Background: Chest CT examination is significant in COVID-19 diagnosis due to its high sensitivity. Although typical chest CT findings have been discussed thoroughly in the literature throughout the pandemic, we aimed to investigate the prevalence of the atypical conclusions during the start of the Omicron variant insurgency and compare the results to studies conducted before its outbreak. Methods: 606 confirmed COVID-19 cases were included in this study based on inclusion and exclusion criteria during January and February 2022. Demographic information of patients, including age and sex, was recorded. The computed tomography (CT) examination was carried out using a 100-slice scanner (Philips Brilliance 6 CT Scanner). One radiology attending and one resident evaluated SARSCoV- 2 RT-PCR-positive patients for atypical pulmonary CT findings. The obtained data were evaluated using R software version 4.1.1. Results: 55% of patients were female, and the median age was 56 (IQR: 42, 69 59% of patients had atypical findings on their pulmonary CT examination. These findings showed that pleural abnormalities were the most frequent atypicalfindings, with pleural thickening being the most common (17%). The double halo sign represented the least frequent atypical sign (0.2%). Conclusion: Atypical findings were more prevalent in this study than its predecessors, while we acknowledge that other factors, such as study design and patient population, could have impacted it. The presence of atypical signs generally was not correlated with specific demographic groups, while some of these signs were more frequent in some groups.
Purpose: To analyze the prevalence of lower urinary tract symptoms (LUTS) in patients who survived moderate and severe forms of COVID-19 and the risk factors for LUTS six months after hospital discharge. Materials and Methods: In this prospective cohort study, patients were evaluated six months after being hospitalized due to COVID-19. LUTS were assessed using the International Prostate Symptom Score. General health was assessed through the Hospital Anxiety and Depression Scale and the EQ5D-L5 scale, which evaluates mobility, ability to perform daily activities, pain and discomfort and completed a self-perception health evaluation. Results: Of 255 participants, 54.1% were men and the median age was 57.3 [44.3 / 66.6] years. Pre-existing comorbidities included diabetes (35.7%), hypertension (54.5%), obesity (30.2%) and physical inactivity (65.5%). 124 (48.6%) had a hospital stay >15 days, 181 (71.0%) were admitted to an ICU and 124 (48.6%) needed mechanical ventilation. Median IPSS score was 6 [3-11] and did not differ between men and women. Moderate to severe LUTS affected 108 (42.4%) patients (40.6% men and 44.4% women; p=0.610). Nocturia (58.4%) and frequency (45.9%) were the most prevalent symptoms and urgency was the only symptom that affected men (29.0%) and women (44.4%) differently (p=0.013). LUTS significantly impacted the quality of life of 60 (23.5%) patients with women more severely affected (p=0.004). Preexisting diabetes, hypertension and self-perception of worse general health were associated with LUTS. Conclusions: LUTS are highly prevalent and bothersome six months after hospitalization due to COVID-19. Assessment of LUTS may help ensure appropriate diagnosis and treatment in these patients.
Abstract Gene expression profiles that connect drug perturbations, disease gene expression signatures, and clinical data are important for discovering potential drug repurposing indications. However, the current approach to gene expression reversal has several limitations. First, most methods focus on validating the reversal expression of individual genes. Second, there is a lack of causal approaches for identifying drug repurposing candidates. Third, few methods for passing and summarizing information on a graph have been used for drug repurposing analysis, with classical network propagation and gene set enrichment analysis being the most common. Fourth, there is a lack of graph-valued association analysis, with current approaches using real-valued association analysis one gene at a time to reverse abnormal gene expressions to normal gene expressions. To overcome these limitations, we propose a novel causal inference and graph neural network (GNN)-based framework for identifying drug repurposing candidates. We formulated a causal network as a continuous constrained optimization problem and developed a new algorithm for reconstructing large-scale causal networks of up to 1,000 nodes. We conducted large-scale simulations that demonstrated good false positive and false negative rates. To aggregate and summarize information on both nodes and structure from the spatial domain of the causal network, we used directed acyclic graph neural networks (DAGNN). We also developed a new method for graph regression in which both dependent and independent variables are graphs. We used graph regression to measure the degree to which drugs reverse altered gene expressions of disease to normal levels and to select potential drug repurposing candidates. To illustrate the application of our proposed methods for drug repurposing, we applied them to phase I and II L1000 connectivity map perturbational profiles from the Broad Institute LINCS, which consist of gene-expression profiles for thousands of perturbagens at a variety of time points, doses, and cell lines, as well as disease gene expression data under-expressed and over-expressed in response to SARS-CoV-2.
Studies have linked reduced respiratory syncytial virus-specific Fc-mediated phagocytic function and complement deposition to more severe infection. This study shows a loss of these functions during the first year of COVID-19 pandemic. These findings corroborate other data supporting a general waning of RSV antibody functions in absence of viral circulation.
