Background: The origin of divergent SARS-CoV-2 spike sequences found in wastewater, but not in clinical surveillance, remains unclear. These cryptic wastewater sequences have harbored many of the same mutations that later emerged in Omicron lineages. We first detected a cryptic lineage in municipal wastewater in Wisconsin in January 2022. Named the Wisconsin Lineage, we sought to determine the geographic origin of this virus and characterize its persistence and evolution over time. Methods: We systematically sampled maintenance holes to trace the origin of the Wisconsin Lineage. We sequenced spike RBD domains, and where possible, whole viral genomes, to characterize the evolution of this lineage over the 13 consecutive months that it was detectable. Findings: The persistence of the Wisconsin Lineage signal allowed us to trace it from a central wastewater plant to a single facility, with a high concentration of viral RNA. The viral sequences contained a combination of fixed nucleotide substitutions characteristic of Pango lineage B.1.234, which circulated in Wisconsin at low levels from October 2020 to February 2021, while mutations in the spike gene resembled those subsequently found in Omicron variants. Interpretation: We propose that prolonged detection of the Wisconsin Lineage in wastewater represents persistent shedding of SARS-CoV-2 from an infected individual, with ongoing within-host viral evolution leading to an ancestral B.1.234 virus accumulating Omicron-like mutations. Funding: The Rockefeller Foundation, Wisconsin Department of Health Services, Centers for Disease Control and Prevention (CDC), National Institute on Drug Abuse (NIDA), and the Center for Research on Influenza Pathogenesis and Transmission.
Background: The COVID-19 pandemic is unceasingly spreading across the globe, and recently a highly transmissible Omicron SARS-CoV-2 variant (B.1.1.529) has been discovered in South Africa and Botswana. Rapid identification of this variant is essential for pandemic assessment and containment. However, variant identification is mainly being performed using expensive and time-consuming genomic sequencing. Methods and results: In this study we propose an alternative RT-qPCR approach for the detection of the Omicron BA.1 variant using a low-cost and rapid SYBR Green method. We have designed specific primers to confirm the deletion mutations in the spike (S ∆143-145) and the nucleocapsid (N ∆31-33) which are characteristics of this variant. For the evaluation, we used 120 clinical samples from patients with PCR-confirmed SARS-CoV-2 infections, and displaying an S-gene target failure (SGTF) when using TaqPath COVID-19 kit (Thermo Fisher Scientific, Waltham, USA) that included the ORF1ab, S, and N gene targets. Our results showed that all the 120 samples harbored S ∆143-145 and N ∆31-33, which was further confirmed by Whole genome sequencing (WGS) of 4 samples thereby validating our SYBR Green-based protocol. Conclusions: This protocol can be easily implemented to rapidly confirm the diagnosis of the Omicron BA.1 variant in COVID-19 patients and prevent its spread among populations, especially in countries with high prevalence of SGTF profile.
To respond to pandemics such as COVID-19, policy makers have relied on interventions that target specific population groups or activities. Because targeting is operationally challenging and contentious, rigorously quantifying its benefits and designing practically implementable policies that achieve some of these benefits is critical for effective and equitable pandemic control. We propose a flexible framework that leverages publicly available data and a novel optimization algorithm based on model predictive control and trust region methods to compute optimized interventions that can target two dimensions of heterogeneity: age groups and the specific activities that individuals normally engage in. We showcase a complete implementation focused on the Ile-de-France region of France and use this case study to quantify the benefits of dual targeting and to propose practically implementable policies. We find that dual targeting can lead to Pareto improvements, reducing the number of deaths and the economic losses. Additionally, dual targeting allows maintaining higher activity levels for most age groups and, importantly, for those groups that are most confined, thus leading to confinements that are arguably more equitable. We then fit decision trees to explain the decisions and gains of dual-targeted policies and find that they prioritize confinements intuitively, by allowing increased activity levels for group-activity pairs with high marginal economic value prorated by social contacts, which generates important complementarities. Because dual targeting can face significant implementation challenges, we introduce two practical proposals inspired by real-world interventions - based on curfews and recommendations - that achieve a significant portion of the benefits without explicitly discriminating based on age.
