Background Following the acute phase of the COVID-19 pandemic, record numbers of people became economically inactive (i.e., neither working nor looking for work, e.g., retired), or non-employed (including unemployed job seekers and economically inactive people). A possible explanation is people leaving the workforce after contracting COVID-19. We aim to investigate whether testing positive for SARS-CoV-2 is related to subsequent economic inactivity and non-employment, among people who were in employment prior to the pandemic. Methods The primary source of data are UK longitudinal population studies linked to English NHS digital data, held by the UK Longitudinal Linkage Collaboration (UK LLC). We pooled data from five studies (1970 British Cohort Study, English Longitudinal Study of Ageing, 1958 National Child Development Study, Next Steps, and Understanding Society), established long before the pandemic with between two and eight follow up surveys during the pandemic. The study population comprised people aged 25-65 years during the study period (March 2020 to March 2021) who were employed pre-pandemic. Outcomes were economic inactivity and non-employment status measured at the time of the last follow-up survey (November 2020 to March 2021, depending on study). For participants who could be linked to NHS England data (n=8,174), COVID-19 infection was indicated by a positive SARS-CoV-2 test. For sensitivity analyses, we used a self-reported measure of COVID-19 infection from participants (n=13,881) in the public use files of the five studies. Potential confounders included sociodemographic variables, pre-pandemic self-rated health and occupational class. Logistic regression models estimated odds ratios (ORs) with 95% confidence intervals (95%CIs). Results In adjusted analyses, testing positive for SARS-CoV-2 was very weakly associated with economic inactivity (OR 1.08 95%CI 0.68-1.73) and non-employment status (OR 1.09. 95%CI 0.77-1.55). In sensitivity analyses, self-reported test-confirmed COVID-19 was not associated with either economic inactivity (OR 1.01: 95%CI 0.70 to 1.44) or non-employment status (OR1.03 95%CI 0.79-1.35). Conclusions Among people employed pre-pandemic, testing positive for SARS-CoV-2 was either weakly or not associated with increased economic inactivity or exiting employment. Wide confidence intervals limit the ability to make definitive conclusions, but it appears unlikely that COVID-19 disease explains the increase in economic inactivity among working-age people.
ABSTRACT Background: Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious hyperinflammatory complication following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The mechanisms underpinning the pathophysiology of MIS-C are poorly understood. Moreover, clinically distinguishing MIS-C from other childhood infectious and inflammatory conditions, such as Kawasaki Disease (KD) or severe bacterial and viral infections is challenging due to overlapping clinical and laboratory features. We aimed to determine a set of plasma protein biomarkers that could discriminate MIS-C from those other diseases. Methods: Seven candidate protein biomarkers for MIS-C were selected based on literature and from whole blood RNA-Sequencing data from patients with MIS-C and other diseases. Plasma concentrations of ARG1, CCL20, CD163, CORIN, CXCL9, PCSK9 and ADAMTS2 were quantified in MIS-C (n=22), KD (n=23), definite bacterial (DB; n=28) and viral (DV, n=27) disease, and healthy controls (n=8). Logistic regression models were used to determine the discriminatory ability of individual proteins and protein combinations to identify MIS-C, and association with severity of illness. Results: Plasma levels of CD163, CXCL9, and PCSK9 were significantly elevated in MIS-C with a combined AUC of 86% (95% CI: 76.8%-95.1%) for discriminating MIS-C from other childhood diseases. Lower ARG1 and CORIN plasma levels were significantly associated with severe MIS-C cases requiring oxygen, inotropes or with shock. Conclusion: Our findings demonstrate the feasibility of a host protein biomarker signature for MIS-C and may provide new insight into its pathophysiology.
