Wastewater-based epidemiology has emerged as a powerful public health tool to trace new outbreaks, detect trends in infection and provide an early warning of COVID-19 community spread. Here, we investigated the spread of SARS-CoV-2 infections across Utah by characterizing lineages and mutations detected in wastewater samples. We sequenced over 1,200 samples from 32 sewersheds collected between November 2021 and March 2022. Wastewater sequencing confirmed the presence of Omicron (B.1.1.529) in Utah in samples collected on November 19, 2021, up to ten days before its corresponding detection via clinical sequencing. Analysis of diversity of SARS-CoV-2 lineages revealed Delta as the most frequently detected lineage during November, 2021 (67.71%), but it started declining in December, 2021 with the onset of Omicron (B.1.1529) and its sub-lineage BA.1 (6.79%). Proportion of Omicron increased to ~58% by January 4th 2022 and completely displaced Delta by February 7th, 2022. Wastewater genomic surveillance revealed the presence of Omicron sub-lineage BA.3, a lineage that is yet to be identified from clinical surveillance in Utah. Interestingly, several Omicron-defining mutations began to appear in early November, 2021 and increased in prevalence across sewersheds from December to January. Our study suggests that tracking epidemiologically relevant mutations is critical in detecting emerging lineages in the early stages of an outbreak. Wastewater genomic epidemiology provides an unbiased representation of community-wide infection dynamics and is an excellent complementary tool to SARS-CoV-2 clinical surveillance, with the potential of guiding public health action and policy decisions.
A minority of people infected with SARS-CoV-2 will develop severe COVID-19 disease requiring invasive respiratory support associated with high mortality. To understand the molecular mechanisms underlying severe pathology, we conducted an unsupervised stratification of the circulating proteome that identified six endophenotypes (EPs) among 731 SARS-CoV-2 PCR-positive hospitalized participants in the Biobanque Québécoise de la COVID-19, with varying degrees of disease severity and times to intensive care unit (ICU) admission. One endophenotype, EP6, was associated with a greater proportion of ICU admission, mechanical ventilation, acute respiratory distress syndrome (ARDS) and death. Clinical features of EP6 included increased levels of C-reactive protein, D-dimers, elevated neutrophils, and depleted lymphocytes. Proteomic, metabolomic, and genomic characterization supported a role for neutrophil-associated procoagulant activity in severe COVID-19 ARDS that is inversely correlated with sphinghosine-1 phosphate plasma levels. Fibroblast Growth Factor Receptor (FGFR) and SH2-containing transforming protein 4 (SHC4) signaling were identified as molecular features associated with severe COVID-19. Mechanical ventilation in EP6 was associated with alterations in lipoprotein metabolism. Importantly, a prognostic model solely based on clinical laboratory measurements was developed and validated on 631 patients that generalizes the EPs to new patients and creates new opportunities for automated identification of high-risk groups in the clinic.
The dynamics of epidemiological phenomena associated to infectious diseases have long been modelled with different approaches. However, recent pandemic events exposed many areas of opportunity to improve over the existing models. We develop a model based on the idea that transitions between epidemiological stages are alike sampling processes. Such processes may involve more than one subset of the pop- ulation (e.g. infection), or they may be mostly dependent on time intervals defined by infectious or clinical criteria. The resulting modelling scheme is robust, easy to implement, and can readily lend itself for extensions aimed at answering questions that emerge from close examination of data trends, such as those emerging from the COVID-19 pandemic, and other infectious diseases.