Background The effectiveness of COVID-19 monoclonal antibody and antiviral therapies against severe COVID-19 outcomes is unclear. Initial benefit was shown in unvaccinated patients and before the Omicron variant emerged. We used the OpenSAFELY platform to emulate target trials to estimate the effectiveness of sotrovimab or molnupiravir, versus no treatment. Methods With the approval of NHS England, we derived population-based cohorts of non-hospitalised high-risk individuals in England testing positive for SARS-CoV-2 during periods of dominance of the BA.1 (16/12/2021-10/02/2022) and BA.2 (11/02/2022-21/05/2022) Omicron sublineages. We used the clone-censor-weight approach to estimate the effect of treatment with sotrovimab or molnupiravir initiated within 5 days after positive test versus no treatment. Hazard ratios (HR) for COVID-19 hospitalisation or death within 28 days were estimated using weighted Cox models. Results Of the 35,856 [BA.1 period] and 39,192 [BA.2 period] patients, 1,830 [BA.1] and 1,242 [BA.2] were treated with molnupiravir and 2,244 [BA.1] and 4,164 [BA.2] with sotrovimab. The estimated HRs for molnupiravir versus untreated were 1.00 (95%CI: 0.81;1.22) [BA.1] and 1.22 (0.96;1.56) [BA.2]; corresponding HRs for sotrovimab versus untreated were 0.76 (0.66;0.89) [BA.1] and 0.92 (0.79;1.06) [BA.2]. Interpretation Compared with no treatment, sotrovimab was associated with reduced risk of adverse outcomes after COVID-19 in the BA.1 period, but there was weaker evidence of benefit in the BA2 period. Molnupiravir was not associated with reduced risk in either period.
Objective: To determine the associated factors with mortality, in addition to age and sex, in a high-complexity hospital in Bogota, Colombia, during the first year of the pandemic. Design: A case-control study. Setting: High-complexity center above 2,640 meters above sea level (masl) in Colombia. Methods: A case-control study was conducted on 564 patients admitted to the hospital with confirmed COVID-19. Deceased patients (n: 282) and a control group (n: 282), matched by age, sex, and month of admission, were included. Clinical and paraclinical variables were retrospectively obtained by systematic revision of clinical records. Multiple imputations by chained equation (MICE) were implemented to account for missing variables. Classification and regression trees (CART) were estimated to evaluate the interaction of associated factors on admission and their role in predicting mortality during hospitalization. Results: Most of the patients included were males in the seventh decade of life. Most of the admissions occurred between July and August 2021. Surprisingly, recovered patients reported heterogeneous symptomatology, whereas deceased patients were most likely to present respiratory distress, dyspnea, and seizures on admission. In addition, the latter group exhibited a higher burden of comorbidities and alterations in laboratory parameters. After the imputation of datasets, CART analysis estimated 14 clinical profiles based on respiratory distress, LDH, dyspnea, hemoglobin, D-dimer, ferritin, blood urea nitrogen, C-reactive protein, PaO2/FiO2, dysgeusia, total bilirubin, platelets, and gastroesophageal reflux disease. The accuracy model for prediction was 85.6% (P < 0.0001). Conclusion: Multivariate analysis yielded a reliable model to predict mortality in COVID-19. This analysis revealed new interactions between clinical and paraclinical features in addition to age and sex. Furthermore, this predictive model could offer new clues for the personalized management of this condition in clinical settings. Keywords: SARS-CoV-2, COVID-19, Mortality, Predictors, Risk Factors
COVID-19 has infected humans worldwide, causing millions of deaths or prolonged symptoms in survivors. The transient or persistent symptoms after SARS-CoV-2 infection have been defined as post-COVID-19 conditions (PCC). We conducted a study of 151 Brazilian PCC patients to analyze symptoms and immunoglobulin profiles, taking into account gender, vaccination, hospitalization and age. Fatigue and myalgia were the most common symptoms and lack of vaccination, hospitalization, and neuropsychiatric and metabolic comorbidities were relevant for the development of PCC. Analysis of serological immunoglobulins showed that IgA was higher in PCC patients, especially in the adult and elderly groups. Also, non-hospitalized and hospitalized PCC patients produced high and similar levels of IgA. Our results indicated that the detection of IgA antibodies against SARS-CoV-2 during the course of the disease could be associated with the development of PCC and may be an immunological signature to predict prolonged symptoms in COVID-19 patients.