Background The COVID-19 pandemic caused significant disruption to routine activity in primary care. Medication reviews are an important primary care activity to ensure safety and appropriateness of ongoing prescribing and a disruption could have significant negative implications for patient care. Aim Using routinely collected data, our aim was to i) describe the SNOMED CT codes used to report medication review activity ii) report the impact of COVID-19 on the volume and variation of medication reviews. Design and setting With the approval of NHS England, we conducted a cohort study of 20 million adult patient records in general practice, in-situ using the OpenSAFELY platform. Method For each month between April 2019 - March 2022, we report the percentage of patients with a medication review coded monthly and in the previous 12 months. These measures were broken down by regional, clinical and demographic subgroups and amongst those prescribed high risk medications. Results In April 2019, 32.3% of patients had a medication review coded in the previous 12 months. During the first COVID-19 lockdown, monthly activity substantially decreased (-21.1% April 2020), but the rate of patients with a medication review coded in the previous 12 months was not substantially impacted according to our classification (-10.5% March 2021). There was regional and ethnic variation (March 2022 - London 21.9% vs North West 33.6%; Chinese 16.8% vs British 33.0%). Following the introduction of “structured medication reviews”, the rate of structured medication review in the last 12 months reached 2.9% by March 2022, with higher percentages in high risk groups (March 2022 - care home residents 34.1%, 90+ years 13.1%, high risk medications 10.2%). The most used SNOMED CT medication review code across the study period was Medication review done - 314530002 (59.5%). Conclusion We have reported a substantial reduction in the monthly rate of medication reviews during the pandemic but rates recovered by the end of the study period.
Background: COVID-19 led to drastic changes worldwide which has affected mental health especially, of the vulnerable student population. Aim: This study aimed to assess psychological distress due to COVID-19 in students during the late phase of pandemic and to establish correlation of academic course, socio-demographics and knowledge-attitude-practices (KAP) with depression and anxiety. Settings and Design: It was an online cross-sectional survey conducted in March-April 2022 among medical and non-medical students of Kolkata. Materials and methods: Survey questionnaire was circulated via Google forms through social media. It included Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, Fear of COVID-19 scale 2020, KAP regarding COVID-19 and socio-demographics. Statistical analysis used: Data was analysed using appropriate statistical methods in Statistical Package for Social Science (Version 22.0) and EpiInfo. P value of less than 0.05 was considered significant. Results: Mild to severe depression was reported among 29.4% of non-medical and 42.5% of medical students. One fourth (25.68%) of non-medical and 39.67% of medical students had mild to severe anxiety. MBBS participants had significantly better scores for knowledge and attitude (p=0.000 in both). Depression was higher in those with previous history of psychiatric illness (p=0.015). Anxiety was influenced by residence (p=0.003), mode of travel to college (p=0.002), history of relatives or friends affected by COVID-19 (p= 0.005). Conclusion: Prevalence of depression and anxiety in college students, especially among medical students, was higher in present study mainly due to long-term effects of the pandemic. This calls for employing student wellness activities and provision of better mental health services across colleges in India.
Atma Jaya Catholic University of Indonesia (AJCUI) COVID-19 Laboratory has become a reference testing site, which contributed to prevent the SARS-CoV-2 transmission in Indonesia. Through the LSSR and CARE, the Indonesian government has implemented moderate yet arguably successful policies to combat this pandemic. This study aims to assess and strengthen public health management while enhancing our understanding of the dynamics of COVID-19. We analyzed the correlation between policies enforced in controlling COVID-19 from July 2020 to December 2022 to the positivity rate and viral intensity. AJCUI, DKI Jakarta, Indonesia demonstrated a similar trend in COVID-19 prevalence. Government policy on mobility restrictions has substantially reduced the positivity rate in Indonesia within the period of study. Our study interpreted that the Ct value in the positive case population of AJCUI data correlated positively with DKI Jakarta and Indonesia; subsequently, it has the potential to serve as an early warning for an anticipated wave. Despite the coverage of vaccines, AJCUI and DKI Jakarta positivity rates are shifting due to evolving virus variants. Altogether, the comprehensively recorded data would enable an understanding of COVID-19 dynamics, serve as a model for unprecedented disaster and public health management in general.
