineage prevalence at the community level.
Objectives: This study aims to assess the progress of geographic, socioeconomic, and demographic disparities in Covid-19 vaccination coverage in Brazil over the first two years of the vaccination campaign. Methods: Data from the National Immunization Program Information System were used to estimate covid-19 vaccine coverage. Brazilian municipalities were divided into two groups based on their vaccine coverage for the booster dose. The first group comprised 20% of municipalities with the lowest coverage, while the second group (80% of municipalities) had higher coverage. The analysis was conducted separately for four age groups: 5-11, 12-17, 18-59, and 60+. Exploratory variables included socioeconomic and health services indicators. Crude and adjusted logistic regression models were used to estimate the probability of a municipality being among those with the worst vaccination coverage according to the categories of exploratory variables. Results: Between January/2021 and December/2022, Brazil administered 448.2 million doses of the covid-19 vaccine. The booster vaccination coverage varied from 24.8% among adolescents to 79.7% among the elderly. The difference between the group with the highest and lowest coverage increased during the national vaccination campaign. Municipalities with lower education levels, higher proportion of Black population, higher Gini index, and worse health service indicators had a greater likelihood of having lower vaccination coverage. Conclusions: High and increasing levels of inequality in Covid-19 vaccination were observed in Brazil across all age groups during the vaccination campaign in 2021-2022.
Long COVID corresponds to the occurrence of symptoms beyond twelve weeks after the onset of acute COVID-19 illness. The study aimed to analyze impacts of long COVID on the general health and psychosocial well-being of the Pakistani population. This cross-sectional study aimed to analyse the impacts of long COVID on general health and psychosocial well-being. For this study, the participants were interviewed, and their responses were recorded on a questionnaire capturing information on demographics, COVID-19 status, duration of symptoms and long COVID symptoms. The psychological impacts of the pandemic were assessed using scales like Short Mood and feeling questionnaire (sMFQ), Warwick-Edinburgh Mental Well-being Scale (WEMWBS), Generalized Anxiety Disorder Assessment (GAD-7) and Perceived Stress Scale (PSS). Regression analysis was conducted to analyse the predictors of long COVID. A total of 300 participants were interviewed, of which 155 (52%) had COVID-19 illness. Of these 54 (35%) had persistent symptoms for a period of more than 12 weeks classified as long COVID. Muscle problems and fatigue were the most frequent (14.7%) symptoms encountered, followed by breathing problems (12.6%) and cognitive issues (12.6%). Symptoms such as decrease in appetite and confusion or disorientation during the initial phase of the infection were associated with long COVID. Majority of the participants (83.3%) had moderate level of perceived stress while moderate to severe levels of stress was observed in 17.3% of the individuals. Moreover, a high level positive mental wellbeing was also observed.
Background: Health services planning and mechanism-focused research would benefit from a clearer picture of symptoms, impact, and personal priorities in post-COVID-19 syndrome (PCS). This study aimed to provide estimates of the symptom, function, and quality of life (QOL) impact of PCS. Methods: People living in Quebec, aged 18 and over, were eligible for the Quebec Action for/pour le Post-COVID (QAPC) study if they had symptoms lasting more than 4 weeks post-acute SARS-CoV-2 infection, with or without a positive COVID-19 test. Recruitment was through conventional and social media between September 2022-January 2023. Standardized and individualized questionnaires, in French or English, were accessed through an online portal. We report cross-sectional results from the baseline visit of the first 414 participants in this ongoing longitudinal study. Results: Individuals spontaneously reported symptoms attributable to an average of 4.5 organ systems. Fatigue was most frequent. Effects on function and quality of life were moderate to severe, and had already persisted for a year or more in the majority. Personal intervention priorities included fatigue and post-exercise malaise, cognitive symptoms, shortness of breath, and impaired taste and smell. Women and men were similar on PCS impact, while older age was associated with lower impact. Interpretation: Symptom clusters defined a range of severity, with fatigue a pervasive symptom at all levels of severity. Participants in this study are likely to be representative of those seeking health care for post-COVID-19 symptoms in Canada and the results can inform next steps for clinical, research, and health services planning.