The Standard of Care Combined With Glucocorticoid in Elderly People With Mild or Moderate COVID-19 - Condition: COVID-19
Intervention: Drug: Glucocorticoid
Sponsor: Huashan Hospital
Not yet recruiting
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
Arginine Replacement Therapy in COVID-19 - Condition: COVID-19
Intervention: Drug: Arginine Hydrochloride
Sponsor: Emory University
Not yet recruiting
Effectiveness of a Second COVID-19 Vaccine Booster in Chinese Adults - Condition: COVID-19
Interventions: Biological: Intramuscularly administered Ad5-nCoV vaccine; Biological: Aerosolized Ad5-nCoV; Biological: DelNS1-2019-nCoV-RBD-OPT1; Biological: SYS6006
Sponsor: Jiangsu Province Centers for Disease Control and Prevention
Not yet recruiting
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
A Pilot Study Evaluating the Efficacy of the Vielight Neuro RX Gamma in the Treatment of Post COVID-19 Cognitive Impairment - Condition: Post COVID-19 Cognitive Impairment
Interventions: Device: Vielight Neuro RX Gamma active device; Device: Vielight Neuro RX Gamma sham device
Sponsor: Vielight Inc.
Not yet recruiting
PAxlovid loNg cOvid-19 pRevention triAl With recruitMent In the Community in Norway - Conditions: Post COVID-19 Condition, Unspecified; SARS-CoV2 Infection; COVID-19
Interventions: Drug: Nirmatrelvir/ritonavir; Drug: Placebo
Sponsors: Haukeland University Hospital; University of Bergen
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
Role of Vit-D Supplementation on BioNTech, Pfizer Vaccine Side Effect and Immunoglobulin G Response - Condition: COVID-19 Respiratory Infection
Intervention: Combination Product: Vitamin-D
Sponsor: Sulaimany Polytechnic university
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
Safety, Tolerability and Immunogenicity of Alveavax-v1.2, a BA.2/Omicron-optimized, DNA Vaccine for COVID-19 Prevention - Condition: Sars-CoV-2 Infection
Interventions: Drug: Alveavax-v1.2; Drug: Janssen Ad26.COV2.S
Sponsor: Alvea Holdings, LLC
Completed
Post Covid-19 Dysautonomia Rehabilitation Randomized Controlled Trial - Conditions: Post-Acute COVID-19 Syndrome; Dysautonomia
Interventions: Procedure: Rehabilitation; Procedure: Standard of Care
Sponsors: Evangelismos Hospital; National and Kapodistrian University of Athens; LONG COVID GREECE; 414 Military Hospital of Special Diseases
Recruiting
Exercise for Health in Patients With Post-acute Sequelae of COVID-19 - Condition: Long COVID
Intervention: Other: Rehabilitation program
Sponsors: Campus docent Sant Joan de Déu-Universitat de Barcelona; Hospital de Mataró; University of Barcelona
Active, not recruiting
Digital Multimodal Rehabilitation for People With Post-acute COVID-19 Syndrome. - Condition: Post-COVID Syndrome
Interventions: Behavioral: RehabCovid_Telematic; Behavioral: RehabCovid_ImmersiveVR; Behavioral: Control_Condition
Sponsors: Consorci Sanitari de Terrassa; University of Barcelona; Universitat de Girona; Unitat Assistencial i Preventiva de l’Esport- Centre d’Alt rendiment; Politecnic University of Catalonia; Corporación Fisiogestión
Recruiting
RADx-UP- Impact of Community Health Worker Deployment - Conditions: Diabetes; COVID-19; Community Health Workers; Health Behavior; Health Knowledge, Attitudes, Practice
Intervention: Behavioral: Impact of Community Health Worker Home Deployment on COVID-19 Vaccine Confidence and Uptake
Sponsor: Morehouse School of Medicine
Active, not recruiting
In silico design of miniprotein to inhibit SARS-CoV-2 variant Omicron spike protein - Omicron is a novel variant of SARS-CoV-2 that is currently spreading globally as the dominant strain. The virus first enters the host cell through the receptor binding domain (RBD) of the spike protein by interacting with the angiotensin-converting enzyme 2 (ACE2). Thus, the RBD protein is an ideal target for the design of drugs against the Omicron variant. Here, we designed several miniprotein inhibitors in silico to combat the SARS-CoV-2 Omicron variant using single- and double-point mutation…