The etiologic mechanisms of post-acute medical morbidities and unexplained symptoms (Long COVID) following SARS-CoV-2 infection are incompletely understood. There is growing evidence that viral persistence and immune dysregulation may play a major role. We performed whole-body positron emission tomography (PET) imaging in a cohort of 24 participants at time points ranging from 27 to 910 days following acute SARS-CoV-2 infection using a novel radiopharmaceutical agent, [18F]F-AraG, a highly selective tracer that allows for anatomical quantitation of activated T lymphocytes. Tracer uptake in the post-acute COVID group, which included those with and without Long COVID symptoms, was significantly higher compared to pre-pandemic controls in many anatomical regions, including the brain stem, spinal cord, bone marrow, nasopharyngeal and hilar lymphoid tissue, cardiopulmonary tissues, and gut wall. Although T cell activation tended to be higher in participants imaged closer to the time of the acute illness, tracer uptake was increased in participants imaged up to 2.5 years following SARS-CoV-2 infection. We observed that T cell activation in spinal cord and gut wall was associated with the presence of Long COVID symptoms. In addition, tracer uptake in lung tissue was higher in those with persistent pulmonary symptoms. Notably, increased T cell activation in these tissues was also observed in many individuals without Long COVID. Given the high [18F]F-AraG uptake detected in the gut, we obtained colorectal tissue for in situ hybridization SARS-CoV-2 RNA and immunohistochemical studies in a subset of participants with Long COVID symptoms. We identified cellular SARS-CoV-2 RNA in rectosigmoid lamina propria tissue in all these participants, ranging from 158 to 676 days following initial COVID-19 illness, suggesting that tissue viral persistence could be associated with long-term immunological perturbations.
With the onset of the COVID-19 pandemic caused by the novel coronavirus (SARS-CoV-2), there has been a surge in the pursuit of potential therapeutic interventions for this deadly disease. Given the urgency of the situation, computational drug repurposing methods have emerged as a promising strategy for identifying effective treatments from a pool of approved drugs. This systematic review and meta-analaysis will assess the existing research on the use of computational approaches for drug repurposing in the context of COVID-19. SARS-CoV-2 Main Protease is a critical enzyme that plays a vital role in the replication cycle of the SARS-CoV-2 virus, and its inhibition is a promising strategy for the development of antiviral therapies. Different databases (PubMed, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL), MEDLINE via EBSCOhost, Google Scholar, and WILEY online Library) will be utilized to identify and incorporate primary research articles in English and French that employed computational methodologies for drug repurposing in the context of COVID-19 and SARS-CoV-2 Main protease inhibition published between March 2020 to May 2023. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-ScR), we will undertake a comprehensive search of relevant studies. Authors will also search peer-reviewed articles, grey literature sources, and reference lists to identify eligible studies. Title screening will be followed by independent abstract and full-text screening by two reviewers. Any study that focuses on the inhibition of the Mpro using computer aided methods will be included. The analysis of data will be carried out by utilizing two software tools - Review Manager software (version 5.3.5) and R software (version 3.6.1). To determine statistical heterogeneity, a standard chi-square test will be applied with a significance level of P < 0.10. Potential biases related to study size (such as publication bias) will be examined through the application of several techniques, including funnel plots, Egger9s test, Begg9s test, as well as Trim and Fill analysis. This study will provide evidence-based information and conduct a comprehensive analysis of the computer-aided drug discovery and repurposing of the SARS-CoV-2 Main protease inhibitors, thereby producing a high-quality synthesis of information. The study will also explore potential innovative therapeutic applications for preventing or treating the novel viral infection by the inhibition of the Main Protease. In addition, the review will highlight research gaps in the treatment of COVID-19 and provide suggestions for future research. The outcomes of this review will be shared through a peer-reviewed publication and presented at relevant conferences while ensuring proper dissemination to reach a wide audience.