Abstract Background Long-term symptoms after a SARS-CoV-2 infection (i.e., post-COVID-19 condition or long COVID), constitute a substantial public health problem. Yet, the prevalence remains currently unclear as different case definitions are used, and negatively tested controls are lacking. We aimed to estimate post-COVID-19 condition prevalence using six definitions. Methods The Prevalence, Risk factors, and Impact Evaluation (PRIME) post-COVID-19 condition study is a population-based sample of COVID-19 tested adults. End 2021, 61,655 adults were invited to complete an online questionnaire, including 44 symptoms plus a severity score (0-10) per symptom. The prevalence was calculated in both positively and negatively tested adults, stratified by time since their COVID-19 test (3-5, 6-11 or ≥12 months ago). Results In positives (n=7,405; 75.6%), the prevalence of long-term symptoms was between 26.9% and 64.1% using the six definitions, while in negatives (n=2,392; 24.4%) the prevalence varied between 11.4% and 32.5%. The prevalence of long-term symptoms potentially accountable to COVID-19 ranged from 17.9% to 26.3%. Conclusion There is a (substantial) variation in prevalence estimates by using different definitions as is current practice, showing limited overlap between definitions, indicating that the essential post-COVID-19 condition criteria are still unclear. Including negatives is important to determine long-term symptoms accountable to COVID-19. Trial registration ClinicalTrials.gov Identifier: NCT05128695.
Despite vaccination and antiviral therapies, immunocompromised individuals are at risk for prolonged SARS-CoV-2 infection, but the immune defects that predispose to persistent COVID-19 remain incompletely understood. In this study, we performed detailed viro-immunologic analyses of a prospective cohort of participants with COVID-19. The median time to nasal viral RNA and culture clearance in the severe hematologic malignancy/transplant group (S-HT) were 72 and 21 days, respectively, which were significantly longer than clearance rates in the severe autoimmune/B-cell deficient (S-A), non-severe, and non-immunocompromised groups (P<0.001). Participants who were severely immunocompromised had greater SARS-CoV-2 evolution and higher risk of developing antiviral treatment resistance. Both S-HT and S-A participants had diminished SARS-CoV-2-specific humoral, while only the S-HT group had reduced T cell-mediated responses. This highlights the varied risk of persistent COVID-19 across immunosuppressive conditions and suggests that suppression of both B and T cell responses results in the highest contributing risk of persistent infection.
Effect of Natural Food on Gut Microbiome and Phospholipid Spectrum of Immune Cells in COVID-19 Patients - Condition: COVID-19
Intervention: Dietary Supplement: Freeze-dried Mare Milk (Saumal)
Sponsor: Asfendiyarov Kazakh National Medical University
Not yet recruiting
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
A Safety and Immune Response Study to Evaluate Varying Doses of an mRNA Vaccine Against Coronavirus Disease 2019 (COVID-19) in Healthy Adults - Condition: COVID-19
Interventions: Biological: mRNA-CR-04 vaccine 10μg; Biological: mRNA-CR-04 vaccine 30μg; Biological: mRNA-CR-04 vaccine 100μg; Drug: Placebo
Sponsor: GlaxoSmithKline
Not yet recruiting
A Phase 3, Randomized, Double-Blinded Study to Evaluate the Safety and Immunogenicity of Omicron Subvariant and Bivalent SARS-CoV-2 rS Vaccines in Adolescents Previously Vaccinated With mRNA COVID-19 Vaccines - Condition: COVID-19
Interventions: Biological: NVX-CoV2601 co-formulated Omicron XBB.1.5 SARS-CoV-2 rS vaccine; Biological: Prototype/XBB.1.5 Bivalent Vaccine (5 µg)
Sponsor: Novavax
Not yet recruiting
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
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-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
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, 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
Directed Topical Drug Delivery for Treatment for PASC Hyposmia - Condition: Post Acute Sequelae Covid-19 Hyposmia
Interventions: Drug: Beclomethasone; Other: Placebo; Device: Microsponge
Sponsor: Duke University
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
Telerehabilitation for Post COVID-19 Condition - Conditions: Long COVID; Chronic Fatigue Syndrome
Intervention: Other: Telerehabilitation program based on cardiorespiratory principles
Sponsors: Université de Sherbrooke; Hotel Dieu Hospital
Completed
Structural-Based Virtual Screening of FDA-Approved Drugs Repository for NSP16 Inhibitors, Essential for SARS-COV-2 Invasion Into Host Cells: Elucidation From MM/PBSA Calculation - NSP16 is one of the structural proteins of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) necessary for its entrance to the host cells. It exhibits 2’O-methyl-transferase (2’O-MTase) activity of NSP16 using methyl group from S-adenosyl methionine (SAM) by methylating the 5-end of virally encoded mRNAs and shields viral RNA, and also controls its replication as well as infection. In the present study, we used in silico approaches of drug repurposing to target and inhibit the SAM…