Conformal Hydrogel-Skin Coating on a Microfluidic Channel through Microstamping Transfer of the Masking Layer - Poly(dimethylsiloxane) (PDMS) is used in microfluidics owing to its biocompatibility and simple fabrication. However, its intrinsic hydrophobicity and biofouling inhibit its microfluidic applications. Conformal hydrogel-skin coating for PDMS microchannels, involving the microstamping transfer of the masking layer, is reported herein. A selective uniform hydrogel layer with a thickness of ∼1 μm was coated in diverse PDMS microchannels with a resolution of ∼3 μm, maintaining its structure and…
The C-terminal 32-mer fragment of hemoglobin alpha is an amyloidogenic peptide with antimicrobial properties - Antimicrobial peptides (AMPs) are major components of the innate immune defense. Accumulating evidence suggests that the antibacterial activity of many AMPs is dependent on the formation of amyloid-like fibrils. To identify novel fibril forming AMPs, we generated a spleen-derived peptide library and screened it for the presence of amyloidogenic peptides. This approach led to the identification of a C-terminal 32-mer fragment of alpha-hemoglobin, termed HBA(111-142). The non-fibrillar peptide has…
Challenges and Progress in Designing Broad-Spectrum Vaccines Against Rapidly Mutating Viruses - Viruses evolve to evade prior immunity, causing significant disease burden. Vaccine effectiveness deteriorates as pathogens mutate, requiring redesign. This is a problem that has grown worse due to population increase, global travel, and farming practices. Thus, there is significant interest in developing broad-spectrum vaccines that mitigate disease severity and ideally inhibit disease transmission without requiring frequent updates. Even in cases where vaccines against rapidly mutating…
Flavonoid as possible therapeutic targets against COVID-19: a scoping review of in silico studies - CONCLUSION: These studies allow us to provide a basis for in vitro and in vivo assays to assist in developing drugs for the treatment and prevention of COVID-19.
Discovery of dual S-RBD/NRP1-targeting peptides: structure-based virtual screening, synthesis, biological evaluation, and molecular dynamics simulation studies - Both receptor-binding domain in spike protein (S-RBD) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human neuropilin-1 (NRP1) are important in the virus entry, and their concomitant inhibition may become a potential strategy against the SARS-CoV-2 infection. Herein, five novel dual S-RBD/NRP1-targeting peptides with nanomolar binding affinities were identified by structure-based virtual screening. Particularly, RN-4 was found to be the most promising peptide targeting S-RBD…
Compounds from myrtle flowers as antibacterial agents and SARS-CoV-2 inhibitors: In-vitro and molecular docking studies - Plants and their related phytochemicals play a key role in the treatment of bacterial and viral infections, which inspire scientists to design and develop more efficient drugs starting from the phytochemical active scaffold. This work aims to characterize the chemical compounds of Myrtus communis essential oil (EO) from Algeria and to evaluate its in vitro antibacterial effect, as well as the in silico anti-SARS-CoV-2 activity. The chemical profile of hydrodistilled EO from myrtle flowers was…
Declined Humoral Immunity of Kidney Transplant Recipients to SARS-CoV-2 Vaccines - CONCLUSION: KTRs’ humoral response after SARS-CoV-2 vaccination is dramatically inhibited and wanes. Antibody levels show a significant decline over time in KTRs with hypertension; receiving triple immunosuppressive therapy or steroid-based or antimetabolite-based regimens; receiving mixed mRNA and viral vector vaccines; and with a transplant of >10 years.