Background: Cardiovascular disease management in primary care in England was disrupted during the COVID-19 pandemic. Objective: We aim to describe the impact of the COVID-19 pandemic on blood pressure screening and hypertension management, based upon a national quality of care scheme (Quality and Outcomes Framework, QOF) across key demographic, regional, and clinical subgroups. To this end, we translate complex clinical quality of care schemes from text descriptions into reusable analytic code. Methods: With the approval of NHS England, a population based cohort study was conducted on 25.2 million patient records in situ using OpenSAFELY-TPP. We included all NHS patients registered at general practices using TPP software between March 2019 and March 2023. Individuals that were eligible for blood pressure screening and with a diagnosis of hypertension were identified according to the QOF 2021/22 business rules. We examined monthly changes in recorded blood pressure screening in the preceding 5 years in patients aged ≥ 45, recorded hypertension prevalence, and the recorded percentage of patients treated to target (i.e., ≤ 140/90 mmHg for patients ≤ 79 years and ≤ 150/90 mmHg for patients ≥ 80 years) in the preceding 12 months, within demographic, regional, and clinical subgroups as well as the variation across practices. Results: The overall percentage of patients aged ≥ 45 who had blood pressure screening recorded in the preceding 5 years decreased from 90% in March 2019 to 85% in March 2023. Recorded hypertension prevalence was relatively stable at 15% throughout the study period. The percentage of patients with a record of hypertension treated to target in the preceding 12 months reduced from a maximum of 71% in March 2020 to a minimum of 47% in February 2021 in patients aged ≤ 79 years, and from 85% in March 2020 to a minimum of 58% in February 2021 in patients aged ≥ 80 years before recovering. Blood pressure screening rates in the preceding 5 years remained stable in older age groups, patients with a record of learning disability, or care home status. Conclusions: There was substantial disruption to hypertension management QOF indicators during the pandemic, which can likely be attributed to a general reduction of blood pressure screening. OpenSAFELY can be used to continuously monitor monthly changes in national quality of care schemes to identify changes in key clinical subgroups early and support prioritisation of recovery from disrupted care caused by COVID-19.
Purpose: Severe SARS-CoV-2 pneumonia remains incompletely understood. We aimed to summarize current evidence regarding clinical features, laboratory findings, and treatment of severe SARS-CoV-2 pneumonia. Methods: Online databases were searched from December 1, 2019, to April 15, 2020. Studies performed in adults, with the definition of severe SARS-CoV-2 pneumonia, enough case number (>10), and data on clinical features or laboratory findings were included. Data were extracted independently by two reviewers. Results: Eighteen articles of 2,435 severe cases were eligible for analysis, with the average ages ranging from 49 to 70 years old, hypertension as the most common comorbidity, fever as the most common manifestation, and acute respiratory distress syndrome (ARDS) as the most common complication. As compared to non-severe cases, severe pneumonia was featured with the lower counts of lymphocytes, CD8+ and CD4+ T cells, and higher levels of D-dimer, lactate dehydrogenase (LDH), IL-6 and IL-10. Antiviral therapy was the mainstay of treatment for severe SARS-CoV-2 pneumonia, and oseltamivir was the most commonly used antiviral reagent. Ventilation therapy, especially mechanical ventilation, was the primary and effective treatment. Conclusions: This study represents the first systematic summarization of the aspects of severe SARS-CoV-2 pneumonia, and its comparison with non-severe cases in symptoms and laboratory findings. Research including elder cases and from regions outside China, especially western countries, would generate benefits in a full understanding of severe SARS-CoV-2 pneumonia. High-quality studies are urgently required to confirm or exclude the possibility of a treatment benefit.