Invalidation of geraniin as a potential inhibitor against SARS-CoV-2 main protease - Recently, geraniin has been identified as a potent antiviral agent targeting SARS-CoV-2 main protease (Mpro). Considering the potential of geraniin in COVID-19 treatment, a stringent validation for its Mpro inhibition is necessary. Herein, we rigorously evaluated the in vitro inhibitory effect of geraniin on Mpro using the fluorescence resonance energy transfer (FRET), fluorescence polarization (FP), and dimerization-dependent red fluorescent protein (ddRFP) assays. Our data indicate that…
Crystal structures of main protease (Mpro) mutants of SARS-CoV-2 variants bound to PF-07304814 - There is an urgent need to develop effective antiviral drugs to prevent the viral infection caused by constantly circulating SARS-CoV-2 as well as its variants. The main protease (M^(pro)) of SARS-CoV-2 is a salient enzyme that plays a vital role in viral replication and serves as a fascinating therapeutic target. PF-07304814 is a covalent inhibitor targeting SARS-CoV-2 M^(pro) with favorable inhibition potency and drug-like properties, thus making it a promising drug candidate for the treatment…
Direct blue 53, a biological dye, inhibits SARS-CoV-2 infection by blocking ACE2 and spike interaction in vitro and in vivo - COVID-19 is a global health problem caused by SARS-CoV-2, which has led to over 600 million infections and 6 million deaths. Developing novel antiviral drugs is of pivotal importance to slow down the epidemic swiftly. In this study, we identified five azo compounds as effective antiviral drugs to SARS-CoV-2, and mechanism study revealed their targets for impeding viral particles’ ability to bind to host receptors. Direct Blue 53, which displayed the strongest inhibitory impact, inhibited five…
Chicoric Acid Presented NLRP3-Mediated Pyroptosis through Mitochondrial Damage by PDPK1 Ubiquitination in an Acute Lung Injury Model - Chicoric acid (CA), a functional food ingredient, is a caffeic acid derivative that is mainly found in lettuce, pulsatilla, and other natural plants. However, the anti-inflammatory effects of CA in acute lung injury (ALI) remain poorly understood. This study was conducted to investigate potential drug usage of CA for ALI and the underlying molecular mechanisms of inflammation. C57BL/6 mice were given injections of liposaccharide (LPS) to establish the in vivo model. Meanwhile, BMDM cells were…
Therapeutic effects of tea polyphenol-loaded nanoparticles coated with platelet membranes on LPS-induced lung injury - Patients with ALI (acute lung injury)/ARDS (acute respiratory distress syndrome) are often septic and with poor prognosis, which leads to a high mortality rate of 25-40%. Despite the advances in medicine, there are no effective pharmacological therapies for ALI/ARDS due to the short systemic circulation and poor specificity in the lungs. To address this problem, we prepared TP-loaded nanoparticles (TP-NPs) through the emulsification-and-evaporation method, and then the platelet membrane vesicles…
Combination of Chinese herbal medicine and conventional western medicine for coronavirus disease 2019: a systematic review and meta-analysis - CONCLUSIONS: Potentially, CHM listed in this study, as an adjunctive therapy, combining with CWM is an effective and safe therapy mode for COVID-19. However, more high-quality RCTs are needed to draw more accurate conclusions.
SARS-CoV-2 main protease targeting potent fluorescent inhibitors: Repurposing thioxanthones - The coronavirus disease, COVID-19, is the major focus of the whole world due to insufficient treatment options. It has spread all around the world and is responsible for the death of numerous human beings. The future consequences for the disease survivors are still unknown. Hence, all contributions to understand the disease and effectively inhibit the effects of the disease have great importance. In this study, different thioxanthone based molecules, which are known to be fluorescent compounds,…
Identification of a small chemical as a lysosomal calcium mobilizer and characterization of its ability to inhibit autophagy and viral infection - We previously identified GAPDH as one of the cyclic adenosine diphosphoribose (cADPR)’s binding proteins and found that GAPDH participates in cADPR-mediated Ca^(2+) release from ER via ryanodine receptors (RyRs). Here we aimed to chemically synthesize and pharmacologically characterize novel cADPR analogues. Based on the simulated cADPR-GAPDH complex structure, we performed the structure-based drug screening, identified several small chemicals with high docking scores to cADPR’s binding pocket…
Discovery and evaluation of active compounds from Xuanfei Baidu formula against COVID-19 via SARS-CoV-2 Mpro - CONCLUSION: Acteoside is regarded as a representative active natural compound in XFBD to inhibit replication of SARS-CoV-2, which provides the antiviral evidence and some insights into the identification of SARS-CoV-2 M^(pro) natural inhibitors.
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…