Background: Long-term sequelae of COVID-19 (long COVID) include muscle weakness, fatigue, breathing difficulties and sleep disturbance over weeks or months. Using UK longitudinal data, we assessed the relationship between long COVID and financial disruption. Methods: We estimated associations between long COVID (derived using self-reported length of COVID-19 symptoms) and measures of financial disruption (subjective financial well-being, new benefit claims, changes in household income) by analysing data from four longitudinal population studies, gathered during the first year of the pandemic. We employed modified Poisson regression in a pooled analysis of the four cohorts adjusting for a range of potential confounders, including pre-pandemic (pre-long COVID) factors. Results: Among 20,112 observations across four population surveys, 13% reported having COVID-19 with symptoms that impeded their ability to function normally - 10.7% had such symptoms for <4 weeks (acute COVID-19), 1.2% had such symptoms for 4-12 weeks (ongoing symptomatic COVID-19) and 0.6% had such symptoms for >12 weeks (post-COVID-19 syndrome). We found that post-COVID-19 syndrome was associated with worse subjective financial well-being (adjusted relative risk ratios (aRRR)=1.57, 95% confidence interval (CI)=1.25, 1.96) and new benefit claims (aRRR=1.79, CI=1.27, 2.53). Associations were broadly similar across sexes and education levels. These results were not meaningfully altered when scaled to represent the population by age. Conclusions: Long COVID was associated with financial disruption in the UK. If our findings reflect causal effects, extending employment protection and financial support to people with long COVID may be warranted.
Routinely collected testing data has been a vital resource for public health response during the COVID-19 pandemic and has revealed the extent to which Black and Hispanic persons have borne a disproportionate burden of SARS-CoV-2 infections and hospitalizations in the United States. However, missing race and ethnicity data and missed infections due to testing disparities limit the interpretation of testing data and obscure the true toll of the pandemic. We investigated potential bias arising from these two types of missing data through a case study in Holyoke, Massachusetts during the pre-vaccination phase of the pandemic. First, we estimated SARS-CoV-2 testing and case rates by race/ethnicity, imputing missing data using a joint modelling approach. We then investigated disparities in SARS-CoV-2 reported case rates and missed infections by comparing case rate estimates to estimates derived from a COVID-19 seroprevalence survey. Compared to the non-Hispanic white population, we found that the Hispanic population had similar testing rates (476 vs. 480 tested per 1,000) but twice the case rate (8.1% vs. 3.7%). We found evidence of inequitable testing, with a higher rate of missed infections in the Hispanic population compared to the non-Hispanic white population (77 vs. 58 infections missed per 1,000).
Introduction: The recurrent multi-wave nature of COVID-19 necessitates updating its symptomatology. Before the omicron era, Hong Kong was relatively unscathed and had a low vaccine uptake rate among the old-old, giving us an opportunity to study the intrinsic severity of SARS-CoV-2 variants. A comparison of symptom patterns across variants and vaccination status in Hong Kong has yet to be undertaken. The intrinsic severity of variants and symptoms predictive of severe outcomes are also understudied as COVID-19 evolves. We therefore aim to characterize the effect of variants on symptom presentation, identify the symptoms predictive and protective of death, and quantify the effect of vaccination on symptom development. Methods: With the COVID-19 case series in Hong Kong from inception to 25 August 2022, an iterative multi-tier text-matching algorithm was developed to identify symptoms from free text. Cases were fully vaccinated if they completed two doses. Multivariate regression was used to measure associations between variants, symptom development, death and vaccination status. A least absolute shrinkage and selection operator technique was used to identify a parsimonious set of symptoms jointly associated with death. Results: Overall, 70.9% (54450/76762) of cases were symptomatic. We identified a wide spectrum of symptoms (n=102), with cough, fever, runny nose and sore throat being the most common (8.16-47.0%). Intrinsically, the wild-type and delta variant caused similar symptoms, with runny nose, sore throat, itchy throat and headache more frequent in the delta cohort; whereas symptoms were heterogeneous between the wild-type and omicron variant, with seven symptoms (fatigue, fever, chest pain, runny nose, sputum production, nausea/vomiting and sore throat) more frequent in the omicron cohort. With full vaccination, omicron was still more likely than delta to cause fever. Fever, blocked nose and shortness of breath were robustly jointly predictive of death as the virus evolved. Number of vaccine doses required for reduction in occurrence varied by symptoms. Discussion: This is the first large-scale study to evaluate the changing symptomatology by COVID-19 variants and vaccination status using free-text reporting by patients. We substantiate existing findings that omicron has a different clinical presentation compared to previous variants. Syndromic surveillance can be bettered with reduced reliance on symptom-based case identification, increased weighing on symptoms robustly predictive of mortality in outcome prediction, strengthened infection control in care homes through universal individual-based risk assessment to enable early risk stratification, adjusting the stockpile of medicine to tally with the changing symptom profiles across vaccine doses, and incorporating free-text symptom reporting by patients.
Importance: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis. Methods: RECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms. Discussion: RECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options.