Background: Despite its high prevalence, the determinants of smelling impairment in COVID-19 remain opaque. Olfactory bulb volumetry has been previously established as a promising surrogate marker of smelling function in multiple otorhinolaryngological diseases. In this work, we aimed to elucidate the correspondence between olfactory bulb volume and the clinical trajectory of COVID-19-related smelling impairment. Therefore, we conducted a large-scale magnetic resonance imaging (MRI)-based investigation of individuals recovered from mainly mild to moderate COVID-19. Methods: Data of 233 COVID-19 convalescents from the Hamburg City Health Study COVID Program were analyzed. Upon recruitment, patients underwent cranial MR imaging and assessment of neuropsychological testing. Automated olfactory bulb volumetry was performed on T2-weighted MR imaging data. Olfactory function was assessed longitudinally after recruitment and at follow-up via a structured questionnaire. Follow-up assessment included quantitative olfactometric testing with Sniffin Sticks. Group comparisons of olfactory bulb volume and olfactometric scores were performed between individuals with and without smelling impairment. The associations of olfactory bulb volume and neuropsychological as well as olfactometric scores were assessed via multiple linear regression. Results: Longitudinal assessment demonstrated a declining prevalence of olfactory dysfunction from 67.6% at acute infection, 21.0% at baseline examination (on average 8.31 +- 2.77 months post infection) and 17.5% at follow-up (21.8 +- 3.61 months post infection). Participants with post-acute olfactory dysfunction had a significantly lower olfactory bulb volume [mm3] at scan-time than normally smelling individuals (mean +- SD, baseline: 40.76 +- 13.08 vs. 46.74 +- 13.66, f=4.07, p=0.046; follow-up: 40.45 +- 12.59 vs. 46.55 +- 13.76, f=4.50, p=0.036). Olfactory bulb volume successfully predicted olfactometric scores at follow-up (r_sp = 0.154, p = 0.025). Performance in neuropsychological testing was not significantly associated with the olfactory bulb volume. Conclusions: Our work demonstrates the association of smelling dysfunction and olfactory bulb integrity in a sample of individuals recovered from mainly mild to moderate COVID-19. Olfactory bulb volume was demonstrably lower in individuals with sustained smelling impairment and predicted smelling function longitudinally. Collectively, our results highlight olfactory bulb volume as a surrogate marker that may inform diagnosis and guide rehabilitation strategies in COVID-19.
Background: Infectious aerosols and droplets generated by SARS–CoV–2–positive patient aerosol generating procedures (AGPs), coughing, or exhalation could potentially contaminate surfaces, leading to indirect SARS–CoV–2 spread via fomites. Our objective was to determine SARS–CoV–2 surface contamination frequency in Emergency Department (ED) patient rooms with respect to patient SARS–CoV–2 status and AGP receipt. Methods: Swabs were collected from fixed surfaces or equipment in the rooms of patients under investigation for COVID–19 or known to be SARS–CoV–2–positive. Environmental swabs were tested for SARS–CoV–2 RNA by RTqPCR; RNA–positive samples were cultured in Vero E6 cells. Room contamination was also evaluated by clinical severity of COVID-19 and time since symptom onset. Results: In total, 202 rooms were sampled: 42 SARS–CoV–2–positive AGP patient rooms, 45 non–AGP SARS–CoV–2–positive patient rooms, and 115 SARS–CoV–2–negative AGP patient rooms. SARS–CoV–2 RNA was detected on 36 (3.6%) surfaces from 29 (14.4%) rooms. RNA contamination was detected more frequently in rooms occupied by non–AGP SARS–CoV–2–positive patients than SARS–CoV–2–positive AGP patients (28.9% vs 14.3%, p=0.078). Infectious virus was cultured from one non-AGP SARS–CoV–2–positive patient room. There was no significant difference in room positivity according to COVID–19 severity or time since symptom onset. Conclusion: SARS–CoV–2 RNA contamination of ED room surfaces was highest and most frequent in rooms occupied by SARS–CoV–2–positive patients who did not undergo an AGP, which may be attributable to disease stage and viral shedding; however, there was no difference in room contamination according to COVID–19 severity or time since symptom onset.
Purpose: In the fight against virus-caused pandemics like COVID-19, the use of diagnostic tests based on RT-qPCR is essential but sometimes limited by their dependence on expensive, specialized equipment and skilled personnel. Consequently, an alternative nucleic acid detection technique that gets over these restrictions, called loop-mediated isothermal amplification following reverse transcription (RT-LAMP), has been broadly investigated. Nevertheless, the developed RT-LAMP assays for SARS-CoV-2 detection still require laboratory devices and are electrically dependent, limiting their widespread use as rapid home tests. In this work, a flexible RT-LAMP assay that gets beyond the drawbacks of the available isothermal LAMP-based SARS-CoV-2 detection was developed, establishing a simple and effective at-home diagnosis tool for COVID-19. Methods: A multiplex direct RT-LAMP assay modified from the previously developed test was applied to simultaneously identify the two genes of SARS-CoV-2. We used a colorimetric readout, lyophilized reagents, and benchmarked an electro-free and micropipette-free method that enables sensitive and specific detection of SARS-CoV-2 in home settings. Results: Forty-one nasopharyngeal swab samples were tested using the home-testing RT-LAMP (HT-LAMP) assay developed, showing 100% agreement with the RT-qPCR results. Conclusions: This is the first electrically independent RT-LAMP assay successfully developed for SARS-CoV-2 detection at home setting. Our HT-LAMP assay is thus an important development for diagnosing COVID-19 or any other infectious pandemic on a population scale.