Enisamium (trade name Amizon® MAX) is an orally available therapeutic that inhibits influenza A virus and SARS-CoV-2 replication in vitro and improves influenza patient recovery. We evaluated the clinical efficacy of enisamium treatment combined with standard care compared to standard care plus treatment with a placebo control in adult, hospitalized patients with moderate COVID-19 requiring external oxygen. Hospitalized patients with laboratory-confirmed SARS-CoV-2 infection were randomly assigned to receive either enisamium (500 mg per dose, 4 times a day) or a placebo. All patients received standard of care as deemed necessary by the investigator and the health status of each patient. The primary outcome was an improvement of at least two points on an 8-point, modified WHO severity rating (SR) scale within 29 days of randomization. A total of 592 patients were enrolled and randomized between May 2020 and March 2021. Patients with a baseline SR of 4 were divided into two groups: 142 (49.8%) were assigned to the enisamium group and 143 (50.2%) to the placebo group. No differences were observed between the safety or patient tolerability profiles of the enisamium and placebo treatment. Analysis of the population showed that if patients were treated within 4 days of the onset of COVID-19 symptoms (n = 33), the median time to improvement was 8 days for the enisamium group and 13 days for the placebo group (p = 0.0051). For patients treated within 10 days of the onset of COVID-19 symptoms (n = 154), the median time to improvement was 10 days for the enisamium group and 12 days for the placebo group (p = 0.002). Comparison of groups using a stratified one-sided Logrank criterion (adjustment using stratification by age categories: “<40 years”, “40-<65 years” and “≥65 years”) showed statistically significant differences between the groups (p = 0.00945, one-sided). Our findings suggest that enisamium is safe to use in COVID-19 patients, and that enisamium treatment offers a clinical benefit when given to patients with moderate COVID-19 requiring supplementary oxygen, if enisamium is given within 10 days of the onset of symptoms. This trial was registered with ClinicalTrials.gov under NCT04682873.
Effects of Exercise Training on Patients With Long COVID-19 - Condition: Long COVID-19
Intervention: Behavioral: Exercise training
Sponsor: Guangdong Provincial People’s Hospital
Recruiting
Lymph Node Aspiration to Decipher the Immune Response of Beta-variant Recombinant Protein Booster Vaccine (VidPrevtyn Beta, Sanofi) Compared to a Bivalent mRNA Vaccine (Comirnaty Original/Omicron BA.4-5, BioNTech-Pfizer) in Adults Previously Vaccinated With at Least 3 Doses of COVID-19 mRNA Vaccine. - Condition: COVID-19
Intervention: Procedure: Lymph node aspiration / Blood sampling
Sponsor: Assistance Publique - Hôpitaux de Paris
Recruiting
COVID-19 Trial of the Candidate Vaccine MVA-SARS-2-S in Adults - Condition: Covid19
Interventions: Biological: MVA-SARS-2-S; Other: Placebo
Sponsors: Universitätsklinikum Hamburg-Eppendorf; German Center for Infection Research; Philipps University Marburg Medical Center; Ludwig-Maximilians - University of Munich; University Hospital Tuebingen; CTC-NORTH
Withdrawn
Immunoadsorption vs. Sham Treatment in Post COVID-19 Patients With Chronic Fatigue Syndrome - Conditions: Fatigue; Post-Acute COVID-19 Syndrome
Intervention: Procedure: Immunoadsorption vs. sham immunoadsorption
Sponsor: Hannover Medical School
Not yet recruiting
Non-ventilated Prone Positioning in the COVID-19 Population - Conditions: COVID-19; Proning; Oxygenation; Length of Stay
Interventions: Other: Proning group; Other: Control group
Sponsor: Baylor St. Luke’s Medical Center
Completed