Background: There are limited studies evaluating the impact of COVID-19-related interruptions on hepatitis B virus (HBV) screening in endemic countries in Sub-Saharan Africa. Methods: We conducted a retrospective study of HBV testing in a community pharmacy in Freetown, Sierra Leone, from October 1, 2019, through September 30, 2022. We compared participant characteristics using Pearson9s chi-square test. We evaluated trends in HBV screening and diagnosis using one-way ANOVA with Tukey9s or Dunnett9s post-test. Results: Of 920 individuals screened, 161 had detectable HBsAg (seroprevalence 17.5% [95% CI 14.9-20.4]). There was a 100% decrease in HBV screening during January-June of 2020; however, screening increased by 27% and 23% in the first and second year after COVID-19, respectively. Mean quarterly tests showed a significant upward trend: 55 − 6 tests during January-March (baseline), 74 − 16 tests during April-June, 101 − 3 tests during July-September, and 107 − 17 tests during October-December (one-way ANOVA test for trend, F = 7.7, p = 0.0254) but not the mean quarterly number of people diagnosed with HBV (F = 0.34, p = 0.7992). Conclusion: Community-based HBV screening dramatically improved following temporary disruptions related to COVID-19. Seasonal variation in HBV screening, but not HBV diagnosis, may have implications for HBV elimination efforts in Sierra Leone and other West African countries.
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
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
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
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
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
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
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
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
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
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
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
Anti-SARS-CoV-2 Monoclonal Antibodies for Long COVID (COVID-19) - Conditions: Long COVID; Post-Acute Sequela of COVID-19; Post-Acute COVID-19
Interventions: Drug: AER002; Other: Placebo
Sponsors: Michael Peluso, MD; Aerium Therapeutics
Not yet recruiting
SARS-CoV-2 ORF3a sensitizes cells to ferroptosis via Keap1-NRF2 axis - Viral infection-induced cell death has long been considered as a double-edged sword in the inhibition or exacerbation of viral infections. Patients with severe Coronavirus Disease 2019 (COVID-19) are characterized by multiple organ dysfunction syndrome and cytokine storm, which may result from SARS-CoV-2-induced cell death. Previous studies have observed enhanced ROS level and signs of ferroptosis in SARS-CoV-2 infected cells or specimens of patients with COVID-19, but the exact mechanism is not…
Utilization of Marine Seaweeds as a Promising Defense Against COVID-19: a Mini-review - COVID-19 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which mainly affects the respiratory system. It has been declared as a “pandemic” in March 2020 by the World Health Organization due to the high spreading rate. SARS-CoV-2 binds with the angiotensin-converting enzyme 2 (ACE2) receptors on the cell surface which leads to the downregulation of ACE2 and upregulation of angiotensin-converting enzyme (ACE) receptors. The elevated level of…
Identification of Host Proteins Interacting with IBV S1 Based on Tracheal Organ Culture - Infectious bronchitis virus (IBV) belongs to the gamma-coronavirus genus of Coronaviridae and causes serious infectious diseases in the poultry industry. However, only a few IBV strains can infect avian passage cell lines, seriously hindering the progress of basic research on IBV pathogenesis. Whereas IBV field strains can replicate in tracheal ring organ culture (TOC) without any previous adaptation in chicken embryos or primary cells. In this study, to investigate the potential use of TOC as…
Transcription Factor Driven Gene Regulation in COVID-19 Patients - SARS-CoV-2 and its many variants have caused a worldwide emergency. Host cells colonised by SARS-CoV-2 present a significantly different gene expression landscape. As expected, this is particularly true for genes that directly interact with virus proteins. Thus, understanding the role that transcription factors can play in driving differential regulation in patients affected by COVID-19 is a focal point to unveil virus infection. In this regard, we have identified 19 transcription factors which…
Genes Involved in miRNA Biogenesis Are Not Downregulated in SARS-CoV-2 Infection - miRNAs, small non-coding RNAs that regulate gene expression, are involved in various pathological processes, including viral infections. Virus infections may interfere with the miRNA pathway through the inhibition of genes involved in miRNA biogenesis. A reduction in the number and the levels of miRNAs expressed in nasopharyngeal swabs of patients with severe COVID-19 was lately observed by us, pointing towards the potential of miRNAs as possible diagnostic or prognostic biomarkers for…
In Silico and In Vitro Evaluation of Some Amidine Derivatives as Hit Compounds towards Development of Inhibitors against Coronavirus Diseases - Coronaviruses, including SARS-CoV-2, SARS-CoV, MERS-CoV and influenza A virus, require the host proteases to mediate viral entry into cells. Rather than targeting the continuously mutating viral proteins, targeting the conserved host-based entry mechanism could offer advantages. Nafamostat and camostat were discovered as covalent inhibitors of TMPRSS2 protease involved in viral entry. To circumvent their limitations, a reversible inhibitor might be required. Considering nafamostat structure and…