A Study for Immunocompromised Patients for Pre Exposure Prophylaxis of COVID-19 With AZD5156. - Condition: Â COVIDÂ 19
Interventions:  Biological: Placebo;  Biological: AZD5156;  Biological: AZD7442 (EVUSHELD™)
Sponsor: Â AstraZeneca
Not yet recruiting
101-PGC-005 for the Treatment of COVID-19 - Condition: Â COVID-19
Interventions: Â Drug:Â 101-PGC-005; Â Drug:Â Dexamethasone
Sponsor: Â 101Â Therapeutics
Recruiting
A Clinical Study to Assess Preliminary Efficacy, Safety and Tolerability of HH-120 Nasal Spray in COVID-19 Patients - Condition:  Coronavirus Disease 2019(COVID-19)
Intervention:  Biological: HH-120 Nasal Spray
Sponsor:  Beijing Ditan Hospital
Recruiting
COVID-19 Booster Study in Healthy Adults in Australia - Condition: Â COVID-19
Interventions:  Biological: Bivalent Moderna;  Biological: Novavax
Sponsors:  Murdoch Childrens Research Institute;  Coalition for Epidemic Preparedness Innovations;  The Peter Doherty Institute for Infection and Immunity
Not yet recruiting
Effect of N-Acetylcysteine on Neutrophil Lymphocyte Ratio And Length of Stay In COVID-19 Patients - Condition: Â COVID-19
Intervention:  Drug: N-acetyl cysteine
Sponsor:  Universitas Sebelas Maret
Completed
Baldachin: Ceiling HEPA-filtration to Prevent Nosocomial Transmission of COVID-19 - Condition: Â COVID-19
Intervention: Â Device:Â Baldachin
Sponsor:  University Hospital Inselspital, Berne
Not yet recruiting
Efficacy and Safety of Ambervin® and Standard Therapy in Hospitalized Patients With COVID-19 - Condition:  COVID-19
Interventions:  Drug: Tyrosyl-D-alanyl-glycyl-phenylalanyl-leucyl-arginine succinate intramuscularly;  Drug: Tyrosyl-D-alanyl-glycyl-phenylalanyl-leucyl-arginine succinate inhaled;  Drug: Standard of care
Sponsor:  Promomed, LLC
Completed
Study of GST-HG171/Ritonavir Compared With Placebo in Patients With Mild to Moderate COVID-19 - Condition: Â COVID-19Â Pneumonia
Interventions: Â Drug:Â GST-HG171/Ritonavir; Â Drug:Â Placebo
Sponsor:  Fujian Akeylink Biotechnology Co., Ltd.
Not yet recruiting
A Phaseâ…ˇ Study to Evaluate the Safety & Immunogenicity of SARS-CoV-2 Alpha/Beta/Delta/Omicron Variants COVID-19 Vaccine - Condition: Â COVID-19Â Pandemic
Interventions:  Biological: SCTV01E;  Biological: Placebo (normal saline)
Sponsor:  Sinocelltech Ltd.