HD-Tdcs and Pharmacological Intervention For Delirium In Critical Patients With COVID-19 - Conditions: COVID-19; Delirium; Critical Illness
Interventions: Combination Product: Active HD-tDCS; Combination Product: Sham HD-tDCS
Sponsors: Suellen Andrade; City University of New York
Completed
RECOVER-VITAL: Platform Protocol, Appendix to Measure the Effects of Paxlovid on Long COVID Symptoms - Conditions: Long COVID-19; Long COVID
Interventions: Drug: Paxlovid 25 day dosing; Drug: Paxlovid 15 day dosing; Drug: Control
Sponsor: Kanecia Obie Zimmerman
Not yet recruiting
A Study on the Safety and Immune Response of a Booster Dose of Investigational COVID-19 mRNA Vaccines in Healthy Adults - Condition: SARS-CoV-2
Interventions: Biological: CV0701 Bivalent High dose; Biological: CV0701 Bivalent Medium dose; Biological: CV0701 Bivalent Low dose; Biological: CV0601 Monovalent High dose; Biological: Control vaccine
Sponsors: GlaxoSmithKline; CureVac
Not yet recruiting
RECOVER-NEURO: Platform Protocol, Appendix_A to Measure the Effects of BrainHQ, PASC CoRE and tDCS Interventions on Long COVID Symptoms - Conditions: Long COVID; Long Covid19; Long Covid-19
Interventions: Other: BrainHQ/Active Comparator Activity; Other: BrainHQ; Other: PASC CoRE; Device: tDCS-active; Device: tDCS-sham
Sponsor: Duke University
Not yet recruiting
PROTECT-APT 1: Early Treatment and Post-Exposure Prophylaxis of COVID-19 - Condition: SARS-CoV-2
Interventions: Drug: Upamostat; Drug: Placebo (PO)
Sponsors: Henry M. Jackson Foundation for the Advancement of Military Medicine; Joint Program Executive Office Chemical, Biological, Radiological, and Nuclear Defense Enabling Biotechnologies; FHI Clinical, Inc.; RedHill Biopharma Limited
Not yet recruiting
RECOVER-NEURO: Platform Protocol to Measure the Effects of Cognitive Dysfunction Interventions on Long COVID Symptoms - Conditions: Long COVID; Long Covid19; Long Covid-19
Interventions: Other: BrainHQ/Active Comparator Activity; Other: BrainHQ; Other: PASC CoRE; Device: tDCS-active; Device: tDCS-sham
Sponsor: Duke University
Not yet recruiting
Impact of COVID-19 on Sinus Augmentation Surgery - Condition: Bone Loss
Interventions: Procedure: Sinus lift in patients with positive COVID-19 history; Procedure: Sinus lift with negative COVID-19 history
Sponsor: Cairo University
Completed
Expressive Interviewing Agents to Support Health-Related Behavior Change - Condition: Mental Stress
Intervention: Other: Expressive Interviewing
Sponsors: University of Michigan; University of Texas at Austin
Completed
Immunogenicity and Safety of an Inactivated SARS-CoV-2 Vaccine Coadministered With Two Attenuated Vaccines - Conditions: SARS-CoV-2 Infection; Varicella; Measles; Mumps; Rubella
Interventions: Biological: Inactivated SARS-CoV-2 vaccine coadministered with vricella vaccine; Biological: Inactivated SARS-CoV-2 vaccine coadministered with MMR; Biological: Inactivated SARS-CoV-2 vaccine administered alone
Sponsors: Shanghai Municipal Center for Disease Control and Prevention; China National Biotec Group Company Limited
Not yet recruiting
Impact of Breathing Exercises and Meditation on Improving Quality of Life in Glaucoma Patients - Conditions: Glaucoma; Depression; Anxiety; Quality of Life; Sleep Disorder
Intervention: Behavioral: Breathing Exercises followed by Meditation
Sponsor: Lawson Health Research Institute
Not yet recruiting
Neurological side effects and drug interactions of antiviral compounds against SARS-CoV-2 - CONCLUSION: Neurological side effects and drug interactions must be considered for antiviral compounds against SARS-CoV-2. Further studies are required to better evaluate their efficacy and adverse events in patients with concomitant neurological diseases. Moreover, evidence from real-world studies will complement the current knowledge.