The Dimeric Peptide (KKYRYHLKPF)2K Shows Broad-Spectrum Antiviral Activity by Inhibiting Different Steps of Chikungunya and Zika Virus Infection - Chikungunya virus (CHIKV) and Zika virus (ZIKV) are important disease-causing agents worldwide. Currently, there are no antiviral drugs or vaccines approved to treat these viruses. However, peptides have shown great potential for new drug development. A recent study described (p-BthTX-I)(2)K [(KKYRYHLKPF)(2)K], a peptide derived from the Bothropstoxin-I toxin in the venom of the Bothrops jararacussu snake, showed antiviral activity against SARS-CoV-2. In this study, we assessed the activity of…
GRP78 Inhibitor YUM70 Suppresses SARS-CoV-2 Viral Entry, Spike Protein Production and Ameliorates Lung Damage - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19 pandemic, has given rise to many new variants with increased transmissibility and the ability to evade vaccine protection. The 78-kDa glucose-regulated protein (GRP78) is a major endoplasmic reticulum (ER) chaperone that has been recently implicated as an essential host factor for SARS-CoV-2 entry and infection. In this study, we investigated the efficacy of YUM70, a small molecule inhibitor of…
IgG4 Antibodies Induced by Repeated Vaccination May Generate Immune Tolerance to the SARS-CoV-2 Spike Protein - Less than a year after the global emergence of the coronavirus SARS-CoV-2, a novel vaccine platform based on mRNA technology was introduced to the market. Globally, around 13.38 billion COVID-19 vaccine doses of diverse platforms have been administered. To date, 72.3% of the total population has been injected at least once with a COVID-19 vaccine. As the immunity provided by these vaccines rapidly wanes, their ability to prevent hospitalization and severe disease in individuals with…
Long COVID and Hybrid Immunity among Children and Adolescents Post-Delta Variant Infection in Thailand - This study aimed to assess long COVID, and describe immunogenicity against Omicron variants following BNT162b2 vaccination. A prospective cohort study was conducted among children (aged 5-11) and adolescents (aged 12-17) who had SARS-CoV-2 infection from July to December 2021 (Delta predominant period). Long COVID symptoms were assessed by questionnaires at 3 months after infection. Immunogenicity was evaluated by using a surrogate virus-neutralizing antibody test (sVNT) against the Omicron…
Natural Product-Based Screening for Lead Compounds Targeting SARS CoV-2 Mpro - Drugs that cure COVID-19 have been marketed; however, this disease continues to ravage the world without becoming extinct, and thus, drug discoveries are still relevant. Since M^(pro) has known advantages as a drug target, such as the conserved nature of the active site and the absence of homologous proteins in the body, it receives the attention of many researchers. Meanwhile, the role of traditional Chinese medicine (TCM) in the control of epidemics in China has also led to a focus on natural…
Hydroxypropyl-β-Cyclodextrin Depletes Membrane Cholesterol and Inhibits SARS-CoV-2 Entry into HEK293T-ACEhi Cells - Vaccination has drastically decreased mortality due to coronavirus disease 19 (COVID-19), but not the rate of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Alternative strategies such as inhibition of virus entry by interference with angiotensin-I-converting enzyme 2 (ACE2) receptors could be warranted. Cyclodextrins (CDs) are cyclic oligosaccharides that are able to deplete cholesterol from membrane lipid rafts, causing ACE2 receptors to relocate to areas devoid of lipid…
Discovery of Chalcone-Based Hybrid Structures as High Affinity and Site-Specific Inhibitors against SARS-CoV-2: A Comprehensive Structural Analysis Based on Various Host-Based and Viral Targets - Previous studies indicated that natural-based chalcones have significant inhibitory effects on the coronavirus enzymes 3CLpro and PLpro as well as modulation of some host-based antiviral targets (HBATs). In this study, a comprehensive computational and structural study was performed to investigate the affinity of our compound library consisting of 757 chalcone-based structures (CHA-1 to CHA-757) for inhibiting the 3CLpro and PLpro enzymes and against twelve selected host-based targets. Our…
Drug Potency Prediction of SARS-CoV-2 Main Protease Inhibitors Based on a Graph Generative Model - The prediction of a ligand potency to inhibit SARS-CoV-2 main protease (M-pro) would be a highly helpful addition to a virtual screening process. The most potent compounds might then be the focus of further efforts to experimentally validate their potency and improve them. A computational method to predict drug potency, which is based on three main steps, is defined: (1) defining the drug and protein in only one 3D structure; (2) applying graph autoencoder techniques with the aim of generating a…
Novel Polymyxin-Inspired Peptidomimetics Targeting the SARS-CoV-2 Spike:hACE2 Interface - Though the bulk of the COVID-19 pandemic is behind, the search for effective and safe anti-SARS-CoV-2 drugs continues to be relevant. A highly pursued approach for antiviral drug development involves targeting the viral spike (S) protein of SARS-CoV-2 to prevent its attachment to the cellular receptor ACE2. Here, we exploited the core structure of polymyxin B, a naturally occurring antibiotic, to design and synthesize unprecedented peptidomimetics (PMs), intended to target contemporarily two…