Interactive network pharmacology and electrochemical analysis reveals electron transport-mediating characteristics of Chinese medicine formula Jing Guan Fang - BACKGROUND: Jing Guan Fang (JGF) is an anti-COVID-19 Chinese Medicine decoction comprised of five medicinal herbs to possess anti-inflammatory and antiviral properties for treatment. This study aims to electrochemically decipher the anti-coronavirus activity of JGF and show that microbial fuel cells may serve as a platform for screening efficacious herbal medicines and providing scientific bases for the mechanism of action (MOA) of TCMs.
Physicochemical characterization of reusable facemasks and theoretical adhesion by a challenged bacterium - CONCLUSION: Such information is valuable to understand attachment of biological particles and to contribute in the inhibition of this attachment.
Screening of SARS-CoV-2 antivirals through a cell-based RNA-dependent RNA polymerase (RdRp) reporter assay - COVID-19 (Coronavirus Disease 2019) caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome CoronaVirus-2) continues to pose an international public health threat and thus far, has resulted in greater than 6.4 million deaths worldwide. Vaccines are critical tools to limit COVID-19 spread, but antiviral drug development is an ongoing global priority due to fast-spreading COVID-19 variants that may elude vaccine efficacies. The RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 is an essential…
SARS-CoV-2 Omicron sub-lineages differentially modulate interferon response in human lung epithelial cells - Although most of the attention was focused on the characterization of changes in the Spike protein among variants of SARS-CoV-2 virus, mutations outside the Spike region are likely to contribute to virus pathogenesis, virus adaptation and escape to the immune system. Phylogenetic analysis of SARS-CoV-2 Omicron strains reveals that several virus sub-lineages could be distinguished, from BA.1 up to BA.5. Regarding BA.1, BA.2 and BA.5, several mutations concern viral proteins with antagonistic…
Purification and characterisation of heparin-like sulfated polysaccharides with potent anti-SARS-CoV-2 activity from snail mucus of Achatina fulica - Heparin-like sulfated polysaccharide, acharan sulfate, was purified from the mucus of an African giant snail with unique sulfated glycosaminoglycans (GAGs). This study reported on finding novel and safe heparin resources from Achatina fulica for further use as well as easy isolation and purification of the active fraction from the initial raw material. Its structure was characterised by a strong-anion exchange combined with high-performance liquid chromatography (HPLC) and nuclear magnetic…
Structure-guided optimization of adenosine mimetics as selective and potent inhibitors of coronavirus nsp14 N7-methyltransferases - The COVID-19 pandemic reveals the urgent need to develop new therapeutics targeting the SARS-CoV-2 replication machinery. The first antiviral drugs were nucleoside analogues targeting RdRp and protease inhibitors active on nsp5 Mpro. In addition to these common antiviral targets, SARS-CoV-2 codes for the highly conserved protein nsp14 harbouring N7-methyltransferase (MTase) activity. Nsp14 is involved in cap N7-methylation of viral RNA and its inhibition impairs viral RNA translation and immune…
Immunization with Recombinant Accessory Protein-Deficient SARS-CoV-2 Protects against Lethal Challenge and Viral Transmission - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a worldwide coronavirus disease 2019 (COVID-19) pandemic. Despite the high efficacy of the authorized vaccines, there may be uncertain and unknown side effects or disadvantages associated with current vaccination approaches. Live-attenuated vaccines (LAVs) have been shown to elicit robust and long-term protection by the induction of host innate and adaptive immune responses. In this study, we sought to verify an attenuation…