Deuteration for Metabolic Stabilization of SARS-CoV-2 Inhibitors GC373 and Nirmatrelvir - Nirmatrelvir and GC373 inhibit the SARS-CoV-2 3CL protease and hinder viral replication in COVID-19. As nirmatrelvir in Paxlovid is oxidized by cytochrome P450 3A4, ritonavir is coadministered to block this. However, ritonavir undesirably alters the metabolism of other drugs. Hydrogens can be replaced with deuterium in nirmatrelvir and GC373 to slow oxidation. Results show that deuterium slows oxidation of nirmatrelvir adjacent to nitrogen by ∼40% and that the type of warhead can switch the site…
Structures of SARS-CoV-2 N7-methyltransferase with DOT1L and PRMT7 inhibitors provide a platform for new antivirals - The RNA N7-methyltransferase (MTase) activity of SARS-CoV-2’s nsp14 protein is essential for viral replication and is a target for the development of new antivirals. Nsp14 uses S-adenosyl methionine (SAM) as the methyl donor to cap the 5’ end of the SARS-CoV-2 mRNA and generates S-adenosyl homocysteine (SAH) as the reaction byproduct. Due to the central role of histone MTases in cancer, many SAM/SAH analogs with properties of cell permeability have recently been developed for the inhibition of…
Mega-scale desalination efficacy (Reverse Osmosis, Electrodialysis, Membrane Distillation, MED, MSF) during COVID-19: Evidence from salinity, pretreatment methods, temperature of operation - The unprecedented situation of the COVID-19 pandemic heavily polluted water bodies whereas the presence of SARS-CoV-2, even in treated wastewater in every corner of the world is reported. The main aim of the present study is to show the effectiveness and feasibility of some well-known desalination technologies which are reverse osmosis (RO), Electrodialysis (ED), Membrane Distillation (MD), multi effect distillation (MED), and multi stage flashing (MSF) during the COVID-19 pandemic. Systems’…
An RBD bispecific antibody effectively neutralizes a SARS-CoV-2 Omicron variant - Potent neutralizing antibodies (nAbs) against SARS-CoV-2 are a promising therapeutic against the ongoing COVID-19 pandemic. However, the continuous emergence of neutralizing antibody escape variants makes it challenging for antibody therapeutics based on monospecific nAbs. Here, we generated an IgG-like bispecific antibody (bsAb), Bi-Nab, based on a pair of human neutralizing antibodies targeting multiple and invariant sites of the spike receptor binding domain (RBD): 35B5 and 32C7. We…
Effects of official information and rumor on resource-epidemic coevolution dynamics - Epidemic-related information and resources have proven to have a significant impact on the spread of the epidemic during the Corona Virus Disease 2019 (COVID-19) pandemic. The various orientation role of information has different effects on the epidemic spreading process, which will affect the individual’ awareness of resources allocation and epidemic spreading scale. Based on this, a three-layer network is established to describe the dynamic coevolution process among information dissemination,…
Deciphering and targeting host factors to counteract SARS-CoV-2 and coronavirus infections: insights from CRISPR approaches - Severe respiratory syndrome coronavirus 2 (SARS-CoV-2) and other coronaviruses depend on host factors for the process of viral infection and replication. A better understanding of the dynamic interplay between viral pathogens and host cells, as well as identifying of virus-host dependencies, offers valuable insights into disease mechanisms and informs the development of effective therapeutic strategies against viral infections. This review delves into the key host factors that facilitate or…
Antibody response to inactivated COVID-19 vaccine in patients with type 2 diabetes mellitus after the booster immunization - CONCLUSIONS: Patients with T2DM showed impaired antibody responses after booster vaccination for more than 6 months. Decreased anti-BA.4/5 responses give rise to the possibility of breakthrough infections for both patients with T2DM and HCs.