Not yet recruiting
ICBT for Psychological Symptoms Related to the COVID-19 Pandemic Remaining After Societal Opening - Condition: Â Depression and Anxiety Symptoms Related to the COVID-19 Pandemic
Intervention: Â Behavioral: Internet-based Cognitive Behavioral Therapy
Sponsor:  Linkoeping University
Not yet recruiting
Effectiveness of Supportive Psychotherapy Through Internet-Based Teleconsultation on Psychological and Somatic Symptoms, Neutrophil-Lymphocyte Ratio, and Heart Rate Variability in Post Covid-19 Syndrome Patients - Condition: Â Post-COVID-19Â Syndrome
Intervention:  Behavioral: Supportive Psychotherapy
Sponsor:  Indonesia University
Not yet recruiting
Graphene Photothermal Adjuvant Therapy for Mild Corona Virus Disease 2019: A Prospective Randomized Controlled Trial - Condition: Â COVID-19
Intervention:  Device: Graphene spectrum light wave therapy room
Sponsors:  Southeast University, China;  Hohhot First Hospital
Recruiting
ARVAC - A New Recombinant Coronavirus Disease 2019 (COVID-19) Vaccine - Condition: Â COVID-19Â Vaccine
Intervention: Â Biological: ARVAC-CG vaccine (recombinant protein vaccine against SARS-CoV-2)
Sponsors:  Laboratorio Pablo Cassara S.R.L.;  Universidad Nacional de San MartĂn (UNSAM);  National Council of Scientific and Technical Research, Argentina
Active, not recruiting
The KIN-FAST Trial (KIN001 For Accelerated Symptoms Termination) in Non Hospitalized Patients Infected With SARS-CoV-2 - Condition: Â COVID-19
Interventions: Â Drug:Â KIN001; Â Drug:Â KIN001-Placebo
Sponsor:  Kinarus AG
Recruiting
The COPE Study: Pilot Intervention to Improve Symptom Self-management and Coping in Adults With Post COVID - Conditions:  Post COVID-19 Condition;  Post-COVID-19 Syndrome
Intervention:  Behavioral: 6-Week Self-Management Group
Sponsor:  University of Washington
Not yet recruiting
Visualization of early RNA replication kinetics of SARS-CoV-2 by using single molecule RNA-FISH - No abstract
Development of Fluorescence-Tagged SARS-CoV-2 Virus-like Particles by a Tri-Cistronic Vector Expression System for Investigating the Cellular Entry of SARS-CoV-2 - No abstract
Nisoldipine Inhibits Influenza A Virus Infection by Interfering with Virus Internalization Process - No abstract
Structural Characteristics of Heparin Binding to SARS-CoV-2 Spike Protein RBD of Omicron Sub-Lineages BA.2.12.1, BA.4 and BA.5 - No abstract
Heparin Inhibits SARS-CoV-2 Replication in Human Nasal Epithelial Cells - No abstract
Neutralizing Antibody and T-Cell Responses against SARS-CoV-2 Wild-Type and Variants of Concern in Chronic Obstructive Pulmonary Disease Subjects after ChAdOx-1/ChAdOx-1 Homologous Vaccination: A Preliminary Study - No abstract
Antibodies Induced by Homologous or Heterologous Inactivated (CoronaVac/BBIBP-CorV) and Recombinant Protein Subunit Vaccines (ZF2001) Dramatically Enhanced Inhibitory Abilities against B.1.351, B.1.617.2, and B.1.1.529 Variants - No abstract
The Inhibition of SARS-CoV-2 and the Modulation of Inflammatory Responses by the Extract of Lactobacillus sakei Probio65 - No abstract
Engagement of the G3BP2-TRIM25 Interaction by Nucleocapsid Protein Suppresses the Type I Interferon Response in SARS-CoV-2-Infected Cells - No abstract
Evaluation of Immunogenicity and Clinical Protection of SARS-CoV-2 S1 and N Antigens in Syrian Golden Hamster - No abstract
Effects of Mangiferin on LPS-Induced Inflammation and SARS-CoV-2 Viral Adsorption in Human Lung Cells - No abstract
Enhanced Nasal Deposition and Anti-Coronavirus Effect of Favipiravir-Loaded Mucoadhesive Chitosan-Alginate Nanoparticles - No abstract
Biologic Functions of Hydroxychloroquine in Disease: From COVID-19 to Cancer - No abstract
Inhibitors of HIV-1 and Cathepsin L Proteases Identified from the Insect Gall of Hypericum kouytchense - No abstract
SARS-CoV-2 Inhibitors Identified by Phenotypic Analysis of a Collection of Viral RNA-Binding Molecules - No abstract