Azithromycin exposure during pregnancy disturbs the fetal development and its characteristic of multi-organ toxicity - AIMS: Azithromycin is widely used in clinical practice for treating maternal infections during pregnancy. Meanwhile, azithromycin, as an “emerging pollutant”, is increasingly polluting the environment due to the rapidly increasing usage (especially after the COVID-19). Previous studies have suggested a possible teratogenic risk of prenatal azithromycin exposure (PAzE), but its effects on fetal multi-organ development are still unclear. This study aimed to explore the potential impacts of PAzE.
Nicotinamide Efficiently Suppresses Porcine Epidemic Diarrhea Virus and Porcine Deltacoronavirus Replication - Porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV), members of the genus Coronavirus, mainly cause acute diarrhea, vomiting and dehydration in piglets, and thus lead to serious economic losses. In this study, we investigated the effects of nicotinamide (NAM) on PEDV and PDCoV replication and found that NAM treatment significantly inhibited PEDV and PDCoV reproduction. Moreover, NAM plays an important role in replication processes. NAM primarily inhibited PEDV and PDCoV…
Analogs of the Catechol Derivative Dynasore Inhibit HIV-1 Ribonuclease H, SARS-CoV-2 nsp14 Exoribonuclease, and Virus Replication - Viral replication often depends on RNA maturation and degradation processes catalyzed by viral ribonucleases, which are therefore candidate targets for antiviral drugs. Here, we synthesized and studied the antiviral properties of a novel nitrocatechol compound (1c) and other analogs that are structurally related to the catechol derivative dynasore. Interestingly, compound 1c strongly inhibited two DEDD box viral ribonucleases, HIV-1 RNase H and SARS-CoV-2 nsp14 3’-to-5’ exoribonuclease (ExoN)….
SARS-CoV-2 Spike Protein Is Capable of Inducing Cell-Cell Fusions Independent from Its Receptor ACE2 and This Activity Can Be Impaired by Furin Inhibitors or a Subset of Monoclonal Antibodies - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was responsible for the COVID-19 pandemic, efficiently spreads cell-to-cell through mechanisms facilitated by its membrane glycoprotein spike. We established a dual split protein (DSP) assay based on the complementation of GFP and luciferase to quantify the fusogenic activity of the SARS-CoV-2 spike protein. We provide several lines of evidence that the spike protein of SARS-CoV-2, but not SARS-CoV-1, induced cell-cell fusion…
SARS-CoV-2 Prevalence and Variant Surveillance among Cats in Pittsburgh, Pennsylvania, USA - Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infects many mammals, and SARS-CoV-2 circulation in nonhuman animals may increase the risk of novel variant emergence. Cats are highly susceptible to SARS-CoV-2 infection, and there were cases of virus transmission between cats and humans. The objective of this study was to assess the prevalence of SARS-CoV-2 variant infection of cats in an urban setting. We investigated the prevalence of SARS-CoV-2 variant infections in domestic and…
IGF2BP1-An Oncofetal RNA-Binding Protein Fuels Tumor Virus Propagation - The oncofetal RNA-binding protein IGF2BP1 has been reported to be a driver of tumor progression in a multitude of cancer entities. Its main function is the stabilization of target transcripts by shielding these from miRNA-mediated degradation. However, there is growing evidence that several virus species recruit IGF2BP1 to promote their propagation. In particular, tumor-promoting viruses, such as hepatitis B/C and human papillomaviruses, benefit from IGF2BP1. Moreover, recent evidence suggests…
Acetate-encapsulated Linolenic Acid Liposomes Reduce SARS-CoV-2 and RSV Infection - Emergent Coronaviridae viruses, such as SARS-CoV-1 in 2003, MERS-CoV in 2012, and SARS-CoV-2 (CoV-2) in 2019, have caused millions of deaths. These viruses have added to the existing respiratory infection burden along with respiratory syncytial virus (RSV) and influenza. There are limited therapies for respiratory viruses, with broad-spectrum treatment remaining an unmet need. Since gut fermentation of fiber produces short-chain fatty acids (SCFA) with antiviral potential, developing a fatty…